Comparative risk of serious infection with vedolizumab vs anti-TNF in inflammatory bowel disease: results from nationwide Swedish registers.

OBJECTIVES: We aimed to assess the risk of serious infection in inflammatory bowel disease (IBD) patients treated with vedolizumab, compared to those treated with anti-tumor necrosis factors (TNF) and the general population. METHODS: In this Swedish cohort study, treatment episodes were identified from nationwide health registers. We used Cox regression with propensity score-matched cohorts to estimate hazard ratios (HRs) for incident serious infections, defined as infections requiring hospital admission. RESULTS: During 1376 treatment-episodes in Crohn's disease, the rate of serious infections per 100 person-years (PY) was 5.18 (95%CI=3.98-6.63) with vedolizumab vs 3.54 (95%CI=2.50-4.85) with anti-TNF; HR=1.72 (95%CI=1.12-2.65), partly explained by more gastrointestinal infections. Compared to the rate of 0.75/100 PYs (95%CI=0.59-0.92) in a matched general population cohort, vedolizumab demonstrated higher risk (HR=7.00; 95%CI=5.04-9.72).During 1294 treatment-episodes in ulcerative colitis, the corresponding rates were 3.74/100 PYs (95%CI=2.66-5.11) with vedolizumab vs 3.42/100 PYs (95%CI=2.31-4.89) with anti-TNF; HR=0.80 (95%CI=0.47-1.36) during the initial 1.1 years and HR=2.03 (95%CI=0.65-6.32) after 1.1 years (truncated due to non-proportional hazards). Pneumonia accounted for 40% of all infections among anti-TNF whereas no case was observed among vedolizumab episodes. Compared to the rate of 0.69/100 PYs (95%CI=0.53-0.87) in a matched general population cohort, vedolizumab showed an HR of 5.45 (95%CI=3.67-8.11). CONCLUSIONS: Vedolizumab was associated with increased risks of serious infections compared to anti-TNF in Crohn's disease, but not in ulcerative colitis. Nonetheless, the panorama of serious infections seemed to differ between the drugs. Our findings underscore the importance of clinical awareness of infections and the safety profile of the two therapies.

Risk Factors Associated with Asthma Control and Quality of Life in Patients with Mild Asthma Without Preventer Treatment, a Cross-Sectional Study.

Purpose: To study risk factors for uncontrolled asthma and insufficient quality of life (QoL) in patients with mild asthma, ie those without preventer treatment. Patients and Methods: Patients aged 18-75 years with a doctor's diagnosis of asthma randomly selected from primary and secondary care in Sweden. Mild asthma was defined as self-reported current asthma and no preventer treatment. Data were collected from self-completed questionnaires in 2012 and 2015. Well-controlled asthma was defined as Asthma Control Test (ACT) ≥20 points and no exacerbation and uncontrolled asthma as ACT<20 points and/or at least one exacerbation in the previous six months. QoL was measured by the Mini Asthma Quality of Life Questionnaire (Mini-AQLQ), where a total mean score of ≥ 6 indicated sufficient and < 6 insufficient QoL. Multivariate logistic regression analyses were performed using asthma control and Mini-AQLQ as dependent variables. Asthma control was dichotomized as controlled and uncontrolled asthma and the Mini-AQLQ as sufficient QoL (mean score ≥6) and insufficient QoL (mean score <6). Results: Among 298 patients, 26% had uncontrolled asthma, 40% insufficient QoL and 20% both uncontrolled asthma and insufficient QoL. Age ≥60 years, obesity, daily smoking, rhinitis and inadequate knowledge of asthma self-management were independently associated with poor asthma control. Factors independently associated with insufficient QoL were age ≥60 years, overweight, obesity, rhinitis, sinusitis and inadequate knowledge of asthma self-management. Age ≥60 years, obesity, rhinitis and inadequate knowledge of asthma self-management were independently associated with both uncontrolled asthma and insufficient QoL. Conclusion: Among asthma patients without preventer medication, 26% had uncontrolled asthma and 40% had insufficient asthma-related QoL. Older age, obesity, and rhinitis were risk factors for both poor asthma control and a reduced QoL, but having good knowledge of asthma self-management reduced this risk. Our findings suggest that this group of patients requires further attention and follow-up.

Many patients with little symptoms of asthma do not take asthma-preventer medication as their asthma is recognized as mild. Still, it is well-known that in this group there are patients with frequent and severe symptoms and acute attacks of asthma, defined as uncontrolled asthma. Quality of life (QoL) is less studied in these patients. Our aim was to study patient characteristics and factors with a higher risk for uncontrolled asthma and insufficient QoL in patients with mild asthma. We studied patients with asthma diagnosis 18­75 of age in Sweden who reported asthma and no asthma preventer medication. They answered questionnaires about characteristics, knowledge of asthma, asthma symptoms, acute asthma attacks and QoL. A test for asthma symptom control, the Asthma Control Test (ACT), was answered, where 20 points or more meant good asthma symptom control. Patients were regarded as having uncontrolled asthma if they had less than 20 points and/or at least one acute asthma attack the last six months. QoL was measured by the Mini Asthma Quality of Life Questionnaire. A mean score of 6 or more meant sufficient and less than 6 insufficient QoL. Of the 298 patients, 26% had uncontrolled asthma, 40% had insufficient QoL and 20% had both. Patients with risk for both uncontrolled asthma and insufficient QoL were 60 years and over, with obesity, rhinitis and those who reported insufficient knowledge of how to handle asthma. Our results suggest that patients with mild asthma need more attention, better management and follow-ups.

Changing diagnostic criteria for gestational diabetes (CDC4G) in Sweden: A stepped wedge cluster randomised trial.

BACKGROUND: The World Health Organisation (WHO) 2013 diagnostic criteria for gestational diabetes mellitus (GDM) has been criticised due to the limited evidence of benefits on pregnancy outcomes in different populations when switching from previously higher glycemic thresholds to the lower WHO-2013 diagnostic criteria. The aim of this study was to determine whether the switch from previous Swedish (SWE-GDM) to the WHO-2013 GDM criteria in Sweden following risk factor-based screening improves pregnancy outcomes. METHODS AND FINDINGS: A stepped wedge cluster randomised trial was performed between January 1 and December 31, 2018 in 11 clusters (17 delivery units) across Sweden, including all pregnancies under care and excluding preexisting diabetes, gastric bypass surgery, or multifetal pregnancies from the analysis. After implementation of uniform clinical and laboratory guidelines, a number of clusters were randomised to intervention (switch to WHO-2013 GDM criteria) each month from February to November 2018. The primary outcome was large for gestational age (LGA, defined as birth weight >90th percentile). Other secondary and prespecified outcomes included maternal and neonatal birth complications. Primary analysis was by modified intention to treat (mITT), excluding 3 clusters that were randomised before study start but were unable to implement the intervention. Prespecified subgroup analysis was undertaken among those discordant for the definition of GDM. Multilevel mixed regression models were used to compare outcome LGA between WHO-2013 and SWE-GDM groups adjusted for clusters, time periods, and potential confounders. Multiple imputation was used for missing potential confounding variables. In the mITT analysis, 47 080 pregnancies were included with 6 882 (14.6%) oral glucose tolerance tests (OGTTs) performed. The GDM prevalence increased from 595/22 797 (2.6%) to 1 591/24 283 (6.6%) after the intervention. In the mITT population, the switch was associated with no change in primary outcome LGA (2 790/24 209 (11.5%) versus 2 584/22 707 (11.4%)) producing an adjusted risk ratio (aRR) of 0.97 (95% confidence interval 0.91 to 1.02, p = 0.26). In the subgroup, the prevalence of LGA was 273/956 (28.8%) before and 278/1 239 (22.5%) after the switch, aRR 0.87 (95% CI 0.75 to 1.01, p = 0.076). No serious events were reported. Potential limitations of this trial are mainly due to the trial design, including failure to adhere to guidelines within and between the clusters and influences of unidentified temporal variations. CONCLUSIONS: In this study, implementing the WHO-2013 criteria in Sweden with risk factor-based screening did not significantly reduce LGA prevalence defined as birth weight >90th percentile, in the total population, or in the subgroup discordant for the definition of GDM. Future studies are needed to evaluate the effects of treating different glucose thresholds during pregnancy in different populations, with different screening strategies and clinical management guidelines, to optimise women's and children's health in the short and long term. TRIAL REGISTRATION: The trial is registered with ISRCTN (41918550).

The Increased Burden of Morbidity Over the Life-Course Among Patients with COPD: A Register-Based Cohort Study in Sweden.

Purpose: Patients with a diagnosis of chronic obstructive pulmonary disease (COPD) often have other chronic disorders. This study aims to describe the life-course pattern of morbidity in patients with COPD. Patients and Methods: Among all residents aged 50-90 years in Sweden in 1997, people with a hospital COPD diagnosis were identified using Swedish national registers (1997-2018). Each patient with COPD was matched by sex, birthyear and county of residency with up to five COPD-free controls. Other chronic disease diagnoses were identified during 1987-2018. Conditional logistic regression calculated risk of diseases diagnosed prior to first COPD diagnosis, producing odds ratios (OR) and 95% confidence intervals (95% CI). Cox regression estimated risk of diagnoses after first COPD diagnosis, producing hazard ratios (HR) and 95% CI. Results: Among 2,706,814 individuals, 225,159 (8.3%) had COPD. The nested case-control sample included 223,945 COPD-cases with 1,062,731 controls. Prior to first COPD diagnosis, future COPD patients had higher risks than controls for most examined conditions. Highest risks were seen for chronic heart failure (OR = 3.25, 3.20-3.30), peripheral arterial disease (OR = 3.12, 3.06-3.18) and lung cancer (OR = 12.73, 12.12-13.37). Following the COPD diagnosis, individuals with COPD had higher risks of most conditions than individuals without COPD. Chronic heart failure (HR = 3.50, 3.46-3.53), osteoporosis (HR = 3.35, 3.30-3.42), depression (HR = 2.58, 2.53-2.64) and lung cancer (HR = 6.04, 5.90-6.18) predominated. The risk of vascular dementia was increased after COPD diagnosis (HR = 1.53, 1.48-1.58) but not Alzheimer's disease. Conclusion: Accumulation of chronic morbidity may precede COPD. Following the diagnosis, an increased burden of cardiovascular disease and cancer is to be expected, but subsequent depression, osteoporosis, and vascular dementia should also be noted. Management strategies for patients with COPD should consider the higher-than-average risk of multimorbidity.

Hospital-treated infections and subsequent Parkinson's disease risk: a register-based sibling comparison study.

Serious infections may result in greater risk of Parkinson's disease. However, high-quality cohort studies focusing on a potential causal role of different types and sites of infection are lacking. Gastrointestinal infections are of a particular interest due to growing evidence implicating gut dysbiosis in Parkinson's disease aetiology. This population-based cohort study used the Swedish Total Population Register to identify individuals born during 1944-77 and resident in Sweden between 1990 and 2018 (N = 3 698 319). Hospital-treated infections at ages 21-30 and 31-40 years were identified from the National Patient Register. Participants were followed to identify Parkinson's disease diagnoses from age 41 years up to December 31, 2018, when the oldest individual reached 75 years. Cox regression with a sibling comparison design to tackle familial genetic and environmental confounding was used to derive hazard ratios and 95% confidence intervals for each infection site, type, or any infections at ages 21-30 and 31-40 years. During a median follow-up of 15.4 years, 8815 unique Parkinson's disease diagnoses were accrued, with a crude rate of 17.3 (95% confidence interval 17.0, 17.7) per 100 000 person-years. After controlling for shared familial factors, hospital-treated gastrointestinal and respiratory infections between 21 and 30 years of age were associated with a greater risk of Parkinson's disease [hazard ratios 1.35 (95% confidence interval: 1.05, 1.75) and 1.45 (95% confidence interval: 1.08, 1.95), respectively]; no association was found for any infections at age 31-40 [hazard ratio 1.05 (95% confidence interval: 0.93, 1.19)]. After adjustment, no statistically significant associations were observed for other sites including genitourinary and skin. These findings suggest that hospital-treated infections of the gastrointestinal tract and lungs, both of which may have an influence on the gut microbiome, by age 30 years may be risk factors for Parkinson's disease.

Spondyloarthritis in first-degree relatives and spouses of patients with inflammatory bowel disease: A nationwide population-based cohort study from Sweden.

BACKGROUND AND AIMS: Register-based research suggests a shared pathophysiology between inflammatory bowel disease [IBD] and spondyloarthritis [SpA], but the role of familial [genetic and environmental] factors in this shared susceptibility is largely unknown. We compared the risk of SpA in first-degree relatives [FDRs] and spouses of IBD patients with FDRs and spouses of matched population-based reference individuals. METHODS: We identified 147,080 FDRs and 25,945 spouses of patients with incident IBD [N=39,203] during 2006-2016 and 1,453,429 FDRs and 258,098 spouses of matched reference individuals [N=390,490], by linking nationwide Swedish registers and gastrointestinal biopsy data. Study participants were followed 1987-2017. Cox regression was used to estimate hazard ratios [HRs] of SpA. RESULTS: During follow-up, 2,430 FDRs of IBD patients [6.5/10,000 person-years] and 17,761 FDRs of reference individuals [4.8/10,000 person-years] were diagnosed with SpA, corresponding to an HR of 1.35 [95%CI:1.29,1.41]. In subgroup analyses, the increased risk of SpA was most pronounced in FDRs of Crohn's disease patients [HR=1.44; 95%CI:1.34,1.56] and of IBD patients aged <18 years at diagnosis [HR=1.46; 95%CI: 1.27,1.68]. IBD patient's spouses also had a higher SpA rate than reference individuals' spouses, but the difference was less pronounced [4.3 vs. 3.5/10,000 person-years; HR=1.22; 95%CI:1.09,1.37]. No subgroup-specific risk pattern was identified among spouses. CONCLUSIONS: The observed shared familial risks between IBD and SpA support shared genetic factors in their pathogenesis. However, spouses of IBD patients were also at increased risk for SpA, reflecting the influence of environmental exposures or similarities in health-seeking patterns.

Expert opinion on the use of contraception in people with multiple sclerosis.

BACKGROUND: Current guidance on the selection of appropriate contraception for people with multiple sclerosis (PwMS) is lacking. OBJECTIVE: To address this gap, an expert-led consensus program developed recommendations to support clinicians in discussing family planning and contraception with women and men with multiple sclerosis (MS). METHODS: A multidisciplinary steering committee (SC) of 13 international clinical experts led the program, supported by an extended faculty of 32 experts representing 18 countries. A modified Delphi methodology was used for decision-making and consensus-building. The SC drafted 15 clinical questions focused on patient-centered care, selection of contraception, and timing of stopping/starting contraception and disease-modifying therapies (DMTs). Statements addressing each question were drafted based on evaluation of published evidence and the experts' clinical experience. Consensus was reached if ⩾75% of respondents agreed (scoring 7-9 on a 9-point scale) with each recommendation. RESULTS: Consensus was reached on 24 of 25 proposed recommendations, including how and when to discuss contraception, types and safety of contraceptives, and how to evaluate the most appropriate contraceptive options for specific patient groups, including those with significant disability or being treated with DMTs. CONCLUSION: These expert recommendations provide the first practical, relevant, and comprehensive guidance for clinicians on the selection of contraception in PwMS.

Viable cartilage allograft outperforms existing treatments for focal knee cartilage defects.

PURPOSE: Viable cartilage allograft (VCA) is a cartilage tissue matrix that contains cryopreserved viable allogeneic cartilage fibres. This study aimed to assess safety and benefits in treating focal knee cartilage defects with VCA. We hypothesized that VCA is a safe single-stage procedure in isolated chondral defects. METHOD: In vitro analysis, in vivo studies and a prospective case series were performed. VCA was evaluated in a goat cartilage repair model. Symptomatic International Cartilage Repair Society grade 3/4A lesions of the femoral condyle or patella were implanted with VCA. International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome (KOOS) subscales, Lysholm, Short Form-12, Visual Analog Scale and pain frequency levels were assessed. Radiographic and magnetic resonance imaging (MRI) was performed at regular intervals postoperatively. Data were analysed by statisticians to determine the power and significance of the results. RESULTS: The goat study confirmed that VCA is effective for cartilage repair. Twenty patients were implanted; the mean age was 28.1 (16-56), the mean body mass index (BMI) was 27.9 ± 5.6 and the mean follow-up was 24.1 months (range = 12.0-36.0 months). Lesions were in either the femoral condyle (7) or patella (13). Lesion sizes ranged from 1.5 to 6.0 cm2 (mean = 4.58 cm2 ). Outcome scores improved from preoperative baseline (POB): IKDC (78.2), Lysholm (89.0), KOOS: Pain (95.8), Symptoms (86.3), ADL (87.8), Sports (85.0) and QOL (75.0). MRI imaging demonstrated excellent osteochondral allograft assimilation. Second-look arthroscopy (two patients) demonstrated complete fill and incorporation (Brittberg scores 11/12). Functional scores were maintained at 24 (M): IKDC (86.24 ± 17.2), Lysholm (87.23 ± 15.0), KOOS: Pain (91.72 ± 17.3), Symptoms (84.92 ± 16.1), ADLs (93.80 ± 16.1), Sports (84.45 ± 27.7), QOL (81.30 ± 20.8). CONCLUSION: VCA is an off-the-shelf, single-stage, conformable allogeneic graft that treats chondral defects with no additional fixation. Preclinical and short-term prospective clinical studies show that VCA can safely treat chondral defects with potential advantages to existing options. LEVEL OF EVIDENCE: Level IV study.

Pharmacological treatment of asthma in Sweden from 2005 to 2015.

OBJECTIVE: Despite access to effective therapies many asthma patients still do not have well-controlled disease. This is possibly related to underuse of inhaled corticosteroids (ICS) and overuse of short-acting ß2-agonists (SABA). Our aim was to investigate longitudinal trends and associated factors in asthma treatment. METHODS: Two separate cohorts of adults with physician-diagnosed asthma were randomly selected from 14 hospitals and 56 primary health centers in Sweden in 2005 (n = 1182) and 2015 (n = 1225). Information about symptoms, maintenance treatment, and use of rescue medication was collected by questionnaires. Associations between treatment and sex, age, smoking, education, body mass index (BMI), physical activity, allergic asthma, and symptom control were analyzed using Pearson's chi2-test. Odds ratios (ORs) were calculated using logistic regression. RESULTS: Maintenance treatment with ICS together with long-acting ß2-agonists (LABA) and/or montelukast increased from 39.2% to 44.2% (p = 0.012). The use of ICS + LABA as-needed increased (11.1-18.9%, p < 0.001), while SABA use decreased (46.4- 41.8%, p = 0.023). Regular treatment with ICS did not change notably (54.2-57.2%, p = 0.14). Older age, former smoking, and poor symptom control were related to treatment with ICS + LABA/montelukast. In 2015, 22.7% reported daily use of SABA. A higher step of maintenance treatment, older age, obesity, shorter education, current smoking, allergic asthma, low or very high physical activity, and a history of exacerbations were associated with daily SABA use. CONCLUSIONS: The use of ICS + LABA both for maintenance treatment and symptom relief has increased over time. Despite this, the problem of low use of ICS and high use of SABA remains.

Association between dementia risk and ulcerative colitis, with and without colectomy: a Swedish population-based register study.

OBJECTIVE: This study aims to investigate the association of ulcerative colitis (UC) with all-cause dementia and assess differences in those with and without a total colectomy. DESIGN, SETTING AND PARTICIPANTS: This Swedish prospective register-based study comprised 4.8 million individuals aged at least 59 years between 1964 and 2018 with the linkage of several Swedish national registers. PRIMARY AND SECONDARY OUTCOME MEASURES: Individuals with dementia were defined according to International Classification of Diseases diagnostic codes and Anatomical Therapeutic Classification codes for medication prescriptions. Fitting Cox hazards models, the risk of developing all-cause dementia in individuals with and without UC was estimated. Further, we compared the risk of all-cause dementia among those with and without a colectomy. RESULTS: Among 4 821 488 individuals (52.6% females) followed for 84.1 million person-years between 1964 and 2018, the incidence rate of all-cause dementia was 63.90 (63.73-64.07) events per 10 000 person-years in individuals without UC, 94.80 (92.04-97.64) among those with UC, 95.01 (92.25-97.86) in those with UC but without colectomy and 63.42 (40.92-98.31) in those with UC and a colectomy. Adjusted Cox models showed an increased all-cause dementia risk in individuals with UC (HR 1.07, 95% CI 1.04 to 1.10). We found no differences between unexposed individuals and those with UC and a colectomy (HR 0.89, 95% CI 0.57 to 1.38). CONCLUSION: The findings are consistent with previous evidence suggesting a slightly increased dementia risk among individuals with UC. This study provided no evidence of further risk increase of dementia among those who had a colectomy.

Study protocol for a randomized controlled trial with rituximab for psychotic disorder in adults (RCT-Rits).

BACKGROUND: The role of inflammation in the aetiology of schizophrenia has gained wide attention and research on the association shows an exponential growth in the last 15 years. Autoimmune diseases and severe infections are risk factors for the later development of schizophrenia, elevated inflammatory markers in childhood or adolescence are associated with a greater risk of schizophrenia in adulthood, individuals with schizophrenia have increased levels of pro-inflammatory cytokines compared to healthy controls, and autoimmune diseases are overrepresented in schizophrenia. However, treatments with anti-inflammatory agents are so far of doubtful clinical relevance. The primary objective of this study is to test whether the monoclonal antibody rituximab, directed against the B-cell antigen CD20 ameliorates psychotic symptoms in adults with schizophrenia or schizoaffective disorder and to examine potential mechanisms. A secondary objective is to examine characteristics of inflammation-associated psychosis and to identify pre-treatment biochemical characteristics of rituximab responders. A third objective is to interview a subset of patients and informants on their experiences of the trial to obtain insights that rating scales may not capture. METHODS: A proof-of-concept study employing a randomised, parallel-group, double-blind, placebo-controlled design testing the effect of B-cell depletion in patients with psychosis. 120 participants with a diagnosis of schizophrenia spectrum disorders (SSD) (ICD-10 codes F20, F25) will receive either one intravenous infusion of rituximab (1000 mg) or saline. Psychiatric measures and blood samples will be collected at baseline, week 12, and week 24 post-infusion. Brief assessments will also be made in weeks 2 and 7. Neuroimaging and lumbar puncture, both optional, will be performed at baseline and endpoints. Approximately 40 of the patients and their informants will be interviewed for qualitative analyses on the perceived changes in well-being and emotional qualities, in addition to their views on the research. DISCUSSION: This is the first RCT investigating add-on treatment with rituximab in unselected SSD patients. If the treatment is helpful, it may transform the treatment of patients with psychotic disorders. It may also heighten the awareness of immune-psychiatric disorders and reduce stigma. TRIAL REGISTRATION: NCT05622201, EudraCT-nr 2022-000220-37 version 2.1. registered 14th of October 2022.

Development and Validation of an XGBoost-Algorithm-Powered Survival Model for Predicting In-Hospital Mortality Based on 545,388 Isolated Severe Traumatic Brain Injury Patients from the TQIP Database.

BACKGROUND: Traumatic brain injury (TBI) represents a significant global health issue; the traditional tools such as the Glasgow Coma Scale (GCS) and Abbreviated Injury Scale (AIS) which have been used for injury severity grading, struggle to capture outcomes after TBI. AIM AND METHODS: This paper aims to implement extreme gradient boosting (XGBoost), a powerful machine learning algorithm that combines the predictions of multiple weak models to create a strong predictive model with high accuracy and efficiency, in order to develop and validate a predictive model for in-hospital mortality in patients with isolated severe traumatic brain injury and to identify the most influential predictors. In total, 545,388 patients from the 2013-2021 American College of Surgeons Trauma Quality Improvement Program (TQIP) database were included in the current study, with 80% of the patients used for model training and 20% of the patients for the final model test. The primary outcome of the study was in-hospital mortality. Predictors were patients' demographics, admission status, as well as comorbidities, and clinical characteristics. Penalized Cox regression models were used to investigate the associations between the survival outcomes and the predictors and select the best predictors. An extreme gradient boosting (XGBoost)-powered Cox regression model was then used to predict the survival outcome. The performance of the models was evaluated using the Harrell's concordance index (C-index). The time-dependent area under the receiver operating characteristic curve (AUC) was used to evaluate the dynamic cumulative performance of the models. The importance of the predictors in the final prediction model was evaluated using the Shapley additive explanations (SHAP) value. RESULTS: On average, the final XGBoost-powered Cox regression model performed at an acceptable level for patients with a length of stay up to 250 days (mean time-dependent AUC = 0.713) in the test dataset. However, for patients with a length of stay between 20 and 213 days, the performance of the model was relatively poor (time-dependent AUC < 0.7). When limited to patients with a length of stay ≤20 days, which accounts for 95.4% of all the patients, the model achieved an excellent performance (mean time-dependent AUC = 0.813). When further limited to patients with a length of stay ≤5 days, which accounts for two-thirds of all the patients, the model achieved an outstanding performance (mean time-dependent AUC = 0.917). CONCLUSION: The XGBoost-powered Cox regression model can achieve an outstanding predictive ability for in-hospital mortality during the first 5 days, primarily based on the severity of the injury, the GCS on admission, and the patient's age. These variables continue to demonstrate an excellent predictive ability up to 20 days after admission, a period of care that accounts for over 95% of severe TBI patients. Past 20 days of care, other factors appear to be the primary drivers of in-hospital mortality, indicating a potential window of opportunity for improving outcomes.

Limosilactobacillus reuteri DSM 17938 supplementation and SARS-CoV-2 specific antibody response in healthy adults: a randomized, triple-blinded, placebo-controlled trial.

Studies have shown that probiotics can decrease the symptoms of respiratory tract infections as well as increase antibody responses following certain vaccinations. We examined the effect of probiotic supplementation on anti-SARS-CoV-2 specific antibody responses upon SARS-CoV-2 infection as well as after COVID-19 vaccination. In this randomized, triple-blinded, placebo-controlled intervention study with a parallel design, 159 healthy adults without prior SARS-CoV-2 infection or COVID-19 vaccination and any known risk factors for severe COVID-19 were randomly allocated into two study arms. The active treatment arm consumed a probiotic product containing a minimum of 1 × 108 colony-forming units of Limosilactobacillus reuteri DSM 17938 + 10 µg vitamin D3 twice daily for 6 months. The placebo arm consumed identical tablets containing only 10 µg vitamin D3. Anti-SARS-CoV-2 specific antibodies and virus neutralizing antibody titers were analyzed from blood samples collected at baseline, after 3 months, and after 6 months. Differences in serum antibody titers between the two study arms were tested with independent t-test using log-transformed values. In the intention-to-treat (ITT) analysis, SARS-CoV-2 infected individuals in the active treatment arm (n = 6) tended to have higher serum anti-spike IgG (609 [168-1480] BAU/ml vs 111 [36.1-1210] BAU/ml, p = 0.080) and anti-receptor binding domain (RBD) IgG (928 [212-3449] BAU/ml vs (83.7 [22.8-2094] BAU/ml, p = 0.066) levels than individuals in the placebo arm (n = 6). Considering individuals who were fully vaccinated with mRNA-based COVID-19 vaccines, the active treatment arm (n = 10) exhibited significantly higher serum levels of anti-RBD IgA (135 [32.9-976] BAU/ml vs 61.3 [26.7-97.1] BAU/ml, p = 0.036) than the placebo arm (n = 7) >28 days postvaccination. Supplementation with specific probiotics might improve the long-term efficacy of mRNA-based COVID-19 vaccines via enhanced IgA response.

Diagnostic spirometry in COPD is increasing, a comparison of two Swedish cohorts.

Spirometry should be used to confirm a diagnosis of chronic obstructive pulmonary disease (COPD). This test is not always performed, leading to possible misdiagnosis. We investigated whether the proportion of patients with diagnostic spirometry has increased over time as well as factors associated with omitted or incorrectly interpreted spirometry. Data from medical reviews and a questionnaire from primary and secondary care patients with a doctors' diagnosis of COPD between 2004 and 2010 were collected. Data were compared with a COPD cohort diagnosed between 2000 and 2003. Among 703 patients with a first diagnosis of COPD between 2004 and 2010, 88% had a diagnostic spirometry, compared with 59% (p < 0.001) in the previous cohort. Factors associated with not having diagnostic spirometry were current smoking (OR 2.21; 95% CI 1.36-3.60), low educational level (OR 1.81; 1.09-3.02) and management in primary care (OR 2.28; 1.02-5.14). The correct interpretation of spirometry results increased (75% vs 82%; p = 0.010). Among patients with a repeated spirometry, 94% had a persistent FEV1/FVC or FEV1/VC ratio <0.70.

Factors Associated with the Non-Exacerbator Phenotype of Chronic Obstructive Pulmonary Disease.

Background: Patients with chronic obstructive pulmonary disease (COPD) and no exacerbations may need less maintenance treatment and follow-up. The aim was to identify factors associated with a non-exacerbator COPD phenotype. Methods: Cross-sectional analysis of 1354 patients from primary and secondary care, with a doctor's diagnosis of COPD. In 2014, data on demographics, exacerbation frequency and symptoms using COPD Assessment Test (CAT) were collected using questionnaires and on spirometry and comorbid conditions by record review. The non-exacerbator phenotype was defined as having reported no exacerbations the previous six months. Multivariable logistic regression with the non-exacerbator phenotype as dependent variable was performed, including stratification and interaction analyses by sex. Results: The non-exacerbator phenotype was found in 891 (66%) patients and was independently associated with COPD stage 1 (OR [95% CI] 5.72 [3.30-9.92]), stage 2 (3.42 [2.13-5.51]) and stage 3 (2.38 [1.46-3.88]) compared with stage 4, and with CAT score <10 (3.35 [2.34-4.80]). Chronic bronchitis and underweight were inversely associated with the non-exacerbator phenotype (0.47 [0.28-0.79]) and (0.68 [0.48-0.97]), respectively. The proportion of non-exacerbators was higher among patients with no maintenance treatment or a single bronchodilator. The association of COPD stage 1 compared with stage 4 with the non-exacerbator phenotype was stronger in men (p for interaction 0.048). In women, underweight and obesity were both inversely associated with the non-exacerbator phenotype (p for interaction 0.033 and 0.046 respectively), and in men heart failure was inversely associated with the non-exacerbator phenotype (p for interaction 0.030). Conclusion: The non-exacerbator phenotype is common, especially in patients with no maintenance treatment or a single bronchodilator, and is characterized by preserved lung function, low symptom burden, and by absence of chronic bronchitis, underweight and obesity and heart failure. We suggest these patients may need less treatment and follow-up, but that management of comorbid conditions is important to avoid exacerbations.

Myopia in late adolescence and subsequent multiple sclerosis among men.

BACKGROUND: Risk factors such as low vitamin D level has been implicated in the etiology of multiple sclerosis (MS) and may be relevant to myopia, such that there may be an association between myopia and MS. METHODS: Using linked Swedish national register data, we conducted a cohort study of men who were born in Sweden between 1950 and 1992, lived in Sweden between 1990 and 2018, and enrolled in military conscription assessment (n = 1,847,754). Myopia was defined based on the spherical equivalent refraction measured at conscription assessment, around age 18 years. Multiple sclerosis was identified using the Patient Register. Cox regression produced hazard ratios (HR) with 95% confidence intervals (95% CI), with adjustment for demographic and childhood socioeconomic characteristics and residential region. Due to changes in the assessment of refractive error, the analysis was stratified into two groups by the year of conscription assessment: 1969-1997 and 1997-2010. RESULTS: Among 1,559,859 individuals during a maximum of 48 years of follow-up from age 20 to 68 years (44,715,603 person-years), there were 3,134 MS events, and the incidence rate 7.0 (95% CI [6.8, 7.3] per 100,000 person-years). Among individuals with conscription assessments during 1997-2010, there were 380 MS events. There was no evidence of an association between myopia and MS, with HR 1.09 (95% CI 0.83, 1.43). Among individuals who underwent conscription assessment in 1969-1997, there were 2754 MS events. After adjusting for all covariates, there was no evidence of an association between myopia and MS (HR 0.99 [95% CI 0.91, 1.09]). CONCLUSION: Myopia in late adolescence is not associated with a subsequent raised risk of MS and thus there does not appear to be important shared risk factors.

Caregiving and changes in health-related behaviour.

Potential health risks for informal caregivers have been hypothesised to be partly related to adverse changes in health-related behaviour, but evidence is limited. We examined whether smoking, drinking, eating, physical activity or leisure pursuits change in relation to co-resident or out-of-home caregiving (for someone outside the household), and if associations differ by sex, educational attainment, and welfare state typology. We conducted a longitudinal study using six waves of the Survey of Health, Ageing and Retirement in Europe, collecting data repeatedly from 2004 to 2017 for adults aged 50 years and older living in 17 European countries (57,962 individuals). To control for measured and unmeasured within-individual time-invariant confounders, we used fixed effects logistic models to analyse the repeated measures of caregiving, behaviour and covariates and estimated odds ratios (OR) with 95% confidence intervals (95%CI). Among male participants, unhealthy eating increased while smoking decreased [ORs 1.26 (95%CI 1.01-1.58) and 0.53 (0.36-0.78), respectively] in survey waves in which they provided co-resident care, compared with the waves that they did not. Among female participants, there was little change in behaviour between waves with and without co-resident caregiving. When providing out-of-home care, lacks of physical activity and leisure pursuits declined. But in the same time, drinking increased both men and women, and especially among individuals with lower educational attainment and residing in non-Nordic countries. To conclude, overall, increased drinking when providing out-of-home care was most consistent, especially among individuals with lower educational attainment and residing in non-Nordic countries. Otherwise, the associations varied by the type of care, behaviour and population subgroups. These findings indicated that not all caregivers are susceptible to behavioural changes, and that not all behaviour may be involved similarly in linking caregiving to health risks. This opens possibilities to target specific behaviour and groups to prevent adverse changes in health behaviour in caregivers.

Previous pre-eclampsia, gestational diabetes mellitus and the risk of cardiovascular disease: A nested case-control study in Sweden.

OBJECTIVE: Pre-eclampsia and gestational diabetes mellitus (GDM) are two common pregnancy complications that affect birth outcomes and are associated with a long-term risk of cardiovascular disease (CVD). The aims of this study were to investigate if the pre-eclampsia association with CVD is independent of GDM and modified by body mass index (BMI) or GDM. DESIGN: Case-control study. SETTING: Sweden. POPULATION: Cases were women with a first CVD event between 1991 and 2008 and a previous pregnancy who were matched with controls without CVD (1:5) by year of birth, age and region of birth. METHODS: Conditional logistic regression was used to evaluate the associations of GDM, pre-eclampsia and maternal BMI with CVD adjusted for potential confounders and effect modifications with interaction tests. MAIN OUTCOME MEASURES: CVD. RESULTS: There were 2639 cases and 13 310 controls with complete data. Pre-eclampsia and GDM were independent risk factors for CVD (adjusted odds ratio [aOR] 2.59, 95% CI 2.12-3.17 and aOR 1.47, 95% CI 1.04-2.09, respectively). After stratifying by maternal BMI, the adjusted association of pre-eclampsia with CVD did not differ notably between BMI groups: normal weight (aOR 2.65, 95% CI 1.90-3.69), overweight (aOR 2.67, 95% CI 1.52-4.68) and obesity (aOR 3.03, 95% CI 0.74-12.4). Similar findings were seen when stratifying on GDM/non-GDM. CONCLUSIONS: Pre-eclampsia and GDM are independent risk factors for later CVD and having both during pregnancy is a major risk factor for later CVD. The association between pre-eclampsia and CVD is not modified by BMI. Effective CVD preventive programs for high-risk women are urgently needed in order to improve women's long-term health.