Swedish Prescribed Drug Register Research Articles

Comorbidities and use of proarrhythmic drugs in patients with torsade de pointes arrhythmia

Abstract Introduction Drug-induced long QT interval syndrome (LQTS) is a risk factor for torsade de pointes (TdP) ventricular arrhythmia. Combining several QT-prolonging drugs can also increase risk. Clinical decision support systems (CDSS) can help prescribers assess the risk for TdP associated with drugs. Use of combination of drugs and prevalence of other risk factors is not fully known in TdP . Purpose To describe 1) comorbidities (risk-diagnoses) 2) dispensed prescription drugs and their risk for TdP (risk-drugs) using two different CDSS. The hypothesis was that individuals with TdP had risk-diagnoses and used risk-drugs. Personalized decision regarding risk stratification and medication is important to prevent TdP. Methods Patients with first episode of TdP (ICD-10 I472.C) in the National Patient Register (NPR) between 2006 and 2018 were included in this retrospective register-based cohort study. Comorbidities within 5 years prior to the hospital care episode and at the time of TdP diagnosis were retrieved. Mortality was analyzed (National Cause of Death Register). Medications dispensed within 90 days prior to TdP were retrieved (Swedish Prescribed Drug Register). Drugs were classified using 2 different CDSS (Credible Meds and Janusmed Risk Profile). Individual medication data linked with Janusmed Risk Profile gave a risk score of combination of drugs according to an algorithm. Results 762 patients with TdP were identified, most were elderly (72% ≥65 years old), 50% females. After TdP, 31 patients (4.1%) died within 7 days, 61 (8.0%) within 30 days, 87 (11%) within 90 days. Five years prior to TdP 338 patients (44%) had ≥1 risk-diagnosis (heart failure, cardiomyopathies, acute/ chronic coronary syndromes, renal failure,liver disease, LQTS, ventricular arrhythmia and/or cardiac arrest). More males vs. females had risk-diagnoses (28% vs. 22%, p<0.0015). A median of 6 drugs (IQR 2-9) were dispensed. Anti-depressants and antiarrhythmics were the most common risk-drugs. According to Credible Meds, 192 (25%) patients used ≥1 drug with known risk, 51 patients (6.7%) ≥1 drug with possible risk and 208 patients (27%) ≥1 drug with conditional risk only. 470 patients (62%) had ≥1 risk-diagnosis and/or ≥ 1 risk-drug (known or possible risk). Another 88 patients had ≥1 risk-diagnosis and/or ≥1 risk-drug (conditional risk). Thus, 558 patients (73%) had ≥1 risk-diagnosis and/or ≥ 1 risk-drug (Credible Meds). Analysis of combination of drugs showed that 290 patients (38 %) had drugs with increased risk, 547 patients (72%) had ≥1 risk-diagnosis and/or a combined drugs associated with increased risk (Janusmed Risk Profile). Conclusion Prior to TdP approximately a third of patients were dispensed prescription drugs with proarrhythmic risk according to two different CDSS. Almost 75% of patients were dispensed drugs associated with proarrhythmic risk and/or had other proarrhythmic risk factors. Vigilance should be undertaken to modify risk factors to prevent TdP.Baseline characteristicsRisk-drugs dispensed prior to TdP

Impact of the COVID-19 pandemic on initiation of antihypertensive drugs in Sweden: an interrupted time series study

ObjectivesAntihypertensives reduce the risk of myocardial infarction and stroke. Restrictions during the COVID-19 pandemic limited access to healthcare, which may have had a negative impact on drug prescribing. This study...

Trends in prognosis and use of SGLT2i and GLP-1 RA in patients with diabetes and coronary artery disease

ObjectiveTo explore trends in prognosis and use of glucose-lowering drugs (GLD) in patients with diabetes and coronary artery disease (CAD).Research design and methodsAll patients with diabetes and CAD undergoing a coronary angiography between 2010 and 2021 according to the Swedish Angiography and Angioplasty Registry were included. Information on GLD (dispended 6 months before or after coronary angiography) was collected from the Swedish Prescribed Drug Registry. Data on major cardiovascular events (MACE; mortality, myocardial infarction, stroke, heart failure) through December 2021 were obtained from national registries. Cox proportional survival analysis was used to assess outcomes where cardioprotective GLD (any of Sodium Glucose Lowering Transport 2 receptor inhibitors [SGLT2i] and Glucagon Like Peptide Receptor Agonists [GLP-1 RA]) served as a reference.ResultsAmong all patients (n = 38,671), 31% had stable CAD, and 69% suffered an acute myocardial infarction. Mean age was 69 years, 67% were male, and 81% were on GLD. The use of cardioprotective GLD increased rapidly in recent years (2016–2021; 7–47%) and was more common in younger patients (66 vs. 68 years) and men (72.9% vs. 67.1%) than other GLD. Furthermore, compared with other GLD, the use of cardioprotective GLD was more common in patients with a less frequent history of heart failure (5.0% vs. 6.8%), myocardial infarction (7.7% vs. 10.5%) and chronic kidney disease (3.7% vs. 5.2%). The adjusted hazard ratio (HR) (95% CI) for MACE was greater in patients on other GLD than in those on cardioprotective GLD (1.10; 1.03–1.17, p = 0.004). Trend analyses for the years 2010–2019 revealed improved one-year MACE in patients with diabetes and CAD (year 2019 vs. 2010; 0.90; 0.81-1.00, p = 0.045), while 1-year mortality was unchanged.ConclusionsThe prescription pattern of diabetes medication is changing quickly in patients with diabetes and CAD; however, there are worrying signals of inefficient use prioritizing cardioprotective GLD to younger and healthier individuals at lower cardiovascular risk. Despite this, there are improving trends in 1-year morbidity.

Factors Influencing Adherence to Adjuvant Endocrine Therapy After Breast Cancer Surgery.

Women with newly diagnosed hormone receptor-positive breast cancer are offered adjuvant endocrine therapy (AET). Despite the survival benefits of the therapy, a significant proportion of breast cancer patients do not adhere to the anti-hormonal medication. The purpose of this study was to analyse demographic, social, psychological and treatment-related factors influencing whether women diagnosed with early-stage breast cancer were adherent to offered therapy. This was a long-term retrospective, medical record study, supplemented with a questionnaire, including 81 women. Data from the Swedish Prescribed Drug Register were used to examine adherence. The women were followed for 5 years of offered AET. Out of 81 women, 67 (83%) were adherent (hade taken out 80% or more of the recommended dose), 10 (12%) were Partially Adherent and 4 (5%) never accepted AET. At baseline, the Never-Adherent group members were younger, more often considered themselves healthy and seemed much more satisfied with their lives. Baseline factors that positively affected adherence were satisfaction with the vocational situation (p = 0.023) and satisfaction with family life (p = 0.040). Cumulative musculoskeletal side effects were more frequently reported among women in the Adherent group than Partially Adherent women, after both 12 and 60 months (p = 0.018 and p = 0.011, respectively). There was also a significant difference in reported cumulative psychological side effects (p = 0.049) in disfavour of the Adherent group. Moreover, according to the questionnaire where the women retrospectively were asked which side effects, they experienced during the treatment period; sexual desire was significantly lower in the Adherent group (p = 0.0402) than in the Partially Adherent group. It is important to consider a woman's life situation, to support those who otherwise would not be able to complete AET and to help all women relieve side effects during AET. It should be investigated why some women did not start the recommended therapy.

Characteristics, demographics, and epidemiology of possible chronic cough in Sweden: A nationwide register-based cohort study.

To show clinical characteristics, treatments, and comorbidities in chronic cough in a nationwide cohort. Two cohorts were created. A national cohort with individuals from two population-based databases; the National Patient Register and Swedish Prescribed Drug Register. Secondly, a regional cohort including primary care data. Adults with at least one cough diagnosis (ICD-10 R05) and/or individuals with ≥2 dispensed prescriptions for relevant cough-medication within the inclusion period, 2016-2018, were identified. Individuals on medications which may instigate cough or suggest acute infection or diagnosed with conditions where cough is a cardinal symptom, were excluded. Those remaining were defined as having possible refractory or unexplained chronic cough (RCC/UCC). Altogether 62,963 individuals were identified with possible RCC/UCC, giving a national prevalence of about 1%. Mean age was 56 years and 60% were females. Many (44%) of the individuals with possible RCC/UCC visited cough relevant specialist clinics during the study period, but less than 20% received a cough diagnosis. A majority (63%) had evidence of RCC/UCC in the 10 years prior to inclusion in the study. In the regional cohort, including primary care data, the prevalence of RCC/UCC was doubled (2%). Cough medicines were mainly prescribed by primary care physicians (82%). Most individuals with possible RCC/UCC sought medical care in primary care, and had a long history of cough, with various treatments tried, indicating a substantial burden of the condition. Referrals to specialist care were very rare. The results underline the need for a structured multidisciplinary approach and future therapeutic options.

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.

Responders to first-line osteoarthritis treatment had reduced frequency of hip and knee joint replacements within 5 years: an observational register-based study of 44,311 patients.

First-line treatment (education, exercise) for patients with hip and knee osteoarthritis (OA) aims to reduce pain and improve function. We aimed to compare progression to joint replacement within 5 years between responders and non-responders to first-line treatment for hip and knee OA, respectively. This observational study included data for 30,524 knee OA and 13,787 hip OA patients from the Swedish Osteoarthritis Register, linked with the Swedish Arthroplasty Register, Statistics Sweden, and the Swedish Prescribed Drug Register. The primary prognostic factor was change in pain between baseline and 3-month follow-up, measured on a numeric rating scale (0-10, best to worst) where an improvement of ≥ 2 was classified as responder and ≤ 1 as non-responder. The main outcome was progression to joint replacement surgery within 5 years, assessed using baseline adjusted multivariable Cox regression analyses. At 5 years, in hip OA, 35% (95% confidence interval [CI] 32.2-37.2) of the responders and 48% (CI 45.9-49.5) of the non-responders and in knee OA 14% (CI 13.0-15.3) of the responders and 20% (CI 18.8-20.8) of the non-responders had progressed to joint replacement. Being a responder to the treatment was associated with having a lower probability of progression to surgery for both hip OA (hazard ratio [HR] 0.4, CI 0.4-0.5) and knee OA (HR 0.6, CI 0.5-0.6). Patients with hip or knee OA who experienced pain relief after a first-line OA treatment program were less likely to progress to joint replacement surgery.

#430 Risk factors for major bleeding in patients with non-valvular atrial fibrillation and CKD G3-G5D on oral anticoagulants

Abstract Background and Aims We previously published a register-based cohort study comparing direct oral anticoagulants (DOAC) and warfarin in patients with atrial fibrillation (AF) and chronic kidney disease (CKD) GFR category 3-5 (G3-G5) including patients on dialysis (G5D) (1). This study showed that DOAC was associated with lower risk of major bleeding but similar risk of ischemic stroke compared to warfarin. Bleedings were however more common than strokes, especially in advanced CKD (G5-G5D) where the risk of major bleeding was up to 10 times higher than the risk of stroke. Subsequently, the stroke- and bleeding risk in patients with AF and advanced CKD must be carefully evaluated when deciding on whether to prescribe oral anticoagulants (OAC) or not. Available stroke- and bleeding scoring systems do not perform well in CKD (2, 3). This study aims to present risk factors associated with major bleeding in a Swedish cohort of OAC-treated patients with CKD G3-G5D. Method Data was collected from high quality Swedish healthcare registers including Swedish Renal Registry and Auricula, a register for atrial fibrillation and oral anticoagulants and the National Patient Register. Patients with eGFR&amp;lt;60 ml/min/1.73m2 and non-valvular atrial fibrillation and either DOAC (apixaban, rivaroxaban, edoxaban and dabigatran) or warfarin treatment between 2009-2018 where included. DOAC treatment periods were collected from the Swedish Prescribed Drug Register (PDR), starting from dispense date covering assumed standard pill use and an additional 30 days grace period. Warfarin treatment periods were collected directly from Auricula. An undefined treatment was a period of no OAC or a period of warfarin from PDR not matching a treatment period in Auricula. All periods of OAC treatment with either DOAC or warfarin were evaluated in a multivariate Cox regression model regarding the risk of major bleeding requiring inpatient care. Time-dependent covariates adjusted for in the model were age, sex, years from study start, GFR category, congestive heart failure, diabetes mellitus, hypertension, excessive alcohol use, liver disease, vascular disease, previous gastrointestinal bleeding, intracranial bleeding, other bleeding, ischemic stroke/ transient ischemic attack (TIA), myocardial infarction, PCI and exposures (DOAC, warfarin and periods of undefined treatment). Results Of 2453 included patients, 59% had warfarin (time in therapeutic range, TTR, 67%) and 41% DOAC at inclusion, predominantly apixaban (81% of DOAC users). The mean age was 77 years, 28.3% had G3, 45.4% G4, 9.1% G5 and 17.3% G5D (Table 1). Mean follow up was 2.2 years. During follow up 424 major bleedings occurred yielding 8.9 (95% confidence interval 8.1-9.8) bleedings per 100 patient-years. Table 2 shows effect estimates of each covariate on the outcome major bleeding. Covariates, besides warfarin, associated with increased risk of major bleeding were GFR category, G5/5D versus G3, hazard ratio 1.92 (95% CI 1.43-2.56), previous GI bleeding, 1.77 (1.39-2.25) and previous other bleeding 1.33 (1.09-1.62). Other factors associated with major bleeding were congestive heart failure 1.36 (1.11-1.68), male sex 1.28 (1.03-1.60) and vascular disease, 1.35 (1.01-1.79). Conclusion Patients with non-valvular atrial fibrillation and CKD G3-G5D on OAC are at high risk of major bleeding. Previous major bleeding and kidney failure are strongly associated with major bleeding, this reiterates the results of many previous studies. The present study also shows an association between OAC-associated major bleeding in CKD and male sex, congestive heart failure and vascular disease. Similar associations have been showed in non-CKD cohorts previously but is inadequately studied in CKD. Knowledge about risk factors for major bleeding on OAC in advanced CKD is essential when deciding on when to anticoagulate or not.

Association of levonorgestrel-releasing intrauterine device with gynecologic and breast cancers: a national cohort study in Sweden

BackgroundThe levonorgestrel-releasing intrauterine device (LNG-IUD) is widely used for the treatment of menorrhagia, dysmenorrhea, and for contraception. However, the association between the use of LNG-IUD and the risk of site-specific gynecologic and breast cancers remains inconclusive. ObjectiveWe aim to address this knowledge gap by investigating whether the use of LNG-IUD is associated with a significant risk of site-specific gynecologic and breast cancers. This will be achieved by accessing the nationwide Swedish Registers, with consideration given to the influence and potential interaction of family history of cancer. Study DesignA total of 514719 women aged 18 to 50 years who have used LNG-IUD between July 2005 and December 2018 were identified from the Swedish Prescribed Drug Register and randomly matched with 1544157 comparisons who did not use LNG-IUD at a ratio of 1:3. The propensity score was calculated and matched among women who used LNG-IUD and the matched comparisons. The follow-up period started from the date of the first prescription of LNG-IUD for users as well as for their matched comparisons and ended at the date of diagnosis of gynecologic and breast cancers, date of death from any cause, and the end of the study period, whichever came first. The Cox proportional hazard model with a competing risk analysis was used to calculate hazard ratios and 95% confidence intervals. Additive interaction was calculated as the relative excess risk for interaction, while multiplicative interaction was calculated by including a product term in the regression model. ResultsThe use of LNG-IUD was associated with a 13% higher risk of breast cancer (adjusted HR, 1.13; 95% CI, 1.10-1.17), a 33% lower risk of endometrial cancer (adjusted HR, 0.67; 95% CI, 0.56-0.80), a 14% lower risk of ovarian cancer (adjusted HR, 0.86; 95% CI, 0.75-0.99) and a 9% reduced risk of cervical cancer (adjusted HR, 0.91; 95% CI, 0.84-0.99) compared to women who did not use LNG-IUD. A significant additive interaction between LNG-IUD use and family history of cancer was observed in breast cancer, indicating a relative 19% excess risk for interaction (P < 0.002), and 1.63 additional cases per 10,000 person-years. ConclusionsThe risk of gynecologic and breast cancers exhibits a site-specific effect among LNG-IUD users. It's important to note that the observed effect is small for breast cancer and the results are limited by the observational study design. Clinical recommendations regarding the use of LNG-IUD should carefully weigh its potential benefits and risks. Close monitoring is advisable for the potential development of breast cancer, particularly among women with a family history of breast cancer.

Do beta-blockers reduce negative intrusive thoughts and anxiety in cancer survivors? – An emulated trial

BackgroundHigh rates of negative intrusive thoughts have been reported among cancer patients. Prevalent users of beta-blocker therapy have reported lower levels of cancer related intrusive thoughts than non-user. The aim of this study is to investigate if initiation of beta-blocker therapy reduces the prevalence and severity of intrusive thoughts (co-primary endpoints) and the prevalence of anxiety, depressed mood, and low quality of life (secondary endpoints) in cancer survivors.MethodsData on patient-reported outcomes from three cohort studies of Swedish patients diagnosed with colon, prostate or rectal cancer were combined with data on beta-blocker prescriptions retrieved from the Swedish Prescribed Drug Register. Two randomized controlled trials were emulated. Trial 1 had follow-up 1 year after diagnosis, trial 2 had follow-up 2 years after diagnosis, baseline in both trials was 12 months before follow-up. Those who initiated beta-blocker therapy between baseline and follow-up was assigned Active group, those who did not was assigned Control group. All endpoints were analysed using Bayesian ordered logistic regression.ResultsTrial 1 consisted of Active group, n = 59, and Control group, n = 3936. Trial 2 consisted of Active group, n = 87, and Control group, n = 3132. The majority of participants were men, 83% in trial 1 and 94% in trial 2. The prevalence and severity of intrusive thoughts were lower in the Active group in trial 1, but no significant differences between groups were found in either trial. The prevalence of depressed mood, worse quality of life and periods of anxiety were higher in the Active group in both trials with significant differences for quality of life in trial 1 and anxiety in trial 2.ConclusionsThe emulated trials demonstrated no evidence of a protective effect of beta-blocker therapy against intrusive thoughts. The Active group had reduced quality of life and elevated anxiety compared to the Control group.Trial registrationThe three cohort studies were registered at isrctn.com/clinicaltrials.gov (ISRCTN06393679, NCT02530593 and NCT01477229).

Effect of a national infection control programme in Sweden on prosthetic joint infection incidence following primary total hip arthroplasty: a cohort study

ObjectivesProsthetic joint infection (PJI) is a serious complication following total hip arthroplasty (THA) entailing increased mortality, decreased quality of life and high healthcare costs.The primary aim was to investigate whether...

Fatal Intoxications with Zopiclone-A Cause for Concern?

Zopiclone, a controlled substance prescribed for insomnia, has become a common toxicological finding in forensic autopsy cases. This study investigated the role and extent of zopiclone use in fatal intoxications in Sweden. All forensic autopsy cases positive for zopiclone in femoral blood during 2012-2020 were selected. Among these cases, fatalities caused by intoxication according to the cause of death certificates issued by the forensic pathologist were identified. Intoxications where zopiclone contributed to the cause of death were included in the study. The Swedish Prescribed Drug Register was utilized to examine whether the included cases were prescribed zopiclone or not. In total 7320 fatal intoxications underwent a forensic autopsy during the study period, 573 of them were caused by zopiclone. Among the zopiclone fatalities, 87% (n = 494) had a prescription for zopiclone, and 8% (n = 43) were monointoxications. Most fatalities, 62% (n = 354) were suicides, and zopiclone was involved in about 17% (n = 354) of all intoxication suicides in Sweden. Women were significantly (p < 0.01) overrepresented in suicides with zopiclone, comprising 56% (n = 291) of fatalities. The median age was 55 years among zopiclone intoxications compared with 44 years amongst all fatal intoxications. This study demonstrates that the toxicity of zopiclone can be lethal both in combination with other substances and on its own. Most individuals dying in fatal zopiclone intoxications were prescribed zopiclone, which potentially indicates that a more restrictive prescribing rate could prevent future intoxication deaths, especially when caring for patients with an increased suicide risk.

Undiagnosed adrenal insufficiency as a cause of premature death in glucocorticoid users.

It is unknown whether glucocorticoid (GC)-induced adrenal insufficiency may cause premature mortality in GC users. We conducted a retrospective cohort study to investigate if undiagnosed and undertreated GC-induced adrenal insufficiency is a contributor to premature death in GC users. Information on dispensed prescriptions in West Sweden from 2007 to 2014 was obtained from the Swedish Prescribed Drug Register. Cause of death was collected from the Swedish Cause of Death Register. Of 223,211 patients who received oral GC prescriptions, 665 died from sepsis within 6 months of their last prescription. Three hundred of these patients who had died in hospital were randomly selected for further investigation. Medical records were initially reviewed by one investigator. Furthermore, two additional investigators reviewed the medical records of patients whose deaths were suspected to be caused by GC-induced adrenal insufficiency. Of 300 patients (121 females, 40%), 212 (75%) were prescribed GC treatment at admission. The mean age was 76 ± 11 years (range 30-99). Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a probable contributor to death by at least two investigators in 11 (3.7%) patients. In five of these 11 cases, long-term GC therapy was abruptly discontinued during hospitalization. Undiagnosed or undertreated GC-induced adrenal insufficiency was considered a possible contributing factor to death in a further 36 (12%) patients. GC-induced adrenal insufficiency is an important contributor to premature death in GC users. Awareness of the disorder during intercurrent illness and following cessation of GC treatment is essential.

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.

Validation of diagnoses of liver disorders in users of systemic azole antifungal medication in Sweden

BackgroundLiver disorders are important adverse effects associated with antifungal drug treatment. However, the accuracy of Clinical International Classification of Diseases (ICD)-10 codes in identifying liver disorders for register based research is not well-established. This study aimed to determine the positive predictive value (PPV) of the ICD-10 codes for identifying patients with toxic liver disease, hepatic failure, and jaundice among patients with systemic antifungal treatment.MethodsData from the Swedish Prescribed Drug Register and the National Patient Register were utilized to identify adult patients who received systemic azole antifungal drugs and had a recorded diagnosis of toxic liver disease (K71.0, K71.1, K71.2, K71.6, K71.8, K71.9), hepatic failure (K72.0, K72.9), or jaundice (R17) between 2005 and 2016. The medical records of all included patients were reviewed. Prespecified criteria were used to re-evaluate and confirm each diagnosis, serving as the gold standard to calculate PPVs with 95% confidence intervals (95% CI) for each diagnostic group.ResultsAmong the 115 included patients, 26 were diagnosed with toxic liver disease, 58 with hepatic failure, and 31 with jaundice. Toxic liver disease was confirmed in 14 out of 26 patients, yielding a PPV of 53.8% (95% CI 33.4–73.4%). Hepatic failure was confirmed in 26 out of 38 patients, resulting in a PPV of 62.1% (95% CI 48.4–74.5%). The highest PPV was found in jaundice, with 30 confirmed diagnoses out of 31, yielding a PPV of 96.8% (95% CI 83.3–99.9%).ConclusionAmong patients who received azole antifungal treatment and were subsequently diagnosed with a liver disorder, the PPV for the diagnosis of jaundice was high, while the PPVs for toxic liver disease and hepatic failure were lower.

Income and Education Affect Prognosis and Treatment in Symptomatic Myeloma: A Population-Based Study on 8672 Multiple Myeloma Patients Diagnosed 2008-2021 from the Swedish Myeloma Registry

Introduction While survival in myeloma has improved with new treatment modalities, a substantial variation in mortality remains. This variation cannot entirely be explained by differences in known prognostic factors, such as age and genetic risk group. A link between socioeconomic factors and prognosis has gained attention during recent years, but most studies derive from populations with unequal access to health care. We tested whether income and education affects myeloma treatment and survival also in a country where nearly all health care is publicly funded. Materials and methods Study population The study base included all Swedish patients with symptomatic myeloma diagnosed between 2008 and 2021 (n=8672) and included in the Swedish Myeloma Registry. Data on stem cell transplants (HSCT) were retrieved from the 1-year follow-up form in the myeloma register. Data on lenalidomide, pomalidomide, and melphalan treatment were retrieved from the Swedish Prescribed Drug Register. Data on comorbidities were retrieved from the Swedish Patient Register and the Swedish Cancer Register and Charlson comorbidity index was constructed based on diagnoses registered within five years preceding myeloma diagnosis. Data on socioeconomic conditions were retrieved from the Integrated Database for Labor Market Research (LISA), held by Statistics Sweden. Education level was divided into three categories; primary school only (≤9 years), some college or university (≥13 years), or anything between these two (10-12 years). To avoid undue effect of outliers, personal and family income were grouped into highest quartile, lowest quartile and those in-between. Patients were followed in Swedish population statistics until death, permanent emigration or 31 st December 2022. Statistical analysis Analyses on overall survival were performed with Kaplan-Meier plots and with Cox proportional hazards models, yielding hazard ratios (HR) with 95% confidence intervals (95% CI) as measures of relative risk of death. Differences in treatment were assessed by Poisson regression. All p-values were two-sided and a value below 0.05 was considered statistically significant. All analyses were performed with SAS 9.4 statistical software (SAS Inc., Cary, NC). Ethical considerations The study has been approved by the Swedish Ethical Review Authority (2020-01729). All data were anonymized before analyses. Results Median survival was doubled in patients with higher education, compared with patients with primary school only (6.0 years vs 3.0 years). Similarly, patients in the highest family income quartile had a median survival of 7.5 years, compared to 2.8 years among patients from the lowest quartile (Figure 1). The survival differences were to some degree explained by differences at baseline, in particular age at diagnosis. In a multivariable proportional hazards regression, with adjustments for age group, sex, year of diagnosis and comorbidity index, low income patients had 40% higher risk of death than high income patients (HR 1.6, 95% CI 1.5-1.8) and patients with primary school only had 30% higher risk of death compared to patients with higher education (HR=1.4, 95% CI=1.3-1.5), p&amp;lt;0.0001 for both analyses. Patients with the highest family incomes were also more likely to have been treated with a stem cell transplant, a lenalidomide containing regimen, or a pomalidomide containing regimen, while patients with the lowest family incomes were more often treated with melphalan-prednisone based regimens (Table 1). Discussion Education and private economy are correlated with survival in myeloma, even in a country where the cost of health care is covered almost completely by taxes. The differences are not explained by age and comorbidities alone. Our data also suggest that doctors' choices of myeloma treatment are influenced by socioeconomic factors. The data indicate that myeloma survival could increase with more than a year if we could achieve the same results for all patients as we do with the wealthiest and most educated quartile.

Validating the risk of hypoparathyroidism after total thyroidectomy in a population-based cohort: plea for improved follow-up.

A previous nationwide study from Sweden showed that the rate of permanent hypoparathyroidism is high and under-rated in the Swedish Quality Register. This retrospective population-based study aimed to validate the rate and diagnosis of permanent hypoparathyroidism found in the previous study. A secondary aim was to assess the relationship between the rate of low parathyroid hormone (PTH) levels within 24 h after surgery and the rate of permanent hypoparathyroidism. All patients who underwent total thyroidectomy from 2005 to 2015 in a region of Sweden were included. Data were retrieved from local health records, the National Patient Registry, the Swedish Prescribed Drug Registry, and the Swedish Quality Register. A strict definition of permanent hypoparathyroidism was used, including biochemical data and attempts to stop the treatment. A total of 1636 patients were included. Altogether, 143 patients (8.7 per cent) developed permanent hypoparathyroidism. Of these, 102 (6.2 per cent) had definitive permanent hypoparathyroidism, whereas 41 (2.5 per cent) had possible permanent hypoparathyroidism, because attempts to stop the treatment were lacking (28) or patients were lost to follow-up (13). The agreement between the Swedish Quality Register and the chart review was 29.3 per cent. A proportion of 23.2 per cent with a PTH level below the reference value corresponded to a 6.7 per cent rate of permanent hypoparathyroidism. The risk of permanent hypoparathyroidism after total thyroidectomy is high. Some patients are overtreated because attempts to stop the treatment are lacking. Quality registers might underestimate the risk of permanent hypoparathyroidism. Approximately one-quarter of all patients with low PTH levels immediately after surgery developed permanent hypoparathyroidism.

Attention-Deficit/Hyperactivity Disorder Medications and Long-Term Risk of Cardiovascular Diseases

Use of attention-deficit/hyperactivity disorder (ADHD) medications has increased substantially over the past decades. However, the potential risk of cardiovascular disease (CVD) associated with long-term ADHD medication use remains unclear. To assess the association between long-term use of ADHD medication and the risk of CVD. This case-control study included individuals in Sweden aged 6 to 64 years who received an incident diagnosis of ADHD or ADHD medication dispensation between January 1, 2007, and December 31, 2020. Data on ADHD and CVD diagnoses and ADHD medication dispensation were obtained from the Swedish National Inpatient Register and the Swedish Prescribed Drug Register, respectively. Cases included individuals with ADHD and an incident CVD diagnosis (ischemic heart diseases, cerebrovascular diseases, hypertension, heart failure, arrhythmias, thromboembolic disease, arterial disease, and other forms of heart disease). Incidence density sampling was used to match cases with up to 5 controls without CVD based on age, sex, and calendar time. Cases and controls had the same duration of follow-up. Cumulative duration of ADHD medication use up to 14 years. The primary outcome was incident CVD. The association between CVD and cumulative duration of ADHD medication use was measured using adjusted odds ratios (AORs) with 95% CIs. Of 278 027 individuals with ADHD aged 6 to 64 years, 10 388 with CVD were identified (median [IQR] age, 34.6 [20.0-45.7] years; 6154 males [59.2%]) and matched with 51 672 control participants without CVD (median [IQR] age, 34.6 [19.8-45.6] years; 30 601 males [59.2%]). Median (IQR) follow-up time in both groups was 4.1 (1.9-6.8) years. Longer cumulative duration of ADHD medication use was associated with an increased risk of CVD compared with nonuse (0 to ≤1 year: AOR, 0.99 [95% CI, 0.93-1.06]; 1 to ≤2 years: AOR, 1.09 [95% CI, 1.01-1.18]; 2 to ≤3 years: AOR, 1.15 [95% CI, 1.05-1.25]; 3 to ≤5 years: AOR, 1.27 [95% CI, 1.17-1.39]; and >5 years: AOR, 1.23 [95% CI, 1.12-1.36]). Longer cumulative ADHD medication use was associated with an increased risk of hypertension (eg, 3 to ≤5 years: AOR, 1.72 [95% CI, 1.51-1.97] and >5 years: AOR, 1.80 [95% CI, 1.55-2.08]) and arterial disease (eg, 3 to ≤5 years: AOR, 1.65 [95% CI, 1.11-2.45] and >5 years: AOR, 1.49 [95% CI, 0.96-2.32]). Across the 14-year follow-up, each 1-year increase of ADHD medication use was associated with a 4% increased risk of CVD (AOR, 1.04 [95% CI, 1.03-1.05]), with a larger increase in risk in the first 3 years of cumulative use (AOR, 1.08 [95% CI, 1.04-1.11]) and stable risk over the remaining follow-up. Similar patterns were observed in children and youth (aged <25 years) and adults (aged ≥25 years). This case-control study found that long-term exposure to ADHD medications was associated with an increased risk of CVDs, especially hypertension and arterial disease. These findings highlight the importance of carefully weighing potential benefits and risks when making treatment decisions about long-term ADHD medication use. Clinicians should regularly and consistently monitor cardiovascular signs and symptoms throughout the course of treatment.

Low agreement between Swedish national registers and parental questionnaires on allergic rhinitis.

Allergic rhinitis (AR) has been well documented using questionnaire-based studies. Here, we examine the agreement between parental-reported data during childhood with the emphasis on 12-year-olds and data from two national Swedish registers to determine whether register data on AR can supplement or replace questionnaire data. Data were collected from a prospective, longitudinal cohort study of children born in western Sweden in 2003. Parental questionnaires were filled out at 6 months and one, four, eight, and 12 years of age. A total of 3634 children were linked to the Swedish Prescribed Drug Register (SPDR) and the National Patient Register (NPR) using personal identity numbers. The agreement between the register and questionnaire data was estimated using Cohen's kappa with 95% confidence intervals. According to the SPDR, 9.9% (n = 360/3634) of the children were dispensed specific AR medication at 11-13 years of age compared with the 12 years questionnaire where 23% reported AR medication use during the last 12 months. The overall agreement between questionnaire and SPDR data on AR medication was slight (kappa 0.05). At 11-12 years, 1.8% (n = 65/3634) of the children received an outpatient AR diagnosis in the NPR, while 10% reported doctor-diagnosed AR in the questionnaire. The overall agreement between questionnaire and NPR data on AR diagnosis was slight (kappa 0.16). There was poor agreement between questionnaire and register data regarding AR and dispensed medication. Explanations could include over-the-counter drugs and diagnosis in primary care, which are not included in the registers.

SAT232 Patients With Chronic Hypoparathyroidism Have Higher Risk Of Vertebral Fracture And Lower Risk Of Femoral Fracture Compared To Controls

Abstract Disclosure: S. Bjornsdottir: None. W. Kamal: None. B.L. Langdahl: None. T. Spelman: None. B.L. Clarke: None. O. Kampe: None. Context: Previous studies have shown that patients with hypoparathyroidism (hypoPT) have reduced bone remodeling, with consequent increases in bone density, and abnormalities in microarchitecture and bone strength. It is still not clear whether there is an increased risk of fractures in patients with hypoPT. Objective: The aim of this study was to evaluate the risk of fractures in patients with hypoPT in Sweden. Patients: The Swedish National Patient Register, the Swedish Prescribed Drug Register and the Total Population Register were used to identify 1982 patients with chronic hypoPT (duration ≥ 12 months), and 19820 controls matched by age, sex and county of residency between 1997-2018. The 10th revision of the International Classification of Diseases (ICD) was used to identify fractures. Results: Patients with hypoPT did not have higher risk of any fracture compared to controls (HR 0.96; 95% CI 0.86-1.08). However, patients with hypoPT had a slightly higher risk of vertebral fractures (HR 1.33; 95% CI 1.01-1.75), p= 0.047 and a lower risk of femoral fractures (HR 0.60; 95% CI 0.45-0.82), p= 0.001. There was no significant difference in the risk of fractures of the forearm, p= 0.177, proximal humerus, p= 0.096 or pelvis, p= 0.446. There was no difference in the risk of any fracture between females and males with hypoPT (p for interaction= 0.511). Patients with surgical hypoPT had a significantly higher risk of any fracture compared with patients with non-surgical hypoPT (p for interaction= 0.006). Conclusion: The risk of any fracture was not increased in patients with hypoPT. However, the risk of vertebral fracture was increased, and the risk of femoral fracture was lower than for matched controls. No difference was found in fracture risk between females and males. Patients with surgical hypoPT had a higher fracture risk compared to patients with non-surgical hypoPT. Presentation: Saturday, June 17, 2023