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AnteayerInterdisciplinares

Ultrasound measurement of traumatic scar and skin thickness: a scoping review of evidence across the translational pipeline of research-to-practice

Por: Meikle · B. · Simons · M. · Mahoney · T. · Reddan · T. · Dai · B. · Kimble · R. M. · Tyack · Z.
Objectives

To identify the ultrasound methods used in the literature to measure traumatic scar thickness, and map gaps in the translation of these methods using evidence across the research-to-practice pipeline.

Design

Scoping review.

Data sources

Electronic database searches of Ovid MEDLINE, Embase, Cumulative Index of Nursing and Allied Health Literature and Web of Science. Grey literature searches were conducted in Google. Searches were conducted from inception (date last searched 27 May 2022).

Data extraction

Records using brightness mode (B-mode) ultrasound to measure scar and skin thickness across the research-to-practice pipeline of evidence were included. Data were extracted from included records pertaining to: methods used; reliability and measurement error; clinical, health service, implementation and feasibility outcomes; factors influencing measurement methods; strengths and limitations; and use of measurement guidelines and/or frameworks.

Results

Of the 9309 records identified, 118 were analysed (n=82 articles, n=36 abstracts) encompassing 5213 participants. Reporting of methods used was poor. B-mode, including high-frequency (ie, >20 MHz) ultrasound was the most common type of ultrasound used (n=72 records; 61% of records), and measurement of the combined epidermal and dermal thickness (n=28; 24%) was more commonly measured than the epidermis or dermis alone (n=7, 6%). Reliability of ultrasound measurement was poorly reported (n=14; 12%). The scar characteristics most commonly reported to be measured were epidermal oedema, dermal fibrosis and hair follicle density. Most records analysed (n=115; 97%) pertained to the early stages of the research-to-practice pipeline, as part of research initiatives.

Conclusions

The lack of evaluation of measurement initiatives in routine clinical practice was identified as an evidence gap. Diverse methods used in the literature identified the need for greater standardisation of ultrasound thickness measurements. Findings have been used to develop nine methodological considerations for practitioners to guide methods and reporting.

A systematic review of the impact of compression therapy on quality of life and pain among people with a venous leg ulcer

Abstract

Aim

To gain a greater understanding of how compression therapy affects quality of life, this systematic review appraised existing published studies measuring the impact of compression therapy on health quality of life (HRQoL), and pain, among people with venous leg ulcers (VLU).

Method

Five databases were searched, and two authors extracted data and appraised the quality of selected papers using the RevMan risk of bias tool. Due to heterogeneity in the types of compression and instruments used to evaluate HRQoL, meta-analysis was not appropriate; thus, a narrative synthesis of findings was undertaken.

Results

Ten studies were included, 9 RCTs and one before-after study. The studies employed nine different HRQoL tools to measure the impact of a variety of compression therapy systems, with or without an additional exercise programme, versus other compression systems or usual care, and the results are mixed. With the use of the Cardiff Cardiff Wound Impact Schedule, the SF-8 and the SF-12, study authors found no differences in QoL scores between the study groups. This is similar to one study using QUALYs (Iglesias et al., 2004). Conversely, for studies using EuroQol-5D, VEINES-QOL, SF-36 and CIVIQ-20 differences in QoL scores between the study groups were noted, in favour of the study intervention groups. Two further studies using QUALYs found results that favoured a two-layer cohesive compression bandage and the TLCCB group, respectively. Results for the five studies that assessed pain are also mixed, with one study finding no difference between study groups, one finding that pain increased over the study period and three studies finding that pain reduced in the intervention groups. All studies were assessed as being at risk of bias in one or more domains.

Conclusion

Results were varied, reflecting uncertainty in determining the impact of compression therapy on quality of life and pain among people with a venous leg ulcer. The heterogeneity of the compression systems and the measures used to evaluate HRQoL make it a challenge to interpret the overall evidence. Further studies should strive for homogeneity in design, interventions and comparators to enhance both internal and external validity.

Allogeneic limbo-deep anterior lamellar keratoplasty (Limbo-DALK)—A novel surgical technique in corneal stromal disease and limbal stem cell deficiency

by Verena Schöneberger, Volkan Tahmaz, Mario Matthaei, Sigrid Roters, Simona L. Schlereth, Friederike Schaub, Claus Cursiefen, Björn O. Bachmann

Purpose

To describe a novel corneal surgical technique combining Deep Anterior Lamellar Keratoplasty (DALK) with grafting of allogeneic limbus (Limbo-DALK) for the treatment of eyes with corneal stromal pathology and limbal stem cell deficiency (LSCD).

Methods

Clinical records of six Limbo-DALKs performed in five patients diagnosed with LSCD and corneal stromal pathology requiring keratoplasty were retrospectively reviewed. All patients were diagnosed with LSCD due to various pathologies including thermal and chemical burns, congenital aniridia or chronic inflammatory ocular surface disease. Parameters analysed included demographics, diagnoses, clinical history, thickness measurements using anterior segment OCT, visual acuity, and epithelial status. Regular follow-up visits were scheduled at 6 weeks as well as 3, 6, 9, and 12 and 18 months postoperatively. Main outcome measures were time to graft epithelialisation and the occurrence of corneal endothelial decompensation.

Results

Two grafts showed complete epithelial closure at 2 days, two at 14 days. In one eye, complete epithelial closure was not achieved after the first Limbo-DALK, but was achieved one month after the second Limbo-DALK. No endothelial decompensation occurred except in one patient with silicone oil associated keratopathy. Endothelial graft rejection was not observed in any of the grafts.

Conclusion

Based on the data from this pilot series, limbo-DALK appears to be a viable surgical approach for eyes with severe LSCD and corneal stromal pathology, suitable for emergency situations (e.g. corneal ulceration with impending corneal perforation), while minimising the risk of corneal endothelial decompensation.

Reallocating time between device-measured 24-hour activities and cardiovascular risk in Asian American immigrant women: An isotemporal substitution model

by Chorong Park, Britta Larsen, Simona C. Kwon, Yuhe Xia, Marianna LaNoue, Victoria V. Dickson, Harmony R. Reynolds, Tanya M. Spruill

The 24-hour day consists of physical activity (PA), sedentary behavior, and sleep, and changing the time spent on one activity affects the others. Little is known about the impact of such changes on cardiovascular risk, particularly in Asian American immigrant (AAI) women, who not only have a higher cardiovascular risk but also place greater cultural value on family and domestic responsibilities compared to other racial/ethnic groups. The purpose of this study was to evaluate the effects of reallocating 30 minutes of each 24-hour activity component for another on BMI, waist circumference, and blood pressure in AAI women. Seventy-five AAI women completed 7 days of hip and wrist actigraphy monitoring and were included in the analysis (age = 61.5±8.0 years, BMI = 25.5±3.6 kg/m2, waist circumference = 85.9±10.2 cm). Sleep was identified from wrist actigraphy data, and moderate-to-vigorous PA (MVPA), light PA, and sedentary behavior identified from hip actigraphy data. On average, the women spent 0.5 hours in MVPA, 6.2 hours in light PA, 10 hours in sedentary activities, and 5.3 hours sleeping within a 24-hour day. According to the isotemporal substitution models, replacing 30 minutes of sedentary behavior with MVPA reduced BMI by 1.4 kg/m2 and waist circumference by 4.0 cm. Replacing that same sedentary time with sleep reduced BMI by 0.5 kg/m2 and waist circumference by 1.4 cm. Replacing 30 minutes of light PA with MVPA decreased BMI by 1.6 kg/m2 and waist circumference by 4.3 cm. Replacing 30 minutes of light PA with sleep also reduced BMI by 0.8 kg/m2 and waist circumference by 1.7 cm. However, none of the behavioral substitutions affected blood pressure. Considering AAI women’s short sleep duration, replacing their sedentary time with sleep might be a feasible strategy to reduce their BMI and waist circumference.

Further psychometric validation and test–retest reproducibility of the WOUND‐Q

Abstract

WOUND-Q is a condition-specific patient-reported outcome measure developed for all types of chronic wounds, located anywhere on the body. To establish reliability and validity of a patient-reported outcome measure, multiple pieces of evidence are required. The purpose of this study was to examine the measurement properties of 9 of the 13 WOUND-Q scales and perform a test–retest reproducibility study in an international sample. In August 2022, we invited members of an international online community (Prolific.com) with any type of chronic wound to complete a survey containing the WOUND-Q scales, the Wound-QoL and EQ-5D. A test–retest survey was performed 7 days after the first survey. It was possible to examine the reliability and validity of eight of the nine WOUND-Q scales by Rasch Measurement Theory (RMT). To examine test–retest reproducibility intraclass correlation coefficients (ICCs), the standard error of the measurement and the smallest detectable change were calculated. In total, 421 patients from 22 different countries with 11 different types of chronic wounds took part in this study. Our analyses provided further evidence of the reliability and validity of the scales measuring wound characteristics (assessment, drainage, smell), health-related quality of life (life impact, psychological, sleep, social) and wound treatment (dressing).

Strategic replacement of soybean meal with local cotton seed meal on growth performance, body composition, and metabolic health status indicators in the major South Asian carp <i>Catla catla</i> for aquaculture

by Muhammad Haroon Aslam, Noor Khan, Mahroze Fatima, Muhammad Afzal Rashid, Simon J. Davies

This study assessed the effect of substituting soybean meal (SBM) with cotton seed meal (CSM) on different biological traits in thaila (Catla catla). Fish (n = 225) with an average initial body weight of 41.53±0.68 g were shifted into hapas (3 (L) x 2 (W) x 1 (D) m) in triplicate (15 fish/replicate). Hapas were divided into five dietary groups: 0CSM, 25CSM, 50CSM, 75CSM, and 100CSM diet treatments were administered diets for a period of 90 days. SBM was replaced by CSM at the levels of 0, 25, 50, 75, and 100%. The results showed that fish survival and growth performance were not affected by the inclusion of CSM in the fish diet up to 50% as a replacement of SBM, but higher replacement levels showed a negative effect. Similarly, body composition and most of the muscle amino acid profiles were not affected significantly (P>0.05) by replacing SBM with CSM. Digestive enzyme activities were significantly (P.05) decreased by increasing the level of CSM in the fish diet. Alanine transaminase (ALT) and aspartate transaminase (AST) levels increased significantly (P.05) with increasing dietary CSM levels, while alkaline phosphatase (ALP) levels remained the same. Malondialdehyde (MDA) and catalase (CAT) activity decreased significantly (P.05), but superoxide dismutase (SOD) activity showed no change. For the intestine, the villus height to villus width ratio and thickness of Tunica muscularis were also better in 25CSM, and their values decreased as the CSM inclusion level increased in the fish diet. In conclusion, SBM could be replaced partially (up to 50%) with CSM without compromising growth performance, whole body proximate composition or immunity of C. catla.

Comparing the long-term outcomes in chronic coronary syndrome patients with prior ST-segment and non-ST-segment elevation myocardial infarction: findings from the TIGRIS registry

Por: Krishnamurthy · S. N. · Pocock · S. · Kaul · P. · Owen · R. · Goodman · S. G. · Granger · C. B. · Nicolau · J. C. · Simon · T. · Westermann · D. · Yasuda · S. · Andersson · K. · Brandrup-Wognsen · G. · Hunt · P. R. · Brieger · D. B. · Cohen · M. G.
Objectives

Compared with ST-segment elevation myocardial infarction (STEMI) patients, non-STEMI (NSTEMI) patients have more comorbidities and extensive coronary artery disease. Contemporary comparative data on the long-term prognosis of stable post-myocardial infarction subtypes are needed.

Design

Long-Term rIsk, clinical manaGement and healthcare Resource utilisation of stable coronary artery dISease (TIGRIS) was a multinational, observational and longitudinal cohort study.

Setting

Patients were enrolled from 350 centres, with >95% coming from cardiology practices across 24 countries, from 19 June 2013 to 31 March 2017.

Participants

This study enrolled 8277 stable patients 1–3 years after myocardial infarction with ≥1 additional risk factor.

Outcome measures

Over a 2 year follow-up, cardiovascular events and deaths and self-reported health using the EuroQol 5-dimension questionnaire score were recorded. Relative risk of clinical events and health resource utilisation in STEMI and NSTEMI patients were compared using multivariable Poisson regression models, adjusting for prognostically relevant patient factors.

Results

Of 7752 patients with known myocardial infarction type, 46% had NSTEMI; NSTEMI patients were older with more comorbidities than STEMI patients. NSTEMI patients had significantly poorer self-reported health and lower prevalence of dual antiplatelet therapy at hospital discharge and at enrolment 1–3 years later. NSTEMI patients had a higher incidence of combined myocardial infarction, stroke and cardiovascular death (5.6% vs 3.9%, p

Conclusions

Post-NSTEMI chronic coronary syndrome patients had a less favourable risk factor profile, poorer self-reported health and more adverse cardiovascular events during long-term follow-up than individuals post STEMI. Efforts are needed to recognise the risks of stable patients after NSTEMI and optimise secondary prevention and care.

Trial registration number

NCT01866904.

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/

Mapping Oral health and Local Area Resources (MOLAR): protocol for a randomised controlled trial connecting emergency department patients with social and dental resources

Por: Simon · L. · Marsh · R. · Sanchez · L. D. · Camargo · C. · Donoff · B. · Cardenas · V. · Manning · W. · Loo · S. · Cash · R. E. · Samuels-Kalow · M. E.
Introduction

There are substantial inequities in oral health access and outcomes in the USA, including by income and racial and ethnic identity. People with adverse social determinants of health (aSDoH), such as housing or food insecurity, are also more likely to have unmet dental needs. Many patients with dental problems present to the emergency department (ED), where minimal dental care or referral is usually available. Nonetheless, the ED represents an important point of contact to facilitate screening and referral for unmet oral health needs and aSDoH, particularly for patients who may not otherwise have access to care.

Methods and analysis

Mapping Oral health and Local Area Resources is a randomised controlled trial enrolling 2049 adult and paediatric ED patients with unmet oral health needs into one of three trial arms: (a) a standard handout of nearby dental and aSDoH resources; (b) a geographically matched listing of aSDoH resources and a search link for identification of geographically matched dental resources; or (c) geographically matched resources along with personalised care navigation. Follow-up at 3, 6, 9 and 12 months will evaluate oral health-related quality of life, linkage to resources and dental treatment, ED visits for dental problems and the association between linkage and neighbourhood resource density.

Ethics and dissemination

All sites share a single human subjects review board protocol which has been fully approved by the Mass General Brigham Human Subjects Review Board. Informed consent will be obtained from all adults and adult caregivers, and assent will be obtained from age-appropriate child participants. Results will demonstrate the impact of addressing aSDoH on oral health access and the efficacy of various forms of resource navigation compared with enhanced standard care. Our findings will facilitate sustainable, scalable interventions to identify and address aSDoH in the ED to improve oral health and reduce oral health inequities.

Trial registration number

NCT05688982.

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.

Women Veterans’ perspectives, experiences, and preferences for firearm lethal means counseling discussions

by Evan R. Polzer, Ryan Holliday, Carly M. Rohs, Suzanne M. Thomas, Christin N. Miller, Joseph A. Simonetti, Lisa A. Brenner, Lindsey L. Monteith

Aims

Firearms have become an increasingly common method of suicide among women Veterans, yet this population has rarely been a focus in firearm suicide prevention research. Limited knowledge is available regarding the preferences, experiences, or needs of women Veterans with respect to firearm lethal means counseling (LMC), an evidence-based suicide prevention strategy. Understanding is necessary to optimize delivery for this population.

Method

Our sample included forty women Veterans with lifetime suicidal ideation or suicide attempt(s) and firearm access following military separation, all enrolled in the Veterans Health Administration. Participants were interviewed regarding their perspectives, experiences, and preferences for firearm LMC. Data were analyzed using a mixed inductive-deductive thematic analysis.

Results

Women Veterans’ firearm and firearm LMC perspectives were shaped by their military service histories and identity, military sexual trauma, spouses/partners, children, rurality, and experiences with suicidal ideation and attempts. Half reported they had not engaged in firearm LMC previously. For those who had, positive aspects included a trusting, caring relationship, direct communication of rationale for questions, and discussion of exceptions to confidentiality. Negative aspects included conversations that felt impersonal, not sufficiently comprehensive, and Veterans’ fears regarding implications of disclosure, which impeded conversations. Women Veterans’ preferences for future firearm LMC encompassed providers communicating why such conversations are important, how they should be framed (e.g., around safety and genuine concern), what they should entail (e.g., discussing concerns regarding disclosure), whom should initiate (e.g., trusted caring provider) and where they should occur (e.g., safe spaces, women-specific groups comprised of peers).

Discussion

This study is the first to examine women Veterans’ experiences with, and preferences for, firearm LMC. Detailed inquiry of the nuances of how, where, why, and by whom firearms are stored and used may help to facilitate firearm LMC with women Veterans.

Prediction models of incontinence and sexual function one year after radical prostatectomy based on data from 20 164 prostate cancer patients

by Nora Tabea Sibert, Tobias Kurth, Clara Breidenbach, Simone Wesselmann, Günther Feick, Ernst-Günter Carl, Sebastian Dieng, Mohamad Hatem Albarghouth, Atiqullah Aziz, Stefan Baltes, Elisabeth Bartolf, Jens Bedke, Andreas Blana, Marko Brock, Stefan Conrad, Christopher Darr, Florian Distler, Konstantinos Drosos, Gregor Duwe, Amr Gaber, Markus Giessing, Nina Natascha Harke, Axel Heidenreich, Sameh Hijazi, Andreas Hinkel, Björn Theodor Kaftan, Shatlyk Kheiderov, Thomas Knoll, Gerd Lümmen, Inga Peters, Bülent Polat, Valentin Schrodi, Jens-Uwe Stolzenburg, Zoltan Varga, Julius von Süßkind-Schwendi, Vahudin Zugor, Christoph Kowalski

Background

Incontinence and sexual dysfunction are long-lasting side effects after surgical treatment (radical prostatectomy, RP) of prostate cancer (PC). For an informed treatment decision, physicians and patients should discuss expected impairments. Therefore, this paper firstly aims to develop and validate prognostic models that predict incontinence and sexual function of PC patients one year after RP and secondly to provide an online decision making tool.

Methods

Observational cohorts of PC patients treated between July 2016 and March 2021 in Germany were used. Models to predict functional outcomes one year after RP measured by the EPIC-26 questionnaire were developed using lasso regression, 80–20 splitting of the data set and 10-fold cross validation. To assess performance, R2, RMSE, analysis of residuals and calibration-in-the-large were applied. Final models were externally temporally validated. Additionally, percentages of functional impairment (pad use for incontinence and firmness of erection for sexual score) per score decile were calculated to be used together with the prediction models.

Results

For model development and internal as well as external validation, samples of 11 355 and 8 809 patients were analysed. Results from the internal validation (incontinence: R2 = 0.12, RMSE = 25.40, sexual function: R2 = 0.23, RMSE = 21.44) were comparable with those of the external validation. Residual analysis and calibration-in-the-large showed good results. The prediction tool is freely accessible: https://nora-tabea.shinyapps.io/EPIC-26-Prediction/.

Conclusion

The final models showed appropriate predictive properties and can be used together with the calculated risks for specific functional impairments. Main strengths are the large study sample (> 20 000) and the inclusion of an external validation. The models incorporate meaningful and clinically available predictors ensuring an easy implementation. All predictions are displayed together with risks of frequent impairments such as pad use or erectile dysfunction such that the developed online tool provides a detailed and informative overview for clinicians as well as patients.

Two distinct mechanisms lead to either oocyte or spermatocyte decrease in <i>C</i>. <i>elegans</i> after whole developmental exposure to γ-rays

by Elizabeth Dufourcq Sekatcheff, Christian Godon, Aymeric Bailly, Loïc Quevarec, Virginie Camilleri, Simon Galas, Sandrine Frelon

Wildlife is subject to various sources of pollution, including ionizing radiation. Adverse effects can impact the survival, growth, or reproduction of organisms, later affecting population dynamics. In invertebrates, reproduction, which directly impacts population dynamics, has been found to be the most radiosensitive endpoint. Understanding the underlying molecular pathways inducing this reproduction decrease can help to comprehend species-specific differences in radiosensitivity. From our previous studies, we found that decrease in reproduction is life stage dependent in the roundworm Caenorhabditis elegans, possibly resulting from an accumulation of damages during germ cell development and gamete differentiation. To go further, we used the same experimental design to assess more precisely the molecular determinants of reproductive toxicity, primarily decreases in gamete number. As before, worms were chronically exposed to 50 mGy·h−1 external gamma ionizing radiation throughout different developmental periods (namely embryogenesis, gametogenesis, and full development). To enable cross species extrapolation, conserved molecular pathways across invertebrates and vertebrates were analysed: apoptosis and MAP kinase Ras/ERK (MPK-1), both involved in reproduction and stress responses. Our results showed that these pathways are life-stage dependent, resulting from an accumulation of damages upon chronic exposure to IR throughout the life development. The Ras/ERK pathway was activated in our conditions in the pachytene region of the gonad where it regulates cell fate including apoptosis, but not in the ovulation zone, where it controls oocyte maturation and ovulation. Additionally, assessment of germ cell proliferation via Ras/ERK pathway showed no effect. Finally, a functional analysis of apoptosis revealed that while the decrease of the ovulation rate is caused by DNA-damaged induced apoptosis, this process does not occur in spermatocytes. Thus, sperm decrease seems to be mediated via another mechanism, probably a decrease in germ cell proliferation speed that needs further investigation to better characterize sex-specific responses to IR exposure. These results are of main importance to describe radio-induced reprotoxic effects and contribute as weight of evidence for the AOP #396 “Deposition of ionizing energy leads to population decline via impaired meiosis”.

Impact of deintensifying hypoglycaemic drugs in older adults with type 2 diabetes: protocol for an emulation of a target trial

Por: Christiaens · A. · Simon-Tillaux · N. · Thompson · W. · Sinclair · A. J. · Henrard · S. · Boland · B. B. · Slaouti-Jegou · Y. · Lekens · B. · Bonnet-Zamponi · D. · Tubach · F. · Zerah · L.
Introduction

In older adults with type 2 diabetes (T2D), overtreatment with hypoglycaemic drugs (HDs: sulfonylureas, glinides and/or insulins) is frequent and associated with increased 1-year mortality. Deintensification of HD is thus a key issue, for which evidence is though limited. The primary objective of this study will be to estimate the effect of deintensifying HD on clinical outcomes (hospital admission or death) within 3 months in older adults (≥75 years) with T2D.

Methods

We will emulate with real-world data a target trial, within The Health Improvement Network cohort, a large-scale database of data collected from electronic medical records of 2000 general practitioners in France. From 1 January 2010 to 28 February 2019, we will include eligible patients ≥75 years who will have T2D, a stable dose of HDs, glycated haemoglobin A1c (HbA1c) value 75 mmol/mol within 1 year. Participants will be followed from baseline to 12 months after randomisation, administrative censoring, or death, whichever occurs first. A pooled logistic regression will be used to estimate the treatment effect on the incidence of the outcomes.

Dissemination and ethics

No ethical approval is needed for using retrospectively this fully anonymised database. The results will be disseminated during conferences and through publications in scientific journals.

Time for You: A process evaluation of the rapid implementation of a multi-level mental health support intervention for frontline workers during the COVID-19 pandemic

by Bryan McCann, Simon C. Hunter, Kareena McAloney-Kocaman, Paul McCarthy, Jan Smith, Eileen Calveley

The coronavirus (COVID-19) pandemic had wide-ranging negative impacts on mental health. The pandemic also placed extraordinary strain on frontline workers who were required to continue working and putting themselves at risk to provide essential services at a time when their normal support mechanisms may not have been available. This paper presents an evaluation of the Time for You service, a rapidly developed and implemented intervention aimed at providing frontline workers with quick access to flexible online mental health support. Time for You provided service users with three service options: self-guided online cognitive behavioural therapy (CBT) resources; guided engagement with online CBT resources; 1–1 psychological therapy with trainee sport and exercise psychologists and trainee health psychologists. A process evaluation informed by the Consolidated Framework for Implementation Research considered service fidelity, adaptations, perceived impact, reach, barriers, and facilitators. Interviews with project managers (n = 5), delivery staff (n = 10), and service users (n = 14) explored perceptions of the service implementation and outcomes, supported by data regarding engagement with the online CBT platform (n = 217). Findings indicated that service users valued the flexibility of the service and the speed with which they were able to access support. The support offered by Trainee Psychologists was perceived to be of high quality, and the service was perceived by service users to have improved mental health and wellbeing. The rapid implementation contributed to issues regarding appropriate service user screening that led to trainee psychologists being unable to provide the service users with the support they needed as the presenting issues were outside of trainees’ competencies. Overall, the findings suggest that interventions offering flexible, online psychological support to frontline workers can be an effective model for future interventions. Trainee psychologists are also able to play an important role in delivering such services when clear screening processes are in place.
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