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Risk factors for COVID-19 symptom severity across clinical categories among hospitalised patients in Kuala Lumpur, Malaysia: a prospective cohort study

Por: Johdi · N. A. · Abdullah · N. · Goh · Y.-X. · Min · J. O. S. · Muhammad Azami · N. A. · Abdul Jalal · M. I. · Mohammed Nawi · A. · Ahmad · N. · Hassan · M. R. · Sulong · A. · Kori · N. · Periyasamy · P. · Hamid · F. · Sapuan · N. M. · Selvam · S. B. P. · Hajib · N. · Mustafa · N. · Rashi
Objectives

This study aimed to quantify how patient risk factors relate to COVID-19 severity across categories 1–5 in a prospective, hospital-based cohort. We hypothesised that greater severity would be associated with higher odds of intensive care unit (ICU) admission and in-hospital mortality. Secondary aims were to assess associations with age, viral variants, symptom clusters, lymphocyte count, fasting blood glucose and cytokine profiles.

Design

Prospective cohort study.

Setting

A secondary-care/tertiary-care hospital and linked community settings in Cheras, Kuala Lumpur, Malaysia.

Participants

This study was nested within the COVGEN project, a prospective COVID-19 cohort conducted at Hospital Canselor Tuanku Muhriz UKM (HCTM), Cheras Health Clinic and the Bandar Tun Razak COVID-19 Assessment Centre in Cheras, Kuala Lumpur, Malaysia, from 1 August 2021 to 31 October 2022. 2532 participants were enrolled at baseline. Eligible participants were Malaysian citizens aged 12–18 years (paediatric/adolescent) or ≥18 years who had reverse transcription-polymerase chain reaction–confirmed COVID-19 at recruitment and resided in Kuala Lumpur or Selangor. Patients who had a clinically unstable condition and those who declined participation (personally or via a next-of-kin or legal representative) were excluded. This analysis included 559 patients hospitalised at HCTM; after excluding five with incomplete questionnaires, 554 remained for analysis (413 admitted to general wards and 141 to ICUs). Categories 3–5 comprised hospitalised patients, whereas categories 1–2 included hospitalised individuals and a subset recruited from community settings.

Primary and secondary outcome measures

Primary outcomes included disease severity (categories 4–5 vs 1–3), ICU admission and in-hospital mortality. Secondary outcomes included associations with age strata, viral variant (delta vs omicron), symptom clusters, lymphocyte count, fasting blood glucose and cytokines: interferon gamma-inducible protein 10, interferon gamma, interleukins 8, 10, 2, 6 and 7 and tumour necrosis factor alpha.

Results

141 of 554 (25.5%) patients required ICU care. Compared with milder categories, category 5 was associated with markedly higher odds of ICU admission (OR 204.50; 95% CI 37.54 to 1114.18; p55 versus

Conclusions

An increasing clinical severity category was strongly associated with ICU admission and mortality. Age, delta infection, specific symptom clusters, lymphopenia, hyperglycaemia and pro-inflammatory cytokines identified higher-risk patients, supporting risk-stratified management and prioritisation for enhanced monitoring.

Analgesic efficacy of peri-operative methadone in orthopaedic surgery: protocol for a systematic review of randomised controlled trials

Por: Evaldsson · B. B. · Nygaard · K. H. · Petersen · S. R. · Moos · C. M. · Stroem · T. · Specht · K. · Schonnemann · J. O.
Introduction

Optimising post-operative pain management is crucial for recovery in orthopaedic surgery. Methadone has attracted interest due to its long half-life, N-methyl-D-aspartate -receptor antagonism and potential to reduce post-operative opioid consumption. Existing reviews combine multiple surgical populations, limiting applicability to orthopaedic settings. This protocol outlines a systematic review assessing the analgesic efficacy and safety of peri-operative methadone in adult and adolescent orthopaedic patients.

Methods and analysis

This review will include randomised controlled trials evaluating intravenous peri-operative methadone vs placebo or standard analgesic regimens in orthopaedic surgery. Primary outcomes are post-operative rescue opioid consumption and pain intensity within 72 hours. Secondary outcomes include adverse events, mobility scores and the length of hospital stay. If available data permit, a methadone dose–response pattern may be investigated. Searches will be conducted in MEDLINE (Ovid), Embase (Ovid), CINAHL, CENTRAL, Web of Science and ClinicalTrials.gov without date restrictions. Two reviewers will independently screen studies, extract data and assess risk of bias using the Cochrane risk-of-bias tool for randomised trials. When appropriate, random-effects meta-analysis methods will be performed. Certainty of evidence will be assessed using Grading of recommendations assesment, development and Evaluation (GRADE).

Ethics and dissemination

As this study uses previously published data, ethical approval is not required. Findings will be disseminated through a peer-reviewed publication and conference presentations.

PROSPERO registration number

CRD42025616291.

Mentorship-infused initiatives for postgraduate research supervision in African higher institutions of learning: a systematic review and meta-synthesis protocol

Por: Oladimeji · O. · Londani · M. · Moyo · S. · Seekoe · E. · Saidi · A. · Mothiba · T. M. · Feza · N. N. · Davhana-Maselesele · M. · Maart · R. · Babalola · J. O. · Okoh · A. I. · Okonofua · F. · Ntusi · N. A. B. · Sibiya · M. N.
Introduction

Strengthening research capacity in Africa is vital for tackling pressing health, educational and socioeconomic challenges facing the continent. At the core of this effort is the cultivation of innovative research leaders through postgraduate training programmes that incorporate mentorship-infused supervision. Such models have demonstrated potential in improving research skills, boosting academic productivity and fostering leadership development among emerging scholars. This systematic review and meta-synthesis protocol aims to examine existing mentorship-infused supervision practices across African higher education institutions. The review seeks to identify effective models, uncover common challenges and barriers, and generate evidence-based recommendations to develop sustainable, contextually relevant strategies. Insights from this work will inform policies and practices to enhance postgraduate research training, advance research leadership and contribute to the broader goal of strengthening research ecosystems across Africa.

Methods and analysis

A systematic review and thematic meta-synthesis will be undertaken, focusing on qualitative research studies as well as the qualitative components of mixed-methods studies. Relevant studies published in English will be identified through a comprehensive search strategy. The electronic databases, including Medline/PubMed, Scopus, Web of Science, African Journals Online, EMBASE and CINAHL, will be searched to capture a wide range of peer-reviewed articles and grey literature. Databases will be searched from March 2026. Two reviewers will independently perform study selection, data extraction, quality assessment and evaluation of risk of bias, using the Critical Appraisal Skills Programme checklist.

Ethics and dissemination

This systematic review and meta-synthesis will analyse publicly available literature and does not require ethical approval, as it involves no primary data collection. It will adhere to established ethical and methodological standards, including proper citation and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The findings will be widely disseminated through open-access journal publication, conference presentations and targeted reports for universities, research institutions and policymakers to inform and support mentorship-based postgraduate research supervision across Africa.

PROSPERO registration number

CDR420251049878. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD420251049878.

Organ donation for research purposes: a qualitative focus group study on the views of donor families, transplant recipients and heart failure patients in the UK

Por: Louca · J. O. · Asemota · N. · Thren · J. · Manara · A. · Bhagra · S. · Wang · L. · Bargehr · J. · Burton · N. · Burton · S. · Rockell · K. · Nunes · J. P. · White · P. · Berman · M. · Pettit · S. · Rubino · A. · Reyahi · A. · Large · S. · Sinha · S. · Wilson · C.
Background

Declined donor organs and explanted recipient organs may hold considerable value for biomedical research, particularly in advancing knowledge of disease mechanisms and supporting drug development. However, public perceptions of such use, and preferences for how consent should be obtained, remain underexplored.

Methods

Four workshops were held across the UK to examine the views of organ donor families and transplant recipients regarding the use of human organs in research, with a focus on myocardial regeneration. Each workshop included three brief presentations on transplantation and cardiac regeneration, followed by facilitated small-group discussions. Observational notes were taken to capture participants’ perspectives on the use of organs unsuitable for transplantation. A follow-up survey generated both quantitative and qualitative data, the latter analysed using thematic analysis.

Results

Participants expressed strong support for the use of declined donor and explanted recipient organs in research. Transplant recipients frequently cited a desire to give back to the National Health Service (NHS), while donor families viewed research use as a meaningful way to honour their loved ones when transplantation was not possible.

Conclusion

This exploratory study highlights widespread support for using non-transplantable organs in research among individuals with personal experience of transplantation. The findings suggest a need for further research into how best to support and inform potential donors and families. Participants emphasised the importance of sensitive communication, clear consent processes and transparency regarding the use of donated organs.

Liberal versus restrictive red blood cell transfusion thresholds in acute acquired brain injury: a systematic review and meta-analysis

Por: Sud · S. · Guyatt · G. · Angriman · F. · Friedrich · J. O. · Scales · D. C. · Turgeon · A. F. · English · S. · Adhikari · N. K.
Objective

To evaluate the effects of liberal transfusion strategy (trigger haemoglobin ≤90–100 g/L) compared with a restrictive strategy (trigger haemoglobin ≤70–80 g/L) on long-term neurological functional outcome in anaemic adult patients with acute acquired brain injury (ABI).

Design

Systematic review and study-level meta-analysis of randomised controlled trials (RCTs).

Data sources

MEDLINE, EMBASE, Cochrane from inception to 6 February 2025.

Study selection

RCTs enrolling patients with acute ABI and anaemia (haemoglobin ≤100 g/L), comparing a liberal vs restrictive transfusion strategy.

Data extraction and synthesis

Two reviewers independently identified eligible studies, extracted data and assessed risk of bias. We performed random-effects meta-analysis of RCTs and applied Grading of Recommendations, Assessment, Development and Evaluation methodology to assess the certainty of evidence. Our primary outcome was an unfavourable neurological functional outcome, using the Glasgow Outcome or modified Rankin scales.

Results

Five trials enrolling 2364 patients with acute ABI and anaemia were included in the primary analysis. Liberal transfusion reduces the risk of unfavourable neurological outcome (risk ratio (RR)=0.89, 95% CI 0.84 to 0.95, high certainty). Liberal transfusion may reduce severe disability (RR=0.82, 95% CI 0.66 to 1.02, moderate certainty), and increase good recovery compared with restrictive transfusion (RR=1.29, 95% CI 0.95 to 1.76, low certainty). We found no difference in the risk of most adverse events, including death. Statistical heterogeneity was low (I2=0%–36%) for neurological outcomes.

Conclusions

In adults with acute ABI and anaemia, liberal transfusion reduces the risk of unfavourable outcome (high certainty) and possibly improves the chances of good recovery (low certainty) when compared with restrictive transfusion.

PROSPERO registration number

CRD42025628732.

Continuous non-invasive electrophysiological monitoring in high-risk pregnancies: study protocol of a cohort intervention random sampling study in a tertiary obstetrical care centre in the Netherlands (NIEM-O study)

Por: de Klerk · N. D. · Berben · P. B. Q. · de Vries · I. R. · Niemarkt · H. · Vullings · R. · van den Heuvel · E. R. · van der Ven · M. · Fransen · A. F. · Oei · S. G. · van Laar · J. O. E. H.
Introduction

Women with high-risk pregnancies (eg, pre-eclampsia, imminent preterm birth) are often hospitalised due to the need for foetal and maternal monitoring. They are monitored for 30–45 min up to three times a day with conventional cardiotocography (CTG). In the meantime, they reside at the hospital, but the foetal status is not monitored. Continuous foetal monitoring is currently not recommended using CTG, due to the potential temperature rise from consistent exposure to ultrasound waves. For safe 24/7 monitoring, newly developed devices using non-invasive electrophysiological cardiotocography (eCTG) instead of conventional CTG offer a promising alternative. Previous research into eCTG has shown favourable results in monitoring foetal heart rate throughout both pregnancy and labour. This study aims to investigate the effect of implementing continuous antepartum eCTG monitoring in hospitalised high-risk pregnancies on perinatal and maternal outcome.

Methods and analysis

In this single centre prospective cohort intervention random sampling study, eligible women will be included on the Obstetric High Care of Máxima MC Veldhoven, the Netherlands. In total, 511 pregnant women with a singleton pregnancy between 23+0 and 32+0 weeks of gestation requiring hospitalisation will be recruited. Eligible women will be prospectively included in the cohort receiving standard treatment: intermittent CTG monitoring. From these women, a random sample of the prospective cohort will be offered a new monitoring method: 24/7 eCTG monitoring. For the eCTG monitoring, a wireless abdominal electrode patch, the Nemo Foetal Monitoring System will be used. Additional data from a historical cohort (2014–2019) of 1400 women receiving standard treatment will be included. Perinatal and maternal outcome, along with satisfaction levels of both patient and caregivers, will be compared between groups.

Ethics and dissemination

The study is registered on 18 October 2022 to the Central Committee on Research Involving Human Subjects (NL82869.015.22) via https://www.toetsingonline.nl/to/ccmo_monitor.nsf/conceptabr?OpenForm and approved by the Medical Ethics Committee of Máxima MC (W22.070) on 7 November 2023. Results of the study will be disseminated in peer-reviewed scientific journals and conference presentations.

Trial registration number

NCT06151613.

Incidence, risk factors and pregnancy outcomes of gestational diabetes mellitus in Ibadan, Southwest Nigeria: a prospective cohort study

Por: Adeoye · I. · Adedapo · K. S. · Sonuga · O. O. · Fagbamigbe · A. F. · Adeleye · J. O. · Olayemi · O. O. · Omigbodun · A. O. · Bamgboye · A. E.
Objective

Gestational diabetes mellitus (GDM) is an emerging public health concern in low and middle-income countries, including Nigeria, because of the associated pregnancy complications, increased healthcare costs and long-term health sequelae among women of reproductive age and their offspring. We determined the cumulative incidence, risk factors and pregnancy outcomes of GDM in Ibadan, Nigeria.

Design

Prospective cohort study.

Setting

Ibadan, Southwest Nigeria.

Participants

721 pregnant women from the Ibadan Pregnancy Cohort Study participated in the one-step 75 g-oral glucose tolerance test at 24–28 weeks’ gestation.

Outcomes

The primary outcome of the study is the cumulative incidence of GDM. GDM was diagnosed according to the International Association of Diabetes and Pregnancy Study Groups criteria. Secondary outcomes were pregnancy outcomes, which included modes of delivery (CS, spontaneous vaginal delivery), macrosomia (birth weight ≥4.0 kg), gestational age at delivery and birth asphyxia. The risk factors (exposures) examined included sociodemographic, obstetric, clinical, behavioural and lifestyle factors. Bivariate and multivariate Log-binomial regression models were used to identify the independent risk factors of GDM (adjusted for maternal age ≥35 years, income, maternal body mass index, history of pregnancy loss and congenital anomaly) and the associated pregnancy outcomes of GDM (adjusted for maternal age, income and maternal body mass index). Adjusted relative risk (aRR) and 95% CI, used to assess the strength of associations, were reported.

Results

The cumulative incidence of GDM was 20.7%, 95% CI (17.9% to 23.9%). The mean time for the diagnosis of GDM is 25.4±1.42 weeks of gestation. After adjusting for other variables, maternal age ≥35 years: (aRR: 1.48). 95% CI (1.07 to 1.97) p=0.016), maternal obesity (aRR: 1.85, 95% CI (1.26 to 2.30) p=0.002) and a previous history of congenital anomaly (aRR: 2.83, 95% CI (1.97 to 4.07) p

Conclusion

The cumulative incidence of GDM is high among pregnant women in Ibadan. Maternal age ≥35 years, maternal obesity and a history of congenital anomaly were significant independent risk factors for GDM. These factors should be targeted for public health interventions, including lifestyle modification among pregnant women with obesity and early screening and diagnosis of GDM.

Association of non-standard working time arrangements with safety incidents: a systematic review

Por: Moen · L. V. · S Lie · J.-A. · Sterud · T. · Christensen · J. O. · Haugen · F. · Skogstad · M. · Nordby · K.-C. · Matre · D.
Objective

To systematically review the evidence on the association between non-standard working time arrangements (such as night work or shift work) and the occurrence of safety incidents.

Design

Systematic review conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and using a structured narrative approach and the Synthesis Without Meta-analysis framework to evaluate and summarise findings.

Data sources

MEDLINE, Embase, PsycINFO, Web of Science and ProQuest Health and Safety Science Abstracts were searched through February 2024.

Eligibility criteria for selecting studies

We included peer-reviewed English-language studies of paid workers (18–70 years) that examined the association between non-standard working time arrangements and safety incidents (accidents, near-accidents, safety incidents or injuries), excluding cross-sectional designs and studies on unpaid workers, athletes or military personnel.

Data extraction and synthesis

Two reviewers independently extracted data and assessed risk of bias using standardised forms, extracting study characteristics (author, year, country, sector and population), working time arrangements and exposure assessment, outcomes and their assessment, and reported risk estimates. We conducted a narrative synthesis, classifying studies into three exposure contrasts (shift worker versus non-shift worker, time-of-day and shift intensity), and summarised risk estimates using forest plots without calculating pooled effects.

Results

A total of 13 569 records were screened, and 24 studies met the inclusion criteria. The results indicated that shift workers generally had an elevated safety incident risk compared with non-shift workers (risk estimates ranged from 1.11 to 5.33). Most of the included studies found an increased risk of safety incidents during or after night shifts. Accumulated exposure to evening or night shifts increased the risk of safety incidents during the following 7 days. However, bias and heterogeneity across studies in design, populations and outcome measures resulted in an overall low to very low certainty of the evidence.

Conclusions

Non-standard working time arrangements, including night and evening shifts, appear to increase the risk of occupational safety incidents. Despite the low certainty of evidence, the findings highlight a potential area for preventive measures in work scheduling. Future longitudinal studies using individual data on daily working hours are needed.

Progression from uncomplicated to severe malaria among children in settings receiving different malaria control interventions in sub-Saharan Africa: a systematic review protocol

Por: Okek · E. J. · Lutwama · J. · Kinengyere · A. A. · Asio · J. · Awor · S. · Le Doare · K. · Musinguzi · B. · Sande · J. O. · Ocan · M. · Kayondo · J.
Background

Different malaria control measures are deployed simultaneously in endemic settings globally, with varying impacts on malaria burden. In sub-Saharan Africa, which bears the greatest burden of malaria, evidence on the impact of implementing various control interventions on malaria immunity remains unknown. This systematic review seeks to collate evidence on the extent of progression from uncomplicated to severe malaria among populations in sub-Saharan Africa settings receiving concurrent deployment of various malaria control measures.

Methods

The review will use a priori criteria contained in the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols. An experienced librarian (AAK) will independently search for articles from the following databases: PubMed, Web of Science, Embase, Scopus and Google Scholar. Boolean operators ‘AND’ and ‘OR’ will be used in the article search. Identified articles will be managed using EndNote. Article screening for inclusion and data extraction will be done in duplicate by two reviewers (EJO, and BM). Data extraction tools will be developed and customised in Excel. Data will be analysed using both narrative and quantitative synthesis. The level of heterogeneity between study outcomes will be measured using the I2 statistic. Subgroup analysis will be conducted to explore heterogeneity and establish the impact of different control interventions on progression from uncomplicated to severe malaria. A full systematic review and meta-analysis is expected to be ready for dissemination by the end of December 2025.

Ethical consideration and dissemination of findings

This study did not involve human participants and so ethical approval was not sought. A full review and a meta-analysis will be published in a peer-reviewed journal and presented at national and international conferences.

PROSPERO registration number

CRD 42024619945.

Non-invasive electrophysiological monitoring vs conventional monitoring during labour in a tertiary obstetric care centre in the Netherlands: study protocol of a cohort intervention random sampling study (NIEM-II study)

Introduction

Conventional cardiotocography (CTG) has been used extensively to monitor the fetal condition during labour. However, conventional non-invasive monitoring is limited by the difficulty of obtaining an adequate signal quality, particularly in the case of obese parturients. Furthermore, the rate of operative deliveries keeps rising despite the ability for conventional intrapartum monitoring. Electrophysiological monitoring is an alternative technique that has been developed over the past decades to improve signal quality. This non-invasive, transabdominal and wireless alternative measures fetal heart rate by fetal electrocardiography (NI-fECG), and uterine activity by electrohysterography (EHG). Both NI-fECG and EHG have been proven to be more accurate and reliable than conventional non-invasive methods and are less affected by maternal Body Mass Index. Nevertheless, it is still unknown whether electrophysiological intrapartum monitoring leads to better obstetric and neonatal outcomes. This study aims to investigate whether electrophysiological monitoring during labour affects the number of operative interventions compared with conventional monitoring during labour.

Methods and analysis

This is a single-centre cohort intervention random sampling study which will be performed in a tertiary obstetric care centre. In total, 3471 term pregnant women with a singleton fetus in cephalic position and indication for continuous fetal monitoring during labour will be included. Eligible women will be prospectively included in the cohort for conventional monitoring. From these women, 90.9% of women will be randomly sampled and will be offered electrophysiological monitoring. A historical cohort of an additional 2100 women who received conventional monitoring will be added to the conventional group. This historical cohort was collected between April 2019 and February 2023. The primary outcome will be the number of operative interventions during labour. Secondary outcome measures include maternal and neonatal outcomes, patient and healthcare professional perspectives and costs.

Ethics and dissemination

This study received approval from the Medical Ethics Committee of Máxima Medical Centre (W22.071) on 1 November 2023. All participants will provide informed consent prior to data collection. Results of the study will be disseminated in peer-reviewed scientific journals and conference presentations.

Trial registration number

NCT06135961.

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