Clinical Health Updates

Neuropsychologic scores marginally predict Alzheimer’s risk

Clinical Question:
Does cognitive performance predict the subsequent development of Alzheimer disease?

Bottom Line:
Baseline scores on the Mayo Cognitive Factor Scales (MCFS) are somewhat predictive of developing Alzheimer disease after 6 years.

Reference:
Powell MR, Smith GE, Knopman DS, et al. Cognitive measures predict pathologic Alzheimer disease. Arch Neurol 2006;63:865-868.

Study Design:
Cohort (prospective)

Synopsis:
Neuropsychologic testing is often used to infer neuropathologic processes, but clinicopathologic correlations for individual cognitive measures are based on a small number of published studies. To examine the usefulness of the age- and education-adjusted Mayo Cognitive Factor Scales (MCFS) obtained at participants’ initial assessments for predicting the presence or absence of pathologic Alzheimer disease (AD). This was a longitudinal study of a cohort of elderly patients with and without cognitive complaints who were followed up until death. Mayo Cognitive Factor Scales age- and education-adjusted standard scores from the participants’ initial evaluations were used to calculate classification accuracy statistics for neuropathologic AD diagnosis obtained approximately 6 years after testing. Subjects with non-AD diagnoses or substantial non-AD-related changes were excluded from the study. SETTING: Academic medical center. These authors recruited one hundred two participants. Evaluated clinically and underwent neuropathologic examination at autopsy. All were part of the Mayo Clinic Alzheimer’s Disease Patient Registry or Alzheimer Disease Research Center. All Mayo Cognitive Factor Scale scores were significantly correlated with AD criteria. Logistic regression modeling including Mayo Cognitive Factor Scales Verbal Comprehension and Retention indices revealed high positive predictive value with moderate sensitivity and specificity for pathologic AD.

Postcoital bleeding of limited use in determining cervical cancer risk

Clinical Question:
Doc, I bleed after intercourse. Could I have cervical cancer?

Bottom Line:
The evidence base for management strategies of postcoital bleeding and calculations of risk for cervical cancer in women with postcoital bleeding are poor. Calculation of risk that a woman in the community developing postcoital bleeding has cervical cancer ranges from 1 in 44,000 at age 20-24 years to 1 in 2 400 aged 45-54 years.

Reference:
Shapley M, Jordan J, Croft PR. A systematic review of postcoital bleeding and risk of cervical cancer. Br J Gen Pract 2006;56:453-460.

Study Design:
Systematic review

Synopsis:
These authors systematically reviewed several databases looking for English-language studies that reported or provided sufficient data to estimate the incidence or prevalence of postcoital bleeding. The authors don’t report looking for unpublished data, independent and paired application of inclusion criteria, or paired data abstraction. Ultimately, they included 38 articles. They found no studies that determined how often women presenting with postcoital bleeding subsequently have cervical cancer. One mass screening study from Finland identified 2648 women with postcoital bleeding of whom 12 (0.45%) had invasive cancer at the time of presentation. Eight of the articles (including hundreds of thousands of women), evaluated women in community settings. The overall rate of women complaining about postcoital bleeding is quite variable (0.7% to 9%); however, the large population-based studies report the prevalence at approximately 1%. It is not known how many of these women will seek medical care. Sixteen studies reported the prevalence of postcoital bleeding in more than 47,000 women with invasive cervical cancer. The range of prevalence in these studies was 0.7% to 39%.

Repeated antenatal doses of steroids reduces neonatal morbidity (ACTORDS)

Clinical Question:
Do repeated doses of steroids reduce neonatal morbidity?

Bottom Line:
Exposure to repeat doses of antenatal corticosteroids reduces neonatal morbidity. Pending long-term outcome results, the short-term benefits for the babies in our study support the use of repeat doses of corticosteroids in women who remain at risk of very preterm birth 7 or more days after an initial course.

Reference:
Crowther CA, Haslam RR, Hiller JE, Doyle LW, Robinson JS, for the Australasian Collaborative Trial of Repeat Doses of Steroids (ACTORDS) Study Group.Neonatal respiratory distress syndrome after repeat exposure to antenatal corticosteroids: a randomised controlled trial. Lancet 2006;367:1913-1919.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
Pregnant women at 32 weeks’ gestation or less (including women carrying twins or triplets) who had received a dose of corticosteroids at least 7 days before and who were judged to be at continued risk for premature delivery were randomly assigned (by concealed allocation) to receive weekly intramuscular injections of 7.8 mg betamethasone sodium phosphate and 6 mg betamethasone acetate (Celestone Chronodose; n = 489 women, 568 babies) or saline placebo (n = 493 women, 578 babies). The researchers excluded women who were in the second stage of labor, had chorioamnionitis needing urgent delivery, had mature lung development, or had been judged to require further corticosteroid therapy. The main outcomes were evaluated by intention to treat, but the authors don’t say if these outcomes were assessed by researchers masked to treatment assignment. The researchers included 100% of the women and babies in the analysis. Overall neonatal mortality was similar in each group (4.6% in the steroid-treated group, 4.8% in the saline group). However, only 33% of the steroid-treated infants developed respiratory distress syndrome compared with 41% of the control infants (number needed to treat=14; 95% CI, 8 – 50).

Warfarin prevents more strokes than clopidorel+ASA in a fib (ACTIVE)

Clinical Question:
Is warfarin better than clopidogrel plus aspirin in preventing strokes in patients with atrial fibrillation?

Bottom Line:
Warfarin is superior to the combination of clopidogrel (Plavix) plus aspirin in preventing strokes and systemic emboli in high-risk patients with atrial fibrillation.

Reference:
ACTIVE Writing Group on behalf of the ACTIVE Investigators; Connolly S, Pogue J, Hart R, et al. Clopidogrel plus aspirin versus oral anticoagulation for atrial fibrillation in the Atrial fibrillation Clopidogrel Trial with Irbesartan for prevention of Vascular Events (ACTIVE W): a randomised controlled trial. Lancet 2006;367:1903-1912.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
Oral anticoagulation therapy reduces risk of vascular events in patients with atrial fibrillation. However, long-term monitoring is necessary and many patients cannot achieve optimum anticoagulation. We assessed whether clopidogrel plus aspirin was non-inferior to oral anticoagulation therapy for prevention of vascular events. Patients were enrolled if they had atrial fibrillation plus one or more risk factor for stroke, and were randomly allocated to receive oral anticoagulation therapy (target international normalised ratio of 2.0-3.0; n=3371) or clopidogrel (75 mg per day) plus aspirin (75-100 mg per day recommended; n=3335). Outcome events were adjudicated by a blinded committee. Primary outcome was first occurrence of stroke, non-CNS systemic embolus, myocardial infarction, or vascular death. Analyses were by intention-to-treat. This study is registered with ClinicalTrials.gov, number NCT00243178. The study was stopped early because of clear evidence of superiority of oral anticoagulation therapy. There were 165 primary events in patients on oral anticoagulation therapy (annual risk 3.93%) and 234 in those on clopidogrel plus aspirin (annual risk 5.60%; relative risk 1.44 (1.18-1.76; p=0.0003). Patients on oral anticoagulation therapy who were already receiving this treatment at study entry had a trend towards a greater reduction in vascular events (relative risk 1.50, 95% CI 1.19-1.89) and a significantly (p=0.03 for interaction) lower risk of major bleeding with oral anticoagulation therapy (1.30; 0.94-1.79) than patients not on this treatment at study entry (1.27, 0.85-1.89 and 0.59, 0.32-1.08, respectively).

Limited evidence on prophylactic antibiotics in acute necrotizing pancreatitis

Clinical Question:
Do prophylactic antibiotics improve outcomes in patients with acute necrotizing pancreatitis?

Bottom Line:
Compared with a control treatment, prophylactic intravenous antibiotics do not significantly improve outcomes in patients with acute necrotizing pancreatitis. The included studies in this meta-analysis, however, were small and of poor quality, so it is likely that there was insufficient power to see important differences. Further studies are needed.

Reference:
Mazaki T, Ishii Y, Takayama T. Meta-analysis of prophylactic antibiotic use in acute necrotizing pancreatitis. Br J Surg 2006;93:674-684.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
Death from infected necrosis in acute pancreatitis is common and prevention has focused on prophylactic antibiotics. This study assesses whether intravenous prophylactic antibiotic use reduces infected necrosis and death in acute necrotizing pancreatitis. A meta-analysis of randomized controlled trials was carried out. Medline, Web of Science, the Cochrane controlled trials register and international conference proceedings were searched, with a citation review of relevant primary and review articles. Six of 328 studies assessed were included in data extraction. Primary outcome measures were infected necrosis and death. Secondary outcome measures were non-pancreatic infections, surgical intervention and length of hospital stay. Prophylactic antibiotic use was not associated with a statistically significant reduction in infected necrosis (relative risk (RR) 0.77 (95 per cent confidence interval (c.i.) 0.54 to 1.12); P = 0.173), mortality (RR 0.78 (95 per cent c.i. 0.44 to 1.39); P = 0.404), non-pancreatic infections (RR 0.71 (95 per cent c.i. 0.32 to 1.58); P = 0.402) and surgical intervention (RR 0.78 (95 per cent c.i. 0.55 to 1.11); P = 0.167). It was, however, associated with a statistically significant reduction in hospital stay (P = 0.040).

Corticosteroids benefit patients with moderate to severe COPD

Clinical Question:
Are inhaled corticosteroids effective in patients with chronic obstructive pulmonary disease ?

Bottom Line:
Inhaled corticosteroids prevent exacerbations in patients with moderate to severe chronic obstructive pulmonary disease (COPD). The benefit is minor, however, and steroids don’t prevent exacerbations in patients with mild COPD. The prevention of exacerbations with steroids must be balanced against the higher rate of fractures and glaucoma.

Reference:
Gartlehner G, Hansen RA, Carson SS, Lohr KN. Efficacy and safety of inhaled corticosteroids in patients with COPD: a systematic review and meta-analysis of health outcomes. Ann Fam Med 2006;4:253-262.

Study Design:
Meta-analysis (randomized controlled trials)

Synopsis:
The author reviewed systematically the efficacy, effectiveness, and safety of inhaled corticosteroids with respect to health outcomes in patients with chronic obstructive pulmonary disease (COPD). They searched MEDLINE, EMBASE, The Cochrane Library, and the International Pharmaceutical Abstracts to identify relevant articles. They limited evidence to double-blinded randomized controlled trials (RCTs) for efficacy, but we also reviewed observational evidence for safety. Outcomes of interest were overall mortality, exacerbations, quality of life, functional capacity, and respiratory tract symptoms. When possible, we pooled data to estimate summary effects for each outcome. Thirteen double-blinded RCTs determined the efficacy of an inhaled corticosteroid compared with placebo; 11 additional studies assessed the safety of inhaled corticosteroid treatment in patients with asthma or COPD. Overall, COPD patients treated with inhaled corticosteroids experienced significantly fewer exacerbations than patients taking placebo (relative risk [RR] = 0.67; 95% CI, 0.59-0.77). No significant difference could be detected for overall mortality (RR = 0.81; 95% CI, 0.60-1.08). Evidence on quality of life, functional capacity, and respiratory tract symptoms is mixed. Adverse events were generally tolerable; pooled discontinuation rates did not differ significantly between inhaled corticosteroid and placebo treatment groups (RR = 0.92; 95% CI, 0.74-1.14). Observational evidence, however, indicates a dose-related risk of cataract and open-angle glaucoma. Severe adverse events, such as osteoporotic fractures, are rare; the clinical importance of the additional risk is questionable.

Statin use may reduce risk of cataracts

Clinical Question:
Do statins reduce the risk of cataracts?

Bottom Line:
Statin use is associated with a reduced incidence of nuclear cataracts, the most common type of age-related cataracts. However, this type of study design (prospective cohort study) does not prove a causal relationship between the use of statins and lower risk of developing cataracts. It is possible that other confounding variables (eg, genetics or patient compliance) are causally related.

Reference:
Klein BE, Klein R, Lee KE, Grady LM. Statin use and incident nuclear cataract. JAMA 2006;295:2752-2758.

Study Design:
Cohort (prospective)

Synopsis:
Statins are widely prescribed for their lipid-lowering effects but also have putative antioxidant properties. Oxidative stress is believed to play a role in the development of nuclear cataract, but little is known regarding the relationship of statin use and cataract incidence. The author evaluate the relationship of use of statins and incident cataract in adults in a midwestern community in the United States. The Beaver Dam Eye Study, an observational, longitudinal, population-based study of age-related eye disease in Beaver Dam, Wis. There were 1299 persons who were seen at the third examination in 1998-2000, had gradable photographs in both eyes, and were deemed to be at risk of developing nuclear cataract within 5 years. Five-year incidence of cataract with respect to statin use. Cataracts were graded from photographs taken through the participant’s dilated pupil. A total of 210 persons developed incident nuclear cataract in the interval from 1998-2000 to 2003-2005. Five-year incidence of nuclear cataract was 12.2% in statin users compared with 17.2% in nonusers (odds ratio [OR], 0.55; 95% confidence interval [CI], 0.36-0.84), controlling for age. When only never smokers without diabetes were assessed, the age-, lipid level-, and sex-adjusted OR was 0.40 (95% CI, 0.18-0.90). Five-year incidence of cortical cataract was 9.9% in statin users and 7.5% in nonusers (OR, 1.28; 95% CI, 0.79-2.08); posterior subcapsular cataract occurred in 3.0% of statin users and 3.4% of nonusers (OR, 0.82; 95% CI, 0.39-1.71).

Role of oral magnesium theraphy in CAD

Clinical Question:
Does oral magnesium theraphy beneficial on patient with coronary artery disease (CAD)?

Bottom Line:
The present study supports the intake of oral Mg and its favorable effects on exercise tolerance and left ventricular function during rest and exercise in stable CAD patients.

Reference:
Oral magnesium therapy, exercise heart rate, exercise tolerance, and myocardial function in coronary artery disease patients.Pokan R, Hofmann P, von Duvillard SP, Smekal G, Wonisch M, Lettner K, Schmid P, Shechter M, Silver B, Bachl N.Br J Sports Med. 2006 Jul 6

Study Design:
Randomized Controlled Trial (double blind)

Synopsis:
Previous studies have demonstrated that in patients with coronary artery disease (CAD) an upward deflection of the heart rate (HR) performance curve can be observed and that this upward deflection and the degree of the deflection is correlated with a diminished stress-dependent left ventricular function. Magnesium (Mg) supplementation improves endothelial function, exercise tolerance, and exercise-induced chest pain in patients with CAD. The author studied the effects of oral Mg therapy on exercise dependent HR as related to exercise tolerance and resting myocardial function in patients with CAD. They did a double-blind controlled trial, 53 male patients with stable CAD, were randomized to either oral Mg 15 mmol twice daily (N = 28, age = 61 inverted exclamation mark&Oacute9 yrs, height = 171 inverted exclamation mark&Oacute7, body weight = 79 inverted exclamation mark&Oacute10 kg, previous myocardial infarction (MI), N = 7) or placebo (N = 25, age = 58 inverted exclamation mark&Oacute10 yrs, height = 172 inverted exclamation mark&Oacute6, body weight = 79 inverted exclamation mark&Oacute10 kg, previous MI, N = 6) for 6 months. Maximal oxygen uptake (VO2max), the degree and direction of the deflection of the HR performance curve described as factor k f not 0 (upward deflection) and the left ventricular ejection fraction (LVEF), were the outcomes measured. Six-month Mg therapy significantly increased intracellular Mg levels (32.7 inverted exclamation mark&Oacute2.5 vs. 35.6 inverted exclamation mark&Oacute2.1 mEq/L, p<0.001) compared to placebo (33.1 inverted exclamation mark&Oacute3.1.9 vs. 33.8 inverted exclamation mark&Oacute 2.0 mEq/L, n.s.), VO2max (28.3 inverted exclamation mark&Oacute6.2 vs. 30.6 inverted exclamation mark&Oacute7.1 ml/kg/min, p<0.001; 29.3 inverted exclamation mark&Oacute5.4 vs. 29.6 inverted exclamation mark&Oacute5.2 ml/kg/min, n.s.), factor k (-0.298 inverted exclamation mark&Oacute0.242 vs. -0.208 inverted exclamation mark&Oacute0.260, p<0.05; -0.269 inverted exclamation mark&Oacute0.336 vs. -0.272 inverted exclamation mark&Oacute0.335, n.s.), LVEF (58 inverted exclamation mark&Oacute11 vs. 67 inverted exclamation mark&Oacute10 %, p<0.001; 55 inverted exclamation mark&Oacute11 vs. 54 inverted exclamation mark&Oacute12 %, n.s.).

Uncertain value of automated chest compression device for cardiac arrest

Clinical Question:
Which method of resuscitation optimizes outcomes of out-of-hospital cardiac arrest: manual chest compression or the use of an automated chest compression device?

Bottom Line:
Current evidence is unable to support a recommendation for the use of either manual chest compression or an automated chest compression device for out-of-hospital cardiac arrest resuscitation. Overall survival with good neurologic function at hospital discharge occurs in fewer than 10% of individuals with the use of either cardiac pulmonary resuscitation (CPR) method.

Reference:
Hallstrom A, Rea TD, Sayre MR, et al. Manual chest compression vs use of an automated chest compression device during resuscitation following out-of-hospital cardiac arrest. A randomized trial. JAMA 2006;295:2620-2628.

Study Design:
Randomized controlled trial (nonblinded)

Synopsis:
High-quality cardiopulmonary resuscitation (CPR) may improve both cardiac and brain resuscitation following cardiac arrest. Compared with manual chest compression, an automated load-distributing band (LDB) chest compression device produces greater blood flow to vital organs and may improve resuscitation outcomes. To compare resuscitation outcomes following out-of-hospital cardiac arrest when an automated LDB-CPR device was added to standard emergency medical services (EMS) care with manual CPR. The author did a multicenter, randomized trial of patients experiencing out-of-hospital cardiac arrest in the United States and Canada. The a priori primary population was patients with cardiac arrest that was presumed to be of cardiac origin and that had occurred prior to the arrival of EMS personnel. Initial study enrollment varied by site, ranging from late July to mid November 2004; all sites halted study enrollment on March 31, 2005. Standard EMS care for cardiac arrest with an LDB-CPR device (n = 554) or manual CPR (n = 517). The primary end point was survival to 4 hours after the 911 call. Secondary end points were survival to hospital discharge and neurological status among survivors. Following the first planned interim monitoring conducted by an independent data and safety monitoring board, study enrollment was terminated. No difference existed in the primary end point of survival to 4 hours between the manual CPR group and the LDB-CPR group overall (N = 1071; 29.5% vs 28.5%; P = .74) or among the primary study population (n = 767; 24.7% vs 26.4%, respectively; P = .62). However, among the primary population, survival to hospital discharge was 9.9% in the manual CPR group and 5.8% in the LDB-CPR group (P = .06, adjusted for covariates and clustering). A cerebral performance category of 1 or 2 at hospital discharge was recorded in 7.5% of patients in the manual CPR group and in 3.1% of the LDB-CPR group (P = .006).

Oral steroids effective for nasal polyps

Clinical Question:
Are oral steroids effective in the management of nasal polyps?

Bottom Line:
This trial clearly establishes clinically significant improvement in the symptoms and pathology of sinonasal polyposis with a short course of systemic corticosteroids. MRI scanning and quantitative nasendoscopic photography are objective and valid tools for assessing the outcome of treatment in this condition.

CLINICAL IMPLICATIONS:
A 14-day course of 50 mg of prednisolone is safe and effective therapy for symptomatic nasal polyposis.

Reference:
Hissaria P, Smith W, Wormald PJ, et al. Short course of systemic corticosteroids in sinonasal polyposis: A double-blind, randomized, placebo-controlled trial with evaluation of outcome measures. J Allergy Clin Immunol 2006;118:128-133.

Study Design:
Randomized controlled trial (double-blinded)

Synopsis:
These investigators identified 41 adults, aged 18 years to 64 years, with symptomatic polyp disease diagnosed by nasendoscopy. Patients randomly received (concealed allocation assignment) prednisolone (50 mg) or matched placebo once daily for 14 days. Individuals assessing outcomes remained blinded to treatment group assignment. Follow-up occurred for more than 97% of patients for 14 days. Subscores from a cluster of 6 nasal symptoms (congestion, rhinorrhea, sneezing, hyposmia, postnasal discharge, and thick nasal debris) derived from a 31-item questionnaire assessing rhinosinusitis outcomes were reported at baseline and after 2 weeks of therapy. Using intention-to-treat analysis, a clinically significant (> 20%) improvement in scores occurred in 95% of prednisolone-treated patients, compared with 37% in the placebo group (number needed to treat = 2; 95% CI, 1-3). Polyp size as assessed by nasendoscopy was also significantly reduced. Insomnia occurred significantly more often in the prednisolone group, but other side effects were infrequent and not different between the treatment groups.