Systematic reviews as a tool for planning and interpreting trials

Background Systematic reviews followed by ameta-analysis are carried out in medical research to combine the results of two or more related studies. Stroke trials have struggled to show beneficial effects and meta-analysis should be used more widely throughout the research process to either speed up the development of useful interventions, or halt more quickly research with hazardous or ineffective interventions. Summary of review. This review summarises the clinical research process and illustrates how and when systematic reviews may be used throughout the development programme. Meta-analyses should be performed after observational studies, preclinical studies in experimental stroke, and after phase I, II, and III clinical trials and phase IV clinical surveillance studies. Although meta-analyses most commonly work with summary data, they may be performed to assess relationships between variables (meta-regression) and, ideally, should utilise individual patient data. Meta-analysis techniques may alsoworkwith ordered categorical outcome data (ordinal meta-analysis) and be used to perform indirect comparisons where original trial data do not exist. Conclusion Systematic review/meta-analyses are powerful tools in medical research and should be used throughout the development of all stroke and other intervention

Increased Hematopoietic Extracellular RNAs and Vesicles in the Lung during Allergic Airway Responses.

Extracellular RNAs (exRNAs) can be released by numerous cell types in vitro, are often protected within vesicles, and can modify recipient cell function. To determine how the composition and cellular sources of exRNAs and the extracellular vesicles (EVs) that carry them change in vivo during tissue inflammation, we analyzed bronchoalveolar lavage fluid (BALF) from mice before and after lung allergen challenge. In the lung, extracellular microRNAs (ex-miRNAs) had a composition that was highly correlated with airway-lining epithelium. Using cell type-specific membrane tagging and single vesicle flow, we also found that 80% of detected vesicles were of epithelial origin. After the induction of allergic airway inflammation, miRNAs selectively expressed by immune cells, including miR-223 and miR-142a, increased and hematopoietic-cell-derived EVs also increased >2-fold. These data demonstrate that infiltrating immune cells release ex-miRNAs and EVs in inflamed tissues to alter the local extracellular environment

Milwaukee Longitudinal School Choice Evaluation: Annual School Testing Summary Report 2007-08

With the passage of the 2005 Wisconsin Act 125, private schools participating in the Milwaukee Parental Choice Program (MPCP) are now required to administer a nationally normed standardized test annually in reading, mathematics, and science to their MPCP (a.k.a. “Choice”) students enrolled in the 4th, 8th, and 10th grades. The law further directs Choice schools to submit copies of the scores from those tests to the School Choice Demonstration Project for processing and reporting to the Legislative Audit Bureau. During the 2007-08 school year, MPCP schools administered either nationally normed tests, such as the Iowa Test of Basic Skills, or the criterion referenced Wisconsin Knowledge and Concepts Examinations (WKCE). The School Choice Demonstration Project (SCDP) received student test scores from 114 of the 115 schools participating in the MPCP that were required to administer tests. Specifically, the SCDP received 5,763 nationally normed student test scores from 81 schools and 1,735 WKCE scores from 36 schools. These school numbers add to 123 because some schools used both types of exams and sent all 4th, 8th, and 10th grade scores to the SCD

Milwaukee Longitudinal School Choice Evaluation: Annual School Testing Summary Report

With the passage of 2005 Wisconsin Act 125, private schools participating in the Milwaukee Parental Choice Program (MPCP) are now required to administer a nationally normed standardized test annually in reading, mathematics, and science to their MPCP (a.k.a. “Choice”) students enrolled in the 4th, 8th, and 10th grades. The law further directs Choice schools to submit copies of the scores from those tests to the School Choice Demonstration Project (SCDP) for processing and reporting to the Legislative Audit Bureau. During the 2006-07 school year, MPCP schools administered either nationally normed tests, such as the Iowa Test of Basic Skills, or the criterion referenced Wisconsin Knowledge and Concepts Examinations (WKCE). The School Choice Demonstration Project received 5,194 nationally normed scores from 66 schools and 1,231 WKCE scores from 40 schools

A systematic review of simulation studies which compare existing statistical methods to account for non-compliance in randomised controlled trials

INTRODUCTION: Non-compliance is a common challenge for researchers and may reduce the power of an intention-to-treat analysis. Whilst a per protocol approach attempts to deal with this issue, it can result in biased estimates. Several methods to resolve this issue have been identified in previous reviews, but there is limited evidence supporting their use. This review aimed to identify simulation studies which compare such methods, assess the extent to which certain methods have been investigated and determine their performance under various scenarios.METHODS: A systematic search of several electronic databases including MEDLINE and Scopus was carried out from conception to 30th November 2022. Included papers were published in a peer-reviewed journal, readily available in the English language and focused on comparing relevant methods in a superiority randomised controlled trial under a simulation study. Articles were screened using these criteria and a predetermined extraction form used to identify relevant information. A quality assessment appraised the risk of bias in individual studies. Extracted data was synthesised using tables, figures and a narrative summary. Both screening and data extraction were performed by two independent reviewers with disagreements resolved by consensus.RESULTS: Of 2325 papers identified, 267 full texts were screened and 17 studies finally included. Twelve methods were identified across papers. Instrumental variable methods were commonly considered, but many authors found them to be biased in some settings. Non-compliance was generally assumed to be all-or-nothing and only occurring in the intervention group, although some methods considered it as time-varying. Simulation studies commonly varied the level and type of non-compliance and factors such as effect size and strength of confounding. The quality of papers was generally good, although some lacked detail and justification. Therefore, their conclusions were deemed to be less reliable.CONCLUSIONS: It is common for papers to consider instrumental variable methods but more studies are needed that consider G-methods and compare a wide range of methods in realistic scenarios. It is difficult to make conclusions about the best method to deal with non-compliance due to a limited body of evidence and the difficulty in combining results from independent simulation studies.PROSPERO REGISTRATION NUMBER: CRD42022370910.</p

Family lifestyle dynamics and childhood obesity: evidence from the millennium cohort study.

Abstract Background The prevalence of childhood obesity has been increasing but the causes are not fully understood. Recent public health interventions and guidance aiming to reduce childhood obesity have focused on the whole family, as opposed to just the child but there remains a lack of empirical evidence examining this relationship. Methods Using data from the longitudinal Millennium Cohort Study (MCS), we investigate the dynamic relationship between underlying family lifestyle and childhood obesity during early childhood. The MCS interviewed parents shortly after the birth of their child and follow up interviews were carried out when the child was 3, 5 and 7 years. We use a dynamic latent factor model, an approach that allows us to identify family lifestyle, its evolution over time (in this case between birth and 7 years) and its influence on childhood obesity and other observable outcomes. Results We find that family lifestyle is persistent, 87.43% of families which were above the 95th percentile on the lifestyle distribution, remained above the 95th percentile when the child was 7 years old. Family lifestyle has a significant influence on all outcomes in the study, including diet, exercise and parental weight status; family lifestyle accounts for 11.3% of the variation in child weight by age 7 years. Conclusion The analysis suggests that interventions should therefore be prolonged and persuasive and target the underlying lifestyle of a family as early as possible during childhood in order to have the greatest cumulative influence. Our results suggest that children from advantaged backgrounds are more likely to be exposed to healthier lifestyles and that this leads to inequalities in the prevalence of obesity. To reduce inequalities in childhood obesity, policy makers should target disadvantaged families and design interventions specifically for these families

Non-exercise equations to estimate fitness in white European and South Asian men

Cardiorespiratory fitness is a strong, independent predictor of health, whether it is measured in an exercise test or estimated in an equation. The purpose of this study was to develop and validate equations to estimate fitness in middle-aged white European and South Asian men.Multiple linear regression models (n=168, including 83 white European and 85 South Asian men) were created using variables that are thought to be important in predicting fitness (VO2 max, mL⋅kg⋅min): age (years); BMI (kg·m); resting heart rate (beats⋅min); smoking status (0=never smoked, 1=ex or current smoker); physical activity expressed as quintiles (0=quintile 1, 1=quintile 2, 2=quintile 3, 3=quintile 4, 4=quintile 5), categories of moderate- to vigorous-intensity physical activity (0=&lt;75 min⋅wk, 1=75-150 min⋅wk, 2=&gt;150-225 min⋅wk, 3=&gt;225-300 min⋅wk, 4=&gt;300 min⋅wk), or minutes of moderate- to vigorous-intensity physical activity (min⋅wk); and, ethnicity (0=South Asian, 1=white). The leave-one-out-cross-validation procedure was used to assess the generalizability and the bootstrap and jackknife resampling techniques were used to estimate the variance and bias of the models.Around 70% of the variance in fitness was explained in models with an ethnicity variable, such as: VO2 max = 77.409 - (age*0.374) - (BMI*0.906) - (ex or current smoker*1.976) + (physical activity quintile coefficient) - (resting heart rate*0.066) + (white ethnicity*8.032), where physical activity quintile 1 is 1, 2 is 1.127, 3 is 1.869, 4 is 3.793, and 5 is 3.029. Only around 50% of the variance was explained in models without an ethnicity variable. All models with an ethnicity variable were generalizable and had low variance and bias.These data demonstrate the importance of incorporating ethnicity in non-exercise equations to estimate cardiorespiratory fitness in multi-ethnic populations