Worse patient-reported outcomes and higher risk of reoperation and adverse events after total hip replacement in patients with opioid use in the year before surgery: a Swedish register-based study on 80,483 patients

Background and purpose — Recent studies indicate that preoperative use of opioids could be associated with higher rates of complications and worse patient-reported outcomes (PROs) after orthopedic surgery. We investigated the prevalence of preoperative opioid use and analyzed its influence on risk of revision, adverse events (AE), and PROs in patients with total hip replacement (THR). Patients and methods — This observational study included 80,483 patients operated on in 2008–2016 with THRs due to osteoarthritis. Data was obtained from the Swedish Hip Arthroplasty Register, Statistics Sweden’s sociodemographic registers, the Swedish National Patient Register, and the Prescribed Drug Register. We focused on patients with ≥ 4 opioid prescriptions filled 1 year prior to THR. To control for confounding, we used propensity scores to weight subjects in our analyses. Logistic and linear regression was used for outcome variables with adjustments for sociodemographic variables and comorbidities. Results — Patients with ≥ 4 opioid prescriptions in the year before THR (n = 14,720 [18%]) had a higher risk of revision within 2 years (1.8% vs. 1.1% OR 1.4, 95% CI 1.3–1.6) and AE within 90 days (9.4% vs. 6.4% OR 1.2, 95% CI 1.2–1.3) compared with patients without opioid treatment in the preoperative period. Patients with ≥ 4 opioid prescriptions rated 5 points worse on a 0–100 scale of Pain VisualAnalogue Scale (VAS) and 9 points worse on a generalhealth (EQ) VAS 1 year postoperatively. Interpretation — Having ≥ 4 opioid prescriptions filled in the year before surgery is associated with a higher risk of revision, adverse events, and worse PROs after THR. Consequently, preoperative opioid treatment should be addressed in the clinical assessment of patients eligible for THR.

Predicting time to relapse in patients with schizophrenia according to patients’ relapse history: a historical cohort study using real-world data in Sweden

Background For patients with schizophrenia, relapse is a recurring feature of disease progression, often resulting in substantial negative impacts for the individual. Although a patient’s relapse history (specifically the number of prior relapses) has been identified as a strong risk factor for future relapse, this relationship has not yet been meticulously quantified. The objective of this study was to use real-world data from Sweden to quantify the relationship of time to relapse in schizophrenia with a patient’s history of prior relapses. Methods Data from the Swedish National Patient Register and Swedish Prescribed Drug Register were used to study relapse in patients with schizophrenia with a first diagnosis recorded from 2006–2015, using proxy definitions of relapse. The primary proxy defined relapse as a psychiatric hospitalisation of ≥7 days’ duration. Hazard ratios (HRs) were calculated for risk of each subsequent relapse, and Aalen-Johansen estimators were used to estimate time to next relapse. Results 2,994 patients were included, and 5,820 relapse episodes were identified using the primary proxy. As the number of previous relapses increased, there was a general trend of decreasing estimated time between relapses. Within 1.52 years of follow-up, 50% of patients with no history of relapse were estimated to have suffered their first relapse episode. 50% of patients with one prior relapse were estimated to have a second relapse within 1.23 years (HR: 1.84 [1.71–1.99]) and time to next relapse further decreased to 0.89 years (HR: 2.77 [2.53–3.03]) and 0.22 years (HR: 18.65 [15.42–22.56]) for 50% of patients with two or ten prior relapses, respectively. Supplementary analyses using different inclusion/exclusion criteria for the study population and redefined proxies of relapse reflected the pattern observed with the primary analyses of a higher number of prior relapses linked with increased risk of/reduced estimated time to the next relapse. Conclusions The results suggested a trend of accelerating disease progression in schizophrenia, each relapse episode predisposing an individual to the next within a shorter time period. These results emphasise the importance of providing early, effective, and tolerable treatments that better meet a patient’s individual needs.

Gestational Diabetes Mellitus Risk in Pregnant Women with Systemic Lupus Erythematosus

Objective To investigate the risk of gestational diabetes mellitus (GDM) associated with systemic lupus erythematosus (SLE) by comparing pregnancies in women with SLE to general population controls. Methods We identified singleton pregnancies among women with SLE and general population controls in the Swedish Medical Birth Register (MBR; 2006-2016), sampled from the populationbased register linkage SLINK (1987-2012). SLE was defined by ≥2 International Classification of Diseases (ICD)-coded visits in the National Patient Register (NPR) and MBR, with ≥1 visit before pregnancy. GDM was defined by ≥1 ICD-coded visit in the NPR or MBR. Glucocorticoid (GC) and hydroxychloroquine (HCQ) dispensations 6 months before and during pregnancy were identified in the Prescribed Drug Register. Risk ratios and 95% confidence intervals (RRs; 95% CI) of GDM associated with SLE were estimated using modified Poisson regression models, stratified by parity and adjusted for maternal age at delivery, year of birth, and obesity. Results We identified 695 SLE pregnancies including 18 (2.6%) with GDM and 4,644 non-SLE pregnancies including 65 (1.4%) with GDM. Adjusted RRs of GDM associated with SLE were 1.11 (95% CI 0.38-3.27) for first deliveries and 2.03 (95% CI 1.21-3.40) for all deliveries. Among SLE pregnancies, GDM occurred in 7/306 (2.3%) with ≥1 GC before and/or during pregnancy, 11/389 (2.8%) without GC, 7/287 (2.4%) with ≥1 HCQ before and/or during pregnancy, and in 11/408 (2.7%) without HCQ. Conclusion When looking at all deliveries, SLE was associated with a two-fold higher risk of GDM. GDM occurrence did not differ by GC or HCQ.

Remission, relapse, and risk of major cardiovascular events after metabolic surgery in persons with hypertension: A Swedish nationwide registry-based cohort study

Background Several studies have shown that metabolic surgery is associated with remission of diabetes and hypertension. In terms of diabetes, factors such as duration, insulin use, weight loss, and age have been shown to contribute to the likelihood of remission. Such factors have not been determined for hypertension. The aim of this study was to evaluate factors associated with the remission and relapse of hypertension after metabolic surgery, as well as the risk for major adverse cardiovascular event (MACE) and mortality in patients with and without remission. Methods and findings All adults who underwent metabolic surgery between January 2007 and June 2016 were identified in the nationwide Scandinavian Obesity Surgery Registry (SOReg). Through cross-linkage with the Swedish Prescribed Drug Register, Patient Register, and Statistics Sweden, individual data on prescriptions, inpatient and outpatient diagnoses, and mortality were retrieved. Of the 15,984 patients with pharmacologically treated hypertension, 6,286 (39.3%) were in remission at 2 years. High weight loss and male sex were associated with higher chance of remission, while duration, number of antihypertensive drugs, age, body mass index (BMI), cardiovascular disease, and dyslipidemia were associated with lower chance. After adjustment for age, sex, BMI, comorbidities, and education, the cumulative probabilities of MACEs (2.8% versus 5.7%, adjusted odds ratio (OR) 0.60, 95% confidence interval (CI) 0.47 to 0.77, p < 0.001) and all-cause mortality (4.0% versus 8.0%, adjusted OR 0.71, 95% CI 0.57 to 0.88, p = 0.002) were lower for patients being in remission at 2 years compared with patients not in remission, despite relapse of hypertension in 2,089 patients (cumulative probability 56.3%) during 10-year follow-up. The main limitations of the study were missing information on nonpharmacological treatment for hypertension and the observational study design. Conclusions In this study, we observed an association between high postoperative weight loss and male sex with better chance of remission, while we observed a lower chance of remission depending on disease severity and presence of other metabolic comorbidities. Patients who achieved remission had a halved risk of MACE and death compared with those who did not. The results suggest that in patients with severe obesity and hypertension, metabolic surgery should not be delayed.

HMG-CoA reductase inhibitors and COVID-19 mortality in Stockholm, Sweden: A registry-based cohort study

Background The relationship between statin treatment and Coronavirus Disease 2019 (COVID-19) mortality has been discussed due to the pleiotropic effects of statins on coagulation and immune mechanisms. However, available observational studies are hampered by study design flaws, resulting in substantial heterogeneity and ambiguities. Here, we aim to determine the relationship between statin treatment and COVID-19 mortality. Methods and findings This cohort study included all Stockholm residents aged 45 or older (N = 963,876), followed up from 1 March 2020 until 11 November 2020. The exposure was statin treatment initiated before the COVID-19-pandemic, defined as recorded statin dispensation in the Swedish Prescribed Drug Register between 1 March 2019 and 29 February 2020. COVID-19-specific mortality was ascertained from the Swedish Cause of Death Registry. Hazard ratios (HRs) were calculated using multivariable Cox regression models. We further performed a target trial emulation restricted to initiators of statins. In the cohort (51.6% female), 169,642 individuals (17.6%) were statin users. Statin users were older (71.0 versus 58.0 years), more likely to be male (53.3% versus 46.7%), more often diagnosed with comorbidities (for example, ischemic heart disease 23.3% versus 1.6%), more frequently on anticoagulant and antihypertensive treatments, less likely to have a university-level education (34.5% versus 45.4%), and more likely to have a low disposable income (20.6% versus 25.2%), but less likely to reside in crowded housing (6.1% versus 10.3%). A total of 2,545 individuals died from COVID-19 during follow-up, including 765 (0.5%) of the statin users and 1,780 (0.2%) of the nonusers. Statin treatment was associated with a lowered COVID-19 mortality (adjusted HR, 0.88; 95% CI, 0.79 to 0.97, P = 0.01), and this association did not vary appreciably across age groups, sexes, or COVID-19 risk groups. The confounder adjusted HR for statin treatment initiators was 0.78 (95% CI, 0.59 to 1.05, P = 0.10) in the emulated target trial. Limitations of this study include the observational design, reliance on dispensation data, and the inability to study specific drug regimens. Conclusions Statin treatment had a modest negative association with COVID-19 mortality. While this finding needs confirmation from randomized clinical trials, it supports the continued use of statin treatment for medical prevention according to current recommendations also during the COVID-19 pandemic.

1254Comorbidity of atopic diseases and gastroesophageal reflux in adults: a co-twin control study

Background Gastroesophageal reflux disease (GERD) is the most common non-allergic comorbidity in adults with asthma, however comorbidity with other atopic diseases such as eczema and hayfever is unclear. The objective was to assess the comorbidity of GERD with atopic diseases in adults, and to investigate possible mechanisms including genetic and affective factors. Methods A co-twin control study harnessing 46 583 adult Swedish twins. Questionnaires on health status were linked to national patient and prescribed drug register data. Within twin-pair comparisons were made between unpaired, monozygotic (MZ) and dizygotic (DZ) twins to assess common genetic liability. Affective traits (depression, anxiety and neuroticism) were added to models to assess their role in comorbidity. Results The risk of GERD in those with asthma was OR1.52 (95% CI 1.38, 1.68); hayfever OR1.22 (95%CI 1.12, 1.34); and eczema OR1.23 (95%CI 1.10, 1.38). Within twin-pair associations attenuated in decreasing order of shared genetics for all atopic diseases e.g. self-report asthma with GERD: DZ twins adjOR1.41 (95%CI 0.96, 2.08), MZ twins adjOR1.24 (95%CI 0.82, 1.87). Adjusting for affective traits only slightly attenuated the comorbidity associations. Conclusions GERD is a common comorbidity in adults with asthma, hayfever and/or eczema. We found evidence for shared genetic factors but not for affective traits. Key messages GERD is a common comorbidity not only in adults with asthma, but also in adults with eczema or hayfever. Twin research has revealed evidence for a common genetic liability to explain comorbidity.

Long-Term Time Trends in Reactivated Herpes Simplex Infections and Treatment in Sweden.

Background: Our aim was to describe the annual prevalence of herpes simplex virus (HSV) reactivation in relation to solar ultraviolet (UV) radiation and antiviral drug use in the Swedish adult population. Methods: The study comprised 2,879 anti-HSV-1 immunoglobulin (Ig) G positive subjects from five different cohorts who had donated serum from 1988–2010. The sera were analyzed for anti-HSV IgM using enzyme-linked immunosorbent assay. Associations between the presence of anti-HSV IgM antibodies, the apolipoprotein E ε4 allele and the serum sampling year were assessed by logistic regression. Seasonality of anti-HSV IgM was evaluated in a UV radiation model. Data of antiviral drugs for the entire Swedish population were compiled from two different nationwide databases: the Swedish Prescribed Drug Register and the Swedish Association of the Pharmaceutical Industry. Results: Cross-sectional and longitudinal analyses indicated that the prevalence of anti-HSV IgM antibodies declined between 1988 and 2010 (odds ratio [OR] = 0.912, P < .001), while the total annual use of antiviral drugs in Sweden gradually increased from 1984 to 2017. Higher UV radiation was associated with higher prevalence of anti-HSV IgM antibodies (OR = 1.071, P = .043). Conclusion: The declining time trend of HSV reactivation coincides with a steady increase of antiviral drug use, indicating improved control of HSV reactivation in the Swedish adult population.

Women with chronic hypoparathyroidism have low risk of adverse pregnancy outcomes

Objective The aim of this study was to evaluate pregnancy outcome and total number of births in chronic hypoparathyroidism (hypoPT). Patients The Swedish National Patient Register, The Swedish Prescribed Drug Register, Swedish Medical Birth Register and the Total Population Register were used to identify 97 women with chronic hypoPT and 1030 age-matched controls who delivered 139 and 1577 singleton infants, respectively, following diagnosis between 1997 and 2017. Results Women in the chronic hypoPT group had more frequent diabetes (DM) and chronic kidney disease (CKD) compared to women in the control group (p=0.043 and p&lt;0.001, respectively). After adjusting for DM, CKD, maternal age at delivery and calendar year of delivery, chronic hypoPT cases were associated with increased risk of induction of labor (OR 1.82; 95% CI 1.13-2.94) and giving birth to infants with lower birth weight (β-coefficient -188 g; 95% CI -312.2- -63.8) compared to controls. No difference was found in infant length, small for gestational age or head circumference after adjustments. Mean gestational age at delivery after controlling for DM, CKD and pre-eclampsia, was not significantly younger (p=0.119). There was no difference in congenital malformations or perinatal death. There was no difference in the total number of infants born to women with chronic hypoPT and controls (p=0.518). Conclusion The majority of women with chronic hypoPT had normal pregnancy outcomes, and the overall risks appear to be low. Maternal chronic hypoPT, is however, associated with a higher risk of induction of labor and slightly lower infant birth weight.

Impact of Adrenalectomy on Morbidity in Patients with Non-Functioning Adrenal Cortical Tumours, Mild Hypercortisolism and Cushing’s Syndrome as Assessed by National and Quality Registries

Background The impact of adrenalectomy on morbidity in patients with mild hypercortisolism and non-functioning adrenocortical adenoma is unclear. The present study evaluated morbidity before and after adrenalectomy in patients with benign adrenocortical tumour with Cushing´s syndrome (CS), autonomous cortisol secretion (ACS) and non-functioning adrenocortical adenoma as assessed by national and quality registries. Methods Patients registered in the Scandinavian Quality Register for Thyroid, Parathyroid and Adrenal Surgery (SQRTPA) 2009–2017 with CS, ACS or non-functioning adrenocortical adenoma, were included in this retrospective study and analysed with age- and sex-matched controls, 1:3. Morbidity associated with CS was assessed pre- and postoperatively by analysing data from the Swedish National Patient Register and the Swedish Prescribed Drug Register. Results Some 271 patients were included, CS (127), ACS (45) and non-functioning adrenocortical adenoma (99), with 813 matched controls. The frequency of hypertension was almost 50% in all tumour groups. Antihypertensive medication preoperatively was more frequent in all tumour groups compared with controls. No preoperative differences in medication were detected between patients with CS and ACS. A decrease in the use of hypertensive drugs was noticed annually for all patient groups after adrenalectomy. Conclusions Hypertension is common in patients with benign adrenocortical tumours regardless of cortisol hypersecretion. The use of antihypertensive drugs in patients with CS, ACS and non-functioning adrenocortical adenoma was reduced after adrenalectomy. These findings highlight the need for a randomized controlled trial to investigate the impact of adrenalectomy on morbidity in patients with mild hypercortisolism.

Type 2 diabetes risk in sarcoidosis patients untreated and treated with corticosteroids

BackgroundThe rate of type 2 diabetes mellitus (T2D) is increased in sarcoidosis patients but it is unknown if corticosteroid treatment plays a role. We investigated whether the T2D risk is higher in untreated and corticosteroid-treated sarcoidosis patients compared to the general population.MethodsIn this cohort study individuals with ≥2 ICD codes for sarcoidosis were identified from the Swedish National Patient Register (NPR; n=5754). Corticosteroid dispensations ±3 months from first sarcoidosis diagnosis were identified from the Prescribed Drug Register (PDR). General population comparators without sarcoidosis were matched to cases 10:1 on age, sex and region of residence (n=61 297). Incident T2D was identified using ICD codes (NPR) and antidiabetic drug dispensations (PDR). Follow-up was from second sarcoidosis diagnosis/matching date until T2D, emigration, death or study end (Dec 2013). Cox regression models adjusted for age, sex, education, country of birth, healthcare regions and family history of diabetes estimated hazard ratios (HR 95%CI). We used flexible parametric models to examine the T2D risk over time.Results40% of sarcoidosis patients were corticosteroid-treated at diagnosis. The T2D rate was 7.7/1000 person-years in untreated sarcoidosis, 12.7 in corticosteroid-treated sarcoidosis and 5.5 in comparators. The HR for T2D was 1.4 (95%CI 1.2–1.8) associated with untreated sarcoidosis and 2.3 (95%CI 2.0–3.0) associated with corticosteroid-treated sarcoidosis. The T2D risk was highest for corticosteroid-treated sarcoidosis in the first 2 years after diagnosis.ConclusionSarcoidosis is associated with an increased risk of T2D especially in older, male, corticosteroid-treated patients at diagnosis. Screening for T2D for these patients is advisable.