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Prevalence, outcomes, and predictors of mortality among adult intensive care unit patients with sepsis at a Tertiary Hospital in Tanzania: A prospective cohort study

by Atala Jongo, Edwin Lugazia, Salehe Mrutu, Amina Abillah Omari, Hassani Msanga, Ansbert Sweetbert Ndebea, Felix Paul Amani

Background

Sepsis continues to pose a significant global health challenge, particularly in low- and middle-income countries, which face a disproportionate burden of sepsis and sepsis-related deaths. The estimated prevalence of sepsis and sepsis-related mortality is higher in intensive care units than in hospitals overall. The burden can be higher in tertiary referral centers that receive patients from different regions.This study aimed to determine the prevalence of sepsis, its outcomes, and the factors associated with these outcomes among adult patients admitted to the Intensive Care Unit (ICU) of the Muhimbili National Hospital (MNH) in Tanzania.

Methodology

This prospective cohort study was conducted over a period of six months from May 16 to November 16, 2023, at MNH. A total of 248 patients were admitted during the study period and screened for sepsis on admission or for the development of sepsis during their ICU stay. Sepsis was defined according to the Sepsis-3 criteria as a suspected infection with a Sequential Organ Failure Assessment (SOFA) score ≥2 within 24 h of ICU admission. Proportions were used for descriptive statistics, and modified Poisson regression analysis was used to identify independent predictors of mortality at a 95% confidence interval, with P  Results

The prevalence of sepsis was 41.5%. The respiratory system was the most common source of infection (32%), and 22.3% of patients had more than one infection site. The ICU mortality rate was 55.3%, with 35% of patients developing systemic complications during their ICU stay.Factors independently associated with mortality included multiple comorbidities (aPR 3.35, 95% confidence interval [CI], 1.20–9.32; p = 0.021) and a higher SOFA score (aPR 7.08, 95% CI 3.48–14.4; p  Conclusion

This study revealed a high prevalence of sepsis and sepsis-related mortality in the ICU. A high SOFA score and multiple complications were independent predictors of mortality. Early initiation of antibiotic therapy was an independent predictor of survival. This underscores the importance of early treatment, close monitoring, and aggressive management in patients with predictors of poor outcome.

Enhancing screening, early diagnosis and treatment initiation of oral, breast and cervical cancer in selected districts of India: an implementation research protocol

Por: Kankaria · A. · Shukla · P. · Vijayakumar · M. · Sachdeva · A. · Subramanian · M. J. · Borah · P. K. · Sahoo · S. S. · Nirgude · A. · Prusty · R. K. · T S · S. · Asuri · K. · Verma · P. · Sharma · J. · Dhaliwal · R. S. · Begum · S. · Kaur · T. · ICMR-NHRP Cancer Screening Group · Bhatla
Introduction

Despite implementation of the National Programme for Prevention and Control of Non-Communicable Diseases (NP-NCD), screening coverage for oral, breast and cervical cancers remains below 2%. Screening quality is inadequately addressed and delays in diagnosis and treatment initiation continue to persist. This multisite implementation research aims to improve district-level coverage and quality of screening, early diagnosis and timeliness of treatment initiation through a model co-developed within the NP-NCD context.

Methods and analysis

The study will be conducted in three phases across seven districts in diverse regions of India. In phase I (formative), the current status, barriers and facilitators of cancer screening, diagnosis and treatment initiation under NP-NCD will be assessed. In phase II (optimisation), a model (package of implementation strategies) will be co-developed and iteratively optimised with multistakeholder engagement at the subdistrict level to improve screening coverage and quality and strengthen the referral system for early diagnosis and treatment initiation. In phase III (scale-up and evaluation), the model will be implemented at the district level and evaluated for improvements in screening, early diagnosis and treatment initiation. A convergent mixed-methods design will be used, incorporating household surveys, facility assessments and stakeholder interviews. Implementation Research Logic Model will guide planning, execution and evaluation in the present study. Determinants of screening coverage and quality, early diagnosis and treatment initiation will be assessed using the Consolidated Framework for Implementation Research. Implementation strategies for the model will be finalised using the Expert Recommendations for Implementing Change framework. Implementation and service outcomes will be evaluated using the Reach, Effectiveness, Adoption, Implementation and Maintenance framework.

Ethics and dissemination

Ethical approval has been obtained from all study sites. The study findings will be disseminated at the state, national and global levels through meetings and conferences and submitted to a peer-reviewed journal for publication.

Trial registration number

CTRI/2025/08/092672.

Cost analysis of the use of digital rectoscopy versus flexible sigmoidoscopy in rectal cancer patients undergoing watch and wait

Por: Sekhon Inderjit Singh · H. K. · Harper · H. · Butnari · V. · Beni · R. · Lozano · E. · Goede · A.
Introduction and objective

Organ preservation strategies for rectal cancer following neoadjuvant treatment require intensive endoscopic monitoring to detect early luminal recurrence. This is termed 'Watch and Wait' (WAW). Standard protocols commonly mandate flexible sigmoidoscopy every 3–4 months for 2 years. Digital proctoscopy with the LumenEye device has been shown to be a safe alternative that can be performed in an outpatient setting without the need for sedation and with less staffing requirements. The study objective is to evaluate the economic implications of using digital proctoscopy compared with flexible sigmoidoscopy for patients with rectal cancer managed under a WAW protocol.

Setting and design

The study was conducted in a secondary care National Health Service (NHS) setting. A cost comparison analysis was performed over a 2 year time horizon (seven procedures per patient). 177 procedures on rectal cancer patients undergoing WAW with digital proctoscopy between August 2023 and November 2024 were included. The control group, that is, flexible sigmoidoscopy was modelled. The base case was flexible sigmoidoscopy without sedation. Scenarios using sedation were also evaluated. Costs were categorised into fixed and variable costs. A one-way sensitivity analysis, probabilistic sensitivity analysis and What-If scenarios were also performed.

Outcome measures and results

The primary outcome was the minimum cost difference between the two procedures. The secondary outcome measure was the robustness of the cost differences. Over 2 years, the total cost per patient was £768.92 (95% CI £656.6 to £900.7) for digital proctoscopy compared with £1,588.15 (95% CI £1458.1 to £1725.2) for flexible sigmoidoscopy without sedation. The absolute minimum cost saving per patient is £820.23 (95% CI £648.7 to £985.1). Cost savings increased to £848.94 (95% CI £677.20 to £1013.83) to £935.62 (95% CI £761.02 to £1103.08) when sedation was used in flexible sigmoidoscopy procedures. Personnel costs during the procedure and recovery phase were the dominant cost drivers for flexible sigmoidoscopy. Probabilistic sensitivity analysis and What-If scenarios confirmed the robustness of the findings, with flexible sigmoidoscopy remaining more costly.

Conclusion

Digital proctoscopy with the LumenEye device is a cost-saving alternative to flexible sigmoidoscopy for patients with rectal cancer on a WAW protocol. Our findings support the integration of digital proctoscopy into WAW pathways as a cost-efficient alternative within resource-constrained healthcare systems. Endoscopy service pressures are also likely to be alleviated.

Can digital self-screening improve identification of chronic dyspnoea in Australian general practice? A proof-of-concept protocol for the BREATHE SMART trial

Por: Jang · K. · Giskes · K. · Martin · A. · Sunjaya · A. P. · Khin · P. · Jenkins · C. · Hespe · C. M. · on behalf of the BREATHE SMART Steering Committee · Hespe · Jenkins · Martin (Humphries) · Giskes · Lowres · Woods · Chua · Pearce · Ben Freedman · Sunjaya · Fardy · Tam
Introduction

Chronic dyspnoea is a prevalent and clinically significant symptom, often indicative of underlying cardiorespiratory disease. It is frequently under-reported by patients and under-recognised in primary care, with these challenges exacerbated in rural and remote communities where disease burden is greater and patients experience barriers to timely diagnosis and management. The BREATHE SMART trial aims to implement and evaluate an innovative, fully digital self-screening system for chronic dyspnoea, integrated into general practice workflows and information technology infrastructure. This approach seeks to enhance early detection and management of chronic cardiorespiratory conditions across diverse practice settings.

Methods and analysis

This multisite proof-of-concept study will test a software platform delivering a preconsultation self-screening questionnaire across 40 general practices in urban, rural and remote Australia. The system identifies eligible patients (≥18 years, consenting to SMS communication with their practice), issues an automated SMS that administers a validated dyspnoea screening questionnaire, and summarises responses for integration into the electronic medical record. Process evaluation will assess acceptability and utility using deidentified audit data, software metrics and qualitative feedback from patients, staff and general practitioners (GPs) via surveys, interviews and focus groups. Approximately 12 000 patients will be screened over 12 months. Primary outcomes will include the proportion completing self-screening and prevalence of chronic dyspnoea and secondary outcomes will include the rate of newly diagnosed chronic dyspnoea-related conditions (ie, asthma, chronic obstructive pulmonary disease and heart failure) in the preceding 12 months and during the intervention period.

Ethics and dissemination

Ethics approval was granted by the University of New South Wales Human Research Ethics Committee (HREC) (iRECS6645) and the University of Notre Dame Australia HREC (2024-155). Participating practices and each GP will provide written, informed consent. All patients being screened will provide electronic informed consent. Results of the study will be disseminated through various forums, including peer-reviewed publications and presentation at national and international conferences. Following the study, participating practices will be provided with a summary of the findings of the study, together with a full copy of any publications and a plain language statement for participants, which will be made available in the practices.

Trial registration number

ACTRN12624001451594.

Candida Drug Resistance in Patients With Diabetic Foot Ulcers: A Systematic Review and Meta‐Analysis

ABSTRACT

Diabetic foot ulcers (DFUs) are one of the most serious and common complications that, if not treated properly, can lead to potential damage and even amputation. The aim of this systematic review and meta-analysis was to assess the drug-resistant Candida species in DFU. PubMed, Web of Science, Scopus and Google Scholar databases were systematically searched for eligible articles up to 22 June 2024. All articles on Candida diabetic foot infections that reported data on drug resistance were included in the study. In addition to general information, data on the type and number of fungi and the percentage of resistance to each drug were collected for analysis. A total of 238 studies were screened and finally, 16 articles were selected and analysed. Candida albicans was the most frequently isolated species in DFUs, followed by Candida tropicalis and Candida parapsilosis. For antifungal agents, the highest resistance was reported to Nystatin (32.48%, p-value = 0.30), Itraconazole (19.46%, p-value = 0.001) and Fluconazole (16.4%, p-value = 0.001). Miconazole (1.18%, p-value = 0.54) and Caspofungin (4.69%, p-value = 0.01) had the lowest resistance rates. For all drugs, resistance was higher in C. albicans than in non-albicans. This study found that antifungal drug resistance in Candida species is high in patients with DFUs, especially to itraconazole and fluconazole. Caspofungin, micafungin and voriconazole were more effective. Antifungal treatment in these patients should prioritize agents with lower resistance rates to improve outcomes and reduce the risk of treatment failure.

Protocol Registration: PROSPERO—CRD42024567133.

Real-time torque behavior of reciprocating nickel–titanium instruments using different irrigating solutions

by Uğur Dursun, Mevlüt Sinan Ocak

Reciprocating nickel–titanium instruments generate mechanical stress during root canal preparation, which may affect instrument safety. Although instrument design is known to influence torque generation, the effect of different irrigating solutions on the real-time operative torque remains unclear. This study aimed to investigate the impact of various irrigating solutions on torque generated during root canal shaping using reciprocating single-file systems. Extracted human mandibular premolars with oval canals were assigned to groups prepared using sodium hypochlorite, ethylenediaminetetraacetic acid, or saline in combination with three reciprocating file systems. All canals were instrumented with a torque-controlled motor, and the real-time operative torque and preparation time were digitally recorded. The mean torque, maximum torque, and shaping duration were statistically compared between the irrigant and instrument groups. The irrigation solution alone did not show a significant main effect on torque values or preparation time. However, a significant interaction between the file system and irrigant type was detected, indicating that the torque response depended on the specific file–irrigant combination. In contrast, the file system type significantly influenced torque behavior, with the T-Endo MUST system producing higher mean and peak torque than the other instruments. These findings suggest that instrument design characteristics may have a greater impact on the development of mechanical stress during root canal preparation than the irrigation solution used.

Longitudinal Mediating Role of Cancer‐Coping Self‐Efficacy Between Symptom Occurrence and Quality of Life Among Cancer Patients: A Cross‐Lagged Panel Model

ABSTRACT

Purpose

Although the positive correlation between self-efficacy and quality of life and the negative correlation between symptom occurrence and self-efficacy are well established in the cancer literature, the underlying mechanism, whether self-efficacy mediates the effect of symptoms on quality of life, remains unclear due to the cross-sectional design of prior studies. Longitudinal investigation is crucial for establishing the causal mechanism of self-efficacy in mitigating the adverse impact of cancer-related symptoms on quality of life.

Aim

To examine the longitudinal mediating effect of self-efficacy on the relationship between symptom occurrence and quality of life among 534 cancer patients on treatment with moderate to high symptoms.

Methods

This is a secondary data analysis of the longitudinal mediating effect. A sample of patients with moderate to high symptoms on cancer treatments (N = 534) from a randomised controlled trial was used. We adopted a cross-lagged panel model (CLPM) approach to test the longitudinal mediating effect with three waves. The longitudinal invariance of the measurement was previously tested.

Results

The results showed that cancer-coping self-efficacy predicted the following assessment of symptom occurrence, but not vice versa. Also, cancer-coping self-efficacy had an immediate direct impact on quality of life and the influence sustained to the following assessment. Our mediating analysis showed that cancer-coping self-efficacy totally mediated the relationship between symptom occurrence and quality of life (unstandardized β = −0.008, standardised B = −0.036, p = 0.036, CI95 = [−0.001, −0.016]).

Conclusion

Our findings provide initial evidence supporting the causal mechanism of cancer-coping self-efficacy in interventions that aim for symptom management and quality of life improvement.

Implications

This study is the first to test the longitudinal mediating mechanism of cancer-coping self-efficacy in the relationship between symptom occurrence and quality of life among the cancer population. Further testing using a randomised controlled trial of a specifically designed self-efficacy-enhancing intervention is needed.

Patient or Public Contribution

No patient or public contribution.

Patient Experiences of Receiving Stroke Discharge Information in Accordance With Preferences

ABSTRACT

Aims

To examine survivors' experiences of discharge information including risk communication after hospitalisation for a stroke and the characteristics associated with receiving information in accordance with their preferences.

Background

With advances in acute stroke care and an ageing population, the number of survivors of stroke is increasing. It is important that healthcare providers ensure patients have adequate information after a stroke-related hospitalisation.

Design

Cross-sectional study.

Methods

Adults recently discharged after a stroke from eight Australian hospitals were mailed a survey. Items examined risk and discharge care information, with participants asked to indicate both their preferences for and receipt of the information. Concordance with preferences was calculated, and characteristics associated with information preference concordance were assessed with binomial logistic regression. Study reported in accordance with STROBE Checklist.

Results

Of 1161 eligible patients invited, 403 (35%) completed the survey. All items were endorsed by 80% or more of respondents as being wanted. However, for all items, fewer respondents reported the care as received. Only 28% of participants received information on all five items according to their preferences. Hospital site, Body Mass Index and age were statistically significantly associated with participants receiving information in accordance with their preferences.

Conclusion

Most participants indicated a preference to receive recommended discharge information. Findings suggest that patients may benefit from increased information provision prior to hospital discharge after stroke.

Relevance to Clinical Practice and Patient Care

Nurses have an important role in the provision of stroke care and information. The findings of this study may be used to improve the provision of post-hospital discharge care and support for survivors of stroke, and assist in identifying patients at lower odds of experiencing information aligned with their preferences and who may benefit from support.

Reporting Method

Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) checklist for cross-sectional studies.

Patient or Public Contribution

No patient or public contribution.

Effect of intravenous vitamin C administration on chemotherapy-induced adverse events in patients with nasopharyngeal cancer

by Peesit Leelasawatsuk, Pasawat Supanimitjaroenporn, Nattida Rodsom, Theepat Wongkittithaworn, Manupol Tangthongkum

Nasopharyngeal carcinoma is prevalent in Thailand, with a substantial proportion of cases diagnosed at advanced stages. The standard treatment, concurrent chemoradiotherapy, is associated with considerable adverse effects, which may compromise therapeutic efficacy and diminish patients’ quality of life. While vitamin C has shown potential in reducing chemotherapy-induced toxicities in some cancers, its effects in nasopharyngeal carcinoma remain unclear. In this randomized, double-blind, placebo-controlled trial, patients with nasopharyngeal carcinoma undergoing concurrent chemoradiotherapy were assigned to receive either 2 g of intravenous vitamin C or placebo prior to chemotherapy. The incidence of gastrointestinal adverse effects—including nausea, anorexia, mucositis, diarrhea, and dysphagia—did not differ significantly between groups. However, longitudinal analysis demonstrated a significantly attenuated decline in platelet counts in the vitamin C group compared with placebo. Although intravenous vitamin C did not reduce gastrointestinal toxicities, the observed platelet preservation suggests a potential supportive effect that warrants further investigation. Trial registration The study was registered with the Thai Clinical Trial Registry (TCTR20190316003) on March 16, 2019.

Body Mass Index: A Key Factor in Surgical Site Infections After Kidney Transplantation?

ABSTRACT

Kidney transplant recipients are at increased risk of surgical site infections (SSIs) due to procedural complexity and immunosuppression. This retrospective single-centre study examines the influence of BMI on SSI risk and identifies common pathogens. A total of 230 renal transplant patients were included in this analysis 2017 and 2019. All patients received a cephalosporin for prophylaxis, and wound swabs were taken from those who developed SSIs. SSIs occurred in 45 patients (19.6%) and were not significantly associated with age, sex or donor type. The most common organisms were coagulase-negative staphylococci (26.7%), Staphylococcus epidermidis (24.4%), Enterococcus faecalis (22.2%) and Candida albicans (22.2%). SSIs were significantly linked to surgical revision (p < 0.001) and higher BMI (p = 0.027). A BMI ≥ 28.1 was associated with threefold higher odds of SSIs (OR = 3.0; p = 0.001). Each one-unit increase in BMI was associated with a 7.2% increase in the odds of SSI occurrence (OR = 1.072; p = 0.020). Staphylococcus (p = 0.019) and Enterococcus (p = 0.048) infections were more common in patients with BMI > 28.1. Therefore, SSIs are a frequent complication posttransplant and are strongly associated with high BMI. Standard antibiotic regimens may not cover all relevant pathogens in obese patients, underscoring the need for tailored prophylactic strategies.

Resilience of anaerobic digestion to polypropylene microplastic contamination: Kinetic and structural evidence

by Napapat Sitthikitpanya, Alissara Reungsang

The increasing occurrence of microplastics (MPs) in organic waste streams raises concerns about their impact on anaerobic digestion (AD). This study examined the effect of polypropylene MPs (PP-MPs) on methane production during AD of food waste for 150 days under batch conditions. PP-MPs were added at 10–300 mg g-1 total solids (TS), covering reported MP levels in food waste and food packaging materials and extending to worst-case scenarios. Methane yields ranged from 310.2 to 324.4 mL CH4 g-1 volatile solids (VS) across treatments versus 334.3 ± 5.2 mL CH4 g-1 VS in the control, with no significant differences (p = 0.634). Kinetic modeling confirmed no consistent inhibitory trends. FTIR and SEM analyses indicated minor surface oxidation and cracking on PP-MPs, while the polymer backbone remained intact, suggesting only superficial aging. These results provide critical assurance for waste-to-energy facilities processing plastic-contaminated organic waste streams. Although PP-MPs do not impair AD performance, their persistence and potential fragmentation pose environmental risks. These findings provide critical insight into the resilience of AD systems and emphasize the need for strategies to mitigate secondary MP formation in biogas production from contaminated waste streams.

Assessing Hand Function Post‐Burn: A Systematic Review of Surgical vs. Enzymatic Debridement Using DASH/Quick‐DASH and MHQ Questionnaires

ABSTRACT

Hand burns, although often limited in surface area, have a major impact on function and quality of life. Debridement—surgical or enzymatic—is a key component of treatment, with enzymatic debridement increasingly used for its selectivity and potential to preserve viable dermis. To evaluate and compare the functional outcomes of hand burns treated with surgical versus enzymatic debridement, using the DASH/Quick-DASH and Michigan Hand Questionnaire (MHQ) assessment tools. A systematic review was conducted according to PRISMA guidelines and registered in PROSPERO (CRD420251034408). Searches were performed in PubMed, Scopus, and Web of Science without date restrictions. Inclusion criteria focused on studies evaluating hand burn function using DASH, Quick-DASH, or MHQ after enzymatic or surgical debridement in patients aged 16 or older. Methodological quality was assessed using the ROBINS-I tool. Of 547 studies identified, 7 met inclusion criteria: 4 surgical and 3 enzymatic. Functional recovery was generally better in cases where enzymatic debridement preserved viable dermis and avoided grafting. DASH and MHQ scores favoured enzymatic approaches, especially when conservative management followed debridement. However, methodological limitations and clinical heterogeneity limited direct comparison. Enzymatic debridement, through preservation of viable dermis and reduced grafting need, appears associated with improved functional outcomes in hand burns. Whilst surgical debridement remains essential for deeper burns, enzymatic methods may offer functional advantages and support early rehabilitation in appropriate cases.

Top 10 priorities for problematic hip replacement research: a priority setting partnership led by the British Hip Society and the James Lind Alliance

Por: Board · T. N. · Khan · A. · Sorial · A. K. · Divecha · H. M. · Lamb · J. N. · Reed · M. · Khanduja · V. · Whitehouse · M. R. · OBrien · F. · Staley · K. · Ellis · P. · on behalf of the Problematic Hip Replacement Steering Group · Jones · Clarke · Harle · Briggs · Kearney · Daboo · A
Objectives

To identify and prioritise research uncertainties regarding the assessment, management and rehabilitation of patients with problematic hip replacements through a national Priority Setting Partnership (PSP).

Design

A national PSP using the James Lind Alliance (JLA) methodology.

Setting

UK.

Participants

Patients, carers and healthcare professionals (HCPs) involved in the care of patients with problematic hip replacements.

Methods

A steering group was established. The James Lind Alliance methodology was followed throughout. A nationwide survey was conducted to collect unanswered questions. These were refined, prioritised through an interim survey and ranked at a final consensus workshop.

Results

The initial survey yielded 201 questions, refined to 32. The interim survey had 191 respondents, leading to 19 questions at the final workshop. The top 10 research priorities were agreed on.

Conclusions

This PSP identified key research priorities for problematic hip replacements, focusing on diagnosis, pain management, perioperative optimisation and infection. These priorities can inform researchers and funders to improve outcomes for affected patients.

Workplace Violence Against Emergency Department Nurses in Low‐ and Middle‐Income Countries: A Systematic Review and Meta‐Analysis

ABSTRACT

Aim

Workplace violence (WPV) against emergency department (ED) nurses is a global concern; however, evidence from low- and middle-income countries (LMICs) remains fragmented despite substantial differences in healthcare infrastructure, staffing and policy capacity compared with high-income settings. This review aimed to synthesise the existing literature to identify the prevalence, risk factors, types and impacts of workplace violence against emergency nurses in low- and middle-income countries.

Design

Systematic review and meta-analysis.

Methods

This review was conducted following PRISMA guidelines. Studies were included if they employed quantitative or mixed-methods designs, focused on emergency nurses in LMICs, and reported WPV prevalence. Quality assessment was conducted using the JBI Critical Appraisal Checklist. A random-effects meta-analysis was performed to examine the prevalence of WPV.

Data Sources

Four databases, CINAHL, PsycINFO, PubMed and Google Scholar, were searched for studies published between 2015 and 2025.

Results

Eleven cross-sectional studies from Africa, Asia, Europe-Asia and South America were included, involving sample sizes ranging from 80 to over 20,000 ED nurses. The pooled prevalence of any WPV was 79% (95% CI: 69%–86%). Verbal violence was the most common form, affecting 82% of nurses (95% CI: 71%–89%). Physical violence was 40% (95% CI: 22%–63%), with substantial heterogeneity across studies. The main risk factors included long waiting times, overcrowding, inadequate staffing and poor security measures. WPV resulted in significant physical, psychological and professional consequences, including stress, depression, burnout and increased turnover intentions.

Conclusion

WPV against ED nurses in LMICs is widespread and severe, affecting 79% of nurses, with verbal abuse being the most prevalent.

Implications for the Profession and/or Patient Care

The high prevalence rates highlight the urgent need for targeted prevention strategies, improved workplace safety measures and comprehensive support systems for emergency nurses.

Reporting Method

We have adhered to relevant EQUATOR guidelines, particularly the PRISMA checklist.

Patient or Public Contribution

No patient or public contribution.

Predicting outcomes in selective fetal growth restriction of monoChOrioNic Twins: an inteRnAtional observational cohort STudy protocol (CONTRAST study)

Por: Noll · A. · Javinani · A. · Slaghekke · F. · Haak · M. C. · van Klink · J. · Van der Meeren · L. · Lopriore · E. · Russo · F. · Aertsen · M. · Shamshirsaz · A. · Shinar · S. · Bennasar · M. · Tiblad · E. · Herling · L. · Lewi · L. · Verweij · E. · CONTRAST Study Group · Keizer · Steggerd
Introduction

Selective fetal growth restriction (sFGR) is a major cause of perinatal morbidity and mortality in monochorionic diamniotic (MCDA) twin pregnancies. Current management relies on umbilical artery Doppler patterns in the smaller twin. These patterns are, however, inconsistent and do not represent a reliable severity scale, complicating clinical decision-making and parental counselling. This study aims to improve risk stratification by identifying predictors of adverse outcomes, while also evaluating the pathophysiology and multi-organ impact of sFGR in early childhood.

Methods and analysis

This is a prospective, international, multicentre cohort study conducted in six tertiary fetal medicine centres with expertise in complicated twin pregnancies. Recruitment began in March 2023 and will continue until December 2026, targeting 274 MCDA twin pairs with complete follow-up to develop a prediction model for adverse perinatal outcomes in sFGR at the time of diagnosis. Standardised data collection includes serial ultrasound examinations, advanced fetal imaging (cardiac, cerebral and 3D volumetric), fetal brain MRI and detailed placental phenotyping. Maternal and parental well-being are assessed during pregnancy and after birth. Neurodevelopmental outcome is evaluated up to 2 years after birth using validated tools. The statistical analysis plan includes predictive modelling with internal validation.

Ethics and dissemination

The study has been approved by the ethical review boards of all participating centres. Findings will be disseminated through peer-reviewed publications, international conferences and engagement with clinical guideline committees.

Trial registration number

NCT05952583.

Chrysin ameliorates methotrexate-induced hippocampal neurogenesis impairment by suppressing of oxidative stress and upregulating antioxidant enzyme activity in rodents

by Tanaporn Anosri, Soraya Kaewngam, Ram Prajit, Kornrawee Suwannakot, Nataya Sritawan, Anusara Aranarochana, Wanassanan Pannangrong, Jariya Umka Welbat, Peter Wigmore, Apiwat Sirichoat

Methotrexate (MTX) is used in treating several malignancies. However, MTX neurotoxicity remains a significant clinical side effect, leading to cell division malformation, and neurogenesis impairment. Chrysin, a flavonoid compound found in natural products, demonstrates various biological characteristics, including neuroprotective and antioxidant properties. The purpose of this study was to investigate the ameliorative effect of chrysin on oxidative damage and neurogenesis impairment caused by MTX. Male Sprague-Dawley rats were randomly divided into four groups, including the vehicle, MTX (75 mg/kg), chrysin (10 mg/kg), and chrysin+MTX groups. Chrysin was orally administered for 15 days. MTX was administered intravenously on days 8 and 15. The hippocampal neural stem cells were evaluated using sex determining region Y-box 2 (sox2) and nestin immunofluorescence staining. Antioxidant enzyme expression and the levels of oxidative stress marker were assessed. Additionally, the expressions of nuclear factor erythroid 2-related factor 2 (Nrf2), brain-derived neurotrophic factor (BDNF), cAMP-response element binding (CREB), and phosphorylated CREB (pCREB) were evaluated using Western blotting. Results showed that MTX significantly decreased the activity of antioxidant enzymes and produced oxidative stress. MTX also impaired neurogenesis, evidenced by decreased sox2 and nestin-positive cells and decreased expression of Nrf2, BDNF, CREB, and pCREB in the hippocampus and prefrontal cortex. However, chrysin significantly reversed the effects of MTX on these parameters. In conclusion, chrysin exhibits neuroprotective effects against MTX-induced neurogenesis impairment by upregulating antioxidant enzyme activity, reducing oxidative stress, and improving protein expression related to neurogenesis.

Pregnancy Risk, Infant Surveillance, and Measurement Alliance (PRISMA) Maternal and Newborn Health Study: protocol for a multisite, prospective, open cohort study of pregnancy and postpartum health outcomes in South Asia and sub-Saharan Africa

Introduction

Maternal and child mortality has markedly decreased worldwide over the past few decades. Despite this success, the decline remains unequal across countries and is overall insufficient to meet the Sustainable Development Goals. South Asia and sub-Saharan Africa bear most of the burden of maternal and child morbidity and mortality. Major gaps persist in our understanding of the causes, timing, diagnostic thresholds and risk factors for adverse outcomes in these regions. Addressing these gaps requires new ways to prevent and treat disease, from novel diagnostics to precision public health strategies, all of which rely on high-quality clinical data from diverse populations. The Pregnancy Risk, Infant Surveillance, and Measurement Alliance (PRISMA) Maternal and Newborn Health Study aims to estimate population-level prevalence of morbidities and mortality and to assess biological, clinical and sociodemographic risk among mother–infant pairs in India, Pakistan, Kenya, Ghana and Zambia.

Methods and analysis

This study is a prospective, open cohort study with a planned recruitment of about 6000 women annually across six research sites in five countries. Participants are pregnant women enrolled less than 20 weeks gestation, as determined by ultrasound, identified through active house-to-house and facility-based surveillance. Robust clinical data will be collected at 12 scheduled study visits during antenatal care, labour and delivery, and through 1 year postpartum. A total of 34 outcomes will be captured. The primary analysis will estimate the burden of adverse outcomes and examine associated risk factors to inform future intervention strategies. Data will also be used to develop normative values for pregnant and postpartum women, as well as predictive models to assess pregnancy risk.

Ethics and dissemination

PRISMA received institutional and national ethical approvals. Findings will be published in peer-reviewed open-access journals and disseminated at national and international forums to inform clinical guidelines and public health practice.

Trial registration number

NCT05904145.

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