Tag: nevin manimala

Lupus Sci Med. 2021 Oct;8(1):e000534. doi: 10.1136/lupus-2021-000534.

ABSTRACT

OBJECTIVES: To evaluate the risk of psychiatric disorders and all-cause mortality associated with belimumab therapy in patients with SLE.

METHODS: A literature search of four electronic bibliographic databases, including PubMed, EMBASE, Scopus and Cochrane databases, was conducted for randomised controlled trials (RCTs) reporting adverse reactions between belimumab and placebo. OR and 95% CI were calculated using the Mantel-Haenszel method with fixed-effects or random-effects model, depending on the heterogeneity test.

RESULTS: In total, 11 eligible RCTs including 8824 patients with SLE were randomised into belimumab (5160 patients with 5552 patient-years) and placebo (3664 patients with 3985 patient-years) groups, respectively. Overall, no increased risk was identified with belimumab therapy at all dosages compared with placebo in patients with SLE regarding all psychiatric disorders (OR 0.89, 95% CI 0.64 to 1.23, I²=58%) and all-cause mortality (OR 1.10, 95% CI 0.64 to 1.89, I²=0%). The subgroup analysis of psychiatric disorders also revealed no statistically elevated risks in serious psychiatric disorders (OR 1.15, 95% CI 0.77 to 1.70, I²=47%), non-serious psychiatric disorders (OR 0.83, 95% CI 0.60 to 1.16, I²=52%), suicidal ideation or behaviour (OR 0.87, 95% CI 0.57 to 1.33, I²=0%), and depression (OR 1.29, 95% CI 0.90 to 1.85, I²=15%). Secondary analysis restricting belimumab at approved dose of 10 mg/kg only yielded similar results.

CONCLUSION: Belimumab therapy overall does not increase psychiatric events and all-cause mortality risks, whereas the results from Belimumab Assessment of Safety in SLE Study are suggestive of increased risk of psychiatric adverse events with belimumab exposure. Consequently, post-marketing data are needed to ascertain its psychiatric safety, especially serious mental disorders.

PMID:34697129 | DOI:10.1136/lupus-2021-000534

In Vivo. 2021 Nov-Dec;35(6):3233-3243. doi: 10.21873/invivo.12618.

ABSTRACT

BACKGROUND: Expression of kallikrein-11 (KLK11) has been found to be related to the prognosis of various human cancer types but its physiological functions in the steps of breast cancer (BC) progression are still unknown.

MATERIALS AND METHODS: BC and adjacent normal breast tissue samples were collected from 28 patients. KLK11 expression levels were determined by real-time polymerase chain reaction for each sample and associations with known prognostic features were statistically analyzed.

RESULTS: Although there was slight up-regulation in tumor tissues overall, significant down-regulation of KLK11 expression in tumor tissue was observed in the elderly and in patients with perineural invasion. Furthermore, tumor size, grade, mitotic score, necrosis, calcification, lymphatic invasion, hormone receptor status and Ki67 expression were associated with altered KLK11 level.

CONCLUSION: Changes in expression levels of KLK11, associated with patient characteristics, might be used as complementary data in order to predict clinical outcome and prognosis in BC.

PMID:34697154 | DOI:10.21873/invivo.12618

BMJ Open. 2021 Oct 25;11(10):e053678. doi: 10.1136/bmjopen-2021-053678.

ABSTRACT

OBJECTIVE: Analysis of participatory approaches to developing health interventions for migrants and how approaches embody core participatory principles of inclusivity and democracy.

DESIGN: A systematic review of original articles. Electronic searches within the databases MEDLINE, Embase, Global Health and PsychINFO (from inception-November 2020).

ELIGIBILITY CRITERIA FOR STUDY SELECTION: Original peer-reviewed articles reporting research to develop and implement a health intervention for migrants, incorporating participatory approaches. We defined migrants as foreign-born individuals. Only articles reporting the full research cycle (inception, design, implementation, analysis, evaluation, dissemination) were included.

DATA EXTRACTION: We extracted information related to who was involved in research (migrants or other non-academic stakeholders), the research stage at which they were involved (inception, design, implementation, analysis, evaluation, dissemination), the method of their involvement and how this aligned with the core principles of participatory research-categorising studies as exhibiting active or pseudo (including proxy and indirect) participation.

RESULTS: 1793 publications were screened, of which 28 were included in our analysis. We found substantial variation in the application of participatory approaches in designing health interventions targeting migrants: across 168 individual research stages analysed across the 28 studies, we recorded 46 instances of active participation of migrants, 30 instances of proxy participation and 24 instances of indirect participation. All studies involved non-academic stakeholders in at least one stage of the research, only two studies exhibited evidence of active participation of migrants across all research stages. Evidence is limited due to the variability of terms and approaches used.

CONCLUSIONS: Important shortfalls in the meaningful inclusion of migrants in developing health interventions exist, suggesting a more rigorous and standardised approach is warranted to better define and deliver participatory research and improve quality.

REGISTRATION: This review followed Preferred Reporting Items for Systematic Review and Meta-Analysis guidelines and is registered on the Open Science Framework (osf.io/2bnz5).

PMID:34697122 | DOI:10.1136/bmjopen-2021-053678

BMJ Open. 2021 Oct 25;11(10):e055125. doi: 10.1136/bmjopen-2021-055125.

ABSTRACT

OBJECTIVE: To assess the magnitude of dietary diversity and associated factors among pregnant women in the rural communities of Jimma Zone, south-west Ethiopia.

DESIGN: A community-based cross-sectional study was conducted from 1 June to 30 June 2020.

SETTINGS: The study was conducted in Seka Chekorsa and Mana districts. From a total of 63 listed kebeles, 21 were randomly selected.

PARTICIPANTS: Three hundred sixty first-trimester pregnant women have participated in this study. We used a systematic random sampling method to select the participants after a home-to-home census.

PRIMARY AND SECONDARY OUTCOMES: Dietary diversity was assessed using a 24 hours dietary recall method. Descriptive statistics were computed to describe the study subjects. Bivariate and multivariable logistic regression was run to control for all possible confounding effects and measure the strength of association between the outcome of interest and predictor.

RESULTS: The overall magnitude of adequate dietary diversity was found to be 186 (51.7%); 95% CI 46.1% to 56.4%). Having attended elementary education (adjusted OR (AOR)=2.45; 95% CI 1.33 to 4.51), completed grade 8 (AOR=6.05; 95% CI 2.65 to 13.80), attended high school (AOR=11.69; 95% CI 3.76 to 36.27), completed high school and above (AOR=2.92; 95% CI 1.16 to 7.32), husbands attended high school (AOR=2.92; 95% CI 1.15 to 7.47), family size of less than five (AOR=3.44; 95% CI to 1.77-6.66) were positively significantly associated with adequate dietary diversity. On the other hand, not had additional meal during pregnancy (AOR=0.42; 95% CI 0.21 to 0.83) was negatively associated with adequate dietary diversity.

CONCLUSIONS: We observed that the adequate dietary diversity score of pregnant women was low compared with the pooled proportion of dietary diversity conducted in Ethiopia. Therefore, strengthening and promoting female education through intersectoral collaborations and additional meal counselling during pregnancy is indispensable.

PMID:34697127 | DOI:10.1136/bmjopen-2021-055125

BMJ Open. 2021 Oct 25;11(10):e052777. doi: 10.1136/bmjopen-2021-052777.

ABSTRACT

OBJECTIVES: We conducted a systematic literature review and meta-analysis of observational studies to investigate the association between diabetes, hypertension, body mass index (BMI) or smoking with the risk of death in patients with COVID-19 and to estimate the proportion of deaths attributable to these conditions.

METHODS: Relevant observational studies were identified by searches in the PubMed, Cochrane library and Embase databases through 14 November 2020. Random-effects models were used to estimate summary relative risks (SRRs) and 95% CIs. Certainty of evidence was assessed using the Cochrane methods and the Grading of Recommendations, Assessment, Development and Evaluations framework.

RESULTS: A total of 186 studies representing 210 447 deaths among 1 304 587 patients with COVID-19 were included in this analysis. The SRR for death in patients with COVID-19 was 1.54 (95% CI 1.44 to 1.64, I²=92%, n=145, low certainty) for diabetes and 1.42 (95% CI 1.30 to 1.54, I²=90%, n=127, low certainty) for hypertension compared with patients without each of these comorbidities. Regarding obesity, the SSR was 1.45 (95% CI 1.31 to 1.61, I²=91%, n=54, high certainty) for patients with BMI ≥30 kg/m² compared with those with BMI <30 kg/m² and 1.12 (95% CI 1.07 to 1.17, I²=68%, n=25) per 5 kg/m² increase in BMI. There was evidence of a J-shaped non-linear dose-response relationship between BMI and mortality from COVID-19, with the nadir of the curve at a BMI of around 22-24, and a 1.5-2-fold increase in COVID-19 mortality with extreme obesity (BMI of 40-45). The SRR was 1.28 (95% CI 1.17 to 1.40, I²=74%, n=28, low certainty) for ever, 1.29 (95% CI 1.03 to 1.62, I²=84%, n=19) for current and 1.25 (95% CI 1.11 to 1.42, I²=75%, n=14) for former smokers compared with never smokers. The absolute risk of COVID-19 death was increased by 14%, 11%, 12% and 7% for diabetes, hypertension, obesity and smoking, respectively. The proportion of deaths attributable to diabetes, hypertension, obesity and smoking was 8%, 7%, 11% and 2%, respectively.

CONCLUSION: Our findings suggest that diabetes, hypertension, obesity and smoking were associated with higher COVID-19 mortality, contributing to nearly 30% of COVID-19 deaths.

TRIAL REGISTRATION NUMBER: CRD42020218115.

PMID:34697120 | DOI:10.1136/bmjopen-2021-052777

BMJ Open. 2021 Oct 25;11(10):e052841. doi: 10.1136/bmjopen-2021-052841.

ABSTRACT

OBJECTIVES: People with epilepsy (PWE) have a higher mortality rate than the general population. Epilepsy-related deaths have increased despite all-cause mortality decreasing in the general population pre-COVID-19. We hypothesised that clinical and lifestyle factors may identify people more at risk.

DESIGN: We used a retrospective cohort study to explore cause of death and a nested case-control study to identify risk factors.

SETTING: We explored factors associated with mortality using primary care population data from 1 April 2004 to 31 March 2014. Data were obtained from the Clinical Practice Research Datalink which compiles anonymised patient data from primary care in the UK. Cause of death data was supplemented from the Office of National Statistics when available.

PARTICIPANTS: The analysis included 70 431 PWE, with 11 241 registered deaths.

RESULTS: The number of deaths within the database increased by 69% between the first and last year of the study. Epilepsy was considered as a contributing cause in approximately 45% of deaths of PWE under 35. Factors associated with increased risk of death included attendance at emergency departments and/or emergency admissions (OR 3.48, 95% CI 3.19 to 3.80), antiepileptic drug (AED) polytherapy (2 AEDs: OR 1.60, 95% CI 1.51 to 1.71; 3 AEDs: OR 2.06, 95% CI 1.86 to 2.29; 4+AEDs: OR 2.62, 95% CI 2.23 to 3.08), status epilepticus (OR 2.78, 95% CI 1.64 to 4.71), depression (OR 1.67, 95% CI 1.57 to 1.76) and injuries (OR 1.54, 95% CI 1.43 to 1.67). No seizures in the prior year (OR 0.52, 95% CI 0.41 to 0.65).

CONCLUSION: Our results add to existing evidence that deaths in epilepsy are increasing. Future studies could focus on identifying PWE at high risk and addressing them with clinical interventions or better self-management. Identifying specific risk factors for younger people should be a priority as epilepsy may be a factor in close to half of deaths of PWE under 35 years of age.

PMID:34697121 | DOI:10.1136/bmjopen-2021-052841

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