Brian H. Rowe

Effects of exercise on breast cancer patients and survivors: a systematic review and meta-analysis

Background: Physical exercise has been identified as a potential intervention to improve quality of life in women with breast cancer. We sought to summarize the available evidence concerning the effects of exercise on breast cancer patients and survivors. Methods: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, CINAHL, PsychINFO, CancerLit, PEDro and SportDiscus as well as conference proceedings, clinical practice guidelines and other unpublished literature resources. We included only randomized controlled trials that examined exercise interventions for breast cancer patients or survivors with quality of life, cardiorespiratory fitness or physical functioning as primary outcomes. We also extracted data on symptoms of fatigue, body composition and adverse effects. Results: Of 136 studies identified, 14 met all the inclusion criteria. Despite significant heterogeneity and relatively small samples, the point estimates in terms of the benefits of exercise for all outcomes were positive even when statistical significance was not achieved. Exercise led to statistically significant improvements in quality of life as assessed by the Functional Assessment of Cancer Therapy–General (weighted mean difference [WMD] 4.58, 95% confidence interval [CI] 0.35 to 8.80) and Functional Assessment of Cancer Therapy–Breast (WMD 6.62, 95% CI 1.21 to 12.03). Exercise also led to significant improvements in physical functioning and peak oxygen consumption and in reducing symptoms of fatigue. Interpretation: Exercise is an effective intervention to improve quality of life, cardiorespiratory fitness, physical functioning and fatigue in breast cancer patients and survivors. Larger trials that have a greater focus on study quality and adverse effects and that examine the long-term benefits of exercise are needed for this patient group.

Diagnosis and Management of Work-Related Asthma: American College of Chest Physicians Consensus Statement

BACKGROUND A previous American College of Chest Physicians Consensus Statement on asthma in the workplace was published in 1995. The current Consensus Statement updates the previous one based on additional research that has been published since then, including findings relevant to preventive measures and work-exacerbated asthma (WEA). METHODS A panel of experts, including allergists, pulmonologists, and occupational medicine physicians, was convened to develop this Consensus Document on the diagnosis and management of work-related asthma (WRA), based in part on a systematic review, that was performed by the University of Alberta/Capital Health Evidence-Based Practice and was supplemented by additional published studies to 2007. RESULTS The Consensus Document defined WRA to include occupational asthma (ie, asthma induced by sensitizer or irritant work exposures) and WEA (ie, preexisting or concurrent asthma worsened by work factors). The Consensus Document focuses on the diagnosis and management of WRA (including diagnostic tests, and work and compensation issues), as well as preventive measures. WRA should be considered in all individuals with new-onset or worsening asthma, and a careful occupational history should be obtained. Diagnostic tests such as serial peak flow recordings, methacholine challenge tests, immunologic tests, and specific inhalation challenge tests (if available), can increase diagnostic certainty. Since the prognosis is better with early diagnosis and appropriate intervention, effective preventive measures for other workers with exposure should be addressed. CONCLUSIONS The substantial prevalence of WRA supports consideration of the diagnosis in all who present with new-onset or worsening asthma, followed by appropriate investigations and intervention including consideration of other exposed workers.

Effectiveness of a home-based balance-training program in reducing sports-related injuries among healthy adolescents: a cluster randomized controlled trial

Background: Sport is the leading cause of injury requiring medical attention among adolescents. We studied the effectiveness of a home-based balance-training program using a wobble board in improving static and dynamic balance and reducing sports-related injuries among healthy adolescents. Methods: In this cluster randomized controlled trial, we randomly selected 10 of 15 high schools in Calgary to participate in the fall of 2001. We then recruited students from physical education classes and randomly assigned them, by school, to either the intervention (n = 66) or the control (n = 61) group. Students in the intervention group participated in a daily 6-week and then a weekly 6-month home-based balance-training program using a wobble board. Students at the control schools received testing only. The primary outcome measures were timed static and dynamic balance, 20-m shuttle run and vertical jump, which were measured at baseline and biweekly for 6 weeks. Self-reported injury data were collected over the 6-month follow-up period. Results: At 6 weeks, improvements in static and dynamic balance were observed in the intervention group but not in the control group (difference in static balance 20.7 seconds, 95% confidence interval [CI] 10.8 to 30.6 seconds; difference in dynamic balance 2.3 seconds, 95% CI 0.7 to 4.0 seconds). There was evidence of a protective effect of balance training in over 6 months (relative risk of injury 0.2, 95% CI 0.05 to 0.88). The number needed to treat to avoid 1 injury over 6 months was 8 (95% CI 4 to 35). Interpretation: Balance training using a wobble board is effective in improving static and dynamic balance and reducing sports-related injuries among healthy adolescents.

Default mode network connectivity as a predictor of post-traumatic stress disorder symptom severity in acutely traumatized subjects

Objective:  The goal of this study was to investigate the relationship between default mode network connectivity and the severity of post‐traumatic stress disorder (PTSD) symptoms in a sample of eleven acutely traumatized subjects.

Utilization of health services following spinal cord injury: a 6-year follow-up study

Study design: Cohort study with 6-years follow-up.Objective: To describe the utilization of health services by persons with spinal cord injury (SCI) and compare it with that of the general population.Setting: Alberta, Canada.Methods: All persons who sustained an SCI in Alberta between April 1992 and March 1994 were followed from date of injury to 6 years postinjury. Cases were matched (1:5) with controls randomly selected from the general population and matched for age, gender, and region of residence. Administrative data from centralized health care databases were compiled to provide a complete picture of health care use, including hospitalizations, physician contacts, long-term care admissions, home care services, and the occurrence of secondary complications.Results: In all, 233 individuals with SCI and 1165 matched controls were followed for 6 years. Compared with the control group, persons with SCI were rehospitalized 2.6 times more often, spent 3.3 more days in hospital, were 2.7 times more likely to have a physician contact, and required 30 times more hours of home care services. Of those with SCI, 47.6% were treated for a urinary tract infection, 33.8% for pneumonia, 27.5% for depression, and 19.7% for decubitus ulcer.Conclusion: SCI places a heavy burden on the health care system. Persons with SCI have greater rates of contact with the health system compared with the general population. Secondary complications continue to affect persons with SCI long after the acute trauma.

Canadian Thoracic Society 2012 guideline update: Diagnosis and management of asthma in preschoolers, children and adults

BACKGROUND In 2010, the Canadian Thoracic Society (CTS) published a Consensus Summary for the diagnosis and management of asthma in children six years of age and older, and adults, including an updated Asthma Management Continuum. The CTS Asthma Clinical Assembly subsequently began a formal clinical practice guideline update process, focusing, in this first iteration, on topics of controversy and⁄or gaps in the previous guidelines. METHODS Four clinical questions were identified as a focus for the updated guideline: the role of noninvasive measurements of airway inflammation for the adjustment of anti-inflammatory therapy; the initiation of adjunct therapy to inhaled corticosteroids (ICS) for uncontrolled asthma; the role of a single inhaler of an ICS⁄long-acting beta(2)-agonist combination as a reliever, and as a reliever and a controller; and the escalation of controller medication for acute loss of asthma control as part of a self-management action plan. The expert panel followed an adaptation process to identify and appraise existing guidelines on the specified topics. In addition, literature searches were performed to identify relevant systematic reviews and randomized controlled trials. The panel formally assessed and graded the evidence, and made 34 recommendations. RESULTS The updated guideline recommendations outline a role for inclusion of assessment of sputum eosinophils, in addition to standard measures of asthma control, to guide adjustment of controller therapy in adults with moderate to severe asthma. Appraisal of the evidence regarding which adjunct controller therapy to add to ICS and at what ICS dose to begin adjunct therapy in children and adults with poor asthma control supported the 2010 CTS Consensus Summary recommendations. New recommendations for the adjustment of controller medication within written action plans are provided. Finally, priority areas for future research were identified. CONCLUSIONS The present clinical practice guideline is the first update of the CTS Asthma Guidelines following the Canadian Respiratory Guidelines Committees new guideline development process. Tools and strategies to support guideline implementation will be developed and the CTS will continue to regularly provide updates reflecting new evidence.

The epidemiology of traumatic spinal cord injury in Alberta, Canada

OBJECTIVES To describe the incidence and pattern of traumatic spinal cord injury and cauda equina injury (SCI) in a geographically defined region of Canada. METHODS The study period was April 1, 1997 to March 31, 2000. Data were gathered from three provincial sources: administrative data from the Alberta Ministry of Health and Wellness, records from the Alberta Trauma Registry, and death certificates from the Office of the Medical Examiner. RESULTS From all three data sources, 450 cases of SCI were identified. Of these, 71 (15.8%) died prior to hospitalization. The annual incidence rate was 52.5/million population (95% CI: 47.7, 57.4). For those who survived to hospital admission, the incidence rate was 44.3/million/year (95% CI: 39.8, 48.7). The incidence rates for males were consistently higher than for females for all age groups. Motor vehicle collisions accounted for 56.4% of injuries, followed by falls (19.1%). The highest incidence of motor vehicle-related SCI occurred to those between 15 and 29 years (60/million/year). Fall-related injuries primarily occurred to those older than 60 years (45/million/year). Rural residents were 2.5 times as likely to be injured as urban residents. CONCLUSION Prevention strategies for SCI should target males of all ages, adolescents and young adults of both sexes, rural residents, motor vehicle collisions, and fall prevention for those older than 60 years.

Canadian Thoracic Society Asthma Management Continuum – 2010 Consensus Summary for Children Six Years of Age and Over, and Adults

BACKGROUND/OBJECTIVE To integrate new evidence into the Canadian Asthma Management Continuum diagram, encompassing both pediatric and adult asthma. METHODS The Canadian Thoracic Society Asthma Committee members, comprised of experts in pediatric and adult respirology, allergy and immunology, emergency medicine, general pediatrics, family medicine, pharmacoepidemiology and evidence-based medicine, updated the continuum diagram, based primarily on the 2008 Global Initiative for Asthma guidelines, and performed a focused review of literature pertaining to key aspects of asthma diagnosis and management in children six years of age and over, and adults. RESULTS In patients six years of age and over, management of asthma begins with establishing an accurate diagnosis, typically by supplementing medical history with objective measures of lung function. All patients and caregivers should receive self-management education, including a written action plan. Inhaled corticosteroids (ICS) remain the first-line controller therapy for all ages. When asthma is not controlled with a low dose of ICS, the literature supports the addition of long-acting beta2-agonists in adults, while the preferred approach in children is to increase the dose of ICS. Leukotriene receptor antagonists are acceptable as second-line monotherapy and as an alternative add-on therapy in both age groups. Antiimmunoglobulin E therapy may be of benefit in adults, and in children 12 years of age and over with difficult to control allergic asthma, despite high-dose ICS and at least one other controller. CONCLUSIONS The foundation of asthma management is establishing an accurate diagnosis based on objective measures (eg, spirometry) in individuals six years of age and over. Emphasis is placed on the similarities and differences between pediatric and adult asthma management approaches to achieve asthma control.

Systematic Review: Implantable Cardioverter Defibrillators for Adults with Left Ventricular Systolic Dysfunction

Left ventricular (LV) systolic dysfunction carries a high risk for sudden cardiac death (1). Implantable cardioverter defibrillators (ICDs) can potentially mitigate this risk by delivering rapid life-saving therapy and have been substantially refined since their initial development in the late 1970s (2). Randomized, controlled trials (RCTs) have tested the efficacy of ICDs in high-risk individuals. We previously reported a systematic review of 8 RCTs (3 RCTs of secondary prevention in survivors of sudden cardiac death; 5 RCTs of primary prevention in patients without a history of ventricular arrhythmias) demonstrating a 26% reduction in all-cause mortality and a 57% reduction in sudden cardiac death with ICDs (3). Since then, additional RCTs of primary prevention have been published, and questions have arisen about the generalizability of the RCT results for ICDs to clinical practice. In particular, it is uncertain whether the benefits of ICDs seen in the trials extend to nontrial populations and whether the risks associated with ICDs may be higher in clinical practice than reported in trials. Given the public policy implications, we extended our previous systematic review of the efficacy (that is, the risks and benefits of a therapy when tested under ideal circumstances) (4) of ICDs in patients with LV systolic dysfunction by updating it with recently published RCTs that examined efficacy. In addition, we expanded the review to include data from observational studies to determine the effectiveness (that is, the risks and benefits of a therapy when tested under usual clinical practice conditions) and safety of ICDs when used in clinical practice. Methods A study protocol meeting Cochrane criteria, including all of the elements described briefly in the following sections, was developed and followed by the study authors in conjunction with the Agency for Healthcare Research and Quality (AHRQ). Search Strategy We sought studies published between 1980 and 27 April 2007 by searching MEDLINE, Ovid MEDLINE In-Process & Other Non-Indexed Citations, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Health Technology Assessment Database, EMBASE, Science Citation Index Expanded (via Web of Science), International Pharmaceutical Abstracts, PubMed, National Library of Medicine Gateway, OCLC ProceedingsFirst and PapersFirst, Computer Retrieval of Information on Scientific Projects, various trial registries (including the National Research Register [United Kingdom], Australian Clinical Trials Registry, ClinicalTrials.gov, and Current Controlled Trials), and U.S. Food and Drug Administration reports. In addition, we hand-searched abstracts from the annual Heart Rhythm Society meetings and the reference lists of review articles and included studies; we also contacted authors of included studies for additional citations and information. Unpublished studies and individual-patient data were sought from device manufacturers, including Medtronic (Minneapolis, Minnesota), Guidant Corp. (Indianapolis, Indiana), and St. Jude Medical (St. Paul, Minnesota). The search was not limited by language or publication status. The search terms included Medtronic InSync, ELA medical, Guidant, St. Jude, implantable defibrillators, implantable cardioverter defibrillators, AICD, ICD, single chamber ICD, dual chamber ICD, congestive heart failure, CHF, chronic heart failure, and heart diseases. A full list of search strategies (adapted for each database) and search results are available at www.ahrq.gov/clinic/tp/defibtp.htm (5). Study Selection We selected original research studies that had at least 25 participants and reported mortality or peri- or postimplantation complications with ICDs in adult patients with LV systolic dysfunction (left ventricular ejection fraction [LVEF]0.35, regardless of whether the patients had heart failure symptoms). To address efficacy questions, we restricted the analyses to RCTs. To address effectiveness questions, we expanded our inclusion criteria to include observational studies with contemporaneous comparison groups (such as cohort studies) and RCTs that did not report efficacy outcomes. To address safety questions, we included evidence from both RCTs and observational studies (including those without contemporaneous control groups, such as case series and registry data). Data Extraction and Analysis Study selection, quality assessment, and data extraction were completed by several investigators in duplicate and independently, using the methods recommended by the Quality of Reporting of Meta-analyses (QUOROM) group (6). We assessed quality by using the methods of Schulz and colleagues (7), the 5-item Jadad scale (8), and the 27-point Downs and Black scale (9). Publication bias was assessed visually by using funnel plots and quantitatively by using the rank correlation test (10), the graphical test (11), and the trim-and-fill method (12). Random-effects models were used to calculate pooled relative risks (RRs) in Review Manager 4.2.5 (Cochrane Collaboration, Copenhagen, Denmark). The length of study follow-up versus all-cause mortality was plotted for each study, and inverse varianceweighted least-squares regression was used to create a best-fit line. Postimplantation complications were expressed per 100 patient-years (calculated by multiplying the frequency of events in each study by the duration of follow-up, and standardizing to a denominator of 100) and are unadjusted rates. All results were reported with 95% CIs and, where appropriate, SDs or SEs. Statistical heterogeneity was quantified by using the I 2 statistic (13). In addition to examining for differences in point estimates across study designs and study quality, we explored device efficacy in different patient subgroups by using meta-regression. Covariates tested included presence of cardiac resynchronization therapy, length of follow-up, ischemic etiology, New York Heart Association (NYHA) class, age, QRS interval, LVEF, and primary versus secondary prevention. Role of the Funding Source The funding source (AHRQ, U.S. Department of Health and Human Services) had no role in the collection, analysis, or interpretation of the data or in the decision to submit the manuscript for publication. Results Literature Search From 4439 citations (Figure 1), we identified 12 RCTs (8516 patients) for the ICD efficacy review (1426), 53 studies (26840 patients from 5 nonefficacy RCTs and 48 observational studies [25 retrospective and 23 prospective]) for the ICD effectiveness review (2778), and 64 studies (86809 patients from 11 efficacy RCTs, 10 RCTs without efficacy outcomes, and 43 observational studies [24 retrospective and 19 prospective]) for the ICD safety review (1417, 1927, 29, 30, 34, 3740, 4245, 47, 48, 52, 54, 60, 61, 6366, 69, 70, 7275, 78101). A full list of search strategies, search results, detailed quality assessments for each included study, and tests for publication bias are available at www.ahrq.gov/clinic/tp/defibtp.htm (5). No publication bias was seen on the funnel plots. Figure 1. Flow diagram of study identification and selection. RCTs with Efficacy Data The 12 efficacy RCTs varied in quality (ranging from 1 to 3 on the Jadad scale) and duration (ranging from 15 to 66 months). All but 2 trials (16, 19) evaluated single-chamber ICDs (although no trials reported protocol adherence to single-chamber vs. dual-chamber ICDs). All patients in the RCTs had LV systolic dysfunction: Mean LVEF ranged from 0.21 to 0.28 in the primary prevention trials and from 0.32 to 0.46 in the secondary prevention trials. Most patients also had symptoms of heart failure: 50% had NYHA class II symptoms at baseline; 36%, class III symptoms; and 3%, class IV symptoms. Eleven percent of trial participants were in NYHA class I at baseline (Appendix Table 1). The mean age of RCT participants was 61 years (SD, 4), 74% were male, and 59% had ischemic heart disease. Appendix Table 1. Description of Randomized Trials Included in the Review Use of ICDs reduced all-cause mortality in patients with LV systolic dysfunction by 20% (95% CI, 10% to 29%; I 2= 44.4%) (Figure 2), largely because of a 54% relative reduction (CI, 37% to 63%; I 2= 0%) in sudden cardiac deaths. In patients with LV systolic dysfunction, ICDs were equally beneficial in reducing all-cause mortality in both primary prevention trials (RR, 0.81 [CI, 0.69 to 0.95]; I 2= 53.1% across 9 RCTs) and secondary prevention trials (RR, 0.77 [CI, 0.65 to 0.91]; I 2= 13.2% across 3 RCTs) (P for this indirect comparison= 0.56). Figure 2. Effect of implantable cardioverter defibrillator ( ICDs ) on all-cause mortality in randomized trials. A single trial included cardiac resynchronization therapy in both study groups for its comparison of ICDs versus control (19). All-cause mortality (RR, 0.83 [CI, 0.66 to 1.05]) was similar to that reported from the remainder of the studies, which did not contain cardiac resynchronization therapy in either study group (RR, 0.79 [CI, 0.69 to 0.91]) (P for indirect comparison= 0.92). Only 1 trial reported a statistically significant difference in the effect of ICDs across NYHA classes: The mortality benefits were greater in patients with NYHA class II symptoms than in those with NYHA class III symptoms in the Sudden Cardiac Death in Heart Failure Trial (P< 0.001 for interaction term of NYHA class and mortality) (22). In a series of univariate meta-regression sensitivity analyses, none of the covariates we examined (duration of follow-up, primary vs. secondary prevention, ischemic cause, presence of cardiac resynchronization therapy, NYHA class, mean age, mean LVEF, or mean QRS duration) contributed to the moderate statistical heterogeneity observed in our meta-analysis of all-cause mortality. In addition, our estimate of treatment effect was not associated with study quality. Implantable cardioverter defibrillators

Parenteral metoclopramide for acute migraine: meta-analysis of randomised controlled trials

Abstract Objective To assess the evidence from controlled trials on the efficacy and tolerability of parenteral metoclopramide for acute migraine in adults. Data sources Cochrane Central Register of Controlled Trials, Medline, Embase, LILACS, CINAHL, conference proceedings, clinical practice guidelines, and other sources. Selection criteria Randomised controlled trials of parenteral metoclopramide for acute migraine in adults. Results We reviewed 596 potentially relevant abstracts and found 13 eligible trials totalling 655 adults. In studies comparing metoclopramide with placebo, metoclopramide was more likely to provide significant reduction in migraine pain (odds ratio 2.84, 95% confidence interval 1.05 to 7.68). Used as the only agent, metoclopramide showed mixed effectiveness when compared with other single agents. Heterogeneity of studies for combination treatment prevented statistical pooling. Treatments that did include metoclopramide were as, or more, effective than comparison treatments for pain, nausea, and relapse outcomes reported in all studies. Conclusions Metoclopramide is an effective treatment for migraine headache and may be effective when combined with other treatments. Given its non-narcotic and antiemetic properties, metoclopramide should be considered a primary agent in the treatment of acute migraines in emergency departments.