The first year after childbirth is a critical yet insufficiently monitored period for parental health. Postpartum mental and physical morbidity can affect both mothers and co-parents, but national longitudinal data remain scarce. The Stress Of Co-parents Related to A Traumatic Experience of birth across Switzerland (SOCRATES) cohort study aims to describe maternal and co-parental health and well-being trajectories during the first year after childbirth.

SOCRATES is a prospective, population-based cohort study conducted in all linguistic regions of Switzerland. Eligible participants include women aged 14 and above who gave birth to a live or stillborn infant (≥22⁺⁰ weeks’ gestation and ≥500 g) and their cohabiting co-parents, provided they speak German, French, Italian or English. Recruitment was conducted in 81 of the 112 Swiss maternity units, birth centres and organisations of midwives over 6 weeks in spring 2025. Clinical data on pregnancy, childbirth and the early postpartum period are extracted from medical records. Postpartum hospitalisation data are obtained through linkage with national medico-administrative databases. Participants complete online questionnaires shortly after birth and at 2, 6 and 12 months post partum, including sociodemographic characteristics and patient-reported outcomes. The primary outcome is the prevalence of childbirth-related post-traumatic stress disorder at 2 months, assessed using the City Birth Trauma Scale. Secondary outcomes include depression, physical recovery, sexual health, quality of life, healthcare use, perceived care quality and overall well-being. A weighting procedure will be used to ensure representativeness and to account for attrition.

Ethical approval was granted by all seven Swiss ethics committees (number 2024-02262). All participants provided informed consent. Findings will be disseminated through national and international conferences, peer-reviewed publications, policy briefs, social media and stakeholder engagement activities.

NCT06886841.

Area-based measures of socioeconomic status (SES) are increasingly used to study health disparities among people living with HIV (PLWH), with wide variation in how they are defined and applied across studies and settings. This study synthesises the types of area-based measures of SES used in Canada and the USA, the domains captured and their associations with health outcomes among PLWH.

A scoping review of studies published in English between 2012 and 2025 was conducted using PubMed and Web of Science. The search combined ‘HIV’ with terms related to area-based SES measures. Eligible studies included PLWH, were based in Canada or the USA, used area-based SES measures and assessed health outcomes.

We screened 3470 studies: 56 met inclusion criteria. Most were US-based (n=53) and focused solely on PLWH (n=46). Area-based SES was measured using composite (n=34), single (n=16) or both types of indicators (n=6), all drawn from census data. The most common SES domain was income/poverty (n=56), the most common geographic unit was census tract (n=19) and the most common health outcome assessed was viral load/suppression (n=29). Most studies linked lower area-based SES with poorer health outcomes among PLWH (n=46).

Our findings highlight the utility of area-based SES as an individual-level SES proxy and tool for capturing broader social determinants of health when assessing a range of health outcomes across studies including PLWH. This review contributes to strengthening methodological approaches and supports future work focused on addressing social determinants and advancing health equity for PLWH.

This scoping review identifies existing registries collecting data on Klinefelter’s syndrome (KS) patients and what data are collected, with the purpose of identifying any KS-specific registries. Findings to be used to inform future registry development.

A comprehensive scoping review was conducted. Multiple sources were reviewed and articles screened based on inclusion criteria and exclusion criteria.

Searches performed across multiple sources including PubMed, Embase, the Cochrane Library, WHO International Clinical Trials Registry Platform, Orphanet, EU Clinical Trials Register, King’s College London Library and charity organisation webpages.

The included studies were required to focus on KS patients with reported data from an active registry that routinely collects data on KS patients.

Basic information about registries identified in included articles was extracted. Registries identified were contacted with a standardised set of questions to collect additional contextual information. Findings are presented in tables.

The scoping review included 18 articles. From those, 10 registries storing KS patient data were identified. Only one of those registries was KS-specific. Only three out of 10 registries collected data that encompassed genetic, clinical and social variables. Most data included in registries were collected exclusively from medical records, although some registries included data from patient surveys. Registries that received government funding had more KS participants than those that did not.

With only one KS-specific registry existing worldwide and none within the UK, this review has identified a need for the development of further KS-specific registries. Data collected could be used to develop an accurate KS phenotype and therefore lead to increased diagnosis of the disorder, improving the lives of people with KS.

Point-of-care technologies (POCTs) are essential to providing clinical care for patients, with their potential for rapid and accurate results on site supporting efficient clinical decision-making.

To understand the current key needs, barriers and challenges of POCT developers for effective development and implementation of POCTs across diverse settings particularly in the domain of cancer, nutrition and infections.

A qualitative semi-structured focus group discussion (FGDs) was employed. The FGDs were guided by the needs assessment process and the Phase Gate Framework. The qualitative data were coded and analysed in NVivo and refined into various themes.

The study was conducted in person at Cornell Tech Campus in May 2024, New York, USA.

24 participants were purposively sampled from the PORTENT (Point-of-Care Technologies for Nutrition, Infection and Cancer) network. Participants included technical developers (eg, engineers, scientists, startup leads) and expert stakeholders (eg, funders, policy advisors, clinicians and academic partners) involved in POCT development, evaluation and implementation.

A total of 24 participants participated in the in-person FGDs in New York (n=24). Key themes identified included gaps in stakeholder engagement, limited regulatory preparedness, insufficient market analysis, challenges in scaling and manufacturing and the need for context-specific adaptation in low- and middle-income country (LMIC) settings. Participants emphasised the importance of user-centred and context-responsive design, strategic partnerships and early planning for regulatory and implementation pathways.

Technical developers and expert stakeholders in the POCT landscape face various barriers to efficient and effective development and implementation of POCTs. It is important to consider their needs when adapting POCTs in LMICs and diverse settings.

To summarise the evidence on long-term and infrequent harms following selected spinal and paraspinal injections and denervation procedures for chronic non-cancer spine pain.

Systematic review and meta-analysis.

MEDLINE, EMBASE and Cumulative Index to Nursing and Allied Health Literature from inception to October 2023.

Non-randomised studies reporting on harms of selected interventional procedures administered to adults living with chronic axial or radicular non-cancer spine pain with ≥4 weeks of follow-up.

A parallel guideline panel provided input on the scope, design and interpretation of this systematic review, including selection of adverse events for consideration. Systematic literature screening, data abstraction and risk of bias appraisal were conducted independently and in duplicate by pairs of reviewers. We used random-effects models for all meta-analyses and the Grading of Recommendations Assessment, Development and Evaluation approach to evaluate the certainty of evidence.

We included 60 longitudinal studies (56 non-comparative, 4 comparative) that enrolled 4966 patients with chronic non-cancer spine-related pain. 31 studies investigated radiofrequency ablation or denervation, 22 epidural injections and 11 joint injections or nerve blocks. Low certainty evidence suggests that joint targeted steroid injection and epidural steroid injection for chronic spine pain may result in temporary altered level of consciousness (incidence: 2.1%; 95% CI 1.1% to 4.0%), joint radiofrequency nerve ablation, joint targeted steroid injection and epidural injection of local anaesthetic and steroids may result in deep infection (incidence: 0.7%; 95% CI 0.3% to 2.0%), epidural steroid injection, joint radiofrequency nerve ablation and joint targeted injection of local anaesthetic and steroids may result in dural puncture (incidence: 1.4%; 95% CI 0.5% to 4.3%), and dorsal root ganglion radiofrequency and joint radiofrequency nerve ablation with or without joint-targeted injection of steroids may result in prolonged pain or stiffness (incidence: 8.6%; 95% CI 6.3% to 11.6%). Several interventional procedures may result in metabolic complications and prolonged sensory deficits, but the supporting evidence was only very low certainty. Most complications resolved spontaneously or with conservative management.

Low certainty evidence suggests that several common interventional procedures for chronic spine pain show risk of deep infection, dural puncture, temporary altered level of consciousness and prolonged pain or stiffness. Other harms are uncertain due to very low certainty evidence, and catastrophic outcomes were not reported in the small studies that contributed to our analyses.

Worldwide, billions of children and young people live in areas affected by war. Suicide remains one of the three leading causes of death worldwide among people aged 15–29 years. However, little is known about the effect of war on suicidal behaviours in this group. This review aims to assess suicides, suicide attempts and suicidal ideation among children and young people exposed to war or armed conflict.

A scoping review of studies was conducted using Web of Science, PubMed, Embase and PsycINFO databases from their inception to 18 November 2025, without any restrictions on geographical location. We included only observational studies with full-text, peer-reviewed English articles reporting any suicides, suicide attempts and suicidal ideation of children and young people aged 0–24 years exposed to war. The quality of the included articles was assessed using the Quality Assessment with Diverse Studies. The protocol of the review was registered with the Open Science Framework on 29 March 2022 (https://osf.io/7kszh/).

Of the 3229 articles retrieved, 37 studies were eligible for review, providing data from 24 countries and covering a period of almost a hundred years (1921–2025). Most studies (>20) focused on conflicts ongoing during or until the 2000s, whereas only three focused on World War II. The reported outcomes were suicides (n=9), suicide attempts (n=15) and suicidal ideation (n=21). Included studies spanned six continents, from Latin America (n=5, Colombia only) to Europe (n=10). We assessed the suicide rates during and after wars. There was some evidence of a decrease in suicide rates during war, but no clear trend in suicide rates post-war was observed. The prevalence rates of suicide attempts and suicidal ideation varied widely, without uniformity in the definitions used. War-related trauma, mental health problems, substance abuse and exposure to suicide or suicide attempts were identified as risk factors, while protective factors included family and social support.

There is a need for more methodologically consistent and rigorous research on suicidal thoughts and behaviours in children and young people exposed to war or armed conflicts. Future research should identify mediator/moderating factors influencing suicidal behaviours and their links to mental health.

Acne vulgaris is a chronic inflammatory condition primarily caused by Cutibacterium acnes, which disrupts skin homeostasis, thereby triggering immune responses and sebum metabolism. Dysbiosis is an imbalance in the skin and gut microbiota identified as a significant factor contributing to acne progression. Standard therapy often relies on antibiotics, but the long-term use has increased antibiotic resistance, including in Indonesia. Consequently, alternative methods, such as probiotics and mesenchymal stromal cell secretomes, are gaining attention for immunomodulatory and regenerative properties. These novel therapies have shown promising results in modulating the skin and gut microbiota while reducing inflammation.

A phase 2 double-blind randomised controlled trial will be conducted using a parallel group design with four arms, namely: (1) standard therapy with oral probiotics and topical secretome (placebo), (2) standard therapy with oral probiotics (placebo) and topical secretome, (3) standard therapy with oral probiotics and topical secretome and (4) standard therapy with oral probiotics (placebo) and topical secretome (placebo). Sixty-four patients with mild to moderate acne vulgaris will be randomly allocated to these groups. Interventions will be administered over a period of 8 weeks, with outcomes to be measured at baseline and post-therapy. This study will be conducted at the Dermatology and Venereology Department of Bali Mandara General Hospital (RSBM). The primary outcome will be the reduction of comedones and inflammatory lesions, assessed using the Yolov8 method. Secondary outcomes will include gut and skin health parameters, such as tryptophan metabolites, collagen, pH, moisture, sebum levels and IL-6, to explore the relationship between microbiome balance, skin condition and inflammation in acne.

This study will be conducted in accordance with the ethical principles outlined in the Declaration of Helsinki and the International Conference on Harmonisation–Good Clinical Practice guidelines. Ethical approval has been granted by the Health Research Ethics Committee of Bali Mandara Regional Hospital (Approval Reference Number: 060/EA/KEPK.RSBM.DINKES/2024). All participants will provide written informed consent prior to enrolment. Data confidentiality and participant safety will be upheld throughout the trial. The results of this study will be disseminated through journals, scientific conferences and relevant academic platforms to ensure wide accessibility and to support further research and clinical application in the field of dermatology, particularly in addressing antibiotic resistance and microbiome-based acne therapies.

NCT06925386.

The growing advancement of innovative stem cell technologies requires careful evaluation of their economic, clinical and societal impacts. Early economic evaluations are essential for developing new medical technologies and supporting key decisions about commercialisation and market access. This scoping review explores Early Health Technology Assessment (eHTA) approaches specifically related to human stem cell technologies. By examining how eHTA can support the commercialisation of these therapies, we aim to clarify its role in optimising resource allocation and enhancing both the clinical and societal benefits of stem cell technologies.

To explore the use of eHTA in the development of stem cell-related technologies, a scoping review will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses - Scoping Review Extension guidelines. Systematic searches were conducted across scientific databases (MEDLINE, International HTA database, EconLit, PAIS Index and EconPapers), grey literature sources (Overton) and through hand-searching to identify eligible articles published from inception to 14 April 2026. No limits were imposed on language. Reviewers will independently record data from eligible studies using a standard data abstraction form. The gathered information will be synthesised both quantitatively and narratively.

Formal ethical approval is not required, as this study does not involve the collection of primary data. The findings will be shared through professional stem cell networks, published in national and international health technology assessment conference proceedings and submitted for open-access, peer-reviewed publication.

To determine the prevalence and clinical characteristics associated with polyneuropathy in kidney transplant recipients (KTRs).

Cross-sectional study.

SENS study at the University Medical Center Groningen, the Netherlands, December 2021–May 2023.

KTR, participating in the ongoing TransplantLines Biobank and Cohort Study, ≥12 months post-transplantation.

Participants underwent a structured neurological assessment including history taking, neurological examination, quantitative sensory testing and nerve conduction studies. An expert panel classified participants into no/possible, probable/definite large fibre polyneuropathy or small fibre neuropathy. Large-fibre subtypes included axonal or demyelinating, pure sensory, pure motor and sensorimotor. To assess potential associations with clinical characteristics, logistic regression analysis was conducted.

We included 160 KTRs with a mean age of 59.8±11.6 years at a median of 6.1 (95% CI 3.9 to 13.1) years post-transplantation, with 16 KTRs (10%) diagnosed with polyneuropathy before study inclusion. In total, 84 KTRs (53%) were identified with large fibre polyneuropathy and 7 KTRs (4%) with small fibre neuropathy. KTRs with large fibre polyneuropathy presented with either sensor-predominant polyneuropathy (40 KTR (48%)) or sensorimotor polyneuropathy (44 KTR (52%)). We found no neurophysiological characteristics of demyelination. Overall, 18% (95% CI 11% to 27%) of KTRs with large fibre polyneuropathy were asymptomatic. Higher age (OR=1.04 (1.01 to 1.08), p=0.01), male sex (OR=2.55 (1.19 to 5.60), p=0.02), diabetes (OR=5.58 (1.36 to 38.14), p=0.03) and elevated urea levels (OR=1.12 (1.04 to 1.23), p=0.01) were significantly associated with polyneuropathy in KTR.

In contrast with previous studies, axonal sensory or sensorimotor polyneuropathy is highly prevalent and often underdiagnosed in KTR. Next to higher age and male sex, it was independently associated with diabetes and higher urea levels. Further research is needed to reveal the aetiology and course of polyneuropathy in KTRs.

NCT04664426.

In individuals at-risk of rheumatoid arthritis (RA), to investigate how joint tenderness and patient-reported joint pain (PRJP) relate to ultrasound abnormalities and assess whether these exploratory results could be used to assist future evaluation of symptom/signs-guided ultrasound scanning approaches in this population.

This is a cross-sectional analysis from a Leeds (UK) cohort of anti-cyclic citrullinated peptide (anti-CCP) positive individuals with new musculoskeletal complaints and no clinical arthritis. Assessments included physical examination, a mannequin where participants ticked joints that were painful and ultrasound scans of wrists, metacarpo-phalangeal joints 1–5 (MCPs1-5), proximal interphalangeal joints 1–5 (PIPs1-5), elbows, knees, ankles, metatarso-phalangeal joints 1–5 (MTPs1-5), finger flexor tendons (2-5) and extensor carpi ulnaris. Grey scale (GS), power Doppler (PD), tenosynovitis and erosions were assessed. A generalised estimating equations model was used to evaluate potential associations between tenderness/PRJP and ultrasound findings at the joint-level, adjusting for age and sex. Positive and negative predictive values for ultrasound changes were calculated.

323 participants were analysed. Joint tenderness was associated with ultrasound abnormalities, predominantly PD in wrists, MCPs, PIPs, elbows, knees and MTPs. GS and erosions were also associated with tenderness, but to a lesser degree. Association of PRJP with ultrasound abnormalities was more inconsistent and mostly for GS in the feet (all p≤0.05). Absence of symptoms and signs had a negative predictive value between 97% and 100% in all joints, except in wrists; which was slightly lower.

In anti-CCP positive individuals at risk of RA, tenderness, predominantly in the small joints, was associated with local inflammatory changes on ultrasound. The association of PRJP and ultrasound was limited. In the absence of tenderness, the presence of PD, tenosynovitis or erosions was uncommon. These findings may inform future studies evaluating symptom/sign-guided ultrasound assessment approaches in at-risk populations.

NCT02012764.

The initiation of buprenorphine for patients with opioid use disorder (OUD) in the emergency department (ED) has been associated with improved outcomes including reduced ED visits and increased treatment engagement. Though both standard-dose (8 mg buprenorphine equivalent) and high-dose (24 mg buprenorphine equivalent) strategies to initiate buprenorphine have been used in the ED, no prospective trials comparing outcomes among patients receiving these treatments have been reported.

This multisite randomised clinical trial is a multisite double-blind, double-dummy, randomised clinical trial enrolling 360 emergency department patients with moderate-to-severe OUD. Enrolled patients will be randomised to one of two study arms: standard-dose induction or high-dose induction, both provided in the ED. This study will engage, train and provide resources to five EDs throughout the US to recruit patients with untreated OUD into a randomised clinical trial. The primary aim is to evaluate the effects of the standard-dose induction and high-dose induction on rates of OUD treatment participation within 10 days post-randomisation. The secondary aims are to evaluate differences between standard-dose induction and high-dose induction on the outcomes of opioid craving, opioid withdrawal symptoms and illicit drug use assessed during 10 days post randomisation and evaluate the effects between treatment arms on rates of OUD treatment participation within 30 days post randomisation.

This study is funded by the National Institute on Drug Abuse and has been approved by the WCG Instutitional Review Board. It has been registered at clinicaltrials.gov. This study will inform the strategy for treatment initiation with buprenorphine among diverse ED settings and will provide ongoing evidence to support the safety and efficacy of initiating treatment for OUD in the ED.

NCT06494904.

Although several systematic reviews and meta-analyses have demonstrated the benefits of exercise interventions in older adults with frailty, the potential harm associated with these interventions has not been systematically synthesised. This systematic review aims to examine the adverse events reported in exercise intervention trials involving older adults with frailty and to compare the risk of adverse events between the intervention and control groups.

Searches will be performed in four electronic databases (PubMed, Cochrane Library, Web of Science and SPORTDiscus) for published trials. Eligible studies will be randomised controlled trials of exercise interventions, including older adults with frailty aged ≥60 years, with frailty identified using a validated method. Five reviewers and three referees, all with expertise in exercise interventions, will be assigned to three independent review teams to ensure efficient screening. Reviewers will independently screen titles, abstracts and full texts using Rayyan, and then extract trial and adverse event data into an Excel spreadsheet. The risk of bias in eligible trials will be assessed using the Cochrane Risk of Bias 2 (RoB-2) tool. The referees will resolve any disagreements between the two reviewers throughout the screening, data extraction and risk-of-bias assessment processes. The primary outcome is adverse events, defined as any unfavourable, unintended signs, symptoms or disease that occurred during the study period. An independent biostatistician will perform a random-effects meta-analysis using a generalised linear mixed model with a binomial likelihood and a logit link to estimate the pooled risk ratios (RRs) for adverse events in the intervention group relative to the control group. Publication bias will be evaluated using funnel plots and Egger’s regression test. Depending on the number of available studies, subgroup analyses will be conducted to examine differences in RRs according to the study quality, duration of intervention, exercise frequency, setting and supervision.

Ethical approval was not required because we did not use specific patient data. The findings of the systematic review and meta-analysis will be disseminated through publication in a peer-reviewed journal and presentation at appropriate conferences.

CRD420251180645.

To examine whether the use of a venous access-site closure device is associated with the occurrence of postoperative nausea and vomiting (PONV) after atrial fibrillation (AF) ablation under propofol sedation.

Observational study.

A single-centre retrospective observational study in Okayama, Japan.

We retrospectively analysed consecutive patients who underwent AF ablation under deep propofol sedation with adaptive servo-ventilation. A total of 686 patients were included. Patients were managed using a standardised sedation protocol with or without low-dose pentazocine. Patients treated with conventional manual compression for haemostasis (n=383) were compared with those treated using a venous access-site closure device (n=303).

Postprocedural bed rest duration and the incidence and timing of PONV were compared between groups. Associations between closure device use and PONV were evaluated using logistic regression analysis.

The primary outcome was the occurrence of PONV following AF ablation.

All procedures were completed under propofol sedation without conversion to general anaesthesia. The duration of postprocedural bed rest was shorter in the device group than in the conventional-compression group (mean difference –14.7 hours, 95% CI –15.2 to –14.0).

PONV occurred in 6/303 patients (2.0%) in the device group and 20/383 patients (5.2%) in the conventional-compression group, corresponding to a relative risk of 0.38 (95% CI 0.15 to 0.93), an OR 0.25 (95% CI 0.10 to 0.62) and a risk difference of –3.2% (95% CI –6.0% to –0.5%).

In multivariable analysis, use of a venous closure device was associated with a lower likelihood of PONV.

In this single-centre observational study, use of a venous access-site closure device was associated with a lower occurrence of PONV after AF ablation under propofol sedation. These findings suggest that postprocedural management strategies enabling earlier mobilisation may be associated with improved patient comfort; however, causal inference is limited by the observational design.

In March 2016, the Centers for Disease Control and Prevention (CDC) released the CDC Guideline for Prescribing Opioids for Chronic Pain, a set of voluntary recommendations for initiating and managing opioid treatment in the ambulatory setting. This scoping review examined guideline effects on patients, providers and health systems.

A scoping review was conducted with a preregistered protocol. Comprehensive searches of PubMed, Embase and Cumulative Index of Nursing and Allied Health Literature were conducted in April 2025. Reports published between 2016 and 2025 that explored the effects of the CDC guideline were included. No restrictions on language or country of study origin were applied, though all retrieved reports were published in the USA and in English. Two authors independently screened titles, abstracts and full-text reports. Data were extracted by healthcare setting, study aims and design, sample size, study population, participant characteristics and study findings and outcomes. Reports were characterised as empirical studies that evaluated guideline effects or implementation studies that assessed uptake. Study findings were presented descriptively and by evidence maps.

Ninety-four studies met the inclusion criteria: 75 empirical studies and 19 implementation studies. Eighty-eight per cent measured changes in opioid prescribing; all but one found significant reductions in at least one prescribing measure, often among people receiving ≥50–90 morphine mg equivalents per day. Effects occurred across specialties and populations, including groups not targeted by the guideline. Studies found increased rates of tapering, with mixed findings on opioid-benzodiazepine coprescription. Legal analyses showed widespread policy adoption at the state level. Implementation studies described expanded risk-mitigation strategies, sometimes beyond guideline text. Few studies reported patient-centred outcomes, participant race or ethnicity or equity measures.

This voluntary federal guideline had significant intended and unintended effects. The guideline was associated with reductions in opioid prescribing among groups targeted and not targeted by its design, with limited evidence on patient outcomes. Future work should prioritise equity-focused patient outcomes to inform implementation of the 2022 CDC guideline.

To explore healthcare professionals’ perspectives on the potential role of molecular breast imaging (MBI) for breast cancer imaging and to inform future clinical study design and implementation.

Qualitative interview study.

UK National Health Service (NHS) breast screening and diagnostic pathways.

Purposively sampled stakeholders.

Semistructured interviews with key professional stakeholders explored potential MBI pathways and routes to adoption, including barriers and facilitators. Data were analysed thematically.

22 participants were recruited between January 2020 and October 2021. Barriers to MBI adoption were identified at three levels: scan-related, system-level, and cultural within the screening programme. Overcoming these is likely necessary for implementation. A further theme highlighted the potential for MBI to improve screening in selected patient groups, contingent on addressing these barriers. Specifically, adoption would require advances in next-generation MBI systems, particularly reductions in radiation dose and scan time, alongside prospective clinical studies in UK populations to assess diagnostic accuracy.

Once identified barriers are overcome, participants perceived that MBI could improve screening pathways, particularly for women with dense breast tissue.

To estimate the burden of household air pollution (HAP) on chronic obstructive pulmonary disease (COPD) and lung cancer in Morocco in 2019 using population attributable fractions (PAFs).

Secondary analytical study based on sex-specific PAF estimation combining Moroccan exposure prevalence from a Moroccan population-based survey conducted in 2010–2011, pooled relative risks from an international meta-analysis, national disease frequency estimates (for COPD, two prevalence sources were used: 2010–2011 observed Moroccan data and 2019 modelling-based estimates), 2019 burden indicators and direct medical costs.

Morocco.

Adults aged 40 years and older included in the Burden of Obstructive Lung Disease (BOLD I) survey in Fez, Morocco.

Sex-specific PAFs, attributable COPD and lung cancer cases, disability-adjusted life years (DALYs) and annual direct medical costs attributable to HAP.

In Morocco, HAP accounted for 14.4% (95% CI 8.4% to 21.6%) of COPD cases in men and 25.3% (95% CI 17.0% to 34.0%) in women, and for 14.2% (95% CI 7.9% to 21.8%) of lung cancer cases in men and 25.0% (95% CI 16.1% to 34.2%) in women. The estimated number of COPD cases attributable to HAP ranged from 661 717 (95% CI 411 046 to 948 444) using modelling-based prevalence estimates to 815 368 (95% CI 509 160 to 1 163 973) using Moroccan BOLD I prevalence estimates, while 1356 (95% CI 775 to 2041) lung cancer cases were attributable to HAP. Total attributable DALYs were estimated at 62 561.2 (95% CI 37 588.4 to 91 439.2). Total annual direct medical costs attributable to HAP ranged from US$529.9 million (95% CI US$328.9 million to US$760.0 million) to US$651.6 million (95% CI US$406.6 million to US$930.6 million), depending on the COPD prevalence source used.

HAP contributes substantially to the respiratory and economic burden in Morocco. These estimates should be interpreted considering the regional source of exposure data and the application of pooled international relative risks to the Moroccan context.

The survival rate of patients with life-threatening diseases primarily depends on the speed of diagnosis. Too often, diseases are detected only after symptoms appear, which usually occurs at later stages of a disease when available treatments may be less effective. Current detection techniques primarily depend on identifying metabolites in biofluids such as blood and urine. The analysis of these fluids is typically performed in laboratories, resulting in lengthy waiting times for patients to receive their results. In severe cases, invasive biopsies and radiative methods are used to diagnose conditions such as cancer. These biopsies can cause distress for patients who are already experiencing significant emotional or physical stress, while imaging techniques involving ionising radiation may pose additional health risks. Additionally, these methods can be costly. In recent years, exhaled breath has become a biofluid matrix of interest for disease detection, allowing for the identification of volatile organic compounds (VOCs) or VOC profiles associated with specific conditions. To improve early disease detection through breath analysis, the VOCORDER project aims to develop a device that provides a fast, simple, user-friendly and cost-effective method for continuous health monitoring to identify diseases in their early stages before symptoms appear.

A literature review was initially conducted to identify five reference diseases of interest (lung cancer, stomach/colon cancer, breast cancer and kidney insufficiency) and previously reported VOC profiles associated with these diseases. In this trial, the project team from the MITERA Hospital will select patients, and the hospital staff will conduct personal interviews with these subjects. Each participant will also complete a questionnaire for the acquisition of demographic and medical history data, after being informed in detail about the purposes of the questionnaire and signing a consent form. The study protocol consists of two phases. Phase 1 is a baseline study designed to detect and identify breath biomarkers for the early diagnosis of the diseases mentioned above using gas chromatography-mass spectrometry (GC-MS) and secondary electrospray ionisation high-resolution mass spectrometry (SESI-HR-MS). Prescreening will select 120 healthy controls and 175 patients for the baseline phase of the clinical trial, for which breath samples will be collected in 1 L Supel-Inert Multi-Layer Foil gas sampling bags. New biomarkers and VOC profiles will be extracted from these data, and further statistical analysis will allow for artificial intelligence (AI) models to be produced and tested. For phase 2 (validation phase), 120 healthy controls and 100 patients will be selected. Breath samples will again be collected in 1 L gas sampling bags for analyses with GC-MS and SESI-HR-MS. The VOCORDER device will also be used, and its functioning with the newly developed AI models will be evaluated.

This clinical study has been approved by the scientific council at the MITERA hospital in Athens, Greece (#513/2024). The outcomes will be disseminated through peer-reviewed journal publications and presentations at scientific conferences.

NCT06711939.