HHAL MEDICAL NEWS MAY 2010

Infrequent Tooth-Brushing Linked to Higher Risk for Heart Disease

Adults who brush their teeth less than once a day face increased risk for heart disease, according to a BMJ study.

Nearly 12,000 Scottish adults answered questions about oral hygiene and then were followed for 8 years. During that time, there were 555 cardiovascular disease events, including 170 fatalities.

After adjustment for confounders, participants who brushed their teeth less than once a day were 70% more likely to suffer cardiovascular disease than those who brushed twice daily. In a subgroup analysis, poor oral hygiene was also linked to elevated C-reactive protein and fibrinogen levels.

The authors say their findings suggest "a possible role of poor oral hygiene in the risk of cardiovascular disease via systemic inflammation," and they stress the importance of counseling patients on the benefits of good oral health.

BMJ article (Free)

 http://www.bmj.com/cgi/content/full/340/may27_1/c2451

Recurrent Clostridium difficile Infection and Proton-Pump Inhibitors

PPI use during treatment for CDI was associated with excess risk for infection recurrence.

 Linsky A et al. Arch Intern Med 2010 May 10; 170:772

Does Fruit and Vegetable Intake Prevent Cancer?

A large prospective study suggests that benefits are modest at best.

 Boffetta P et al. J Natl Cancer Inst 2010 Apr 21; 102:529

Willett WC. J Natl Cancer Inst 2010 Apr 21; 102:510

Mammography in Women Who Are Younger Than 40

In women aged 35–39, the cancer detection rate was 1.6 per 1000 mammograms.

In 1992, the American Cancer Society dropped its recommendation of a "baseline mammogram" at age 35, but some people still espouse the practice. For example, on a recent Internet search of "mammography at age 35," I encountered endorsements at sites for newspaper health columns, hospitals and clinics, and women's health groups. I also encountered blogs voicing complaints by 35-year-old women that their insurance companies "didn't pay for a mammogram recommended by doctors."

To examine the yield of mammography in young women, U.S. researchers pooled data from six mammography registries that included 120,000 women who underwent first mammograms at ages 18–39. For every 10,000 screened women in the 35–39 age subgroup (which accounted for most of the screening mammograms), 1266 underwent further work-ups, with 16 cancers detected (true-positive mammograms) and 1250 false-positive mammograms. Stated another way, 79 work-ups were conducted for each cancer detected. The detection rate was no better among women who had first-degree relatives with breast cancer. The detection rate was considerably better for symptomatic women (e.g., those with breast lumps) undergoing diagnostic mammography than for asymptomatic women undergoing screening.

http://www.ncbi.nlm.nih.gov/pubmed/20439838?dopt=Abstract

Probiotics Prevent Necrotizing Enterocolitis

Should they become standard of care?

Numerous studies suggest that probiotics prevent the development of necrotizing enterocolitis (NEC) in preterm infants (JW Pediatr Adolesc Med Mar 26 2008). In an updated meta-analysis of data from 11 randomized clinical trials, including 4 recent trials, and involving 2176 preterm infants with birth weights <1500 g, investigators found that infants treated with probiotics were significantly less likely to develop NEC (relative risk, 0.35; number needed to treat [NNT], 25) and to die from any cause (RR, 0.42; NNT, 20). Probiotics were not associated with increased risk for culture-positive sepsis.

http://pediatrics.jwatch.org/cgi/content/full/2010/526/2

http://www.ncbi.nlm.nih.gov/pubmed/20403939?dopt=Abstract

Prolonged Breast-Feeding Promotes Psychological Health

Breast-feeding for <6 months was associated with increased risk for mental health problems during childhood and adolescence.

Oddy WH et al. J Pediatr 2010 Apr 156:568

Kramer MS. J Pediatr 2010 Apr 156:523

Heart risks are higher in women with irregular menstrual periods
A 10-year study of more than 23,000 Dutch women found that the likelihood of developingheart disease is 28% greater in those with a history of irregular menstrual cycles compared with those who have more regular cycles. The study, published in Fertility and Sterility, also found that the risk for heart problems was similar in women with regularly long or short menstrual cycles.

http://www.nationalpost.com/story-printer.html?id=39a7390c-d7bc-42c9-8b90-f2a7d72308c8

Autonomic function change and insulin resistance
Cardiac autonomic function altered in predisease subjects with one or more metabolic abnormalities, while insulin resistance existed in subjects with two or more metabolic abnormalities. Thus, autonomic function change may precede insulin resistance in the initiation of metabolic syndrome

http://www.amjmed.com/article/S0002-9343(09)01057-2/fulltext

What's the key to osteoporosis diagnosis and treatment?
Accurate assessment of bone structure, especially porosity producing cortical remnants, could improve identification of individuals at high and low risk of fracture and therefore assist targeting of treatment. http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60320-0/abstract

Beta-blockers for uncomplicated hypertension? Think again
These authors point out that newer β-blocker agents, such as nebivolol and carvedilol, show vasodilating properties and a more favourable hemodynamic and metabolic profile. However, whether they will be more efficacious in reducing morbidity and mortality still remains to be determined.

http://www.ajconline.org/article/S0002-9149(10)00078-0/fulltext

Beta-Blockers May Benefit Patients with COPD

Beta-blockers, long withheld from patients with chronic obstructive pulmonary disease over concerns that they would worsen symptoms, actually seem to lessen mortality and exacerbations, according to an Archives of Internal Medicine study.

Researchers followed some 2200 patients (average age, 65) in the Netherlands for 7 years; all either had COPD at study entry or developed it over the course of the study. Patients taking beta-blockers were about a third less likely to die during the study and about a quarter less likely to have a COPD exacerbation.

Editorialists call for confirmation in a randomized trial and, pending that, say clinicians have a rationale for using beta-blockers "cautiously" in their patients with COPD and a coexisting heart condition.

http://archinte.ama-assn.org/cgi/content/short/170/10/880

Raised triglycerides: How big the risk?
These data are consistent with a causal association between triglyceride-mediated pathways and coronary heart disease

http://www.thelancet.com/journals/lancet/article/PIIS0140-6736(10)60545-4/abstract

CREST Trial Points to Endarterectomy as Preferred Stroke Preventive Strategy

A comparison of endarterectomy versus stenting in treating carotid artery stenosis shows that stent recipients are at higher risk for stroke within 30 days of the procedure, according to a New England Journal of Medicine study released online.

Investigators in the CREST trial randomized some 2500 patients with carotid artery stenosis to either stenting or endarterectomy. After a median follow-up of 2.5 years, the groups showed no significant difference in the primary endpoint — a composite of stroke, myocardial infarction, or death from any cause during the periprocedural period, or ipsilateral stroke within 4 years.

However, the 4-year rate of stroke or death significantly favored endarterectomy. When the individual outcomes were examined, there were significantly more periprocedural strokes after stenting, and more MIs after endarterectomy.

Editorialists conclude that "endarterectomy remains the preferred treatment for most patients."

http://content.nejm.org/cgi/content/full/NEJMoa0912321

New Orlistat Label Notes Rare Cases of Severe Liver Injury with the Drug

The FDA has approved revised labeling for the weight-loss drug orlistat to note that severe liver injury has occurred, albeit rarely, in patients on the drug.

Of the 13 cases reported (out of approximately 40 million users globally), 12 were linked to the prescription version of orlistat (Xenical) and 1 was linked to the over-the-counter version (Alli). Two resulted in death, and three in liver transplantation.

The FDA notes that a cause-effect relationship has not been established. Some of the patients were using other drugs or had conditions that might have led to their liver dysfunction. Nonetheless, the agency recommends that clinicians advise patients using orlistat to report signs of liver injury (e.g., anorexia, jaundice, dark urine).

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm213448.htm

FDA: Proton-Pump Inhibitors Might Increase Risk for Wrist, Hip, and Spine Fractures

The FDA is revising the labels of proton-pump inhibitors to warn about a possible increased risk for hip, spine, and wrist fractures in patients taking either prescription or over-the-counter versions of the drugs.

The label change follows a review of seven epidemiological studies, six of which showed increased fracture risk with PPIs. The greatest risk was observed in patients on high doses or who had been taking the drugs for at least 1 year. In addition, the risk was seen mainly in adults aged 50 or older.

The FDA says that when prescribing PPIs, clinicians should consider whether lower doses or shorter courses of treatment would be appropriate for individual patients.

http://www.fda.gov/Safety/MedWatch/SafetyInformation/SafetyAlertsforHumanMedicalProducts/ucm213321.htm

Reduced Intake of Sugary Drinks Linked to Decreases in Blood Pressure

Drinking just one less sugar-sweetened beverage per day may lead to significant reductions in blood pressure, according to an observational study in Circulation.

Researchers examined prospective data on some 800 adults with pre- or stage 1 hypertension(systolic BP, 120–159 mm Hg; diastolic, 80–95 mm Hg) who were participating in a trial of behavioral interventions to lower BP. Over the 18-month study, participants who cut out one sugar-sweetened beverage per day had significant reductions in both systolic and diastolic BP (–0.7 and –0.4 mm Hg, respectively). (Analyses were adjusted for confounders such as other dietary changes, physical activity, and weight.)

The sugar content of the drinks, rather than the caffeine, appeared to account for the observed association. The authors suggest that enhanced sympathetic nervous system activity may underlie sugar's effect on BP.

http://circ.ahajournals.org/cgi/content/abstract/CIRCULATIONAHA.109.911164v1

Risk for False-Positive Lung Cancer Screening Is Substantial

Nine percent of patients with false-positives on computed tomography required invasive testing.

Despite lack of proven efficacy, lung cancer screening has been widely promoted. In the ongoing National Lung Screening Trial (NLST), about 50,000 current or former smokers have been randomized to screening by either chest x-ray or computed tomography (CT).

In a preparative feasibility study for the NLST, 3318 current or past smokers (age range, 55–74) were randomly assigned to receive annual chest radiography or annual low-dose CT. A false-positive was defined as a positive test result followed by a negative completed work-up or no diagnosis of lung cancer within 12 months. After two screening tests 1 year apart, risk for a false-positive result was 15% for participants in the chest radiography group and 33% for those in the CT group. Four percent of those with false-positive chest radiographsand 7% of those with false-positive CT scans underwent at least one invasive procedure as a result. Overall, 1% to 2% of participants had true-positive test results.

Comment: Lung cancer screening with CT scan (or chest radiography) has theoretical but unproven benefits and substantial proven harms. If screening is eventually proven to reduce lung cancer–specific mortality, we will need to understand better the ramifications of false-positive results.

Croswell JM et al. Ann Intern Med 2010 Apr 20; 152:505

http://www.ncbi.nlm.nih.gov/pubmed/20404381?dopt=Abstract

Treatment-Induced Diabetic Neuropathy

An unusual complication of rapid intensive glycemic control

In sporadic case reports — some published more than 50 years ago — clinicians have described acute severe painful neuropathy that can occur during intensive treatment of patients with poorly controlled diabetes. Researchers now describe 16 patients with this condition who were referred to a Boston diabetic neuropathy clinic.

Each patient developed severe neuropathic pain within 8 weeks of initiating intensive glycemic control. Nine patients (age range, 19–29) had type 1 diabetes, and 7 patients (age range, 31–58) had type 2 diabetes. Other common causes of neuropathy were ruled out. Average glycosylated hemoglobin levels were about 14% before intensive glycemic control and about 7% afterward. Pain was in a stocking-glove distribution in 13 patients and was diffuse in 3 patients. Autonomic symptoms (e.g., orthostatic hypotension, gastrointestinal dysfunction) occurred commonly, and standardized tests of sympathetic and parasympathetic function were abnormal in most patients. Retinopathy also worsened during the first 6 months of sustained glycemic control. Pain subsided eventually in most patients, but only after 1 to 2 years of combination drug therapies for neuropathic pain.

http://www.ncbi.nlm.nih.gov/pubmed/20437589?dopt=Abstract

Pesticide Exposure Linked to Attention-Deficit/Hyperactivity Disorder in Kids

Children with greater exposure to widely used pesticides are more likely to have attention-deficit/hyperactivity disorder, according to a cross-sectional study in Pediatrics. (Diet is the main source of pesticide exposure among children.)

Using NHANES data, researchers assessed ADHD prevalence and urinary concentrations of dialkyl phosphate metabolites (markers of ongoing organophosphate pesticide exposure) in some 1100 children aged 8 to 15 years.

Some 10% of the children met diagnostic criteria for ADHD. Overall, as levels of dialkyl phosphate metabolites increased, so did ADHD prevalence. In particular, children with elevations in the most commonly detected metabolite, dimethyl thiophosphate, had twice the odds of having ADHD.

The authors say their results "support the hypothesis that organophosphate exposure, at levels common among US children, may contribute to ADHD prevalence." They propose several possible explanations for their findings — for example, organophosphates inhibit acetylcholinesterase, and cholinergic signaling is thought to be disrupted in ADHD.

http://pediatrics.aappublications.org/cgi/reprint/peds.2009-3058v1

Working Too Much Is Bad for the Heart

Working 3 to 4 extra hours a day is associated with increased risk for coronary heart disease (CHD), according to a study in the European Heart Journal.

Some 6000 British civil servants underwent clinical exams and completed lifestyle questionnaires, and then were followed for an average of 11 years. During that time, their rate of new CHD was 5.5 per 1000 person-years.

After adjustment for lifestyle, conventional cardiac risk factors, and other potential confounders, participants who worked 3 to 4 hours of overtime a day (beyond the standard 7–8 hours/day) faced a 60% increase in risk for CHD, compared with those who didn't work any overtime. Less overtime (1–2 hours/day) was not associated with increased risk

http://eurheartj.oxfordjournals.org/content/early/2010/05/04/eurheartj.ehq124.abstract

High-Dose Vitamin D Increases Risks for Falls and Fractures in Older Women

Unexpectedly, a single very high dose of vitamin D appears to increase risks for falls and fractures among older women, according to a JAMA study. Editorialists emphasize that the findings "do not alter the importance of correcting widespread vitamin D deficiency."

In the study, some 2300 high-risk women aged 70 or older were randomized to annual treatment with 500,000 IU of cholecalciferol (self-administered as 10 pills on 1 day) or placebo. The treatments were taken during autumn or winter months for up to 5 years.

Vitamin D recipients showed a higher rate of falls than placebo recipients — 83.4 versus 72.7 per 100 person-years. Fracture rates were similarly increased — 4.9 versus 3.9 per 100 person-years.

The editorialists speculate that very high doses may trigger metabolic protective reactions, leading to paradoxical decreases in vitamin D levels. Alternatively, vitamin D increases may lead to increased mobility, and thus more chances for fracture. They conclude that "daily, weekly, or monthly dosing ... appears to be the best option."

Omega-3 Fatty Acids and Prevention of Dementia

No evidence of benefit was noted in a 24-month trial.

Among many proposed interventions to lower risk for or severity of dementia is supplementation with  -3 fatty acids, such as eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), which are commonly found in oily fish.

U.K. investigators enrolled 867 patients (age range, 70–79) from general practices; none had diabetes, and all had normal cognition (Mini-Mental State Examination scores  24). Participants were randomized to daily supplementation with EPA (200 mg) plus DHA (500 mg) or to olive oil placebo. The EPA and DHA dosages were based on U.K. dietary recommendations for fish consumption. The withdrawal and death rates were similar in the two groups — roughly 14% total.

At 24 months' follow-up, no differences were found between the two groups in a validated assessment of cognitive function based on verbal memory or in secondary outcomes related to global cognitive function, memory, or executive function. Adverse events were minor and similar in both groups, with a small incremental risk for flatulence, loose stools, and belching in the treated group.

Comment: This randomized controlled trial is reportedly the longest and largest to evaluate  -3 fatty acid supplementation for prevention of dementia. The negative results are consistent with the conclusions of a recent Institute of Medicine report that showed no clear support for any interventions that are purported to prevent dementia.

Coronary Artery Calcium Scoring: Ready for Routine Use?

CAC improved predictive accuracy when added to traditional risk factors.

Coronary artery calcium (CAC) scores as assessed by computed tomography correlate with burden of atherosclerosis and risk for future adverse coronary events. In this analysis, U.S. investigators examined a cohort of 5878 ethnically diverse patients without known atherosclerosis or diabetes to assess whether CAC scoring at baseline, added to traditional risk factors, allowed reclassification of patients into higher- or lower-risk groups for subsequent adverse cardiac events.

Of 209 events that occurred during 6 years of follow-up, 122 were death, myocardial infarction, or resuscitated cardiac arrest. Patients were categorized as low (5-year risk, 0%–<3%), intermediate (3%–10%), and high (>10%) risk for incident adverse cardiac events by demographics and traditional risk factors (i.e., tobacco use, systolic blood pressure, antihypertensive use, and total and HDL cholesterol levels). When CAC scoring was added to this model, risk prediction improved significantly; more patients were categorized to low- or high-risk groups (77% with CAC vs. 69% without CAC), and fewer patients were in the intermediate-risk category.

Comment: In this analysis, CAC scores added value to standard risk factors in the prediction of subsequent events. Editorialists emphasize that CAC score is a promising predictor but that routine use cannot be recommended until its effect on outcomes, as well as risks and costs, is evaluated. Moreover, several promising novel risk factors, such as high-sensitivity C-reactive protein and carotid intima-media thickness, are under investigation and should be considered alongside CAC score as possible predictors.

Neutrophil Count — A Simple Marker for Cardiovascular Risk?

High peripheral neutrophil counts correlated with excess cardiovascular risk in postmenopausal women with essential hypertension.

http://womens-health.jwatch.org/cgi/content/full/2010/429/1