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Cohort profile: BioMD-Y (biopsychosocial factors of major depression in youth) - a biobank study on the molecular genetics and environmental factors of depression in children and adolescents in Munich

Por: Scherff · A. D. · Feldmann · L. · Piechaczek · C. · Pehl · V. · Wagenbüchler · P. · Wermuth · I. · Ghotbi · N. · Allgaier · A.-K. · Freisleder · F. J. · Beins · E. C. · Forstner · A. J. · Nöthen · M. M. · Czamara · D. · Rex-Haffner · M. · Ising · M. · Binder · E. · Greimel · E. · Sch
Purpose

BioMD-Y is a comprehensive biobank study of children and adolescents with major depression (MD) and their healthy peers in Germany, collecting a host of both biological and psychosocial information from the participants and their parents with the aim of exploring genetic and environmental risk and protective factors for MD in children and adolescents.

Participants

Children and adolescents aged 8–18 years are recruited to either the clinical case group (MD, diagnosis of MD disorder) or the typically developing control group (absence of any psychiatric condition).

Findings to date

To date, four publications on both genetic and environmental risk and resilience factors (including FKBP5, glucocorticoid receptor activation, polygenic risk scores, psychosocial and sociodemographic risk and resilience factors) have been published based on the BioMD-Y sample.

Future plans

Data collection is currently scheduled to continue into 2026. Research questions will be further addressed using available measures.

Did the COVID-19 pandemic affect levels of burnout, anxiety and depression among doctors and nurses in Bangladesh? A cross-sectional survey study

Por: Hutchings · H. A. · Rahman · M. · Carter · K. · Islam · S. · O'Neill · C. · Roberts · S. · John · A. · Fegan · G. · Dave · U. · Hawkes · N. · Ahmed · F. · Hasan · M. · Azad · A. K. · Rahman · M. M. · Kibria · M. G. · Rahman · M. M. · Mia · T. · Akhter · M. · Williams · J. G.
Introduction

COVID-19 has caused severe disruption to clinical services in Bangladesh but the extent of this, and the impact on healthcare professionals is unclear. We aimed to assess the perceived levels of anxiety, depression and burnout among doctors and nurses during COVID-19 pandemic.

Methods

We undertook an online survey using RedCap, directed at doctors and nurses across four institutions in Bangladesh (The Sheikh Russel Gastro Liver Institute & Hospital (SRNGIH), Dhaka Medical College Hospital (DMCH), Mugda Medical College Hospital (MMCH) and M Abdur Rahim Medical College (MARMC) Hospital). We collected information on demographics, awareness of well-being services, COVID-19-related workload, as well as anxiety, depression and burnout using two validated questionnaires: the Hospital Anxiety and Depression Scale (HADS) and the Maslach Burnout Inventory (MBI).

Results

Of the 3000 participants approached, we received responses from 2705 (90.2%). There was a statistically significant difference in anxiety, depression and burnout scores across institutions (p

Conclusion

We identified a high prevalence of perceived anxiety, depression and burnout among doctors and nurses during the COVID-19 pandemic. This was worse in staff engaged in COVID-19-related activities. These findings could help healthcare organisations to plan for future similar events.

Knowledge, attitude and practices of insulin therapy among patients with type 2 diabetes: a cross-sectional study

Por: Almheiri · A. · Binjab · E. A. · Albloushi · M. M. · Alshamsi · M. T. · Khansaheb · H. H. · Zidan · M. · Hassoun · A. A. K.
Objectives

This study aimed to assess the knowledge, attitude and practices of patients with type 2 diabetes on insulin regarding insulin therapy.

Design

A cross-sectional study.

Setting

This study was conducted at the Dubai Diabetes Center from 1 December 2018 to 1 March 2020.

Participants

Face-to-face interviews were conducted for 350 participants with type 2 diabetes at the Dubai Diabetes Center. Interviews followed the structured format of a questionnaire designed to obtain demographic details and score participants on knowledge, attitude and practices. We included patients aged >18 years and receiving insulin therapy. Patients with type 1 diabetes, pregnant women with gestational diabetes, those aged

Results

The median age of participants was 61 years (first quartile, 53 years; third quartile, 67 years); 35.7% were male individuals and 64.3% were female individuals. The median percentage scores for knowledge, attitude and practices were 62.5% (62.5%, 75%), 85.7% (71.4%, 100%) and 77.7% (66.6%, 88.8%), respectively. Highly educated participants had a high level of knowledge. Significant negative correlations were found between the percentage knowledge scores and participants’ age and between the participants’ percentage attitude scores and haemoglobin A1C levels; Spearman’s correlations were –0.182 (p

Conclusion

Patients with type 2 diabetes receiving insulin therapy and attending the Dubai Diabetes Center had adequate knowledge, a positive attitude and correct practice regarding insulin therapy. However, knowledge of specific facts did not always translate into correct behaviours and practices.

Prevalence and determinants of antibiotics self-medication among indigenous people of Bangladesh: a cross-sectional study

Por: Mannan · A. · Chakma · K. · Dewan · G. · Saha · A. · Chy · N. U. H. A. · Mehedi · H. M. H. · Hossain · A. · Wnaiza · J. · Ahsan · M. T. · Rana · M. M. · Alam · N.
Objectives

Self-medication with antibiotics (SMA) contributes significantly to the emergence of antimicrobial resistance (AMR), especially in low-income countries including Bangladesh. This study aimed to generate evidence on the self-reported prevalence of antibiotic self-medication and its determinants among indigenous people residing in Bangladesh’s Chittagong Hill Tracts (CHT) districts.

Design

This study used a cross-sectional design with data collected through a survey using a semi-structured questionnaire.

Setting

This study was conducted from late January to early July 2021; among different indigenous group populations aged 18 years or more olders residing in the three districts of CHT.

Participants

A total of 1336 indigenous people residing in Bangladesh’s CHT districts were included.

Primary outcome and explanatory variables

The primary outcome measure was SMA while explanatory variables were socio-demographic characteristics, health status of participants, and knowledge of antibiotics usage and its side effects.

Results

Among the study participants, more males (60.54%) than females (51.57%) reported using antibiotics. The SMA rate was high among individuals with education levels below secondary (over 50%) and those in the low-income group (55.19%). The most common diseases reported were cough, cold and fever, with azithromycin being the most frequently used antibiotic. Levels of education, family income, having a chronic illness and place of residence were found to be the significant predictors of having good knowledge of antibiotic use as found in the ordered logit model. Findings from a logistic regression model revealed that men had 1.6 times higher odds (adjusted OR (AOR) 1.57; 95% CI 1.12 to 2.19) of SMA than women. Participants with ≥US$893 per month family income had lowest odds (AOR 0.14; 95% CI 0.03 to 0.64) of SMA than those who earned

Conclusion

Male gender, family income, place of residence and knowledge of antibiotics were the significant predictors of antibiotic self-medication. Hence, it is important to streamline awareness-raising campaigns at the community level to mitigate the practice of SMA in indigenous people and ultimately address the devastating effects of Antimicrobial resistance (AMR) in Bangladesh.

Enhanced active case finding of drug-resistant tuberculosis in Namibia: a protocol for the hotspots, hospitals, and households (H3TB) study

Por: Shavuka · O. · Iipumbu · E. · Boois · L. · Günther · G. · Hoddinott · G. · Lin · H.-H. · Nepolo · E. · Niemann · S. · Ruswa · N. · Seddon · J. · Claassens · M. M.
Introduction

Namibia is a high tuberculosis (TB)-burden country with an estimated incidence of 460/100 000 (around 12 000 cases) per year. Approximately 4.5% of new cases and 7.9% of previously treated TB cases are multidrug resistant (MDR) and 47% of patients with MDR-TB are HIV coinfected. Published data suggest a clustering of MDR-TB transmission in specific areas. Identifying transmission clusters is key to implementing high-yield and cost-effective interventions. This includes knowing the yield of finding TB cases in high-transmission zones (eg, community hotspots, hospitals or households) to deliver community-based interventions. We aim to identify such transmission zones for enhanced case finding and evaluate the effectiveness of this approach.

Methods and analysis

H3TB is an observational cross-sectional study evaluating MDR-TB active case finding strategies. Sputum samples from MDR-TB cases in three regions of Namibia will be evaluated by whole genome sequencing (WGS) in addition to routine sputum investigations (Xpert MTB/RIF, culture and drug susceptibility testing). We will collect information on household contacts, use of community spaces and geographical map intersections between participants, synthesising these data to identify transmission hotspots. We will look at the feasibility, acceptability, yield and cost of case finding strategies in these hotspots, and in households of patients with MDR-TB and visitors of hospitalised patients with MDR-TB. A compartmental transmission dynamic model will be constructed to evaluate the impact and cost-effectiveness of the strategies if scaled.

Ethics and dissemination

Ethics approval was obtained. Participants will give informed consent. H3TB will capitalise on a partnership with the Ministry of Health and Social Services to follow up individuals diagnosed with MDR-TB and integrate WGS data with innovative contact network mapping, to allow enhanced case finding. Study data will contribute towards a systems approach to TB control. Equally important, it will serve as a role model for similar studies in other high-incidence settings.

Cohort profile: PRESTIGIO, an Italian prospective registry-based cohort of people with HIV-1 resistant to reverse transcriptase, protease and integrase inhibitors

Por: Clemente · T. · Galli · L. · Lolatto · R. · Gagliardini · R. · Lagi · F. · Ferrara · M. · Cattelan · A. M. · Foca · E. · Di Biagio · A. · Cervo · A. · Calza · L. · Maggiolo · F. · Marchetti · G. · Cenderello · G. · Rusconi · S. · Zazzi · M. · Santoro · M. M. · Spagnuolo · V. · Castagna · A.
Purpose

The PRESTIGIO Registry was established in 2017 to collect clinical, virological and immunological monitoring data from people living with HIV (PLWH) with documented four-class drug resistance (4DR). Key research purposes include the evaluation of residual susceptibility to specific antiretrovirals and the validation of treatment and monitoring strategies in this population.

Participants

The PRESTIGIO Registry collects annual plasma and peripheral blood mononuclear cell samples and demographic, clinical, virological, treatment and laboratory data from PLWH followed at 39 Italian clinical centres and characterised by intermediate-to-high genotypic resistance to ≥1 nucleoside reverse transcriptase inhibitors, ≥1 non-nucleoside reverse transcriptase inhibitors, ≥1 protease inhibitors, plus either intermediate-to-high genotypic resistance to ≥1 integrase strand transfer inhibitors (INSTIs) or history of virological failure to an INSTI-containing regimen. To date, 229 people have been recorded in the cohort. Most of the data are collected from the date of the first evidence of 4DR (baseline), with some prebaseline information obtained retrospectively. Samples are collected from the date of enrollment in the registry.

Findings to date

The open-ended cohort has been used to assess (1) prognosis in terms of survival or development of AIDS-related or non-AIDS-related clinical events; (2) long-term efficacy and safety of different antiretroviral regimens and (3) virological and immunological factors predictive of clinical outcome and treatment efficacy, especially through analysis of plasma and cell samples.

Future plans

The registry can provide new knowledge on how to implement an integrated approach to study PLWH with documented resistance to the four main antiretroviral classes, a population with a limited number of individuals characterised by a high degree of frailty and complexity in therapeutic management. Given the scheduled annual updates of PLWH data, the researchers who collaborate in the registry can send study proposals at any time to the steering committee of the registry, which evaluates every 3 months whether the research studies can be conducted on data and biosamples from the registry and whether they are aimed at a better understanding of a specific health condition, the emergence of comorbidities or the effect of potential treatments or experimental drugs that may have an impact on disease progression and quality of life. Finally, the research studies should aim to be inclusive, innovative and in touch with the communities and society as a whole.

Trial registration number

NCT04098315.

Use of drugs for hyperlipidaemia and diabetes and risk of primary and secondary brain tumours: nested case-control studies using the UK Clinical Practice Research Datalink (CPRD)

Por: Robinson · J. W. · Martin · R. · Ozawa · M. · Elwenspoek · M. M. C. · Redaniel · M. T. · Kurian · K. · Ben-Shlomo · Y.
Objectives

Previous studies have suggested that fibrates and glitazones may have a role in brain tumour prevention. We examined if there is support for these observations using primary care records from the UK Clinical Practice Research Datalink (CPRD).

Design

We conducted two nested case–control studies using primary and secondary brain tumours identified within CPRD between 2000 and 2016. We selected cases and controls among the population of individuals who had been treated with any anti-diabetic or anti-hyperlipidaemic medication to reduce confounding by indication.

Setting

Adults older than 18 years registered with a general practitioner in the UK contributing data to CPRD.

Results

We identified 7496 individuals with any brain tumour (4471 primary; 3025 secondary) in total. After restricting cases and controls to those prescribed any anti-diabetic or anti-hyperlipidaemic medication, there were 1950 cases and 7791 controls in the fibrate and 480 cases with 1920 controls in the glitazone analyses. Longer use of glitazones compared with all other anti-diabetic medications was associated with a reduced risk of primary (adjusted OR (aOR) 0.89 per year, 95% CI 0.80 to 0.98), secondary (aOR 0.87 per year, 95% CI 0.77 to 0.99) or combined brain tumours (aOR 0.88 per year, 95% CI 0.81 to 0.95). There was little evidence that fibrate exposure was associated with risk of either primary or secondary brain tumours.

Conclusions

Longer exposure to glitazones was associated with reduced primary and secondary brain tumour risk. Further basic science and population-based research should explore this finding in greater detail, in terms of replication and mechanistic studies.

Systematic review of best practices for GPS data usage, processing, and linkage in health, exposure science and environmental context research

Por: Pearson · A. L. · Tribby · C. · Brown · C. D. · Yang · J.-A. · Pfeiffer · K. · Jankowska · M. M.

Global Positioning System (GPS) technology is increasingly used in health research to capture individual mobility and contextual and environmental exposures. However, the tools, techniques and decisions for using GPS data vary from study to study, making comparisons and reproducibility challenging.

Objectives

The objectives of this systematic review were to (1) identify best practices for GPS data collection and processing; (2) quantify reporting of best practices in published studies; and (3) discuss examples found in reviewed manuscripts that future researchers may employ for reporting GPS data usage, processing and linkage of GPS data in health studies.

Design

A systematic review.

Data sources

Electronic databases searched (24 October 2023) were PubMed, Scopus and Web of Science (PROSPERO ID: CRD42022322166).

Eligibility criteria

Included peer-reviewed studies published in English met at least one of the criteria: (1) protocols involving GPS for exposure/context and human health research purposes and containing empirical data; (2) linkage of GPS data to other data intended for research on contextual influences on health; (3) associations between GPS-measured mobility or exposures and health; (4) derived variable methods using GPS data in health research; or (5) comparison of GPS tracking with other methods (eg, travel diary).

Data extraction and synthesis

We examined 157 manuscripts for reporting of best practices including wear time, sampling frequency, data validity, noise/signal loss and data linkage to assess risk of bias.

Results

We found that 6% of the studies did not disclose the GPS device model used, only 12.1% reported the per cent of GPS data lost by signal loss, only 15.7% reported the per cent of GPS data considered to be noise and only 68.2% reported the inclusion criteria for their data.

Conclusions

Our recommendations for reporting on GPS usage, processing and linkage may be transferrable to other geospatial devices, with the hope of promoting transparency and reproducibility in this research.

PROSPERO registration number

CRD42022322166.

Effectiveness of dexmedetomidine during surgery under general anaesthesia on patient-centred outcomes: a systematic review and Bayesian meta-analysis protocol

Por: Verret · M. · Le · J. B. P. · Lalu · M. M. · McIsaac · D. I. · Nicholls · S. · Turgeon · A. F. · Hutton · B. · Zivkovic · F. · Graham · M. · Le · M. · Geist · A. · Berube · M. · Gilron · I. · Poulin · P. · Daudt · H. · Martel · G. · McVicar · J. · Moloo · H. · Fergusson · D. A.
Introduction

Dexmedetomidine is a promising pharmaceutical strategy to minimise opioid use during surgery. Despite its growing use, it is uncertain whether dexmedetomidine can improve patient-centred outcomes such as quality of recovery and pain.

Methods and analysis

We will conduct a systematic review and meta-analysis following the recommendations of the Cochrane Handbook for Systematic Reviews. We will search MEDLINE, Embase, CENTRAL, Web of Science and CINAHL approximately in October 2023. We will include randomised controlled trials evaluating the impact of systemic intraoperative dexmedetomidine on patient-centred outcomes. Patient-centred outcome definition will be based on the consensus definition established by the Standardised Endpoints in Perioperative Medicine initiative (StEP-COMPAC). Our primary outcome will be the quality of recovery after surgery. Our secondary outcomes will be patient well-being, function, health-related quality of life, life impact, multidimensional assessment of postoperative acute pain, chronic pain, persistent postoperative opioid use, opioid-related adverse events, hospital length of stay and adverse events. Two reviewers will independently screen and identify trials and extract data. We will evaluate the risk of bias of trials using the Cochrane Risk of Bias Tool (RoB 2.0). We will synthesise data using a random effects Bayesian model framework, estimating the probability of achieving a benefit and its clinical significance. We will assess statistical heterogeneity with the tau-squared and explore sources of heterogeneity with meta-regression. We have involved patient partners, clinicians, methodologists, and key partner organisations in the development of this protocol, and we plan to continue this collaboration throughout all phases of this systematic review.

Ethics and dissemination

Our systematic review does not require research ethics approval. It will help inform current clinical practice guidelines and guide development of future randomised controlled trials. The results will be disseminated in open-access peer-reviewed journals, presented at conferences and shared among collaborators and networks.

PROSPERO registration number

CRD42023439896.

Integrating 4 methods to evaluate physical function in patients with cancer (In4M): protocol for a prospective cohort study

Por: Thanarajasingam · G. · Kluetz · P. · Bhatnagar · V. · Brown · A. · Cathcart-Rake · E. · Diamond · M. · Faust · L. · Fiero · M. H. · Huntington · S. · Jeffery · M. M. · Jones · L. · Noble · B. · Paludo · J. · Powers · B. · Ross · J. S. · Ritchie · J. D. · Ruddy · K. · Schellhorn · S. · Tarv
Introduction

Accurate, patient-centred evaluation of physical function in patients with cancer can provide important information on the functional impacts experienced by patients both from the disease and its treatment. Increasingly, digital health technology is facilitating and providing new ways to measure symptoms and function. There is a need to characterise the longitudinal measurement characteristics of physical function assessments, including clinician-reported outcome, patient-reported ported outcome (PRO), performance outcome tests and wearable data, to inform regulatory and clinical decision-making in cancer clinical trials and oncology practice.

Methods and analysis

In this prospective study, we are enrolling 200 English-speaking and/or Spanish-speaking patients with breast cancer or lymphoma seen at Mayo Clinic or Yale University who will receive intravenous cytotoxic chemotherapy. Physical function assessments will be obtained longitudinally using multiple assessment modalities. Participants will be followed for 9 months using a patient-centred health data aggregating platform that consolidates study questionnaires, electronic health record data, and activity and sleep data from a wearable sensor. Data analysis will focus on understanding variability, sensitivity and meaningful changes across the included physical function assessments and evaluating their relationship to key clinical outcomes. Additionally, the feasibility of multimodal physical function data collection in real-world patients with breast cancer or lymphoma will be assessed, as will patient impressions of the usability and acceptability of the wearable sensor, data aggregation platform and PROs.

Ethics and dissemination

This study has received approval from IRBs at Mayo Clinic, Yale University and the US Food and Drug Administration. Results will be made available to participants, funders, the research community and the public.

Trial registration number

NCT05214144; Pre-results.

Protocol for the challenge non-typhoidal Salmonella (CHANTS) study: a first-in-human, in-patient, double-blind, randomised, safety and dose-escalation controlled human infection model in the UK

Por: Smith · C. · Smith · E. · Rydlova · A. · Varro · R. · Hinton · J. C. D. · Gordon · M. A. · Choy · R. K. M. · Liu · X. · Pollard · A. J. · Chiu · C. · Cooke · G. S. · Gibani · M. M.
Introduction

Invasive non-typhoidal Salmonella (iNTS) serovars are a major cause of community-acquired bloodstream infections in sub-Saharan Africa (SSA). In this setting, Salmonella enterica serovar Typhimurium accounts for two-thirds of infections and is associated with an estimated case fatality rate of 15%–20%. Several iNTS vaccine candidates are in early-stage assessment which—if found effective—would provide a valuable public health tool to reduce iNTS disease burden. The CHANTS study aims to develop a first-in-human Salmonella Typhimurium controlled human infection model, which can act as a platform for future vaccine evaluation, in addition to providing novel insights into iNTS disease pathogenesis.

Methods and analysis

This double-blind, safety and dose-escalation study will randomise 40–80 healthy UK participants aged 18–50 to receive oral challenge with one of two strains of S. Typhimurium belonging to the ST19 (strain 4/74) or ST313 (strain D23580) lineages. 4/74 is a global strain often associated with diarrhoeal illness predominantly in high-income settings, while D23580 is an archetypal strain representing invasive disease-causing isolates found in SSA. The primary objective is to determine the minimum infectious dose (colony-forming unit) required for 60%–75% of participants to develop clinical or microbiological features of systemic salmonellosis. Secondary endpoints are to describe and compare the clinical, microbiological and immunological responses following challenge. Dose escalation or de-escalation will be undertaken by continual-reassessment methodology and limited within prespecified safety thresholds. Exploratory objectives are to describe mechanisms of iNTS virulence, identify putative immune correlates of protection and describe host–pathogen interactions in response to infection.

Ethics and dissemination

Ethical approval has been obtained from the NHS Health Research Authority (London—Fulham Research Ethics Committee 21/PR/0051; IRAS Project ID 301659). The study findings will be disseminated in international peer-reviewed journals and presented at national/international stakeholder meetings. Study outcome summaries will be provided to both funders and participants.

Trial registration number

NCT05870150

Service readiness for the management of non-communicable diseases in publicly financed facilities in Malawi: findings from the 2019 Harmonised Health Facility Assessment census survey

Por: Ahmed · S. · Cao · Y. · Wang · Z. · Coates · M. M. · Twea · P. · Ma · M. · Chiwanda Banda · J. · Wroe · E. · Bai · L. · Watkins · D. A. · Su · Y.
Introduction

Non-communicable diseases (NCDs) are rising in low-income and middle-income countries, including Malawi. To inform policy-makers and planners on the preparedness of the Malawian healthcare system to respond to NCDs, we estimated NCD service readiness in publicly financed healthcare facilities in Malawi.

Methods

We analysed data from 564 facilities surveyed in the 2019 Harmonised Health Facility Assessment, including 512 primary healthcare (PHC) and 52 secondary and tertiary care (STC) facilities. To characterise service readiness, applying the law of minimum, we estimated the percentage of facilities with functional equipment and unexpired medicines required to provide NCD services. Further, we estimated permanently unavailable items to identify service readiness bottlenecks.

Results

Fewer than 40% of PHC facilities were ready to deliver services for each of the 14 NCDs analysed. Insulin and beclomethasone inhalers had the lowest stock levels at PHC facilities (6% and 8%, respectively). Only 17% of rural and community hospitals (RCHs) have liver and kidney diagnostics. STC facilities had varying service readiness, ranging from 27% for managing acute diabetes complications to 94% for chronic type 2 diabetes management. Only 38% of STC facilities were ready to manage chronic heart failure. Oral pain medicines were widely available at all levels of health facilities; however, only 22% of RCHs and 29% of STCs had injectable morphine or pethidine. Beclomethasone was never available at 74% of PHC and 29% of STC facilities.

Conclusion

Publicly financed facilities in Malawi are generally unprepared to provide NCD services, especially at the PHC level. Targeted investments in PHC can substantially improve service readiness for chronic NCD conditions in local communities and enable STC to respond to acute NCD complications and more complex NCD cases.

Adverse drug events associated with nortriptyline compared with paroxetine and alternative medications in an older adult population: a retrospective cohort study in Southern California

Por: George · M. M. · Deamer · R. L. · Do · D.
Objective

Investigate risk for falls, fractures and syncope in older adult patients treated with nortriptyline compared with paroxetine and alternative medications.

Design

Retrospective cohort study.

Setting

The electronic medical record and prescription drug database of a large integrated healthcare system in Southern California.

Participants

Ambulatory patients, age ≥65 years diagnosed with depression, anxiety disorder or peripheral neuropathy, dispensed one or more of ten study medications between 1 January 2008 and 31 December 2018.

Main outcome measures

HR for falls, fractures and syncope with exposure to study medications adjusted for patient demographic variables and comorbidities.

Results

Among 195 207 subjects, 19 305 falls, 15 088 fractures and 11 313 episodes of syncope were observed during the study period. Compared with the reference medication, nortriptyline, the adjusted HRs (aHRs) for falls were statistically significantly greater for: paroxetine (aHR 1.48, 95% CI 1.39 to 1.57), amitriptyline (1.20, 95% CI 1.08 to 1.33), venlafaxine (1.44, 95% CI 1.34 to 1.56), duloxetine (1.25, 95% CI 1.12 to 1.40), fluoxetine (1.51, 95% CI 1.44 to 1.59), sertraline (1.53, 95% CI 1.44 to 1.62), citalopram (1.61, 95% CI 1.52 to 1.71) and escitalopram (1.37, 95% CI 1.21 to 1.54), but not gabapentin (0.95, 95% CI 0.89 to 1.02). For fractures, compared with nortriptyline, aHRs were significantly greater for: paroxetine, venlafaxine, duloxetine, fluoxetine, sertraline, citalopram, escitalopram and gabapentin, with aHRs ranging from 1.30 for gabapentin to 1.82 for escitalopram; risk was statistically similar for amitriptyline. For syncope, the aHRs were significantly greater for: paroxetine, venlafaxine, fluoxetine, sertraline and citalopram, with aHRs ranging from 1.19 for fluoxetine and paroxetine up to 1.30 for citalopram and sertraline; risk was similar for amitriptyline, duloxetine, escitalopram and gabapentin.

Conclusions

Compared with therapeutic alternatives, nortriptyline was found to represent a lower risk for falls, fractures and syncope, versus comparator medications, except for a few instances that had equivalent risk. The risk for these adverse events from paroxetine was comparable to the alternative medications.

Genital tract infections, the vaginal microbiome and gestational age at birth among pregnant women in South Africa: a cohort study protocol

Por: Gigi · R. M. S. · Mdingi · M. M. · Jung · H. · Claassen-Weitz · S. · Bütikofer · L. · Klausner · J. D. · Muzny · C. A. · Taylor · C. M. · van de Wijgert · J. H. H. M. · Peters · R. P. H. · Low · N.
Introduction

Preterm birth complications are the most common cause of death in children under 5 years. The presence of multiple microorganisms and genital tract inflammation could be the common mechanism driving early onset of labour. South Africa has high levels of preterm birth, genital tract infections and HIV infection among pregnant women. We plan to investigate associations between the presence of multiple lower genital tract microorganisms in pregnancy and gestational age at birth.

Methods and analysis

This cohort study enrols around 600 pregnant women at one public healthcare facility in East London, South Africa. Eligible women are ≥18 years and at Chlamydia trachomatis and Neisseria gonorrhoeae, with treatment if test results are positive. At these visits, additional vaginal specimens are taken for: PCR detection and quantification of Trichomonas vaginalis, Candida spp., Mycoplasma genitalium, M. hominis, Ureaplasma urealyticum and U. parvum; microscopy and Nugent scoring; and for 16S ribosomal RNA gene sequencing and quantification. Pregnancy outcomes are collected from a postnatal visit and birth registers. The primary outcome is gestational age at birth. Statistical analyses will explore associations between specific microorganisms and gestational age at birth. To explore the association with the quantity of microorganisms, we will construct an index of microorganism load and use mixed-effects regression models and classification and regression tree analysis to examine which combinations of microorganisms contribute to earlier gestational age at birth.

Ethics and dissemination

This protocol has approvals from the University of Cape Town Research Ethics Committee and the Canton of Bern Ethics Committee. Results from this study will be uploaded to preprint servers, submitted to open access peer-reviewed journals and presented at regional and international conferences.

Trial registration number

NCT06131749; Pre-results.

Protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant: a systematic review and meta-analysis

Por: Rahman · M. O. · Kamigaki · T. · Thandar · M. M. · Haruyama · R. · Yan · F. · Shibamura-Fujiogi · M. · Khin Maung Soe · J. · Islam · M. R. · Yoneoka · D. · Miyahara · R. · Ota · E. · Suzuki · M.
Objectives

The rapid spread of the SARS-CoV-2 Omicron variant has raised concerns regarding waning vaccine-induced immunity and durability. We evaluated protection of the third-dose and fourth-dose mRNA vaccines against SARS-CoV-2 Omicron subvariant and its sublineages.

Design

Systematic review and meta-analysis.

Data sources

Electronic databases and other resources (PubMed, Embase, CENTRAL, MEDLINE, CINAHL PLUS, APA PsycINFO, Web of Science, Scopus, ScienceDirect, MedRxiv and bioRxiv) were searched until December 2022.

Study eligibility criteria

We included studies that assessed the effectiveness of mRNA vaccine booster doses against SARS-CoV-2 infection and severe COVID-19 outcomes caused by the subvariant.

Data extraction and synthesis

Estimates of vaccine effectiveness (VE) at different time points after the third-dose and fourth-dose vaccination were extracted. Random-effects meta-analysis was used to compare VE of the third dose versus the primary series, no vaccination and the fourth dose at different time points. The certainty of the evidence was assessed by Grading of Recommendations, Assessments, Development and Evaluation approach.

Results

This review included 50 studies. The third-dose VE, compared with the primary series, against SARS-CoV-2 infection was 48.86% (95% CI 44.90% to 52.82%, low certainty) at ≥14 days, and gradually decreased to 38.01% (95% CI 13.90% to 62.13%, very low certainty) at ≥90 days after the third-dose vaccination. The fourth-dose VE peaked at 14–30 days (56.70% (95% CI 50.36% to 63.04%), moderate certainty), then quickly declined at 61–90 days (22% (95% CI 6.40% to 37.60%), low certainty). Compared with no vaccination, the third-dose VE was 75.84% (95% CI 40.56% to 111.12%, low certainty) against BA.1 infection, and 70.41% (95% CI 49.94% to 90.88%, low certainty) against BA.2 infection at ≥7 days after the third-dose vaccination. The third-dose VE against hospitalisation remained stable over time and maintained 79.30% (95% CI 58.65% to 99.94%, moderate certainty) at 91–120 days. The fourth-dose VE up to 60 days was 67.54% (95% CI 59.76% to 75.33%, moderate certainty) for hospitalisation and 77.88% (95% CI 72.55% to 83.21%, moderate certainty) for death.

Conclusion

The boosters provided substantial protection against severe COVID-19 outcomes for at least 6 months, although the duration of protection remains uncertain, suggesting the need for a booster dose within 6 months of the third-dose or fourth-dose vaccination. However, the certainty of evidence in our VE estimates varied from very low to moderate, indicating significant heterogeneity among studies that should be considered when interpreting the findings for public health policies.

PROSPERO registration number

CRD42023376698.

Socio-economic inequalities in and factors associated with minimum dietary diversity among children aged 6-23 months in South Asia: a decomposition analysis

Por: Rahman · M. A. · Kundu · S. · Rashid · H. O. · Tohan · M. M. · Islam · M. A.
Objective

This study aimed to determine the factors associated with minimum dietary diversity (MDD) and estimate the socioeconomic inequalities in MDD among children from five South Asian countries.

Design

Cross-sectional.

Setting

The study used the most recent round of secondary databases of Demographic Health Survey data of Bangladesh (2017–2018), India (2019–2021), Maldives (2016–2017), Nepal (2018) and Pakistan (2017–2018).

Participants

This study used information on MDD and other explanatory variables from a total of 136 980 (weighted) children aged 6–23 months.

Methods

Multivariable logistic regression was employed to identify the factors associated with MDD and concentration index (CIX) and Lorenz curve were used to measure the socioeconomic inequalities in MDD.

Results

The overall weighted prevalence of MDD in South Asia was 23.37%. The highest prevalence of MDD was found among children from Maldives (70.7%), while the lowest was in Pakistan (14.2%). Living in affluent versus poor households, having a mother who is employed versus a mother who is unemployed, exposure to various forms of media (newspapers and magazines), seeking antenatal care (ANC) more than four times compared with those who sought ANC less than four times and having children older than 4 years old are the most common significant factors associated with MDD deficiency. This study found the value of the CIX for MDD (MDD: CI=0.0352; p

Conclusion

Inequality in the prevalence of MDD favours the affluent. Health policy and intervention design should prioritise minimising socioeconomic inequalities concerning the MDD. In addition, policy-makers should prioritise the associated factors of MDD such as education, wealth status, employment, media exposure while designing intervention or policies.

Comparative analysis of silver-nanoparticles and whey-encapsulated particles from olive leaf water extracts: Characteristics and biological activity

by Hanem M. M. Mansour, Mohamed G. Shehata, Eman M. Abdo, Mona Mohamad Sharaf, El-sayed E. Hafez, Amira M. Galal Darwish

Nanotechnology applications have been employed to improve the stability of bioactive components and drug delivery. Natural-based extracts, especially olive leaf extracts, have been associated with the green economy not only as recycled agri-waste but also in the prevention and treatment of various non-communicable diseases (NCDs). The aim of this work was to provide a comparison between the characteristics, biological activity, and gene expression of water extract of olive leaves (OLE), green synthesized OLE silver nanoparticles (OL/Ag-NPs), and OLE whey protein capsules (OL/WPNs) of the two olive varieties, Tofahy and Shemlali. The particles were characterized by dynamic light scattering, scanning electron microscope (SEM), and Fourier transform infrared. The bioactive compounds of the preparations were evaluated for their antioxidant activity and anticancer effect on HCT-116 colorectal cells as well as for their regulatory effects on cytochrome C oxidase (Cox1) and tumor necrosis factor α (TNF-α) genes. (OL/Ag-NPs) were found to be smaller than (OL/WPNs) with sizes of (37.46±1.85 and 44.86±1.62 nm) and (227.20±2.43 and 553.02±3.60 nm) for Tofahy and Shemlali, respectively. SEM showed that Shemlali (OL/Ag-NPs) had the least aggregation due to their highest Ƹ-potential (-31.76 ± 0.87 mV). The preparations were relatively nontoxic to Vero cells (IC50 = 151.94–789.25 μg/mL), while they were cytotoxic to HCT-116 colorectal cells (IC50 = 77.54–320.64 μg/mL). Shemlali and Tofahy OLE and Tofahy OL/Ag-NPs had a higher selectivity index (2.97–7.08 μg/mL) than doxorubicin (2.36 μg/mL), indicating promising anticancer activity. Moreover, Shemlali preparations regulated the expression of Cox1 (up-regulation) and TNF-α (down-regulation) on HCT-116 cells, revealing their efficiency in suppressing the expression of genes that promote cancer cell proliferation. (OL/Ag-NPs) from Tofahy and Shemlali were found to be more stable, effective, and safe than (OL/WPNs). Consequently, OL/Ag-NPs, especially Tofahy, are the best and safest nanoscale particles that can be safely used in food and pharmaceutical applications.

Suppression of pathogens in properly refrigerated raw milk

by M. E. Coleman, T. P. Oscar, T. L. Negley, M. M. Stephenson

Conflicting claims exist regarding pathogen growth in raw milk. A small pilot study was designed to provide definitive data on trends for pathogen growth and decline in raw bovine milk hygienically produced for direct human consumption. An independent laboratory conducted the study, monitoring growth and decline of pathogens inoculated into raw milk. Raw milk samples were inoculated with foodborne pathogens (Campylobacter, E. coli O157:H7, Listeria monocytogenes, or Salmonella) at lower (L. monocytogenes in 8 of 12 replicates (P = 0.001 to P = 0.028). Analysis of variance confirmed significant increases for L. monocytogenes at both initial levels in week 2. No evidence of growth was documented over 14 days for the three pathogens predominantly associated with raw milk outbreaks in the US (Campylobacter, E. coli O157:H7, and Salmonella). Further research is needed to characterize parameters for pathogen growth and decline to support re-assessment of risks that were based on incorrect assumptions about interactions of pathogens with the raw milk microbiota.

Test negative case-control study of COVID-19 vaccine effectiveness for symptomatic SARS-CoV-2 infection among healthcare workers: Zambia, 2021-2022

Por: Mweso · O. · Simwanza · J. · Malambo · W. · Banda · D. · Fwoloshi · S. · Sinyange · N. · Yoo · Y. M. · Feldstein · L. R. · Kapina · M. · Mulenga · L. B. · Liwewe · M. M. · Musonda · K. · Kapata · N. · Mwansa · F. D. · Agolory · S. · Bobo · P. · Hines · J. · Chilengi · R.
Objectives

The study aim was to evaluate vaccine effectiveness (VE) of COVID-19 vaccines in preventing symptomatic COVID-19 among healthcare workers (HCWs) in Zambia. We sought to answer the question, ‘What is the vaccine effectiveness of a complete schedule of the SARS-CoV-2 vaccine in preventing symptomatic COVID-19 among HCWs in Zambia?’

Design/setting

We conducted a test-negative case–control study among HCWs across different levels of health facilities in Zambia offering point of care testing for COVID-19 from May 2021 to March 2022.

Participants

1767 participants entered the study and completed it. Cases were HCWs with laboratory-confirmed SARS-CoV-2 and controls were HCWs who tested SARS-CoV-2 negative. Consented HCWs with documented history of vaccination for COVID-19 (vaccinated HCWs only) were included in the study. HCWs with unknown test results and unknown vaccination status, were excluded.

Primary and secondary outcome measures

The primary outcome was VE among symptomatic HCWs. Secondary outcomes were VE by: SARS-CoV-2 variant strains based on the predominant variant circulating in Zambia (Delta during May 2021 to November 2021 and Omicron during December 2021 to March 2022), duration since vaccination and vaccine product.

Results

We recruited 1145 symptomatic HCWs. The median age was 30 years (IQR: 26–38) and 789 (68.9%) were women. Two hundred and eighty-two (24.6%) were fully vaccinated. The median time to full vaccination was 102 days (IQR: 56–144). VE against symptomatic SARS-CoV-2 infection was 72.7% (95% CI: 61.9% to 80.7%) for fully vaccinated participants. VE was 79.4% (95% CI: 58.2% to 90.7%) during the Delta period and 37.5% (95% CI: –7.0% to 63.3%) during the Omicron period.

Conclusions

COVID-19 vaccines were effective in reducing symptomatic SARS-CoV-2 among Zambian HCWs when the Delta variant was circulating but not when Omicron was circulating. This could be related to immune evasive characteristics and/or waning immunity. These findings support accelerating COVID-19 booster dosing with bivalent vaccines as part of the vaccination programme to reduce COVID-19 in Zambia.

Metformin for knee osteoarthritis with obesity: study protocol for a randomised, double-blind, placebo-controlled trial

Por: Lim · Y. Z. · Wang · Y. · Urquhart · D. M. · Estee · M. M. · Wluka · A. E. · Heritier · S. · Cicuttini · F. M.
Introduction

Over half of the populations with knee osteoarthritis (OA) have obesity. These individuals have many other shared metabolic risk factors. Metformin is a safe, inexpensive, well-tolerated drug that has pleiotropic effects, including structural protection, anti-inflammatory and analgesic effects in OA, specifically the knee. The aim of this randomised, double-blind, placebo-controlled trial is to determine whether metformin reduces knee pain over 6 months in individuals with symptomatic knee OA who are overweight or obese.

Methods and analysis

One hundred and two participants with symptomatic knee OA and overweight or obesity will be recruited from the community in Melbourne, Australia, and randomly allocated in a 1:1 ratio to receive either metformin 2 g or identical placebo daily for 6 months. The primary outcome is reduction of knee pain [assessed by 100 mm Visual Analogue Scale (VAS)] at 6 months. The secondary outcomes are OMERACT-OARSI (Outcome Measures in Rheumatology-Osteoarthritis Research Society International) responder criteria [Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) pain, function and participant’s global assessment (VAS)] at 6 months; change in knee pain, stiffness, function using WOMAC at 6 months and quality of life at 6 months. Adverse events will be recorded. The primary analysis will be by intention to treat, including all participants in their randomised groups.

Ethics and dissemination

Ethics approval has been obtained from the Alfred Hospital Ethics Committee (708/20) and Monash University Human Research Ethics Committee (28498). Written informed consent will be obtained from all the participants. The findings will be disseminated through peer-review publications and conference presentations.

Trial registration number

ACTRN12621000710820 .

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