Showing papers in "Canadian Medical Association Journal in 2009"

Intensive insulin therapy and mortality among critically ill patients: a meta-analysis including NICE-SUGAR study data

Abstract: Background: Hyperglycemia is associated with increased mortality in critically ill patients. Randomized trials of intensive insulin therapy have reported inconsistent effects on mortality and increased rates of severe hypoglycemia. We conducted a meta-analysis to update the totality of evidence regarding the influence of intensive insulin therapy compared with conventional insulin therapy on mortality and severe hypoglycemia in the intensive care unit (ICU). Methods: We conducted searches of electronic databases, abstracts from scientific conferences and bibliographies of relevant articles. We included published randomized controlled trials conducted in the ICU that directly compared intensive insulin therapy with conventional glucose management and that documented mortality. We included in our meta-analysis the data from the recent NICE-SUGAR (Normoglycemia in Intensive Care Evaluation — Survival Using Glucose Algorithm Regulation) study. Results: We included 26 trials involving a total of 13 567 patients in our meta-analysis. Among the 26 trials that reported mortality, the pooled relative risk (RR) of death with intensive insulin therapy compared with conventional therapy was 0.93 (95% confidence interval [CI] 0.83–1.04). Among the 14 trials that reported hypoglycemia, the pooled RR with intensive insulin therapy was 6.0 (95% CI 4.5–8.0). The ICU setting was a contributing factor, with patients in surgical ICUs appearing to benefit from intensive insulin therapy (RR 0.63, 95% CI 0.44–0.91); patients in the other ICU settings did not (medical ICU: RR 1.0, 95% CI 0.78–1.28; mixed ICU: RR 0.99, 95% CI 0.86–1.12). The different targets of intensive insulin therapy (glucose level ≤ 6.1 mmol/L v. ≤ 8.3 mmol/L) did not influence either mortality or risk of hypoglycemia. Interpretation: Intensive insulin therapy significantly increased the risk of hypoglycemia and conferred no overall mortality benefit among critically ill patients. However, this therapy may be beneficial to patients admitted to a surgical ICU.

Defining knowledge translation

Abstract: We cannot pick up a magazine or surf the Internet without facing reminders of the challenges to health care and the “sorry state” of health systems. [1][1] All health care systems are faced with the challenges of improving quality of care and reducing the risk of adverse events. [2][2] Globally

A population-based study of the drug interaction between proton pump inhibitors and clopidogrel

Abstract: Background: Most proton pump inhibitors inhibit the bioactivation of clopidogrel to its active metabolite. The clinical significance of this drug interaction is unknown. Methods: We conducted a population-based nested case–control study among patients aged 66 years or older who commenced clopidogrel between Apr. 1, 2002, and Dec. 31, 2007, following hospital discharge after treatment of acute myocardial infarction. The cases in our study were those readmitted with acute myocardial infarction within 90 days after discharge. We performed a secondary analysis considering events within 1 year. Event-free controls (at a ratio of 3:1) were matched to cases on age, percutaneous coronary intervention and a validated risk score. We categorized exposure to proton pump inhibitors before the index date as current (within 30 days), previous (31–90 days) or remote (91–180 days). Results: Among 13 636 patients prescribed clopidogrel following acute myocardial infarction, we identified 734 cases readmitted with myocardial infarction and 2057 controls. After extensive multivariable adjustment, current use of proton pump inhibitors was associated with an increased risk of reinfarction (adjusted odds ratio [OR] 1.27, 95% confidence interval [CI] 1.03–1.57). We found no association with more distant exposure to proton pump inhibitors or in multiple sensitivity analyses. In a stratified analysis, pantoprazole, which does not inhibit cytochrome P450 2C19, had no association with readmission for myocardial infarction (adjusted OR 1.02, 95% CI 0.70–1.47). Interpretation: Among patients receiving clopidogrel following acute myocardial infarction, concomitant therapy with proton pump inhibitors other than pantoprazole was associated with a loss of the beneficial effects of clopidogrel and an increased risk of reinfarction.

Effect of school-based physical activity interventions on body mass index in children: a meta-analysis

Abstract: Background: The prevalence of childhood obesity is increasing at an alarming rate. Many local governments have enacted policies to increase physical activity in schools as a way to combat childhood obesity. We conducted a systematic review and meta-analysis to determine the effect of school-based physical activity interventions on body mass index (BMI) in children. Methods: We searched MEDLINE, EMBASE, CINAHL and the Cochrane Central Register of Controlled Trials up to September 2008. We also hand-searched relevant journals and article reference lists. We included randomized controlled trials and controlled clinical trials that had objective data for BMI from before and after the intervention, that involved school-based physical activity interventions and that lasted for a minimum of 6 months. Results: Of 398 potentially relevant articles that we identified, 18 studies involving 18 141 children met the inclusion criteria. The participants were primarily elementary school children. The study duration ranged from 6 months to 3 years. In 15 of these 18 studies, there was some type of co-intervention. Meta-analysis showed that BMI did not improve with physical activity interventions (weighted mean difference –0.05 kg/m 2 , 95% confidence interval –0.19 to 0.10). We found no consistent changes in other measures of body composition. Interpretation: School-based physical activity interventions did not improve BMI, although they had other beneficial health effects. Current population-based policies that mandate increased physical activity in schools are unlikely to have a significant effect on the increasing prevalence of childhood obesity.

Long-term use of thiazolidinediones and fractures in type 2 diabetes: a meta-analysis

Abstract: Background: Rosiglitazone and pioglitazone may increase the incidence of fractures. We aimed to determine systematically the risk of fractures associated with thiazolidinedione therapy and to evaluate the effect of the therapy on bone density. Methods: We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), other trial registries and product information sheets through June 2008. We selected long-term (≥ 1 year) randomized controlled trials involving patients with type 2 diabetes and controlled observational studies that described the risk of fractures or changes in bone density with thiazolidinediones. We calculated pooled odds ratios (ORs) for fractures and the weighted mean difference in bone density. Results: We analyzed data from 10 randomized controlled trials involving 13 715 participants and from 2 observational studies involving 31 679 participants. Rosiglitazone and pioglitazone were associated with a significantly increased risk of fractures overall in the 10 randomized controlled trials (OR 1.45, 95% confidence interval [CI] 1.18–1.79; p p p = 0.98). The 2 observational studies demonstrated an increased risk of fractures associated with rosiglitazone and pioglitazone. Bone mineral density in women exposed to thiazolidinediones was significantly reduced at the lumbar spine (weighted mean difference –1.11%, 95% CI –2.08% to –0.14%; p = 0.02) and hip (weighted mean difference –1.24%, 95%CI –2.34% to –0.67%; p Interpretation: Long-term thiazolidinedione use doubles the risk of fractures among women with type 2 diabetes, without a significant increase in risk of fractures among men with type 2 diabetes.

Asthma: epidemiology, etiology and risk factors.

Abstract: Asthma is one of the most common chronic conditions affecting both children and adults, yet much remains to be learned of its etiology. This paper evolved from the extensive literature review undertaken as part of a proposal for a longitudinal birth cohort study to examine risk factors for the

Prescribing of opioid analgesics and related mortality before and after the introduction of long-acting oxycodone

Abstract: Introduction: Opioid-related mortality appears to be increasing in Canada. We examined the true extent of the problem and the impact of the introduction of long-acting oxycodone. Methods: We examined trends in the prescribing of opioid analgesics in the province of Ontario from 1991 to 2007. We reviewed all deaths related to opioid use between 1991 and 2004. We linked 3271 of these deaths to administrative data to examine the patients’ use of health care services before death. Using time-series analysis, we determined whether the addition of long-acting oxycodone to the provincial drug formulary in January 2000 was associated with an increase in opioid-related mortality. Results: From 1991 to 2007, annual prescriptions for opioids in creased from 458 to 591 per 1000 individuals. Opioidrelated deaths doubled, from 13.7 per million in 1991 to 27.2 per million in 2004. Prescriptions of oxycodone increased by 850% between 1991 and 2007. The addition of long-acting oxycodone to the drug formulary was associated with a 5fold increase in oxycodone-related mortality (p < 0.01) and a 41% increase in overall opioid-related mortality (p = 0.02). The manner of death was deemed unintentional by the coroner in 54.2% and undetermined in 21.9% of cases. Use of health care services in the month before death was common: for example, of the 3066 patients for whom data on physician visits were available, 66.4% had visited a physician in the month before death; of the 1095 patients for whom individual-level prescribing data were available, 56.1% had filled a prescription for an opioid in the month before death. Interpretation: Opioid-related deaths in Ontario have in creased markedly since 1991. A significant portion of the increase was associated with the addition of long-acting oxycodone to the provincial drug formulary. Most of the deaths were deemed unintentional. The frequency of visits to a physician and prescriptions for opioids in the month before death suggests a missed opportunity for prevention.

Efficacy of pneumococcal vaccination in adults: a meta-analysis

Abstract: Background: Clinical trials and meta-analyses have produced conflicting results of the efficacy of unconjugated pneumococcal polysaccharide vaccine in adults. We sought to evaluate the vaccine9s efficacy on clinical outcomes as well as the methodologic quality of the trials. Methods: We searched several databases and all bibliographies of reviews and meta-analyses for clinical trials that compared pneumococcal polysaccharide vaccine with a control. We examined rates of pneumonia and death, taking the methodologic quality of the trials into consideration. Results: We included 22 trials involving 101 507 participants: 11 trials reported on presumptive pneumococcal pneumonia, 19 on all-cause pneumonia and 12 on all-cause mortality. The current 23-valent vaccine was used in 8 trials. The relative risk (RR) was 0.64 (95% confidence interval [CI] 0.43–0.96) for presumptive pneumococcal pneumonia and 0.73 (95% CI 0.56–0.94) for all-cause pneumonia. There was significant heterogeneity between the trials reporting on presumptive pneumonia ( I 2 = 74%, p I 2 = 90%, p I 2 = 44%, p = 0.053). Trial quality, especially regarding double blinding, explained a substantial proportion of the heterogeneity in the trials reporting on presumptive pneumonia and all-cause pneumonia. There was little evidence of vaccine protection in trials of higher methodologic quality (RR 1.20, 95% CI 0.75–1.92, for presumptive pneumonia; and 1.19, 95% CI 0.95–1.49, for all-cause pneumonia in double-blind trials; p for heterogeneity > 0.05). The results for all-cause mortality in double-blind trials were similar to those in all trials combined. There was little evidence of vaccine protection among elderly patients or adults with chronic illness in analyses of all trials (RR 1.04, 95% CI 0.78–1.38, for presumptive pneumococcal pneumonia; 0.89, 95% CI 0.69–1.14, for all-cause pneumonia; and 1.00, 95% CI 0.87–1.14, for all-cause mortality). Interpretation: Pneumococcal vaccination does not appear to be effective in preventing pneumonia, even in populations for whom the vaccine is currently recommended.

Neurobiological mechanisms in major depressive disorder

Abstract: Nearly 1 in 5 people will experience a major depressive episode at some point in their lives.[1][1] In this review, we discuss data describing how genes, psychosocial adversity in childhood, and ongoing or recent psychosocial stress may impact multiple neurobiological systems relevant to major

Relation between fractures and mortality: results from the Canadian Multicentre Osteoporosis Study

Abstract: Background: Fractures have largely been assessed by their impact on quality of life or health care costs. We conducted this study to evaluate the relation between fractures and mortality. Methods: A total of 7753 randomly selected people (2187 men and 5566 women) aged 50 years and older from across Canada participated in a 5-year observational cohort study. Incident fractures were identified on the basis of validated self-report and were classified by type (vertebral, pelvic, forearm or wrist, rib, hip and “other”). We subdivided fracture groups by the year in which the fracture occurred during follow-up; those occurring in the fourth and fifth years were grouped together. We examined the relation between the time of the incident fracture and death. Results: Compared with participants who had no fracture during follow-up, those who had a vertebral fracture in the second year were at increased risk of death (adjusted hazard ratio [HR] 2.7, 95% confidence interval [CI] 1.1–6.6); also at risk were those who had a hip fracture during the first year (adjusted HR 3.2, 95% CI 1.4–7.4). Among women, the risk of death was increased for those with a vertebral fracture during the first year (adjusted HR 3.7, 95% CI 1.1–12.8) or the second year of follow-up (adjusted HR 3.2, 95% CI 1.2–8.1). The risk of death was also increased among women with hip fracture during the first year of follow-up (adjusted HR 3.0, 95% CI 1.0–8.7). Interpretation: Vertebral and hip fractures are associated with an increased risk of death. Interventions that reduce the incidence of these fractures need to be implemented to improve survival.

Integration of evidence from multiple meta-analyses: a primer on umbrella reviews, treatment networks and multiple treatments meta-analyses

Abstract: Meta-analysis is an important research design for appraising evidence and guiding medical practice and health policy. [1][1] Meta-analyses draw strength from combining data from many studies. However, even if perfectly done with perfect data, a single meta-analysis that addresses 1 treatment

Outcomes of planned home birth with registered midwife versus planned hospital birth with midwife or physician

Abstract: Results: The rate of perinatal death per 1000 births was 0.35 (95% confidence interval [CI] 0.00–1.03) in the group of planned home births; the rate in the group of planned hospital births was 0.57 (95% CI 0.00–1.43) among women attended by a midwife and 0.64 (95% CI 0.00–1.56) among those attended by a physician. Wo men in the planned home-birth group were significantly less likely than those who planned a midwife-attended hospital birth to have obstetric interventions (e.g., electronic fetal monitoring, relative risk [RR] 0.32, 95% CI 0.29–0.36; assisted vaginal delivery, RR 0.41, 95% 0.33–0.52) or adverse maternal outcomes (e.g., third- or fourth-degree perineal tear, RR 0.41, 95% CI 0.28–0.59; postpartum hemorrhage, RR 0.62, 95% CI 0.49–0.77). The findings were similar in the comparison with physician-assisted hospital births. Newborns in the home-birth group were less likely than those in the midwife-attended hospital-birth group to require resuscitation at birth (RR 0.23, 95% CI 0.14–0.37) or oxygen therapy beyond 24 hours (RR 0.37, 95% CI 0.24–0.59). The findings were similar in the comparison with newborns in the physician-assisted hospital births; in addition, newborns in the home-birth group were less likely to have meconium aspiration (RR 0.45, 95% CI 0.21–0.93) and more likely to

Acclimation during space flight: Effects on human physiology

Abstract: See related review by Thirsk and colleagues, page [1324][1] Patients on earth with illness can be described as people who live in a normal earth environment but who have abnormal physiology. In contrast, astronauts are people with normal physiology who live in an abnormal environment. It is this

Early detection of disease outbreaks using the Internet

Abstract: Rapidly identifying an infectious disease outbreak is critical, both for effective initiation of public health intervention measures and timely alerting of government agencies and the general public. Surveillance capacity for such detection can be costly, and many countries lack the public health

Selective serotonin reuptake inhibitors and risk of suicide: a systematic review of observational studies

Abstract: Background It is unclear whether the use of selective serotonin reuptake inhibitors (SSRIs) and other antidepressant drugs reduce the risk of suicide in people with depression. We explored the association between exposure to SSRIs and risk of suicide completion or attempt. Methods We conducted a systematic review of observational studies that reported completed or attempted suicide in depressed individuals who were exposed to SSRIs compared with those who were not exposed to antidepressants. We assessed the overall risk of completed or attempted suicide. Results Eight studies involving more than 200 000 patients with moderate or severe depression were included in the meta-analysis. Although exposure to SSRIs increased the risk of completed or attempted suicide among adolescents (odds ratio [OR] 1.92, 95% confidence interval [CI] 1.51-2.44), the risk was decreased among adults (OR 0.57, 95% CI 0.47-0.70). Among people aged 65 or more years, exposure to SSRIs had a protective effect (OR 0.46, 95% CI 0.27-0.79). Sensitivity analyses did not change these findings. In particular, for studies that used completed suicide as an outcome, exposure to SSRIs was associated with increased risk among adolescents (OR 5.81, 95% CI 1.57-21.51) and decreased risk among adults (OR 0.66, 95% CI 0.52-0.83) and older people (OR 0.53, 95% CI 0.26-1.06). Interpretation Based on data from observational studies, use of SSRIs may be associated with a reduced risk of suicide in adults with depression. Among adolescents, use of SSRIs may increase suicidality.

A network meta-analysis of randomized controlled trials of biologics for rheumatoid arthritis: a Cochrane overview

Abstract: Background: We sought to compare the benefits and safety of 6 biologics (abatacept, adalimumab, anakinra, etanercept, infliximab and rituximab) in patients with rheumatoid arthritis. Methods: In this network meta-analysis, we included all completed and updated Cochrane reviews on biologics for rheumatoid arthritis. We included data from all placebo-controlled trials that used standard dosing regimens. The major outcomes were benefit (defined as a 50% improvement in patient- and physician-reported criteria of the American College of Rheumatology [ACR50]) and safety (determined by the number of withdrawals related to adverse events). We used mixed-effects logistic regression to carry out an indirect comparison of the treatment effects between biologics. Results: Compared with placebo, biologics were associated with a clinically important higher ACR50 rate (odds ratio [OR] 3.35, 95% confidence interval [CI] 2.62–4.29) and a number needed to treat for benefit of 4 (95% CI 4–6). However, biologics were associated with more withdrawals related to adverse events (OR 1.39, 95% CI 1.13–1.71), with a number needed to treat for harm of 52 (95% CI 29–152). Anakinra was less effective than all of the other biologics, although this difference was statistically significant only for the comparison with adalimumab (OR 0.45, 95% CI 0.21–0.99) and etanercept (OR 0.34, 95% CI 0.14–0.81). Adalimumab, anakinra and infliximab were more likely than etanercept to lead to withdrawals related to adverse events (adalimumab OR 1.89, 95% CI 1.18–3.04; anakinra OR 2.05, 95% CI 1.27–3.29; and infliximab OR 2.70, 95% CI 1.43–5.26). Interpretation: Given the limitations of indirect comparisons, anakinra was less effective than adalimumab and etanercept, and etanercept was safer than adalimumab, anakinra and infliximab. This summary of the evidence will help physicians and patients to make evidence-based choices about biologics for the treatment of rheumatoid arthritis.

The emergence of Lyme disease in Canada

Abstract: Lyme disease, caused by the bacterium Borrelia burgdorferi and transmitted by tick vectors, is the most commonly reported vector-borne disease in the temperate zone. [1][1] More than 20 000 cases are recorded annually in the United States. [2][2] In about 80% of cases, early Lyme disease is

Trends in risk factors for cardiovascular disease in Canada: temporal, socio-demographic and geographic factors

Abstract: Background: Temporal trends in risk factors for cardiovascular disease and the impact of socio-economic status on these risk factors remain unclear. Methods: Using data from the National Population Health Survey and the Canadian Community Health Survey, we examined national trends in heart disease, hypertension, diabetes mellitus, obesity and smoking prevalence from 1994 to 2005, adjusting for age and sex. We stratified data by income adequacy category, body mass index and region of residence. Results: An estimated 1.29 million Canadians reported having heart disease in 2005, representing increases of 19% for men and 2% for women, relative to 1994. Heart disease increased significantly in the lowest income category (by 27%), in the lower middle income category (by 37%) and in the upper middle income category (by 12%); however, it increased by only 6% in the highest income group. Diabetes increased in all but the highest income group: by 56% in the lowest income group, by 93% in the lower middle income group and by 59% in the upper middle income group. Hypertension increased in all income groups: by 85% in the lowest income group, by 80% in the lower middle income group, by 91% in the upper middle income group and by 117% in the highest income group. Obesity also increased in all income groups: by 20% in the lowest income group, by 25% in the lower middle income group, by 33% in the upper middle income group and by 37% in the highest income group. In addition to socio-economic status, obesity and overweight also modified the trends in risk factors. Diabetes increased to a greater extent among obese participants (61% increase) and overweight participants (25% increase), as did hypertension, which increased by 80% among obese individuals and by 74% among overweight individuals. Trends in diabetes, hypertension and obesity were consistent for all provinces. Interpretation: During the study period, heart disease, hypertension, diabetes and obesity increased for all or most income groups in Canada. Further interventions supporting modification of lifestyle and risk factors are needed to prevent future cardiovascular disease.

Efficacy and safety of insulin analogues for the management of diabetes mellitus: a meta-analysis

Abstract: Results: We included 68 randomized controlled trials in the analysis of rapid-acting insulin analogues and 49 in the analysis of long-acting insulin analogues. Most of the studies were of short to medium duration and of low quality. In terms of hemoglobin A1c, we found minimal differences between rapid-acting insulin analogues and regular human insulin in adults with type 1 diabetes (weighted mean difference for insulin lispro: ‐0.09%, 95% confidence interval [CI] ‐0.16% to ‐0.02%; for insulin aspart: ‐0.13%, 95% CI ‐0.20% to ‐0.07%). We observed similar outcomes among patients with type 2 diabetes (weighted mean difference for insulin lispro: ‐0.03%, 95% CI ‐0.12% to ‐0.06%; for insulin aspart: ‐0.09%, 95% CI ‐0.21% to 0.04%). Differences between long-acting insulin analogues and neutral protamine Hagedorn insulin in terms of hemoglobin A1c were marginal among adults with type 1 diabetes (weighted mean difference for insulin glargine: ‐0.11%, 95% CI ‐0.21% to ‐0.02%; for insulin detemir: ‐0.06%, 95% CI ‐0.13% to 0.02%) and among adults with type 2 diabetes (weighted mean difference for insulin glargine: ‐0.05%, 95% CI ‐0.13% to 0.04%; for insulin detemir: 0.13%, 95% CI 0.03% to 0.22%). Benefits in terms of reduced hypoglycemia were inconsistent. There were insufficient data to determine whether insulin analogues are better than conventional insulins in reducing longterm diabetes-related complications or death. Interpretation: Rapid- and long-acting insulin analogues offer little benefit relative to conventional insulins in terms

National trends in rates of death and hospital admissions related to acute myocardial infarction, heart failure and stroke, 1994–2004

Abstract: Background: Rates of death from cardiovascular and cerebrovascular diseases have been steadily declining over the past few decades. Whether such declines are occurring to a similar degree for common disorders such as acute myocardial infarction, heart failure and stroke is uncertain. We examined recent national trends in mortality and rates of hospital admission for these 3 conditions. Methods: We analyzed mortality data from Statistic Canada’s Canadian Mortality Database and data on hospital admissions from the Canadian Institute for Health Information’s Hospital Morbidity Database for the period 1994–2004. We determined age- and sex-standardized rates of death and hospital admissions per 100 000 population aged 20 years and over as well as in-hospital case-fatality rates. Results: The overall age- and sex-standardized rate of death from cardiovascular disease in Canada declined 30.0%, from 360.6 per 100 000 in 1994 to 252.5 per 100 000 in 2004. During the same period, the rate fell 38.1% for acute myocardial infarction, 23.5% for heart failure and 28.2% for stroke, with improvements observed across most age and sex groups. The age- and sex-standardized rate of hospital admissions decreased 27.6% for stroke and 27.2% for heart failure. The rate for acute myocardial infarction fell only 9.2%. In contrast, the relative decline in the inhospital case-fatality rate was greatest for acute myocardial infarction (33.1%; p Interpretation: The rates of death and hospital admissions for acute myocardial infarction, heart failure and stroke in Canada changed at different rates over the 10-year study period. Awareness of these trends may guide future efforts for health promotion and health care planning and help to determine priorities for research and treatment.

Individualized electronic decision support and reminders to improve diabetes care in the community: COMPETE II randomized trial

Abstract: Background: Diabetes mellitus is a complex disease with serious complications. Electronic decision support, providing information that is shared and discussed by both patient and physician, encourages timely interventions and may improve the management of this chronic disease. However, it has rarely been tested in community-based primary care. Methods: In this pragmatic randomized trial, we randomly assigned adult primary care patients with type 2 diabetes to receive the intervention or usual care. The intervention involved shared access by the primary care provider and the patient to a Web-based, colour-coded diabetes tracker, which provided sequential monitoring values for 13 diabetes risk factors, their respective targets and brief, prioritized messages of advice. The primary outcome measure was a process composite score. Secondary outcomes included clinical composite scores, quality of life, continuity of care and usability. The outcome assessors were blinded to each patient’s intervention status. Results: We recruited sequentially 46 primary care providers and then 511 of their patients (mean age 60.7 [standard deviation 12.5] years). Mean follow-up was 5.9 months. The process composite score was significantly better for patients in the intervention group than for control patients (difference 1.27, 95% confidence interval [CI] 0.79–1.75, p p p = 0.02), including significantly greater declines in blood pressure (−3.95 mm Hg systolic and −2.38 mm Hg diastolic) and glycated hemoglobin (−0.2%). Patients in the intervention group reported greater satisfaction with their diabetes care. Interpretation: A shared electronic decision-support system to support the primary care of diabetes improved the process of care and some clinical markers of the quality of diabetes care. (ClinicalTrials.gov trial register no. NCT00813085.)

Benefits and harms of erythropoiesis-stimulating agents for anemia related to cancer: a meta-analysis

Abstract: Background: Erythropoiesis-stimulating agents are used to treat anemia in patients with cancer. However, their safety and effectiveness is controversial. We did a systematic review of the clinical efficacy and harms of these agents in adults with anemia related to cancer or chemotherapy. Methods: We conducted a systematic review of published and unpublished randomized controlled trials (RCTs) using accepted methods for literature searches, article selection, data extraction and quality assessment. We included RCTs involving anemic adults with cancer. We compared the use of erythropoiesis-stimulating agents with nonuse and assessed clinical outcomes (all-cause mortality, cardiovascular events and hypertension, health-related quality of life, blood transfusions and tumour response) and harms (serious adverse events) between groups. Results: We identified 52 trials (n = 12 006) that met our selection criteria. The pooled all-cause mortality during treatment was significantly higher in the group receiving erythropoiesis-stimulating therapy than in the control group (relative risk [RR] 1.15, 95% confidence interval [CI] 1.03 to 1.29). Compared with no treatment, use of erythropoiesis-stimulating agents led to clinically detectable improvements in disease-specific measures of quality of life. It also reduced the use of blood transfusions (RR 0.64, 95% CI 0.56 to 0.73). However, it led to an increased risk of thrombotic events (RR 1.69, 95% CI 1.27 to 2.24) and serious adverse events (RR 1.16, 95% CI 1.08 to 1.25). Interpretation: Use of erythropoiesis-stimulating agents in patients with cancer-related anemia improved some disease-specific measures of quality of life and decreased the use of blood transfusions. However, it increased the risk of death and serious adverse events. Our findings suggest that such therapy not be used routinely as an alternative to blood transfusion in patients with anemia related to cancer.

Avoiding hospital admission through provision of hospital care at home: a systematic review and meta-analysis of individual patient data

Abstract: Background: Avoidance of admission through provision of hospital care at home is a scheme whereby health care professionals provide active treatment in the patient9s home for a condition that would otherwise require inpatient treatment in an acute care hospital. We sought to compare the effectiveness of this method of caring for patients with that type of in-hospital care. Methods: We searched the MEDLINE, EMBASE, CINAHL and EconLit databases and the Cochrane Effective Practice and Organisation of Care Group register from the earliest date in each database until January 2008. We included randomized controlled trials that evaluated a service providing an alternative to admission to an acute care hospital. We excluded trials in which the program did not offer a substitute for inpatient care. We performed meta-analyses for trials for which the study populations had similar characteristics and for which common outcomes had been measured. Results: We included 10 randomized trials (with a total of 1327 patients) in our systematic review. Seven of these trials (with a total of 969 patients) were deemed eligible for meta-analysis of individual patient data, but we were able to obtain data for only 5 of these trials (with a total of 844 patients [87%]). There was no significant difference in mortality at 3 months for patients who received hospital care at home (adjusted hazard ratio [HR] 0.77, 95% confidence interval [CI] 0.54–1.09, p = 0.15). However, at 6 months, mortality was significantly lower for these patients (adjusted HR 0.62, 95% CI 0.45–0.87, p = 0.005). Admissions to hospital were greater, but not significantly so, for patients receiving hospital care at home (adjusted HR 1.49, 95% CI 0.96–2.33, p = 0.08). Patients receiving hospital care at home reported greater satisfaction than those receiving inpatient care. These programs were less expensive than admission to an acute care hospital ward when the analysis was restricted to treatment actually received and when the costs of informal care were excluded. Interpretation: For selected patients, avoiding admission through provision of hospital care at home yielded similar outcomes to inpatient care, at a similar or lower cost.

Capitation and enhanced fee-for-service models for primary care reform: a population-based evaluation

Abstract: Background: Primary care reform in Ontario, Canada, included the initiation of a blended capitation model in 2001–2002 and an enhanced fee-for-service model in 2003. Both models involve patient rostering, incentives for preventive care and requirements for after-hours care. We evaluated practice characteristics and patterns of care under both models. Methods: Using administrative data, we identified physicians belonging to either the capitation or the enhanced fee-for-service group throughout the period from Sept. 1, 2005, to Aug. 31, 2006, and their enrolled patients. Practices were stratified by location (urban v. rural). We compared the groups in terms of practice characteristics and patterns of care, including comprehensiveness of care, continuity of care, after-hours care, visits to the emergency department and uptake of new patients. Results: Patients in the capitation and enhanced fee-for-service practices had similar demographic characteristics. Patients in capitation practices had lower morbidity and comorbidity indices. Comprehensiveness and continuity of care were similar between the 2 groups. Compared with patients in enhanced fee-for-service practices, those in capitation practices had less after-hours care (adjusted rate ratio [RR] 0.68, 95% confidence interval [CI] 0.61–0.75) and more visits to emergency departments (adjusted RR 1.20, 95% CI 1.15–1.25). Overall, physicians in the capitation group enrolled fewer new patients than did physicians in the enhanced fee-for-service group (37.0 v. 52.0 per physician); the same was true of new graduates (60.3 v. 72.1 per physician). Interpretation: Physicians enrolled in the capitation model had different practice characteristics than those in the enhanced fee-for-service model. These characteristics appeared to be pre-existing and not due to enrolment in a new model. Although the capitation model provides an alternative to fee-for-service practice, its characteristics should be the focus of future policy development and research.

The safety of aprotinin and lysine-derived antifibrinolytic drugs in cardiac surgery: a meta-analysis

Abstract: Background: Because of recent concerns about the safety of aprotinin, we updated our 2007 Cochrane review that compared the relative benefits and risks of aprotinin and the lysine analogues tranexamic acid and epsilon aminocaproic acid. Methods: We searched electronic databases, including CENTRAL, MEDLINE, EMBASE, Google and Google Scholar for trials of antifibrinolytic drugs used in adults scheduled for cardiac surgery. Searches were updated to January 2008. By comparing aprotinin and the 2 lysine analogues to control, we derived indirect head-to-head comparisons of aprotinin to the other drugs. We derived direct estimates of risks and benefits by pooling estimates from head-to-head trials of aprotinin and tranexamic acid or epsilon aminocaproic acid. Results: For indirect estimates, we identified 49 trials involving 182 deaths among 7439 participants. The summary relative risk (RR) for death with aprotinin versus placebo was 0.93 (95% confidence interval [CI] 0.69–1.25). In the 19 trials that included tranexamic acid, there were 24 deaths among 1802 participants. The summary RR was 0.55 (95% CI 0.24–1.25). From the risk estimates derived for individual drugs, we calculated an indirect summary RR of death with use of aprotinin versus tranexamic acid of 1.69 (95% CI 0.70–4.10). To calculate direct estimates of death for aprotinin versus tranexamic acid, we identified 13 trials with 107 deaths among 3537 participants. The summary RR was 1.43 (95% CI 0.98–2.08). Among the 1840 participants, the calculated estimates of death for aprotinin compared directly to epsilon aminocaproic acid was 1.49 (95% CI 0.98–2.28). We found no evidence of an increased risk of myocardial infarction with use of aprotinin compared with the lysine analogues in either direct or indirect analyses. Compared with placebo or no treatment, all 3 drugs were effective in reducing the need for red blood cell transfusion. The RR of transfusion with use of aprotinin was 0.66 (95% CI 0.61–0.72). The RR of transfusion was 0.70 (95% CI 0.61–0.80) for tranexamic acid, and it was 0.75 (95% CI 0.58–0.96) for use of epsilon aminocaproic acid. Aprotinin was also effective in reducing the need for re-operation because of bleeding (RR 0.48, 95% CI 0.34–0.67). Interpretation: The risk of death tended to be consistently higher with use of aprotinin than with use of lysine analogues. Aprotinin had no clear advantages to offset these harms. Either tranexamic acid or epsilon aminocaproic acid should be recommended to prevent bleeding after cardiac surgery.

Mild glucose intolerance in pregnancy and risk of cardiovascular disease: a population-based cohort study

Abstract: Background: Pregnant women commonly receive screening for gestational diabetes mellitus by use of a 50 g glucose challenge test, followed by a diagnostic oral glucose tolerance test for those whose glucose challenge test result is abnormal. Although women with gestational diabetes have an increased risk of cardiovascular disease, it is not known whether mild glucose intolerance during pregnancy is also associated with cardiovascular disease. Thus, we sought to determine whether pregnant women with an abnormal glucose challenge test result but without gestational diabetes have an increased risk of cardiovascular disease. Methods: We conducted a retrospective population-based cohort study that included all women in Ontario aged 20–49 years with live deliveries between April 1994 and March 1998. We excluded women with pregestational diabetes. The population was stratified into 3 cohorts: women with gestational diabetes (n = 13 888); women who received an antepartum oral glucose tolerance test (suggestive of an abnormal result of the glucose challenge test) but who did not have gestational diabetes (n = 71 831); and women who did not receive an oral glucose tolerance test (suggestive of a normal result of the glucose challenge test) (n = 349 977). The primary outcome was cardiovascular disease (admission to hospital for acute myocardial infarction, coronary bypass, coronary angioplasty, stroke or carotid endarterectomy). Results: Compared with women who did not receive an oral glucose tolerance test, women with gestational diabetes and women who received an oral glucose tolerance test but did not have gestational diabetes had a higher risk of cardiovascular disease over 12.3 years of median follow-up (adjusted hazard ratio [HR] for women with gestational diabetes 1.66, 95% confidence interval [CI] 1.30–2.13, p Interpretation: Mild glucose intolerance in pregnancy may be associated with an increased risk of cardiovascular disease.

Medication errors in critical care: risk factors, prevention and disclosure

Abstract: Mr. S, a 63-year-old man with a recent history of peptic ulcer disease who is taking proton pump inhibitor therapy (his only medication) as an outpatient, is admitted to the intensive care unit (ICU) with respiratory distress. Community-acquired pneumonia is diagnosed, although pulmonary embolism

Do educational materials change knowledge and behaviour about crying and shaken baby syndrome? A randomized controlled trial

Abstract: Background: Shaken baby syndrome often occurs after shaking in response to crying bouts. We questioned whether the use of the educational materials from the Period of PURPLE Crying program would change maternal knowledge and behaviour related to shaking. Methods: We performed a randomized controlled trial in which 1279 mothers received materials from the Period of PURPLE Crying program or control materials during a home visit by a nurse by 2 weeks after the birth of their child. At 5 weeks, the mothers completed a diary to record their behaviour and their infants9 behaviour. Two months after giving birth, the mothers completed a telephone survey to assess their knowledge and behaviour. Results: The mean score (range 0–100 points) for knowledge about infant crying was greater among mothers who received the PURPLE materials (63.8 points) than among mothers who received the control materials (58.4 points) (difference 5.4 points, 95% confidence interval [CI] 4.1 to 6.5 points). The mean scores were similar for both groups for shaking knowledge and reported maternal responses to crying, inconsolable crying and self-talk responses. Compared with mothers who received control materials, mothers who received the PURPLE materials reported sharing information about walking away if frustrated more often (51.5% v. 38.5%, difference 13.0%, 95% CI 6.9% to 19.2%), the dangers of shaking (49.3% v. 36.4%, difference 12.9%, 95% CI 6.8% to 19.0%), and infant crying (67.6% v. 60.0%, difference 7.6%, 95% CI 1.7% to 13.5%). Walking away during inconsolable crying was significantly higher among mothers who received the PURPLE materials than among those who received control materials (0.067 v. 0.039 events per day, rate ratio 1.7, 95% CI 1.1 to 2.6). Interpretation: The receipt of the Period of PURPLE Crying materials led to higher maternal scores for knowledge about infant crying and for some behaviours considered to be important for the prevention of shaking. (ClinicalTrials.gov trial register no. NCT00175422.)

Marijuana and chronic obstructive lung disease: a population-based study

Abstract: Background: Our aim was to determine the combined and independent effects of tobacco and marijuana smoking on respiratory symptoms and chronic obstructive pulmonary disease (COPD) in the general population. Method: We surveyed a random sample of 878 people aged 40 years or older living in Vancouver, Canada, about their respiratory history and their history of tobacco and marijuana smoking. We performed spirometric testing before and after administration of 200 μg of salbutamol. We examined the association between tobacco and marijuana smoking and COPD. Results: The prevalence of a history of smoking in this sample was 45.5% (95% confidence interval [CI] 42.2%–48.8%) for marijuana use and 53.1% (95% CI 49.8%–56.4%) for tobacco use. The prevalence of current smoking (in the past 12 months) was 14% for marijuana use and 14% for tobacco use. Compared with nonsmokers, participants who reported smoking only tobacco, but not those who reported smoking only marijuana, experienced more frequent respiratory symptoms (odds ratio [OR] 1.50, 95% CI 1.05–2.14) and were more likely to have COPD (OR 2.74, 95% CI 1.66–4.52). Concurrent use of marijuana and tobacco was associated with increased risk (adjusted for age, asthma and comorbidities) of respiratory symptoms (OR 2.39, 95% CI 1.58–3.62) and COPD (OR 2.90, 95% CI 1.53–5.51) if the lifetime dose of marijuana exceeded 50 marijuana cigarettes. The risks of respiratory symptoms and of COPD were related to a synergistic interaction between marijuana and tobacco. Interpretation: Smoking both tobacco and marijuana synergistically increased the risk of respiratory symptoms and COPD. Smoking only marijuana was not associated with an increased risk of respiratory symptoms or COPD.

Association between statin-associated myopathy and skeletal muscle damage

Abstract: Background: Many patients taking statins often complain of muscle pain and weakness. The extent to which muscle pain reflects muscle injury is unknown. Methods: We obtained biopsy samples from the vastus lateralis muscle of 83 patients. Of the 44 patients with clinically diagnosed statin-associated myopathy, 29 were currently taking a statin, and 15 had discontinued statin therapy before the biopsy (minimal duration of discontinuation 3 weeks). We also included 19 patients who were taking statins and had no myopathy, and 20 patients who had never taken statins and had no myopathy. We classified the muscles as injured if 2% or more of the muscle fibres in a biopsy sample showed damage. Using reverse transcriptase polymerase chain reaction, we evaluated the expression levels of candidate genes potentially related to myocyte injury. Results: Muscle injury was observed in 25 (of 44) patients with myopathy and in 1 patient without myopathy. Only 1 patient with structural injury had a circulating level of creatine phosphokinase that was elevated more than 1950 U/L (10× the upper limit of normal). Expression of ryanodine receptor 3 was significantly upregulated in patients with biopsy evidence of structural damage (1.7, standard error of the mean 0.3). Interpretation: Persistent myopathy in patients taking statins reflects structural muscle damage. A lack of elevated levels of circulating creatine phosphokinase does not rule out structural muscle injury. Upregulation of the expression of ryanodine receptor 3 is suggestive of an intracellular calcium leak.