Isometric Exercise Training for Blood Pressure Management: A Systematic Review and Meta-analysis

ObjectiveTo conduct a systematic review and meta-analysis quantifying the effects of isometric resistance training on the change in systolic blood pressure(SBP), diastolic blood pressure (DBP), and mean arterial pressure in subclinical populations and to examine whether the magnitude of change in SBP and DBP was different with respect to blood pressure classification.Patients and MethodsWe conducted a systematic review and meta-analysis of randomized controlled trials lasting 4 or more weeks that investigated the effects of isometric exercise on blood pressure in healthy adults (aged ≥18 years) and were published in a peer-reviewed journal. PubMed, CINAHL, and the Cochrane Central Register of Controlled Trials were searched for trials reported between January 1, 1966, and July 31, 2013. We included 9 randomized trials, 6 of which studied normotensive participants and 3 that studied hypertensive patients, that included a total of 223 participants (127 who underwent exercise training and 96 controls).ResultsThe following reductions were observed after isometric exercise training: SBP—mean difference (MD), −6.77 mm Hg (95% CI, −7.93 to −5.62 mm Hg; P<.001); DBP—MD, −3.96 mm Hg (95% CI, −4.80 to −3.12 mm Hg; P<.001); and mean arterial pressure—MD, −3.94 mm Hg (95% CI, −4.73 to −3.16 mm Hg; P<.001). A slight reduction in resting heart rate was also observed (MD, −0.79 beats/min; 95% CI, −1.23 to −0.36 beats/min; P=.003).ConclusionIsometric resistance training lowers SBP, DBP, and mean arterial pressure. The magnitude of effect is larger than that previously reported in dynamic aerobic or resistance training. Our data suggest that this form of training has the potential to produce significant and clinically meaningful blood pressure reductions and could serve as an adjunctive exercise modality.     

Effect of Soft Braces on Pain and Physical Function in Patients With Knee Osteoarthritis: Systematic Review With Meta-Analyses

ObjectivesTo systematically review and synthesize the effects of soft braces on pain and on self-reported and performance-based physical function in patients with knee osteoarthritis.Data SourcesThe following electronic databases were searched from inception to April 20, 2016: The Cochrane Central Register of Controlled Trials (CENTRAL), PubMed, EMBASE, CINAHL, SPORTDiscus, Web of Science, and PEDro.Study SelectionRandomized controlled trials (RCTs) and nonrandomized controlled trials (non-RCTs), such as controlled clinical trials, crossover studies, and case-control studies, were included. Two reviewers independently screened articles and determined inclusion through predefined criteria.Data ExtractionData related to participant demographics, study design and methods, interventions, and outcomes, including numerical means and SDs, were extracted by 1 reviewer. Methodological quality assessment was independently performed by 2 reviewers.Data SynthesisEleven studies were identified, including 6 RCTs and 5 non-RCTs. The methodological quality of included RCTs was low. There was a moderate improvement in pain (standardized mean difference [SMD]=.52; 95% confidence interval [CI], .14–.89; P=.007; 284 participants) in favor of wearing a brace compared with not wearing a brace for the immediate, within-group comparison. There was a moderate improvement in pain (SMD=.61; 95% CI, .33–.89; P<.001; 206 participants) and a small to moderate improvement in self-reported physical function (SMD=.39; 95% CI, .11–.67; P=.006; 206 participants) in favor of patients receiving a soft brace versus standard care for the prolonged effect, between-group comparison.ConclusionsCurrently available evidence indicates that soft braces have moderate effects on pain and small to moderate effects on self-reported physical function in knee osteoarthritis. These findings highlight the importance of soft braces as a technique to improve pain and physical function in both the short- and long-term. Additional high-quality studies are warranted to improve confidence in the findings.     

Association of Exercise Heart Rate Response and Incidence of Hypertension in Men

ObjectiveTo examine the association of heart rate (HR) responses at rest, during exercise, and after exercise with incident hypertension (HTN) in men.Participants and MethodsA total of 10,418 healthy normotensive men without abnormalities on electrocardiography or a history of myocardial infarction, stroke, cancer, or diabetes underwent a maximal exercise test and were followed up for incidence of HTN. Heart rate reserve was defined as the maximal HR minus resting HR. Heart rate recovery was defined as HR 5 minutes after the exercise test.ResultsDuring a mean follow-up of 6 years, there were 2831 cases of HTN. Compared with men who had lower HR reserve, the risk of incident HTN was significantly lower for men with higher HR reserve (hazard ratio, 0.84; 95% CI, 0.74-0.95 for the highest quartile vs the lowest quartile of HR reserve; P=.002) when adjusted for age, baseline examination year, smoking, heavy drinking, body mass index, resting blood pressure, cholesterol and glucose levels, and cardiorespiratory fitness. Compared with men who had higher HR recovery, the risk of incident HTN was significantly lower for men with lower HR recovery (hazard ratio, 0.90; 95% CI, 0.80-0.99 for quartile 3 vs highest quartile; P=.04) after adjusting for the aforementioned confounders. However, the overall linear trend for HR recovery was not significant (P=.26).ConclusionThe risk of HTN decreased in men with higher HR reserve. Therefore, HR reserve may be considered as a useful exercise parameter for predicting the risk of HTN in men.     

Relationship of Body Mass Index With Total Mortality,Cardiovascular Mortality,and Myocardial Infarction After Coronary Revascularization: Evidence From a Meta-analysis

ObjectiveTo investigate the relationship of body mass index (BMI) with total mortality, cardiovascular (CV) mortality, and myocardial infarction (MI) after coronary revascularization procedures (coronary artery bypass grafting [CABG] and percutaneous coronary intervention [PCI]).Patients and MethodsSystematic search of studies was conducted using PubMed, CINAHL, Cochran CENTRAL, Scopus, and the Web of Science databases. We identified studies reporting the rate of MI, CV mortality, and total mortality among coronary artery disease patients' postcoronary revascularization procedures in various BMI categories: less than 20 (underweight), 20-24.9 (normal reference), 25-29.9 (overweight), 30-34.9 (obese), and 35 or more (severely obese). Event rates were compared using a random effects model assuming interstudy heterogeneity.ResultsA total of 36 studies (12 CABG; 26 PCI) were selected for final analyses. The risk of total mortality (relative risk [RR], 2.59; 95% CI, 2.09-3.21), CV mortality (RR, 2.67; 95% CI, 1.63-4.39), and MI (RR, 1.79; 95% CI, 1.28-2.50) was highest among patients with low BMI at the end of a mean follow-up period of 1.7 years. The risk of CV mortality was lowest among overweight patients (RR, 0.81; 95% CI, 0.68-0.95). Increasing degree of adiposity as assessed by BMI had a neutral effect on the risk of MI for overweight (RR, 0.92; 95% CI, 0.84-1.01), obese (RR, 0.99; 95% CI, 0.85-1.15), and severely obese (RR, 0.93; 95% CI, 0.78-1.11) patients.ConclusionAfter coronary artery disease revascularization procedures (PCI and CABG), the risk of total mortality, CV mortality, and MI was highest among underweight patients as defined by low BMI and CV mortality was lowest among overweight patients.     

Immediate Open Repair vs Surveillance in Patients with Small Abdominal Aortic Aneurysms: Survival Differences by Aneurysm Size

ObjectiveTo assess whether survival differences exist between patients undergoing immediate open repair vs surveillance with selective repair for 4.0- to 5.4-cm abdominal aortic aneurysms (AAAs) and whether these differences vary by diameter, within sexes, or overall.Patients and MethodsThe study cohort included 2226 patients randomized to immediate repair or surveillance for the UK Small Aneurysm Trial (September 1, 1991, through July 31, 1998; follow-up, 2.6-6.9 years) or the Aneurysm Detection and Management trial (August 1, 1992, through July 31, 2000; follow-up, 3.5-8.0 years). Survival differences were assessed with proportional hazard models, adjusted for a comprehensive array of clinical and nonclinical risk factors. Interaction between treatment and AAA size was added to the model to assess whether the effect of immediate open repair vs surveillance varied by AAA size.ResultsThe adjusted analysis revealed no statistically significant survival difference between immediate open repair and surveillance patients (hazard ratio [HR], 0.99; 95% CI, 0.83-1.18; mean follow-up time, 1921 days for both study groups). This lack of treatment effect persisted when men (HR, 1.01; 95% CI, 0.84-1.21) and women (HR, 0.96; 95% CI, 0.49-1.86) were examined separately and did not vary by AAA size (P=.39 for the entire cohort and P=.24 for women).ConclusionImmediate open repair offered no significant survival benefit, even in patients with the largest AAAs and highest risk of rupture. Because recent trials failed to find a survival benefit of immediate endovascular repair over surveillance for small asymptomatic AAAs, our findings suggest that the gray area of first-line management for these patients should be resolved in favor of surveillance.     

Myocardial Infarction Risk Among Patients With Fractures Receiving Bisphosphonates

ObjectiveTo determine if bisphosphonates are associated with reduced risk of acute myocardial infarction (AMI).Patients and MethodsA cohort of 14,256 veterans 65 years or older with femoral or vertebral fractures was selected from national administrative databases operated by the US Department of Veterans Affairs and was derived from encounters at Veterans Affairs facilities between October 1, 1998, and September 30, 2006. The time to first AMI was assessed in relationship to bisphosphonate exposure as determined by records from the Pharmacy Benefits Management Database. Time to event analysis was performed using multivariate Cox proportional hazards regression. An adjusted survival analysis curve and a Kaplan-Meier survival curve were analyzed.ResultsAfter controlling for atherosclerotic cardiovascular disease risk factors and medications, bisphosphonate use was associated with an increased risk of incident AMI (hazard ratio, 1.38; 95% CI, 1.08-1.77; P=.01). The timing of AMI correlated closely with the timing of bisphosphonate therapy initiation.ConclusionOur observations in this study conflict with our hypothesis that bisphosphonates have antiatherogenic effects. These findings may alter the risk-benefit ratio of bisphosphonate use for treatment of osteoporosis, especially in elderly men. However, further analysis and confirmation of these findings by prospective clinical trials is required.     

The Effect of Resistance Exercise on All-Cause Mortality in Cancer Survivors

ObjectiveTo examine the independent associations of leisure-time aerobic physical activity (PA) and resistance exercise (RE) on all-cause mortality in cancer survivors.Patients and MethodsPatients included 2863 male and female cancer survivors, aged 18 to 81 years, who received a preventive medical examination between April 8, 1987, and December 27, 2002, while enrolled in the Aerobics Center Longitudinal Study in Dallas, Texas. Physical activity and RE were assessed by self-report at the baseline medical examination. Cox proportional hazards regression analysis was performed to determine the independent associations of PA and RE with all-cause mortality in participants who had a history of cancer.ResultsPhysical activity in cancer survivors was not associated with a lower risk of all-cause mortality. In contrast, RE was associated with a 33% lower risk of all-cause mortality (95% CI, 0.45-0.99) after adjusting for potential confounders, including PA.ConclusionIndividuals who participated in RE during cancer survival had a lower risk for all-cause mortality. The present findings provide preliminary evidence for benefits of RE during cancer survival. Future randomized controlled trials examining RE and its effect on lean body mass, muscular strength, and all-cause mortality in cancer survivors are warranted.     

Determining Reliability of a Dual-Task Functional Mobility Protocol for Individuals With Lower Extremity Amputation

ObjectiveTo determine the relative and absolute reliability of a dual-task functional mobility assessment.DesignCross-sectional study.SettingAcademic rehabilitation hospital.ParticipantsIndividuals (N=60) with lower extremity amputation attending an outpatient amputee clinic (mean age, 58.21±12.59y; 18, 80% male) who were stratified into 3 groups: (1) transtibial amputation of vascular etiology (n=20); (2) transtibial amputation of nonvascular etiology (n=20); and (3) transfemoral or bilateral amputation of any etiology (n=20).InterventionsNot applicable.Main Outcome MeasuresTime to complete the L Test measured functional mobility under single- and dual-task conditions. The addition of a cognitive task (serial subtractions by 3's) created dual-task conditions. Single-task performance on the cognitive task was also reported. Intraclass correlation coefficients (ICCs) measured relative reliability; SEM and minimal detectable change with a 95% confidence interval (MDC₉₅) measured absolute reliability. Bland-Altman plots measured agreement between assessments.ResultsRelative reliability results were excellent for all 3 groups. Values for the dual-task L Test for those with transtibial amputation of vascular etiology (n=20; mean age, 60.36±7.84y; 19, 90% men) were ICC=.98 (95% confidence interval [CI], .94–.99), SEM=1.36 seconds, and MDC₉₅=3.76 seconds; for those with transtibial amputation of nonvascular etiology (n=20; mean age, 55.85±14.08y; 17, 85% men), values were ICC=.93 (95% CI, .80–.98), SEM=1.34 seconds, and MDC₉₅=3.71 seconds; and for those with transfemoral or bilateral amputation (n=20; mean age, 58.21±14.88y; 13, 65% men), values were ICC=.998 (95% CI, .996–.999), SEM=1.03 seconds, and MDC₉₅=2.85 seconds. Bland-Altman plots indicated that assessments did not vary systematically for each group.ConclusionsThis dual-task assessment protocol achieved approved levels of relative reliability values for the 3 groups tested. This protocol may be used clinically or in research settings to assess the interaction between cognition and functional mobility in the population with lower extremity amputation.     

Characteristics Associated With Postdischarge Medication Errors

ObjectiveTo examine the association of patient- and medication-related factors with postdischarge medication errors.Patients and MethodsThe Vanderbilt Inpatient Cohort Study includes adults hospitalized with acute coronary syndromes and/or acute decompensated heart failure. We measured health literacy, subjective numeracy, marital status, cognition, social support, educational attainment, income, depression, global health status, and medication adherence in patients enrolled from October 1, 2011, through August 31, 2012. We used binomial logistic regression to determine predictors of discordance between the discharge medication list and the patient-reported list during postdischarge medication review.ResultsAmong 471 patients (mean age, 59 years), the mean total number of medications reported was 12, and 79 patients (16.8%) had inadequate or marginal health literacy. A total of 242 patients (51.4%) were taking 1 or more discordant medication (ie, appeared on either the discharge list or patient-reported list but not both), 129 (27.4%) failed to report a medication on their discharge list, and 168 (35.7%) reported a medication not on their discharge list. In addition, 279 participants (59.2%) had a misunderstanding in indication, dose, or frequency in a cardiac medication. In multivariable analyses, higher subjective numeracy (odds ratio [OR], 0.81; 95% CI, 0.67-0.98) was associated with lower odds of having discordant medications. For cardiac medications, participants with higher health literacy (OR, 0.84; 95% CI, 0.74-0.95), with higher subjective numeracy (OR, 0.77; 95% CI, 0.63-0.95), and who were female (OR, 0.60; 95% CI, 0.46-0.78) had lower odds of misunderstandings in indication, dose, or frequency.ConclusionMedication errors are present in approximately half of patients after hospital discharge and are more common among patients with lower numeracy or health literacy.     

Resting Heart Rate in First Year Survivors of Myocardial Infarction and Long-term Mortality: A Community Study

ObjectiveTo evaluate the long-term prognostic effect of resting heart rate (HR) at index myocardial infarction (MI) and during the first year after MI among 1-year survivors.Patients and MethodsThe community-based cohort consisted of 1571 patients hospitalized with an incident MI from January 1, 1983, through December 31, 2007, in Olmsted County, Minnesota, who were in sinus rhythm at index MI and had HR measurements on electrocardiography at index and during the first year after MI. Outcomes were all-cause and cardiovascular deaths.ResultsDuring a median follow-up of 7.0 years, 627 deaths and 311 cardiovascular deaths occurred. Using patients with HRs of 60/min or less as the referent, this study found that long-term all-cause mortality risk increased progressively with increasing HR at index (hazard ratio, 1.62; 95% CI, 1.25-2.09) and even more with increasing HR during the first year after MI (hazard ratio, 2.16; 95% CI, 1.64-2.84) for patients with HRs greater than 90/min, adjusting for clinical characteristics and β-blocker use. Similar results were observed for cardiovascular mortality (adjusted hazard ratio, 1.66; 95% CI, 1.14-2.42; and adjusted hazard ratio, 1.93; 95% CI, 1.27-2.94; for HR at index and within 1 year after MI, respectively).ConclusionThese data from a large MI community cohort indicate that HR is a strong predictor of long-term all-cause and cardiovascular mortality not only at initial presentation of MI but also during the first year of follow-up.     

Safety and Efficacy of Extracorporeal Shock Wave Myocardial Revascularization Therapy for Refractory Angina Pectoris

ObjectiveTo assess the safety and efficacy of extracorporeal shockwave myocardial revascularization (ESMR) therapy in treating patients with refractory angina pectoris.Patients and MethodsA single-arm multicenter prospective trial to assess safety and efficacy of the ESMR therapy in patients with refractory angina (class III/IV angina) was performed. Screening exercise treadmill tests and pharmacological single-photon emission computed tomography (SPECT) were performed for all patients to assess exercise capacity and ischemic burden. Patients were treated with 9 sessions of ESMR to ischemic areas over 9 weeks. Efficacy end points were exercise capacity by using treadmill test as well as ischemic burden on pharmacological SPECT at 4 months after the last ESMR treatment. Safety measures included electrocardiography, echocardiography, troponin, creatine kinase, and brain natriuretic peptide testing, and pain questionnaires.ResultsFifteen patients with medically refractory angina and no revascularization options were enrolled. There was a statistically significant mean increase of 122.3±156.9 seconds (38% increase compared with baseline; P=.01) in exercise treadmill time from baseline (319.8±157.2 seconds) to last follow-up after the ESMR treatment (422.1±183.3 seconds). There was no improvement in the summed stress perfusion scores after pharmacologically induced stress SPECT at 4 months after the last ESMR treatment in comparison to that at screening; however, SPECT summed stress score revealed that untreated areas had greater progression in ischemic burden vs treated areas (3.69±6.2 vs 0.31±4.5; P=.03). There was no significant change in the mean summed echo score from baseline to posttreatment (0.4±5.1; P=.70). The ESMR therapy was performed safely without any adverse events in electrocardiography, echocardiography, troponins, creatine kinase, or brain natriuretic peptide. Pain during the ESMR treatment was minimal (a score of 0.5±1.2 to 1.1±1.2 out of 10).ConclusionIn this multicenter feasibility study, ESMR seems to be a safe and efficacious treatment for patients with refractory angina pectoris. However, larger sham-controlled trials will be required to confirm these findings.     

Chronic Obstructive Pulmonary Disease and Association With Mild Cognitive Impairment: The Mayo Clinic Study of Aging

ObjectiveTo investigate the association of chronic obstructive pulmonary disease (COPD) with mild cognitive impairment (MCI) and MCI subtype: amnestic MCI and nonamnestic MCI, in a population-based study of elderly patients.Patients and MethodsParticipants included 1927 individuals aged 70 to 89 years enrolled in the population-based Mayo Clinic Study of Aging. Participants were evaluated by using a nurse assessment, neurological evaluation, and neuropsychological testing, and the diagnosis of MCI was made by a consensus panel according to the standardized criteria. Chronic obstructive pulmonary disease was identified by the review of medical records. The study was conducted from October 1, 2004, through July 31, 2007. The associations of COPD and disease duration with MCI and its subtypes were evaluated by using logistic regression models adjusted for potential covariates.ResultsOf 1927 participants, 288 had COPD (men vs women: 18% vs 12%; P<.001). As compared with patients without COPD, patients with COPD had a higher prevalence of MCI (27% vs 15%; P<.001). The odds ratio (OR) for MCI was almost 2 times higher in patients with COPD than in those without (OR, 1.87; 95% CI, 1.34-2.61), with a similar effect in men and women. The OR for MCI increased from 1.60 (95% CI, 0.97-2.57) in patients with a COPD duration of 5 years or less to 2.10 (95% CI, 1.38-3.14) in patients with a COPD duration of more than 5 years.ConclusionThis population-based study suggests that COPD is associated with increased odds of having MCI and its subtypes. There was a dose-response relationship with the duration of COPD after controlling for the potential covariates.     

Supervised Exercise–Based Intervention to Prevent Excessive Gestational Weight Gain: A Randomized Controlled Trial

ObjectiveTo study the effect on maternal weight gain of a supervised light- to moderate-intensity exercise–based intervention performed from the ninth week of pregnancy.Participants and MethodsA total of 962 healthy pregnant women were randomly assigned to a standard care or exercise intervention group conducted between September 1, 2007, and January 31, 2011. The intervention included light- to moderate-intensity aerobic and resistance exercises performed 3 days a week (50-55 minutes per session). Excessive gestational weight gain was calculated on the basis of the 2009 Institute of Medicine (IOM) recommendations. Gestational body weight gain was calculated on the basis of the weight measured at the first prenatal visit (fifth to sixth weeks of gestation) and weight measured at the last visit to the clinic before delivery. Women were categorized into normal weight or overweight or obese.ResultsWomen in the intervention group gained less weight (adjusted mean difference, 1.039 kg; 95% CI, 0.534-1.545 kg; P<.001) and were less likely to gain weight above the IOM recommendations (odds ratio, 0.625; 95% CI, 0.461-0.847) compared with those in the standard care group. The main treatment effects according to body mass index category were that normal weight women in the intervention group gained less weight (adjusted mean difference, 1.393 kg; 95% CI, 0.813-1.972 kg; P<.001) and were less likely to gain weight above the IOM recommendations (odds ratio, 0.508; 95% CI, 0.334-0.774) than normal weight women who received standard care. No significant treatment effect was observed in overweight or obese women.ConclusionSupervised exercise of light to moderate intensity can be used to prevent excessive gestational weight gain, especially in normal weight women.Trial registrationclinicaltrials.gov Identifier: NCT01790347     

Examining the Function In Sitting Test for Validity,Responsiveness, and Minimal Clinically Important Difference in Inpatient Rehabilitation

ObjectivesTo determine the responsiveness of the Function In Sitting Test (FIST), compare scores at admission and discharge from inpatient rehabilitation (IPR) with other balance and function measures, and determine the minimal clinically important difference (MCID).DesignProspective, nonblinded, reference-standard comparison study.SettingFour accredited inpatient rehabilitation units.ParticipantsPopulation-based sample of adults (N=125) with sitting balance dysfunction, excluding persons with spinal cord injury, significant bracing/orthotics, and inability to perform testing safely.InterventionsNot applicable.Main Outcome MeasuresFIST, FIM, and Berg Balance Scale (BBS) at admission and discharge, and Global Rating of Change for function and balance at discharge.ResultsThe FIST demonstrated good to excellent concurrent validity with the BBS and FIM at admission and discharge (Spearman ρ=.71–.85). Significant improvement (P<.000; 95% confidence interval [CI], 10.73–15.41) occurred in the FIST from admission (mean ± SD: 36.81±15.53) to discharge (mean ± SD: 49.88±6.90). The standard error of measurement for the FIST was 1.40, resulting in a minimal detectable change of 5.5 points. The receiver operator characteristic curve differentiated participants with meaningful balance changes (area under the curve, .78; P>.000; 95% CI, .66–.91), with a change in FIST score of ≥6.5 points designating the MCID. Findings support the strong responsiveness of the FIST during IPR as evidenced by the large effect size (.83), standardized response mean (1.04), and index of responsiveness (1.07).ConclusionsIn this study, the FIST correlated well with balance and function measures (concurrent validity) and was responsive to change during IPR. A clinically meaningful change was indicated by an increase in score of ≥6.5 points.     

The influence of post-rewarming temperature management on post-rewarming fever development after cardiac arrest

Aim of the studyWe evaluated the influence of post-rewarming temperature management (PRTM) on post-rewarming fever development and determined the association between the temperature in the immediate post-targeted temperature management (TTM) period and outcomes.MethodsThis retrospective observational study included consecutive adult cardiac arrest survivors treated with TTM from January 2008 to December 2013. Beginning in August 2010, our institution implemented a PRTM protocol involving continued use of temperature management device to maintain normothermia during the first 24 h after rewarming. The outcomes were in-hospital mortality and neurologic outcome at discharge. We evaluated the effect on clinical outcomes of post-rewarming fever defined at a temperature over 38 °C within 48 h after rewarming.ResultsOf 277 included patients, 55.2% underwent PRTM. The incidence of post-rewarming fever did not differ between the PRTM and no-PRTM groups (odds ratio [OR] 0.963, confidence interval [CI] 0.519, 1.787). Post-rewarming fever was associated with decreased in-hospital mortality (OR 0.243, CI 0.110, 0.534) and decreased rate of unfavorable neurologic outcome (OR 0.312, CI 0.182, 0.534). During 48 h following rewarming, mean temperature was 36.5 °C (36.2–36.8 °C), and peak temperature was 37.5 °C (36.8–38.1 °C). On multivariate analyses, lower mean temperature was associated with increased in-hospital mortality (OR 0.099, CI 0.037, 0.262) and unfavorable neurologic outcome (OR 0.071, CI 0.026, 0.193).ConclusionIt appeared that PRTM did not prevent post-rewarming fever development. Post-rewarming fever was associated with favorable outcomes while lower body temperature after rewarming was associated with unfavorable outcomes. Our results require further confirmation by larger prospective studies.     

Skilled Nursing Facility Use and Hospitalizations in Heart Failure: A Community Linkage Study

ObjectivesTo examine the effect of skilled nursing facility (SNF) use on hospitalizations in patients with heart failure (HF) and to examine predictors of hospitalization in patients with HF admitted to a SNF.Patients and MethodsOlmsted County, Minnesota, residents with first-ever HF from January 1, 2000, through December 31, 2010, were identified, and clinical data were linked to SNF utilization data from the Centers for Medicare and Medicaid Services. Andersen-Gill models were used to determine the association between SNF use and hospitalizations and to determine predictors of hospitalization.ResultsOf 1498 patients with incident HF (mean ± SD age, 75±14 years; 45% male), 605 (40.4%) were admitted to a SNF after HF diagnosis (median follow-up, 3.6 years; range, 0-13.0 years). Of those with a SNF admission, 225 (37%) had 2 or more admissions. After adjustment for age, sex, ejection fraction, and comorbidities, SNF use was associated with a 50% increased risk of hospitalization compared with no SNF use (adjusted hazard ratio, 1.52; 95% CI, 1.31-1.76). In SNF users, arrhythmia, asthma, chronic kidney disease, and the number of activities of daily living requiring assistance were independently associated with an increased risk of hospitalization.ConclusionApproximately 40% of patients with HF were admitted to a SNF at some point after diagnosis. Compared with SNF nonusers, SNF users were more likely to be hospitalized. Characteristics associated with hospitalization in SNF users were mostly noncardiovascular, including reduced ability to perform activities of daily living. These findings underscore the effect of physical functioning on hospitalizations in patients with HF in SNFs and the importance of strategies to improve physical functioning.     

Association Between Alcohol Consumption and Risk of Cardiovascular Disease and All-Cause Mortality in Patients With Hypertension: A Meta-Analysis of Prospective Cohort Studies

ObjectiveTo conduct a meta-analysis summarizing the risk of cardiovascular disease (CVD) and all-cause mortality (ACM) in relation to alcohol consumption in patients with hypertension, focusing on clarifying dose-response associations.Patients and MethodsPubMed and EMBASE were searched for eligible prospective cohort studies from December 3, 1949, through January 18, 2014. The semi-parameter method and dose-response analysis were used.ResultsNine studies (11 cohorts) were included in the meta-analysis. Compared with the lowest alcohol level (abstainers/occasional drinkers), the pooled relative risk (RR) was 0.72 (95% CI, 0.68-0.77) for the third highest category (median, 10 g/d), 0.81 (95% CI, 0.71-0.93) for the second highest category (median, 20 g/d), and 0.60 (95% CI, 0.54-0.67) for the highest category (median, 30 g/d). A J-shaped relationship between alcohol use and ACM was observed, and the nadir (RR, 0.82; 95% CI, 0.76-0.88) was found to be at a dose of 8 to 10 g of alcohol consumption per day.ConclusionFindings of this meta-analysis suggest that low-to-moderate alcohol consumption was inversely significantly associated with the risk of CVD and ACM in patients with hypertension.     

Treatment Discontinuations With New Oral Agents for Long-term Anticoagulation: Insights From a Meta-analysis of 18 Randomized Trials Including 101,801 Patients

ObjectiveTo systematically examine discontinuation rates with new US Food and Drug Administration–approved oral anticoagulants (NOACs) in patients with various indications for long-term anticoagulation.Patients and MethodsPoor adherence to medications is considered a potential and frequent cause of treatment failure. We searched the PubMed, Cochrane Central Register of Controlled Trials, EMBASE, EBSCO, Web of Science, and CINAHL databases for articles published from January 1, 2001, through September 15, 2013. The following Medical Subject Heading terms and/or keywords were used for our database searches: rivaroxaban, dabigatran, apixaban, new oral anticoagulants, oral thrombin inhibitors, and oral factor Xa inhibitors. Articles in English that focused on randomized controlled trials (RCTs) comparing NOACs (apixaban, dabigatran, and rivaroxaban) with conventional therapy or placebo were abstracted. Independent extraction of relevant data was performed by 2 authors. The primary end point of interest was discontinuation due to all causes. Other end points of interest were discontinuation due to adverse events, consent withdrawal, and nonadherence.ResultsEighteen RCTs including a total of 101,801 patients were included for analysis. Total study drug discontinuation rates were not statistically different with NOACs in comparison to pharmacologically active comparators for treatment of venous thromboembolism/pulmonary embolism (risk ratio [RR], 0.91; 95% CI, 0.74-1.13; P=.40) and for NOACs in comparison to warfarin and aspirin for prevention of stroke in patients with atrial fibrillation (RR, 1.01; 95% CI, 0.87-1.17; P=.92). In contrast, in acute coronary syndromes, total study drug discontinuation with NOACs was significantly higher than with placebo (RR, 1.40; 95% CI, 1.07-1.83; P=.01). Overall discontinuations were comparable to those with active comparators.ConclusionStudy drug discontinuations with NOACs were not significantly different from those with conventional drugs in treatment of venous thromboembolism/pulmonary embolism and prevention of stroke in patients with atrial fibrillation but were worse in acute coronary syndromes as noted in evidence from contemporary RCTs.     

Incidence of Leukocytoclastic Vasculitis, 1996 to 2010: A Population-Based Study in Olmsted County,Minnesota

ObjectiveTo determine the population-based incidence of leukocytoclastic vasculitis (LCV).Patients and MethodsThis is a retrospective population-based study of all Olmsted County, Minnesota, residents with a skin biopsy–proven diagnosis of LCV from January 1, 1996, through December 31, 2010.ResultsA total of 84 patients (mean age at diagnosis, 48.3 years) with newly diagnosed skin biopsy–proven LCV (43 women and 41 men) were identified. The incidence rate (age and sex adjusted to the 2000 US white population) was 4.5 per 100,000 person-years (95% CI, 3.5-5.4). The incidence of LCV increased significantly with age at diagnosis (P<.001) and did not differ between female and male patients. Subtypes of LCV were cutaneous small-vessel vasculitis (CSVV), 38 patients (45%); IgA vasculitis, 25 (30%); urticarial vasculitis, 10 (12%); cryoglobulinemic vasculitis, 3 (4%); and antineutrophil cytoplasmic antibody–associated vasculitis, 8 (10%). LCV was idiopathic in 29 of 38 patients with CSVV (76%) and 24 of 25 patients with IgA vasculitis (96%). Thirty-nine of 84 patients (46%) had systemic involvement, with the renal system most commonly involved (17 of 39 [44%]). Twenty-four of 80 patients (30%) with follow-up data available had recurrent disease. Compared with the Minnesota white population, observed survival in the incident LCV cohort was significantly poorer than expected (P<.001), including the subset of patients with idiopathic CSVV (P=.03).ConclusionThe incidence of LCV was higher than that reported in previously published studies. Idiopathic LCV was more common in our population-based cohort than that described previously. Overall survival was significantly poorer (P<.001) and should be explored further in future studies.     

Comparative Efficacy of Biologic Therapy in Biologic-Naïve Patients With Crohn Disease: A Systematic Review and Network Meta-analysis

ObjectiveTo study the comparative efficacy of biologic therapy in the management of biologic-naïve patients with Crohn disease (CD).Patients and MethodsWe conducted a systematic review of randomized controlled trials published from January 1, 1985, through September 30, 2013, comparing biologic agents (infliximab [IFX], adalimumab [ADA], certolizumab pegol, natalizumab, vedolizumab, and ustekinumab) with each other or placebo for inducing and maintaining clinical remission in adults with moderate to severe CD. To increase comparability across trials, we focused on a subset of biologic-naïve patients for the induction end point and on responders to induction therapy for the maintenance end point. We followed a Bayesian network meta-analysis approach.ResultsWe identified 17 randomized controlled trials of good methodological quality comparing 6 biologic agents with placebo, with no direct comparison of biologic agents. In network meta-analysis, we observed that IFX (relative risk [RR], 6.11; 95% credible interval [CrI], 2.49-18.29) and ADA (RR, 2.98; 95% CrI, 1.12-8.18), but not certolizumab pegol (RR, 1.48; 95% CrI, 0.76-2.93), natalizumab (RR, 1.36; 95% CrI, 0.69-2.86), vedolizumab (RR, 1.40; 95% CrI, 0.63-3.28), and ustekinumab (RR, 0.61; 95% CrI, 0.15-2.49), were more likely to induce remission than placebo. Similar results were observed for maintenance of remission. Infliximab had the highest probability of being ranked as the most efficacious agent for induction (86%) and ADA for maintenance of remission (48%).ConclusionOn the basis of network meta-analysis, IFX may be most efficacious agent for inducing remission in CD in biologic-naïve patients. In the absence of head-to-head treatment comparison, the confidence in these estimates is low. Future comparative efficacy studies are warranted.