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Ayer — Mayo 14th 2024Interdisciplinares

Identification of triciribine as a novel myeloid cell differentiation inducer

by Souma Suzuki, Susumu Suzuki, Yuri Sato-Nagaoka, Chisaki Ito, Shinichiro Takahashi

Differentiation therapy using all-trans retinoic acid (ATRA) for acute promyelocytic leukemia (APL) is well established. However, because the narrow application and tolerance development of ATRA need to be improved, we searched for another efficient myeloid differentiation inducer. Kinase activation is involved in leukemia biology and differentiation block. To identify novel myeloid differentiation inducers, we used a Kinase Inhibitor Screening Library. Using a nitroblue tetrazolium dye reduction assay and real-time quantitative PCR using NB4 APL cells, we revealed that, PD169316, SB203580, SB202190 (p38 MAPK inhibitor), and triciribine (TCN) (Akt inhibitor) potently increased the expression of CD11b. We focused on TCN because it was reported to be well tolerated by patients with advanced hematological malignancies. Nuclear/cytoplasmic (N/C) ratio was significantly decreased, and myelomonocytic markers (CD11b and CD11c) were potently induced by TCN in both NB4 and acute myeloid leukemia (AML) M2 derived HL-60 cells. Western blot analysis using NB4 cells demonstrated that TCN promoted ERK1/2 phosphorylation, whereas p38 MAPK phosphorylation was not affected, suggesting that activation of the ERK pathway is involved in TCN-induced differentiation. We further examined that whether ATRA may affect phosphorylation of ERK and p38, and found that there was no obvious effect, suggesting that ATRA induced differentiation is different from TCN effect. To reveal the molecular mechanisms involved in TCN-induced differentiation, we performed microarray analysis. Pathway analysis using DAVID software indicated that “hematopoietic cell lineage” and “cytokine-cytokine receptor interaction” pathways were enriched with high significance. Real-time PCR analysis demonstrated that components of these pathways including IL1β, CD3D, IL5RA, ITGA6, CD44, ITGA2B, CD37, CD9, CSF2RA, and IL3RA, were upregulated by TCN-induced differentiation. Collectively, we identified TCN as a novel myeloid cell differentiation inducer, and trials of TCN for APL and non-APL leukemia are worthy of exploration in the future.

Distribution and dynamics of <i>Anopheles gambiae</i> s.l. larval habitats in three Senegalese cities with high urban malaria incidence

by Fatou Ndiaye, Abdoulaye Diop, Joseph Chabi, Katherine Sturm-Ramirez, Massila Senghor, El Hadji Diouf, Badara Samb, Seynabou Mocote Diedhiou, Omar Thiaw, Sarah Zohdy, Ellen Dotson, Doudou Sene, Mame Birame Diouf, Valerie Koscelnik, Lilia Gerberg, Abdoulaye Bangoura, Tiffany Clark, Ousmane Faye, Ibrahima Dia, Lassana Konate, El Hadji Amadou Niang

Urban malaria has become a challenge for most African countries due to urbanization, with increasing population sizes, overcrowding, and movement into cities from rural localities. The rapid expansion of cities with inappropriate water drainage systems, abundance of water storage habitats, coupled with recurrent flooding represents a concern for water-associated vector borne diseases, including malaria. This situation could threaten progress made towards malaria elimination in sub-Saharan countries, including Senegal, where urban malaria has presented as a threat to national elimination gains. To assess drivers of urban malaria in Senegal, a 5-month study was carried out from August to December 2019 in three major urban areas and hotspots for malaria incidence (Diourbel, Touba, and Kaolack) including the rainy season (August-October) and partly dry season (November–December). The aim was to characterize malaria vector larval habitats, vector dynamics across both seasons, and to identify the primary eco- environmental entomological factors contributing to observed urban malaria transmission. A total of 145 Anopheles larval habitats were found, mapped, and monitored monthly. This included 32 in Diourbel, 83 in Touba, and 30 in Kaolack. The number of larval habitats fluctuated seasonally, with a decrease during the dry season. In Diourbel, 22 of the 32 monitored larval habitats (68.75%) were dried out by December and considered temporary, while the remaining 10 (31.25%) were classified as permanent. In the city of Touba 28 (33.73%) were temporary habitats, and of those 57%, 71% and 100% dried up respectively by October, November, and December. However, 55 (66.27%) habitats were permanent water storage basins which persisted throughout the study. In Kaolack, 12 (40%) permanent and 18 (60%) temporary Anopheles larval habitats were found and monitored during the study. Three malaria vectors (An. arabiensis, An. pharoensis and An. funestus s.l.) were found across the surveyed larval habitats, and An. arabiensis was found in all three cities and was the only species found in the city of Diourbel, while An. arabiensis, An. pharoensis, and An. funestus s.l. were detected in the cities of Touba and Kaolack. The spatiotemporal observations of immature malaria vectors in Senegal provide evidence of permanent productive malaria vector larval habitats year-round in three major urban centers in Senegal, which may be driving high urban malaria incidence. This study aimed to assess the presence and type of anopheline larvae habitats in urban areas. The preliminary data will better inform subsequent detailed additional studies and seasonally appropriate, cost-effective, and sustainable larval source management (LSM) strategies by the National Malaria Control Programme (NMCP).

Mental-somatic multimorbidity in trajectories of cognitive function for middle-aged and older adults

by Siting Chen, Corey L. Nagel, Ruotong Liu, Anda Botoseneanu, Heather G. Allore, Jason T. Newsom, Stephen Thielke, Jeffrey Kaye, Ana R. Quiñones

Introduction

Multimorbidity may confer higher risk for cognitive decline than any single constituent disease. This study aims to identify distinct trajectories of cognitive impairment probability among middle-aged and older adults, and to assess the effect of changes in mental-somatic multimorbidity on these distinct trajectories.

Methods

Data from the Health and Retirement Study (1998–2016) were employed to estimate group-based trajectory models identifying distinct trajectories of cognitive impairment probability. Four time-varying mental-somatic multimorbidity combinations (somatic, stroke, depressive, stroke and depressive) were examined for their association with observed trajectories of cognitive impairment probability with age. Multinomial logistic regression analysis was conducted to quantify the association of sociodemographic and health-related factors with trajectory group membership.

Results

Respondents (N = 20,070) had a mean age of 61.0 years (SD = 8.7) at baseline. Three distinct cognitive trajectories were identified using group-based trajectory modelling: (1) Low risk with late-life increase (62.6%), (2) Low initial risk with rapid increase (25.7%), and (3) High risk (11.7%). For adults following along Low risk with late-life increase, the odds of cognitive impairment for stroke and depressive multimorbidity (OR:3.92, 95%CI:2.91,5.28) were nearly two times higher than either stroke multimorbidity (OR:2.06, 95%CI:1.75,2.43) or depressive multimorbidity (OR:2.03, 95%CI:1.71,2.41). The odds of cognitive impairment for stroke and depressive multimorbidity in Low initial risk with rapid increase or High risk (OR:4.31, 95%CI:3.50,5.31; OR:3.43, 95%CI:2.07,5.66, respectively) were moderately higher than stroke multimorbidity (OR:2.71, 95%CI:2.35, 3.13; OR: 3.23, 95%CI:2.16, 4.81, respectively). In the multinomial logistic regression model, non-Hispanic Black and Hispanic respondents had higher odds of being in Low initial risk with rapid increase and High risk relative to non-Hispanic White adults.

Conclusions

These findings show that depressive and stroke multimorbidity combinations have the greatest association with rapid cognitive declines and their prevention may postpone these declines, especially in socially disadvantaged and minoritized groups.

Untargeted lipidomics analysis in women with morbid obesity and type 2 diabetes mellitus: A comprehensive study

by Laia Bertran, Jordi Capellades, Sonia Abelló, Carmen Aguilar, Teresa Auguet, Cristóbal Richart

There is a phenotype of obese individuals termed metabolically healthy obese that present a reduced cardiometabolic risk. This phenotype offers a valuable model for investigating the mechanisms connecting obesity and metabolic alterations such as Type 2 Diabetes Mellitus (T2DM). Previously, in an untargeted metabolomics analysis in a cohort of morbidly obese women, we observed a different lipid metabolite pattern between metabolically healthy morbid obese individuals and those with associated T2DM. To validate these findings, we have performed a complementary study of lipidomics. In this study, we assessed a liquid chromatography coupled to a mass spectrometer untargeted lipidomic analysis on serum samples from 209 women, 73 normal-weight women (control group) and 136 morbid obese women. From those, 65 metabolically healthy morbid obese and 71 with associated T2DM. In this work, we find elevated levels of ceramides, sphingomyelins, diacyl and triacylglycerols, fatty acids, and phosphoethanolamines in morbid obese vs normal weight. Conversely, decreased levels of acylcarnitines, bile acids, lyso-phosphatidylcholines, phosphatidylcholines (PC), phosphatidylinositols, and phosphoethanolamine PE (O-38:4) were noted. Furthermore, comparing morbid obese women with T2DM vs metabolically healthy MO, a distinct lipid profile emerged, featuring increased levels of metabolites: deoxycholic acid, diacylglycerol DG (36:2), triacylglycerols, phosphatidylcholines, phosphoethanolamines, phosphatidylinositols, and lyso-phosphatidylinositol LPI (16:0). To conclude, analysing both comparatives, we observed decreased levels of deoxycholic acid, PC (34:3), and PE (O-38:4) in morbid obese women vs normal-weight. Conversely, we found elevated levels of these lipids in morbid obese women with T2DM vs metabolically healthy MO. These profiles of metabolites could be explored for the research as potential markers of metabolic risk of T2DM in morbid obese women.

Spatial variations in the osteocyte lacuno-canalicular network density and analysis of the connectomic parameters

by Junning Chen, Marta Aido, Andreas Roschger, Alexander van Tol, Sara Checa, Bettina M. Willie, Richard Weinkamer

Osteocyte lacuno-canalicular network (LCN) is comprised of micrometre-sized pores and submicrometric wide channels in bone. Accumulating evidence suggests multiple functions of this network in material transportation, mechanobiological signalling, mineral homeostasis and bone remodelling. Combining rhodamine staining and confocal laser scanning microscopy, the longitudinal cross-sections of six mouse tibiae were imaged, and the connectome of the network was quantified with a focus on the spatial heterogeneities of network density, connectivity and length of canaliculi. In-vivo loading and double calcein labelling on these tibiae allowed differentiating the newly formed bone from the pre-existing regions. The canalicular density of the murine cortical bone varied between 0.174 and 0.243 μm/μm3, and therefore is three times larger than the corresponding value for human femoral midshaft osteons. The spatial heterogeneity of the network was found distinctly more pronounced across the cortex than along the cortex. We found that in regions with a dense network, the LCN conserves its largely tree-like character, but increases the density by including shorter canaliculi. The current study on healthy mice should serve as a motivating starting point to study the connectome of genetically modified mice, including models of bone diseases and of reduced mechanoresponse.

Exploring community participation in vectorborne disease control in Southeast Asia: a scoping review protocol

Por: Naserrudin · N. A. · Adhikari · B. · Culleton · R. · Hod · R. · Saffree Jeffree · M. · Ahmed · K. · Hassan · M. R.
Introduction

Vector borne diseases (VBDs) present significant public health challenges in Southeast Asia (SEA), and the increasing number of cases threatens vulnerable communities. Inadequate vector control and management have been linked to the spread of VBDs. To address these issues, community participation has been proposed as a promising approach to enhance health programmes and control of VBDs. This article outlines a protocol for a scoping review of the published literature on community-participation approaches to control VBDs in the SEA region. The primary research question is ‘How does community participation complement the control of VBDs in SEA?’ This review aims to provide an overview of various approaches and identify barriers and facilitators to effective implementation.

Methods and analysis

The research questions will guide the scoping review. In stage 1, peer-reviewed publications from PubMed, Web of Science and Scopus will be searched using predefined search terms related to community-based approaches and VBDs in the SEA region, English, Indonesian and Malay published between 2012 and 2022. In stage 2, the references from relevant articles will be screened for eligibility. In stage 3, eligible articles will be charted in Microsoft Excel to facilitate the review process, and studies will be characterised based on the investigated diseases; this review will also highlight the methodological context of these studies. In stage 4, a thematic analysis will be conducted to derive meaningful findings from the dataset relevant to the research inquiry, followed by writing the results in stage 5. This scoping review aims to be the first to explore community participation in VBD control in the SEA population, providing valuable insights for future research and stakeholders involved in disease control.

Ethics and dissemination

This scoping review does not require ethical approval because the methodology synthesises information from available articles. This review is planned for dissemination in academic journals, conference presentations and shared with stakeholders as part of knowledge sharing among those involved in VBD control.

Utilising a 'Community of Practice to support pharmacists to work in residential aged care: protocol for a longitudinal evaluation

Por: Lee · K. · Etherton-Beer · C. · Johnson · J. · Lobo · E. · Wang · K. · Ailabouni · N. · Mavaddat · N. · Clifford · R. M. · Page · A. T.
Introduction

A Community of Practice is briefly defined as a group of people with a shared interest in a given area of practice who work collaboratively to grow collective knowledge. Communities of Practice have been used to facilitate knowledge exchange and improve evidence-based practice. Knowledge translation within the residential aged care sector is lacking, with barriers such as inadequate staffing and knowledge gaps commonly cited. In Australia, a Federal inquiry into residential aged care practices led to a recommendation to embed pharmacists within residential aged care facilities. Onsite practice in aged care is a new role for pharmacists in Australia. Thus, support is needed to enable pharmacists to practice in this role.

The primary aim is to evaluate the processes and outcomes of a Community of Practice designed to support pharmacists to work in aged care.

Methods and analysis

A longitudinal, single-group, pretest–post-test design in which the intervention is a Community of Practice. The Community of Practice will be established and made available for 3 years to all Australian pharmacists interested in, new to or established in aged care roles. The Community of Practice will be hosted on online discussion platforms, with additional virtual meetings and annual symposia. The following data will be collected from all members of the Community of Practice: self-evaluation of the processes and outcomes of the Community of Practice (via the CoPeval scale) and confidence in evidence-based practice (EPIC scale), collected via online questionnaires annually; and discussion platform usage statistics and discussion transcripts. A subset of members will be invited to participate in annual semi-structured individual interviews.

Data from the online questionnaire will be analysed descriptively. Discussion transcripts will be analysed using topic modelling and content analysis to identify the common topics discussed and their frequencies. Qualitative data from individual interviews will be thematically analysed to explore perceptions and experiences with the intervention for information/knowledge exchange, impact on practice, and sharing/promoting/implementing evidence-based practice.

Ethics and dissemination

Human ethics approval has been granted by the University of Western Australia’s Human Ethics Committee (2023/ET000000). No personal information will be included in any publications and reports to funding bodies.

Findings will be disseminated to all members of the Community of Practice, professional organisations, social and mass media, peer-review journals, research and professional conferences and annual reports to the funding body.

Low-dose naltrexone for post-COVID fatigue syndrome: a study protocol for a double-blind, randomised trial in British Columbia

Por: Naik · H. · Cooke · E. · Boulter · T. · Dyer · R. · Bone · J. N. · Tsai · M. · Cristobal · J. · McKay · R. J. · Song · X. · Nacul · L.
Introduction

A significant proportion of individuals suffering from post COVID-19 condition (PCC, also known as long COVID) can present with persistent, disabling fatigue similar to myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and post-viral fatigue syndromes. There remains no clear pharmacological therapy for patients with this subtype of PCC, which can be referred to as post-COVID fatigue syndrome (PCFS). A low dose of the opioid antagonist naltrexone (ie, low-dose naltrexone (LDN)) has emerged as an off-label treatment for treating fatigue and other symptoms in PCC. However, only small, non-controlled studies have assessed LDN in PCC, so randomised trials are urgently required.

Methods and analysis

A prospective, randomised, double-blind, parallel arm, placebo-controlled phase II trial will be performed to assess the efficacy of LDN for improving fatigue in PCFS. The trial will be decentralised and open to eligible individuals throughout the Canadian province of British Columbia (BC). Participants will be recruited through the province-wide Post-COVID-19 Interdisciplinary Clinical Care Network (PC-ICCN) and research volunteer platform (REACH BC). Eligible participants will be 19–69 years old, have had a confirmed or physician-suspected SARS-CoV-2 infection at least 3 months prior and meet clinical criteria for PCFS adapted from the Institute of Medicine ME/CFS criteria. Individuals who are taking opioid medications, have a history of ME/CFS prior to COVID-19 or history of significant liver disease will be excluded. Participants will be randomised to an LDN intervention arm (n=80) or placebo arm (n=80). Participants in each arm will be prescribed identical capsules starting at 1 mg daily and follow a prespecified schedule for up-titration to 4.5 mg daily or the maximum tolerated dose. The trial will be conducted over 16 weeks, with assessments at baseline, 6, 12 and 16 weeks. The primary outcome will be fatigue severity at 16 weeks evaluated by the Fatigue Severity Scale. Secondary outcomes will include pain Visual Analogue Scale score, overall symptom severity as measured by the Patient Phenotyping Questionnaire Short Form, 7-day step count and health-related quality of life measured by the EuroQol 5-Dimension questionnaire.

Ethics and dissemination

The trial has been authorised by Health Canada and approved by The University of British Columbia/Children’s and Women’s Health Centre of British Columbia Research Ethics Board. On completion, findings will be disseminated to patients, caregivers and clinicians through engagement activities within existing PCC and ME/CFS networks. Results will be published in academic journals and presented at conferences.

Trial registration number

NCT05430152.

Hungarian general practice paediatricians antibiotic prescribing behaviour for suspected respiratory tract infections: a qualitative study

Por: Babarczy · B. · Hajdu · A. · Benko · R. · Matuz · M. · Papp · R. · Antoniou · P. · Kandelaki · K. · Lo Fo Wong · D. · Warsi · S. K.
Objectives

Inappropriate antibiotic prescribing is a major cause of antimicrobial resistance (AMR). The aim of this study was to explore paediatric general practitioners’ (GP Peds) antibiotic prescription practice in suspected respiratory tract infections (RTIs), using the capability–opportunity–motivation–behaviour framework.

Design

The design is a qualitative study based on individual, semistructured telephone or virtual interviews.

Setting

Paediatric general practice in Hungary. We applied stratified maximum variation sampling to cover the categories of age, sex and geographical location of participants.

Participants

We interviewed 22 GP Peds. Nine were male and 13 were female: 2 of them were less than 40 years old, 14 were between 40 and 60 years, and 6 were above 60 years. 10 worked in low-antibiotic prescription areas, 5 in areas with medium levels of antibiotic prescription, 3 in high-antibiotic prescription areas, and 4 in and around the capital city.

Results

Study participants had varying antibiotic prescription preferences. Personal experience and physical examination play a central role in GP Peds’ diagnostic and treatment practice. Participants emphasised the need to treat children in their entirety, taking their personal medical record, social background and sometimes parents’ preferences into account, besides the acute clinical manifestation of RTI. Most respondents were confident they apply the most effective therapy even if, in some cases, this meant prescribing medicines with a higher chance of contributing to the development of AMR. Some participants felt antibiotic prescription frequency has decreased in recent years.

Conclusions

Our findings suggest that a more prudent attitude toward antibiotic prescribing may have become more common but also highlight relevant gaps in both physicians’ and public knowledge of antibiotics and AMR. To reinforce awareness and close remaining gaps, Hungary should adopt its national AMR National Action Plan and further increase its efforts towards active professional communication and feedback for primary care physicians.

SurLym trial: study protocol for a multicentre pragmatic randomised controlled trial on the added value of reconstructive lymphatic surgery to decongestive lymphatic therapy for the treatment of lymphoedema

Por: Devoogdt · N. · De Vrieze · T. · Heroes · A.-K. · Bechter-Hugl · B. · Fieuws · S. · Godderis · L. · Segers · K. · Maleux · G. · Deltombe · T. · Frippiat · J. · Servaes · M. · Berners · A. · Fosseprez · P. · Krug · B. · Kayser · F. · Falticeanu · A. · Randon · C. · Monten · C. · Van Landuyt
Introduction

Lymphoedema is a chronic condition caused by lymphatic insufficiency. It leads to swelling of the limb/midline region and an increased risk of infection. Lymphoedema is often associated with mental and physical problems limiting quality of life. The first choice of treatment is a conservative treatment, consisting of exercises, skin care, lymph drainage and compression. Reconstructive lymphatic surgery is also often performed, that is, lymphovenous anastomoses, lymph node transfer or a combination. However, robust evidence on the effectiveness of reconstructive lymphatic surgery is missing. Therefore, the objective of this trial is to investigate the added value of reconstructive lymphatic surgery to the conservative treatment in patients with lymphoedema.

Methods and analysis

A multicentre randomised controlled and pragmatic trial was started in March 2022 in three Belgian university hospitals. 90 patients with arm lymphoedema and 90 patients with leg lymphoedema will be included. All patients are randomised between conservative treatment alone (control group) or conservative treatment with reconstructive lymphatic surgery (intervention group). Assessments are performed at baseline and at 1, 3, 6, 12, 18, 24 and 36 months. The primary outcome is lymphoedema-specific quality of life at 18 months. Key secondary outcomes are limb volume and duration of wearing the compression garment at 18 months. The approach of reconstructive lymphatic surgery is based on presurgical investigations including clinical examination, lymphofluoroscopy, lymphoscintigraphy, lymph MRI or CT angiography (if needed). All patients receive conservative treatment during 36 months, which is applied by the patient’s own physical therapist and by the patient self. From months 7 to 12, the hours a day of wearing the compression garment are gradually decreased.

Ethics and dissemination

The study has been approved by the ethical committees of University Hospitals Leuven, Ghent University Hospital and CHU UCL Namur. Results will be disseminated via peer-reviewed journals and presentations.

Trial registration number

NCT05064176

Understanding associations between the COVID-19 pandemic and menstrual hygiene management among adolescent girls in Ethiopia: findings from a mixed-methods longitudinal study

Por: Murphy · M. · Dutton · R. · Gezahegne · K. · Jones · N. · Seager · J. · Baird · S.
Objective

To understand the relationship between the COVID-19 pandemic and menstrual hygiene management (MHM) among adolescent girls in Ethiopia and to explore which girls were most affected by pandemic disruptions.

Design

Two rounds of data from surveys and interviews were collected with adolescent girls immediately prior to and during the COVID-19 pandemic. The primary analysis is cross-sectional, controlling for pre-COVID-19 covariates.

Setting

The setting was three zones in two regions of Ethiopia: East Hararghe and East Shewa Zones in Oromia and South Gondar Zone in Amhara. Data were collected in December 2019–March 2020 and September 2020–February 2021.

Participants

742 adolescent girls, ages 11–25 years.

Outcome measures

Four primary outcomes were explored (1) the number of challenges girls experienced; (2) adolescent-identified challenges managing menstrual hygiene; (3) adolescent-identified difficulties accessing MHM products and (4) adolescent-identified difficulties accessing soap or water.

Results

Girls who were more vulnerable to COVID-19 were more likely to have worse MHM outcomes. An SD increase in household vulnerability to COVID-19 was associated with an 8.7 percentage point increase in the likelihood that the respondent had difficulty getting MHM products (p

Conclusions

The results of this study suggest that MHM was left behind in the COVID-19 response. New programming and policy interventions need to address financial hardship and disruptions to supplies to manage menstruation as well as tackle the inequitable gender norms that stigmatise menstruation during emergencies.

Interventions to promote medical student well-being: an overview of systematic reviews

Por: Bennett-Weston · A. · Keshtkar · L. · Jones · M. · Sanders · C. · Lewis · C. · Nockels · K. · Solomon · J. · Howick · J.
Objective

To conduct an overview of systematic reviews that explore the effectiveness of interventions to enhance medical student well-being.

Design

Overview of systematic reviews.

Data sources

The Cochrane Library of Systematic Reviews, MEDLINE, APA PsychInfo, CINAHL and Scopus were searched from database inception until 31 May 2023 to identify systematic reviews of interventions to enhance medical student well-being. Ancestry searching and citation chasing were also conducted.

Data extraction and synthesis

The Assessing the Methodological Quality of Systematic Reviews V.2 tool was used to appraise the quality of the included reviews. A narrative synthesis was conducted, and the evidence of effectiveness for each intervention was rated.

Results

13 reviews (with 94 independent studies and 17 616 students) were included. The reviews covered individual-level and curriculum-level interventions. Individual interventions included mindfulness (n=12), hypnosis (n=6), mental health programmes (n=7), yoga (n=4), cognitive and behavioural interventions (n=1), mind-sound technology (n=1), music-based interventions (n=1), omega-3 supplementation (n=1), electroacupuncture (n=1) and osteopathic manipulative treatment (n=1). The curriculum-level interventions included pass/fail grading (n=4), problem-based curriculum (n=2) and multicomponent curriculum reform (n=2). Most interventions were not supported by sufficient evidence to establish effectiveness. Eleven reviews were rated as having ‘critically low’ quality, and two reviews were rated as having ‘low’ quality.

Conclusions

Individual-level interventions (mindfulness and mental health programmes) and curriculum-level interventions (pass/fail grading) can improve medical student well-being. These conclusions should be tempered by the low quality of the evidence. Further high-quality research is required to explore additional effective interventions to enhance medical student well-being and the most efficient ways to implement and combine these for maximum benefit.

Did COVID-19 ICU patient mortality risk increase as Colorado hospitals filled? A retrospective cohort study

Por: Johnson · D. R. · Ghosh · D. · Wagner · B. D. · Carlton · E. J.
Objectives

To assess whether increasing levels of hospital stress—measured by intensive care unit (ICU) bed occupancy (primary), ventilators in use and emergency department (ED) overflow—were associated with decreasing COVID-19 ICU patient survival in Colorado ICUs during the pre-Delta, Delta and Omicron variant eras.

Design

A retrospective cohort study using discrete-time survival models, fit with generalised estimating equations.

Setting

34 hospital systems in Colorado, USA, with the highest patient volume ICUs during the COVID-19 pandemic.

Participants

9196 non-paediatric SARS-CoV-2 patients in Colorado hospitals admitted once to an ICU between 1 August 2020 and 1 March 2022 and followed for 28 days.

Outcome measures

Death or discharge to hospice.

Results

For Delta-era COVID-19 ICU patients in Colorado, the odds of death were estimated to be 26% greater for patients exposed every day of their ICU admission to a facility experiencing its all-era 75th percentile ICU fullness or above, versus patients exposed for none of their days (OR: 1.26; 95% CI: 1.04 to 1.54; p=0.0102), adjusting for age, sex, length of ICU stay, vaccination status and hospital quality rating. For both Delta-era and Omicron-era patients, we also detected significantly increased mortality hazard associated with high ventilator utilisation rates and (in a subset of facilities) states of ED overflow. For pre-Delta-era patients, we estimated relatively null or even protective effects for the same fullness exposures, something which provides a meaningful contrast to previous studies that found increased hazards but were limited to pre-Delta study windows.

Conclusions

Overall, and especially during the Delta era (when most Colorado facilities were at their fullest), increasing exposure to a fuller hospital was associated with an increasing mortality hazard for COVID-19 ICU patients.

Evaluation of adherence to pharmacological treatments by undocumented migrants with chronic diseases: a 10-year retrospective cohort study

Por: Fiorini · G. · Pellegrini · G. · Franchi · M. · Rigamonti · A. E. · Marazzi · N. · Sartorio · A. · Corrao · G. · Cella · S. G.
Objectives

To investigate the time course of medication adherence and some of the factors involved in this process in undocumented migrants with chronic diseases.

Design

Retrospective cohort study.

Setting

A big non-governmental organisation in Milano, Italy, giving medical assistance to undocumented migrants.

Participants

1918 patients, 998 females and 920 males, with at least one chronic condition (diabetes, cardiovascular diseases (CVDs), mental health disorders) seen over a period of 10 years (2011–2020). Their mean age was 49.2±13 years.

Results

Adherence to medications decreased over 1 year in all patients. This was more evident during the first 2 months of treatment. Patients on only one medication were less adherent than those on more than one medication; at 6 months the percentage of patients with high adherence was 33% vs 57% (p

Conclusions

Interventions to increase medication adherence of undocumented migrants with chronic diseases are necessary, particularly in the first 2 months after beginning treatment. These should be aimed at people-centred care and include more outpatient consultations. Educational interventions should especially be taken into consideration for patients on monotherapy.

Cohort profile: the Environmental Reproductive and Glucose Outcomes (ERGO) Study (Boston, Massachusetts, USA) -- a prospective pregnancy cohort study of the impacts of environmental exposures on parental cardiometabolic health

Por: Preston · E. V. · Quinn · M. R. · Williams · P. L. · McElrath · T. F. · Cantonwine · D. E. · Seely · E. W. · Wylie · B. J. · Hacker · M. R. · O'Brien · K. · Brown · F. M. · Powe · C. E. · Bellavia · A. · Wang · Z. · Tomsho · K. S. · Hauser · R. · James-Todd · T. · the Environmental Rep
Purpose

Pregnancy and the postpartum period are increasingly recognised as sensitive windows for cardiometabolic disease risk. Growing evidence suggests environmental exposures, including endocrine-disrupting chemicals (EDCs), are associated with an increased risk of pregnancy complications that are associated with long-term cardiometabolic risk. However, the impact of perinatal EDC exposure on subsequent cardiometabolic risk post-pregnancy is less understood. The Environmental Reproductive and Glucose Outcomes (ERGO) Study was established to investigate the associations of environmental exposures during the perinatal period with post-pregnancy parental cardiometabolic health.

Participants

Pregnant individuals aged ≥18 years without pre-existing diabetes were recruited at

Findings to date

We enrolled 653 unique pregnancies and retained 633 through delivery. Participants had a mean age of 33 years, 10% (n=61) developed gestational diabetes and 8% (n=50) developed pre-eclampsia. Participant pregnancy and postpartum urinary phthalate metabolite concentrations and postpartum glycaemic biomarkers were quantified. To date, studies within ERGO found higher exposure to phthalates and phthalate mixtures, and separately, higher exposure to radioactive ambient particulate matter, were associated with adverse gestational glycaemic outcomes. Additionally, certain personal care products used in pregnancy, notably hair oils, were associated with higher urinary phthalate metabolite concentrations, earlier gestational age at delivery and lower birth weight.

Future plans

Future work will leverage the longitudinal data collected on pregnancy and cardiometabolic outcomes, environmental exposures, questionnaires, banked biospecimens and paediatric data within the ERGO Study.

Wildfire, deforestation and health in tropical rainforest areas: a scoping review protocol

Por: Casais · G. · Guimaraes · N. S. · Cortes · T. R. · Pescarini · J. · Reboucas de Magalhaes · P. · Wells · V. · de Sousa Filho · J. F. · Delgado Neves · D. J. · Shimonovich · M. · Olsen · J. R. · de Carvalho Neto · E. M. · Cooper · P. · Katikireddi · S. V. · Emanuel · L. · Andrade · R
Introduction

Wildfires and deforestation potentially have direct effects on multiple health outcomes as well as indirect consequences for climate change. Tropical rainforest areas are characterised by high rainfall, humidity and temperature, and they are predominantly found in low-income and middle-income countries. This study aims to synthesise the methods, data and health outcomes reported in scientific papers on wildfires and deforestation in these locations.

Methods and analysis

We will carry out a scoping review according to the Joanna Briggs Institute’s (JBI) manual for scoping reviews and the framework proposed by Arksey and O’Malley, and Levac et al. The search for articles was performed on 18 August 2023, in 16 electronic databases using Medical Subject Headings terms and adaptations for each database from database inception. The search for local studies will be complemented by the manual search in the list of references of the studies selected to compose this review. We screened studies written in English, French, Portuguese and Spanish. We included quantitative studies assessing any human disease outcome, hospitalisation and vital statistics in regions of tropical rainforest. We exclude qualitative studies and quantitative studies whose outcomes do not cover those of interest. The text screening was done by two independent reviewers. Subsequently, we will tabulate the data by the origin of the data source used, the methods and the main findings on health impacts of the extracted data. The results will provide descriptive statistics, along with visual representations in diagrams and tables, complemented by narrative summaries as detailed in the JBI guidelines.

Ethics and dissemination

The study does not require an ethical review as it is meta-research and uses published, deidentified secondary data sources. The submission of results for publication in a peer-reviewed journal and presentation at scientific and policymakers’ conferences is expected.

Study registration

Open Science Framework (https://osf.io/pnqc7/).

Cohort profile: the Adverse Childhood Experiences cohort of the Malawi Longitudinal Study of Families and Health

Por: Kidman · R. · Mwera · J. · Rui · Y. · Breton · E. · Zulu · A. · Behrman · J. · Kohler · H.-P.
Purpose

The Adverse Childhood Experiences (ACE) cohort of the Malawi Longitudinal Study of Families and Health (MLSFH-ACE) is a study of adolescents surveyed during 2017–2021. It provides an important opportunity to examine the longitudinal impact of ACEs on health and development across the early life course. The MLSFH-ACE cohort provides rich data on adolescents, their children and adult caregivers in a low-income, high-HIV-prevalence context in sub-Saharan Africa (SSA).

Participants

The MLSFH-ACE cohort is a population-based study of adolescents living in three districts in rural Malawi. Wave 1 enrolment took place in 2017–2018 and included 2061 adolescents aged 10–16 years and 1438 caregivers. Wave 2 took place in 2021 and included data on 1878 adolescents and 208 offspring. Survey instruments captured ACEs during childhood and adolescence, HIV-related behavioural risk, mental and physical health, cognitive development and education, intimate partner violence (IPV), marriage and aspirations, early transitions to adulthood and protective factors. Biological indicators included HIV, herpes simplex virus and anthropometric measurements.

Findings to date

Key findings include a high prevalence of ACEs among adolescents in Malawi, a low incidence of HIV and positive associations between ACE scores and composite HIV risk scores. There were also strong associations between ACEs and both IPV victimisation and perpetration.

Future plans

MLSFH-ACE data will be publicly released and will provide a wealth of information on ACEs and adolescent outcomes in low-income, HIV-endemic SSA contexts. Future expansions of the cohort are planned to capture data during early adulthood.

Sex and gender-based analysis and diversity metric reporting in acute care trials published in high-impact journals: a systematic review

Por: Granton · D. · Rodrigues · M. · Raparelli · V. · Honarmand · K. · Agarwal · A. · Friedrich · J. O. · Perna · B. · Spaggiari · R. · Fortunato · V. · Risdonne · G. · Kho · M. · VanderKaay · S. · Chaudhuri · D. · Gomez-Builes · C. · D'Aragon · F. · Wiseman · D. · Lau · V. I. · Lin · C. · Reid
Objective

To characterise sex and gender-based analysis (SGBA) and diversity metric reporting, representation of female/women participants in acute care trials and temporal changes in reporting before and after publication of the 2016 Sex and Gender Equity in Research guideline.

Design

Systematic review.

Data sources

We searched MEDLINE for trials published in five leading medical journals in 2014, 2018 and 2020.

Study selection

Trials that enrolled acutely ill adults, compared two or more interventions and reported at least one clinical outcome.

Data abstraction and synthesis

4 reviewers screened citations and 22 reviewers abstracted data, in duplicate. We compared reporting differences between intensive care unit (ICU) and cardiology trials.

Results

We included 88 trials (75 (85.2%) ICU and 13 (14.8%) cardiology) (n=111 428; 38 140 (34.2%) females/women). Of 23 (26.1%) trials that reported an SGBA, most used a forest plot (22 (95.7%)), were prespecified (21 (91.3%)) and reported a sex-by-intervention interaction with a significance test (19 (82.6%)). Discordant sex and gender terminology were found between headings and subheadings within baseline characteristics tables (17/32 (53.1%)) and between baseline characteristics tables and SGBA (4/23 (17.4%)). Only 25 acute care trials (28.4%) reported race or ethnicity. Participants were predominantly white (78.8%) and male/men (65.8%). No trial reported gendered-social factors. SGBA reporting and female/women representation did not improve temporally. Compared with ICU trials, cardiology trials reported significantly more SGBA (15/75 (20%) vs 8/13 (61.5%) p=0.005).

Conclusions

Acute care trials in leading medical journals infrequently included SGBA, female/women and non-white trial participants, reported race or ethnicity and never reported gender-related factors. Substantial opportunity exists to improve SGBA and diversity metric reporting and recruitment of female/women participants in acute care trials.

PROSPERO registration number

CRD42022282565.

Defining practices suitable for care via teleconsultation in gynaecological and obstetrical care: a French Delphi survey

Por: Rousseau · A. · Baumann · S. · Constant · J. · Deplace · S. · Multon · O. · Lenoir-Delpierre · L. · Gaucher · L.
Objective

Delineate the scope of teleconsultation services that can be effectively performed to provide women with comprehensive gynaecological and obstetrical care.

Design

Based on the literature and experts’ insights, we identified a list of gynaecological and obstetrical care practices suitable for teleconsultation. A three-round Delphi consensus survey was then conducted online among a panel of French experts. Experts using a 9-point Likert scale assessed the relevance of each teleconsultation practice in four key domains: prevention, gynaecology and antenatal and postnatal care. Consensus was determined by applying a dual-criteria approach: the median score on a 9-point Likert scale and the percentage of votes either below 5 or 5 and higher.

Setting

The study was conducted at a national level in France and involved multiple healthcare centres and professionals from various geographical locations.

Participants

The panel comprised 22 French experts with 19 healthcare professionals, including 12 midwives, 3 obstetricians-gynaecologists, 4 general practitioners and 3 healthcare system users. Participants were selected to include diverse practice settings encompassing hospital and private practices in both rural and urban areas.

Primary and secondary outcome measures

The study’s primary outcome was the identification of gynaecological and obstetrical care practices suitable for teleconsultation. Secondary outcomes included the level of professional consensus on these practices.

Results

In total, 71 practices were included in the Delphi survey. The practices approved for teleconsultation were distributed as follows: 92% in prevention (n=12/13), 55% in gynaecology (n=18/33), 31% in prenatal care (n=5/16) and 12% in postnatal care (n=1/9). Lastly, 10 practices remained under discussion: 7 in gynaecology, 2 in prenatal care and 1 in postnatal care.

Conclusions

Our consensus survey highlights both the advantages and limitations of teleconsultations for women’s gynaecological and obstetrical care, emphasising the need for careful consideration and tailored implementation.

Impact of androgenic anabolic steroid use on cardiovascular and mental health in Danish recreational athletes: protocol for a nationwide cross-sectional cohort study as a part of the Fitness Doping in Denmark (FIDO-DK) study

Por: Buhl · L. F. · Lehmann Christensen · L. · Diederichsen · A. · Lindholt · J. S. · Kistorp · C. M. · Glintborg · D. · Andersen · M. · Frystyk · J.
Introduction

The use of androgenic anabolic steroids (AASs) among recreational athletes is steadily increasing. However, knowledge regarding the potentially harmful effects of AAS primarily originates from case reports and small observational studies. This large-scale study aims to investigate the impact of AAS use on vascular plaque formation, preclinical coronary disease, cardiac function, circulating cardiovascular risk markers, quality of life (QoL) and mental health in a broad population of illicit AAS users.

Methods and analyses

A nationwide cross-sectional cohort study including a diverse population of men and women aged ≥18 years, with current or previous illicit AAS use for at least 3 months. Conducted at Odense University Hospital, Denmark, the study comprises two parts. In part A (the pilot study), 120 recreational athletes with an AAS history will be compared with a sex-matched and age-matched control population of 60 recreational athletes with no previous AAS use. Cardiovascular outcomes include examination of non-calcified coronary plaque volume and calcium score using coronary CT angiography, myocardial structure and function via echocardiography, and assessing carotid and femoral artery plaques using ultrasonography. Retinal microvascular status is evaluated through fundus photography. Cardiovascular risk markers are measured in blood. Mental health outcomes include health-related QoL, interpersonal difficulties, body image concerns, aggression dimensions, anxiety symptoms, depressive severity and cognitive function assessed through validated questionnaires. The findings of our comprehensive study will be used to compose a less intensive investigatory cohort study of cardiovascular and mental health (part B) involving a larger group of recreational athletes with a history of illicit AAS use.

Ethics and dissemination

The study received approval from the Regional Committee on Health Research Ethics for Southern Denmark (S-20210078) and the Danish Data Protection Agency (21/28259). All participants will provide signed informed consent. Research outcomes will be disseminated through peer-reviewed journals and scientific conferences.

Trial registration number

NCT05178537.

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