Individual-level Data Meta-analysis Research Articles

Antihypertensive drug effects on long-term blood pressure: an individual-level data meta-analysis of randomised clinical trials

ObjectiveEvidence from randomised trials of pharmacological treatments on long-term blood pressure (BP) reduction is limited. We investigated the antihypertensive drug effects on BP over time and across different participant characteristics.MethodsWe...

Long-term Natural History of Atrophy in Eyes with Choroideremia—A Systematic Review and Meta-analysis of Individual-Level Data

To conduct a systematic review and meta-analysis of the natural history of atrophy secondary to choroideremia (CHM). A sensitive and reliable anatomic measure to monitor disease progression is needed in treatment trials for CHM. However, the long-term natural history of the residual retinal pigment epithelium (RPE) is unclear, with reported RPE area decline rates varying widely among patients. We searched in 7 literature databases up through July 17, 2019, to identify studies that assessed the residual RPE area in untreated eyes with CHM using fundus autofluorescence (FAF). We sought individual-eye data and investigated the RPE decline pattern using 3 models: the area linear model (ALM), radius linear model (RLM), and area exponential model (AEM), in which the area, radius, and log-transformed area of RPE change linearly with time, respectively. To account for different eyes' entry times into the studies, we added a horizontal translation factor to each dataset. The RPE decline rate was estimated using a 2-stage random-effects meta-analysis. We assessed the risk of bias using the Quality In Prognosis Studies tool. Of 807 articles screened, we included 9 articles containing cross-sectional data (257 eyes) from 6 studies and longitudinal data (229 visits from 68 eyes) from 5 studies. The residual RPE area followed a trend of exponential decay as a function of patient age. After the introduction of horizontal translation factors to longitudinal datasets of individual eyes, the datasets fit along a straight line in the AEM over nearly 60 years (r2= 0.997). The decline rate of log-transformed RPE area was 0.050 (95% confidence interval, 0.046-0.055) log(mm2)/year and was independent of the baseline RPE area (r= -0.18; P= 0.15) and age (r= 0.06; P= 0.63). In contrast, the decline rates of the area and effective radius of residual RPE strongly correlated with the baseline RPE area (r= 0.90 and 0.61, respectively; P < 0.001). The loss of residual RPE area in untreated eyes with CHM follows the AEM over approximately 60 years. Log-transformed residual RPE area measured by FAF can serve as an anatomic endpoint to monitor CHM.

Serum potassium and adverse outcomes across the range of kidney function: a CKD Prognosis Consortium meta-analysis.

Both hypo- and hyperkalaemia can have immediate deleterious physiological effects, and less is known about long-term risks. The objective was to determine the risks of all-cause mortality, cardiovascular mortality, and end-stage renal disease associated with potassium levels across the range of kidney function and evaluate for consistency across cohorts in a global consortium. We performed an individual-level data meta-analysis of 27 international cohorts [10 general population, 7 high cardiovascular risk, and 10 chronic kidney disease (CKD)] in the CKD Prognosis Consortium. We used Cox regression followed by random-effects meta-analysis to assess the relationship between baseline potassium and adverse outcomes, adjusted for demographic and clinical characteristics, overall and across strata of estimated glomerular filtration rate (eGFR) and albuminuria. We included 1217986 participants followed up for a mean of 6.9 years. The average age was 55 ± 16 years, average eGFR was 83 ± 23 mL/min/1.73 m2, and 17% had moderate- to-severe increased albuminuria levels. The mean baseline potassium was 4.2 ± 0.4 mmol/L. The risk of serum potassium of >5.5 mmol/L was related to lower eGFR and higher albuminuria. The risk relationship between potassium levels and adverse outcomes was U-shaped, with the lowest risk at serum potassium of 4-4.5 mmol/L. Compared with a reference of 4.2 mmol/L, the adjusted hazard ratio for all-cause mortality was 1.22 [95% confidence interval (CI) 1.15-1.29] at 5.5 mmol/L and 1.49 (95% CI 1.26-1.76) at 3.0 mmol/L. Risks were similar by eGFR, albuminuria, renin-angiotensin-aldosterone system inhibitor use, and across cohorts. Outpatient potassium levels both above and below the normal range are consistently associated with adverse outcomes, with similar risk relationships across eGFR and albuminuria.

Positron emission tomography (PET) for prediction of glioma histology: protocol for an individual-level data meta-analysis of test performance

IntroductionGliomas, the most commonly diagnosed primary brain tumours, are associated with varied survivals based, in part, on their histological subtype. Therefore, accurate pretreatment tumour grading is essential for patient care...

The Development of the Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS): A Large-Scale Data Sharing Initiative

IntroductionIn 2008, the Ministry of Health, Welfare and Sport commissioned the National Care for the Elderly Programme. While numerous research projects in older persons’ health care were to be conducted under this national agenda, the Programme further advocated the development of The Older Persons and Informal Caregivers Survey Minimum DataSet (TOPICS-MDS) which would be integrated into all funded research protocols. In this context, we describe TOPICS data sharing initiative (www.topics-mds.eu).Materials and MethodsA working group drafted TOPICS-MDS prototype, which was subsequently approved by a multidisciplinary panel. Using instruments validated for older populations, information was collected on demographics, morbidity, quality of life, functional limitations, mental health, social functioning and health service utilisation. For informal caregivers, information was collected on demographics, hours of informal care and quality of life (including subjective care-related burden).ResultsBetween 2010 and 2013, a total of 41 research projects contributed data to TOPICS-MDS, resulting in preliminary data available for 32,310 older persons and 3,940 informal caregivers. The majority of studies sampled were from primary care settings and inclusion criteria differed across studies.DiscussionTOPICS-MDS is a public data repository which contains essential data to better understand health challenges experienced by older persons and informal caregivers. Such findings are relevant for countries where increasing health-related expenditure has necessitated the evaluation of contemporary health care delivery. Although open sharing of data can be difficult to achieve in practice, proactively addressing issues of data protection, conflicting data analysis requests and funding limitations during TOPICS-MDS developmental phase has fostered a data sharing culture. To date, TOPICS-MDS has been successfully incorporated into 41 research projects, thus supporting the feasibility of constructing a large (>30,000 observations), standardised dataset pooled from various study protocols with different sampling frameworks. This unique implementation strategy improves efficiency and facilitates individual-level data meta-analysis.

Job Strain and Health-Related Lifestyle: Findings From an Individual-Participant Meta-Analysis of 118 000 Working Adults

We examined the associations of job strain, an indicator of work-related stress, with overall unhealthy and healthy lifestyles. We conducted a meta-analysis of individual-level data from 11 European studies (cross-sectional data: n = 118,701; longitudinal data: n = 43,971). We analyzed job strain as a set of binary (job strain vs no job strain) and categorical (high job strain, active job, passive job, and low job strain) variables. Factors used to define healthy and unhealthy lifestyles were body mass index, smoking, alcohol intake, and leisure-time physical activity. Individuals with job strain were more likely than those with no job strain to have 4 unhealthy lifestyle factors (odds ratio [OR] = 1.25; 95% confidence interval [CI] = 1.12, 1.39) and less likely to have 4 healthy lifestyle factors (OR = 0.89; 95% CI = 0.80, 0.99). The odds of adopting a healthy lifestyle during study follow-up were lower among individuals with high job strain than among those with low job strain (OR = 0.88; 95% CI = 0.81, 0.96). Work-related stress is associated with unhealthy lifestyles and the absence of stress is associated with healthy lifestyles, but longitudinal analyses suggest no straightforward cause-effect relationship between work-related stress and lifestyle.

Prediction of childhood obesity by infancy weight gain: an individual‐level meta‐analysis

To assess the predictive ability of infant weight gain on subsequent obesity we performed a meta-analysis of individual-level data on 47,661 participants from 10 cohort studies from the UK, France, Finland, Sweden, the US and Seychelles. For each individual, weight SD scores at birth and age 1 year were calculated using the same external reference (British 1990). Childhood obesity was defined by International Obesity Task Force criteria. Each +1 unit increase in weight SD scores between 0 and 1 year conferred a twofold higher risk of childhood obesity (odds ratio = 1.97 [95% confidence interval (CI) 1.83, 2.12]), and a 23% higher risk of adult obesity (odds ratio = 1.23 [1.16, 1.30]), adjusted for sex, age and birthweight. There was little heterogeneity between studies. A risk score for childhood obesity comprising weight gain 0-1 year, mother's body mass index, birthweight and sex was generated in a random 50% selection of individuals from general population cohorts with available information (n = 8236); this score showed moderate predictive ability in the remaining 50% sample (area under receiving operating curve = 77% [95% CI 74, 80%]). A separate risk score for childhood overweight showed similar predictive ability (area under receiving operating curve = 76% [73, 79%]). In conclusion, infant weight gain showed a consistent positive association with subsequent obesity. A risk score combining birthweight and infant weight gain (or simply infant weight), together with mother's body mass index and sex may allow early stratification of infants at risk of childhood obesity.

Gene-Environment Interactions

JAMA Interaction Between the Serotonin Transporter Gene (5-HTTLPR), Stressful Life Events, and Risk of Depression: A Meta-analysis Neil Risch, PhD; Richard Herrell, PhD; Thomas Lehner, PhD; Kung-Yee Liang, PhD; Lindon Eaves, PhD; Josephine Hoh, PhD; Andrea Griem, BS; Marika Kovacs, PhD; Jurg Ott, PhD; Kathleen Ries Merikangas, PhD Context: Substantial resources are being devoted to identify candidate genes for complex mental and behavioral disorders through inclusion of environmental exposures following the report of an interaction between the serotonin transporter linked polymorphic region ( 5-HTTLPR ) and stressful life events on an increased risk of major depression. Objective: To conduct a meta-analysis of the interaction between the serotonin transporter gene and stressful life events on depression using both published data and individual-level original data. Data Sources: Search of PubMed, EMBASE, and PsycINFO databases through March 2009 yielded 26 studies of which 14 met criteria for the meta-analysis. Study Selection: Criteria for studies for the meta-analyses included published data on the association between 5-HTTLPR genotype (SS, SL, or LL), number of stressful life events (0, 1, 2, 3) or equivalent, and a categorical measure of depression defined by the Diagnostic and Statistical Manual of Mental Disorders (Fourth Edition) or the International Statistical Classification of Diseases, 10th Revision (ICD-10) or use of a cut point to define depression from standardized rating scales. To maximize our ability to use a common framework for variable definition, we also requested original data from all studies published prior to 2008 that met inclusion criteria. Of the 14 studies included in the meta-analysis, 10 were also included in a second sex-specific meta-analysis of original individual-level data. Data Extraction: Logistic regression was used to estimate the effects of the number of short alleles at 5-HTTLPR , the number of stressful life events, and their interaction on depression. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated separately for each study and then weighted averages of the individual estimates were obtained using random-effects meta-analysis. Both sex-combined and sex-specific meta-analyses were conducted. Of a total of 14 250 participants, 1769 were classified as having depression; 12 481 as not having depression. Results: In the meta-analysis of published data, the number of stressful life events was significantly associated with depression (OR, 1.41; 95% CI,1.25-1.57). No association was found between 5-HTTLPR genotype and depression in any of the individual studies nor in the weighted average (OR, 1.05; 95% CI, 0.98-1.13) and no interaction effect between genotype and stressful life events on depression was observed (OR, 1.01; 95% CI, 0.94-1.10). Comparable results were found in the sex-specific meta-analysis of individual-level data. Conclusion: This meta-analysis yielded no evidence that the serotonin transporter genotype alone or in interaction with stressful life events is associated with an elevated risk of depression in men alone, women alone, or in both sexes combined. JAMA. 2009;301(23):2462-2471..

Large‐scale analysis of association between GDF5 and FRZB variants and osteoarthritis of the hip, knee, and hand

GDF5 and FRZB have been proposed as genetic loci conferring susceptibility to osteoarthritis (OA); however, the results of several studies investigating the association of OA with the rs143383 polymorphism of the GDF5 gene or the rs7775 and rs288326 polymorphisms of the FRZB gene have been conflicting or inconclusive. To examine these associations, we performed a large-scale meta-analysis of individual-level data. Fourteen teams contributed data on polymorphisms and knee, hip, and hand OA. For rs143383, the total number of cases and controls, respectively, was 5,789 and 7,850 for hip OA, 5,085 and 8,135 for knee OA, and 4,040 and 4,792 for hand OA. For rs7775, the respective sample sizes were 4,352 and 10,843 for hip OA, 3,545 and 6,085 for knee OA, and 4,010 and 5,151 for hand OA, and for rs288326, they were 4,346 and 8,034 for hip OA, 3,595 and 6,106 for knee OA, and 3,982 and 5,152 for hand OA. For each individual study, sex-specific odds ratios (ORs) were calculated for each OA phenotype that had been investigated. The ORs for each phenotype were synthesized using both fixed-effects and random-effects models for allele-based effects, and also for haplotype effects for FRZB. A significant random-effects summary OR for knee OA was demonstrated for rs143383 (1.15 [95% confidence interval 1.09-1.22]) (P=9.4x10(-7)), with no significant between-study heterogeneity. Estimates of effect sizes for hip and hand OA were similar, but a large between-study heterogeneity was observed, and statistical significance was borderline (for OA of the hip [P=0.016]) or absent (for OA of the hand [P=0.19]). Analyses for FRZB polymorphisms and haplotypes did not reveal any statistically significant signals, except for a borderline association of rs288326 with hip OA (P=0.019). Evidence of an association between the GDF5 rs143383 polymorphism and OA is substantially strong, but the genetic effects are consistent across different populations only for knee OA. Findings of this collaborative analysis do not support the notion that FRZB rs7775 or rs288326 has any sizable genetic effect on OA phenotypes.

Genetic Risk for Osteoporosis and Fractures

Although bone-mineral density (BMD) and fracture risk have a genetic basis, the specific genes involved are still under investigation. One of the most widely studied candidate genes for osteoporosis is the estrogen receptor α (ESR1) gene. In a meta-analysis of individual-level data, researchers examined …

Preventing injuries in older people by preventing falls: a meta-analysis of individual-level data.

Our falls prevention research group has conducted four controlled trials of a home exercise program to prevent falls in older people. The objectives of this meta-analysis of these trials were to estimate the overall effect of the exercise program on the numbers of falls and fall-related injuries and to identify subgroups that would benefit most from the program. We pooled individual-level data from the four trials to investigate the effect of the program in those aged 80 and older, in those with a previous fall, and in men and women. Nine cities and towns in New Zealand. One thousand sixteen community dwelling women and men aged 65 to 97. A program of muscle strengthening and balance retraining exercises designed specifically to prevent falls and individually prescribed and delivered at home by trained health professionals. Main outcomes were number of falls and number of injuries resulting from falls during the trials. The overall effect of the program was to reduce the number of falls and the number of fall-related injuries by 35% (incidence rate ratio (IRR) = 0.65, 95% confidence interval (CI) = 0.57-0.75; and, respectively IRR = 0.65, 95% CI = 0.53-0.81.) In injury prevention, participants aged 80 and older benefited significantly more from the program than those aged 65 to 79. The program was equally effective in reducing fall rates in those with and without a previous fall, but participants reporting a fall in the previous year had a higher fall rate (IRR = 2.34, 95% CI = 1.64-3.34). The program was equally effective in men and women. This exercise program was most effective in reducing fall-related injuries in those aged 80 and older and resulted in a higher absolute reduction in injurious falls when offered to those with a history of a previous fall.