Nevin Manimala

BMJ Open. 2022 Dec 6;12(12):e059463. doi: 10.1136/bmjopen-2021-059463.

ABSTRACT

INTRODUCTION: Incisional hernia has an incidence of up to 20% following laparotomy and is associated with significant morbidity and impairment of quality of life. A variety of surgical strategies including techniques and mesh types are available to manage patients with incisional hernia. Previous works have reported significant heterogeneity in outcome reporting for abdominal wall herniae, including ventral and inguinal hernia. This is coupled with under-reporting of important clinical and patient-reported outcomes. The lack of standardisation in outcome reporting contributes to reporting bias, hinders evidence synthesis and adequate data comparison between studies. This project aims to develop a core outcome set (COS) of clinically important, patient-oriented outcomes to be used to guide reporting of future research in incisional hernia.

METHODS: This project has been designed as an international, multicentre, mixed-methods project. Phase I will be a systematic review of current literature to examine the current clinical and patient-reported outcomes for incisional hernia and abdominal wall reconstruction. Phase II will identify the outcomes of importance to all key stakeholders through in depth qualitative interviews. Phase III will achieve consensus on outcomes of most importance and for inclusion into a COS through a Delphi process. Phase IV will achieve consensus on the outcomes that should be included in a final COS.

ETHICS AND DISSEMINATION: The adoption of this COS into clinical and academic practice will be endorsed by the American, British and European Hernia Societies. Its utilisation in future clinical research will enable appropriate data synthesis and comparison and will enable better clinical interpretation and application of the current evidence base. This study has been registered with the Core Outcome Measures in Effectiveness Trials initiative.

PROSPERO REGISTRATION NUMBER: CRD42018090084.

PMID:36600359 | DOI:10.1136/bmjopen-2021-059463

BMJ Open. 2022 Dec 6;12(12):e066814. doi: 10.1136/bmjopen-2022-066814.

ABSTRACT

OBJECTIVES: To examine how drug shop clients’ expenditures are affected by subsidies for malaria diagnostic testing and for malaria treatment, and also to examine how expenditures vary by clients’ malaria test result and by the number of medications they purchased.

DESIGN: Secondary cross-sectional analysis of survey responses from a randomised controlled trial.

SETTING: The study was conducted in twelve private drug shops in Western Kenya.

PARTICIPANTS: We surveyed 836 clients who visited the drug shops between March 2018 and October 2019 for a malaria-like illness. This included children >1 year of age if they were physically present and accompanied by a parent or legal guardian.

INTERVENTIONS: Subsidies for malaria diagnostic testing and for malaria treatment (conditional on a positive malaria test result).

PRIMARY AND SECONDARY OUTCOME MEASURES: Expenditures at the drug shop in Kenya shillings (Ksh).

RESULTS: Clients who were randomised to a 50% subsidy for malaria rapid diagnostic tests (RDTs) spent approximately Ksh23 less than those who were randomised to no RDT subsidy (95% CI (-34.6 to -10.7), p=0.002), which corresponds approximately to the value of the subsidy (Ksh20). However, clients randomised to receive free treatment (artemisinin combination therapies (ACTs)) if they tested positive for malaria had similar spending levels as those randomised to a 67% ACT subsidy conditional on a positive test. Expenditures were also similar by test result, however, those who tested positive for malaria bought more medications than those who tested negative for malaria while spending approximately Ksh15 less per medication (95% CI (-34.7 to 3.6), p=0.102).

CONCLUSIONS: Our results suggest that subsidies for diagnostic health products may result in larger household savings than subsidies on curative health products. A better understanding of how people adjust their behaviours and expenditures in response to subsidies could improve the design and implementation of subsidies for health products.

TRIAL REGISTRATION NUMBER: NCT03810014.

PMID:36600353 | DOI:10.1136/bmjopen-2022-066814

BMJ Open. 2022 Dec 6;12(12):e065234. doi: 10.1136/bmjopen-2022-065234.

ABSTRACT

INTRODUCTION: A proportion of those who survive the acute phase of COVID-19 experience prolonged symptoms, commonly known as long COVID-19. Given that healthcare workers (HCWs) face an elevated risk of acute COVID-19 compared with the general population, the global burden of long COVID-19 in HCWs is likely to be large; however, there is limited understanding of the prevalence of long COVID-19 in HCWs, or its symptoms and their clustering. This review will aim to estimate the pooled prevalence and the symptoms of long COVID-19 among HCWs infected with SARS-CoV-2 globally, and investigate differences by country, age, sex, ethnicity, vaccination status and occupation.

METHODS AND ANALYSIS: A systematic review and meta-analysis will be conducted. Medline (via Ovid), CINAHL (via EBSCO), Embase (via Ovid), PsycINFO (via EBSCO), OpenGrey (grey literature) and medRxiv (preprint server) will be searched from the 31 December 2019 onward. All research studies and preprint articles reporting any primary data on the prevalence and/or the symptoms of long COVID-19 among adult HCWs will be included. Methodological quality will be assessed using the Joanna Briggs Institute Critical Appraisal Checklist for Studies Reporting Prevalence Data. Outcomes are anticipated to be the prevalence of long COVID-19 among HCWs around the world and trajectory of symptoms. Data synthesis will include random-effect meta-analysis for studies reporting prevalence data of long COVID-19 following SARS-CoV-2 infection among HCWs. The results will be presented with a 95% CI as an estimated effect across studies. Heterogeneity will be assessed using I² statistic. Where meta-analysis is inappropriate, a narrative synthesis of the evidence will be conducted.

ETHICS AND DISSEMINATION: Ethical approval is not needed as data will be obtained from published articles. We will publish our findings in a peer-reviewed journal and disseminate the results of our review at conferences.

PROSPERO REGISTRATION NUMBER: CRD42022312781.

PMID:36600349 | DOI:10.1136/bmjopen-2022-065234

BMJ Open. 2022 Dec 9;12(12):e067656. doi: 10.1136/bmjopen-2022-067656.

ABSTRACT

OBJECTIVES: To describe the extent to which pragmatic trials underachieved or overachieved their target sample sizes, examine explanations and identify characteristics associated with under-recruitment and over-recruitment.

STUDY DESIGN AND SETTING: Secondary analysis of an existing database of primary trial reports published during 2014-2019, registered in ClinicalTrials.gov, self-labelled as pragmatic and with target and achieved sample sizes available.

RESULTS: Of 372 eligible trials, the prevalence of under-recruitment (achieving <90% of target sample size) was 71 (19.1%) and of over-recruitment (>110% of target) was 87 (23.4%). Under-recruiting trials commonly acknowledged that they did not achieve their targets (51, 71.8%), with the majority providing an explanation, but only 11 (12.6%) over-recruiting trials acknowledged recruitment excess. The prevalence of under-recruitment in individually randomised versus cluster randomised trials was 41 (17.0%) and 30 (22.9%), respectively; prevalence of over-recruitment was 39 (16.2%) vs 48 (36.7%), respectively. Overall, 101 025 participants were recruited to trials that did not achieve at least 90% of their target sample size. When considering trials with over-recruitment, the total number of participants recruited in excess of the target was a median (Q1-Q3) 319 (75-1478) per trial for an overall total of 555 309 more participants than targeted. In multinomial logistic regression, cluster randomisation and lower journal impact factor were significantly associated with both under-recruitment and over-recruitment, while using exclusively routinely collected data and educational/behavioural interventions were significantly associated with over-recruitment; we were unable to detect significant associations with obtaining consent, publication year, country of recruitment or public engagement.

CONCLUSIONS: A clear explanation for under-recruitment or over-recruitment in pragmatic trials should be provided to encourage transparency in research, and to inform recruitment to future trials with comparable designs. The issues and ethical implications of over-recruitment should be more widely recognised by trialists, particularly when designing cluster randomised trials.

PMID:36600344 | DOI:10.1136/bmjopen-2022-067656

BMJ Open. 2022 Dec 9;12(12):e066214. doi: 10.1136/bmjopen-2022-066214.

ABSTRACT

OBJECTIVES: The aim of this analysis is to identify the patterns of social deprivation and childhood mortality; and identify potential points where public health, social and education interventions, or health policy may be best targeted.

DESIGN: Decile of deprivation and underlying population distribution was derived using Office for National Statistics data. The risk of death was then derived using a Poisson regression model, calculating the increasing risk of death for each increasing deprivation decile.

SETTING: England.

PARTICIPANTS: 2688 deaths before 18 years of age reviewed between April 2019 and March 2020.

MAIN OUTCOME MEASURES: The relationship between deprivation and risk of death; for deaths with, and without modifiable factors.

RESULTS: There was evidence of increasing mortality risk with increase in deprivation decile, with children in the least deprived areas having a mortality of 13.25 (11.78-14.86) per 100 000 person-years, compared with 31.14 (29.13-33.25) in the most deprived decile (RR 1.08 (95% CI 1.07 to 1.10)); with the gradient of risk stronger in children who died with modifiable factors than those without (RR 1.12 (95% CI 1.09 to 1.15)) vs (RR 1.07 (95% CI 1.05 to 1.08)). Deprivation subdomains of employment, adult education, barriers to housing and services, and indoor living environments appeared to be the most important predictors of child mortality CONCLUSIONS: There is a clear gradient of increasing child mortality across England as measures of deprivation increase; with a striking finding that this varied little by area, age or other demographic factor. Over one-fifth of all child deaths may be avoided if the most deprived half of the population had the same mortality as the least deprived. Children dying in more deprived areas may have a greater proportion of avoidable deaths. Adult employment, and improvements to housing, may be the most efficient place to target resources to reduce these inequalities.

PMID:36600341 | DOI:10.1136/bmjopen-2022-066214

BMJ Open. 2022 Dec 9;12(12):e064949. doi: 10.1136/bmjopen-2022-064949.

ABSTRACT

OBJECTIVE: To explore the factors that influence institutional care for the disabled elderly in China and the key factors that influence individuals based on the Andersen model.

DESIGN: Cross-sectional survey.

SETTING: The research was conducted in 18 cities in Henan Province, China.

MAIN OUTCOME MEASURES: A multistage, stratified sampling design was employed. The χ² test was used to compare the differences in basic information of the disabled elderly. A binary Logit model was used to examine the factors influencing the willingness to institutionalise elderly people with disabilities. The determinants of willingness to care in an institution were also explored in a stratified study by gender, age and region to identify the key differences affecting institutionalisation. The Andersen model was used as the theoretical framework to infer the impact strength of each model.

RESULTS: Of the 2810 disabled elderly people in Henan, China, 7.4% of the elderly had a willingness for institutional care. In the binary logistic regression analysis, whether living alone (OR (95% CI)=0.596 (0.388 to 0.916)), medical payment method (basic medical insurance for urban employees: OR (95% CI)=2.185 (1.091 to 4.377)), having mental illness (OR (95% CI)=2.078 (1.044 to 4.137)) had a statistically significant difference (p<0.05) on the impact on the willingness of the disabled elderly to receive institutional care. Validation of the fitted coefficients of the model revealed that the needs factor had the most significant effect on the enabling variable, while the predisposing factor had more minerally effect.

CONCLUSIONS: Several factors influence the willingness of the disabled elderly to institutionalise. Therefore, it is recommended that relevant authorities take targeted measures to focus on the disabled elderly to identify more precise elderly care services to deal with the ageing crisis.

PMID:36600340 | DOI:10.1136/bmjopen-2022-064949

BMJ Open. 2022 Dec 9;12(12):e065401. doi: 10.1136/bmjopen-2022-065401.

ABSTRACT

INTRODUCTION: There has been renewed interest in the therapeutic use of bacteriophages (phages); however, standardised therapeutic protocols are lacking, and there is a paucity of rigorous clinical trial data assessing efficacy.

METHODS AND ANALYSIS: We propose an open-label, single-arm trial investigating a standardised treatment and monitoring protocol for phage therapy. Patients included will have exhausted other therapeutic options for control of their infection and phage therapy will be administered under Australia’s Therapeutic Goods Administration Special Access Scheme. A phage product with high in vitro activity against the targeted pathogen(s) must be available in line with relevant regulatory requirements. We aim to recruit 50-100 patients over 5 years, from any public or private hospitals in Australia. The standardised protocol will specify clinical assessments and biological sampling at scheduled time points. The primary outcome is safety at day 29, assessed by the frequency of adverse events, and overseen by an independent Data Safety Monitoring Board. Secondary outcomes include long-term safety (frequency of adverse events until at least 6 months following phage therapy), and feasibility, measured as the proportion of participants with>80% of minimum data available for analysis. Additional endpoints assessed include clinical response, patient/guardian reported quality of life measures, phage pharmacokinetics, human host immune responses and microbiome analysis. All trial outcomes will be summarised and presented using standard descriptive statistics.

ETHICS AND DISSEMINATION: Participant inclusion will be dependent on obtaining written informed consent from the patient or guardian. The trial protocol was approved by the Sydney Children’s Hospitals Network Human Research Ethics Committee in December 2021 (Reference 2021/ETH11861). In addition to publication in a peer-reviewed scientific journal, a lay summary of study outcomes will be made available for participants and the public on the Phage Australia website (https://www.phageaustralia.org/).

TRIAL REGISTRATION NUMBER: Registered on ANZCTR, 10 November 2021 (ACTRN12621001526864; WHO Universal Trial Number: U1111-1269-6000).

PMID:36600337 | DOI:10.1136/bmjopen-2022-065401

BMJ Open. 2022 Dec 9;12(12):e066067. doi: 10.1136/bmjopen-2022-066067.

ABSTRACT

INTRODUCTION: Familial hypercholesterolaemia (FH) is a frequent (1:300) autosomal dominantly inherited condition which causes premature (women <60 years, men <55 years) cardio-cerebrovascular disease (CVD). Early detection and initiation of treatment can prevent the development of CVD and premature death. Our pilot study aims to investigate the prevalence of FH, the feasibility and efficacy of a screening based on a capillary blood test performed during a school medicine visit in primary school children.

METHODS AND ANALYSIS: In this cross-sectional study, all children (n=3200) between 7 and 12 years, attending primary school in the city of Luxembourg and invited for their mandatory medical school examinations between 2021 and 2023 are invited to participate. A study nurse performs a capillary blood test to analyse the lipid profile. Families receive the result including an interpretation and invitation to seek medical advice if indicated. If FH is confirmed, a reverse cascade screening in that family will be proposed. The child will receive standard care. Primary outcome is the occurrence of confirmed FH in the study population. Secondary outcomes include the percentage of children screened, percentage of children with abnormal lipid values, percentage of families screened and percentage of families with additionally identified members suffering from hypercholesterolaemia. A health economic analysis will be performed.

ETHICS AND DISSEMINATION: Ethics approval (reference number 202108/01) has been obtained from the National Research Ethics Committee (CNER (Luxembourg)) and was authorised by the ministry of health in Luxembourg. Families receive written information with an informed consent form. Participation requires an informed consent form signed by the parents. The results will be disseminated in peer-reviewed publications, conference presentations and by public media to the general public.

TRIAL REGISTRATION NUMBER: NCT05271305.

PMID:36600332 | DOI:10.1136/bmjopen-2022-066067

BMJ Open. 2022 Dec 9;12(12):e059666. doi: 10.1136/bmjopen-2021-059666.

ABSTRACT

BACKGROUND: The cardiovascular disease (CVD) burden among South Asians is high. Lifestyle interventions have been effective in the primary prevention of CVD, but this has not been replicated, through a synthesis of randomised trials, in South Asians.

METHODS: Four electronic databases (MEDLINE, Embase, CENTRAL and CINAHL), two clinical trial registries and references of included articles were searched through June 2022 (featuring ≥90% South Asian participants). Random-effects pairwise meta-analyses were performed, and heterogeneity was quantified with the I² statistic. The Grades of Recommendation, Assessment, Development, and Evaluation (GRADE) framework was used to report on the quality of evidence (International Prospective Register of Systematic Reviews registration (PROSPERO).

RESULTS: Thirty-five studies were included. Twelve tested diet and physical activity interventions; 18 tested diet alone; and 5 tested physical activity alone. All reported effects of the intervention(s) on at least one established risk factor for CVD, including blood pressure (systolic blood pressure (SBP), diastolic blood pressure (DBP) and blood lipids (high-density lipoprotein cholesterol (HDLc), low-density lipoprotein cholesterol (LDLc) or triglycerides). No trials reported clinical CVD. There is moderate-quality evidence that diet and physical activity interventions improve SBP (mean difference (MD) -2.72 mm Hg, 95% CI -4.11 to -1.33) and DBP (MD -1.53 mm Hg, 95% CI -2.57 to -0.48); high-quality to moderate-quality evidence that diet-only interventions improve DBP (MD -2.05 mm Hg, 95% CI -2.93 to -1.16) and blood lipids (triglycerides (MD -0.10 mmol/L, 95% CI -0.14 to -0.06) and LDLc (MD -0.19 mmol/L, 95% CI -0.32 to -0.06)); and moderate-quality evidence that physical activity-only interventions improve SBP (MD -9.7 mm Hg, 95% CI -11.05 to -8.35), DBP (MD -7.29 mm Hg, 95% CI -8.42 to -6.16) and HDLc (MD 0.08 mmol/L, 95% CI 0.04 to 0.11) compared with usual care.

CONCLUSIONS: Lifestyle interventions improve blood pressure and blood lipid profiles in adult South Asians at risk of CVD. Tailored interventions should be used to modify cardiovascular risk factors in this at-risk group.

PROSPERO REGISTRATION NUMBER: CRD42018090419.

PMID:36600330 | DOI:10.1136/bmjopen-2021-059666

BMJ Open. 2022 Dec 9;12(12):e066480. doi: 10.1136/bmjopen-2022-066480.

ABSTRACT

INTRODUCTION: Congenital anomalies affect over 2% of pregnancies. Surgical advances have reduced mortality and improved survival for patients with congenital anomalies potentially requiring surgical (CAPRS) intervention. However, our understanding of aetiology, diagnostic methods, optimal management, outcomes and prognostication is limited. Existing birth cohorts have low numbers of individual heterogenous CAPRS. The Surgical Paediatric congEnital Anomalies Registry with Long term follow-up (Surgical-PEARL) study aims to establish a multicentre prospective fetal, child and biological parent cohort of CAPRS.

METHODS AND ANALYSIS: From 2022 to 2027, Surgical-PEARL aims to recruit 2500 patients with CAPRS alongside their biological mothers and fathers from up to 15 UK centres. Recruitment will be antenatal or postnatal dependent on diagnosis timing and presentation to a recruitment site. Routine clinical data including antenatal scans and records, neonatal intensive care unit (NICU) records, diagnostic and surgical data and hospital episode statistics will be collected. A detailed biobank of samples will include: parents’ blood and urine samples; amniotic fluid if available; children’s blood and urine samples on admission to NICU, perioperatively or if the child has care withdrawn or is transferred for extracorporeal membrane oxygenation; stool samples; and surplus surgical tissue. Parents will complete questionnaires including sociodemographic and health data. Follow-up outcome and questionnaire data will be collected for 5 years. Once established we will explore the potential of comparing findings in Surgical-PEARL to general population cohorts born in the same years and centres.

ETHICS AND DISSEMINATION: Ethical and health research authority approvals have been granted (IRAS Project ID: 302251; REC reference number 22/SS/0004). Surgical-PEARL is adopted onto the National Institute for Health Research Clinical Research Network portfolio. Findings will be disseminated widely through peer-reviewed publication, conference presentations and through patient organisations and newsletters.

TRIAL REGISTRATION NUMBER: ISRCTN12557586.

PMID:36600324 | DOI:10.1136/bmjopen-2022-066480