HHAL MEDICAL NEWS MAY 2011

Diet and MRI-Confirmed Infarcts in Elders

Among people aged 65 or older, compliance with a Mediterranean diet significantly reduced the prevalence of brain infarcts.

Scarmeas N et al. Ann Neurol 2011 Feb 69:257

Zolpidem and Driving

A single dose may impair driving the next morning in people older than 55.

Bocca M-L et al. Psychopharmacology (Berl) 2011 Apr 214:699

Add-On Drugs Compared for Uncontrolled Type 2 Diabetes

In the treatment of type 2 diabetes not controlled by metformin and a sulfonylurea, no add-on drug has an obvious advantage over another, according to an Annals of Internal Medicine network network meta-analysis.

Researchers examined 18 trials comprising 4500 participants with uncontrolled diabetes. (The add-on treatments were thiazolidinediones, glucagon-like peptide-1 agonists, dipeptidyl peptidase-4 inhibitors, insulins, and acarbose.) The following effects were noted:

· No drug class had an advantage in controlling glycated hemoglobin levels.

· Insulins and thiazolidinediones were associated with weight gain.

· Glucagon-like peptide-1 agonists were associated with weight loss.

· Insulins were associated with a doubled frequency of hypoglycemic episodes.

The authors acknowledge the limitations of network meta-analysis, in which some treatments are compared indirectly. They conclude that, in choosing a third drug, an individual patient's clinical features such as weight and hypoglycemia need to be considered.

Annals of Internal Medicine article article -and 3% in women were attributable to drinking.

Schütze M et al. BMJ 2011 Apr 7; 342:d1584

FDA Approves Linagliptin for Type 2 Diabetes

The FDA has approved linagliptin (marketed as Tradjenta) to improve glucose control in patients with type 2 diabetes, the agency announced on Monday.

Linagliptin inhibits dipeptidyl peptidase-4, thus boosting incretin hormones that stimulate postprandial insulin release. It is an oral treatment intended to complement diet and exercise.

Eight trials have found linagliptin effective as a stand-alone treatment or when used in combination with metformin, glimepiride, or pioglitazone. It is not intended to be used in patients with diabetic ketoacidosis or type 1 diabetes.

The drug's most common side effects include upper respiratory infection, stuffy or runny nose,sore throat, muscle pain, and headache.

Linagliptin prescribing informationLinagliptin prescribing informationLinagliptin prescribing information

Bisphosphonates and Atypical Fractures: New Data from Sweden

Relative risk was higher among bisphosphonate users, but absolute risk was small; risk fell rapidly after drug discontinuation.

A recent population-based study suggested that long-term bisphosphonate use raised risk for atypical femoral fractures involving the subtrochanteric region or shaft (JW Gen Med Mar 3 2011). Now, investigators have reviewed fractures that occurred during 2008 among all older Swedish women (age, 55). Of 1271 subtrochanteric or femoral shaft fractures, 59 were atypical according to strict radiological criteria.

The relative risk for atypical fracture associated with bisphosphonate use, compared with no use, was 47.3; this corresponded to 5 additional cases per 10,000 patient-years of bisphosphonate use. In a comparison between the 59 atypical cases and 263 controls with typical subtrochanteric or shaft fractures, 78% of cases and 10% of controls had used bisphosphonates (adjusted odds ratio, 33.3). This elevated risk was similar with use of alendronate and risedronate, and was not further increased with concomitant use of corticosteroids or proton-pump inhibitors. Likelihood of atypical fracture rose with duration of bisphosphonate use (risk was elevated 10-fold within the first 2 years of use and 50-fold with longer use), but fell after discontinuation: A 70% reduction in risk was observed for each year after last use, regardless of duration of prior use.

· Medline abstract

Greater Role for Leukotriene-Receptor Antagonists in Asthma?

In real-world practices, these drugs compared favorably with guideline-recommended first-line agents.

NIH asthma guidelines recommend inhaled corticosteroids (ICS) as first-line treatment for patients who have mild persistent asthma, with addition of a long-acting β-agonist (LABA) for uncontrolled symptoms. Previous double-blind randomized trials — conducted with tightly managed methodology — typically showed that ICS and LABAs were superior to leukotriene-receptor antagonists (LTRAs) for those indications. Now, two open-label randomized pragmatic U.K. studies provide a real-world perspective.

In one study, 300 treatment-naive asthma patients received oral LTRAs (montelukast [Singulair] or zafirlukast [Accolate and generics]) or ICS (beclomethasone, budesonide, or fluticasone). In the other study, 350 patients with uncontrolled symptoms who already were receiving low-dose ICS received an LTRA or a LABA. The patients (age range, 12–80) were managed in 53 primary care practices; patients' primary physicians determined asthma diagnoses and need for step-up therapy. The primary outcome was asthma-related quality of life, and secondary endpoints included asthma control and exacerbations. In both the first-line and add-on studies, no significant differences were found between the LTRA groups and the comparison groups for any outcomes during 2-year follow-up. Adherence rates were higher for LTRAs than for ICS (65% vs. 41% in the first-line trial) or LABAs (74% vs. 46% in the add-on trial).

Medline abstract (Free)

Conventional Wisdom on Salt Questioned

A JAMA study calls into question the current dogma on limiting the population's salt intake and on salt's health effects. Initial reaction to the study, as reported in the New York Times, is skeptical.

Researchers followed a European cohort comprising roughly 3700 subjects without cardiovascular disease at baseline. All had 24-hour urine sodium excretion measured at enrollment.

After a median follow-up of almost 8 years, cardiovascular mortality was highest among participants in the lowest tertile of sodium excretion, and the inverse-association trend retainedstatistical significance after multivariable adjustment. Sodium excretion was not associated with all-cause mortality.

The incidence of hypertension did not rise with increasing tertiles of sodium excretion. Each 100-mmol increase in excretion was associated with a 1.7-mm Hg increase in systolic pressure, but diastolic pressure did not correlate with excretion.

The authors note that their findings "do not negate the blood pressure-lowering effects of a dietary salt reduction in hypertensive patients." Critics echo the authors' own list of their study's limitations, including the relative youthfulness of the cohort (averaging about age 40), and the inclusion of only white Europeans.

JAMA article article

Study questions guidelines on salt consumption
European researchers looked at data on almost 3,700 people and found that 4% of those with the lowest salt consumption died from cardiovascular disease, compared with 1% among those who had the highest intake, although consumption was not linked to a risk of heart and blood vessel disease. Dr. Jan Staessen, lead author of the study, which appears in the Journal of the American Medical Association, said the results don't back salt-intake guidelines, noting that lower salt consumption might have benefits but also adverse effects. Reuters (5/3),CNN/Health.com
High Dietary Calcium Has No Apparent Beneficial Effect on Fracture Risk
Dietary calcium intake above certain levels has little effect on women's risk for fracture orosteoporosis, according to a BMJ study.
Researchers followed some 60,000 women, aged about 55 at study entry, for 20 years. Calcium intakes were estimated with food-frequency questionnaires, and a subcohort underwent measurements of bone mineral density.
Subjects were separated into quintiles by cumulative calcium intake. Those in the lowest quintile were at greatest risk for having a first fracture of any type, hip fracture, or osteoporosis during follow-up, when compared with the middle quintile (reference group). After multivariable adjustment, those in the remaining higher-intake quintiles showed no greater advantage for avoiding fracture. In fact, hip fracture risk increased among those with the highest calcium intakes.
The authors say their results suggest that in preventing osteoporotic fractures, "emphasis should be placed on individuals with a low intake of calcium rather than increasing the intake of those already consuming satisfactory amounts."
BMJ article article
Angiotensin-Receptor Blockers Aren't Associated with Adverse Cardiovascular Outcomes
In contrast to results from a 2004 study, a meta-analysis showed no excess risk.
In 2004, a randomized trial suggested that valsartan (Diovan), an angiotensin-receptor blocker (ARB), was associated with excess risk for myocardial infarction (MI; JW Gen Med Jul 13 2004). In this systematic review and meta-analysis, investigators assessed whether risks for adverse cardiovascular (CV) and other outcomes were associated with use ofARBs.
The analysis included 37 randomized trials in which placebo or active antihypertensive treatments were compared with ARBs (147,000 patients with average follow-up of 3.3 years). Compared with placebo or active-treatment, ARBs were not associated with excess risk for all-cause death, CV-related death, or angina (relative risks, 1.0 for all outcomes). Furthermore, ARBs were not associated with excess risk for MI (RR, 0.99; 95% confidence interval, 0.92–1.07). In contrast, ARBs were associated with significantly lower risks for stroke (relative reduction, 10%), heart failure (13%), and new-onset diabetes (15%). The results were similar when ARBs were compared with either placebo alone or with active treatment alone.
Comment: In this large meta-analysis, ARBs were not associated with excess risk for MI, all-cause death, CV-related death, or angina. Furthermore, ARBs lowered risks for stroke, heart failure, and diabetes. These results should reassure clinicians who prescribe ARBs and patients who use ARBs to combat hypertension
Medline abstract
In England, cessation of antibiotic prophylaxis for dental procedures was not associated with a significant increase in the incidence of infective endocarditis.
Thornhill MH et al. BMJ 2011 May 3; 342:d2392
Selenium for Graves Orbitopathy?
May 19, 2011 | Allan S. Brett, MD
A small randomized trial suggests that selenium is safe and effective.
Marcocci C et al. N Engl J Med 2011 May 19; 364:1920
Memantine Is Not Effective for Mild Alzheimer Disease
Off-label use of memantine for mild AD is not supported by the findings of a meta-analysis that focused specifically on patients with mild disease.
Memantine is an N-methyl-D-aspartate receptor antagonist that has been approved in the U.S. and Europe as a treatment for moderate-to-severe Alzheimer disease (AD). It is also frequently used off-label for mild AD. To determine whether such use is warranted, researchers conducted a meta-analysis of randomized, double-blind, placebo-controlled, memantine trials that included patients with mild AD. They identified three such trials, each lasting 24 weeks: two U.S. studies of patients with Mini-Mental State Examination (MMSE) scores of 10 to 22 (1 study allowed concurrent use of cholinesterase inhibitors) and a European study of patients with MMSE scores of 11 to 23. Of the 1128 participants in these trials, 431 (38%) had mild AD (MMSE score, 20–23).
In none of the trials (either individually or combined) did patients specifically with mild AD derive a significant benefit from memantine over placebo in cognitive function, global functioning, activities of daily living, or observed behavior. Given that placebo recipients with mild AD tended to improve on cognitive measures and to remain stable on global measures, drug effects, if any, would have been difficult to discern in trials of this size and duration.
Comment: This study involved a clever re-examination of data from six memantine trials included in two previous manufacturer-funded meta-analyses that reported positive findings. A meta-analysis from Europe (Alzheimers Dement 2007; 3:7) specifically excluded patients with mild AD, and the other, from the U.S. (Dement Geriatr Cogn Disord 2007; 24:20), collectively analyzed patients at all disease stages. The current, non–industry-supported meta-analysis, which focused specifically on patients with mild AD, documented no advantage of memantine over placebo on any analyzed measures. Off-label use of memantine in patients with mild AD, which is common in clinical practice, is simply not supported by these newly published data.
Stop taking aspirin? Beware of dosage
Regular aspirin use is associated with gastrointestinal bleeding. Risk seems more strongly related to dose than duration of aspirin use. Efforts to minimize adverse effects of aspirin therapy should emphasize using the lowest effective dose among both short- and long-term users. The American Journal of Medicine
Painkillers might increase risk of death or heart attack recurrence
Heart attack survivors taking a nonsteroidal anti-inflammatory drug or a selective Cox-2 inhibitor for a week have a 45% higher overall risk of death or recurrence, and using the medicine for three months increases the risk to 55%, according to a Danish study in Circulation: Journal of the American Heart Association. The findings reinforce the group's 2007 recommendation "that NSAID use should be avoided and if unavoidable should be used at the smallest doses for the shortest time possible," said Elliott Antman, who authored the advisory.WebMD

Panel: Lifestyle has not been proven to alter Alzheimer's risk
While several studies on links between Alzheimer's disease and lifestyle changes are available, the evidence is insufficient to conclude that lifestyle interventions would reduce the risk for the illness, an NIH panel said. The panel said old age and family history are still the most reliable indicators of Alzheimer's risk, noting a need for large, long-term, population-targeted investigations on how to slow or stop Alzheimer's progression. Reuters
For some, heart failure means fracture risk
The authors report that for this community, the association with fracture risk was about as strong before as after the diagnosis of heart failure and was nearly entirely attributable to hip fractures. Additional work is needed to identify common underlying mechanisms for heart failure and hip fracture, which may define prevention opportunities. The American Journal of Medicine
CDC reports increasing rates of asthma
The CDC reported that the number of Americans with asthma rose from 20.3 million to 24.6 million between 2001 and 2009, with children, adult women, blacks and low-income or "near poor" people having higher rates of the condition. Researchers noted that the reasons for the increase remain unclear but that death rates from the disease have dropped over the same time span. The Wall Street Journal (tiered subscription model) (5/4), Reuters
Study challenges use of BMI to predict mortality
A study conducted in the U.S. and three other countries suggests that fat distribution may more comprehensively gauge the link between being overweight or obese and mortality risk than body mass index. Researchers also wrote in the Journal of the American College of Cardiology that the mortality risk for patients with clogged or obstructed arteries is better determined using waist circumference and waist-to-hip ratio than BMI. Los Angeles Times/Booster Shots blog
WHO Group Says Cell Phones 'Possibly' Carcinogenic
Electromagnetic radiation generated by cell phones is "possibly carcinogenic" to humans, the WHO's International Agency for Research on Cancer concludes.
According to a WHO press release, an international working group of 31 scientists analyzed hundreds of studies and found — on the basis of "limited" evidence — a positive association between wireless telephone use and glioma. The group cited one study that showed a 40% increased risk for glioma among the heaviest users (people who reported using their cell phones 30 minutes daily over 10 years). However, chance, bias, or confounding could not yet be ruled out, so electromagnetic radiation was given the "2B" classification as being possibly carcinogenic.
IARC director Christopher Wild said that further research needs to be done on heavy, long-term use of cell phones. Until those results are published, he added, "it is important to take pragmatic measures to reduce exposure such as hands-free devices or texting."
IARC news release
New York Times "Well" blog
Exercise the Arms, Benefit the Legs
Supervised arm exercises improved walking distance in patients with vascular claudication.
Saxton JM et al. J Vasc Surg 2011 May 53:1265

Vitamin D Deficiency and Death?
In an 11-year observational study among critically ill patients, hypovitaminosis D was a risk factor for positive blood cultures, sepsis, and mortality.
Braun A et al. Crit Care Med 2011 Apr 39:671
Drug combo improves BP of senior patients with diabetes, experts say

Patients with diabetes ages 55 and up treated with aliskiren-hydrochlorothiazide had better systolic blood pressure rates than those who had hydrochlorothiazide treatment alone, according to a study by the Medical University of South Carolina in Charleston. Experts found that 47.1% of patients with metabolic syndrome or diabetes who went on aliskiren-HCTZ medication attained ideal BP levels compared with 34.6% of those in HCTZ therapy alone.Renal and Urology News
Preterm birth predicts increased blood pressure
Children born preterm show higher risk for increased blood pressure and arterial stiffness at age 14.(Full-text access is time-limited) Journal of Adolescent Health
Obesity raises risk of infection for colectomy patients
Obese patients undergoing colectomies were 60% more likely to develop surgical-site infections than their nonobese counterparts, according to a study in the Archives of Surgery. Researchers found that 14.5% of obese patients suffered infections compared with 9.5% of nonobese patients. Medscape
Eating Fish to Prevent Preterm Birth: No Need to Go Overboard
Moderate dietary fish consumption was associated with lower risk for recurrent PTB; greater intake did not provide further protection.
Supplementation with -3 fatty acids beginning at 16 to 21 weeks' gestation does not prevent recurrent preterm birth (PTB) in high-risk women, but is prior dietary fish intake beneficial? In a substudy of their trial of -3 supplementation to avert PTB in women who had experienced one or more preterm deliveries, U.S. investigators from the Maternal Fetal Medicine Units Network evaluated fish consumption before study enrollment. A total of 852 participants completed food frequency questionnaires to assess fish intake during the time from last menstrual period to randomization.
PTB occurred in 49% of the 253 women who ate fish once monthly or not at all compared with 36% of the 599 women who ate fish more often (P<0.001). In analysis adjusted for many variables (e.g., age, education, smoking status, body-mass index, race or ethnicity, number of previous PTBs), risk for PTB fell with increasing fish consumption, reaching a nadir at an intake of three times weekly (adjusted odds ratio, 0.60).
Klebanoff MA et al. Fish consumption, erythrocyte fatty acids, and preterm birth. Obstet Gynecol 2011 May; 117:1071.
Medline abstract (Free)
Vitamin B for PMS?
Higher dietary intake of thiamine and riboflavin was associated with lower risk for new-onset premenstrual syndrome.
The etiology of premenstrual syndrome (PMS) remains elusive. To evaluate possible associations between dietary B vitamin intake and development of PMS, investigators conducted a case-control study nested within the Nurses' Health Study, a longitudinal cohort of women who provide biennial reports of diet and lifestyle factors and health outcomes. During 10 years of follow-up, PMS was diagnosed in 1057 participants (36%); 1968 women were identified who did not have PMS or other menstrual symptoms.
Women in the highest quintile of thiamine intake were 25% less likely to develop PMS than were those in the lowest quintile, and women in the highest quintile of riboflavin intake were 35% less likely to develop PMS. Intake of B vitamins from supplements did not lower risk for PMS — probably a reflection that such supplements often are prescribed for management of PMS.
Chocano-Bedoya PO et al. Dietary B vitamin intake and incident premenstrual syndrome. Am J Clin Nutr 2011 May; 93:1080.
Medline abstract (Free)
Trial of Niacin to Increase HDL in High-Risk Patients Stopped Early After Showing No Benefit
A major government study has been stopped early because it showed no benefit to raising HDL levels with niacin in patients at high risk for cardiovascular events, the National Heart, Lung, and Blood Institute announced Thursday.
In the AIM-HIGH trial, the rate of MI, stroke, hospitalization for acute coronary syndrome, or revascularization among some 3400 patients did not differ between a group taking statin plus high-dose niacin and one taking statin plus placebo during 32 months' follow-up. All patients had well-controlled LDL levels at entry, but had low HDL levels and high triglycerides.
Asked to comment, Dr. Harlan Krumholz of Journal Watch Cardiology wrote: "This study reinforces that medications that change a risk factor do not necessarily change patient risk. Niacin, fibrates, and ezetimibe have so far failed to show that they improve patient outcomes in patients on statins. Be on guard for claims that are based only on how an intervention affects a risk factor — we need studies that show us the effect of these drugs on outcomes that patients experience."
NIH news release
Kids Who Sleep More Are Less Likely to Become Overweight
The more sleep that young children get, the less likely they are to become overweight, according to a longitudinal study in BMJ.
Researchers in New Zealand followed some 240 children from ages 3 to 7. Sleep was measured with accelerometers at ages 3, 4, and 5, while body mass index and body composition were measured yearly.
After multivariable adjustment, each additional hour of sleep from ages 3 to 5 was associated with a reduction in BMI of 0.49 at age 7 — corresponding to a reduction in body weight of 0.7 kg in a child of median height. Differences in fat mass index, rather than fat-free mass index, accounted for the reduced BMI. In addition, each extra hour of sleep was associated with a 61% reduction in the risk for being overweight at age 7.
The authors speculate that both behavioral and hormonal factors may play a role in the sleep-weight connection.
BMJ article
For Which Conditions Is Tai Chi Effective?
Systematic review finds benefit only for falls prevention and psychological health.
Tai chi, a gentle exercise program that emphasizes controlled breathing and relaxation, has been evaluated as a potential therapy for many diseases and chronic conditions, but results are inconsistent (JW Gen Med May 3 2011 and JW Gen Med Aug 19 2010). Several recent systematic reviews have been conducted to resolve these inconsistencies, and this study is a "review of the reviews." After a search of the English, Chinese, and Korean medical literature, researchers identified 35 systematic reviews of tai chi; at least 11 reviews were conducted by one of the authors of this meta-review.
The 35 reviews addressed the value of tai chi in more than 15 diseases and chronic conditions, including cancer, Parkinson disease, rheumatoid arthritis, and cardiovascular disease. Of the four reviews that addressed falls prevention, three showed positive benefit, and one was equivocal. Of the five reviews that addressed psychological health, four were positive, and one was equivocal. The remaining reviews showed no consistent benefit for
Lee MS and Ernst E. Systematic reviews of t'ai chi: An overview. Br J Sports Med 2011 May 16; [e-pub ahead of print]. (http://dx.doi.org/10.1136/bjsm.2010.080622
What best predicts mortality in acute chest pain?
B-type natriuretic peptide (BNP) accurately predicts mortality in unselected patients with acute chest pain independently of and more accurately than cardiac troponin T. However, these authors report that BNP does not seem to help in the early diagnosis of acute myocardial infarction. The American Journal of Medicine
How to prevent contrast-induced nephropathy in angiography

This study concluded that sodium chloride plus sodium bicarbonate is more effective than sodium chloride alone for prophylaxis of contrast-induced nephropathy, and can lead to the retention of a better long-term renal function. The American Journal of Cardiology