An evidence-based medicine methodology to bridge the gap between clinical and environmental health sciences

Physicians and other clinicians could help educate patients about hazardous environmental exposures, especially to substances that could affect their reproductive health. But the relevant scientific evidence is voluminous, of variable quality, and largely unfamiliar to health professionals caring for people of childbearing age. To bridge this gap between clinical and environmental health, we created a methodology to help evaluate the quality of evidence and to support evidence-based decision making by clinicians and patients. The methodology can also support professional societies, health care organizations, government agencies, and others in developing prevention-oriented guidelines for use in clinical and policy settings.     

再论观察与实验：大数据现实世界研究不能取代随机对照试验

传统上,流行病学多以干预划分观察和实验,干预研究等于实验研究,还认为干预研究的科学性高于观察性研究。在一般科学实验里,干预指人为施加的改变自然状况的措施。干预并不一定是有益的,也并不一定是研究者当下施加的,研究者、受试者或第三者目前或过去施加的措施都可以形成"有效的"干预。例如,由研究者、受试者和第三者通过某种方法致使视神经损伤,都可以形成有效改变视神经正常功能的干预,研究者可以由此观察到视神经和视力的关系。以此推论,由受试者自己过去施加的不良干预（如吸烟）也属于干预,那么研究吸烟和肺癌的观察性队列研究就等同于实验研究了。由此看来,干预本身并不足以有效地区分观察和实验。如果认为实验的科学性高于观察,那么在干预的基础上,只能从科学性上（即设计特征）区分观察和实验。在评估医学干预效果的临床试验中,随机分组是在传统认为的观察研究基础上引入的最重要的偏倚控制措施,应该是区分观察和实验的核心属性。如果一定要把人群研究分成观察和实验,随机对照试验才是真正的实验研究,非随机分组形成的干预研究属于试验,但不是实验。基于大数据的现实世界研究,如果没有随机分组,不能构成实验,也不能成为对干预效果的最终检验。大数据现实世界研究不能取代随机对照试验,这是本文希望传达的最重要的信息。     

Comparison of directed and self-directed learning in evidence-based medicine: a randomised controlled trial

OBJECTIVES: To compare 2 educational programmes for teaching evidence-based medicine (EBM). DESIGN: Prospective randomised controlled trial accompanied by a qualitative evaluation. SETTING: University of Oslo, Norway, 2002-03. PARTICIPANTS: A total of 175 students entered the study. All tenth semester medical students from 3 semesters were eligible for inclusion if they completed baseline assessment and consent forms and either attended teaching on the first day of the semester or gave reasons for their absence on the first day in advance. Interventions One intervention was based on computer-assisted, self-directed learning (self-directed intervention), whilst the other was organised as workshops based on social learning theory (directed intervention). Both educational interventions consisted of 5 half-day sessions. MAIN OUTCOME MEASURES: The primary outcomes were knowledge about EBM and skills in critical appraisal. A secondary outcome measured attitudes to EBM. Outcomes were compared on an intention-to-treat basis using a stratified Wilcoxon rank-sum test. RESULTS: There were no differences in outcomes for the 2 study groups in terms of EBM knowledge (mean deviation 0.0 [95% confidence interval - 1.0, 1.0], P = 0.8), critical appraisal skills (MD 0.1 [95% CI - 0.9, 1.1], P = 0.5), or attitudes to EBM (MD - 0.3 [95% CI - 1.4, 0.8], P = 0.5). Follow-up rates were 96%, 97% and 63%, respectively. CONCLUSIONS: This trial and its accompanying qualitative evaluation suggest that self-directed, computer-assisted learning may be an alternative format for teaching EBM. However, further research is needed to confirm this and investigate alternative educational models.     

Lipid-lowering medication for secondary prevention of coronary heart disease in a German outpatient population: the gap between treatment guidelines and real life treatment patterns

BACKGROUND: Few published data in particular from the United States indicate that the implementation of guidelines for prevention of coronary heart disease (CHD) is far from optimal. The objective of our study was to identify the type and prevalence of lipid-lowering medications in a German outpatient CHD population and to examine the impact of applied treatment regimens on serum lipid levels. METHODS: Retrospective analysis of the washout phase of 2,856 CHD patients requiring lipid-lowering medication. Data are derived from a multicenter, randomized, open-label, parallel group clinical trial comparing the safety and efficacy of atorvastatin versus simvastatin in 591 centers in Germany. Medical history, physical examination, and serum lipid levels were obtained at the beginning of the washout phase (Week -6) and at the end of the washout phase (Week -1, i.e., 5 weeks after the discontinuation of all prior lipid-lowering medications). The data at Week -6 represented the lipid levels under real life conditions. The difference from the data at Week -1 reflected the therapeutic effects achieved by the previous lipid-lowering treatment. RESULTS: The mean low-density lipoprotein cholesterol (LDL-C) level at Week -6 was 173.4 +/- 42.5 mg/dl. Only 176 (6.2%) of 2,856 CHD patients were found to meet the target LDL-C level of <115 mg/dl at Week -6, only 76 (2.7%) patients had LDL-C levels <100 mg/dl, and 363 (12.7%) patients had LDL-C levels <130 mg/dl. After discontinuation of all prior lipid-lowering medications, mean LDL-C increased to 187.2 +/- 44.0 mg. This means that only a marginal 7.4% reduction in LDL-C level was achieved under real life treatment conditions. This limited LDL-C reduction was due mainly to the low prevalence of lipid-lowering treatment (65.5% of patients did not receive any medication at all) and inadequate dosing. With respect to the effect on LDL-C and total cholesterol, statins alone were superior to fibrates. CONCLUSION: The study shows that there is a wide gap between treatment guidelines and real life treatment patterns in Germany. Awareness of the risks of high cholesterol levels has to be increased among both patients and physicians. Available treatment guidelines should be better implemented.     

Antibody response to influenza immunization in coronary artery disease patients: A controlled trial

Safety of and humoral immune response to the anti-influenza vaccine in coronary artery disease (CAD) patients were evaluated. The trivalent vaccine was administered to 137 eligible CAD patients and 67 age- and sex-matched healthy individuals. Antibody (Ab) titers were measured before and 1 month after vaccination. CAD and HC groups were not significantly different in serologic response and magnitude of change in antibody titers against each of the vaccine antigens. In multivariate analyses, regular exercise and using multivitamin supplements were independently associated with better antibody response among CAD patients. There were no major cardiac or general adverse effects. Influenza vaccine was found safe in CAD patients and antibody responses were similar to HCs.     

The value of explicitly emulating a target trial when using real world evidence: an application to colorectal cancer screening

Observational analyses for causal inference often rely on real world data collected for purposes other than research. A frequent goal of these observational analyses is to use the data to emulate a hypothetical randomized experiment, i.e., the target trial, that mimics the design features of a true experiment, including a clear definition of time zero with synchronization of treatment assignment and determination of eligibility. We review a recent observational analysis that explicitly emulated a target trial of screening colonoscopy using insurance claims from U.S. Medicare. We then compare this explicit emulation with alternative, simpler observational analyses that do not synchronize treatment assignment and eligibility determination at time zero and/or do not allow for repeated eligibility. This empirical comparison suggests that lack of an explicit emulation of the target trial leads to biased estimates, and shows that allowing for repeated eligibility increases the statistical efficiency of the estimates.     

Treatment adjustment and medication adherence for complex patients with diabetes, heart disease, and depression: a randomized controlled trial

PURPOSE

Medication nonadherence, inconsistent patient self-monitoring, and inadequate treatment adjustment exacerbate poor disease control. In a collaborative, team-based, care management program for complex patients (TEAMcare), we assessed patient and physician behaviors (medication adherence, self-monitoring, and treatment adjustment) in achieving better outcomes for diabetes, coronary heart disease, and depression.

METHODS

A randomized controlled trial was conducted (2007–2009) in 14 primary care clinics among 214 patients with poorly controlled diabetes (glycated hemoglobin [HbA_1c] ≥8.5%) or coronary heart disease (blood pressure >140/90 mm Hg or low-density lipoprotein cholesterol >130 mg/dL) with coexisting depression (Patient Health Questionnaire-9 score ≥10). In the TEAMcare program, a nurse care manager collaborated closely with primary care physicians, patients, and consultants to deliver a treat-to-target approach across multiple conditions. Measures included medication initiation, adjustment, adherence, and disease self-monitoring.

RESULTS

Pharmacotherapy initiation and adjustment rates were sixfold higher for antidepressants (relative rate [RR] = 6.20; P <.001), threefold higher for insulin (RR = 2.97; P <.001), and nearly twofold higher for antihypertensive medications (RR = 1.86, P <.001) among TEAMcare relative to usual care patients. Medication adherence did not differ between the 2 groups in any of the 5 therapeutic classes examined at 12 months. TEAMcare patients monitored blood pressure (RR = 3.20; P <.001) and glucose more frequently (RR = 1.28; P = .006).

CONCLUSIONS

Frequent and timely treatment adjustment by primary care physicians, along with increased patient self-monitoring, improved control of diabetes, depression, and heart disease, with no change in medication adherence rates. High baseline adherence rates may have exerted a ceiling effect on potential improvements in medication adherence.     

A multifaceted intervention according to the Audit Project Odense method improved secondary prevention of ischemic heart disease: a randomised controlled trial

BACKGROUND: No single quality improvement instrument has proved consistently effective, but multifaceted interventions are believed to have the greatest impact. However, only little is known regarding what combinations are likely to be successful. OBJECTIVE: To evaluate the impact of a multifaceted intervention strategy combining GP registrations, outreach visits and feedback, targeting secondary prevention of ischemic heart disease in general practice. METHODS: A randomised controlled trial including 28 GPs in Ringkj?bing County, Denmark. Half of the GPs received outreach visits and feedback on their prescribing of heart disease drugs. Evaluation was based on registration of consultations with patients suffering from ischemic heart disease. RESULTS: The intervention had a statistically significant impact on prescribing of lipid lowering drugs [odds ratio 1.59; 95% confidence interval (CI) 1.00 to 2.53] and acetylsalicylic acid (odds ratio 2.54; 95% CI 1.21 to 5.31). CONCLUSION: An intervention strategy combining outreach visits, feedback and GP registrations is a promising way of improving the quality of preventive treatment in general practice.     

Case-based training of evidence-based clinical practice in primary care and decreased mortality in patients with coronary heart disease

PURPOSE We investigated the 10-year mortality rates in a trial that tested a case-based intervention in primary care aimed at reducing the gap between evidence-based goals and clinical practice in patients with coronary heart disease (CHD).METHODS A prospective randomized controlled pragmatic trial was undertaken in a primary care setting. New evidence-based guidelines, with intensified lipid-lowering recommendations in CHD, were mailed to all general practitioners in the region and presented at a lecture in 1995. General practitioners (n = 54) and patients with CHD (n = 88) were assigned according to their primary health care center to 2 balanced groups and randomly allocated to usual care as a control or to an active intervention. General practitioners in the intervention group participated in repeated case-based training during a 2-year period. Patients whose CHD was treated by specialists (n = 167) served as an internal specialist comparison group. Altogether, 255 consecutive patients were included. Cox regression analysis was used to detect any survival benefit of the intervention.RESULTS At 10 years, 22% of the patients in the intervention group had died as compared with 44% in the control group (P = .02), with a hazard ratio of 0.45 (95% confidence interval, 0.20–0.95). This difference was mainly due to reduced cardiovascular mortality in the intervention group (P = .01). In addition, the mortality rate of 22% in the intervention group was comparable to the rate of 23% seen in patients treated by a specialist.CONCLUSIONS Use of case-based training to implement evidence-based practice in primary care was associated with decreased mortality at 10 years in patients with CHD.     

Randomised controlled trial of a shared care programme for newly referred cancer patients: bridging the gap between general practice and hospital

Objective: To determine the effect of a shared care programme on the attitudes of newly referred cancer patients towards the healthcare system and their health related quality of life and performance status, and to assess patients' reports on contacts with their general practitioner (GP).     

Differentiating between trust and dependence of patients with coronary heart disease: furthering the sociology of trust

Sociological health research on the concept of trust has been bedevilled by its multivocalities. This article extends Luhmann's attempts to clarify a sociology of trust. Luhmann argued a semantic distinction between trust and confidence. In this article, we use empirical data on patient ‘trust’ in doctors to argue that there is also a semantic distinction between trust and dependence. We conducted 37 semi-structured interviews with patients with coronary heart disease in Adelaide, Australia in 2008 and 2009. Our findings indicate that risk, familiarity and time were critical to understand the distinction between trust and dependence. We argue that patients in situations of emergency (heightened risk) ‘depended’ on, rather than trusted, doctors, given the patients lack of familiarity with their doctors. Time was a mediating factor, as the more ‘urgent’ the situation, the more likely it was that dependence came into play, since the situation was ‘unfamiliar’. Rather than juxtaposing trust and dependence, in this article we show how dependence may coexist with trust in the health care system in times of emergency.     

The relation of serum cholesterol to risk of coronary heart disease: implications for the elderly

Elevated cholesterol is a known risk factor for coronary heart disease (CHD) in young and middle-aged persons. Because of the high prevalence of CHD in a growing elderly population, physicians must decide whether to devote clinical attention to this condition in older patients. Longitudinal cohort studies show that while the association between serum cholesterol and CHD decreases after age 55 years, it still persists. Primary prevention trials performed mostly on middle-aged men have reduced the incidence rate of CHD through cholesterol lowering but they have yet to show a reduction in overall mortality. Secondary prevention studies of lipid alteration have reported decreased mortality and slowed progression of coronary stenoses, again in predominantly male subjects aged less than 60 years. Implications of these findings for care of older patients are discussed along with recommendations for clinical management and future research.     

Erectile dysfunction: a significant health need in patients with coronary heart disease

BACKGROUND AND AIMS: Erectile dysfunction (ED) is a common condition, which negatively affects quality of life, and shares similar risk factors with Coronary Heart Disease (CHD). Studies from the pre - sildenafil era confirm a higher risk of ED in patients with cardiovascular disease. The high profile and success of sildenafil therapy has made it easier for some men to discuss erectile difficulties with healthcare professionals. Our aim therefore was to estimate the prevalence of ED in our cardiac rehabilitation patients . METHODS AND RESULTS: We surveyed 150 random male cardiac rehabilitation patients using the International Index of Erectile Function (IIEF) questionnaire. 61% of all respondents had erectile difficulties, rising to 75% in the over 55 age group. 48% of respondents indicated their wish to discuss erectile problems with the healthcare team. CONCLUSION: ED and CHD commonly co-exist. A large proportion of our respondents wished further discussion of erectile insufficiency. We recommend that cardiac rehabilitation programmes should adopt a proactive approach to detection and treatment of ED.     

集束化循证护理在冠心病患者经PCI治疗围手术期中的构建及应用

目的 探讨集束化循证护理在冠心病患者经皮冠状动脉介入治疗(PCI)围手术期中的构建及应用效果.方法 选取2019年1月-2019年6月在我院心内科进行经皮冠状动脉介入治疗的162例冠心病患者作为本次研究对象.并将本次研究对象按随机数字表法随机分为对照组以及实验组(各81例).其中对照组实施传统常规护理,实验组实施集束化...     

含植物甾醇酯牛奶对高胆固醇血症患者血脂水平影响的随机对照研究

目的 研究摄入含有植物甾醇酯的牛奶对血脂指标的影响。方法 从社区招募血胆固醇异常患者,随机分入植物甾醇酯牛奶组(n=59)、普通牛奶组(n=58)和不饮奶组(n=62),为期2个月。基线时3组受试者均接受健康教育和高胆固醇血症防治宣教。植物甾醇酯牛奶组和普通牛奶组每天饮用500 g牛奶,其中植物甾醇酯牛奶组的植物甾醇摄入量为1.58 g/d;不饮奶组在整个实验期内不食用任何奶制品。了解受试者身体活动水平,并每月随访一次血脂指标。结果 共157人完成实验。干预1个月时,植物甾醇酯牛奶组的总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)水平显著低于普通牛奶组,经校正后植物甾醇酯牛奶组与基线时相比TC差异无统计学意义,甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)水平显著升高,LDL-C水平显著降低,与普通牛奶组和不饮奶组相比时,各项血脂指标均无差异。干预2个月时,植物甾醇酯牛奶组的TC和LDL-C水平显著低于普通牛奶组和不饮奶组,经校正后植物甾醇酯牛奶组与基线时相比TC和LDL-C水平显著降低,TG水平显著升高,HDL-C水平无明显变化,与普通牛奶组和不饮奶组相比时,TC和LDL-C水平明显降低,TG和HDL-C在各组间差异无显著性。结论 植物甾醇酯牛奶可显著降低血胆固醇异常患者的TC和LDL-C水平。     

住院冠心病患者健康功能与家庭关怀关系

目的 探讨住院冠心病(CHD)患者健康功能损失程度与家庭关怀的关系。方法 采用疾病影响程度量表(SIP)和家庭关怀度指数问卷(Family APGAR index)对182例住院CHD患者进行问卷调查。结果 住院CHD患者总体健康功能损失得分为(25.285±8.577)分,躯体功能损失得分为(18.925±10.203)分,社会心理功能损失得分为(28.286±9.596)分;Logistic回归分析显示,总体健康功能损失程度的影响因素为年龄、心功能、疾病程度、家庭关怀,其OR值分别为1.278、10.839、25.874、0.380;患者家庭功能障碍者占47.2%,健康功能损失程度与家庭关怀呈负相关(r=-0.355,P<0.05)。结论 住院CHD患者健康功能与家庭关怀密切相关,提高家庭关怀度对维持患者生理-心理-社会全方位的健康功能状态意义重大。