Conectar
The management of diabetic foot ulcers in patients with peripheral artery disease remains challenging. Human placenta-derived cells (PDA-002), a mesenchymal stromal cell-like population obtained from full-term placental tissue, possess angiogenic and tissue regenerative properties. Participants were stratified based on peripheral artery disease status. A total of 159 individuals were randomly assigned to receive intramuscular PDA-002 at one of three doses (3 × 106, 10 × 106 and 30 × 106 cells) or a placebo. This Phase 2 multi-center, randomised, double-blind, placebo-controlled trial evaluated adults with chronic diabetic foot ulcers with and without peripheral artery disease. The primary efficacy endpoint was the proportion of participants achieving complete wound closure of the index ulcer within 3 months, with sustained closure maintained for an additional 4 weeks. PDA-002 was well-tolerated, with no treatment-related serious adverse events. Intramuscular PDA-002 treatment achieved the highest efficacy at the 3 × 106 cell dose within the peripheral artery disease subgroup (38.5% vs. 22.6% for placebo), meeting a stringent 4-week durability endpoint that surpassed the U.S. Food and Drug Administration's recommended 2-week sustainability criterion. PDA-002 shows promise as a breakthrough treatment for diabetic foot ulcers and peripheral artery disease, demonstrating efficacy with two intramuscular doses and no re-treatment.
Trial Registration: ClinicalTrials.gov identifier: NCT # 02264288
Social determinants of health (SDOH) factors are known to influence patient outcomes, but their effect on sepsis remains insufficiently studied. This research aims to investigate the relationship between SDOH factors and sepsis outcomes, highlighting opportunities to reduce health disparities and enhance patient care.
Retrospective study.
Level I trauma centre in Baton Rouge, Louisiana, USA.
Patients with sepsis aged 18–89 years. Patients discharged or transferred to hospice were excluded to prevent bias and misinterpretation of the findings.
Social Vulnerability Index (SVI), the Gini Index and the average distance to the nearest urgent care, emergency department and clinic.
In-hospital mortality, 30-day readmission and hospital length of stay (LOS).
2 tests, Mann-Whitney U tests and Cox regression.
Distance from urgent care is significantly associated with mortality (4.14 vs 3.24 miles, p
Mortality and LOS are closely linked to proximity to urgent care, while high SVI is notably associated with longer LOS. These findings highlight the significant impact of SDOH factors on sepsis outcomes and underscore the need for targeted interventions to address disparities in healthcare access and contextual health practices.
Opioid use disorder (OUD) is a chronic and severe psychiatric condition defined by a level of opioid use which significantly impairs interpersonal and social functioning. In the biopsychosocial model of addiction, research has shown that psychiatric, sociological and neurobiological factors individually affect OUD severity. However, how these factors interact in the determination of OUD severity remains poorly understood.
The Epigenetic Bonds of Opioid Use Profiles are a multidisciplinary project whose primary objective is to characterise psychiatric and social factors of OUD in a large cohort of patients. The secondary objectives are, first, to correlate psychosocial severity with blood-derived epigenetic biomarkers to provide a deeper understanding of determinants of OUD and, second, to examine over a 2 year follow-up the correlation between the evolution of OUD and psychosocial severity with epigenetic biomarkers at inclusion. An additional objective is to analyse the impact of drug consumption rooms on access to care for most severely affected patients with OUD. In total, 300 opioid users will be recruited at supervised injection sites in Strasbourg and Paris and at addiction care centres in Strasbourg and Lyon to explore four psychiatric (substance use disorders beyond opioids, depression, anxiety, post-traumatic stress disorder) and five social (social support and status, traumatic experiences, housing, imprisonment, access to care) factors. Opioid users will be followed for 24 months and reassessed for psychosocial factors at 3, 6, 12, 18 and 24 months. Opioid consumption will be measured in all subjects using questionnaires, complemented by toxicological screenings (mass spectrometry). Finally, DNA methylation and gene expression will be characterised in capillary blood using next-generation sequencing. Mixed models will be used to model the primary and secondary outcomes.
This ongoing study was approved by the French Ethics Committee ‘Sud Méditerranée III’ of University Hospital of Nîmes (approval 2023–2024, protocol IDRCB number 2022-A02477-36) and authorised by the French Data Protection Authority (authorisation decision DR-2023–277 in December 2023). Results will be presented in international and national conferences and published in peer-reviewed international journals.
by Tessy Luger, Felix Uhlemann, Florestan Wagenblast, Thomas Läubli, Barbara Munz, Manfred Schmolz, Monika A. Rieger, Benjamin Steinhilber
BackgroundWork-related musculoskeletal disorders (WMSDs) are prevalent in occupations characterised by high repetition and high force demands. Both factors not only evoke inflammatory and degenerative processes in affected musculoskeletal tissue, but also systemic responses identified by biomarkers in blood serum. Clarifying methodological aspects of biomarkers may provide insights into their predictive role in the pathway of developing WMSDs. This study will primarily assess reliability of systemic inflammatory biomarkers (CRP, TNF-α, IL-6, IL-1β) and immune cell reactivity by repeated measures in workers with constant workloads over time.
MethodsThis observational cross-sectional study will include two groups of workers: exposed group including workers exposed to higher upper-extremity physical workloads, especially affecting the elbow/forearm/hand-area; unexposed group, including office workers exposed to lower upper-extremity physical workloads. Recruited persons are screened against eligibility criteria followed by a medical anamnesis and blood analysis. Enrolled participants undergo nine repeated measurements once every two weeks, taking blood among others. Blood analyses will determine values of systemic inflammatory biomarkers and reactivity of immune cells. The absolute test-retest reliability of biomarkers and immune cell reactivity over time is assessed by the intra-class correlation coefficient applying two-way mixed-effects models. The relative test-retest reliability is assessed by the standard error of measurement.
DiscussionKnowledge of and models currently describing the pathological role of systemic inflammatory biomarkers are based on highly-controlled laboratory rat experiments. This study has the strength of assessing a human population under real-life conditions. The major challenge is in participant recruitment given the intensive and complex study design. The results of this study could provide fundamentals for initiating a cohort study and be used for developing work-related stress-recovery concepts for occupations with different physical demands to identify workers who may be at risk for developing WMSDs. German Clinical Trials Register (DRKS00031872, 25 May 2023).
by Francesco Colussi, Jacopo Favaro, Claudio Ancona, Edoardo Passarotto, Maria Federica Pelizza, Eleonora Lorenzon, Simone Ruzzante, Stefano Masiero, Giorgio Perilongo, Giovanni Sparacino, Irene Toldo, Stefano Sartori, Maria Rubega
Brain maturation from birth to adolescence involves profound transformations in neural dynamics, which can be studied in a minimally invasive manner using quantitative EEG. Most of the results published in the literature are based on spectral analysis approaches, which are extremely effective in detecting and assessing EEG rhythms. However, some aspects of EEG dynamics can only be investigated using nonlinear approaches, the use of which is still relatively unexplored in the pediatric population. The aim of the present paper is to assess the EEG differentiation of wakefulness from deep sleep (quiet sleep in neonates, stage N3 in older children) and its maturation across a wide developmental window (0–17 years) using the fractal dimension. Specifically, Higuchi fractal dimension (HFD) algorithm is used to analyse both wakefulness and sleep EEG recordings collected from 63 infants (aged 0-1 year) and 160 children (aged 2-17 years). To ensure methodological consistency, a data-driven criterion for the selection of HFD user parameters is implemented to enhance reproducibility. Our results show that HFD during wakefulness increases during the first year of life, followed by a stabilization or slight decrease in later years. In contrast, HFD during sleep exhibits a more stable profile, with only a mild increase over development. These findings are consistent with known neurodevelopmental processes—including synaptogenesis, pruning, and white matter maturation—and support the interpretation of HFD as a sensitive marker of large-scale integrative brain dynamics. These physiological trajectories of HFD both in wakefulness and sleep could be used as reference for future clinical applications in pediatric neurology and developmental monitoring.
by Jakob Morén, Barbro Persson, Anna Sörman, Åke Lundkvist, Hanin Shihab, Marie Studahl, Malin Veje, Göran Günther, Gabriel Westman
BackgroundTick-borne encephalitis is a viral infection of the central nervous system that may cause severe illness and long-term sequelae, to which underlying mechanisms are not completely understood. Autoantibodies against the N-methyl-D-aspartate receptor (anti-NMDAR) may be triggered by immunologic events, occur sporadically, and can cause autoimmune encephalitis. Following herpes simplex encephalitis and Japanese encephalitis, anti-NMDAR autoantibodies may develop and have been associated with relapse or impaired cognitive recovery. Tick-borne encephalitis has been shown to trigger anti-NMDAR encephalitis in sporadic cases, but the frequency of autoimmunization is unknown.
ObjectivesThe objective of this study was to assess the frequency of intrathecal anti-NMDAR antibody development following tick-borne encephalitis and to explore whether such antibodies could be relevant to cognitive complaints.
MethodsAdult patients with tick-borne encephalitis were included retrospectively from one cohort and prospectively from another. A stored post-acute cerebrospinal fluid sample was required for anti-NMDAR analysis. Two commercial kits (Euroimmun AG, Lübeck, Germany) were used to detect anti-NMDAR IgG antibodies in cerebrospinal fluid.
ResultsA total of 71 cerebrospinal fluid samples from 53 patients were analyzed for anti-NMDAR antibodies. Samples were obtained at a median of 91 days (range 21–471) after onset of central nervous system symptoms. Anti-NMDAR antibodies were detected in two samples from a single tick-borne encephalitis patient, corresponding to 1.9% of patients (95% CI: 0.05–10.1%).
ConclusionsThe development of intrathecal anti-NMDAR autoantibodies following tick-borne encephalitis is a rare event, and further studies are needed to clarify their potential relevance to cognitive outcomes in a minority of cases. Testing for anti-NMDAR antibodies in cerebrospinal fluid may be considered in patients who experience clinical deterioration following an initial recovery.
by Tom A. W. Schoufour, Linda Voogd, Kees L.M.C. Franken, Tom H.M. Ottenhoff, Ruud H.M. Wijdeven, Simone A. Joosten
Human leukocyte antigen E (HLA-E) communicates cellular health to natural killer (NK) cells through presentation of peptides derived from the leader sequence of classical major histocompatibility complex class I (MHC-I), inhibiting NK cell activation and lysis of healthy cells. Besides this canonical role, HLA-E can also present peptides from pathogens such as Mycobacterium tuberculosis (Mtb) to T cells and can inhibit phagocytosis by engaging with LILRB1/2. To identify additional HLA-E binding surface molecules, we utilized a CRISPR/Cas9 activation screen with HLA-E tetramers, which identified Stabilin (STAB)1 and STAB2 as novel interactors. This interaction depended on the nature of the peptide/HLA-E complex, whereby high affinity peptides did not permit the interaction while low affinity peptides did. Functionally, expression of STAB1 or STAB2 on THP-1 monocytes increased phagocytic uptake of HLA-E coated microbeads. These results provide the first evidence of an interaction between Stabilin receptors and specific HLA-E conformations.
by Mostafa Bondok, Moses Kasadhakawo, John Onyango, Oscar Turya, Khumbo Kalua
PurposeTo determine the prevalence and causes of blindness and vision impairment (VI) among adults aged ≥50 years in Western Uganda.
MethodsA population-based cross-sectional survey was conducted in Western Uganda (July-August 2023) using RAAB7. Adults aged ≥50 years who had resided in the study districts for at least six months in the past year were eligible. Participants were identified through door-to-door household visits using a two-stage cluster sampling approach. Primary outcomes include prevalence of blindness and VI and its causes. Secondary outcomes include cataract surgical coverage (CSC), effective CSC (eCSC), refractive error coverage (REC), and effective REC (eREC).
ResultsA total of 3,125 participants were examined (54.1% female). The adjusted prevalence of blindness (presenting visual acuity (PVA) Conclusion
Blindness and vision impairment remain major public health issues in Western Uganda, primarily due to untreated cataract and uncorrected refractive error. Poor post-operative outcomes highlight the urgent need to improve surgical quality. These findings may guide targeted interventions and policy to strengthen eye care services.
Targeted biologic therapies have transformed outcomes for individuals with psoriasis, a common immune-mediated inflammatory skin disease. The widespread use of these highly effective treatments has led to a growing number of individuals with clear or nearly clear skin remaining on continuous, long-term treatment. Personalised strategies to minimise drug exposure may sustain long-term disease control while reducing treatment burden, associated risks and healthcare costs. This study aims to evaluate the feasibility of a definitive pragmatic effectiveness trial of two personalised dose minimisation strategies compared with continuous treatment (standard care) in adults with well-controlled psoriasis receiving the exemplar biologic risankizumab.
This is a multicentre, assessor-blind, parallel group, open-label randomised controlled feasibility trial in the UK, evaluating two personalised biologic dose minimisation strategies for psoriasis. 90 adults with both physician-assessed and patient-assessed clear or nearly clear skin on risankizumab monotherapy for ≥12 months will be randomised in a 1:1:1 ratio to (1) patient-led ‘as-needed’ treatment, where risankizumab is administered at the first sign of self-assessed psoriasis recurrence, (2) therapeutic drug monitoring-guided treatment, with personalised dosing intervals determined using a pharmacokinetic model or (3) continuous treatment as per standard care, for 12 months. Participants will be invited to submit self-reported outcomes and self-taken photographs every 3 months using a bespoke remote monitoring system (mySkin app) and will attend an in-person assessment at 12 months. They may also request additional patient-initiated follow-up appointments during the trial if needed. The primary outcome is the practicality and acceptability of the two personalised biologic dose minimisation strategies, assessed as a composite measure including recruitment and retention rates, adherence to the assigned strategies and acceptability to both patients and clinicians. The feasibility of collecting healthcare cost and resource utilisation data will also be evaluated to inform a future cost-effectiveness analysis. A nested qualitative study, involving semistructured interviews with patients and clinicians, will explore perspectives on the personalised biologic dose minimisation strategies. These findings will inform the design of a future definitive trial.
This study received ethical approval from the Seasonal Research Ethics Committee (reference 24/LO/0089). Results will be disseminated through scientific conferences, peer-reviewed publications and patient/public engagement events. Lay summaries and infographics will be codeveloped with patient partners to ensure the findings are accessible for the wider public.
Smoking and vaping are especially prevalent among people with experience of psychosis (EoP), potentially increasing their toxicant exposure. Switching from tobacco smoking to vaping e-cigarettes reduces exposure to tobacco-related toxicants and likely associated diseases. We compared levels of nicotine and tobacco-related toxicant exposure among people with versus without EoP.
Cross-sectional study, secondary data analysis of Wave 5 (2018) of the Population Assessment of Tobacco and Health Study.
Data collection took place in the USA at the home of participants.
Data were from 5750 adults (aged >18 years) with and without EoP who smoked, vaped, did both or did neither. EoP was defined as ever being told by a health professional that you have schizophrenia, schizoaffective disorder, psychosis, a psychotic illness or psychotic episode.
Levels of urinary toxicants: nicotine metabolites, metals, volatile organic compounds (VOCs) and tobacco-specific nitrosamines (TSNAs) among people with and without EoP. Analyses were adjusted for demographics, cannabis use and past 30-day smoking/vaping status, and were repeated after stratifying by smoking /vaping status.
Of the 5750 participants, 6.3% (n=361) reported EoP, and 93.7% reported no EoP. Levels of nicotine and TSNA metabolites, cadmium, uranium and some VOCs were significantly higher among participants with EoP compared with those without. However, when smoking, vaping and cannabis use were taken into account, the associations of EoP with nicotine and TSNA metabolites, and most of the VOCs, were attenuated and no longer significant.
Participants with EoP are exposed to more nicotine and tobacco-related toxicants than those without EoP, likely largely due to the high prevalence of smoking, vaping and cannabis use among this population.
Nicotine vaping is common among children and youth, and even more so among those with mental health concerns. Identifying and managing nicotine vaping in child and youth mental health treatment settings is key to addressing this modifiable risk factor for poorer physical and mental health in young people. Recommendations exist for screening, assessment and treatment of youth vaping; however, it remains unclear whether current practices in child and youth mental health programmes align with recommended standards.
An explanatory sequential mixed methods design with three stages will be employed. In the first stage, a cross-sectional survey will be distributed to all eligible Canadian hospitals to identify practices in assessment and treatment of nicotine vaping within their child and youth mental health and addictions programmes. This survey will also assess barriers and facilitators for the uptake of the 2021 Canadian Paediatric Society recommendations on management of youth vaping. Semi-structured focus groups and interviews will be conducted in stage two, with clinicians, managers, youth and caregivers. Qualitative data will be analysed using a reflexive thematic approach. In stage three, findings and proposed behaviour change interventions will be reviewed at a knowledge mobilisation meeting with the goal of developing a national knowledge mobilisation plan to improve assessment and treatment of youth vaping in hospital-based mental health and addictions programmes.
This study has received ethics approval from the Research Ethics Board at the Children’s Hospital of Eastern Ontario (Protocol #25/19X). Participants will provide informed consent prior to participating. Results will be published in peer-reviewed journals and presented at scientific conferences. Summaries will be provided to the funders of the study and to participating hospitals.
The aim of the study was to evaluate the healthcare costs and effects of a remote person-centred care (PCC) add-on intervention compared with usual care for people with chronic heart failure (CHF) and/or chronic obstructive pulmonary Disease (COPD) from a societal perspective.
A cost-effectiveness analysis (CEA) based on the results from a randomised controlled trial.
The study was conducted from August 2017 until June 2021 within nine primary care centres across Western Sweden.
Participants in the study had a diagnosis of COPD (J43.0, J44.0–J44.9) and/or CHF (I50.0–I50.9).
224 patients were randomly allocated to the study groups. After two withdrawals, the final intention-to-treat analysis included 110 participants in the intervention group and 112 in the control group.
Both the intervention and control group received usual care through their primary care centres. In addition, the intervention group participated in a remote PCC add-on intervention consisting of a digital platform and structured telephone support.
Incremental cost-effectiveness ratio using direct healthcare costs, productivity loss and prescription drug costs, compared with health effects measured using the EuroQoL questionnaire (EQ-5D-3L) over a 2-year time horizon.
The intervention group had lower healthcare utilisation in inpatient care, specialised outpatient care and reduced productivity loss. The CEA showed incremental effects of 0.0469 quality-adjusted life years and incremental costs of SEK –68 533 (Swedish crowns). The PCC alternative was both more effective and resulted in lower healthcare costs compared with usual care, that is, PCC was dominant.
The results of this CEA demonstrated that a remote PCC add-on intervention for people with COPD and/or CHF had lower healthcare costs and higher health-related quality of life compared with usual care.
NCT03183817 ClinicalTrials.gov.
Frequent use of emergency departments (EDs) places a considerable burden on healthcare systems. Although frequent attenders are known to have complex physical, mental health and social needs, national-level evidence on their characteristics and patterns of attendance remains limited. This study aimed to provide a comprehensive, population-level description of frequent ED attendance in England, with a focus on age-based subgroups.
Retrospective cohort study.
EDs in England via the Hospital Episode Statistics and the Emergency Care Dataset data linked with primary care prescribing and mortality data, between March 2016 and March 2021.
The dataset received from National Health Service Digital contained approximately 150 million ED attendances by 30 million adult (>18 years) patients over the time period April 2016 to March 2021. A random sample of 5 million people was used for this analysis.
The primary outcome was the number of attendances in each financial year by frequent attenders compared with the remaining patients, split by age bands. Patients were classified as frequent attenders if they had ≥5 or ≥10 ED attendances within a rolling 12-month period. Secondary outcomes included demographic, diagnostic and prescribing characteristics, as well as the number of different ED sites visited.
A Gaussian mixture model was used to identify age-based subgroups. Descriptive statistics were used to summarise key features; 95% CIs were reported where applicable. Among 3.91 million unique adult ED attenders, there were 8.7 million attendances. Of these, 222 160 individuals (5.7%) had ≥5 attendances in a year, accounting for 12.6% of total attendances. A trimodal age distribution was identified, with three distinct peaks corresponding to ages 18–34, 35–64 and 65+. Frequent attenders were more likely to live in deprived areas and have a history of psychotropic or analgesic prescribing. Mental health diagnoses and polypharmacy were particularly common in the younger and middle-aged groups. Multisite attendance was uncommon, with over 80% of frequent attenders using only one ED site annually.
This national analysis reveals a trimodal age pattern among frequent ED attenders, with differing clinical and socio-demographic profiles across age groups. These findings highlight the need for age-tailored approaches to managing high-intensity ED use and inform targeted service development.
To describe the usage patterns of patients and healthcare professionals (HCPs) using a person-centred telehealth and e-health intervention.
An exploratory, descriptive, observational study embedded in the "Person-centred care at a distance (PROTECT)" randomised controlled trial (ClinicalTrials.gov: NCT03183817) as part of a process evaluation. Data on intervention use and time spent on the intervention were collected. Descriptive statistics were calculated.
Participants were recruited from nine public primary healthcare facilities located in various areas of Gothenburg, Sweden.
110 patients participating in the intervention group in the PROTECT trial were included. Participants were diagnosed with chronic heart failure (CHF, n=42), chronic obstructive pulmonary disease (COPD, n=56) or both (n=12). They were 33–93 years old (mean 71 years).
A secondary outcome report on resource use.
The 6-month-long intervention was performed as an add-on to standard care and comprised person-centred telephone support and access to a digital platform. Per-protocol use included co-creation of a health plan via the telephone and use of the digital platform at least once. Forms of use were tailored to the preferences and needs of the patients.
Most intervention activities took place in the first 3 months of the intervention. Most patients used a combination of phone and digital support, spending most of their time using the digital platform. Overall, patients and HCPs spent 6 and 2.5 hours/patient using the intervention, respectively. Of this time, 1.5 hours involved synchronous communication through phone calls, with health-plan calls averaging 77 min.
The intervention usage patterns of patients and HCPs differed. Despite HCPs being accessible when required, patients dedicated most of their time to self-care practices. Based on time distribution data, 15 full-time HCPs could potentially co-create, document and follow-up on health plans for 10 000 patients under study conditions.
ClinicalTrials.gov: NCT03183817.
To evaluate the associations between anthropometric indices and components of metabolic syndrome (MetS), including blood pressure, fasting blood sugar (FBS), triglycerides, high-density lipoprotein cholesterol and waist circumference (WC) in Iranian adults.
Cross-sectional analysis of baseline data from a population-based cohort.
Fasa adults’ cohort study, a rural community-based cohort in Fars province, Iran.
A total of 1550 adults aged 35–70 years with MetS, identified from among 10 118 cohort participants using the National Cholesterol Education Programme Adult Treatment Programme III criteria.
The anthropometric indices include abdominal volume index (AVI), a body shape index (ABSI), atherogenic index of plasma (AIP), body roundness index (BRI), body adiposity index (BAI), conicity index, ponderal index and visceral adiposity index (VAI).
Participants (56.1% female) with a mean age of 49.8±9.5 years. AVI was significantly associated with systolic blood pressure (SBP) (β=0.010, p
Anthropometric indices, including VAI, AIP, BAI, BRI and AVI, exhibit significant associations with key components of MetS in Iranian adults, particularly blood pressure, glycaemic markers and central adiposity. Among these, BAI showed the strongest correlation with MetS parameters, while ABSI displayed the weakest.
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