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Objectives: among patients undergoing noncardiac surgery, our objectives were to: (1) determine the feasibility of undertaking a large international cohort study; (2) estimate the current incidence of major perioperative vascular events; (3) compare the observed event rates to the expected event rates according to the Revised Cardiac Risk Index (RCRI); and (4) provide an estimate of the proportion of myocardial infarctions without ischemic symptoms that may go undetected without perioperative troponin monitoring.

Design: An international prospective cohort pilot study.

Participants: Patients undergoing noncardiac surgery who were >45 years of age, receiving a general or regional anesthetic, and requiring hospital admission.

Measurements: Patients had a Roche fourth-generation Elecsys troponin T measurement collected 6 to 12 hours postoperatively and on the first, second, and third days after surgery. Our primary outcome was major vascular events (a composite of vascular death [i.e., death from vascular causes], nonfatal myocardial infarction, nonfatal cardiac arrest, and nonfatal stroke) at 30 days after surgery. Our definition for perioperative myocardial infarction included: (1) an elevated troponin T measurement with at least one of the following defining features: ischemic symptoms, development of pathologic Q waves, ischemic electrocardiogram changes, coronary artery intervention, or cardiac imaging evidence of myocardial infarction; or (2) autopsy findings of acute or healing myocardial infarction.

Results: We recruited 432 patients across 5 hospitals in Canada, China, Italy, Colombia, and Brazil. During the first 30 days after surgery, 6.3% (99% confidence interval 3.9-10.0) of the patients suffered a major vascular event (10 vascular deaths, 16 nonfatal myocardial infarctions, and 1 nonfatal stroke). The observed event rate was increased 6-fold compared with the event rate expected from the RCRI. Of the 18 patients who suffered a myocardial infarction, 12 (66.7%) had no ischemic symptoms to suggest myocardial infarction.

Conclusions: This study suggests that major perioperative vascular events are common, that the RCRI underestimates risk, and that monitoring troponins after surgery can assist physicians to avoid missing myocardial infarction. These results underscore the need for a large international prospective cohort study.

Background: Although there is general agreement that metformin should be used as first-line pharmacotherapy in patients with type 2 diabetes, uncertainty remains regarding the choice of second-line therapy once metformin is no longer effective. We conducted a systematic review and meta-analysis to assess the comparative safety and efficacy of all available classes of antihyperglycemic therapies in patients with type 2 diabetes inadequately controlled on metformin monotherapy.

Methods: MEDLINE, EMBASE, BIOSIS Previews, PubMed and the Cochrane Central Register of Controlled Trials were searched for randomized controlled trials published in English from 1980 to October 2009. Additional citations were obtained from grey literature and conference proceedings and through stakeholder feedback. Two reviewers independently selected studies, extracted data and assessed risk of bias. Key outcomes of interest were hemoglobin A1c, body weight, hypoglycemia, quality of life, long-term diabetes-related complications, serious adverse drug events and mortality. Mixed-treatment comparison and pairwise meta-analyses were conducted to pool trial results, when appropriate.

Results: We identified 49 active and non-active controlled randomized trials that compared 2 or more of the following classes of antihyperglycemic agents and weight-loss agents: sulfonylureas, meglitinides, thiazolidinediones (TZDs), dipeptidyl peptidase-4 (DPP-4) inhibitors, glucagon-like peptide-1 (GLP-1) analogues, insulins, alpha-glucosidase inhibitors, sibutramine and orlistat. All classes of second-line antihyperglycemic therapies achieved clinically meaningful reductions in hemoglobin A1c (0.6% to 1.0%). No significant differences were found between classes. Insulins and insulin secretagogues were associated with significantly more events of overall hypoglycemia than the other agents, but severe hypoglycemia was rarely observed. An increase in body weight was observed with the majority of second-line therapies (1.8 to 3.0 kg), the exceptions being DPP-4 inhibitors, alpha-glucosidase inhibitors and GLP-1 analogues (0.6 to -1.8 kg). There were insufficient data available for diabetes complications, mortality or quality of life.

Interpretation: DPP-4 inhibitors and GLP-1 analogues achieved improvements in glycemic control similar to those of other second-line therapies, although they may have modest benefits in terms of weight gain and overall hypoglycemia. Further long-term trials of adequate power are required to determine whether newer drug classes differ from older agents in terms of clinically meaningful outcomes.

Background: Physicians often experience work-related stress that may lead to personal harm and impaired professional performance. Biofeedback has been used to manage stress in various populations.

Objective: To determine whether a biofeedback-based stress management tool, consisting of rhythmic breathing, actively self-generated positive emotions and a portable biofeedback device, reduces physician stress.

Design: Randomized controlled trial measuring efficacy of a stress-reduction intervention over 28 days, with a 28-day open-label trial extension to assess effectiveness.

Setting: Urban tertiary care hospital.

Participants: Forty staff physicians (23 men and 17 women) from various medical practices (1 from primary care, 30 from a medical specialty and 9 from a surgical specialty) were recruited by means of electronic mail, regular mail and posters placed in the physicians' lounge and throughout the hospital.

Intervention: Physicians in the intervention group were instructed to use a biofeedback-based stress management tool three times daily. Participants in both the control and intervention groups received twice-weekly support visits from the research team over 28 days, with the intervention group also receiving re-inforcement in the use of the stress management tool during these support visits. During the 28-day extension period, both the control and the intervention groups received the intervention, but without intensive support from the research team.

Main outcome measure: Stress was measured with a scale developed to capture short-term changes in global perceptions of stress for physicians (maximum score 200).

Results: During the randomized controlled trial (days 0 to 28), the mean stress score declined significantly for the intervention group (change -14.7, standard deviation [SD] 23.8; p = 0.013) but not for the control group (change -2.2, SD 8.4; p = 0.30). The difference in mean score change between the groups was 12.5 (p = 0.048). The lower mean stress scores in the intervention group were maintained during the trial extension to day 56. The mean stress score for the control group changed significantly during the 28-day extension period (change -8.5, SD 7.6; p < 0.001).

Conclusion: A biofeedback-based stress management tool may be a simple and effective stress-reduction strategy for physicians.

Background: Social determinants of health (SDOH) may influence the probability of people living with HIV also being infected with hepatitis C virus (HCV). We compared the SDOH of adults co-infected with HCV/HIV with that of HIV mono-infected adults to identify factors independently associated with HCV infection.

Methods: In this cross-sectional study, face-to-face interviews were conducted with 509 HIV-infected adults affiliated with or receiving services from community-based AIDS service organizations (CBAOs). The primary outcome measure was self-reported HCV infection status. Chi-square, Student's t tests, and Wilcoxon rank-sum tests were performed to compare SDOH of HCV/HIV co-infected participants with that of HIV mono-infected participants. Multivariable hierarchical logistic regression was used to identify factors independently associated with HCV co-infection.

Results: Data on 482 (95 HCV/HIV co-infected and 387 HIV mono-infected) adults were analyzed. Compared with participants infected with HIV only, those who were co-infected with HIV and HCV were more likely to be heterosexual, Aboriginal, less educated and unemployed. They were more likely to have a low income, to not be receiving antiretroviral treatment, to live outside the Greater Toronto Area (GTA), to use/abuse substances, experience significant depression, and utilize addiction counselling and needle-exchange services. They also were more likely to report a history of homelessness and perceived housing-related discrimination and to have moved twice or more in the previous 12 months. Factors independently associated with HCV/HIV co-infection were history of incarceration (odds ratio [OR] 8.81, 95% CI 4.43-17.54), history of homelessness (OR 3.15, 95% CI 1.59-6.26), living outside of the GTA (OR 3.13, 95% CI 1.59-6.15), and using/abusing substances in the past 12 months (OR 2.05, 95% CI 1.07-3.91).

Conclusion: Differences in SDOH exist between HIV/HCV co-infected and HIV mono-infected adults. History of incarceration, history of homelessness, substance use, and living outside the GTA were independently associated with HCV/HIV co-infection. Interventions that reduce homelessness and incarceration may help prevent HCV infection in people living with HIV.

In April 2010, the Ontario government announced another reduction in the maximum price of generic drugs permitted under the Ontario Drug Benefit (ODB) program, demanding that generic drugs now be sold for no more than 25% of the branded product's price. Other provinces are following Ontario in setting unprecedentedly low price-caps to reduce the cost of generic drugs. Generic product substitution legislation is vital to reducing costs to provincial drug plans, yet lower and lower price-caps may undo some of the benefits of substitution legislation if generics find it difficult to survive.