Quantitative impacts of meteorology and emissions on the long-term trend of O3 in the Yangtze River Delta (YRD), China from 2015 to 2022.

Extensive spatiotemporal analyses of long-trend surface ozone in the Yangtze River Delta (YRD) region and its meteorology-related and emission-related have not been systematically analyzed. In this study, by using 8-year-long (2015-2022) surface ozone observation data, we attempted to reveal the variation of multiple timescale components using the Kolmogorov-Zurbenko filter, and the effects of meteorology and emissions were quantitatively isolated using multiple linear regression with meteorological variables. The results showed that the short-term, seasonal, and long-term components accounted for daily maximum 8-hr average O3 (O3-8 hr) concentration, 46.4%, 45.9%, and 1.0%, respectively. The meteorological impacts account for an average of 71.8% of O3-8 hr, and the YRD's eastern and northern sections are meteorology-sensitive areas. Based on statistical analysis technology with empirical orthogonal function, the contribution of meteorology, local emission, and transport in the long-term component of O3-8 hr were 0.21%, 0.12%, and 0.6%, respectively. The spatiotemporal analysis indicated that a distinct decreasing spatial pattern could be observed from coastal cities towards the northwest, influenced by the monsoon and synoptic conditions. The central urban agglomeration north and south of the YRD was particularly susceptible to local pollution. Among the cities studied, Shanghai, Anqing, and Xuancheng, located at similar latitudes, were significantly impacted by atmospheric transmission-the contribution of Shanghai, the maximum accounting for 3.6%.

Long-term ambient sulfur dioxide exposure during gestation and preterm birth in North Carolina, 2003-2015.

BACKGROUND: Coal-fired power plants are major contributors of ambient sulfur dioxide (SO2) air pollution. Epidemiological literature suggests an adverse association between SO2 exposure during gestation and preterm birth (PTB; <37 weeks completed gestation). PTB is strongly associated with infant mortality and increased risk for later life morbidities. OBJECTIVE: We investigated associations between SO2 and PTB in North Carolina and evaluated whether the associations were modified by race/ethnicity. METHODS: We assembled a retrospective, administrative cohort of singleton births in North Carolina from 2003-2015. We used US EPA EQUATES data to assign long-term SO2 gestational exposures to eligible births for the entire pregnancy and by trimester. We used multivariable generalized linear regression to estimate risk differences (RD (95%CI)) per 1-ppb increase in SO2, adjusted for gestational parent education, Medicaid status, marital status, and season of conception. Multi-pollutant models were additionally adjusted for other criteria air co-pollutants (O3, PM2.5, NO2). RESULTS: The median SO2 (24-hour average) across exposure windows was ~1.5 (IQR: 1.8) ppb. The overall baseline risk for PTB was 8,756 per 100,000 live births. When stratified by race/ethnicity, the baseline risk for PTB was 12215, 7824, and 7187 per 100,000 live births among non-Hispanic Black, non-Hispanic white, and Hispanic births, respectively. RDs per 1-ppb increase in SO2 averaged across the entire pregnancy were 317.0 (95%CI: 279.4, 354.5) and 568.2 (95%CI: 500.3, 636.1) per 100,000 live births for single- and multi-pollutant models, respectively. For the PTB multi-pollutant models, we observed similar RDs for non-Hispanic Black participants (669.6 [95%CI: 573.9, 765.2]) and non-Hispanic white participants (635.4 [95%CI: 557.2, 713.6]) with smaller RDs for Hispanic participants (336.8 [95%CI: 241.3, 432.2]). SIGNIFICANCE: The results for our adjusted single- and multi-pollutant models showed adverse associations between SO2 and PTB, with some evidence of effect measure modification by race/ethnicity within subcategories of PTB.

Evaluating the Therapeutic Efficiency and Efficacy of Blood Purification for Treating Severe Acute Pancreatitis: A Single-Center Data Based on Propensity Score Matching.

Purpose: To evaluate the long-term efficacy and cost-efficiency of blood purification (BP) in severe acute pancreatitis (SAP) through single-center data. Patients and Methods: A total of 155 SAP patients were collected and followed up for 6 months. The participants were divided into control (49 cases) and BP group (106 cases) according to whether they received BP treatment or not. The primary outcomes were 6-month mortality, length of hospital stay, and hospitalization costs. Propensity score matching (PSM) analysis was performed based on various factors such as gender, age, etiology, SOFA score, JSS score, and creatinine value on day 1. Results: There were significant differences in all baseline data between BP and control groups (p<0.05). However, there was a significant difference in the mortality, length of hospital stay, hospital costs and infection aggravation rate the in outcome data for 6-months (all p<0.05). BP was not considered a death factor in any adjusted models, with p-values ranging from 0.81 to 0.93. The results of subgroup analysis after PSM showed that BP mode had no significant impact on prognostic indicators, but the length of ICU stay and total costs were significantly increased (all p<0.001). There was no significant difference in mortality among the cases that did not require early intervention after 6 months (p=0.487). However, the patients in BP group had longer ICU stays (p=0.001) and higher hospitalization costs (p<0.001) compared to the control group. Conclusion: The utilization of BP therapy did not decrease the 6-month mortality in SAP patients. Additionally, BP therapy has a significant impact on the duration of ICU stay or hospitalization expenses. However, the effectiveness and cost-efficiency of this therapy are unsatisfactory, and early intervention does not enhance survival benefits. Furthermore, there was no substantial variation in survival benefits between continuous veno-venous hemofiltration (CVVH) alone and compound BP.

Decadal variation and temporal stability of the macrobenthic community in the Bohai Sea, China.

Biodiversity in the Bohai Sea is threatened by climate change and human activities. An analysis based on decadal macrobenthic community data was conducted to assess the ecological health. These findings revealed the temporal and spatial variations in species composition and biodiversity, which were primarily influenced by depth, temperature and dissolved oxygen content. The community structure in 2014 exhibited a 70 % dissimilarity compared to other years, and biodiversity was lower in 2014. The dominant species showed a trend towards miniaturization. Abundance-biomass comparison curves indicated that community disturbance improved by implementing various policies. Overall, communities in the Bohai Sea remained stable, except in the Bohai Strait (BH), where synchronous fluctuations with an increasing trend were observed. Enhancing biodiversity and addressing the risks associated with losing single species are essential for maintaining community stability. The community also displayed synchronous tendencies in Laizhou Bay, emphasizing the need for continued long-term monitoring.

Oral Anticoagulant Use and Post-Fall Mortality in Long-Term Care Home Residents.

OBJECTIVES: Long-term care (LTC) residents are susceptible to falling and the risk of subsequent morbidity and mortality may be compounded with concurrent anticoagulation use. Uncertainty exists around the benefit and harm of anticoagulation use for residents with a high risk for falls because of concerns of major bleeding complications. We aimed to examine if anticoagulant use increases mortality risk among LTC residents who fall. DESIGN: A retrospective cohort study. SETTING AND PARTICIPANTS: Older adults (≥65 years) admitted to a LTC facility in Ontario, Canada between January 1, 2010, and December 1, 2019, who were transferred to emergency departments for fall-related injuries. METHODS: The exposure was the use of an oral anticoagulant (OAC). The primary outcome was mortality within 30 days of transfer. Secondary outcomes were major hemorrhage and care utilization. We used hierarchical logistic regression models to examine the association between the use of OAC and 30-day mortality. RESULTS: There were 56,419 residents transferred to the hospital for a fall, of whom 9611 (17.0%) were on an OAC. At 30 days, 5794 (10.3%) of the cohort had died: 12.0% (1151) on an OAC and 9.90% (4643) not on an OAC (risk difference [RD], 2.1%; 95% CI, 1.40%-2.82%). There were 485 major hemorrhage cases: 1.3% (125) on an OAC and 0.8% (360) not on an OAC (RD, 0.5%; 95% CI, 0.26%-0.74%). Multivariable analysis found no significant association between OAC use and 30-day mortality (odds ratio [OR], 0.98; 95% CI, 0.90-1.06), but an increased risk of major hemorrhage (OR, 1.31; 95% CI, 1.04-1.66). Both groups had similar health system and neurosurgical care utilization. CONCLUSIONS AND IMPLICATIONS: Among LTC residents transferred to the emergency department for fall-related injuries, OACs did not increase the risk of post-fall mortality. OAC prescribing for frail older adults who experience falls should consider their individual risk profile.

Understanding facilitators and barriers to oxygen therapy for patients with interstitial lung disease.

BACKGROUND: Interstitial lung disease (ILD) is comprised of a heterogeneous group of pulmonary diseases. Oxygen therapy is used in patients with advanced lung disease; however, there are challenges associated with initiation of oxygen therapy specific to individuals with ILD. The key objectives of this study were to create a common understanding of the facilitators and barriers to oxygen therapy for patients with ILD, and healthcare professionals (HCP) caring for patients with ILD. METHODS: This qualitative study included 1 hour semistructured focus groups/interviews. An iterative and concurrent process was used for data collection and analysis to allow for supplementary development of themes and concepts generated. Data analysis used a three-phase approach: coding, categorising and development of themes. RESULTS: A total of 20 patients and/or caregivers and 31 HCP took part in 34 focus groups/interviews held over 3 months (November 2022-January 2023). Facilitators to oxygen therapy were identified including support from HCP and support groups, the perseverance and self-advocacy of patients, a straightforward administrative process and vendors/private industry that expedite access to oxygen therapy. There were also several barriers to accessing oxygen therapy for patients with ILD. The themes identified include rural disparity, testing requirements and qualifying for funding and the need for ILD-specific evidence base for oxygen therapy. CONCLUSION: Further research is needed to facilitate development of specific exertional oxygen criteria for patients with ILD, to create supports for oxygen use and monitoring and to enable providers to tailor therapy to patients. Oxygen therapy education for ILD should address the benefits and risks of oxygen therapy.

Cumulative re-operation rates during follow-up after hypospadias repair.

OBJECTIVE: To assess the cumulative rates of re-operations after hypospadias repair and evaluate long-term surgical outcomes at a tertiary paediatric urology centre. PATIENTS AND METHODS: Retrospective analysis of 293 boys born between 1991 and 2003 undergoing hypospadias surgery was conducted. The study included 274 patients: 165 with distal, 34 with midshaft, and 75 with proximal hypospadias. Kaplan-Meier methods were used to evaluate the re-operation data. RESULTS: The median age at primary surgery was 1.3 years, with a median follow-up of 14.4 years. The overall re-operation rate was 48.2%, with approximately half of the problems detected within the first 3 months after surgery. The risk of re-operation was correlated with hypospadias severity, with 5- and 15-year re-operation risks at 39.3% and 51.8%, respectively. Limitations of the study include its retrospective nature and variations in surgical techniques from current standards. CONCLUSION: There is a significant risk of unplanned re-operations following hypospadias repair, increasing with the severity of the original condition. This underscores the need for extended follow-up and effective communication with patients and their families about the likelihood of requiring multiple surgeries for optimal outcomes.

Long-term Efficacy and Safety of Sodium Oxybate in Treating Alcohol Use Disorder: A Systematic Review and Meta-Analysis.

BACKGROUND: Worldwide, three million deaths each year are reported due to the harmful use of alcohol. To date, only a few drugs have been approved for the treatment of Alcohol Use Disorder (AUD). This systematic review and meta-analysis aim to assess the long-term efficacy and safety of sodium oxybate (SMO) treatment in patients with AUD. METHODS: We followed the PRISMA statement guidelines and searched PubMed and ISI Web of Science to retrieve the studies of interest. In total, 13 studies on long-term (>12 weeks) SMO administra- tion in patients with AUD were included in this systematic review, and 7 were included in the meta- analysis. RESULTS: Overall, the abstinence rate after 12 weeks of treatment was similar in the SMO and placebo groups, while it was significantly in favour of SMO compared to Naltrexone (NTX). The completion rate was similar in all three conditions. Mean corpuscular volume (MCV) levels favoured SMO over NTX, while Alcohol Craving Scale (ACS) scores did not favour SMO. The incidence of adverse reactions varied widely between studies. CONCLUSION: SMO in the chronic treatment of patients with AUD showed no superiority to placebo in our analysis of published RCTs, although many observational studies reported its beneficial effect in the long term. On the contrary, SMO was superior to NTX treatment on abstinence. The rate of study completion was similar in the three groups. Safety was not an issue in any of the studies included. Further studies are needed to better assess SMO efficacy and safety in the long term.

Two 5-year studies of bictegravir/emtricitabine/tenofovir alafenamide in people with HIV: a plain-language summary.

WHAT IS THIS SUMMARY ABOUT?: This is a plain-language summary of an article that reported on two studies of the medication bictegravir/emtricitabine/tenofovir alafenamide (shortened to B/F/TAF). B/F/TAF is a single pill containing three different drugs used to treat human immunodeficiency virus (known as HIV). The drugs work together to lower the levels of HIV (called viral load) in the body and make the virus undetectable in the blood. Researchers measured whether B/F/TAF was safe and effective when taken over 5 years in over 400 people in 10 countries who had never taken HIV medication before. WHAT WERE THE RESULTS?: After 5 years, almost all (99%) of the people who took B/F/TAF had an undetectable viral load. This does not mean that they were cured, but that the levels of HIV were so low that the tests used by researchers could not detect the virus in the blood. CD4 is a type of immune system cell. HIV causes CD4 cell numbers to decrease. On average, the number of CD4 cells increased by more than 300 cells per microliter (cells/µL) of blood over 5 years. This means that the immune system was improving. HIV is able to change its genes to escape the effects of the drugs. This is known as HIV resistance to treatment. Nine people had a viral load high enough to suggest that the drugs might not be working, but no resistance to B/F/TAF was seen. Some people (less than one in three) experienced medical problems thought to be linked to B/F/TAF treatment, known as side effects. The most common side effects were headache, diarrhea, nausea, tiredness (fatigue), dizziness, and difficulty falling or staying asleep (insomnia). On average, people's body weight increased by 3 kg in the first year of taking B/F/TAF. This might be because their general health improved after starting HIV treatment. Weight gained after that time was similar to the level of weight gain expected in the general population. Very few people (less than 1 in 100) stopped taking B/F/TAF because of side effects thought to have been caused by B/F/TAF. WHAT DO THE RESULTS MEAN?: B/F/TAF was effective at treating HIV in people who had never taken HIV medication before. Most (70%) people were still taking B/F/TAF after 5 years.Clinical Trial Registration: NCT02607930 (Study 1489); NCT02607956 (Study 1490) (ClinicalTrials.gov).

Connecting working and long-term memory: Bayesian-hierarchical multinomial model-based analyses reveal storage next to retrieval differences.

Individual differences in working memory capacity (WMC) are correlated with long-term memory (LTM) differences. Whether this is because high-WMC individuals encode more effectively, resulting in better LTM storage, or because they better retrieve information from LTM is debated. In two experiments, we used Bayesian-hierarchical multinomial modeling to correlate participant-level storage and retrieval processes from LTM recall to WMC abilities estimated from operation and symmetry complex span tasks. In Experiment 1, we presented participants with 20 consecutive words, including semantically associated pairs (e.g., knife and fork), to assess LTM processes. Participants received standard (n = 242) or associative-storage instructions (n = 222) and then completed a free recall task. In Experiment 2, we instructed participants (N = 239) to memorize 40 cue-target words as pairs before completing free and cued recall tasks. Correlations with WMC emerged with storage and retrieval processes and only when an associative storage strategy was instructed (Experiment 1). When associative processing was inherent to the task (Experiment 2), only the associative storage, not the retrieval advantage, replicated. The strategy reports suggest that high-WMC individuals use associative encoding strategies more effectively, resulting in better storage in LTM.

Efficacy assessment of different cryoprotectants for preserving the viability of Enterobacterales strains at - 20 °C.

The preservation of microorganisms is pivotal in microbiological practice. Currently, cryopreservation is assumed to be an effective and inexpensive approach for the storage of microorganisms, including bacteria. The key point of cryopreservation is optimal cryoprotectant selection. In the present study, different cryoprotectant compositions were tested for long-term storage of 15 Enterobacterales bacterial strains at - 20 °C. The survival rates of the bacterial strains were evaluated in four different cryoprotectant solutions containing 70% glycerin only (cryoprotectants 1 and 4), 10% dimethyl sulfoxide (DMSO) with 70% glycerin (cryoprotectant 2), and 10% DMSO (cryoprotectant 3). In addition, cryoprotectants 1 and 2 contained peptone and yeast extract as nutritional supplements. The general survival rates of the bacterial strains were evaluated after 12 months of storage. After 12 months, the survival rates of the different cryoprotectants were as follows: cryoprotectant 1-88.87%; cryoprotectant 2-84.85%; cryoprotectant 3-83.50%; and cryoprotectant 4-44.81%. Thus, the composition of cryoprotectant 1 (70% glycerin with nutrient supplements) was optimal for preserving 15 tested strains of the order Enterobacterales. Despite these findings, the biochemical properties of the tested strains changed after cryopreservation for 12 months in the presence of 1 or 3 cryoprotectants. Alterations in the biochemical profile could be related to changes in environmental conditions and cold adaptation. We assume that the composition of cryoprotectant 1 can be optimal for storing the order Enterobacterales at - 20 °C. However, further investigations are needed to elucidate the problem of cryopreservation and to support our assumption.

Motivations of family advisors in engaging in research to improve a palliative approach to care for persons living with dementia: an interpretive descriptive study.

BACKGROUND: A Strategic Guiding Council (SGC) was created within a Family Carer Decisions Support study, to engage family carers of persons with advanced dementia as advisors to inform the design and implementation of the study. The SGC consists of an international group of family advisors from Canada, the Republic of Ireland, the United Kingdom, the Netherlands, and the Czech Republic. There are limited studies that have explored the integration of Patient and Public Involvement (PPI) in dementia research, end-of-life care and long-term care. Therefore, this study explores PPI engagement in health research with family carers to understand further their interest in being involved in the SCG within the FCDS intervention which is focused on supporting caregivers to make decisions about end-of-life care for residents with advanced dementia. METHODS: This study utilized an interpretive descriptive design and explored the motivations of ten family advisors from Canada, the Republic of Ireland, the United Kingdom, and the Netherlands in being part of the SGC. Semi-structured interviews were conducted by phone or videoconferencing and were recorded, transcribed, and analyzed using thematic analysis. RESULTS: Three themes generated from the findings of the study were (1) engaging in reciprocal learning; (2) using lived experience to support other family carers; and (3) creating a collective momentum for advocacy and change. CONCLUSIONS: Family carers motivations to being part of the SCG was driven by their intent to help carers navigate the health system and to create a psychosocial support system for other carers experiencing end-of-life with their loved ones. Being part of the SCG provided a benefit to family carers which provided a venue for them to contribute meaningful information from their experience, learn from other health professionals, research and other advisors and an avenue for advocacy work to improve access to end-of-life care supports through education. To our knowledge, this is the first study that explores the motivations of an international group of family advisors' engagement in health research to promote integration of a palliative approach to dementia care in long-term care homes. This study further contributes to the literature from an international perspective the importance of PPI in research. Further research is warranted that explores PPI in research to improve access to end-of-life supports.

Patient and public involvement (PPI) in research has been growing worldwide and ensures that research conducted is relevant to the needs of patients. Within the Family Carer Decisions Support study, we created a Strategic Guiding Council (SGC) to engage family carers of persons with advanced dementia as advisors to improve access to a palliative approach to care. The SGC includes family advisors from Canada, the Republic of Ireland, the United Kingdom, the Netherlands, Italy and the Czech Republic. The goal of the strategy was to engage with family advisors in research activities to improve access to a palliative approach and quality of care provided to people with dementia receiving end-of-life care. Including patients and family in research is extremely important, therefore our aim in this study was to explore family advisors' motivations to engaging in the SGC. Family advisors reported encountering challenges with navigating the health system with end-of-life care and they chose to participate in the SGC to support other carers who are experiencing a similar situation. Being part of the SGC also provided the family advisors with an avenue to advocate on the importance of improving access to end-of-lifesupports and the opportunity to learn from other advisors, health professionals and researchers.

Asian Low-Carbohydrate Diet with Increased Whole Egg Consumption Improves Metabolic Outcomes in Metabolic Syndrome: A 52-Week Intervention Study.

BACKGROUND: The low-carbohydrate-ketogenic diet, an effective strategy to address metabolic syndrome (MetS) and obesity has raised concerns about high fat consumption on atherogenic lipoproteins. OBJECTIVE: The aim of this study was to compare the Asian ketogenic diet (AKD), which incorporates balanced protein and fat intake from Asian foods, with a balanced low-caloric diet (BLC) in individuals diagnosed with MetS. METHODS: A 52-week randomized clinical trial included three parallel groups: AKD with increased whole egg intake (Yolk-AKD, n = 28), yolk-free ketogenic diet with egg white supplementation (White-AKD, n = 26), and BLC (n = 22). Primary outcomes were anthropometric and metabolic changes. RESULTS: The AKD groups achieved significant reductions in weight and waist circumference (P < 0.05). Compared to the BLC group, the AKD groups demonstrated significant improvements in insulin resistance at week 6 and in triglyceride levels at weeks 12 (Yolk-AKD) and 35 (White-AKD) (P < 0.05). The AKD groups experienced improvements in hormones associated with insulin sensitivity and appetite, while only the Yolk-AKD group had a significant decrease in inflammation-related hormones (P < 0.05). From weeks 35 to 52, the AKD maintained reductions in anthropometric measurements, blood pressure, improved glucose tolerance, enhanced lipid profiles, and better liver function compared to the BLC. CONCLUSIONS: The AKD proved safe and effective, yielding various metabolic improvements in individuals with Mets compared to the BLC. Emphasizing a low-saturated fat diet while disregarding dietary cholesterol, this approach holds promise for MetS and obesity management. The inclusion of both White-AKD and Yolk-AKD groups allowed for a comprehensive assessment of the AKD's impact, elucidating the differential effects of whole egg consumption on metabolic outcomes. Further studies are warranted. This trial was registered at clinicaltrials.gov as NCT04608136.

Delirium Incidence and Predictors in SARS-CoV-2 Vaccinated Residents in Long-Term Care Facilities (LTCF): Insights From the GeroCovid Vax Study.

OBJECTIVE: SARS-CoV-2 vaccination can bring an important benefit for older people in terms of reduction of mortality and hospitalization; however, reports of rare adverse effects like altered consciousness and delirium among this demographic have raised concerns. This study aimed to assess delirium incidence post-SARS-CoV-2 vaccination and its predictors in older residents across 60 Italian long-term care facilities (LTCFs). DESIGN: This is a prospective cohort study considering data from GeroCovid Vax, a multicenter cohort study jointly performed by the Italian Society of Gerontology and Geriatrics (SIGG) (Florence, Italy) and the Italian National Institute of Health (Istituto Superiore di Sanità-ISS, Rome, Italy), and sponsored by the Italian Medicines Agency (Agenzia Italiana del Farmaco-AIFA). SETTING AND PARTICIPANTS: GeroCovid Vax enrolled LTCFs residents aged ≥60 who received at least 1 anti-SARS-CoV-2 vaccine dose. METHODS: Baseline data covered sociodemographic details, chronic diseases, medications, nutritional status, cognitive and functional assessments, mobility, and frailty. Delirium was assessed post-first, second, and booster vaccine doses using DSM-5 criteria. Data analysis involved descriptive statistics, multivariate logistic regression, and network analysis. RESULTS: A total of 2521 participants (mean age 83.10 ± 9.21 years, 70.7% female) were analyzed. Delirium incidence post-first, second, and booster doses was 3.5%, 1.6%, and 1.5%, respectively. Age, preexisting cognitive disorders, and frailty were significant predictors of delirium, with odds ratios (ORs) of 1.70 (95% CI, 1.08-2.77), 2.05 (95% CI, 1.40-2.97), and 1.77 (95% CI, 1.25-2.52), respectively. Prior use of antipsychotics (OR, 1.75; 95% CI, 1.22-2.51) and antidepressants (OR, 1.77; 95% CI, 1.25-2.52) correlated significantly with delirium. Network analysis indicated a strong association between anorexia and delirium. CONCLUSION AND IMPLICATIONS: Post-vaccination delirium is infrequent and decreases with subsequent doses. Timely assessments for frailty and cognitive impairment could aid in stratifying delirium risk among LTCF residents, facilitating enhanced prevention measures and close monitoring for delirium indicators.

Long-term quality of life and social disconnection 20 years after a first episode psychosis, results from the 20-year follow-up of the OPUS trial.

OBJECTIVE: Schizophrenia disorders severely impact social and occupational function and reduce quality of life, furthermore patients often suffer from social withdrawal and isolation. The aim of this study was to investigate long-term quality of life and social disconnection and determine 10-year changes in quality of life and social disconnection later in life in association with changes in symptom severity, cognition, and global function. METHODS: We used assessments of quality of life and assessor rated social disconnection from the 10- and 20-year follow-up of the OPUS trial to examined 10-year changes in self-rated quality of life and social disconnection in the later stage of illness following a first episode psychosis. Self-rated social disconnection was only assessed in the 174 participants of the 20-year follow-up. RESULTS: Twenty years after a first episode psychosis only half of the participants reported having face-to-face contact with someone in their network more than once a week, while 90 % reported often or always being able to get emotional support when needed. Quality of life ratings were lower in our study population compared to the general population. On average physical and environmental quality of life worsened from the 10- to the 20-year follow-up while psychological and social quality of life remained stable. All quality-of-life domains were associated with negative symptoms (physical QoL: b = -6.6, p < 0.001, psychological QoL: b = -8, p < 0.001, social QoL: b = -5.7, p < 0.001 and environmental QoL: b = -6.5, p < 0.001) and global function (physical QoL: b = -0. 47, p < 0.001, psychological QoL: b = 0.52, p < 0.001, social QoL: b = 0.31, p < 0.001 and environmental QoL: b = 0.49, p < 0.001). CONCLUSION: Social disconnection seems to persist over time. Social disconnection and quality of life were associated with negative symptoms and poor functioning, therefore interventions aimed at improving global and social function might likely also improve quality of life.

Effectiveness of structured, multidisciplinary long-term care for pediatric cancer survivors: protocol of the multicenter, randomized-controlled AELKI study.

BACKGROUND: In Germany, around 2.250 children and adolescents are diagnosed with cancer each year. Despite generally positive long-term survival rates, many patients must cope with late effects of the disease and its treatment. This highlights the need for a well-structured, long-term approach addressing both physical and mental health issues. Currently, the German healthcare system lacks such comprehensive structures. Our study aims to evaluate the effectiveness of a structured, multidisciplinary long-term approach compared to conventional "treatment as usual" (TAU). METHODS: A prospective, multicenter study with ten pediatric university clinics in Germany will be conducted. The cluster-randomization takes place at the clinic level. Children and adolescents who completed their cancer treatment at least five years ago and their parents will be eligible to participate. While the control group (CG) receives TAU, the intervention group (IG) participates in a structured program. This program includes risk-based medical treatment and psychosocial interventions tailored to each patient's individual needs within a two-month timeframe. The primary outcome is the improvement of self-efficacy. Secondary outcomes are satisfaction with health care, improvement of health-related quality of life (HRQoL), reduction of mental health problems, and improvement of transition readiness. DISCUSSION: This approach has the potential to optimize the health care for individuals who survived cancer during childhood or adolescence. It addresses the challenges of overuse, underuse, and misuse of health care resources. By considering both medical and psychosocial factors and promoting increased self-efficacy, independent from parental involvement, it may facilitate a smoother transition to adult medicine and enhance adherence to lifelong aftercare. If proven successful, this approach will contribute to the integration of multidisciplinary strategies into standard healthcare practice. TRIAL REGISTRATION: German Clinical Trials Register DRKS00029269. Registered on December 23, 2022.

Case management for people with acquired brain injury: feasibility and effectiveness of a two-year pragmatic randomized controlled trial.

BACKGROUND: Case management (CM) aims to facilitate access to and integration of health care and social services. We investigated the feasibility and effectiveness of CM. METHODS: Randomized controlled trial with 219 patients and 114 caregivers randomly allocated to CM (109/59) or care as usual (110/55). CM was based on early and continuous online monitoring of problems and needs. Outcomes were assessed every 6 months with the Hospital Anxiety and Depression Scale (HADS). Secondary outcome domains were participant restrictions, life satisfaction, self-efficacy, caregiver burden, and needs. Multilevel modeling was used. Feasibility aspects were protocol delivery, participants' and case managers' satisfaction, and factors affecting implementation. RESULTS: There were no significant differences between groups. Participation restrictions and unmet needs decreased in both groups within 6 months. Monitoring was successful in 38, and 10 participants asked the CM for support. CM consisted mostly of providing information. DISCUSSION: CM based on early and continuous online monitoring does not have benefit in identifying and addressing problems early after relatively mild injury. Unsuccessful monitoring may have hindered access to the case manager and prevented us from evaluating CM as a complex intervention. It remains a challenge to early identify those who could benefit from care coordination.

Randomized Controlled Trial on Silicone Intubation in Endoscopic Mechanical Dacryocystorhinostomy (SEND): An 11-year Outcome Report.

PURPOSE: To compare the long-term outcomes of mucosal-sparing mechanical endoscopic dacryocystorhinostomy (MMED) for primary acquired nasolacrimal duct obstruction (PANDO) with or without silicone intubation. METHODS: An 11-year follow-up study of the Silicone intubation in Endoscopic Dacryocystorhinostomy (SEND) randomized controlled trial (RCT) was conducted at a university-affiliated dacryology clinic from December 2019 to March 2023. Questionnaires on symptoms, anterior segment examination, endoscopic examination with functional endoscopic dye test (FEDT) and FICI grading, and ostial size measurements using Image J software were performed by a masked ophthalmologist. The primary outcome was surgical success, defined by Munk's score ≤1 and a positive fluorescein endoscopic dye test. Secondary outcomes included risk factors for failure and outcomes of revision surgeries. RESULTS: Fifty-three of the original 118 patients were evaluated at 155 ± 21 (136-218) months postoperatively. Seventy-seven percent (46/60) ostia remained successful, including 70% (19/27) of unstented and 82% (27/33) of stented ostia (p = .3). Stented ostia had larger size (p = .003), but this did not confer higher success (p = .14). Successful ostia had higher FICI scores and better ostial dynamicity (p < .05). Ostium movement was the only parameter associated with surgical success on multivariate analysis (OR 13.1, p = .01). Four (1 stented) underwent revision MMED, intraoperative mitomycin-C, and 12-week intubation. All revision ostia were functional after 141 ± 43 months. CONCLUSIONS: Surgical success of MMED after 11-years was 77%, a notable reduction compared to 96% success at 1-year. Statistical advantage of silicone intubation for primary MMED was not demonstrated, though clinically, stented ostia had a higher success (82% vs 70%). The presence of a dynamic internal common opening was highly associated with long-term surgical success.

A first-in-kind MAPK13 inhibitor that can correct stem cell reprogramming and post-injury disease.

The stress kinase MAPK13 (aka p38δ-MAPK) is an attractive entry point for therapeutic intervention because it regulates the structural remodeling that can develop after epithelial barrier injury in the lung and likely other tissue sites. However, a selective, safe, and effective MAPK13 inhibitor is not yet available for experimental or clinical application. Here we identify a first-in-kind MAPK13 inhibitor using structure-based drug design combined with a screening funnel for cell safety and molecular specificity. This inhibitor (designated NuP-4) down-regulates basal-epithelial stem cell reprogramming, structural remodeling, and pathophysiology equivalently to Mapk13 gene-knockout in mouse and mouse organoid models of post-viral lung disease. This therapeutic benefit persists after stopping treatment as a sign of disease modification and attenuates key aspects of inflammation and remodeling as an indication of disease reversal. Similarly, NuP-4 treatment can directly control cytokine-stimulated growth, immune activation, and mucinous differentiation in human basal-cell organoids. The data thereby provide a new tool and potential fix for long-term stem cell reprogramming after viral injury and related conditions that require MAPK13 induction-activation.

Long-term effect of mavacamten in obstructive hypertrophic cardiomyopathy.

BACKGROUND AND AIMS: Long-term safety and efficacy of mavacamten in patients with obstructive hypertrophic cardiomyopathy (HCM) are unknown. MAVA-LTE (NCT03723655) is an ongoing, 5-year, open-label extension study designed to evaluate the long-term effects of mavacamten. METHODS: Participants from EXPLORER-HCM (NCT03470545) could enrol in MAVA-LTE upon study completion. RESULTS: At the latest data cut-off, 211 (91.3%) of 231 patients originally enrolled in MAVA-LTE still received mavacamten. Median (range) time on study was 166.1 (6.0-228.1) weeks; 185 (80.1%) and 99 (42.9%) patients had completed the week 156 and 180 visits, respectively. Sustained reductions from baseline to week 180 occurred in left ventricular outflow tract gradients (mean [standard deviation]: resting, -40.3 [32.7] mmHg; Valsalva, -55.3 [33.7] mmHg), NT-proBNP (median [interquartile range]: -562 [-1162.5, -209] ng/L), and EQ-5D-5L score (mean [standard deviation]: 0.09 [0.17]). Mean left ventricular ejection fraction (LVEF) decreased from 73.9% (baseline) to 66.6% (week 24) and 63.9% (week 180). At week 180, 74 (77.9%) of 95 patients improved by at least one New York Heart Association class from baseline. Over 739 patient-years exposure, 20 patients (8.7%; exposure-adjusted incidence: 2.77/100 patient-years) experienced 22 transient reductions in LVEF to <50% resulting in temporary treatment interruption (all recovered LVEF of ≥50%). Five (2.2%) patients died (all considered unrelated to mavacamten). CONCLUSIONS: Long-term mavacamten treatment resulted in sustained improvements in cardiac function and symptoms in patients with obstructive HCM, with no new safety concerns identified. Transient, reversible reductions in LVEF were observed in a small proportion of patients during long-term follow-up.