Search Results for: GPG: Versione 5.7.5 (Novembre 2021)

This cross-sectional study investigates trends in outpatient psychotherapy use among US adults from 2018 to 2021.

This cross-sectional study examines prescription claims for contraceptives and medications for opioid use disorder among commercially insured women in the US from 2016 to 2021.

Objectives
To examine the prevalence and days of long-term sickness absence (LTSA) by occupational class and by most important diagnostic groups in Finland during 2011–2021.

Design
Population-based cross-sectional study.

Setting and participants
National comprehensive register data were linked for all employed persons and entrepreneurs in Finland aged 25–64 for years 2011–2021 (yearly number of individuals in the study population around 2 million persons).

Main outcome measures
LTSA was measured by sickness allowance that covers over 10-day long absences. Yearly age-standardised LTSA prevalences and average number of LTSA days were calculated for women and men in four occupational classes, separately for all-cause LTSA and LTSA due to mental disorders, musculoskeletal diseases and injuries. Modified Poisson regression and negative binomial regression models were run to assess relative differences between occupational classes, adjusted for age, marital status, education and region of residence.

Results
All-cause LTSA slightly decreased between years 2011 and 2021, but the trends varied by occupational class and diagnostic group. LTSA due to mental disorders increased in all occupational classes after 2016 among both sexes, while LTSA due to musculoskeletal diseases and injuries continued to decrease in all occupational classes. The increase in LTSA due to mental disorders was largest among lower non-manual employees, especially among women, whereby all-cause LTSA prevalence among female lower non-manual employees reached the level of female manual workers. Men showed broadly similar trends, but manual workers still had the highest all-cause LTSA prevalence at the end of the study period. The main results were similar adjusted for covariates.

Conclusions
The magnitude and order of the occupational-class differences in LTSA changed between 2011 and 2021, along with increasing LTSA due to mental disorders, especially among employees, and decreasing LTSA due to somatic diagnoses, especially among manual workers. Occupational-class differences should be taken into account when aiming to prevent LTSA and especially further increases in LTSA due to mental disorders.

Circulation, Ahead of Print. Aim:The “2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes” incorporates new evidence since the “2013 ACCF/AHA Guideline for the Management of ST-Elevation Myocardial Infarction” and the corresponding “2014 AHA/ACC Guideline for the Management of Patients With Non–ST-Elevation Acute Coronary Syndromes” and the “2015 ACC/AHA/SCAI Focused Update on Primary Percutaneous Coronary Intervention for Patients With ST-Elevation Myocardial Infarction.” The “2025 ACC/AHA/ACEP/NAEMSP/SCAI Guideline for the Management of Patients With Acute Coronary Syndromes” and the “2021 ACC/AHA/SCAI Guideline for Coronary Artery Revascularization” retire and replace, respectively, the “2016 ACC/AHA Guideline Focused Update on Duration of Dual Antiplatelet Therapy in Patients With Coronary Artery Disease.”Methods:A comprehensive literature search was conducted from July 2023 to April 2024. Clinical studies, systematic reviews and meta-analyses, and other evidence conducted on human participants were identified that were published in English from MEDLINE (through PubMed), EMBASE, the Cochrane Library, Agency for Healthcare Research and Quality, and other selected databases relevant to this guideline.Structure:Many recommendations from previously published guidelines have been updated with new evidence, and new recommendations have been created when supported by published data.

Objective
This study aimed to assess the length of hospital stay after caesarean delivery and the associated factors from 15 March to 15 May 2021.

Design
We conducted an institution-based, cross-sectional study.

Setting
The study was conducted at a government hospital in Northeast Ethiopia.

Participants
The study was conducted among 405 mothers who delivered by caesarean section. All mothers who delivered by caesarean section at the hospital during the study period and who consented to participate were included in the study.

Primary and secondary outcome
The primary outcome of this study was length of hospital stay following caesarean section delivery. The secondary outcomes were factors associated with length of hospital stay.

Results
The overall mean length of hospital stay after caesarean delivery was 2.81 (±1.72) days. Gestational age at birth less than 38 weeks (B=0.547), being hypertensive (B=1.235) and having postoperative complications (B=0.909) were significantly associated with length of hospital stay following caesarean delivery at a 0.05 level of significance.

Conclusion
In this study, the mean length of hospital stay following caesarean delivery was 2.8 days. Women with hypertension, gestational age at birth less than 38 weeks and postoperative complications have prolonged length of hospital stay. Healthcare professionals should identify those mothers at risk of prolonged length of hospital stay following caesarean delivery and implement preventive strategies to reduce the clinical as well as economic burden posed by prolonged length of hospital stay. Moreover, researchers should conduct further multicentre longitudinal follow-up studies.

Introduction
The diversity of participating investigators representing diverse disciplines, career stages, stakeholder groups, regions and types of institutions is essential for the success of large-scale research programmes. In 2021, the National Institutes of Health introduced a requirement for some of its large grants to include a separate section that describes the project’s plan for enhancing diverse perspectives (PEDPs). Our project aims to develop consensus-based PEDP evaluation metrics and instruments that can be systematically and sustainably collected across the projects.

Methods and analysis
Evaluation work is organised into three objectives. First, shared knowledge about PEDP infrastructures, activities and outcomes will be elicited through the review of the PEDP texts of funded projects, with 15 as the target sample size. Data will be analysed using a cultural domain analysis approach and assessed for recurrence and salience of PEDP metrics. Second, consensus-based evaluation metrics will be developed using a three-round Delphi method. The descriptive statistics (mean, SD and IQR) and cultural consensus analyses will be applied to the first and last rounds of the Delphi survey. Third, metrics will be piloted for implementation and validation within one of the Human BioMolecular Atlas Programme sites. Work will be completed by Fall 2025.

Ethics and dissemination
The long-term goal of the effort reported in this paper is to develop PEDP common metrics that are generalisable and feasible across diverse projects. This rigorous, focused evaluation development effort aims to inform scientific practices and policies around implementing the plans to enhance diverse perspectives.

Objectives
The postdischarge period is crucial for vulnerable newborns at risk of morbidity, readmission and mortality in low- and middle-income countries (LMICs). Addressing gaps in care during this period could improve outcomes. This review consolidates evidence on caregiver information needs and relevant information tools used in postdischarge care for vulnerable newborns in LMICs.

Design
Scoping review using the methodological framework developed by Arksey and O’Malley.

Data sources
We searched six databases for relevant articles published in English between 2001 and 2021. Additional articles were identified through citation and reference checking.

Eligibility criteria
Articles on postdischarge care for newborns in LMICs, excluding economic and technical development studies, discharge to other healthcare facilities (rather than to home) and maternal-focused studies.

Data extraction and synthesis
Data extraction followed Arksey and O’Malley’s data charting method. Using a descriptive synthesis approach, heterogeneous data were collated in narrative format.

Results
From 5190 articles, 22 were included. Only a small number of articles discussed caregiver challenges, like receiving insufficient information at discharge which led to uncertainty in caring for vulnerable newborns. Caregivers had a number of needs in relation to maternal and newborn care, including in terms of coordination of follow-up care. Although a number of tools have been used to support relevant needs (for postnatal care in general rather than specifically for postdischarge care of vulnerable newborns), these have shown mixed effectiveness due to challenges with completeness, lack of training and support, supply chain issues and cultural barriers to adoption, such as preference for alternative providers.

Conclusion
Our understanding of postdischarge information needs for those looking after vulnerable newborns in LMICs remains limited. More effective use of information tools could help address some of these needs and contribute towards reducing neonatal mortality rates.

Introduction
Cognitive–behavioural therapy (CBT) works—but not equally well for all patients. Less than 50% of patients with internalising disorders achieve clinically meaningful improvement, with negative consequences for patients and healthcare systems. The research unit (RU) 5187 seeks to improve this situation by an in-depth investigation of the phenomenon of treatment non-response (TNR) to CBT. We aim to identify bio-behavioural signatures associated with TNR, develop predictive models applicable to individual patients and enhance the utility of predictive analytics by collecting a naturalistic cohort with high ecological validity for the outpatient sector.

Methods and analysis
The RU is composed of nine subprojects (SPs), spanning from clinical, machine learning and neuroimaging science and service projects to particular research questions on psychological, electrophysiological/autonomic, digital and neural signatures of TNR. The clinical study SP 1 comprises a four-centre, prospective-longitudinal observational trial where we recruit a cohort of 585 patients with a wide range of internalising disorders (specific phobia, social anxiety disorder, panic disorder, agoraphobia, generalised anxiety disorder, obsessive–compulsive disorder, post-traumatic stress disorder, and unipolar depressive disorders) using minimal exclusion criteria. Our experimental focus lies on emotion (dys)-regulation as a putative key mechanism of CBT and TNR. We use state-of-the-art machine learning methods to achieve single-patient predictions, incorporating pretrained convolutional neural networks for high-dimensional neuroimaging data and multiple kernel learning to integrate information from various modalities. The RU aims to advance precision psychotherapy by identifying emotion regulation-based biobehavioural markers of TNR, setting up a multilevel assessment for optimal predictors and using an ecologically valid sample to apply findings in diverse clinical settings, thereby addressing the needs of vulnerable patients.

Ethics and dissemination
The study has received ethical approval from the Institutional Ethics Committee of the Department of Psychology at Humboldt-Universität zu Berlin (approval no. 2021-01) and the Ethics Committee of Charité-Universitätsmedizin Berlin (approval no. EA1/186/22).
Results will be disseminated through peer-reviewed journals and presentations at national and international conferences. Deidentified data and analysis scripts will be made available to researchers within the RU via a secure server, in line with ethical guidelines and participant consent. In compliance with European and German data protection regulations, patient data will not be publicly available through open science frameworks but may be shared with external researchers on reasonable request and under appropriate data protection agreements.

Trial registration number
DRKS00030915.

Introduction
Wolfram syndrome (WFS1-Spectrum Disorder) is an ultra-rare monogenic form of progressive neurodegeneration and diabetes mellitus. In common with most rare diseases, there are no therapies to slow or stop disease progression. Sodium valproate, an anticonvulsant with neuroprotective properties, is anticipated to mediate its effect via alteration of cell cycle kinetics, increases in p21cip1 expression levels and reduction in apoptosis and increase in Wolframin protein expression. To date, there have been no multicentre randomised controlled trials investigating the efficacy of treatments for neurodegeneration in patients with Wolfram syndrome.

Methods and analysis
TREATWOLFRAM is an international, multicentre, double-blind, placebo-controlled, randomised clinical trial designed to investigate whether 36-month treatment with up to 40 mg/kg/day of sodium valproate will slow the rate of loss of visual acuity as a biomarker for neurodegeneration in patients with Wolfram syndrome. Patients who satisfied the eligibility criteria were randomly assigned (2:1) to receive two times per day oral gastro-resistant sodium valproate tablets up to a maximum dose of 800 mg 12 hourly or sodium valproate-matched placebo. Using hierarchical repeated measures analyses with a 5% significance level, 80% power and accounting for an estimated 15% missing data rate, a sample size of 70 was set. The primary outcome measure, visual acuity, will be centrally reviewed and analysed on an intention-to-treat population.

Ethics and dissemination
The protocol was approved by the National Research Ethics Service (West of Scotland; 18/WS/0020) and by the Medicines and Healthcare products Regulatory Agency. Recruitment into TREATWOLFRAM started in January 2019 and ended in November 2021. The treatment follow-up of TREATWOLFRAM participants is ongoing and due to finish in November 2024. Updates on trial progress are disseminated via Wolfram Syndrome UK quarterly newsletters and at family conferences for patient support groups. The findings of this trial will be disseminated through peer-reviewed publications and international presentations.

Trial registration number
NCT03717909.

Objective
Targeted temperature management (TTM), through its physiological effects on intracranial pressure, may impede the progression to brain death (BD) in severe anoxic brain injury post-cardiac arrest (CA). We examined the potential association between the use of TTM and the occurrence of BD after CA.

Design
Monocentric, retrospective study.

Setting
Intensive care unit, Versailles Hospital, France.

Participants
Comatose survivors of CA who died from BD or postanoxic encephalopathy (PAE) after 24 hours.

Main outcome measures
PAE deaths corresponded to withdrawal of life-sustaining therapy (WLST) due to irreversible postanoxic coma or vegetative state according to prognostication guidelines. BD corresponded to the cessation of cerebral vascularisation secondary to intracranial hypertension. The diagnosis of BD was definite by clinical diagnosis of deep coma according to the Glasgow Coma Scale 3, loss of all brainstem reflexes and the demonstration of apnoea during a hypercapnia test. A cerebral omputed tomography (CT) scan or two isoelectric and unreactive electroencephalograms were used to confirm BD. To identify the independent association between TTM and BD, we conducted a multivariable logistic regression analysis.

Results
Out of 256 patients included between 2005 and 2021, 54.3% received TTM for at least 24 hours, and 56 patients (21.9%) died from BD. In the multivariable analysis, TTM for 24 hours or more was not associated with a decrease in BD (Odds Ratio 1.08, 95% CI 0.51 to 2.32). Factors associated with BD included a total duration of no-flow plus low-flow exceeding 30 min, CA due to neurological causes or hanging and a high arterial partial pressure of carbon dioxide between days 1 and 2 after admission.

Conclusions
This exploratory analysis of post-CA patients with severe anoxic brain injury did not find an association between TTM ≥24 hours and a reduction in BD. Further studies are needed to identify specific subgroups of post-CA patients for whom TTM may be especially futile or even harmful.

Objectives
Despite widespread vaccination programmes and consensus recommendations, the understanding of the durability of COVID-19 vaccination against ensuing infection and transmission at the individual level is incomplete. The objective of this study was to estimate the effects of time-varying covariates including time since vaccination and symptoms on subsequent positive SARS-CoV-2 test results and assess the stability of these effects between March 2020 and April 2022.

Design
Prospective cohort study.

Setting
Urban university in the USA.

Participants
Drexel University students, faculty, and staff (n=15 527) undergoing mandatory COVID-19 symptom tracking, testing and vaccinations.

Intervention
Systematic symptom tracking and SARS-COV-2 testing starting in September 2020 and mandatory COVID-19 vaccination starting in September 2021.

Main outcomes and measures
COVID-19 vaccine effectiveness modified by time since vaccination and symptoms.

Results
Using fit-for-purpose digitally based symptom and vaccine tracking and mandatory comprehensive testing for SARS-CoV-2 infection, we estimate the time-dependent effects of vaccination, symptoms and covariates on the risk of infection with a Cox proportional hazards model based on calendar time scale. We found a strong protective effect of vaccination against symptomatic infection. However, there was strong evidence of a protective effect against infection only in the first 90 days after completed vaccination, and only against symptomatic versus asymptomatic infection. The overall estimated effect of vaccination within 30 days, including asymptomatic infections, was 37.3% (95% CI 26%, 47%). Vaccine effect modification by reported symptoms and time period was estimated, revealing the protective effect of vaccination within 90 days against symptomatic infection that varied from 90% (95% CI 84%, 94%) to 49%(95% CI –77%, 85%) across time periods.

Conclusions
This study is among the first to prospectively capture complete COVID-19 symptom, testing and vaccination data over a multiyear period. Overall effectiveness of the COVID-19 vaccine against subsequent infection, including transmissible asymptomatic infections, is modest and wanes after 90 days. Vaccination policies may need to take these issues into account.

Objectives
The aim of the study was to assess the feasibility of conducting a definitive multicentre randomised controlled trial (RCT) testing an online exercise rehabilitation and behavioural/motivational support intervention for people with postural tachycardia syndrome (PoTS).

Design
Feasibility RCT.

Setting
Two secondary care centres.

Participants
Adults aged 18 to 60 years with PoTS. Exclusions were serious mental health/cognitive problem preventing safe participation; currently undertaking physical activity equivalent to the Chief Medical Officer guidelines; pregnancy.

Interventions
Participants were randomly assigned (1:1) to best-practice usual care (a single 1:1 session of advice) or the ‘postural tachycardia syndrome exercise’ (PULSE) intervention: (1) individual online consultation, (2) 12 weeks of supervised online group exercise and behavioural/motivational support, and (3) home exercise programme with recumbent exercise bike.

Outcomes
The primary outcome was feasibility: (1) patients screened, eligible, recruited, randomised, withdrawn; (2) adherence; (3) physiological, clinical and patient-reported outcomes (4 and 7 months); and (4) embedded qualitative study to evaluate acceptability.

Results
209 patients screened between 5 May 2021 and 1 December 2022, 44 (female 98%; age 29.9 SD, 7.5) were randomised to usual care (n=21) or PULSE (n=23) (71% of target). Follow-up at 4 months was n=12 and n=17 respectively (66% of target). Median live exercise/support session attendance was 15 (IQR 12 to 17) of 18 sessions. Home exercise bike usage was highly variable. There were two serious adverse events in each treatment arm, both unrelated to the trial. Exercise rehabilitation was considered important by participants, and trial procedures, outcomes and interventions were acceptable.

Conclusions
The PULSE trial procedures and interventions were acceptable, and important design considerations were identified. A definitive RCT testing a remotely supervised exercise rehabilitation and behavioural/motivational support intervention for people with PoTS is feasible in the UK National Health Service.

Trial registration number
ISRCTN45323485.

Background
The introduction of immune checkpoint inhibitors (ICIs) has modified treatment modalities for patients with lung cancer, offering new alternatives for treatment. Despite improved survival benefits, ICIs may cause side effects impacting patients’ quality of life (QoL). We aim to study the changes in global QoL (gQoL) of patients with advanced-stage lung cancer up to 18 months after treatment with ICIs between 2015 and 2021.

Methods and analysis
A longitudinal cohort study was conducted using the Oncological Life Study: Living well as a cancer survivor data-biobank from the University Medical Center Groningen. Participants completed the European Organisation for Research and Treatment of Cancer QoL 30-item questionnaire, at the beginning of their ICI treatment (baseline) and then at 6, 12 and 18 months. Using joint modelling, changes in predicted mean gQoL were studied by treatment regimens from baseline to 18 months, while accounting for the competing risk of death and adjusting for prespecified covariates.

Results
Of the 418 participants with median age of 66 years, 39% were women. Patients receiving first-line immuno-monotherapy with palliative intent had a small improvement in their gQoL within 6 months and no clinically significant change thereafter. Patients receiving first-line immune-chemotherapy with palliative intent had a small improvement in their gQoL within 12 months and no clinically significant change thereafter. Patients with second/further line immunotherapy with palliative intent or first-line chemoradiotherapy followed by durvalumab with curative intent had no clinically significant change in their gQoL over 18 months.

Conclusion
The changes in gQoL over time among patients with advanced-stage lung cancer may vary by treatment regimens based on drug intensity, line and intent of treatment, which will help clinicians and patients understand the potential dynamic of treatments on QoL. It may further influence treatment decisions and patient management strategies, reflecting the practical implications of different treatment regimens.

Objective
This study aims to calculate the global warming potential, in carbon dioxide (CO2) equivalent emissions, from all in-scope activities involved in phase 1, 2, 3 and 4 clinical trials spanning multiple disease areas.

Design
The study design involved a retrospective analysis of completed clinical trials.

Setting
Select set of seven clinical trials conducted between 2018 and 2023 and sponsored by Johnson & Johnson Innovative Medicine: TMC114FD1HTX1002, 77242113PSO2001, 42756493BLC2002, 54767414MMY3012, VAC18193RSV3006, R092670PSY3016 and 28431754DIA4032

Participants
While participants and the public were involved in all seven trials, the life cycle assessments (LCAs) were performed as an independent retrospective analysis after the clinical trials were completed. As a retrospective analysis, we leveraged clinical trial documentation and interviews with the sponsor trial staff and trial site staff. None of the participating trial subjects were involved specifically in the LCA analysis, nor was any personal identifying information from the trial subjects collected or shared.
The underlying clinical trials were performed in accordance with the Declaration of Helsinki and Guidelines for Good Pharmacoepidemiology Practice. All participating investigators were required to obtain full governing board approval for conducting research involving humans. Sponsor approval and continuing review were obtained through the appropriate Institutional Review Board/Ethics Committee (IRB) and Health Authority channels. For academic investigative sites that did not receive authorisation to use the central IRB, full board approval was obtained from their respective governing IRBs, and documentation of approval was submitted to Johnson & Johnson Innovative Medicine, LLC, before the site’s participation and initiation of any trial procedures. All registry participants provided written informed consent and authorisation before participating.

Primary outcome measure
Primary outcome measure CO2 equivalents (CO2e) for in-scope clinical trial activities calculated according to Intergovernmental Panel on Climate Change 2021 impact assessment methodology.

Results
The TMC114FD1HTX1002 phase 1 trial was the smallest trial both in terms of number of patients (39) and sites (1) and had the smallest emissions at 17 648 kgCO2e. The 54767414MMY3012 phase 3 trial was not the largest trial in terms of number of participating patients (517) but had the largest number of participating sites (129) and had the largest emissions at 3 107 436 kg CO2e. Across all seven trials analysed, the mean emissions per patient were 3260 kg CO2e. When the overall trial footprints are broken down by phase, the phase 2 mean per patient was 5722 kg CO2e and the phase 3 mean per patient emissions were 2499 kg CO2e. The five largest contributors of greenhouse gas (GHG) emissions were drug product (50% mean), patient travel (10% mean), travel for on-site monitoring visits (10% mean), collection and processing of laboratory samples (9% mean) and sponsor staff commuting (6% mean). Patient travel was the only consistent GHG hotspot across all seven trials, as other hotspots appeared intermittently in some trials but not others based on variations in trial design. Across the multisite phase 2, 3 and 4 trials we analysed, a combination of the observed five largest contributors to GHG emissions were responsible for no less than 79% of GHG emissions for any one trial.

Conclusions
Based on our LCAs of seven clinical trials spanning all four phases of development and multiple disease areas, there are five activities that drive no less than 79% of the average clinical trial’s GHG footprint. These are drug product manufacture, packaging, and distribution; patient travel; on-site monitoring visit travel; the collection, transport and processing of laboratory samples; and sponsor staff commuting between their homes and the office. Understanding the activities that drive GHG emissions in clinical trials can both guide trial designers in avoiding or minimising reliance on these activities when designing new trials and guide trial sponsors in taking targeted actions to reduce GHG emissions from these activities where their use cannot be avoided.

Trial registration number
TMC114FD1HTX1002 (ClinicalTrials.gov: NCT04208061), 77242113PSO2001 (ClinicalTrials.gov: NCT05364554), 42756493BLC2002 (ClinicalTrials.gov: NCT03473743), 54767414MMY3012 (ClinicalTrials.gov: NCT03277105), VAC18193RSV3006 (ClinicalTrials.gov: NCT05070546), R092670PSY3016 (ClinicalTrials.gov: NCT04072575) and 28431754DIA4032 (ClinicalTrials.gov: NCT04288778).

Objectives
This study aimed to compare mortality rates and length of hospital stay between patients with critical COVID-19 transferred to another hospital due to capacity constraints and those who remained at their initial admission hospital.

Design
Single-centre cohort study.

Setting and participants
665 patients were treated for SARS-CoV-2 at two intensive care units (ICUs) in Stockholm, Sweden, from 1 March 2020 to 30 June 2021. Data on interhospital transfers (IHTs) were retrieved from medical records and patient data management systems according to predefined protocols.

Main outcome measures
The outcomes were 30-day and 90-day mortality, days alive and out of ICU. HR with 95% CI were calculated using Cox proportional hazard models with adjustments for age, sex, body mass index, severity of illness, comorbidity, invasive ventilation, treatment limitations and pandemic waves.

Results
Of 665 patients, 133 (20%) were transferred to another hospital. The mortality rate of transferred patients compared with non-transferred patients at 30 days was 19% vs 26% (p=0.13) and at 90 days 26% vs 30% (p=0.43). In the adjusted Cox regression analysis, IHT was associated with a lower mortality risk at 30 days (HR 0.47, 95% CI 0.30 to 0.76) and 90 days (HR 0.52, 95% CI 0.34 to 0.79). However, the number of days alive and out of ICU was significantly lower for the IHT group at 30 days.

Conclusion
In our study, IHT due to capacity constraints among critically ill COVID-19 patients was not associated with a higher mortality risk. The suitability for transfer was likely associated with lower mortality, although residual confounding cannot be ruled out. The requirement for invasive ventilation among transferred patients might account for the extended length of ICU stay, rather than the transfer itself. However, the difficulty in studying this issue lies in the fact that while patients are likely exposed to risks during transfer, they are simultaneously the patients stable enough to be transported.

Worldwide, the rate of deaths from drowning decreased by 38% over the past 2 decades, from 6.1 to 3.8 per 100 000 people. The first-ever status report on drowning prevention from the World Health Organization (WHO) estimated that 300 000 people died from drowning in 2021, down from 375 000 in 2000.