• New Orlistat Label Notes Rare Cases of Severe Liver Injury with the Drug
• FDA: Proton-Pump Inhibitors Might Increase Risk for Wrist, Hip, and Spine Fractures.
• Hormone Replacement Therapy: Patch Less Risky for Stroke than Pill?
• Hamburgers, Hot Dogs, and Heart Health.
• Probiotics Prevent Necrotizing Enterocolitis.
• Recurrent Clostridium difficile Infection and Proton-Pump Inhibitors.
• Stool-Transplant Enema for Recurrent Clostridium difficile Infection.
• Another Trial of Proton-Pump Inhibitor Therapy for Asthma.
• Pesticides and Attention-Deficit/Hyperactivity Disorder.
• Effects of Estrogen-Only Hormone Therapy on Mammograms and Indication for Biopsies.
• Does Vitamin E Protect Against Cisplatin Neurotoxicity?
• Dietary Sugars and Lipid Metabolism.
• Treating Bronchiolitis Through the Nose
• Symptom Patterns in 2009 Pandemic Influenza vs. Seasonal Influenza.
• How Much Sunlight Is Equivalent to Vitamin D Supplementation?
• Kids' Use of Chronic Prescription Medications Rises 5%.
• FDA Approves Injectable Monoclonal Antibody for Osteoporosis.
• Aspirin Recommended as Preventive for Cardiovascular Events in Diabetics.
• Group Meetings Lower BP — But Not Glucose — in Patients with Diabetes.
• The Effect of Implementing Guidelines on Proton-Pump Inhibitor Use.
• First-Trimester Vaginal Bleeding as a Marker of Unfavorable Pregnancy Outcomes.
• Excessive Nausea and Vomiting During Early Pregnancy Runs in Families.
• Metoclopramide vs. Promethazine for Hyperemesis Gravidarum.
• Single-Focus Glasses Reduce Danger of Falls in Active Elderly.
New Orlistat Label Notes Rare Cases of Severe Liver Injury with the Drug
Orlistat (marketed as Alli and Xenical): Labeling Change
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).
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FDA: Proton-Pump Inhibitors Might Increase Risk for Wrist, Hip, and Spine Fractures
Proton Pump Inhibitors (PPI): Class Labeling Change including Nexium, Dexilant, Prilosec, Zegerid, Prevacid, Protonix, Aciphex, Vimovo, Prilosec OTC, Zegerid OTC, and Prevacid 24HR 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.
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BMJ 2010;340:c2519, doi: 10.1136/bmj.c2519 (Published 3 June 2010)
Hormone Replacement Therapy: Patch Less Risky for Stroke than Pill?
The risk for stroke associated with hormone replacement therapy (HRT) in postmenopausal women seems lower among those on low-dose transdermal regimens, according to a nested case-control study in BMJ.
From a cohort of almost 900,000 women over age 50, researchers age-matched 16,000 women who had a stroke over a follow-up period averaging 7 years with some 60,000 controls. Current users of oral estrogens, alone or in combination, had a higher stroke rate than nonusers of HRT.
When comparing oral and transdermal HRT directly, researchers found a lower stroke risk among transdermal users. However, high-dose patch users (>50 μg of estrogen) actually had a higher risk relative to nonusers (rate ratio, 1.88).
The authors warn that although their results suggest that the low-dose transdermal route may be safer, they "do not represent definitive evidence."
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Circulation 2010 Jun 1; 121:2271
Hamburgers, Hot Dogs, and Heart Health
In a meta-analysis of observational data, consumption of processed meat conferred higher risks for coronary heart disease and diabetes than consumption of unprocessed red meat.
We make dietary choices and recommendations with less-than-complete evidence to guide us. A current controversy concerns the effects of meat, particularly red and processed meats, on cardiovascular risk. These investigators conducted a systematic review and meta-analysis of studies evaluating the associations between red and processed meat consumption and risks for coronary heart disease (CHD), stroke, and diabetes.
The researchers did not identify any trials; their analysis included 17 prospective cohort studies and 3 case-control studies. Consumption of unprocessed red meat was not associated with CHD (4 studies; relative risk, 1.00 per 100-g serving/day; 95% confidence interval, 0.81–1.23) or diabetes (5 studies; RR, 1.16; 95% CI, 0.92–1.46). Consumption of processed meat was associated with a 42% increase in risk for CHD (5 studies; RR, 1.42 per 50-g serving/day; 95% CI, 1.07–1.89) and a 19% increase in risk for diabetes (7 studies; RR, 1.19; 95% CI, 1.11–1.27). Neither type of meat was associated with an elevated risk for stroke.
Comment: This meta-analysis encompasses relatively few studies, and confounding by imprecise or unmeasured factors is likely. Moreover, the CIs do not exclude substantial risks associated with unprocessed meat. Nevertheless, the main finding of an increase in risk with processed meats, with their high salt and preservative content, bolsters available evidence and should lead us to advise our patients to be cautious about consuming these products.
— Harlan M. Krumholz, MD, SM Published in Journal Watch Cardiology June 2, 2010
Citation(s): Micha R et al. Red and processed meat consumption and risk of incident coronary heart disease, stroke, and diabetes mellitus: A systematic review and meta-analysis. Circulation 2010 Jun 1; 121:2271.
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Pediatrics 2010 May; 125:921
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.
Comment: These results certainly indicate that probiotics are effective. However, in two spirited editorials, opinion was divided about whether probiotic supplementation should become standard of care. One editorialist argues that, as is often the case with meta-analyses, the effective probiotic type and dosage cannot be determined. Another unknown is whether the beneficial effects of probiotics are independent of type of feeding (formula or breast). In contrast, the other editorialists believe that evidence of benefit is sufficient and that additional trials will not change that conclusion. My suggestion is to discuss with parents the benefits, as well as arguments against routine probiotic use, and let them decide.
— Howard Bauchner, MD Published in Journal Watch Pediatrics and Adolescent Medicine May 26, 2010
Citation(s): Deshpande G et al. Updated meta-analysis of probiotics for preventing necrotizing enterocolitis in preterm neonates. Pediatrics 2010 May; 125:921.
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Arch Intern Med 2010 May 10; 170:772.
Recurrent Clostridium difficile Infection and Proton-Pump Inhibitors
PPI use during treatment for CDI was associated with excess risk for infection recurrence.
The incidence of Clostridium difficile infection (CDI) has risen dramatically during the last decade, and the relapse rate for this infection can be high. Proton-pump inhibitor (PPI) use has been associated with excess risk for infections such as CDI.
To determine whether PPI use is associated with risk for recurrent CDI, investigators conducted a retrospective study of patients identified from the New England Veterans Healthcare System from October 2003 through September 2008. A total of 1166 patients (97% male; median age, 74) with CDI documented by toxin assays were treated with metronidazole or vancomycin. Of this cohort, 527 (45.2%) received PPIs during initial treatment (within 14 days of CDI diagnosis), and most of these patients (82.4%) received PPIs during the 15- to 90-day follow-up period. Of the 639 patients (54.8%) who did not receive PPIs during initial treatment, only a few (6.4%) received PPIs during follow-up.
Overall, 251 patients (21.5%) experienced toxin-confirmed CDI recurrence during follow-up. Patients who received PPIs during initial treatment for CDI were more likely to experience recurrence than those who did not (25.2% vs. 18.5%; hazard ratio, 1.42; P=0.006). After adjustments for comorbidities, hospitalization, antibiotic use, and other factors, the hazard ratio remained unchanged.
Comment: The data from this study suggest that PPI therapy might increase the risk for recurrent CDI. However, the study had limitations: Some patients who experienced recurrence might have had persistent disease (only 40% had an intervening negative toxin assay), confounding factors might have increased both the use of PPIs and disease recurrence, and the study could not capture nonprescription PPI use. Whether the results can be generalized from the elderly male veterans in the study is unclear. Additional prospective studies are needed to clarify the relationship between PPI use and CDI.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.) Published in Journal Watch Gastroenterology May 21, 2010
Citation(s): Linsky A et al. Proton pump inhibitors and risk for recurrent Clostridium difficile infection. Arch Intern Med 2010 May 10; 170:772.
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Clin Gastroenterol Hepatol 2010 May; 8:471
Stool-Transplant Enema for Recurrent Clostridium difficile Infection
Self-administered fecal transplantation achieved 100% clinical success.
Patients with Clostridium difficile (CD) infection are typically given prolonged courses of metronidazole or vancomycin, high-dose or tapering regimens of vancomycin, or sequential therapy involving vancomycin followed by rifampin or rifaximin. Several reports have explored fecal transplantation for treating patients with recurrent CD infection (e.g., JW Gastroenterol Apr 29 2003).
A new case series focused on the efficacy of these "stool transplants," self-administered via enema, in seven patients with refractory CD infection. All had been treated with 125 mg of vancomycin four times per day for 14 days, then quadruple that dose for the same duration, and then tapering regimens of vancomycin in combination with Saccharomyces boulardii administration. Six of the patients had also failed at least two courses of oral metronidazole.
Family members who were stool donors were tested for HIV; human T-cell lymphotropic virus I and II; syphilis; hepatitis A, B, and C; and Helicobacter pylori antibody. Recipients had routine blood tests as well as tests for serum protein electrophoresis, serum immunoglobulins, HIV, and antigliadin antibodies. Stools from both donors and recipients were tested for culture and sensitivity, ova and parasites, cryptosporidia, microspora, and CD toxin. The recipients were started on maintenance therapy with oral S. boulardii (Florastor; 500 mg twice daily), plus metronidazole until 24 to 48 hours prior to the transplant.
The home-based transplant involved mixing a 50-mL sample of stool with 200 mL of saline, homogenizing it, and delivering it by enema. All the patients responded (100% clinical success).
Comment: This article is useful for its explicit description of how to prepare and administer a fecal transplant to a patient who has failed multiple medical therapies for recurrent CD infection. The treatment protocol was approved by the Institutional Review Board, and patients gave consent for experimental therapy. Physicians using the treatment in clinical practice should consider whether some form of informed consent is required.
— Douglas K. Rex, MD Published in Journal Watch Gastroenterology June 4, 2010
Citation(s):Silverman MS et al. Success of self-administered home fecal transplantation for chronic Clostridium difficile infection. Clin Gastroenterol Hepatol 2010 May; 8:471.
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Am J Respir Crit Care Med 2010 May 15; 181:1042
Another Trial of Proton-Pump Inhibitor Therapy for Asthma
Esomeprazole provided no clinically important benefits.
In two recent studies of patients with asthma and gastroesophageal reflux disease (GERD), esomeprazole did not significantly improve asthma control (JW Gen Med Jun 6 2006 and Apr 16 2009). Now, in yet another trial, industry-sponsored researchers randomized 961 patients with asthma and symptomatic GERD to receive esomeprazole (40 mg either once or twice daily) or placebo.
At 26 weeks, neither of the two esomeprazole groups differed from the placebo group in the primary outcome, morning peak expiratory flow. Asthma symptom scores, numbers of asthma exacerbations, percentage of asthma-free days, and use of rescue bronchodilators were also similar in the esomeprazole and placebo groups. For several secondary outcomes, statistically significant — but not clinically impressive — differences between esomeprazole recipients and placebo recipients were noted (e.g., a 100-mL difference in FEV1).
Comment: This is the third randomized trial in recent years to show that a proton-pump inhibitor (PPI) conferred no clinically important improvement in asthma control for patients with both asthma and GERD. The authors call for future studies limited to asthma patients with the most severe GERD, but that effort seems unnecessary: Such patients would likely receive a PPI to treat their GERD anyway.
— Allan S. Brett, MD Published in Journal Watch General Medicine May 25, 2010
Citation(s):Kiljander TO et al. Effect of esomeprazole 40 mg once or twice daily on asthma: A randomized, placebo-controlled study. Am J Respir Crit Care Med 2010 May 15; 181:1042.
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Pediatrics 2010 Jun; 125:e1270
Pesticides and Attention-Deficit/Hyperactivity Disorder
Results from a cross-sectional study support an association between organophosphate exposure in children and ADHD but cannot confirm causality.
Children are exposed to organophosphate pesticides primarily in food and drinking water. These pesticides might be particularly toxic to developing brains. Using data derived from a national health survey, investigators assessed the relation between exposure to organophosphates and development of attention-deficit/hyperactivity disorder (ADHD). Exposure was determined from one urinary sample, and ADHD was diagnosed by structured parent interview.
Among the 1139 children (age range, 8–15 years), 119 were diagnosed with ADHD. Most children (94%) had detectable levels of at least one of six urinary metabolites of organophosphates. The association between total exposure to organophosphates (total urinary metabolite concentrations) and ADHD approached statistical significance (adjusted odds ratio, 1.21; 95% confidence interval, 0.97–1.51). Exposure to a group of three related metabolites was significantly associated with ADHD (AOR, 1.55). In an analysis restricted to the most commonly detected metabolite, children with levels above the median detectable concentration were significantly more likely to have ADHD than children with levels below the detection limit (AOR, 1.93).
Comment: The authors note a number of study limitations, including assessment of exposure from a single urine sample and the possibility that children with ADHD engage in behaviors that expose them to higher levels of organophosphates. In addition, although a structured parental interview was used to make the diagnosis of ADHD, information from other sources was not available. These results are likely to fuel concern that exposure to pesticides adversely affects development in children. However, causality cannot be confirmed with this type of study design.
— Howard Bauchner, MD Published in Journal Watch Pediatrics and Adolescent Medicine June 2, 2010
Citation(s): Bouchard MF et al. Attention-deficit/hyperactivity disorder and urinary metabolites of organophosphate pesticides. Pediatrics 2010 Jun; 125:e1270.
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J Clin Oncol 2010 Jun 1; 28:2690
Effects of Estrogen-Only Hormone Therapy on Mammograms and Indication for Biopsies
Unlike estrogen-progestin HT, estrogen alone did not compromise diagnostic performance of breast cancer screening.
Unlike estrogen-progestin hormone therapy (HT), estrogen alone does not raise risk for breast cancer; however, whether estrogen-only HT affects breast cancer detection is unknown. Investigators from the Women's Health Initiative (WHI) sought to clarify the effect of estrogen HT (conjugated equine estrogen; 0.625 mg daily) versus placebo on screening mammogram findings (recommendations for short-interval follow-up imaging) and likelihood of clinically indicated breast biopsies.
At 5 years, women in the estrogen group were more likely than those in the placebo group to have screening mammography findings that warranted short-interval follow-up (31% of 5310 vs. 22% of 5429; P<0.001). However, incidence of mammograms that were suggestive or highly suggestive of cancer was similar in the two groups. At 7 years, cumulative incidence of undergoing breast biopsy for clinical (i.e., not imaging-related) indications was significantly higher in the estrogen group (12% vs. 11%; P=0.04). Cancer was diagnosed in 112 of 1007 women in the estrogen group who underwent breast biopsies (9%) and 127 of 831 of women in the placebo group (16%; P=0.04). Receiver operating curves showed that overall diagnostic performance of mammography was compromised during the first 2 years of estrogen use, but this effect did not persist during subsequent follow-up.
Comment: In counseling women about the safety of HT, clinicians should keep in mind that estrogen-only therapy has a more favorable risk profile than does estrogen-progestin therapy. As the authors note, although estrogen-only HT is associated with higher incidence of mammographic screens prompting short-interval follow-up and clinically indicated biopsies, this relation did not extend to incidence of screens with more serious findings or to incidence of invasive breast cancer. In general, mammograms in women who received estrogen served to diagnose breast cancer in a timely fashion. By contrast, previous WHI evaluation of estrogen-progestin HT versus placebo indicated that 5 years of combination HT raised risk for mammograms yielding serious findings, compromised overall diagnostic performance of mammography, and modestly raised risk for invasive breast cancer
(JW Womens Health Apr 10 2008). The authors speculate that increases in breast density associated with combination HT but not estrogen HT might affect diagnostic performance of screening mammography differentially.
— Andrew M. Kaunitz, MD Published in Journal Watch Women's Health June 3, 2010
Citation(s):Chlebowski RT et al. Estrogen alone in postmenopausal women and breast cancer detection by means of mammography and breast biopsy. J Clin Oncol 2010 Jun 1; 28:2690. http://dx.doi.org/10.1200/JCO.2009.24.8799
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Neurology 2010 Mar 2; 74:762
Does Vitamin E Protect Against Cisplatin Neurotoxicity?
The jury is still out.
Neuropathy caused by cisplatin, which is used to treat various cancers, often limits the dosage that can be used. Doses of more than 300 mg/m2 cause a sensory neuropathy. The mechanism may be apoptosis caused by formation of free radicals. Vitamin E has been found to at least partially prevent this effect of reactive oxygen species (J Neurosci Res 1998; 54:778). To assess the protective effect of vitamin E supplementation against cisplatin-induced neuropathy, researchers randomized 108 patients with different solid tumors in double-blind fashion to alpha-tocopherol (400 mg/day) or placebo. Cisplatin was the only neurotoxic agent the patients received.
Forty patients dropped out because of disease progression or stopped taking vitamin E before reaching the target cumulative cisplatin dose of more than 300 mg/m2. Another 27 patients also did not reach the target dose of cisplatin, leaving 17 patients treated with vitamin E and 24 with placebo. Before and after treatment, the authors assessed patients' neuropathy with the Total Neuropathy Score (TNS), which is based on clinical findings and sensory nerve conduction studies of the median and sural nerves. The authors report that sensory nerve action potentials and neuropathic symptoms were significantly less abnormal in the vitamin E group than in the placebo group. The authors do not discuss possible adverse effects of the high vitamin E dose.
Comment: These findings are of interest because other measures to protect against cisplatin-induced neuropathy have proven futile. However, the study needs confirmation in a larger group of patients for several reasons. First, many patients dropped out, reducing the population below the number of specified study participants, and possibly introducing bias. Second, the incidence and extent of neuropathy is highly correlated with the dose of cisplatin above 300 mg/m2 (Brain 2007; 130:1076). Although the median dose (among study completers) appears similar in the groups, the authors do not consider this important aspect. Third, the drop in mean sural amplitude was essentially the same in the two groups (21% with vitamin E, 23% with placebo) but was described as statistically different using a t-test, without evidence of normally distributed values. Thus, the study adds limited evidence to the hypothesis that antioxidant therapy may confer protection against neurotoxicity caused by cisplatin.
— Christian Krarup, MD, DMSc, FRCP Dr. Krarup is Professor and Chairman, Department of Clinical Neurophysiology, Rigshospitalet, Copenhagen, Denmark.
Published in Journal Watch Neurology June 1, 2010
Citation(s): Pace A et al. Vitamin E neuroprotection for cisplatin neuropathy: A randomized, placebo-controlled trial. Neurology 2010 Mar 2; 74:762.
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JAMA 2010 Apr 21; 303:1490
Dietary Sugars and Lipid Metabolism
Added sugar intake is associated with some markers of dyslipidemia.
Higher carbohydrate consumption is associated with lower HDL cholesterol (HDL-C) and higher LDL cholesterol (LDL-C) levels. Now, investigators have examined the association between dyslipidemia and consumption of added sugars (defined as caloric sweeteners — usually sucrose from beets or cane, or high-fructose corn syrup — that are added to processed foods), which account for nearly 16% of the average daily calorie intake for people in the U.S.
In a cross-sectional study, researchers assessed the diets and lipid profiles of about 6000 adult participants in a U.S. nutrition and health survey for 1999–2006. Survey participants were excluded if they were pregnant, had extremely high or low caloric intake or body-mass index, had diabetes, or were taking cholesterol medications. Greater consumption of added sugars was associated with lower HDL-C levels, higher triglyceride (TG) levels, and higher LDL-C levels in women. In analyses adjusted for a wide range of clinical and dietary factors, adults who consumed 25% of total calories as added sugars were roughly 3 times more likely to have low HDL-C levels (<50 mg/dL for women; <40 mg/dL for men) and 60% more likely to have high TG/HDL-C ratios (>3.8) than those whose intake of added sugars was <5% of total calories. For example, the mean HDL-C level in respondents who consumed less than 5% of total calories as added sugar was 58.7 mg/dL, compared with 47.7 mg/dL for those consuming 25% of total calories as added sugar.
Comment: Chemically, sucrose and fructose are not much different from their naturally occurring counterparts, yet increasing consumption of these sweeteners (lacking any nutritional value) in processed foods apparently leads to a greater likelihood of dyslipidemia and, possibly, atherogenesis. In light of these data, the American Heart Association recommendation to limit intake of added sugars to <5% of total calories appears prudent, while we await prospective trials of such dietary modification.
— Thomas L. Schwenk, MD Published in Journal Watch General Medicine May 4, 2010
Citation(s): Welsh JA et al. Caloric sweetener consumption and dyslipidemia among US adults. JAMA 2010 Apr 21; 303:1490.
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J Pediatr 2010 Apr; 156:634
Treating Bronchiolitis Through the Nose
High-flow nasal cannulae have potential as a treatment for severe bronchiolitis.
Young children with bronchiolitis must rely largely on supportive care because few treatments have proved effective. Nasal continuous positive airway pressure (CPAP) has shown promise as a treatment for infants with bronchiolitis, but it is often poorly tolerated. Treatment with high-flow nasal cannulae (HFNC) allows delivery of up to 8 liters per minute of heated, humidified air with or without an increased oxygen concentration and has been proposed as a treatment option. In a retrospective chart review, researchers compared infants (age, <24 months) with bronchiolitis who were admitted to a pediatric intensive care unit (PICU) during successive winters before (57 infants) and after
(58 infants) HFNC treatment was available (51 infants actually received HFNC).
Infants in the two groups were similar at baseline except that those in the HFNC group had a significantly higher median respiratory rate (61 vs. 47 breaths per minute). Before the introduction of HFNC treatment, 23% of infants required intubation. After the introduction of HFNC, 9% of infants required intubation. This difference was statistically significant and persisted after adjusting for age, weight, and respiratory syncytial virus status. Median PICU length of stay was 2 days shorter after introduction of HFNC. In a comparison of all infants in both groups who did or did not receive HFNC, those who received HFNC had a greater decrease in respiratory rate after 1 hour of therapy, and those with the greatest decrease were the least likely to be intubated. HFNC was well tolerated.
Comment: Studies show that HFNC can deliver a pressure of up to 5 cm H2O, albeit in a less-controlled, more-variable manner than nasal CPAP. But HFNC seems to be less cumbersome and better tolerated, and, for severe bronchiolitis, it might be one treatment that actually leads to improved outcomes compared with regular supportive care.
— Cornelius W. Van Niel, MD Published in Journal Watch Pediatrics and Adolescent Medicine
May 26, 2010
Citation(s): McKiernan C et al. High flow nasal cannulae therapy in infants with bronchiolitis. J Pediatr 2010 Apr; 156:634.
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Arch Intern Med 2010 May 24; 170:861
Symptom Patterns in 2009 Pandemic Influenza vs. Seasonal Influenza
A study conducted in Singapore showed significant differences between these illnesses.
Although 2009 pandemic H1N1 influenza has been well characterized, symptom patterns have not been compared between this illness and seasonal influenza. Now, investigators have conducted such a comparison among individuals who were treated or tested for influenza in Singapore between May and July 2009. The researchers also examined viral strain displacement and replacement.
A total of 2683 individuals were evaluated. Although most of them had symptoms, a few asymptomatic individuals (contacts of people with confirmed or suspected influenza; travelers returning from 2009 H1N1 influenza–affected areas) were also included.
Multivariate analysis demonstrated significant differences among seasonal, pandemic, and influenza-negative groups in age (P<0.001), as well as in likelihood of fever (P<0.001), cough (P<0.001), sore throat (P=0.002), rhinorrhea (P=0.001), and dyspnea (P<0.001). Overall, patients with 2009 H1N1 influenza were younger than those with seasonal influenza; in addition, they were less likely to develop fever or dyspnea, and their illness was slightly milder. The predominant circulating seasonal influenza virus (H3N2) in Singapore was replaced by the 2009 pandemic H1N1 virus approximately 1 month after the first imported case was detected there.
Comment: This study involved a large cohort in an area of high temperatures and high humidity — conditions least favorable to influenza virus survival. Characteristics of disease presentation and epidemiology in tropical Asia could differ greatly from those seen in temperate regions. Knowledge of these differences could affect future decisions about patient management and disease control and prevention.
— Larry M. Baddour, MD Published in Journal Watch Infectious Diseases June 2, 2010
Citation(s): Tang JW-T et al. Differing symptom patterns in early pandemic vs seasonal influenza infections. Arch Intern Med 2010 May 24; 170:861.
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J Am Acad Dermatol 2010 Jun; 62:929.e1
How Much Sunlight Is Equivalent to Vitamin D Supplementation?
Now is the winter of our vitamin D discontent.
Vitamin D is essential for bone mineralization and may have other health benefits. Experts disagree on the serum vitamin D level necessary to maintain health. Some recommend concentrations above 30 ng/mL and consider the range between 20 and 30 ng/mL insufficient and concentrations lower than 20 ng/mL deficient. By this reckoning, many Americans are vitamin D insufficient or deficient. Because it is difficult to obtain enough vitamin D from food intake, oral supplements and sunlight have been recommended for individuals with low serum D levels. The suggested dose for supplements is 400 to 1000 IU/day. It has been suggested that a few minutes of sunlight each day to the face, neck, hands, and arms are all that is necessary to restore vitamin D sufficiency, but the amount of sunlight required for photoconversion of 7-dehydrocholesterol to pre–vitamin D varies considerably depending on a person's age, Fitzpatrick sun-reactive skin type, geographic location, and season. (The six Fitzpatrick skin types classify sensitivity to ultraviolet light; skin type I is fair skin that always burns, never tans; type III is darker white skin that burns and tans; type V is brown skin that rarely burns, tans easily.) Investigators employed the FastRT computational tool to predict the length of daily exposure required to obtain the sunlight equivalent of 400 and 1000 IU oral vitamin D supplementation.
At noon in Miami, someone with Fitzpatrick skin type III would require 6 minutes to synthesize 1000 IU of vitamin D in the summer and 15 minutes in the winter. Someone with skin type V would need 15 and 29 minutes, respectively. At noon in the summer in Boston, necessary exposure times approximate those in Miami, but in winter, it would take about 1 hour for type III skin and 2 hours for type V skin to synthesize 1000 IU of D. After 2 PM in the winter in Boston, it is impossible for even someone with Fitzpatrick type I skin to receive enough sun to equal even 400 IU of vitamin D.
Comment: These findings raise serious questions about the recommendation that a "little bit" of outdoor sun exposure is sufficient to maintain adequate vitamin D levels. Moreover, predictions of the time required to achieve adequate vitamin D photosynthesis are probably underestimates, because it is unlikely that people would walk around Boston for an hour or two in the winter with face, neck, and arms exposed. These findings corroborate other observations (e.g., J Clin Endocrinol Metab 2007; 92:2130) that cast doubt on sun exposure as a way to prevent vitamin D deficiency.
— Craig A. Elmets, MD Published in Journal Watch Dermatology June 4, 2010
Citation(s):Terushkin V et al. Estimated equivalency of vitamin D production from natural sun exposure versus oral vitamin D supplementation across seasons at two US latitudes. J Am Acad Dermatol 2010 Jun; 62:929.e1
Tsiaras WG and Weinstock MA. Ultraviolet irradiation and oral ingestion as sources of optimal vitamin D. J Am Acad Dermatol 2010 Jun; 62:935
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Kids' Use of Chronic Prescription Medications Rises 5%
More than one-in-four children take medications to treat ongoing health conditions. In growing numbers in America, children are adding a dose of medicine to their daily routine. In 2009, prescription spending growth increased 10.8 percent, driven by a 5 percent increase in drug utilization and higher medication costs, according to the Medco 2010 Drug Trend Report. The growth in prescription drug use among children was nearly four times higher than the rise seen in the overall population.
A corresponding analysis of pediatric medication use found that in 2009, more than one in four insured children in the U.S. and nearly 30 percent of adolescents (10- to 19-year olds) took at least one prescription medication to treat a chronic condition; the most substantial increases were seen in the use of antipsychotic, diabetes, and asthma drugs over the past nine years.
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FDA Approves Injectable Monoclonal Antibody for Osteoporosis
The FDA has approved an injectable monoclonal antibody, denosumab (Prolia), for the prevention of fracture in postmenopausal women with osteoporosis and high fracture risk.
Patients at high risk include those who have a history of osteoporotic fracture, have several risk factors, or have failed other treatments.
Injection with denosumab is recommended twice a year. The most common adverse effects include back and musculoskeletal pain, pain in the extremities, hyperlipidemia, and bladder infection. In addition, the FDA notes that because denosumab suppresses bone turnover, it may increase risk for osteonecrosis of the jaw.
Denosumab costs $825 per injection — a price the manufacturer deems comparable to other osteoporosis treatments — according to the Associated Press.
Prolia is manufactured by Amgen Manufacturing Limited
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Aspirin Recommended as Preventive for Cardiovascular Events in Diabetics
Low-dose aspirin (75 to 162 mg/day) is a "reasonable" choice for adults with diabetes who have a 10-year risk for cardiovascular disease above 10% and are not at increased risk for bleeding, according to a statement from the American Diabetes Association, the American Heart Association, and the American College of Cardiology.
The statement, published in Circulation, is based on meta-analysis of nine trials examining the effects of aspirin to prevent cardiovascular disease events in patients with diabetes. It also recommends the following:
• Adults with diabetes who are at increased risk for cardiovascular disease (e.g., men over 50 or women over 60 with an additional CVD risk factor) should receive aspirin for primary prevention.
• Patients at intermediate risk for cardiovascular disease (e.g., younger patients with at least one risk factor, older patients with no risk factors, or patients with a 10-year risk of 5% to 10%) may consider taking daily aspirin.
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Group Meetings Lower BP — But Not Glucose — in Patients with Diabetes
Group meetings of patients with hypertension and poorly controlled diabetes lead to better blood pressure control, according to an Annals of Internal Medicine study.
Researchers randomized 239 patients either to usual care or to group medical appointments. The eight-patient groups met with their care team for 2 hours every 2 months. Care teams comprised an internist, pharmacist, and a nurse or diabetes educator.
After a median follow-up of 13 months, mean systolic blood pressure in the intervention groups dropped significantly more than in controls (13.7 mm Hg vs. 6.4). Similarly, intervention patients had significantly fewer emergency room visits. Reductions in glycosylated hemoglobin did not differ significantly, however.
Editorialists, pointing to the anticipated increase in insured people in the U.S. and the paucity of primary care physicians, call the group approach one way to address the "urgent need for innovations in health care delivery."
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Arch Intern Med 2010 May 10; 170:779
The Effect of Implementing Guidelines on Proton-Pump Inhibitor Use
Use of PPIs to prevent nosocomial upper gastrointestinal bleeding declined for patients not already receiving PPIs at hospital admission.
Proton-pump inhibitors (PPIs) are often prescribed to prevent nosocomial upper gastrointestinal bleeding (UGIB). However, multiple studies have shown that these agents are overused for this indication. Would implementing guidelines on PPI use for inpatients influence prescribing practices?
To find out, investigators at Massachusetts General Hospital compared the use of PPIs in patients admitted 1 month before and 1 month after implementation of standardized guidelines regarding PPI use for prophylaxis of nosocomial UGIB. Patients with UGIB and those treated in intensive care units were excluded.
Thirty-six percent of patients were taking PPIs at admission, 49% were prescribed PPIs during hospitalization, and 41% were prescribed PPIs at discharge. No differences in PPI use — either during hospitalization or at discharge — were noted before and after guideline implementation. However, the number of patients prescribed new PPI therapy (i.e., those not already taking PPIs at admission) was lower after guideline implementation than before, both during hospitalization (16% vs. 27%; P=0.001) and at discharge (10% vs. 16%; P=0.03). The authors concluded that guideline implementation decreased PPI use in the subset of patients not already taking PPIs at admission.
Comment: The guidelines and education in this study were targeted at the house staff (i.e., residents), not attending physicians. Whether this experience can be generalized outside a tertiary teaching hospital (in which residents prescribe most medications) is unclear. If the guidelines were maximally effective in limiting PPI use to appropriate indications, we should have seen PPI therapy discontinued in some patients after admission. Changing physician behavior remains one of the greatest challenges to cost-effective care.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.) Published in Journal Watch Gastroenterology
May 28, 2010
Citation(s): Yachimski PS et al. Proton pump inhibitors for prophylaxis of nosocomial upper gastrointestinal tract bleeding: Effect of standardized guidelines on prescribing practice. Arch Intern Med 2010 May 10; 170:779
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Obstet Gynecol 2010 May; 115:935.
First-Trimester Vaginal Bleeding as a Marker of Unfavorable Pregnancy Outcomes
Bleeding early during pregnancy was associated with complications in current and future pregnancies.
First-trimester vaginal bleeding occurs in as many as 25% of pregnancies. Does this event predict other pregnancy complications? In a retrospective cohort study, Danish investigators evaluated the association between first-trimester bleeding and risk for complications later in the same pregnancy or in a second pregnancy. Data were extracted from a national registry of all singleton births from 1978 through 2007. Outcomes were preterm delivery, preterm premature rupture of membranes, fetal growth, stillbirth after 20 weeks' gestation, placental abruption, and hypertensive pregnancy disorders.
First-trimester bleeding was associated with higher risk for preterm delivery during gestational weeks 32 through 36 (3.6% without bleeding vs. 6.1% with bleeding; odds ratio, 1.6) and during weeks 28 through 31 (0.3% vs. 0.9%; OR, 3.0). Such bleeding also was associated with higher risk for placental abruption (1.0% vs. 1.4%; OR, 1.48). Early bleeding during a first pregnancy was associated with higher risk for complications in a second pregnancy: Risk for bleeding rose from 2.2% to 8.2% (OR, 4.0), risk for preterm birth rose from 2.7% to 4.8% (OR, 1.8), and risk for placental abruption rose from 0.9% to 1.0% (OR, 1.3).
Comment: These results add to the evidence that first-trimester bleeding is a marker for subsequent complications such as preterm birth, preterm premature rupture of membranes, and placental abruption in current and future pregnancies. Stricter surveillance of women who experience early bleeding could lead to better follow-up and outcomes while also providing opportunities for counseling about possible complications.
— Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC Published in Journal Watch Women's Health
May 27, 2010
Citation(s): Lykke JA et al. First-trimester vaginal bleeding and complications later in pregnancy. Obstet Gynecol 2010 May; 115:935.
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BMJ 2010 Apr 29; 340:c2050
Excessive Nausea and Vomiting During Early Pregnancy Runs in Families
Women whose mothers experienced hyperemesis gravidarum were at threefold excess risk for the condition themselves.
Hyperemesis gravidarum (HG; excessive nausea and vomiting in pregnancy, starting before gestational week 22) is associated with weight loss, dehydration, and nutritional deficiencies. The condition's etiology is unknown; however, genetic factors might play a role. Accordingly, investigators used the Norwegian birth registry from 1967 through 2006 to assess HG recurrence in 544,000 pairs of mothers and daughters and 400,000 pairs of mothers and female partners of sons.
Daughters of women who experienced HG had threefold higher risk for the condition than did daughters of women who did not have HG (3.00% vs. 1.06%). Female partners of sons, however, had similar risk for HG whether the sons' mothers had the condition (1.18%) or not (1.13%). Excess risk for HG in daughters also occurred if their mothers' HG complicated previous or subsequent pregnancies.
Comment: This population-based study confirms the anecdotal theory that hyperemesis gravidarum "runs in families." Ascertaining maternal HG history in a first-trimester pregnant woman should alert the clinician to the patient's excess risk for HG, allowing him or her to educate the patient and to provide proactive treatment as needed.
— Wendy S. Biggs, MD Published in Journal Watch Women's Health May 27, 2010
Citation(s): Vikanes Å et al. Recurrence of hyperemesis gravidarum across generations: Population based cohort study. BMJ 2010 Apr 29; 340:c2050.
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Obstet Gynecol 2010 May; 115:975
Metoclopramide vs. Promethazine for Hyperemesis Gravidarum
Both agents were effective, but promethazine had more adverse effects — and has a black box warning.
The 2004 American College of Obstetricians and Gynecologists guidelines on nausea and vomiting in pregnancy specify use of intravenous (IV) dimenhydrinate, metoclopramide, or promethazine as first-line agents for dehydrated women with hyperemesis gravidarum (HG). In an intent-to-treat, randomized, double-blind trial, researchers assessed 24-hour outcomes in 149 Malaysian women who were admitted to a university hospital and treated for HG with IV promethazine (25 mg every 8 hours) or metoclopramide (10 mg every 8 hours). Participants recorded episodes of vomiting and reported well-being on a visual numerical rating scale.
Perceived well-being and frequency of vomiting did not differ significantly between groups. Certain adverse effects were more common with promethazine than with metoclopramide (drowsiness, 84% vs. 59%; dizziness, 71% vs. 34%; and dystonia, 19% vs. 6%), whereas rates of other adverse events (difficulty sleeping, dry mouth, diarrhea, headache, palpitations, and skin rash) were similar between groups. Three participants declined to receive all doses of medication (revealed as promethazine at unblinding) because of injection pain.
Comment: In September 2009, the FDA issued a black box warning about risk for local tissue damage (including gangrene) associated with injectable promethazine. This study showed metoclopramide to be as effective as promethazine and to be better tolerated. Moreover, the safety of metoclopramide has been demonstrated in a large Israeli study (JW Womens Health Jun 10 2009). Thus, clinicians should consider metoclopramide preferentially for managing patients with HG.
— Wendy S. Biggs, MD Published in Journal Watch Women's Health May 27, 2010
Citation(s): Tan PC et al. Promethazine compared with metoclopramide for hyperemesis gravidarum: A randomized controlled trial. Obstet Gynecol 2010 May; 115:975.
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BMJ 2010;340:c2265, doi: 10.1136/bmj.c2265
Single-Focus Glasses Reduce Danger of Falls in Active Elderly
Active elderly who wear multifocal glasses reduce their risk for falls if they use single-focus, distance-vision lenses during outdoor activities, according to a BMJ study.
Australian researchers randomized elderly users of multifocal glasses (bifocals, trifocals, or progressive lenses) to receive supplementary single-focus glasses for use in their outdoor activities, or to receive just an updated multifocal prescription. After 1 year of follow-up, the fall rates did not differ significantly between groups.
However, when patients were stratified according to their physical activity levels, the more active patients showed a significant decline in risk for falls when using single-focus lenses, while less active patients actually did worse with single-focus lenses.
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