High prevalence of potential biases threatens the interpretation of trials in patients with chronic disease

BACKGROUND: The complexity of chronic diseases is a challenge for investigators conducting randomized trials. The causes for this include the often difficult control for confounding, the selection of outcomes from many potentially important outcomes, the risk of missing data with long follow-up and the detection of heterogeneity of treatment effects. Our aim was to assess such aspects of trial design and analysis for four prevalent chronic diseases. METHODS: We included 161 randomized trials on drug and non-drug treatments for chronic obstructive pulmonary disease, type 2 diabetes mellitus, stroke and heart failure, which were included in current Cochrane reviews. We assessed whether these trials defined a single outcome or several primary outcomes, statistically compared baseline characteristics to assess comparability of treatment groups, reported on between-group comparisons, and we also assessed how they handled missing data and whether appropriate methods for subgroups effects were used. RESULTS: We found that only 21% of all chronic disease trials had a single primary outcome, whereas 33% reported one or more primary outcomes. Two of the fifty-one trials that tested for statistical significance of baseline characteristics adjusted the comparison for a characteristic that was significantly different. Of the 161 trials, 10% reported a within-group comparison only; 17% (n = 28) of trials reported how missing data were handled (50% (n = 14) carried forward last values, 27% (n = 8) performed a complete case analysis, 13% (n = 4) used a fixed value imputation and 10% (n = 3) used more advanced methods); and 27% of trials performed a subgroup analysis but only 23% of them (n = 10) reported an interaction test. Drug trials, trials published after wide adoption of the CONSORT (CONsolidated Standards of Reporting Trials) statement (2001 or later) and trials in journals with higher impact factors were more likely to report on some of these aspects of trial design and analysis. CONCLUSION: Our survey showed that an alarmingly large proportion of chronic disease trials do not define a primary outcome, do not use appropriate methods for subgroup analyses, or use naïve methods to handle missing data, if at all. As a consequence, biases are likely to be introduced in many trials on widely prescribed treatments for patients with chronic disease

Change in maternal body mass index is associated with offspring body mass index: a 21-year prospective study

High body-mass index (BMI; defined as 25 kg/m(2) or greater) is associated with increased risk of cancer. To inform public health policy and future research, we estimated the global burden of cancer attributable to high BMI in 2012

Risk of Parkinson's disease after tamoxifen treatment

<p>Abstract</p> <p>Background</p> <p>Women have a reduced risk of developing Parkinson's disease (PD) compared with age-matched men. Neuro-protective effects of estrogen potentially explain this difference. Tamoxifen, commonly used in breast cancer treatment, may interfere with the protective effects of estrogen and increase risk of PD. We compared the rate of PD in Danish breast cancer patients treated with tamoxifen to the rate among those not treated with tamoxifen.</p> <p>Methods</p> <p>A cohort of 15,419 breast cancer patients identified from the Danish Breast Cancer Collaborative Group database was linked to the National Registry of Patients to identify PD diagnoses. Overall risk and rate of PD following identification into the study was compared between patients treated with tamoxifen as adjuvant hormonal therapy and patients not receiving tamoxifen. Time-dependent effects of tamoxifen treatment on PD rate were examined to estimate the likely induction period for tamoxifen.</p> <p>Results</p> <p>In total, 35 cases of PD were identified among the 15,419 breast cancer patients. No overall effect of tamoxifen on rate of PD was observed (HR = 1.3, 95% CI: 0.64-2.5), but a PD hazard ratio of 5.1 (95% CI: 1.0-25) was seen four to six years following initiation of tamoxifen treatment.</p> <p>Conclusions</p> <p>These results provide evidence that the neuro-protective properties of estrogen against PD occurrence may be disrupted by tamoxifen therapy. Tamoxifen treatments may be associated with an increased rate of PD; however these effects act after four years, are of limited duration, and the adverse effect is overwhelmed by the protection against breast recurrence conferred by tamoxifen therapy.</p

American College of Critical Care Medicine Clinical Practice Parameters for Hemodynamic Support of Pediatric and Neonatal Septic Shock

OBJECTIVES: The American College of Critical Care Medicine provided 2002 and 2007 guidelines for hemodynamic support of newborn and pediatric septic shock. Provide the 2014 update of the 2007 American College of Critical Care Medicine “Clinical Guidelines for Hemodynamic Support of Neonates and Children with Septic Shock.” DESIGN: Society of Critical Care Medicine members were identified from general solicitation at Society of Critical Care Medicine Educational and Scientific Symposia (2006–2014). The PubMed/Medline/Embase literature (2006–14) was searched by the Society of Critical Care Medicine librarian using the keywords: sepsis, septicemia, septic shock, endotoxemia, persistent pulmonary hypertension, nitric oxide, extracorporeal membrane oxygenation, and American College of Critical Care Medicine guidelines in the newborn and pediatric age groups. MEASUREMENTS AND MAIN RESULTS: The 2002 and 2007 guidelines were widely disseminated, translated into Spanish and Portuguese, and incorporated into Society of Critical Care Medicine and American Heart Association/Pediatric Advanced Life Support sanctioned recommendations. The review of new literature highlights two tertiary pediatric centers that implemented quality improvement initiatives to improve early septic shock recognition and first-hour compliance to these guidelines. Improved compliance reduced hospital mortality from 4% to 2%. Analysis of Global Sepsis Initiative data in resource rich developed and developing nations further showed improved hospital mortality with compliance to first-hour and stabilization guideline recommendations. CONCLUSIONS: The major new recommendation in the 2014 update is consideration of institution—specific use of 1) a “recognition bundle” containing a trigger tool for rapid identification of patients with septic shock, 2) a “resuscitation and stabilization bundle” to help adherence to best practice principles, and 3) a “performance bundle” to identify and overcome perceived barriers to the pursuit of best practice principles

Atypical cancer pattern in patients with Parkinson's disease.

Among 14,088 patients, with a primary diagnosis of Parkinson's disease during the period 1977-98 identified from the National Register of Patients, 1282 cancers were subsequently recorded in the Danish Cancer Registry, compared with 1464 expected, with a standardised incidence ratio (SIR) of 0.88 (95% confidence interval (CI), 0.8-0.9). Significantly reduced risks were found for smoking-related cancers, for example, cancers of the lung (SIR, 0.38), larynx (0.47) and urinary bladder (0.52), although moderate reductions in risk were also seen for several nonsmoking-related cancers. In contrast, increased risks were seen for malignant melanoma (SIR, 1.95; 95% CI, 1.4-2.6), nonmelanocytic skin cancer (1.25; 1.1-1.4) and breast cancer (1.24; 1.0-1.5). The observed cancer pattern supports the hypothesis that constituents of tobacco smoke inhibit or delay the development of Parkinson's disease, but a low smoking prevalence appears to be only part of the explanation for the decreased cancer incidence. The increased relative risks of melanoma and nonmelanoma skin cancer are not likely to be artefactual, but further investigations of potential mechanisms are warranted

Young people with depression and their experience accessing an enhanced primary care service for youth with emerging mental health problems: a qualitative study

Despite the emergence of mental health problems during adolescence and early adulthood, many young people encounter difficulties accessing appropriate services. In response to this gap, the Australian Government recently established new enhanced primary care services ( headspace ) that target young people with emerging mental health problems. In this study, we examine the experience of young people with depression accessing one of these services, with a focus on understanding how they access the service and the difficulties they encounter in the process

Association of weight misperception with weight loss in a diabetes prevention program

BACKGROUND: Weight misperception may have an impact on perceived risk and susceptibility for chronic diseases. Little has been reported on the long term effects of this misperception in chronic disease interventions, particularly in field of diabetes prevention. The aim of this study was to investigate the relationship between weight misperception and weight loss during a diabetes prevention project conducted in south-east Australia with individuals at moderate to high risk of developing diabetes. METHODS: A total of n=251 at risk individuals provided self-reported weight during recruitment from 2004-2006. Objectively measured weight was assessed at baseline (0-21 days after recruitment), and subsequently at three months and 12 months after the intervention. Differences between self-reported and actual weight status are presented as percentages. Linear regression was used to investigate the relationship between weight misperception and weight loss, adjusting for baseline weight and BMI. RESULTS: Those who had high levels of under-reporting at baseline had greater weight loss at three and 12 months compared with those who under-reported to some degree, and those over-reporting their weight. A significant association was found between weight misperception and weight loss at the three and the 12 month time points. Baseline weight was not associated with weight loss. CONCLUSIONS: Weight misperception should be acknowledged as a factor to be addressed when screening and identifying individuals at risk for diabetes. Screening and giving feedback is important in terms of awareness of participants' actual weight status and may have an effect on program outcomes

Adolescents bullying and young adults body mass index and obesity: a longitudinal study

Objective: To examine whether adolescent males and females who were victims of bullying were at greater risk of a higher body mass index (BMI) and obesity by young adulthood. Design: Secondary analysis of data from a community-based cohort study. Subjects: A sub-sample of 1694 offspring (50% males) who were participants in the Mater-University of Queensland Study of Pregnancy (MUSP), Brisbane, and who provided bullying information at 14 years and physical assessment at 21 years.Main Outcome Measures:BMI and its categories as normal, overweight or obese at 21 years. Results: One in two adolescent males and one in three adolescent females reported that they had been bullied at school by others. We found that adolescent males and females who were bullied were at a significantly greater risk of a higher BMI and obesity by young adulthood. Fourteen-year-old males who were occasionally/often bullied at school had 0.64 (95% confidence interval (CI): 0.02, 1.27) kg m 2 greater mean BMI by 21 years compared with males who were never bullied by 14 years. This mean difference in BMI was 1.52, (95% CI: 0.75, 2.29) kg m 2 for females. Similarly, the odds of being obese were 2.54 (95% CI: 1.58, 4.09) times at 21 years for those males who were bullied occasionally/often compared with adolescent males who were never bullied. For females, this was 2.18 (95% CI: 1.40, 3.39). Overweight adolescents who experienced bullying had the greatest increase in BMI by young adulthood. Adjusting for potential confounding or mediating factors, the associations remain strong for males but are attenuated for females. Conclusions: The findings of this study suggest that both male and female adolescents who were bullied often/sometimes by their peer group at 14 years were at greater risk of higher BMI and obesity by young adulthood