Time Trends in Survival Following First Hemorrhagic or Ischemic Stroke Between 1991 and 2015 in the Rotterdam Study

Background and Purpose- The introduction of stroke units and the implementation of evidence-based interventions have been a breakthrough in the management

Potential impact of missing outcome data on treatment effects in systematic reviews: imputation study

AbstractObjective To assess the risk of bias associated with missing outcome data in systematic reviews. Design Imputation study. Setting Systematic reviews. Population 100 systematic reviews that included a group level meta-analysis with a statistically significant effect on a patient important dichotomous efficacy outcome. Main outcome measures Median percentage change in the relative effect estimate when applying each of the following assumption (four commonly discussed but implausible assumptions (best case scenario, none had the event, all had the event, and worst case scenario) and four plausible assumptions for missing data based on the informative missingness odds ratio (IMOR) approach (IMOR 1.5 (least stringent), IMOR 2, IMOR 3, IMOR 5 (most stringent)); percentage of meta-analyses that crossed the threshold of the null effect for each method; and percentage of meta-analyses that qualitatively changed direction of effect for each method. Sensitivity analyses based on the eight different methods of handling missing data were conducted. Results 100 systematic reviews with 653 randomised controlled trials were included. When applying the implausible but commonly discussed assumptions, the median change in the relative effect estimate varied from 0% to 30.4%. The percentage of meta-analyses crossing the threshold of the null effect varied from 1% (best case scenario) to 60% (worst case scenario), and 26% changed direction with the worst case scenario. When applying the plausible assumptions, the median percentage change in relative effect estimate varied from 1.4% to 7.0%. The percentage of meta-analyses crossing the threshold of the null effect varied from 6% (IMOR 1.5) to 22% (IMOR 5) of meta-analyses, and 2% changed direction with the most stringent (IMOR 5). Conclusion Even when applying plausible assumptions to the outcomes of participants with definite missing data, the average change in pooled relative effect estimate is substantive, and almost a quarter (22%) of meta-analyses crossed the threshold of the null effect. Systematic review authors should present the potential impact of missing outcome data on their effect estimates and use this to inform their overall GRADE (grading of recommendations assessment, development, and evaluation) ratings of risk of bias and their interpretation of the results

Meta-Analyses Proved Inconsistent in How Missing Data Were Handled Across Their Included Primary Trials: A Methodological Survey

Background: How systematic review authors address missing data among eligible primary studies remains uncertain. Objective: To assess whether systematic review authors are consistent in the way they handle missing data, both across trials included in the same meta-analysis, and with their reported methods. Methods: We first identified 100 eligible systematic reviews that included a statistically significant meta-analysis of a patient-important dichotomous efficacy outcome. Then, we successfully retrieved 638 of the 653 trials included in these systematic reviews' meta-analyses. From each trial report, we extracted statistical data used in the analysis of the outcome of interest to compare with the data used in the meta-analysis. First, we used these comparisons to classify the "analytical method actually used" for handling missing data by the systematic review authors for each included trial. Second, we assessed whether systematic reviews explicitly reported their analytical method of handling missing data. Third, we calculated the proportion of systematic reviews that were consistent in their "analytical method actually used" across trials included in the same meta-analysis. Fourth, among systematic reviews that were consistent in the "analytical method actually used" across trials and explicitly reported on a method for handling missing data, we assessed whether the "analytical method actually used" and the reported methods were consistent. Results: We were unable to determine the "analytical method reviews actually used" for handling missing outcome data among 397 trials. Among the remaining 241, systematic review authors most commonly conducted "complete case analysis" (n=128, 53%) or assumed "none of the participants with missing data had the event of interest" (n=58, 24%). Only eight of 100 systematic reviews were consistent in their approach to handling missing data across included trials, but none of these reported methods for handling missing data. Among seven reviews that did explicitly report their analytical method of handling missing data, only one was consistent in their approach across included trials (using complete case analysis), and their approach was inconsistent with their reported methods (assumed all participants with missing data had the event). Conclusion: The majority of systematic review authors were inconsistent in their approach towards reporting and handling missing outcome data across eligible primary trials, and most did not explicitly report their methods to handle missing data. Systematic review authors should clearly identify missing outcome data among their eligible trials, specify an approach for handling missing data in their analyses, and apply their approach consistently across all primary trials

Using patient values and preferences to inform the importance of health outcomes in practice guideline development following the GRADE approach

Q2Q1Artículo de investigación1-10Background: There are diverse opinions and confusion about defining and including patient values and preferences (i.e. the importance people place on the health outcomes) in the guideline development processes. This article aims to provide an overview of a process for systematically incorporating values and preferences in guideline development. Methods: In 2013 and 2014, we followed the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach to adopt, adapt and develop 226 recommendations in 22 guidelines for the Ministry of Health of the Kingdom of Saudi Arabia. To collect context-specific values and preferences for each recommendation, we performed systematic reviews, asked clinical experts to provide feedback according to their clinical experience, and consulted patient representatives. Results: We found several types of studies addressing the importance of outcomes, including those reporting utilities, non-utility measures of health states based on structured questionnaires or scales, and qualitative studies. Guideline panels used the relative importance of outcomes based on values and preferences to weigh the balance of desirable and undesirable consequences of alternative intervention options. However, we found few studies addressing local values and preferences. Conclusions: Currently there are different but no firmly established processes for integrating patient values and preferences in healthcare decision-making of practice guideline development. With GRADE Evidence-to-Decision (EtD) frameworks, we provide an empirical strategy to find and incorporate values and preferences in guidelines by performing systematic reviews and eliciting information from guideline panel members and patient representatives. However, more research and practical guidance are needed on how to search for relevant studies and grey literature, assess the certainty of this evidence, and best summarize and present the findings

Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts Consortium.

Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence

Trends in the incidence of dementia: design and methods in the Alzheimer Cohorts Consortium

Several studies have reported a decline in incidence of dementia which may have large implications for the projected burden of disease, and provide important guidance to preventive efforts. However, reports are conflicting or inconclusive with regard to the impact of gender and education with underlying causes of a presumed declining trend remaining largely unidentified. The Alzheimer Cohorts Consortium aggregates data from nine international population-based cohorts to determine changes in the incidence of dementia since 1990. We will employ Poisson regression models to calculate incidence rates in each cohort and Cox proportional hazard regression to compare 5-year cumulative hazards across study-specific epochs. Finally, we will meta-analyse changes per decade across cohorts, and repeat all analysis stratified by sex, education and APOE genotype. In all cohorts combined, there are data on almost 69,000 people at risk of dementia with the range of follow-up years between 2 and 27. The average age at baseline is similar across cohorts ranging between 72 and 77. Uniting a wide range of disease-specific and methodological expertise in research teams, the first analyses within the Alzheimer Cohorts Consortium are underway to tackle outstanding challenges in the assessment of time-trends in dementia occurrence

Twenty-seven-year time trends in dementia incidence in Europe and the United States: The Alzheimer Cohorts Consortium

OBJECTIVE: To determine changes in the incidence of dementia between 1988 and 2015. METHODS: This analysis was performed in aggregated data from individuals >65 years of age in 7 population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause dementia, and then defined nonoverlapping 5-year epochs within each study to determine trends in incidence. Estimates of change per 10-year interval were pooled and results are presented combined and stratified by sex. RESULTS: Of 49,202 individuals, 4,253 (8.6%) developed dementia. The incidence rate of dementia increased with age, similarly for women and men, ranging from about 4 per 1,000 person-years in individuals aged 65-69 years to 65 per 1,000 person-years for those aged 85-89 years. The incidence rate of dementia declined by 13% per calendar decade (95% confidence interval [CI], 7%-19%), consistently across studies, and somewhat more pronouncedly in men than in women (24% [95% CI 14%-32%] vs 8% [0%-15%]). CONCLUSION: The incidence rate of dementia in Europe and North America has declined by 13% per decade over the past 25 years, consistently across studies. Incidence is similar for men and women, although declines were somewhat more profound in men. These observations call for sustained efforts to finding the causes for this decline, as well as determining their validity in geographically and ethnically diverse populations

Dementia Risk Following Ischemic Stroke: A Systematic Review and Meta-Analysis of Factors Collected at Time of Stroke Diagnosis

Background: The majority of stroke cases are ischemic in origin and ischemic stroke survivors represent a high-risk population for progression to dementia. Objective: To determine incidence rates and predictors of dementia after ischemic stroke. Methods: A systematic review and meta-analysis compliant with Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA). Results: 5,843 studies were screened for title and abstract. 292 eligible studies were screened for full text. A total of 22 studies met the inclusion criteria and were included, representing 55,929 ischemic stroke survivors. Cumulative incidence of dementia after stroke was 20% at 5 years, 30% at 15 years, and 48% at 25 years of follow-up. Dementia incidence rates were 1.5 times higher among patients with recurrent ischemic stroke compared to patients with first-time stroke. Predictors of dementia after ischemic stroke included female gender (OR 1.2, 95% CI (1.1, 1.4)), hypertension (1.4, (1.1, 2.0)), diabetes mellitus (1.6, (1.3, 2.1)), atrial fibrillation (1.9, (1.2, 3.0)), previous stroke (2.0, (1.6, 2.6)), presence of stroke lesion in dominant hemisphere (2.4, (1.3, 4.5)), brain stem or cerebellum (OR 0.5, (0.3, 0.9)) or frontal lobe (3.7, (1.2, 12.0)), presence of aphasia (OR 7.9, (2.4, 26.0)), dysphasia (5.8, (3.0, 11.3)), gait impairment (1.7, (1.1, 2.7)), presence of white matter hyperintensities (3.2, (2.0, 5.3)), and medial temporal lobe atrophy (3.9, (1.9, 8.3)). Conclusion: Factors routinely collected for stroke patients are a useful resource for monitoring dementia progression in this population. In the present meta-analysis, cardiovascular factors, stroke location, stroke-related disability and chronic brain changes were predictors of dementia after ischemic stroke

Clinical epidemiology of hepatocellular carcinoma among people with hepatitis B or hepatitis C infection

Background: Hepatitis B virus (HBV) and hepatitis C virus (HCV) infections are the major causes of hepatocellular carcinoma (HCC). Improved HBV and HCV antiviral therapy may have impacted the burden, the individual risk and survival following HCC. Aims: This thesis aimed to evaluate 1) Trends in incidence; and 2) All-cause survival following HCC in people with HBV or HCV notification; 3) Determinants of HCC survival in patients with untreated HCV in the pre-DAA era; and 4) Risk of HCC occurrence and recurrence following HCV antiviral sustained virological response (SVR, cure). Methods: In chapters two and three, population-level data on HBV and HCV notifications in NSW (1993-2012) were linked to the NSW hospitalization database (2000-2014), NSW cancer registry (2000-2009) and NSW death registry. In chapter four, patient-level data was obtained through a prospective cohort of patients diagnosed with HCV-related HCC at a national level centre in Egypt (2013-2016). In chapter five, study-level data was obtained through a systematic review, meta-analysis and meta-regression analyses of HCC occurrence and recurrence following HCV therapy (2000-2017).Key findings: 1) Individual-level risk of HBV-related HCC declined and HCV-related HCC risk did not change; 2) The population-level burden of HBV-HCC stabilized and HCV-HCC burden increased; 3) All-cause survival following HBV-HCC improved; while HCV-HCC survival did not improve; 4) Child-Pugh score was a key determinant of survival, even following adjustment for HCC stage and management; 5) In patients with HCV-related cirrhosis, SVR was associated with reduced risk of HCC occurrence; 6) In patients who received curative HCC treatment, SVR was associated with reduced risk of HCC recurrence and; 7) Direct-acting antiviral (DAA) and interferon (IFN)-based cure had a similar impact on HCC occurrence or recurrence risk. Conclusion: HBV-related HCC burden has declined in NSW, suggesting an impact of more effective antiviral therapy over the study period and earlier HCC diagnosis. In contrast, the burden of HCV-HCC has escalated in the pre-DAA era, suggesting no impact of IFN-based therapy at the population level. There is no evidence to support higher risk of HCC occurrence or recurrence following HCV treatment with DAA therapy. HCV cure is associated with reduced risk of HCC regardless of type of HCV treatment