Hot flashes are a common symptom of menopause. Lasting from two to 30 minutes per episode, they usually begin with a sensation of intense heat on the face or chest which then spreads to other parts of the body. This sensation is often associated with sweating and tachycardia.

Not all women experience hot flashes, and for many others the symptoms amount to little more than a minor annoyance. But for some, hot flashes are down right debilitating. They have been known to precipitate fainting, for example. Some women experience several dozen hot flashes per day, and each one is severe enough to interrupt sleep or force them to cease normal activities until it subsides.
 
Hormone replacement therapy works like a charm for nearly all affected women, but it has fallen out of favor in the last decade or so, after scientists showed the therapy increased the risk of cardiovascular disease and breast cancer, among other things.

Women who suffer debilitating hot flashes, and the physicians who treat them will thus be heartened to learn that the antidepressant Lexapro reduces the frequency and severity of hot flash symptoms.

That’s the conclusion reached by Ellen Freeman and colleagues at the University of Pennsylvania, who recently published their findings in JAMA.

To reach this conclusion, Freeman’s team randomized 205 healthy menopausal women to receive either Lexapro or a placebo. Each volunteer reported experiencing at least 28 hot flashes per week. As a group, they averaged 9.8 hot flashes per day before the study began.

Women who didn’t have a favorable response after 4 weeks had their dose doubled from one pill to two (for those receiving Lexapro, this meant doubling the dose from 10mg to 20 mg).

After the 8-week study, women who took Lexapro reported experiencing 5.3 hot flashes per day, a 47% drop from baseline levels. Interestingly, the women who took placebo saw their hot flashes drop by 33%, to 6.4 per day, a finding that was significant in its own right.

In addition, Lexapro rendered the hot flashes less bothersome. Women in the Lexapro group said the severity of their hot flashes dropped by 0.6 on a 4-point scale, which compared favorably to the 0.4 point drop reported by women who received placebo.

Freemen’s group suggested that their findings were impressive enough for the drug to be given consideration as a first-line treatment for hot flashes. They cautioned however that the sizable placebo effect suggests “the importance of nondrug factors in clinical care and the potential for nonmedical approaches as other possible therapies for reduction of hot flashes.”

Still, the results of this study suggest Lexapro isn’t nearly as effective as hormone replacement therapy, which eradicates the symptoms in fully 95% of women. What is more, scientists have little knowledge about the long-term effects of Lexapro on healthy, non-depressed women, or what might happen when the drug is withdrawn.

“Will these women become depressed; will they have withdrawal problems?”wondered Wulf Utian, in an email to MedPageToday responding to Freeman’s report. “We simply do not know, and until such time as there is adequate safety information, I would advise clinicians to tread carefully before prescribing, and women to be cautious,” added Utian, who is the former executive director of the North American Menopause Society.

In developed nations, human life expectancy has increased steadily for over a century. One of the few negative consequences of this trend has been a marked increase in the prevalence of Alzheimer’s disease, an age-related untreatable condition that has driven enormous health spending on a national scale and wrecked the finances of millions of families in the US alone. Now, with the oldest Baby Boomers just reaching age 65, Alzheimer’s disease seems destined to become a true national health crisis.

Two of the most vexing problems with this nasty disease are determining who has it and diagnosing it early enough (so scientists can understand how it progresses and someday, intervene to either cure it or halt its progression).

With current technology, the only way to accurately diagnose Alzheimer’s disease is at autopsy. Special tests of the deceased’s brain reveal the sine qua non of Alzheimer’s disease: amyloid plaques.

But last week, 2 studies appearing in JAMA provided rays of hope in this otherwise dismal state of affairs. We review them both below:

Brain Scan Detects Plaques
In the first study, scientists injected a radioactive dye known as Flobetapir F 18 into the blood of elderly volunteers, and then used PET scans to image their brains.  Florbetapir F 18 had been designed by Christopher Clark and colleagues at Avid Radiopharmaceuticals to bind to amyloid proteins—which are the main constituents of amyloid plaques—and thus make them visible in vivo using the PET scan.

The PET scans correctly identified amyloid plaques in 97% of the volunteers that actually had them, as proven at autopsy. In addition, PET scans performed after the dye had been injected into young, healthy volunteers revealed no plaques.

Scientists believe the Florbetapir F 18 PET scans could be helpful as a means to exclude the diagnosis of Alzheimer’s. If no plaques are found in a patient with symptoms of dementia, physicians would be compelled to consider other causes of the symptom complex. The PET scans could also potentially be used to test drugs designed to remove amyloid from the brain.

A Blood Test for Alzheimer’s
The second study showed that blood levels of amyloid protein, as detected by a new blood test, were correlated with memory problems.

The study was directed by Kristine Yaffe at UCSF. Her group recruited 997 elderly volunteers and followed them with memory tests and amyloid blood tests for 9 years.

Yaffe’s group found that subjects with the highest blood levels of amyloid protein were less likely to experience declining mental abilities, a result that seems counterintuitive but is in fact consistent with what scientists had expected based on their knowledge of amyloid protein physiology as the disease progresses.

Interestingly, the inverse relation between blood amyloid protein levels and mental capacity was less apparent in subjects with higher educational levels at study onset. Yaffe’s group was careful not to suggest that people who remain mentally active could be spared from Alzheimer’s disease, but suggested that the finding demands further study.

Quick Take
Yaffe’s test is, unfortunately not accurate enough to be useful in clinical settings right now, and the PET scanning approach mentioned above is too expensive for routine clinical use. Nevertheless, these 2 studies represent progress in an area where it is badly needed. We’ll take what we can get and keep our fingers crossed that the science moves as fast as the epidemic.

People know it’s important to avoid excessive weight gain as they get older, and that exercise is a key to success in this regard. But until recently, scientists had published surprisingly few studies purporting to quantify the impact of habitual exercise on weight gain over the long haul.

Arlene Hankinson and her colleagues at Northwestern set out to do just that. Using data from a prospective follow-up study, Hankinson’s group showed that men who were able to maintain high activity levels over an extended period gained 6 fewer pounds, and 5 fewer centimeters of waist circumference than those in the lowest activity group. Women in the highest activity group gained 13 fewer pounds and nearly 7 centimeters less around their waists.

To reach these conclusions, the scientists examined data from the Coronary Artery Risk Development in Young Adults (CARDIA) study, which is a 20-year longitudinal study that began in 1985. CARDIA included complete historical data for 3,554 men and women from Chicago, Birmingham, Minneapolis and Oakland. Enrollees were 18 to 30 years old at study onset. 

During each follow-up visit, CARDIA enrollees completed questionnaires regarding their activities and exercise habits. Each activity had been assigned a numerical score ranging from 108-288 by the scientists. Activity scores were summed for each individual to yield a total score.

The authors subsequently divided study participants into 3 tertiles according to their total score. To be assigned into a more active tertile, subjects had to qualify on points for at least 2/3 of all follow-up visits.

Remarkably, only 12% of study participants met criteria for the highest activity group. The reason, Hankinson said in an interview with USNews, is consistency. “It’s not that it’s hard to achieve high levels of activity,” she remarked. “It’s that it’s difficult to maintain them over time.”

Hankinson therefore recommends finding activities that are enjoyable. “Whatever activity you do, the whole point is that you’re doing something that you are going to maintain over a lifetime,” she explained. And vigorous activities like marathons and lifting heavy weights are not necessary to fall into that “high activity” group in Hankinson’s study. All that’s required is about 2 ½ hours per week doing things that get one’s heart rate up. So things like step aerobics, dance, speed walking and the like are perfectly adequate.

It’s also essential to note that folks in all activity groups in Hankinson’s study did gain at least some weight. The take-home message is that exercise alone isn’t going to be enough to maintain a stable body weight into and beyond mid-life. There’s simply no getting around the fact that dietary intake is the single most important factor in determining weight gain.

Hankinson’s write-up appears in the Journal of the American Medical Association.

Scientists have known for years that people with type 2 diabetes can benefit from exercise, although the precise roles played by aerobic exercise and resistance training have been somewhat of a mystery. Until now, that is.

In a paper published last month in JAMA, Timothy Church and colleagues from LSU showed that type 2 diabetes patients benefit more from an exercise regimen that combines the 2 forms of exercise than programs based on either one, alone.

To assess the relative effects of aerobic training and resistance training, Church’s group studied 262 sedentary male and female patients that had type 2 diabetes. In the 9-month study, dubbed HART-D, the average age of the patients was 56. They had diabetes for an average of 7 years. Their average HbA1c level was 7.7%, indicating moderately well controlled diabetes at study onset. Nearly half the patients were not Caucasian.

The scientists randomized enrollees into a non-exercise control group, a resistance training only group, an aerobic training only group, and a group that underwent combined aerobic and resistance training.

Participants in the 3 intervention groups spent about 140 minutes in supervised exercise per week, including time spent warming-up and cooling-down. Aerobic exercise involved walking fast enough on a treadmill to burn 12 kcal/kg per hour. Resistance training was divided into 3 sessions per week, and focused on the upper body, legs, abs and back. Participants in the combination training program engaged in resistance training only twice per week in order to keep total exercise time the same as the other groups.

The scientists found that the absolute change in HbA1c in the combination group compared to the control group was -0.34%. This compared favorably with an absolute change of -0.16% and -0.24% for the resistance only and the aerobic only groups.

Church’s group estimated that if such reductions were maintained for years, people with type 2 diabetes would reduce the risk of cardiovascular disease risk by 5% to 7% and the risk of microvascular complications by 12%.

Of great significance, Church’s group also noted that the frequency with which oral hypoglycemic drugs had to be increased was 18% in the combination group. This was significantly lower than the 22% for the aerobic training only group, 32% for the resistance training only group, and 39% in the controls. Without these aggressive interventions, the absolute improvements in HbA1c levels in the combined exercise group would almost certainly have been much greater, according to the scientists.

All exercise groups reduced waist circumference by about the same amount [-.75 to -1.1 inches] when compared to the control group.

In an accompanying editorial, Canadian researchers, Ronald  Sigal and Glen Kenny concluded that, “based on the results of the HART-D trial, patients with type 2 diabetes who wish to maximize the effects of exercise on their glycemic control should perform both aerobic and resistance exercise. The HART-D trial clarifies that, given a specific amount of time to invest in exercise, it is more beneficial to devote some time to each form of exercise rather than devoting all the time to just one form of exercise.”

One note of caution: Although this is clearly good news, the study may not be easily generalizable to the population at large because the study design required that all exercise sessions be supervised.  It turns out that without that pesky trainer and the forced adherence to an exercise regimen, many folks, whether they have diabetes or not, can’t manage to stick with an exercise plan.

The US health care system is generally recognized to be obscenely wasteful and to deliver poor value for the money. But even the most jaded observers are likely to be shocked by the results of a new study which shows that many patients with advanced or metastatic cancer and a correspondingly short life expectancy undergo routine screening tests like cholesterol checks, Pap smears, mammograms and PSA tests.

For example, 14% of male Medicare beneficiaries with advanced pancreatic cancer underwent PSA testing. Similarly, 18% of women with this condition had at least one mammogram and 5.4% had a Pap smear. Nearly 20% of these patients had a cholesterol test.

The appalling findings come from a study by Camelia Sima and colleagues at the Memorial Sloan-Kettering Cancer Center. These scientists looked at Medicare billing data from 88,000 beneficiaries that had been diagnosed with advanced cancer between 1998 and 2005.

The scientists compared utilization rates for screening tests in this group with a control group of Medicare enrollees that did not have cancer, but were matched by gender, age, race and area of residence.

The first group included patients with stage IIIb to IV lung cancer, advanced stage pancreatic cancer and stage IV breast,colorectal, and gastroesophageal cancer. The vast majority of these patients have a life expectancy of less than 2 years.

Screening rates for the cancer patients were about half that of their matched controls. There were no differences in screening rates for patients with each kind of cancer. Married and more affluent cancer patients tended to get more screening tests than their counterparts.

“In an ideal healthcare system, healthcare practitioners would discontinue cancer screening for patients whose prognosis is too limited for the benefits of early detection to be realized,” Sima’s team wrote. “Each medical specialty needs to engage in thoughtful self-scrutiny to identify episodes of unnecessary care,” they added.

The write-up appears in JAMA.

Physicians often have negative attitudes regarding obesity, and many express dissatisfaction about caring for obese patients. Meanwhile, obese patients often feel their physicians are disrespectful or biased against them because of their appearance.  Such observations raise concern that obese patients may receive lower quality care than non-obese patients.
 
Thankfully however, a recent study by Virginia Chang and colleagues from the University of Pennsylvania has shown that medical care for obese patients is at least as good, and in some instances marginally better than that provided to other patients.

To reach these conclusions, Chang’s group compared physicians’ performance on 8 common outpatient quality measures for obese vs. non-obese patients. The study population included 36,122 patients from the Medicare Beneficiary Survey (1994-2006) and 33,500 patients from the Veterans Health Administration (2003-2004).

The scientists tracked performance for diabetes care (eye examination, glycated hemoglobin testing and lipid screening), pneumococcal vaccination, influenza vaccination, screening mammography, colorectal cancer screening, and cervical cancer screening. Data were obtained from administrative claims, survey data and chart review.

Overall, they found no evidence to suggest that obese or overweight patients received “recommended care” less frequently than normal-weight patients. In fact, obese patients received recommended care for lipid screening (72% versus 65%) and glycated hemoglobin testing (74% versus 62%) more frequently than normal-weight diabetic patients.

“Even though physicians might harbor negative attitudes towards obese patients, it doesn’t seem to be borne out in the quality of care they’re delivering,” Chang told MedPage Today. “So I think both physicians and patients can feel some degree of relief on that front.”

The write-up appears in the Journal of the American Medical Association.

Clinical trials are often stopped early when they show a convincing, apparent difference between an experimental intervention and either a placebo or an existing standard of care. The rationale for halting such trials is to let participants who were randomized to the placebo switch to the apparently effective intervention, and to help get the presumably improved therapy to market.

However, a recent study by Dirk Bassler and colleagues at McMaster University suggests that halting trials early may lead to misleading overstatements concerning the apparent benefits of the intervention.

To reach this conclusion, Bassler’s team compared treatment effects from truncated randomized clinical trials (RCTs) with those observed in trials that addressed the same question but that were not halted early.

The analysis included 91 truncated RCTs and 424 matched, non-truncated RCTs. The results showed that the halted trials had reached exaggerated or misleading conclusions. Remarkably, 62% of the non-truncated RCTs showed no benefit at all for the intervention. Large differences between truncated and non-truncated trials were common when the truncated RCTs had fewer than 500 outcome events.

“Our research shows that in most cases early stopping of clinical trials resulted in misleading estimates of treatment effects,” Victor Montori, a Mayo Clinic endocrinologist and corresponding author of the study told BurrillReport.
 
The authors recommended that scientists truncate clinical trials only near the very end of a study and then only with “a very good reason.” Otherwise patients and physicians will be making treatment choices based on inaccurate information, or worse, opting for a treatment when another one may be more effective.

The study appears in the Journal of the American Medical Association.

Ever wonder how safe and reliable Granny’s new pacemaker is? In most cases it turns out nobody really knows, because the quality of the evidence used by the FDA to approve these devices is poor, according to a study published in JAMA last week.

Sanket Dhruva and colleagues from UCSF drew these conclusions after examining the premarket approval process (PMA) for 78 high-risk cardiovascular devices that received FDA approval between January 2000 and December 2007.

PMA is the most stringent FDA review process for medical devices. The scientists found that 65% of the PMA applications for devices were supported by exactly one study.

And overall, the quality of the studies was abysmal. Some failed to provide details like the number of enrolled participants. Only 27% of them were randomized and even less, 14%, were blinded (blinded, randomized, controlled trials represent state-of-the-art scientific research).

The scientists concluded that in general, the FDA’s premarket approval process for cardiovascular devices lacked statistical firepower required to control for bias and hence draw valid conclusions.

The scientists understood that it is more difficult to subject medical devices to blinded studies, since there is no way to produce a “sugar pill” (that is, placebo) for medical devices.

“But we were surprised that so many devices were approved on the basis of a single study,” Dhruva told the Los Angeles Times.

The FDA started approving medical devices in 1976. Recently, there has been a marked increase in the number of cardiovascular devices implanted in Americans.  In 2008, 1.2 million people received stents in the US alone. 350,000 people received pacemakers and 140,000 received implantable cardioverter-defibrillators.

When the so-called “atypical antipsychotic” drugs hit the market 15 years ago, psychiatrists and PCPs began prescribing them like crazy for schizophrenia and bipolar disorder.

They were motivated the poor side-effect profile of previously available drugs, and encouraged by relentless and occasionally unscrupulous marketing campaigns promulgated by drug makers and paid clinical spokespeople.

Last year, the drugs generated $14.6 billion in US sales alone, according to IMS Health.

Unfortunately, the newer drugs proved to be, at best, marginally more effective than their older, cheaper brethren, and have a nasty tendency to promote weight gain and diabetes, particularly in children—for whom they are rarely indicated, according to the FDA.

Now, Christolph Correll and colleagues at Feinstein Institute for Medical Research have quantified the weight gain problem, and it’s a lot.

According to their report in JAMA, atypical antipsychotic drugs caused youths between the ages of 4-19 years old to gain up to 19 pounds on average in just 11 weeks.

“The weight gain is much larger than we thought,” Correll told the Wall Street Journal. “It’s massive, and it’s the medication” that caused it, he added.

Correll’s study involved 272 youths who were seen at semi-urban, tertiary care, academic inpatient and outpatient clinics. It included the 4 top-sellers in the space: Zyprexa (Lilly), Abilify (BMS), Risperdal (J&J) and Seroquel (AZ). Participants had not taken the drugs previously.

Of the 4, Zyprexa caused the most weight gain—nearly 19 pounds—a 15% increase over baseline. The corpulence was associated with significant increases in glucose and cholesterol levels.

The other drugs caused weight gains between 10-13 pounds on average, and had variable effects on glucose and cholesterol.

The scientists encouraged physicians to be extremely careful when prescribing these drugs to youths and to check their patients’ weight and blood tests every 3 months.

The FDA will soon decide whether to approve these drugs for use in youths. Any bets how that turns out?

The Mediterranean diet may protect against age-related cognitive decline, according to 2 studies published in JAMA.

The diet, which is long on vegetables, fruits, whole grains and fish, and short on red meat and poultry, has already been lauded for its cardio-protective and cancer preventing effects.

The first of the 2 studies, organized by Nikolaos Scarmeas and colleagues at Columbia, showed that the diet and physical activity were independently associated with a reduced risk of Alzheimer’s disease.

Scarmeas’ team enrolled 1,880 older patients with no cognitive impairment at study onset, and performed neuropsychological testing every 18 months for a mean follow-up of 5.4 years.

Alzheimer’s disease was diagnosed in 282 subjects during the study. Subjects who followed the Mediterranean diet were 40% less likely to develop Alzheimer’s than those who did not.

Similarly, a high amount of physical activity, which the scientists defined for this elderly population to be 1.3 hours of vigorous, 2.4 hours of moderate, or 4 hours of light physical activity per week, cut the risk of Alzheimer’s by 33%.

In the second study, Catherine Feart and colleagues at Universite Victor Segalen showed that the Mediterranean diet slowed cognitive decline, though it did not decrease the risk of dementia per se.

In particular, Feart’s team found that those adhering to the diet had fewer errors on the Mini Mental State Examination, but performed no better on 3 other tests of cognition.

In an accompanying editorial, the Mayo Clinic’s David Knopman said the 2 studies “provide moderately compelling evidence that adherence to the Mediterranean-type diet is linked to less late-life cognitive impairment.”

Whether these findings “should be translated into recommendations for the public is the question,” added Knopman. “For now, it is reasonable to nibble on these findings and savor them, but not to swallow them whole.”