Immunoglobulin A nephropathy and ischemic heart disease: a nationwide population-based cohort study

Background Chronic kidney disease has been linked to cardiovascular disease and specifically ischemic heart disease (IHD), but large-scale population data in patients with immunoglobulin A nephropathy (IgAN) are missing. Objective To examine absolute and relative risks for IHD in patients with IgAN. Methods Population-based register-based cohort study in Sweden. We identified 3945 patients with biopsy-verified IgAN, and 19,272 age- and sex-matched reference individuals from the general population. To reduce residual confounding from genetic factors and early environmental factors we carried out secondary analyses, where we compared 3039 IgAN patients with 6729 siblings, whereas a spousal analysis consisted of 2377 married couples where one of the spouses had IgAN. Data on IHD and end-stage renal disease (ESRD) were retrieved from the nationwide Patient Register. Cox regression estimated hazard ratios (HRs) adjusted for matching variables, education, country of birth, cancer, diabetes mellitus, and other systemic inflammatory diseases. Results During a follow-up of 55,527 person-years (py; mean follow-up 14.1 years), 371 patients (9.4%) with IgAN developed IHD (6.7/1000 py), compared with 1070 (5.6%) in 287,677 py in reference individuals (3.7/1000 py). The corresponding adjusted HR was 1.86 (95%CI = 1.63–2.13), equivalent to one extra case of IHD per 34 IgAN patients followed-up for 10 years. HRs were similar in men and women with IgAN, but higher in the first year after diagnosis and in patients born outside the Nordic countries. Patients with IgAN were at increased risk of IHD also compared to siblings (HR = 2.07; 95%CI = 1.62–2-64) and spouses (HR = 1.91; 95%CI = 1.40–2.61). Conclusions In this nationwide population-based study, patients with IgAN were at an 86% increased risk of future IHD

Eccentric and Isometric Shoulder Rotation Strength and Range of Motion: Normative Values for Adolescent Competitive Tennis Players

[EN] The aim of this cross-sectional study was to investigate isometric internal rotation (IR), external rotation (ER), abduction (ABD), and eccentric external rotation (eccER) shoulder strength and rotational range of motion (ROM) in adolescent male and female competitive tennis players. Additional aims of the study were to provide a tennis-specific normative database based on a large sample of players to deepen the knowledge regarding shoulder strength and ROM for adolescent competitive tennis players, and to discuss differences based on sex, age, and level of play. Shoulder strength and ROM was assessed in 301 adolescent competitive tennis players, 176 boys and 125 girls with a mean age of 14.6 and 14.4 years, respectively. Outcome variables of interest were isometric IR and ER strength, ABD strength, eccER shoulder strength, intermuscular strength ratios ER/IR and eccER/IR, IR ROM, ER ROM, and total range of motion (TROM). A General Linear Model two-way ANOVA was used to analyze differences in sex, age, and level of play. The findings of this study demonstrated age, side, and sex differences in the shoulder isometric strength, the eccER strength and ROM in adolescent competitive tennis players. Furthermore, when strength was expressed as ratios ER/IR and eccER/IR both sexes showed a lower ratio for eccER/IR in national players (0.95 ± 0.22 and 0.95 ± 0.23) compared to regional players (1.01 ± 0.32 and 1.07 ± 0.29) for male and female players, respectively. In conclusion, this paper presents a tennis-specific normative database for shoulder rotation strength and ROM in adolescent male and female competitive players. The key points in this evaluation are strength values normalized to body mass, intermuscular ratios, and TROM.SIThis study was funded by the Swedish Naprapathic AssociationThe authors thank the Swedish Tennis Association, and they also want to express their gratitude to all regional and national players who participated in the SMASH study. A special thank you to Cecilia Palmqvist for coordinating the team. Clara Onell for back-office support. Thank you also to Filip Allerkrans, Kristin Haugland, Gustav Knutas, Jonathan Kull, Linnea Lindberg, Daniel Sjödin, Emilie Kristine Slatleim, and David Tveit for assistance in data collection

Acute central nervous system toxicity during treatment of pediatric acute lymphoblastic leukemia : phenotypes, risk factors and genotypes

Publisher Copyright: © 2022 Ferrata Storti Foundation Published under a CC BY-NC license.Central nervous system (CNS) toxicity is common at diagnosis and during treatment of pediatric acute lymphoblastic leukemia (ALL). We studied CNS toxicity in 1, 464 children aged 1.0-17.9 years, diagnosed with ALL and treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol. Genome-wide association studies, and a candidate single-nucleotide polymorphism (SNP; n=19) study were performed in 1, 166 patients. Findings were validated in an independent Australian cohort of children with ALL (n=797) in whom two phenotypes were evaluated: diverse CNS toxicities (n=103) and methotrexate-related CNS toxicity (n=48). In total, 135/1, 464 (9.2%) patients experienced CNS toxicity for a cumulative incidence of 8.7% (95% confidence interval: 7.31-10.20) at 12 months from diagnosis. Patients aged ≥10 years had a higher risk of CNS toxicity than had younger patients (16.3% vs. 7.4%; P<0.001). The most common CNS toxicities were posterior reversible encephalopathy syndrome (n=52, 43 with seizures), sinus venous thrombosis (n=28, 9 with seizures), and isolated seizures (n=16). The most significant SNP identified by the genome-wide association studies did not reach genomic significance (lowest P-value: 1.11x10-6), but several were annotated in genes regulating neuronal functions. In candidate SNP analysis, ATXN1 rs68082256, related to epilepsy, was associated with seizures in patients <10 years (P=0.01). ATXN1 rs68082256 was validated in the Australian cohort with diverse CNS toxicities (P=0.04). The role of ATXN1 as well as the novel SNP in neurotoxicity in pediatric ALL should be further explored.Peer reviewe

Feeling the zeros : Modeling individual responses, measured against time, to treatment of chronic myeloid leukemia.

In this paper response curves of patients with chronic myeloid leukemia are modeled using one and two-level censored models. Two-level models (also called mixed models) allow random effects and censored models are used to account for the large amount of values too small to be detected. The curves are observed from start of medication to a maximum of 36 months (9 measurement points). The data set is divided into two: "excellent responders" and "other". The "excellent responders" are modeled with a simple cubic censored model, and only one of the background variables measured at time zero ("blasts"), is found to be significant in explaining variation in the change curves, and even this with certain reservations. "Other" are modeled with a cubic two-level censored model and hemoglobin and eosinophile levels, as well as amount of blasts, are significant in explaining variation in this group

Sweden’s first Take-Home Naloxone program: participant characteristics, dose endpoints and predictors for overdose reversals

Abstract Background Opioid overdoses are a growing concern, particularly among people who inject drugs. Sweden, with a comparatively high proportion of drug-related mortality, introduced its first Take-Home Naloxone (THN) program in 2018, at the Stockholm needle and syringe program (NSP). In this study we compare THN participant characteristics regarding refills and overdose reversals as well as investigate predictors associated with number of reversals. We also investigate interventions performed in overdose situations and endpoints for naloxone doses. Methods This was a prospective open inclusion cohort study conducted between January 24th 2018 and March 31st 2022 at the Stockholm NSP. Participants received THN, free of charge, after a training session and provided data regarding drug use and overdose experiences. During refill visits, participants reported if the naloxone was used for overdose reversal and, if so, responded to a ten-item questionnaire which included stating whether the naloxone recipient was the participant themselves or somebody else. Questionnaire data was combined with NSP database demographic data. Zero-inflated Poisson regression was applied to analyse predictors for number of reported overdose reversals. Results Among study participants (n = 1,295), 66.5% stated opioids as their primary drug, and 61.4% and 81.0% had previous experience of a personal or witnessed overdose, respectively. Overall, 44.0% of participants reported a total of 1,625 overdose reversals and the victim was known to have survived in 95.6% of cases. Stimulant use (aIRR 1.26; 95% CI 1.01, 1.58), benzodiazepine use (aIRR 1.75; 95% CI 1.1, 2.78) and homelessness (aIRR 1.35; 95% CI 1.06, 1.73) were predictors associated with an increased number of reported overdose reversals. Mortality was higher among those who reported at least one overdose reversal (HR 3.4; 95% CI 2.2, 5.2). Conclusions An NSP’s existent framework can be utilised to effectively implement a THN program, provide basic training and reach numerous high-risk individuals. During the four-year study, THN participants reversed a sizeable number of potentially fatal overdoses, of which many were reported by participants whose primary drug was not opioids. Naloxone refill rate was high, indicating that participants were motivated to maintain a supply of naloxone in case of future overdose events

Are psychosocial work factors and work-home interference associated with time to first full return-to-work after sick leave due to common mental disorders?

Objective To (1) examine the time to first full return-to-work (RTW), and (2) investigate whether psychosocial work factors and work-home interference are associated with time to first full RTW after sick leave due to common mental disorders (CMDs). Methods The cohort study comprised 162 employees on sick leave due to CMDs participating in a two-armed cluster-randomised controlled trial in Sweden. Baseline data consisted of a web-based questionnaire and follow-up data of repeated text messages every fourth week for 12 months. The time to first full RTW was estimated using the Kaplan–Meier Estimator. Parametric Weibull survival models with interval-censored outcomes were used to determine associations between psychosocial work factors and work-home interference with time to first full RTW. In a post hoc analysis, time-interval differences in associations for 0– ≤ 6- versus &gt; 6–12 months were tested. Results During the 12-month follow-up, n = 131 (80.9%) reported a first full RTW. The median time to this RTW was 16 weeks (95% CI 12; 20). High psychological job demands, high emotional job demands, high work-to-home interference (WHI), and low social job support were independently associated with a longer time to first full RTW. Time-interval differences were found for job control and emotional job demands. Conclusions Psychosocial work demands and WHI are associated with a longer time to RTW after sick leave due to CMDs. Work organisations and rehabilitation practices should include accommodations for high psychological and emotional job demands during RTW, as well as pay attention to the risk of spill-over of high job demands into employees’ private lives

Evaluation of Whole Brain Radiotherapy among Lung Cancer Patients with Brain Metastases in Relation to Health Care Level and Survival

Whole-brain radiotherapy (WBRT) as a treatment for brain metastases has been questioned over the last years. This study aimed to evaluate health care levels and survival after WBRT in a cohort of lung cancer patients with brain metastases receiving WBRT in Stockholm, Sweden, from 2008 to 2019 (n = 384). If the patients were able to come home again was estimated using logistic regression and odds ratios (OR) and survival by using Cox regression. The median age in the cohort was 65.6 years, the median survival following WBRT was 2.4 months (interquartile range (IQR) 1.2&ndash;6.2 months), and 84 (22%) patients were not able to come home after treatment. Significantly more males could come home again after WBRT compared to women (OR = 0.37, 95%CI 0.20&ndash;0.68). Patients with performance status scores WHO 3&ndash;4 had a median survival of 1.0 months, hazard ratio (HR) = 4.69 (95%CI 3.31&ndash;6.64) versus WHO score 0&ndash;1. Patients admitted to a palliative ward before WBRT had a median survival of 0.85 months, HR = 2.26 (95%CI 1.53&ndash;3.34) versus being at home. In conclusion, patients treated with WBRT had a short median survival and 20% could not be discharged from the hospital following treatment. Significantly more women did not come home again

Immunoglobulin A nephropathy and ischemic heart disease : a nationwide population-based cohort study

Background: Chronic kidney disease has been linked to cardiovascular disease and specifically ischemic heart disease (IHD), but large-scale population data in patients with immunoglobulin A nephropathy (IgAN) are missing. Objective: To examine absolute and relative risks for IHD in patients with IgAN. Methods: Population-based register-based cohort study in Sweden. We identified 3945 patients with biopsy-verified IgAN, and 19,272 age- and sex-matched reference individuals from the general population. To reduce residual confounding from genetic factors and early environmental factors we carried out secondary analyses, where we compared 3039 IgAN patients with 6729 siblings, whereas a spousal analysis consisted of 2377 married couples where one of the spouses had IgAN. Data on IHD and end-stage renal disease (ESRD) were retrieved from the nationwide Patient Register. Cox regression estimated hazard ratios (HRs) adjusted for matching variables, education, country of birth, cancer, diabetes mellitus, and other systemic inflammatory diseases. Results: During a follow-up of 55,527 person-years (py; mean follow-up 14.1 years), 371 patients (9.4%) with IgAN developed IHD (6.7/1000 py), compared with 1070 (5.6%) in 287,677 py in reference individuals (3.7/1000 py). The corresponding adjusted HR was 1.86 (95%CI = 1.63-2.13), equivalent to one extra case of IHD per 34 IgAN patients followed-up for 10 years. HRs were similar in men and women with IgAN, but higher in the first year after diagnosis and in patients born outside the Nordic countries. Patients with IgAN were at increased risk of IHD also compared to siblings (HR = 2.07; 95%CI = 1.62-2-64) and spouses (HR = 1.91; 95%CI = 1.40-2.61). Conclusions: In this nationwide population-based study, patients with IgAN were at an 86% increased risk of future IHD