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Risk factors and glycaemic control in small-for-gestational-age infants born to mothers with gestational diabetes mellitus: a case-control study using propensity score matching based on a large population

Por: Li · J. · Pan · Y. · Zheng · Q. · Chen · X. · Jiang · X. · Liu · R. · Zhu · Y. · Huang · L.
Background

Small for gestational age (SGA) poses a significant concern for newborns, being linked to neonatal complications and potential metabolic disorders in adulthood, especially when born to mothers with gestational diabetes mellitus (GDM), elevating their risk of complications and mortality. However, the pregnancy risk factors and glycaemic control associated with SGA infants born to mothers with GDM remain unclear.

Aim

To identify the pregnancy risk factors and glycaemic control associated with SGA infants born to mothers with GDM.

Method

This case–control study was conducted among 1910 women with GDM in China. Data were collected by the integrated electronic medical record system. Using 1:4 propensity score matching analysis, we adjusted for gestational age as confounder. Univariate and multivariate analyses were performed to identify risk factors.

Results

Risk factors for SGA born to mothers with GDM included a history of low birth weight, gestational hypertension, oligohydramnios, short maternal height, underweight pre-pregnancy body mass index and inadequate weight growth. While SGA was protected by weakly positive ketonuria levels in the first trimester, multiparous, anaemia and previous uterine scar were protective factors for SGA. Moreover, 2-hour postprandial glucose and haemoglobin A1c in the second trimester, as well as the 0-hour and 2-hour 75 g oral glucose tolerance test (OGTT) were linked to risk of SGA.

Conclusions

SGA infants are the result of multifactorial interactions among GDM pregnant women. Notably, glycaemic control levels were associated with SGA. There is a need for enhanced perinatal monitoring and antenatal care to reduce SGA.

Protection against Incidences of Serious Cardiovascular Events Study with daily fish oil supplementation in dialysis patients (PISCES): protocol for a randomised controlled trial

Por: Lok · C. E. · Hemmelgarn · B. R. · Moist · L. M. · Polkinghorne · K. · Tomlinson · G. · Tonelli · M.
Introduction

Patients with kidney failure with replacement therapy (KFRT) suffer premature cardiovascular (CV) mortality and events with few proven pharmacological interventions. Omega-3 polyunsaturated essential fatty acids (n-3 PUFAs) are associated with a reduced risk of CV events and death in non-dialysis patients and in patients with established CV disease but n-3 PUFAs have not been evaluated in the high risk KFRT patient population.

Methods and analysis

This multicentre randomised, placebo controlled, parallel pragmatic clinical trial tests the hypothesis that oral supplementation with n-3 PUFA, when added to usual care, leads to a reduction in the rate of serious CV events in haemodialysis patients when compared with usual care plus matching placebo. A target sample size of 1100 KFRT patients will be recruited from 26 dialysis units in Canada and Australia and randomised to n-3 PUFA or matched placebo in a 1:1 ratio with an expected intervention period of at least 3.5 years. The primary outcome to be analysed and compared between intervention groups is the rate of all, not just the first, serious CV events which include sudden and non-sudden cardiac death, fatal and non-fatal myocardial infarction, stroke, and peripheral vascular disease events.

Ethics and dissemination

This study has been approved by all institutional ethics review boards involved in the study. Participants could only be enrolled following informed written consent. Results will be published in peer-reviewed journals and presented at scientific and clinical conferences.

Trial registration number

ISRCTN00691795

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.

Psychometric properties of the living with long term conditions scale in an English-speaking population living with long term conditions in the UK

Por: Ambrosio · L. · Hislop-Lennie · K. · Serrano-Fuentes · N. · Driessens · C. · Portillo · M. C.
Objective

To present the psychometric properties of the living with long-term condition (LwLTCs) scale in an English-speaking population of people with different LTCs.

Design

An observational and cross-sectional study, with retest was conducted. Psychometric properties including feasibility, internal consistency, confirmatory factor analysis, reproducibility and content validity were tested.

Setting

The study took place across the UK via primary care surgeries and voluntary organisations, between December 2021 and June 2022.

Participants

The study included 577 patients living with different LTCs, as chronic obstructive pulmonary disease, arthritis, chronic heart failure, Parkinson’s disease, chronic kidney disease and type 2 diabetes mellitus. Inclusion criteria included: (a) having been diagnosed with one or more of the conditions; (b) being able to read, understand and answer written questionnaires; (c) being fluent in English and (d) being able to provide written informed consent. Patients were involved in the design and pilot study of the scale.

Results

A total sample of 577 people with an age range of 37–97 years (98±9.65) were recruited. Internal consistency of the total 26-item LwLTCs scale score was excellent (ordinal alpha=0.90) but confirmatory factor analysis showed better fit indices (Normed Fit Index=0.96; standardised root mean square residual=0.051; Goodness of Fit Index=0.98) for a 20-item LwLTCs scale.

Conclusions

A shorter version of the LwLTCs scale, with just 20 items and with excellent psychometric properties, is recommended. Having a short scale is key when considering the implementation of the scale in clinical practice to develop person-centred pathways and more comprehensive care plans.

Wearables for early detection of atrial fibrillation and timely referral for Indigenous people >=55 years: mixed-methods protocol

Por: Henson · C. · Rambaldini · B. · Freedman · B. · Carlson · B. · Parter · C. · Christie · V. · Skinner · J. · Meharg · D. · Kirwan · M. · Ward · K. · Speier · S. N. K. · Gwynne · K.
Introduction

Digital health technologies have the potential to provide cost-effective care to remote and underserved populations. To realise this potential, research must involve people not traditionally included. No research focuses on the acceptability and feasibility of older Indigenous people using wearables for early atrial fibrillation (AF) detection. This protocol compares digital augmentation against standard practice to detect AF, evaluate heart health self-efficacy and health literacy changes and identify barriers in collaboration with Aboriginal Community Controlled Health Organisations. It will establish a framework for implementing culturally safe and acceptable wearable programmes for detecting and managing AF in Indigenous adults ≥55 years and older.

Methods

This mixed-methods research will use the Rambaldini model of collective impact, a user-centred, co-design methodology and yarning circles, a recognised Indigenous research methodology to assess the cultural safety, acceptability, feasibility and efficacy of incorporating wearables into standard care for early AF detection.

Analysis

Qualitative data will be analysed to create composite descriptions of participants' experiences and perspectives related to comfort, cultural safety, convenience, confidence, family reactions and concerns. Quantitative device data will be extracted and analysed via Statistical Product and Service Solutions (SPSS).

Conclusion

Prioritising perspectives of older Indigenous adults on using wearables for detecting and monitoring cardiovascular disease will ensure that the findings are effective, relevant and acceptable to those impacted.

Ethics and dissemination

Findings will be published in open-source peer-reviewed journals, shared at professional conferences, described in lay terms and made available to the public. The AHMRC HREC Reference Number approved 1135/15.

INdigenous Systems and Policies Improved and Reimagined for Ear and hearing care (INSPIRE): a multi-method study protocol

Por: Nash · K. · Gwynne · K. · Dimitropoulos · Y. · Fitzpatrick · M. · Gunasekera · H. · Halvorsen · L. · Kong · K. · Lumby · N. · Macniven · R. · Parter · C. · Wingett · A. · McMahon · C.
Introduction

Otitis media (middle ear disease) severity and chronicity among Aboriginal and Torres Strait Islander people, as well as gaps in socioeconomic outcomes related to hearing loss, indicates a breakdown in the current ear and hearing care system. The ear and hearing care system spans multiple sectors due to long-term impacts of otitis media and hearing loss in health, education and employment, necessitating a multi-disciplinary cross-sectorial approach to ear and hearing care. Public policies shape the current ear and hearing care system and here it is argued that a critical public policy analysis across different sectors is needed, with strong Aboriginal and Torres Strait Islander leadership and guidance. The current study aims to establish consensus-based ear and hearing care policy solutions for Aboriginal and Torres Strait Islander people in Australia.

Methods and analysis

This multi-method study will be guided by a Brains Trust with strong Aboriginal and Torres Strait Islander leadership. Public policies in hearing health, social services, and education will be scoped to identify policy gaps, using the World Health Organization framework. Qualitative data will be collected through a culturally specific process of yarning circles to identify policy challenges and/or limitations in enabling accessible ear and hearing care programs/services for Aboriginal and Torres Strait Islander people, using dimensions of Morestin’s public policy appraisal tool as an interview guide for stakeholders. Themes from the yarning circles will be used to inform an expert Delphi process to establish consensus-based policy solutions for optimising the ear and hearing care system for Aboriginal and Torres Strait Islander people.

Ethics and dissemination

This study has approval from the Australian Institute of Aboriginal and Torres Strait Islander Studies Ethics Committee. Study findings will be disseminated to community through Brains Trust members and study participants, as well as through publications in peer-reviewed journals and research forum presentations.

Exercise therapy for knee osteoarthritis pain: how does it work? A study protocol for a randomised controlled trial

Por: Beckwee · D. · Nijs · J. · Bierma-Zeinstra · S. M. A. · Leemans · L. · Leysen · L. · Puts · S. · Rice · D. · Schiphof · D. · Bautmans · I.
Introduction

Muscle strengthening training (MST) and behavioural graded activity (BGA) show comparable effects on knee osteoarthritic (KOA) pain, but the mechanisms of action remain unclear. Both exercise-induced anti-inflammation and central sensitisation are promising pathways for pain relief in response to exercise therapy in patients with KOA: MST has the potential to decrease inflammation and BGA has the potential to decrease central sensitisation. Hence, this study aims to examine inflammation and central sensitisation as mediators for the effect of MST and/or BGA on pain in patients with KOA.

Methods and analysis

The Knee OsteoArthritis PAIN trial started on 10 January 2020 (anticipated end: April 2024). The three-arm clinical trial aims to recruit 90 KOA patients who will be randomly allocated to 12 weeks of (1) MST, (2) BGA or (3) care as usual. Assessments will be performed at baseline, 13 and 52 weeks after finishing the intervention. Outcomes, including pain (Knee injury and Osteoarthritis Outcome Score), were chosen in line with the OARSI recommendations for clinical trials of rehabilitation interventions for OA and the IMMPACT/OMERACT recommendations for the assessment of physical function in chronic pain clinical trials. Inflammation as well as features of central sensitisation (including conditioned pain modulation, offset analgesia, temporal summation of pain and event-related potentials following electrical stimulation), will be considered as treatment mediators. A multiple mediators model will be estimated with a path-analysis using structural equation models. In July 2023, all 90 KOA patients have been included and 42 participants already finished the study.

Ethics and dissemination

This study obtained ethics approval (B.U.N. 143201941843). Unravelling the mechanisms of action of exercise therapy in KOA will not only be extremely valuable for researchers, but also for exercise immunology and pain scientists and clinicians.

Trial registration number

NCT04362618.

Predictive factors for the treatment success of peri-implantitis: a protocol for a prospective cohort study

Por: Zhu · Y. · Lu · H. · Yang · S. · Liu · Y. · Zhu · P. · Li · P. · Waal · Y. C. M. D. · Visser · A. · Tjakkes · G.-H. E. · Li · A. · Xu · S.
Introduction

Peri-implantitis, a common biological complication of dental implant, has attracted considerable attention due to its increasing prevalence and limited treatment efficacy. Previous studies have reported several risk factors associated with the onset of peri-implantitis (eg, history of periodontitis, poor plaque control and smoking). However, inadequate data are available on the association between these risk factors and successful outcome after peri-implantitis therapy. This prospective cohort study aims to identify the local and systemic predictive factors for the treatment success of peri-implantitis.

Methods and analysis

A single-centre cohort study will be conducted by recruiting 275 patients diagnosed with peri-implantitis. Sociodemographic variables, healthy lifestyles and systemic disorders will be obtained using questionnaires. In addition, clinical and radiographic examinations will be conducted at baseline and follow-up visits. Treatment success is defined as no bleeding on probing on more than one point, no suppuration, no further marginal bone loss (≥0.5 mm) and probing pocket depth ≤5 mm at the 12-month follow-up interval. After adjustment for age, sex and socioeconomic status, potential prognostic factors related to treatment success will be identified using multivariable logistic regression models.

Ethics and dissemination

This cohort study in its current version (2.0, 15 July 2022) is in accordance with the Declaration of Helsinki and was approved by the Ethics Committee of Stomatological Hospital, Southern Medical University (EC-CT-(2022)34). The publication will be on behalf of the study site.

Trial registration number

ChiCTR2200066262.

Evaluation of a codesigned group cognitive-behavioural therapy intervention for trans young people (TAG TEAM): protocol for a feasibility trial and a subsequent pilot RCT

Por: Chinsen · A. · Cronin · T. J. · Pace · C. C. · Tollit · M. A. · Pang · K. C.
Introduction

Trans young people are at a higher risk of mental health difficulties such as depression, anxiety and suicidality than their cisgender peers, due in part to their experiences of minority stress. This protocol describes a feasibility trial and subsequent pilot randomised controlled trial (RCT) of a codesigned group cognitive–behavioural therapy intervention for trans young people, named Trans Adolescent Group ThErapy for Alleviating Minority stress (TAG TEAM).

Methods and analysis

To evaluate TAG TEAM, we will conduct a feasibility trial followed by a pilot RCT with trans young people aged 14–16 years who have been referred to the Royal Children’s Hospital Gender Service in Melbourne, Australia. In the feasibility trial, we aim to enrol 32 participants who will be randomised at a 1:1 ratio to either in-person or online intervention arms. Participants will be assessed at baseline and post-treatment, with a nested qualitative evaluation post-treatment. Primary outcomes are the feasibility and acceptability of the intervention and the study design and associated procedures, including comparison of the in-person and online delivery modes. In the subsequent pilot RCT, we aim to enrol 64 participants who will be randomised at a 1:1 ratio to an intervention or waitlist control arm, with delivery mode determined by the feasibility trial. Participants will complete assessments at baseline, post-treatment and 3-month follow-up. Primary outcomes are the feasibility and acceptability of the RCT study design. In both the feasibility trial and pilot RCT, participants will complete assessments related to mood, anxiety, suicidality, quality of life, minority stress, family support and social transition. Quantitative data will be analysed using descriptive statistics. Qualitative data will be analysed using thematic and interpretive analysis.

Ethics and dissemination

The Royal Children’s Hospital Human Research Ethics Committee has approved this study (#91162). Informed consent will be obtained in writing from all participants and a legal guardian. Findings will inform the development of a full-scale RCT to evaluate the efficacy of TAG TEAM and will be disseminated through conferences and peer-reviewed journals.

Trial registration number

ACTRN12623000302651, ACTRN12623000318684.

Extended pancreatic neck transection versus conventional pancreatic neck transection during laparoscopic pancreaticoduodenectomy (LPDEXCEPT): protocol for a multicentre superiority randomised controlled trial

Por: You · J. · Zhang · J. · Cai · H. · Wang · X. · Wang · H. · Li · Y. · Yu · C. · Wang · L. · Zhou · X. · Peng · B. · Cai · Y.
Introduction

Postoperative pancreatic fistula (POPF) remains one of the most severe complications of laparoscopic pancreaticoduodenectomy (LPD). Theoretically, transecting the pancreatic neck more distally has both advantages (more blood supply, and more central pancreatic duct) and disadvantages (maybe smaller the pancreatic duct) in preventing POPF. This theoretical contradiction pushed us to organise this trial to explore the impact of the level of pancreatic transection in clinical practice. We conduct this randomised trial with the hypothesis that extended pancreatic neck transection has superiority to conventional pancreatic neck transection.

Methods and analysis

The LPDEXCEPT (Extended pancreatic neck transection versus conventional pancreatic neck transection during laparoscopic pancreaticoduodenectomy) trial is a multicentre, randomised-controlled, open-label, superiority trial in 4 centres whose annual surgical volume for LPD is more than 25 cases with pancreatic surgeons who had completed their learning curve. A total of 154 patients who meet the inclusive and exclusive criteria are randomly allocated to the extended pancreatic neck transection group or conventional pancreatic neck transection group in a 1:1 ratio. The stratified randomised block design will be applied, with stratified factors are surgical centre and the diameter of the main pancreatic duct measured by preoperative CT scan (preMPD). The primary outcome is the incidence of the clinically relevant pancreatic fistula.

Ethics and dissemination

Ethics Committee on Biomedical Research of West China Hospital of Sichuan University has approved this trial in March 2023 (approval no. 2023-167). Results of this trial will be published in peer-reviewed journals and conference proceedings.

Trial registration number

NCT05808894.

Impact of multimorbidity and complex multimorbidity on healthcare utilisation in older Australian adults aged 45 years or more: a large population-based cross-sectional data linkage study

Por: Kabir · A. · Conway · D. P. · Ansari · S. · Tran · A. · Rhee · J. J. · Barr · M.
Objectives

As life expectancy increases, older people are living longer with multimorbidity (MM, co-occurrence of ≥2 chronic health conditions) and complex multimorbidity (CMM, ≥3 chronic conditions affecting ≥3 different body systems). We assessed the impacts of MM and CMM on healthcare service use in Australia, as little was known about this.

Design

Population-based cross-sectional data linkage study.

Setting

New South Wales, Australia.

Participants

248 496 people aged ≥45 years who completed the Sax Institute’s 45 and Up Study baseline questionnaire.

Primary outcome

High average annual healthcare service use (≥2 hospital admissions, ≥11 general practice visits and ≥2 emergency department (ED) visits) during the 3-year baseline period (year before, year of and year after recruitment).

Methods

Baseline questionnaire data were linked with hospital, Medicare claims and ED datasets. Poisson regression models were used to estimate adjusted and unadjusted prevalence ratios for high service use with 95% CIs. Using a count of chronic conditions (disease count) as an alternative morbidity metric was requested during peer review.

Results

Prevalence of MM and CMM was 43.8% and 15.5%, respectively, and prevalence increased with age. Across three healthcare settings, MM was associated with a 2.02-fold to 2.26-fold, and CMM was associated with a 1.83-fold to 2.08-fold, increased risk of high service use. The association was higher in the youngest group (45–59 years) versus the oldest group (≥75 years), which was confirmed when disease count was used as the morbidity metric in sensitivity analysis.

When comparing impact using three categories with no overlap (no MM/CMM, MM with no CMM, and CMM), CMM had greater impact than MM across all settings.

Conclusion

Increased healthcare service use among older adults with MM and CMM impacts on the demand for primary care and hospital services. Which of MM or CMM has greater impact on risk of high healthcare service use depends on the analytic method used. Ageing populations living longer with increasing burdens of MM and CMM will require increased Medicare funding and provision of integrated care across the healthcare system to meet their complex needs.

Effects of the enhanced recovery after surgery intervention for preventing postpartum depression: a protocol for systematic review and meta-analysis

Por: Yang · C. · Chen · K. · Zhang · P. · Xue · M. · Li · H.
Introduction

Postpartum depression (PPD), a prevalent public health problem, is a debilitating mental disorder for which preventive interventions could yield dramatic benefits. However, viable approach focusing the prevention of PPD for caesarean section (CS) patients remains limited currently. In recent decades, enhanced recovery after surgery (ERAS) has gradually been implemented in CS and appears to be a potential and favourable preventive intervention for PPD, but systematic evidence on this issue is lacking. Therefore, a meta-analysis is designed to systematically explore the potential effect of ERAS on the prevention of PPD in CS patients.

Methods and analysis

Meta-analysis will be performed according to the Preferred Reporting Items for Systematic Review and Meta-Analyses statement. A systematic search across the PubMed, Embase, Cochrane Library, China National Knowledge Infrastructure, Chinese Biomedical Literature Database, Chinese Scientific Journal Database, grey literature and Wanfang Database will be conducted from inception to July 2023. Relevant studies investigating the association between ERAS and PPD will be included. Two reviewers will independently carry out the literature selection, data extraction and risk of bias assessment. Disagreements will be resolved by group consensus. Statistical analyses will use the RevMan V.5.3 and STATA V.13 software. The Grading of Recommendations Assessment, Development, and Evaluation system will be used to evaluate the strength of evidence.

Ethics and dissemination

This study raises no ethical issues. The pending meta-analysis may provide reliable evidence supporting ERAS as a viable preventive option for PPD in CS patients, further providing a useful reference for the health authorities and promoting the future clinical practice in this field. The formal results of this study will be submitted to a professional journal for publication.

PROSPERO registration number

CRD42023485929.

Serotype 3 Experimental Human Pneumococcal Challenge (EHPC) study protocol: dose ranging and reproducibility in a healthy volunteer population (challenge 3)

Por: Hazenberg · P. · Robinson · R. E. · Farrar · M. · Solorzano · C. · Hyder-Wright · A. · Liatsikos · K. · Brunning · J. · Fleet · H. · Bettam · A. · Howard · A. · Kenny-Nyazika · T. · Urban · B. · Mitsi · E. · El Safadi · D. · Davies · K. · Lesosky · M. · Gordon · S. B. · Ferreira · D. M.
Introduction

Since the introduction of pneumococcal conjugate vaccines, pneumococcal disease rates have declined for many vaccine-type serotypes. However, serotype 3 (SPN3) continues to cause significant disease and is identified in colonisation epidemiological studies as one of the top circulating serotypes in adults in the UK. Consequently, new vaccines that provide greater protection against SPN3 colonisation/carriage are urgently needed. The Experimental Human Pneumococcal Challenge (EHPC) model is a unique method of determining pneumococcal colonisation rates, understanding acquired immunity, and testing vaccines in a cost-effective manner. To enhance the development of effective pneumococcal vaccines against SPN3, we aim to develop a new relevant and safe SPN3 EHPC model with high attack rates which could be used to test vaccines using small sample size.

Methods and analysis

This is a human challenge study to establish a new SPN3 EHPC model, consisting of two parts. In the dose-ranging/safety study, cohorts of 10 healthy participants will be challenged with escalating doses of SPN3. If first challenge does not lead into colonisation, participants will receive a second challenge 2 weeks after. Experimental nasopharyngeal (NP) colonisation will be determined using nasal wash sampling. Using the dose that results in ≥50% of participants being colonised, with a high safety profile, we will complete the cohort with another 33 participants to check for reproducibility of the colonisation rate. The primary outcome of this study is to determine the optimal SPN3 dose and inoculation regime to establish the highest rates of NP colonisation in healthy adults. Secondary outcomes include determining density and duration of experimental SPN3 NP colonisation and characterising mucosal and systemic immune responses to SPN3 challenge.

Ethics and dissemination

This study is approved by the NHS Research and Ethics Committee (reference 22/NW/0051). Findings will be published in peer-reviewed journals and reports will be made available to participants.

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

Comparing the efficacy and safety of three surgical approaches for total hysterectomy (TSATH): protocol for a multicentre, single-blind, parallel-group, randomised controlled trial

Por: Zhang · W. · Deng · L. · Yang · F. · Liu · J. · Chen · S. · You · X. · Gou · J. · Zi · D. · Li · Y. · Qi · X. · Wang · Y. · Zheng · Y.
Introduction

Hysterectomy is the most common surgical procedure in the field of gynaecology. The traditional multiport laparoscopy, transumbilical laparoendoscopic single-site surgery (TU-LESS) and transvaginal natural orifice transluminal endoscopic surgery (vNOTES) hysterectomy approaches have been implemented to varying degrees in clinical practice. At present, although their feasibility has been proven, there are no large randomised controlled studies on postoperative rehabilitation. This study aims to evaluate postoperative recovery and assess the safety and effectiveness of these three surgical approaches for total laparoscopic hysterectomy.

Method and analysis

This is a multicentre, randomised, single-blind, three-arm, parallel-group, interventional clinical trial. Recruitment will be carried out in five tertiary hospitals in China. Patients diagnosed with benign uterine disease or precancerous lesions will be assigned to the vNOTES group, TU-LESS group and conventional laparoscopy group at a 1:1:1 ratio. The achievement rate of comprehensive indices of enhanced recovery after surgery (ERAS) within 24 hours postoperatively will be considered the primary outcome (the comprehensive indicators of ERAS include fluid intake, passing flatus, urination after catheter removal, ambulation and a Visual Analogue Scale score ≤3.) This study will use a non-inferiority test, with a power (1–ß) of 80% and a margin of –0.15, at a one-sided α of 0.0125. The sample size will be 480 patients (including an assumed 15% dropout rate), calculated according to the primary outcome.

Ethics and dissemination

This study was approved on 25 April 2022 by the Medical Ethics Committee of West China Second University Hospital (2022(057)), Sichuan University, Chengdu, China. All participants will be required to provide informed consent before their participation in the study. The results of the trial will be submitted for publication in a peer-reviewed journal and presented at international conferences.

Protocol version

V.3.0, 31 August 2023.

Trial registration number

ChiCTR2200057405.

Feasibility and acceptability of offering breast cancer risk assessment to general population women aged 30-39 years: a mixed-methods study protocol

Por: Hindmarch · S. · Howell · S. J. · Usher-Smith · J. A. · Gorman · L. · Evans · D. G. · French · D. P.
Introduction

Breast cancer incidence starts to increase exponentially when women reach 30–39 years, hence before they are eligible for breast cancer screening. The introduction of breast cancer risk assessment for this age group could lead to those at higher risk receiving benefits of earlier screening and preventive strategies. Currently, risk assessment is limited to women with a family history of breast cancer only. The Breast CANcer Risk Assessment in Younger women (BCAN-RAY) study is evaluating a comprehensive breast cancer risk assessment strategy for women aged 30–39 years incorporating a questionnaire of breast cancer risk factors, low-dose mammography to assess breast density and polygenic risk. This study will assess the feasibility and acceptability of the BCAN-RAY risk assessment strategy.

Methods and analysis

This study involves women undergoing risk assessment as part of the BCAN-RAY case-control study (n=750). They will be aged 30–39 years without a strong family history of breast cancer and invited to participate via general practice. A comparison of uptake rates by socioeconomic status and ethnicity between women who participated in the BCAN-RAY study and women who declined participation will be conducted. All participants will be asked to complete self-report questionnaires to assess key potential harms including increased state anxiety (State Trait Anxiety Inventory), cancer worry (Lerman Cancer Worry Scale) and satisfaction with the decision to participate (Decision Regret Scale), alongside potential benefits such as feeling more informed about breast cancer risk. A subsample of approximately 24 women (12 at average risk and 12 at increased risk) will additionally participate in semistructured interviews to understand the acceptability of the risk assessment strategy and identify any changes needed to it to increase uptake.

Ethics and dissemination

Ethical approval was granted by North West—Greater Manchester West Research Ethics Committee (reference: 22/NW/0268). Study results will be disseminated through peer-reviewed journals, conference presentations and charitable organisations.

Trial registration number

NCT05305963.

Older adults attitudes towards deprescribing and medication changes: a longitudinal sub-study of a cluster randomised controlled trial

Por: Jungo · K. T. · Weir · K. R. · Cateau · D. · Streit · S.
Objective

To investigate the association between older patients’ willingness to have one or more medications deprescribed and: (1) change in medications, (2) change in the appropriateness of medications and (3) implementation of prescribing recommendations generated by the electronic decision support system tested in the ‘Optimising PharmacoTherapy In the Multimorbid Elderly in Primary CAre’ (OPTICA) trial.

Design

A longitudinal sub-study of the OPTICA trial, a cluster randomised controlled trial.

Setting

Swiss primary care settings.

Participants

Participants were aged ≥65 years, with ≥3 chronic conditions and ≥5 regular medications recruited from 43 general practitioner (GP) practices.

Exposures

Patients’ willingness to have medications deprescribed was assessed using three questions from the ‘revised Patient Attitudes Towards Deprescribing’ (rPATD) questionnaire and its concerns about stopping score.

Measures/analyses

Medication-related outcomes were collected at 1 year follow-up. Aim 1 outcome: change in the number of long-term medications between baseline and 12 month follow-up. Aim 2 outcome: change in medication appropriateness (Medication Appropriateness Index). Aim 3 outcome: binary variable on whether any prescribing recommendation generated during the OPTICA medication review was implemented. We used multilevel linear regression analyses (aim 1 and aim 2) and multilevel logistic regression analyses (aim 3). Models were adjusted for sociodemographic variables and the clustering effect at GP level.

Results

298 patients completed the rPATD, 45% were women and 78 years was the median age. A statistically significant association was found between the concerns about stopping score and the change in the number of medications over time (per 1-unit increase in the score the average number of medications use was 0.65 higher; 95% CI: 0.08 to 1.22). Other than that we did not find evidence for statistically significant associations between patients’ agreement with deprescribing and medication-related outcomes.

Conclusions

We did not find evidence for an association between most measures of patient agreement with deprescribing and medication-related outcomes over 1 year.

Trial registration number

NCT03724539.

Characterising respiratory infections among hospitalised children during the COVID-19 pandemic in southeastern China: a cross-sectional study of pathogens and clinical association

Por: Huang · H. · Wu · B. · Lin · W.
Objective

Children with acute respiratory tract infections (ARTIs) pose significantly burden on healthcare facilities due to high hospitalisation rates and mortality. However, limited epidemiological and clinical characteristics data on ARTIs in southeastern China during the COVID-19 pandemic exists.

Design

Cross-sectional.

Setting

Tertiary hospital associated with the First Affiliated Hospital, Fujian Medical University, China.

Participants

1007 hospitalised children diagnosed with ARTIs, aged 30 days to 15 years, were enrolled in this study from 1 January 2020 to 31 December 2021.

Outcome measure

The primary outcomes are the rate of pathogen infections in children with ARTIs. Secondary outcomes are the description of risk factors associated with ARTIs in children.

Results

Of the 1007 enrolled children, 28.2%, 42.2%, 21.8% and 7.7% were diagnosed with upper respiratory tract infection, bronchopneumonia, bronchitis and pneumonia, respectively. Mycoplasma pneumoniae (MP) was the most prevalent pathogen (31.9%), followed by influenza B virus (IFVB; 29.1%) and influenza A virus (IFVA; 19.1%). The study found that children under 1 year old (older than 30 days: ORIFVB=12.50; ORMP=8.53), children aged 1–3 years (ORMP=1.62), the winter season (ORIFVA=1.36), the time from symptoms onset to hospitalisation (ORMP=1.10) and increased precipitation (ORLP=1.01) were high-risk factors for ARTIs.

Conclusion

This investigation offers significant insights into the prevalence and distribution of common pathogens among children experiencing ARTIs in the context of the COVID-19 pandemic. The discernment of high-risk factors linked to these pathogens enhances our understanding of the epidemiological characteristics of ARTIs in children.

How do they cope? A national cross-sectional study of coping in hospital doctors in Ireland

Por: Doherty · A. · Prihodova · L. · Walsh · G. · Hayes · B.
Objectives

To measure coping strategies and associated psychological distress, burnout and work ability in hospital doctors in Ireland.

Design

National cross-sectional study of randomised sample of trainee and consultant hospital doctors.

Setting

Irish publicly funded hospitals and residential institutions.

Participants

1749 doctors returned surveys (55% response rate).

Outcome measures

Dependent variables were psychological distress (measured using 12-item General Health Questionnaire), burnout (Maslach Burnout Inventory) and work ability (single-item measure). Adaptive and maladaptive coping strategies (Brief Coping Orientation to Problems Experienced) were covariates.

Results

The coping mechanism most frequently reported by this cohort was the adaptive strategy of active planning. Increased mean hours worked (MHW) (OR 1.02; 95% CI 1.01 to 1.03), a low Work Ability Score (OR 3.23; 95% CI 2.47 to 4.23) and maladaptive coping strategies (OR 1.26; 95% CI 1.22 to 1.31) were significantly associated with psychological distress. Adaptive coping was associated with decreased psychological distress (OR 0.98; 95% CI 0.97 to 1.00). Increased MHW (OR 0.98; 95% CI 0.97 to 0.99), insufficient work ability (OR 0.62; 95% CI 0.48 to 0.80) and maladaptive coping (OR 0.87; 95% CI 0.85 to 0.89) were significantly associated with burnout. Increased MHW (OR 0.99; 95% CI 0.98 to 1.00) and maladaptive coping (OR 0.90, 95% CI 0.88 to 0.92) were significantly associated with insufficient work ability.

Conclusions

Adaptive coping is associated with decreased psychological distress but does not mitigate the effect of increased work hours, which are associated with burnout, distress and insufficient work ability, regardless of a doctor’s coping style. The burden of psychological distress on doctors cannot be mitigated meaningfully unless workplace factors are addressed.

Impact of a peer-support programme to improve loneliness and social isolation due to COVID-19: does adding a secure, user friendly video-conference solution work better than telephone support alone? Protocol for a three-arm randomised clinical trial

Por: Lee · J. S. · Rose · L. · Borgundvaag · B. · McLeod · S. L. · Melady · D. · Mohindra · R. · Sinha · S. K. · Wesson · V. · Wiesenfeld · L. · Kolker · S. · Kiss · A. · Lowthian · J.
Introduction

The COVID-19 pandemic has forced the implementation of physical distancing and self-isolation strategies worldwide. However, these measures have significant potential to increase social isolation and loneliness. Among older people, loneliness has increased from 40% to 70% during COVID-19. Previous research indicates loneliness is strongly associated with increased mortality. Thus, strategies to mitigate the unintended consequences of social isolation and loneliness are urgently needed. Following the Obesity-Related Behavioural Intervention Trials model for complex behavioural interventions, we describe a protocol for a three-arm randomised clinical trial to reduce social isolation and loneliness.

Methods and analysis

A multicentre, outcome assessor blinded, three-arm randomised controlled trial comparing 12 weeks of: (1) the HOspitals WoRking in Unity (‘HOW R U?’) weekly volunteer-peer support telephone intervention; (2) ‘HOW R U?’ deliver using a video-conferencing solution and (3) a standard care group. The study will follow Consolidated Standard of Reporting Trials guidelines.

We will recruit 24–26 volunteers who will receive a previously tested half day lay-training session that emphasises a strength-based approach and safety procedures. We will recruit 141 participants ≥70 years of age discharged from two participating emergency departments or referred from hospital family medicine, geriatric or geriatric psychiatry clinics. Eligible participants will have probable baseline loneliness (score ≥2 on the de Jong six-item loneliness scale). We will measure change in loneliness, social isolation (Lubben social network scale), mood (Geriatric Depression Score) and quality of life (EQ-5D-5L) at 12–14 weeks postintervention initiation and again at 24–26 weeks.

Ethics and dissemination

Approval has been granted by the participating research ethics boards. Participants randomised to standard care will be offered their choice of telephone or video-conferencing interventions after 12 weeks. Results will be disseminated through journal publications, conference presentations, social media and through the International Federation of Emergency Medicine.

Trial registration number

NCT05228782.

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