真实世界研究与随机对照试验、单病例随机对照试验在临床治疗性研究中的关系比较

真实世界研究、随机对照试验及单病例随机对照试验在设计及具体的实施环节上存在明显不同.随机对照试验属于新治疗措施实施前的研究,真实世界研究属于新治疗措施实施后的研究.两者不是对同一个问题的平行论证,而是承启关系.精心设计的随机对照试验是临床上任何干预措施效果评价的基础,其结果需要真实世界研究的进一步验证及拓展补充,综合考虑二者才是最佳的选择.单病例随机对照试验更易在短时间内获得一些特殊病例的信息,是随机对照试验结果的良好补充,也是一定条件下最经济的真实世界研究.临床工作及其研究是十分复杂的过程.不同个体虽患同种疾病,但临床表现互有差异,且临床反应的变化也不尽相同.因此,无法获得同一干预措施下不同个体的相同治疗效果;加之有的治疗措施缺乏真实性和实用价值,从而使得疗效评价成为一个难题.近些年来,普遍采用试验性的研究结果作为证据指导临床实践活动,其中以随机对照试验(RCT)最为受到重视,但由于RCT属于药物面市前研究,对研究对象的选择、治疗措施的应用等均有严格的限定.     

Randomized controlled trial of gamma-linolenic acid and eicosapentaenoic acid in peripheral arterial disease

BACKGROUND AND AIMS: epidemiological studies suggest polyunsaturated fatty acids protect against the development of atherosclerosis. The aim of this study was to perform a randomized controlled trial of gamma-linolenic and eicosapentaenoic acids in patients with lower limb atherosclerosis. Main outcome measures were: cholesterol and lipoprotein concentrations; haemostatic and rheological variables; the ankle brachial pressure index; walking distance; and cardiovascular events and death. METHODS: 120 men and women with stable intermittent claudication were randomized to 2 years treatment with either a combination of gamma-linolenic and eicosapentaenoic acids, or placebo. RESULTS: 39 (65.0 cent) of those taking fatty acids and 36 (60.0 cent) of those taking placebo completed the trial. Lipid concentrations did not differ significantly during the trial. In those taking fatty acids, haematocrit was significantly higher than in the placebo group after 6 months (46.1 cent compared with 44.6 cent, P 0.05). CONCLUSIONS: a combination of polyunsaturated fatty acids produced a statistically significant reduction in systolic blood pressure, but no other significant benefits on risk factors. The trend towards fewer coronary events in those taking fatty acids warrants further investigation.     

大肠癌序贯筛检方案在人群中应用的前瞻性评估

目的 建立并验证大肠癌序贯筛检方案在我国人群中应用的效果。方法 以大肠癌高发区嘉善县１９８９年３０岁及以上者作为目标人群,采用随机分组空白对照研究设计,以免疫法粪便潜血试验结合个体危险度隶属度函数（ＡＤ值）为初筛手段,纤维肠为复筛的序贯筛检方案。结果 经筛检后筛检人群与对照人群的大肠癌８年累积发病率分别为３．９５‰（９５％ＣＩ为３．８１～４．１０）和４．０１‰（９５％ＣＩ为３．８６～４．１６）,两     

抗菌药物预防胰胆管造影术后胆管炎随机对照试验的荟萃分析

目的评价预防性应用抗菌药物能否降低内镜逆行胰胆管造影(ERCP)术后胆管炎的发生率。方法检索MEDLINE、EMBASE.com、Cochrane Controlled Trial Register、中国生物医学文献数据库,收集抗菌药物预防ERCP术后胆管炎的临床随机对照研究,筛选、评价文献并提取数据进行荟萃(meta)分析。结果共纳入9篇文献,荟萃分析结果显示,抗菌药物预防并不能降低ERCP术后胆管炎的发生率(RR=0.681,95%CI0.407~1.139,P>0.05),敏感性分析结果与荟萃分析结果一致,偏倚分析提示无显著发表偏倚存在,故上述结果具有一定的可信度。结论ERCP术前不推荐常规进行抗菌药物预防。     

A post-hoc analysis of serotype-specific vaccine efficacy of 13-valent pneumococcal conjugate vaccine against clinical community acquired pneumonia from a randomized clinical trial in the Netherlands

BackgroundSerotype-specific vaccine efficacy (VE) against adult community acquired pneumonia (CAP) remains poorly defined, yet such data are important for assessing the utility of adult pneumococcal conjugate vaccine (PCV) programs.MethodsWe evaluated the Community Acquired Pneumonia Immunization Trial in Adults to assess serotype-specific VE for CAP. This parallel-arm randomized clinical trial assessed 13-valent PCV (PCV13) VE among community dwelling persons aged ≥65 years in The Netherlands. In the original analysis, PCV13 VE against first episodes of vaccine-type (VT) chest radiology confirmed CAP was 45.6% (95% confidence interval [CI] 21.8–62.5%). Unlike the original analysis, we included any subject that met a clinical definition of CAP regardless of radiographic findings. VT-CAP was identified by culture (sterile or non-sterile) or serotype-specific urinary antigen detection (SSUAD) test. Only the five serotypes with at least 10 episodes in the control arm, based on the original analysis, were included for VE assessment.ResultsOf 272 clinical CAP visits with VT serotypes identified, 253 (93%) were identified by SSUAD including 210 (77%) by SSUAD alone. VE was determined for serotypes 1, 3, 6A, 7F, and 19A, with total first episodes of, respectively, 27, 36, 25, 38, and 48. VE (95%CI) for the five evaluated serotypes against first clinical CAP episodes were: serotype 1, 20.0% (−83.1% to 65.8%); serotype 3, 61.5% (17.6–83.4%); serotype 6A, 33.3% (−58.6% to 73.2%); serotype 7F, 73.3% (40.5–89.4%); and serotype 19A, 45.2% (−2.2% to 71.5%).DiscussionStatistically significant VE was observed for serotypes 3 and 7F for clinical CAP among elderly community dwelling adults. The VE point estimates and CIs for serotypes 1, 6A, and 19A were lower but consistent with the overall VT-CAP VE of 45.6% previously reported. These findings may be relevant in models to accurately account for the potential impact of adult PCV13 immunization.     

Bias was reduced in an open-label trial through the removal of subjective elements from the outcome definition

ObjectiveTo determine whether modifying an outcome definition to remove subjective elements reduced bias in a trial that could not use blinded outcome assessment.Study Design and SettingReanalysis of an open-label trial comparing a restrictive vs. liberal transfusion strategy for gastrointestinal bleeding. The usual definition of the primary outcome, further bleeding, allows subjective clinical symptoms to be used alone for diagnosis, whereas the definition used in the trial required more objective confirmation by endoscopy. We compared treatment effect estimates for these two definitions.ResultsFewer subjective symptom-identified events were confirmed using more objective methods in the restrictive arm (18%) than in the liberal arm (56%), indicating differential assessment between arms. An analysis using all events (both subjective and more objective) led to an odds ratio of 0.83 (95% confidence interval [CI]: 0.50–1.37). When only events confirmed using more objective methods were included, the odds ratio was 0.50 (95% CI: 0.32–0.78). The ratio of the odds ratios was 1.66, indicating that including unconfirmed events in the definition biased the treatment effect upward by 66%.ConclusionModifying the outcome definition to exclude subjective elements substantially reduced bias. This may be a useful strategy for reducing bias in trials that cannot blind outcome assessment.     

Mifepristone versus laminaria: a randomized controlled trial of cervical ripening in midtrimester termination

BACKGROUND: Mifepristone was compared with laminaria for cervical ripening in second-trimester induction of labor (IOL). STUDY DESIGN: We performed a randomized, controlled, open-label study of women undergoing second-trimester IOL for fetal demise, aneuploidy or anomalies at a single tertiary care center from January 2004 to May 2006. Main outcome measures were induction-to-delivery time and pain with cervical ripening. RESULTS: Of 50 eligible women, 37 were enrolled in the study, of whom 33 completed the study: 16 were randomized to laminaria and 17 to mifepristone. Induction-to-delivery time was significantly shorter in the mifepristone arm (mean=10 h vs. 16 h, p=.01; median=7.5 h vs. 13.4 h, p=.01). Pain with cervical ripening was also significantly less in the mifepristone group than in the laminaria group (median=1 vs. 6 on an 11-point visual analogue scale, p<.001). Maternal age, parity, gestational age, fetal demise prior to induction, need for postpartum curettage, blood loss, pain during induction, delivery and at the time of discharge were not significantly different between the two groups. CONCLUSION: Mifepristone shortens the induction-to-delivery time and decreases pain with cervical ripening when compared with laminaria for second-trimester induction.     

Computer-assisted cognitive rehabilitation in persons with multiple sclerosis: Results of a multi-site randomized controlled trial with six month follow-up

Background

The effects of multiple sclerosis (MS) on cognition have gained increasing recognition as one of the major disabling symptoms of the disease. Despite the prevalence of these symptoms and their impact on quality of life, limited attention has been given to strategies that might help manage the cognitive changes commonly experienced by persons with MS.

Randomized trial of a clinic-based, community-supported, lifestyle intervention to improve physical activity and diet: the North Carolina enhanced WISEWOMAN project

OBJECTIVE: To determine if a clinic-based behavioral intervention program for low-income mid-life women that emphasizes use of community resources will increase moderate intensity physical activity (PA) and improve dietary intake. METHODS: Randomized trial conducted from May 2003 to December 2004 at one community health center in Wilmington, NC. A total of 236 women, ages 40-64, were randomized to receive an Enhanced Intervention (EI) or Minimal Intervention (MI). The EI consisted of an intensive phase (6 months) including 2 individual counseling sessions, 3 group sessions, and 3 phone calls from a peer counselor followed by a maintenance phase (6 months) including 1 individual counseling session and 7 monthly peer counselor calls. Both phases included efforts to increase participants' use of community resources that promote positive lifestyle change. The MI consisted of a one-time mailing of pamphlets on diet and PA. Outcomes, measured at 6 and 12 months, included the comparison of moderate intensity PA between study groups as assessed by accelerometer (primary outcome) and questionnaire, and dietary intake assessed by questionnaire and serum carotenoids (6 months only). RESULTS: For accelerometer outcomes, follow-up was 75% at 6 months and 73% at 12 months. Though moderate intensity PA increased in the EI and decreased in the MI, the difference between groups was not statistically significant (p=0.45; multivariate model, p=0.08); however, moderate intensity PA assessed by questionnaire (92% follow-up at 6 months and 75% at 12 months) was greater in the EI (p=0.01; multivariate model, p=0.001). For dietary outcomes, follow-up was 90% for questionnaire and 92% for serum carotenoids at 6 months and 74% for questionnaire at 12 months. Dietary intake improved more in the EI compared to the MI (questionnaire at 6 and 12 months, p<0.001; serum carotenoid index, p=0.05; multivariate model, p=0.03). CONCLUSION: The EI did not improve objectively measured PA, but was associated with improved self-reported and objective measures of dietary intake.     

临床干预措施效力-效果差距弥合的方法学研究进展（一）：改善真实世界研究的效果估计

目的 干预措施在临床实践中的实际干预效果与随机对照试验（RCT）中表现的效力存在差异，即效力-效果差距。RCT结果与真实世界研究（RWS）结果的差异可能无法代表真实的效力-效果差距，这是因为当RWS与RCT在研究设计上有较大差异，或RWS结果估计存在偏倚时，效力-效果的估计可能是有偏的。其次，当发现干预措施存在效力-效果差距，不能对所有患者实行一刀切的临床决策，而需要进一步评估影响干预措施效果的真实世界因素，识别可能取得期望效用的患者群体。方法 检索PubMed、Embase、Web of Science、万方数据知识服务平台、维普数据库、中国知网6个数据库从建库至2022年12月31日的中英文文献，采用概括性综述的方法，对如何改进RWS设计从而弥合效力-效果差距的方法进行归纳整合和定性描述。结果 共纳入10篇文献，探讨如何以RCT研究方案为模板，制定相应的RWS方案，在正确估计效力-效果差距的基础上，进一步评估干预措施在患者亚群中的效果，选取能获得预期收益风险比的患者亚群，从而弥合效力-效果差距。结论 使用医疗大数据，模拟目标试验方案关键特征，可以提高研究结果的真实性和有效性，弥合效力-效果差距。     

Effectiveness of Tailored Dietary Counseling in Treating Malnourished Outpatients with Chronic Obstructive Pulmonary Disease: A Randomized Controlled Trial

BackgroundMalnutrition in patients with chronic obstructive pulmonary disease (COPD) is common and associated with poor prognosis. Nutrition interventions are necessary, but there is a lack of evidence regarding the effectiveness of tailored nutrition advice.ObjectiveThis study investigated whether tailored nutrition counseling could improve dietary intake, nutritional status, functional outcomes, and health-related quality of life (QoL) of malnourished outpatients with COPD.DesignWe conducted a randomized controlled trial in which participants were randomly assigned to either the intervention group (IG) or the control group (CG).Participants/settingOne hundred and twenty malnourished outpatients with COPD participated in the study between May and November 2017 at the National Lung Hospital, Hanoi, Vietnam.InterventionThe IG received tailored nutrition counseling once per month for 3 months based on a specifically developed written nutrition resource for COPD. The CG received the same educational resource at baseline without any discussion.Main outcome measuresThe main outcome measures were energy and protein intakes, body weight change, nutritional status (Subjective Global Assessment score), muscle strength, and QoL.Statistical analysesDifferences between groups before and after the intervention were assessed using two-way repeated measures analysis of variance. Generalized estimating equation modeling was used to investigate the differences between groups over time.ResultsAt baseline, there were no significant differences in outcomes of interest between the two groups. After 3 months of intervention, time–intervention interactions for energy intake, protein intake, and body weight change were significant (945 kcal/day, 95% CI 792 to 1,099 kcal/day, P<0.001; 50.0 g protein/day, 95% CI 43.9 to 56.1 g protein/day, P<0.001; and 1.0 kg, 95% CI 0.5 to 1.5 kg, P<0.001, respectively). Subjective Global Assessment scores improved in the IG and worsened in the CG. Significant improvements were found in inspiratory muscle strength in the IG (5.4 cmH₂O, 95% CI 2.3 to 8.6 cmH₂O, P=0.001) and significant decreases in handgrip strength were found in the CG after 3 months of the intervention (1.4 kg, 95% CI 0.4 to 2.4 kg, P=0.007). There was a significant interaction effect for all QoL scores (analysis of variance two-way repeated, P≤0.003). The IG also significantly improved all QoL scores from baseline to 3 months (P<0.004).ConclusionsTailored nutritional counseling has the potential to improve dietary intakes, nutritional status, functional outcomes, and QoL in malnourished outpatients with COPD.     

Zinc supplementation fails to increase the immunogenicity of oral poliovirus vaccine: A randomized controlled trial

BackgroundPolio eradication remains a challenge in Pakistan and the causes for the failure to eradicate poliomyelitis are complex. Undernutrition and micronutrient deficiencies, especially zinc deficiency, are major public health problems in Pakistan and could potentially affect the response to enteric vaccines, including oral poliovirus vaccine (OPV).ObjectiveTo assess the impact of zinc supplementation among infants on immune response to oral poliovirus vaccine (OPV).MethodsA double-blind, randomized placebo-controlled trial was conducted in newborns (aged 0–14 days). Subjects were assigned to either receive 10 mg of zinc or placebo supplementation daily for 18 weeks. Both groups received OPV doses at birth, at 6 weeks, 10 weeks and 14 weeks. Data was collected on prior immunization status, diarrheal episodes, breastfeeding practices and anthropometric measurements at recruitment and at 6 and 18 weeks. Blood samples were similarly collected to determine the antibody response to OPV and for micronutrient analysis. Logistic regression was used to determine the relationship between seroconversion and zinc status.ResultsOverall, 404 subjects were recruited. At recruitment, seropositivity was already high for poliovirus (PV) serotype 1 (zinc: 91.1%; control: 90.5%) and PV2 (90.0%; 92.7%), with lower estimates for PV3 (70.0%; 64.8%). By week 18, the proportion of subjects with measured zinc levels in the normal range (i.e. ≥60 μg/dL) was significantly greater in the intervention group compared to the control group (71.9%; 27.4%; p < 0.001). No significant difference in seroconversion was demonstrated between the groups for PV1, PV2, or PV3.ConclusionsThere was no effect of zinc supplementation on OPV immunogenicity. These conclusions were confirmed when restricting the analysis to those with measured higher zinc levels.     

A controlled, randomized, comparative study of a radiant heat bandage on the healing of stage 3-4 pressure ulcers: a pilot study

OBJECTIVES: Pressure ulcers, like other chronic wounds, fail to proceed through an orderly and timely process to produce anatomical or functional integrity. Treatment of pressure ulcers is directed to improving host factors and providing an optimum wound environment. In addition to providing a moist wound environment, it has been theorized that preventing hypothermia in a wound and maintaining a normothermic state might improve wound healing. DESIGN/SETTING: Forty-one subjects with a stage 3 or stage 4 truncal pressure ulcer >1.0 cm(2) were recruited from outpatient clinics, long-term care nursing homes, and a rehabilitation center. The experimental group was randomized to a radiant-heat dressing device and the control group was randomized to a hydrocolloid dressing, with or without a calcium alginate filler. Subjects were followed until healed or for 12 weeks. RESULTS: Eight subjects (57%) in the experimental group had complete healing of their pressure ulcer compared with 7 subjects (44%) with complete healing in the control group (P = .46). CONCLUSION: Although a 13% difference in healing rate between the two arms of the study was found, this difference was not statistically significant. At almost all points along the healing curve, the proportion not healed was higher in the control arm.     

A community-based randomized trial of a faith-placed intervention to reduce cervical cancer burden in Appalachia

Objective

Faith Moves Mountains assessed the effectiveness of a faith-placed lay health advisor (LHA) intervention to increase Papanicolaou (Pap) test use among middle-aged and older women in a region disproportionately affected by cervical cancer and low screening rates (regionally, only 68% screened in prior 3 years).

Method

This community-based RCT was conducted in four Appalachian Kentucky counties (December 2005-June 2008). Women aged 40-64 and overdue for screening were recruited from churches and individually randomized to treatment (n = 176) or wait-list control (n = 169). The intervention provided LHA home visits and newsletters addressing barriers to screening. Self-reported Pap test receipt was the primary outcome.

Results

Intention-to-treat analyses revealed that treatment group participants (17.6% screened) had over twice the odds of wait-list controls (11.2% screened) of reporting Pap test receipt post-intervention, OR = 2.56, 95% CI: 1.03-6.38, p = 0.04. Independent of group, recently screened participants (last Pap > 1 but < 5 years ago) had significantly higher odds of obtaining screening during the study than rarely or never screened participants (last Pap ≥ 5 years ago), OR = 2.50, 95% CI: 1.48-4.25, p = 0.001.

Conclusions

The intervention was associated with increased cervical cancer screening. The faith-placed LHA addressing barriers comprises a novel approach to reducing cervical cancer disparities among Appalachian women.     

Nutritional intakes of patients at risk of pressure ulcers in the clinical setting

ObjectiveMalnutrition is a risk factor for pressure ulcers. The aim of this study was to describe the energy and protein intakes of hospitalized patients at risk for pressure ulcers and to identify predictors of eating inadequately.MethodsAn observational study was conducted in four wards at two hospitals in Queensland, Australia. Adult patients with restricted mobility were observed for 24 h, and information such as oral intake and observed nutritional practices was collected. A chart audit gathered other demographic characteristics, clinical, anthropometric, and dietary information. t Tests or one-way analysis of variances were used to identify differences in total energy and protein intakes. Univariate and multivariate regression analyses were conducted to determine predictors of eating inadequately (i.e., intake of <75% of estimated energy and protein requirements).ResultsMean energy and protein intakes of the 184 patients were 5917 ± 2956 kJ and 54 ± 28 g, respectively. Estimated energy and protein requirements were calculated for 93 patients. Only 45% (n = 42) and 53% (n = 49) met ≥75% of estimated energy and protein requirements, respectively. In multivariate analysis, patients on the renal ward were 4.1 and 4.6 times more likely to be eating inadequately for energy and protein, respectively (P < 0.05). Patients who consumed any amount of oral nutrition support were 5.1 and 15.5 times more likely be eating adequately for energy and protein, respectively (P < 0.05).ConclusionsRenal patients are more likely to be eating inadequately, although any consumption of oral nutrition support seems to increase likelihood of eating adequately.