Stroke, Ahead of Print. BACKGROUND:Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is recommended for secondary prevention in patients with a minor stroke or transient ischemic attack. However, the effectiveness of DAPT can be significantly influenced by genetic variations. This study aimed to estimate the impact of multiple single-nucleotide polymorphisms across various genes on DAPT efficacy using polygenic risk score (PRS).METHODS:In this post hoc analysis, we included 2905 patients from the CHANCE trial (Clopidogrel in High-Risk Patients With Acute Nondisabling Cerebrovascular Events), which enrolled a total of 5170 patients in China between October 2009 and July 2012. The primary outcome was new stroke within 90 days. Sixteen single-nucleotide polymorphisms across 7 genes involved in clopidogrel metabolism were selected for PRS development. PRS were calculated by summing single-nucleotide polymorphisms from each individual. The Cox proportional-hazards regression model was utilized to estimate the hazard ratio (HR) and 95% CIs of PRS. The predictive value of PRS was estimated by C statistic and compared with a previously validated model.RESULTS:The elevated PRSs were associated with an increased risk of new stroke within 90 days (Ptrend=0.01). The efficacy of DAPT versus aspirin alone in preventing 1-year composite vascular events was significantly different between patients with low (adjusted HR, 0.47 [95% CI, 0.31–0.71]) and high PRSs (adjusted HR, 0.84 [95% CI, 0.60–1.18];Pinteraction=0.03). In patients receiving DAPT, higher PRSs were associated with increased risk of new stroke and composite vascular events at 90 days (adjusted HR per SD increase was 1.51 [95% CI, 1.15–1.99]) and at 1 year (adjusted HR per SD increase was 1.34 [95% CI, 1.08–1.67]). The C statistic for predicting 90-day new stroke using the PRS developed in this study was 0.57 (95% CI, 0.52–0.62), compared with 0.52 (95% CI, 0.48–0.55) for the ABCD-GENE score.CONCLUSIONS:Using PRS integrating multiple genes may enhance the precision of secondary prevention strategies for patients with minor stroke or transient ischemic attack in the short and long term.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT00979589.
Risultati per: Gestione dell’ansia, stress post-traumatico e dei disordini ossessivo-compulsivi
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Early tumour necrosis factor antagonist treatment prevents perianal fistula development in children with Crohns disease: post hoc analysis of the RISK study
Background
One in three children with Crohn’s disease develop perianal fistula complications (PFCs), among the most disturbing and difficult-to-treat disease-related complications. Retrospective evidence suggests PFCs may be preventable.
Objective
We aimed to determine if early antitumour necrosis factor-alpha (anti-TNF) therapy prevents PFC development in a well-characterised prospective cohort of paediatric patients with Crohn’s disease who were free from PFC at enrolment.
Design
RISK was a multicentre inception cohort of children newly diagnosed with Crohn’s disease. We included all patients who had never experienced PFCs 30 days after study enrolment. We conducted nearest-neighbour propensity score-matched triad analyses. Matching was performed to balance patient characteristics across three mutually exclusive treatment groups based on therapy prior to either PFC development or the end of the observation period.
Results
Among 873 patients without perianal fistula, 447 matched patients were included (149 per treatment group). The presence of non-penetrating perianal lesions (large skin tags, ulcers and/or fissures) was significantly associated with PFC development, with 4-fold greater odds of PFC (OR 4.08, 95% CI (95% CI) 1.70 to 9.78; p=0.0016). Early anti-TNF therapy was associated with an 82% decrease in the odds of PFC (OR 0.18, 95% CI 0.05 to 0.66; p=0.01). Among those with perianal lesions, anti-TNF therapy was associated with 94% reduced odds of PFC development (OR 0.055, 95% CI 0.006 to 0.50; p=0.010). No other treatment group was associated with reduced risk of PFC.
Conclusion
Early anti-TNF therapy prevents perianal fistula development, especially among patients at increased risk.
Le donne più a rischio ansia e depressione, ma gli studi ignorano il genere
Gli esperti, ‘anche i medici responsabili, colmare il divario’
Nurse retention in peri- and post-COVID-19 work environments: a scoping review of factors, strategies and interventions
Objectives
The COVID-19 pandemic highlighted the deterioration of nurses’ working conditions and a growing global nursing shortage. Little is known about the factors, strategies and interventions that could improve nurse retention in the peri- and post-COVID-19 period. An improved understanding of strategies that support and retain nurses will provide a foundation for developing informed approaches to sustaining the nursing workforce. The aim of this scoping review is to investigate and describe the (1) factors associated with nurse retention, (2) strategies to support nurse retention and (3) interventions that have been tested to support nurse retention, during and after the COVID-19 pandemic.
Design
Scoping review.
Data sources
This scoping review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Extension for Scoping Reviews. MEDLINE, Embase, CINAHL and Scopus databases were searched on 17 April 2024. The search was limited to a publication date of ‘2019 to present’.
Eligibility criteria
Qualitative, quantitative, mixed-methods and grey literature studies of nurses (Registered Nurse (RN), Licenced Practical Nurse (LPN), Registered Practical Nurse (RPN), Publlic Health Nurse (PHN), including factors, strategies and/or interventions to support nurse retention in the peri- and post-COVID-19 period in English (or translated into English), were included. Systematic reviews, scoping reviews and meta-syntheses were excluded, but their reference lists were hand-screened for suitable studies.
Data extraction and synthesis
The following data items were extracted: title, journal, authors, year of publication, country of publication, setting, population (n=), factors that mitigate intent to leave (or other retention measure), strategies to address nurse retention, interventions that address nurse retention, tools that measure retention/turnover intention, retention rates and/or scores. Data were evaluated for quality and synthesised qualitatively to map the current available evidence.
Results
Our search identified 130 studies for inclusion in the analysis. The majority measured some aspect of nurse retention. A number of factors were identified as impacting nurse retention including nurse demographics, safe staffing and work environments, psychological well-being and COVID-19-specific impacts. Nurse retention strategies included ensuring safe flexible staffing and quality work environments, enhancing organisational mental health and wellness supports, improved leadership and communication, more professional development and mentorship opportunities, and better compensation and incentives. Only nine interventions that address nurse retention were identified.
Conclusions
Given the importance of nurse retention for a variety of key outcomes, it is imperative that nursing leadership, healthcare organisations and governments work to develop and test interventions that address nurse retention.
Randomised controlled trial of LGBTQ-affirmative cognitive-behavioural therapy for sexual minority womens minority stress, mental health and hazardous drinking: Project EQuIP protocol
Introduction
Sexual minority women represent one of the highest-risk groups for hazardous drinking and comorbid mental health problems (eg, depression, anxiety). Research has identified cognitive (eg, expectations of rejection), affective (eg, emotion dysregulation) and behavioural (eg, avoidant coping) pathways through which minority stress (eg, stigma) places sexual minority women at disproportionate risk of hazardous drinking and comorbid depression/anxiety; yet no evidence-based interventions have been tested to address these pathways in this population. This article describes the design of Project EQuIP (Empowering Queer Identities in Psychotherapy), a randomised controlled trial of a transdiagnostic lesbian, gay, bisexual, transgender, queer (LGBTQ)-affirmative cognitive-behavioural therapy intervention (CBT) designed to improve minority stress coping and reduce sexual minority women’s hazardous drinking and mental health comorbidities.
Methods and analysis
This two-arm randomised controlled trial, funded by the National Institute on Alcohol Abuse and Alcoholism, has two objectives: (1) test the efficacy of 10 sessions of LGBTQ-affirmative CBT compared with 10 sessions of supportive counselling for sexual minority women in the community (anticipated n=450) who report hazardous alcohol use and meet criteria for a Diagnostic and Statistical Manual of Mental Disorders – 5 diagnosis of a depression or anxiety disorder and (2) examine psychosocial mechanisms and demographic factors as potential mediators and moderators, respectively, of the treatment-outcome relationship. This study’s primary outcome is change in the proportion of heavy drinking days. Secondary outcomes are changes in depressive and anxious symptoms.
Ethics and dissemination
The Yale University Human Subjects Committee reviewed and approved the research protocol. Results of this study will be disseminated to researchers and practitioners through peer-review publications and conference presentations, and directly to study participants.
Trial registration number
Registered on 17 August 2022 (ClinicalTrials.gov identifier: NCT05509166).
Brexpiprazole and Sertraline for Posttraumatic Stress Disorder
This parallel-design, double-blind, randomized clinical trial investigates if combination treatment with brexpiprazole and sertraline is efficacious, safe, and well tolerated in patients with posttraumatic stress disorder.
Linee guida per la gestione dei pazienti con sindromi coronariche acute
Clinical Severity and Outcomes in Large Infarcts With Endovascular Therapy: A Post Hoc Analysis of the ANGEL-ASPECT Trial
Stroke, Ahead of Print. BACKGROUND:Endovascular therapy (EVT) has been proven effective for patients with acute ischemic stroke with large infarcts. This study aimed to explore the impact of clinical severity on the efficacy of EVT in such patients.METHODS:This was a post hoc analysis of the ANGEL-ASPECT trial (Endovascular Therapy in Acute Anterior Circulation Large Vessel Occlusive Patients With a Large Infarct Core), a randomized controlled trial that enrolled patients from 46 centers across China between October 2, 2020, and May 18, 2022. These patients had large infarcts (defined as Alberta Stroke Program Early CT Score of 3–5 or infarct-core volume 70–100 mL) due to anterior-circulation large vessel occlusion within 24 hours after stroke onset with a National Institutes of Health Stroke Scale score of 6 to 30. Patients were randomized into either the EVT group or the medical management alone (MM) group. For this analysis, we categorized the patients into 2 subgroups: moderate stroke and severe stroke, based on a baseline National Institutes of Health Stroke Scale score of either
Regarding “Stool-Based Testing for Post-Polypectomy Colorectal Cancer Surveillance Safely Reduces Colonoscopies: The MOCCAS Study”
Contemporary European practice in left atrial appendage closure: results from a survey focusing on planning, techniques and post-implantation management
Objectives
The purpose of this European survey was to describe current preprocedural planning, procedure techniques and post-implantation management of left atrial appendage closure (LAAC).
Design
Prospective survey regarding current practice for LAAC between March and August 2023.
Setting
357 participating European LAAC centres in 14 countries.
Results
In 2022, the participating centres performed a total number of 9447 LAAC procedures, with a mean of 26 LAAC cases per centre (median 20; IQR 10–35). Preprocedure planning was performed with transoesophageal echocardiography (TOE) in 63% of centres, cardiac CT in 16%, or both in 21%. LAAC procedures were performed under general anaesthesia (59%), conscious sedation (36%) or with local anaesthesia only (5%). Device implantation was guided by conventional TOE (94%), intracardiac echocardiography (6%), miniaturised TOE probes (4%) or CT/fluoroscopy fusion (2%). The standard post-procedural antithrombotic regimen was dual antiplatelet therapy (73%), followed by single antiplatelet therapy (18%), conventional dose direct oral anticoagulant (DOAC) (7%) or half dose DOAC (1%), and no antithrombotic treatment (1%). There was a large heterogeneity between regions in terms of procedure volumes, hospital organisation, preprocedural planning, as well as procedural techniques and post-procedure management.
Conclusions
The present survey indicates that LAAC has become a widespread procedure in Europe. The findings highlight considerable heterogeneity among European countries in terms of preprocedural planning, procedural techniques including guidance and the post-procedural antithrombotic regimen. There is a need to evaluate the outcomes of different practices.
Psychological stress-induced local immune response to food antigens increases pain signaling across the gut in mice
We recently showed that a bacterial infection can break oral tolerance to food and lead to IgE-dependent mast cell activation and food-induced abdominal pain, which could constitute an important pathogenic mechanism in post-infectious irritable bowel syndrome (IBS). Here, we investigated whether similar immune mechanisms in response to psychological stress lead to food-evoked pain signaling, and thus potentially explain the pathophysiology in a larger group of patients with IBS.
[Articles] First-Episode Psychosis incidence pre-, during, and post-COVID-19 pandemic: a six-year natural quasi-experimental study in South London
FEP incidence in South London increased during the peak of the COVID-19 pandemic, particularly among Black and Asian individuals.
Cluster analysis of post-COVID-19 physical and mental health outcomes 3-6 months after SARS-CoV-2 infection: results of the French Prospective ALCOVID Cohort Study
Objectives
This study aims to characterise the diversity of post-COVID-19 physical and mental health outcomes, known as the post-COVID-19 condition (PCC), and the determining factors 3–6 months after acute SARS-CoV-2 infection.
Design
This is a prospective cohort study.
Setting
This study took place at the European Hospital of Marseille, France.
Participants
Participants include patients with acute COVID-19 treated as inpatients or outpatients.
Interventions
Interventions include face-to-face assessment of physical and mental health symptoms.
Main outcome measures
Main outcome measures include symptom scores and scales, as well as paraclinical elements (thoracic CT scan, pulmonary functional tests). Multiple component analysis was used to identify clinical phenotypic clusters of PCC patients, as well as their initial comorbidity groups. A multinomial regression model was used to evaluate the association between the initial comorbidities and disease severity with PCC phenotype.
Results
A total of 210 patients agreed to participate, of which 157 (75%) reported at least one symptom at the 3–6 months visit; mostly asthenia, dyspnoea, psychiatric disorders such as anxiety, depression, post-traumatic stress disorder and cognitive disorders. Four PCC clusters were recognised: (1) paucisymptomatic PCC (n=82, 39%); (2) physical sequelae PCC (n=39, 18.6%), (3) pre-existing pulmonary comorbidities PCC (n=29, 13.8%); and (4) functional somatic and/or mental symptoms PCC (n=60, 28.6%). In addition to their PCC symptoms, the patients in these clusters differed in terms of their demographic characteristics (sex), comorbidities and severity of COVID-19.
Conclusions
The four identified PCC clusters corresponded to distinct and coherent clinical and paraclinical entities, making it possible to consider adapted and personalised prognosis and therapeutic interventions.
Gestione farmacologica degli adulti con dislipidemia: linee guida
Effects of manual osteopathic interventions on psychometric and psychophysiological indicators of anxiety, depression and stress in adults: a systematic review and meta-analysis of randomised controlled trials
Objectives
To evaluate whether osteopathic and related manual interventions improve adult mental health (depression, anxiety, stress) and psychophysiological measures (eg, heart rate variability, skin conductance).
Design
Systematic review and meta-analysis of randomised controlled trials (RCTs).
Data sources
PubMed, MEDLINE (Ovid), Scopus, Cochrane, and AMED, searched through September 2024.
Eligibility criteria
English-language RCTs with ≥30 participants investigating osteopathic or related manual therapies (eg, myofascial release, high-velocity low-amplitude thrusts) delivered by qualified practitioners, compared with no treatment or sham, and reporting immediate postintervention mental health or psychophysiological outcomes.
Data extraction and synthesis
Full-text screening, risk-of-bias assessment and data extraction were conducted independently by multiple reviewers using a standardised Joanna Briggs Institute (JBI) Extraction Form. Risk of bias was assessed using the JBI Critical Appraisal Checklist. For meta-analyses, Hedges’ g (with 95% CIs) was calculated from postintervention means and SD. Random-effects models accounted for heterogeneity, and prediction intervals were calculated to assess uncertainty in effect estimates.
Results
20 RCTs were included. Osteopathic interventions reduced depression (Hedges’ g=–0.47, 95% CI: –0.86 to –0.09, p=0.02) and increased skin conductance (Hedges’ g=0.67, 95% CI: 0.00 to 1.34, p=0.05). Depression improvements were greater in pain populations (Hedges’ g=–0.61, 95% CI: –1.06 to –0.17, p=0.01). However, wide prediction intervals and moderate heterogeneity indicate uncertainty in true effect sizes, and limited studies and sample sizes restrict assessment of publication bias.
Conclusions
Osteopathic and related manual therapies may reduce depression and influence certain psychophysiological markers, particularly in pain populations, but uncertainty and heterogeneity limit confidence. More rigorous, larger, and longitudinal RCTs are needed.
Trial registration number
This meta-analysis was not formally registered, though the protocol and search strategy can be found at Open Science Framework, registration identification: https://osf.io/jrtpx/.
Interventions for the management of post-COVID-19 condition (long COVID): protocol for a living systematic review and network meta-analysis
Background
Up to 15% of survivors of COVID-19 infection experience long-term health effects, including fatigue, myalgia and impaired cognitive function, termed post-COVID-19 condition or long COVID. Several trials that study the benefits and harms of various interventions to manage long COVID have been published and hundreds more are planned or are ongoing. Trustworthy systematic reviews that clarify the benefits and harms of interventions are critical to promote evidence-based practice.
Objective
To create and maintain a living systematic review and network meta-analysis addressing the benefits and harms of pharmacologic and non-pharmacologic interventions for the treatment and management of long COVID.
Methods
Eligible trials will randomise adults with long COVID to pharmacologic or non-pharmacologic interventions, placebo, sham or usual care. We will identify eligible studies by searching MEDLINE, EMBASE, CINAHL, PsycINFO, AMED and CENTRAL from inception, without language restrictions.
Reviewers will work independently and in duplicate to screen search records, collect data from eligible trials, including trial and patient characteristics and outcomes of interest and assess risk of bias. Our outcomes of interest will include patient-reported fatigue, pain, postexertional malaise, changes in education or employment status, cognitive function, mental health, dyspnoea, quality of life, physical function, recovery and serious adverse events.
For each outcome, when possible, we will perform a frequentist random-effects network meta-analysis. When there are compelling reasons to suspect that certain interventions are only applicable or effective for a subtype of long COVID, we will perform separate network meta-analyses. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) approach will guide our assessment of the certainty of evidence.
We will update our living review biannually, on the publication of a seminal trial, or when new evidence emerges that may change clinical practice.
Conclusion
This living systematic review and network meta-analysis will provide comprehensive, trustworthy and up-to-date summaries of the evidence addressing the benefits and harms of interventions for the treatment and management of long COVID. We will make our findings available publicly and work with guideline-producing organisations to inform their recommendations.
Ethics and dissemination
The study describes the protocol for a systematic review that uses data from published trial reports. Therefore, the study is exempt from ethics review. We intend to deposit all data in a public repository and publish each iteration of the living review online.