Category: Statistics

BMJ Open. 2021 Oct 25;11(10):e051136. doi: 10.1136/bmjopen-2021-051136.

ABSTRACT

INTRODUCTION: Postpartum fatigue is a common symptom among new mothers after their pregnancy. It has a considerable negative impact on women’s functional and mental status as well as the development of babies. Identifying effective interventions to prevent or reduce postpartum fatigue is meaningful to improve the quality of life and avoid adverse outcomes of this vulnerable population. This systematic review aims to synthesise non-pharmacological evidence and evaluate the effectiveness of interventions for reducing postpartum fatigue among puerperas.

METHODS AND ANALYSIS: This review will be conducted in accordance with the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. We will systematically search the Cochrane Library, PubMed, Embase, Web of Science, PsycINFO, CINAHL and ProQuest databases to identify clinical trials implementing non-pharmacological interventions conducted during 0-78 weeks postpartum for fatigue reduction. An additional search of OpenGrey will be conducted to identify grey literature. The search will be performed on 30 March 2021 without restrictions on time and language. Two independent reviewers will be responsible for study selection, data extraction and study quality assessment. The Cochrane risk-of-bias tool will be adopted to evaluate the risk biases of the included randomised controlled trials, and the Risk of Bias in Non-randomised Studies of Interventions will be applied to evaluate non-randomised controlled trials. Any disagreements will be referred to a third reviewer to reach a consensus. Findings will be qualitatively synthesised, and a meta-analysis will be conducted for the statistical combination if outcome data are sufficient and available.

ETHICS AND DISSEMINATION: This systematic review will not involve the collection of primary data and will be based on published data. Therefore, ethics approval is not required. The final findings will be disseminated through peer-reviewed journals and academic conferences.

PROSPERO REGISTRATION NUMBER: CRD42021234869.

PMID:34697115 | DOI:10.1136/bmjopen-2021-051136

BMJ Open. 2021 Oct 25;11(10):e052610. doi: 10.1136/bmjopen-2021-052610.

ABSTRACT

INTRODUCTION: This paper presents a study protocol for a comparative effectiveness evaluation of abiraterone acetate against enzalutamide in clinical practice, two cancer drugs given to patients suffering from advanced prostate cancer.

METHOD AND ANALYSIS: The protocol designs a comparative-effectiveness analysis of abiraterone acetate against enzalutamide. With the substantial number of covariates a two-step procedure is suggested in choosing relevant covariates in the matching design. In the first step, an exploratory factor analysis reduces the dimension of a large set of continuous covariates to nine factors. In the second step, we reduce the dimension of the covariates, interactions and second order terms for the continuous covariates using propensity score estimation. The final design makes use of a genetic matching algorithm. The study protocol provides a detailed statistical analysis plan of the analysis sample derived from the matching design. The analysis will make use of linear regression and robust inference adjusted for multisignificance testing.

DISCUSSION: As in a randomised experiment the focus is on the design of the assignment to treatment. This allows the publication of this preanalysis plan before having access to outcome data. This means that the p values will be correct if the maintained assumption of uncounfoundedness is valid. Given that is p-hacking is substantial problem in empirical research, this is a substantial strength of this study. However, while design yields, balance on the observed covariates one cannot discard the possibility that unobserved confounders are not balanced. For that reason, sensitivity tests for the maintained assumption of uncounfoundedness are presented.

ETHICS AND DISSEMINATION: The study was approved by the Regional Ethical Review Board in Uppsala, Sweden (Dnr 2017/482). Results will be published in a peer-reviewed journal and distributed to relevant stakeholders in healthcare.

PMID:34697119 | DOI:10.1136/bmjopen-2021-052610

BMJ Open. 2021 Oct 25;11(10):e049267. doi: 10.1136/bmjopen-2021-049267.

ABSTRACT

INTRODUCTION: 24-hour movement behaviours (physical activity, sedentary behaviour and sleep) during the early years are associated with health and developmental outcomes, prompting the WHO to develop Global guidelines for physical activity, sedentary behaviour and sleep for children under 5 years of age. Prevalence data on 24-hour movement behaviours is lacking, particularly in low-income and middle-income countries (LMICs). This paper describes the development of the SUNRISE International Study of Movement Behaviours in the Early Years protocol, designed to address this gap.

METHODS AND ANALYSIS: SUNRISE is the first international cross-sectional study that aims to determine the proportion of 3- and 4-year-old children who meet the WHO Global guidelines. The study will assess if proportions differ by gender, urban/rural location and/or socioeconomic status. Executive function, motor skills and adiposity will be assessed and potential correlates of 24-hour movement behaviours examined. Pilot research from 24 countries (14 LMICs) informed the study design and protocol. Data are collected locally by research staff from partnering institutions who are trained throughout the research process. Piloting of all measures to determine protocol acceptability and feasibility was interrupted by COVID-19 but is nearing completion. At the time of publication 41 countries are participating in the SUNRISE study.

ETHICS AND DISSEMINATION: The SUNRISE protocol has received ethics approved from the University of Wollongong, Australia, and in each country by the applicable ethics committees. Approval is also sought from any relevant government departments or organisations. The results will inform global efforts to prevent childhood obesity and ensure young children reach their health and developmental potential. Findings on the correlates of movement behaviours can guide future interventions to improve the movement behaviours in culturally specific ways. Study findings will be disseminated via publications, conference presentations and may contribute to the development of local guidelines and public health interventions.

PMID:34697112 | DOI:10.1136/bmjopen-2021-049267

Cochrane Database Syst Rev. 2021 Oct 25;10:CD012612. doi: 10.1002/14651858.CD012612.pub2.

ABSTRACT

BACKGROUND: Stroke affects millions of people every year and is a leading cause of disability, resulting in significant financial cost and reduction in quality of life. Rehabilitation after stroke aims to reduce disability by facilitating recovery of impairment, activity, or participation. One aspect of stroke rehabilitation that may affect outcomes is the amount of time spent in rehabilitation, including minutes provided, frequency (i.e. days per week of rehabilitation), and duration (i.e. time period over which rehabilitation is provided). Effect of time spent in rehabilitation after stroke has been explored extensively in the literature, but findings are inconsistent. Previous systematic reviews with meta-analyses have included studies that differ not only in the amount provided, but also type of rehabilitation.

OBJECTIVES: To assess the effect of 1. more time spent in the same type of rehabilitation on activity measures in people with stroke; 2. difference in total rehabilitation time (in minutes) on recovery of activity in people with stroke; and 3. rehabilitation schedule on activity in terms of: a. average time (minutes) per week undergoing rehabilitation, b. frequency (number of sessions per week) of rehabilitation, and c. total duration of rehabilitation.

SEARCH METHODS: We searched the Cochrane Stroke Group trials register, CENTRAL, MEDLINE, Embase, eight other databases, and five trials registers to June 2021. We searched reference lists of identified studies, contacted key authors, and undertook reference searching using Web of Science Cited Reference Search.

SELECTION CRITERIA: We included randomised controlled trials (RCTs) of adults with stroke that compared different amounts of time spent, greater than zero, in rehabilitation (any non-pharmacological, non-surgical intervention aimed to improve activity after stroke). Studies varied only in the amount of time in rehabilitation between experimental and control conditions. Primary outcome was activities of daily living (ADLs); secondary outcomes were activity measures of upper and lower limbs, motor impairment measures of upper and lower limbs, and serious adverse events (SAE)/death.

DATA COLLECTION AND ANALYSIS: Two review authors independently screened studies, extracted data, assessed methodological quality using the Cochrane RoB 2 tool, and assessed certainty of the evidence using GRADE. For continuous outcomes using different scales, we calculated pooled standardised mean difference (SMDs) and 95% confidence intervals (CIs). We expressed dichotomous outcomes as risk ratios (RR) with 95% CIs.

MAIN RESULTS: The quantitative synthesis of this review comprised 21 parallel RCTs, involving analysed data from 1412 participants. Time in rehabilitation varied between studies. Minutes provided per week were 90 to 1288. Days per week of rehabilitation were three to seven. Duration of rehabilitation was two weeks to six months. Thirteen studies provided upper limb rehabilitation, five general rehabilitation, two mobilisation training, and one lower limb training. Sixteen studies examined participants in the first six months following stroke; the remaining five included participants more than six months poststroke. Comparison of stroke severity or level of impairment was limited due to variations in measurement. The risk of bias assessment suggests there were issues with the methodological quality of the included studies. There were 76 outcome-level risk of bias assessments: 15 low risk, 37 some concerns, and 24 high risk. When comparing groups that spent more time versus less time in rehabilitation immediately after intervention, we found no difference in rehabilitation for ADL outcomes (SMD 0.13, 95% CI -0.02 to 0.28; P = 0.09; I² = 7%; 14 studies, 864 participants; very low-certainty evidence), activity measures of the upper limb (SMD 0.09, 95% CI -0.11 to 0.29; P = 0.36; I² = 0%; 12 studies, 426 participants; very low-certainty evidence), and activity measures of the lower limb (SMD 0.25, 95% CI -0.03 to 0.53; P = 0.08; I² = 48%; 5 studies, 425 participants; very low-certainty evidence). We found an effect in favour of more time in rehabilitation for motor impairment measures of the upper limb (SMD 0.32, 95% CI 0.06 to 0.58; P = 0.01; I² = 10%; 9 studies, 287 participants; low-certainty evidence) and of the lower limb (SMD 0.71, 95% CI 0.15 to 1.28; P = 0.01; 1 study, 51 participants; very low-certainty evidence). There were no intervention-related SAEs. More time in rehabilitation did not affect the risk of SAEs/death (RR 1.20, 95% CI 0.51 to 2.85; P = 0.68; I² = 0%; 2 studies, 379 participants; low-certainty evidence), but few studies measured these outcomes. Predefined subgroup analyses comparing studies with a larger difference of total time spent in rehabilitation between intervention groups to studies with a smaller difference found greater improvements for studies with a larger difference. This was statistically significant for ADL outcomes (P = 0.02) and activity measures of the upper limb (P = 0.04), but not for activity measures of the lower limb (P = 0.41) or motor impairment measures of the upper limb (P = 0.06).

AUTHORS’ CONCLUSIONS: An increase in time spent in the same type of rehabilitation after stroke results in little to no difference in meaningful activities such as activities of daily living and activities of the upper and lower limb but a small benefit in measures of motor impairment (low- to very low-certainty evidence for all findings). If the increase in time spent in rehabilitation exceeds a threshold, this may lead to improved outcomes. There is currently insufficient evidence to recommend a minimum beneficial daily amount in clinical practice. The findings of this study are limited by a lack of studies with a significant contrast in amount of additional rehabilitation provided between control and intervention groups. Large, well-designed, high-quality RCTs that measure time spent in all rehabilitation activities (not just interventional) and provide a large contrast (minimum of 1000 minutes) in amount of rehabilitation between groups would provide further evidence for effect of time spent in rehabilitation.

PMID:34695300 | DOI:10.1002/14651858.CD012612.pub2

J Genet Couns. 2021 Oct 25. doi: 10.1002/jgc4.1527. Online ahead of print.

ABSTRACT

Expanded carrier screening (ECS) is used to identify individuals and couples at risk for having children with recessive or X-linked genetic conditions; however, personal health risks (PHR) can also be identified through this testing. There is limited data on how genetic counseling regarding PHR from ECS is perceived by the individual, or how they use this information. This study quantitatively surveyed individuals identified with these risks between September 2013 and March 2020. The 30-item survey included the validated Genomics Outcome Scale Short Form, the validated Genetic Counseling Satisfaction Scale, and original questions. Survey topics included pre-test knowledge of the possibility of discovering PHR through testing, satisfaction with pre-test education that addresses potential risks, perceived severity of PHR, empowerment by and understanding of information, anxiety levels related to their PHR, perceived genetic counseling support, and satisfaction with telehealth. A total of 416 completed surveys were analyzed using descriptive statistics, and linear and logistic regressions. The majority of participants were satisfied or extremely satisfied with pre-test education (n = 328; 78.8%) and telehealth (n = 329; 79.1%). However, more participants who were aware of the possibility of identifying PHR through ECS prior to testing were satisfied with pre-test education compared to those who were not aware. Additionally, a lack of prior awareness of PHR was associated with lower empowerment scores (p = .004). Those who were highly satisfied with genetic counseling were more likely to feel empowered and understand the information presented (p = .001). The majority of individuals used their PHR information following their results appointment (n = 391; 94.0%). The results of this study suggest that receiving PHR information was useful and was positively influenced by both pre-test education and the genetic counseling process.

PMID:34695254 | DOI:10.1002/jgc4.1527

Int J Gynaecol Obstet. 2021 Oct 25. doi: 10.1002/ijgo.13984. Online ahead of print.

ABSTRACT

OBJECTIVE: To compare between 200 μg and 800 μg of vaginal misoprostol for cervical ripening prior to operative hysteroscopy.

METHODS: Quadruble-blind randomized clinical trial conducted between November 2019 and September 2020 involving 76 patients undergoing cervical dilatation prior to surgical hysteroscopy at teaching hospitals in Pernambuco, Brazil. Women received the vaginal misoprostol dosage of 200 μg or 800 μg,10-12 hours before operative hysteroscopy. The cervical width was the primary outcome, and the secondaries were patient’s satisfaction, side effects, surgical complications and duration of cervical dilatation. Chi-square tests of association, Fisher’s exact and Mann-Whitney tests were used with an alpha error of less than 5%.

RESULTS: There was no statistical difference between the groups in the mean of the cervical width (800 μg: 6.5 ± 1.6mm versus 200 μg: 5.8 ± 1.8mm, p=0.055), patient’s satisfaction and surgical findings except for the duration of cervical dilatation, that was lower in the 800 μg group (28.16 ± 28.5s versus 41.97 ± 31.0s, p=0.035). Among the side effects, diarrhea was more frequent in 800 μg group with statistical difference (100% versus 0%; p=0.01).

CONCLUSION: For cervical ripening, 200 μg misoprostol is equally effective with less adverse effects than 800 μg before operative hysteroscopy.

PMID:34695232 | DOI:10.1002/ijgo.13984

Scand J Med Sci Sports. 2021 Oct 25. doi: 10.1111/sms.14085. Online ahead of print.

ABSTRACT

Physical activity (PA) is a complex human behaviour, which implies that multiple dimensions need to be taken into account in order to reveal a complete picture of the PA behaviour profile of an individual. This scoping review aimed to map advanced analytical methods and their summary variables, hereinafter referred to as wearable-specific indicators of PA behaviour (WIPAB), used to assess PA behaviour. The strengths and limitations of those indicators as well as potential associations with certain health-related factors were also investigated. Three databases (MEDLINE, Embase and Web of Science) were screened for articles published in English between January 2010 and April 2020. Articles, which assessed the PA behaviour, gathered objective measures of PA using tri-axial accelerometers and investigated WIPAB were selected. All studies reporting WIPAB in the context of PA monitoring were synthesised and presented in four summary tables: study characteristics, details of the WIPAB, strengths and limitations, and measures of association between those indicators and health-related factors. In total, 7247 records were identified, of which 24 articles were included after assessing titles, abstracts and full-texts. Thirteen WIPAB were identified, which can be classified into three different categories specifically focussing on 1) the activity intensity distribution, 2) activity accumulation and 3) the temporal correlation and regularity of the acceleration signal. Only five of the thirteen WIPAB identified in this review have been used in the literature so far to investigate the relationship between PA behaviour and health, while they may provide useful additional information to the conventional PA variables.

PMID:34695249 | DOI:10.1111/sms.14085

Bioinformatics. 2021 Oct 25;37(20):3514-3520. doi: 10.1093/bioinformatics/btab223.

ABSTRACT

MOTIVATION: Gene-environment interaction (GEI) studies are a general framework that can be used to identify genetic variants that modify the effects of environmental, physiological, lifestyle or treatment effects on complex traits. Moreover, accounting for GEIs can enhance our understanding of the genetic architecture of complex diseases and traits. However, commonly used statistical software programs for GEI studies are either not applicable to testing certain types of GEI hypotheses or have not been optimized for use in large samples.

RESULTS: Here, we develop a new software program, GEM (Gene-Environment interaction analysis in Millions of samples), which supports the inclusion of multiple GEI terms, adjustment for GEI covariates and robust inference, while allowing multi-threading to reduce computation time. GEM can conduct GEI tests as well as joint tests of genetic main and interaction effects for both continuous and binary phenotypes. Through simulations, we demonstrate that GEM scales to millions of samples while addressing limitations of existing software programs. We additionally conduct a gene-sex interaction analysis on waist-hip ratio in 352 768 unrelated individuals from the UK Biobank, identifying 24 novel loci in the joint test that have not previously been reported in combined or sex-specific analyses. Our results demonstrate that GEM can facilitate the next generation of large-scale GEI studies and help advance our understanding of the genetic architecture of complex diseases and traits.

AVAILABILITY AND IMPLEMENTATION: GEM is freely available as an open source project at https://github.com/large-scale-gxe-methods/GEM.

SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

PMID:34695175 | DOI:10.1093/bioinformatics/btab223

Eur J Prev Cardiol. 2021 Oct 25;28(13):1445-1451. doi: 10.1177/2047487320915342.

ABSTRACT

AIMS: Cumulative blood pressure (BP) is a measure that incorporates the severity and duration of BP exposure. The prognostic significance of cumulative BP in young adults for cardiovascular diseases (CVDs) in comparison to BP severity alone is, however, unclear.

METHODS AND RESULTS: We investigated 3667 Coronary Artery Risk Development in Young Adults participants who attended six visits over 15 years (year-0 (1985-1986), year-2, year-5, year-7, year-l0, and year-15 exams). Cumulative BP was calculated as the area under the curve (mmHg × years) from year 0 through year 15. Cox models assessed the association between cumulative BP (year 0 through year 15), current BP (year 15), and BP change (year 0 and year 15) and CVD outcomes. Mean (standard deviation) age at year 15 was 40.2 (3.6) years, 44.1% were men, and 44.1% were African-American. Over a median follow-up of 16 years, there were 47 heart failure (HF), 103 coronary heart disease (CHD), 71 stroke, and 191 CVD events. Cumulative systolic BP (SBP) was associated with HF (hazard ratio (HR) = 2.14 (1.58-2.90)), CHD (HR = 1.49 (1.19-1.87)), stroke (HR = 1.81 (1.38-2.37)), and CVD (HR = 1.73 (1.47-2.05)). For CVD, the C-statistic for SBP (year 15) was 0.69 (0.65-0.73) and change in C-statistic with the inclusion of SBP change and cumulative SBP was 0.60 (0.56-0.65) and 0.72 (0.69-0.76), respectively. For CVD, using year-15 SBP as a reference, the net reclassification index (NRI) for cumulative SBP was 0.40 (p < 0.0001) and the NRI for SBP change was 0.22 (p = 0.001).

CONCLUSIONS: Cumulative BP in young adults was associated with the subsequent risk of HF, CHD, stroke, and CVD. Cumulative BP provided incremental prognostic value and improved risk reclassification for CVD, when compared to single BP assessments or changes in BP.

PMID:34695218 | DOI:10.1177/2047487320915342

PLoS One. 2021 Oct 25;16(10):e0258764. doi: 10.1371/journal.pone.0258764. eCollection 2021.

ABSTRACT

BACKGROUND: Parents play a key role in providing nurturance and nurturing care to their child during the first 1000 days which is important for optimal child development. Various factors have been found to influence parenting but the contribution of these factors toward parental nurturance within the first 1000 days is not yet known in the South African context. This paper describes a protocol for a project that aims to develop a logic model of change for the determinants of parental nurturance in the first 1000 days in the South African context.

METHOD: This study will apply a mixed methods approach with a sequential design within an intervention mapping framework. The study will occur in two phases. The first phase will identify the problem, which will be done via a scoping review, a policy review and a needs assessment for parents and stakeholders. This phase will recruit approximately 35 participants (20 parents and 15 stakeholders) for the qualitative component and then approximately 398 participants for the quantitative component. Data will be collected via semi-structured interviews and with questionnaires (Home Observation for Measurement of the Environment Inventory, the Depression and Anxiety Scale, and the Multidimensional Perceived Social Support Scale). Data will be thematically analysed, and the Statistical Package for Social Science (SPSS) will be used to determine descriptive statistics, both of which will inform the development of the model in phase 2. The second phase will be the development of a logic model of change for determinants for parental nurturance in the first thousand days. This phase will consist of one stage- a consensus workshop which will be attended by approximately 20 participants (5 parents, 5 pregnant woman/new mothers, and 10 stakeholders). The data collected in this stage will be thematically analysed and will contribute to the refinement of the model.

DISCUSSION: The first thousand days (FTD) is a period in which rapid growth occurs in all domains of development. If children do not receive sensitive and responsive care in an environment that is conducive for their optimal development, children may not reach their full developmental potential.

PMID:34695150 | DOI:10.1371/journal.pone.0258764