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A meta‐analysis evaluating wound infections and other complications following distal versus complete gastrectomy for gastric cancer

Abstract

A meta-analysis investigation was carried out to measure the wound infections (WIs) and other postoperative problems (PPs) of distal gastrectomy (DG) compared with total gastrectomy (TG) for gastric cancer (GC). A comprehensive literature investigation till February 2023 was used and 1247 interrelated investigations were reviewed. The 12 chosen investigations enclosed 2896 individuals with GC in the chosen investigations' starting point, 1375 of them were TG, and 1521 were DG. Odds ratio (OR) in addition to 95% confidence intervals (CIs) were utilized to compute the value of the WIs and other PPs of DG compared with TG for GC by the dichotomous approaches and a fixed or random model. TG had significantly higher overall PP (OR, 1.58; 95% CI, 1.15–2.18, p = 0.005), WIs (OR, 1.69; 95% CI, 1.07–2.67, p = 0.02), peritoneal abscess (PA) (OR, 2.99; 95% CI, 1.67–5.36, p < 0.001), anastomotic leakage (AL) (OR, 1.90; 95% CI, 1.21–2.97, p = 0.005) and death (OR, 2.26; 95% CI, 1.17–4.37, p = 0.02) compared to those with DG in individuals with GC. TG had significantly higher overall PP, WIs, PA, AL and death compared to those with DG in individuals with GC. However, care must be exercised when dealing with its values because of the low sample size of some of the nominated investigations for the meta-analysis.

Efficient assessment of brain fog and fatigue: Development of the Fatigue and Altered Cognition Scale (FACs)

by Timothy R. Elliott, Yu-Yu Hsiao, Kathleen Randolph, Randall J. Urban, Melinda Sheffield-Moore, Richard B. Pyles, Brent E. Masel, Tamara Wexler, Traver J. Wright

Debilitating symptoms of fatigue and accompanying “brain fog” are observed among patients with various chronic health conditions. Unfortunately, an efficient and psychometrically sound instrument to assess these co-occurring symptoms is unavailable. Here, we report the development and initial psychometric properties of the Fatigue and Altered Cognition Scale (the FACs), a measure of self-reported central fatigue and brain fog. Traumatic brain injury (TBI) was chosen to model and develop the FACs due to research team expertise and established links between TBI and the symptom complex. Potential items were generated by researchers and clinicians with experience treating these symptoms, drawing from relevant literature and review of patient responses to measures from past and current TBI studies. The 20 candidate items for the FACs—ten each to assess altered cognition (i.e., brain fog) and central fatigue–were formatted on an electronic visual analogue response scale (eVAS) via an online survey. Demographic information and history of TBI were obtained. A total of 519 participants consented and provided usable data (average age = 40.23 years; 73% female), 204 of whom self-reported a history of TBI (75% reported mild TBI). Internal consistency and reliability values were calculated. Confirmatory factor analysis (CFA) examined the presumed two-factor structure of the FACs and a one-factor solution for comparison. A measurement invariance test of the two latent constructs (altered cognition, fatigue) among participants with and without TBI was conducted. All items demonstrated normal distribution. Cronbach’s alpha coefficients indicated good internal consistency for both factors (α’s = .95). Omega reliability values were favorable (α’s = .95). CFA supported the presumed two-factor model and item loadings which outperformed the one-factor model. Measurement invariance found the two-factor structure was consistent between the two groups. Implications of these findings, study limitations, and potential use of the FACs in clinical research and practice are discussed.

Investigating automated regression models for estimating left ventricular ejection fraction levels in heart failure patients using circadian ECG features

by Sona M. Al Younis, Leontios J. Hadjileontiadis, Aamna M. Al Shehhi, Cesare Stefanini, Mohanad Alkhodari, Stergios Soulaidopoulos, Petros Arsenos, Ioannis Doundoulakis, Konstantinos A. Gatzoulis, Konstantinos Tsioufis, Ahsan H. Khandoker

Heart Failure (HF) significantly impacts approximately 26 million people worldwide, causing disruptions in the normal functioning of their hearts. The estimation of left ventricular ejection fraction (LVEF) plays a crucial role in the diagnosis, risk stratification, treatment selection, and monitoring of heart failure. However, achieving a definitive assessment is challenging, necessitating the use of echocardiography. Electrocardiogram (ECG) is a relatively simple, quick to obtain, provides continuous monitoring of patient’s cardiac rhythm, and cost-effective procedure compared to echocardiography. In this study, we compare several regression models (support vector machine (SVM), extreme gradient boosting (XGBOOST), gaussian process regression (GPR) and decision tree) for the estimation of LVEF for three groups of HF patients at hourly intervals using 24-hour ECG recordings. Data from 303 HF patients with preserved, mid-range, or reduced LVEF were obtained from a multicentre cohort (American and Greek). ECG extracted features were used to train the different regression models in one-hour intervals. To enhance the best possible LVEF level estimations, hyperparameters tuning in nested loop approach was implemented (the outer loop divides the data into training and testing sets, while the inner loop further divides the training set into smaller sets for cross-validation). LVEF levels were best estimated using rational quadratic GPR and fine decision tree regression models with an average root mean square error (RMSE) of 3.83% and 3.42%, and correlation coefficients of 0.92 (p

Feasibility, enablers and challenges of using timeliness metrics for household contact tracing and TB preventive therapy in Pakistan

by Bushra Jamil, Divya Nair, Pruthu Thekkur, Neelofar Laeeq, Anum Adil, Mohammed Khogali, Rony Zachariah, Selma Dar Berger, Srinath Satyanarayana, Ajay M. V. Kumar, Aaron Bochner, Amanda McClelland, Razia Fatima, Anthony D. Harries

Introduction

Screening household contacts of TB patients and providing TB preventive therapy (TPT) is a key intervention to end the TB epidemic. Global and timely implementation of TPT in household contacts, however, is dismal. We adapted the 7-1-7 timeliness metric designed to evaluate and respond to infectious disease outbreaks or pandemics, and assessed the feasibility, enablers and challenges of implementing this metric for screening and management of household contacts of index patients with bacteriologically-confirmed pulmonary TB in Karachi city, Pakistan.

Methods

We conducted an explanatory mixed methods study with a quantitative component (cohort design) followed by a qualitative component (descriptive design with focus group discussions).

Results

From January-June 2023, 92% of 450 index patients had their household contacts line-listed within seven days of initiating anti-TB treatment (“first 7”). In 84% of 1342 household contacts, screening outcomes were ascertained within one day of line-listing (“next 1”). In 35% of 256 household contacts eligible for further evaluation by a medical officer (aged ≤5 years or with chest symptoms), anti-tuberculosis treatment, TPT or a decision for no drugs was made within seven days of symptom screening (“second 7”). The principal reason for not starting anti-tuberculosis treatment or TPT was failure to consult a medical officer: only 129(50%) of 256 contacts consulted a medical officer. Reasons for poor performance in the “second 7” component included travel costs to see a medical officer, loss of daily earnings and fear of a TB diagnosis. Field staff reported that timeliness metrics motivated them to take prompt action in household contact screening and TPT provision and they suggested these be included in national guidelines.

Conclusions

Field staff found “7-1-7” timeliness metrics to be feasible and useful. Integration of these metrics into national guidelines could improve timeliness of diagnosis, treatment and prevention of TB within households of index patients.

Pulmonary expansion manoeuvres compared to usual care on ventilatory mechanics, oxygenation, length of mechanical ventilation and hospital stay, extubation, atelectasis, and mortality of patients in mechanical ventilation: A randomized clinical trial

by Karina da Silva, Cristino Carneiro Oliveira, Leandro Ferracini Cabral, Carla Malaguti, Anderson José

Pulmonary expansion manoeuvres are therapeutic techniques used to prevent and reverse atelectasis; however, no randomized controlled trials have provided evidence supporting the use of this intervention among individuals on mechanical ventilation. Objective: To evaluate the effects of chest compression-decompression and chest block manoeuvres compared to usual care among patients on mechanical ventilation. Methods: The current study was a randomized clinical trial of adult subjects on mechanical ventilation for 12 to 48 hours. The control group received usual care (passive or active mobilization, manoeuvres for airway clearance and tracheal aspiration). The intervention group received usual care plus two lung expansion manoeuvres, i.e., chest decompression and chest block, while remaining on mechanical ventilation. Assessments were performed before and after usual care, immediately after the intervention and 30 minutes after the intervention. The primary outcome was static compliance. The secondary outcomes were the incidence of atelectasis, dynamic compliance, airway resistance, driving pressure, oxygenation, duration of mechanical ventilation, extubation success, length of hospital and ICU stay, and mortality. Results: Fifty-one participants (67±15 years old, 53% men, 26 in the control group and 25 in the intervention group) were evaluated. No differences in static compliance were observed between groups (intervention minus control) before and after expansion manoeuvres [3.64 ml/cmH2O (95% CI: -0.36–7.65, p = 0.074)]. Peripheral oxygen saturation differed between groups before and after expansion manoeuvres, with more favourable outcome observed in the control group [-1.04% (95% CI: -1.94 –-0.14), p = 0.027]. No differences were found in other outcomes. Conclusion: Chest compression-decompression and chest block manoeuvres did not improve ventilatory mechanics, the incidence of atelectasis, oxygenation, the duration of mechanical ventilation, the length of stay in the ICU and hospital, or mortality in individuals on mechanical ventilation. The findings of this study can be valuable for guiding evidence-based clinical practice and developing a therapeutic approach that provides real benefits for this population.

Could <i>Cratylia argentea</i> replace Tifton 85 hay on growing and finishing lamb diets in tropical areas?

by Elaine Cristina Teixeira, Lucas Freires Abreu, Fernando Antônio de Souza, Walter José Rodrigues Matrangolo, Karina Toledo da Silva, Luciano Soares de Lima, Hemilly Cristina Menezes de Sa, Ângela Maria Quintão Lana

Legumes shrubs such as Cratylia argentea have an ability to thrive in environments with low water availability and poor soil. On the other hand, forage grasses such as Tifton 85 have a greater demand for inputs to be productive. The objective of this study was to evaluate the performance of growing and finishing Lacaune lambs fed Cratylia argentea hay as an alternative to Tifton 85 (Cynodon spp). Twenty-four Lacaune lambs aged between five and six months (average body weight [BW] 21.50 ± 3.38 kg) were arranged in a split-plot randomized block design. The plots consisted of different Cratylia to Tifton 85 hay proportions (0, 20%, 40%, or 100%, dry matter [DM] basis) as a roughage replacement in the total diet. The subplots represented two evaluation times, entitled “initial period” and “final period”, which consisted of the early seven days of total feces and urine collection, and the last seven days of the experiment, respectively. The lambs were blocked by weight with six replicates per treatment. The results show that the level of Tifton 85 replacement for Cratylia hay in the roughage portion of the lamb diet did not influence (P > 0.05) weight gain (WG), dry matter intake or dry matter digestibility; feed conversion, feed efficiency; and the evaluated nitrogen balance variables. The digestibility coefficient of neutral detergent fiber decreased linearly as Tifton 85 replacement for Cratylia level was increased, which probably happened due to the presence of highly lignified material within the Cratylia hay. However, the alternative legume maintained animal performance of Tifton 85. In conclusion, Cratylia hay can be recommended as a potential substitute for Tifton 85 hay, which requires greater inputs for the production. Cratylia may be considered a feeding strategy for livestock production, especially for smallholder livestock systems and regions with unfavorable soil and climate.

COVID-19’s impact on worker stress in human service organizations: The mediating role of inclusion

by Magdalena Calderón-Orellana, Andrés Aparicio, Nicolás López–Huenante

Human service organizations faced extraordinary challenges due to COVID-19. Despite the increasing interest and research in this new scenario, there has been limited discussion about the impact of COVID-19 on workers, the challenges they faced, and the resulting stress. This study aimed to analyze the impact of COVID-19 on work-related stress and the mediating role of inclusion among workers in human service organizations in Chile during the pandemic. The research design was quantitative and involved a sample of 173 workers from civil society organizations who were contacted during the pandemic. The study confirmed that individuals most affected by the pandemic experienced higher levels of work-related stress, and that inclusion played a negative mediating role in this relationship. This article highlights the importance of relationships, decision-making processes, and access to information in reducing stress in post-COVID scenarios for organizations that traditionally handle crises.

Family-focused intervention to promote adolescent mental health and well-being in Moldova and North Macedonia (FLOURISH): feasibility study protocol

Por: Shenderovich · Y. · Piolanti · A. · Babii · V. · Calovska-Hertzog · N. · Evans · R. E. · Heinrichs · N. · Burgund Isakov · A. · Lesco · G. · Moore · G. · Mueller · J. · Raleva · M. · Shimbov · B. · Simon · J. · Waller · F. · Wienand · D. · Foran · H. M.
Introduction

Family-Focused Adolescent & Lifelong Health Promotion (FLOURISH) project will adapt, implement and evaluate a programme to support adolescent mental health and well-being through strategies, such as strengthening parenting practices, adolescent-caregiver relationships, adolescent and parent socioemotional skills, and social support.

Methods and analysis

The project will focus on adolescents aged 10–14 years and their caregivers in North Macedonia and Moldova. The countries were selected based on implementation readiness of two organisations and a need for accessible evidence-informed services to help mitigate health risks due to economic, social and political challenges. Parenting for Lifelong Health (PLH) for Parents and Teens is a family-based programme developed for low-resource settings. PLH has been adapted with input from advisory groups. The programme includes additional components to strengthen impacts on adolescents: adolescent mental health tools, based on UNICEF’s Helping Adolescents Thrive, adolescent peer support and participation booster. This pilot is first of three study phases. The pilot will be a feasibility testing of the adapted intervention and the assessment and implementation procedures to determine further refinements. The pilot will examine if the adapted programme is acceptable for adolescents, their families and providers, explore contextual factors relevant to embedding this programme into longer-term scale-up and investigate whether the programme can be delivered with fidelity and participation; whether the participants report changes in adolescent emotional and behavioural problems, well-being and other outcomes; and whether the study tools are feasible and appropriate. Pre-post adolescent and caregiver questionnaires will provide outcome data. Process evaluation will include attendance and fidelity data, and focus groups. We will examine delivery cost and resource requirements.

Ethics and dissemination

The study was approved at the University of Klagenfurt (Austria), Medical Faculty at St. Cyril and Methodius University (North Macedonia) and National Committee of Ethical Expertise for Clinical Trials (Moldova). Through stakeholder engagement and dissemination, FLOURISH will advance scale-up of open-source family interventions.

Trial registration number

Trial registration: ID101095528; project page: https://www.flourish-study.org/about.html; https://www.linkedin.com/company/flourish-study/

Influence of physical fitness components on personality factors and risk perception of children and adolescents: a cross-sectional study

Objectives

To examine the associations of cardiorespiratory fitness (VO2 max) and muscular strength with indicators related to the risk scale, such as perceived competence, sensation seeking, competitiveness, risk taking and risk perception in sports.

Design

Cross-sectional study.

Setting

High schools from the Region of Murcia (Spain).

Participants

Three-hundred-and-seventeen adolescents participated (mean age: 13.69±1.2 years old).

Primary and secondary outcome measures

Body mass, body height, Course-Navette test, upper limb strength and psychoeducational factors that determine the propensity towards sports accidents in school children, the Sports Accident Propensity Scale were evaluated. It was performance t-test for independent samples, stepwise multiple linear regression models and a multiple mediation analysis.

Results

The analysis showed significant differences with respect to sex in height, VO2 max, handgrip strength and in all factors of the questionnaire (p=0.02-2 max, strength in the handgrip test and age showed a higher score in factors 1 and 3. Higher scores in factor 2 were associated with better VO2 max and strength in handgrip test. Youngers and better values of strength in the handgrip showed higher score in factors 4 and 5. The mediation analysis with two mediating variables (handgrip strength and VO2 max) showed a significant indirect effect. When handgrip strength and VO2 max were included in the equations, the association between sex and each factor ceased to be significant.

Conclusion

This study highlights the potential benefits of muscular strength (handgrip) and VO2 max in the perceived risk scale, and the variable of age on this.

Trial registration number

Clinical trial: NCT05544370 (pre-results).

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

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

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

Design/setting

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

Participants

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

Primary and secondary outcome measures

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

Results

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

Conclusions

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

Perspectives of HPV vaccination among young adults: a qualitative systematic review and evidence synthesis protocol

Por: Mantina · N. M. · Nakayima Miiro · F. · Smith · J. · McClelland · D. J. · Magrath · P. A. · Madhivanan · P.
Introduction

Human papillomavirus (HPV) is the causative agent of nearly all cervical cancers. Despite the proven safety and efficacy of HPV vaccines in preventing HPV-related cancers, the global vaccine coverage rate is estimated to only be 15%. HPV vaccine coverage rates are more actively tracked and reported for adolescents 17 years and younger but there is still a critical window of opportunity to intervene and promote HPV vaccination among young adults aged 18–26 years who are still eligible to be vaccinated. This protocol for a qualitative evidence synthesis aims to review perspectives of HPV vaccination among young adults (18–26 years) and identify facilitators and barriers that influence HPV vaccination uptake and decision-making.

Methods and analysis

Seven databases will be searched from 1 January 2006 to the date of final search. For inclusion, studies must report HPV vaccination perspectives of young adults aged 18–26 years and use qualitative study methods or analysis techniques. Studies will be screened in a two-stage process guided by the eligibility criteria. Final included studies will be evaluated for methodological strengths and limitations using the Critical Appraisal Skills Programme quality assessment tool for qualitative studies. After data extraction, framework analysis will be used to analyse the data applying the socioecological model. Finally, the Grading of Recommendations Assessment, Development and Evaluation - Confidence in the Evidence from Reviews of Qualitative research will be applied to evaluate the confidence in synthesised qualitative findings. The methodology of this review follows the Cochrane Handbook guidelines on qualitative evidence syntheses.

Ethics and dissemination

Formal ethical approval is not required for this study. Findings will be disseminated through peer-reviewed publications, conference presentations and professional networks.

PROSPERO registration number

CRD42023417052.

Specialist healthcare services for concussion/mild traumatic brain injury in England: a consensus statement using modified Delphi methodology

Por: Karvandi · E. · Helmy · A. · Kolias · A. G. · Belli · A. · Ganau · M. · Gomes · C. · Grey · M. · Griffiths · M. · Griffiths · T. · Griffiths · P. · Holliman · D. · Jenkins · P. · Jones · B. · Lawrence · T. · McLoughlin · T. · McMahon · C. · Messahel · S. · Newton · J. · Noad · R. · Raymont
Objective

To establish a consensus on the structure and process of healthcare services for patients with concussion in England to facilitate better healthcare quality and patient outcome.

Design

This consensus study followed the modified Delphi methodology with five phases: participant identification, item development, two rounds of voting and a meeting to finalise the consensus statements. The predefined threshold for agreement was set at ≥70%.

Setting

Specialist outpatient services.

Participants

Members of the UK Head Injury Network were invited to participate. The network consists of clinical specialists in head injury practising in emergency medicine, neurology, neuropsychology, neurosurgery, paediatric medicine, rehabilitation medicine and sports and exercise medicine in England.

Primary outcome measure

A consensus statement on the structure and process of specialist outpatient care for patients with concussion in England.

Results

55 items were voted on in the first round. 29 items were removed following the first voting round and 3 items were removed following the second voting round. Items were modified where appropriate. A final 18 statements reached consensus covering 3 main topics in specialist healthcare services for concussion; care pathway to structured follow-up, prognosis and measures of recovery, and provision of outpatient clinics.

Conclusions

This work presents statements on how the healthcare services for patients with concussion in England could be redesigned to meet their health needs. Future work will seek to implement these into the clinical pathway.

Self-reported prevalence of asthma and its associated factors among adult rural population in Bangladesh: a cross-sectional study using WHO PEN protocol

Por: Rakhshanda · S. · Abedin · M. · Wahab · A. · Barua · L. · Faruque · M. · Banik · P. C. · Shawon · R. A. · Rahman · A. F. · Mashreky · S. R.
Objective

For over a decade, the prevalence of asthma remained unchanged at around 7% in Bangladesh. Although asthma causes significant morbidity among both children and adults, updates on epidemiological data are limited on the prevalence in Bangladesh. This study attempted to determine the prevalence of asthma, and its modifiable and non-modifiable lifestyle predictors in a rural population of Bangladesh.

Method

This study was part of a cross-sectional study that applied the WHO Package of Essential Noncommunicable Disease Interventions via census in a rural area of Bangladesh, where self-reported data on asthma were recorded. Data on anthropometric measurement, sociodemographic characteristics and behavioural risk factors were collected following the standard protocol described in the WHO STEP-wise approach to surveillance (STEPS) questionnaire. Analysis included descriptive statistics to assess the prevalence of asthma and its risk factors, and binary logistic regression to determine contributing factors.

Result

The overall prevalence of asthma was 4.2%. Asthma was predominant among people above 60 years (8.4%). Higher asthma was noted among males (4.6%), self-employed (5.1%), with a family history of asthma (9.1%), with comorbidities besides asthma (7.8%) and underweight (6.0%) compared with their counterparts. The OR of having asthma was 1.89, 1.93, 1.32, 1.50, 2.60, 0.67, 0.67 and 0.78 if a respondent was 45 years old or more, married, underweight, ever smoker, with a family history of asthma, housewife, employed and consumed red meat, respectively, while considering all other variables constant, compared with their counterparts.

Conclusion

The study emphasised asthma to be a public health concern in Bangladesh, although it seems to have decreased over the last decade. Among others, red meat intake and nutritional status were strongly associated with asthma, and the linkage among these is still a grey area that needs further exploration.

ProFertil study protocol for the investigation of gonadotropin-releasing hormone agonists (GnRHa) during chemotherapy aiming at fertility protection of young women and teenagers with cancer in Sweden--a phase III randomised double-blinded placebo-controll

Por: Rodriguez-Wallberg · K. A. · Nilsson · H. P. · Bergh · J. · Malmros · J. · Ljungman · P. · Foukakis · T. · Stragliotto · C. L. · Friman · E. I. · Linderholm · B. · Valachis · A. · Andersson · A. · Harrysson · S. · Vennström · L. · Frisk · P. · Mörse · H. · Eloranta · S.
Background

Gonadotropin-releasing hormone agonists (GnRHa) cotreatment used to transiently suppress ovarian function during chemotherapy to prevent ovarian damage and preserve female fertility is used globally but efficacy is debated. Most clinical studies investigating a beneficial effect of GnRHa cotreatment on ovarian function have been small, retrospective and uncontrolled. Unblinded randomised studies on women with breast cancer have suggested a beneficial effect, but results are mixed with lack of evidence of improvement in markers of ovarian reserve. Unblinded randomised studies of women with lymphoma have not shown any benefit regarding fertility markers after long-term follow-up and no placebo-controlled study has been conducted so far. The aim of this study is to investigate if administration of GnRHa during cancer treatment can preserve fertility in young female cancer patients in a double-blind, placebo-controlled clinical trial.

Methods and analysis

A prospective, randomised, double-blinded, placebo-controlled, phase III study including 300 subjects with breast cancer. In addition, 200 subjects with lymphoma, acute leukemias and sarcomas will be recruited. Women aged 14–42 will be randomised 1:1 to treatment with GnRHa (triptorelin) or placebo for the duration of their gonadotoxic chemotherapy. Follow-up until 5 years from end of treatment (EoT). The primary endpoint will be change in anti-Müllerian hormone (AMH) recovery at follow-up 12 months after EoT, relative to AMH levels at EoT, comparing the GnRHa group and the placebo group in women with breast cancer.

Ethics and dissemination

This study is designed in accordance with the principles of Good Clinical Practice (ICH-GCP E6 (R2)), local regulations (ie, European Directive 2001/20/EC) and the ethical principles of the Declaration of Helsinki. Within 6 months of study completion, the results will be analysed and the study results shall be reported in the EudraCT database.

Study registration

The National Institutional review board in Sweden dnr:2021–03379, approval date 12 October 2021 (approved amendments 12 June 2022, dnr:2022-02924-02 and 13 December 2022, dnr:2022-05565-02). The Swedish Medical Product Agency 19 January 2022, Dnr:5.1-2021-98927 (approved amendment 4 February 2022). Manufacturing authorisation for authorised medicinal products approved 6 December 2021, Dnr:6.2.1-2020-079580. Stockholm Medical Biobank approved 22 June 2022, RBC dnr:202 253.

Trial registration number

NCT05328258; EudraCT number:2020-004780-71.

Abdominal fat depots and their association with insulin resistance in patients with type 2 diabetes

by Umesh Kumar Garg, Nitish Mathur, Rahul Sahlot, Pradeep Tiwari, Balram Sharma, Aditya Saxena, Raj Kamal Jainaw, Laxman Agarwal, Shalu Gupta, Sandeep Kumar Mathur

Background

Asian-Indians show thin fat phenotype, characterized by predominantly central deposition of excess fat. The roles of abdominal subcutaneous fat (SAT), intra-peritoneal adipose tissue, and fat depots surrounding the vital organs (IPAT-SV) and liver fat in insulin resistance (IR), type-2 diabetes (T2D) and metabolic syndrome (MetS) in this population are sparsely investigated.

Aims and objectives

Assessment of liver fat, SAT and IPAT-SV by MRI in subjects with T2D and MetS; and to investigate its correlation with IR, specifically according to different quartiles of HOMA-IR.

Methods

Eighty T2D and the equal number of age sex-matched normal glucose tolerant controls participated in this study. Abdominal SAT, IPAT-SV and liver fat were measured using MRI. IR was estimated by the Homeostatic Model Assessment for Insulin Resistance (HOMA-IR).

Results

T2D and MetS subjects have higher quantity liver fat and IPAT-SV fat than controls (P = 9 x 10−4 and 4 x 10−4 for T2D and 10−4 and 9 x 10−3 for MetS subjects respectively). MetS subjects also have higher SAT fat mass (P = 0.012), but not the BMI adjusted SAT fat mass (P = 0.48). Higher quartiles of HOMA-IR were associated with higher BMI, W:H ratio, waist circumference, and higher liver fat mass (ANOVA Test P = 0.020, 0.030, 2 x 10−6 and 3 x 10−3 respectively with F-values 3.35, 3.04, 8.82, 4.47 respectively). In T2D and MetS subjects, HOMA-IR showed a moderately strong correlation with liver fat (r = 0.467, P −5 and r = 0.493, P −7), but not with SAT fat and IPAT-SV. However, in MetS subjects IPAT-SV fat mass showed borderline correlation with IR (r = 0.241, P r = 0.13, P = 0.26). In non-T2D and non-MetS subjects, no such correlation was seen. On analyzing the correlation between the three abdominal adipose compartment fat masses and IR according to its severity, the correlation with liver fat mass becomes stronger with increasing quartiles of HOMA-IR, and the strongest correlation is seen in the highest quartile (r = 0.59, P −3). On the other hand, SAT fat mass tended to show an inverse relation with IR with borderline negative correlation in the highest quartile (r = -0.284, P P = 0.07).

Conclusion

In individuals suffering from T2D and MetS, IR shows a trend towards positive and borderline negative correlation with liver fat and SAT fat masses respectively. The positive trend with liver fat tends to become stronger with increasing quartile of IR. Therefore, these findings support the theory that possibly exhaustion of protective compartment’s capacity to store excess fat results in its pathological deposition in liver as ectopic fat.

HBV prevalence in Sub-continental countries: A systematic review and meta-analysis

by Sam Hogan, Andrew Page, Sameer Dixit, Kate A. McBride

Background

Hepatitis B virus (HBV) is a major source of disease burden worldwide, with an estimated 296 million individuals living with infections worldwide. Although vaccine programs exist to control infections, certain sub-populations around the world continue to have very high prevalence of HBV infection.

Methods

A systematic search of studies of HBV published after 2010 was conducted for India, Pakistan, Bangladesh, Nepal, Sri Lanka and Bhutan. Each paper was independently screened for risk of bias and inclusion. Data were extracted from included studies before being analysed to estimate pooled prevalence, and to conduct sub-group analyses. Random-effects models were used for estimating summary prevalence due to a high level of heterogeneity between studies, and funnel plots were combined with Egger’s test to assess publication bias. Meta-regression was conducted to investigate sources of between-study heterogeneity.

Results

The pooled prevalence of HBV across all studies was 3% (95% CI 0.02, 0.05). For countries with multiple studies, the pooled prevalence in India was 3% (95% CI 0.02, 0.04), in Pakistan 6% (95% CI 0.03, 0.09), in Bangladesh 5% (95% CI of 0.02, 0.12), and in Nepal 1% (95% CI 0.00, 0.08). There was some evidence of publication bias, and a high level of heterogeneity across studies. Risk of bias analysis found most studies to be of fair or moderate quality.

Conclusions

The prevalence of HBV among countries in the sub-continent was higher than the global average, but was not as high as some other regions. Countries with greater numbers of displaced persons had higher prevalence of HBV, with a wide range of prevalence between subpopulations likely reflecting differential uptake, and implementation, of vaccination programs.

Comparing estimates of psychological distress using 7-day and 30-day recall periods: Does it make a difference?

by Miranda R. Chilver, Richard A. Burns, Ferdi Botha, Peter Butterworth

Self-report measures are widely used in mental health research and may use different recall periods depending on the purpose of the assessment. A range of studies aiming to monitor changes in mental health over the course of the COVID-19 pandemic opted to shorten recall periods to increase sensitivity to change over time compared to standard, longer recall periods. However, many of these studies lack pre-pandemic data using the same recall period and may rely on pre-existing data using standard recall periods as a reference point for assessing the impact of the pandemic on mental health. The aim of this study was to assess whether comparing scores on the same questionnaire with a different recall period is valid. A nationally representative sample of 327 participants in Australia completed a 7-day and 30-day version of the six-item Kessler Psychological Distress Scale (K6) and a single-item measure of psychological distress (TTPN item) developed for the Taking the Pulse of the Nation survey. Linear mixed models and mixed logistic regression models were used to assess whether altering the recall period systematically changed response patterns within subjects. No substantive recall period effects were found for the K6 or the TTPN, although there was a trend towards higher K6 scores when asked about the past 30 days compared to the past 7 days (b = 1.00, 95% CI: -0.18, 2.17). This may have been driven by the “feeling nervous” item which was rated higher using the 30-day compared to the 7-day recall period. Neither the K6 nor the TTPN item were significantly affected by the recall period when reduced to a binary variable of likely severe mental illness. The results indicate that altering the recall period of psychological distress measures does not substantively alter the score distribution in the general population of Australian adults.

Protocol for a realist evaluation of Recovery College dementia courses: understanding coproduction through ethnography

Por: Birt · L. · West · J. · Poland · F. · Wong · G. · Handley · M. · Litherland · R. · Hackmann · C. · Moniz-Cook · E. · Wolverson · E. · Teague · B. · Mills · R. · Sams · K. · Duddy · C. · Fox · C.
Introduction

Support following a dementia diagnosis in the UK is variable. Attending a Recovery College course with and for people with dementia, their supporters and healthcare professionals (staff), may enable people to explore and enact ways to live well with dementia. Recovery Colleges are established within mental health services worldwide, offering peer-supported short courses coproduced in partnership between staff and people with lived experience of mental illness. The concept of recovery is challenging in dementia narratives, with little evidence of how the Recovery College model could work as a method of postdiagnostic dementia support.

Methods and analysis

Using a realist evaluation approach, this research will examine and define what works, for whom, in what circumstances and why, in Recovery College dementia courses. The ethnographic study will recruit five case studies from National Health Service Mental Health Trusts across England. Sampling will seek diversity in new or long-standing courses, delivery methods and demographics of population served. Participant observations will examine course coproduction. Interviews will be undertaken with people with dementia, family and friend supporters and staff involved in coproducing and commissioning the courses, as well as people attending. Documentary materials will be reviewed. Analysis will use a realist logic of analysis to develop a programme theory containing causal explanations for outcomes, in the form of context-mechanism-outcome-configurations, at play in each case.

Ethics and dissemination

The study received approval from Coventry & Warwickshire Research Ethics Committee (22/WM/0215). Ethical concerns include not privileging any voice, consent for embedded observational fieldwork with people who may experience fluctuating mental capacity and balancing researcher ‘embedded participant’ roles in publicly accessible learning events. Drawing on the realist programme theory, two stakeholder groups, one people living with dementia and one staff will work with researchers to coproduce resources to support coproducing Recovery College dementia courses aligned with postdiagnostic services.

ARCHERY: a prospective observational study of artificial intelligence-based radiotherapy treatment planning for cervical, head and neck and prostate cancer - study protocol

Por: Aggarwal · A. · Court · L. E. · Hoskin · P. · Jacques · I. · Kroiss · M. · Laskar · S. · Lievens · Y. · Mallick · I. · Abdul Malik · R. · Miles · E. · Mohamad · I. · Murphy · C. · Nankivell · M. · Parkes · J. · Parmar · M. · Roach · C. · Simonds · H. · Torode · J. · Vanderstraeten · B. · Lan
Introduction

Fifty per cent of patients with cancer require radiotherapy during their disease course, however, only 10%–40% of patients in low-income and middle-income countries (LMICs) have access to it. A shortfall in specialised workforce has been identified as the most significant barrier to expanding radiotherapy capacity. Artificial intelligence (AI)-based software has been developed to automate both the delineation of anatomical target structures and the definition of the position, size and shape of the radiation beams. Proposed advantages include improved treatment accuracy, as well as a reduction in the time (from weeks to minutes) and human resources needed to deliver radiotherapy.

Methods

ARCHERY is a non-randomised prospective study to evaluate the quality and economic impact of AI-based automated radiotherapy treatment planning for cervical, head and neck, and prostate cancers, which are endemic in LMICs, and for which radiotherapy is the primary curative treatment modality. The sample size of 990 patients (330 for each cancer type) has been calculated based on an estimated 95% treatment plan acceptability rate. Time and cost savings will be analysed as secondary outcome measures using the time-driven activity-based costing model. The 48-month study will take place in six public sector cancer hospitals in India (n=2), Jordan (n=1), Malaysia (n=1) and South Africa (n=2) to support implementation of the software in LMICs.

Ethics and dissemination

The study has received ethical approval from University College London (UCL) and each of the six study sites. If the study objectives are met, the AI-based software will be offered as a not-for-profit web service to public sector state hospitals in LMICs to support expansion of high quality radiotherapy capacity, improving access to and affordability of this key modality of cancer cure and control. Public and policy engagement plans will involve patients as key partners.

Automated, high-throughput quantification of EGFP-expressing neutrophils in zebrafish by machine learning and a highly-parallelized microscope

by John Efromson, Giuliano Ferrero, Aurélien Bègue, Thomas Jedidiah Jenks Doman, Clay Dugo, Andi Barker, Veton Saliu, Paul Reamey, Kanghyun Kim, Mark Harfouche, Jeffrey A. Yoder

Normal development of the immune system is essential for overall health and disease resistance. Bony fish, such as the zebrafish (Danio rerio), possess all the major immune cell lineages as mammals and can be employed to model human host response to immune challenge. Zebrafish neutrophils, for example, are present in the transparent larvae as early as 48 hours post fertilization and have been examined in numerous infection and immunotoxicology reports. One significant advantage of the zebrafish model is the ability to affordably generate high numbers of individual larvae that can be arrayed in multi-well plates for high throughput genetic and chemical exposure screens. However, traditional workflows for imaging individual larvae have been limited to low-throughput studies using traditional microscopes and manual analyses. Using a newly developed, parallelized microscope, the Multi-Camera Array Microscope (MCAM™), we have optimized a rapid, high-resolution algorithmic method to count fluorescently labeled cells in zebrafish larvae in vivo. Using transgenic zebrafish larvae, in which neutrophils express EGFP, we captured 18 gigapixels of images across a full 96-well plate, in 75 seconds, and processed the resulting datastream, counting individual fluorescent neutrophils in all individual larvae in 5 minutes. This automation is facilitated by a machine learning segmentation algorithm that defines the most in-focus view of each larva in each well after which pixel intensity thresholding and blob detection are employed to locate and count fluorescent cells. We validated this method by comparing algorithmic neutrophil counts to manual counts in larvae subjected to changes in neutrophil numbers, demonstrating the utility of this approach for high-throughput genetic and chemical screens where a change in neutrophil number is an endpoint metric. Using the MCAM™ we have been able to, within minutes, acquire both enough data to create an automated algorithm and execute a biological experiment with statistical significance. Finally, we present this open-source software package which allows the user to train and evaluate a custom machine learning segmentation model and use it to localize zebrafish and analyze cell counts within the segmented region of interest. This software can be modified as needed for studies involving other zebrafish cell lineages using different transgenic reporter lines and can also be adapted for studies using other amenable model species.
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