• The Post-Election Healthcare Landscape
• Does Early Otitis Media Lead to IBD?
• Fish Oil Fails to Reduce Postoperative AF
• Shingles Vaccine Protection Wanes
• Stroke Risk After TIA
• Statins as Anticancer Drugs?
• FDA Approves New Oral Therapy for Rheumatoid Arthritis
• Continuity of Midwife-Led Care: What Effect on Pregnancy Outcomes?
• Higher Calcium Intake Is Associated with Lower Risk for Primary Hyperparathyroidism
• Long-Term PPI Use Does Not Accelerate Loss of Bone Mineral Density
• Low-Intensity Aerobic Activity Improves Gait Instability in Parkinson Disease
• Is CT Useful for Determining the Cause of Vertigo?
• Understanding the Effect of Healthcare Workers' Hand Hygiene
• Daily Acetazolamide Is Effective for Preventing Acute Mountain Sickness
• New Benzodiazepine Use Is Associated with Risk for Dementia
• Chelation Therapy Shows Unexpected, Albeit Limited, Success in CVD
• Oral Scopolamine Augmentation for Major Depression
The Post-Election Healthcare Landscape
With the U.S. elections mercifully past, there are a few health policy developments worth noting.
The Affordable Care Act — much derided by the Republican candidates — seems safe from the post-election repeal promised by Mitt Romney. Healthcare bloggers, such as Health Affairs' Timothy Jost and the Washington Post's Wonkblog, lay out the implications of Barack Obama's reelection. Both point to the fact that between now and January 2014 much needs to be done and decided, because that's when the requirement that everyone have health insurance takes effect.
http://healthaffairs.org/blog/2012/11/07/election-2012-a-win-for-health-reform-but-much-work-remains/
http://www.washingtonpost.com/blogs/ezra-klein/wp/2012/11/07/obamacare-stands-now-states-need-to-make-it-work/
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J Pediatr 2012 Oct 19
Does Early Otitis Media Lead to IBD?
Another potential long-term consequence of indiscriminate antibiotic use
Rates of inflammatory bowel disease (IBD) in children are rising. One etiologic hypothesis is that early use of antibiotics causes alterations in gastrointestinal flora that contribute to the development of IBD (JW Pediatr Adolesc Med Oct 31 2012). Researchers examined the association between an early diagnosis of otitis media (by age 5 years) — the most common diagnosis associated with antibiotic treatment — and IBD using population-based data from Manitoba, Canada. They compared 294 children (mean age, 13 years) diagnosed with IBD between 1989 and 2008 and 2377 matched controls.
By age 1 year, 50% of IBD cases and 48% of controls had at least one diagnosis of otitis media. By age 5 years, only 11% of IBD cases and 18% of controls did not have at least one diagnosis of otitis media. In logistic regression, compared with cases and controls without a diagnosis of otitis media, those with a diagnosis of otitis media by age 5 years were 2.8 times more likely to have IBD, 2.7 times more likely to have Crohn disease, and 3.0 times more likely to have ulcerative colitis. Penicillins were the most common antibiotics prescribed for both cases and controls with otitis media (on the basis of available drug data since 1995).
Comment: The authors of this population-based analysis found a strong statistical association between early diagnosis of otitis media and IBD. They propose that otitis media serves as a proxy for antibiotic prescription and that antibiotic treatment alters the flora in the gastrointestinal tract early in life, thereby contributing to the development of IBD. Although these retrospective data do not prove a causal link between otitis media and IBD, they serve as a reminder of the long-term potential consequences of indiscriminate antibiotic use in young children.
— F. Bruder Stapleton, MD Published in Journal Watch Pediatrics and Adolescent Medicine November 7, 2012
CITATION(S): Shaw SY et al. Association between early childhood otitis media and pediatric inflammatory bowel disease: An exploratory population-based analysis. J Pediatr 2012 Oct 19; [e-pub ahead of print].
(http://dx.doi.org/10.1016/j.jpeds.2012.08.037)
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MM: I’m not surprised that short term use of fish oil showed no significant benefit. Nutritional supplements and foods do not work like drugs. They modify over time and if benefits are founf, then they are more likely to occur longitudinally. I know of many patients and clinicians who have seen benefits for this patient type with fish oil so I will continue to recommend it as a cardio beneficial product.
JAMA 2012 Nov 5
Fish Oil Fails to Reduce Postoperative AF
In patients undergoing cardiac surgery, supplemental n-3 PUFAs provided no protection against arrhythmias.
Postoperative atrial fibrillation (AF) is a common cause of morbidity and mortality after cardiac surgery. In experimental settings, long-chain n-3-polyunsaturated fatty acids (PUFAs) have been shown to have antiarrhythmic effects. To determine whether perioperative supplemental intake of n-3 PUFAs reduces postoperative AF, investigators enrolled 1516 patients (48% of those screened and 94% of those eligible; mean age, 64; 72% men) in a double-blind, placebo-controlled, randomized trial. All patients were scheduled for cardiac surgery (valve surgery, 52%) between August 2010 and June 2012, and fish oil or placebo supplements were started at randomization, between 1 and 5 days before the procedure. Postoperative medications were similar in both treatment groups and included beta-blockers in 77% of patients and amiodarone in 37% of patients.
The primary endpoint — postoperative AF lasting 
30 seconds — occurred in 30.7% of the placebo group and 30.0% of the n-3 PUFA group, a nonsignificant difference. None of the secondary endpoints, including various postoperative AF events and other arrhythmias, differed significantly between the two groups. Rates of in-hospital major adverse cardiovascular events were 2.6% in the placebo group and 1.7% in the n-3 PUFA group (P=0.18).
Comment: According to this large clinical trial in patients undergoing cardiac surgery, perioperative supplementation with n-3 PUFAs does not reduce the risk for postoperative atrial fibrillation. Researchers must continue to explore the physiologic mechanisms of postoperative AF in order to better understand — and develop drugs to prevent — this serious event.
— Joel M. Gore, MD Published in Journal Watch Cardiology November 6, 2012
CITATION(S): Mozaffarian D et al. Fish oil and postoperative atrial fibrillation: The omega-3 fatty acids for prevention of post-operative atrial fibrillation (OPERA) randomized trial. JAMA 2012 Nov 5; [e-pub ahead of print].
(http://dx.doi.org/10.1001/jama.2012.28733)
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Clin Infect Dis 2012 Nov 15; 55:1320
Shingles Vaccine Protection Wanes
Boosters might be needed.
The efficacy of the shingles vaccine was first established in a large Veterans Affairs cooperative study in which patients were followed during the first 4 years after vaccination (JW Gen Med Jun 14 2005). Estimates of longer-term efficacy now are provided by a substudy in which follow-up of some of the original patients continued in years 5 to 7 after vaccination.
In the original study, overall incidence of herpes zoster (HZ) was halved in vaccine recipients (5.4 vs. 11.1 cases per 1000 person-years). Among about 14,000 patients (mean age, 73) in the follow-up study, overall HZ rates remained lower in vaccine recipients (8.4 vs. 14.0 cases per 1000 person-years). Incidence of postherpetic neuralgia also was lower in the vaccine group, but not significantly so. The vaccine was estimated to lower the burden of illness by about 50% among individuals who developed HZ. The vaccine efficacy for all three outcome measures generally was lower than that seen in the initial study and, for all the measures, efficacy reached a low point in year 6 — a finding due, at least in part, to a rise in the incidence of HZ among vaccine recipients.
Comment: Efficacy of the zoster vaccine appears to wane with time (and with the aging of the observed population). Ongoing long-term studies will provide additional information on this phenomenon; however, it seems likely that booster doses eventually will be needed.
— Abigail Zuger, MD Published in Journal Watch General Medicine November 8, 2012
CITATION(S): Schmader KE et al. Persistence of the efficacy of zoster vaccine in the shingles prevention study and the short-term persistence substudy. Clin Infect Dis 2012 Nov 15; 55:1320.
(http://dx.doi.org/10.1093/cid/cis638)
http://www.ncbi.nlm.nih.gov/pubmed/22828595?dopt=Abstract
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Neurology 2012 Sep 25; 79:1356
Stroke Risk After TIA
Seven-day risk was highest after small-vessel (lacunar) transient ischemic attacks.
Given the growing focus on early recognition of stroke, short-term stroke rates following transient ischemic attacks (TIAs) are of interest. In this study from Oxfordshire, U.K., researchers describe early outcomes in 1000 consecutive patients who experienced TIAs. By subtype, initial TIAs were cardioembolic in 16% of patients, large-artery arteriosclerotic in 14%, small-vessel in 11%, undetermined in 47%, and multiple or other in 13%.
During the first 7 days after TIAs, 25% of patients suffered first recurrent cerebrovascular events (TIA in 17% and stroke in 9%). None of the TIA subtypes were significantly more likely than others to be associated with recurrent TIA. However, the small-vessel disease subtype was significantly more likely than others to be followed by stroke: 7-day stroke rates were 20% in patients with single small-vessel TIAs (17 of 85 patients) and 42% in patients with recurrent small-vessel TIAs (10 of 24 patients). By contrast, 7-day stroke rates were about 10% for patients with single or recurrent cardioembolic or large-artery arteriosclerotic TIAs, and <5% in those with single or recurrent TIAs of undetermined etiology.
Comment: Small-vessel TIAs accounted for only one tenth of the clinical presentations in this study, but they were associated with the highest early stroke risk. Most small-vessel strokes were lacunar internal capsule strokes with motor weakness. A take-home point is that patients with multiple stereotyped episodes of motor weakness might be having small-vessel TIAs (although other etiologies, such as seizures, are possible). Unfortunately, evidence-based interventions for such patients are lacking.
— Allan S. Brett, MD Published in Journal Watch General Medicine October 9, 2012
CITATION(S): Paul NLM et al. Population-based study of capsular warning syndrome and prognosis after early recurrent TIA. Neurology2012 Sep 25; 79:1356.
(http://dx.doi.org/10.1212/WNL.0b013e31826c1af8)
http://www.ncbi.nlm.nih.gov/pubmed/22972645?dopt=Abstract
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N Engl J Med 2012 Nov 8; 367:1792
Statins as Anticancer Drugs?
In an observational study with limitations, statin use by cancer patients was associated with lower 3-year mortality.
In some basic science studies, statins inhibit cancer growth through various pathways. These observations raise the following question: Could statins lower cancer-related mortality? Danish researchers used national databases to address this question.
Among nearly 300,000 people who received cancer diagnoses between 1995 and 2007, 6% had used statins regularly before and after their diagnoses. During average follow-up of 3 years (but as long as 15 years in some cases), two thirds of the patients died. In analyses adjusted for several confounding variables, statin use was associated with a significant 15% drop in all-cause and cancer-related deaths. Mortality reductions were noted for most cancer types (although differences did not reach statistical significance for every type).
Comment: This observational study suggests that statins might influence tumor growth favorably in patients with cancer. In contrast, a recent meta-analysis of randomized trials showed that statins did not increase or decrease the incidence of cancer (PLoS One 2012; 7:e29849). An editorialist notes that the current analysis could not be controlled for several potentially important confounding factors — for example, patients' smoking status was not available and recommends caution in interpreting the findings. Until these results are confirmed or refuted by additional research, clinicians will have to decide whether to apply them to cancer patients; at the least, one might argue that patients who already are taking statins (and tolerating them) at the time of cancer diagnosis should continue.
— Allan S. Brett, MD Published in Journal Watch General Medicine November 8, 2012
Citation(s): Nielsen SF et al. Statin use and reduced cancer-related mortality. N Engl J Med 2012 Nov 8; 367:1792.
(http://dx.doi.org/10.1056/NEJMoa1201735)
Caporaso NE. Statins and cancer-related mortality — Let's work together. N Engl J Med 2012 Nov 8; 367:1848.
(http://dx.doi.org/10.1056/NEJMe1210002)
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FDA Approves New Oral Therapy for Rheumatoid Arthritis
Tofacitinib (marketed as Xeljanz) has been approved to treat adults with moderately to severely active rheumatoid arthritis, the FDA announced on Tuesday. It is the first new oral therapy for RA to be approved in nearly 15 years.
The twice-daily pill, a novel Janus kinase inhibitor, is indicated for patients who have not improved with, or can't tolerate, the usual first-line therapy for RA (methotrexate). In seven clinical trials, patients who received tofacitinib showed greater clinical response and physical functioning than those on placebo.
Tofacitinib carries increased risks for serious infections, cancers, and lymphoma, and will carry a boxed warning about these risks. Common side effects include diarrhea, headache, and upper respiratory tract infections; more serious adverse events could include decreases in blood counts and increases in liver enzyme and cholesterol levels.
http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm327152.htm
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MM: It makes sense that an advocate would improve outcomes.Anxiety and stress can be very detrimental to the progression of a birth, surgery or other physiological event. I wouldn’t be surprised if a doula’s presence would show similar results.
BJOG 2012 Nov; 119:1483
Continuity of Midwife-Led Care: What Effect on Pregnancy Outcomes?
One-to-one midwifery lowered cesarean rates over standard care in a low-risk obstetric population.
Cesarean delivery rates continue to rise despite drawbacks for maternal and neonatal health. A 2008 Cochrane review of midwife-led care (primarily midwives in teams) versus standard care showed no difference in cesarean rates. Now, investigators have conducted a randomized trial at a Melbourne, Australia, hospital to determine whether a one-to-one model of midwifery care ("caseload midwifery") compared with standard care was associated with lower cesarean risk. A total of 2314 eligible participants had uncomplicated singleton pregnancies and no prior cesarean deliveries. Women who were randomized to caseload midwifery received most of their care from a primary midwife during pregnancy, labor, delivery, and immediately postpartum (although occasionally births were assisted by a backup midwife). For those allocated to standard care, options included care by midwives or various combinations of other clinicians.
Women in the caseload midwifery group were less likely than women who received standard care to have cesarean births (19% vs. 35%; P=0.001) and more likely to have spontaneous vaginal deliveries (this difference was most pronounced for primiparous women at 52% vs. 41%; P<0.001). Episiotomy was less common in the caseload group (23% vs. 29%; P=0.003), as was the use of epidural analgesia (31% vs. 35%; P=0.04). Newborns of mothers who received caseload care were less likely to require neonatal intensive care (4% vs. 6%; P=0.01); no infant outcome favored standard care.
Comment: To understand why these results differ from those of the Cochrane analysis, the variable definitions of maternity care models should be reexamined. In this study, backup midwives provided care at least once for 85% of women scheduled for one-on-one care; and in the standard-care group, 78% of women received antenatal care from midwives. Future studies should involve clearer distinctions between treatments; researchers should also recruit more-diverse patient populations and include cost analyses, which probably would favor one-on-one midwifery models.
— Diane J. Angelini, EdD, CNM, FACNM, FAAN, NEA-BC Published in Journal Watch Women's Health November 8, 2012
CITATION(S): McLachlan HL et al. Effects of continuity of care by a primary midwife (caseload midwifery) on caesarean section rates in women of low obstetric risk: The COSMOS randomised controlled trial. BJOG 2012 Nov; 119:1483.
http://www.ncbi.nlm.nih.gov/pubmed/22830446?dopt=Abstract
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MM: The calcium use debate continues. Note that this article deals with the PARAthyroids, not the THYROID gland. Also, the “high” dose of calcium in this study was 1070mg, not the 1200-1800mg recommended by many dietitians, physicians and nutritionists. This higher amount of calcium (1200-1800) has been associated with a variety of cardiovascular dangers. Once again, the questions are not simple, nor are the answers. As consumers and clinicians, we must always weigh the risks vs. the benefits of a practice or treatment.
BMJ 2012 Oct 18; 345:e6390
Higher Calcium Intake Is Associated with Lower Risk for Primary Hyperparathyroidism
Calcium intake affects serum parathyroid hormone levels and, hence, might be associated with risk for developing primary hyperparathyroidism. Using data from the prospective Nurses' Health Study, investigators determined the association between calcium intake and risk for primary hyperparathyroidism.
More than 58,000 women (age range, 39–66) without primary hyperparathyroidism at baseline participated in the study. Participants were categorized into five groups according to calcium intake, which was assessed every 4 years using a validated survey. During 22 years of follow-up, 277 new cases of primary hyperparathyroidism were confirmed. In an analysis adjusted for multiple variables, participants with the highest daily dietary calcium intake (median, 1070 mg) had significantly lower risk for primary hyperparathyroidism (relative risk, 0.56) than participants with the lowest daily dietary calcium intake (median, 443 mg); a significant dose-response trend was observed. Similar results were obtained in analyses of total calcium intake and supplemental calcium intake.
Comment: In this large prospective study, higher calcium intake and modest calcium supplementation were associated with lower risk for primary hyperparathyroidism. The study results are biologically plausible: Low levels of calcium intake might induce clonal expansion of parathyroid cells, leading to adenoma formation and primary hyperparathyroidism. These results have public health implications: As noted by the authors, >100,000 new cases of primary hyperparathyroidism are diagnosed annually in the U.S.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine November 6, 2012
CITATION(S): Paik JM et al. Calcium intake and risk of primary hyperparathyroidism in women: Prospective cohort study. BMJ2012 Oct 18; 345:e6390.
(http://dx.doi.org/10.1136/bmj.e6390)
http://www.ncbi.nlm.nih.gov/pubmed/23080543?dopt=Abstract
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MM: This study brings up a lot of question. When compared to some of the European studies that used anywhere from 30 to 100 times more participants and showed definitive bone mineral density loss, one must question the validity of this study. Undoubtedly this relatively small study will be used to bolster PPI sales and use.
Am J Gastroenterol 2012 Sep; 107:1361
Long-Term PPI Use Does Not Accelerate Loss of Bone Mineral Density
Proton-pump inhibitor users had lower bone mineral density values than nonusers at study entry, but there was no difference in bone mineral density changes during the next 10 years.
Large case-control studies have suggested a possible relationship between the use of proton-pump inhibitors (PPIs) and an increase in osteoporosis and fractures. However, the strength of this association varies among studies (JW Gastroenterol Jul 30 2010).
Investigators in Canada suggest that demonstrating a link between PPI use and a loss of bone mineral density (BMD) would support the idea that PPIs increase risk for fracture. To identify this possible link, the researchers assessed prospectively collected data from the Canadian Multicentre Osteoporosis Study, which involved a population-based sample of patients who provided medical and medication history and underwent BMD testing of the lumbar spine, femoral neck, and total hip at the beginning of the study and at years 5 and 10. Risk factors for osteoporosis and PPI use were entered into a multivariate linear regression model.
Of 8340 study participants enrolled at baseline, 4512 (55%) were followed for 10 years, during which time 4.3% of patients used PPIs continuously. The adjusted BMD values at baseline were lower in PPI users than nonusers in the total hip (P=0.028) and femoral neck (P=0.002), but not the lumbar spine (P=0.179). However, no association was found between PPI use and change in BMD between baseline and year 5, years 5 and 10, or baseline and year 10. This finding remained true in subgroup analyses of patients older than 50 and those using glucocorticoids or osteoprotective medications. No interactions between PPI use and bisphosphonate use were detected.
Comment: As the authors indicate, the reason for the association of a lower BMD with PPI use at baseline is unclear, but may be attributable to confounding factors rather than PPI use. The lack of any acceleration in BMD loss over 10 years suggests that confounding factors also might have contributed to the association with fractures seen in large case-control studies. Whereas this is the first large cohort study to address this issue, the low number of patients taking long-term PPI therapy and the low frequency of bone fractures suggest that the study might have been underpowered to detect small differences in BMD. Larger, well-controlled cohort trials and studies are clearly needed to identify potential mechanisms, perhaps independent of BMD, by which PPI use might increase the risk for fractures.
— David J. Bjorkman, MD, MSPH (HSA), SM (Epid.) Published in Journal Watch Gastroenterology October 5, 2012
CITATION(S): Targownik LE et al. The relationship between proton pump inhibitor use and longitudinal change in bone mineral density: A population-based from the Canadian Multicentre Osteoporosis Study (CaMos). Am J Gastroenterol 2012 Sep; 107:1361.
http://www.ncbi.nlm.nih.gov/pubmed/22777336?dopt=Abstract
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Low-Intensity Aerobic Activity Improves Gait Instability in Parkinson Disease
A low-intensity treadmill regimen improves gait instability and cardiovascular fitness in patients with Parkinson disease, according to a study in the Archives of Neurology.
Roughly 70 patients with Parkinson's and gait instability were randomized to one of three physical activity interventions to be performed three times a week for 3 months: higher-intensity treadmill exercise, lower-intensity treadmill exercise, or stretching and resistance training. All patients underwent a screening exercise test for cardiopulmonary safety.
The primary outcome — distance on a 6-minute walk test — improved in all groups, but only the 12% improvement in the lower-intensity treadmill group achieved statistical significance. Cardiovascular fitness improved significantly in the two treadmill groups, while muscle strength improved in the stretching-resistance group.
The authors write: "The fact that the lower-intensity treadmill exercise is the most feasible exercise for most patients with PD has important implications for clinical practice."
http://archneur.jamanetwork.com/article.aspx?articleid=1389386
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Emerg Radiol2012 Sept 2;
Is CT Useful for Determining the Cause of Vertigo?
Not at all.
Distinguishing between peripheral and central causes of vertigo is challenging, and computed tomography (CT) is often used in the hope of providing key discriminatory information. Researchers reviewed the charts of 448 patients who underwent CT for dizziness at an academic emergency department to determine if a cause was identified and if follow-up imaging (performed in 104 patients) led to a change in diagnosis.
Acute or subacute findings (bleed, neoplasm with or without midline shift or herniation, new or worsening hydrocephalus) were identified on 2.2% of initial CT scans; there were no findings of posterior fossa stroke. Follow-up magnetic resonance imaging (MRI) led to a change in diagnosis in 16% of patients, most often by identifying ischemic strokes not seen on the initial CT scan. CT had a negative predictive value of 88% and a sensitivity of 40% for detecting the cause of vertigo.
Comment: As the authors note, a negative CT result does not exclude a central cause for vertigo, and CT has a low sensitivity for ischemic stroke. CT is not a good first-line test for vertigo, and patients deemed to require imaging should undergo MRI.
— J. Stephen Bohan, MD, MS, FACP, FACEP Published in Journal Watch Emergency Medicine October 19, 2012
CITATION(S): Lawhn-Heath C et al. Utility of head CT in the evaluation of vertigo/dizziness in the emergency department. Emerg Radiol2012 Sept 2; [e-pub ahead of print].
(http://dx.doi.org/10.1007/s10140-012-1071-y)
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J Infect Dis 2012 Nov 15; 206:1549
Understanding the Effect of Healthcare Workers' Hand Hygiene
Using a novel method, investigators revealed marked heterogeneity in healthcare worker interactions and in the potential consequences of their hand hygiene.
Attempts to understand disease transmission in healthcare settings have generally assumed that healthcare workers (HCWs) move and interact uniformly. However, observational studies have suggested the possibility of peripatetic "superspreaders" who have greater-than-average mobility and interactivity — and thus more opportunity to spread infection. In a recent study conducted in the medical intensive care unit of a university hospital, researchers assessed this possibility.
The researchers used small electronic badges worn by HCWs, together with fixed-position beacons, to determine patterns of HCW movement and interactions within this 20-bed unit. They then used these data to mathematically model the effect of HCW hand hygiene on pathogen transmission.
During the 48-hour period of analysis, the average number of contacts (HCW–HCW and HCW–patient) per HCW was 80.1 for day shifts and 76.1 for night shifts. However, a few HCWs were responsible for a disproportionately large share of the contacts. Modeling the effect of hand-hygiene activity on disease transmission showed that spread of a pathogen would be significantly greater with noncompliance of a few high-contact staff members than with noncompliance of an equal number of low-contact workers.
Comment: Hand hygiene is a central tenet of infection control, yet since the original work of Semmelweis, there has been relatively little research on the direct effects of hand-hygiene behavior on disease transmission. Hornbeck and colleagues have provided new insights into HCW contacts, which can help us to understand the role of hand hygiene in preventing nosocomial spread of pathogens and thus to develop more-sophisticated approaches for improving its efficacy.
— Richard T. Ellison III, MD Published in Journal Watch Infectious Diseases November 7, 2012
CITATION(S): Hornbeck T et al. Using sensor networks to study the effect of peripatetic healthcare workers on the spread of hospital-associated infections. J Infect Dis 2012 Nov 15; 206:1549.
http://www.ncbi.nlm.nih.gov/pubmed/23045621?dopt=Abstract
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BMJ 2012 Oct 18; 345:e6779
Daily Acetazolamide Is Effective for Preventing Acute Mountain Sickness
Higher doses were more effective than lower doses but were more likely to be associated with adverse effects.
Acetazolamide, which induces metabolic acidosis and increases ventilation, is prescribed widely to prevent acute mountain sickness. In this meta-analysis of 11 randomized controlled trials that involved more than 1500 participants, investigators assessed the efficacy of acetazolamide in preventing acute mountain sickness.
In all trials, participants were randomized to daily placebo or acetazolamide (250 mg, 500 mg, or 750 mg) and ascended to an elevation of >3000 m. The first dose was given the day of ascent in 5 trials and 1 day or more before ascent in 6; treatment duration (reported in 10 trials) ranged from 2 to 6 days. The combined incidence of acute mountain sickness was 33% in the control groups and 16% in the acetazolamide groups. At doses of 250 mg, 500 mg, and 750 mg, acetazolamide was associated with significantly lower risk for acute mountain sickness (relative risks, 0.54, 0.47, and 0.35, respectively). Corresponding numbers needed to treat were 6, 7, and 3.
Comment: In this meta-analysis, daily acetazolamide was effective in preventing acute mountain sickness. Higher doses of acetazolamide might be more effective than lower doses. Whether to prescribe higher doses, however, depends partly on risk for adverse effects, such as paresthesia, polyuria, rash, and dysgeusia. Indeed, in this analysis, patients who received higher doses of acetazolamide were more likely to experience those adverse effects.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine November 6, 2012
CITATION(S): Low EV et al. Identifying the lowest effective dose of acetazolamide for the prophylaxis of acute mountain sickness: Systematic review and meta-analysis. BMJ 2012 Oct 18; 345:e6779.
(http://dx.doi.org/10.1136/bmj.e6779)
http://www.ncbi.nlm.nih.gov/pubmed/23081689?dopt=Abstract
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BMJ 2012 Sep 27; 345:e6231
New Benzodiazepine Use Is Associated with Risk for Dementia
Risk rose by about 60% among elders in whom treatment with these drugs was initiated.
Benzodiazepines are prescribed often for insomnia and anxiety; however, such symptoms can be early manifestations of dementia when reported in older adults. Although the short-term adverse effects of benzodiazepine use on cognition are recognized, whether benzodiazepine use is associated with excess risk for dementia is unclear. In this prospective, population-based study, investigators assessed the association between benzodiazepine use and incident dementia.
Participants were older adults (mean age, 78) who were free of dementia at baseline and at 5-year follow-up. Ninety-five participants were classified as new benzodiazepine users (no declared benzodiazepine use at baseline or at 3 years of follow-up but declared use at 5 years of follow-up), and 968 participants were classified as nonusers (no declared benzodiazepine use at baseline or at 3 or 5 years of follow-up). During 15 years of follow-up, incident dementia was diagnosed in 32% of new benzodiazepine users and in 23% of nonusers. In two statistical analyses, risk for dementia was 50% to 60% higher among new benzodiazepine users after adjustment for confounding variables. Similar results were obtained when recent and past users were compared with nonusers. The researchers provided no information on dosage of benzodiazepine or duration of use.
Comment: In this study, new benzodiazepine use was associated with higher risk for dementia. However, the results of this study do not establish causality. Patients with early unrecognized dementia can develop anxiety or insomnia that leads to benzodiazepine prescriptions, or benzodiazepine use might lower the threshold at which incipient dementia becomes apparent clinically.
— Paul S. Mueller, MD, MPH, FACP Published in Journal Watch General Medicine November 6, 2012
CITATION(S): de Gage SB et al. Benzodiazepine use and risk of dementia: Prospective population based study. BMJ 2012 Sep 27; 345:e6231.
(http://dx.doi.org/10.1136/bmj.e6231)
http://www.ncbi.nlm.nih.gov/pubmed/23045258?dopt=Abstract
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Chelation Therapy Shows Unexpected, Albeit Limited, Success in CVD
Patients may ask about reports on the success of chelation therapy to remove calcium from patients with cardiovascular disease. Skeptics are — well, skeptical. The study was presented on Sunday at the American Heart Association meeting.
According to a New York Times account, some 1700 patients with previous myocardial infarction were randomized to about a year's worth of chelation therapy or placebo. During nearly 5 years' follow-up, 26% of those on active therapy experienced a cardiovascular event, as opposed to 30% of those on placebo.
One critic called the work "fatally flawed," according to the Times, and said that wide adoption of the procedure would be "a public health catastrophe."
http://www.nytimes.com/2012/11/05/health/chelation-therapy-shows-slight-benefit-in-heart-disease-clinical-trial.html
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J Clin Psychiatry 2012 Oct 16
Oral Scopolamine Augmentation for Major Depression
Scopolamine pill added to citalopram produces higher response and remission rates than add-on placebo.
Evidence is accumulating that cholinergic pathways in the brain help to regulate mood, and researchers have shown that intravenous scopolamine (an anticholinergic) is effective for moderate-to-severe depression (JW Psychiatry Mar 29 2010). This 6-week, Iranian, double-blind study tested whether oral scopolamine (0.5 mg twice daily), added to citalopram as an initial treatment produces greater antidepressant effects than citalopram plus placebo. Participants were 40 patients with moderate-to-severe major depression (baseline score on the 17-item Hamilton Rating Scale for Depression, 
22).
At days 4, 28, and 42, patients receiving scopolamine augmentation had significantly greater reduction in symptoms than patients taking add-on placebo, with an overall large effect size (0.9). Response rates were higher with scopolamine than placebo at week 4 (65% vs. 30%) but not at week 6. Remission rates for scopolamine-treated patients were higher at week 6 (65% vs. 20%). Dry mouth, dizziness, and blurred vision were each noted by at least 40% of scopolamine recipients.
Comment: This study shows that scopolamine given orally (a much preferable route of administration for routine clinical practice) adds significantly to the effect of a selective serotonin reuptake inhibitor for initial treatment of moderate-to-severe depression, although whether it is worth the side effect burden is unclear. Unfortunately, we also do not know whether scopolamine would benefit patients with treatment-resistant depression, although this study's effects in relatively severe depression suggest that such a trial might be pursued. The study's high rate of placebo response (but not remission) and the absence of formal cognitive testing compromise the generalizability of the findings.
— Peter Roy-Byrne, MD Published in Journal Watch Psychiatry October 29, 2012
Citation(s): Khajavi D et al. Oral scopolamine augmentation in moderate to severe major depressive disorder: A randomized, double-blind, placebo-controlled study. J Clin Psychiatry 2012 Oct 16; [e-pub ahead of print].
(http://dx.doi.org/10.4088/JCP.12m07706)
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