Matched Control Population Research Articles

Influence of therapy exposures on specific late morbidities, prescription drug purchases, and mortality in aging male survivors of childhood cancer: A registry-based study.

Childhood cancer treatments predispose to late health problems and premature death. Our aim was to use national registry data to study associations between cancer therapy exposures and late health outcomes in aging male childhood cancer survivors (CCS). The study comprised 200 male CCS (survival ≥5 years) treated with conventional cancer therapy at a single institution in 1964-2000 and 1000 matched population controls. Analyses involved registry-based data on prescription drug purchases, reimbursements for chronic conditions, hospital admissions, and deaths that occurred ≥5 years after the cancer diagnosis. Mean age of CCS was 45.4 years. Compared to population controls, CCS had a higher risk for hospital admissions due to cardiovascular diseases and late mortality, both of which increased after age 40 years. CCS also had a higher risk for purchases of antihypertensives and lipid-lowering drugs within the last year of the study. Heart radiation ≥10 Gy was associated with hospitalizations due to cardiovascular diseases (HR 4.14, 95%CI 1.81-9.48), purchases of antihypertensives (OR 3.05, 95%CI 1.32-7.36), and purchases of lipid-lowering drugs (OR 2.93, 95%CI 1.08-7.73). Testosterone deficiency developed typically during pediatric follow-up, and it was associated with testicular radiation ≥20 Gy (HR 41.2, 95%CI 15.4-110) but not with alkylating agents. Of patients treated with testicular radiation ≥20 Gy, 91% had purchased testosterone within the last year. Reassuringly, CCS had no excess risk for purchases of opioids, anxiolytics, antiepileptics, or antidepressants. These findings emphasize the need for risk-based follow-up. Middle-aged male CCS are at an increased risk of premature cardiovascular morbidity and excess mortality.

Diagnosis of Enlarged Vestibular Aqueduct Using Wideband Tympanometry.

Background: Wideband tympanometry (WBT) has the potential to distinguish various mechanical middle ear and inner ear pathologies noninvasively. This study investigated the diagnostic value of WBT in the diagnosis of enlarged vestibular aqueduct (EVA). Methods: The absorbance and resonance frequency (RF) of patients with EVA (40 ears, 25 patients) and matched population controls (39 ears, 28 subjects) were compared, alongside receiver operating characteristic (ROC) analysis. Correlations between VA width and RF were also examined. Results: Patients with EVA had higher absorbance at low frequencies (226-917 Hz) and lower absorbance at high frequencies (2520-4896 Hz) compared to controls. The RF of the EVA group was significantly lower versus controls (751 [391-1165] vs. 933 [628-1346] Hz). The ROC analysis revealed area under the curve values of 0.771 and 0.801, respectively, for absorbance and RF. RF had a sensitivity, specificity, positive predictive value, and negative predictive value of 74.4%, 82.5%, 76.7%, and 80.6%, respectively, for diagnosing EVA. In the EVA group, the VA midpoint width (r = -0.334) and VA petrous width (r = -0.402) both significantly correlated with RF. Conclusions: Our findings support the utility of WBT for diagnosing EVA, with RF as the optimal index used.

Hepatitis E virus prevalence among HIV-2 infected individuals in central Portugal.

To date, no studies comparing the prevalence of hepatitis E virus (HEV) infection between the general and human immunodeficiency virus 2 (HIV-2) populations are available. With the purpose of filling this gap, this prevalence was assessed in the HIV-2 population from central Portugal. HEV seropositivity was 19.4%, which did not differ significantly from that found in the matched control population, and was not associated with CD4 cell count, HIV-2 viral load, and geographic origin or travel history to regions considered highly endemic for HEV. The results suggest that HIV-2 is not a risk factor for HEV infection, neither for an increased occurrence of chronic HEV infection.

Refractive Error in Inherited Retinal Disease

PurposeInherited retinal dystrophies (IRDs) lead to significant vision impairment. Refractive errors (RE) are also associated with vision impairment and an increased risk of ocular comorbidities and may compound impairment caused by IRDs. Identifying the pattern of RE in IRDs may assist in the better management of patients with IRD and provide insights into understanding genetic associations with RE. The aim of this study was to investigate the patterns of RE in patients with IRD from three academic ophthalmology referral centers. DesignRetrospective tri-center cohort study. MethodsChart review of clinically and molecularly confirmed IRD cases seen at the University of California San Diego, Oregon Health & Science University, and Children's Hospital Los Angeles. Data retrieved included: demographics, disease phenotype, genotype, best-corrected visual acuity, objective, and/or subjective refraction. ResultsA total of 1942 patient notes were reviewed, of these 634 patients (1255 eyes) had refractive data. For genes associated with myopia, NYX (n=14 [1%]) was associated with the highest SER of myopia (mean -9.26 diopters (D) [95% CI -11.867, -6.651], P<0.001) followed by IMPG2 (n=16 [1.1%]) (mean -4.062 D [95% CI -6.254, -1.871], P=0.002), then RPGR (n=104 [7.2%]) (mean -2.664 D [95% CI [-3.618, -1.710], P=0.016) and for genes associated with hyperopia, BEST1 (n= 38 [2.6%]) had the highest SER for hyperopia (mean 2.996 D [95% CI 1.830, 4.162], P<0.001) followed by RS1 (n=26 [1.8%]) (mean 2.562 D [95% CI 1.454, 3.671], P<0.001), then CNGA3 (n=28 [1.9%]) (mean 0.603 D [(95% CI -0.48, 1.686]), P=0.009). Overall patients with IRD were significantly more myopic than age matched population controls. (n=eyes) ConclusionBy combining genetic testing with refraction data from a large cohort of patients, we identify IRD genes associated with myopia and hyperopia. However, we find that the pattern of ametropia varies widely not only by gene but also within a gene cohort. The genes identified to be associated with RE are candidates for further in-depth investigation to understand their functional role in RE.

Cardiac surgery and long-term risk for incident cancer: A nationwide population-based study

ObjectivePrevious studies indicate an increased long-term risk for incident cancer and cancer-specific mortality in patients undergoing cardiac surgery. We compared the risk for incident cancer and cancer-specific mortality between patients and matched control subjects from the general population. MethodsAll patients (n = 127,119) undergoing first-time coronary artery or heart valve surgery in Sweden during 1997-2020 were included in a population-based observational cohort study based on individual data from the SWEDEHEART registry and 4 other mandatory national registries. The patients were compared with an age-, sex-, and place of residence–matched control population (n = 415,287) using multivariable Cox proportional hazards regression models adjusted for baseline characteristics, comorbidities, and socioeconomic factors. A propensity score–matched analysis with 81,522 well-balanced pairs was also performed. ResultsMedian follow-up was 9.2 (range, 0-24) years. A total of 31,361/127,119 patients (24.7%) and 102,959/415,287 control subjects (24.8%) developed cancer during follow-up. The crude event rates were 2.75 and 2.83 per 100 person-years, respectively. The adjusted risk for cancer and cancer-specific mortality was lower in patients (adjusted hazard ratios 0.86 [95% CI, 0.85-0.88] and 0.64 [95% CI, 0.62-0.65], respectively). The propensity score–matched analysis showed similar results (hazard ratios, 0.88 [95% CI, 0.86-0.90] and 0.65 [95% CI, 0.63-0.68], respectively). The results were consistent in subgroups based on sex, age, and comorbidities. ConclusionsPatients who underwent cardiac surgery have lower risk for cancer and cancer-specific mortality than matched control subjects.

Clinical Profile of Patients Presenting With Eclampsia at a Semi-urban Tertiary Care Center.

Introduction Pregnancies complicated by hypertensive disorders contribute to enormous burden on economy and health-care facilities.Eclampsia is one of the clinical markers of near-miss mortality. To achieve optimal outcomes, efforts should be directed at both periphery and tertiary care levels. This study aimed to compare the feto-maternal outcome in patients presenting with eclampsia and a matched control population. Methodology A comparative observational study was conducted among 70 cases and 70 controls. Detailed historyand general and obstetrical examinations were carried out. Data was extracted from case files, labor room, and ICU records. Maternal and fetal outcomes were noted from January 2023 to January 2024. Statistical software STATA 14.2 (StataCorp LLC, College Station, Texas, USA) was used for data analysis. Observational descriptive statistics and chi-square and Fisher extract tests were applied. Results In our study, the incidence of eclampsia was 0.7% (70 per 1000 live births). The maternal mortality rate was 102.8/100000 live births and the perinatal mortality rate was 10.2/ 1000 live births in our study. The study observed a relatively young aged population and a significant bulk of cases belonged to late gestation or post-partum. Events like HELLP syndrome, abruption, liver, and renal failure were found to be frequently linked to eclampsia. Neonatal asphyxia (P-0.005), NICU requirement 41.43% vs 29% (P<0.01) preterm delivery 45.7% vs 14% (P=<0.001), and low birth weight were more commonly observed among the cases than the controls. Conclusions Eclampsia was found to be a significant contributor to elevated rates of morbidity and mortality in mothers and newborns. Poor antenatal care, severe anemia, and late referrals were some of the modifiable risk factors. Health care and economic burden on society is immense due to the significant utilization of intensive care and high dependency units.

Risk and predictors of fractures in early rheumatoid arthritis – A long term follow up study of an inception cohort

ObjectivesTo examine the risk of fractures in a cohort of patients with newly diagnosed rheumatoid arthritis (RA), compared to the background population, and predictors of fractures detectable early in RA. MethodsAn inception cohort of patients with RA (N = 233; 164 women/69 men, recruited 1995–2005) was evaluated according to a structured program, including repeated clinical assessments and measures of bone mineral density (BMD), from diagnosis to 10 years later. Matched population controls were identified using the national census register. Fractures through 2019 were identified based on ICD codes. Cox regression models were used to assess the risk of fractures in RA patients compared with controls, and for assessment of potential predictors for fractures in the RA population. ResultsRA patients had an increased risk of fractures (fully adjusted hazard ratio (HR) 1.52, 95 % CI 1.13; 2.06). In the RA cohort, high age, low body mass index, and low BMD were significant baseline predictors of future fractures in multivariate analyses, but baseline RA disease characteristics were not. Worse disability (i.e. higher Health Assessment Questionnaire (HAQ) scores) over time was significantly associated with increased risk of fractures (age-sex-adjusted HR 1.33 per SD, 95 % CI 1.09; 1.63) and there was an inverse association between BMD Z-scores over time and fractures. ConclusionPatients with RA had higher risk of fractures than controls. Fracture risk was related to BMD at baseline and over time in patients with RA. In addition, worse disability (measured by HAQ) over time was associated with higher risk of fractures.

Survival among people with HIV and their families in Denmark 1995–2021: a nationwide population-based cohort study

Survival among people with HIV (PWH) has vastly improved globally over the last few decades but remains lower than among the general population. We aimed to estimate time trends of survival among PWH and their families from 1995 to2021. We conducted a registry-based, nationwide, population-based, matched cohort study. We included all Danish-born PWH from 1995 to 2021 who had been on antiretroviral therapy for 90 days, did not report intravenous drug use, and were not co-infected with hepatitis C (n=4168). We matched population controls from the general population 10:1 to PWH by date of birth and sex (n=41,680). For family cohorts, we identified siblings, mothers, and fathers of PWH and population controls. From Kaplan-Meier tables with age as time scale, we estimated survival from age 25. We compared PWH with population controls and families of PWH with families of population controls to calculate mortality rate ratios adjusted for sex, age, comorbidities, and education (aMRR). The median age of death among PWH increased from 27.5 years in 1995-1997 to 73.9 years (2010-2014), but thereafter survival increased only marginally. From 2015 to 2021, mortality was increased among PWH (aMRR 1.87 (95% CI: 1.65-2.11)) and siblings (aMRR: 1.25 (95% CI: 1.07-1.47)), mothers (aMRR: 1.30 (95% CI: 1.17-1.43)), and fathers (aMRR: 1.15 (95% CI: 1.03-1.29)) of PWH compared to their respective control cohorts. Mortality among siblings of PWH who reported heterosexual route of HIV transmission (aMRR: 1.51 (95% CI: 1.16-1.96)) was higher than for siblings of PWH who reported men who have sex with men as route of HIV transmission (aMRR 1.19 (95% CI: 0.98-1.46)). Survival among PWH improved substantially until 2010, after which it increased only marginally. This may partly be due to social and behavioural factors as PWH families also had higher mortality. Preben and Anna Simonsen's Foundation and Independent Research Fund Denmark.

A Nationwide Cohort Study of Delta and Omicron SARS-CoV-2 Outcomes in Vaccinated Individuals With Chronic Lung Disease

BackgroundIndividuals with chronic-lung-disease (CLD) are more susceptible to respiratory viral infections; however, there is significant heterogeneity in the literature on CLD and COVID-19 outcomes. Data is lacking on outcomes with newer variants (eg. Omicron) and in vaccinated/boosted populations. Research QuestionWhat are the outcomes of SARS-CoV-2 infection in individuals with CLD during Delta and Omicron transmission, in a highly vaccinated/boosted population-based cohort? Study Design and MethodsOutcomes of Delta/Omicron SARS-CoV-2 infection in a highly vaccinated/boosted cohort of adult Singaporeans with CLD (including asthma, chronic-obstructive-pulmonary-disease [COPD], bronchiectasis and pulmonary fibrosis) were contrasted against matched population controls. Calendar time-scale Cox regressions were used to compare risk of infection, COVID-19-related hospitalizations and severe COVID-19 disease, adjusting for sociodemographic factors/comorbidities. ResultsOverall, 68,782 individual patients with CLD and 534,364 matched population controls were included. 92.7% of CLD patients were boosted by the end of the Omicron wave. Compared with controls, higher risk of SARS-CoV-2 infection, COVID-19-related hospitalization and severe COVID-19 was observed amongst patients with CLD during both Delta (infection: adjusted-hazards-ratio, aHR=1.22[1.17-1.28]; hospitalization: aHR=1.76[1.61-1.92]; severe-COVID-19: aHR=1.75[1.50-2.05]) and Omicron waves (infection: aHR=1.15[1.14-1.17]; hospitalization: aHR=1.82[1.74-1.91]; severe-COVID-19: aHR=2.39[2.18-2.63]). During Omicron, significantly higher risk of infection, hospitalization and severe-COVID-19 was observed amongst patients with asthma (severe-COVID-19: aHR=1.31[1.10-1.55]) and COPD (severe-COVID-19: aHR=1.36[1.12-1.66]) compared with controls. Severe exacerbation (requiring hospitalization) in the preceding year was associated with higher risk of poorer outcomes (Delta-severe-COVID-19: aHR=9.84[6.33-15.28]; Omicron-severe-COVID-19: aHR=19.22[15.35-24.06]). Risk was attenuated in the boosted group, with numerically lower HRs against hospitalization/severe-COVID-19 in the 4-dose group compared with the 3-dose group. InterpretationIncreased risk of COVID-19-related hospitalization and severe-COVID-19 was observed amongst patients with CLD compared with matched population controls, during Delta/Omicron predominance. Boosting attenuated serious COVID-19 outcomes.

Impact of previous treatment history and B-cell depletion treatment duration on infection risk in relapsing-remitting multiple sclerosis: a nationwide cohort study

BackgroundB-cell depletion displays striking effectiveness in relapsing-remitting multiple sclerosis (RRMS), but is also associated with increased infection risk. To what degree previous treatment history, disease-modifying therapy (DMT) switching pattern and...

Assessing Uveitis Risk following Pediatric Down Syndrome Diagnosis: A TriNetX Database Study.

Background and Objectives: The risks of uveitis development among pediatric patients with Down syndrome (DS) remain unclear. Therefore, we aimed to determine the risk of uveitis following a diagnosis of DS. Materials and Methods: This multi-institutional retrospective cohort study utilized the TriNetX database to identify individuals aged 18 years and younger with and without a diagnosis of DS between 1 January 2000 and 31 December 2023. The non-DS cohort consisted of randomly selected control patients matched by selected variables. This included gender, age, ethnicity, and certain comorbidities. The main outcome is the incidence of new-onset uveitis. Statistical analysis of the uveitis risk was reported using hazard ratios (HRs) and 95% confidence intervals (CIs). Separate analyses of the uveitis risk among DS patients based on age groups and gender were also performed. Results: A total of 53,993 individuals with DS (46.83% female, 58.26% white, mean age at index 5.21 ± 5.76 years) and 53,993 non-DS individuals (45.56% female, 58.28% white, mean age at index 5.21 ± 5.76 years) were recruited from the TriNetX database. Our analysis also showed no overall increased risk of uveitis among DS patients (HR: 1.33 [CI: 0.89-1.99]) compared to the non-DS cohort across the 23-year study period. Subgroup analyses based on different age groups showed that those aged 0-1 year (HR: 1.36 [CI: 0.68-2.72]), 0-5 years (HR: 1.34 [CI: 0.75-2.39]), and 6-18 years (HR: 1.15 [CI: 0.67-1.96]) were found to have no association with uveitis risk compared to their respective non-DS comparators. There was also no increased risk of uveitis among females (HR: 1.49 [CI: 0.87-2.56]) or males (HR: 0.82 [CI: 0.48-1.41]) with DS compared to their respective non-DS comparators. Conclusions: Our study found no overall increased risk of uveitis following a diagnosis of DS compared to a matched control population.

Long-term cardiovascular risk reduction after gastric cancer surgery: a nationwide cohort study.

Gastrectomy for gastric cancer is associated with postoperative changes in cardiovascular risk factors, however, the impact of gastrectomy on cardiovascular events remains unclear. We assessed the incidence of cardiovascular events between patients undergoing gastrectomy or endoscopic resection for gastric cancer, and the general population. This retrospective nationwide cohort study included patients with gastric cancer undergoing gastrectomy(n=37,698), endoscopic resection(n=2,773), and matched control population(n=161,887) between 2004 and 2013. We included patients without a history of cancer other than gastric cancer, myocardial infarction, or ischemic stroke. The primary outcome was the incidence of major adverse cardiovascular events (MACE) such as acute myocardial infarction, revascularization, or acute ischemic stroke, in patients with gastric cancer. Among patients who underwent gastrectomy for gastric cancer, 2.9% (4.69 per 1000 person-years) developed novel MACE within the seven-year follow-up period. The gastrectomy group demonstrated a significantly decreased risk for MACE than the control population (hazard ratio[HR], 0.65; 95% confidence interval[CI], 0.61-0.69; P <0.001). Among the patients undergoing endoscopic resection for gastric cancer, 5.4% (8.21 per 1000 person-years) developed novel MACE within the seven-year follow-up period. The risk for MACE in the endoscopic resection group was not significantly different from the control population. Patients with gastric cancer who have undergone gastrectomy exhibit a reduced risk of cardiovascular diseases in comparison to the general population. In contrast, the risk for cardiovascular diseases in patients with gastric cancer who underwent endoscopic resection did not demonstrate a significant difference in cardiovascular risk in comparison to the general population.

Impact of risk-based therapy on late morbidity and mortality in neuroblastoma survivors: a report from the Childhood Cancer Survivor Study.

Early efforts at risk-adapted therapy for neuroblastoma are predicted to result in differential late effects; the magnitude of these differences has not been well described. Late mortality, subsequent malignant neoplasms (SMNs), and severe/life-threatening chronic health conditions (CHCs), graded according to CTCAE v4.03, were assessed among 5-year Childhood Cancer Survivor Study (CCSS) survivors of neuroblastoma diagnosed 1987-1999. Using age, stage at diagnosis, and treatment, survivors were classified into risk groups (low [n = 425]; intermediate [n = 252]; high [n = 245]). Standardized mortality ratios (SMRs) and standardized incidence ratios (SIRs) of SMNs were compared with matched population controls. Cox regression models estimated hazard ratios (HRs) and 95% confidence intervals for CHC compared with 1029 CCSS siblings. Among survivors (49.8% male; median age = 21 years, range = 7-42; median follow-up = 19.3 years, range = 5-29.9), 80% with low-risk disease were treated with surgery alone, whereas 79.1% with high-risk disease received surgery, radiation, chemotherapy ± autologous stem cell transplant (ASCT). All-cause mortality was elevated across risk groups (SMRhigh = 27.7 [21.4-35.8]; SMRintermediate = 3.3 [1.7-6.5]; SMRlow = 2.8 [1.7-4.8]). SMN risk was increased among high- and intermediate-risk survivors (SIRhigh = 28.0 [18.5-42.3]; SIRintermediate = 3.7 [1.2-11.3]) but did not differ from the US population for survivors of low-risk disease. Compared with siblings, survivors had an increased risk of grade 3-5 CHCs, particularly among those with high-risk disease (HRhigh = 16.1 [11.2-23.2]; HRintermediate = 6.3 [3.8-10.5]; HRlow = 1.8 [1.1-3.1]). Survivors of high-risk disease treated in the early days of risk stratification carry a markedly elevated burden of late recurrence, SMN, and organ-related multimorbidity, whereas survivors of low/intermediate-risk disease have a modest risk of late adverse outcomes.

24-hour Urine Calcium Predicts Reduced Fracture Incidence and Improved BMD After Surgery for Primary Hyperparathyroidism.

Contemporary patients with primary hyperparathyroidism are diagnosed with milder disease than previously. Clinical and biochemical factors predictors with impact on fracture incidence and bone mineral density after surgery have not been firmly established. To investigate predictors of fracture incidence and bone mineral density preoperatively and after surgery for primary hyperparathyroidism (pHPT). Prospectively collected surgical cohort with matched population controls. Data were cross-linked with the Swedish National Patient Register, the Prescribed Drug Register, and the Cause of Death Register. Tertiary referral center. 709 patients with successful parathyroidectomy for pHPT, and 2,112 controls matched on sex, age, and municipality were included in the study. Fracture incidence, absolute change and ≥2.77% increase in bone mineral density of femoral neck, L2-L4 and distal third of radius at 1-year follow-up. Patients with pHPT had an increased fracture incidence before surgery but not after pHPT surgery. Fracture incidence after surgery was inversely related to preoperative 24-hour urine calcium (IRR for the highest tertile 220- mg/d 0.29, CI 95% 0.11-0.73). Serum and 24-hour urine calcium, parathyroid hormone, osteocalcin and adenoma weight were all associated with bone mineral density recovery after surgery. 24-hour urine calcium is the most important biochemical variable to predict a decreased fracture incidence and improved bone mineral density after surgery for pHPT.

The combined effect of systemic antibiotics and proton pump inhibitors on Clostridioides difficile infection and recurrence.

Antibiotics and proton pump inhibitors (PPI) are recognized risk factors for acquisition and recurrence of Clostridioides difficile infection (CDI), yet combined effects remain unclear. To assess the short- and long-term effects of antibiotics and PPIs on CDI risk and recurrence. Population-based study including all 43 152 patients diagnosed with CDI in Sweden (2006-2019), and 355 172 matched population controls without CDI. The impact of antibiotics and PPIs on CDI risk and recurrence was explored for recent (0-30 days) and preceding (31-180 days) use prior to their first CDI diagnosis, using multivariable conditional logistic regression presented as odds ratios (ORs) and 95% confidence interval, adjusted for demographics, comorbidities and other drugs. Compared to controls, the combined effect of recent PPIs and antibiotics [ORAB+PPI = 17.51 (17.48-17.53)] on CDI risk was stronger than the individual effects [ORAB = 15.37 (14.83-15.93); ORPPI = 2.65 (2.54-2.76)]. Results were less pronounced for exposure during the preceding months. Dose-response analyses showed increasing exposure correlated with CDI risk [recent use: ORAB = 6.32 (6.15-6.49); ORPPI = 1.65 (1.62-1.68) per prescription increase].Compared to individuals without recurrence (rCDI), recent [ORAB = 1.30 (1.23-1.38)] and preceding [ORAB = 1.23 (1.16-1.31); ORPPI = 1.12 (1.03-1.21)] use also affected the risk of recurrence yet without significant interaction between both. Recent macrolides/lincosamides/streptogramins; other antibacterials including nitroimidazole derivates; non-penicillin beta lactams and quinolones showed the strongest association with CDI risk and recurrence, particularly for recent use. PPI use, both recent and preceding, further increased the CDI risk associated with almost all antibiotic classes. Recent and less recent use of PPIs and systemic antibiotics was associated with an increased risk of CDI, particularly in combination.

Mental health from 5 years before to 10 years after bariatric surgery in adolescents with severe obesity: a Swedish nationwide cohort study with matched population controls

The long-term effects of bariatric surgery on the mental health of adolescents with severe obesity remain uncertain. We aimed to describe the prevalence of psychiatric health-care visits and filled prescription psychiatric drugs among adolescents with severe obesity undergoing bariatric surgery in the 5 years preceding surgery and throughout the first 10 years after surgery, and to draw comparisons with matched adolescents in the general population. Adolescents with severe obesity and who underwent bariatric surgery were identified through the Scandinavian Obesity Surgery Registry. We included adolescents who had bariatric surgery between 2007 and 2017 and were younger than 21 years at time of surgery. Each adolescent patient was matched with ten adolescents from the general population by age, sex, and county of residence. Specialist psychiatric care and filled psychiatric prescriptions were retrieved from nationwide data registers. 1554 adolescents (<21 years) with severe obesity underwent bariatric surgery between 2007 and 2017, 1169 (75%) of whom were female. At time of surgery, the mean age was 19·0 years [SD 1·0], and the mean BMI was 43·7 kg/m2 (SD 5·5). 15 540 adolescents from the general population were matched with adolescents in the surgery group. 5 years before the matched index date, 95 (6·2%) of 1535 surgery patients and 370 (2·5%) of 14 643 matched adolescents had a psychiatric health-care visit (prevalence difference 3·7%; 95% CI 2·4-4·9), whereas 127 (9·8%) of 1295 surgery patients and 445 (3·6%) of 12 211 matched adolescents filled a psychiatric drug prescription (prevalence difference 6·2%; 95% CI 4·5-7·8). The year before the matched index date, 208 (13·4%) of 1551 surgery patients and 844 (5·5%) of 15 308 matched adolescents had a psychiatric health-care visit (prevalence difference 7·9%; 95% CI 6·2-9·6), whereas 319 (20·6%) of 1551 surgery patients and 1306 (8·5%) of 15 308 matched adolescents filled a psychiatric drug prescription (prevalence difference 12·0%; 10·0-14·1). The prevalence difference in psychiatric health-care visits peaked 9 years after the matched index date (12·0%; 95% CI 9·0-14·9), when 119 (17·6%) of 675 surgery patients and 377 (5·7%) of 6669 matched adolescents had a psychiatric health-care visit. The prevalence difference in filled psychiatric drug prescription was highest 10 years after the matched index date (20·4%; 15·9-24·9), when 171 (36·5%) of 469 surgery patients and 739 (16·0%) of 4607 matched adolescents filled a psychiatric drug prescription. The year before the matched index date, 19 (1·2%) of 1551 surgery patients and 155 (1·0%) of 15304 matched adolescents had a health-care visit associated with a substance use disorder diagnosis (mean difference 0·2%, 95% CI -0·4 to 0·8). 10 years after the matched index date, the prevalence difference had increased to 4·3% (95% CI 2·3-6·4), when 24 (5·1%) of 467 surgery patients and 37 (0·8%) of 4582 matched adolescents had a health-care visit associated with a substance use disorder diagnosis. Psychiatric diagnoses and psychiatric drug prescriptions were more common among adolescents with severe obesity who would later undergo bariatric surgery than among matched adolescents from the general population. Both groups showed an increase in prevalence in psychiatric diagnoses and psychiatric drug prescriptions leading up to the time of surgery, but the rate of increase in the prevalence was higher among adolescents with severe obesity than among matched adolescents. With the exception of health-care visits for substance use disorders, these prevalence trajectories continued in the 10 years of follow-up. Realistic expectations regarding mental health outcomes should be set preoperatively. Swedish Research Council, Swedish Research Council for Health, Working Life and Welfare.

Increased risk of lower limb osteoarthritis among former professional soccer (football) players.

Soccer is a high-speed contact sport with risk of injury. Despite long-standing concern, evidence to date remains inconsistent as to the association between playing professional-level soccer and lifelong musculoskeletal consequences. The objectives were to assess risk of osteoarthritis in former professional soccer players compared to matched general population controls, and subsequently assess associated musculoskeletal disorders which may contribute to, or result from, osteoarthritis-specifically meniscal injury and joint replacement. We conducted a retrospective cohort study using national electronic health records (EHRs) on a cohort of 7676 former professional soccer players aged 40 or over at recruitment, matched on year of birth, sex (all male) and socio-economic status with 23 028 general population controls. Outcomes of interest were obtained by utilizing individual-level record linkage to EHRs from general hospital inpatient and day-case admissions. Compared to controls, former soccer players showed a greater risk of hospital admission for osteoarthritis (hazard ratio [HR] 3.01; 95% confidence interval [CI] 2.80-3.25; P < 0.001). This increased risk appeared age dependant, normalizing over age 80 years and reflective of increased risk of lower limb osteoarthritis. Further, risk of hospital admissions for meniscal injury (HR 2.73; 95% CI 2.42-3.08; P < 0.001) and joint replacement (HR 2.82; 95% CI 2.23-3.57; P < 0.001) were greater among former soccer players. We report an increased risk of lower limb osteoarthritis in former soccer players when compared with matched population controls. The results of this research add data in support of lower limb osteoarthritis among former soccer players representing a potential industrial injury.

Thrombotic Thrombocytopenic Purpura (TTP) Survivors Exhibit Impaired Stress Perfusion on Cardiac MRI

Introduction: Thrombotic thrombocytopenic purpura (TTP) survivors have increased rates of cardiovascular morbidity and mortality when compared with the general population. In this prospective pilot study, we sought to further characterize the long-term cardiovascular sequelae of TTP survivors through pharmacologic stress cardiac magnetic resonance imaging (CMR). Stress CMR has been increasingly utilized to detect clinical and subclinical structural and functional changes. A CMR biomarker of myocardial remodeling is extracellular volume (ECV); an increase in ECV may indicate the development of interstitial myocardial fibrosis. ECV was chosen for structural assessment as it has been implicated with diastolic dysfunction and other cardiac issues in other hematologic diseases, like sickle cell anemia. Methods: Adult patients (age ≥18 years of age) with TTP (immune-mediated or congenital) in the Ohio State University (OSU) TTP registry were prospectively consented and enrolled from March 2023 through July 2023 to undergo adenosine stress CMR at standard clinical dosing. All patients in the TTP cohort had confirmed diagnosis based on ADAMTS13 activity &amp;lt;15% during an acute episode and were in clinical remission at the time of CMR testing. Standard baseline and stress CMR parameters were obtained and compared with an age and sex matched control population, selected from patients without TTP who underwent identical stress CMR protocol for other indications and demonstrated normal stress perfusion. Patients in the control cohort predominantly had diagnoses of arrhythmia, stable angina, or heart failure. We collected data on patient demographics, details of TTP history, and underlying comorbidities. On CMR standard structural measurements were evaluated, and ECV was calculated (normal range 25.3 ± 3.5%). Perfusion was measured per standard protocols via global myocardial blood flow (MBF) as ml/min/g. Differences between the TTP and control populations were tested using the Fischer's exact test for categorical variables and Mann-Whitney U test for continuous variables. Results: A total of 10 TTP patients (9 immune-mediated, 1 congenital) were enrolled between March and July 2023. Median age at enrollment was 44.5 years (IQR 40.8-49.5) and 80% (8/10) were female. Patients were in documented clinical and ADAMTS13 activity remission with median ADAMTS13 activity of 68% (64.0-84.5), excluding the activity level of the congenital patient. Median time from initial diagnosis was 15 years (range 0.5 - 41 years) and median number of acute TTP episodes was 2 (IQR 1.0-4.5). Characteristics of the study (n= 10) and control cohort (n = 13) are summarized in Table 1. There were no significant differences in the TTP and control cohorts with respect to age, sex, race, and presence of hypertension or diabetes. Patients in the TTP cohort had significantly higher BMI (median 34.5 mg/m 2 vs 26.5 mg/m 2, p = .012), diastolic blood pressure (94 mmHg vs 82 mmHg, p = .003), and a lower rate of known cardiac disease (10% vs 85%, p&amp;lt;.001). Stress CMR showed reduced myocardial perfusion in TTP survivors: Nine out of 10 (90%) TTP survivors had evidence of structural or perfusion deficits on CMR. The median ECV in the TTP cohort (28.5%, 24.8 - 31.5) was increased compared with controls (26%, 23.5 - 27.5) though it did not reach significance (p = .08). There were no significant differences in median global MBF at rest in the TTP group (1.30, 1.16 - 1.37) compared with controls (1.18, 1.07 - 1.31, p = .210). However, TTP survivors had significantly reduced stress MBF (3.28, 2.21 - 3.53) vs controls (4.1, 3.88 - 4.22, p &amp;lt;.001) with adenosine. Reductions in quantitative stress perfusion in the TTP cohort was primarily noted in the subendocardium as shown in Figure 2. Conclusion: Asymptomatic structural changes and reduction in quantitative perfusion are common in TTP survivors. The study is ongoing to recruit more patients to ensure clinical significance and generalizability of these preliminary findings. Stress CMR may detect subclinical myocardial damage in TTP survivors who otherwise do not exhibit overt cardiovascular symptoms until a later time and may provide the basis to understand increased cardiovascular morbidity and mortality in this population.

Cardiac manifestations of MIS-C: cardiac magnetic resonance and speckle-tracking data.

Cardiac involvement is central in MIS-C and represents the main cause of morbidity. In this study, we aimed to assess myocardial damage in patients with MIS-C using cardiac magnetic resonance (CMR) during the acute phase, as well as left ventricular and atrial longitudinal strain on admission, at discharge, and after 3 months. We performed a single-center prospective cohort study and case-control study. Between September 2020 and February 2022, we enrolled 39 patients hospitalized for MIS-C at our center. We performed left ventricular and atrial longitudinal 2D strain analysis on admission and during follow-up; echocardiographic data were compared to a matched control population. Patients above 4 years old with increased troponin underwent CMR. Of 24 patients (mean age: 8.2 ± 4.9 years) who underwent CMR, 14 (58%) presented myocardial edema and 6 (25%) late gadolinium enhancement (LGE). LGE was associated with older age (p < 0.01), increased BMI (p = 0.03), increased ferritin levels (p < 0.001), lower left ventricular (LV) ejection fraction (p < 0.001), LV longitudinal strain (p = 0.004), left atrial (LA) strain (p = 0.05), and prolonged hospital stay (p = 0.02). On admission, LV ejection fraction, LV longitudinal strain, and LA strain were impaired, but each improved gradually over time; LVEF was the fastest to recover, while global LV longitudinal strain was still impaired as compared to controls after 3 months (p = 0.01). Our study demonstrates that myocardial injury is present in a quarter of MIS-C patients, and impaired LA and LV myocardial deformation persist for at least several weeks after the acute phase. CMR and LV/LA strain could help us to individualize follow-up of MIS-C patients.

Prevalence of pre-eclampsia in 265 patients with an intracranial aneurysm, 393 female relatives versus a control cohort: Acase-control study.

There is emerging evidence on the connection between pre-eclampsia and saccular intracranial aneurysms (sIAs). Our aim was to study the prevalence of pre-eclampsia in sIA patients, their female relatives, and matched controls, and to examine familial sIA disease and familial pre-eclampsia in sIA patients' families. We included all female sIA patients in the Kuopio Intracranial Aneurysm Patient and Family Database from 1995 to 2018. First, we identified the sIA patients, their female relatives, and matched population controls with the first birth in 1987 or later and studied the prevalence of pre-eclampsia. Second, all female sIA patients and all female relatives were analyzed for familial sIA disease and familial pre-eclampsia. Using the Finnish nationwide health registries, we obtained data on drug purchases, hospital diagnoses, and causes of death. In total, 265 sIA patients, 57 daughters, 167 sisters, 169 nieces, and 546 matched controls had the first birth in 1987 or later. Among them, 29 (11%) sIA patients, 5 (9%) daughters, 10 (6%) sisters, 10 (6%) nieces, and 32 (6%) controls had pre-eclampsia. Of all the 1895 female sIA patients and 12,141 female relatives, 68 sIA patients and 375 relatives had pre-eclampsia, including 32 families with familial pre-eclampsia. Pre-eclampsia was significantly more common in the sIA patients than in their matched controls. Familial sIA disease and familial pre-eclampsia co-occurred in seven families. Further studies of the mechanisms by which pre-eclampsia could affect the walls of brain arteries and increase the rupture risk in sIA disease are indicated.