Nevin Manimala

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

Clin Epigenetics. 2023 Jan 4;15(1):1. doi: 10.1186/s13148-022-01394-5.

ABSTRACT

Depression is a multifactorial disorder representing a significant public health burden. Previous studies have linked multiple single nucleotide polymorphisms with depressive phenotypes and suicidal behavior. MAD1L1 is a mitosis metaphase checkpoint protein that has been linked to depression in GWAS. Using a longitudinal EWAS approach in an adolescent cohort at two time points (n = 216 and n = 154), we identified differentially methylated sites that were associated with depression-related genetic variants in MAD1L1. Three methylation loci (cg02825527, cg18302629, and cg19624444) were consistently hypomethylated in the minor allele carriers, being cross-dependent on several SNPs. We further investigated whether DNA methylation at these CpGs is associated with depressive psychiatric phenotypes in independent cohorts. The first site (cg02825527) was hypomethylated in blood (exp(β) = 84.521, p value ~ 0.003) in participants with severe suicide attempts (n = 88). The same locus showed increased methylation in glial cells (exp(β) = 0.041, p value ~ 0.004) in the validation cohort, involving 29 depressed patients and 29 controls, and showed a trend for association with suicide (n = 40, p value ~ 0.089) and trend for association with depression treatment (n = 377, p value ~ 0.075). The second CpG (cg18302629) was significantly hypomethylated in depressed participants (exp(β) = 56.374, p value ~ 0.023) in glial cells, but did not show associations in the discovery cohorts. The last methylation site (cg19624444) was hypomethylated in the whole blood of severe suicide attempters; however, this association was at the borderline for statistical significance (p value ~ 0.061). This locus, however, showed a strong association with depression treatment in the validation cohort (exp(β) = 2.237, p value ~ 0.003) with 377 participants. The direction of associations between psychiatric phenotypes appeared to be different in the whole blood in comparison with brain samples for cg02825527 and cg19624444. The association analysis between methylation at cg18302629 and cg19624444 and MAD1L1 transcript levels in CD¹⁴⁺ cells shows a potential link between methylation at these CpGs and MAD1L1 expression. This study suggests evidence that methylation at MAD1L1 is important for psychiatric health as supported by several independent cohorts.

PMID:36600305 | DOI:10.1186/s13148-022-01394-5

World J Emerg Surg. 2023 Jan 4;18(1):2. doi: 10.1186/s13017-022-00472-6.

ABSTRACT

BACKGROUND: A structured approach involves systematic management of trauma patients. We aim to conduct an overview of reviews about the clinical efficacy and safety of structured approach (i.e., primary and secondary survey) by guideline checklist compared to non-structured approach (i.e. clinical examination); moreover, routine screening whole-body computer tomography (WBCT) was compared to non-routine WBCT in patients with suspected major trauma.

METHODS: We systematically searched MEDLINE (PubMed), EMBASE and Cochrane Database of Systematic Reviews up to 3 May 2022. Systematic reviews (SRs) that investigated the use of a structured approach compared to a non-structured approach were eligible. Two authors independently extracted data, managed the overlapping of primary studies belonging to the included SRs and calculated the corrected covered area (CCA). The certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology.

RESULTS: We included nine SRs investigating two comparisons in stable trauma patients: structured approach vs non-structured approach (n = 1) and routine WBCT vs non-routine WBCT (n = 8). The overlap of included primary studies was generally high across outcomes (CCA ranged between 20.85 and 42.86%) with some discrepancies in the directions of effects across reviews. The application of a structured approach by checklist may improve adherence to guidelines (e.g. Advanced Trauma Life Support) during resuscitation and might lead to a reduction in mortality among severely injured patients as compared to clinical examination (Adjusted OR 0.51; 95% CI 0.30-0.89; p = 0.018; low certainty of evidence). The use of routine WBCT seems to offer little to no effects in reducing mortality and time spent in emergency room or department, whereas non-routine WBCT seems to offer little to no effects in reducing radiation dose, intensive care unit length of stay (LOS) and hospital LOS (low-to-moderate certainty of evidence).

CONCLUSIONS: The application of structured approach by checklist during trauma resuscitation may improve patient- and process-related outcomes. Including non-routine WBCT seems to offer the best trade-offs between benefits and harm. Clinicians should consider these findings in the light of their clinical context, the volume of patients in their facilities, the need for time management, and costs.

PMID:36600301 | DOI:10.1186/s13017-022-00472-6

Arch Public Health. 2023 Jan 4;81(1):2. doi: 10.1186/s13690-022-01022-x.

ABSTRACT

BACKGROUND: Reinforcing self-efficacy in patients is important in person-centered care; therefore, reliable and valid measures of a person’s self-efficacy is of clinical relevance. A questionnaire suitable for self-efficacy and patient engagement that is not limited to a particular condition is the Self-efficacy to Manage Chronic Disease (SEMCD). This study aims to evaluate the measurement properties of a Swedish translation of the SEMCD with a Rasch analysis.

METHODS: The translation and cultural adaptation of the SEMCD was performed according to the International Society for Pharmacoeconomics and Outcomes Research (ISPOR) recommendations. Self-reported data was collected from two cohorts: patients with pituitary tumors (n = 86) and patients on sick leave due to common mental disorders (n = 209). Measurement properties were evaluated with a Rasch analysis in RUMM2030.

RESULTS: The original six-item SEMCD did not fit to a unidimensional scale. Two items, item 5 and item 6, deviated both statistically and conceptually and were removed. A four-item solution, the SEMCD-4 with collapsed thresholds for mid-range response options, showed good targeting and unidimensionality, no item misfit, and a reliability of 0.83.

CONCLUSION: In a Swedish context with a mix of patients with pituitary tumors or common mental disorders, SEMCD-4 showed satisfactory measurement properties. Thus, SEMCD-4 could be used to identify patient self-efficacy in long-term illnesses. This knowledge about patient self-efficacy may be of importance to tailor person-centered support based on each patient´s resources, needs and goals.

PMID:36600298 | DOI:10.1186/s13690-022-01022-x

BMC Med. 2023 Jan 5;21(1):9. doi: 10.1186/s12916-022-02703-8.

ABSTRACT

BACKGROUND: Understanding the relationship between chronic pain conditions and suicidal behavior-suicide attempt, other intentional self-harm, and death by suicide-is imperative for suicide prevention efforts. Although chronic pain conditions are associated with suicidal behaviors, these associations might be attributed to unmeasured confounding or mediated via pain comorbidity.

METHODS: We linked a population-based Swedish twin study (N=17,148 twins) with 10 years of longitudinal, nationwide records of suicidal behavior from health and mortality registers through 2016. To investigate whether pain comorbidity versus specific pain conditions were more important for later suicidal behavior, we modeled a general factor of pain and two independent specific pain factors (measuring pain-related somatic symptoms and neck-shoulder pain, respectively) based on 9 self-reported chronic pain conditions. To examine whether the pain-suicidal behavior associations were attributable to familial confounding, we applied a co-twin control model.

RESULTS: Individuals scoring one standard deviation above the mean on the general pain factor had a 51% higher risk of experiencing suicidal behavior (odds ratio (OR), 1.51; 95% confidence interval (CI), 1.34-1.72). The specific factor of somatic pain was also associated with increased risk for suicidal behavior (OR, 1.80; 95% CI, 1.45-2.22]). However, after adjustment for familial confounding, the associations were greatly attenuated and not statistically significant within monozygotic twin pairs (general pain factor OR, 0.89; 95% CI, 0.59-1.33; somatic pain factor OR, 1.02; 95% CI, 0.49-2.11) CONCLUSION: Clinicians might benefit from measuring not only specific types of pain, but also pain comorbidity; however, treating pain might not necessarily reduce future suicidal behavior, as the associations appeared attributable to familial confounding.

PMID:36600296 | DOI:10.1186/s12916-022-02703-8