Nevin Manimala

BMJ Sex Reprod Health. 2023 Sep 12:bmjsrh-2023-201931. doi: 10.1136/bmjsrh-2023-201931. Online ahead of print.

ABSTRACT

OBJECTIVE: We used the newly developed Abortion Care Quality Tool (ACQTool) to compare client-reported quality of medication abortion care by source (facility-managed vs pharmacy-sourced self-managed abortion (SMA)) in Bangladesh.

METHODS: We leveraged exit and 30-day follow-up surveys collected to develop and validate the ACQTool collected at nongovernmental organisation (NGO)-supported or -operated facilities in the public and private sector and pharmacies from three districts in Bangladesh. We used bivariate statistics to compare 18 client-reported quality indicators grouped in six domains and eight abortion outcomes, by source (facility vs pharmacy). We used multivariable logistic regression to identify factors associated with selected quality indicators and outcomes (abortion affordability, information provision, and knowing what to do for an adverse event), controlling for client sociodemographic characteristics.

RESULTS: Of 550 abortion clients, 146 (26.5%) received a facility-managed medication abortion and 404 (73.5%) had a pharmacy-sourced SMA. Clients reported higher quality in facilities for five indicators, and higher in pharmacies for two indicators; the remaining 11 indicators were not different by source. Compared with facility-based clients, pharmacy clients had higher odds of reporting that the cost of abortion was affordable (adjusted odds ratio (aOR) 3.55; 95% CI 2.27 to 5.58) but lower odds of reporting high information provision (aOR 0.14; 95% CI 0.09 to 0.23). Seven of eight abortion outcomes showed no differences; pharmacy clients had lower odds of knowing what to do if an adverse event occurred (aOR 0.45; 95% CI 0.23 to 0.82).

CONCLUSIONS: In Bangladesh, there is no difference in client-reported quality of medication abortion care between health facilities and pharmacies for the majority of quality and outcome indicators. However, information provision and preparedness were higher quality at facilities, while pharmacies were more affordable.

PMID:37699668 | DOI:10.1136/bmjsrh-2023-201931

J Epidemiol Community Health. 2023 Sep 12:jech-2023-220353. doi: 10.1136/jech-2023-220353. Online ahead of print.

ABSTRACT

BACKGROUND: The social determinants of ethnic disparities in risk of SARS-CoV-2 infection during the first wave of the pandemic in the UK remain unclear.

METHODS: In May 2020, a total of 20 195 adults were recruited from the general population into the UK Biobank SARS-CoV-2 Serology Study. Between mid-May and mid-November 2020, participants provided monthly blood samples. At the end of the study, participants completed a questionnaire on social factors during different periods of the pandemic. Logistic regression yielded ORs for the association between ethnicity and SARS-CoV-2 immunoglobulin G antibodies (indicating prior infection) using blood samples collected in July 2020, immediately after the first wave.

RESULTS: After exclusions, 14 571 participants (mean age 56; 58% women) returned a blood sample in July, of whom 997 (7%) had SARS-CoV-2 antibodies. Seropositivity was strongly related to ethnicity: compared with those of White ethnicity, ORs (adjusted for age and sex) for Black, South Asian, Chinese, Mixed and Other ethnic groups were 2.66 (95% CI 1.94-3.60), 1.66 (1.15-2.34), 0.99 (0.42-1.99), 1.42 (1.03-1.91) and 1.79 (1.27-2.47), respectively. Additional adjustment for social factors reduced the overall likelihood ratio statistics for ethnicity by two-thirds (67%; mostly from occupational factors and UK region of residence); more precise measurement of social factors may have further reduced the association.

CONCLUSIONS: This study identifies social factors that are likely to account for much of the ethnic disparities in SARS-CoV-2 infection during the first wave in the UK, and highlights the particular relevance of occupation and residential region in the pathway between ethnicity and SARS-CoV-2 infection.

PMID:37699665 | DOI:10.1136/jech-2023-220353

Genome Res. 2023 Sep 12. doi: 10.1101/gr.277397.122. Online ahead of print.

ABSTRACT

Three-dimensional (3D) chromatin structure has been shown to play a role in regulating gene transcription during biological transitions. Although our understanding of loop formation and maintenance is rapidly improving, much less is known about the mechanisms driving changes in looping and the impact of differential looping on gene transcription. One limitation has been a lack of well-powered differential looping data sets. To address this, we conducted a deeply sequenced Hi-C time course of megakaryocyte development comprising four biological replicates and 6 billion reads per time point. Statistical analysis revealed 1503 differential loops. Gained loop anchors were enriched for AP-1 occupancy and were characterized by large increases in histone H3K27ac (over 11-fold) but relatively small increases in CTCF and RAD21 binding (1.26- and 1.23-fold, respectively). Linear modeling revealed that changes in histone H3K27ac, chromatin accessibility, and JUN binding were better correlated with changes in looping than RAD21 and almost as well correlated as CTCF. Changes to epigenetic features between-rather than at-boundaries were highly predictive of changes in looping. Together these data suggest that although CTCF and RAD21 may be the core machinery dictating where loops form, other features (both at the anchors and within the loop boundaries) may play a larger role than previously anticipated in determining the relative loop strength across cell types and conditions.

PMID:37699658 | DOI:10.1101/gr.277397.122

Ann Rheum Dis. 2023 Sep 12:ard-2023-224482. doi: 10.1136/ard-2023-224482. Online ahead of print.

ABSTRACT

OBJECTIVES: To investigate the efficacy and safety of otilimab, an antigranulocyte-macrophage colony-stimulating factor antibody, in patients with active rheumatoid arthritis.

METHODS: Two phase 3, double-blind randomised controlled trials including patients with inadequate responses to methotrexate (contRAst 1) or conventional synthetic/biologic disease-modifying antirheumatic drugs (cs/bDMARDs; contRAst 2). Patients received background csDMARDs. Through a testing hierarchy, subcutaneous otilimab (90/150 mg once weekly) was compared with placebo for week 12 endpoints (after which, patients receiving placebo switched to active interventions) or oral tofacitinib (5 mg two times per day) for week 24 endpoints.

PRIMARY ENDPOINT: proportion of patients achieving an American College of Rheumatology response ≥20% (ACR20) at week 12.

RESULTS: The intention-to-treat populations comprised 1537 (contRAst 1) and 1625 (contRAst 2) patients.

PRIMARY ENDPOINT: proportions of ACR20 responders were statistically significantly greater with otilimab 90 mg and 150 mg vs placebo in contRAst 1 (54.7% (p=0.0023) and 50.9% (p=0.0362) vs 41.7%) and contRAst 2 (54.9% (p<0.0001) and 54.5% (p<0.0001) vs 32.5%). Secondary endpoints: in both trials, compared with placebo, otilimab increased the proportion of Clinical Disease Activity Index (CDAI) low disease activity (LDA) responders (not significant for otilimab 150 mg in contRAst 1), and reduced Health Assessment Questionnaire-Disability Index (HAQ-DI) scores. Benefits with tofacitinib were consistently greater than with otilimab across multiple endpoints. Safety outcomes were similar across treatment groups.

CONCLUSIONS: Although otilimab demonstrated superiority to placebo in ACR20, CDAI LDA and HAQ-DI, improved symptoms, and had an acceptable safety profile, it was inferior to tofacitinib.

TRIAL REGISTRATION NUMBERS: NCT03980483, NCT03970837.

PMID:37699654 | DOI:10.1136/ard-2023-224482

BMJ Open. 2023 Sep 12;13(9):e071658. doi: 10.1136/bmjopen-2023-071658.

ABSTRACT

OBJECTIVES: The primary objective of our study was to evaluate the effectiveness of renal cell carcinoma (RCC) screening in renal transplant (RT) recipients.

DESIGN: Single-centre retrospective study.

SETTING AND PARTICIPANTS: 1998 RT recipients who underwent RT at Memorial Hermann Hospital (MHH) Texas Medical Center (TMC) between 1 January 1999 and 31 December 2019 were included and we identified 16 patients (0.8%) with RCC. An additional four patients with RCC who underwent RT elsewhere but received follow-up at MHH TMC were also included. Subject races included white (20%), black (50%), Hispanic (20%) and Asian (10%).

OUTCOME MEASURES: The RCC stage at diagnosis and outcomes were compared between patients who were screening versus those who were not.

RESULTS: We identified a total of 20 patients with post-RT RCC, 75% of whom were men. The median age at diagnosis was 56 years. RCC histologies included clear cell (75%), papillary (20%) and chromophobe (5%). Patients with post-RT RCC who had screening (n=12) underwent ultrasound or CT annually or every 2 years, whereas eight patients had no screening. All 12 patients who had screening had early-stage disease at diagnosis (stage I (n=11) or stage II (n=1)) and were cured by nephrectomy (n=10) or cryotherapy (n=2). In patients who had no screening, three (37.5%) had stage IV RCC at diagnosis and all of whom died of metastatic disease. There was a statistically significant difference in RCC-specific survival in patients who were screened (p=0.01) compared with those who were not screened.

CONCLUSION: All RT recipients who had RCC diagnosed based on screening had early-stage disease and there were no RCC-related deaths. Screening is an effective intervention in RT recipients to reduce RCC-related mortality.

PMID:37699639 | DOI:10.1136/bmjopen-2023-071658

BMJ Open. 2023 Sep 12;13(9):e075598. doi: 10.1136/bmjopen-2023-075598.

ABSTRACT

OBJECTIVE: To determine current UK medical students’ career intentions after graduation and on completing the Foundation Programme (FP), and to ascertain the motivations behind these intentions.

DESIGN: Cross-sectional, mixed-methods survey of UK medical students, using a non-random sampling method.

SETTING: All 44 UK medical schools recognised by the General Medical Council.

PARTICIPANTS: All UK medical students were eligible to participate. The study sample consisted of 10 486 participants, approximately 25.50% of the medical student population.

OUTCOME MEASURES: Career intentions of medical students postgraduation and post-FP, motivations behind these career intentions, characterising the medical student population and correlating demographic factors and propensity to leave the National Health Service (NHS).

RESULTS: The majority of participating students (8806/10 486, 83.98%) planned to complete both years of the FP after graduation, with under half of these students (4294/8806, 48.76%) intending to pursue specialty training thereafter. A subanalysis of career intentions after the FP by year of study revealed a significant decrease in students’ intentions to enter specialty training as they advanced through medical school. Approximately a third of surveyed students (3392/10 486, 32.35%) intended to emigrate to practise medicine, with 42.57% (n=1444) of those students not planning to return. In total, 2.89% of students intended to leave medicine altogether (n=303). Remuneration, work-life balance and working conditions were identified as important factors in decision-making regarding emigration and leaving the profession. Subgroup analyses based on gender, type of schooling, fee type and educational background were performed. Only 17.26% of surveyed students were satisfied or very satisfied with the overall prospect of working in the NHS.

CONCLUSIONS: The Ascertaining the career Intentions of UK Medical Students study highlights UK students’ views and career intentions, revealing a concerning proportion of those surveyed considering alternative careers or emigration. Addressing factors such as remuneration, work-life balance and working conditions may increase retention of doctors and improve workforce planning efforts.

PMID:37699638 | DOI:10.1136/bmjopen-2023-075598

BMJ Open. 2023 Sep 12;13(9):e069499. doi: 10.1136/bmjopen-2022-069499.

ABSTRACT

INTRODUCTION: Recent preclinical studies have discovered unique synergism between radiotherapy and immune checkpoint inhibitors, which has already brought significant survival benefit in lung cancer. In locally advanced rectal cancer (LARC), neoadjuvant radiotherapy plus immune checkpoint inhibitors have also achieved surprisingly high pathological complete response (pCR) rates even in proficient mismatch-repair patients. As existing researches are all phase 2, single-cohort trials, we aim to conduct a randomised, controlled trial to further clarify the efficacy and safety of this novel combination therapy.

METHODS AND ANALYSIS: Eligible patients with LARC are randomised to three arms (two experiment arms, one control arm). Patients in all arms receive long-course radiotherapy plus concurrent capecitabine as neoadjuvant therapy, as well as radical surgery. Distinguishingly, patients in arm 1 also receive anti-PD-1 (Programmed Death 1) treatment starting at Day 8 of radiation (concurrent plan), and patients in arm 2 receive anti-PD-1 treatment starting 2 weeks after completion of radiation (sequential plan). Tislelizumab (anti-PD-1) is scheduled to be administered at 200 mg each time for three consecutive times, with 3-week intervals. Randomisation is stratified by different participating centres, with a block size of 6. The primary endpoint is pCR rate, and secondary endpoints include neoadjuvant-treatment-related adverse event rate, as well as disease-free and overall survival rates at 2, 3 and 5 years postoperation. Data will be analysed with an intention-to-treat approach.

ETHICS AND DISSEMINATION: This protocol has been approved by the institutional ethical committee of Beijing Friendship Hospital (the primary centre) with an identifying serial number of 2022-P2-050-01. Before publication to peer-reviewed journals, data of this research will be stored in a specially developed clinical trial database.

TRIAL REGISTRATION NUMBER: NCT05245474.

PMID:37699634 | DOI:10.1136/bmjopen-2022-069499

BMJ Open. 2023 Sep 12;13(9):e075007. doi: 10.1136/bmjopen-2023-075007.

ABSTRACT

INTRODUCTION: Following the discovery of various effects on skin function by modifying endocannabinoid systems, multiple preclinical studies have revealed the promise of cannabis and cannabinoids in the treatment of a variety of skin diseases. However, its clinical efficacy is still debated.

METHODS AND ANALYSIS: The protocol has been prepared using the Preferred Items for Systematic Review and Meta-analysis Protocols guidelines. A systematic search will be conducted using PubMed, EMBASE, SCOPUS, the Cochrane Central Register of Controlled Trials and Web of Science. We will include randomised controlled trials and observational studies investigating alterations to dermatological characteristics following administration of cannabis and cannabinoids for dermatological diseases and disorders. The two reviewers will perform both the title and abstract and full-text screenings. The Cochrane Risk-of-Bias 2 and ROBINS-1 tools will be used to evaluate the risk of bias. If a group of comparable studies for each quantitative outcome can be discovered, we will conduct a random effects meta-analysis. We will investigate heterogeneity using a combination of visual inspection of the forest plot, the Cochran’s Q test and Higgins’ test [I2]. Sensitivity analyses will be performed to assess the statistical robustness of the primary outcome. To evaluate a publication bias, the Egger’s regression asymmetry test and funnel plots will be considered.

ETHICS AND DISSEMINATION: This study does not require ethical approval because no original data will be collected. The findings will be presented at conferences and published in peer-reviewed journals.

PROSPERO REGISTRATION NUMBER: CRD42023397189.

PMID:37699631 | DOI:10.1136/bmjopen-2023-075007

BMJ Open. 2023 Sep 12;13(9):e073735. doi: 10.1136/bmjopen-2023-073735.

ABSTRACT

OBJECTIVES: Patient experiences are critical when determining the acceptability of novel interventional pharmaceuticals. Here, we report the development and validation of a product acceptability questionnaire (SPRAY PAL) assessing feasibility, acceptability and tolerability of an intranasal Q-Griffithsin (Q-GRFT) drug product designed for COVID-19 prophylaxis.

DESIGN: SPRAY PAL validation was undertaken as part of an ongoing phase 1 clinical trial designed to test the safety, pharmacokinetics and tolerability of intranasally administered Q-GRFT for the prevention of SARS-CoV-2 infection.

SETTING: The phase 1 clinical trial took place at a University Outpatient Clinical Trials Unit from November 2021 to September 2023.

PARTICIPANTS: The initial SPRAY PAL questionnaire was piloted among healthy volunteers ages 25 to 55 in phase 1a of the clinical trial (N=18) and revised for administration in phase 1b for participants ages 24-59 (N=22).

RESULTS: Spearman correlations tested convergent and discriminant validity. Internal consistency was assessed using Cronbach’s alpha, and test-retest reliability was assessed using intraclass correlation coefficients of responses collected from three repeated questionnaire administrations. The initial version demonstrated excellent internal consistency. The revised version demonstrated very good internal consistency after removal of one item (alpha=0.739). Excellent test-retest reliability (intraclass coefficient=0.927) and adequate convergent (r’s=0.208-0.774) and discriminant (r’s=0.123-0.392) validity were achieved. Subscales adequately distinguished between the constructs of acceptability, feasibility and tolerability.

CONCLUSIONS: The SPRAY PAL product acceptability questionnaire is a valid and reliable patient-reported outcomes measure that can be considered a credible tool for assessing patient-reported information about product acceptability, feasibility of use, tolerability of product and side effects and cost of product for novel intranasal drug formulations. The SPRAY PAL is generalisable, and items may be readily adapted to assess other intranasal formulations.

TRIAL REGISTRATION NUMBERS: NCT05122260 and NCT05437029.

PMID:37699630 | DOI:10.1136/bmjopen-2023-073735

BMJ Open. 2023 Sep 12;13(9):e071032. doi: 10.1136/bmjopen-2022-071032.

ABSTRACT

OBJECTIVES: To illustrate the utility of unsupervised machine learning compared with traditional methods of analysis by identifying archetypes within the population that may be more or less likely to get the COVID-19 vaccine.

DESIGN: A longitudinal prospective cohort study (n=2009 households) with recurring phone surveys from 2020 to 2022 to assess COVID-19 knowledge, attitudes and practices. Vaccine questions were added in 2021 (n=1117) and 2022 (n=1121) rounds.

SETTING: Five informal settlements in Nairobi, Kenya.

PARTICIPANTS: Individuals from 2009 households included.

OUTCOME MEASURES AND ANALYSIS: Respondents were asked about COVID-19 vaccine acceptance (February 2021) and vaccine uptake (March 2022). Three distinct clusters were estimated using K-Means clustering and analysed against vaccine acceptance and vaccine uptake outcomes using regression forest analysis.

RESULTS: Despite higher educational attainment and fewer concerns regarding the pandemic, young adults (cluster 3) were less likely to intend to get the vaccine compared with cluster 1 (41.5% vs 55.3%, respectively; p<0.01). Despite believing certain COVID-19 myths, older adults with larger households and more fears regarding economic impacts of the pandemic (cluster 1) were more likely to ultimately to get vaccinated than cluster 3 (78% vs 66.4%; p<0.01), potentially due to employment requirements. Middle-aged women who are married or divorced and reported higher risk of gender-based violence in the home (cluster 2) were more likely than young adults (cluster 3) to report wanting to get the vaccine (50.5% vs 41.5%; p=0.014) but not more likely to have gotten it (69.3% vs 66.4%; p=0.41), indicating potential gaps in access and broader need for social support for this group.

CONCLUSIONS: Findings suggest this methodology can be a useful tool to characterise populations, with utility for improving targeted policy, programmes and behavioural messaging to promote uptake of healthy behaviours and ensure equitable distribution of prevention measures.

PMID:37699627 | DOI:10.1136/bmjopen-2022-071032