Risultati per: Long COVID: principali risultati, meccanismi e raccomandazioni

Introduction
The HOLA study is a 12-month randomised, hybrid implementation-effectiveness, phase IV, double-arm, open-label, multicentric study including virologically suppressed people living with HIV (PWH). HOLA, which started in September 2023, evaluates acceptability, appropriateness, feasibility and satisfaction of out-of-hospital administration of cabotegravir and rilpivirine long-acting (CAB+RPV LA).

Methods
A total of 110 PWH who are already under treatment with CAB+RPV LA or switch their antiretroviral therapy to CAB+RPV LA will be recruited from two main hospitals in Barcelona (Germans Trias I Pujol and Vall d’Hebrón) and Costa del Sol Hospital, in Marbella. The patients will be randomised 1:1 into a hospital group (administration of CAB+RPV LA in the hospital) and the outpatient group (out-of-hospital administration), including community or primary care centres. The main objectives of the study are to compare the acceptability at month 12 of the administration of CAB+RPV LA in and out-of-hospital centres from the perspective of patients, and assess and compare the safety and tolerability of CAB+RPV LA. The study takes place at nine clinical units in Catalonia and Andalusia (three tertiary hospitals (recruiting centres), one community centre, one sexually transmitted infection clinic and four primary care centres).

Ethics and dissemination
The current publication refers to V.3.0 of the protocol, with issue date 14 April 2024, as approved by the Comité de Ética de la Investigación con medicamentos del Hospital Universitari Germans Trias i Pujol (approval number AC-23-042-HGT-CEIM). The clinical trial will be conducted according to the principles of the Declaration of Helsinki, Fortaleza, Brazil, October 2013. This study will be conducted according to Spanish regulations regarding clinical trials (Royal Decree 1090/2015) and biomedical investigations (Organic Law 14/2007 of biomedical investigation and the Royal Decree 1716/2011), and the Clinical Trial Regulation (Regulation EU No 536/2014). Confidentiality requirements will follow the required Data Protection legislation. Enrolment completion in the study is expected by the end of May 2024, with an end of study expected in May 2025. Results emerging from this study will be reported in HIV national and international meetings as well as published in international journals with a high impact factor. If the outcome is deemed positive, we will also develop and propose policy guidelines for the integration of the administration of CAB+RPV LA in alternative outpatient facilities into the standard of care in the HIV care pathway.

Trial registration number
NCT06185452/EUCT number: 2023-503963-41-00.

Participants who completed the program maintained blood pressure control 42 months after enrollment.

Objectives
In this study, we evaluate the long-term effects (±1.5 years postintervention) of 6-year exposure to the Lekker Fit! intervention on physical fitness and physical activity (PA).

Design
The retrospective intervention evaluation is embedded within the Generation R Study in Rotterdam, the Netherlands, a population-based prospective birth cohort study.

Setting
Measurements took place in the research centre of the Generation R cohort study.

Participants
5489 adolescents from the Generation R Study were eligible for inclusion within this study. Successful linking to school career data was possible for 4129 adolescents who were then retrospectively subdivided into a Lekker Fit! group, mixed group and regular school group based on their primary school career.

Interventions
The Lekker Fit! intervention is a multicomponent primary school-based intervention for the prevention of overweight. It focuses on a healthy diet and healthy lifestyle rather than focusing directly on the reduction of overweight. The intervention targets individual behaviour of children as well as their obesogenic environment and parental engagement in shaping their children’s behaviour.

Primary and secondary outcome measures
Aged 13/14 years old, physical fitness was measured with an incremental ergometer test. The actual highest achieved work rate was divided by the expected highest achieved work rate (age- and sex-related Dutch population-based reference data), and converted into z-scores. PA was determined by the number of days with at least 1 hour of PA, obtained by a self-reported questionnaire. Propensity score matching was performed to correct for non-random selection bias. Linear regression analyses were performed to estimate intervention effects.

Results
Children from the Lekker Fit! group had significantly lower fitness z-scores (–0.18 (95% CI –0.29 to –0.06), n=1826) compared with children from the matched regular school group. No Lekker Fit! intervention effect was found on PA (–0.12 (95% CI –0.36 to 0.12), n=1258).

Conclusions
No evidence was found for long-term favourable effects of a school-based multicomponent intervention on physical fitness and PA. Recommendations for policy and future research are discussed.

Objectives
To explore trial participants’ experience of long-term catheters (LTC), the acceptability of washout policies, their experience of the CATHETER II trial (a randomised controlled trial comparing the clinical effectiveness of various washout policies versus no washout policy in preventing catheter associated complications in adults living with long-term catheters) and their satisfaction with the outcomes. The objectives of the healthcare professionals (HCPs) focus group and interview were to explore their attitudes towards weekly prophylactic catheter washout, views on the provision of training and participants’ ability to enact washout behaviours.

Methodology
A longitudinal qualitative study embedded within the CATHETER II randomised controlled trial, which included semi-structured interviews and focus groups with participants from multiple trial sites. Data were analysed using the Theoretical Framework of Acceptability and Theoretical Domains Framework. This UK community-based study included 50 (24 female, 26 male) CATHETER II trial participants, aged between 23 and 100 years, with LTC and able to self-manage the washout and study documentation either independently or with the help of a carer. Seven HCPs (five female, two male) also participated.

Results
The participants had positive attitudes towards weekly prophylactic saline or acidic catheter washouts and other trial elements, such as washout training, catheter calendar and monthly phone calls. Participants and HCPs found the ‘ask’ of the CATHETER II trial and the weekly self-administered prophylactic washout policies to be feasible. The participants reported that the catheter washout training provided during the trial enhanced their self-efficacy, skills and self-reported capability to carry out the washouts. Participants reported having positive outcomes from the weekly washout. These included reduced blockage, pain or infection, reduced need for HCP support and greater psychological reassurance. HCPs attested to the participants’ understanding of and adherence to the weekly washouts and other elements of the trial.

Conclusions
This study shows acceptability, feasibility and self-reported fidelity of the CATHETER II trial on a behavioural level. Self-management for prophylactic catheter washouts is both feasible and, following training, achievable without any need for additional support.

Trial registration number
ISRCTN17116445.

Circulation, Ahead of Print. BACKGROUND:Despite reported racial disparities between Black and White adults in short-term outcomes after abdominal aortic aneurysmal intervention, there is a paucity of literature aimed at understanding long-term disparities. The present study aims to characterize racial disparities in long-term outcomes, perioperative outcomes, and health care use after endovascular aortic aneurysm repair.METHODS:We conducted a retrospective cohort study from 2011 to 2019 with outcome assessment through 2020. Using a 100% sample of national Medicare data, we identified beneficiaries ≥66 years of age who underwent intact infrarenal endovascular aortic aneurysm repair. The primary outcome was a composite of endovascular or open aortic reintervention, late aneurysm rupture, and all-cause mortality. Secondary outcomes included other reinterventions, perioperative outcomes, and annual rates of health care use.RESULTS:A cohort of 107 636 Black (3.9%) and White (96.1%) beneficiaries was identified. The cumulative incidence of the primary outcome was 72.9% (95% CI, 71.8%–73.9%) in White patients versus 80.0% (95% CI, 76.4–83.0) in Black patients (P

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.

Lo studioso di pandemie: “nuovo avvertimento con il virus H5N1”

Circulation, Ahead of Print. BACKGROUND:Shared genetic and lifestyle risk factors may underlie the development of both coronary artery disease (CAD) and dementia. We examined whether an increased genetic risk for CAD is associated with long-term risk of developing all-cause, Alzheimer’s, or vascular dementia, and investigated whether differences in potentially modifiable lifestyle factors in the mid- to late-life period may attenuate this risk.METHODS:A prospective cohort study of 365 782 participants free from dementia for at least 5 years after baseline assessment was conducted within the UK Biobank cohort. Genetic risk was assessed using a genomewide polygenic risk score (PRS) for CAD and lifestyle risk using a modified version of the American Heart Association’s Life’s Essential 8 Lifestyle Risk Score (LRS). Higher values for both scores were deemed to represent increased risk. Primary outcomes were incident all-cause, Alzheimer’s, and vascular dementia diagnoses obtained from electronic health records. Secondary outcomes were neuroimaging phenotypes measured in 32 028 participants recalled for magnetic resonance imaging. Sensitivity analyses were conducted to test the extent by which biological and behavioral risk factors contributed to observed associations.RESULTS:A total of 8870 cases of all-cause dementia were observed over a median 13.9-year follow-up. Both genetic (PRS) and lifestyle (LRS) risk scores for CAD were associated with a modestly elevated risk of all-cause dementia (subhazard ratio per SD increase, 1.10 [1.08, 1.12],P

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.

Objectives
This study aims to provide an in-depth analysis of the symptoms, coexisting conditions and service utilisation among people with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) and long COVID. The major research questions include the clustering of symptoms, the relationship between key factors and diagnosis time, and the perceived impact of National Institute for Health and Care Excellence (NICE) guidelines on patient care.

Design
Cross-sectional survey using secondary data analysis.

Setting
Community-based primary care level across the UK, incorporating online survey participation.

Participants
A total of 10 458 individuals responded to the survey, of which 8804 confirmed that they or a close friend/family member had ME/CFS or long COVID. The majority of respondents were female (83.4%), with participants from diverse regions of the UK.

Primary and secondary outcome measures
Primary outcomes included prevalence and clustering of symptoms, time to diagnosis, and participant satisfaction with National Health Service (NHS) care, while secondary outcomes focused on symptom management strategies and the perceived effect of NICE guidelines.

Results
Fatigue (88.2%), postexertional malaise (78.2%), cognitive dysfunction (88.4%), pain (87.6%) and sleep disturbances (88.2%) were the most commonly reported symptoms among participants with ME/CFS, with similar patterns observed in long COVID. Time to diagnosis for ME/CFS ranged widely, with 22.1% diagnosed within 1–2 years of symptom onset and 12.9% taking more than 10 years. Despite updated NICE guidelines, only 10.1% of participants reported a positive impact on care, and satisfaction with NHS services remained low (6.9% for ME/CFS and 14.4% for long COVID).

Conclusions
ME/CFS and long COVID share overlapping but distinct symptom clusters, indicating common challenges in management. The findings highlight significant delays in diagnosis and low satisfaction with specialist services, suggesting a need for improved self-management resources and better-coordinated care across the NHS.

Objectives
To explore the association between smoking status (current vs former), changes in smoking habits (among current smokers only) and negative changes in dietary and physical activity habits during the initial COVID-19 lockdown in Israel.

Design
A secondary analysis of an online cross-sectional study (6 April 2020 to 28 April 2020). Dependent variables included deteriorations in dietary habits score and odds of reporting worsening of physical activity habits during the first COVID-19 lockdown. The study analysed the association between these variables and ‘smoking status’ (current vs former) and, within smokers, changes in smoking habits, using multivariate logistic and linear regression models. For changes in physical activity habits, there was a significant interaction with baseline physical activity levels (p=0.04), therefore, analysis was stratified accordingly.

Setting
Online data collection.

Participants
660 participants, current or former smokers in Israel, Hebrew speakers and ≥18 years old.

Primary outcomes
Self-reported negative changes in dietary habits and physical activity during the first COVID-19 lockdown.

Results
The sample (n=660) included 66.2% (n=437) current smokers and 33.8% (n=223) former smokers. Among current smokers, 43.5% (n=190) indicated an increase in their smoking habits. Of all respondents, 25% (n=170) reported a negative dietary change and 48% (n=192) spent less time engaging in physical activity, with 66% (n=437) reporting increased levels of stress. No significant association was found between smoking status and the dietary habits score in the multivariate linear regression (B=–0.046, CI –0.493 to 0.401, reference group: former smokers). This indicates that being a current smoker was associated with a non-significant 0.046 point decrease in the dietary habits score compared with former smokers. Similarly, no significant association was found between smoking status and odds of reporting worsening of physical activity, even after stratifying by baseline physical activity levels. Among participants who currently smoke, no significant association was found between changes in smoking habits and the dietary habits score (B=0.391, 95% CI –0.061 to 0.843, p=0.090, reference group: those who smoke the same or less) or with odds of reporting worsening of physical activity (OR=1.16, 95% CI 0.688 to 1.956, p=0.577, reference group: those who smoke the same or less).

Conclusion
Among current and former smokers, high rates of negative health habit changes were found, emphasising the need for interventions during future crises. Smoking status and/or changes in smoking habits among current smokers were not associated with negative changes in dietary and physical activity habits.

Objectives
To assess the prevalence of SARS-CoV-2 antibodies in the residents of Kibera informal settlement in Nairobi, Kenya, before vaccination became widespread, and explore demographic and health-related risk factors for infection.

Design
A cross-sectional study.

Setting
Kibera informal settlement, Nairobi, Kenya.

Participants
Residents of Kibera informal settlement between October 2019 and August 2021, age 1 year and above who reported no current symptoms of COVID-19.

Main outcome measures
Associations were determined between SARS-CoV-2 positive tests measured with one rapid test and two ELISAs and demographic and health-related factors, using Pearson’s 2 test. Crude OR and adjusted OR were calculated to quantify the strength of associations between variables and seropositive status.

Results
A total of 438 participants were recruited. Most (79.2%) were age 18–50 years; females (64.2%) exceeded males. More than one-third (39.1%) were unemployed; only 7.4% were in formal, full-time employment. Less than one-quarter (22.1%) self-reported any underlying health conditions. Nearly two-thirds (64.2%) reported symptoms compatible with COVID-19 in the previous 16 months; only one (0.23%) had been hospitalised with a reported negative COVID-19 test. 370 (84.5%) participants tested positive in any of the three tests. There was no significant difference in SARS-CoV-2 seropositivity across age, sex, presence of underlying health conditions, on medication or those ever tested for SARS-CoV-2. Multiple logistic regression analysis showed that COVID-19 symptoms in the previous 16 months were the only significant independent predictor of seropositivity (p=0.0085).

Conclusion
High SARS-CoV-2 exposure with limited morbidity was found in the residents of Kibera informal settlement. The study confirms other reports of high SARS-CoV-2 exposure with limited morbidity in slum communities. Reasons cited include the high infectious disease burden on the African continent, demographic age structure and underreporting due to limited testing and lack of access to healthcare services; genetic factors may also play a role. These factors require further investigation.

Stroke, Ahead of Print. BACKGROUND:The VIPS (Vascular Effects of Infection in Pediatric Stroke) II prospective cohort study aimed to better understand published findings that common acute infections, particularly respiratory viruses, can trigger childhood arterial ischemic stroke (AIS). The COVID-19 pandemic developed midway through enrollment, creating an opportunity to assess its impact.METHODS:Twenty-two sites (North America, Australia) prospectively enrolled 205 children (aged 28 days to 18 years) with AIS from December 2016 to January 2022, including 100 cases during the COVID-19 pandemic epoch, defined here as January 2020 to January 2022. To assess background rates of subclinical infection, we enrolled 100 stroke-free well children, including 39 during the pandemic. We measured serum SARS-CoV-2 nucleocapsid total antibodies (present after infection, not vaccination; half-life of 3–6 months). We assessed clinical infection via parental interview.RESULTS:The monthly rate of eligible AIS cases declined from spring through fall 2020, recovering in early 2021 and peaking in the spring. The prepandemic and pandemic cases were similar except pandemic cases had fewer clinical infections in the prior month (17% versus 30%;P=0.02) and more focal cerebral arteriopathy (20% versus 11%;P=0.09). Among pandemic cases, 26 of 100 (26%) had positive antibodies, versus 4 of 39 (10%) of pandemic-era well children (P=0.04). The first SARS-CoV-2 positive case occurred in July 2020. Ten of the 26 (38%) positive cases had a recent infection by parental report, and 7 of those 10 had received a diagnosis of COVID-19. Only 1 had multisystem inflammatory syndrome in children. Median (interquartile range) nucleocapsid IgG total levels were 50.1 S/CO (specimen to calibrator absorbance ratio; 26.9–95.3) in the positive cases and 18.8 (12.0–101) in the positive well children (P=0.33).CONCLUSIONS:The COVID-19 pandemic may have had dual effects on childhood AIS: an indirect protective effect related to public health measures reducing infectious exposure in general, and a deleterious effect as COVID-19 emerged as another respiratory virus that can trigger childhood AIS.

In a phase 2 manufacturer-funded trial, lepodisiran safely reduced Lp(a) levels in a dose-dependent manner.

Annals of Internal Medicine, Ahead of Print.

This cohort study examines the safety and efficacy of rituximab for patients with pempigus foliaceus.