Cardioversion for atrial fibrillations: not better than ventricular rate control

Atrial fibrillation is a frequent cardiac arrhythmia in the elderly, which can be treated either by rate control, or by rhythm control through chemical or electrical cardioversion. Rate control is easily achieved, but leaves the arrhythmia with its inherent risk of heart failure and stroke intact. Although rhythm control is logistically more complex to obtain, it does restore normal sinus rhythm. However, dangerous antiarrhythmics are then needed to maintain this. Recently, two randomised trials showed that rate control is not inferior to rhythm control. Restoration and maintenance of sinus rhythm was accompanied by a higher incidence of death, ventricular arrhythmias, heart failure, stroke and the need for permanent pacemaker implantation. Recurrent atrial fibrillation can be treated optimally by rate control through digitalis, beta-blockers or calcium antagonists, accompanied by oral anticoagulation. Once the sinus rhythm has been restored, oral anticoagulation should be continued.     

Sample size formulae for intervention studies with the cluster as unit of randomization

This paper presents sample size formulae for both continuous and dichotomous endpoints obtained from intervention studies that use the cluster as the unit of randomization. The formulae provide the required number of clusters or the required number of individuals per cluster when the other number is given. The proposed formulae derive from Student's t-test with use of cluster summary measures and a variance that consists of within and between cluster components. Power contours are provided to help in the design of intervention studies that use cluster randomization. Sample size formulae for designs with and without stratification of clusters appear separately.     

The search for better markers for prostate cancer than prostate-specific antigen

Prostate-specific antigen (PSA) is currently the most important biochemical marker for the diagnosis of prostate cancer. Because of the limited specificity of PSA, clinically irrelevant tumours and benign abnormalities are also detected that potentially lead to over-treatment and the accompanying physical and emotional burden for the patient. In addition, PSA is used as an indicator of progression or clinical response after treatment for prostate cancer, but the prognostic value of this marker is limited. Current studies are evaluating a number of alternative markers, such as PSA-related parameters, human kallikrein 2, osteoprotegerin and the gene DD3(PCA3), that may improve the specificity of current PSA-based diagnostics and the prognostic value of PSA.     

Evidence in favour of lifestyle intervention for cancer prevention with special reference to colorectal cancer

Randomized controlled trials are recognized as having the strongest type of study design for generating evidence on prevention of disease. They are, however, the most labor- and time-intensive and costly to conduct. Intervention studies on the recurrence of colorectal adenomas might serve as a model with relevance to the etiology of not only large bowel cancer but also other sites of neoplastic development. The results of intervention studies assessing the effect of calcium, antioxidants and fiber on the recurrence of colorectal adenomas have been conflicting, showing a beneficial effect in some cases but not others. There are methodological issues in intervention trials for colorectal cancer, regarding study subjects, end point, dose, interaction, duration and timing, and compliance, for example. Although relatively few trials have been conducted to investigate the effects of an explicit dietary change on the recurrence of adenoma, results obtained so far have demonstrated that modifying the lifestyle may reduce the risk of chronic diseases including cancer. Furthermore, recent progress in molecular epidemiology has allowed clarification of many of the molecular mechanisms underlying susceptibility. Eventually, it may be possible to target intervention programs to genetically susceptible individuals, including molecular targeting, for the prevention of cancer.     

Electronic mail was not better than postal mail for surveying residents and faculty

OBJECTIVE: To compare response rate, time to response, and data quality of electronic and postal surveys in the setting of postgraduate medical education. STUDY DESIGN AND SETTING: A randomized controlled trial in a university-based internal medicine residency program. We randomized 119 residents and 83 faculty to an electronic versus a postal survey with up to two reminders and measured response rate, time to response, and data quality. RESULTS: For residents, the e-survey resulted in a lower response rate than the postal survey (63.3% versus 79.7%; difference -16.3%, 95% confidence interval (95% CI) -32.3% to -0.4%%; P=.049), but a shorter mean response time, by 3.8 days (95% CI 0.2-7.4; P=.042). For faculty, the e-survey did not result in a significantly lower response rate than the postal survey (85.4% vs. 81.0%; difference 4.4%, 95% CI -11.7 to 20.5%; P=.591), but resulted in a shorter average response time, by 8.4 days (95% CI 4.4 to 12.4; P < 0.001). There were no differences in the quality of data or responses to the survey between the two methods. CONCLUSION: E-surveys were not superior to postal surveys in terms of response rate, but resulted in shorter time to response and equivalent data quality.     

Determinants of health-promoting lifestyle in ambulatory cancer patients

The Health Promotion Model was tested as an explanatory framework for health-promoting lifestyle in a sample of 385 ambulatory cancer patients undergoing treatment in 13 clinical sites in the midwestern United States. The aim of this study was to determine the extent to which cognitive/perceptual and modifying variables identified in the Health Promotion Model explain the occurrence of health-promoting behaviors in adults with cancer. A secondary aim was to determine the potential of illness-specific cognitive/perceptual and modifying variables for further explaining the occurrence of health-promoting behaviors in adults with cancer. Multiple regression analyses revealed that 23.5% of the variance in health-promoting lifestyle was explained by the model cognitive/perceptual variables definition of health, perceived health status and perceived control of health and the modifying variables education, income, age and employment. When illness-specific variables were included in the analysis, initial reaction to the diagnosis of cancer was found to be a significant contributor to the regression. Study results support the importance of both general health-related and cancer-specific cognitive/perceptual factors in explaining the occurrence of health-enhancing behaviors among ambulatory cancer patients; these factors may therefore be suitable targets for interventions to encourage adoption of healthy lifestyles.     

Palliation in patients with metastatic breast cancer often better with antitumour treatment than with only symptomatic treatment

Two women, aged 57 and 55 years, with metastatic breast cancer were admitted for uncontrolled pain due to bone metastases. Despite the fact that progressive disease was evident, a change in antitumour therapy had not been recommended. The pain control was optimised in both patients. In one patient, palliative chemotherapy was installed, combined with trastuzumab because of HER2/neu overexpression. She was still alive after one and a half year of treatment. The other patient could not adjust mentally to the fact that her palliative therapy was changed to antitumour therapy; she died one month later. It is important to be aware of the various kinds of therapy in metastatic breast cancer because palliative treatment is more than just symptomatic treatment. Systemic antitumour therapy includes hormone therapy, chemotherapy and targeted therapy. Furthermore, in patients with bone metastases, radiotherapy combined with bisphosphonates results in pain relief and can reduce skeletal complications. Because of the ensuing complexity of the treatment of metastatic breast cancer, these patients should be regularly managed by a breast-cancer care team in order to improve the quality of care.     

Noncompliance in lifestyle intervention studies: the instrumental variable method provides insight into the bias

ObjectiveIn lifestyle intervention trials, participants of the control group often change their behavior despite the request to maintain their usual lifestyle pattern. These changes in the control group and changes in addition to the intended in the intervention group can lead to undesirable confounding effects.Study Design and SettingWe address several considerations for study design to prevent noncompliance or minimize its effects. Furthermore, we demonstrate how the instrumental variable method can give insight into the extent of bias introduced by noncompliance in randomized trials, within the context of the Sex Hormones and Physical Exercise study.ResultsNoncompliance can be prevented by measures taken in the design phase of a study, for example, limited duration of the study, clear recommendations, power calculation, intensity of the intervention, involvement of the control group, waiting-list control group, and single-consent design nested within an observational study. When nevertheless noncompliance does occur, the instrumental variable method estimates the intervention effect of treatment among the compliers.ConclusionNoncompliance can seriously affect validity of lifestyle trial results. Its occurrence should be prevented by taking measures during the design phase of a study. The instrumental variable method can give insight into confounding by noncompliance in randomized trials.     

Dietary fiber and cancer: a supplement for intervention studies

Dietary fiber is one of several variables being considered in the study of the relationship between diet and cancer. Intervention trials in which dietary fiber is increased are the most direct way of assessing the possible role of fiber in this disease. Two dietary snack products have been developed for use in a fiber intervention study: the high-fiber snack (HFS), which supplies 23 g of dietary fiber per day (mostly from wheat bran) and the low-fiber product (LFS), which provides 3.5 g. Over a 12-week period, 28 volunteers consumed the HFS for 6 weeks and the LFS for 6 weeks. Compliance, as assessed by reports, through recovery of a riboflavin marker in the urine and fecal fiber analysis, was good. The only adverse effects reported were mild abdominal discomfort and gas. Serum ferritin and calcium decreased in some subjects, indicating a need to supplement the products with these essential minerals. Consumption of the snacks did not affect total energy intake or the intake of the nutrients monitored.     

Dietary fiber and cancer: A supplement for intervention studies

Dietary fiber is one of several variables being considered in the study of the relationship between diet and cancer. Intervention trials in which dietary fiber is increased are the most direct way of assessing the possible role of fiber in this disease. Two dietary snack products have been developed for use in a fiber intervention study: the high‐fiber snack (HFS), which supplies 23 g of dietary fiber per day (mostly from wheat bran) and the low‐fiber product (LFS), which provides 3.5 g. Over a 12‐week period, 28 volunteers consumed the HFS for 6 weeks and the LFS for 6 weeks. Compliance, as assessed by reports, through recovery of a riboflavin marker in the urine and fecal fiber analysis, was good. The only adverse effects reported were mild abdominal discomfort and gas. Serum ferritin and calcium decreased in some subjects, indicating a need to supplement the products with these essential minerals. Consumption of the snacks did not affect total energy intake or the intake of the nutrients monitored.     

Adiposity in adolescents: change in actual BMI works better than change in BMI z score for longitudinal studies

PURPOSE: Longitudinal epidemiologic studies often relate adiposity changes to suspected causal factors. In growing adolescents, this becomes complicated. Many investigators use within-child change in body mass index (BMI) z scores (Delta z) from sex- and age-specific BMI charts developed by the Centers for Disease Control and Prevention (CDC). These charts, derived from cross-sectional data, may not represent BMI growth patterns of real children. Furthermore, because cross-sectional BMIs are not Gaussian, these z scores are from month-specific transformed distributions, with possible unintended consequences when used longitudinally. Alternatively, we can directly analyze BMI change (Delta BMI). We compare these two widely used measures of change in adiposity. METHODS AND RESULTS: With real adolescent data, we show that annual Delta BMIs have nonlinear peaks that are inconsistent with the CDC curves. We also show that a specified Delta z represents a broad range of adiposity changes for children measured at the same two ages. To see how this affects power, we performed simulation studies confirming that analyzing Delta BMIs in models with hypothesized factors is more powerful than analyzing Delta zs. CONCLUSIONS: In longitudinal studies of adolescent adiposity, investigators should be encouraged to analyze Delta BMI rather than Delta z because analyses using BMI are more powerful and findings presented in BMI units are more interpretable.     

A combined comorbidity score predicted mortality in elderly patients better than existing scores

Objective

To develop and validate a single numerical comorbidity score for predicting short- and long-term mortality, by combining conditions in the Charlson and Elixhauser measures.

Study Design and Setting

In a cohort of 120,679 Pennsylvania Medicare enrollees with drug coverage through a pharmacy assistance program, we developed a single numerical comorbidity score for predicting 1-year mortality, by combining the conditions in the Charlson and Elixhauser measures. We externally validated the combined score in a cohort of New Jersey Medicare enrollees, by comparing its performance to that of both component scores in predicting 1-year mortality, as well as 180-, 90-, and 30-day mortality.

Results

C-statistics from logistic regression models including the combined score were higher than corresponding c-statistics from models including either the Romano implementation of the Charlson Index or the single numerical version of the Elixhauser system; c-statistics were 0.860 (95% confidence interval [CI]: 0.854, 0.866), 0.839 (95% CI: 0.836, 0.849), and 0.836 (95% CI: 0.834, 0.847), respectively, for the 30-day mortality outcome. The combined comorbidity score also yielded positive values for two recently proposed measures of reclassification.

Conclusion

In similar populations and data settings, the combined score may offer improvements in comorbidity summarization over existing scores.     

Effect of a grade 6 HIV risk reduction intervention four years later among students who were and were not enrolled in the study trial

PurposeTo assess the long-term impact of HIV-prevention interventions delivered to youth before sexual initiation and the effects of interventions delivered in nonstudy settings.MethodsA five-group comparison of HIV knowledge, and condom-use skills, self-efficacy, intentions, and practice among 1,997 grade 10 students attending one of the eight government high schools in Nassau, The Bahamas. Group 1 received an HIV-prevention intervention, Focus on Youth in the Caribbean (FOYC), in grade 6 as part of a randomized trial; group 2 received FOYC as part of the regular school curriculum but outside of the trial; group 3 received the control condition as part of the trial; group 4 received the control condition as part of the school curriculum but outside of the trial; and individuals in group 5 (naive controls) were not enrolled in a school receiving FOYC or the control conditon and did not participate in the trial.ResultsFOYC youth compared with the control youth and naive controls had higher HIV knowledge, condom-use skills, and self-efficacy 4 years later. By subgroups, group 1 demonstrated higher HIV/AIDS knowledge than all groups except group 2, higher condom skills than all groups, and higher condom self-efficacy than Naive Controls. Youth in group 2 demonstrated higher HIV knowledge than youth in groups 3–5. Behavioral effects were not found.ConclusionsFOYC delivered to grade 6 students continued to have protective effects 4 years later. Positive effects are present among youth who received FOYC as part of the school curriculum but were not enrolled in the trial.     

Cost effectiveness of an internet-delivered lifestyle intervention in primary care patients with high cardiovascular risk

ObjectiveTo assess the cost-effectiveness of an online adaptation of the diabetes prevention program (ODPP) lifestyle intervention.MethodsODPP was a before–after evaluation of a weight loss intervention comprising 16 weekly and 8 monthly lessons, incorporating behavioral tools and regular, brief, web-based individualized counseling in an overweight/obese cohort (mean age 52, 76% female, 92% white, 28% with diabetes). A Markov model was developed to estimate ODPP cost effectiveness compared with usual care (UC) to reduce metabolic risk over 10 years. Intervention costs and weight change outcomes were obtained from the study; other model parameters were based on published reports. In the model, diabetes risk was a function of weight change with and without the intervention.ResultsCompared to UC, the ODPP in our cohort cost $14,351 and $29,331 per quality-adjusted life-year (QALY) gained from the health care system and societal perspectives, respectively. In a hypothetical cohort without diabetes, the ODPP cost $7777 and $18,263 per QALY gained, respectively. Results were robust in sensitivity analyses, but enrolling cohorts with lower annual risk of developing diabetes (≤ 1.8%), enrolling fewer participants (≤ 15), or increasing the hourly cost (≥$91.20) or annual per-participant time (≥ 1.45 h) required for technical support could increase ODPP cost to >$20,000 per QALY gained. In probabilistic sensitivity analyses, ODPP was cost-effective in 20–58% of model iterations using an acceptability threshold of $20,000, 73–92% at $50,000, and 95–99% at $100,000 per QALY gained.ConclusionsThe ODPP may offer an economical approach to combating overweight and obesity.     

生活方式干预对代谢综合征患者动脉血管早期病变检测指标的影响

目的探讨生活方式干预对非糖尿病代谢综合征（MS）患者动脉血管早期病变检测指标的影响。方法入选非糖尿病MS患者87例,随机分为干预组（47例）和对照组（40例）。干预组实施健康管理,包括健康教育、合理膳食、规律运动、纠正不良习惯等生活方式干预。对照组未行健康管理干预。随访9个月,所有患者随访前后均进行体重指数（BMI）、腰围（WC）、收缩压（SBP）、舒张压（DBP）、三酰甘油（TG）、总胆固醇（TC）、高密度脂蛋白胆固醇（HDL—C）、低密度脂蛋白胆固醇（LDL—C）、空腹血糖（FPG）、糖化血红蛋白（HbAlc）、空腹胰岛素（FINS）、胰岛素抵抗指数（HOMA—IR）、高敏C反应蛋白（hs—CRP）、颈动脉内膜中层厚度（IMT）、臂踝脉搏波速度（baPWV）、踝臂指数（ABI）的测定。结果（1）干预组BMI、WC、SBP、TG、FIDL—C、FPG、HbAlc、FINS、HOMA—IR和hs—CRP在干预后6个月、9个月与干预前相比均显著改善,差异有统计学意义（P〈0．05）,并且HDL—C、FPG、HbAlc、FINS、HOMA-IR和hs—CRP在干预后9个月与干预后6个月相比又进一步改善,差异有统计学意义（P〈0．05）。与对照组相比,干预后9个月干预组BMI、WC、HDL—C、FPG、HbAlc、FINS、HOMA—IR和hs—CRP有改善,差异有统计学意义（P〈0．05）。（2）干预组baPWV和ABI在干预后6个月、干预后9个月与干预前相比有改善,差异有统计学意义（F值分别为：32．98,45．81;P〈0．05）。与对照组相比,干预后9个月干预组baPWV和ABI有改善,差异有统计学意义（t值分别为：-5．62,5．99;P〈0．05）。（3）干预组baPWV在干预后9个月的异常率为44．68％,与干预前（68．09％）相比有改善,差异有统计学意义（X。=5．23,P〈0．05）。（4）baPWV与hs—CRP、HOMA—IR相关（OR值分别为：0．436,0．565）;ABI与hs—CRP、HOMA—IR相关（OR值分别为：0．543,0．502）。结论对MS患者实施健康管理,加强生活方式的调控,能明显改善非糖尿病MS患者的胰岛素抵抗,调节糖脂代谢,减轻炎症反应,并在一定程度上能延缓动脉粥样硬化的进程。