Cedars-Sinai Medical Center

BMI may be most vital determinant of basal metabolic rate in PCOS.

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The BMI of patients with polycystic ovary syndrome appeared to be the most important factor in basal metabolic rate, independent of the polycystic ovary syndrome phenotype and insulin resistance, according to Margareta D. Pisarska, MD, who presented the data at the conjoint meeting of the International Federation of Fertility Societies and the American Society for Reproductive Medicine.

“Based on our study — since we do think obesity does play a significant role — we believe it is important for endocrinologists to help counsel these women in a fashion similar to those who are obese by emphasizing that weight loss and lowering BMI are important,” Pisarska, director of the division of reproductive endocrinology and infertility; director of the Fertility and Reproductive Medicine Center at Cedars-Sinai Medical Center; associate professor at Cedars-Sinai Medical Center and the David Geffen School of Medicine at UCLA, told Endocrine Today.

 

The researchers conducted the case-control study examining the metabolic changes (ie, lean body mass, body fat mass, body fat percentage, skeletal muscle mass, BMI and basal metabolic rate) in 128 patients with PCOS (mean age, 28.1 years) and 72 eumenorrheic, non-hirsute controls (mean age, 32.9 years).

In terms of hormonal profile, patients with PCOS had greater testosterone, dehydroepiandrosterone sulfate (DHEA-sulfate), fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels compared with controls.

After controlling for age and BMI differences, there was no difference in body composition parameters between patients with PCOS and controls. There were no significant results regarding changes to the basal metabolic rate (P=.0162), lean body mass (P=.0153) or skeletal muscle mass (P=.0169), she said.

However, differences in fasting insulin and HOMA-IR remained significant. When looking at insulin resistance in women with PCOS as a potential factor affecting body composition and metabolic rates, there was also no difference between these groups.

“It is not necessarily PCOS; BMI and age are probably the more important determinants of basal metabolic rate, regardless of PCOS phenotype and insulin resistance,” Pisarska said.

BMI may be most vital determinant of basal metabolic rate in PCOS.

Posted by

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The BMI of patients with polycystic ovary syndrome appeared to be the most important factor in basal metabolic rate, independent of the polycystic ovary syndrome phenotype and insulin resistance, according to Margareta D. Pisarska, MD, who presented the data at the conjoint meeting of the International Federation of Fertility Societies and the American Society for Reproductive Medicine.

“Based on our study — since we do think obesity does play a significant role — we believe it is important for endocrinologists to help counsel these women in a fashion similar to those who are obese by emphasizing that weight loss and lowering BMI are important,” Pisarska, director of the division of reproductive endocrinology and infertility; director of the Fertility and Reproductive Medicine Center at Cedars-Sinai Medical Center; associate professor at Cedars-Sinai Medical Center and the David Geffen School of Medicine at UCLA, told Endocrine Today.

The researchers conducted the case-control study examining the metabolic changes (ie, lean body mass, body fat mass, body fat percentage, skeletal muscle mass, BMI and basal metabolic rate) in 128 patients with PCOS (mean age, 28.1 years) and 72 eumenorrheic, non-hirsute controls (mean age, 32.9 years).

In terms of hormonal profile, patients with PCOS had greater testosterone, dehydroepiandrosterone sulfate (DHEA-sulfate), fasting insulin and homeostasis model assessment of insulin resistance (HOMA-IR) levels compared with controls.

After controlling for age and BMI differences, there was no difference in body composition parameters between patients with PCOS and controls. There were no significant results regarding changes to the basal metabolic rate (P=.0162), lean body mass (P=.0153) or skeletal muscle mass (P=.0169), she said.

However, differences in fasting insulin and HOMA-IR remained significant. When looking at insulin resistance in women with PCOS as a potential factor affecting body composition and metabolic rates, there was also no difference between these groups.

“It is not necessarily PCOS; BMI and age are probably the more important determinants of basal metabolic rate, regardless of PCOS phenotype and insulin resistance,” Pisarska said.

Outcomes similar with different low-osmolar iodinated contrast agents.

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Among patients undergoing coronary angiography or percutaneous coronary interventions with low-osmolar contrast media (LOCM), adverse outcomes are uncommon, with no advantage apparent between different agents.

That finding comes from a retrospective look at data on more than 100,000 patients, reported in theAmerican Journal of Cardiology online March 22 by Dr. James K. Min, with Cedars-Sinai Medical Center in Los Angeles, California, and colleagues.

“In contrast to previous studies that compared LOCM to iso-osmolar contrast media, our study directly compared alternate LOCM for differences in clinical outcomes,” the authors point out.

They note that previous reports have suggested that iohexol may be associated with increased rates of contrast-induced nephropathy (CIN) compared to an iso-osmolar contrast medium, whereas this has not been reported with other LOCM such as ioversol and iopamidol.

To determine if there is any difference between LOCMs, the team looked at outcomes in patients exposed to iohexol (n = 20,136), iopamidol (n = 21,539), or ioversol (n = 66,319) during invasive coronary procedures.

Propensity scoring generated 19,482 matched pairs of patients exposed to iohexol versus ioversol, and 10,204 pairs exposed to iohexol versus iopamidol.

The researchers found no significant difference between the iohexol-ioversol pairs in rates of new inpatient hemodialysis (relative risk 0.72; p = 0.05), inpatient mortality (RR 0.90; p = 0.42), or 30-day readmission for CIN (RR 0.81; p = 0.52).

Outcomes were also similar between the matched iohexol-iopamidol patients in terms of inpatient hemodialysis (RR 1.18; p = 0.45), inpatient mortality (RR 1.09; p = 0.60), or 30-day CIN readmission (RR 1.11; p = 0.82).

“Encouragingly, in this large dataset, even before matching, rates of in-hospital hemodialysis and mortality and 30-day readmission rates for CIN were low for all patients, irrespective of contrast medium used,” Dr. Min and colleagues comment.

“After matching,” they conclude, “we could not identify any significant differences in adverse events for patients who underwent ICA and/or PCI with different LOCM.”

 

Source: Am J Cardiol 

 

Half of referred Parkinson’s disease patients are appropriate candidates for deep brain stimulation therapy.

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An interesting point made by US researchers in favour of early referrals for deep brain stimulation therapy:

While deep brain stimulation has gained recognition by referring physicians as a treatment for Parkinson’s disease and other movement disorders, just half of the patients they recommend are appropriate candidates to begin this relatively new therapy immediately, researchers at Cedars-Sinai Medical Center in Los Angeles and The Mount Sinai Medical Center in New York say.

 

Researchers looked back to a 2004 study, which found that just 5% of referrals then were good candidates; they compared their new figures and surmised that referring physicians have increased their awareness and acceptance of deep brain stimulation.

But physicians still often refer patients for this therapy before other treatment options have been exhausted or because they have unrealistically high expectations for it, said Michele Tagliati, director of the Movement Disorders Program at Cedars-Sinai’s Department of Neurology.
Of 197 patients referred for evaluation for deep brain stimulation, 50% were found to be good candidates for immediate therapy, 25% were possible future candidates and 24% were poor candidates because of other neurological or medical conditions.

 

Analysing the referral sources ― movement disorder specialists, primary care physicians, general neurologists, other physicians and patients ― the researchers found that movement disorder specialists referred more patients and most were good therapy candidates.

Over the four-year study period, which ended in late 2009, researchers noted that the number of patients referred for deep brain stimulation therapy at earlier stages of the disease increased. “The study does not address this change specifically and we have no proof, but we speculate that doctors became more liberal in sending patients for surgery for deep brain stimulation,” Tagliati said. “Maybe they are accepting this therapy more and sending patients earlier for it instead of at the very end stage of disease. While doctors may be sending some patients too early to be treated immediately with deep brain stimulation therapy, it is better to see these patients too early than too late. As long as they are evaluated in a responsible, reputable movement disorders centre, they can be reevaluated months or even years later and have the surgery appropriately timed. It is not always clear exactly what is the right time for this therapy, but especially for Parkinson’s disease, if the patient is amenable to medication changes, it is not appropriate to jump to the surgery right away.”

Deep brain stimulation was approved by the Food and Drug Administration for essential tremor in 1997, Parkinson’s disease in 2002, dystonia in 2003 and extreme cases of obsessive-compulsive disorder in 2009″

Source: BMJ

Panel Recommends Easing Restrictions on Rosiglitazone Despite Concerns About Cardiovascular Safety.

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Three years ago, amid concerns that rosiglitazone (Avandia) increases the risk of myocardial infarction and death due to cardiovascular causes, the US Food and Drug Administration (FDA) severely curtailed use of the blood glucose–lowering drug. But now an FDA advisory committee has recommended easing the severe restrictions on prescribing rosiglitazone, used to treat type 2 diabetes mellitus, even though cardiovascular safety concerns remain.

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At the joint meeting of the Endocrinologic and Metabolic Drugs Advisory Committee and the Drug Safety and Risk Management Advisory Committee, held June 5 and 6 at FDA headquarters in Silver Spring, Maryland, 13 members voted to modify the highly restrictive risk evaluation and mitigation strategy (REMS) applying to use of rosiglitazone, 7 voted to remove the REMS altogether, 5 voted to keep the REMS as is, and 1 voted for removal of rosiglitazone from the market. The REMS restricts access to rosiglitazone so that only prescribers who acknowledge the potential increased risk of myocardial infarction are prescribing the drug. The REMS also restricts rosiglitazone to patients who are already taking the drug or who are unable to achieve glycemic control with other medications and, in consultation with their physician, have decided not to take pioglitazone (Actos, the only other thiazolidinedione marketed in the United States) for medical reasons.

The vote was somewhat of a reversal from a 2010 FDA meeting of the same advisory committees (although with somewhat different personnel) in which 10 members voted to restrict availability of rosiglitazone and 12 voted to remove it entirely from the market, while another 3 voted to leave the label unchanged and 7 voted to add warnings. The 2010 vote, and subsequent action by the FDA, followed a decade of increasing concerns about the drug’s cardiovascular safety.

An advisory panel, after hearing testimony by researchers, is recommending the US Food and Drug Administration ease severe restrictions on rosiglitazone.

Rosiglitazone was given FDA approval in 1999 and quickly became a blockbuster drug for its manufacturer, GlaxoSmithKline (then SmithKline Beecham), ultimately generating more than $2 billion in annual sales, with about 120 000 US patients taking the medication. But researchers began to sound a safety alarm just a year later. Then, in 2007, a meta-analysis found that rosiglitazone increased the risk of myocardial infarction by more than 40% compared with a control (placebo or comparator drug) (Nissen SE and Wolski K. N Engl J Med. 2007;356[24]:2457-2471). And just before the 2010 advisory meeting, another study, observational and retrospective, found that compared with pioglitazone, rosiglitazone increased the risk of stroke, heart failure, and death (Graham DJ et al. JAMA. 2010;304[4]:411-418).

Even as studies were attacking the cardiovascular safety of rosiglitazone, a randomized controlled trial, RECORD, published results showing that compared with a treatment combination of metformin and sulfonylurea, rosiglitazone did not increase the risk of overall cardiovascular morbidity or mortality, although it did increase the risk of heart failure and some fractures (the latter mainly in women) (Home PD et al.Lancet. 2009;373[9681]:2125-2135). But at the 2010 advisory committee meeting, RECORD faced stiff criticism, as its design was open label, with GlaxoSmithKline employees having access to the data, and it appeared some data were missing. The FDA ultimately instituted the REMS, and today only about 3000 US patients take the drug.

The questions surrounding RECORD were such that the FDA asked the company to fund a readjudication of the data. That readjudication was the main reason for the June advisory committee meeting. There, results from the readjudication, performed by the Duke Clinical Research Institute, confirmed the original findings of RECORD. The readjudication gave some of the advisory panel members enough confidence to vote to ease prescribing restrictions on rosiglitazone, but others said the reexamination could never overcome the design flaws of the study.

David Juurlink, MD, PhD, head of the division of clinical pharmacology at the University of Toronto in Canada, who was not a panel member but who has raised cardiovascular safety concerns about rosiglitazone, said he found the RECORD readjudication reassuring to a point. “I have more confidence in the RECORD trial than I did before, but it’s not a well designed or executed trial,” Juurlink said. “So Duke had a flawed study to readjudicate, and it was ‘garbage in, garbage out.’”

Steven Nissen, MD, department chair of cardiovascular medicine at the Cleveland Clinic and coauthor of the 2007 meta-analysis, said he thought the June advisory meeting was intended by the FDA to get a recommendation to ease access to rosiglitazone—not only because of the readjudication of RECORD, but also to take pressure off the agency from critics who wondered why the drug was still on the market.

“The panel basically voted to keep the drug on restricted access, and from my perspective, it’s a good outcome,” Nissen said. “This is really about a bureaucracy that never wants to admit it made a mistake. It is tragic for public health that the people who approve the drug in the first place remain to act against the drug. It’s like a parent admitting their child is ugly.”

Jerry Avorn, MD, professor of medicine, Harvard Medical School, and chief of the Division of Pharmacoepidemiology and Pharmacoeconomics at Brigham and Women’s Hospital in Boston, questioned why the FDA even called for this advisory meeting. “For a drug that has quite impressive evidence of cardiovascular toxicity and heart failure and hip fracture, why would I want access to it?” Avorn said. “With all the pressing work regarding drug approvals and postmarketing surveillance, this seems like an odd prioritization for FDA’s time.”

Harlan Krumholz, MD, professor of medicine at Yale University School of Medicine in New Haven, Connecticut, called the hearing a waste of time. “I was perplexed why this merited 2 days of the FDA’s time and why there were changes in the recommendations when, by and large, the evidence remained the same since the previous meeting.”

But others justified the meeting, saying the evidence was still open for debate.

Sanjay Kaul, MD, MPH, director of the vascular physiology and thrombosis research laboratory at the Burns and Allen Research Institute at Cedars-Sinai Medical Center in Los Angeles, who was a member of both the 2013 and 2010 advisory panels, voted both times for restricting access to rosiglitazone, although at the latest meeting he favored easing the restrictions. He believes the safety evidence, both in 2010 and today, remains inconclusive. “This is a drug that was virtually killed on the basis of evidence that is not very convincing at best and dubious at worst,” Kaul said. “When confronted with uncertainty and the data are not of high quality, I say let the physicians make the choice on whether to give a medicine or not.”

Source: JAMA