Suzy Cohen, Columnist Published 5:02 a.m. ET Feb. 1, 2021

Having an autoimmune condition, or a thyroid condition can make you more susceptible to COVID-19 complications.(Photo: Eraxion / Getty Images)

Having an autoimmune condition, or a thyroid condition can make you more susceptible to COVID-19 complications. Think of autoimmune conditions in the same manner you would other immunosuppressive disorders (i.e. cancer, organ transplantation, history of radiation treatment or chemotherapy).

As it pertains to Hashimotos thyroiditis, Graves disease or hypothyroidism you need to be extra vigilant while youre out in public because your immunity is compromised.

The right dose of thyroid medication, and the right kind are critical because you may not be getting enough active thyroid hormone (T3) to your immune system which resides primarily in the intestines. While your body struggles to make do with whatever hormone is available in your body, you may experience symptoms such as poor concentration, chronic fatigue, hair loss, apathy, sensations of being cold, depression and/or anxiety.

If you have autoimmune thyroid disease, or hypothyroidism, your immune system may not be able to protect you from foreign antigens or invaders. These include new cancer cells, microorganisms, toxins, and even simplistic signals that your body should see and dont due to low thyroid. If youre low in thyroid, your protection against invaders is hindered.

When you have poor T4 to T3 conversion, I call it being thyroid sick and the solution is thoroughly discussed in my best-selling book called, Thyroid Healthy, available on Amazon. The situation makes you hypothyroid and you could have many, if not all, the symptoms that go with it, especially suppressed immune function, and more frequent colds, fever blisters, rashes and UTIs.

Some doctors prescribe both medications to a patient, meaning both T4 drugs and T3, but getting the right dose is tough on doctors (and patients) because its like trying to hit a moving target.

Generally speaking, because the cytokines will be imbalanced in a person with autoimmunity, the recovery time from an infection could be lengthened. There are vitamins that can keep your immune system in tip-top shape during the season. And, Im passionate about herbal medicine. One reason that herbs work well and have strong anti-viral, anti-bacterial and anti-parasitic effect is because they have a wide spectrum of medicinally active constituents.

This means they have a wide range of beneficial impacts in the body aside from their kill action.

I want each of you to be very thoughtful while reading this and remember to never suddenly go off your medication because of something you read. Going off a medication can be problematic for two main reasons:

If youd like to receive my newest ebook on immunity, download it now at https://www.store.suzycohen.com/strengthen-immune.

More: Ask the Pharmacist: How hawthorn lowers blood pressure

And: Ask the Pharmacist: Solutions for gastrointestinal upset

Also: Ask the Pharmacist: Five effective tips to lose weight

Suzy Cohen is a registered pharmacist. The information presented here is not intended to treat, cure or diagnose any condition. Visit SuzyCohen.com.

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Ask the Pharmacist: Autoimmune disorders and infection risk - Marco News

Recommendation and review posted by Bethany Smith

During a Targeted Oncology Case-Based Peer Perspective Roundtable, Sara M. Tolaney, MD, MPH, associate director, Susan F. Smith Center for Womens Cancers, director, Clinical Trials, Breast Oncology, director, Breast Immunotherapy Clinical Research, senior physician, Dana-Farber Cancer Institute, and associate professor of Medicine, Harvard Medical School, discussed therapies available for the treatment of a 42-year0old women with HER2-positive breast cancer.

Targeted OncologyTM: What are your thoughts on the results of the poll?

TOLANEY: It looks like most people voted for TCHP [docetaxel, carboplatin, trastuzumab (Herceptin), pertuzumab (Perjeta)] and then 1 voted for AC [doxorubicin, cyclophosphamide] + THP [paclitaxel, trastuzumab, pertuzumab]. I think these are both reasonable choices. I think knowing that there is lymph node involvement is prompting people to use pertuzumab-based therapy. So, the question [is:] do you want to give anthracycline-based therapy versus nonanthracycline-based treatment? Given some newer data, I [tend] to now use nonanthracycline- based therapy for the vast majority of my patients since I have been using TCHP.

How would you assess this patients risk, and what factors should you keep in mind when assessing risk?

This was a fairly sizable tumor with nodal involvement [that was] high grade, HER2 positive, ER negative...These are all high-risk features. And so, certainly prior to the advent of trastuzumab [Herceptin], this patient would have a high risk of recurrence. The issue about ER will often come up as to whether or not it is truly a prognostic indicator in HER2-positive disease, where so much of the benefit from therapy is really driven by HER2.

If you look at long-term outcomes from HER2-positive patients in the adjuvant setting, and you were to compare the ER-positive versus ER-negative patients, you can see that their long-term outcomes are not that dissimilar. ER-positive, HER2-positive patients tend to do slightly better. They have a different time frame to recurrence, though. Youll see that ER-positive, HER2- positive cancers tend to have recurrences a bit later than the ER-negative, HER2-positive cancers. But in the long run, when you follow them out 8 to 10 years, the difference is quite small between their long-term outcomes. But we do know that in a preoperative setting that the ER-positive, HER2-positive patients do have a lower likelihood of achieving pCR [pathologic complete response] to preoperative therapy, even though...their long-term outcomes are not that dissimilar.

Would you recommend neoadjuvant systemic therapy for such patients?

I find it hard to know what to do for that patient because if they ended up having, [for example], 1.2-cm HER2-positive cancer that was node negative, you take them straight to surgery and they could get away with just TH [paclitaxel, trastuzumab]. We know that their long-term outcomes will be good with TH [in the] stage I setting, with 98% recurrence-free interval out to now almost 7 years.1

But the problem that I have is I dont know their nodal status, and I dont really know how much cancer they have. So, Im always a little worried that Im either under- or over- treating them, depending on what you end up finding out later. Because of that fear, I have tended to take most of my patients [with masses] under 2 cm to surgery first, so that I know what [they are dealing with, in order to make] that final treatment decision.

It does put you at risk potentially for finding [a patient with] stage II disease, which is problematic, because I would have wanted to give them preoperative therapy. Then I could potentially give them postoperative T-DM1 [ado-trastuzumab emtansine; Kadcyla] if they had residual disease. But on the flip side, I worry that if the patient who I think has stage I disease ends up having stage II disease and has nodal involvement, then Ive undertreated them. And so, I find it a little tricky to know how much to give them if [their tumor is] small. I think its a balance, because you dont want to overtreat, you dont want to undertreat, particularly when you are at this high 1s1.8, 1.9 cm; that is where I struggle a bit.

There are a lot of studies ongoing that I think could...make this a little more comfortable. There is a preoperative trial through the [National Cancer Institute], the CompassHER2- pCR study [NCT04266249], which is looking at preoperative THP. And if someone achieves pCR, they go on to [receive] HP [trastuzumab, pertuzumab]. In my mind, if that study pans out and shows that we could potentially get away with THP in stage 2 patients, for example, then I would not feel so bad about giving my [patient with a] 1.8-cm mass THP up front because it was probably an effective amount of therapy; maybe they didnt need the pertuzumab. We know from the APHINITY study [NCT01358877], for example, [that] there is no benefit from pertuzumab in our node- negative patients.

But at least I didnt give them a ton of chemotherapy that they didnt need; TCHP, in my mind, is difficult; with carboplatin, pertuzumab, they have a chance of diarrhea, so thats not easy. Whereas weekly THP is easy for most patients; its not so bad. And so, we need to find a middle ground and were just not quite there yet. It sort of seems [as though] were picking between extremes of TH and then TCHP. And I think thats part of whats driving some of this problem.

For [a patient such as] this, it would be clear to do preoperative treatment.

Would you consider using anthracyclines in a patient such as this in the preoperative setting?

[You may] remember BCIRG 006 [NCT00021255], which compared TCH [docetaxel, carboplatin, trastuzumab] with ACT [AC followed by docetaxel] or AC-TH, showed that the anthracycline and nonanthracycline arms had fairly similar disease-free survival [DFS]. This was prior to pertuzumab becoming a standard, and it was also at a time when the study wasnt powered to technically compare AC-TH to TCH, but we knew the DFS looked similar regardless of nodal status.2

But a more modern era trial is the TRAIN-2 trial [NCT01996267]. In this case, it was a different because they used paclitaxel with carboplatin and HP, not the traditional docetaxel and carboplatin. The comparator arm is also a little different than I typically would use because its FEC [5-fluorouracil, epirubicin, and cyclo- phosphamide] with HP followed by the taxane with HP.

What we showed was that the pCR was the same with either armanthracycline versus nonanthracycline. Now we have follow-up to almost 50 months,3 and the event-free survival is also the same. So, [there was] no statistically significant difference in event-free or overall survival.

There is also a subgroup analysis that showed that even if you looked at the high-risk, node-positive patients in this study, there was still no difference in event-free survival between the 2 arms. And [analysis showed] less cardiac toxicity, numerically less leukemia, and less febrile neutropenia with a nonanthracycline-based therapy.

Since these data have emerged, it has made me feel much more comfortable using nonanthracycline therapy because were seeing that, even with long-term follow-up in a modern era of pertuzumab-based therapy, there is no difference in long-term outcomes between anthracycline and nonanthracycline therapy. In my mind, there isnt much rationale to consider anthracycline- based treatment for HER2-positive patients.

Do you agree with this approach?

If you look at the preoperative trials, generally pCR rates are in the 60% range from TCHP. So, it is a highly effective preoperative therapy. We do know that those patients who achieve pCR have better long-term outcomes than those who have residual disease. And so, trying to maximize chances to get pCR makes sense for patients, and generally that is my approach, as well.

Obviously, there is interest in trying to develop less-toxic approaches. I fully admit that were seeing more toxicity with anthracycline-based therapy. I think we all are seeing that HER2- directed therapies are improving. With time were seeing better biologic treatments. There is a potential that we could get rid of some of the chemotherapy. Do we need to give everyone TCHP, I think, is the question. I think there are some patients who probably dont need all this chemotherapy and probably would be fine with single-agent taxane and dual HER2-directed therapy. The problem is, how do we identify who those patients are? And who really needs the full TCHP?

I think [its being thought of now as], Well, maybe we can use the achievement of pCR to help us figure that out. Could we, for example, as COMPASS is doing, take THP and give it a test run and see if it works? Does it give a pCR? If it does well, we did good. If it doesnt, then we need to escalate therapy, then we can give those patients who didnt get the pCR more treatment. Could they get AC, followed by T-DM1, for example? They would have completed AC-THP and T-DM1 as if they had received AC-THP preoperatively and then T-DM1 out back.

I think this is what were trying to learn, how can we tailor therapy. Were not quite there yet. Outside of clinical trials, I try to follow more textbook-like approaches, rather than these deescalation approaches, which I think should be reserved for trials at this point in time. I generally recommend TCHP.

What are some of these escalation/ deescalation strategies?

There are other trials that are ongoing in this space, and there are lots of deescalation approaches, [which try] to give less therapy. One deescalation approach could be to use T-DM1.

The KRISTINE trial [NCT02131064] had taken patients and randomized them to get TCHP or to get T-DM1 and pertuzumab. Technically the T-DM1 [arm], from a preoperative standpoint, had a higher pCR rate.4 But what was interesting to me is if you followed all the patients out for invasive disease-free survival [iDFS] after surgery, it was the same in both arms. So iDFS, if you follow people postop was exactly the same with T-DM1 + pertuzumab and TCHP.

The problem was in the preoperative setting. Some of the T-DM1 + pertuzumab patients had local regional progression, and those tended to be patients who had heterogeneous HER2 expression. If you think about it, these are patients who youre trying to get to pCR by just HER2-directed therapy. So, if they have any HER2 heterogeneity, its not going to work perfectly right. If you have a HER2-positive 2+ patient who is borderline FISH-amplified, T-DM1 probably isnt going to be a home run for this patient.

I think thats another issue thats going to come up as we try these deescalation approaches. Maybe it does need to be [an individual] who is strongly HER2-positive, 3+, to get away with an ADC [antibody-drug conjugate] such as T-DM1, which in my opinion, is much better tolerated than something [such as] TCHP and could be a wave of the future to try to deescalate therapy.

But on the flip side, I think were also trying to escalate treatment for the individuals who need it. There are trials ongoing trying to do more. One study, for example, in the high-risk population would be to potentially add immunotherapy to chemotherapy and HER2-directed therapy. There is a Roche study [NCT03135171] thats adding a tocilizumab [Actemra] to AC-THP in the preoperative setting. And there are some investigator-initiated trials also adding pembrolizumab to THP preoperatively.

There are some studies that are trying to replace trastuzumab with margetuximab [Margenza] in the preoperative setting, trying to escalate therapy. There is work on both sides of the spectrum, trying to get the right amount of treatment to the right patient. I think as we learn more, hopefully, well be able to do that. Its going to be interesting to see if well ever have biomarkers that will help us or if it will need to be something else.

There are some data that suggest early [PET scan] response could be a way to judge if youre giving an appropriately deescalated therapy. That could be a way to have early markers of response to know if we can get away with a little bit less.

Whats your approach to a suboptimal response pathologically after neoadjuvant chemotherapy?

This patient received TCHP and had residual disease. Generally speaking, I tend to give 14 cycles of T-DM1, as per the KATHERINE trial [NCT01772472], because we know that that will reduce chances of recurrence by about half.5 But if they achieve pCR, then I tend to complete HP-based therapy outback. I think the question that will arise is, do you give [a patient] neratinib [Nerlynx] after completion of adjuvant HER2- directed therapy?

We have data from the ExteNET trial [NCT00878709], for example, that showed that giving a year of neratinib after completion of trastuzumab did have a significant improvement in iDFS.6 I think my challenge is that that study was done at a time when we were not giving pertuzumab. We were not giving postrehab T-DM1. And so, we dont know what the benefit of neratinib would be in a modern-era patient.

That being said, the big benefit in ExteNET was in the hormone receptorpositive, HER2-positive patients, where, if you looked at the subgroup in that trial that had residual disease that was ER-positive and HER2-positive, there was a 7% absolute difference in iDFS and a trend toward survival benefit. And so, I have taken the stance, even though its completely not data driven, if [a patient] has ER-positive, HER2-positive disease and has residual disease after preoperative therapy, then goes on to complete their T-DM1 afterward, I offer neratinib.

What about the risk of diarrhea associated with neratinib?

[There are] some newer antidiarrheal approaches. The one that I tend to like best is the dose-escalation strategy, where you can start at just 2 pills a day and then escalate up a pill a week. [In my opinion,] just purine loperamide works well because patients tachyphylaxed to the diarrhea. If you start low and go up to full dose, Ive noticed that they tolerate that well.

In fact, in the CONTROL trial [NCT02400476], which looked at various antidiarrheal regimens with neratinib, that was the best- tolerated approach with the lowest rate of discontinuation.7 The other approaches include budesonide with loperamideso thats the oral steroid thats not absorbable or using colestipol, which is a bile acid sequestering [agent], and that works well with purine loperamide I find.

Any of those strategiescolestipol/loperamide, budesonide/ loperamide, or dose-escalation neratinibhave been much better than the days of using a purine loperamide, which doesnt work as [we have seen] with the 40% rate of grade 3/4 diarrheas reported in ExteNET.6

If this patient has pCR, would you still do trastuzumab and pertuzumab because of the nodal status?

We have no answer because no one has done that study to see if you could deescalate the pertuzumab in a pCR patient. But there was a large meta-analysis, where they looked at patients who had a pCR and they looked at their risk of recurrence, and they found that baseline nodal status and tumor size were still prognostic. They were still independent prognostic indicators, even in a pCR patient. Those patients with upfront nodal involvement still have a higher rate of recurrence than the upfront node-negative patient with pCR; their baseline risk is still prognostic.

In this patient who does have high-risk [disease], we know that pertuzumab-based therapy for a year, based on APHINITY, did [lead to] risk reduction.

What is next in terms of adjuvant therapies?

There are studies that are ongoing trying to see if we can do even better than KATHERINE. Certainly, KATHERINE was very impressive with a 3-year iDFS of 88% with a 50% risk reduction.5 But there still was no reduction in CNS [central nervous system] recurrences in KATHERINE. And if you look at the node-positive subgroup of KATHERINE, their iDFS was about 83% at 3 years. So, in my mind, theres still room for improvement in the high- risk, node-positive patients.

There are studies ongoing. One is called the CompassHER2-RD study [NCT04457596], which is looking at taking patients with residual disease and randomizing them to get T-DM1 or T-DM1 plus tucatinib [Tukysa] with the idea that there are some data to suggest tucatinib, the oral TKI [tyrosine kinase inhibitor] [works] synergistically with T-DM1. Could it enhance activity and potentially even prevent CNS recurrences, knowing that tucatinib penetrates CNS?

That study will take patients with residual disease, and, just [as in] KATHERINE, randomize them to T-DM1 with or without tucatinib. And then theres a study opening through NRG [Oncology], looking at trastuzumab deruxtecan [Enhertu] in patients with residual disease [DESTINY-Breast05; NCT04622319]. Its randomizing the residual disease patient to trastuzumab deruxtecan or T-DM1, again trying to escalate therapy for that high-risk patient.

I think well see more with time about whether we can do even better for the high-risk patients, but for now, outside of a trial, T-DM1 would be the standard.

What adjustments have you made in treatment as a result of the coronavirus disease 2019 (COVID-19) pandemic?

One thing our group has started thinking about is using subcutaneous HP [Phesgo]. There are now data that compared the IV [intravenous] and subcutaneous formulations in the preoperative setting [from] the FeDeriCa study [NCT03493854].

The pCR rates were the same [59.5% vs 59.7%].8 They looked at pharmacokinetics between the 2, and they were also the same. [In terms of] adverse events, there werent any significant differences. There was a little more skin reaction at the site of the injection with the subcutaneous [formulation], but outside of that no real differences in toxicity profiles.

The other thing that I think is interesting, and I think this is a pretty cool study, is a preference study called PHranceSCa [NCT03674112], where they took people who received IV HP and then switched them to subcutaneous or did the reverse. They asked [the patients what they preferred], because every patient had been exposed to either formulation, and [more than] 80% of people preferred subcutaneous when they had received both.9

Obviously, the chair time and infusion are a lot less if you just give a 10-minute push of both drugs, rather than having to give 2 IV drugs 30 minutes each. Our group has started switching people over. It turns out when we compared the cost of subcutaneous with IV, subcutaneous was [less expensive]. I think Roche was clever in the way they priced it to try to encourage utilization. I think there are even some more advantages to chair time in the infusion center by using subcutaneous.

Our new practice has been that when we start, for example, TCHP, we just give everyone the subcutaneous formulation instead of IV. And then Ive started offering my other patients who are in maintenance HP in the adjuvant setting after their pCR, for example, the subcutaneous version because they can be in and out of infusion much [more quickly].

We usually use the thigh [for the subcutaneous infusion], and youre supposed to rotate location. Its 1 shot, theyre both drugs are mixed into 1. Thats why its nice. The problem is, it is quite a bit of volume. And so, its, [for instance], 10 cc of fluid getting pushed subcutaneously and it has to be a very slow push for 10 to 12 minutes. So, its not like a quick subcutaneous push. But patients have really liked it.

There is a study ongoing where theyre sending nurses to [patients homes] and administering the HP there. I think particularly during COVID-19 theres a big push to figure out how to do home administration of drugs. And since so many patients are on maintenance afterward, its nice for them not to have to come into clinic so much. I think well see more about the feasibility of home administration, but for now, this has to be done by a nurse in our infusion center; its not something that can be done by patients at this time.

I also use the subcutaneous trastuzumab, as well. For example, when I give TH, Ive switched over to using just subcutaneous trastuzumab, because thats also quicker, particularly when youre on just the trastuzumab maintenance. After the first 12 weeks, thats in and out of infusion very fast. I havent had any insurance pushback, which is quite interesting, when using the subcutaneous trastuzumab formulation. Its gone through just fine.

The rest is here:
Use of Anthracycline or Nonanthracycline Therapy Is Considered in HER2+ Breast Cancer - Targeted Oncology

Recommendation and review posted by Bethany Smith

Diabetes is a group of diseases that negatively affect how your body uses glucose or blood sugar. This is an issue because glucose is important to our health, it is an important source of energy for our body. It is also a main fuel source for our brain. Individuals affected by diabetes can either have Type 1 diabetes or Type 2 diabetes or pre-diabetes.

In Type 1 diabetes, the body just doesnt make insulin. Typically, the body is supposed to break down carbs that are eaten into glucose that it then uses for energy, and insulin is the hormone that is necessary to get blood sugar from the bloodstream into the cells. The Centers for Disease Control and Prevention (CDC), estimates that around 1.6 million Americans have Type 1 diabetes, with about 187,000 of that number being children and adolescents. Type 1 diabetes can occur in anyone at any age and it affects every race, and people of every size. The exact cause of type 1 diabetes is unknown. What is known is that your immune system which normally fights harmful bacteria or viruses attacks and destroys your insulin-producing cells in the pancreas. This leaves you with little or no insulin. Instead of being transported into your cells, sugar builds up in your bloodstream. Type 1 is thought to be caused by a combination of genetic susceptibility and environmental factors, though exactly what those factors are is still unclear. Weight is not believed to be a factor in type 1 diabetes. There are resources available to anyone affected by it. This is a condition that can be managed, by practicing healthy lifestyle habits (exercise and proper diets). Individuals with this condition can live a full and normal life.

Type 2 diabetes is when the body doesnt use insulin properly, and this is the most common type of diabetes. Different people require different treatment plans, some people can control their glucose levels by eating healthy and exercising but some may need to use medication or insulin to help them. Either way, there are resources and support available to help everyone affected.

A large and important part of managing type 2 diabetes is maintaining a healthy diet and exercising. It is essential to find a diet that can be maintained, by finding a healthy diet that you actually enjoy. Fitness is also important, and thankfully there are many options available to those who want to get moving. Find activities that you enjoy doing and do them in your free time. Working with your physician to determine what physical activity level you can actually handle and that you should engage in, is a good first step to take to get active.

Another health condition related to diabetes is prediabetes. This is where your glucose levels are higher than normal but not quite high enough to be diagnosed as type 2 diabetes. According to the CDC, 88 million American adults have prediabetes, with more than 80% of them knowing that they have it. Prediabetes puts you at risk of developing type 2 diabetes, stroke, and heart disease. However, if you have prediabetes lifestyle changes can be made to delay or even prevent the onset of type 2 diabetes and the other serious health problems that prediabetes puts you at risk for.

Regardless of the type of diabetes certain signs and symptoms occur. They include increased thirst, frequent urination, extreme hunger, unexplained weight loss, presence of ketones in the urine (ketones are a byproduct of the breakdown of muscle and fat that happens when theres not enough available insulin), fatigue, irritability, blurred vision, slow-healing sores, frequent infections, such as gums or skin infections and vaginal infections. Ask your healthcare provider for help and testing if you notice any of these symptoms.

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Originally posted here:
LIVE WELL: The importance of knowing the aspects of diabetes - Stillwater News Press

Recommendation and review posted by Bethany Smith

Choosing to avoid meat and eat a plant-based diet has never seemed so virtuous and necessary. Between the intrinsic cruelty of industrial livestock production and livestocks climate footprintestimated by the U.N.s Food and Agriculture Organization to be 14.5% of all greenhouse gases world-wide, significantly greater than that of plant agricultureit has become increasingly difficult to defend the place of meat and animal-sourced foods in our diets. Jonathan Safran Foer, the novelist turned animal-rights activist, may have best captured this thinking in his 2019 nonfiction book, We Are the Weather: Saving the Planet Begins at Breakfast. As he writes, We cannot keep the kind of meals we have known and also keep the planet we have known. We must either let some eating habits go or let the planet go. It is that straightforward, that fraught.

An essential part of this argument is the proposition that animal-sourced foods, and particularly red and processed meats, arent just bad for the planet but harmful for the people who eat them. As the journalist Michael Pollan famously urged in his 2008 bestseller In Defense of Food, that is why we should eat mostly plants. This has become the lone piece of dietary counseling on which most nutritional authorities seemingly agree. It creates a win-win proposition: By eating mostly (or even exclusively) fruits, vegetables, whole grains and legumes, while getting our proteins and fats from plant-based sources, we maximize our likelihood of living a long and healthy life while also doing whats right for the planet.

But is it that simple? A growing body of evidence suggests it isnt, at least not for many of us.

The other food movement that has won increased acceptance over the past decade is the low-carbohydrate, high-fat ketogenic dietketo, for shortwhich has emerged as a direct response to the explosive rise in the incidence of obesity and diabetes. More than 70% of American adults are now obese or overweight, according to the Centers for Disease Control and Prevention; nearly one in 10 is severely obese, and more than one in 10 is diabetic. An unavoidable implication of these numbers is that the conventional wisdom on weight losseat less, move your body morehas failed tens of millions of Americans.

These are the people who, sooner or later, may well experiment with alternative approaches, venturing into the realm of fad diets. They may try plant-based eatingvegetarian or even veganand if those dont return them to health, try keto or one of the many variations on low-carbohydrate, high-fat diets, from the original Atkins diet to the South Beach diet to paleo to the latest trend, carnivore. If they find that an unconventional approach works for them, allowing them to achieve and maintain a relatively healthy weight without enduring hunger, that will be their motivation to sustain it. But because this way of eating is most easily accomplished with animal-sourced foods, they may come to believe that whats good for them (and even their children) isnt good for the planet.

See more here:
The Keto Way: What If Meat Is Our Healthiest Diet? - The Wall Street Journal

Recommendation and review posted by Bethany Smith

While regular use of contraceptives is the best choice to prevent pregnancy, emergency contraception is a safe way to prevent an unwanted pregnancy after having unprotected sex.

If you've recently had unprotected sex and are looking for emergency contraception your main options are:

Here's a breakdown of the pros and cons of each type and how to choose the best emergency contraception for you.

Levonorgestrel is a synthetic hormone that stops the release of the egg from the ovaries to prevent fertilization, says Julie Levitt, MD, a gynecologist at The Women's Group of Northwestern.While there are several popular brands, including Plan B One-Step, My Way, and After, the effectiveness is the same no matter which pill you take.

When can I use it? You can use levonorgestrel for up to 72 hours (3 days) after unprotected sex, but it is best to take the pill as soon as possible for better efficacy.

How effective is it? Numerous studies have found levonorgestrel to be 60% to 94% effective in preventing pregnancy depending on how soon you take the pill.

Do I need a prescription? No, you can buy the pill over the counter and most pharmacies or drug stores carry it.

Ella is an emergency oral contraceptive that contains a drug called ulipristal acetate. While it does not contain estrogen or progesterone, it is a single-dose steroid medication. Taking a single tablet prevents ovulation, delaying a woman from releasing the egg from her ovary.

When can I use it? Ella is effective up to five days (120 hours) after unprotected sex. Like the copper IUD, this method does not diminish over time, but it is best to take it as soon as possible to avoid ovulation. If you vomit within three hours after taking the pill, ask your medical provider whether you should take another one.

How effective is it? It's around 65% to 85% effective at preventing pregnancy depending on how soon you take the pill, says Bartz.

Do I need a prescription? Yes, you need a prescription for Ella. There are some certified online prescription services or contact your doctor as soon as you can after unprotected sex.

A copper intrauterine device, or IUD, is a small T-shaped frame that is inserted into the uterus. The device contains no hormones and instead copper keeps sperm from the egg, preventing pregnancy from occurring. This makes it a good option for those who are sensitive to hormonal side effects or can't use hormones due to medical conditions. The copper IUD can provide up t

When can I use it? You can use a copper IUD as emergency contraception up to five days (120 hours) after unprotected sex, but some studies have found it can be effective up to 10 days after.

How effective is it? The copper IUD is the most effective emergency contraception, says Deborah Bartz, MD, MPH, a gynecologist at Brigham and Women's Hospital in Boston, MA. It is over 99% effective in preventing pregnancy and works just as effectively on day one as day five.

Do I need a prescription? No, you do not need a prescription, but a copper IUD must be inserted by a medical professional, such as a women's doctor or nurse. It may be challenging to rely on this method because it requires a prompt appointment.

Birth control pills are an oral contraceptive that contains the hormones estrogen and progestin, which prevents pregnancy by blocking the release of the egg from the ovaries. While these pills are normally taken as a form of daily birth control, they may be also used as emergency contraception after unprotected sex. This is known as the Yuzpe regimen.

There are many different types of birth control pills some with hormone levels that change each week, others with a steady dose daily. For this reason, the exact number of tablets to take for the first dose may vary, and a second dose is generally taken 12 hours later.

The exact dosage needed in total is 200 mcg Ethinyl estradiol the estrogen component and 1 mg progesterone. However, it is not recommended that you do this independently due to the irregularity of the dosing and the high possibility for side effects. Speak with your OBGYN to determine if this is the right method for you to pursue.

When can I use it? The Yuzpe regimen is effective up to 72 hours (3 days) after unprotected sex, but it is recommended to use only if the other contraceptive methods are not readily available. You should also only use it under the direction of a healthcare provider.

How effective is it? Much like the other oral contraceptives, the longer you wait to take the birth control dose, the less effective the method will be. The American College of Obstetricians and Gynecologists no longer recommend this method because it is the least effective (with an average of 74% effectiveness) and has high side effect risks, such as nausea and vomiting.

Do I need a prescription? Yes. You can get a prescription from a healthcare professional, such as an OBGYN, a physician at a Planned Parenthood, or a licensed pharmacist.

When considering which emergency contraception to use, there are some factors to keep in mind.

When you last had sex: Non-hormonal contraceptives, i.e. Ella and the copper IUD, can work up to five days after, or possibly longer, while most hormonal options plan B and the pill are limited to 72 hours.

Weight: If you weigh more than 155lb, pills containing levonorgestrel, like plan B, may be less effective, and you should ask your doctor for an Ella prescription. However, if you weigh over 195 lbs, Ella may not be as effective.Weight has no effect on the copper IUD.

What research says: A 2015 study found that the rate of pregnancy in women over 165 lbs increased significantly (5% to 6%) when taking levonorgestrel. Another large 2012 study found the rate of pregnancy in obese women increased by 7% when taking ulipristal acetate.

Affordability and accessibility: Generally, contraceptives with levonorgestrel are the easiest to find. Meanwhile, Ella is less common in pharmacies and requires a prescription.

Planned Parenthood can be an affordable option for emergency contraception, says Levitt, since they are able to provide care at a lower cost. The organization also has a nifty quiz you can take to determine which emergency contraception is right for you.

Emergency contraception after unprotected sex can come in non-hormonal and hormonal options that vary in effectiveness and method. Choosing which is best for you can depend on various factors, such as weight, when you last had sex, and accessibility, and should be discussed further with your healthcare provider.

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Emergency contraception: Which type is best for you? - Insider - INSIDER

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Investigators are seeking to determine whether amcenestrant (SAR439859), an investigational oral endocrine therapy, can generate meaningful antitumor activity when administered as short-term preoperative therapy to postmenopausal patients with newly diagnosed early breast cancer.

The phase 2 AMEERA-4 trial (NCT04191382) is testing 2 dose levels of amcenestrant versus letrozole given for 14 days to patients with estrogen receptor (ER)-positive, HER2-negative localized breast cancer who are candidates for breast conserving therapy or upfront mastectomy.1

The study will measure the impact of the short course of endocrine therapy on Ki-67, a protein biomarker of cellular proliferation that has been shown to be a prognostic indicator of survival and recurrence in patients with early breast cancer, with higher levels associated with worse outcomes.2

Ki-67 expression has been correlated with poor cancer-specific survival at a cutoff point greater than 14% of tumor nuceli.3 AMEERA-4 is a window of opportunity study, a validated strategy for rapid exploration of proof-of concept treatment approaches, investigators said in a poster presentation at the 2020 American Society of Clinical Oncology Virtual Scientific Program.4

The trials goals include determining the best dosage for further study of amcenestrant in this clinical setting, said principal investigator Mario Campone, MD, a medical oncologist at the Institut de Cancrologie de lOuest, Ren Gauducheau, in St Herblain, France.

Some clinical trials have demonstrated that when you have a decrease in Ki-67 after 2 weeks you have a better outcome compared with the patients who do not have a decrease in this surrogate marker, he said in an interview with OncologyLive.

Amcenestrant is a selective ER degrader (SERD), a class of drugs that works by serving as a competitive antagonist to the ER, inducing conformational changes that lead to degradation of the receptors. In preclinical studies, the agent has demonstrated antitumor efficacy and regression in ER-positive breast cancer models.5 Further, amcenestrant can be administered as an oral therapy because of its favorable pharmacokinetic profile, as opposed to fulvestrant (Faslodex), a SERD that must be given via intramuscular injection because of pharmacokinetic limitations.5,6

AMEERA-4, an international, open-label study, was initiated in December 2019 and is being conducted at 16 active sites with 34 planned sites, Campone said.

Participants are being randomized 1:1:1 to receive daily amcenestrant at 400 mg, daily amcenestrant at 200 mg, or daily letrozole at 2.5 mg for 14 days, with the last dose administered on the day before surgery. Biopsies are performed at baseline and during surgery (FIGURE).1,4

The primary end point is a change in Ki-67 expression measured by immunohistochemistry after a 14-day treatment period compared with baseline levels. Secondary end points include the proportion of patients with relative decrease from baseline in Ki-67 expression of 50% or more, change in ER expression compared with baseline, and safety and tolerability.

Efficacy will be assessed via pathological complete response (pCR), which is defined as no histologic evidence of invasive tumor cells in the surgical breast specimen and axillary nodes after treatment. ECOG performance status response will be measured after the 14-day treatment based on breast tumor shrinkage and pCR. Additionally, a preoperative endocrine prognostic index derived from pathologic tumor and node stages, Ki-67 levels, and ER status of the surgical specimen will be assessed after the 14-day treatment period.

Investigators are seeking to recruit 126 patients for the study. So far, 14 patients have been enrolled, and the study could be completed sometime this year, with data analysis projected for 2022, Campone said.

After completion of the AMEERA-4 study, Sanofi, the agents developer, plans to initiate a pivotal clinical trial to study amcenestrant in early breast cancer.7 AMEERA-6 will be a registrational study with invasive disease-free survival as the primary end point. This study will be supported in part by data generated from AMEERA-4, which is expected in to be available in 2021, according to a Sanofi spokesperson. AMEERA-6 is expected to begin recruiting patients by the end of 2021.

The use of amcenestrant as monotherapy has shown encouraging signals in the ongoing phase 1/2 AMEERA-1 trial (NCT03284957). In interim results reported at the 2020 San Antonio Breast Cancer Symposium, amcenestrant monotherapy elicited antitumor activity in heavily pretreated, postmenopausal women with advanced or metastatic ER-positive breast cancer.8

Results showed that the objective response rate (ORR) was 8.5% with amcenestrant with a clinical benefit rate (CBR) of 33.9% among pooled results from 59 patients who received amcenestrant at 150 mg or more daily. In a cohort of 33 patients who had received 3 or fewer prior lines of therapy in the metastatic setting, the ORR was 15.2% and the CBR was 42.4%. Moreover, in a subgroup of 14 patients who did not receive prior CDK4/6 inhibitors, mTOR inhibitors, or fulvestrant, the ORR was 21.4% and the CBR was 64.3%.8

In AMEERA-1, which is a first-in-human study, investigators are evaluating the safety and efficacy of amcenestrant as a single agent and in combination with targeted therapies in patients with ER-positive, HER2-negative metastatic breast cancer. In part A of the trial, which was the dose-escalation phase, investigators evaluated amcenestrant at oncedaily doses ranging from 20 mg to 600 mg. In part B, which was the dose-expansion phase, the recommended dose for amcenestrant as monotherapy was determined to be 400 mg once daily.

Amcenestrant was found to have a favorable safety profile with 62.9% of patients experiencing treatment-related adverse events (TRAEs), none of which were grade 3 or higher. The most common (5%) TRAEs in the pooled population of patients who were treated with amcenestrant at the 150-mg or higher daily dose included hot f lush (16.1%), constipation (9.7%), arthralgia (9.7%), decreased appetite (8.1%), vomiting (8.1%), diarrhea (8.1%), nausea (8.1%), and fatigue (6.5%).8

Pivotal results are expected in the f irst half of 2021, according to Sanofi. Amcenestrant as a monotherapy may be available as a second- and third-line treatment for patients with metastatic breast cancer in 2022, the company said.7

Amcenestrant monotherapy is also being evaluated versus physicians choice of therapy in the open label, phase 2 trial AMEERA-3 trial (NCT04059484), which will enroll 372 patients. The control treatment involves choosing monotherapy from a list of agents with different mechanisms of action: anastrozole, letrozole, or exemestane, which are aromatase inhibitors; tamoxifen, a selective estrogen receptor modulator; or fulvestrant. The primary end point is progression-free survival (PFS). Secondary end points include OS, ORR, disease control rate, CBR, and duration of response (DOR).9

Another study, AMEERA-5 (NCT04478266), is testing amcenestrant in combination with palbociclib (Ibrance), a CDK4/6 inhibitor, versus letrozole plus palbociclib as a first-line therapy for patients with ER-positive, HER2negative locoregional or metastatic breast cancer. The study, which aims to recruit 810 patients, has a primary end point of PFS and secondary end points of OS, ORR, DOR, and CBR.10

Additionally, the Quantum Leap Healthcare Collaborative announced in June 2020 that amcenestrant was selected to be part of a new I-SPY 2 study arm.

The study, known as the I-SPY 2 Endocrine Optimization Protocol (EOP), is focused on patients with molecularly low-risk, clinically high-risk, hormone receptorpositive, HER2negative clinical stage II or III invasive breast cancer. Amcenestrant will be tested as a monotherapy and in combination with up to 3 other agents.11

The I-SPY program was designed to identify therapies that are most effective in specific patient subgroups based on biomarker signatures. Sanofi is supplying the drug and providing financial support.

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Trial Explores Preoperative Window for Amcenestrant Therapy in Early Breast Cancer - OncLive

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Introduction

Obesity is an important chronic disease all over the world because of the increasing prevalence and harms to public health. Obesity can result in multiple alterations in the endocrine systems, including altered circulating blood hormone concentrations, because of changes in the pattern of secretion and/or metabolism, abnormal hormonal transport, and/or actions at levels of target tissues.1 It has been demonstrated that obesity has an impact on male reproductive system. And obesity has been considered as a risk for male hypotestosteronemia with low testosterone levels. It has been reported that there are 2064% of obese men with low total testosterone (TT) or free testosterone (FT) levels.2 Related studies have reported that the increasing BMI is associated with low testosterone and sex-hormone-binding-globulin (SHBG) levels in the male population.36 Weight reduction by lifestyle intervention or bariatric surgery can increase the levels of TT and SHBG.3

Metabolic syndrome (MS), gathering of abdominal obesity, hypertension, hyperglycemia, and dyslipidemia is an important challenge for health problem. The prevalence of metabolic syndrome ranges from 1034% according to different definitions or populations.7 Several studies have pointed that metabolic syndrome can be regarded as an independent association with low levels of total testosterone in males.811 And low levels of TT and SHBG can be considered as independent risk factors for metabolic syndrome.12,13 However, the relationship of TT with metabolic syndrome remains inconsistent. A cross-sectional study reported that there was no significant difference of total testosterone among MS and non-metabolic syndrome group. It is supposed that the other parameters were abnormal, the lower levels of SHBG would be measured, without alternations of TT.14 And several studies have concluded that their data were not consistent with the hypothesis that low levels of TT were associated with incidence of metabolic syndrome.15,16

Recent studies have demonstrated that not all obese individuals have metabolic abnormal risk factors, and not all lean individuals are metabolically healthy.17 Therefore, different metabolic phenotypes of obesity have attracted researchers attention in recent years. Although obesity may induce decreased serum TT concentration by some related mechanisms, the fact is that only a small proportion of obese men are hypotestosteronemia, probably those genetically predisposed or morbidly obese.18 Metabolic healthy overweight/obesity (MHO) is considered to be overweight/obesity (BMI25 kg/m2) without metabolic diseases (hypertension, type 2 diabetes mellitus (T2DM), and dyslipidemia). In addition, metabolically unhealthy overweight/obesity (MUO) refers to a proportion of overweight/obese subjects with metabolic diseases. A recent study based on 4,945 men with sexual dysfunction and 231 male partners of infertile couples demonstrated that men in the MHO groups had lower total testosterone levels compared to men of normal weight.19 However, the effect of specific metabolic obesity phenotypes on total testosterone in the general male population remains unknown. Hypotestosteronemia is classified into primary hypotestosteronemia which results from testicular defects and is associated with low testosterone levels and elevated LH and FSH levels and secondary hypotestosteronemia which results from dysfunction of hypothalamus and/or pituitary and refers to patients with low testosterone levels and low or inappropriately normal LH and FSH levels. And whether the influence of different metabolic obesity phenotypes on TT levels is caused by affecting hypothalamus and/or pituitary levels or testicular levels remains unknown.

Thus, we performed the study to verify the separate influence of MS and overweight/obesity on male hypotestosteronemia, and investigate the relationship of different metabolic obesity phenotypes and male total testosterone levels in a large-scale male population.

We recruited nearly 11,000 persons who participated in the population-based cross-sectional study in Ningyang County (Taian, Shandong Province, China) from June to November 2011. All participants were local-registered residents aged 40 years and older who have lived there for at least 5 years. All participants were asked to complete a self-reported questionnaire and provided an overnight fasting blood sample. In our study, the exclusion criteria were as follows: i) female; ii) no information on vital statistics (such as age, sex, height, or weight) or missing data on serum total testosterone (TT), blood pressure, fasting serum glucose, or lipid levels; iii) taking medications that might affect TT level (such as androgens, steroid hormones); and iv) severe hepatic or renal disorders, lung diseases, hypothalamus and/or pituitary gland diseases, neurologic diseases, or tumors that might affect TT level (such as brain cancer or prostate cancer). At last, a total of 4,081 participants were recruited in this study. The study protocol conformed to the 1975 Declaration of Helsinki and was approved by the Committee on Human Research at Ruijin Hospital, Shanghai Jiao Tong University School of Medicine. All study participants provided written informed consent.

Height and WC were measured adjusting by 0.1 cm. Weight was measured adjusting by 0.1 kg. BMI was obtained by dividing weight in kilograms by the square of height in meters. The average of the three blood pressure measurements in sitting position after a 5-minute rest was used in the analysis. Past medical history, smoking status, and alcohol consumption were obtained by a questionnaire. The diseases (hypertension, diabetes mellitus, and coronary heart disease) were based on previous diagnosis by a physician. Smoking status and alcohol consumption were defined as never, ever, and current.

Venous blood samples were collected from all patients after at least 10-hours overnight fast and samples were separated and preserved in 80C. The concentrations of total cholesterol (TC), triglyceride (TG), high density lipoprotein cholesterol (HDL-C), fasting plasma glucose (FPG), and glycosylated hemoglobin (HbA1c) were measured directly with an ARCHITECT ci16200 Integrated System (Abbott). Serum TT, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) were measured using electrochemiluminescent procedures (Cobas E601; Roche) at the clinical laboratory of Shandong Provincial Hospital.

Total testosterone level <12 nmol/L is suggestive of hypotestosteronemia.20 Secondary hypotestosteronemia refers to patients with low testosterone levels and low or inappropriately normal LH and FSH levels. Primary hypotestosteronemia is associated with low testosterone levels and elevated LH (>8.6 mIU/L) and FSH (>12.4 mIU/L) levels. We used the Adult Treatment Panel III definition of metabolic syndrome in male population: having three or more following criteria: waist circumference >102 cm, triglycerides >1.7 mmol/L (or treatment for hyperlipidemia), HDL-C <1 mmol/L, plasma fasting glucose >100 mg/dL, and systolic/diastolic blood pressure >130/85 mmHg (or treatment for hypertension).21 And we classified the population as normal weight (BMI<25.0) and overweight/obesity (BMI25.0) with or without metabolic syndrome. Then, according to a previous study, the participants were classified as four groups: metabolically healthy normal weight (MHNW) (BMI<25.0, without metabolic syndrome); metabolically healthy overweight/obese (MHO) (BMI25.0, without metabolic syndrome); metabolically unhealthy normal weight (MUNW) (BMI<25.0, with metabolic syndrome), and metabolically unhealthy overweight/obese (MUO) (BMI25.0, with metabolic syndrome).22

SPSS22.0 software was used for the statistical analysis. Continuous variables were presented as meanstandard deviations, and between-group differences were assessed by a single-factor analysis of variance (ANOVA). Categorical variables were presented as percentages, and between-group differences were assessed by Chi-squared test. Multiple logistic regression analysis was performed to assess the risk factors of hypotestosteronemia. All P-values were 2-sided, and less than 0.05 were considered statistically significant.

A total of 4,081 male participants aged from 4075 years were enrolled into the final analysis. There were 563 participants suffering from hypotestosteronemia (13.80%). Within metabolic categories, overweight/obese men tended to be younger with a high level of BMI and WC than men with normal weight. And overweight/obese men were more likely to have a high level of TC, TG, LDC-C, ALT, GGT, and DBP, and a low level of HDL-C, TT, LH, and FSH, without difference of AST, FBG, and HbA1C. As expected, compared to the metabolic healthy group, metabolic unhealthy patients were more likely to have a high level of TG, TC, ALT, AST, GGT, FPG, HbA1C, systolic blood pressure, and diastolic blood pressure, and a low level of HDL-C and TT. There was a high prevalence of diabetes mellitus, hypertension, and coronary heart disease in the metabolic unhealthy population. Compared to the MHNW group, the MHO, MUNW, and MUO groups tended to have a high level of BMI, WC, elevated liver function index, altered metabolic syndrome components, and high risk of developing hypertension and coronary heart disease, as well as decreased levels of serum TT, LH, and FSH (Table 1). There was no significant difference of serum testosterone level between the MHO and MUNW groups. The significant differences in the composition of the four groups with respect to smoking status and alcohol consumption are also shown in Table 1.

Table 1 Baseline Characteristics in Different Metabolic Obesity Phenotypes

To compare the difference of prevalence of hypotestosteronemia among different metabolic obesity phenotypes, we performed a Chi-squared test between each two groups. We observed an obvious elevated trend of prevalence of hypotestosteronemia in these four metabolic obesity phenotypes in Figure 1. Compared to the MHNW group, the other three groups have been demonstrated to have a higher risk of hypotestosteronemia. At the same time, compared to the MUO group, the other three groups were more likely to have a lower risk of hypotestosteronemia. However, no difference existed between MUNW and MHO group (Figure 1A). The results of comparison of prevalence of secondary hypotestosteronemia in four groups were similar to hypotestosteronemia (Figure 1B). However, the prevalence of primary hypotestosteronemia in the MHNW and MHO groups was significantly lower than in the MUO group. No significant difference existed in the prevalence of primary hypotestosteronemia in other groups (Figure 1C). These differences demonstrated that different metabolic obesity phenotypes could have different impacts on serum testosterone levels.

Figure 1 (A) Prevalence of hypotestosteronemia in different metabolic phenotypes of obesity; (B) Prevalence of secondary hypotestosteronemia in different metabolic phenotypes of obesity; (C) Prevalence of primary hypotestosteronemia in different metabolic phenotypes of obesity. Metabolically healthy normal weight (MHNW); metabolically healthy overweight/obese (MHO); metabolically unhealthy normal weight (MUNW), and metabolically unhealthy overweight/obese (MUO). (Graph pad prism8 used to create the artwork.)

To examine the separated and synergistic effect of overweight/obesity and metabolic status on serum TT concentration, we carried out multivariate logistic regression analysis of hypotestosteronemia with low serum TT levels (<12 nmol/L) adjusting for age, LH, smoking status (never, ever, current), and alcohol intake (never, ever, current). Both overweight/obesity and metabolic syndrome, considered separately, were risk factors of low serum TT levels. The multivariate-adjusted Odd Ratio (OR) of low serum TT levels in overweight/obesity men was 3.072 (95% CI= 2.4143.911). The risk of low serum TT levels increased appropriately 3.294-fold in metabolic syndrome individuals compared to metabolic healthy individuals (Table 2). Although the risk of hypotestosteronemia in overweight/obesity and metabolic syndrome individuals was attenuated after mutual analysis, the OR of low serum TT levels remained statistically significant adjusting for age, LH, smoking status (never, ever, current), and alcohol intake (never, ever, current) (Table 2).

Table 2 Adjusted Correlations of BMI and Presence of the MS with Total Testosterone

Table 3 Logistic Regression Analysis of Hypotestosteronemia According to Different Metabolic Phenotypes of Obesity

To study the independence of different metabolic obesity phenotypes for male hypotestosteronemia, we performed logistic regression analysis to observe the OR of hypotestosteronemia in four groups. Compared to participants in the MHNW group, the risk of developing hypotestosteronemia in the MHO, MUNW, and MUO groups significantly increased. ORs of hypotestosteronemia in the MHO, MUNW, and MUO groups were 2.736 (95% CI=2.1323.512), 3.332 (2.3144.799), and 6.213 (4.8427.972), respectively (Table 3). After adjusted for age, OR of hypotestosteronemia in MHO and MUO groups decreased, but it was still significant. Male subjects in the MHO, MUNW, and MUO groups also had a significantly increased risk of hypotestosteronemia in contrast to those in the MHO group after adjusted for age, LH, smoking status (never, ever, current), and alcohol intake (never, ever, current).

Obesity and metabolic syndrome are both considered to be risk factors of low serum TT levels. We provided precise insight into the association between different metabolic obesity phenotypes and low serum TT levels in a large-scale population of Chinese men aged from 4075 years old. It demonstrated that individuals with different metabolic obesity phenotypes including MHO, MUNW, and MUO, respectively, can all have a higher risk of developing low serum TT levels, especially significantly in the MUO group.

In our study, we draw a conclusion that both overweight/obese men and metabolic unhealthy men had a higher risk of developing low serum TT levels than normal weight and metabolic healthy individuals, which is consistent with the results in previous studies.811,13 It demonstrated that serum TT levels in the male population were associated with BMI and different components of metabolic syndrome. A Korean study has shown that serum TT levels were negatively associated with BMI, WC, FPG, TG, and blood pressure, and positively associated with HDL-L levels.11 A meta-analysis that included 9,525 men of different ethnicities proved that serum TT levels were negatively correlated with each component of metabolic syndrome.8 It has been reported that hyperinsulinemia which was associated with metabolic syndrome can inhibit the secretion of testosterone through insulin receptors which were expressed on Leydig cells.23 And excess adiposity tissue could lead to high levels of leptin, which can inhibit the steroidogenesis and the secretion of testosterone. Inflammatory cytokines, especially IL-1, IL-6, and TNF-, which were elevated in obesity or metabolic unhealthy individuals, can directly inhibit the steroidogenesis and subsequent testosterone production.24 Although there are several studies investigating the association of overweight/obesity and metabolic syndrome components with testosterone levels separately, there is still quite a gap in the literature considering the relationship between different metabolic obesity phenotypes and total testosterone levels.

As we have proved, different metabolic obesity phenotypes except for the MHNW group are at a high risk of developing low serum TT levels. Among these groups, MUO individuals are more likely to have a low level of serum TT than others. Studies have demonstrated that age, smoking status, and alcohol consumption were associated with different metabolic obesity phenotypes.25,26 However, after adjusting these above confounding factors, the relationship between TT levels and metabolic obesity phenotypes remained significant. To the best of our knowledge, the only study on this topic was performed to explore male sexual dysfunction with different metabolic obesity phenotypes.19 It showed that the men with MHO and metabolically complicated obesity (MCO) had lower testosterone levels and only MCO men had worse erectile function compared with normal weight men. However, the results were derived from male patients with sexual dysfunction or infertility, which could have different characteristics compared with the general male population. Whats more, the definition of MCO was the presence of at least one abnormality among hypertension, low HDL-C, and diabetes in obese men, and the contrast group was men with normal weight regardless of metabolic status.

In our study, there was a higher risk of developing hypotestosteronemia in male patients in MHO compared to the MHNW group, but a lower risk than the MUO group. MHO individuals referred to overweight/obese people without the risk factor of metabolic syndrome, and several studies have reported that these individuals were fat but fit with more favorable inflammatory and metabolic profiles.27 However, the recent systematic review and meta-analysis showed that MHO subjects had an increased risk for the development of cardiovascular diseases and all-cause mortality in contrast to MHNW subjects.28 And our results indicated that MHO individuals had a decreased total testosterone level compared to MHNW individuals. It has been reported that metabolic healthy obese individuals have certain differences in multiple aspects, such as fat distribution, inflammatory status, insulin resistance, and postprandial lipemia, compared with metabolic unhealthy obese individuals.29,30 Compared with MUO individuals, MHO was shown to have increased subcutaneous fat relative to visceral fat, lower liver fat, and insulin sensitivity. Excessive visceral fat or insulin resistance rather than general adiposity in obese individuals were at high risk of developing pre-diabetes and type 2 diabetes mellitus. Metabolic healthy subjects displayed lower postprandial response of plasma TG and higher postprandial response of hs-CRP, compared with those metabolic unhealthy, independent of whether or not they were obese. We also observed that testosterone levels were decreased in male subjects with MUO compared to MHO. Clinical features and metabolism difference caused by metabolic healthy obesity phenotype can partly explain the alternations of testosterone concentration in MHO group compared to MHNW and MUO group. Since MHO is a dynamic state (with a significant proportion of MHO subjects progressing to MUO over time), it is necessary to encourage weight control in MHO phenotypes to prevent the development of metabolic related disease including hypotestosteronemia.

We also observed that testosterone levels in male subjects with MUNW were decreased compared to the MHNW group, but these were increased in the MUNW group compared to the MUO group, and no significant difference to the MHO group. MUNW individuals displayed several metabolic abnormal risks including insulin resistance, atherogenic lipid profiles, visceral adiposity accumulation, and lower physical energy expenditures, despite having a normal BMI, and eventually had the increased risk of cardiovascular disease.31 It has been reported that MUNW phenotype exhibited increased arterial stiffness and carotid atherosclerosis compared to MHNW or MHO subjects.32 And another report has shown that MUNW individuals had a higher risk of cardiovascular disease than MHO, as well as reduced morbidity and mortality.33 The MHO phenotype was associated with a better overall metabolic profile and less oxidative stress than that observed in MUNW individuals.34 In our study, there is no significant difference of testosterone levels between MUNW and MHO group, which indicated that both MUNW and MHO can exert an influence on total testosterone levels. The underlying mechanism needs further study. It was shown that male subjects in the MUO group have decreased serum TT levels compared to MHO and MUNW groups, which can be explained by synergistic effect of obesity and metabolic unhealthy on TT levels in patients with MUO. It also indicated that male patients with MHO or MUNW should pay attention to losing weight or improving metabolic status in order to prevent the further drop of TT levels.

It is well known that testosterones are mainly synthesized in Leydig cells, which could be modulated by hypothalamus-pituitary levels. In our study, we also found that gonadotropins FSH and LH were significantly reduced in MHO and MUO groups compared to MHNW. However, there was no significant difference of FSH and LH levels between MHNW and MUNW, as well as MHO and MUO groups. There was an increasing conversion of androgen precursors into estrogens by aromatase system in adipose tissue among obese male population. Inappropriate effects of increasing estrogens might reduce LH secretory mass per secretory burst without any alternation in burst number.35 The exact mechanism for decreased gonadotrophins in male obesity could also include leptin, inflammatory mediators, and hypothalamic kisspeptin affecting gonadotropins- releasing hormone secretion.36 These results indicated that low levels of gonadotropins can partly explain the decreasing total testosterone levels in obesity participants, but not affected by metabolic status. To observe the effect of metabolic obesity phenotypes on pituitary or testicular levels, we further compared the difference of prevalence of secondary hypotestosteronemia and primary hypotestosteronemia in four metabolic obesity phenotypes. It showed that the difference of prevalence of secondary hypotestosteronemia and primary hypotestosteronemia in four groups was similar to hypotestosteronemia. The results were confusing, which was inconsistent with the results that LH and FSH levels were only affected by obesity. Although we did not get information about the pulse and frequency of LH and FSH secretory, which also played an important role in regulating the production of testosterone levels. Therefore, further studies about the pulse and frequency of LH and FSH secretory, the alternations of structure and function in testis need to be performed in different metabolic obesity phenotypes.

This is the first study to investigate the relationship of different metabolic obesity phenotypes with serum TT concentration in a large-scale male population. In our study, other potential risk factors of low TT levels such as age, LH levels, smoking status, and alcohol consumption were taken into account to make the result more convincing. However, several limitations also existed in our study. We did not obtain information about other sex hormones such as SHBG and estrogen, which can have an effect on TT levels. Meanwhile, we cannot draw a conclusion about the association of different metabolic obesity phenotypes and other sex hormones. Whats more, the cross-sectional study was unable to detect any causal relationship between different metabolic obesity phenotypes and testosterone levels. Large prospective studies are needed to validate this relationship.

In conclusion, both overweight/obesity and metabolic abnormalities are important risk factors for low serum TT levels. Different metabolic obesity phenotypes have influence on lower serum testosterone level in different degrees, especially in the MUO group with a lowest serum TT concentration. Male subjects in the MHO and MUNW groups had significantly decreased testosterone levels compared to the MHNW group, however, there was no significant difference of testosterone levels between the MHOand MUNW groups. Clinical physicians should pay attention to the weight combined with metabolic status of patients when we explore the reason of decreasing concentration of serum TT in male populations. Individual weight control and prevention of metabolic syndrome may be used for the primary prevention of male hypotestosteronemia. Patients with low level of serum TT can improve by losing weight or improving metabolic status.

The data used to support the findings of this study are available from the corresponding author, Qingbo Guan, upon request.

The research used data collected as part of a longitudinal study (REACTION) which was a multi-center, prospective, observational cohort study in Chinese people. We gratefully acknowledge the REACTION study group for organizing the national epidemiological REACTION study in China.

This work was supported in part by grants from the National Natural Science Foundation of China (81770860, 81471078 and 81641030) and Key Research and Development Plan of Shandong Province (2016GSF201007).

The authors declare that there is no conflict of interest.

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3. Escobar-Morreale HF, Santacruz E, Luque-Ramrez M, Botella Carretero JI. Prevalence of obesity-associated gonadal dysfunction in severely obese men and women and its resolution after bariatric surgery: a systematic review and meta-analysis. Hum Reprod Update. 2017;119.

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8. Brand JS, Rovers MM, Yeap BB, et al. Testosterone, sex hormone-binding globulin and the metabolic syndrome in men: an individual participant data meta-analysis of observational studies. PLoS One. 2014;9(7):e100409. doi:10.1371/journal.pone.0100409

9. Corona G, Monami M, Rastrelli G, et al. Testosterone and metabolic syndrome: a meta-analysis study. J Sex Med. 2011;8(1):272283. doi:10.1111/j.1743-6109.2010.01991.x

10. Angelova P, Kamenov Z, Tsakova A, El-Darawish Y, Okamura H. Interleukin-18 and testosterone levels in men with metabolic syndrome.. Aging Male. 2018;21(2):130137. doi:10.1080/13685538.2017.1401993

11. Hong D, Kim Y-S, Son ES, et al. Total testosterone and sex hormone-binding globulin are associated with metabolic syndrome independent of age and body mass index in Korean men. Maturitas. 2013;74:148153. doi:10.1016/j.maturitas.2012.10.016

12. S EQ, S FC, Oliveira KC, Feres F, Verreschi IT. Association between sex hormone-binding globulin (SHBG) and metabolic syndrome among men. Sao Paulo Med J. 2014;132(2):111115. doi:10.1590/1516-3180.2014.1322666

13. Zhang J, Huang X, Liao M, et al. Both total testosterone and sex hormone-binding globulin are independent risk factors for metabolic syndrome: results from fangchenggang area male health and examination survey in China. Diabetes Metab Res Rev. 2013;29:391397. doi:10.1002/dmrr.2405

14. Siddiqui K, Al-Rubeaan K, Nawaz SS, Aburisheh KH, Alaabdin AMZ, Tolba IA. Serum Sex Hormone Binding Globulin (SHBG) relation with different components of metabolic syndrome in men with type 2 diabetes. Horm Metab Res. 2018;50(2):138144. doi:10.1055/s-0043-123348

15. Callou de S EQ, Feij de S FC, e Silva RDS, et al. Endogenous oestradiol but not testosterone is related to coronary artery disease in men. Clin Endocrinol (Oxf). 2011;75(2):177183. doi:10.1111/j.1365-2265.2011.04017.x

16. Bhasin S, Jasjua GK, Pencina M, et al. Sex hormone-binding globulin, but not testosterone, is associated prospectively and independently with incident metabolic syndrome in men: the framingham heart study. Diabetes Care. 2011;34(11):24642470. doi:10.2337/dc11-0888

17. Lopez-Miranda J, Perez-Martinez P. It is time to define metabolically obese but normal-weight (MONW) individuals. Clin Endocrinol (Oxf). 2013;79(3):314315. doi:10.1111/cen.12181

18. Martini AC, Molina RI, Ruiz RD, Fiol de Cuneo M. Obesity and male fertility. Rev Fac Cien Med Univ Nac Cordoba. 2012;69:2.

19. Lotti F, Rastrelli G, Maseroli E, et al. Impact of metabolically healthy obesity in patients with andrological problems. J Sex Med. 2019;16(6):821832. doi:10.1016/j.jsxm.2019.03.006

20. Wang C, Nieschlag E, Swerdloff R, et al. Investigation, treatment, and monitoring of late-onset hypogonadism in males: ISA, ISSAM, EAU, EAA, and ASA recommendations. J Androl. 2008;30(1):19. doi:10.2164/jandrol.108.006486

21. Lauer MS, Fontanarosa PB. Executive summary of the third report of the National Cholesterol Education Program (NCEP) expert panel on detection, evaluation, and treatment of high blood cholesterol in adults (adult treatment panel III). JAMA. 2001;285(19):24862497. doi:10.1001/jama.285.19.2486

22. Kim JM, Kim BH, Lee H, et al. The relationship between thyroid function and different obesity phenotypes in Korean euthyroid adults. Diabetes Metab J. 2019;43(6):867878.

23. Pitteloud N, Hardin M, Dwyer AA, et al. Increasing insulin resistance is associated with a decrease in leydig cell testosterone secretion in men. J Clin Endocrinol Metab. 2005;90:26362641. doi:10.1210/jc.2004-2190

24. Lin T, Wang D, Stocco DM. Interleukin-1 inhibits leydig cell steroidogenesis without affecting steroidogenic acute regulatory protein messenger ribonucleic acid or protein levels. J Endocrinol. 1998;156:461467. doi:10.1677/joe.0.1560461

25. Primeau V, Coderre L, Karelis AD, et al. Characterizing the profile of obese patients who are metabolic healthy. Int I Obes (Lond). 2011;35:971981. doi:10.1038/ijo.2010.216

26. Wang B, Zhang M, Wang S, et al. Dynamic status of metabolically healthy overweight/obesity and metabolically unhealthy and normal weight and the risk of type 2 diabetes mellitus: a cohort study of a rural adult Chinese population. Obes Res Clin Pract. 2018;12(1):6171. doi:10.1016/j.orcp.2017.10.005

27. Ortega FB, Cadenas-Sanchez C, Migueles JH, et al. Role of physical activity and fitness in the characterization and prognosis of the metabolically healthy obesity phenotype: a systematic review and meta-analysis. Prog Cardiovasc Dis. 2018;61(2):190205. doi:10.1016/j.pcad.2018.07.008

28. Yeh T-L, Chen -H-H, Tsai S-Y, Lin C-Y, Liu S-J, Chien K-L. The relationship between metabolically healthy obesity and the risk of cardiovascular disease: a systematic review and meta-analysis. J Clin Med. 2019;8(8):1228. doi:10.3390/jcm8081228

29. Perez-Martinez P, Alcala-Diaz JF, Delgado-Lista J, et al. Metabolic phenotypes of obesity influence triglyceride and inflammation homoeostasis. Eur J Clin Invest. 2014;44(11):10531064. doi:10.1111/eci.12339

30. Wildman RP, Muntner P, Reynolds K, et al. The obese without cardiometabolic risk factor clustering and the normal weight with cardiometabolic risk factor clustering: prevalence and correlates of 2 phenotypes among the US population (NHANES 19992004). Arch Intern Med. 2008;168:16171624. doi:10.1001/archinte.168.15.1617

31. Karelis AD, St-Pierre DH, Conus F, Rabasa-Lhoret R, Poehlman ET. Metabolic and body composition factors in subgroups of obesity: what do we know? J Clin Endocrinol Metab. 2004;89(6):2569e75. doi:10.1210/jc.2004-0165

32. Yoo HJ, Hwang SY, Hong HC, et al. Association of metabolically abnormal but normal weight (MANW) and metabolically healthy but obese (MHO) individuals with arterial stiffness and carotid atherosclerosis. Atherosclerosis. 2014;234(1):218223. doi:10.1016/j.atherosclerosis.2014.02.033

33. Choi KM, Cho HJ, Choi HY, et al. Higher mortality in metabolically obese normal-weight people than in metabolically healthy obese subjects in elderly Koreans. Clin Endocrinol (Oxf). 2013;79(3):364370. doi:10.1111/cen.12154

34. Kim M, Paik JK, Kim KR, et al. Increased oxidative stress in normal-weight postmenopausal women with metabolic syndrome compared with metabolically healthy overweight/obese individuals. Metabolism. 2012;62(4):554560. doi:10.1016/j.metabol.2012.10.006

35. Vermeulen A, Kaufman JM, Deslypere JP, Thomas G. Attenuated luteinizing hormone (LH) pulse amplitude but normal LH pulse frequency, and its relation to plasma androgens in hypogonadism of obese men. J Clin Endocrinol Metab. 1993;76(5):11401146. doi:10.1210/jcem.76.5.8496304

36. George JT, Millar RP, Anderson RA. Hypothesis: kisspeptin mediates male hypogonadism in obesity and type 2 diabetes. Neuroendocrinology. 2010;91(4):302307. doi:10.1159/000299767

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Abu Dhabi: For decades, cancer has evoked fear. The first mention of the disease can be paralysing for both patients and families, and overcoming the fear of mortality to fight it is often one of the hardest battles.

On the occasion of World Cancer Day, marked internationally on February 4, experts say that advances in the diagnosis and treatment of various cancers should help people take positive action when faced with the disease. This includes being proactive about screening, and seeking treatment even during a global pandemic, they say.

Dr Humaid Al Shamsi

Even today, many people in the Middle East avoid discussing cancer. But we need to talk much more about it, and make people more familiar with screening requirements.

"The best way to beat cancer, after all, is to live healthy and screen early, Dr Humaid Al Shamsi, president of Emirates Oncology Society and director of oncology at Bujeel Cancer Institute, told Gulf News.

In the UAE, 4,500 new cancer cases are diagnosed each year, with cancers being the third leading cause of death after cardiovascular illnesses and injuries.

Dr Arun Karanwal, medical oncology specialist at Prime Hospital, reminded that beating cancer is about focussing on the fight and not the fright.

Dr Arun Karanwal

In the last decade or so, there has been an overall improvement in five-year cancer survival rate from 50 per cent to 55 per cent. More importantly, when diagnosed in early stages, the five-year survival rate is more than 90 per cent for Hodgkins lymphoma, breast cancer, testicular cancer and prostate cancer, Dr Karanwal said.

Tremendous headway in cancer therapy today even allows for some kinds of cancers to be managed.

While cancer may still be a serious illness, more and more types of cancers are being managed as chronic diseases, like high blood pressure and diabetes. It still needs to be managed, and new methods of control are certainly needed, but the advances of the past 20 to 30 years have really allowed many people to live with their cancer, said Dr Mustaqeem Siddiqui, haematologist and consultant at Department of Haematology and Oncology at Sheikh Shakhbout Medical City (SSMC).

Dr Siddiqui added that advances have been seen in the treatment of all kinds of cancers

Dr Mustaqeem Siddiqui

While it is true some cancers have had more advances than others, I am hopeful that we will come to a day where all cancers will see drastic improvements in survival rates. I believe what has enabled this improvement in survival is continued investment in understanding basic biology, understanding how cancer develops, understanding how a cancer cell behaves, and understanding how the cancer affects our body including the immune system, he explained.

On World Cancer Day, the physician, who has long been involved in cancer research with the Mayo Clinic, also extended his gratitude to cancer patients who have participated in clinical studies.

What is cancer?

Cancer is a large group of diseases that can start in almost any organ or tissue of the body when abnormal cells grow uncontrollably, go beyond their usual boundaries to invade adjoining parts of the body and/or spread to other organs. The latter process is called metastasizing and is a major cause of death from cancer. A neoplasm and malignant tumour are other common names for cancer.

They are true trailblazers on the forefront of treating cancer and their experiences have informed how we treat cancer today. It is my hope that with continued support of research and clinical studies, one day cancer will be a footnote in history, he added.

A number of survivors discussed their challenging journeys with Gulf News on the occasion. And while each involves its own trajectory, what shines through is the way all of them advocated for their own health.

Lung cancer: I didnt understand how my cancer could possibly be treatable

The rest of the world was battling a pandemic, but Karen Johnsons position was even more complicated.

Just before cities around the world had come to a halt, on January 19, 2020, Johnson was diagnosed with Stage IV lung cancer. Specifically ALK-positive non-small cell lung cancer, a type of cancer that is typically detected in its advanced stages.

Usually, Im the most positive person I know. I thrive on challenges and look for the good in everyone and everything. But being told I had cancer was a whole different kind of challenge. I was in new territory, and scared. I even lost my positive self for a short while, the 49-year-old British sales and education executive told Gulf News.

She was therefore tremendously surprised when her oncologist said that her cancer, which had spread from her left lung to her abdomen, pelvis and bones, was both controllable and treatable with a regimen of just pills.

My first question when I heard of my diagnosis was, How long do I have? And then I was prescribed eight miracle tablets to take every day, and an injection once a month, Johnson said.

Johnson had lost her younger sister to cervical cancer eight years ago, so the diagnosis was particularly scary. Added to that, the COVID-19 outbreak made the situation scarier. Not only did Johnson have to worry about her two children being unable to visit from miles away in the UK, she was worried that the cancer might make her more prone to contracting COVID-19.

In a way, the hardest thing Ive ever had to do as a mother was telling my children on a video call that I had cancer. I will never forget the look on their faces when I said those words I have cancer. Right after, I had to quickly reassure them and tell them it was controllable, but they both looked so hurt and helpless, Johnson said.

The children couldnt visit right away but Johnson began the treatment, which included eight pills to be taken every day, along with an injection every month. She also needed a session of radiotherapy to treat a brain lesion.

The treatment has significantly reduced her cancer, and Johnsons children a 26-year-old son and 29-year-old daughter were able to visit her during 2020.

She did face a setback when a particularly stubborn lesion required 15 sessions of radiotherapy, but Johnson believes that things will get better.

I had tremendous support from my husband, children and friends. In fact, my husband has been like my cancer PA, and oftentimes, he has arranged everything so that all I have to do is just show up for my doctors appointments. I was worried about the toll on my family, especially since my mom and sisters havent been able to meet me for more than a year. But I decided I was going to keep an I-will-beat-this attitude, and trust the professionals treating me, Johnson said.

She also credits her doctor Dr Humaid Al Shamsi with bringing humour into cancer, and helping her bear some of the mental toll of the illness.

With that being said, it was important for Johnson herself to find her own strength and positivity.

As clichd is it sounds, what helps is reminding myself that my diagnosis doesnt define me, and that it is just part of my journey, she added.

Colon cancer: I had to remove 30 centimetres of my colon

Ahmad Ayyash was convinced his low haemoglobin readings pointed to something, but his concerns were initially dismissed.

A general physician recommended he resolve the issue with simple iron tablets, but the 66-year-old senior management executive from Palestine persisted. In follow-up testing, another physician suggested he was losing blood, and recommended an endoscopy and colonoscopy to trace the source of the problem. That was when the cancer was discovered, affecting about five centimetres of his colon.

The word cancer still strikes a sense of fear, and I cannot say I was immune to it. But after the initial diagnosis, I decided to put my faith in medicine, and in my doctors, Ayyash told Gulf News.

He was first diagnosed in February 2017. A month or so later, Ayyash underwent surgery to remove 30 centimetres of his colon. The procedure was laparoscopic, and therefore only involved about four small cuts on his abdomen. But it left him in hospital for nine days, and relegated him to IV nutrition for eight or so days. Even beyond that, he was only able to stomach soft foods as his body recovered.

The best thing to do when you have a procedure that involves your digestive system is not to eat, so it was obviously not easy. But beyond then, I have recovered well, Ayyash said.

What also helped was that Ayyashs cancer had few effects that were visible, the father-of-four said.

My family would have been more worried had I been in visible pain, but thankfully, that was not the case with my cancer. I honestly feel like I discovered it by coincidence, and because I insisted that there was something that needed checking, Ayyash said.

Despite the initial dismissal of his symptoms, Ayyash went on to find much support from his physicians as well.

My surgeon Dr Sadir Alrawi, director of oncology at VPS Healthcare put me very much at ease. He told me that if I had to choose a cancer, Id rather choose this because it was treatable, he said.

Because his cancer was in its early stages, Ayyash did not require any chemotherapy or radiation.

In fact, the 30 centimetres of bowel that was resected included areas that looked cancer-free but may have been affected, Ayyash said.

Since the surgery, the 66-year-old has continued to live a largely regular life, still working in senior management. He is regular with his follow-up blood tests, as well as with an annual colonoscopy and CT scan.

But he did learn some important lessons from the experience.

Cancer should be viewed as a treatable disease as much as possible, and people should not be afraid to undergo screenings, or to insist when they believe something is wrong. After all, there really is a big difference in prognosis when a cancer is discovered at five months and when one is discovered at five years, Ayyash said.

He also urged primary health professionals not to ignore sudden changes in parameters like haemoglobin level.

In fact, I learnt to take any such changes seriously, and to pursue it till I am comfortable, he said.

Lymphoma: 'I chose not to Google survival rates'

It was after a routine meal that 53-year-old business development manager Ajay Chaturvedi first felt that something was wrong.

Feeling nauseated and suffering from diarrhea, he had gone to an emergency unit for treatment, and was sent home with medicines to treat what appeared very much like gastroenteritis a stomach bug.

Still, he sought out another physician, who discovered a swelling in his abdomen. Scans subsequently revealed that his spleen and liver were enlarged.

I was shocked to see how my mesenteric arteries, which deliver blood from the heart to the gastrointestinal tract, were sandwiched in cancerous, enlarged lymph nodes, Chaturvedi, an Indian expat, told Gulf News.

Further tests revealed that he was suffering from the initial stages of B-cell non-Hodgkins lymphoma a cancer that affects the bodys lymphatic system, which manages immune response.

I am a strong person, but along this journey, I sometimes found myself weak and broken. I needed support from friends and family, but eventually, I decided to concentrate on my work, and on beating this, Chaturvedi said.

Diagnosed in 2015, the Dubai resident was prescribed six sessions of chemotherapy.

I handled the first four sessions very well. But by the fifth one, I was anxious, stressed, weak. I remember distinctly how it was sometimes difficult to even get up once I had sat down in a chair. There was nausea and insomnia to counter, and after each session, I could barely walk for three to four days, Chaturvedi said.

Cancer support

The UAE has a range of cancer support groups and organisations, which help patients and families all the way from diagnosis and treatment until post-cancer therapy. -Friends of Cancer Patients: 06-5065542 -Bosom Buddies: bosombuddiesad.org -Brest Friends: 800-ALJALILA -Breast Cancer Arabia -Cancer Patient Care Society Rahma: 80090 In addition to these, various community organisations also provide support, including financial means for patients.

Mustering all his strength, he continued with the chemotherapy sessions, scheduled about three weeks apart, even though he lost his hair and felt wretched.

Fortunately, his friends and family were very encouraging, and kept reminding Chaturvedi that survival rates were as high as 70 per cent when his specific type of lymphoma was discovered early.

I would look up articles on the Internet, but I eventually chose not to read up about the cancer because it was easy to come across worrying figures and accounts, Chaturvedi said.

He received the cancer all-clear in October 2017, and still keeps a close watch on his blood count with regular tests and doctors visits.

I know I was scared, but eventually, I fought the fear and focused on conquering the illness. Having beat it, I would remind other people in the same position that there are today a multitude of targeted therapies and effective interventions, Chaturvedi said.

In addition to keeping a watch on himself, Chaturvedi has also since undergone genetic testing to check if his children are at risk.

I also derived a lot of strength from my family and friends, but I would urge anyone who feels alone to seek out the many cancer support groups in the UAE, he added.

Breast cancer: The UAE has very advanced cancer treatment options

Following the discovery of a lump in 2014, Sofia Khalid had undergone a lumpectomy. Within two years however, the then-51-year-old economist from Pakistan was once again in pain.

Insisting on a battery of tests, including an MRI, her physicians discovered a lobular invasive carcinoma in its very early stages.

My doctors told me that the cancer a slow-growing variety is rarely discovered in its first few stages, especially because it is not apparent through mammograms, physical exams or even ultrasound exams. I had however felt a lump in the same area, and even when everyone insisted it was just scar tissue, I insisted on further screenings, Khalid told Gulf News.

The diagnosis, Khalid said, nevertheless felt like a death sentence.

It felt like a bullet, especially since I had, for years, worried about a cancer. The first lump had turned out to be benign, but in 2016, I was convinced there was something more, she said.

According to her physicians, Khalids cancer was rare for women under the age of 60 years, and was hard to detect because the cancer tissue looks very similar to breast tissue.

Still, Khalid took charge of her treatment, and opted for a full mastectomy with reconstruction. One of her daughters flew down from Canada, as well as an aunt from Pakistan, and Khalid said her workplace remained extremely supportive throughout the ordeal.

Since her cancer had not yet spread, there was no follow-up chemotherapy or radiotherapy. Instead, Khalid was prescribed hormone therapy in the form of a daily pill.

When I consulted other experts, everyone told me I had been given some of the best medical treatment possible. The UAE does have very advanced cancer treatment available, and I was lucky to have access to it, Khalid said. The Malaffi health information system in Abu Dhabi helped her keep track of all her appointments, and to go through all the follow-up checks. Moreover, she was able to both have her cancer tissue removed, and her breast reconstructed, during a single procedure.

But the ordeal had brought along its own trauma, and Khalid signed up for psychotherapy to resolve her feelings of depression.

Its taken me three years to work on my mental health, and I am glad I have chosen to do it. An atmosphere of doom and gloom helps nobody, she said. The mother-of-four has also taken up regular exercise after her brush with cancer.

Following her experience, Khalid advised that women advocate for their own health.

Had I not insisted on so many tests or discussed my concern repeatedly with my doctors, the cancer might not have been discovered so early. What I learnt was that if there are cancer symptoms, you may already be too late. So it is important to be proactive all the time, she urged.

I keep looking over my shoulder

Shyam A. Krishna, Senior Associate Editor

It will be back, the doctor said, referring to my lymphoma. That was eight years ago. Cancer hasnt returned, but Im still worried. I guess, the fear will always remain.

I do blood tests every six months, and a CT scan annually. So far, Ive been cancer-free. But every time I have a sore throat (from acid reflux), I involuntarily check my lymph nodes in the neck. Whenever I have a shaft of pain anywhere in my abdomen, the alarm bells keep ringing.

Call it hypochondria or survival instinct; I make more visits to my gastroenterologist than necessary. Thats more for my GERD (Gastroesophageal Reflux Disease). He was the one who diagnosed my cancer even after the initial battery of tests turned up nothing. The pain in my lower abdomen kept recurring every week. As the final throw of dice, the doctor called for a CT-Scan that revealed a growth in a lymph node. Non-Hodgins Lymphoma, that was the diagnosis. Immunotherapy and radiotherapy helped heal.

How was my cancer journey? What did I learn from it? Not much. Whatever little I learned, I forgot. Because life became normal. Im reminded of my cancer only when the reminders for the tests pop on my phone. Yet, there are moments when I look back at the dark days with trepidation. And realise how lucky I was.

My doctor called it the best cancer anyone can get. Its treatable, he added. Those words helped calm me. Later during my intense research on the internet, I found that its treatable but not curable. Which means theres no 100% cure. So when the oncologist warned me that it might return I wasnt surprised. By then, my initial shock had worn off. I was sure that I would survive.

I didnt just survive, I live a full life. An active life. Cancer didnt stop, and I didnt allow cancer to disrupt. It was a bump on the road. Im cruising again. But the doctors words continue to reverberate in my ears. So Im always looking over my shoulder.

Over the last decade, major advancements have been made towards turning cancers into more treatable, easily detectable conditions.

Dr Humaid Al Shamsi, president of Emirates Oncology Society, offered his take on the game changers that are available today, and those that are shaping up.

Precision medicine:

In the simplest of terms, a blood test is used to assess a patients DNA. The analysis of tumour fragments gives clues on specific mutations that can be targeted during therapy.

Essentially, mutations are like locks on cancer cells, and the targeted therapy, administered intravenously or in the form of pills, acts like keys to those locks. This means that two patients with the same cancer could receive different therapies to target their specific cancers. The targeted therapy acts to stop the growth of the specific cancer tissue. In fact, a treatment that targets a specific mutation or genetic feature could be used to target vastly different cancer types, and the United States Food and Drug Administration has already approved treatments that act on specific cancer biomarkers rather than the site where the cancer originates.

Why this is a game changer: Targeted therapies are more effective at fighting the cancer when a patient responds to them. There are also potentially fewer side effects, and less harm to normal cells.

This aims to activate the bodys immune response, which is often put to sleep by cancer tissues.

Cancer cells grow by persuading the patients immune system that they are friendly, and eventually make this immune response dormant so that the cancer can grow. A PDL1 test, which looks for the PDL1 protein on cancer cells is usually carried out. This protein helps the immune system recognise non-harmful cells in the body, and cancers that have high amounts of PDL1 can therefore trick the human body and prevent the launch of an immune response.

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World Cancer Day: Survivors in the UAE share their journey of fighting the disease - Gulf News

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Global ovarian cancer drug marketis rise gradually to an estimated value of USD 5.6 Billion by 2026 substantial CAGR of 20.1% in the forecast period of 2019-2026. Rising incidence of ovarian cancer, growing geriatric population, and robust drug pipeline for treating ovarian cancer are the key factors for enhancing the market growth.

The winning Ovarian Cancer Drug business report offers a platform for marketing and business managers to obtain critical information about their consumers so that existing customers can be retained and new ones can be got onboard. The market research report helps in understanding customer inclination towards purchasing products. It also gives the details regarding whether the customers will spend a certain amount of money for their products, inclination levels among customers about upcoming features or products, what are their thoughts about the competitor products etc. Market data collected while generating Ovarian Cancer Drug market report is instrumental in making major changes in the business which reduces the degree of risks involved in taking important business decisions.

Download Sample PDF Copy of Reporthttps://www.databridgemarketresearch.com/request-a-sample/?dbmr=global-ovarian-cancer-drug-market

Few of the major competitors currently working in the ovarian cancer market areAllergan Plc, AstraZeneca, F. Hoffmann-La Roche Ltd, Pfizer Inc., Merck KGaA, Syndax, Clovis Oncology, Boehringer Ingelheim International GmbH, GlaxoSmithKline plc, Exelixis, Inc., DelMar Pharmaceuticals, Inc., Bristol-Myers Squibb Company, Novartis AG, Johnson & Johnson Services, Inc., AbbVie Inc., Oasmia Pharmaceutical AB, TESARO, Inc., Amgen, Inc., and among others.

Market Drivers

Market Restraints

Key Developments in the Market:

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Segmentation: Global Ovarian Cancer Drug Market

By Type

By Drug Type

By Treatment

By Route Of Administration

By End Users

By Geography

For More Insights Get Detailed TOC https://www.databridgemarketresearch.com/toc/?dbmr=global-ovarian-cancer-drug-market

Key Insights in the report:

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Global Ovarian Cancer Drug Market Size, Revenue and Growth Rate Through 2026||Pfizer Inc., Merck KGaA, Syndax, Clovis Oncology, Boehringer Ingelheim...

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Introduction

Binge eating disorder (BED) is the most prevalent eating disorder (ED), with estimates of 25% of the general adult population, although its recognition as a single diagnosis only occurred in 2013 by the Diagnostic and Statistical Manual of Mental Disorders (DSM), fourth edition. In its latest edition, BED is defined by recurrent episodes of eating unusually large amounts of food while experiencing a feeling of losing control in the absence of regular use of inappropriate compensatory behavior. Marked distress regarding binge eating is present and the binge episodes occur, on average, at least 1 day a week for 3 months.1

Lifetime prevalence of BED ranged from 1.2% to 4.5% (when included subthreshold BED) and was noted to be more similar between men and women when compared to the distribution as observed with anorexia and bulimia nervosa.2 Typically, its symptoms begin during childhood and adolescence, but it can also be seen in the elderly with longer duration of illness reported.2 A previous study has shown a 12-month persistence of 44.2%, meaning that half of the patients could have achieved spontaneous remission on the course of the disorder.3 However, it can also assume an intermittent behavior.

Medical and psychiatric comorbidities are commonly observed in individuals with BED. At least one core DSM-5 disorder can be found co-occurring in up to 80% of BED patients, mainly depression and anxiety disorders, although other psychiatric disorders, including bipolar disorder, borderline personality disorder, and substance abuse have also been found to be related to BED.4,5 However, its association to general psychopathology, the presence of clinical comorbidity must not be forgotten. Higher prevalence rates of BED are found in overweight and obese individuals,6 and indeed, the presence of psychopathology as associated to obesity seems to be more severe in the presence of BED.7 Also, individuals with BED have an increased risk to develop type 2 diabetes, are more likely to develop nonalcoholic fatty liver disease, gastrointestinal problems, and disrupted sleep. An even higher prevalence was noted among infertile women.8,9

Previous studies have found impaired quality of life (QL) in individuals with BED. In addition, obese individuals with BED have shown reduction in QL when compared to non-obese BED patients. For instance, when using the Medical Outcomes Short Form-36 Health Survey (SF-36) to estimate QL, obese BED patients showed lower scores in comparison to the non-obese BED sample (45.3 [9.6] vs 53.6 [9.4], respectively, P = 0.001).10 Interestingly, obesity seemed to impact more on the physical variables of QL while BED was linked with poorer mental health and social functioning. Particularly, both the presence of depressive symptoms and a poor body image attitude seemed to objectively impact BED-QL.11

Despite its high prevalence rate and common association to clinical and other psychiatric problems, BED patients commonly remain either undiagnosed or receive inadequate treatment.12 Frequently, BED patients are referred to treat medical comorbidities without specialized eating disorder (ED) treatment.13 Considered underestimated in comparison to other frequently psychiatric complaints, such as depressive and anxiety-related symptoms which may culminate into inadequate psychological or pharmacological treatment choices.

Before considering BED treatment, an extensive evaluation should be made in order to identify and estimate problems in the 3 main areas of concern, namely, eating-behavior and related psychopathology, general psychological and psychiatric disorders, and presence of obesity with other medical problems possibly associated with BED.14 As a result, treatment algorithms should reflect the hierarchy and severity of problems in each individual area and should include the choice of different strategies that may include nutritional, psychological and pharmacological treatments. The American Psychiatric Association recommends a multidisciplinary approach that includes psychological treatment as a main approach and considerations for medication as adjunctive therapy.15 In contrast, the National Institute and Care Excellence also includes the possibility of medication monotherapy.16 However, both guidelines do not clarify which specific best practices of weight management should be offered, including dieting-based approaches, medication or even bariatric surgery.

A recent meta-analysis concluded that among BED adults, there is strong evidence that favors the use of cognitive-behavior therapy (CBT) and medications that include lisdexamfetamine (LDX), second-generation antidepressants, sibutramine (discontinued in many countries mainly due to cardiovascular risk) and topiramate. However, several limitations were found, which included methodological issues, fewer reports of adverse effects and discontinuation of drug trials, and the heterogeneity of outcomes.17 In this last regard, an optimal treatment related to eating, general psychopathology, and obesity severity is still required for a subset of patients.

Considering the lack of evidence on sufficient drug efficacy and the urge for new approved treatment options, this paper aimed to update recent pharmacological treatment data for BED by using the last 5 years as a timeframe. Reviews including interventions with previous timeframes had already been published and showed benefits of pharmacological treatment for BED. For instance, a previous meta-analysis that included 33 placebo-controlled trials showed a significant advantage of the pharmacological treatment over placebo for achieving short-term remission from BED (48.7% vs 28.5%).18 Despite that, only one agent emerged as an approved drug for BED treatment. Since 2015, when LDX received approval from the US Food and Drug Administration (FDA) for moderate/severe BED treatment in adults, no other medications have been approved and, in general, they have solely been used in an off label fashion. It is important to take into consideration the adverse effects that often lead to discontinuation: dry mouth, decreased appetite, insomnia and headache.

Pharmacological BED treatment in clinical practice usually follows hierarchic principles related to the patients complaints, the physicians evaluation and findings in physical examination or laboratory. Evaluation on each potential drug treatment for BED should be done taking into account clinical and psychiatric aspects, that may argue against the use of specific agents. Considering the importance to explore recent data on pharmacological trials on BED (including those that investigated new promising agents in order to point out to the best options available and future directions to remission achievement), this review was performed and condensed in Table 1. To enrich our findings, we also included sections related to novelty treatments for BED based on animal studies and advantages of each medication regarding adverse events.

In order to allow for a better understanding of the drugs role in BED, some neuromechanisms associated to a possible development and maintenance are exposed. In fact, many neurotransmitters, hormones and agents seem to be involved in BED induction and maintenance of BED. Below are listed some of the most significant findings related to this topic.

When BED is evaluated in the light of impulsive/compulsive food consumption theory, and its regulation by the brain rewards system hypotheses, dopaminergic neurotransmission seems the most appealing neuropathway to explore.19 In this model, the dopaminergic release, possibly due to an altered function in cortical and striatal regions, would otherwise be associated to motivational and control aspects of feeding (i.e., impulsivity/compulsive behaviors).19

Following a different neuropsychological path in accordance by many authors, the neurotransmitter serotonin (5-hydroxytryptamine [5-HT]), would be considered to have a key role in ED development. To support this hypothesis, studies show that serotonin is derived exclusively from dietary tryptophan, an essential amino acid. In excessive dieting and food restriction, a significant reduced ratio of tryptophan is found (mostly in anorexic patients). Furthermore, alterations on serotonin are associated to perfectionism and mood regulation. In a small study with obese binge eaters and non-obese binge eaters, decreased 5H-T transporter binding in the midbrain was found in the first group but not in the second.20

An agent with these properties, vortioxetine, was also tested for BED treatment. This substance is a serotonin stimulator which also increases noradrenaline, dopamine, and acetylcholine in certain areas of the brain, as well as modulating -aminobutyric acid and glutamate neurotransmission.21 More details of this study will be discussed later in this article.

Glucagon-like peptide-1 (GLP-1) is a hormone secreted from the small intestine in response to food ingestion. It can regulate food intake by slowing gastric emptying and through appetite inhibition in the brain thus reducing activation in appetite-related brain regions (possible brain areas involved: vagus nerve, nodose ganglia, hypothalamic nuclei, and the brain stem). Liraglutide, a GLP-1 receptor agonist, has been recently also approved for obesity management as an adjunct to physical activity and diet recommendations. It was previously approved in the type-2 diabetes treatment due to its effects associated with releasing insulin from the pancreas and decreasing glucagon release. 22

Oxytocin, another important hormone receiving attention in the last years, seems to play a strong effect on food consumption. Besides its anxiolytic properties and cortisol reactivity towards food,23 oxytocin appears to be also implicated in regulating reward-driven eating. This last hypothesis would be linked by the down-regulation of neural circuits related to the addictive theory of BED and bulimia nervosa.24

The two following agents, LDX and dasotraline used for ADHD treatment, were also tested for BED due to their co-occurrence, high levels of impulsivity in BED and growing findings, therefore suggesting that binge eating is associated with the dysfunction of dopamine and/or norepinephrine neurotransmission.19

Abbreviated from l-lysine-dextroamphetamine, LDX is a novel prodrug of dextroamphetamine (d-amphetamine) linked to the amino acid l-lysine, itself inactive and metabolized by mechanisms associated with red blood cells. With LDX hydrolysis, there is an inhibition of the reuptake of dopamine and norepinephrine from the synaptic cleft which simultaneously enhances the release of both, besides serotonin.25

Additionally, there is dasotraline, a novel dual-acting dopamine and norepinephrine re-uptake inhibitor which is the only drug being currently tested in trials for BED treatment. Following developments with LDX, methylphenidate is another psychostimulant used for ADHD and presumed to exert its effects by means of dopamine transporter blockage and is overall well tolerated by patients with low levels of treatment attrition.26 At last, although not a psychostimulant per se, we present a study with BED and armodafinil. This agent presents waking-promotion actions similar to the agents cited above and has psychoactive and euphoric effects. It is an indirect dopamine receptor agonist.

The use of agents such as naltrexone for BED is based on the model of an association between eating behavior and substance abuse. Considering that opioid system dysregulation underlies addictive binge eating, blockade of opioid receptors would diminish food intake and food craving thus being a form of anticipatory reward regulated by endogenous opioid and mesolimbic dopaminergic systems.27

Carbamates (disulfiram) act by inhibiting aldehyde dehydrogenase and as an alcohol deterrent, altering the intermediary metabolism of alcohol. This substance produces a sensitivity to alcohol, therefore when alcohol is ingested, blood acetaldehyde concentrations are increased, leading to: flushing, systemic vasodilation, respiratory difficulties, nausea, hypotension, and other symptoms.28 Certain BED features resemble those of alcohol users, such as the urge to consume (food/alcohol) and the lack of control over their consumption.29

Antiepileptic agents, specifically topiramate, due to its modulatory effects on GABAa receptors (involved in calory intake) contribute to an improvement in eating behavior and weight loss. Sympathomimetic amine (in this case, the agent phentermine) is associated with a decrease in appetite reduction and food consumption mostly for its action in releasing norepinephrine in the hypothalamus. The two are approved for obesity treatment by the FDA. The combination of both phentermine-topiramate involves the coadministration of drugs with opposing side-effect profiles. Phentermine stimulant-like properties may reduce topiramate sedative and cognitive side effects.30

Table 1 summarizes all results.

This drug is a dual dopamine and norepinephrine reuptake inhibitor and had been initially developed for attention deficit disorder (ADHD) treatment and Phase 3 trials had already been published. Its advantage, when compared to other stimulants or non-stimulant drugs used to treat ADHD, is its slow absorption rate and long elimination half-life which could diminish the potential for abuse and eliminate the problem of multiple dosing.

Three studies from the same pharmaceutic company, Sunovion, were performed for BED. The first one was a randomized 12-week treatment with placebo at a flexible dose (4, 6, 8 mg/day) with 317 patients. Significant reduction in binge eating was found starting from 6mg/d (3.74 vs 2.75; P<0.0001) and the drug presented good tolerability after 1-year follow-up.32 The second study investigated the impact of dasotraline on weight in this very same cohort of patients in a 3-month trial. Weight changes were observed at week 12 for completers treated with dasotraline vs Placebo and evaluated by the body mass index (BMI) categories: normal weight (4.6 vs 0.2), overweight (5.8 vs +1.3), and combined obesity classes IIII (6.2 vs +0.3).33

In the third trial, a different sample of 486 participants with BED were selected and randomized to a placebo, dasotraline 4 mg/day, or dasotraline 6 mg/day. Dasotraline 6 mg/day, but not 4 mg/day, was superior to placebo for reducing binge eating episode days (3.5 vs 2.9; P=0.004). Both doses produced significant reductions in obsessive-compulsive features of binge eating (P<0.001 and P<0.02) and global BED severity (P<0.01 and P<0.03). The drug was well tolerated in both studies, with the most common side effects being decreased appetite, dry mouth, anxiety, nausea, headache, constipation, and a modest increase in both pulse and blood pressure.34 On July 30, 2019, Sunovion announced the acceptance by the US FDA of the New Drug Application for dasotraline for the treatment of adults with moderate-to-severe BED. However, on May 13, 2020, Sunovion withdrew the application, citing that further clinical studies would be necessary to support regulatory approval. It should be noted that, previously, on August 31, 2018, the FDA had issued a letter determining that the drug could not be approved for the treatment of ADHD without additional data.

Commercially known as Vyvanse, LDX was primarily developed as a treatment for ADHD tailored to increase attention span and decrease restlessness. This is an inactive prodrug derived from amphetamine by means of a unique mechanism involving an enzymatic process predominantly associated with the red blood cells. It was developed with the aim of providing a long-lasting and consistent effect throughout the day along with reducing the potential for abuse.35

Since 2015, a robust development program carried by the same research group composed by 3 short-term trials: one dose-finding Phase II study, two dose-optimization Phase III studies,36,37 and two long-term trials, were performed in order to investigate its safety and efficacy in BED treatment.38,39

In the first study, a 11-week fixed-dose, parallel-group multicenter trial, with 259 adults across 30 sites in the USA diagnosed with BED and BMI between 25 and 40 kg/m, were randomized to receive LDX 30, 50, 70 mg/day or placebo. Seventy-eight percent of subjects completed the double-blind phase of the study. Binge eating episodes significantly decreased in the 50 and 70 mg/day treatment groups, but not in the 30 mg/day treatment group as compared to the placebo group. Specifically, in the LDX 50 mg/day group, binge days/week decreased from 4.5 to 0.4 (P0.008) and in the LDX 70 mg/day group binge days/week decreased from 4.6 to 0.5 (P0.001).36

With the same participants sample, two subsequent trials used an enrichment strategy according to the following scheme: 1) 12-week open-label phase (dose optimization: 4 weeks of 50 or 70 mg); 2) dose maintenance of 8 weeks; 3) a 26-week, double-blind, randomized withdrawal phase; and 4) a follow-up visit. LDX was superior to placebo for reducing binge eating day frequency, global BED severity, and obsessive-compulsive features of binge eating. Significantly more LDX recipients had cessation of binge eating in both studies (36.2% and 40%) compared to placebo (13.1% and 14.1%, p < 0.001) and more significant body weight loss. In regards to the safety profile, adverse reaction rates beyond 50% were not higher than those found with other psychotropic agents and were equally distributed across both active drug and placebo groups. In addition, both studies did not show elevated discontinuation rates due to adverse effects (6.3% and 3.9%). Also, although weight loss was not a primary endpoint, it was comparable to what have been found in trials with anti-obesity agents, ranging between 5 and 12 kg for the 12-week open-label phase. Finally, and not to be disregarded, there was some evidence that LDX has a low potential risk of abuse.36,37,40

The randomized withdrawal maintenance of efficacy study38 examined rates of binge eating relapse in LDX treatment responders following 12 weeks of open-label treatment. The risk of binge eating relapse over a 6-month period was significantly lower in participants randomized to continuing LDX than in those randomized to placebo. The long-term safety and tolerability study consisted of a 1-year open-label extension trial of LDX in BED participants who had completed one of the three short-term trials. A mean (SD) of 7.04 (7.53) kg in weight reduction was reported at the end of the study.39

LDX was the first medication to receive regulatory approval for the treatment of BED in the world (2015). It is specifically approved for moderate and severe BED in adults at 5070 mg/day. The recommended starting dose in BED treatment is 30 mg/day with increments of 20 mg/day to achieve the recommended target dose of 50 to 70 mg/day.31

Due to the strong association between dopamine and eating behavior, methylphenidate was selected to a randomized comparison with CBT in order to improve BED symptoms. Twenty two patients took a flexible-dosage ranging from 18 mg/d - 72 mg/d by the end of the fourth week and 27 patients completed the psychological treatment composed by 12 sessions. Both groups presented binge-free patients: 47% for medication and 60% for CBT, 2 = 0.62, p = 0.43; subjective binge episode remission: 41% for medication and 35% for CBT, 2 = 0.15, p = 0.70. As to weight loss, a significant difference in BMI was found at Week 12 compared to Week 0 for the methylphenidate group= 5.18, p < 0.001, but not for the CBT group= 1.54, p = 0.13. Despite the drug potential, the study hardly mentioned the side effects.41

A 10-week, randomized placebo-controlled trial was conducted with 30 BED patients for placebo and 30 BED patients for the armodafinil group (150250 mg/d) neither with a current history of anorexia or bulimia nervosa. In the first analysis, there were no significant differences between the groups in reducing binge-eating day frequency. Armodafinil was associated to a greater reduction in binge eating frequency, BMI and obsessive symptoms.42

The effects of oxytocin on food intake, 24-h caloric consumption, salivary cortisol, and stress were measured in a randomized, placebo-controlled, crossover laboratory study in 25 women with BN or BED and 27 weight-matched women without a history of eating disorders. Participants attended the lab for two experimental sessions, received a divided dose of 64IU of intranasal oxytocin in one session and an equivalent volume of a placebo nasal spray in the other. There were no significant effects of oxytocin on any measurements.24

Naltrexone extended-release + bupropion ER combination (NB) is an anti-obesity agent approved in the USA as an auxiliary component to dieting and physical activity for chronic weight management. Their combination was developed based on pre-clinical evidence that this association has complementary effects in the reduction of food intake. The first component is an opioid antagonist that has a high affinity for the -opioid receptor which is related to eating behavior.43 The second one is an antidepressant (norepinephrinedopamine reuptake inhibitor) that has shown efficacy in smoking remission and on weight loss. However, the use of bupropion alone did not improve binge eating behavior in a previous randomized trial.44 Interestingly, in a small retrospective cohort study, bupropion was effective in reducing binge frequency and, when compared to sertraline, achieved greater weight loss and improved sexual performance.

An open-label prospective study of 24 weeks was performed in 2017. The authors evaluated the NB combination therapy (32 mg/day of naltrexone ER and 360 mg/day bupropion ER) associated to diet and physical activity guidance in 25 overweight/obese subjects with depression. Medication was initiated at one-quarter of the daily maintenance dose and raised over the first 4 weeks of treatment. The binge eating scale (BES) scores were improved and maintained during the trial and, by week 8, there were no more patients that fulfilled the criteria for severe BDE. Overall, BED symptoms and weight loss improved.45 An important limitation of the study was that 12 patients dropped out before week 24 (n=10 due to adverse events). Forty-eight percent of the patients considered these adverse effects moderate, mostly consisting of constipation (n = 8; 32%), headache (n = 8; 32%), insomnia (n = 8; 32%), dizziness (n = 7; 28%), and hot flushes (n = 7; 28%).

In 2020, a 16-week open label-trial, with 23 patients with obesity and BED and a control group of 20 obese non-BED patients, was concluded. All patients should have undergone at least five weight-loss programs without success. NB of prolonged-release containing 8 mg of naltrexone and 90 mg of bupropion was initiated and slowly increased from 1 tablet a day up to a maximum of 2 tablets twice a day after the third week and followed by another 13 weeks maintenance phase. In parallel to NB, a 16-week lifestyle program, consisted of hypo-caloric diet, behavioral counseling and moderate aerobic physical activity was also implemented. Binge eating behavior weight loss improved in BED patients (p=0.003). By the end of the treatment, achieved BMI was statistically similar between both groups (BED group = 35.8 6.8 vs Control group = 40.3 8.8; t = 1.687; p = 0.101).46

The premise for vortioxetine use in BED was based on the fact that a varied circuitries appear to be involved in BED physiopathology.47,48 Thus, a multi-modal target medication, such as vortioxetine, could be helpful. Also, it appears to have a cognitive enhancing potential which may be useful in disorders that display an impaired executive control.49 For at least a year, eighty adults with BED were recruited for a double-blind, placebo-controlled pilot study. Participants received a 12-week treatment with vortioxetine (10mg/day for the first week and subsequently 20mg/day) or placebo in a parallel design. Binge eating frequency was noted to be significantly reduced over time in both groups. Weight and BMI did not change over time (p>0.10). Thus, vortioxetine failed to be more effective than placebo for BED treatment. (NCT02528409)

GLP-1 was developed as a type 2 diabetes management; however, it is also used as an anti-obesity drug and sold in the form of a once-daily injection with effects known to inhibit appetite and delay gastric emptying in non-diabetic obese participants with BED symptoms.

In a small randomized pilot study, 44 obese binge eaters were assigned to either a liraglutide 1.8mg + diet and exercise group or a control (diet + exercise) group for 12 weeks. Liraglutide participants showed significant reductions in BES [20 (IQR 1827) to 11 (IQR 716), p < 0.001] and 81% (n=17/21) of them experienced a change in status from a binge eating to a non-binge eating category. Other measures were also improved such as body weight (94.5418.14kg to 90.1419.70kg, p<0.001) and BMI (36.15 3.84 kg/m2 to 34.40 4.77 kg/m2, p<0.001). Nausea was the most prevalent adverse symptom.50

In 2017, the binge eating liraglutide intervention study (BELIEVE) was initiated. A 17-week, randomized placebo-controlled trial tested the efficacy of liraglutide 3.0 mg/d compared to placebo in achieving remission of binge eating episodes and other clinical variables. The active comparator was a pre-filled, multi-dose pen that delivered doses of 0.6 mg, 1.2 mg, 1.8 mg, 2.4 mg, or 3 mg via subcutaneous injections. The medication was initiated at 0.6 mg daily for 1 week and then increased by 0.6 mg/day in weekly intervals until a dose of 3.0 mg/day was achieved. However, the study was terminated due to not meeting its recruitment goals.51 (NCT03279731)

In a 16-week study, doses of disulfiram 250mg/day were given to twelve obese patients with BED and without a history of alcoholism and heart disease. The agent significantly decreased the mean frequency of binge eating episodes per week from 7.9 1.2 to 0.9 0.6 (p b 0.001) and 7 participants (58.3%) achieved remission of binge eating. No changes in weight were observed and 11 participants presented important side effects. Additionally, three participants dropped out during the study, remaining a total of 9.52

Two previous open-label studies and one placebo-controlled trial had shown improvement in appetite and weight loss in obese BED patients.53 However, more controlled-trials aimed to establish optimal dosing and length of treatment were not performed. Also, cognitive impairment and somnolence were some of the most frequent adverse events that interfered with the patients' tolerability. The phentermine-topiramate (PHEN-TOP) combination was approved by FDA in 2012 for chronic weight management as an adjunct to a reduced-calorie diet and increased physical activity. The investigation of PHEN-TOP in BED treatment was based on a suggested evidence, in contrast to previous topiramate studies, that by lowering doses of topiramate in this combination it would be potentially effective in reducing binge eating behavior thus being safer and more tolerable. The potential role for this drug association in BED treatment was that, in the present study, 18 participants with BED and 4 with BN over 18 years of age were enrolled in a flexible dosage (3.75mg/23mg-15mg/92mg) placebo-controlled crossover trial of 34 weeks.54

LDX, despite FDA approval for BED treatment, definitely presents some significant pros and cons; Table 1 shows details of every study efficacy. The amphetaminic risk of abuse and dependence requires a careful evaluation before prescription. The safety profile is consistent with what was seen in studies using LDX in adults with ADHD; the most common adverse events in the adequate dose of 5070 mg/d are: dry mouth (52%), decreased appetite (25%) and insomnia (19%) and 1.5% has serious adverse effects. The treatment group demonstrates efficacy compared to the placebo group in terms of decrease in BE days and cessation, and global improvement.36

Overall, the second substance mostly investigated was dasotraline. Due to the smaller risk of abuse and dependence, compared to LDX, its development program was very encouraged, showing significant results with 68 mg/d on BE episodes vs placebo (3.5 vs 2.9; P=0.0045). The most common adverse events on dasotraline were: insomnia, dry mouth, headache, decreased appetite, nausea, and anxiety.34 Despite the results, the laboratory withdraw the substance for BED treatment due to the need of further regulatory approval.

In the liraglutide study, forty-four obese BE participants were randomly assigned to intervention or control groups for 12 weeks. All participants received standard advice for diet and exercise. 81% (n=17/21) of those receiving liraglutide improved from binge eating to non-binge eating category, and 2 patients developed nausea. These results are still very scarce. In our opinion, sometimes the non-friendly presentation (injection pen) and the prevalence of nausea as the most common adverse effect are some weak points of the substance use.50

The combination naltrexone-bupropion (already approved for obesity treatment in 2014), despite small groups of patients, was well succeeded for diminishing BE severity and scores, as well as weight loss (89%). The most common side effects had very high rates: nausea (67%) and anxiety (22%), what may impair a sensitive group of patients to proceed. Another combination: phentermine-topiramate was evaluated in two small studies with favorable results, especially on weight loss (average of 6%). The most reported symptoms were: 52.4% (dry mouth), insomnia and paresthesia (28%).

Agents tested in few studies or small samples, such as armodafinil, oxytocin and vortioxetine despite being well tolerated, and presenting some impact of BE and weight, did not present significant differences when compared to the control group. Findings in a methylphenidate and CBT study showed that both interventions were effective in BE measures, with a higher effect of the agent on weight loss (week 0 to week 12 = 5.18, p < 0.001).

Some experimental drugs have been successfully tested in validated animal models of binge-like eating and could represent future investigations in clinical studies:

Corticotropin releasing factor (CRF) represents a hormonal marker of BE induced by cyclic food restrictions and stress and may represent a novel pharmacological treatment for binge-related eating disorders. Indeed, systemic injections of R121919, but not of the metyrapone, were able to block binge-like eating behavior in female rats.55

Sig-1R system seems to contribute to the neurobiological adaptations driving compulsive-like eating, and thus pointing towards pharmacological treating of BED. The authors proved that the treatment with the selective Sig-1R antagonist BD-1063 dose-dependently decreased food responding in binge eating rats.56

Brain orexin 1 receptors (OX1Rs) are involved in food-motivated behavior. A study investigated the ability of OXR antagonist to block BE episodes and to evaluate the involvement of OX1 and OX2 mechanisms in the control of BE episodes in restricted and stressed animals. The results clearly indicate that the OX1R is involved in the control of BE episodes and suggested a potential role of OX1R antagonists to reverse BE episodes induced by stress and restricted diet.57 Other results with rats also suggest that hindbrain OX1Rs play a role in motivation for palatable food and that hindbrain OX1R stimulation can increase palatable, energy-dense food intake.58

Authors examined the effect of two A(2A) adenosine receptor (AR) agonists, CGS 21,680 and VT 7, on high-palatability food (HPF) intake in a model of BE in sated rats and on low-palatability food (LPF) intake in food-deprived rats. BE was induced in female rats by three 8-day cycles of food restriction/refeeding, followed by acute stress. The present study confirmed that the combination of stress and repeated episodes of food restriction is able to induce a pronounced binge eating response for HPF in rats.59

Since its categorization as an ED diagnosis in 2013, various studies have been published that investigated the effectiveness of different pharmacological treatments. Yet, up until now, the only drug approved by the FDA for BED treatment is LDX, which is not necessarily fit for all individuals with BED. Actually, in a real-life scenario, BED treatment could follow a variety of different algorithms and, in everyday practice, different off-label drugs are notably used as first-line agents.

Since 2015, only two antidepressant drug-trials have their efficacy in BED treatment investigated. In contrast to a previous study, which did not show improvement in binge eating behavior with bupropion treatment alone, NB treatment has been associated with BED improvement and some weight loss. According to previous evidence, it seems that for BED patients presenting with mood-related psychopathology, bupropion use might improve eating psychopathology as well. However, obese BED patients who did not present with clinically depressive symptoms would benefit more from NB treatment. Nevertheless, it should be noted that NB has been studied in small open-label trials and more extensive studies should still be performed. The second antidepressant investigated in BED treatment was vortioxetine. In spite of a lack of previous clinical evidence, findings showed that this drug has a limited efficacy of second-generation antidepressants when used alone in BED.

The next new promising agent, dasotraline, was chosen and is still expecting FDA approval. Overall, results from 2 double-blind studies, published by the same pharmaceutical industry, were favorable to its use in the reduction of BED episodes and reduction on obsessive traits related to eating behavior. In one of those investigations, dasotraline was also related to some modest weight loss. Nevertheless, the discontinuation of the dasotraline program diminished the chance to have a second FDA approved agent for the treatment of BED in the near future. In this regard, a similar discussion could be made in relation to the use of liraglutide for the treatment of BED. Though only a pilot open-label study has been demonstrated for its benefits in reducing eating psychopathology in a small sample of obese patients with high binge eating scale scores not formally diagnosed as BED and with an evident impact on weight reduction and safety profile much expectation was given towards further studies. However, termination of its double-blind randomized trial also temporally puts away the chance of having liraglutide approved for BED. Of note, in clinical practice however, a significant percentage of patients that have been treated for obesity with liraglutide might have also been treated for BED, even if not clinically diagnosed, due to the higher prevalence of their comorbidity.

Considering the lack of evidence of armodafinil and oxytocin, the modest effect of disulfiram in an open trial and a favorable result of methylphenidate in a small randomized trial, the next drug awaiting for promising results in the treatment of BED might be the PHEN-TOP combination. Although only 2 small studies investigated its use for BED, some considerations might be worthy taking into account. Firstly, topiramate alone had previously showed to be effective in BED trials. Secondly, the premise to use a drug combination that allows smaller doses of topiramate to be tested increases its safety. Indeed, this can be evidenced in face of the PHEN-TOP approval for adjunct treatment of obesity in 2012. Lastly, the inclusion of patients with bulimia nervosa in one of the studies might shed some light on a future new drug for another ED.

The last 5 years have shown how difficult it is to prove sufficient efficacy and safety for new drugs in BED treatment. Since 2015, LDX has remained the only drug treatment option approved by the FDA. Interestingly, most studies of investigational drugs in this period were performed with agents that had already shown a positive impact on previous eating-related psychopathologies (though used in a different fashion as in naltrexone added on bupropion and phentermine added on topiramate) or had been known for its efficacy on obesity (liraglutide). However, much effort still needs to be employed as new studies are urgently needed especially given the negative impact of BED on QL and clinical morbidity. Meanwhile, guidelines for BED treatment, particularly those targeting non-psychiatrists, should be considered towards a recommendation on the use of off-label agents and the need for individualizing drug treatment choices in accordance to clinical and psychiatric status.

Jose C Appolinario reports grants from Takeda Pharmaceutical, during the conduct of the study. The authors report no other potential conflicts of interest for this work.

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11. Vancampfort D, Probst M, Adriaens A, et al. Clinical correlates of global functioning in obese treatment seeking persons with binge eating disorder. Psychiatr Danub. 2014;26(3):256260.

12. de Zwaan M, Herpertz S, Zipfel S, et al. INTERBED: internet-based guided self-help for overweight and obese patients with full or subsyndromal binge eating disorder. A multicenter randomized controlled trial. Trials. 2012;13(1):220. doi:10.1186/1745-6215-13-220

13. Wassenaar E, Friedman J, Mehler PS. Medical complications of binge eating disorder. Psychiatr Clin North Am. 2019;42(2):275286. doi:10.1016/j.psc.2019.01.010

14. Cossrow N, Pawaskar M, Witt EA, et al. Estimating the prevalence of binge eating disorder in a community sample from the United States: comparing DSM-IV-TR and DSM-5 criteria. J Clin Psychiatry. 2016;77(8):e968e974. doi:10.4088/JCP.15m10059

15. Yager J, Devlin M, Halmi K, et al. Guideline Watch Practice Guideline for the Treatment of Patients with Eating Disorders. 3. Arlington, VA: American Psychiatric Assoc; 2012:118.

16. National Institute for Health and Care Excellence [NICE]; 2013. Available from: http://www.nice.org.uk. Accessed January 12, 2021.

17. Brownley KA, Berkman ND, Peat CM, et al. Binge-eating disorder in adults: a systematic review and meta-analysis. Ann Intern Med. 2016;165(6):409420. doi:10.7326/M15-2455

18. Reas DL, Grilo CM. Review and meta-analysis of pharmacotherapy for binge-eating disorder. Obesity (Silver Spring). 2008;16(9):20242038. doi:10.1038/oby.2008.333

19. Kessler RM, Hutson PH, Herman BK, et al. The neurobiological basis of binge-eating disorder. Neurosci Biobehav Rev. 2016;63:223238. doi:10.1016/j.neubiorev.2016.01.013

20. Kuikka JT, Tammela L, Karhunen L, et al. Reduced serotonin transporter binding in binge eating women. Psychopharmacology (Berl). 2001;155(3):310314. doi:10.1007/s002130100716

21. Gibb A, Deeks ED. Vortioxetine: first global approval. Drugs. 2014;74(1):135145. doi:10.1007/s40265-013-0161-9

22. McElroy SL, Mori N, Guerdjikova AI, et al. Would glucagon-like peptide-1 receptor agonists have efficacy in binge eating disorder and bulimia nervosa? A review of the current literature. Med Hypotheses. 2018;111:9093. doi:10.1016/j.mehy.2017.12.029

23. Culbert KM, Racine S, Klump KL. Hormonal factors and disturbances in eating disorders. Curr Psychiatry Rep. 2016;18(7). doi:10.1007/s11920-016-0701-6

24. Leslie M, Leppanen J, Paloyelis Y, et al. The influence of oxytocin on eating behaviours and stress in women with bulimia nervosa and binge eating disorder. Mol Cell Endocrinol. 2019;497:110354. doi:10.1016/j.mce.2018.12.014

25. Guerdjikova AI, Mori N, Casuto LS, McElroy SL. Novel pharmacologic treatment in acute binge eating disorder - role of lisdexamfetamine. Neuropsychiatr Dis Treat. 2016;12:833841. doi:10.2147/NDT.S80881

26. Zhou FC, Lesch KP, Murphy DL. Serotonin uptake into dopamine neurons via dopamine transporters: a compensatory alternative. Brain Res. 2002;942:109119. doi:10.1016/S0006-8993(02)02709-9

27. Valbrun LP, Zvonarev V. The opioid system and food intake: use of opiate antagonists in treatment of binge eating disorder and abnormal eating behavior. J Clin Med Res. 2020;12(2):4163. doi:10.14740/jocmr4066

28. National Center for Biotechnology Information PubChem compound summary for CID 3117, disulfiram; 2020 Available from: https://pubchem.ncbi.nlm.nih.gov/compound/Disulfiram. Accessed January 12, 2021.

29. Koob GF, Volkow ND. Neurocircuitry of addiction. Neuropsychopharmacology. 2010;35:217238. doi:10.1038/npp.2009.110

30. Safer DL, Adler S, Dalai SS, et al. A randomized, placebo-controlled crossover trial of phentermine-topiramate ER in patients with binge-eating disorder and bulimia nervosa. Int J Eat Disord. 2020;53(2):266277. doi:10.1002/eat.23192

31. Appolinario JC, Nardi AE, McElroy SL. Investigational drugs for the treatment of binge eating disorder (BED): an update. Expert Opin Investig Drugs. 2019;28(12):10811094. doi:10.1080/13543784.2019.1692813

32. Citrome L, Goldman R, Tsai J, et al. Dasotraline for treatment of adults with binge-eating disorder: effect on binge-related obsessions and compulsions. CNS Spectr. 2020;25(2):307308.

33. Citrome L, Goldman R, Tsai J, et al. Effect of dasotraline on body weight in patients with binge-eating disorder. CNS Spectr. 2020;25(2):307.

34. Tsai J, Navia B, McElroy SL, et al. 170 efficacy and safety of dasotraline in adults with binge-eating disorder: a randomized, double-blind, fixed-dose trial. CNS Spectr. 2020;25(2):308309. doi:10.1017/S1092852920000863

35. Goodman DW. Lisdexamfetamine dimesylate (vyvanse), a prodrug stimulant for attention-deficit/hyperactivity disorder. P & T. 2010;35(5):273287.

36. McElroy SL, Hudson JI, Mitchell JE, et al. Efficacy and safety of lisdexamfetamine for treatment of adults with moderate to severe binge-eating disorder: a randomized clinical trial. JAMA Psychiatry. 2015;72(3):235246. doi:10.1001/jamapsychiatry.2014.2162

37. McElroy SL, Hudson J, Ferreira-Cornwell MC, et al. Lisdexamfetamine dimesylate for adults with moderate to severe binge eating disorder: results of two pivotal phase 3 randomized controlled trials. Neuropsychopharmacology. 2016;41(5):12511260. doi:10.1038/npp.2015.275

38. Hudson JI, McElroy SL, Ferreira-Cornwell MC, et al. Efficacy of lisdexamfetamine in adults with moderate to severe binge-eating disorder: a randomized clinical trial. JAMA Psychiatry. 2017;74(9):903910. doi:10.1001/jamapsychiatry.2017.1889

39. Gasior M, Hudson J, Quintero J, et al. A phase 3, multicenter, open-label, 12-month extension safety and tolerability trial of lisdexamfetamine dimesylate in adults with binge eating disorder. J Clin Psychopharmacol. 2017;37(3):315322. doi:10.1097/JCP.0000000000000702

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[Full text] Binge Eating Disorder: A 5-Year Retrospective Study on Experimental Dr | JEP - Dove Medical Press

Recommendation and review posted by Bethany Smith

Medical science has come a long way since the days of "bikini medicine," when the only time doctors managed a woman's health differently than a man's was when treating the parts of her body found under a bikini.

Over the past few decades, researchers have uncovered countless ways in which women's and men's bodies react differently to the same diseases. And just as it's now widely recognized women experience heart disease differently than men, scientists are beginning to understand why the sexes experience illness differently in another vital organ the brain.

It's not that male and female brains are built differently, said Lisa Mosconi, director of the Women's Brain Initiative at Weill Cornell Medicine in New York. It's that they age differently.

Women bear the brunt of Alzheimer's disease, the most common form of dementia, accounting for 2 of every 3 people diagnosed. Women are twice as likely as men to experience major depression. They are three times more likely to be diagnosed with autoimmune disorders that attack the brain, such as multiple sclerosis. They are four times more likely to have migraines and also are more likely to die from strokes.

What's driving these disparities? While multiple factors are at play, Mosconi said, it's hormones testosterone in men and estrogen in women that are the orchestral conductors of the brain. They are responsible for whether it performs well, or not.

"We are used to thinking of sex hormones as important for fertility and reproduction," Mosconi said. "But hormones also play crucial roles in brain health."

Estradiol, the type of estrogen produced by the ovaries during a woman's reproductive years, is the most important driver of brain health, said Dr. Kejal Kantarci, director of the Women's Health Research Center and a radiology professor at Mayo Clinic in Rochester, Minnesota. Her research suggests longer exposure to estradiol may offer some protection to the brain.

In a 2020 study published in Brain Communications, she showed women with longer reproductive periods measured from the time they start menstruation to the time they enter menopause were better protected against progressive forms of multiple sclerosis. The study also showed the more pregnancies a woman had, the less her disease progressed, suggesting that the flood of estrogen during pregnancy increased protection.

Losing estradiol, on the other hand, can harm the brain. The end of a woman's reproductive years and the accompanying drop in estradiol triggers numerous brain changes, some of which, researchers are learning, may not become evident until decades later.

For example, studies show Alzheimer's disease, typically diagnosed in a woman's 70s, likely begins to develop while she is still in her 50s. Mosconi's research found evidence that amyloid plaques, the proteins associated with the development of Alzheimer's disease, were already accumulating in the brains of women as they transitioned to menopause, though the women showed no evidence of cognitive decline at that age. She also found shrinkage in the memory centers of the women's brains.

"We never talk about Alzheimer's disease as something that happens in midlife," Mosconi said. "But for women, that's the timeline we need to think about."

There are other signs the brain is changing at midlife, when the loss of estradiol makes women more vulnerable to disease, Mosconi said. Studies have shown an increase in anxiety, depression, multiple sclerosis and other immune disorders during menopause. "For women with a predisposition to these conditions, this is when the condition seems to get activated."

Mosconi has used imaging to track brain energy levels, showing that, on average, it "declines by 20% or more during menopause." Men at the same age showed no changes, she said, which could be because they don't typically experience a hormone decline as rapidly or as early as women do.

But more estrogen isn't always better, Kantarci said. "You can't just say estrogens are good for you. It's not that simple."

A growing body of research suggests that it's not just about how much estrogen a woman's brain gets exposed to but when.

For example, a 2005 review published in The Lancet Neurology about clinical trials in postmenopausal women 65 or older showed women who received hormone therapy, including estrogen, had an increased risk for dementia and other types of cognitive decline. But a more recent study in 2019 in the journal Menopause found taking estrogen therapy earlier within the first five years of menopause might protect against cognitive decline. It also showed women exposed longer to natural estrogen because of more reproductive years had better cognitive function later in life.

Kantarci's work supports the idea that the transition to menopause offers a critical window for intervention. Her research found women given estradiol in a patch during their 50s showed less brain shrinkage in later years. "The front of the brain, which is used for decision-making and attention, was relatively preserved," she said. "It did not decline as much as it did in the placebo group."

In an ongoing study, she and her team will continue to explore whether hormone therapy given during the transition to menopause is associated with any long-term cognitive impacts.

But Kantarci cautioned against placing all the blame on hormones.

"Women are also the caregivers to dementia patients, and they are at higher risk for mental health issues that may also increase their risk of cognitive impairment," she said. "They live longer, and they are caregivers. And because they are caregivers, they are at higher risk. It's a circular problem."

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Hormones are key in brain health differences between men and women - The Philadelphia Tribune

Recommendation and review posted by Bethany Smith

Finding good health care can be challenging, but for certain communities, including queer and trans people, it can be nearly impossible. Stigma, lack of training and insensitivity are rampant for these groups of people, and with something as important as health care, the effects can be mentally and physically devastating.

A new startup, Folx Health, is working to change all that through a personalized approach that matches trans and queer people seeking care with providers and services who understand their unique needs. Folx just raised $25 million in series A venture funding and is accepting patients now.

When a patient contacts Folx, they begin by filling out a complete online medical history. If their need requires a consultation with a health provider, theyll be matched with someone for a virtual appointment by phone or video. Medication, labs and supplies are delivered to the patients door, according to the Folx Health website. One of the companys foundational principles is care on our terms, which means no judgement, gatekeeping or having to explain yourself.

One 2015 study conducted with more than 27,000 transgender people found that 19% reported being refused medical care, 28% harassed by providers and 50% had to educate health care providers on transgender care. Twenty-eight percent of respondents also told researchers that they avoid going to the doctor altogether because of such treatment.

Folx founder and CEO A.G. Breitenstein told Fast Company that theyre on the verge of becoming a one-stop resource for members of the queer and trans community from information you might find in subreddit threads to clinical information from sources like the Mayo Clinic.

Were about to launch what we call The Library, which is a set of resources, Breitenstein said. Well have a balance between really well clinically vetted information, but presented in a way thats accessible and usable for folks.

Current topics in The Library include sexual health, hormone treatment and company news. There are tips like how to overcome needle fears for self-injection, and explainers on hormone lab results.

In the future Folx is also preparing to expand services to include treatments for sexually transmitted infections, erectile dysfunction and lab samples taken at home.

Right now, users must pay a $59 monthly fee for access to the service, in addition to any treatment costs. Breitenstein said that theyre working to integrate with insurance companies so patients can take advantage of their health care plans. Folx is also working on creating a grant program for people who cant afford the monthly subscription cost, according to Axios.

Folx service is currently available in 12 states, including New York, California and Florida. The company plans to expand nationwide by the end of 2021.

Excerpt from:
Folx Makes Health Care More Accessible for the Trans Community - The Mighty

Recommendation and review posted by Bethany Smith

Are there updated data for LIBTAYO in advanced CSCC? What do they show?

Longer-term data from EMPOWER-CSCC-1 were presented at the 2020 American Society of Clinical Oncology (ASCO) virtual meeting. These results showed an ORR of 46% (95% CI: 39%-53%) following treatment with LIBTAYO, with a median time to response of 2 months (interquartile range: 2-4 months) across the three treatment groups, which were metastatic CSCC and locally advanced CSCC dosed at 3mg/kg every 2 weeks and metastatic CSCC dosed at 350mg every 3 weeks. The median time to CR was 11 months (interquartile range: 7.4-14.8months) among those who achieved a CR in any group. The median DoR hadyet to be reached for any treatment group (range for groups combined: 1.9-34.3 months).4,10

Updated response rates arein the table below.4,10

Safety was generally consistent with previous data. The most common adverse reactions reported were fatigue (35%), diarrhea (28%) and nausea (24%). The most common Grade 3 or higher adverse reactions were pneumonitis (3%), autoimmune hepatitis (2%), anemia, colitis and diarrhea (each 1%).

Warnings and Precautions

Severe and Fatal Immune-Mediated Adverse Reactions

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue at any time after starting treatment. While immune-mediated adverse reactions usually occur during treatment, they can also occur after discontinuation. Immune-mediated adverse reactions affecting more than one body system can occur simultaneously. Early identification and management are essential to ensuring safe use of PD-1/PD-L1 blocking antibodies. The definition of immune-mediated adverse reactions included the required use of systemic corticosteroids or other immunosuppressants and the absence of a clear alternate etiology. Monitor closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

No dose reduction for LIBTAYO is recommended. In general, withhold LIBTAYO for severe (Grade 3) immune-mediated adverse reactions. Permanently discontinue LIBTAYO for life-threatening (Grade 4) immune-mediated adverse reactions, recurrent severe (Grade 3) immune-mediated adverse reactions that require systemic immunosuppressive treatment, or an inability to reduce corticosteroid dose to 10 mg or less of prednisone equivalent per day within 12 weeks of initiating steroids.

Withhold or permanently discontinue LIBTAYO depending on severity. In general, if LIBTAYO requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids.

Immune-mediated pneumonitis:LIBTAYO can cause immune-mediated pneumonitis. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation. Immune-mediated pneumonitis occurred in 3.7% (22/591) of patients receiving LIBTAYO, including fatal (0.3%), Grade 4 (0.3%), Grade 3 (1.0%), and Grade 2 (1.9%). Pneumonitis led to permanent discontinuation in 1.9% of patients and withholding of LIBTAYO in 1.9% of patients. Systemic corticosteroids were required in all patients with pneumonitis. Pneumonitis resolved in 59% of the 22 patients. Of the 11 patients in whom LIBTAYO was withheld, 7 reinitiated after symptom improvement; of these 1/7 (14%) had recurrence of pneumonitis. Withhold LIBTAYO for Grade 2, and permanently discontinue for Grade 3 or 4. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids.

Immune-mediated colitis: LIBTAYO can cause immune-mediated colitis. The primary component of immune-mediated colitis was diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1 blocking antibodies. In cases of corticosteroid-refractory immune-mediated colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 1.2% (7/591) of patients receiving LIBTAYO, including Grade 3 (0.3%) and Grade 2 (0.7%). Colitis led to permanent discontinuation in 0.2% of patients and withholding of LIBTAYO in 0.7% of patients. Systemic corticosteroids were required in all patients with colitis. Colitis resolved in 71% of the 7 patients. Of the 4 patients in whom LIBTAYO was withheld, none reinitiated LIBTAYO. Withhold LIBTAYO for Grade 2 or 3, and permanently discontinue for Grade 4. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids.

Immune-mediated hepatitis:LIBTAYO can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 1.9% (11/591) of patients receiving LIBTAYO, including fatal (0.2%), Grade 4 (0.2%), and Grade 3 (1.5%). Hepatitis led to permanent discontinuation of LIBTAYO in 0.8% of patients and withholding of LIBTAYO in 0.8% of patients. Systemic corticosteroids were required in all patients with hepatitis. Additional immunosuppression with mycophenolate was required in 9% (1/11) of these patients. Hepatitis resolved in 64% of the 11 patients. Of the 5 patients in whom LIBTAYO was withheld, none reinitiated LIBTAYO.

For hepatitis with no tumor involvement of the liver: Withhold LIBTAYO if AST or ALT increases to more than 3 and up to 8 times the upper limit of normal (ULN) or if total bilirubin increases to more than 1.5 and up to 3 times the ULN. Permanently discontinue LIBTAYO if AST or ALT increases to more than 8 times the ULN or total bilirubin increases to more than 3 times the ULN.

For hepatitis with tumor involvement of the liver: Withhold LIBTAYO if baseline AST or ALT is more than 1 and up to 3 times ULN and increases to more than 5 and up to 10 times ULN. Also, withhold LIBTAYO if baseline AST or ALT is more than 3 and up to 5 times ULN and increases to more than 8 and up to 10 times ULN. Permanently discontinue LIBTAYO if AST or ALT increases to more than 10 times ULN or if total bilirubin increases to more than 3 times ULN. If AST and ALT are less than or equal to ULN at baseline, withhold or permanently discontinue LIBTAYO based on recommendations for hepatitis with no liver involvement.

Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids.

Immune-mediated endocrinopathies: For Grade 3 or 4 endocrinopathies, withhold until clinically stable or permanently discontinue depending on severity.

Immune-mediated nephritis with renal dysfunction: LIBTAYO can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.5% (3/591) of patients receiving LIBTAYO, including Grade 3 (0.3%) and Grade 2 (0.2%). Nephritis led to permanent discontinuation in 0.2% of patients and withholding of LIBTAYO in 0.3% of patients. Systemic corticosteroids were required in all patients with nephritis. Nephritis resolved in all 3 patients. Of the 2 patients in whom LIBTAYO was withheld, none reinitiated LIBTAYO. Withhold LIBTAYO for Grade 2 or 3 increased blood creatinine, and permanently discontinue for Grade 4 increased blood creatinine. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids.

Immune-mediated dermatologic adverse reactions: LIBTAYO can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), toxic epidermal necrolysis (TEN), and Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) has occurred with PD-1/PD-L1 blocking antibodies. Immune-mediated dermatologic adverse reactions occurred in 2.0% (12/591) of patients receiving LIBTAYO, including Grade 3 (1.0%) and Grade 2 (0.8%). Immune-mediated dermatologic adverse reactions led to permanent discontinuation in 0.3% of patients and withholding of LIBTAYO in 1.4% of patients. Systemic corticosteroids were required in all patients with immune-mediated dermatologic adverse reactions. Immune-mediated dermatologic adverse reactions resolved in 42% of the 12 patients. Of the 8 patients in whom LIBTAYO was withheld for dermatologic adverse reaction, 5 reinitiated LIBTAYO after symptom improvement; of these 60% (3/5) had recurrence of the dermatologic adverse reaction. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold LIBTAYO for suspected SJS, TEN, or DRESS. Permanently discontinue LIBTAYO for confirmed SJS, TEN, or DRESS. Resume in patients with complete or partial resolution (Grade 0 to 1) after corticosteroid taper. Permanently discontinue if no complete or partial resolution within 12 weeks of initiating steroids or inability to reduce prednisone to less than 10 mg per day (or equivalent) within 12 weeks of initiating steroids.

Other immune-mediated adverse reactions: The following clinically significant immune-mediated adverse reactions occurred at an incidence of <1% in 591 patients who received LIBTAYO or were reported with the use of other PD-1/PD-L1 blocking antibodies. Severe or fatal cases have been reported for some of these adverse reactions.

Infusion-related reactions

Severe infusion-related reactions (Grade 3) occurred in 0.2% of patients receiving LIBTAYO. Monitor patients for signs and symptoms of infusion-related reactions. Interrupt or slow the rate of infusion for Grade 1 or 2, and permanently discontinue for Grade 3 or 4.

Complications of Allogeneic HSCT

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host-disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT. Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-fetal toxicity

LIBTAYO can cause fetal harm when administered to a pregnant woman due to an increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Advise women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with LIBTAYO and for at least 4 months after the last dose.

Adverse reactions

Use in specific populations

Please click here for full Prescribing Information.

INDICATIONAND USAGE

LIBTAYO is indicated for the treatment of patients with metastatic cutaneous squamous cell carcinoma (mCSCC) or locally advanced CSCC (laCSCC) who are not candidates for curative surgery or curative radiation.

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References:

1. LIBTAYO (cemiplimab-rwlc) injection full U.S. prescribing information. Regeneron Pharmaceuticals, Inc., and sanofi-aventis U.S. LLC. Available at: https://www.regeneron.com/sites/default/files/Libtayo_FPI.pdf

2. Mansouri B, Housewright C. The treatment of actinic keratosesthe rule rather than the exception. J Am Acad Dermatol 2017; 153(11):1200. doi:10.1001/jamadermatol.2017.3395.

3.Schmults CD, et al. High-Risk Cutaneous Squamous Cell Carcinoma A Practical Guide for Patient Management. Springer. ISBN 978-3-662-47081-7 (eBook).DOI 10.1007/978-3-662-47081-7.

4. Data on File. Regeneron Pharmaceuticals Inc. 2020.

5. Data on File. Regeneron Pharmaceuticals Inc. 2018.

6. Migden M, Rischin D, Schmults C, Guminski A, Hauschild A, Lewis K et al. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. New England Journal of Medicine. 2018;379(4):341-351.

7. NCCNClinical Practice Guidelines in Oncology (NCCN Guidelines) forSquamous Cell Skin Cancer V.2.2020. National Comprehensive CancerNetwork, Inc. 2020.

8. Califano JA, Lydiatt WM, Nehal KS, et al. Cutaneous squamous cell carcinoma of the head and neck. In: Amin MB, Edge SB, Greene FL, et al, eds. AJCC Cancer Staging Manual. 8th ed. Springer; 2017:171-181.

9. Jennings L, Schmults CD. Management of high-risk cutaneous squamous cell carcinoma. J Clin Aesthet Dermatol. 2010;3(4):39-48.

10. RischinD, Khushalani NI, Schmults CD, et al. Phase 2 study of cemiplimab in patients with advanced cutaneous squamous cell carcinoma (CSCC): longer follow-up. Poster presented at: American Society of Clinical Oncology (ASCO) 2020 Virtual Scientific Program; May 29-31, 2020.

LIB.20.04.0063 1/21

Read the original here:
Transforming Outcomes in Advanced CSCC with Immunotherapy - LWW Journals

Recommendation and review posted by Bethany Smith

The Youth Fountain, a health and wellness clinic in New Jersey, is offering holistic weight loss treatments for patients. The clinic is spearheaded by Dr. Rada and Dr. Emil Shakov.

According to the CDC, the prevalence of obesity was 42.4% in 2017-2018, up from 30% in 1999-2000. Obesity brings along with it health conditions that can lead to premature death. These health conditions are diabetes, heart disease, stroke, and some types of cancer. In the United States alone, obesity is a contributor to anywhere from 100,000 to 400,000 deaths every year. The medical cost for people with obesity was on an average $1429 higher than one without. Apart from dangers to physical health, the stigma and ridicule associated with obesity are also known to cause psychological distress leading to poor quality of life.

Though obesity has a negative impact on ones health it is also completely preventable through lifestyle changes that include changes in diet. The Youth Fountain believes in holistic treatment that looks at not just short term weight loss goals but prepares the patient for lifelong wellness as well. The doctors first take the time to understand a patients health goals. They then quiz them about their lifestyle, trying to arrive at a treatment that will suit them the best. This attention to detail is provided to every patient. Dr. Emil and Rada understand that every patient is unique and no size fits all. The doctors then craft a treatment regiment that incorporates all the tools at their disposal. The doctors can also set up follow up appointments to monitor a patients progress throughout the treatment.

When asked about the clinics philosophy, Dr. Emil says, When clients come to us, they are doing so because they are looking for a change in their lives. We do our best to live up to the trust that they put in us. We listen and understand the clients problems. We come up with solutions that best suit them on a case by case basis. The goal is to not just hit your target weight but to give you the tools to stay there for the rest of your life. Follow us on our Facebook page to stay up to date with our services.

The Youth Fountain offers skincare treatments such as tattoo removal, IPL, laser genesis, Picogenesis, chemical peel, Dermapen, vein treatments, hair removal, and SecretRF. The clinic also offers injectable treatments such as fillers, BOTOX, Dysport, PRP, and Jeuveau. The clinics wellness treatments include IV Infusions, weight loss, anti-aging, hormone replacement, and peptides. They provide hair restoration treatments such as medical treatment, laser cap, mesotherapy, PRP, and surgery. They also provide body sculpting treatments such as EmSculpt, Coolsculpting, truSculpt iD, mesotherapy, and Laser Liposculpting.

Dr. Emil Shakov is a board-certified surgeon at The Youth Fountain with extensive experience and training in advanced surgical techniques, advanced aesthetics, anti-aging, weight-loss, and hair transplantation. Fellowship trained in Advanced GI, Bariatrics, and Minimally Invasive Surgery (MIS), he continued to further his training and education at The American Academy of Procedural Medicine and The American Academy of Aesthetic Medicine where he mastered aesthetic procedures, anti-aging, and medical weight-loss. Dr. Shakov brings his unique skill set to The Youth Fountain to provide a pleasant experience with the confidence you can trust.

Dr. Rada Shakov is a board-certified gastroenterologist at The Youth Fountain who specializes in all aspects of aesthetic medicine. She has extensive training in a variety of procedures and is always continuing her education to stay on the cutting edge of the newest and best practices. In practice since 2010, Dr. Shakov believes in seeing the patient as more than just their problem areas; taking an emphatic and whole-body approach.

A review of the clinics service by Rachel K. says, Dr. Rada Shakov and Dr. Emil Shakov are the finest doctors around. They are not only knowledgeable in their field but are also incredibly kind, helpful, and care tremendously about their patients. So happy with my outcome and I would highly recommend them and their wonderful office staff to anyone. I'm so glad I found them! More reviews can be viewed on the clinics GMB listing.

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For more information about The Youth Fountain, contact the company here:

The Youth FountainDr. Shakov+1 732-333-5992info@theyouthfountain.com501 Iron Bridge Rd Suite 9, Freehold,NJ 07728, United States

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New Jersey Health And Wellness Clinic The Youth Fountain Is Offering Holistic Weight Loss Treatments - Press Release - Digital Journal

Recommendation and review posted by Bethany Smith

President Joe Biden is already proving to be a better friend to the LGBTQ community than his predecessor. During his first week in office, Biden issuedan executive orderextending federal LGBTQ protections, reversedTrumps trans military ban, and includedgender-neutral pronouns and honorificson the White Houses contact page.

With these victories came the inevitable backlash. Abigail Shrier, author of the controversial bookIrreversible Damage: The Transgender Craze Seducing Our Daughters,denounced Bidens executive order on Twitter, claiming that it unilaterally eviscerates womens sports. Other self-described gender critical (i.e., anti-trans) feminists agreed, creating the hashtag#BidenErasesWomento voice their opposition. Meanwhile, at least 14 states have introduced aslew ofanti-trans bills. Contrary to what lawmakers and gender critical feminists say, its not about protecting women and children. Its an organized effort to legislate trans bodies based on misinformation, ignorance, and bigotry.

Earlier this year, Montana lawmakers introducedHB 113, which wouldvebarred health care professionals from providing gender-affirming services to trans adolescents such as puberty blockers and hormones. The bill died on its third reading in anarrow 51-49 voteon January 26 after five Republicans who initially supported HB 113 changed theirminds. Similar bills inUtah,Alabama,Missouri,Texas,Mississippi,Indiana, andNew Hampshireare still on the table.

The argument supporting these bills is the same that Shrier makes in her book, which is that providing puberty blockers and hormones to minors can cause a lifetime of damage. The facts are more nuanced. According to the MayoClinic, puberty blockers dontchange an adolescents body permanently. Instead, theMayo Clinics websiteexplains, it pauses puberty, providing time to determine if a child's gender identity is long lasting. If a child decides not to continue medical transitioning, normal development will resume once the child stops taking puberty blockers.

Atalking point among anti-trans activists is that 70 to 80 percent of adolescents diagnosed with gender dysphoria eventually grow out of it, or desist. The exact numbers are hard to pin down. A2008 studyfound that 61 percent of children with gender dysphoria desisted by the age of 29, while a2019 studyfound that about 10percent desisted within 18months of seeking treatment. The 80 percent number comes from a2013 study whichinitially reported that out of 127 Dutch children who sought gender-affirming health care at a clinic, 47 of them still went to the clinic as adolescents, while 80 of them stopped. It was initially reported that the 80 desisted, but asJame M. CantorandJesse Singalrespectively point out, only 56 of the 80 said they desisted, while the rest didntrespond to the researchers questionnaires. The actual study says 54 percent desisted, not 80.

Cantor and Singalwhovebeenheavily criticizedfor theirviews on trans issuesconclude that most children who initially report having gender dysphoria eventually grow out of it. Even if this is true, making gender-affirmingcare for children illegal isntthe solution. A study published inPediatricslast year shows that having access to puberty blockers in adolescence reduces the risk of suicidal thoughts in transgender adults. Is it worth risking the lives of trans kids who legitimately need puberty blockers and hormones because a few might later change their minds?

While Montanas HB 113 has been defeated,HB112remains. Known as the Save Womens Sports Act, the bill seeks to ban young trans girls from competing in girls sports. This is the latest example of an ongoing debate; the main argument against including trans women in sports is that since trans women naturally produced testosterone for a significant period before undergoing hormone replacement therapy (HRT), they have an unfair physical advantage over cis women. Once again, the truth is more complex.

Medicalphysicist Joanna Harper, whosalso an athlete and a trans woman, publisheda study in 2015that looked at run times for eight trans distance runners over a seven-year period, and found littledifference from cis runners times. Likewise, a2017 literature reviewfound no direct or consistent research that proves trans women have an unfair physical advantage. However,a 2019 studyshows only modest changes in muscle mass in trans women after a year on estrogen, as did amore recent studythat looked at the athletic abilities of trans women serving in the Air Force.

It's still no excuse to outright ban trans women from sports because rules can be adjusted. Dr. Timothy Roberts, who led the most recent study, toldNBC Newshe suggests making it so trans women athletes have to be on HRT for at least two years instead of the International Olympic Committees current one-year rule.Even then, Robertspointedout that many cis female athletes have physical advantages over others. We have a lot of elite female athletes who tend to be tall and thin with slender hips, he said, and we're not outlawing them.

HB 112 and HB 113 are just the latest attempts to banish trans women from public life. Like bathroom bills, these new bills perpetuate the ideathat the trans rights movement seeks to harm women andchildren. No evidence supports this; trans people, for the most part, just want to live their lives in peace with full bodily autonomy like everyone else.

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Lost in Translation - Splice Today

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National Review

President Joe Bidens recent executive order to expand food assistance to U.S. households, while well-intentioned, represents a substantial overreach of the executive branch and a blatant attempt to override the intent of Congress. If successful, this dangerous precedent would open the door to major expansions of the social safety net without congressional approval. Congress must resist the presidents attempts to subvert the intent of existing law. Less than one week into the Biden presidency, the new administration issued a series of executive orders focused on COVID-19 economic relief. One such order seeks to expand food assistance through the Supplemental Nutrition Assistance Program (SNAP), or food stamps. In it, President Biden instructed the Department of Agriculture (USDA) to take immediate steps to make it easier for the hardest-hit families to enroll and claim more generous benefits in the critical food and nutrition assistance area. In reality, the executive order asks a federal agency the USDA to intentionally misinterpret the Families First Act and subvert the constitutional authority of Congress over the legislative process. The Families First Act, which passed in March 2020, clearly outlined that states could request waivers from the Agriculture Department to provide emergency allotments to SNAP households not greater than the applicable maximum monthly allotment for the household size. In normal times, 60 percent of households enrolled in SNAP do not receive the maximum benefit because they have income from other sources such as earnings that they can use for purchasing food. The emergency allotments recognized that millions of people lost jobs or faced other employment disruptions when the pandemic hit, and that those enrolled in SNAP were at particular risk for job loss in the early aftermath of the pandemic. Rather than requiring SNAP households to report a job or income change to their state agency and wait for bureaucrats to recalculate their benefits, the emergency allotments gave every SNAP recipient the maximum allowed. This was, admittedly, not a very targeted effort. Some families received a boost in SNAP dollars without a change in household income or financial circumstances. But the immediacy of the economic shock brought on by the pandemic, and the employment instability that persists today, necessitated an equally expedient policy response. The Agriculture Department, under President Trump, had approved emergency allotment plans for all 50 states, the District of Columbia, Guam, and the U.S. Virgin Islands but only in accordance with the law. The department extended these emergency-allotment waivers numerous times, most recently extending them through January 2021. The USDA and Congress itself also offered states flexibility in the aftermath of the pandemic. According to federal government spending data, all of the efforts outlined above have caused SNAP benefits to rise more than 40 percent in the last fiscal year, with more than $31 billion in added spending compared to FY 2019. Class-action suits have been filed in Pennsylvania and California by people who disagree with the USDAs interpretation of the law: that regular SNAP plus emergency allotments cannot extend benefits beyond the maximum benefit level. Lawyers for the lawsuits argue that the law allows the USDA to approve emergency allotments in the amount of the maximum benefit, which if true, would mean that households could receive the maximum SNAP benefit plus the maximum emergency allotment essentially doubling benefit amounts. A federal judge in California agreed with the USDA, while the Pennsylvania case is ongoing. The Biden administrations executive order is encouraging its USDA to misinterpret the 2020 law in a similar way. The legislative text is not ambiguous. It is hard to imagine Congress being any clearer than, to address temporary food needs not greater than the applicable maximum monthly allotment for the household size. If Congress had wanted to give people more than the SNAP maximum, it would have done so. In fact, Congress eventually did just that expanding benefits by 15 percent in the COVID-19 relief package passed last month. If the Biden administration is successful in this attempt, it will open the door to a number of executive actions aimed at expanding the safety net without congressional action. If political appointees in the Biden administration feel unconstrained by the law, we will see larger benefits directed to an increasing number of people. Such action not only undermines the integrity of the social safety net by going around Congress, it disregards the separation of powers ensconced in the founding documents of our republic. The American public has been largely supportive of efforts by Congress to provide economic relief to struggling households. Lets keep that authority in its proper place.

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The GOP's future is in flux as the party divides over support for Representatives Marjorie Taylor Greene and Liz Cheney - Yahoo News

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Introduction

The onset of lactation results in a sudden and considerable demand for calcium, imposing arduous physiologic challenges to calcium homeostasis in dairy cows.1 Cows that are unable to adapt to this change in calcium demand develop hypocalcemia. Cows with hypocalcemia (colloquially referred to as milk fever) present with weakness, depression, inappetence, and an inability to rise.1 Cows with clinical hypocalcemia are more likely to develop secondary mastitis, as well as muscle and nerve damage from prolonged periods of recumbency.2 As the condition name would suggest, subclinical hypocalcemia shows no overt clinical signs in affected animals, despite low blood calcium; however, there are other negative health consequences. Hypocalcemia reduces the ability of immune cells to respond to stimuli, thus contributing to infections, such as mastitis or metritis.3,4 Hypocalcemia also reduces smooth muscle contraction,5 which can result in reduced rumen and abomasal motility, leading to reduced feed intake and subsequent transition disorders (displaced abomasum, mastitis, metritis, retained fetal membranes, ketosis, etc).6 Subclinical hypocalcemia has also been shown to negatively affect early lactation milk production and reproduction.7 An increased culling rate was also observed for animals with subclinical hypocalcemia.8 Clinical hypocalcemia may occur in up to 510% of dairy cows, whereas its subclinical form is more prevalent, with estimates ranging up to 50% of mature fresh cows.9 Some authors have estimated the overall economic cost of subclinical hypocalcemia to be 4 times that of clinical cases, resulting in a substantial impact on the profitability of dairy operations.10

Several strategies have been studied to enhance the ability of periparturient dairy cows to maintain calcium homeostasis. These practices include limiting total calcium intake prepartum (which may be difficult to achieve), adding a calcium chelator to the prepartum transition ration, and modifying the dietary cation-anion difference (DCAD) by feeding anionic salts prepartum, which has become the mainstay in many herds. Oral supplementation of calcium at calving has proven effective in reducing clinical milk fever.11 Research has shown that, even in very well-managed herds with a low incidence of clinical hypocalcemia, oral calcium supplementation may have health, reproductive, and increased production benefitsmost notably in lame and high producing cows.1214

There are several commercial boluses with substantial differences in composition, primarily with calcium chloride, calcium sulfate, and calcium carbonate. The dissolution properties of the commercial boluses will affect the delivery of product to the animal. Moreover, not all calcium salts are absorbed by the animal in the same manner. Calcium chloride and calcium sulfate are absorbed through the rumen wall by passive transport, whereas calcium carbonate is absorbed in the small intestine by vitamin D-dependant active transport.15 In addition, the acidogenic properties of calcium chloride and calcium sulfate stimulate parathyroid hormone (PTH) function, thereby increasing calcium resorption from bone, kidney tubular reabsorption of calcium, as well as absorption of calcium in the intestine.16

In order to evaluate differences in bolus composition with respect to calcium delivery, this study measured the dissolution times of three different boluses in fistulated animals and the in vivo uptake of two calcium sources utilizing two administration protocols.

The dissolution rate was evaluated for three commercially available boluses, each with different calcium chloride and calcium carbonate compositions: Bolus 1 (high calcium chloride, no calcium carbonate bolus): 209-g Bolus supplying 43 g of calcium from 112 g of calcium chloride dihydrate and 53.6 g of calcium sulfate (Cal-Boost Bolus, Solvet Animal Health, Calgary, Alberta, Canada); Bolus 2 (intermediate calcium chloride, intermediate calcium carbonate bolus): 176-g Bolus supplying 39.0 g of calcium from 106.9 g of calcium chloride, 4.5 g of calcium propionate, and 22.3 g of calcium carbonate (Transition Bolus, Vetoquinol N.-A Inc, Lavaltrie, Quebec, Canada); and Bolus 3 (low calcium chloride, high calcium carbonate bolus): 206-g Bolus supplying 54 g of calcium from 92.2 g of calcium chloride and 72.8 g of calcium carbonate (RumiLife CAL24 Bolus, Genex Cooperative Inc, Shawano, Wisconsin, USA). Table 1 shows the composition of these boluses. The research facility provided two fistulated steers, approximately 28 months of age and weighing 450 kg, 1-year post-cannulation. The steers were housed in an open-air feedlot pen approximately 18 meters deep and 36 meters wide and fed a total mixed ration (TMR) including barley silage, minerals, and vitamins from a feed mixer truck once daily (late afternoon) in a cement feed bunk upon the completion of the bolus study each day. Well water was supplied ad libitum from an automatic cattle waterer. A bolus was placed in a pre-weighed coarse mesh net with a recovery cord. The net and bolus were then placed in the rumen through a fistula. A pretreatment pH was determined using pH strips (pH Test Strips, EMD Millipore) and a pH meter (LRCpH logger, DASCOR Inc., Oceanside, California, USA). After 30, 60, 90, 120, 180, and 240 minutes, the bolus was recovered, weighed, described, and photographed. The recovered bolus was then returned to the rumen. The rumen pH was determined at each sampling time using pH strips, in order to ensure that the boluses were not causing acidosis. If the entire bolus was dissolved at the time of sample collection, sampling was terminated. Each animal only received one bolus at a time, with a minimum of one full day between tests. Each bolus type was tested a total of three times, meaning that it was tested twice in one animal and once in the other; the decision of which animal received which bolus type twice was made at random.

Table 1 Composition of the Commercially Available Boluses Used in This Study

A 380-cow Holstein dairy herd in the province of Quebec, Canada was selected. The study was conducted from November 2019 to March 2020. Cattle were housed in two tie-stall barns for the duration of their lactation, with a third tie stall barn dedicated to the dry and transition cows. Dry cows were moved to this third barn and were fed a dry cow ration. One month prior to their expected calving date, cows were transitioned to a prepartum ration consisting of 20 kg of grass silage, 5 kg of dry hay, 0.85 kg of soybean meal 48% and a 200-g mineral pack. The mineral concentration of this total ration was as follows: calcium 0.52% dry mass (DM.), phosphorus 0.33% DM, magnesium 0.38% DM, and potassium 2.4% DM. In mid-December, the potassium in the close-up ration was lowered. The new ration consisted of 7.85 kg of grass silage, 8 kg of corn silage, 3 kg of dry hay, and 4 kg of a supplement created for this farm. The modified mineral concentrations were calcium 0.56% DM, phosphorus 0.31% DM, magnesium 0.50% DM, and potassium 1.41% DM. The pre-partum ration was not prepared as a Total Mixed Ration (TMR) and therefore implementing a Dietary Cation-Anion Difference (DCAD) strategy was not deemed a practical option. Each cow was transferred to one of the milking barns the morning following calving.

Only cows in their second and third lactations were enrolled in this study. Because of the high level of potassium in both rations, all older cows (>third lactation) received intravenous calcium at calving to prevent clinical milk fever, sometimes followed by oral calcium supplementation, and were therefore not included in this study. Twenty-seven healthy second- and third-lactation cows with body condition score (BCS) of 2.753.5 and an estimated average weight of 767 kg (second lactation) or 787 kg (third lactation) were randomly allocated to one of three oral calcium treatment protocols (9 cows per group irrespective of parity). Treatment 1 received two high calcium chloride boluses (Cal-Boost Bolus, Solvet Animal Health, Calgary Alberta, Canada) at time 0; Treatment 2 received one high calcium chloride Cal-Boost Bolus (Solvet Animal Health, Calgary Alberta, Canada) at time 0 with a second bolus 12 hours later; and Treatment 3 received two high calcium carbonate boluses (RumiLife CAL24 Bolus, Genex Cooperative Inc, Shawano, Wisconsin, USA) at time 0. Treatments were initiated within 12 hours following calving and this was considered Time 0 (t=0). The intermediate calcium chloride/calcium carbonate bolus was excluded from this study as we were most interested in the two extremes (high calcium chloride vs high calcium carbonate). Cows calving between 5:00 p.m. and 5:00 a.m. commenced the protocol at 5:00 am. Cows calving between 5:00 a.m. and 5:00 p.m. started their protocol at 5:00 p.m. Blood was taken in a 10-mL red-topped vacutainer vial from the coccygeal vein pretreatment at time 0, and at 1, 6, 12, 13, and 24 hours post-treatment. The blood was immediately centrifuged on the farm (3000 rpm, 10 minutes) and the serum was transferred into a 3-mL red-topped vacutainer tube for storage at 18C. Total calcium was analyzed by an in-clinic Idexx Catalyst One Chemistry Analyzer. One cow in the Treatment 2 group developed clinical milk fever within 12 hours after receiving the initial bolus and was removed from the study because it did not receive the second bolus. Another cow in Treatment 3 also developed clinical milk fever; however, this was the day after the 24-hour study period and she was therefore included in the trial.

Even though allocation to treatment groups was randomized, there was an age discrepancy between groups. There were more older cows in Treatment 1, which explains the lower Time 0 serum calcium levels (Table 2). Upon analyzing the raw data from the first 27 animals, cows with more severe hypocalcemia had a greater response to oral calcium supplementation than cows with moderate hypocalcemia. With this new information, it was decided to end the original trial and to evaluate serum response to calcium supplementation depending on whether the cow had moderate (1.8 mmol/L) or severe (<1.8 mmol/L) hypocalcemia. The new trial consisted of second and third lactation cows assigned to Treatment 1. The additional enrollment resulted in 11 animals in the moderate and 10 in the severe hypocalcemia groups as depicted in Table 3.

Table 2 Initial Serum Calcium Concentration by Treatment Group

Table 3 Initial Serum Calcium Concentration in Animals with Severe vs Moderate Hypocalcemia

Statistical significance was determined based on a mixed model with repeated measures. Multiple comparisons (treatment effects at each time point) were analyzed using Tukeys multiple comparisons test or Sidaks multiple comparisons test. Data were assessed for normality using a ShapiroWilk test. The cut-off for significance was P < 0.05. The experimental unit was defined as each individual animal. Statistical analyses were carried out in Prism v 8.4.3 (GraphPad Software, San Diego, California, USA).

The dissolution rate of Bolus 1 (high calcium chloride, no calcium carbonate bolus) was the most rapid of the three calcium boluses tested, with the entire bolus being dissolved before 90 minutes in all three trials (Figure 1 and Table 4). Bolus 2 (intermediate calcium chloride, intermediate calcium carbonate bolus) was slower to dissolve, with complete dissolution by 240 minutes in two trials and 180 minutes in the third (Figure 1 and Table 4). Bolus 3 (low calcium chloride, high calcium carbonate bolus) was very slow to dissolve where, after 240 minutes, 75% of the original bolus weight was still present (Figure 1 and Table 4). No major fluctuations in rumen pH were observed over the time course for any of the tested boluses (Table 4).

Table 4 Wet Weights and Rumen pH of Various Calcium Boluses After Incubation in the Rumen of Fistulated Cattle

Figure 1 Dissolution of various calcium boluses in the rumen of fistulated cattle. Representative images of each bolus type are shown for each time point. Note that Bolus 1 had to be photographed in the recovery net at 30, 60, and 90 minutes due to its compromised structural integrity.

Treatment 2 (the single-dose regimen of high calcium chloride) yielded significantly higher serum calcium levels than Treatment 3 (the double dose of calcium carbonate bolus) at 1 hour, with similar calcium levels over the remainder of the time course (Figure 2). Treatment 1 (the double dose of the High Calcium Chloride bolus) yielded significantly higher serum calcium levels at 1 and 6 hours relative to Treatment 3, with similar levels over the remainder of the time course. Importantly, Treatment 1 yielded significantly higher serum calcium levels over the first 13 hours than Treatment 2 (Figure 2), indicating that two calcium chloride boluses at time 0 lead to a greater increase in serum calcium than the traditional regimen of giving one bolus each at t=0 and t=12 hours.

Figure 2 Changes in serum calcium upon treatment with commercial boluses. Treatments were initiated within 12 hours following calving (not before) and this time is considered Time 0 (t=0). Treatment 1 = two high calcium chloride boluses at Time 0; Treatment 2 = one high calcium chloride bolus at t=0 and another at t=12 hours; Treatment 3 = two high calcium carbonate boluses at t=0. Data represent the mean SEM (standard error of the mean) for 9 independent animals per treatment group. *P<0.05; **P<0.01; ***P<0.001, ****P<0.0001. Blue, orange, and red asterisks denote statistically significant differences between Treatment 1 vs 3, 2 vs 3, and 1 vs 2, respectively.

The severe hypocalcemia cattle had a greater and more persistent response to calcium supplementation than cows suffering from moderate hypocalcemia, with statistically significantly higher serum calcium levels at 6, 12, and 13 hours (Figure 3). The moderately hypocalcemic cows receiving Treatment 1 returned to their baseline value after 24 hours, while severely hypocalcemic cows receiving treatment 1 remained well above their baseline value even after 24 hours (Figure 3). These data suggest that two high calcium chloride boluses administered rapidly after calving are more effective at raising serum calcium compared to the traditional treatment of one bolus followed by a second bolus twelve hours later.

Figure 3 Changes in serum calcium upon treatment with two high calcium chloride boluses (Treatment 1) in animals with moderate hypocalcemia (>1.8 mmol/L) versus severe hypocalcemia (<1.8 mmol/L). Treatments were initiated within 12 hours following calving (not before) and this time is considered Time 0 (t=0). Data represent the mean SEM for 10 (severe hypocalcemic cows, treated with 2 high calcium chloride at t=0) or 11 (moderate hypocalcemic cows, treated with 2 high calcium chloride at t=0) animals. *P<0.05.

The objectives of this study were to evaluate dissolution times of boluses containing different calcium salts, and their effect on serum calcium in postpartum dairy cows. Calcium chloride and calcium sulfate are absorbed passively through the rumen wall by a process called paracellular absorption. Resistance to movement across the tight junction between epithelial cells can be overcome if the concentration of a mineral, in a freely ionized state, on the luminal side of the tight junction greatly exceeds the ionized concentration of that mineral in the extracellular fluids within the interstitial space on the other side of the tight junction.17 When ionized calcium in the rumen is greater than 6 millimoles (a fivefold increase from the extracellular fluid concentration), the diffusional force created by this difference will be great enough to push the calcium through the tight junction into the interstitial space, and from there it passes through the openings in the capillary endothelium and into the blood.17 This process is very rapid and serum calcium will peak in about an hour. Calcium carbonate is absorbed in the duodenum through the cell wall by vitamin D-dependent active transport. Parathyroid hormone (PTH) stimulates the kidneys to produce vitamin D which, in turn, activates the calcium-binding protein and the ATPase pump to transfer calcium ions through the cell wall into the blood. This process has little effect on raising serum calcium levels for at least 6 hours15 and this was confirmed in our study. In addition, calcium chloride and calcium sulfate are acidifying agents that increase the sensitivity of receptor cells to PTH. The in vivo dissolution study demonstrates that calcium boluses that contain calcium carbonate dissolve at a slower rate in the rumen. When comparing Bolus 2 and Bolus 3, the concentration of calcium carbonate is a good indicator of the boluss dissolution rate. The calcium uptake study confirmed that the bolus containing a high concentration of calcium carbonate did not raise serum calcium levels before at least 6 hours, even though two boluses were administered at once. Although this high calcium carbonate bolus contains approximately 44% calcium chloride, this calcium does not appear to be available to the cow before 6 hours. This is an important observation as cows need a rapid supplementation of calcium in the early postpartum period.15 The traditional protocol of administering one high calcium chloride bolus shortly after calving followed by a second bolus 12 hours later resulted in a similar two peak graph as reported in a Sampson et al (2009) study.16 Notably, the present study compared the traditional protocol (suggested by all brands) of giving one bolus at t=0 and another bolus 12 hours later to the more convenient protocol of giving two boluses at t=0, as the latter approach would be very appealing to a producer. Although it was not surprising that blood calcium peaked at a higher level following an initial dose of two high calcium chloride boluses because of the greater rumen calcium osmolarity, the persistence of this increase was higher than expected. Serum calcium levels were significantly superior to the two-bolus at a 12-hour interval regimen over the first 13 hours and remained numerically higher after 24 hours. When the trial involving Treatment 1 was prolonged to compare the response of cows with severe subclinical hypocalcemia to cows with normal/moderate hypocalcemia, both the serum calcium peak and serum calcium persistence was greater in the severe group. Both calcium chloride and calcium sulfate dissolve rapidly in the rumen. Passive transport of calcium ions between rumen epithelial cells into the extracellular fluid is dependent on diffusion down a concentration gradient.15 It stands to reason that the greater the difference between rumen calcium concentration and blood calcium concentration, the more efficient this passive transport will be, thus positively affecting the increase in serum calcium.

Before the arrival on the market of the calcium bolus, cows were commonly drenched with calcium salts. In one trial, various amounts of calcium chloride were administered to hypocalcemic cows as an oral drench. Three different amounts of calcium, provided by calcium chloride, were evaluated. Cows were orally administered either 50, 75 or 100 grams of calcium chloride twice within 24 hours. As expected, blood calcium concentrations increased as the doses of calcium chloride increased. However, three hours after the second treatment of 100 grams of calcium, the cow presented signs of severe metabolic acidosis with heavy and deep breathing. A treatment protocol of 75 grams of calcium from calcium chloride twice over 24 hours had no ill effects.15 In this study, calcium was provided as a pure calcium chloride solution.

In a more recent trial, cows received 86 grams of calcium for the first 2 days post calving followed by 3 consecutive days of 43 grams. Calcium was provided by triglyceride-coated oral boluses containing a combination of calcium chloride and calcium sulfate.18 They determined that the Blood pH did not differ with administration of oral calcium and averaged 7.488, 7.483, and 7.483 0.012 for 0, 43, and 86 g of calcium, respectively. Therefore, any negative health effects were not due to metabolic acidosis.

The present study suggests that administering two high calcium chloride/calcium sulfate boluses shortly after calving will be more effective in preventing clinical milk fever than the traditional protocol of one bolus after calving followed by a second bolus twelve hours later. Convenience is a huge factor when it comes to making decisions on the dairy farm and the recommendation to give two boluses 12 hours apart is neither convenient nor management or cow friendly.

Dairy cows experience many metabolic challenges around the time of calving. Some of these cows will experience clinical milk fever (510%), while up to 50% of mature cows in some herds will show no symptoms but have subclinical hypocalcemia (SCH).9,19 Recent studies have shown that chronic SCH is more damaging to health than transitory SCH.19,20 Our study focused on the serum calcium effects of supplementing calcium. Research conducted in the last decade has shown that SCH is associated with metabolic diseases,6 an increased susceptibility to metritis in the early postpartum period,3,4,6 a compromised reproductive performance,7 and increased culling rates in the early lactation.8 The awareness of the effects of subclinical hypocalcemia in postpartum dairy cows on the farm level has increased thanks to communication efforts by veterinarians and publications. The case for calcium supplementation has been made but many questions are left to answer on timing, composition, benefits, and dosing regimen of these boluses. Oetzel and Miller (2012) found that cows with higher previous lactation mature-equivalent milk production at 105% of their herd mates, that were supplemented with oral calcium boluses, produced 2.9 kg more milk at first DHIA (Dairy Herd Information Association) test than similar high producing cows not administered postpartum calcium supplementation.13 They also found that lame cows benefited from calcium supplementation. Martinez et al (2016) provided calcium boluses on multiple days with more than one bolus given at a time.21 High producing cows supplemented with calcium produced 0.8 to 2.7 kg more milk per day than their high producing peers not supplemented with calcium. They also concluded that supplementing cows with oral calcium reduced the incidence and prevalence of SCH, but that oral calcium increased the incidence of metritis. This negative effect was primarily observed in primiparous cows considered to be at low risk of metritis. However, reproductive performance improved in multiparous cows with this same regimen. Martinez et al (2016) suggested that this multiple-dose treatment regimen for oral calcium should be avoided in primiparous cows and target only populations at high risk of developing hypocalcemia.21 Domino et al (2017) found that cows with a high relative herd milk rank, that received calcium either subcutaneously or as a bolus, were almost half as likely as non-supplemented cows to be diagnosed with mastitis in the first 60 Days in Milk (DIM).22 They did not report any other health or production benefits between the control group and the two supplemented groups. Leno et al (2018) researched the effects of a single dose of oral calcium on postpartum plasma calcium concentration in Holstein cows and found that a single dose of an oral calcium bolus did not increase the blood calcium concentration between 1 and 24 hours following administration.12 However, responses observed for health and performance outcomes suggest that, in primiparous cows with higher age at first calving or higher body condition score (BCS) at parturition, calcium supplementation positively affected health status and early lactation performance, respectively.12 In multiparous cows, supplementation of cows with higher parity, higher BCS, and lameness also resulted in improved health status. Leno suggested that supplementing Ca could alleviate some of the underlying causes of increased risk for metabolic disease in these animals by supporting gut motility, which can be compromised when blood Ca declines.12 Improved gut motility could support a more rapid increase in postpartum intake and lead to a reduction in the rate or severity of metabolic disease, and higher DMI would support greater milk yield in these cows.12 For multiparous cows, those with low plasma calcium responded with decreased health disorders but cows with higher plasma calcium had varied responses. The authors concluded that low blood calcium concentration was less reliable than other periparturient risk factors to identify cows with a potential to favorably respond to calcium supplementation.

Target group calcium supplementation strategies have been found to be cost-effective.23 A two-bolus regimen, one administered after calving and the second about 24 hours later, was applied to herds following four treatment strategies: lame cows only, high producers only, lame cows and high producers, and all multiparous cows. Although there was a minor herd net impact with the blanket multiparous cow treatment strategy, the greatest return on investment was with the lame cows.

The question remains to be asked whether two boluses at once would be able to amplify these positive responses and whether giving two boluses simultaneously would reduce the number of animals in a herd with a persistent or delayed subclinical hypocalcemia. Giving two boluses at once would negate the need for additional handling (and the accompanying risk of injury to the animal) and likely reduce the behavioral impact of giving boluses the traditional way 12 hours apart. Our study demonstrates that a treatment of two initial high calcium chloride boluses significantly increases blood calcium over the first 13 hours after administration compared to the traditional administration of two boluses at a 12-hour interval. Furthermore, the persistence of these calcium levels remains numerically greater over the 24-hour period. Therefore, the recommendation to provide two boluses at once after calving is practical, convenient, safe, and will more than likely improve the compliance rate of providing the suggested application of two boluses.

A limitation of this study is the lack of blinding of farm personnel to treatments for the first part of the on-farm trial (27 cows) involving two different calcium boluses. However, treatments were administered to cows according to a randomized list prepared before commencement of the study. Farm personnel abided strictly by this list as well as the pre-established blood collection protocol. For the second part of the on-farm trial, all second- and third-lactation cows were administered the same type of bolus (Bolus 1; high calcium chloride) according to the same treatment regimen (two boluses simultaneously, within 12 hours of calving).

The dissolution study and the serum calcium response study in Quebec clearly demonstrate the complexity of a proper calcium supplementation. Boluses containing calcium carbonate may cause a delayed delivery of calcium when it is needed most, and this may ultimately have an impact on the health and wellbeing of the animal. Further research on the impact of calcium carbonate as it relates to the ability and to the timing of a serum calcium increase seems warranted. There are many different calcium boluses on the Canadian market and the dairy producer would likely benefit from the involvement of the herd veterinarian to help design a calcium bolus strategy. This study demonstrated that the increase in total calcium concentrations lasted for 24 hours when two high calcium chloride boluses were administered shortly after calving. Based on our study findings and on a literature review, the recommendation to provide two boluses at once after calving is practical, convenient, safe, and will likely improve the compliance rate of providing the suggested application of two boluses.

BCS, body condition score; DCAD, dietary cation-anion difference; DHIA, dairy herd information association; PTH, parathyroid hormone; SCH, subclinical hypocalcemia; TMR, total mixed ration.

The present field-based study was conducted in compliance with the best practice of veterinary care in accordance with the research guidelines set forth by the Canadian Council on Animal Care and was approved by the Institutional Animal Care and Use Committee (Airdrie, Alberta, Canada) and the Lacombe Research and Development Centre Animal Care Committee.

The owners provided informed consent for their animals to be used in the present study.

The authors wish to acknowledge the producer and the farm staff responsible for treatment administration, blood sample collection, centrifugation, and storage, as well as the technicians, the researchers, and the dairy animals that contributed to this study.

All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.

The funding of both studies was entirely provided by Solvet Animal Health.

Dr Walter Verhoef reports personal fees from Solvet Canada, during the conduct of the study; personal fees from Bureau Vtrinaire de Richmond and Solvet Canada, outside the submitted work; is a partner in Bureau Vtrinaire de Richmond, and was consulting for Solvet. Dr Brenda Ralston reports Dr Merle Olson was her Masters supervisor in 2001; they have published numerous other papers and have collaborated on various grants. Dr Joseph A Ross reports compensation paid to his employer (Chinook Contract Research) for time spent writing, preparing figures, and statistical analyses for Alberta Veterinary Laboratories, during the conduct of the study. Dr Merle Olson reports personal fees from Alberta Veterinary Laboratories, during the conduct of the study; receives salary from Solvet, and Sjoert Zuidhof is providing consulting services to Solvet, which markets the Cal-Boost bolus. The authors report no other potential conflicts of interest for this work.

1. The Merck Veterinary Manual. 8th ed. Harcourt Brace & Co.; 1998.

2. Curtis CR, Erb HN, Sniffen CJ, et al. Association of parturient hypocalcemia with eight periparturient disorders in Holstein cows. J Am Vet Med Assoc. 1983;183(5):559561.

3. Martinez N, Risco CA, Lima FS, et al. Evaluation of peripartal calcium status, energetic profile, and neutrophil function in dairy cows at low or high risk of developing uterine disease. J Dairy Sci. 2012;95(12):71587172. doi:10.3168/jds.2012-5812

4. Martinez N, Sinedino LD, Bisinotto RS, et al. Effect of induced subclinical hypocalcemia on physiological responses and neutrophil function in dairy cows. J Dairy Sci. 2014;97(2):874887. doi:10.3168/jds.2013-7408

5. Daniel RC. Motility of the rumen and abomasum during hypocalcaemia. Can J Comp Med. 1983;47(3):276280.

6. Rodrguez EM, Ars A, Bach A. Associations between subclinical hypocalcemia and postparturient diseases in dairy cows. J Dairy Sci. 2017;100(9):74277434. doi:10.3168/jds.2016-12210

7. Chapinal N, Carson M, Duffield TF, et al. The association of serum metabolites with clinical disease during the transition period. J Dairy Sci. 2011;94(10):48974903. doi:10.3168/jds.2010-4075

8. Roberts T, Chapinal N, Leblanc SJ, Kelton DF, Dubuc J, Duffield TF. Metabolic parameters in transition cows as indicators for early-lactation culling risk. J Dairy Sci. 2012;95(6):30573063. doi:10.3168/jds.2011-4937

9. Reinhardt TA, Lippolis JD, McCluskey BJ, Goff JP, Horst RL. Prevalence of subclinical hypocalcemia in dairy herds. Vet J. 2011;188(1):122124. doi:10.1016/j.tvjl.2010.03.025

10. Sasidharan V. Prevent milk fever and economic loss with oral calcium supplements. Prog Dairyman. 2014.

11. Goff JP. Macromineral physiology and application to the feeding of the dairy cow for prevention of milk fever and other periparturient mineral disorders. Animal Feed Sci Technol. 2006;126(34):237257. doi:10.1016/j.anifeedsci.2005.08.005

12. Leno BM, Neves RC, Louge IM, et al. Differential effects of a single dose of oral calcium based on postpartum plasma calcium concentration in Holstein cows. J Dairy Sci. 2018;101(4):32853302. doi:10.3168/jds.2017-13164

13. Oetzel GR, Miller BE. Effect of oral calcium bolus supplementation on early-lactation health and milk yield in commercial dairy herds. J Dairy Sci. 2012;95(12):70517065. doi:10.3168/jds.2012-5510

14. Neves RC, Leno BM, Stokol T, Overton TR, McArt JAA. Risk factors associated with postpartum subclinical hypocalcemia in dairy cows. J Dairy Sci. 2017;100(5):37963804. doi:10.3168/jds.2016-11970

15. Goff JP, Horst RL. Oral administration of calcium salts for treatment of hypocalcemia in cattle. J Dairy Sci. 1993;76(1):101108. doi:10.3168/jds.S0022-0302(93)77328-2

16. Sampson JD, Spain JN, Jones C, Carstensen L. Effects of calcium chloride and calcium sulfate in an oral bolus given as a supplement to postpartum dairy cows. Vet Ther Fall. 2009;10(3):131139.

17. Goff JP. Invited review: mineral absorption mechanisms, mineral interactions that affect acid-base and antioxidant status, and diet considerations to improve mineral status. J Dairy Sci. 2018;101(4):27632813. doi:10.3168/jds.2017-13112

18. Martinez N, Sinedino LDP, Bisinotto RS, et al. Effects of oral calcium supplementation on mineral and acid-base status, energy metabolites, and health of postpartum dairy cows. J Dairy Sci. 2016;99(10):83978416. doi:10.3168/jds.2015-10527

19. Caixeta LS, Ospina PA, Capel MB, Nydam DV. Association between subclinical hypocalcemia in the first 3 days of lactation and reproductive performance of dairy cows. Theriogenology. 2017;94:17. doi:10.1016/j.theriogenology.2017.01.039

20. McArt JAA, Neves RC. Association of transient, persistent, or delayed subclinical hypocalcemia with early lactation disease, removal, and milk yield in Holstein cows. J Dairy Sci. 2020;103(1):690701. doi:10.3168/jds.2019-17191

21. Martinez N, Sinedino LDP, Bisinotto RS, et al. Effects of oral calcium supplementation on productive and reproductive performance in Holstein cows. J Dairy Sci. 2016;99(10):84178430. doi:10.3168/jds.2015-10529

22. Domino AR, Korzec HC, McArt JAA. Field trial of 2 calcium supplements on early lactation health and production in multiparous Holstein cows. J Dairy Sci. 2017;100(12):96819690. doi:10.3168/jds.2017-12885

23. McArt JA, Oetzel GR. A stochastic estimate of the economic impact of oral calcium supplementation in postparturient dairy cows. J Dairy Sci. 2015;98(10):74087418. doi:10.3168/jds.2015-9479

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[Full text] Dissolution Rates of Calcium Boluses and Their Effects on Serum Calciu | VMRR - Dove Medical Press

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Participants and study design

The BioCycle Study (20052007) was a prospective cohort study designed to evaluate the relationship between reproductive hormones and oxidative stress levels throughout the menstrual cycle [26, 27]. The participant cohort consisted of 259 regularly menstruating, healthy women between the ages of 1844years, recruited from western New York. Participants were recruited in a variety of ways, including: advertising in clinical practices and the University at Buffalo student health center, paid advertising in print media, radio and television interviews, notices sent via list serves, and flyers at the university and throughout the region. For those interested, an initial screening phone call was conducted, followed by a mailing and an in-person visit. Exclusion criteria included factors that may interfere with a normal menstrual cycle or vitamin levels, such as: use of oral contraceptives during the study period or in the previous three months; use of Depo provera, implant or IUD in previous twelve months; current use of vitamin, mineral, or herbal supplements; use of prescription medications; pregnancy or breast feeding in the previous six months; reported attempts to conceive in the previous six months; diagnosis of uterine abnormalities or chronic conditions, such as ovulatory disorders and premenstrual dysphoric disorder (PMDD); and a self-reported body mass index (BMI) of <18 or >35kg/m2 at screening [27]. Those eligible and interested after the screening visit were scheduled for a baseline enrollment visit 12weeks prior to the start of their next menses. Women were followed for one (n=9) or two (n=250) menstrual cycles (Additional file 1: Figure S1).

Women completed up to 8 clinic visits per cycle for up to 2 cycles. Study visits were scheduled using fertility monitors (Clearblue Easy Fertility Monitor; Inverness Medical, Waltham, Massachusetts) to coincide with critical phases of the menstrual cycle, including menstruation; mid- and late follicular phases; luteinizing hormone (LH) surge (predicted ovulation); and early, mid-, and late luteal phases [28]. At each of these visits, fasting blood samples were collected from participants from which the antioxidant vitamins and oxidative stress concentrations were measured. Participants were highly compliant with the study protocol; 94% of the women completed 7 or 8 clinic visits, and 100% completed at least 5 clinic visits per cycle.

The University at Buffalo Health Sciences Institutional Review Board (IRB) approved this study and served as the IRB designated by the National Institutes of Health under a reliance agreement. All participants provided written informed consent. Further details of the study design are described elsewhere [27].

Ascorbic acid (vitamin C), retinol (vitamin A), and - and - tocopherol (vitamin E) were measured in all blood samples taken from participants across a menstrual cycle and subsequently averaged to reflect the mean levels across a cycle. Total ascorbic acid was determined by the dinitrophenylhydrazine (DNPH) method. Samples for ascorbate analysis were stabilized immediately following phlebotomy and centrifugation by adding 0.5mL of heparin plasma to 2.0mL of 6% meta-phosphoric acid and centrifuging at 3000g for 10min. Clear supernatant was decanted and frozen at 80C for analysis. The absorbance of each DNPH derivatized sample was determined at 520nm on a Shimadzu 160U spectrophotometer (Shimadzu Scientific Instruments, Inc.). Across the study period, the coefficient of variation (CV) for this test reported by the laboratory was 10%.

Fat-soluble vitamins (including retinol, and vitamin E components: - and -tocopherol) were measured at the Kaleida Health Center (Buffalo, New York) simultaneously in serum using high performance liquid chromatography with photodiode array detection [29]. -tocopherol was also detected but was below the lower limit of quantification for our assay (0.28). The limits of detection were 0.0054 for retinol, 0.0768 for -tocopherol, and 0.1052 for -tocopherol. The CV for these tests across the study period were <6% for retinol and <2% for - and -tocopherol. Continuous monitoring of standard reference material 968c from the National Institute of Standards and Technology (NIST) and participation in the NIST Micronutrients Measurement Quality Assurance Program provided external checks on analytical accuracy.

Mean concentrations of antioxidants, including vitamin A, vitamin C, -tocopherol, and -tocopherol, were calculated per cycle and were used in all analyses. Overall median concentrations were also compared with levels reported previously by reproductive aged women (i.e., 2039years) in the 2012 National Health and Nutrition Examination Survey (NHANES) to assess the comparability of our results with those of a nationally representative population [30].

Plasma free F2-isoprostane, a breakdown product of ROS and a marker of oxidative stress, was measured with a gas chromatography-mass spectrometrybased method by the Molecular Epidemiology and Biomarker Research Laboratory (University of Minnesota, Minneapolis, Minnesota) (CV=9.4%).

Frequency and severity of 20 premenstrual symptoms was assessed through questionnaires completed at four time points of each menstrual cycle: menses, follicular phase, peri-ovulation, and luteal phase (Additional file 2: Figure S2). Participants recalled the occurrence and severity of symptoms in the prior week. The symptoms included in this assessment were: sadness, crying spells, anger, nervousness, insomnia, tension, abdominal bloating, cravings of chocolates, cravings of sweets, cravings of salty foods, cravings of other foods, breast tenderness, lower abdominal cramping, general aches, backache, headache, acne outbreaks, change in appetite, fatigue, and swelling of the hands/feet. The severity of each symptom was ranked by the participant on a scale of 0 to 3 (0=none, 1=mild, 2=moderate, 3=severe). The symptoms included in this questionnaire were adapted from validated surveysincluding the Daily Record of Severity of Problems (DRSP) and the Premenstrual Symptoms Screening Tool (PSST)but slightly modified, given that DRSP and the PSST were designed to identify patients with PMDD specifically (a population excluded in our study) [31,32,33,34].

We categorized severity as none/mild (reference group) or moderate/severe to estimate odds of having a moderate or severe symptom during the premenstrual week. We then calculated severity scores for groups of related symptoms by summing the severity score of symptoms (as reported in the premenstrual week) within each grouping to generate an overall score. The groupings were established based on clinical expertise and included: depression (sadness, crying spells, anger) and anxiety (nervousness, insomnia, tension); hydration (abdominal bloating) and cravings (chocolate cravings, sweets cravings, salty food cravings, other food cravings); pain (breast tenderness, lower abdominal cramping, general aches, backache, headache); and other (acne outbreak, change in appetite, fatigue, swelling of hands or feet).

Overall PMS severity was evaluated using four different approaches, which utilize information on all symptoms from the luteal and follicular phase questionnaires from each cycle: (1) 5 or more moderate or severe symptoms during the luteal phase; (2) 8 or more moderate or severe symptoms during the luteal phase; (3) 3 or more moderate or severe symptoms where the luteal phase score was 30% greater than the follicular phase and at least one symptom was psychological (referred to as PMS-1 in the tables and results); and (4) 5 or more moderate or severe symptoms where the luteal phase score was 30% greater than the follicular phase and at least one symptom was psychological (referred to as PMS-2 in the tables and results) [8, 35, 36]. When summing the number of moderate or severe symptoms for each cycle, each of the individual cravings symptoms were combined into a single variable. These criteria were based upon various defintions of PMSincluding those of the National Institute of Mental Health, [37] the American College of Obstetrics and Gynecology, [38] the American Psychiatric Association, [39] and the International Society for Premenstrual disorders (ISPMD) [40]which were further expanded and implemented in studies such as Gollenberg et al. [35] and Borenstein et al. [8] Of note, these approaches attempt to establish the necessary temporality between pre- and post-menstrual symptoms in line with traditional PMS definitions and diagnoses that assume resolution of symptoms within 12days of the onset of menses.

At study enrollment, a trained research assistant measured height and weight for the calculation of BMI using standardized protocols. Demographics such as age, race, education, smoking habits, reproductive history, and physical activity were also collected at baseline through self-reported questionnaires. Physical activity was assessed at baseline using the International Physical Activity Questionnaire, and estimated for high, moderate, and low levels of activity based upon accepted cutoffs [41]. Dietary information was obtained using 24-h recalls (up to 4 times per cycle) and analyzed using the Nutrition Data System for Research software (version 2005) developed by the Nutrition Coordinating Center of the University of Minnesota (Minneapolis, Minnesota). Cycle-averaged measures of total energy (kcal/day) and fiber (g/day) were used in these analyses, as we previously found these intakes do not vary significantly across the cycle [42]. All covariates assessed had at least a 95% response rate.

Demographic characteristics were compared between those with <5 versus 5 moderate or severe symptoms during the luteal phase of either study menstrual cycle, and between those with <8 versus 8 moderate or severe luteal phase symptoms in either cycle. Repeated measures ANOVA and McNemars tests were used for comparisons.

We estimated associations between mean antioxidant concentrations and F2-isoprostane concentrations from each menstrual cycle and odds of reporting a moderate/severe symptom during the premenstrual week for each cycle using generalized linear models. Next, we evaluated associations between antioxidant concentrations, F2-isoprostane concentrations, and scores for symptom severity within groups during the premenstrual week (e.g., depression, cravings, pain) using linear mixed models. We used generalized linear models to assess the association between mean antioxidant concentrations, F2-isoprostane concentrations, and overall PMS severity in each cycle using the four different classifications of PMS severity (5 or more moderate or severe symptoms, 8 or more moderate or severe symptoms, PMS-1 criterion, PMS-2 criterion). All models were adjusted for age, race, BMI, physical activity, smoking status, alcohol use, pain reliever use, and average total energy intake per cycle and accounted for repeated measures (i.e., multiple cycles per woman). Results were adjusted for multiple comparisons using the false discovery rate (FDR). An alpha of 0.05 was considered statistically significant. As antioxidants and oxidative stress measures have been shown to vary somewhat over the menstrual cycle [26, 43], we also evaluated associations between time-varying measures of antioxidants and oxidative stress, with time-varying symptoms as a sensitivity analysis. Splines were used to evaluate the assumption of linearity. We did not find evidence to suggest that linear modeling was inappropriate (e.g., quadratic or restricted cubic spline modeling did not help explain the associations in our population). All statistical analyses were calculated using SAS 9.4 (SAS Institute, Cary, North Carolina).

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National Review

President Joe Bidens recent executive order to expand food assistance to U.S. households, while well-intentioned, represents a substantial overreach of the executive branch and a blatant attempt to override the intent of Congress. If successful, this dangerous precedent would open the door to major expansions of the social safety net without congressional approval. Congress must resist the presidents attempts to subvert the intent of existing law. Less than one week into the Biden presidency, the new administration issued a series of executive orders focused on COVID-19 economic relief. One such order seeks to expand food assistance through the Supplemental Nutrition Assistance Program (SNAP), or food stamps. In it, President Biden instructed the Department of Agriculture (USDA) to take immediate steps to make it easier for the hardest-hit families to enroll and claim more generous benefits in the critical food and nutrition assistance area. In reality, the executive order asks a federal agency the USDA to intentionally misinterpret the Families First Act and subvert the constitutional authority of Congress over the legislative process. The Families First Act, which passed in March 2020, clearly outlined that states could request waivers from the Agriculture Department to provide emergency allotments to SNAP households not greater than the applicable maximum monthly allotment for the household size. In normal times, 60 percent of households enrolled in SNAP do not receive the maximum benefit because they have income from other sources such as earnings that they can use for purchasing food. The emergency allotments recognized that millions of people lost jobs or faced other employment disruptions when the pandemic hit, and that those enrolled in SNAP were at particular risk for job loss in the early aftermath of the pandemic. Rather than requiring SNAP households to report a job or income change to their state agency and wait for bureaucrats to recalculate their benefits, the emergency allotments gave every SNAP recipient the maximum allowed. This was, admittedly, not a very targeted effort. Some families received a boost in SNAP dollars without a change in household income or financial circumstances. But the immediacy of the economic shock brought on by the pandemic, and the employment instability that persists today, necessitated an equally expedient policy response. The Agriculture Department, under President Trump, had approved emergency allotment plans for all 50 states, the District of Columbia, Guam, and the U.S. Virgin Islands but only in accordance with the law. The department extended these emergency-allotment waivers numerous times, most recently extending them through January 2021. The USDA and Congress itself also offered states flexibility in the aftermath of the pandemic. According to federal government spending data, all of the efforts outlined above have caused SNAP benefits to rise more than 40 percent in the last fiscal year, with more than $31 billion in added spending compared to FY 2019. Class-action suits have been filed in Pennsylvania and California by people who disagree with the USDAs interpretation of the law: that regular SNAP plus emergency allotments cannot extend benefits beyond the maximum benefit level. Lawyers for the lawsuits argue that the law allows the USDA to approve emergency allotments in the amount of the maximum benefit, which if true, would mean that households could receive the maximum SNAP benefit plus the maximum emergency allotment essentially doubling benefit amounts. A federal judge in California agreed with the USDA, while the Pennsylvania case is ongoing. The Biden administrations executive order is encouraging its USDA to misinterpret the 2020 law in a similar way. The legislative text is not ambiguous. It is hard to imagine Congress being any clearer than, to address temporary food needs not greater than the applicable maximum monthly allotment for the household size. If Congress had wanted to give people more than the SNAP maximum, it would have done so. In fact, Congress eventually did just that expanding benefits by 15 percent in the COVID-19 relief package passed last month. If the Biden administration is successful in this attempt, it will open the door to a number of executive actions aimed at expanding the safety net without congressional action. If political appointees in the Biden administration feel unconstrained by the law, we will see larger benefits directed to an increasing number of people. Such action not only undermines the integrity of the social safety net by going around Congress, it disregards the separation of powers ensconced in the founding documents of our republic. The American public has been largely supportive of efforts by Congress to provide economic relief to struggling households. Lets keep that authority in its proper place.

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New York, Feb. 01, 2021 (GLOBE NEWSWIRE) -- Reportlinker.com announces the release of the report "Global CRISPR Gene Editing Market: Focus on Products, Applications, End Users, Country Data (16 Countries), and Competitive Landscape - Analysis and Forecast, 2020-2030" - https://www.reportlinker.com/p06018975/?utm_source=GNW Application Agricultural, Biomedical (Gene Therapy, Drug Discovery, And Diagnostics), Industrial, and Other Applications [Genetically Modified Foods (GM Foods), Biofuel, And Animal (Livestock) Breeding] End-User - Academic Institutes and Research Centers, Biotechnology Companies, Contract Research Organizations (CROs), and Pharmaceutical and Biopharmaceutical Companies

Regional Segmentation

North America U.S., Canada Europe Germany, France, Italy, U.K., Spain, Switzerland, and Rest-of-Europe Asia-Pacific China, Japan, India, South Korea, Singapore, Australia, and Rest-of-Asia-Pacific (RoAPAC) Latin America Brazil, Mexico, and Rest-of-the-Latin America Rest-of-the-World

Growth Drivers

Prevalence of Genetic Disorders and Use of Genome Editing Government and Private Funding Technology Advancement in CRISPR Gene Editing

Market Restraints

CRISPR Gene Editing: Off Target Effects and Delivery Ethical Concerns and Implications with Respect to Human Genome Editing

Market Opportunities

Expanding Gene and Cell Therapy Area CRISPR Gene Editing Scope in Agriculture

Key Companies ProfiledAbcam, Inc., Applied StemCell, Inc., Agilent Technologies, Inc., Cellecta, Inc., CRISPR Therapeutics AG, Thermo Fisher Scientific, Inc., GeneCopoeia, Inc., GeneScript Biotech Corporation, Horizon Discovery Group PLC, Integrated DNA Technologies, Inc., Merck KGaA, New England Biolabs, Inc., Origene Technologies, Inc., Rockland Immunochemicals, Inc., Synthego Corporation, System Biosciences LLC, ToolGen, Inc., Takara Bio

Key Questions Answered in this Report: What is CRISPR gene editing? What is the timeline for the development of CRISPR technology? How did the CRISPR gene editing market evolve, and what is its scope in the future? What are the major market drivers, restraints, and opportunities in the global CRISPR gene editing market? What are the key developmental strategies that are being implemented by the key players to sustain this market? What is the patent landscape of this market? What will be the impact of patent expiry on this market? What is the impact of COVID-19 on this market? What are the guidelines implemented by different government bodies to regulate the approval of CRISPR products/therapies? How is CRISPR gene editing being utilized for the development of therapeutics? How will the investments by public and private companies and government organizations affect the global CRISPR gene editing market? What was the market size of the leading segments and sub-segments of the global CRISPR gene editing market in 2019? How will the industry evolve during the forecast period 2020-2030? What will be the growth rate of the CRISPR gene editing market during the forecast period? How will each of the segments of the global CRISPR gene editing market grow during the forecast period, and what will be the revenue generated by each of the segments by the end of 2030? Which product segment and application segment are expected to register the highest CAGR for the global CRISPR gene editing market? What are the major benefits of the implementation of CRISPR gene editing in different field of applications including biomedical research, agricultural research, industrial research, gene therapy, drug discovery, and diagnostics? What is the market size of the CRISPR gene editing market in different countries of the world? Which geographical region is expected to contribute to the highest sales of CRISPR gene editing market? What are the reimbursement scenario and regulatory structure for the CRISPR gene editing market in different regions? What are the key strategies incorporated by the players of global CRISPR gene editing market to sustain the competition and retain their supremacy?

Market OverviewThe development of genome engineering with potential applications proved to reflect a remarkable impact on the future of the healthcare and life science industry.The high efficiency of the CRISPR-Cas9 system has been demonstrated in various studies for genome editing, which resulted in significant investments within the field of genome engineering.

However, there are several limitations, which need consideration before clinical applications.Further, many researchers are working on the limitations of CRISPR gene editing technology for better results.

The potential of CRISPR gene editing to alter the human genome and modify the disease conditions is incredible but exists with ethical and social concerns. The global CRISPR gene editing market was valued at $846.2 million in 2019 and is expected to reach $10,825.1 million by 2030, registering a CAGR of 26.86% during the forecast.

The growth is attributed to the increasing demand in the food industry for better products with improved quality and nutrient enrichment and the pharmaceutical industry for targeted treatment for various diseases. Further, the continued significant investments by healthcare companies to meet the industry demand and growing prominence for the gene therapy procedures with less turnaround time are the prominent factors propelling the growth of the global CRISPR gene editing market.

Research organizations, pharmaceutical and biotechnology industries, and institutes are looking for more efficient genome editing technologies to increase the specificity and cost-effectiveness, also to reduce turnaround time and human errors.Further, the evolution of genome editing technologies has enabled wide range of applications in various fields, such as industrial biotech and agricultural research.

These advanced methods are simple, super-efficient, cost-effective, provide multiplexing, and high throughput capabilities. The increase in the geriatric population and increasing number of cancer cases, and genetic disorders across the globe are expected to translate into significantly higher demand for CRISPR gene editing market.

Furthermore, the companies are investing huge amounts in the research and development of CRISPR gene editing products, and gene therapies. The clinical trial landscape of various genetic and chronic diseases has been on the rise in recent years, and this will fuel the CRISPR gene editing market in the future.

Within the research report, the market is segmented based on product type, application, end-user, and region. Each of these segments covers the snapshot of the market over the projected years, the inclination of the market revenue, underlying patterns, and trends by using analytics on the primary and secondary data obtained.

Competitive LandscapeThe exponential rise in the application of precision medicine on a global level has created a buzz among companies to invest in the development of novel CRISPR gene editing. Due to the diverse product portfolio and intense market penetration, Merck KGaA, and Thermo Fisher Scientific Inc. have been the pioneers in this field and have been the major competitors in this market. The other major contributors of the market include companies such as Integrated DNA Technologies (IDT), Genscript Biotech Corporation, Takara Bio Inc, Agilent Technologies, Inc., and New England Biolabs, Inc.

Based on region, North America holds the largest share of CRISPR gene editing market due to substantial investments made by biotechnology and pharmaceutical companies, improved healthcare infrastructure, rise in per capita income, early availability of approved therapies, and availability of state-of-the-art research laboratories and institutions in the region. Apart from this, Asia-Pacific region is anticipated to grow at the fastest CAGR during the forecast period.

Countries Covered North America U.S. Canada Europe Germany Italy France Spain U.K. Switzerland Rest-of-Europe Asia-Pacific China India Australia South Korea Singapore Japan Rest-of-Asia-Pacific Latin America Brazil Mexico Rest-of-Latin America Rest-of-the-WordRead the full report: https://www.reportlinker.com/p06018975/?utm_source=GNW

About ReportlinkerReportLinker is an award-winning market research solution. Reportlinker finds and organizes the latest industry data so you get all the market research you need - instantly, in one place.

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Global CRISPR Gene Editing Market: Focus on Products, Applications, End Users, Country Data (16 Countries), and Competitive Landscape - Analysis and...

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Gene Editing Tools Marketresearch report is the new statistical data source added byA2Z Market Research.

Gene Editing Tools Marketresearch is an intelligence report with meticulous efforts undertaken to study the right and valuable information. The data which has been looked upon is done considering both, the existing top players and the upcoming competitors. Business strategies of the key players and the new entering market industries are studied in detail. Well explained SWOT analysis, revenue share and contact information are shared in this report analysis. It also provides market information in terms of development and its capacities.

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Some of the Top companies Influencing in this Market includes:

Thermofisher Scientific, CRISPR Therapeutics, Editas Medicine, NHGRI, Intellia Therapeutics, Merck KGaA.

Various factors are responsible for the markets growth trajectory, which are studied at length in the report. In addition, the report lists down the restraints that are posing threat to the global Gene Editing Tools market. It also gauges the bargaining power of suppliers and buyers, threat from new entrants and product substitute, and the degree of competition prevailing in the market. The influence of the latest government guidelines is also analyzed in detail in the report. It studies the Gene Editing Tools markets trajectory between forecast periods.

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Key Factors Impacting Market Growth:

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Regions Covered in the Global Gene Editing Tools Market Report 2021:The Middle East and Africa(GCC Countries and Egypt)North America(the United States, Mexico, and Canada)South America(Brazil etc.)Europe(Turkey, Germany, Russia UK, Italy, France, etc.)Asia-Pacific(Vietnam, China, Malaysia, Japan, Philippines, Korea, Thailand, India, Indonesia, and Australia)

The cost analysis of the Global Gene Editing Tools Market has been performed while keeping in view manufacturing expenses, labor cost, and raw materials and their market concentration rate, suppliers, and price trend. Other factors such as Supply chain, downstream buyers, and sourcing strategy have been assessed to provide a complete and in-depth view of the market. Buyers of the report will also be exposed to a study on market positioning with factors such as target client, brand strategy, and price strategy taken into consideration.

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Table of Content (TOC)

Global Gene Editing Tools Market Report 2021 Growth, Trend and Forecast to 2027

Chapter 1 Gene Editing Tools Market Overview

Chapter 2 Global Economic Impact on Gene Editing Tools Industry

Chapter 3 Global Gene Editing Tools Market Competition by Manufacturers

Chapter 4 Global Production, Revenue (Value) by Region (2014-2020)

Chapter 5 Global Supply (Production), Consumption, Export, Import by Regions (2014-2020)

Chapter 6 Global Production, Revenue (Value), Price Trend by Type

Chapter 7 Global Market Analysis by Application

Chapter 8 Manufacturing Cost Analysis

Chapter 9 Industrial Chain, Sourcing Strategy and Downstream Buyers

Chapter 10 Marketing Strategy Analysis, Distributors/Traders

Chapter 11 Market Effect Factors Analysis

Chapter 12 Global Gene Editing Tools Market Forecast (2021-2027)

Chapter 13 Appendix

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Massive Growth of Gene Editing Tools Market 2021 | Size, Demand, Opportunities & Forecast To 2027 | Thermofisher Scientific, CRISPR Therapeutics,...

Recommendation and review posted by Bethany Smith

CRISPR-wielder Mammoth Biosciences will team up with Agilent Technologies to help launch its upcoming COVID-19 diagnostic test, designed to handle more than 4,000 samples per day.

Applying the gene editing technology allows the system to operate much faster than standard PCR-based molecular lab tests, according to Mammoth. The companys CRISPR-based DETECTR assay uses Cas12 enzymes to identify and tag the coronaviruss specific genomic sequences and provides a visual result that can be read by a machine.

The two companies hope to increase the tests throughput speed even more by connecting it with Agilents automated liquid handling systems and sample readers. Dubbed DETECTR BOOST, the platform aims to process about 1,500 samples over an eight-hour shift.

Blazing a Trail to Clinical Trial Diversity: Four-Part Webinar Series from Syneos Health, Featuring Pharma, Clinical Research and Community Health Leaders

This series will identify obstacles that stifle appropriate patient diversity in trials; unpack the organizational overhaul needed; share how sponsors, patients & investigators have come together to overcome hurdles; and explore how policy innovations can move the industry forward.

"A highly-automated workstation for SARS-CoV-2 testing provides the capacity needed to bring routine, robust testing to the broader market, said David Edwards, associate marketing vice president for Agilents mass spectrometry division. By partnering with Mammoth Biosciences, we will be able to provide a simplified workflow that addresses the specific needs of high-throughput clinical testing laboratories.

Similar methods have been explored for COVID-19 tests that can be read with a smartphone camera and a darkened box using fluorescent molecules that produce a faint glow when matched up with the viruss specific genetic material. Prior to the pandemic, the technology was being developed for HIV testing in low-resource areas.

GlaxoSmithKline has also tapped Mammoth to develop a CRISPR-based coronavirus test that could be available over the counter.

More recently, Mammoth announced a contract with MRIGlobal through the U.S. Defense Advanced Research Projects Agency, known as DARPA, to develop CRISPR-based diagnostics and biosurveillance technologies for the Department of Defense. This includes the development of a hand-held device capable of screening for 10 pathogens simultaneously and a lab system that can spot more than 1,000 targets at once.

RELATED: Pairing CRISPR with a smartphone camera, this COVID-19 test finds results in 30 minutes

Co-founded by CRISPR pioneer and Nobel laureate Jennifer Doudna, Ph.D., Mammoth previously received funding support from the National Institutes of Health through its Shark Tank-esque diagnostics competition known as the Rapid Acceleration of Diagnostics initiative, or RADx. The company said it plans to submit its test for an FDA emergency authorization in the near future.

Mammoths mission is to address challenges across healthcare by harnessing the full potential of the CRISPR platform to read and write the code of life," said Mammoths co-founder and CEO, Trevor Martin, Ph.D. This partnership will help address the need for more widespread testing options for COVID-19, helping to fill the gap in the market as testing labs run into supply issues or reach capacity.

Read more here:
Mammoth Biosciences teams with Agilent to deliver CRISPR-based coronavirus tests - FierceBiotech

Recommendation and review posted by Bethany Smith

In recent months, even as our attention has been focused on the coronavirus outbreak, there have been a slew of scientific breakthroughs in treating diseases that cause blindness.

Researchers at U.S.-based Editas Medicine and Ireland-based Allergan have administeredCRISPR for the first time to a person with a genetic disease. This landmark treatment uses the CRISPR approach to a specific mutation in a gene linked to childhood blindness. The mutation affects the functioning of the light-sensing compartment of the eye, called the retina, and leads to loss of the light-sensing cells.

According to the World Health Organization,at least 2.2 billion peoplein the world have some form of visual impairment. In the United States, approximately200,000 people suffer from inherited forms of retinal diseasefor which there is no cure. But things have started to change for good. We can now see light at the end of the tunnel.

I am an ophthalmology and visual sciences researcher, and am particularly interested in these advances becausemy laboratory is focusingon designing new and improved gene therapy approaches to treat inherited forms of blindness.

Gene therapy involves inserting the correct copy of a gene into cells that have a mistake in the genetic sequence of that gene, recovering the normal function of the protein in the cell. The eye is an ideal organ for testing new therapeutic approaches, including CRISPR. That is because the eye is the most exposed part of our brain and thus is easily accessible.

The second reason is that retinal tissue in the eye is shielded from the bodys defense mechanism, which would otherwise consider the injected material used in gene therapy as foreign and mount a defensive attack response. Such a response would destroy the benefits associated with the treatment.

In recent years, breakthrough gene therapy studies paved the way to thefirst ever Food and Drug Administration-approved gene therapy drug, Luxturna TM, for a devastating childhood blindness disease,Leber congenital amaurosisType 2.

This form of Leber congenital amaurosis is caused by mutations in a gene that codes for a protein called RPE65. The protein participates in chemical reactions that are needed to detect light. The mutations lessen or eliminate the function of RPE65, which leads to our inability to detect light blindness.

The treatment method developed simultaneously by groups at University of Pennsylvania and at University College London and Moorefields Eye Hospital involvedinserting a healthy copy of the mutated genedirectly into the space between the retina and the retinal pigmented epithelium, the tissue located behind the retina where the chemical reactions takes place. This gene helped the retinal pigmented epithelium cell produce the missing protein that is dysfunctional in patients.

Although the treated eyes showed vision improvement, as measured by the patients ability to navigate an obstacle course at differing light levels,it is not a permanent fix. This is due to the lack of technologies that can fix the mutated genetic code in the DNA of the cells of the patient.

Lately, scientists have been developing a powerful new tool that is shifting biology and genetic engineering into the next phase. This breakthroughgeneeditingtechnology, which is called CRISPR, enables researchers to directly edit the genetic code of cells in the eye and correct the mutation causing the disease.

Children suffering from the disease Leber congenital amaurosis Type 10 endure progressive vision loss beginning as early as one year old. This specific form of Leber congenital amaurosis is caused by a change to the DNA that affects the ability of the gene called CEP290 to make the complete protein. The loss of the CEP290 protein affects the survival and function of our light-sensing cells, called photoreceptors.

One treatment strategy is to deliver the full form of the CEP290 gene using a virus as the delivery vehicle. But the CEP290 gene is too big to be cargo for viruses. So another approach was needed. One strategy was to fix the mutation by using CRISPR.

The scientists at Editas Medicine first showed safety and proof of the concept of the CRISPR strategy in cells extracted from patient skin biopsy and in nonhuman primate animals.

These studies led to the formulation of thefirst ever in human CRISPR gene therapeutic clinical trial. This Phase 1 and Phase 2 trial will eventually assess the safety and efficacy of the CRISPR therapy in 18 Leber congenital amaurosis Type 10 patients. The patients receive a dose of the therapy while under anesthesia when the retina surgeon uses a scope, needle and syringe to inject the CRISPR enzyme and nucleic acids into the back of the eye near the photoreceptors.

To make sure that the experiment is working and safe for the patients, the clinical trial has recruited people with late-stage disease and no hope of recovering their vision. The doctors are also injecting the CRISPR editing tools into only one eye.

An ongoing project in my laboratory focuses on designing a gene therapy approach for the same gene CEP290. Contrary to the CRISPR approach, which can target only a specific mutation at one time, my team is developing an approach that would work for all CEP290 mutations in Leber congenital amaurosis Type 10.

This approach involves usingshorter yet functional forms of the CEP290 proteinthat can be delivered to the photoreceptors using the viruses approved for clinical use.

Gene therapy that involves CRISPR promises a permanent fix and a significantly reduced recovery period. A downside of the CRISPR approach is the possibility of an off-target effect in which another region of the cells DNA is edited, which could cause undesirable side effects, such as cancer. However, new and improved strategies have made such likelihood very low.

Although the CRISPR study is for a specific mutation in CEP290, I believe the use of CRISPR technology in the body to be exciting and a giant leap. I know this treatment is in an early phase, but it shows clear promise. In my mind, as well as the minds of many other scientists, CRISPR-mediated therapeutic innovation absolutely holds immense promise.

In another study just reported in the journal Science, German and Swiss scientists have developeda revolutionary technology, which enables mice and human retinas to detect infrared radiation. This ability could be useful for patients suffering from loss of photoreceptors and sight.

The researchers demonstrated this approach, inspired by the ability of snakes and bats to see heat, by endowing mice and postmortem human retinas with a protein that becomes active in response to heat. Infrared light is light emitted by warm objects that is beyond the visible spectrum.

The heat warms a specially engineered gold particle that the researchers introduced into the retina. This particle binds to the protein and helps it convert the heat signal into electrical signals that are then sent to the brain.

In the future, more research is needed to tweak the ability of the infrared sensitive proteins to different wave lengths of light that will also enhance the remaining vision.

This approach is still being tested in animals and in retinal tissue in the lab. But all approaches suggest that it might be possible to either restore, enhance or provide patients with forms of vision used by other species.

Hemant Khanna is an Associate Professor of Ophthalmology at the University of Massachusetts Medical School. His lab investigates molecular and cell biological bases of severe photoreceptor degenerative disorders, such as Retinitis Pigmentosa (RP) and Leber Congenital Amaurosis (LCA). Find Hemant on Twitter @khannacilialab

A version of this article was originally published at the Conversation and has been republished here with permission. The Conversation can be found on Twitter @ConversationUS

Visit link:
Inherited blindness has a new cure, thanks to CRISPR - Genetic Literacy Project

Recommendation and review posted by Bethany Smith

The mosquitoes that carry zika, like Aedes aegypti, are considered by all but the most activist ecologists to be useless disease vectors. There is nothing they do in nature that isn't easily done by other mosquitoes and they can safely join the 99.999999999% of species that have gone extinct without causing a cascade of doom.

Seriously, Send me your hate mail, @ me on Twitter, try to cancel me, I don't care, that is absolutely correct. They are ecologically useless and have survived despite that, because evolution is not always fair.

After years of study across two different administrations, the EPA signed off on a plan that would allow release of genetically engineered mosquitoes that can't reproduce - since their range is limited their area of effect would be only what we want, like the Florida Keys. In the Los Angeles Times years earlier, I had debunked the claims of an anti-science Florida "Karen" who was convinced biologists didn't know what they were doing and we were all going to be dead, the environmental equivalent of that lawyer who filed a lawsuit claiming the Large Hadron Collider would create a black hole and swallow the planet. Lawyer-run groups that wrap themselves in the flag of environmentalism have also been raising money opposing natural control of mosquitoes recently, conspiratorially insisting Trump controlled every career scientist in government so it can't be science if an approval was made during his four years. They argue using the blanket denier-for-hire mantra; there could be unintended consequences.

Like what? The outcomes they invent are more magic than mosquito reality, such as that Frankenflies will escape and create mutant offspring. In science realty, male Aedes aegypti mosquitoes are harmless, they don't bite us. These time-limited males mate with females and simply can't have pestilence offspring.

A new study thinks it can fill the gap in the concern activists say they have.(1) What the scientists behind the paper use as their selling point is they won't have the "environmental complications" of GMO mosquitoes that can't reproduce, because by using CRISPR they have created mosquitoes that can't replicate the Zika virus at all, so females won't send it to humans when they bite.

Scientifically, that is great, but people with experience fighting the war on science know that it won't change anything. Science is a veneer for environmentalists. Activists hate CRISPR as much as they hate GMOs or RNAi or everything except the organic food created using Mutagenesis chemical and radiation baths. They will oppose this because the trait that keeps them from transmitting zika is heritable. It can be passed down. That will be spun into world-class "environmental complications" and Frankenbug unintended consequences so dumb even that terrible Dustin Hoffman movie Outbreak didn't try to use them.

If this gets close to testing, and the propaganda campaign against it ensues, the authors will then scramble to assure the public that Aedes aegypti proteins are not expressed salivary glands so humans are not at risk, this cannot mutate, etc., but they are not equipped to combat the disinformation and misinformation of a $2 billion-a-year marketing machine. By then half the public is already against it, the same way Democrats oppose the Keystone Pipeline despite Obama administration scientists clearing it - twice, the second time after Obama staffers made them do it again because they wanted to ban it.

That's a problem down the road, though. For now, applied use isn't even a discussion, it is just intriguing basic research on how we might solve an infectious disease problem in a way that might make people feel better than pesticides.

The problem is that environmentalists have turned all of biology into their new "Silent Spring" fundraisers. That's ironic, because Rachel Carson believed biological solutions like this were the ideal replacement for pesticides.

NOTES:

(1) Which falls into the real trap of activists; it is not about science, they claim you can fix the thing they object to but they will then move onto another. See Golden Rice. Academics believed that the concern was really about corporate control over food, and was not a war on science itself, so they created a public domain fortified bowl of rice. They quickly learned it was not about Monsanto at all. Having no corporate sponsor, they had no lawyers, but environmentalists are lawyer-heavy, and blocked its approval easily, while their marketing groups and academic allies insisted it would not work anyway.

Continue reading here:
An Alternate Approach To Stopping Mosquitoes That Spread Zika - Using CRISPR To Make Them Resistant To Carrying It - Science 2.0

Recommendation and review posted by Bethany Smith

Global CRISPR and CAS GeneMarket, By Product Type (Vector-based Cas and DNA-free Cas), By Application (Genome Engineering, Disease models, Functional Genomics, Knockdown/activation, and Other Applications), By End User (Biotechnology and Pharmaceutical Companies,Academic Government Research Institutes, and Contract Research Organizations), and By Region (North America, Latin America, Europe, Asia Pacific, Middle East, and Africa) was valued at US$ 1,388.1 million in 2017, and is projected to exhibit a CAGR of 20.8% over the forecast period (2018 2026).

Manufacturers in the CRISPR and CAS gene are collaborating with many companies for sponsoring clinical trials. Editas Medicine has licensed CRISPR and other gene editing patent rights from the Broad Institute, the Massachusetts Institute of Technology (MIT), Harvard University, and others. In March 2017, Editas reportedly entered into an agreement with Irish pharmaceutical company Allergan under, which Editas was to receive a US$ 90 million up-front payment for an option to license up to five preclinical programs targeting eye disease. Moreover, various organizations are also focusing on new clinical trials for the CRISPR and CAS gene for cancer treatment. In 2018, CRISPR Therapeutics and Vertex launched the first in-human clinical trial of CRISPR genome editing technology sponsored by U.S. companies. The trial is testing an experimental therapy for the blood disorder -thalassemia in Regensburg, Germany.

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Increasing research and studies regarding the CRISPR and CAS gene technology is majorly driving the growth of CRISPR and CAS gene market. In 2017, Editas partnered with Juno Therapeutics for cancer-related research using CRISPR. Under the terms of the agreement, Juno had to pay Editas an initial payment of US$ 25 million, in which up to US$ 22 million will be used in research support for three programs over five years. Editas has also engaged in a three-year research and development (R&D) collaboration deal with San Raffaele Telethon Institute for Gene Therapy to research and develop next generation stem cell and T-cell therapies for the treatment of rare diseases.

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Read more:
CRISPR and CAS Gene Market to Score Past US$ 7603.8 Million Valuation by 2027: CMI KSU | The Sentinel Newspaper - KSU | The Sentinel Newspaper

Recommendation and review posted by Bethany Smith