Swedish National Patient Register Research Articles

Prognostic impact of permanent pacemaker implantation after cardiac surgery

Abstract Introduction Brady-arrhythmias with subsequent need for permanent pacemaker implantation is after cardiac surgery. It is not known whether the need of a permanent pacemaker influences long-term prognosis after cardiac surgery. Methods This large, nationwide study included all patients who underwent cardiac surgery in Sweden 2006-2020. Data was obtained from the Swedish Cardiac Surgery Registry, The Swedish ICD and Pacemaker Registry, The Swedish National Patient Register, and the Swedish Cause of Death Register. Patients who received a permanent pacemaker within 30 days were compared to those who did not. Exclusion criteria were previous pacemaker or implantable cardioverter defibrillator implantation and death within 30 days. Missing data were handled by multiple imputation. Cox regressions models were used to obtain hazard ratios (HR) with 95% confidence intervals (95%CI). The model was adjusted for age at operation, sex, left ventricular ejection fraction (EF), type of surgery, previous myocardial infarction, diabetes, peripheral artery disease, chronic respiratory disease, hypertension and atrial fibrillation. Results In total, 74 606 patients were included out of which 2 150 (2.9%) received a pacemaker within the first 30 days after cardiac surgery. Those who had a pacemaker implanted were older, more often female, had lower EF and significantly more often atrial fibrillation and peripheral artery disease. These patients were less likely to have diabetes, hypertension and previous myocardial infarction. Pacemaker implantation was associated with a higher risk of all-cause mortality (adjusted HR: 1.09 (95%CI=1.00-1.19), p=0.035, Figure 1) and heart failure hospitalization (adjusted HR: 1.45 (95%CI=1.30-1.62), p<0.001). Cardiovascular mortality had similar estimates but did not reach statistical significance (HR: 1.09 (95%CI=0.99-1.24), p=0.15). Conclusions The presence of brady-arrhythmias requiring permanent pacemaker implantation after cardiac surgery is associated with a higher risk of mortality and heart failure hospitalization. Measures should be taken to minimize the risk of injury to the conduction system leading to brady-arrhythmias during cardiac surgery.

Increased risk of venous thromboembolism in young and middle-aged individuals with hereditary angioedema: a family study

Hereditary angioedema (HAE) due to C1 inhibitor protein (C1-INH) deficiency was recently shown to be associated with increased risk of venous thromboembolism (VTE). This is the first national family study of HAE with the aim to determine the familial risk of VTE. The Swedish Multi-Generation Register was linked to the Swedish National Patient Register during the period 1964-2018. Only HAE patients with a validated diagnosis were included in the study and were linked to their family members. Hazard ratios (HRs) and 95% confidence intervals (CIs) for VTE were calculated for HAE patients compared with relatives without HAE. Among 2,006 individuals (from 276 pedigrees of 365 patients with HAE), 103 individuals were affected by VTE. In total 35 (9.6%) of HAE patients compared to 68 (4.1%) of non-HAE relatives were affected by VTE (p<0.001). The adjusted HR for VTE among HAE patients was 2.51 (95% CI 1.67-3.77). HAE patients were younger at the first VTE than their non-HAE relatives (mean age 51 versus 63 years, p<0.001). Before the age of 70 years the HR for VTE among HAE patients was 3.62 (95%CI 2.26-5.80). The HR for VTE for HAE patients born after 1964 was 8.29 (95%CI 2.90-23.71). The HR for VTE for HAE patients born 1964 or earlier was 1.82 (95%CI 1.14-2.91). HAE is associated with VTE among young and middle-aged individuals in Swedish families with HAE. The effect size of the association is in the order of other thrombophilias. We suggest that HAE may be considered a new rare thrombophilia.

Intentional self-harm and death by suicide in body dysmorphic disorder:A nationwide cohort study

Body dysmorphic disorder (BDD) is thought to be associated with considerable suicide risk. This nationwide cohort study quantified the risks of intentional self-harm - including non-suicidal self-injuries and suicide attempts - and death by suicide in BDD. Individuals with a validated ICD-10 diagnosis of BDD in the Swedish National Patient Register, registered between January 1, 1997 and December 31, 2020, were matched with 10 unexposed individuals from the general population on birth year, sex, and county of residence. Conditional Poisson regression models estimated incidence rate ratios (IRR) and 95% confidence intervals (CIs) for intentional self-harm and stratified Cox proportional hazards models estimated hazard ratios (HRs) and 95% CIs for death by suicide. Models adjusted for sociodemographic variables and lifetime psychiatric comorbidities. Among 2,833 individuals with BDD and 28,330 unexposed matched individuals, 466 (16.45%) and 1,071 (3.78%) had at least one record of intentional self-harm during the study period, respectively (IRR=3.37; 95% CI, 3.02-3.76). In the BDD cohort, about two thirds (n=314; 67%) had their first recorded self-harm event before their first BDD diagnosis. A total of 17 (0.60%) individuals with BDD and 27 (0.10%) unexposed individuals died by suicide (HR=3.47; 95% CI, 1.76-6.85). All results remained robust to additional adjustment for lifetime psychiatric comorbidities. A higher proportion of individuals with BDD who died by suicide had at least one previous record of intentional self-harm, compared to unexposed individuals (52.94% vs. 22.22%; p=0.0363). BDD was associated with a three-fold increased risk of intentional self-harm and death by suicide.

Concomitant autoimmunity and risk of multiple sclerosis disability worsening

BackgroundFew studies have examined the effect of concomitant autoimmune diseases on multiple sclerosis (MS) disability worsening. We set out to examine whether concomitant Crohn's Disease (CD), Ulcerative Colitis (UC), or Type 1 Diabetes (T1D) affect MS disability worsening in a nationwide cohort of MS patients as defined by reaching expanded disability scale status (EDSS) scores 3.0, 4.0 and 6.0. MethodsPatients with MS onset between January 2004 and January 2019 were identified from the Swedish MS registry and the Swedish National Patient Register. Kaplan-Meier analysis was used to estimate the median time to reach sustained disability milestones. Adjusted Cox proportional hazard regression models were used to calculate the risk of reaching disability milestones among persons with and without CD, UC, or T1D. ResultsOut of 8972 persons with MS, 88 (1.0%) had T1D, 47 (0.8%) had UC, and 78 (0.9%) had CD. There was a significantly higher risk of disability progression, for persons with MS and T1D for reaching EDSS 6.0, hazard ratio (HR) = 2.21 (95% confidence interval (CI) =1.48 -3.31) and persons with MS and comorbid CD for reaching EDSS 3.0, HR=2.30 (95%CI=1.74-3.04) and 4.0, HR=1.59 (95%CI=1.09-2.32), and persons with MS and comorbid UC for reaching EDSS 3.0 HR=1.57 (95%CI=1.15-2.14). As defined by Charlson's comorbidity index, the co-existence of other co-morbidities conferred a significant increase in the risk of reaching all endpoints, with HR ranging from 1.23 to 1.62. ConclusionComorbidity is associated with a significantly increased risk of reaching disability end-points, and T1D, CD, and UC increase the risk further. Thus, there appears to be a need for increased vigilance of comorbidites in persons with MS in order to optimise the long-term outcome of MS

Healthcare resource utilisation and direct medical cost for individuals with 5q spinal muscular atrophy in Sweden.

Spinal muscular atrophy (SMA) is a rare, progressive, neuromuscular disorder. Recent advances in treatment require an updated assessment of burden to inform reimbursement decisions. To quantify healthcare resource utilisation (HCRU) and cost of care for patients with SMA. Cohort study of patients with SMA identified in the Swedish National Patient Registry (2007-2018), matched to a reference cohort grouped into four SMA types (1, 2, 3, unspecified adult onset [UAO]). HCRU included inpatient admissions, outpatient visits, procedures, and dispensed medications. Direct medical costs were estimated by multiplying HCRU by respective unit costs. Average annual HCRU and medical costs were modelled for SMA versus reference cohorts to estimate differences attributable to the disease (i.e., average treatment effect estimand). The trajectory of direct costs over time were assessed using synthetic cohorts. We identified 290 SMA patients. Annualised HCRU was higher in SMA patients compared with reference cohorts. Highest risk ratios were observed for inpatient overnight stays for type 1 (risk ratio [RR]: 29.2; 95% confidence interval [CI]: 16.0, 53.5) and type 2 (RR: 23.3; 95% CI: 16.4,33.1). Mean annual direct medical costs per patient for each year since first diagnosis were greatest for type 1 (€114,185 and SMA-attributable: €113,380), type 2 (€61,876 and SMA-attributable: €61,237), type 3 (€45,518 and SMA-attributable: €44,556), and UAO (€4046 and SMA-attributable: €2098). Costs were greatest in the 2-3years after the first diagnosis for all types. The economic burden attributable to SMA is significant. Further research is needed to understand the burden in other European countries and the impact of new treatments.

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

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. 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. 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. 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.

Time trends and outcomes of gastrostomy placement in a Swedish national cohort over two decades

BACKGROUND Percutaneous endoscopic gastrostomy (PEG) and laparoscopically inserted gastrostomy have become the gold standard for adult patients and children, respectively, requiring long-term enteral nutrition support. Procedure-related mortality is a rare event, often reported to be zero in smaller studies. National data on 30-d mortality and long-term survival rates after gastrostomy placement are scarce in the literature. AIM To study the use of gastrostomies in Sweden from 1998-2019 and to analyze procedure-related mortality and short-term (&lt; 30 d) and long-term survival. METHODS In this retrospective, population-based cohort study, individuals that had received a gastrostomy between 1998-2019 in Sweden were included. Individuals were identified in the Swedish National Patient Register, and survival analysis was possible by cross-referencing the Swedish Death Register. The cohort was divided into three age groups: Children (0-18 years); adults (19-64 years); and elderly (≥ 65 years). Kaplan-Meier with log-rank test and Cox regression were used for survival analysis. RESULTS In total 48682 individuals (52% males, average age 60.9 ± 25.3 years) were identified. The cohort consisted of 12.0% children, 29.5% adults, and 58.5% elderly. An increased use of gastrostomies was observed during the study period, from 13.7/100000 to 22.3/100000 individuals (P &lt; 0.001). The use of PEG more than doubled (about 800 to 1800/year), with a corresponding decrease in open gastrostomy (about 700 to 340/year). Laparoscopic gastrostomy increased more than ten-fold (about 20 to 240/year). Overall, PEG, open gastrostomy, and laparoscopic gastrostomy constituted 70.0% (n = 34060), 23.3% (n = 11336), and 4.9% (n = 2404), respectively. Procedure-related mortality was 0.1% (n = 44) overall (PEG: 0.05%, open: 0.24%, laparoscopic: 0.04%). The overall 30-d mortality rate was 10.0% (PEG: 9.8%, open: 12.4%, laparoscopic: 1.7%) and decreased from 11.6% in 1998-2009 vs 8.5% in 2010-2019 (P &lt; 0.001). One-year and ten-year survival rates for children, adults, and elderly were 93.7%, 67.5%, and 42.1% and 79.9%, 39.2%, and 6.8%, respectively. The most common causes of death were malignancies and cardiovascular and respiratory diseases. CONCLUSION The annual use of gastrostomies in Sweden increased during the study period, with a shift towards more minimally invasive procedures. Although procedure-related death was rare, the overall 30-d mortality rate was high (10%). To overcome this, we believe that patient selection should be improved.

Mental and physical health in children of women with a history of anorexia nervosa.

Few studies have investigated the offspring of women with anorexia nervosa (AN). The aim of this study was to examine perinatal status, mental and physical health in the offspring of mothers with a history of AN. Fifty-one individuals with adolescent-onset AN and 51 matched controls (COMP) have been followed prospectively. Presently, 30years after AN onset, at a mean age of 44years, female participants who had given birth (nAN = 40, nCOMP = 40) were interviewed regarding psychiatric health in their offspring using the Developmental and Well-Being Assessment and the MINI International Neuropsychiatric Interview. In addition, information on the offspring's perinatal status, psychiatric- and physical health was obtained from the Swedish Medical Birth Register and The Swedish National Patient Register. Data regarding mental and physical health were available for 83 and 86 offspring in the AN and COMP groups, respectively. At birth, all of weight, length, head circumference and ponderal index were significantly reduced in the offspring of mothers with a history of AN. In adolescence, parental interviews indicated an overrepresentation of current psychiatric diagnoses in the offspring of mothers with AN. Compared with the offspring in the COMP group, endocrinological, immune and metabolic disorders were much more common in the offspring of the AN group. In conclusion, a history of AN increases the risk of worse perinatal outcome of the offspring. Later on, in childhood and adolescence, psychiatric and physical morbidity may be overrepresented in the offspring of women with AN.

Adverse Childhood Experiences and Adult Mental Health Outcomes

Exposure to adverse childhood experiences (ACEs) has consistently been associated with multiple negative mental health outcomes extending into adulthood. However, given that ACEs and psychiatric disorders cluster within families, it remains to be comprehensively assessed to what extent familial confounding contributes to associations between ACEs and clinically confirmed adult psychiatric disorders. To investigate whether associations between ACEs and adult mental health outcomes remain after adjusting for familial (genetic and environmental) confounding. This Swedish twin cohort study used a discordant twin pair design based on monozygotic (MZ) and dizygotic (DZ) twins. A total of 25 252 adult twins (aged 18-47 years) from the Swedish Twin Registry born between 1959 and 1998 were followed up from age 19 years until 2016, with a maximum follow-up time of 39 years. Data were analyzed from April 2022 to November 2023. A total of 7 ACEs, including family violence, emotional abuse or neglect, physical neglect, physical abuse, sexual abuse, rape, and hate crime, were assessed with items from the Life Stressor Checklist-Revised in a web-based survey. Adult (ages >18 years) clinical diagnosis of psychiatric disorders (ie, depressive, anxiety, alcohol or drug misuse, or stress-related disorders) were obtained from the Swedish National Patient Register. Of 25 252 twins included in the study (15 038 female [59.6%]; mean [SD] age at ACE assessment, 29.9 [8.7] years), 9751 individuals (38.6%) reported exposure to at least 1 ACE. A greater number of ACEs was associated with increased odds of any psychiatric disorder in the full cohort (odds ratio [OR] per additional ACE, 1.52; 95% CI, 1.48-1.57). The association remained but ORs per additional ACE were attenuated in DZ (1.29; 95% CI, 1.14-1.47) and MZ (1.20; 95% CI, 1.02-1.40) twin pairs. Individuals who were exposed to sexual abuse compared with those who were not exposed had increased odds of any clinically confirmed psychiatric disorder in all comparisons: full cohort (OR, 3.09; 95% CI, 2.68-3.56), DZ twin pairs (OR, 2.10; 95% CI, 1.33-3.32), and MZ twin pairs (1.80; 95% CI, 1.04-3.11). This study found that associations between ACEs and adult mental health outcomes remained after controlling for shared genetic and environmental factors, which was particularly evident after multiple ACEs or sexual abuse. These findings suggest that targeted interventions may be associated with reduced risks of future psychopathology.

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.

Health care utilization, mental disorders and behavioural disorders among perpetrators of intimate partner homicide in 2000-2016: A registry-based case-control study from Sweden.

Little is known about intimate partner homicide (IPH) perpetrator´s healthcare contacts and mental health problems before the killing. The aim was to compare male and female IPH perpetrators with matched controls from the general population by analysing differences in healthcare utilization and mental and behavioural disorders. This study includes 48 males and 10 females who perpetrated IPH between 2000 and 2016 in the Västra Götaland Region of Sweden. Controls (n = 458) were randomly selected from the general population and matched for sex, birth year and residential area. Data were retrieved from the Swedish National Patient Register and the Western Swedish Healthcare Register. Mental and behavioural disorders were classified according to ICD-10 (F00-F99). The Mann-Whitney U test was used to test for differences in health care utilization and mental and behavioural disorders. Compared to their controls, male perpetrators had more registered contacts with primary care ≤ 30 (p = < .001) and ≤ 365 days (p = .019), respectively, before the homicide; with specialist outpatient care ≤ 30 (p = < .001) and ≤ 365 days (p = < .001), respectively, before the homicide: and with inpatient care ≤ 30 (p = < .001) and ≤ 365 days (p = .024), respectively, before the homicide. Female perpetrators had more specialized outpatient care (p = .040) and inpatient care (p = .003) contacts ≤ 365 days before the homicide, compared to controls. Male perpetrators had at least one mental or behavioral disorder diagnosed in any studied healthcare setting except in inpatient care ≤ 30 days before homicide. Female perpetrators had more mental health disorders diagnosed in specialized outpatient care ≤ 365 days before the homicide (p < .001). Perpetrators had more healthcare contacts and mental disorders one year and one month prior to the homicide compared to their controls. Health care professionals should obtain necessary skills in routinely enquiring about intimate partner violence perpetration.

Increased incidence of motor neuron disease in Sweden: a population-based study during 2002–2021

BackgroundMotor neuron diseases (MND), with amyotrophic lateral sclerosis constituting most cases, are rare conditions of unknown etiology. There have been reports of an increase in incidence during the latter half of the twentieth century in various Western countries, including Sweden. This study provides updated data on the incidence of MND in Sweden during the last 20 years.MethodsData was obtained from the Swedish National Patient Register on individuals diagnosed with MND from 2002 to 2021 and analysed in relation to group level data for the entire Swedish population. Incidence rates were calculated and presented in relation to year, age, sex, and region.ResultsIn the early 2000s, there was a crude incidence rate of 3.5–3.7 per 100,000 person-years, which then increased to 4.0–4.6 from 2008 onward. Age standardization to the starting year (2002) partially mitigated this increase. The incidence rate was greater among men compared to women and was highest within the age range of 70 to 84 years. There were indications of a higher incidence rate in the northernmost parts of the country, although the difference was not statistically significant.ConclusionsThe incidence rate of MND in Sweden now seems to have surpassed 4 cases per 100,000 person-years. This is higher when compared to both other European countries and previous Swedish studies. It remains to be determined if this increase reflects an actual increasing incidence of MND in Sweden or is due to other factors such as better registry coverage.

Breast-feeding decreases the risk of developing psoriasis through early adulthood.

Psoriasis is a genetically determined systemic skin disease, although environmental trigger factors are required for disease manifestation. Some of these triggers, such as stress, infections, and drug exposure, have been identified. To explore the role of early nutrition as a risk factor for the development of psoriasis. Parents in the ABIS (All Babies in Southeast Sweden) (n= 16145) prospective birth cohort answered questionnaires at birth and by the child's age of 1 and 3 years. Diagnosis of psoriasis was received from the Swedish National Patient Register and National Drug Prescription Register. Statistical analyses were conducted using custom-written R scripts. Individuals breastfed for less than 4 months and receiving infant formula before 4 months were associated with a higher risk of psoriasis (OR 1.84; p=0.018, and OR 1.88; p=0.015 respectively). At the 3-year follow-up, the increased consumption of fish, especially from the Baltic Sea, increased the risk of psoriasis (OR9.61; p=0.003). In addition, the risk of psoriasis increased following large milk consumption (OR2.53; p=0.040). Our study underscores, for the first time, the impact of very early nutrition on the manifestation of psoriasis through early adulthood. Exclusive breastfeeding for 4 months seems protective.

Increased Risk of Long-Term Disabilities Following Childhood Bacterial Meningitis in Sweden

Few studies have examined the incidence of long-term disabilities due to bacterial meningitis in childhood with extended follow-up time and a nationwide cohort. To describe the long-term risks of disabilities following a childhood diagnosis of bacterial meningitis in Sweden. This nationwide retrospective registry-based cohort study included individuals diagnosed with bacterial meningitis (younger than 18 years) and general population controls matched (1:9) by age, sex, and place of residence. Data were retrieved from the Swedish National Patient Register from January 1, 1987, to December 31, 2021. Data were analyzed from July 13, 2022, to November 30, 2023. A diagnosis of bacterial meningitis in childhood recorded in the National Patient Register between 1987 and 2021. Cumulative incidence of 7 disabilities (cognitive disabilities, seizures, hearing loss, motor function disorders, visual disturbances, behavioral and emotional disorders, and intracranial structural injuries) after bacterial meningitis in childhood. The cohort included 3623 individuals diagnosed with bacterial meningitis during childhood and 32 607 controls from the general population (median age at diagnosis, 1.5 [IQR, 0.4-6.2] years; 44.2% female and 55.8% male, median follow-up time, 23.7 [IQR, 12.2-30.4] years). Individuals diagnosed with bacterial meningitis had higher cumulative incidence of all 7 disabilities, and 1052 (29.0%) had at least 1 disability. The highest absolute risk of disabilities was found for behavioral and emotional disorders, hearing loss, and visual disturbances. The estimated adjusted hazard ratios (HRs) showed a significant increased relative risk for cases compared with controls for all 7 disabilities, with the largest adjusted HRs for intracranial structural injuries (26.04 [95% CI, 15.50-43.74]), hearing loss (7.90 [95% CI, 6.68-9.33]), and motor function disorders (4.65 [95% CI, 3.72-5.80]). The adjusted HRs for cognitive disabilities, seizures, hearing loss, and motor function disorders were significantly higher for Streptococcus pneumoniae infection (eg, 7.89 [95% CI, 5.18-12.02] for seizure) compared with Haemophilus influenzae infection (2.46 [95% CI, 1.63-3.70]) or Neisseria meningitidis infection (1.38 [95% CI, 0.65-2.93]). The adjusted HRs for cognitive disabilities, seizures, behavioral and emotional disorders, and intracranial structural injuries were significantly higher for children diagnosed with bacterial meningitis at an age below the median. The findings of this cohort study of individuals diagnosed with bacterial meningitis during childhood suggest that exposed individuals may have had an increased risk for long-term disabilities (particularly when diagnosed with pneumococcal meningitis or when diagnosed at a young age), highlighting the need to detect disabilities among surviving children.

Menopausal hormone therapy and risk of sarcoidosis: a population-based nested case–control study in Sweden

Sarcoidosis incidence peaks in women between 50 and 60 years old, which coincides with menopause, suggesting that certain sex hormones, mainly estrogen, may play a role in disease development. We investigated whether menopausal hormone therapy (MHT) was associated with sarcoidosis risk in women and whether the risk varied by treatment type. We performed a nested case–control study (2007–2020) including incident sarcoidosis cases from the Swedish National Patient Register (n = 2593) and matched (1:10) to general population controls (n = 20,003) on birth year, county, and living in Sweden at the time of sarcoidosis diagnosis. Dispensations of MHT were obtained from the Swedish Prescribed Drug Register before sarcoidosis diagnosis/matching. Adjusted odds ratios (aOR) of sarcoidosis were estimated using conditional logistic regression. Ever MHT use was associated with a 25% higher risk of sarcoidosis compared with never use (aOR 1.25, 95% CI 1.13–1.38). When MHT type and route of administration were considered together, systemic estrogen was associated with the highest risk of sarcoidosis (aOR 1.51, 95% CI 1.23–1.85), followed by local estrogen (aOR 1.25, 95% CI 1.11–1.42), while systemic estrogen-progestogen combined was associated with the lowest risk compared to never users (aOR 1.12, 95% CI 0.96–1.31). The aOR of sarcoidosis did not differ greatly by duration of MHT use. Our findings suggest that a history of MHT use is associated with increased risk of sarcoidosis, with women receiving estrogen administered systemically having the highest risk.

Familial risk of vasospastic angina: a nationwide family study in Sweden

ObjectivesVasospastic angina (VSA) is a complex coronary vasomotor disorder associated with an increased risk of myocardial infarction and sudden death. Despite considerable advances in understanding VSA pathophysiology, the interplay between...

The impact of genetic risk for schizophrenia on eating disorder clinical presentations

A growing body of literature recognizes associations between eating disorders (EDs) and schizophrenia and suggests that familial liability to schizophrenia in individuals with anorexia nervosa (AN) reveals distinct patterns of clinical outcomes. To further investigate the influence of schizophrenia genetic liability among individuals with EDs, we evaluated the associations between schizophrenia polygenic risk scores (PRS) and clinical presentations of individuals with EDs including their overall health condition and ED-related symptoms. Using data from two previous studies of the genetics of EDs comprising 3,573 Anorexia Nervosa Genetics Initiative (ANGI) cases and 696 Binge Eating Genetics Initiative (BEGIN) cases born after 1973 and linked to the Swedish National Patient Register, we examined the association of schizophrenia PRS on ED clinical features, psychiatric comorbidities, and somatic and mental health burden. Among ANGI cases, higher schizophrenia PRS was statistically significantly associated with higher risk of major depressive disorder (MDD) measured by hazard ratio (HR) with 95% confidence interval (CI) (HR [95% CI]: 1.07 [1.02, 1.13]) and substance abuse disorder (SUD) (HR [95% CI]: 1.14 [1.03, 1.25]) after applying multiple testing correction. Additionally, higher schizophrenia PRS was associated with decreased clinical impairment assessment scores (−0.56, 95% CI: [−1.04, −0.08]) at the conventional significance level (p < 0.05). Further, in BEGIN cases, higher schizophrenia PRS was statistically significantly associated with earlier age at first ED symptom (−0.35 year, 95% CI: [−0.64, −0.06]), higher ED symptom scores (0.16, 95% CI: [0.04, 0.29]), higher risk of MDD (HR [95% CI]: 1.18 [1.04, 1.34]) and SUD (HR [95% CI]: 1.36 [1.07, 1.73]). Similar, but attenuated, patterns held in the subgroup of exclusively AN vs other eating disorder (OED) cases. These results suggest a similar pattern of influence of schizophrenia PRS for AN and OED cases in terms of psychiatric comorbidities, but a different pattern in terms of ED-related clinical features. The disparity of the effect of schizophrenia PRS on AN vs OED merits further investigation.

Fusion of electronic health records and radiographic images for a multimodal deep learning prediction model of atypical femur fractures

Atypical femur fractures (AFF) represent a very rare type of fracture that can be difficult to discriminate radiologically from normal femur fractures (NFF). AFFs are associated with drugs that are administered to prevent osteoporosis-related fragility fractures, which are highly prevalent in the elderly population. Given that these fractures are rare and the radiologic changes are subtle currently only 7% of AFFs are correctly identified, which hinders adequate treatment for most patients with AFF. Deep learning models could be trained to classify automatically a fracture as AFF or NFF, thereby assisting radiologists in detecting these rare fractures. Historically, for this classification task, only imaging data have been used, using convolutional neural networks (CNN) or vision transformers applied to radiographs. However, to mimic situations in which all available data are used to arrive at a diagnosis, we adopted an approach of deep learning that is based on the integration of image data and tabular data (from electronic health records) for 159 patients with AFF and 914 patients with NFF. We hypothesized that the combinatorial data, compiled from all the radiology departments of 72 hospitals in Sweden and the Swedish National Patient Register, would improve classification accuracy, as compared to using only one modality. At the patient level, the area under the ROC curve (AUC) increased from 0.966 to 0.987 when using the integrated set of imaging data and seven pre-selected variables, as compared to only using imaging data. More importantly, the sensitivity increased from 0.796 to 0.903. We found a greater impact of data fusion when only a randomly selected subset of available images was used to make the image and tabular data more balanced for each patient. The AUC then increased from 0.949 to 0.984, and the sensitivity increased from 0.727 to 0.849.These AUC improvements are not large, mainly because of the already excellent performance of the CNN (AUC of 0.966) when only images are used. However, the improvement is clinically highly relevant considering the importance of accuracy in medical diagnostics. We expect an even greater effect when imaging data from a clinical workflow, comprising a more diverse set of diagnostic images, are used.

Comorbidity patterns and health-related outcomes in older adults with atrial fibrillation: nationwide population-based findings from swedish national patient register

Abstract Background Older individuals with atrial fibrillation (AF) often present with multiple comorbidities that might challenge their clinical management and worsen the prognosis. Identifying homogenous groups of individuals within similar patterns of comorbidities and health trajectories could potentially facilitate a better integrated care targeting patient-centred needs in AF management. Purpose To characterize the comorbidity patterns and to explore their prognostic value in health outcomes among older adults with AF. Methods We used population-wide registry data from the Swedish National Patient Register and identified individuals ≥65 years old by 1 January 2017 with AF diagnosis during the period 1 January 2012 - 1 January 2017. Chronic diseases were grouped into 60 clinically relevant disease categories coded by the International Classification of Diseases 10th revision. We performed latent class analysis (LCA) to identify homogeneous groups of AF patients with similar underlying comorbidity patterns. Two measures, disease exclusivity ≥25% and an observed/expected ratio ≥2, were applied to determine the overexpressed diseases in each class. Cox regression models (adjusted by age, sex, education, income, civil status, polypharmacy, vitamin K antagonists, direct oral anticoagulants, antiplatelets, and antiarrhythmics) were fitted to investigate the association between comorbidity patterns and clinical outcomes including two-year risk of all-cause and cardiovascular (CV) mortality, stroke, major bleedings, all-cause and CV hospitalization. Results A total of 203,042 AF individuals (mean age 79.6 [7.9] years, 45% female) were included. Seven classes were identified based on the optimal output of LCA (Figure 1), i.e., unspecific pattern (39.3%), metabolic disease (12.3%), complex comorbidity (11.7%), neuropsychiatric disease (11.0%), CV disease (10.6%), musculoskeletal disease (9.0%) and eye disease (6.2%). Compared with patients showing an unspecific comorbidity pattern, patients with complex comorbidity had the highest increased risk of all-cause mortality (hazard ratio, HR 2.02, 95% confidence, 95%CI 1.96-2.08), CV mortality (HR 2.31, 95%CI 2.20-2.41), all-cause hospitalization (HR 2.45, 95%CI 2.40-2.50), CV hospitalization (HR 2.68, 95%CI 2.60-2.77), and bleedings (HR 1.55, 95%CI 1.40-1.72); patients within the neuropsychiatric disease pattern had the highest increased risk of stroke (HR 1.44, 95%CI 1.30-1.59); and patients within the musculoskeletal disease pattern had reduced risk of all-cause and CV mortality (HR 0.70, 95%CI 0.66-0.74; HR 0.67, 95%CI 0.62-0.74, respectively) and increased risk of all-cause and CV hospitalization (HR 1.37, 95%CI 1.34-1.41; HR 1.19, 95%CI 1.14-1.25, respectively). Conclusions The characterization of comorbidity patterns may help to improve clinical outcomes by targeting patient-centred needs among multimorbid older patients with AF.

Consistent excess mortality risk after heart failure onset in patients with atrial fibrillation, survival trends over 30 years of follow up, a nationwide registry-based study

Abstract Background Atrial fibrillation and heart failure often coexist which is strongly associated with worse outcomes. Overall, the management and prognosis of heart failure has improved over time, however, to which extent this applies to low-risk patients with AF who were subsequently diagnosed with heart failure remains unclear. Purpose To investigate temporal survival trend of patients with AF and without other cardiovascular risk factors after HF onset from 1987 to 2017. Methods All patients from the Swedish National Patient Register, with a first-time diagnosis of AF between 1987 and 2017 were identified and compared with two matched controls without AF from the Total Population Register. Patients &amp;lt; 18 years, or any previous cardiovascular disease, diabetes mellitus and renal failure at baseline were excluded, along with their matched controls. The observation time was divided into two periods: 1987-2002 and 2003-2017. The study population was divided in following age categories: 18-34, 35-54, 55-54 and &amp;gt;75 years. Hazard ratios for survival were estimated using Cox regression models. Results In total we identified 227,811 patients with AF defined as low risk and 452,712 controls, 55.5% men, mean age (SD) in men 65.5 (15.0) and in women 72.7 (13.0) years. Mean follow up time for patients and controls was 8.7 (6.8) years. Between 1987 and 2002 mortality during the first year after onset in patients who were diagnosed with HF was 27.1% in AF patients while patients with AF who remained free from heart failure had a corresponding mortality of 10.6%. All-cause mortality rates within one year for controls were significantly lower in all groups. Compared with 1987-2002, one-year mortality in 2003-2017 decreased for in those with AF and HF (17.5%) as well as in those with AF who remained free of HF (7.5%). Compared to controls the relative mortality hazard within one year was 4.78 (95% CI 4.39-5.20) during the period 1987-2002 for patients with AF and HF-onset and 2.56 (95%CI 2.48-2.64) for AF patients without HF. HRs during 2003-2017 HR for 1-year all-cause mortality were 4.38 (95% CI 4.00-4.79) and 2.96 (95% CI 2.87-3.06), respectively. The highest hazard associated with HF in patients with AF 1987-2002 was found among patients 18-34 years [HR 13.87 (95%CI: 1.71-112.72) that decreased to HR 5.57 (95%CI: 2.01-15.47) 2003-2017. The mortality hazard decreased with increasing age in both periods, more in the later period. However, compared to controls in Cox regression adjusted for age and sex, patients who developed HF had HR 4.92 (95% CI:4.52-5.36) between 1987-2002 that declined only marginally in the later period to HR 4.51 (95%CI:4.12-4.93). Conclusion In low-risk patients with AF, the addition of HF raises 1-year mortality substantially. The 1-year mortality rates declined between the two periods but excess risk in patients with AF and HF compared to controls remained almost constant four times higher in patients with AF and HF than in controls.