Swedish Patient Research Articles

Waiting for hip fracture surgery: Analysis of individual heterogeneity and discriminatory accuracy

Abstract Background Evaluation of healthcare inequality could be improved by considering (i) the intersection of socioeconomic axes of inequality, (ii) the existence of individual heterogeneity and (iii) criteria to quantify group differences and how those differences translate into recommendations for universal or targeted interventions. In this study we illustrate how to achieve these improvements. Methods We applied analysis of individual heterogeneity and discriminatory accuracy (AIHDA) to analyze data from the Swedish patient registry for the quality indicator hip fracture (HF) surgery within the same day. We analyzed 57,340 patients residing in Sweden during 2011-2014 and belonging to 36 socioeconomic strata defined by age, sex, income, and country of birth and the 21 Swedish regions. We calculated prevalences and 95% confidence intervals as well as the absolute number of cases. The benchmark was set to 80%. To quantify group differences, we evaluated the discriminatory accuracy (DA) using the area under the ROC curve (AUC). Results 68% (39,073/57,340) of the patients were operated in time. The prevalence across the 36 sociodemographic strata ranged from 51% (43-58%) to 81% (67-91%). However, the DA was low (AUC= 0.562) indicating very small group differences. About half of the operated HP (n = 20,287) occurs in 18/36 strata with the lowest prevalences of operations in time. The regions’ prevalences ranged from 37% (36-38%) to 88% (88-89%) with a rather high DA (AUC= 0.736) indicating larger differences. About half of the operated HP (n = 19,677) occurs in 12/21 regions with the lowest prevalence of operations in time. Conclusions The 80% benchmark was only achieved in one socioeconomic stratum and the group differences were very small. 6/21 regions achieved the benchmark and the group differences were large. Interventions aiming to reach the benchmark in the entire population should proportionately target regions and be universal and tailored to sociodemographic strata. Key messages • The AIHDA-framework improves evaluations of healthcare inequalities. • Both differences between group averages and the groups’ DA need be considered when planning healthcare interventions.

Decade-long analysis of postoperative endophthalmitis in Sweden: Insights from insurance and national quality registers

PurposeTo analyse clinical characteristics and risk factors for post-operative endophthalmitis (POE) in a Swedish patient insurance database and compare prevalence of POE with two national quality registers. MethodsWe analysed 218 medical records of patients who claimed compensation for POE following ocular surgery from 2010 to 2020. The data were cross-referenced with national quality registers. ResultsIn total, 189 of 218 patients presented with severe ocular inflammation with no visibility into the posterior fundus and 160 of 218 had hypopyon. After treatment, the best corrected visual acuity improved from 2.4 to 1.8 LogMAR in mean (p < 0.01). Poorer visual outcome was associated with POE caused by Staphylococcus aureus, Enterococcus faecalis, and Streptococcus infections, as compared to coagulase-negative staphylococci (p < 0.01). Retinal detachment was linked to worse visual prognosis (p = 0.01). Eighteen patients required enucleation or evisceration, three of these had initially undergone vitrectomy, compared with 124 of 200 where the eyes were preserved. Peripheral vitrectomy showed better outcome compared to central vitrectomy (p = 0.02). Financial compensation was granted for 92 % of patients. However, a discrepancy was noted when comparing the number of patients with insurance claims to those reported by the national quality registers, indicating underreporting in both. ConclusionThis study highlights the impact of bacterial type on visual recovery in POE. Peripheral vitrectomy showed better outcomes than central vitrectomy. Most patients needing enucleation or evisceration were not treated with vitrectomy. Significant discrepancies were found between POE prevalence in quality registers and insurance reports, indicating the need for better reporting, though the exact magnitude of underreporting remains unclear.

Trends in Antiseizure Medication Initiation, Switch, or Termination in Patients With Newly Diagnosed Epilepsy: A Nationwide Study.

Few studies evaluate physicians' choice of antiseizure medication (ASM) to treat patients with newly diagnosed epilepsy. The objective of this study was to analyze the choice of ASM and its use by age, sex, psychiatric comorbidities, and concurrent treatment with other drugs (antidepressant medications and contraceptives) in patients who initiated epilepsy treatment using monotherapy. Included in this study were persons (any age) with an incident hospital diagnosis of epilepsy during 2010-2022 in the Swedish Patient Register (SPR), preceding a first dispensing of any ASM (as reported in the Swedish Prescribed Drug Register, SPDR) for the period 2010-2022. Incident patients were identified using retrospective information during 2000-2009 in the SPR. Primary outcome was first dispensed ASM by age, sex, comorbidity, and comedication with antidepressants or contraceptives (SPDR). Secondary outcomes were time to ASM switch or termination assessed by survival analyses. Of 67,984 patients included (mean age 46; 46% female), 66,441 initiated ASM treatment using monotherapy. Relative risk (RR) for initiating treatment using monotherapy did not differ between age groups, sex, or patients with concurrent treatment with antidepressants, contraceptives, or psychiatric illness (RR and 95% CI did include 1.0). The share initiating treatment using levetiracetam increased from 10% in 2010 to 55% in 2022; valproic acid: 10%-5%. The likelihood of initiating treatment using 1 of the 5 most frequent ASMs differed between all compared groups (0.3 < RR < 1; 95% CI < 1; 1 < RR < 15; 1 <95% CI). Seven percent of female patients of childbearing age initiated treatment with valproic acid, levetiracetam was the most frequent initial ASM in patients with psychiatric comorbidity (40.2%), and lamotrigine the most prescribed initial ASM to women on contraceptives (50.4%). Highest likelihoods of treatment termination were found among children (1.72 < RR < 3.07; 1 <95% CI) and among patients with psychiatric comorbidity (initiated on carbamazepine, RR 1.38; 1 <95% CI or lamotrigine, RR 1.31; 1 <95% CI). Thirty-one percent to 47% of patients switched from an initial monotherapy to a new monotherapy within 5 years. Twenty percent to 42% terminated ASM treatment within 5 years. Levetiracetam and lamotrigine were the most frequently dispensed initial ASMs, also among patients with comorbidities or comedications complicating the use of these ASMs, highlighting the need for improved education of prescribers concerning ASM selection in relation to individual patient characteristics. Use of ASMs in hospital is not captured in the SPDR.

Heart failure: the grim reaper of the cardio-renal-metabolic triad.

Current understanding of the prognosis for patients with chronic kidney disease (CKD) and overlapping cardio-renal-metabolic components, specifically heart failure (HF) and diabetes mellitus (DM), remains limited. While previous studies have explored the interactions between CKD, HF, and DM, they have predominantly focused on cohorts of HF or DM patients. This study aims to fill this gap by investigating the long-term outcomes and treatment patterns in a cohort of CKD patients, particularly those with coexisting HF and DM. We analysed data from the Swedish national CKD patient cohort, the Swedish Renal Registry, with a follow-up period extending up to 10years. The study examined the risks of all-cause mortality, major adverse cardiovascular events (MACE)-defined as a composite of non-fatal myocardial infarction, hospitalization for congestive HF, non-fatal stroke, or cardiovascular death-and the initiation of kidney replacement therapy (KRT). Analyses were conducted using Cox proportional hazards and competing risk models. Among the 27647 patients, 48% had CKD alone, 12% had CKD with HF, 27% had CKD with DM, and 13% had CKD with both HF and DM. After 5years, mortality rates were 23% for patients with CKD, 30% for those with CKD/DM, 54% for CKD/HF, and 55% for CKD/HF/DM. The 10year absolute risk of MACE was 28% for CKD alone, 35% for CKD/DM, 67% for CKD/HF, and 73% for CKD/HF/DM. The adjusted hazard ratio (HR) for mortality was approximately three times higher in patients with any HF combination, with HRs of 2.57 [95% confidence interval (CI) 2.43-2.71] for CKD/HF and 3.22 (95% CI 3.05-3.39) for CKD/HF/DM, compared with CKD alone. The impact of HF on MACE prognosis was even more pronounced, with adjusted sub-hazard ratios (SHRs) of 3.33 (95% CI 3.14-3.53) for CKD/HF and 4.26 (95% CI 4.04-4.50) for CKD/HF/DM. Additionally, CKD patients diagnosed with HF were less likely to commence KRT, and the risk of death prior to KRT initiation was roughly twice as high for these groups, with SHRs of 2.05 (95% CI 1.93-2.18) for CKD+HF and 2.43 (95% CI 2.29-2.58) for CKD+HF+DM. In a cohort of CKD patients, having HF contributes substantially to increased mortality and the risk of MACE, and these patients are less likely to start KRT. These findings highlight the urgent need for targeted therapeutic strategies and management plans for CKD patients, particularly those with concurrent HF, to enhance patient prognosis.

Reduced dementia risk in patients with optimized anticoagulation therapy undergoing atrial fibrillation ablation

BackgroundAtrial fibrillation (AF) is associated with the development of dementia, and observational studies have shown that oral anticoagulation and catheter ablation reduce dementia risk. However, such studies did not consistently report on periprocedural anticoagulation and long-term oral anticoagulation coverage, for which reason the separate effect of AF ablation on dementia risk could not be established. ObjectiveWe evaluated the protective effect of AF ablation in a large cohort of patients who received optimized anticoagulation and compared them with patients who were managed medically. MethodsWe retrospectively included 5912 consecutive patients who underwent first-time catheter ablation for AF between 2008 and 2018 and compared them with 52,681 control individuals from the Swedish Patient Register. Propensity score matching produced 2 cohorts of equal size (n = 3940) with similar baseline characteristics. Dementia diagnosis was identified by International Classification of Diseases codes from the patient register. ResultsMost propensity score–matched patients were taking an oral anticoagulant at the start (94.5%) and end (75.0%) of the study. Mean follow-up was 4.9 ± 2.8 years. Catheter ablation was associated with lower risk for the dementia diagnosis compared with the control group (hazard ratio [HR], 0.44; 95% confidence interval [CI], 0.22–0.86; P = .017). The result was similar when including patients with a stroke diagnosis before inclusion (HR, 0.50; 95% CI, 0.28–0.89; P = .019) and after adjustment for the competing risk of death (HR, 0.41; 95% CI, 0.20–0.86; P = .018). ConclusionCatheter ablation of AF in patients with optimized oral anticoagulation therapy was associated with a reduction in dementia diagnosis, even after adjustment for potential confounders and for competing risk of death.

P1073 Opioid use Before and After First Diagnosis of Crohn’s Disease: A Swedish Nationwide Cohort Study 2008-2020

Abstract Background The ongoing opioid misuse epidemic, initially sparked by over-prescription, presents challenges in managing severe pain in Crohn’s disease (CD). Despite associated negative effects, such as narcotic bowel syndrome and susceptibility to chronic use, opioids are frequently prescribed for CD patients. However, data on the evolution of opioid use before and after the initial CD diagnosis in a European context are limited. Methods This nationwide cohort study utilized the Swedish Patient Register to identify adults with a first CD diagnosis between 1 January 2008 and 31 December 2017, residing in Sweden at least two years before and three years after the diagnosis. For each CD patient, we included up to 10 reference individuals from the general population matched on birth year, sex, calendar year, and place of residence. Data on dispensed opioid prescriptions were retrieved from the National Prescribed Drug Register. Opioid use history was categorized into non-users (no dispensations), intermittent users (≥1 dispensation in 1–3 periods), and chronic users (≥1 dispensation in all periods) based on the four preceding six-month periods before the first CD diagnosis. Opioid use per six-month period was estimated from two years before to five years following CD diagnosis (corresponding index date for matched reference individuals) and coarsened exact matching was employed to account for confounding (birth year, sex, education, and history of psychiatric disorders and cancer). Results We included 12,539 incident CD patients and 116,073 matched reference individuals. During the two years before the first CD diagnosis, CD patients (and 3.9% vs 10.4% and 1.4%, respectively) were more often intermittent (22.3% vs 10.4%) or chronic (3.9% vs 1.4%) opioid users than matched reference individuals. Prior to diagnosis, opioid use per six-month period was twice as common among CD patients than in reference individuals. Following a peak in the first year after the diagnosis, the prevalence of dispensed opioids per six-month period stabilized at a three-fold level among CD patients (13.6%; 95% CI: 13.0, 14.3) compared with the reference individuals (5.5%; 95% CI: 5.4, 5.7) (Figure 1). The 6-month prevalence of opioid use five years after CD diagnosis was 7.6% (95% CI: 7.0, 8.2), 22.9% (95% CI: 21.1, 24.6), and 79.5.4% (95% CI: 73.2, 85.7) for CD patients classified as non-users, intermittent, or chronic users two years before diagnosis, respectively. Conclusion CD patients exhibited elevated opioid use two years before their initial diagnosis, which persisted at a three-fold level compared to matched reference individuals for five years post-diagnosis. This pattern persisted despite publicly-funded healthcare and modern CD therapy accessibility.

P256 Relationship and sexuality in Inflammatory Bowel Disease: results from a patient questionnaire

Abstract Background Health-related quality of life has been studied for almost 30 years in patients with Inflammatory Bowel Disease (IBD). However, the knowledge concerning consequences of illness like fatigue, psychological illness, and relationship and sexuality is still sparse. The aim of this study was to gather more information about the IBD patient´s view concerning relationship and sexuality and how patients experience the support and help from the healthcare professionals. Methods A questionnaire was sent digitally to all members with an IBD diagnosis in the Swedish patient association. The questionnaire contained seven questions. Four of them concerned background data (age, gender, diagnosis, IBD-surgery). The final three questions concerned relationships and sexuality and were qualitatively analyzed with content analysis. Results Out of 2274 patients who received the questionnaire, a total of 556 answered (24%). The median age was 55 years of age, 69% were women, 46% had ulcerative colitis, 45% Crohn´s disease, 6% microscopic colitis, and 3% had a mixed form. A total of 36% had undergone surgery due to IBD. Question 5: "What kind of problems have you experienced regarding relationships and sexuality?" A total of 78% stated some kind of problem. The most common physical problems were pain (14%), incontinence/urgency (11%), and gas/bloating (9%). The most frequent psychological problems were fear of leakage (13%), decreased sexual drive (11%), and loss of energy (8%). Several patients described that their sexual life always needed to be carefully planned, and some described that they avoided having a partner because of difficulties to initiate relationships. Question 6: "What kind of help and support from the healthcare do you want?" A total of 64% wished that healthcare professionals raised questions concerning relationships and sexuality as an equal natural part as the rest of health status. Question 7: "Have you spontaneously raised questions concerning relationships and sexuality in your contacts with healthcare professionals?" A total of 84% answered no. Reasons stated were that it was felt uncomfortable, embarrassing, due to lack of time and that other concerns were prioritized. Some patients expressed that they had no contact with their healthcare center at all. Conclusion A total of 78% of the patients answering this questionnaire acknowledged that they experienced physical issues and fears concerning relationships and sexuality, mostly due to pain and leakage. A more active support was wanted from 64% of the patients, but only 14% had themselves raised the topic to health care professionals. More knowledge and awareness concerning relationships and sexuality are needed to ensure person-centered care for all IBD-patients.

Incidence of type 2 diabetes after gastric by-pass surgery in a Swedish controlled cohort study

AimsTo assess the long-term risk of developing type 2 diabetes in patients with obesity who have undergone gastric bypass surgery compared to non-operated patients with obesity and the general population. MethodsThis study included 71,495 patients aged 20–65 years with a principal diagnosis of obesity in the Swedish Patient Register in 2001–2013. Of these, 23,099 had undergone gastric bypass and 32,435 had not. Each patient was matched by age, sex and geographic region with two controls from the general population without obesity diagnosis, i.e., 44,735 controls for the gastric bypass cohort and 62,522 controls for the non-operated cohort with obesity. Operated and non-operated patients with obesity were also directly compared using Cox regression analysis, providing hazard ratios (HR) with 95% confidence intervals (CI) adjusted for age, education, and sex. ResultsDuring a median follow-up of 4.3 years (interquartile range [IQR] 2.4, 7.0 years), 3792 (11.7%) non-operated patients with obesity developed type 2 diabetes (incidence rate 22.8/1000 person-years, 95% CI 22.1–23.6) compared to 394 (1.7%) among gastric bypass patients (incidence rate 4.0/1000 person-years, 95% CI 3.6–4.5). The latter incidence was comparable to population controls (3.5/1000 person-years, 95% CI 3.2–3.8). Gastric bypass patients had 85% lower risk of diabetes compared to non-operated patients with obesity during the first six years of follow-up (HR 0.15; 95% CI 0.13–0.17). ConclusionGastric bypass surgery for obesity seems to reduce the risk of developing type 2 diabetes to levels similar to that of the general population during the first six years of follow-up but not thereafter.

Trajectories of primary health care utilization: a 10-year follow-up after the Swedish Patient Choice Reform of primary health care

BackgroundIn January 2010, the choice reform was instituted in Swedish primary health care establishing free entry for private primary health care providers and enabling patients to choose freely among primary health care centers. The motivation behind the reform was to improve access to primary care and responsiveness to patient expectations. Reform effects on health care utilization have previously been investigated by using subgroup analyses assuming a pattern of homogeneous subgroups of the population. By using a different methodological approach, the aim of this study was to, from an equity perspective, investigate long term trends of primary health care utilization following the choice reform.MethodA closed cohort was created based on register data from Region Skåne, the third most populated region in Sweden, describing individuals’ health care utilization between 2007–2017. Using a novel approach, utilization data, measured as primary health care visits, was matched with socioeconomic and geographic determinants, and analyzed using logistic regression models.ResultsA total of 659,298 individuals were included in the cohort. Sex differences in utilization were recorded to decrease in the older age group and to increase in the younger age group. Multivariable logistic regression showed increasing utilization in older men to be associated with higher socioeconomic position, while in women it was associated with lower socioeconomic position. Furthermore, groups of becoming high utilizers were all associated with lower socioeconomic position and with residence in urban areas.ConclusionThe impact of demographic, socioeconomic and geographic determinants on primary health care utilization varies in magnitude and direction between groups of the population. As a result, the increase in utilization as observed in the general population following the choice reform is unevenly distributed between different population groups.

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.

Inflammatory biomarkers and long-term outcome in young stable patients 3 months after a first myocardial infarction

Abstract Background Inflammation is an important driver of coronary artery disease (CAD). Several circulating inflammatory biomarkers have been associated with outcome, both before and after established CAD. However, studies in established CAD have often been limited by short follow-up period or blood sampling in the acute phase of a coronary event, which introduces a bias from the inflammatory response activated during a myocardial infarction (MI). Purpose This study aimed to compare the predictive value of several inflammatory biomarkers in a population of young stable patients 3 months after a first time MI. Methods 382 men and women ≤60 years of age with a first time MI were included from three Swedish hospitals between 1996 and 2000. 383 age- and sex-matched healthy controls were recruited from the general population. Individuals with previous MI, chronic inflammatory disease, kidney disease (creatinine &amp;gt;200 µmol/L), diabetes mellitus type 1, drug addiction or psychiatric disease were excluded. Three months after the acute index event, 15 biomarkers known to be involved in atherosclerosis were analysed; C-reactive protein (CRP), serum amyloid A (SAA), interleukin (IL)-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-18, interferon-gamma (IFN-γ), tumor necrosis factor-alfa (TNF-α), monocyte chemoattractant protein-1 (MCP-1), matrix metalloproteinase (MMP)-1, MMP-3 and MMP-9. The Swedish population register and national patient register were used to analyse cardiovascular outcome including all-cause mortality, recurrent MI and heart failure (HF) during 20 years of follow-up. A variable importance analysis and a Cox regression model were used. Biomarkers were divided in tertiles and compared with the lowest tertile as a reference. Results At inclusion, 82% of cases were men with a mean age of 52 years. 19% were smokers, 34% had a diagnosis of hypertension and 11% had diabetes mellitus. The level of each biomarker in cases and controls is shown in Table. When biomarkers were compared, IL-6 was identified as the most important biomarker to predict outcome. In cases, IL-6 was associated with a composite outcome of all-cause mortality, non-fatal MI and non-fatal HF in a model adjusted for age, sex and cardiovascular risk factors (HR 1.96, 95% CI 1.37-2.80) (Figure). IL-6 also was associated with all-cause mortality (HR 2.42, 95% CI 1.45-4.04) and HF (HR 2.58, 95% CI 1.54-4.33). Conclusions When 15 inflammatory markers involved in atherosclerosis were analysed, IL-6 was the most important biomarker to predict long-term cardiovascular outcome. This study is unique considering the extended follow-up period of 20 years in young individuals with blood sampled in a convalescent phase after a first myocardial infarction. IL-6 is a promising biomarker to predict long-term prognosis and a possible treatment target.Table.Medians for all 15 biomarkersOutcome in relation to IL-6 level

Errors, Omissions, and Offenses in the Health Record of Mental Health Care Patients: Results from a Nationwide Survey in Sweden.

Previous research reports that patients with mental health conditions experience benefits, for example, increased empowerment and validation, from reading their patient-accessible electronic health records (PAEHRs). In mental health care (MHC), PAEHRs remain controversial, as health care professionals are concerned that patients may feel worried or offended by the content of the notes. Moreover, existing research has focused on specific mental health diagnoses, excluding the larger PAEHR userbase with experience in MHC. The objective of this study is to establish if and how the experiences of patients with and those without MHC differ in using their PAEHRs by (1) comparing patient characteristics and differences in using the national patient portal between the 2 groups and (2) establishing group differences in the prevalence of negative experiences, for example, rates of errors, omissions, and offenses between the 2 groups. Our analysis was performed on data from an online patient survey distributed through the Swedish national patient portal as part of our international research project, NORDeHEALTH. The respondents were patient users of the national patient portal 1177, aged 15 years or older, and categorized either as those with MHC experience or with any other health care experience (nonmental health care [non-MHC]). Patient characteristics such as gender, age, education, employment, and health status were gathered. Portal use characteristics included frequency of access, encouragement to read the record, and instances of positive and negative experiences. Negative experiences were further explored through rates of error, omission, and offense. The data were summarized through descriptive statistics. Group differences were analyzed through Pearson chi-square. Of the total sample (N=12,334), MHC respondents (n=3131) experienced errors (1586/3131, 50.65%, and non-MHC 3311/9203, 35.98%), omissions (1089/3131, 34.78%, and non-MHC 2427/9203, 26.37%) and offenses (1183/3131, 37.78%, and non-MHC 1616/9203, 17.56%) in the electronic health record at a higher rate than non-MHC respondents (n=9203). Respondents reported that the identified error (MHC 795/3131, 50.13%, and non-MHC 1366/9203, 41.26%) and omission (MHC 622/3131, 57.12%, and non-MHC 1329/9203, 54.76%) were "very important," but most did nothing to correct them (MHC 792/3131, 41.29%, and non-MHC 1838/9203, 42.17%). Most of the respondents identified as women in both groups. About 1 in 2 MHC patients identified an error in the record, and about 1 in 3 identified an omission, both at a much higher rate than in the non-MHC group. Patients with MHC also felt offended by the content of the notes more commonly (1 in 3 vs 1 in 6). These findings validate some of the worries expressed by health care professionals about providing patients with MHC with PAEHRs and highlight challenges with the documentation quality in the records.

Risk of Infections in Multiple Myeloma in the Era of Novel Agents, a Population-Based Study Based on 8672 Multiple Myeloma Patients Diagnosed 2008-2021 from the Swedish Myeloma Registry

Introduction Despite modern therapies, infections are still a major cause of morbidity and mortality in patients with myeloma (MM). We therefore performed a large population-based study to evaluate the risk of bacterial, viral and fungal infections among 8672 Swedish symptomatic MM patients diagnosed 2008-2021 compared to 34,567 matched controls. Materials and methods Symptomatic patients reported to the Swedish Myeloma Registry and four matched controls per patient were analysed with occurrence and date of all infections in the centralized Swedish Patient registry that captures information on individual patient-based discharge diagnosis from inpatient and outpatient care. The Swedish MM patients were followed until death or until 31 st December 2022. Statistical analysis Cox proportional hazard models, with the occurrence of infection as a time dependant co-variate and cumulative incidence with competing risk models were used to estimate the risk of infections in MM compared to controls. All models were adjusted for sex, age and year of diagnosis. The effect of gender, age and calendar period of were evaluated separately. Hazard ratio (HR) and confidence intervals (95% CI) were calculated for the risk of different infections. All p-values were two-sided and a value below 0.05 was considered statistically significant. All analyses were performed with R version 4.3.1 and ethics approved. Results In this population-based study, 8672 Swedish symptomatic MM patients diagnosed 2008-2021 and 34,567 matched controls were included. The majority of patients (73 %) were 65 years or older at diagnosis, 57% were male, and 30 % treated with up-front autologous stem cell transplantation (auto-SCT). The median time of follow-up was 5 years. Overall, MM patients had a 5-fold (HR=4.73; [95% CI=4.59-4.89]) risk of developing any infection compared to matched controls. Bacterial infection had a 4-fold increased risk (HR=4.40; [4.24-4.57]), viral infection 6-fold (HR=6.11; [5.76-6.49]), and fungal infection 6-fold (HR=6.14; [5.56-6.79]) compared to controls. More specifically, MM patients had an increased risk (p&amp;lt;0.05) of the following bacterial infections compared to controls: meningitis (HR=19.6; [ 10.0-38.1]), septicaemia (HR=8.05; [7.52-8.62]), pneumonia (HR=7.72; [7.21-8.27]), endocarditis (HR=4.9; [3.70-6.48]), cellulitis (HR=3.13;[2.57-3.80]), osteomyelitis (HR=2.89; [1.95-2.92]), pyelonephritis (HR=2.3; [2.03-2.59]), and for the viral infections influenza (HR=9.40; [8.19-10.8]) and herpes zoster (HR=9.33; [8.19-10.6]) (Table 1). The risk of infections compared to controls was 4 to 5-fold the first year after diagnosis and remained elevated up to 5 years after the myeloma diagnosis. Figure 1 illustrates the cumulative incidence of infections compared to controls over time. MM patients diagnosed 2018 to 2021 had a slightly lower risk of infection, (HR=0.87 ([0.82-0.93] p&amp;lt; 0.05) compared to patients diagnosed 2008-2012, whilst the risk of infections was slightly higher 2013-2017 compared to the first time period (HR=1.06 ([1.00-1.11], p&amp;lt; 0.05). The cumulative risk of infection compared to controls remained 5-fold in patients diagnosed 2008-2012 (HR=5.03; [4.78-5.29], p&amp;lt;0.05) and 2013-2017 (HR=4.82; [4.59-5.06], p&amp;lt;0.05), and 4-fold (HR=3.93, [3.66-4.21], p&amp;lt;0.05) in patients diagnosed 2018-2021. Females had a significantly lower risk of infections compared to males (p&amp;lt;0.001). Older age at diagnosis increased the risk of a first infection (p&amp;lt;0.001). Discussion This study constitutes the largest population-based study to date on the risk of infections compared to the normal population in the era of modern MM therapies. Infections still represent a major threat to myeloma patients, with an equally about five-fold increased risk for bacterial, viral and fungal infections during the first year and up to 5 years after the myeloma diagnosis, even in more recent years.

Vaccine-Preventable Infections in Multiple Myeloma: A Population-Based Study on 8672 Myeloma Patients Diagnosed 2008-2021 from the Swedish Myeloma Registry

Background: Infections are a major clinical problem in the management of multiple myeloma (MM) due to both disease and treatment related factors. Measures to prevent infection, such as vaccination, are therefore of paramount importance in the clinical care of MM patients. Data on vaccine-preventable infections in MM treated with modern therapy is sparse. Aim: To estimate the risk of vaccine-preventable infections in myeloma patients compared to a healthy population using real-world data. Methods: The study population included all patients with symptomatic MM diagnosed between 2008 and 2021 and included in the Swedish Myeloma Registry (n=8,672). Four controls per MM patient were identified randomly from the Swedish population database matched for age, sex and county of residence (n=34,567). Diagnoses of infectious diseases were retrieved from the Swedish patient registry, with good coverage on diagnostic codes for different infections among inpatient and outpatient registries. Both MM patients and controls were followed until death or till 31 st December 2022. A multi-state Cox proportional hazard model with infection as a time dependent co-variate was used to estimate the overall, 1-and 5-year risk of infections compared to controls. All models were adjusted for sex, age and year of diagnosis. Hazard-ratios (HR) with 95% Confidence Intervals were calculated. Effects of age, sex and autologous stem cell transplantation (auto-SCT) were evaluated separately. When total number of cases with a specific infectious diseases were below 10, no statistical analyses were performed. The Cause of Death Registry was used to find deaths where specific infections were listed as cause of death or contributing to cause of death. We used a logistic regression model to estimate the difference between patients and controls. Odds-ratios (OR) with 95% Confidence Intervals were calculated. Results: A majority of patients (73 %) were 65 years or older at diagnosis, 57 % were male and 30 % were treated with up-front autologous stem cell transplantation (auto-SCT). The median time of follow-up was 5 years. The risk of acquiring a vaccine-preventable infection was 8-fold in MM patients compared to matched controls (HR=7.5; [7.0-8.0]). The risk- and number of infections for vaccine preventable infections are shown in Table 1. The risk of acquiring vaccine-preventable infections was higher in males (p=0.03). In the group treated with auto-SCT, the risk of vaccine preventable infections was slightly higher (HR=1.4; [1.2-1.6]) compared to patients not treated with auto-SCT, where the risk of herpes zoster was more than two-fold (HR=2.2; [1.7-2.8]). The incidence of vaccine preventable infections was 6-fold higher in MM patients compared to controls in the first year following diagnosis and remained high or increased for certain infections (pneumococcal infection, influenza and herpes zoster) during follow-up. See Figure 1. The risk of dying from influenza was 3-fold higher (0.5% vs 0.2%), OR=2.7; [1.4-5.3], p=0.002, in myeloma patients compared to controls. The risk of dying from a pneumococcal infection was low: 0.1% vs 0.04%, but 4-fold higher in MM-patients (OR=3.7; [1.0-14.8], p=0.049). Conclusion: The risk of vaccine-preventable infections was high in MM patients, especially pneumococcal infection where the risk compared to a healthy population was 17-fold. The risk of influenza, herpes zoster and haemophilus influenzae was manyfold in patients with MM and remained high or increased during follow-up. Recent studies have shown that vaccinations are underutilized in multiple myeloma and the current results suggest that they should be encouraged.

Clinical and genetic analyses of a Swedish patient series diagnosed with ataxia.

Hereditary ataxia is a heterogeneous group of complex neurological disorders. Next-generation sequencing methods have become a great help in clinical diagnostics, but it may remain challenging to determine if a genetic variant is the cause of the patient's disease. We compiled a consecutive single-center series of 87 patients from 76 families with progressive ataxia of known or unknown etiology. We investigated them clinically and genetically using whole exome or whole genome sequencing. Test methods were selected depending on family history, clinical phenotype, and availability. Genetic results were interpreted based on the American College of Medical Genetics criteria. For high-suspicion variants of uncertain significance, renewed bioinformatical and clinical evaluation was performed to assess the level of pathogenicity. Thirty (39.5%) of the 76 families had received a genetic diagnosis at the end of our study. We present the predominant etiologies of hereditary ataxia in a Swedish patient series. In two families, we established a clinical diagnosis, although the genetic variant was classified as "of uncertain significance" only, and in an additional three families, results are pending. We found a pathogenic variant in one family, but we suspect that it does not explain the complete clinical picture. We conclude that correctly interpreting genetic variants in complex neurogenetic diseases requires genetics and clinical expertise. The neurologist's careful phenotyping remains essential to confirm or reject a diagnosis, also by reassessing clinical findings after a candidate genetic variant is suggested. Collaboration between neurology and clinical genetics and combining clinical and research approaches optimizes diagnostic yield.

Genetic Contribution to the Heterogeneity of Major Depressive Disorder: Evidence From a Sibling-Based Design Using Swedish National Registers.

Major depressive disorder (MDD) is highly heterogeneous. Standard typology partly captures the disorder's symptomatic heterogeneity, although whether it adequately captures etiological heterogeneity remains elusive. The aim of this study was to investigate the genetic characterization of MDD heterogeneity. Using Swedish patient register data on 1.5 million individuals, the authors identified 46,255 individuals with specialist-diagnosed MDD. Eighteen subgroups were identified based on nine comparison groups defined by clinical and psychosocial features, including severity, recurrence, comorbidities, suicidality, impairment, disability, care unit, and age at diagnosis. A sibling-based design and classic quantitative genetic models were applied to estimate heritability of MDD subgroups and genetic correlations between subgroups. Estimates of heritability ranged from 30.5% to 58.3% across subgroups. The disabled and youth-onset subgroups showed significantly higher heritability (55.1%-58.3%) than the overall MDD sample (45.3%, 95% CI=43.0-47.5), and the subgroups with single-episode MDD and without psychiatric comorbidity showed significantly lower estimates (30.5%-34.4%). Estimates of genetic correlations between the subgroups within comparison groups ranged from 0.33 to 0.90. Seven of nine genetic correlations were significantly smaller than 1, suggesting differences in underlying genetic architecture. These results were largely consistent with previous work using genomic data. The findings of differential heritability and partially distinct genetic components in subgroups provide important insights into the genetic heterogeneity of MDD and a deeper etiological understanding of MDD clinical subgroups.

Bayesian monitoring of COVID-19 in Sweden

In an effort to provide regional decision support for the public healthcare, we design a data-driven compartment-based model of COVID-19 in Sweden. From national hospital statistics we derive parameter priors, and we develop linear filtering techniques to drive the simulations given data in the form of daily healthcare demands. We additionally propose a posterior marginal estimator which provides for an improved temporal resolution of the reproduction number estimate as well as supports robustness checks via a parametric bootstrap procedure.From our computational approach we obtain a Bayesian model of predictive value which provides important insight into the progression of the disease, including estimates of the effective reproduction number, the infection fatality rate, and the regional-level immunity. We successfully validate our posterior model against several different sources, including outputs from extensive screening programs. Since our required data in comparison is easy and non-sensitive to collect, we argue that our approach is particularly promising as a tool to support monitoring and decisions within public health.Significance: Using public data from Swedish patient registries we develop a national-scale computational model of COVID-19. The parametrized model produces valuable weekly predictions of healthcare demands at the regional level and validates well against several different sources. We also obtain critical epidemiological insights into the disease progression, including, e.g., reproduction number, immunity and disease fatality estimates. The success of the model hinges on our novel use of filtering techniques which allows us to design an accurate data-driven procedure using data exclusively from healthcare demands, i.e., our approach does not rely on public testing and is therefore very cost-effective.

Body Weight in Adolescent Men in Sweden and Risk of an Early Acute Coronary Event: A Prospective Population-Based Study.

Background Coronary heart disease remains the dominant cause of death worldwide. To improve cardiovascular disease prevention, knowledge of early key risk factors, especially those that are modifiable, is essential. The ongoing global obesity epidemic is of particular concern. We aimed to determine whether body mass index at conscription predicts early acute coronary events among men in Sweden. Methods and Results This was a population-based Swedish cohort study of conscripts (n=1 668 921; mean age, 18.3 years; 1968-2005), with follow-up through linkage to the nationwide Swedish patient and death registries. Risk of a first acute coronary event (hospitalization for acute myocardial infarction or coronary death) during follow-up (1-48 years) was calculated with generalized additive models. Objective baseline measures of fitness and cognition were included in the models in secondary analyses. During follow-up, there were 51 779 acute coronary events, of which 6457 (12.5%) were fatal within 30 days. Compared with men at the lowest end of the normal body mass index spectrum (body mass index, 18.5 kg/m2), an increasing risk for a first acute coronary event was observed, with hazard ratios (HRs) peaking at 40 years of age. After multivariable adjustments, men with a body mass index of 35 kg/m2 had an HR of 4.84 (95% CI, 4.29-5.46) for an event before the age of 40 years. Conclusions An increased risk of an early acute coronary event was detectable within normal levels of body weight at the age of 18 years, increasing to almost 5-fold in the highest weight category at 40 years of age. Given increasing levels of body weight and prevalence of overweight and obesity in young adults, the current decrease in coronary heart disease incidence in Sweden may flatten or even reverse in the near future.

Validation of myocarditis diagnoses in the Swedish patient register for analyses of potential adverse reactions to COVID-19 vaccines.

Coronavirus disease 2019 (COVID-19) mRNA vaccines are associated with an increased risk of myocarditis using hospital discharge diagnoses as an outcome. The validity of these register-based diagnoses is uncertain. Patient records for subjects < 40 years of age and a diagnosis of myocarditis in the Swedish National Patient Register were manually reviewed. Brighton Collaboration diagnosis criteria for myocarditis were applied based on patient history, clinical examination, laboratory data, electrocardiograms, echocardiography, magnetic resonance imaging and myocardial biopsy. Poisson regression was used to estimate incidence rate ratios, comparing the register-based outcome variable to validated outcomes. Interrater reliability was assessed by a blinded re-evaluation. Overall, 95.6% (327/342) of cases registered as myocarditis were confirmed (definite, probable or possible myocarditis according to Brighton Collaboration diagnosis criteria, positive predictive value 0.96 [95% CI 0.93-0.98]). Of the 4.4% (15/342) cases reclassified as no myocarditis or as insufficient information, two cases had been exposed to the COVID-19 vaccine no more than 28 days before the myocarditis diagnosis, two cases were exposed >28 days before admission and 11 cases were unexposed to the vaccine. The reclassification had only minor impact on incidence rate ratios for myocarditis following COVID-19 vaccination. In total, 51 cases were sampled for a blinded re-evaluation. Of the 30 randomly sampled cases initially classified as either definite or probably myocarditis, none were re-classified after re-evaluation. Of the in all 15 cases initially classified as no myocarditis or insufficient information, 7 were after re-evaluation re-classified as probable or possible myocarditis. This re-classification was mostly due to substantial variability in electrocardiogram interpretation. This validation of register-based diagnoses of myocarditis by manual patient record review confirmed the register diagnosis in 96% of cases and had high interrater reliability. Reclassification had only a minor impact on the incidence rate ratios for myocarditis following COVID-19 vaccination.

Gallstones, Cholecystectomy, and Kidney Cancer: Observational and Mendelian Randomization Results Based on Large Cohorts

Gallstones (cholelithiasis) constitute a major health burden with high costs related to surgical removal of the gallbladder (cholecystectomy), generally indicated for symptomatic gallstones. The association between gallstones and cholecystectomy and kidney cancer is controversial. We comprehensively investigated this association, considering age at cholecystectomy and time from cholecystectomy to kidney cancer diagnosis, and assessed the causal effect of gallstones on kidney cancer risk by Mendelian randomization (MR). We compared the risk of kidney cancer in cholecystectomized and noncholecystectomized patients (16.6 million in total) from the Swedish nationwide cancer, census, patient, and death registries using hazard ratios (HRs). For 2-sample and multivariable MR, we used summary statistics based on 408,567 UK Biobank participants. During a median follow-up of 13 years, 2627 of 627,870 cholecystectomized Swedish patients developed kidney cancer (HR, 1.17; 95% CI, 1.12-1.22). Kidney cancer risk was particularly increased in the first 6 months after cholecystectomy (HR, 3.79; 95% CI, 3.18-4.52) and in patients cholecystectomized before age 40 years (HR, 1.55; 95% CI, 1.39-1.72). MR results based on 18,417 patients with gallstones and 1788 patients with kidney cancer from the United Kingdom revealed a causal effect of gallstones on kidney cancer risk (9.6% risk increase per doubling in gallstone prevalence; 95% CI, 1.2%-18.8%). Both observational and causal MR estimates based on large prospective cohorts support an increased risk of kidney cancer in patients with gallstones. Our findings provide solid evidence for the compelling need to diagnostically rule out kidney cancer before and during gallbladder removal, to prioritize kidney cancer screening in patients undergoing cholecystectomy in their 30s, and to investigate the underlying mechanisms linking gallstones and kidney cancer in future studies.