Epilepsy in childhood and school performance: a nation-wide cohort study.

Childhood epilepsy has been linked to poor academic performance, but large-scale studies are lacking. In this nation-wide study of school-aged children, we examined the association between childhood epilepsy and school performance in standardized tests according to phenotypic and treatment-related characteristics. We performed a matched register-based cohort study of children born in Denmark (1997-2009) who participated in the Danish National School Test Programme between 2010 and 2019. We used population and health registers to identify children with epilepsy and a randomly sampled sex- and age-matched reference cohort without epilepsy (ratio 1:10). Norm-based test scores from language and mathematics reflecting performance as a percentile of the nation-wide distribution of scores (scale 1-100) were used to assess academic performance. Adjusted differences in mean standardized scores between children with and without epilepsy were estimated using linear regression models. Among 582 840 children participating in the School Test Programme, we identified 4659 (0.8%) children with epilepsy (52.8% males) and 46 590 matched reference children. Median age at epilepsy onset was 7.5 years (interquartile range: 4.0-10.6). Childhood epilepsy was associated with poorer school performance overall (mean score = 48.2 versus references = 56.7; adjusted difference = -6.7, 95% CI: -7.4 to -6.0), and worse performance was found in all epilepsy subgroups, including in 3534 children with uncomplicated epilepsy (i.e. no other pre-existing neurologic or intellectual disabilities and no identified possible cause for epilepsy; adjusted difference = -6.0, 95% CI: -6.8 to -5.2). No major variation by sex, age or subject was observed, but larger score differences were seen in children using antiseizure medication at time of testing (e.g. valproate monotherapy, adjusted difference = -9.3, 95% CI: -11.5 to -7.0 and lamotrigine monotherapy, adjusted difference = -13.1, 95% CI: -15.0 to -11.3) and in children with psychiatric comorbidity, especially epilepsy with comorbid intellectual disability (adjusted difference = -27.0, 95% CI: -30.0 to -23.9) and epilepsy with comorbid attention deficit/hyperactivity disorder (adjusted difference = -15.7, 95% CI: -19.0 to -12.4). Children with epilepsy scored significantly lower than their unaffected siblings (adjusted difference = -6.2, 95% CI: -7.1 to -5.4). In conclusion, childhood epilepsy was associated with impaired academic performance throughout schooling, which suggest that there is a widespread need for educational support of children with epilepsy, even when the child has no other comorbidities and when the epilepsy appears well-managed.

Early mortality in children with cancer in Denmark and Sweden: The role of social background in a setting with universal healthcare.

Socioeconomic differences in overall survival from childhood cancer have been shown previously, but the underlying mechanisms remain unclear. We aimed to investigate if social inequalities were seen already for early mortality in settings with universal healthcare. From national registers, all children diagnosed with cancer at ages 0-19 years, during 1991-2014, in Sweden and Denmark, were identified, and information on parental social characteristics was collected. We estimated odds ratios (OR) and 95% confidence intervals (CI) of early mortality (death within 90 days after cancer diagnosis) by parental education, income, employment, cohabitation, and country of birth using logistic regression. For children with acute lymphoblastic leukaemia (ALL), clinical characteristics were obtained. Among 13,926 included children, 355 (2.5%) died within 90 days after diagnosis. Indications of higher early mortality were seen among the disadvantaged groups, with the most pronounced associations observed for maternal education (ORadj_Low_vs_High 1.65 [95% CI 1.22-2.23]) and income (ORadj_Q1(lowest)_vs_Q4(highest) 1.77 [1.25-2.49]). We found attenuated or null associations between social characteristics and later mortality (deaths occurring 1-5 years after cancer diagnosis). In children with ALL, the associations between social factors and early mortality remained unchanged when adjusting for potential mediation by clinical characteristics. In conclusion, this population-based cohort study indicated differences in early mortality after childhood cancer by social background, also in countries with universal healthcare. Social differences occurring this early in the disease course requires further investigation, also regarding the timing of diagnosis.

Mothers of twins had higher old-age survival than mothers of singletons in Estonian 19th-century birth cohorts.

STUDY QUESTION: Do the mothers of twins and singletons differ regarding post-partum and old-age mortality? SUMMARY ANSWER: Twin deliveries were associated with higher post-partum maternal mortality than singleton deliveries, but the lifetime post-partum mortality risk was similar for mothers of twins and singletons; survival of twinners was higher than survival of the mothers of singletons after the 67th lifespan percentile. WHAT IS KNOWN ALREADY: Twinning is typically associated with higher post-partum maternal mortality. The evidence about whether twinning incurs long-term survival costs of reproduction or is a trait pertinent to long-lived women is scarce and contradictory. STUDY DESIGN, SIZE, DURATION: The study is based on the data of the Estonian Family Register (operating from 1926 to 1943) and involves 5565 mothers of twins and 119 613 mothers of singletons born between 1850 and 1899. The subset for comparing maternal lifespans included 1703-1884 mothers of twins and 19 747-36 690 mothers of singletons. PARTICIPANTS/MATERIALS, SETTING, METHODS: Post-partum maternal mortality was analyzed in the whole sample (including mothers of a single child) by logistic regression. Most of the analyses were performed in samples where each mother of twins was matched against mothers of singletons based on parity (or number of deliveries), urban versus rural and inland versus coastal origin, whether their lifespan was known, date of birth and age at first birth. Lifespans were compared in linear mixed models. Quantile regression was used to analyze age-dependent variations in maternal mortality rates. All models were adjusted for relevant biodemographic covariates. MAIN RESULTS AND THE ROLE OF CHANCE: The twinning rate in the whole sample was 4.4%. During the year after giving birth, maternal mortality for twin deliveries was 0.75% (17/2273) and 0.37% (449/122 750) for singleton deliveries (OR = 2.05, 95% CI = 1.21-3.23). However, the lifetime post-partum mortality risk for mothers of twins (0.51%; 28/5557) and singletons (0.37%; 438/119 466) did not differ significantly (OR = 1.38, 95% CI = 0.91-1.98). The life spans of the mothers of twins and singletons did not differ in matched samples. Past the 67th lifespan percentile, the odds of survival were significantly higher for mothers of twins than mothers of singletons, as indicated by non-overlapping 95% confidence intervals. LIMITATIONS, REASONS FOR CAUTION: Relatively low number of individuals (22 802-28 335) with known age at death in matched datasets due to discontinuation of the register after 1943. WIDER IMPLICATIONS OF THE FINDINGS: The finding that mothers of twins had higher odds of old-age survival than mothers of singletons is consistent with the contention that twinners represent a non-random subset of women whose robust phenotypic quality allows them to outlive the mothers of singletons in old age. STUDY FUNDING/COMPETING INTEREST(S): The study was funded by the Estonian Research Council grants PRG1137, PRG2248, and PSG669. The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Clozapine, relapse, and adverse events: a 10-year electronic cohort study in Canada.

BACKGROUND: Clozapine is the most effective medication for treatment-resistant psychoses, but the balance of benefits and risks is understudied in real-world settings. AIMS: To examine the relative re-hospitalisation rates for mental health relapse and adverse events associated with clozapine and other antipsychotics in adult and child/youth cohorts. METHOD: Data were obtained from the Canadian Institute of Health Information for adults (n = 45 616) and children/youth (n = 1476) initially hospitalised for mental health conditions in British Columbia, Manitoba and Saskatchewan from 2008 to 2018. Patient demographics and hospitalisations were linked with antipsychotic prescriptions dispensed following the initial visit. Recurrent events survival analysis for relapse and adverse events were created and compared between clozapine and other antipsychotics. RESULTS: In adults, clozapine was associated with a 14% lower relapse rate versus other drugs (adjusted hazard ratio: 0.86, 95% CI: 0.83-0.90) over the 10-year follow-up. In the first 21 months, the relapse rate was higher for clozapine but then reversed. Over 1000 person-months, clozapine-treated adults could be expected to have 38 relapse hospitalisations compared with 45 for other drugs. In children/youth, clozapine had a 38% lower relapse rate compared with other antipsychotic medications (adjusted hazard ratio: 0.62, 95% CI: 0.49-0.78) over the follow-up period. This equates to 29 hospitalisations for clozapine and 48 for other drugs over 1000 person-months. In adults, clozapine had a higher risk for adverse events (hazard ratio: 1.34, 95% CI: 1.18-1.54) over the entire follow-up compared with other antipsychotics. This equates to 1.77 and 1.30 hospitalisations over 1000 person-months for clozapine and other drugs, respectively. CONCLUSIONS: Clozapine was associated with lower relapse overall, but this was accompanied by higher adverse events for adults. For children/youth, clozapine was associated with lower relapse all throughout and had no difference in adverse events compared with other antipsychotics.

Mapping review of register-based cohort studies of bipolar disorder.

OBJECTIVES: Register-based cohorts allow us to better understand bipolar disorder over a life course. They are inclusive and their long-term data collection provides a longer scope than most clinical trials. This mapping review provides an overview of register-based cohort studies of bipolar disorder to inform researchers of the strengths and limitations to this body of research and identify gaps for future research. METHODS: A systematic search was performed of Medline, EMBASE, and PsycINFO databases. Cohort studies were included if they focused on bipolar disorder and had a minimum of 1 year of longitudinal data. Studies needed to be from databases that monitor the whole state or national population. A descriptive analysis of the studies' populations and methodology provides an overview of this field of study and identifies evidence gaps. RESULTS: A hundred and forty-six studies were included. The majority were from databases in Taiwan (n = 63), Denmark (n = 38), Sweden (n = 23), and Finland (n = 11). Forty-eight studies focused on aetiological questions. Sixty prognostic studies identified cohorts with bipolar disorder and described the impact of the illness by considering comorbidity, prescribing patterns, social functioning, and mortality. Thirty-six treatment studies focused on the efficacy and adverse effects of pharmaceuticals and ECT. No studies focused on psychological treatments. CONCLUSION: Bipolar disorder research should include register-based cohorts with greater geopolitical and cultural diversity. Custodians of health registers should consider how non-pharmaceutical interventions such as psychotherapy are captured. Register-based cohorts investigating treatments of bipolar disorder should consider long-term social outcomes alongside the usual clinical outcomes.

Traumatic brain injury and long-term associations with work, divorce and academic achievement.

OBJECTIVE: Traumatic brain injuries (TBI), irrespective of severity, may have long-term social implications. This study explores the relationships between TBI severity and outcomes related to work stability, divorce, and academic achievement. METHODS: Using a Danish nationwide sample of persons with and without TBI, we employed case-control and longitudinal cohort designs. The case-control design utilized individuals aged 18 to 60 years and examined work stability. Each case, employed at time of TBI, was compared with 10 matched controls. The cohort design utilized individuals alive from 1980 to 2016 with and without TBI and assessed the likelihood of 1) divorce and 2) higher-level education. TBI exposures included concussion, skull fractures, or confirmed TBI. RESULTS: TBI cases exhibited higher odds ratios (OR) for work instability at all follow-ups compared to controls. Increased TBI severity was associated with a higher risk of work instability at 2-year follow-up (concussion: OR = 1.83; skull fracture: OR = 2.22; confirmed TBI: OR = 4.55), and with a higher risk of not working at 10-year follow-up (confirmed TBI: OR = 2.82; concussion: OR = 1.63). The divorce incidence rate ratio (IRR) was elevated in individuals with TBI (males: IRR = 1.52; females: IRR = 1.48) compared to those without TBI. Individuals with childhood TBI had reduced chances of attaining high school degree or higher (males: IRR = 0.79; females: IRR = 0.85) compared to those without TBI. CONCLUSION: TBI is associated with an increased long-term risk of social consequences, including work instability, divorce, and diminished chances of higher education, even in cases with concussion.

Early specialised treatment for bipolar disorder: Long-term follow-up from the early intervention in affective disorders (EIA) randomised controlled trial.

BACKGROUND: It is unclear whether treatment early after onset in bipolar disorder may improve the long-term illness course. The early intervention in affective disorders (EIA) randomised controlled trial found that 2-years treatment in a specialised mood disorder clinic combining evidence-based pharmacological treatment with group psychoeducation improved clinical outcomes compared with standard treatment in patients with bipolar disorder discharged after their 1st, 2nd, or 3rd hospital admission. We aimed to assess the 16 years long-term outcomes after randomisation of the participants in the EIA trial. METHODS: Data were obtained by linking nation-wide Danish population-based registers. All 158 participants of the EIA trial (Trial Registration Number NCT00253071) were followed from time of randomisation (2005-2009) to end of study (31 December 2021). The primary outcome was risk of psychiatric readmission. Secondary outcomes were total admissions and costs, medication use, intentional self-harm or suicide attempt or suicide, and socio-economic measures. RESULTS: The absolute mean risk of psychiatric readmission was 49.3% in the intervention group and 59.8% in the control group, with no statistically significant difference between the groups (b = -0.10, 95% CI: -0.26 to 0.047, p = 0.18). Compared with the control group, patients in the intervention group had numerically fewer total admission days (mean (SD) 44 (77) versus 62 (109)), lower total cost of psychiatric hospital admissions and hospital-based outpatient visits (mean (SD) 22,001 (36793) euros versus 29,822 (52671) euros) and higher use of lithium and antipsychotics, but the differences were not statistically significant. Fewer patients in the intervention group had an event of intentional self-harm or suicide attempt or suicide during follow-up (OR 0.25, 95% CI: 0.15-0.40, p < 0.001) compared with the control group and more patients in the intervention group used antiepileptics (OR 2.21, 95% CI: 1.08-4.60, p = 0.031). CONCLUSION: Analyses of very long-term outcomes of the EIA trial may potentially indicate a beneficial effect of the intervention at the long term but were likely underpowered to detect a more subtle effect and for most outcomes the differences between groups were not statistically significant.

Precarious employment in young adulthood and later alcohol-related morbidity: a register-based cohort study.

OBJECTIVES: The prevalence of precarious employment is increasing, particularly among young adults where less is known about the long-term health consequences. The present study aims to test if being precariously employed in young adulthood is associated with an increased risk of alcohol-related morbidity later in life. METHODS: A register-based cohort study was conducted in Sweden. The Swedish Work, Illness, and Labor-market Participation (SWIP) cohort was used to identify individuals who were aged 27 years between 2000 and 2003 (n=339 403). Information on labour market position (precarious employment, long-term unemployment, substandard employment and standard employment relations) was collected for young people 3 years after graduation from school using nationwide registers. Details about alcohol-related morbidity during a 28-year follow-up period were collected from the National Hospital Discharge Register. Data on sex, age, country of birth, education and previous poor health were also obtained from the registers. RESULTS: Young adults in precarious employment had an increased risk of alcohol-related morbidity compared with individuals of the same age in standard employment (HR 1.43, 95% CI 1.32 to 1.55), after adjusting for several important covariates. A stronger association was found among young men who were precariously employed compared with young women. CONCLUSION: This nationwide register-based study conducted in Sweden with a long-term follow-up suggests that being precariously employed in young adulthood is associated with an increased risk of alcohol-related morbidity later in life.

Consistency between the National Patient Register and the Swedish Cancer Register.

PURPOSE: The Swedish National Patient Register (NPR) is widely used as a data source in epidemiological studies, but the consistency of all cancer diagnoses compared to the Swedish Cancer Register (SCR) remains unclear. Using NPR supplementary for detecting safety signals is beneficial due to shorter data extraction delays compared to using SCR alone. This study aims to evaluate the consistency of NPR for cancer diagnoses compared to SCR and its potential use in pharmacoepidemiology. METHODS: Patients with a cancer diagnosis recorded in SCR during 2018-2020 were included. To measure the consistency of NPR diagnoses with SCR as the gold standard, positive predictive value (PPV), and sensitivity were calculated. As an empirical example showing differences in identification of cancer diagnoses in NPR and SCR, two nested case-control studies for the association between antidiabetic medications and pancreatic cancer were repeated using the two registers. Conditional logistic regression was performed and the 95% confidence intervals (CIs) for the odds ratios (ORs) were checked for overlaps. RESULTS: For breast, male genital organs, and oral cancers consistency was high (PPV: 87.5%-97.4%, sensitivity: 82.2%-91.0%), while for female genital organs, thyroid, and ill-defined, secondary, and unspecified sites cancers it was low (PPV: 8.8%-90.0%, sensitivity: 19.9%-32.3%). All the CIs for the ORs from the nested case-control studies overlapped when pancreatic cancer was identified in NPR or SCR. CONCLUSION: Consistency of cancer diagnoses in NPR when compared to SCR depends on cancer type with higher consistency for some cancers and lower for others. Differences in diagnostic processes for different cancer types and coding of cancer in the two registers may explain part of the inconsistent results.

Obstetric claims in Finland 2012-2022-A nationwide patient insurance registry study.

INTRODUCTION: Maternal and infant mortality rates in Finland are among the lowest in the world, yet preventable obstetric injuries occur every year. The aim of this study was to describe obstetric claims, their compensation rates, and temporal trends of claims reported to the Patient Insurance center. MATERIAL AND METHODS: A nationwide, register-based study was conducted. Data consisted of obstetric claims reported to the Patient Insurance Center between 2012 and 2022. Data analyzed included the year of injury, compensation criteria, maternal age, birth hospital, delivery method, reported causes of injury, and maternal or neonatal injury. The data were analyzed with descriptive statistics and logistic regression models. RESULTS: A total of n = 849 obstetric claims were filed during the study period, of which n = 224 (26.4%) received compensation. The rate of claims was 0.15%, and the rate of compensation was 0.04% in relation to the total volume of births during the period. Substandard care was the most common (97.3%) criterion for compensation. There was a curvilinear increase in the claims rate and a linear increase in compensation rates from 2013 to 2019. More claims were filed and compensated for cesarean and vacuum-assisted deliveries than for unassisted vaginal deliveries. Delayed delivery (18.7%) and surgical technique failure (10.9%) were the most reported causes of injuries. Retained surgical bodies were the induced cause of injury with the highest rate of compensated claims (86.7%). The most common maternal injury was infection (17.9%) and pain (11.7%). Among neonatal injuries, severe (19.2%) and mild asphyxia (16.6%) were the most frequent. Burn injuries (93.3%) and fetal or neonatal death (60.5%) had the highest rate of compensated claims. CONCLUSIONS: The study provided new information on substandard care and injuries in obstetric care in Finland. An increasing trend in claims and compensation rates was found. Identifying contributors to substandard care that lead to fetal asphyxia is important for improving obstetric safety. Further analysis of the association of claims and compensation rates with operative deliveries is needed to determine their causality. Frequent review of obstetric claims would be useful in providing more recent data on substandard care and preventable injuries.

Neonatal outcome following metformin-treated gestational diabetes mellitus: A population-based cohort study.

INTRODUCTION: Neonatal hypoglycemia is a common complication associated with gestational diabetes and therefore relevant to consider in evaluations of maternal treatment. We aimed to investigate the risk of neonatal hypoglycemia in offspring exposed to metformin treatment alone (MT) or combined with insulin (MIT) in comparison with nutrition therapy alone (NT), and insulin treatment alone (IT). In addition, we investigated MT in comparison with MIT. Secondary outcomes included neonatal anthropometrics, respiratory morbidity, hyperbilirubinemia, 5-min Apgar score, and preterm birth. MATERIAL AND METHODS: This Swedish population-based cohort included 16 181 women diagnosed with gestational diabetes, and their singleton offspring born in 2019-2021. We estimated risk as adjusted odds ratio (aOR) with 95% confidence interval (CI), using individual-level, linkage register-data in multivariable logistic regression models. RESULTS: In the main analysis, MT was associated with a lower risk of neonatal hypoglycemia vs NT (aOR 0.85, 95% CI: 0.74-0.96), vs MIT (0.74 [0.64-0.87]), and vs IT (0.47 [0.40-0.55]), whereas MIT was associated with a similar risk of neonatal hypoglycemia vs NT (1.14 [0.99-1.30]) and with lower risk vs IT (0.63 [0.53-0.75]). However, supplemental feeding rates were lower for NT vs pharmacological treatments (p < 0.001). In post hoc subgroup analyses including only exclusively breastfed offspring, the risk of neonatal hypoglycemia was modified and similar among MT and NT, and higher in MIT vs NT. Insulin exposure, alone or combined with metformin, was associated with increased risk of being large for gestational age. Compared with NT, exposure to any pharmacological treatment was associated with significantly lower risk of 5-min Apgar score < 4. All other secondary outcomes were comparable among the treatment categories. CONCLUSIONS: The risk of neonatal hypoglycemia appears to be comparable among offspring exposed to single metformin treatment and nutrition therapy alone, and the lower risk that we observed in favor of metformin is probably explained by a difference in supplemental feeding practices rather than metformin per se. By contrast, the lower risk favoring metformin exposure over insulin exposure was not explained by supplemental feeding. However, further investigations are required to determine whether the difference is an effect of metformin per se or mediated by other external factors.

Analysis of traumatic event emergency department visits among care home residents aged 65 + years in Southern Jutland, Denmark: implications for comprehensive care and subsequent hospital admissions - a register-based cohort study.

BACKGROUND: Care home residents aged 65 + years frequently experience acute health issues, leading to emergency department visits. Falls and associated injuries are a common cause of these visits and falls in a geriatric population can be a symptom of an incipient acute illness such as infection. Conversely, the traumatic event can cause illnesses to arise due to consequences of the fall, e.g. delirium or constipation due to opioid use. We hypothesised that a traumatic event treat-and-release emergency department visit serves as an indicator for an upcoming acute hospital admission due to non-trauma-related conditions. METHODS: We studied emergency department visits for traumatic events among all care home residents aged 65+ (n = 2601) living in Southern Jutland, Denmark, from 2018 to 2019. Data from highly valid national registers were used to evaluate diagnoses, mortality, and admissions. Cox Regression was used to analyse the hazard of acute hospital admission following an emergency department treat-and-release visit. RESULTS: Most visits occurred on weekdays and during day shifts, and 72.0% were treated and released within 6 h. Contusions, open wounds, and femur fractures were the most common discharge diagnoses, accounting for 53.3% of all cases (n = 703). In-hospital mortality was 2.3%, and 30-day mortality was 10.4%. Among treat-and-release visits (n = 506), 25% resulted in a new hospital referral within 30 days, hereof 13% treat-and-release revisits (duration ≤ 6 h), and 12% hospital admissions (duration > 6 h). Over half (56%) of new hospital referrals were initiated within the first seven days of discharge. Almost three-fourths of subsequent admissions were caused by various diseases. The hazard ratio of acute hospital admissions was 2.20 (95% CI: 1.52-3.17) among residents with a recent traumatic event treat-and-release visit compared to residents with no recent traumatic event treat-and-release visit. CONCLUSION: Traumatic event treat-and-release visits among care home residents serve as an indicator for subsequent hospitalisations, highlighting the need for a more comprehensive evaluation, even for minor injuries. These findings have implications for improving care, continuity, and resource utilisation. TRIAL REGISTRATION: Not relevant.

Poor socioeconomic outcomes: Completion of the final examination after lower secondary education mitigates risks associated with gestational age.

AIM: To investigate the influence of gestational age (GA) on the association between completion of the final examination after 10-11 years of basic education and education, financial independence and income in early adulthood. METHODS: A nationwide register-based study including individuals born in Denmark between 1990 and 1992. Completion of the examination was evaluated at age 18 and education, financial independence and income at age 28. RESULTS: Of 165 683 individuals included, 15.7%, 10.8% and 5.5% had low educational level, were not financially independent and had low income. For those who completed the examination odds ratio (OR) ranged from 1.03 at GA = 32-36 weeks to 1.25 at ≤27 weeks for low education, from 1.10 to 0.91 for not being financial independent and from 1.06 to 1.48 for low income. For those who did not complete the examination, OR increased from 7.55 at ≥37 weeks to 15.03 at ≤27 weeks for low education and from 4.68 to 15.31 for not being financial independent. For low income, OR was 2.57 and independent of GA. CONCLUSION: For individuals who completed the examination, the odds of poor socioeconomic outcomes were independent of GA. Individuals who did not complete the examination had increased odds of poor socioeconomic outcomes, particularly as GA decreased.

Five-year neurodevelopmental assessment of extremely preterm or extremely low birthweight infants: Association with school performance.

AIM: We investigated the associations between motor performance and IQ at 5 years of age and school difficulties and grade point averages (GPAs) at 18 years of age. Additionally, the accuracy of preschool IQ in predicting school difficulties was examined. METHODS: A nationwide follow-up study of children born in 1994-1995 who were <28 weeks of gestation or had a birthweight <1000 g. The Danish personal identification number was used to merge data from a national cohort study with population-based registries. Logistic regression analyses examined the associations between motor performance/IQ and school difficulties. Linear regression analyses and the area under the receiver operator curve (AUC) were used to examine the relationship between IQ and GPAs. RESULTS: The study population comprised 248 children, 37% were classified with school difficulties. Motor performance and IQ were associated with school difficulties. The odds of having school difficulties increased as IQ decreased, and the same pattern was observed for GPAs. IQ predicted school difficulties, with an AUC of 0.80 (confidence interval: 0.74-0.86). CONCLUSION: Preschool motor performance and IQ were associated with school difficulties. Additionally, IQ was linked to GPAs. As a screening tool, the predictive ability of preschool IQ for academic difficulties was moderate/high in this cohort.

Reliability of thoracolumbar burst fracture classification in the Swedish Fracture Register.

BACKGROUND: The Swedish Fracture Register (SFR) is a national quality register for all types of fractures in Sweden. Spine fractures have been included since 2015 and are classified using a modified AOSpine classification. The aim of this study was to determine the accuracy of the classification of thoracolumbar burst fractures in the SFR. METHODS: Assessments of medical images were conducted in 277 consecutive patients with a thoracolumbar burst fracture (T10-L3) identified in the SFR. Two independent reviewers classified the fractures according to the AOSpine classification, with a third reviewer resolving disagreement. The combined results of the reviewers were considered the gold standard. The intra- and inter-rater reliability of the reviewers was determined with Cohen's kappa and percent agreement. The SFR classification was compared with the gold standard using positive predictive values (PPV), Cohen's kappa and percent agreement. RESULTS: The reliability between reviewers was  high (Cohen's kappa 0.70-0.97). The PPV for correctly classifying burst fractures in the SFR was high irrespective of physician experience (76-89%), treatment (82% non-operative, 95% operative) and hospital type (83% county, 95% university). The inter-rater reliability of B-type injuries and the overall SFR classification compared with the gold standard was low (Cohen's kappa 0.16 and 0.17 respectively). CONCLUSIONS: The SFR demonstrates a high PPV for accurately classifying burst fractures, regardless of physician experience, treatment and hospital type. However, the reliability of B-type injuries and overall classification in the SFR was found to be low. Future studies on burst fractures using SFR data where classification is important should include a review of medical images to verify the diagnosis.

Eosinophilic esophagitis and risk of incident major adverse cardiovascular events: a nationwide matched cohort study.

BACKGROUND: Inflammatory diseases have been associated with an increased cardiovascular risk. However, data on incident major adverse cardiovascular events (MACE) from large population-based cohorts of patients with eosinophilic esophagitis (EoE) is lacking. METHODS: This study included all Swedish adults with EoE without a record of previous cardiovascular disease (CVD) (1990-2017, N = 1546) with follow-up until 2019. Individuals with EoE were identified from prospectively recorded histopathology reports from all Swedish pathology departments (n = 28). EoE patients were matched at index date for age, sex, calendar year and county with up to five general population reference individuals (N = 7281) without EoE or CVD. Multivariable-adjusted hazard ratios (aHRs) for MACE (ischemic heart disease, congestive heart failure, stroke and cardiovascular mortality) were calculated using Cox proportional hazards models. Full sibling comparisons and adjustment for cardiovascular medication were performed. RESULTS: During a median follow-up of 6.0 years, we observed 65 incident MACE in patients with EoE (6.4/1000 person-years (PY)) and 225 in reference individuals (4.7/1000 PY). EoE was not associated with a higher risk of MACE (aHR = 1.14, 95% CI = 0.86-1.51) or any of its components. No differences between age, sex and follow-up time were observed. The results remained stable in sensitivity analyses, including when adjusting for relevant cardiovascular medications and a full sibling comparison. CONCLUSIONS: In this large population-based cohort study, patients with EoE had no increased risk of MACE compared to reference individuals and full siblings. The results are reassuring for patients with EoE.

Incidence of childhood leukemia before and after shut down of nuclear power plants in Germany in 2011: A population-based register study during 2004 to 2019.

The association between leukemia and proximity to nuclear-power-plants (NPPs) has been assessed in several countries with inconsistent results. A case-control study from Germany had shown an increased risk for childhood leukemia (diagnoses 1980-2003) near NPPs. Germany began shutting down nuclear reactors in 2011, following the Fukushima disaster. We tested whether the previously observed association between leukemia and proximity to NPP persisted despite the shutdown. We used an ecological study design to investigate the incidence of leukemia during 2004 to 2019 in children aged 0 to 14 years living near NPPs where at least one reactor was shut down in 2011. We defined study and control areas as municipalities whose surface area was at least 75% within 10 km or between 10 and 50 km of NPPs, respectively. We calculated age-standardized rates and incidence rate ratios (IRR) using control-areas as the reference. We also computed standardized incidence ratios (SIR) separately for each NPP using incidence rates of the German population as a reference. IRR decreased from 1.20 (95% confidence interval: 0.81-1.77) in 2004 to 2011 to 1.12 (0.75-1.68) in 2012 to 2019. Analyses of single plants showed an excess of childhood leukemia during 2004 to 2019 for the Unterweser-NPP, based only on three cases, and the Krümmel-NPP (n = 14; SIR: 1.98, 1.17-3.35). We found slightly decreasing of leukemia incidence rate ratios after the shutdown of nuclear reactors in 2011. Due to the small number of cases, risk estimates have large uncertainty. Further research including a longer follow-up is warranted. The consistent excess of incidence cases around Krümmel may require analytical epidemiological analysis.

Childcare attendance and risk of childhood acute lymphoblastic leukaemia: A register study based on the Danish childcare database.

Childhood acute lymphoblastic leukaemia (ALL) is suggested to result from a dysregulated immune response to infections in children with a preleukaemic state. Childcare in early life supposedly may protect against childhood ALL by facilitating sufficient exposure to infections to stimulate and ensure normal maturation of the immune system. We assessed the association between childcare attendance before age 2 years and risk of childhood ALL in a register-based cohort study, including all children aged 2 to 14 years born in Denmark during 1991 to 2014 with available childcare information recorded in the Danish Childcare Database (n = 1 116 185). Cox regression was used to estimate hazard ratios (HRs) comparing children enrolled in childcare and children not enrolled before age 2 years. Further, we assessed the association according to age at enrolment, type of childcare facility and specific ALL subtypes. During 10 460 811 person-years of follow-up, 460 children developed ALL at ages 2 to 14 years. Of these, 57 (12.4%) never attended childcare before age 2 years compared with 10.6% in the total cohort. Compared with homecare, childcare attendance before age 2 years was associated with a statistically non-significantly, marginally decreased risk of childhood ALL with adjusted HR = 0.87 (95% confidence interval [CI]: 0.65-1.16). Risk estimates did neither vary statistically significantly by age at enrolment nor by type of childcare facility and also not between childhood ALL subtypes, including frequently prenatally initiated ALL subtypes. Results from this large, nationwide register-based study provided no evidence that childcare attendance in the first years of life protects against childhood ALL.

Patients With Microscopic Colitis Are at Higher Risk of Major Adverse Cardiovascular Events: A Matched Cohort Study.

BACKGROUND AND AIMS: Inflammatory diseases are associated with an increased risk of incident major adverse cardiovascular events (MACE). However, data on MACE are lacking in large population-based histopathology cohorts of microscopic colitis (MC). METHODS: This study included all Swedish adults with MC without previous cardiovascular disease (1990-2017; N = 11,018). MC and subtypes (collagenous colitis and lymphocytic colitis) were defined from prospectively recorded intestinal histopathology reports from all pathology departments (n = 28) in Sweden. MC patients were matched for age, sex, calendar year, and county with up to 5 reference individuals (N = 48,371) without MC or cardiovascular disease. Sensitivity analyses included full sibling comparisons, and adjustment for cardiovascular medication and healthcare utilization. Multivariable-adjusted hazard ratios for MACE (any of ischemic heart disease, congestive heart failure, stroke, and cardiovascular mortality) were calculated using Cox proportional hazards modelling. RESULTS: Over a median of 6.6 years of follow-up, 2181 (19.8%) incident cases of MACE were confirmed in MC patients and 6661 (13.8%) in reference individuals. MC patients had a higher overall risk of MACE outcomes compared with reference individuals (adjusted hazard ratio [aHR], 1.27; 95% confidence interval [CI], 1.21-1.33) and higher risk of its components: ischemic heart disease (aHR, 1.38; 95% CI, 1.28-1.48), congestive heart failure (aHR, 1.32; 95% CI, 1.22-1.43), and stroke (aHR, 1.12; 95% CI, 1.02-1.23) but not cardiovascular mortality (aHR, 1.07; 95% CI, 0.98-1.18). The results remained robust in the sensitivity analyses. CONCLUSIONS: Compared with reference individuals, MC patients had a 27% higher risk of incident MACE, equal to 1 extra case of MACE for every 13 MC patients followed for 10 years.

Descemet Stripping Automated Endothelial Keratoplasty versus Descemet Membrane Endothelial Keratoplasty for Fuchs Endothelial Corneal Dystrophy: A National Registry-Based Comparison.

PURPOSE: To compare the outcome between posterior lamellar corneal transplant procedures for Fuchs endothelial corneal dystrophy, taking preoperative patient characteristics in consideration. Surgical methods compared were Descemet membrane endothelial keratoplasty (DMEK), Descemet stripping automated endothelial keratoplasty (DSAEK), and DSAEK with concomitant cataract surgery (phacoemulsification plus DSAEK). DESIGN: Registry-based study with propensity score matching. PARTICIPANTS: One thousand six hundred seventy-seven patients from all Swedish corneal transplantation units treated from 2012 through 2019. METHODS: All patients undergoing endothelial keratoplasty performed from 2012 through 2019 with completed 2-year follow-up data reported to The Swedish Corneal Transplant Register were included, totaling 1677 patients. Three comparable groups (DMEK, DSAEK, and phacoemulsification plus DSAEK) with 216 patients in each group were generated with propensity score matching based on preoperative visual acuity, age, sex, year of surgery, and preoperative risk factors such as inflammation, vascularization, and glaucoma. MAIN OUTCOME MEASURES: Best-corrected visual acuity (BCVA) at the 2-year follow-up, frequency of graft dislocation, graft rejection episodes, and graft failure within 2 years including primary graft failure. RESULTS: The preoperative corneal status was affected more severely in the DSAEK group before matching. In the matched groups, the median BCVA 2 years after surgery was 0.1 logarithm of the minimum angle of resolution (logMAR) in both the DMEK and the phacoemulsification plus DSAEK groups and 0.15 logMAR in the DSAEK group (P = 0.001). The frequency of graft dislocation was higher among the patients undergoing phacoemulsification plus DSAEK, but the frequency of graft failure and primary graft failure was higher in the DMEK group. CONCLUSIONS: Visual acuity improved in most patients (90%) with all 3 surgical methods. However, DMEK and phacoemulsification plus DSAEK reached higher levels of visual acuity 2 years after surgery, and phacoemulsification plus DSAEK was superior considering graft survival rate. All 3 surgical procedures showed both strengths and weaknesses, suggesting that the choice of surgical method should be individualized, taking into consideration not only the cornea, but each patient's complete medical status as well as the entire course of postoperative medical care. FINANCIAL DISCLOSURE(S): The author(s) have no proprietary or commercial interest in any materials discussed in this article.