by Anni Varjonen, Toni Saari, Sari Aaltonen, Teemu Palviainen, Mia Urjansson, Paula Iso-Markku, Jaakko Kaprio, Eero Vuoksimaa
We examined the associations of midlife and old-age cardiovascular risk factors, education, and midlife dementia risk scores with cognition at 90 + years, using data from a population-based study with 48 years of follow-up. Participants were 96 individuals aged 90–97 from the older Finnish Twin Cohort study. Individual cardiovascular risk factors assessed via questionnaires in 1975, 1981, 1990, and 2021–2023 included blood pressure, body mass index, physical activity, and cholesterol, and self-reported educational attainment. The Cardiovascular Risk Factors, Aging, and Dementia (CAIDE) score and an educational-occupational attainment score were used as midlife dementia risk scores. Cognitive assessments included semantic fluency, immediate and delayed recall from a 10-word list learning task, and a composite cognitive score. Regression analyses were conducted with dementia risk factors predicting cognition at 90 + years, adjusting for age, sex, education, follow-up time, and apolipoprotein E genotype (ε4-carrier vs non-carriers). Results showed that higher education and higher educational-occupational score were associated with better cognitive performance in all cognitive measures. Those with high midlife blood pressure scored significantly higher in all cognitive tests than those with normal blood pressure. Conversely, those with high old-age blood pressure scored lower in semantic fluency and composite cognitive score, but not in immediate or delayed recall. Other cardiovascular risk factors and the CAIDE score did not show consistent associations with cognition. Education appears to have a long-lasting protective effect in cognitive aging, whereas midlife and old-age cardiovascular risk factors were not significantly associated with cognition at 90 + years.The effect of prophylactic clipping for colorectal cold snare polypectomy (CSP) on delayed bleeding (DB) in patients with antithrombotic drugs remains unverified. The aim of the PERCOLD study is to demonstrate the non-inferiority of DB rates in cases without prophylactic clips compared with cases with prophylactic clips in patients taking antithrombotic drugs for colorectal CSP through randomised controlled trial (RCT).
This study is a multicentre prospective parallel-group RCT phase 3 trial that is being conducted at 14 institutions in Japan at the time of writing this manuscript. After providing consent, patients will undergo screening and assessment for study enrolment eligibility. Patients taking antithrombotic drugs (aged 20 years or older at the time of consent and who have agreed to participate in this study) will be selected if they have a preoperative suspected adenoma (including sessile serrated lesion) with an endoscopic diameter of
The trial protocol has been approved by the Chiba University Certified Clinical Research Reviewer Board (CRB3180015), which serves as the central ethics committee, and registered with Japan Registry of Clinical Trials. The current protocol V.1.7, dated 4 October 2024. Written informed consent for participation in the study will be obtained from all participating patients. All participating institutions have formally agreed to conduct the study in accordance with this central approval, and local site permissions were obtained as required by each institution. The results of this study will be submitted for publication in international peer-reviewed journals and the key findings will be presented at international scientific conferences.
Japan Registry of Clinical Trials (jRCT1032230086).
by Denis Sereno, Tahar Kernif, Renato Leon, Kholoud Kahime, Souad Guernaoui, Chaymaa Harkat, Mario J. Grijalva, Omar Hamarsheh, Anita G. Villacis, Bachir Medrouh, Thiago Vasconcelos Dos Santos, Razika Beniklef, Naouel Eddaikra, Phlippe Holzmuller
IntroductionLeishmaniases are a vector-borne parasitic diseases with diverse clinical manifestations involving multiple Leishmania species and animal hosts. While most leishmaniasis cases are caused by a few well characterized Leishmania species, reports describe infections by unconventional or emerging Leishmania taxa, atypical clinical presentations from classical species, and occurrences of atypical Leishmania in animal hosts. These underrecognized infections present diagnostic and therapeutic challenges and are rarely reflected in surveillance systems or clinical guidelines. A systematic mapping of this evolving landscape is needed to guide future diagnostics, policy, and research priorities.
Methods and analysisFollowing the Joanna Briggs Institute (JBI) methodology and PRISMA-ScR guidelines, we will search PubMed, Embase, Cochrane Library (CENTRAL), PROSPERO, Web of Science, and Global Index Medicus, as well as relevant grey literature. Eligible studies will include human cases with clinical presentations that diverge from those typically associated with well-characterized Leishmania species, reports involving unconventional or emerging Leishmania species, and animal cases of veterinary relevance caused by non-classical species, regardless of study design. Dual independent screening of records and data extraction using a standardized charting form will be conducted. Discrepancies between reviewers will be resolved by consensus. Data will be summarized descriptively through tables, figures, and thematic synthesis. Research gaps will be identified to inform future studies and public health strategies.
DisseminationThis review will use data from published sources and findings will be disseminated through publication in a peer-reviewed journal, presentations at scientific conferences, and sharing with relevant stakeholders. The results are intended to inform clinicians, researchers, and policymakers about the evolving landscape of leishmaniasis and to highlight priorities for future research and surveillance.
This study aimed to assess the prevalence of depression and anxiety and to identify factors associated with these conditions among caregivers of children and adolescents with epilepsy attending the paediatric neurology clinic at Muhimbili National Hospital (MNH) in Tanzania.
A hospital-based cross-sectional study.
The paediatric neurology clinic of a national referral hospital in Dar es Salaam, Tanzania.
427 caregivers of children with epilepsy (CWE) were consecutively enrolled. Eligibility criteria included being 18 years or older and having provided care for the child for at least 6 months. Caregivers unable to read and write in Swahili or previously diagnosed with a mental illness before assuming the caregiving role were excluded.
Primary outcomes were the prevalence of depression (assessed with the Patient Health Questionnaire-9 (PHQ-9), cut-off ≥10), anxiety (assessed with the Generalised Anxiety Disorder-7 tool (GAD-7), cut-off ≥10), and their co-occurrence. Secondary outcomes were the factors associated with these conditions, analysed using logistic regression and reported as adjusted odds ratios (aORs).
Depression was observed in 74 (17.3%, 95% CI: 13.8 to 21.3) participants and anxiety was found in 74 caregivers (17.3%,95% CI: 14.1 to 20.8). 38 (9.0%, 95% CI: 6.3 to 11.7) participants had concurrent depression and anxiety. Factors associated with depression were having a child: less than 5 years old (adjusted OR (aOR)=6.56, p=0.012), epilepsy duration of more than 5 years (aOR=2.80, p=0.048), history of epilepsy-related injuries (aOR=2.64, p=0.015) and three or more admissions (aOR=2.56, p=0.046). Caregivers whose children had not started school or were in primary school had lower odds of depression compared with counterparts in secondary school (aOR=0.02, p=0.003) and (aOR=0.03, p=0.005), respectively. Caregivers' anxiety was associated with having a child with: another comorbidity (aOR=1.93, p=0.020), a history of epilepsy-related injuries (aOR=2.37, p=0.030), three or more admissions (aOR=2.98, p=0.015) and caregiver age between 41 to 50 years (aOR=3.06, p=0.042).
Depression and anxiety are prevalent among caregivers of CWE. The findings indicate a need for the integration of mental health services within paediatric neurology clinics to support caregiver well-being.
by Mario Gómez-Martínez, Greta Arias-Merino, Juan Benito-Lozano, Ana Villaverde-Hueso, Renata Linertová, Verónica Alonso-Ferreira
Inherited Epidermolysis Bullosa (EB) is a group of rare, genetic skin diseases characterized by extreme fragility of the skin and mucous membranes, leading to blistering and wounds in response to minimal trauma or friction. These clinical manifestations significantly reduce health-related quality of life (HRQoL). The objective of this protocol article is to provide information about the methods planned to be used to assess the measurement properties of HRQoL instruments specifically developed for EB patients of all age groups through a systematic review and meta-analysis. The protocol followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses Protocols (PRISMA-P) guideline. The literature search will be conducted in PubMed, Web of Science (WOS) and EMBASE, including terminology that aligns with the four key elements of the COSMIN (COnsensus-based Standards for the selection of health Measurement INstruments) research question (construct, target population, measurement properties and type of PROM), as well as the terminology proposed by COSMIN for measurement properties. Studies that include information on measurement properties (specifically, validity and/or reliability) with a sample of patients with inherited EB will be selected. Both title and abstract screening and full text review, will be conducted by two independent reviewers using the Rayyan tool. In addition, the risk of bias will be assessed using the COSMIN-Risk of Bias checklist. The data from each study and each measurement property will be summarized in accordance with the COSMIN guidelines. The evidence gathered will strive to adjudicate data on measurements properties of HRQoL instruments used in EB patients, and the limitations of the future systematic review will be discussed. Ultimately, results of the future systematic review will help develop more personalized guidelines for the assessment of HRQoL in EB patients of all age groups. The protocol is registered in OSF with registration number vrm87: https://osf.io/vrm87/In deprived urban areas of South America, young people face heightened risks of mental disorders. Research suggests an association exists between social media engagement (SME), depression and anxiety.
This study explored the associations of SME with symptoms of depression, anxiety and subjective quality of life among young people from South American deprived urban areas.
Our cross-sectional survey study used an adapted version of the Multidimensional Facebook Intensity Scale to categorise 2399 participants into four SME groups: low, moderate, high and very high. Symptoms of depression (Patient Health Questionnaire-8), anxiety (Generalised Anxiety Disorder-7) and quality of life (Manchester Short Assessment) were assessed and compared using F and Tukey tests.
Each step of increased SME was associated with more symptoms of depression and anxiety and poorer quality of life. Statistically significant differences were observed across all groups (p
The findings suggest an association exists between SME, increased mental distress and lower quality of life in young people from deprived South American urban areas. This influence seems to apply across the spectrum of engagement levels, not only to extremes. However, due to the cross-sectional nature of the study, causal relationships cannot be established.
SME should be explored in clinical settings, as lower levels are associated with lower symptom levels and better quality of life. Policies addressing youth SME should be developed and evaluated in the challenging contexts of deprived urban areas.
Persistent epithelial defect (PED) management can be challenging. First line of treatment includes lubrication, bandage contact lenses and punctal plugs. The second line of treatment includes autologous serum (AS). Topical insulin has been shown to be safe for topical use and improve corneal epithelial healing. Therefore, a controlled clinical trial (control group with current standard treatment, ie, AS) multicentre, randomised and with a blind third observer will be conducted to evaluate the efficacy and safety of the use of insulin eye-drops in the treatment of PED.
A preselection of patients with epithelial defect after 1 week of treatment will be made and blood tests will be obtained in order to dispense AS if necessary. After 2 weeks of standard treatment, if the PED persists and the patient meets criteria, patients will be enrolled after signing an informed consent form. Patients will be randomly allocated to receive either insulin (1 UI/mL, 4 times a day) or AS (20%, 5–6 times a day) eye-drops for 3 months. 234 patients will be included, 117 in each treatment group. The main variable (PED size) will be obtained from slit-lamp photographs, an objective and easily quantifiable variable which will be evaluated by a blinded investigator (third observer). Patients will be examined every 3–5 days until week 4 of study treatment and once a week until 6 weeks, to continue with a visit every 2 weeks until reaching 3 months of follow-up. Primary endpoints are: complete epithelialisation, epithelialisation rate (initial defect area/days until epithelialisation) and time until complete closure.
Ethical approval has been obtained from Hospital Clinico San Carlos in Madrid and Agencia Española del Medicamento y Productos Sanitarios (AEMPS). The findings will be disseminated in peer-reviewed publications and presentations at meetings.
EudraCT 2022-003589-19.
To investigate whether quantitative retinal markers, derived from multimodal retinal imaging, are associated with increased risk of mortality among individuals with proliferative diabetic retinopathy (PDR), the most severe form of diabetic retinopathy.
Longitudinal retrospective cohort analysis.
This study was nested within the AlzEye cohort, which links longitudinal multimodal retinal imaging data routinely collected from a large tertiary ophthalmic institution in London, UK, with nationally held hospital admissions data across England.
A total of 675 individuals (1129 eyes) with PDR were included from the AlzEye cohort. Participants were aged ≥40 years (mean age 57.3 years, SD 10.3), and 410 (60.7%) were male.
The primary outcome was all-cause mortality. Quantitative retinal markers were derived from fundus photographs and optical coherence tomography using AutoMorph and Topcon Advanced Boundary Segmentation, respectively. We used unadjusted and adjusted Cox-proportional hazards models to estimate hazard ratios (HR) for the association between retinal features and time to death.
After adjusting for sociodemographic factors, each 1-SD decrease in arterial fractal dimension (HR: 1.54, 95% CI: 1.18 to 2.04), arterial vessel density (HR: 1.59, 95% CI: 1.15 to 2.17), arterial average width (HR: 1.35, 95% CI: 1.02 to 1.79), central retinal arteriolar equivalent (HR: 1.39, 95% CI: 1.05 to 1.82) and ganglion cell-inner plexiform layer (GC-IPL) thickness (HR: 1.61, 95% CI: 1.03 to 2.50) was associated with increased mortality risk. When also adjusting for hypertension, arterial fractal dimension (HR: 1.45, 95% CI: 1.08 to 1.92), arterial vessel density (HR: 1.47, 95% CI: 1.05 to 2.08) and GC-IPL thickness (HR: 1.56, 95% CI: 1.03 to 2.38) remained significantly associated with mortality.
Several quantitative retinal markers, relating to both microvascular morphology and retinal neural thickness, are associated with increased mortality among individuals with PDR. The role of retinal imaging in identifying those individuals with PDR most at risk of imminent life-threatening sequelae warrants further investigation.
by Juliana Rodrigues Tovar Garbin, Franciéle Marabotti Costa Leite, Ana Paula Brioschi dos Santos, Larissa Soares Dell’Antonio, Cristiano Soares da Silva Dell’Antonio, Luís Carlos Lopes-Júnior
A comprehensive understanding of the factors influencing the epidemiological dynamics of COVID-19 across the pandemic waves—particularly in terms of disease severity and mortality—is critical for optimizing healthcare services and prioritizing high-risk populations. Here we aim to analyze the factors associated with short-term and prolonged hospitalization for COVID-19 during the first three pandemic waves. We conducted a retrospective observational study using data from individuals reported in the e-SUS-VS system who were hospitalized for COVID-19 in a state in a southeast state of Brazil. Hospitalization duration was classified as short or prolonged based on a 7-day cutoff, corresponding to the median length of hospital stay during the second pandemic wave. Bivariate analyses were performed using the chi-square test for heterogeneity. Logistic regression models were used to estimate odds ratios (ORs) and their respective 95% confidence intervals (CIs), with statistical significance set at 5%. When analyzing hospitalization duration across the three waves, we found that 51.1% (95%CI: 49.3–53) of hospitalizations in the first wave were prolonged. In contrast, short-duration hospitalizations predominated in the second (54.7%; 95% CI: 52.4–57.0) and third (51.7%; 95% CI: 50.2–53.2) waves. Factors associated with prolonged hospitalization varied by wave. During the first wave, older adults (≥60 years) (OR=1.67; 95%CI: 1.35–2.06), individuals with ≥10 symptoms (OR=2.03; 95%CI: 1.04–3.94), obese individuals (OR=2.0; 95%CI: 1.53–2.74), and those with ≥2 comorbidities (OR=2.22; 95%CI: 1.71–2.89) were more likely to experience prolonged hospitalization. In the second wave, he likelihood of extended hospital stays was higher among individuals aged ≥60 years (OR=2.04; 95%CI: 1.58–2.62) and those with ≥2 comorbidities (OR=1.77; 95%CI: 1.29–2.41). In the third wave, prolonged hospitalization was more frequent among older adults (OR=1.89; 95%CI: 1.65–2.17,), individuals with 5–9 symptoms (OR=1.52; 95%CI: 1.20–1.92), obese individuals (OR=2.2; 95%CI: 1.78–2.73), and those with comorbidities (OR=1.45; 95%CI: 1.22–1.72 and OR=2.0; 95%CI: 1.69–2.45). In conclusion, we identified variations in hospitalization patterns across the pandemic waves, although the differences were relatively subtle. These variations likely reflect gradual shifts in the risk factors associated with prolonged hospital stays. Our findings highlight t the importance of implementing targeted public health interventions, particularly those designed to reduce disease severity and improve clinical outcomes among vulnerable populations at greater risk of extended hospitalization.To explore patient perspectives on using a digital adherence technology (DAT) for tuberculosis (TB) treatment, specifically, the TB Treatment Support Tools (TB-TST) intervention, which integrates a mobile app designed to enhance patient-centred support, monitoring and communication, alongside a drug metabolite test.
Qualitative study conducted as part of a pragmatic randomised controlled trial.
Four public reference hospitals in Argentina. All patients in the intervention group were invited to participate; 33 patients in the intervention group and five treatment supporters were included.
Data collection and analysis: semistructured interviews were conducted. The normalisation process theory guided analysis to understand factors that enable or hinder the intervention’s integration into routine practice for TB treatment medication adherence.
Patients identified medication reminders, educational messages and direct communication with treatment supporters (TSs) as the most helpful components of the intervention. Many reported using the app to ask TSs questions they felt uncomfortable raising with physicians in person. Initially, many patients did not fully understand the purpose and use of the metabolite test. Over time, their understanding of the app improved, though some continued to misinterpret the test results. Motivation to adhere to TB treatment was primarily driven by a desire to protect family members and resume normal daily activities. Reported barriers to app use included time constraints due to work, technical issues, limited internet connectivity and the burden of medication side effects. While the intervention was generally perceived as supportive and user-friendly, patients suggested improvements such as faster response times from TSs, expanded availability and better technical reliability and internet access.
These findings highlight the importance of tailoring digital adherence interventions to meet the diverse needs of patients and reinforce the pivotal role of the TS as a trusted and accessible source of guidance throughout TB treatment.
NCT04221789;
The rapid growth in the cancer survivor population in Chile and Latin America raises new challenges in addressing their care needs. This study assesses the health status and compares the quality of care and quality of life in cancer survivors at a primary care network and a private cancer centre in Santiago, Chile.
Retrospective cohort study.
Three primary care clinics and one cancer centre in Chile.
All breast and colorectal cancer patients identified from a primary care retrospective cohort of 61 174 were followed from 2018 to 2023 and compared with an equivalent sample of patients from a university cancer centre identified during the same period.
Quality of care was assessed based on American Cancer Society standards, while quality of life was measured using the EuroQol 5 Dimensions-5 Levels survey instrument.
A total of 420 cancer survivors participated in the study; 208 from primary care and 212 from the cancer centre. All participants received substandard care. Patients in primary care had lower educational levels and higher rates of comorbidity. They reported a lower quality of life score (72.22 vs 78.43, p
Cancer survivors face a significant disease burden and receive substandard care in Chile. As the primary source of care for this population, primary care is challenged to better integrate with speciality care to develop an effective shared care model for cancer survivors.
To synthesise current evidence on physiotherapists’ use of electronic health records (EHRs), with a focus on the determinants of adoption, implementation processes and associated implementation outcomes.
A systematic review employing a narrative synthesis approach.
PubMed, Cochrane, Scopus and Web of Science, covering all records from the inception of each database to 10 May 2024.
Studies conducted in physiotherapy clinical settings and using the International Classification of Functioning, Disability and Health (ICF).
Two authors independently screened articles and assessed methodological quality. Risk of bias was assessed using the Critical Appraisal Skills Programme tool for qualitative and for cohort studies, the Mixed Methods Appraisal Tool for mixed-methods studies and the JBI Critical Appraisal Checklist for analytical cross-sectional studies.
From 3820 records screened, 9 observational studies met inclusion criteria. Key factors influencing EHR adoption included organisational readiness, perceived usefulness, managerial support and training availability. Implementation patterns clustered into three domains: recorded content, ICF framework integration and record quality. Reported outcomes focused on care quality metrics and evidence of clinical effectiveness.
Persistent challenges in physiotherapy EHR use were identified, notably in data quality, completeness and alignment with the ICF framework. Improving EHR practices is crucial to improve clinical assessment and support digital health integration. However, limited evidence and methodological heterogeneity remain key limitations.
CRD42023420267.
Traditional peoples and communities (TPCs), such as indigenous peoples and quilombolas (communities descended from escaped African slaves), face challenges related to food security and the impact of the food environment on their health. Changes in food systems, urbanisation and loss of territorial rights have contributed to less healthy eating patterns, with increased consumption of ultra-processed foods and a higher prevalence of chronic non-communicable diseases. Despite this, there are gaps in knowledge about how the food environments of these communities are investigated, especially in relation to the physical, economic, political and sociocultural dimensions.
This scoping review will be conducted following the methodological framework developed by the Joanna Briggs Institute for scoping reviews, and its reporting will adhere to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses-Extension for Scoping Reviews checklist. A systematic search will be carried out in the following databases: PubMed, SciELO, Web of Science, Embase and EBSCO, using terms related to traditional populations and food environments. The studies to be included will be selected according to the inclusion and exclusion criteria defined based on the population, concept and context technique. The study population will include TPCs, such as indigenous peoples and quilombolas; the concept will address the food environment in its physical, economic, political and sociocultural dimensions; and the context will encompass studies conducted at a global level, without any restrictions on geographic location. The study type will include original articles and grey literature. The screening of studies will involve independent reviewers and predefined inclusion and exclusion criteria. Data synthesis will be presented in tables, including information on focus, geographic scope and methodology of the selected studies. The risk of bias will be assessed using the Risk of Bias in Non-randomised Studies of Exposure tool.
As the study does not involve the collection of primary data or human participants, it does not require ethical approval. The results will be submitted to peer-reviewed journals and presented at public health and nutrition conferences, contributing to the advancement of knowledge on food environments of TPCs.
This study aimed to determine the prevalence of non-communicable diseases (NCDs) among pregnant women in Sri Lanka and examine the association between NCDs and maternal and fetal outcomes.
A hospital-based, descriptive cross-sectional study.
The study was conducted in three tertiary care hospitals in the Western Province and one intermediate obstetrics care facility in the Southern Province of Sri Lanka, encompassing diverse, multiethnic populations, over 3 months.
Data from 1350 pregnant women were collected from discharged bed head tickets of the postnatal obstetric wards using a standardised checklist.
The primary outcomes were the prevalence of NCDs. Secondary outcomes included associations between maternal NCDs and adverse fetal outcomes such as preterm births and neonatal complications.
Among the participants, 68.5% (n=926) had one or more NCDs, with anaemia (37.9%), obesity (18.1%), gestational diabetes mellitus (14.9%) and hypertensive disorders (13.6%) being the most prevalent. Women with NCDs were at significantly higher odds of adverse fetal outcomes, including preterm birth (OR=2.3, 95% CI: 1.5 to 3.4), neonatal sepsis (OR=2.5, 95% CI: 1.5 to 4.04) and hypoglycaemia (OR=3.5, 95% CI: 1.2 to 10.0). Maternal complications, including postpartum haemorrhage (3.3%) and placental abruption (0.7%), were also more frequent in this group.
NCDs are highly prevalent among pregnant women in Sri Lanka and are significantly associated with adverse maternal and fetal outcomes. Enhanced screening and management strategies during antenatal care are essential to mitigate risks and improve health outcomes, aligning with global efforts to reduce maternal and neonatal morbidity and mortality.
Primary care nurses (PCNs) are the second largest workforce in primary care and play a critical role in facilitating access to coordinated care and reducing health disparities. There is renewed interest in team-based primary care as a solution for health workforce challenges. Some team models enable PCNs (ie, nurse practitioners, registered nurses, licensed/registered practical nurses) to leverage one another’s expertise to work to optimal scope; the extent to which this happens depends on multiple context-dependent factors. We will conduct an umbrella review to synthesise and compare international knowledge syntheses focused on scope of practice enactment (ie., roles and activities) of PCNs in primary care.
We will conduct the umbrella review according to the Joanna Briggs Institute methodology, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Protocol (PRISMA-P) guidelines, and using the Nursing Care Organization Framework as guidance. We will search a wide range of scientific electronic databases and grey literature sources, and consider articles published in English and French by the Organization for Economic Cooperation and Development and designated key partner countries for inclusion, with no publication date limits. Two independent reviewers will screen titles, abstracts and full-text articles, and any disagreements will be resolved through discussion or by a third reviewer. We will use the Risk of Bias Assessment Tool for Systematic Reviews to assess the quality and risk of bias in the included systematic and scoping reviews.
Results will be presented in a PRISMA Scoping Review flow diagram. We will synthesise data from included studies in a detailed literature review table and develop visual aids to communicate the shared and unique roles and activities of PCN scope of practice. We will disseminate the results of the review through peer-reviewed publications and conferences related to this field. Ethics approval is not required.
Patients with stage III non-small cell lung cancer (NSCLC) are at high risk of developing post-treatment recurrences (50–78%) during follow-up. As more effective treatments are now available, especially for patients with oligometastatic disease, earlier detection of recurrences may prolong survival and health-related quality of life (HRQOL). With the use of 2'-deoxy-2'-[18F]fluoroglucose positron emission tomography/CT ([18F]FDG PET/CT) during follow-up, recurrences may be detected earlier. Therefore, the primary objective of this study is to compare the 3-year overall survival of patients with stage III NSCLC during follow-up surveillance with [18F]FDG PET/CT versus follow-up with conventional CT (usual care). Secondary objectives address the number, location and timing of recurrences, as well as HRQOL, cost-effectiveness and patient experiences of PET/CT scans.
In this multicentre randomised controlled clinical trial, 690 patients with stage III NSCLC (8th edition International Association for the Study of Lung Cancer (IASLC) Tumor, Nodes, Metastasis (TNM) classification) who completed curative intended treatment and started follow-up care (which may include adjuvant therapy) will be randomised 1:1 to either the intervention ([18F]FDG PET/CT) or the control group (CT). Patients will undergo follow-up scans during visits at 6, 12, 18, 24 and 36 months. Data will be collected using validated questionnaires, electronic case report forms and data extractions from the electronic health records. Additionally, blood samples will be collected, and interviews will be conducted.
The study protocol has been approved by the Medical Ethical Committee of the Radboudumc and review boards of all participating centres. Written informed consent will be obtained from all participants. Study results will be published in international peer-reviewed scientific journals and presented at relevant scientific conferences. Data will be published in a data repository or other online data archive.
Salvage prostatic bed radiotherapy (PBRT) is a standard in case of biochemical recurrence following radical prostatectomy (RP) for prostate cancer (PC). The management of isolated prostatic bed recurrence following RP and PBRT is debated. Reirradiation within stereotactic body radiotherapy (SBRT) guided by metabolic imaging could be a relevant option in this case. In parallel, metformin, an economically viable and well-tolerated oral antidiabetic agent, has demonstrated its radiosensitising properties. This phase I/II clinical trial aims to (i) determine the optimal dose for SBRT reirradiation, (ii) conduct safety assessments and (iii) evaluate the efficacy of the metformin and SBRT combination.
We conducted a prospective, non-randomised, open-label, multicentre, dose escalation, phase I/II study involving a minimum of 44 patients. Eligible patients must have biochemical recurrence (Prostate Specific Antigen (PSA)>0.2 ng/mL and confirmed ascending trend in at least two successive assays), occurring at least 2 years after PBRT and prior RP for PC (including low, intermediate and high risk with a single risk factor) and no Common Terminology Criteria for Adverse Events (CTCAE) grade>=2 toxicity following PBRT. The recurrence should be visible on MRI and/or Positron Emission Tomography (PET) Choline and/or PET PSMA, without evidence of pelvic lymph node recurrence or metastatic disease. The primary objective of phase I is to determine the optimal SBRT dose (5x6, 6x6, or 5x5 Gy) based on dose-limiting toxicity (DLT). The dose will be chosen using a time-to-event continual reassessment method based on DLT, defined as CTCAE grade ≥3 gastrointestinal or genitourinary toxicity, or any other grade 4 adverse event. The primary outcome of the phase II is to estimate the efficacy of SBRT in combination with metformin in terms of biological relapse-free survival (bRFS) rate at 3 years. Secondary outcomes include 5-year bRFS rate, early/late genitourinary and gastrointestinal toxicities, quality of life, biochemical response rate, clinical progression-free survival and overall survival (OS).
Ethical approval has been obtained from the Ethics committee "SUD EST III Bron" Ref.CPP 2020-042B (20.05.07.72735) and the National Agency for the Safety of Medicines (ANSM) Ref. ANSM MEDAECNAT-2020-05-00009. The ethics approval obtained covers all the sites that will take part in this study. The study’s findings will be disseminated through publications and conference presentations.
NCT04536805, Registration Date: 2020-08-17
Dyspnoea affects 10% of the general population, and 12% of hospitalised patients report experiencing dyspnoea at rest. It is a common and distressing symptom experienced by people living with chronic obstructive pulmonary disease (COPD). Neuromodulation, which uses electrical stimulation to modulate neural pathways, is a validated clinical procedure offering a potential therapeutic approach. We speculate that non-invasive transcutaneous vagus nerve stimulation (tVNS) and trigeminal transcutaneous electric nerve stimulation (TENS) could improve dyspnoea management by targeting relevant neural circuits.
We will conduct a feasibility cross-over trial in people with severe COPD and significant exertional dyspnoea referred for pulmonary rehabilitation. Patients will be recruited following the prerehabilitation assessment visit comprising a clinical evaluation and a maximal cardiopulmonary exercise testing on ergocycle. Subsequently, two study visits will be conducted within 2 weeks apart from each other. Eight participants will perform a submaximal constant work rate at 80% workload of the VO2 max, either with cervical tVNS (n=4) or trigeminal TENS (n=4). In a cross-over design, both patient groups will undergo sham and active treatment of the neuromodulation technique in a randomly assigned order. The main outcome will be feasibility, assessed by the percentage of patients who attend all visits and complete all tests. Secondary outcomes include other feasibility endpoints, the acceptability and suitability of the interventions (including an evaluation of sham as an exploratory outcome), and the incidence of adverse or undesirable events related to the procedures. Exploratory outcomes include changes in dyspnoea symptoms, measured using standardised questionnaires, such as Borg scale and the Visual Analogue Scale.
The protocol is approved by the institutional research ethics committee of the Centre intégré universitaire de santé et de services sociaux (CIUSSS) de l’Estrie—CHUS, Sherbrooke, Quebec, Canada (#2025-5604) and follows 2013 Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines. Results will be communicated in international meetings and submitted to peer-reviewed journals with respect to the 2010 CONsolidated Standards Of Reporting Trials (CONSORT) statement for feasibility studies.
Opioid use disorder (OUD) is a debilitating condition characterised by the overuse of opioid medications and the development of physical and/or psychological dependence. Consequences of this condition include chronic impairment, distress and later life-altering health conditions such as overdose, all of which have been highlighted by the prominence of OUD in the USA in recent years. Buprenorphine is a standard OUD treatment and commonly used for pain management. Understanding changes in distribution patterns across the USA is vital for continuing to improve outcomes for OUD patients.
This study used the Drug Enforcement Administration’s Automated Reports and Consolidated Ordering System (ARCOS) and the US Census Bureau Population Estimates databases to analyse changes in buprenorphine distribution among pharmacies and hospitals from 2019 to 2023, to determine temporal patterns and to identify state-level disparities using the data. The data were corrected for population to identify patterns of buprenorphine distribution in the USA from 2021 to 2022 and 2022 to 2023 through examining percent changes in milligrams per 100 population at the national and state levels.
The year-to-year percent change of national buprenorphine distribution from pharmacies has remained positive but changed from a 12.2% increase from 2019 to 2020 (figure 4) to a four per cent increase every year from 2020 to 2023. From 2021 to 2022, there was a +4.9% increase in total grams of buprenorphine distributed to pharmacies and a 95% CI [–5.1, 14.9], with the District of Columbia, South Dakota and Nebraska outside of the 95% CI. Distribution to hospitals increased by 10.2% [-32.3, 52.7] during 2021–2022, with Hawaii, New Hampshire and Delaware being outside of 95% CI. From 2022 to 2023, there was an increase of +5.7% and 95% CI [–3.5, 14.9] in pharmacy distribution, with states including Washington, Rhode Island and Kansas remain outside of the 95% CI. Hospital distribution has decreased from twenty per cent between 2019 and 2020 (figure 4) to eighteen per cent between 2022 and 2023.
Following increases in buprenorphine distribution during the COVID pandemic, a consistent increase has continued year-over-year in most states and the country overall by both pharmacies and hospitals. Some states (eg, Rhode Island, Georgia, District of Columbia) have not followed this pattern. Notably, Hawaii went from the most negative percent change in hospital distribution to the most positive change in the timeframe analysed. This may offer opportunities to analyse more specific impacts of the increased buprenorphine distribution on populations and their outcomes associated with OUD.