Search Results for: Sorveglianza nella post polipectomia nel cancro al colon-retto

Background
Common genetic variation at 11q23.1 is associated with colorectal cancer (CRC) risk, exerting local expression quantitative trait locus (cis-eQTL) effects on POU2AF2, COLCA1 and POU2AF3 genes. However, complex linkage disequilibrium and correlated expression has hindered elucidation of the mechanisms by which genetic variants impart underlying CRC risk.

Objective
Undertake an interdisciplinary approach to understand how variation at 11q23.1 locus imparts CRC risk.

Design
We employ analysis of RNA sequencing, single-cell RNA sequencing, chromatin immunoprecipitation sequencing and single-cell ATAC sequencing data to identify, prioritise and characterise the genes that contribute to CRC risk. We further validate these findings using mouse models and demonstrate parallel effects in human colonic mucosa.

Results
We establish rs3087967 as a prime eQTL variant at 11q23.1, colocalising with CRC risk. Furthermore, rs3087967 influences expression of 21 distant genes, thereby acting as a trans-eQTL hub for a gene-set highly enriched for tuft cell markers. Epigenomic analysis implicates POU2AF2 as controlling the tuft cell-specific trans-genes, through POU2F3-correlated genomic regulation. Immunofluorescence confirms rs3087967 risk genotype (T) to be associated with a tuft cell deficit in the human colon. CRISPR-mediated deletion of the 11q23.1 risk locus genes in the mouse germline exacerbated the ApcMin/+ mouse phenotype on abrogation of Pou2af2 expression specifically.

Conclusion
We demonstrate that genotype at rs3087967 controls a portfolio of genes through misregulation of POU2AF2. POU2AF2 is the primary transcriptional activator of tuft cells with a tumour suppressive role in mouse models. We therefore implicate tuft cells as having a key tumour-protective role in the large bowel epithelium.

Background
Low-dose amitriptyline, a tricyclic antidepressant (TCA), was superior to placebo for irritable bowel syndrome (IBS) in the AmitripTyline at Low-dose ANd Titrated for Irritable bowel syndrome as Second-line treatment (ATLANTIS) trial.

Objective
To perform post hoc analyses of ATLANTIS for predictors of response to, and tolerability of, a TCA.

Design
ATLANTIS randomised 463 adults with IBS to amitriptyline (232) or placebo (231). We examined the effect of baseline demographic and disease-related patient characteristics on response to amitriptyline and the effect of amitriptyline on individual symptoms and side effects by subtype.

Results
There was a quantitative difference in amitriptyline effectiveness in those ≥50 years vs

Stroke, Ahead of Print. BACKGROUND:The prevalence of cerebral small vessel disease (CSVD) imaging markers is high, yet their influence on stroke prognosis remains unclear. This study aimed to estimate the effects of CSVD on the efficacy and safety of clopidogrel+aspirin versus aspirin among patients with minor stroke or high-risk transient ischemic attack.METHODS:This was a post hoc subgroup analysis of the INSPIRES trial (Intensive Statin and Antiplatelet Therapy for Acute High-Risk Intracranial or Extracranial Atherosclerosis), which was a double-blind, placebo-controlled, 2×2 factorial, and randomized clinical trial conducted at 222 centers in China from September 2018 to October 2022. Patients were classified into CSVD score 0 to 2 and CSVD score ≥3 groups based on a modified CSVD burden score without microbleeds. The primary efficacy and safety outcomes were stroke recurrence and moderate-to-severe bleeding risk within 90-day follow-up. We used Cox proportional hazards models to test the treatment-by-CSVD group interaction for stroke and bleeding risk.RESULTS:A total of 5126 patients (median age, 65 [57–71] years; 3915 [64.2%] males) were enrolled and 2131 (41.57%) had a modified CSVD score ≥3. Patients with CSVD score ≥3 had numerically higher stroke recurrence rate (9.10% versus 8.05%) and lower risk of moderate-to-severe bleeding (0.56% versus 0.80%) than those with CSVD score 0 to 2 within 90 days. Clopidogrel+aspirin versus aspirin reduced stroke recurrence to a similar relative degree in both CSVD score 0 to 2 (adjusted hazard ratio, 0.78 [95% CI, 0.61–1.01];P=0.06) and CSVD score ≥3 groups (adjusted hazard ratio, 0.82 [95% CI, 0.62–1.09];P=0.12) with no evidence of statistical interaction (P=0.84). Clopidogrel+aspirin versus aspirin increased bleeding risk to a similar relative degree in both CSVD score 0 to 2 (adjusted hazard ratio, 2.83 [95% CI, 1.52–5.27];P=0.03) and CSVD score ≥3 groups (adjusted hazard ratio, 2.13 [95% CI, 1.08–4.19];P=0.22) with no statistical interaction (P=0.68).CONCLUSIONS:In this post hoc subgroup analysis, no significant interaction effect was observed between the antiplatelet treatment and the modified CSVD score, suggesting that clopidogrel+aspirin may not provide a significantly different benefit-risk profile across patients with CSVD score 0 to 2 versus CSVD score ≥3.REGISTRATION:URL:https://www.clinicaltrials.gov; Unique identifier: NCT03635749.

Background
Immigrant women frequently encounter ethnic discrimination (ED) and/or stressful events in their daily lives. To mitigate the risk of resulting health impairments, we developed an ecological momentary music intervention (EMMI-T) to reduce psychological and biological stress levels in the daily lives of Turkish immigrant women. The feasibility of the EMMI-T was confirmed in a pilot study (n=20). Here, we present the protocol of our proposed study to investigate the effectiveness of the EMMI-T.

Methods
Fifty Turkish immigrant women perceiving chronic ED will take part in the 35-day study. During all three study periods (ie, baseline, intervention and post-intervention), participants will use a smartphone-based app to provide discrimination-related and stress-related data four times a day. Additionally, they will report every discriminatory and/or stressful event. During the intervention period, subsequently after such event-based data entries, participants will be allocated to either an intervention event (music listening for 10 or 20 min) or a control event (no music listening). Irrespective of event type, the app will signal 20 min after the initial event-based data entry for additional data collection. Every data entry will be accompanied by the collection of a saliva sample for analysis of biological stress markers (alpha-amylase, cortisol).

Analysis
This intraindividual randomised design will allow us to test immediate (ie, before vs after music listening) and intermediate (ie, baseline period vs postintervention period) effects of the EMMI-T on psychological and biological stress levels. To test our hypotheses, we will use multilevel modelling.

Ethics and dissemination
Positive ethical approval was given by the institutional review board of the University of Vienna (reference number 00575). The results of our study will be disseminated at conferences and submitted to a peer-reviewed journal.

Trial registration number
NCT05829031.

Background
Infectious agents such as SARS-CoV-2 require strategies to contain outbreaks, particularly in hospitals where the spread of infection is most likely. Biometric monitoring of heart rate, temperature, oxygen saturations and sleep might provide important early warning signs for SARS-CoV-2. This study aimed to determine whether a smart medical device (E4 wristband) and a pulse oximeter used to continuously measure heart rate, skin temperature and oxygen saturation would predict the onset of SARS-CoV-2 infection.

Methods
A single-centre, prospective observational cohort of 30 healthcare workers (HCWs) working in areas at high risk for exposure to SARS-CoV-2 were enrolled. HCWs were tested for SARS-CoV-2 using RT-qPCR of daily self-administered swabs for 30 days. Each participant was asked to wear an E4 wristband to measure changes in their heart rate, skin temperature and sleep throughout the study.

Results
Nine (30%) HCWs (median (range) age of 39 (27–57) years) tested positive for COVID-19. No significant differences were found in the pre-infection and post-infection variations in the heart rate (p=0.31) or skin temperature (p=0.44). Seven of the nine positive subjects reported symptoms at some point during the study period: unusual fatigue (40%), headache (33%) and runny nose (22%) were the most frequent. Analysis of daily trends in observations demonstrated significant fluctuations in biometric parameters.

Conclusion
These results suggest that wearable technology might be useful in documenting signs of SARS-CoV-2 infection in exposed HCWs.

Trial registration number
NCT04363489.

Objectives
To describe the post-marketing safety profile of respiratory syncytial virus prefusion F (RSVpreF) vaccine among pregnant individuals.

Design
This study analysed adverse event (AE) reports submitted to the U.S. Food and Drug Administration’s Vaccine Adverse Event Reporting System (VAERS) database following RSVpreF immunisation from 1 September 2023 to 23 February 2024.

Setting
VAERS, as a national spontaneous vaccine safety surveillance system, provides insights into the safety profile of the RSVpreF vaccine in a real-world setting.

Participants
Surveillance data included all AE reports submitted to VAERS in pregnant individuals following vaccination.

Exposure
Receipt of RSVpreF vaccine among pregnant individuals in the USA.

Primary and secondary outcome measures
Descriptive statistics were used to assess all AE reports with RSVpreF, including frequency, gestational age at vaccination, time to AE onset, reported outcomes and proportion of serious reports. Data mining techniques were employed to identify disproportionate reporting of RSVpreF-event pairs. Reports of preterm births were clinically reviewed.

Results
VAERS received 77 reports pertaining to RSVpreF vaccination in pregnant individuals, with 42 (54.55%) classified as serious. The most frequently reported non-pregnancy-specific AEs were headache, injection site erythema and injection site pain. For pregnancy-specific AEs, preterm birth was the most frequently reported (12.8%), followed by AE terms such as preterm premature rupture of membranes and caesarean section (each at 3.3%), and cervical dilatation, haemorrhage during pregnancy and uterine contractions during pregnancy (each at 1.4%). Our disproportionality analysis indicated signals for various AEs, particularly preterm birth, indicating that reports of preterm birth in conjunction with RSVpreF vaccination were observed more frequently than statistically expected. Most of the reported preterm births were moderate to late, occurring between 32 and less than 37 weeks of gestation. The median time from immunisation to the onset of preterm birth was 3 days, with two-thirds of cases reported within a week of vaccination.

Conclusions
The AEs reported to VAERS among pregnant individuals vaccinated with RSVpreF largely aligned with the safety profile observed in prelicensure studies; however, this analysis also highlights the previously observed safety signal for preterm birth. Active surveillance studies focusing on maternal and perinatal outcomes are needed to further evaluate this signal and guide future clinical recommendations.

Objectives
Research indicates the effectiveness of participatory interventions to address rapid rises in type 2 diabetes in low-income countries. Understanding their transferability to different contexts is a priority. We aimed to analyse how the COVID-19 post-lockdown context and adjustments to a participatory learning and action intervention affected theorised mechanisms of effect in rural Bangladesh and to examine the broader implications of this context and intervention adjustments for developing optimal contexts for participatory interventions.

Design
Mixed methods using longitudinal qualitative and quantitative observation data, focus group discussions and interviews with group and community members and project personnel. We used descriptive content analysis, guided by realist evaluation research questions about context, implementation and mechanisms. We used team reflection to enhance the rigour of our analysis.

Setting
Cluster-randomised trial in Alfadanga upazila, Faridpur district, in the central region of Bangladesh. The intervention was implemented between January 2020 and December 2022, during the COVID-19 pandemic.

Participants
Participatory group members, community members and project personnel (n=32). Structured observations of participatory groups (n=1820) and unstructured observations of groups and their environments (n=15).

Interventions
Participatory learning and action community groups of men and women implemented by community-based facilitators.

Results
Due to COVID-19, the participatory learning and action (PLA) intervention was not implemented as planned, which had major effects on the time available to develop the intervention with communities. Communities learnt about diabetes and were motivated to address its causes at an individual level, but community action was a more challenging mechanism to trigger. The post-pandemic context made it difficult to build community rapport, and strategies to engage communities through home visits were challenging. Communities’ prior negative experience in working together and in working with non-governmental organisations led to low community cohesion and low motivation to address diabetes collectively. This also resulted in expectations that the implementing organisation would implement community actions and incentivise attendance at meetings. This misalignment of expectations further disabled relationship building, and community strategies addressing the social causes of diabetes were largely not enacted.

Conclusion
PLA has optimal effects when time is available to build trust and social cohesion. These are contextual elements and mechanisms that need to be activated to enable critical reflection and community action to develop an enabling environment to address type 2 diabetes.

Trial registration number
ISRCTN42219712.

Introduction
A significant number of critically ill patients who survive their illness will experience new sequelae or a worsening of their baseline health status following their discharge from the hospital. These consequences may be physical, cognitive and/or psychological and have been labelled postintensive care syndrome (PICS). Prior research has demonstrated that spiritual care aligned with a specific creed during hospitalisation in the intensive care unit (ICU), as part of a comprehensive care plan, may be an effective strategy for preventing psychological sequelae in surviving critically ill patients. However, there is a gap in clinical literature regarding the effectiveness of generalist spiritual care in preventing psychological sequelae associated with PICS. This pilot study aims to explore the feasibility of implementing a generalist spiritual care strategy in the ICU and to evaluate its preliminary effectiveness in preventing anxiety and depression symptoms and post-traumatic stress disorder in critically ill patients.

Methods and analysis
This is a single-site, feasibility randomised controlled pilot trial of a generalist spiritual care intervention compared with the current standard of care. A total of 30 adults who are critically ill and have undergone invasive mechanical ventilation for a minimum of 72 hours without alterations in consciousness will be randomly assigned to either the spiritual care group or the usual care group at a ratio of 1:1. The primary outcome will be the feasibility and acceptability of the spiritual care strategy in critically ill patients. Secondary aims include evaluating the differences in anxiety and depression symptoms and post-traumatic stress disorder between the spiritual care group and the usual care control group at 3 months after ICU discharge. Subjects will be followed up until 3 months post-ICU discharge.

Ethics and dissemination
The Ethics Committee for Medical Sciences of Pontificia Universidad Católica de Chile (#220111005) and the Ethics Committee of Servicio de Salud Metropolitano Sur Oriente approved the study. Pontificia Universidad Católica de Chile funded the study (project number 105699/DPCC2021). The findings will be widely disseminated through peer-reviewed publications, academic conferences, local community-based presentations, partner organisations and the Chilean Intensive Care Society.

Trial registration number
NCT06048783.

Stroke, Ahead of Print. BACKGROUND:Chronic cerebellar lesions of presumed ischemic origin are frequently found in patients with ischemic stroke and as incidental findings. However, the differentiation of embolic lesions from lesions caused by cerebral small vessel disease (SVD) is unclear. We aimed to investigate whether the location of chronic cerebellar ischemic lesions (deep versus cortical) indicates the underlying cause (embolic versus SVD).METHODS:This study was a post hoc data analysis from the multinational ELAN trial (Early Versus Late Initiation of Direct Oral Anticoagulants in Patients With Postischemic Stroke With Atrial Fibrillation), which included patients with acute ischemic stroke and atrial fibrillation cohort between 2017 and 2022. For comparison, data from 2 cohorts (DiViNAS [Disease Variability in NOTCH3-Associated SVD] and VASCAMY [Vascular and Amyloid Predictors of Neurodegeneration and Cognitive Decline in Nondemented Subjects]) consisting of participants with hereditary cerebral SVD (ie, Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy) were analyzed (Cerebral Autosomal Dominant Arteriopathy With Subcortical Infarcts and Leukoencephalopathy cohort). Brain magnetic resonance imaging scans were evaluated for presence and location of chronic cerebellar ischemic lesions. The association between these lesions and the severity of supratentorial SVD was analyzed using univariable and multivariable models, adjusting for key covariables.RESULTS:In the atrial fibrillation cohort (N=790), 278 (35%) patients had chronic cerebellar ischemic lesions (cortical: n=242; deep: n=36). In multivariable analyses, features of cerebral SVD were associated with deep cerebellar ischemic lesions (summary SVD score; odds ratio per point, 2.5 [95% CI, 1.5–3.5];P

Objectives
To understand the help-seeking experiences of young people from culturally and linguistically diverse (CALD) backgrounds who have experienced suicidal thoughts and behaviours (STB).

Design
Qualitative study using semistructured interviews and reflexive thematic analysis.

Setting
A specialist, youth-focused Hospital Outreach Post-suicidal Engagement (HOPE) aftercare service delivered by Orygen in North-West Melbourne, Australia.

Participants
Eight young people aged 16–24 years (mean: 18.7±3.1 years, 50% female) from various CALD backgrounds who had been discharged from the HOPE aftercare service within the past 12 months.

Results
Four themes were identified: (1) cultural taboos and generational differences create challenges in communicating with family; (2) isolation is a barrier to reaching out; (3) it’s hard to disclose and discuss STB with clinicians and (4) not being taken seriously in clinical settings.

Conclusion
These findings highlight social, cultural and organisational barriers that shape the help-seeking journeys of young people from CALD backgrounds experiencing STB. Results suggest a need for culturally sensitive suicide prevention strategies, enhanced cultural competency in healthcare settings and efforts to improve mental health literacy within CALD communities.

Background
Over 6 million people have fled their homes in response to the full-scale invasion of Russian armed forces into Ukraine and are forcibly displaced since the start on 4 February 2022. Refugees, both adults and children, have a high risk of developing mental health disorders, in particular post-traumatic stress disorder, depression and anxiety disorders. Research into the mental health of Ukrainian families and their needs is urgently needed. The primary aim of this study is to increase our understanding of the consequences of potentially traumatic events for the mental health of parents and children. This may inform the development of mental health and psychosocial support interventions which can be readily implemented in the family context.

Methods and analysis
We will conduct a four-wave longitudinal online survey study among Ukrainian families displaced to the Netherlands. This study is a part of the Nadiya data collection, intended to assess the mental health responses of Ukrainian refugee families to the stress of war, forced migration, family separation and adaptation to new circumstances in their hosting country. Participants are assessed at four time points, approximately 6 months apart. Data collection for T1 started in May 2023. We aim to recruit a total of n=1500 participants at T1, of which n=1000 adults (18 years and older) and n=500 children (8–11 years) and teenagers (12–17 years). To investigate symptom profiles and associated risk and protective factors among parents and children, we will use latent class growth modelling.

Ethics and dissemination
The data collection procedure has been approved by the Ethical Committee of the Faculty of Social Sciences of Utrecht University. Data will be deposited, stored and shared using Utrecht University’s institutional research data repository Yoda. This research project is part of the Global Collaboration on Traumatic Stress; all authors are affiliated with this network. The findings will be published in peer-reviewed, open access journals and further disseminated through conference presentations, news updates at the project website and on the websites of the Dutch Society for Traumatic Stress Studies (www.ntvp.nl), and the European Society of Traumatic Stress Studies, as well as through media contributions.

Trial registration number
The current study was registered on 26 March 2024 on The Open Science Framework (OSF): https://doi.org/10.17605/OSF.IO/9FP7U.

Objective
To assess HIV testing and status disclosure rates and explore their associated predictors among young adolescents (10–17 years) who received health education through the Orphans and Vulnerable Children programme in Nimule, South Sudan.

Design
A pre–post evaluation study with data collected at baseline (December 2020) and at the endline (December 2022).

Setting
The study was conducted in Nimule, a densely populated periurban town characterised by high HIV prevalence and substantial cross-border movement between Uganda and South Sudan, making it a relevant setting for an HIV prevention project.

Intervention
The primary intervention was HIV risk education delivered through forty peer-led health clubs. Adolescents were screened for HIV risk factors and referred for HIV and other sexually transmitted infection testing at health facilities.

Participants
The study included young adolescents aged 10–17 years recruited from HIV-affected households within 17 neighbourhoods in Nimule periurban town. Informed consent was obtained from both caregivers and adolescents.

Primary and secondary outcome measures
The primary outcome was self-reported HIV testing and status disclosure. Binary logistic regression was used to assess the association between the study outcome variables and associated sociodemographic factors.

Results
A total of 557 (73.0%) of the 768 enrolled adolescents were surveyed at baseline and endline, including 301 (54.0%) females and 276 (46.0%) males. The median age was 14 years (IQR: 11–16) at baseline and 15 years (IQR: 12–17) at endline.
HIV testing increased from 315 (56.7%) at baseline to 557 (100%). The odds of undisclosed HIV status were 49% lower at endline adjusted OR (aOR) 0.51 (95% CI 0.92, 0.67; p

Stroke, Ahead of Print. BACKGROUND:rtPA (recombinant tissue-type plasminogen activator) and its variant, TNK (tenecteplase), are the currently approved thrombolytic drugs for the treatment of acute ischemic stroke, but they are ineffective in a proportion of patients due to rtPA resistance of platelet-rich thrombi. A novel thrombolytic, constitutively active caADAMTS13 (constitutively active a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) has been shown to improve experimental stroke outcomes where platelet-rich thrombi are present but have not been directly compared with rtPA or TNK.METHODS:We conducted a direct comparison of caADAMTS13 versus rtPA versus TNK versus vehicle control in the ferric chloride–mediated distal middle cerebral artery occlusion model in mice, which features platelet and VWF (von Willebrand Factor)–rich thrombi that reproduce rtPA-resistant occlusion. Treatments were administered intravenously 1 hour after ferric chloride application by bolus injection or bolus followed by infusion, as translationally applicable. Laser speckle contrast imaging measured early reperfusion over the hour following treatment, and magnetic resonance imaging measured cerebral blood flow and lesion volume at 24 hours.RESULTS:Reperfusion 1 hour after treatment was greatest in caADAMTS13-treated animals. Later cerebral blood flow, 24 hours post-treatment, within the stroke-affected hypoperfused area was higher in caADAMTS13 and rtPA but not TNK-treated mice. Functionally, this led to the absence of an initial behavioral deficit in caADAMTS13-treated mice, alongside a smaller lesion volume at 24 hours and reduced extent of bleeding.CONCLUSIONS:These findings demonstrate an overall suggestion that caADAMTS13 has improved thrombolytic efficacy, compared with current stroke treatments, against platelet-rich thrombi, for which there is currently an unmet clinical need.

In the Original Investigation titled “Opioid Prescribing and Outcomes in Patients With Sickle Cell Disease Post–2016 CDC Guideline,” published online on March 11, 2024, and in the May 2024 issue, the study sample was inaccurately described. In the original article, the included study participants were referred to as individuals with sickle cell disease who were at least 1 year of age, had no cancer diagnosis, and had pharmacy coverage for the month of measurement. However, the participants included in the study were those who met these criteria and had at least 1 health care encounter (inpatient or outpatient) in the month. All data were reanalyzed using the sample described in the published article (ie, patients with sickle cell disease, regardless of their health care visit history). Corrections were made to the Key Points, Abstract, Results, Discussion, Table 2, Figures 1 to 3, eTables 3 to 7, and eFigures 2 and 4 to 6 in Supplement 1. The overall sample size remained unchanged, but the mean (range) number of patients included in each month was corrected, which impacted 4 outcomes that used monthly sample size as the denominator. In addition, the statistical significance of 2 outcomes shifted: the monthly opioid prescription rate lost statistical significance, and the monthly rate of pain-related emergency department visits gained statistical significance. The interpretations and conclusions of the study were not affected. The article was corrected online.

To the Editor On behalf of my coauthors, I write to report an error in our Original Investigation, “Opioid Prescribing and Outcomes in Patients with Sickle Cell Disease Post–2016 CDC Guideline,” published online on March 11, 2024, and the May 2024 issue of JAMA Internal Medicine. In this cohort study of 14 979 individuals with sickle cell disease (SCD), we reported that our interrupted time series analysis found significant downward trends in opioid prescribing practices and significant upward trends in pain-related hospitalizations after the release of the 2016 Centers for Disease Control and Prevention (CDC) guideline for prescribing opioids for chronic pain.