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Background: The duration of forensic psychiatric care is in Sweden not determined at the time of sentencing; instead, offenders are regularly evaluated, often with regard to risk of criminal recidivism. The length and justifiability of such a sanction have been greatly debated; however, previous estimates of treatment duration based on datasets delimited to discharged patients--have provided an uncertain groundwork for these deliberations. The aim of this study was to use a more suitable approach to calculate average duration of forensic psychiatric care and to examine the relationship between length of treatment and subsequent recidivism after discharge. Methods: This retrospective cohort study focused on offenders sentenced to forensic psychiatric care in Sweden between 2009 and 2019 and registered in the Swedish National Forensic Psychiatric Register (n = 2064), with a follow-up period until May 2020. We used Kaplan-Meier estimator to calculate and visualize treatment duration including analyses comparing levels of relevant variables, and then evaluated criminal recidivism in patients discharged from treatment between 2009 and 2019 (n = 640), after stratification for the same variables and dichotomization by treatment duration. Results: The median duration of forensic psychiatric care was estimated to 89.7 months (95% CI 83.2-95.8). Treatment was longer in offenders who committed violent crimes, suffered from psychosis, or had a history of substance use disorder, and in offenders whose sentences included special court supervision. The cumulative incidence of recidivism in patients discharged from treatment was estimated to 13.5% at 12 months (95% CI 10.6-16.2) and 19.5% at 24 months (95% CI 16.0-22.8). Corresponding cumulative incidence of violent crime post discharge was 6.3% at 12 months (95% CI 4.3-8.3) and 9.9% at 24 months (95% CI 7.3-12.4). Among other findings, in patients without a history of substance use disorder and patients whose sentences did not include special court supervision, recidivism was significantly higher in those with a shorter treatment duration. Conclusion: Using the entirety of a suitable, contemporary, prospectively enrolled cohort of mentally ill offenders, we were able to estimate--with greater accuracy than previous studies--the average duration of Swedish forensic psychiatric care and rate of subsequent criminal recidivism. [ABSTRACT FROM AUTHOR]

Objectives: Warm autoimmune hemolytic anemia (wAIHA) is a rare autoantibody-mediated disorder, and first-line treatment primarily relies on corticosteroids. This study assessed overall survival (OS) and treatment patterns of wAIHA in Sweden., Methods: Adults with ≥ 1 primary diagnosis code for wAIHA (or AIHA plus oral corticosteroids (OCS)/immunosuppressants as sensitivity analyses) between 2011 and 2022 were identified from five Swedish national registers and linked through each patient's unique identity number. Kaplan-Meier curves with log-rank tests and Cox regressions were performed to assess OS for patients with primary versus secondary wAIHA and patients with wAIHA and long-term versus short-term (≥ 3 vs. < 3 months) OCS users., Results: The main analysis included 292 patients; 1791 patients were included in the sensitivity analysis. At a median 3.7-year follow-up, a median OS in primary wAIHA was not reached versus 6.0 years for secondary wAIHA (log-rank test: p = 0.003). Subgroup analyses showed no significant difference in risk of death between long-term and short-term OCS users; however, in the sensitivity analysis, long-term OCS users showed significantly higher risk of death (adjusted hazard ratio: 1.45; 95% confidence interval: 1.180, 1.781; p < 0.001) versus short-term OCS users., Conclusion: Secondary wAIHA or long-term OCS use was associated with lower OS, underscoring the disease burden and unmet need for efficacious wAIHA treatments., (© 2024 The Author(s). European Journal of Haematology published by John Wiley & Sons Ltd.)

Introduction: β-site amyloid precursor protein (APP) cleaving enzyme 2 (BACE2) cleaves APP which is ubiquitously expressed in a variety of cell types including cancer cells. BACE2 can process APP in several ways and appears to be involved in the pathogenesis of cancer. Our purpose was to assess the association of mRNA expression and genetic polymorphism of BACE2 in colorectal cancer (CRC) susceptibility and its association to clinicopathological factors in Swedish patients with CRC., Methods: A total of 720 CRC patients and 470 healthy controls were genotyped for BACE2 gene polymorphism rs2012050, using TaqMan single nucleotide polymorphism (SNP) assays based on polymerase chain reaction. Reverse transcription quantitative PCR was used to investigate the BACE2 gene expression in 192 CRC tissue and 181 paired normal tissue., Results: Assessing clinicopathological factors, we noted that carrying of T allele in C/T and C/T+T/T was significantly associated with a protective role against disseminated cancer and higher lymph node status. Moreover, individuals carrying T/T genotype were significantly more likely to have poorly differentiated cancer. Follow-up data for patients in poorly differentiated cancer and the Kaplan-Meier analysis showed that the cancer-specific survival curves differed between C/C and C/T+T/T for the BACE2 gene polymorphism and that the carriers of the genotype C/C were associated with more favorable prognosis. We found no significant differences in the genotypic frequencies between the patients and healthy controls. BACE2 mRNA level was significantly 2.2-fold upregulated in CRC tissue when compared to noncancerous tissue. A higher BACE2 mRNA level was observed in smaller tumors and in rectal cancer when compared to colon cancer., Conclusion: In patients with CRC, our results indicate BACE2 rs2012050 as a useful potential predictor of poor differentiation, disseminated cancer and lymph node status and that the BACE2 mRNA expression is associated to tumor size and cancer location., (© 2024 The Author(s). Published by S. Karger AG, Basel.)

Multidisciplinary team meetings (MDTs) are recommended for patients with esophageal cancer. Improved staging, timeliness to surgery and better adherence to guidelines have been attributed to MDTs, but there are few studies published on the MDTs' effect on survival. All patients with esophageal cancer in Sweden between 2006 and 2018 were grouped according to whether they had been discussed at an MDT as part of their clinical pathway. Factors affecting group allocation were explored with multivariable logistic regression, and the impact of MDT on survival was studied with Cox-regression and the Kaplan-Meier estimator. Of 6837 included patients, 1338 patients (20%) were not discussed at an MDT. Advanced age (80-90 years; odds ratio [OR] 0.25, 0.16-0.42 (95% confidence interval)) and clinical stage IVb (OR 0.65, 0.43-0.98) decreased the probability of being presented at an MDT, whereas high education level (OR 1.31, 1.02-1.67), being married (OR 1.20, 1.01-1.43), squamous histology (OR 1.50, 1.22-1.84) and later year of diagnosis (OR 1.33, 1.29-1.37 per year) increased the probability of an MDT. In multivariable adjusted analysis, MDT discussion was associated with improved survival (hazard ratios 0.72, 0.66-0.78) and median survival increased from 4.5 to 10.7 months. MDTs were associated with improved survival for esophageal cancer patients. Elderly patients with advanced disease and poor socioeconomic status were less likely to be presented at an MDT, but had clear survival-benefits if they were discussed in a multidisciplinary setting., (© The Author(s) 2024. Published by Oxford University Press on behalf of International Society for Diseases of the Esophagus.)

Previous solid organ transplantation has been associated with worse survival among colorectal cancer (CRC) patients. This study investigates the contribution of CRC characteristics and treatment-related factors to the differential survival. Using the Swedish register-linkage CRCBaSe, all patients with solid organ transplantation before CRC diagnosis were identified and matched with non-transplanted CRC patients. Associations between transplantation history and clinical CRC factors and survival were estimated using the Kaplan-Meier estimator and logistic, multinomial, and Cox regression, respectively. Ninety-eight transplanted and 474 non-transplanted CRC patients were followed for 5 years after diagnosis. Among patients with stage I-III cancer, transplanted patients had lower odds of treatment with abdominal surgery [odds ratio (OR):0.27, 95% confidence interval (CI):0.08-0.90], than non-transplanted patients. Among those treated with surgery, transplanted colon cancer patients had lower odds of receiving adjuvant chemotherapy (OR:0.31, 95% CI:0.11-0.85), and transplanted rectal cancer patients had higher rate of relapse (hazard ratio:9.60, 95% CI:1.84-50.1), than non-transplanted patients. Five-year cancer-specific and overall survival was 56% and 35% among transplanted CRC patients, and 68% and 57% among non-transplanted. Accordingly, transplanted CRC patients were treated less intensely than non-transplanted patients, and had worse cancer-specific and overall survival. These patients might benefit from multidisciplinary evaluation including transplantation specialists., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Benoni, Nordenvall, Hellström, Dietrich, Martling, Smedby and Eloranta.)

Background: While immediate breast reconstruction rates in breast cancer are increasing, they remain low in women over 65 years old. The aim was to investigate surgical outcomes in women older than 65 years receiving implant-based immediate breast reconstruction., Method: The population-based Stockholm Breast Reconstruction Database includes all adult women with breast cancer receiving an implant-based immediate breast reconstruction in Stockholm, Sweden, 2005-2015. Primary outcomes within 30 days from immediate breast reconstruction were: infection requiring antibiotics and reoperation on. Implant removal was a secondary outcome. Women more than 65 years were compared with younger age groups. Chi-square tests and multivariable logistic regression were applied for the primary outcomes, and Kaplan-Meier analysis for the secondary outcome., Results: Among 1749 cases of immediate breast reconstruction, 140 (8.0%) were in women more than 65 years. Median follow-up was 74 months (1-198). Postoperative infection was not more common in women older than 65 years old (22 of 140, 15.7%) than in women under 65 years old (303 of 1609, 18.8%; P = 0.221). Reoperation on was more frequent in women older than 65 years than in other age groups (more than 65: 8.6%; 50-64: 6.5%; 40-49: 3.5%; less than 40: 1.6%; P < 0.001), however, age older than 65 years was not an independent risk factor in the multivariable analysis (OR 1.00, 95% c.i. 0.44 to 2.28). Overall, 6-year probability of implant removal was 11.4%, (8.1% due to complications and 3.3% due to patient preference). There was no statistically significant difference between age groups for either reason (P = 0.085 and P = 0.794 respectively)., Conclusion: Older age alone was not associated with worse surgical outcomes after implant-based immediate breast reconstruction in highly selected patients older than 65 years when compared with their younger counterparts., (© The Author(s) 2024. Published by Oxford University Press on behalf of BJS Foundation Ltd.)

Objectives: This study aimed to compare the long-term effects of maintenance electroconvulsive therapy (M-ECT) with medication and medication only in patients with depression., Methods: A randomized controlled trial of 1 year of M-ECT with medication or medication only investigated relapse/recurrence among 56 patients in remission after electroconvulsive therapy (ECT) for depression was conducted. The results of the first year are published already and showed a significant advantage of M-ECT with medication.The current study was a long-term follow-up. When the randomized treatment allocation ended, medication was continued in both groups but M-ECT was terminated. Patients were followed for up to 10 years via Swedish national registers until the study endpoint of a new psychiatric diagnosis as an inpatient, suicide, suspected suicide, or death of another cause. Time to relapse was compared between the M-ECT with medication group and the medication-only group using Kaplan-Meier estimates., Results: The median follow-up time was 6.5 years for the M-ECT and medication group and 3.1 years for the medication-only group. One year after randomization 22 patients remained in the M-ECT and medication group, and 14 patients remained in the medication-only group. Relapse patterns between the treatment groups after the completion of M-ECT seemed to be similar according to visual inspection., Conclusions: This long-term follow-up study suggests that most of the benefit achieved during the treatment period with M-ECT is maintained over several years, but the small sample size, with accompanying large statistical imprecision, makes the results uncertain. More long-term studies of M-ECT are required.Trial registration: ClinicalTrials.gov identifier: NCT00627887., Competing Interests: Uppsala-Örebro Regional Research Council and Research Committee of Örebro County Council, Örebro, Sweden, supported the research. A.N. has received lecturer honoraria from Lundbeck outside the submitted work. The other authors have no conflicts of interest or financial disclosures to report., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc.)

Objectives: Some studies have examined survival trends among critically ill COVID-19 patients, but most were case reports, small cohorts, and had relatively short follow-up periods. We aimed to examine the survival trend among critically ill COVID-19 patients during the first two and a half years of the pandemic and investigate potential predictors across different variants of concern periods., Design: Prospective cohort study., Setting: Swedish ICUs, between March 6, 2020, and December 31, 2022., Patients: Adult COVID-19 ICU patients of 18 years old or older from the Swedish Intensive Care Register (SIR) that were linked to multiple other national registers., Measurement and Main Results: Survival probability and predictors of COVID-19 death were estimated using Kaplan-Meier and Cox regression analysis. Of 8975 patients, 2927 (32.6%) died. The survival rate among COVID-19 critically ill patients appears to have changed over time, with a worse survival in the Omicron period overall. The adjusted hazard ratios (aHRs) comparing older and younger ages were consistently strong but slightly attenuated in the Omicron period. After adjustment, the aHR of death was significantly higher for men, older age (40+ yr), low income, and with comorbid chronic heart disease, chronic lung disease, impaired immune disease, chronic renal disease, stroke, and cancer, and for those requiring invasive or noninvasive respiratory supports, who developed septic shock or had organ failures ( p < 0.05). In contrast, foreign-born patients, those with booster vaccine, and those who had taken steroids had better survival (aHR = 0.87; 95% CI, 0.80-0.95; 0.74, 0.65-0.84, and 0.91, 0.84-0.98, respectively). Observed associations were similar across different variant periods., Conclusions: In this nationwide Swedish cohort covering over two and a half years of the pandemic, ICU survival rates changed over time. Older age was a strong predictor across all periods. Furthermore, most other mortality predictors remained consistent across different variant periods., Competing Interests: Dr. Nyberg’s institution received funding from the Swedish government and the county councils, the ALF agreement (grants ALFGBG-938453, ALFGBG-971130, and ALFGBG-978954), the Swedish Research Council for Health, Working Life and Welfare, and the Swedish Research Council for Environment, Agricultural Sciences and Spatial Planning grant (2020-02828); he disclosed he shared with AstraZeneca. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the Society of Critical Care Medicine and Wolters Kluwer Health, Inc.)

Background: It has been estimated that 80% of cases of out-of-hospital cardiac arrest (OHCA) are due to cardiac causes. It is well-documented that diabetes is a risk factor for conditions associated with sudden cardiac arrest. Type 1 diabetes (T1D) displays a threefold to fivefold increased risk of cardiovascular disease and death compared with the general population., Objective: This study aims to assess the characteristics and survival outcomes of individuals with and without T1D who experienced an OHCA. Design : A registry-based nationwide observational study with two cohorts, patients with T1D and patients without T1D. Setting : All emergency medical services and hospitals in Sweden were included in the study., Participants: Using the Swedish Cardiopulmonary Resuscitation Registry, we enrolled 54 568 cases of OHCA where cardiopulmonary resuscitation was attempted between 2010 and 2020. Among them, 448 patients with T1D were identified using International Classification of Diseases-code: E10., Methods: Survival analysis was performed using Kaplan-Meier and logistic regression. Multiple regression was adjusted for age, sex, cause of arrest, prevalence of T1D and time to cardiopulmonary resuscitation., Main Outcome Measures: The outcomes were discharge status (alive vs dead), 30 days survival and neurological outcome at discharge., Results: There were no significant differences in patients discharged alive with T1D 37.3% versus, 46% among cases without T1D. There was also no difference in neurological outcome. Kaplan-Meier curves yielded no significant difference in long-term survival. Multiple regression showed no significant association with survival after accounting for covariates, OR 0.99 (95% CI 0.96 to 1.02), p value=0.7. Baseline characteristics indicate that patients with T1D were 5 years younger at OHCA occurrence and had proportionally fewer cases of heart disease as the cause of arrest (57.6% vs 62.7%)., Conclusion: We conclude, with the current sample size, that there is no statistically significant difference in long-term or short-term survival between patients with and without T1D following OHCA., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background/aim: Matrix metalloproteinase 13 (MMP13) has been reported to be involved in tumor development and progression, including of colorectal cancer (CRC). This study aimed at evaluating whether the MMP13 rs2252070 gene polymorphism is associated with clinicopathological factors and its influence on long-term survival in Swedish patients with CRC., Patients and Methods: A total of 723 patients with CRC were genotyped using TaqMan single nucleotide polymorphism assays based on polymerase chain reaction., Results: Assessing clinicopathological factors, we demonstrated that having the G/G genotype for MMP13 rs2252070 was significantly associated with poor differentiation, higher serum level of carcinoembryonic antigen and higher lymph node status. Moreover, the presence of a G allele was significantly related to larger tumor size in rectal cancer but had a significantly protective role against mucinous cancer, perineural invasion and lymphovascular invasion. Kaplan-Meier analysis showed no difference between genotypes regarding cancer-specific survival., Conclusion: Our findings highlight the potential of MMP13 rs2252070 polymorphism as a useful predictor of poor differentiation, serum level of carcinoembryonic antigen, lymph node status, tumor size, mucinous cancer, perineural invasion and lymphovascular invasion in patients with CRC., (Copyright © 2024, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.)

Purpose: Vitamin D has some anticancer properties that may decrease breast cancer risk and improve prognosis. The aim was to investigate associations between four previously studied VDR SNPs (Taq1, Tru91, Bsm1, and Fok1) and prognosis in different groups of breast cancer patients., Methods: VDR genotyping of 1,017 breast cancer patients included 2002-2012 in Lund, Sweden, was performed using Oncoarray. Follow-up was until June 30, 2019. Clinical data and patient information were collected from medical records and questionnaires. Cox regression was used for survival analyses., Results: Genotype frequencies were as follows: Fok1 (AA 15.7%, AG 49.1%, GG 35.1%), Bsm1 (CC 37.2%, CT 46.1%, TT 16.7%), Tru91 (CC 77.8%, CT 20.7%, TT 1.5%), and Taq1 (AA 37.2%, AG 46.2%, GG 16.6%). During follow-up there were 195 breast cancer events. The homozygous variants of Taq1 and Bsm1 were associated with reduced risk of breast cancer events (adjusted HR = 0.59, 95% CI 0.38-0.92 for Taq1 and adjusted HR = 0.61, 95% CI 0.40-0.94 for Bsm1). The G allele of the Fok1 was associated with increased risk of breast cancer events in small tumors (pT1, adjusted HR = 1.83, 95% CI 1.04-3.23) but not in large tumors (pT2/3/4, adjusted HR = 0.80, 95% CI 0.41-1.59) with a borderline interaction (P interaction  = 0.058). No interactions between VDR genotypes and adjuvant treatments regarding breast cancer prognosis were detected., Conclusion: VDR genotypes were associated with breast cancer prognosis and the association might be modified by tumor size. Further research is needed to confirm the findings and elucidate their potential clinical implications., (© 2024. The Author(s).)

Background: In health technology assessment, restricted mean survival time and life expectancy are commonly evaluated. Parametric models are typically used for extrapolation. Spline models using a relative survival framework have been shown to estimate life expectancy of cancer patients more reliably; however, more research is needed to assess spline models using an all-cause survival framework and standard parametric models using a relative survival framework., Aim: To assess survival extrapolation using standard parametric models and spline models within relative survival and all-cause survival frameworks., Methods: From the Swedish Cancer Registry, we identified patients diagnosed with 5 types of cancer (colon, breast, melanoma, prostate, and chronic myeloid leukemia) between 1981 and 1990 with follow-up until 2020. Patients were categorized into 15 cancer cohorts by cancer and age group (18-59, 60-69, and 70-99 y). We right-censored the follow-up at 2, 3, 5, and 10 y and fitted the parametric models within an all-cause and a relative survival framework to extrapolate to 10 y and lifetime in comparison with the observed Kaplan-Meier survival estimates. All cohorts were modeled with 6 standard parametric models (exponential, Weibull, Gompertz, log-logistic, log-normal, and generalized gamma) and 3 spline models (on hazard, odds, and normal scales)., Results: For predicting 10-y survival, spline models generally performed better than standard parametric models. However, using an all-cause or a relative survival framework did not show any distinct difference. For lifetime survival, extrapolating from a relative survival framework agreed better with the observed survival, particularly using spline models., Conclusions: For extrapolation to 10 y, we recommend spline models. For extrapolation to lifetime, we suggest extrapolating in a relative survival framework, especially using spline models., Highlights: For survival extrapolation to 10 y, spline models generally performed better than standard parametric models did. However, using an all-cause or a relative survival framework showed no distinct difference under the same parametric model.Survival extrapolation to lifetime within a relative survival framework agreed well with the observed data, especially using spline models.Extrapolating parametric models within an all-cause survival framework may overestimate survival proportions at lifetime; models for the relative survival approach may underestimate instead., Competing Interests: The authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article. The authors disclosed receipt of the following financial support for the research, authorship, and/or publication of this article: This research was funded by research grants by the Swedish Research Council and Cancerfonden (The Swedish Cancer Society). The funding agreement ensured the authors’ independence in designing the study, interpreting the data, writing, and publishing the report.

Importance: Mortality in patients with tetralogy of Fallot (TOF) has decreased substantially since the start of surgical correction of this abnormality in the 1950s. However, nationwide data in Sweden comparing survival trends among pediatric patients with TOF with the general population are still limited., Objective: To study survival trends in pediatric patients with TOF and compare them with matched controls., Design, Setting, and Participants: A Swedish registry-based, nationwide, matched cohort study was conducted; data were collected from national health registers from January 1, 1970, to December 31, 2017. Patients with a registered diagnosis of TOF as well as controls without TOF matched by birth year and sex were included in the study. Follow-up data were collected from birth to age 18 years, death, or the end of follow-up (December 31, 2017), whichever occurred first. Data analysis was performed from September 10 to December 20, 2022. Survival trends among patients with TOF were compared with matched controls using Cox proportional hazards regression and Kaplan-Meier survival analyses., Main Outcomes and Measures: All-cause mortality during childhood in patients with TOF and matched controls., Results: The population included 1848 patients (1064 [57.6%] males; mean [SD] age, 12.4 [6.7] years) with TOF and 16 354 matched controls. The number of patients who underwent congenital cardiac surgery (henceforth, surgery group) was 1527 (897 [58.7%] males). In the whole TOF population from birth until age 18 years, 286 patients (15.5%) died during a mean (SD) follow-up time of 12.4 (6.7) years. In the surgery group, 154 of 1527 patients (10.1%) died during a follow-up time of 13.6 (5.7) years with a mortality risk of 21.9 (95% CI, 16.2-29.7) compared with matched controls. When stratified by birth period, a substantial decrease in the mortality risk was noted in the surgery group, from 40.6 (95% CI, 21.9-75.4) in those born in the 1970s to 11.1 (95% CI, 3.4-36.4) in those born in the 2010s. Survival increased from 68.5% to 96.0%. The risk of mortality for surgery decreased from 0.52 in the 1979s to 0.19 in the 2010s., Conclusions and Relevance: The findings of this study suggest there has been substantial improvement in survival in children with TOF who underwent surgery from 1970 to 2017. However, the mortality rate is still significantly higher in this group compared with matched controls. Predictors of good and poor outcomes in this group need to be further explored, with the modifiable ones evaluated for further outcome improvements.

Introduction The aim was to assess survival in the Swedish population of teeth treated by nonsurgical root canal treatment during 2009. Methods Data from the Swedish Social Insurance Agency were analyzed by Kaplan-Meier analysis to assess cumulative tooth survival during a period of 5–6 years of all teeth that were root-filled during 2009. Results In 2009, 248,299 teeth were reported as root-filled. The average age of the patients at the time of the root filling was 55 years (range, 20–102 years). The teeth most frequently root-filled were the maxillary and mandibular first molars. During the 5- to 6-year period 25,228 of the root-filled teeth (10.2%) were reported to have been extracted; thus 223,071 teeth (89.8%) survived. Tooth survival was highest in the youngest age group (93.2%). The highest survival (93.0%) was for the mandibular premolars, and the lowest (87.5%) was for the mandibular molars. Teeth restored with indirect restorations within 6 months of the root filling had higher survival rates (93.1%) than those restored with a direct filling (89.6%). Conclusions In the adult population of Sweden, teeth that are root-filled by general practitioners under the tax-funded Swedish Social Insurance Agency have a 5- to 6-year survival rate of approximately 90%. [ABSTRACT FROM AUTHOR]

Objective: The aim of this study was to evaluate the contemporary population based incidence of acute lower limb ischaemia (ALI) and factors associated with major amputation/death at one year., Methods: In this retrospective observational study, in hospital, operation, radiological, and autopsy registries were scrutinised to capture 161 citizens of Malmö, Sweden, with ALI between 2015 and 2018. Age and sex specific incidence rates were calculated in the population of Malmö between 2015 and 2018, expressed as number of patients per 100 000 person years (PY). Independent risk factors for major amputation/death at one year were identified by multivariable logistic regression analysis and expressed as odds ratios (ORs) with 95% confidence intervals (CIs)., Results: One hundred and sixty-one patients with ALI gave an overall incidence of 12.2/100 000 PY (95% CI 10.3 - 14.1), with no sex related differences. Embolism (42.2%) was the most common cause of ALI. Among 52 patients with atrial fibrillation, 38.5% were on anticoagulant medication. Endovascular or open vascular revascularisation was performed in 54.7% of patients. The total cause specific mortality ratio was 2.63 (95% CI 1.66 - 3.61)/1 000 deaths, without no sex related differences. The combined major amputation/mortality rate at one year for the whole cohort was 46.6%. Rutherford ≥ IIb ALI (OR 4.19, 95% CI 1.94 - 9.02; p < .001), age (OR 1.03/year, 95% CI 1.00 - 1.06; p = .036), female sex (OR 2.37, 95% 1.07 - 5.26; p = .034), and anaemia (OR 2.46, 95% CI 1.08 - 5.62; p = .033) were associated with an increased risk of major amputation/death at one year. The major amputation/mortality rate at one year was 100% (n = 14/14) for patients living in a nursing home on admission., Conclusion: The incidence of ALI appears to be unchanged, and major amputation and mortality at one year remain high. It is necessary to include the substantial proportion of patients with ALI that do not undergo revascularisation in epidemiological studies. There is room for improvement in anticoagulation therapy in patients with atrial fibrillation to prevent ALI due to embolism. Research on gender inequalities in patients with ALI is warranted., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objective: The aim was to describe the microbiology of surgically treated infective native (mycotic) aortic aneurysms (INAAs), and associated survival and development of infection-related complications (IRCs)., Methods: Data were pooled from 2 nationwide studies on surgically treated patients with INAAs in Sweden, between 1994 - 2016. Patients were grouped and analyzed according to culture results: 1) Staphylococcus aureus, 2) Streptococcus species (sp.), 3) Salmonella sp., 4) Enterococcus sp., 5) Gram-negative intestinal bacteria, 6) Other sp. (all other species found in culture), and 7) Negative cultures., Results: A sum of 182 patients were included, mean age 71 years (standard deviation; SD: 8.9). The median follow-up was 50.3 months (range 0 - 360). 128 (70.3%) patients had positive blood and/or tissue culture; Staphylococcus aureus n = 38 (20.9%), Streptococcus sp. n = 37 (20.3%), Salmonella sp. n = 19 (10.4%), Enterococcus sp. n = 16 (8.8%), Gram-negative intestinal bacteria n = 6, (3.3%), Other sp. n = 12 (6.6%) and Negative cultures n = 54 (29.7%). The estimated survival for the largest groups at 2-years after surgery was: Staphylococcus aureus 62% (95% Confidence interval 53.9 - 70.1), Streptococcus sp. 74.7% (67.4 - 82.0), Salmonella sp. 73.7% (63.6 - 83.8), Enterococcus sp. 61.9% (49.6 - 74.2), and Negative cultures 89.8% (85.5 - 94.1), P = .051. There were 37 IRCs (20.3%), and 19 (51.4%) were fatal, the frequency was insignificant between the groups. The majority of IRCs, 30/37 (81%), developed during the first postoperative year., Conclusion: In this assessment of microbiological findings of INAAs in Sweden, 50% of the pathogens were Staphylococcus aureus, Streptococcus sp., or Salmonella sp.. The overall 20%-frequency of IRCs, and its association with high mortality, motivates long-term antibiotic treatment regardless of microbial findings., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background and Objectives: Extensive abdominal surgery is associated with the risk of postoperative pulmonary complications. This study aims to explore the incidence and risk factors for developing postoperative pulmonary complications after cytoreductive surgery and hyperthermic intraperitoneal chemotherapy and to analyze how these complications affect overall survival., Methods: Data were collected on 417 patients undergoing surgery between 2007 and2017 at Uppsala University Hospital, Sweden. Postoperative pulmonary complications were graded according to the Clavien-Dindo classification system where Grade ≥ 3 was considered a severe complication. A logistic regression analysis was used to analyze risk factors for postoperative pulmonary complications and a Cox proportional hazards model to assess impact on survival., Results: Seventy-two patients (17%) developed severe postoperative pulmonary complications. Risk factors were full thickness diaphragmatic injury and/or diaphragmatic resection [OR 5.393, 95% CI 2.924-9.948, p = < 0.001]. Severe postoperative pulmonary complications, in combination with non-pulmonary complications, contributed to decreased overall survival [HR 2.285, 95% CI 1.232-4.241, p = 0.009]., Conclusions: Severe postoperative pulmonary complications were common and contributed to decreased overall survival. Full thickness diaphragmatic injury and/or diaphragmatic resection were the main risk factors. This finding emphasizes the need for further research on the mechanisms behind pulmonary complications and their association with mortality., Competing Interests: The authors have declared that no competing interests exist.

Background: Elevated apolipoprotein B (apoB) and elevated apoB/apoA-1 ratio increase the risk of myocardial infarction (MI) and stroke, whereas high apoA-1 is protective. We study how these apolipoproteins are associated with major adverse cardiovascular events (MACEs), whether apoA-1 contributes to this association, and whether abnormal values occur decades before such events develop., Methods and Findings: In the Swedish AMORIS (Apolipoprotein-related MOrtality RISk) cohort study, 137,100 men and women aged 25-84 years were followed an average 17.8 years. ApoB, apoA-1, and the apoB/apoA-1 ratio were analysed in relation to MACEs (non-fatal MI, stroke, and cardiovascular [CV] mortality), yielding 22,473 events. Hazard ratios (HRs) were estimated using Cox regression. Kaplan-Meier estimates were used to investigate the relationship of MACEs with increasing quintiles of the apoB/apoA-1 ratio in all age groups for both sexes. In nested case-control analyses, cases were randomly matched to age- and sex-matched controls, yielding population trajectories for apolipoproteins. Increased level of apoB and increased apoB/apoA-1 ratio were associated with risk of MACE and all clinical sub-components in both men and women across all ages (10th versus first decile in both sexes combined: HR 1.7 for MACE and 2.7 for non-fatal MI). Decreased values of apoA-1 potentiated the impact of apoB at all levels of apoB (on average across apoB range: 40% increase in HR for MACE and 72% increase in HR for non-fatal MI), indicating that the apoB/apoA-1 ratio covers a broader range of persons with dyslipidaemia at risk than apoB alone. In both men and women, MACEs occurred earlier on average for each increasing quintile of the apoB/apoA-1 ratio. Individuals with the highest levels of apoB/apoA-1 ratio experienced CV events on average several years earlier than those with lower ratios. Higher apoB/apoA-1 ratio in cases of MACE versus controls was seen already about 20 years before the event. A limitation of this study was that adjustment for tobacco smoking and hypertension was only possible in a small validation study., Conclusions: An imbalance between apoB and apoA-1 resulting in an increased apoB/apoA-1 ratio is strongly associated with the outcome MACE and its sub-components, in both men and women of all ages. An increased apoB/apoA-1 ratio already 2 decades before events calls for early recognition and primary prevention. Simple evidence-based cut values should be considered in future cardiovascular guidelines., Competing Interests: No authors have competing interests.

Background: Differences in comorbidity, pharmacotherapy, cardiovascular (CV) outcome, and mortality between myocardial infarction (MI) patients and peripheral arterial disease (PAD) patients are not well documented., Aim: The aim of this study was to compare comorbidity, treatment patterns, CV outcome, and mortality in MI and PAD patients, focusing on sex differences., Methods: This observational, population-based study used data retrieved from mandatory Swedish national registries. The risks of MI and death were assessed by Kaplan-Meier analysis. Secondary preventive drug use was characterized. Cox proportional risk hazard modelling was used to determine the risk of specific events., Results: Overall, 91,808 incident MI patients and 52,408 PAD patients were included. CV mortality for MI patients at 12, 24, and 36 months after index was 12.3%, 19.3%, and 25.4%, and for PAD patients it was 15.5%, 23.4%, and 31.0%. At index, 89% of MI patients and 65% of PAD patients used aspirin and 74% and 53%, respectively, used statins. Unlike MI women, women with PAD had a lower rate of other CV-related comorbidities and a lower risk of CV events (age-adjusted hazard ratio 0.81, 95% confidence interval 0.79‒0.84), CV death (0.78, 0.75‒0.82), and all-cause death (0.78, 0.76‒0.80) than their PAD male counterparts., Conclusion: PAD patients were less intensively treated and had a higher CV mortality than MI patients. Women with PAD were less likely than men to present with established polyvascular disease, whereas the opposite was true of women with MI. This result indicates that the lower-limb vasculature may more often be the index site for atherosclerosis in women., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Favorable survival in malignant cutaneous melanoma (melanoma) has increased the likelihood of second primary cancer (SPC). We assess the influence of patient characteristics at diagnosis of first melanoma and the type of SPC (second melanoma and other SPC) on overall survival., Methods: We used the Swedish Cancer Registry data to assess overall survival in melanoma for the period 1990 to 2015. Kaplan-Meier curves were plotted and hazard ratios (HRs) were estimated with Cox regression models by considering SPC diagnosis as a time-dependent variable., Results: A total of 46,726 patients were diagnosed with melanoma, and 15.3% of them developed SPC, among which, two thirds were other SPCs. Second melanomas were diagnosed early (31% during the first year) compared to non-melanoma SPCs (9.5%). Survival for women with second melanoma or other SPC (56 and 21% alive after 25 years of follow-up, respectively) exceeded the male rates (21 and 10%, respectively) but all these figures were lower than for females (60% alive) or males (48%) without SPC. Time dependent analysis showed vastly increased HRs for cancer types that are fatal also as first cancers, but SPC-specific HRs remained relatively uniform, irrespective of SPC diagnosed soon or late after first melanoma. In early-onset melanoma, SPC diagnosis after 10 years may not negatively influence overall survival., Conclusions: As the overall survival of patients with many types of SPCs is unfavorable, advice about health lifestyle should benefit smoking patients and early detection methods may be recommended for SPCs of the breast, prostate and colorectum., (© 2021. The Author(s).)

Introduction: Multidisciplinary team (MDT) assessment is associated with improved survival in locally advanced rectal cancer, but the effect of an MDT assessment on survival in locally advanced colon cancer has not been reported. The aim of this national population-based cohort study was to establish if preoperative MDT assessment affects prognosis in patients with primary locally advanced colon cancer., Material and Methods: All patients in Sweden with locally advanced colon cancer, without metastatic disease, who underwent an elective colon resection between 2010 and 2017 were identified through the Swedish Colorectal Cancer Registry (SCRCR), and the cohort was linked to national registers. Data on patient characteristics, preoperative staging, surgical procedures, recurrence and survival were collected from SCRCR. The association between MDT assessment and colon cancer-specific survival was evaluated using Kaplan-Meier survival curves and Cox proportional hazards models. The multivariable analysis was adjusted for sex, age, ASA grade, CCI, time period, pN, region and preoperative MDT., Results: MDT assessment was performed in 2663 patients (84.4%) of 3157 eligible patients. The 3-year colon cancer-specific survival was higher following MDT, compared with no MDT assessment (80% versus 68%). MDT assessment was independently associated with reduced colon cancer-specific mortality (HR 0.70, 0.57-0.84 95% CI)., Conclusion: Preoperative MDT assessment is associated with an improved long-term survival in patients with locally advanced colon cancer and should be mandatory in patients with suspected locally advanced colon cancer., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objective: The epidemiology of sub-aneurysmal aortic dilatation (SAA) 25 - 29 mm is not fully understood, and the management of SAA is debated. Lack of evidence is particularly problematic in the screening setting. This study aimed to evaluate the long term outcome of men with screen detected SAAs, focusing on progression to an abdominal aortic aneurysm (AAA), and on the AAAs reaching the threshold diameter for surgical repair., Methods: Between 2006 and 2015, all 65 year old men with a screen detected SAA in middle Sweden were re-examined with ultrasound after five and 10 years. The primary outcomes were expansion to AAA ≥ 30 mm and progression to AAA ≥ 55 mm. Secondary outcomes were risk factors for progression, repair rate, and mortality., Results: A total of 1 020 65 year old men with a SAA were identified, of whom 940 (92.2%; 95% confidence interval 91.0 - 93.8) had follow up. The Kaplan-Meier estimated incidence of AAA ≥ 30 mm development after the five year follow up (which was de facto carried out after a mean of 4.9 years) was 65.8% (61.6 - 69.4), all < 55 mm. The corresponding KM-estimated incidence after the 10 year follow up (carried out after a mean of 11.9 years) was 95.1% (90.1 - 97.4), and 29.7% (18.0 - 39.7) reached ≥ 55 mm. All 41 SAAs eventually expanding to ≥ 55 mm were ≥ 30 mm at the five year follow up. Of these, 32 had surgical repair with 100% survival, six have scheduled repairs, and three (7.3%) were unfit for repair. The KM estimated all cause mortality rates at five and 10 years were 7.0% and 17.9%, respectively, with no proven AAA related deaths., Conclusion: A majority of SAAs eventually progress to an AAA, of which 30% are estimated to eventually reach the threshold for repair within 10 years. A follow up policy with an ultrasound examination after five years can safely and effectively identify those SAAs at risk of developing into clinically significant AAAs needing repair and may be considered for anyone with reasonably good life expectancy., (Copyright © 2021 The Author(s). Published by Elsevier B.V. All rights reserved.)

Objectives: The objective of this cohort study was to analyse long-term relative survival in patients with bicuspid aortic valve (BAV) who underwent aortic valve surgery., Methods: We studied 865 patients with BAVs who participated in three prospective cohort studies of elective, open-heart, aortic valve surgery at the Karolinska University Hospital, Stockholm, Sweden, between 2007 and 2020. The expected survival for the age, sex and calendar year-matched general Swedish population was obtained from the Human Mortality Database. The Ederer II method was used to calculate relative survival, which was used as an estimate of cause-specific survival., Results: No differences were found in the observed versus expected survival at 1, 5, 10 or 12 years: 99%, 94%, 83% and 76% vs 99%, 93%, 84% and 80%, respectively. The relative survival at 1, 5, 10 and 12 years was 100% (95% CI 99% to 100%), 101% (95% CI 99% to 103%), 99% (95% CI 95% to 103%) and 95% (95% CI 87% to 102%), respectively. The relative survival at the end of follow-up tended to be lower for women than men (86% vs 95%). The mean follow-up was 6.3 years (maximum 13.3 years)., Conclusions: The survival of patients with BAV following aortic valve surgery was excellent and similar to that of the general population. Our results suggest that the timing of surgery according to current guidelines is correct and provide robust long-term survival rates, as well as important information about the natural history of BAV in patients following aortic valve surgery., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY. Published by BMJ.)

Objective: Monoclonal gammopathy of undetermined significance (MGUS) is the asymptomatic precursor of multiple myeloma (MM). Lytic bone lesions and fractures are hallmarks of MM and although there are no lytic lesions in MGUS, it has also been associated with fractures. The causes of fractures in MGUS are currently unclear but potential causes include inherent MGUS bone disease, undiagnosed MM, and peripheral neuropathy (PN). We therefore conducted a large population-based study including 8395 individuals with MGUS and 30 851 matched controls from Sweden., Methods: Data on fractures, PN, and confounders were acquired from high-quality registers in Sweden., Results: Monoclonal gammopathy of undetermined significance and PN were independently associated with fractures (hazard ratio [HR]: 1.29; 95% confidence interval [95% CI]: 1.21-1.37; P < .001 and HR: 1.34; 95% CI: 1.16-1.55; P < .001). Imminent MGUS progression increased the risk of fractures (odds ratio: 1.66; 95% CI: 1.27-2.16; P < .001). Fractures were not associated with long-term risk of MGUS progression (HR: 1.08; 95% CI: 0.77-1.53; P = .64)., Discussion: Based on these findings, we speculate that MGUS leads to fractures through at least 3 independent mechanisms: undetected MGUS progression to MM, MGUS inherent bone disease, and PN through falls. These findings highlight the need for further study of MGUS inherent bone disease and can inform further research into fracture prevention in MGUS., (© 2021 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: Prior studies investigating the long-term clinical outcomes of patients who have undergone permanent pacemaker implantation after aortic valve replacement reported conflicting results., Objective: To investigate long-term outcomes after primary surgical aortic valve replacement among patients who underwent postoperative permanent pacemaker implantation., Design, Setting, and Participants: This cohort study included all patients who underwent surgical aortic valve replacement in Sweden from 1997 to 2018. All patients who underwent primary surgical aortic valve replacement in Sweden and survived the first 30 days after surgical treatment were included. Patients who underwent preoperative permanent pacemaker implantation, concomitant surgical treatment for another valve, or emergency surgical treatment were excluded. Patients who underwent concomitant coronary artery bypass grafting or surgical treatment of the ascending aorta were included. Follow-up data were complete for all patients. Data were analyzed from October through December 2020., Exposures: Patients underwent implantation of a permanent pacemaker or implantable cardioverter defibrillator within 30 days after aortic valve replacement., Main Outcomes and Measures: The primary outcome was all-cause mortality., Results: Among 24 983 patients who underwent surgical aortic valve replacement, 849 patients (3.4%) underwent permanent pacemaker implantation within 30 days after surgical treatment and 24 134 patients (96.6%) did not receive pacemakers in that time. The mean (SD) age of the total study population was 69.7 (10.8) years, and 9209 patients were women (36.9%). The mean (SD) and maximum follow-up periods were 7.3 (5.0) years and 22.0 years, respectively. At 10 years and 20 years after surgical treatment, the Kaplan-Meier estimated survival rates were 52.8% and 18.0% in the pacemaker group, respectively, and 57.5% and 19.6% in the nonpacemaker group, respectively. All-cause mortality was statistically significantly increased in the pacemaker group compared with the nonpacemaker group (hazard ratio [HR], 1.14; 95% CI, 1.01-1.29; P = .03), and so was risk of heart failure hospitalization (HR, 1.58; 95% CI, 1.31-1.89; P < .001). No statistically significant increase was found in the risk of endocarditis in the pacemaker group., Conclusions and Relevance: This study found that there were increased risks of all-cause mortality and heart failure hospitalization among patients who underwent permanent pacemaker implantation after surgical aortic valve replacement, suggesting that these risks are important considerations, especially in an era when transcatheter aortic valve replacement is used in younger patients at lower risk of adverse surgical outcomes. These findings further suggest that future research should investigate how to avoid permanent pacemaker dependency after surgical and transcatheter aortic valve replacement.

Objective: To examine the patterns of recurrence and how these patterns are associated with survival in vulvar squamous cell carcinoma. We also explored the survival impact of surgical groin staging (SGS)., Methods: Nationwide population-based study including women diagnosed with vulvar squamous cell carcinoma between 2012 and 2015 and registered in the Swedish Quality Registry for Gynecologic Cancer. Cumulative incidence rates (CIR), recurrence-free (RFS) and overall survival (OS) were calculated by Kaplan Meier estimates. The impact of SGS on RFS and OS was analyzed by proportional hazards models., Results: 489 eligible women were included. Median follow-up time was 64 months. The overall recurrence rate was 22.3%. Site of recurrence: local in 61.0%, groin in 30.0%, distant in 9.0%. The CIR for local recurrences increased with time (5.9% at 2-years, 14.7% at 5-years) while the rate of groin and distant recurrences was nearly steady (5.5% to 6.3% and 1.5% to 1.7%, respectively). Median 2-year and 4-year OS post-recurrence was 57.8% and 37.4% for local, 17.2%, 10.3% for groin and 0% for distant recurrences, respectively. SGS was omitted in 23.7% of surgically treated women with FIGO stages IB-II and significantly associated with worse RFS (Hazard ratio, HR, 1.9; 95%CI, 1.0-3.5; p = 0.04) and OS (HR 2.0; 95%CI, 1.1-3.8; p = 0.04) after adjustment for age, FIGO stage, tumor size, resection margins and performance status., Conclusion: The cumulative incidence of isolated vulvar recurrence was low but for those affected the prognosis was poor. Surgical groin staging is a crucial part of primary treatment and should not be omitted., Competing Interests: Declaration of Competing Interest EÅL: Honoraria, Roche. Advisory boards, Clovis Oncology; Astra Zeneca; Tesaro; Genmab. All other authors have no conflicts of interest to declare., (Copyright © 2021. Published by Elsevier Inc.)

Importance: Clinically used breast cancer markers, such as tumor size, tumor grade, progesterone receptor (PR) status, and Ki-67 status, are known to be associated with short-term survival, but the association of these markers with long-term (25-year) survival is unclear., Objective: To assess the association of clinically used breast cancer markers with long-term survival and treatment benefit among postmenopausal women with lymph node-negative, estrogen receptor [ER]-positive and ERBB2-negative breast cancer who received tamoxifen therapy., Design, Setting, and Participants: This study was a secondary analysis of data from a subset of 565 women with ER-positive/ERBB2-negative breast cancer who participated in the Stockholm tamoxifen (STO-3) randomized clinical trial. The STO-3 clinical trial was conducted from 1976 to 1990 and comprised 1780 postmenopausal women with lymph node-negative breast cancer who were randomized to receive adjuvant tamoxifen therapy or no endocrine therapy. Complete 25-year follow-up data through December 31, 2016, were obtained from Swedish national registers. Immunohistochemical markers were reannotated in 2014. Data were analyzed from April to December 2020., Interventions: Patients in the original STO-3 clinical trial were randomized to receive 2 years of tamoxifen therapy vs no endocrine therapy. In 1983, patients who received tamoxifen therapy without cancer recurrence during the 2-year treatment and who consented to continued participation in the STO-3 study were further randomized to receive 3 additional years of tamoxifen therapy or no endocrine therapy., Main Outcomes and Measures: Distant recurrence-free interval (DRFI) by clinically used breast cancer markers was assessed using Kaplan-Meier and multivariable Cox proportional hazards analyses adjusted for age, period of primary diagnosis, tumor size (T1a and T1b [T1a/b], T1c, and T2), tumor grade (1-3), PR status (positive vs negative), Ki-67 status (low vs medium to high), and STO-3 clinical trial arm (tamoxifen treatment vs no adjuvant treatment). A recursive partitioning analysis was performed to evaluate which markers were able to best estimate long-term DRFI., Results: The study population comprised 565 postmenopausal women (mean [SD] age, 62.0 [5.3] years) with lymph node-negative, ER-positive/ERBB2-negative breast cancer. A statistically significant difference in long-term DRFI was observed by tumor size (88% for T1a/b vs 76% for T1c vs 63% for T2 tumors; log-rank P < .001) and tumor grade (81% for grade 1 vs 77% for grade 2 vs 65% for grade 3 tumors; log-rank P = .02) but not by PR status or Ki-67 status. Patients with smaller tumors (hazard ratio [HR], 0.31 [95% CI, 0.17-0.55] for T1a/b tumors and 0.58 [95% CI, 0.38-0.88] for T1c tumors) and grade 1 tumors (HR, 0.48; 95% CI, 0.24-0.95) experienced a significant reduction in the long-term risk of distant recurrence compared with patients with larger (T2) tumors and grade 3 tumors, respectively. A significant tamoxifen treatment benefit was observed among patients with larger tumors (HR, 0.53 [95% CI, 0.32-0.89] for T1c tumors and 0.34 [95% CI, 0.16-0.73] for T2 tumors), lower tumor grades (HR, 0.24 [95% CI, 0.07-0.82] for grade 1 tumors and 0.50 [95% CI, 0.31-0.80] for grade 2 tumors), and PR-positive status (HR, 0.38; 95% CI, 0.24-0.62). The recursive partitioning analysis revealed that tumor size was the most important characteristic associated with long-term survival, followed by clinical trial arm among patients with larger tumors., Conclusions and Relevance: This secondary analysis of data from the STO-3 clinical trial indicated that, among the selected subgroup of patients, tumor size followed by tumor grade were the markers most significantly associated with long-term survival. Furthermore, a significant long-term tamoxifen treatment benefit was observed among patients with larger tumors, lower tumor grades, and PR-positive tumors.

Background: Chronic kidney disease has been linked to cardiovascular disease and specifically ischemic heart disease (IHD), but large-scale population data in patients with immunoglobulin A nephropathy (IgAN) are missing., Objective: To examine absolute and relative risks for IHD in patients with IgAN., Methods: Population-based register-based cohort study in Sweden. We identified 3945 patients with biopsy-verified IgAN, and 19,272 age- and sex-matched reference individuals from the general population. To reduce residual confounding from genetic factors and early environmental factors we carried out secondary analyses, where we compared 3039 IgAN patients with 6729 siblings, whereas a spousal analysis consisted of 2377 married couples where one of the spouses had IgAN. Data on IHD and end-stage renal disease (ESRD) were retrieved from the nationwide Patient Register. Cox regression estimated hazard ratios (HRs) adjusted for matching variables, education, country of birth, cancer, diabetes mellitus, and other systemic inflammatory diseases., Results: During a follow-up of 55,527 person-years (py; mean follow-up 14.1 years), 371 patients (9.4%) with IgAN developed IHD (6.7/1000 py), compared with 1070 (5.6%) in 287,677 py in reference individuals (3.7/1000 py). The corresponding adjusted HR was 1.86 (95%CI = 1.63-2.13), equivalent to one extra case of IHD per 34 IgAN patients followed-up for 10 years. HRs were similar in men and women with IgAN, but higher in the first year after diagnosis and in patients born outside the Nordic countries. Patients with IgAN were at increased risk of IHD also compared to siblings (HR = 2.07; 95%CI = 1.62-2-64) and spouses (HR = 1.91; 95%CI = 1.40-2.61)., Conclusions: In this nationwide population-based study, patients with IgAN were at an 86% increased risk of future IHD.

Objectives: To explain apparent differences among mammography screening services in Sweden using individual data on participation in screening and with breast cancer-specific survival as an outcome., Methods: We analysed breast cancer survival data from the Swedish Cancer Register on breast cancer cases from nine Swedish counties diagnosed in women eligible for screening. Data were available on 38,278 breast cancers diagnosed and 4312 breast cancer deaths. Survival to death from breast cancer was estimated using the Kaplan-Meier estimate, for all cases in each county, and separately for cases of women participating and not participating in their last invitation to screening. Formal statistical comparisons of survival were made using proportional hazards regression., Results: All counties showed a reduction in the hazard of breast cancer death with participation in screening, but the reductions for individual counties varied substantially, ranging from 51% (95% confidence interval 46-55%) to 81% (95% confidence interval 74-85%). Survival rates in nonparticipating women ranged from 53% (95% confidence interval 40-65%) to 74% (95% confidence interval 72-77%), while the corresponding survival in women participating in screening varied from 80% (95% confidence interval 77-84%) to 86% (95% confidence interval 83-88%), a considerably narrower range., Conclusions: Differences among counties in the effect of screening on breast cancer outcomes were mainly due to variation in survival in women not participating in screening. Screening conferred similarly high survival rates in all counties. This indicates that the performance of screening services was similar across counties and that detection and treatment of breast cancer in early-stage reduces inequalities in breast cancer outcome.

Mitochondrial dysfunction is an important factor of the aging process and may play a key role in various diseases. Mitochondrial DNA copy number (mtDNA-CN) is an indirect measure of mitochondrial dysfunction and is associated with type 2 diabetes mellitus (T2DM); however, whether mtDNA-CN can predict the risk of developing T2DM is not well-known. We quantified absolute mtDNA-CN in both prevalent and incident T2DM by well-optimized droplet digital PCR (ddPCR) method in a population-based follow-up study of middle aged (50-59 years) Swedish women (n = 2387). The median follow-up period was 17 years. Compared to those who were free of T2DM, mtDNA-CN was significantly lower in both prevalent T2DM and in women who developed T2DM during the follow-up period. Mitochondrial DNA-copy number was also associated with glucose intolerance, systolic blood pressure, smoking status and education. In multivariable Cox regression analysis, lower baseline mtDNA-CN was prospectively associated with a higher risk of T2DM, independent of age, BMI, education, smoking status and physical activity. Moreover, interaction term analysis showed that smoking increased the effect of low mtDNA-CN at baseline on the risk of incident T2DM. Mitochondrial DNA-copy number may be a risk factor of T2DM in women. The clinical usefulness of mtDNA-CN to predict the future risk of T2DM warrants further investigation.

Importance: Concerns about the cardiovascular safety of recombinant human growth hormone (rhGH) treatment in childhood have recently been raised; however, long-term studies are limited., Objective: To investigate the long-term risk of overall and severe cardiovascular events in patients previously treated with rhGH in childhood and whether there is an association with treatment duration or dose., Design, Setting, and Participants: This nationwide population-based cohort study included patients treated with rhGH during childhood from January 1, 1985, to December 31, 2010, in Sweden, with follow-up through December 31, 2014. Included patients were treated with rhGH owing to isolated growth hormone deficiency (GHD), small for gestational age (SGA), and idiopathic short stature (ISS). For each patient, 15 age-, sex-, and region-based matched control individuals were randomly selected from the general population as a comparison group. Data on cardiovascular outcomes and covariates including gestational age, birth weight, birth length, socioeconomic status, and height were obtained through linkage with several health care and population-based registers. Data were analyzed from January 1, 1985, to December 31, 2014., Exposures: Treatment with rhGH during childhood and adolescence (aged 0-18 years)., Main Outcomes and Measures: The primary outcome was the first cardiovascular event recorded after the start of follow-up, and the secondary outcome was the first severe cardiovascular event., Results: A total of 53 444 individuals (3408 patients and 50 036 controls; 67.7% men; mean [SD] age at study end, 25.1 [8.2] years) were followed up for as long as 25 years (median follow-up, 14.9 [range, 0-25] years; total, 795 125 person-years). Among 1809 recorded cardiovascular events, the crude incidence rates were 25.6 events per 10 000 person-years for patients and 22.6 events per 10 000 person-years for controls. The adjusted hazard ratio (HR) for all cardiovascular events was higher in patients compared with controls (HR, 1.69; 95% CI, 1.30-2.19), especially for women (HR, 2.05; 95% CI, 1.31-3.20) compared with men (HR, 1.55; 95% CI, 1.12-2.13). All subgroups had increased HRs (SGA, 1.97 [95% CI, 1.28-3.04]; GHD, 1.66 [95% CI, 1.21-2.26]; and ISS, 1.55 [95% CI, 1.01-2.37]). Longer duration of rhGH treatment (HR, 2.08; 95% CI, 1.35-3.20) and total cumulative dose (HR, 2.05; 95% CI, 1.18-3.55) were associated with higher risk for overall cardiovascular disease. The adjusted HR for severe cardiovascular disease was 2.27 (95% CI, 1.01-5.12)., Conclusions and Relevance: In this cohort study, treatment with rhGH during childhood due to GHD, SGA, or ISS was associated with increased risks of cardiovascular events in early adulthood, particularly in women; however, conclusions of causality are still limited and the absolute risk remains low.

Objective: Patients with alcohol-related liver disease (ALD) are at increased risk of death, but studies have rarely investigated the significance of histological severity or estimated relative risks compared with a general population. We examined mortality in a nationwide cohort of biopsy-proven ALD., Design: Population-based cohort study in Sweden comparing 3453 individuals with an International Classification of Disease (ICD) code for ALD and a liver biopsy from 1969 to 2017 with 16 535 matched general population individuals. Swedish national registers were used to ascertain overall and disease-specific mortality, starting follow-up at the latest of first ICD diagnosis or liver biopsy plus 3 months. Cox regression adjusted for relevant confounders was used to estimate HRs in ALD and histopathological subgroups., Results: Median age at diagnosis was 58 years, 65% were men and 52% had cirrhosis at baseline. Five-year cumulative mortality was 40.9% in patients with ALD compared with 5.8% in reference individuals. The risk for overall mortality was significantly increased (adjusted HR (aHR)=4.70, 95% CI 4.35 to 5.08). The risk of liver-related death was particularly high (43% of all deaths, aHR=167.6, 95% CI 101.7 to 276.3). Mortality was significantly increased also in patients with ALD without cirrhosis and was highest in the first year after baseline but persisted after ≥10 years of follow-up (aHR=2.74, 95% CI 2.37 to 3.16)., Conclusion: Individuals with biopsy-proven ALD have a near fivefold increased risk of death compared with the general population. Individuals with ALD without cirrhosis were also at increased risk of death, reaffirming the need to increase vigilance in the management of these individuals., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: To evaluate the 10-year survival rate of root filled teeth treated by general dental practitioners (GDPs), and to identify possible prognostic factors., Methodology: In 2006, 3676 individuals had at least one tooth root filled by a GDP within the Norrbotten Public Dental Service, Sweden. Over the next 10 years, 331 individuals died and were excluded. A random sample of 302 of the remaining individuals was included in the study, of whom 280 (n = 280 teeth) were included in the analysis. Dental records were reviewed retrospectively by a calibrated researcher to collect predetermined data regarding individual, pre-operative, intra-operative and post-operative factors. The outcome measure was tooth extraction over time, and cases with no events were censored, regardless of apical status or symptoms, until last known date of tooth survival. In case of missing data, individuals were recalled for a control visit. Kaplan-Meier survival tables and Cox regression models were used for analysis. P < 0.05 was considered statistically significant., Results: The cumulative 10-year survival was 81.7% (standard error: 2.6%), and the mean incidence of tooth extraction during the 10 years was 1.8% per year. The univariate analysis identified three possible prognostic factors (P < 0.05) that were associated with extraction: molars, two or more emergency inter-appointment visits during the treatment, and root canal treatments consisting of five or more separate sessions. A multivariate regression analysis revealed no significant relationships for the variables gender, tooth type, number of contacts, any emergency visits during endodontic treatment, number of sessions to complete endodontic treatment, pulp diagnosis, or type of permanent restoration and extraction., Conclusions: The mean incidence of tooth loss over the first 10 years after completion of root canal treatment performed by a GDP was approximately 2% per year. No prognostic factors could be identified., (© 2020 International Endodontic Journal. Published by John Wiley & Sons Ltd.)

Introduction: The aim of this study was to assess time on treatment with abiraterone and enzalutamide, two androgen receptor targeted (ART) drugs, the impact on time on treatment of time interval without drug supply between prescription fillings, and adherence to treatment., Material and Methods: By use of data from The National Prostate Cancer Register, The Prescribed Drug Registry and the Patient Registry, time on treatment with the abiraterone and enzalutamide was analyzed in all men with castration resistant prostate cancer (CRPC) in Sweden 2015-2019. Three time intervals between consecutive fillings, i.e. time without drug supply, were assessed. Adherence to the treatment was evaluated by use of the Medication Possession Ratio. Kaplan Meier analysis and multivariable Cox regression model were used to assess factors affecting time on treatment., Results: Between January 2015 and October 2019, 1803 men filled a prescription for abiraterone and 4 534 men filled a prescription for enzalutamide. With a time interval of 30 days or less between two fillings, median time on treatment was 4.9 months (IQR 2.6-11.7) for abiraterone and 8.0 months (IQR 3.6-16.4) for enzalutamide. In sensitivity analyses, allowing for no more than 14 days without drug supply between fillings, median time on treatment was 3.9 months (IQR 2.1-9.0) for abiraterone and 5.9 months (IQR 2.8-12.1) for enzalutamide. Allowing for any time period without drug between fillings, median time on treatment was 5.7 months (IQR 2.7-14.0) for abiraterone and 9.8 months (IQR 4.4-21.0) for enzalutamide. Adherence to treatment was above 90% for both drugs., Conclusion: Time on treatment with abiraterone and enzalutamide was shorter in clinical practice than in randomized controlled trials and varied almost two-fold with time interval without drug. Adherence to treatment was high. The main limitation of our study was the lack of data on use of chemotherapy., Competing Interests: The authors have declared that no competing interests exist.

Objective: To describe risk and risk factors of epilepsy after hospitalization for brain infection in adults in Sweden., Methods: This was a matched retrospective cohort study based on the comprehensive National Patient and Cause of Death Registers. All individuals age >18 without prior epilepsy who received inpatient care in 2000-2010 for a brain infection were included, with 3 age- and sex-matched unexposed controls per exposed individual (n = 12,101 exposed and 36,228 controls). Kaplan-Meier risks of epilepsy after different brain infections were calculated and risk factors identified by Cox regression. Patients were followed until the end of 2017., Results: The 10-year risk of epilepsy was 5.9% (95% confidence interval [CI] 5.5-6.3) in cases and 1.2% (95% CI 1.0-1.4) in controls: 1.7% (95% CI 0.7-2.7) after tick-borne encephalitis, 4.1% (95% CI 3.3-4.9) after bacterial meningitis, 26.0% (95% CI 21.5-30.5) after herpes simplex virus encephalitis, and 30.2% (95% CI 27.1-33.3) after brain abscess. In Cox regression, seizure during the index admission and mechanical ventilation were epilepsy risk factors., Conclusions: Epilepsy is common after several types of brain infections in adults. The type of infection, its severity, and propensity to cause seizures in the acute phase influence the risk of subsequent epilepsy., Classification of Evidence: This study provides Class II evidence that in adults, brain infection is associated with an increased risk of subsequent epilepsy., (© 2020 American Academy of Neurology.)

Background Despite advances in pediatric health care over recent decades, it is not clear whether survival in children with congenital heart disease (CHD) is still increasing. Methods and Results We identified all patients with CHD using nationwide Swedish health registries for 1980 to 2017. We examined the survival trends in children with CHD; we investigated the mortality risk in patients with CHD compared with matched controls without CHD from the general population using Cox proportional regression models and Kaplan-Meier survival analysis. Among 64 396 patients with CHD and 639 012 matched controls without CHD, 3845 (6.0%) and 2235 (0.3%) died, respectively. The mean study follow-up (SD) was 11.4 (6.3) years in patients with CHD. The mortality risk was 17.7 (95% CI, 16.8-18.6) times higher in children with CHD compared with controls. The highest mortality risk was found during the first 4 years of life in patients with CHD (hazard ratio [HR], 19.6; 95% CI, 18.5-20.7). When stratified by lesion group, patients with non-conotruncal defects had the highest risk (HR, 97.2; 95% CI, 80.4-117.4). Survival increased substantially according to birth decades, but with no improvement after the turn of the century where survivorship reached 97% in children with CHD born in 2010 to 2017. Conclusions Survival in children with CHD has increased substantially since the 1980s; however, no significant improvement has been observed this century. Currently, >97% of children with CHD can be expected to reach adulthood highlighting the need of life-time management.

Women with lower levels of serum selenium (Se) may have a worse survival in breast cancer than women with higher levels, despite no difference in incidence of the disease. Our study was conducted to test whether Se is associated with the aggressiveness of breast tumors. Both the risk of having a tumor characteristic associated with worse prognosis, as well as the overall and breast cancer-specific mortality, were studied. We identified breast cancer cases and controls within the Malmö Diet and Cancer Study, a population-based cohort with 17 035 women recruited between 1991 and 1996. Inclusion criteria were incident breast cancer. Exclusion criteria were carcinoma in situ and bilateral breast cancer. Controls were selected among breast cancer-free women both from matching (n = 694) as well as randomization (n = 492). After exclusion, 1066 cases remained and were compared to controls regarding their prediagnostic serum Se levels and subsequent risk of having a certain tumor characteristic or intrinsic subtype. We also followed breast cancer patients regarding overall and breast cancer-specific mortality, comparing different Se quartiles. No association between serum Se quartile and any tumor characteristic or intrinsic subtype was found. Lower overall mortality was found among women in the highest Se quartile compared to the lowest using an adjusted Cox proportional hazards model, hazard ratio 0.63 (95% confidence interval: 0.44-0.89). Similar results were seen for breast cancer-specific mortality, 0.60 (0.37-0.98). The results of our study support that Se is associated with a lower mortality in breast cancer, not related to established prognostic factors., (© 2020 The Authors. International Journal of Cancer published by John Wiley & Sons Ltd on behalf of UICC.)

Background: Use of immunohistochemistry-based surrogates of molecular breast cancer subtypes is common in research and clinical practice, but information on their comparative validity and prognostic capacity is scarce., Methods: Data from 2 PAM50-subtyped Swedish breast cancer cohorts were used: Stockholm tamoxifen trial-3 with 561 patients diagnosed 1976-1990 and Clinseq with 237 patients diagnosed 2005-2012. We evaluated 3 surrogate classifications; the immunohistochemistry-3 surrogate classifier based on estrogen receptor, progesterone receptor, and HER2 and the St. Gallen and Prolif surrogate classifiers also including Ki-67. Accuracy, kappa, sensitivity, and specificity were computed as compared with PAM50. Alluvial diagrams of misclassification patterns were plotted. Distant recurrence-free survival was assessed using Kaplan-Meier plots, and tamoxifen treatment benefit for luminal subtypes was modeled using flexible parametric survival models., Results: The concordance with PAM50 ranged from poor to moderate (kappa = 0.36-0.57, accuracy = 0.54-0.75), with best performance for the Prolif surrogate classification in both cohorts. Good concordance was only achieved when luminal subgroups were collapsed (kappa = 0.71-0.69, accuracy = 0.90-0.91). The St. Gallen surrogate classification misclassified luminal A into luminal B; the reverse pattern was seen with the others. In distant recurrence-free survival, surrogates were more similar to each other than PAM50. The difference in tamoxifen treatment benefit between luminal A and B for PAM50 was not replicated with any surrogate classifier., Conclusions: All surrogate classifiers had limited ability to distinguish between PAM50 luminal A and B, but patterns of misclassifications differed. PAM50 subtyping appeared to yield larger separation of survival between luminal subtypes than any of the surrogate classifications., (© The Author(s) 2020. Published by Oxford University Press.)

Introduction: This study aims to disentangle heterogeneity in the survival of bladder cancer (BC) patients of different socioeconomic status (SES) by identifying potential mediators of the relationship., Methods: The Bladder Cancer Database Sweden (BladderBaSe) was used to select patients diagnosed between 1997 and 2014 with Tis/Ta-T4 disease. The education level was used as a proxy for SES. Accelerated failure time models were used to investigate the association between SES and survival. Mediation analysis was used to investigate potential mediators of the association also accounting for interaction., Results: The study included 37 755 patients from the BladderBaSe. Patients diagnosed with both non-muscle invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC) who had high SES were found to have increased overall and BC-specific survival, when compared to those with low SES. In the NMIBC patients, Charlson Comorbidity Index was found to mediate this relationship by 10% (percentage of the total effect explained by the mediator) and hospital type by 4%. The time from referral to TURBT was a considerable mediator (14%) in the MIBC patients only., Conclusions: Mediation analysis suggests that the association between SES and BC survival can be explained by several factors. The mediators identified were not, however, able to fully explain the theoretical causal pathway between SES and survival, therefore, future studies should also include the investigation of other possible mediators to help explain this relationship further. These results highlight the importance of standardization of clinical care across SES groups., (© 2020 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Treatment of patients with Crohn's disease has evolved in recent decades, with increasing use of immunomodulatory medication since 1990 and biologicals since 1998. In parallel, there has been increased use of active disease monitoring. To what extent these changes have influenced the incidence of primary and repeat surgical resection remains debated., Methods: In this nationwide cohort study, incident patients of all ages with Crohn's disease, identified in Swedish National Patient Registry between 1990 and 2014, were divided into five calendar periods of diagnosis: 1990-1995 and 1996-2000 with use of inpatient registries, 2001, and 2002-2008 and 2009-2014 with use of inpatient and outpatient registries. The cumulative incidence of first and repeat abdominal surgery (except closure of stomas), by category of surgical procedure, was estimated using the Kaplan-Meier method., Results: Among 21 273 patients with Crohn's disease, the cumulative incidence of first abdominal surgery within 5 years of Crohn's disease diagnosis decreased continuously from 54·8 per cent in 1990-1995 to 40·4 per cent in 1996-2000 (P < 0·001), and again from 19·8 per cent in 2002-2008 to 17·3 per cent in 2009-2014 (P < 0·001). Repeat 5-year surgery rates decreased from 18·9 per cent in 1990-1995 to 16·0 per cent in 1996-2000 (P = 0·009). After 2000, no further significant decreases were observed., Conclusion: The 5-year rate of surgical intervention for Crohn's disease has decreased significantly, but the rate of repeat surgery has remained stable despite the introduction of biological therapy., (© 2020 The Authors. British Journal of Surgery published by John Wiley & Sons Ltd on behalf of BJS Society Ltd.)

Objective: Ultra-radical surgery to achieve complete resection in advanced epithelial ovarian cancer (EOC) has been widely accepted without strong supporting data. Our objective was to assess overall survival after a structured shift to an ultra-radical upfront surgical treatment algorithm and to investigate changes in the distribution of primary treatments after this shift., Patients and Methods: In this population-based cohort study, all women with suspected EOC in the Stockholm-Gotland region of Sweden reported to the Swedish Quality Registry for Gynecologic Cancer (SQRGC) and National Cancer Registry (NCR) were selected in two 3-year cohorts, based on year of diagnosis (before (cohort1) or after (cohort 2) change in surgical treatment algorithm) and followed for at least three years. 5-year overall survival (OS) in non-surgically and surgically treated women was analyzed. Moreover, proportional distribution of primary treatment was evaluated., Results: 752 women were included in the final analysis (n = 364 and 388 in cohort 1 and 2 respectively) with a median follow-up of 29 and 27 months. The complete resection rate increased from 37 to 67% (p ≤ 0.001) as well as proportion non-surgically treated women, 24 to 33%. No improvement in OS was observed in non-surgically (HR 0.76 (95% CI, 0.58-1.01); p = 0.06) or surgically treated (HR 0.94 (95% CI, 0.75-1.18); p = 0.59) women, even when complete resection was achieved (HR 1.31 (95% CI, 0.89-1.92); p = 0.17)., Conclusion: A shift to ultra-radical upfront surgery in EOC did not improve survival despite a significant increase in complete resection rate. Identifying the limitations of surgical treatment remains a challenge., Competing Interests: Declaration of competing interest All authors declare no conflicts of interest., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

Background: Developing dementia is feared by many for its detrimental effects on cognition and independence. Experimental and clinical evidence suggests that sepsis is a risk factor for the later development of dementia. We aimed to investigate whether intensive care-treated sepsis is an independent risk factor for a later diagnosis of dementia in a large cohort of intensive care unit (ICU) patients., Methods: We identified adult patients admitted to an ICU in 2005 to 2015 and who survived without a dementia diagnosis 1 year after intensive care admission using the Swedish Intensive Care Registry, collecting data from all Swedish general ICUs. Comorbidity, the diagnosis of dementia and mortality, was retrieved from the Swedish National Patient Registry, the Swedish Dementia Registry, and the Cause of Death Registry. Sepsis during intensive care served as a covariate in an extended Cox model together with age, sex, and variables describing comorbidities and acute disease severity., Results: One year after ICU admission 210,334 patients were alive and without a diagnosis of dementia; of these, 16,115 (7.7%) had a diagnosis of sepsis during intensive care. The median age of the cohort was 61 years (interquartile range, IQR 43-72). The patients were followed for up to 11 years (median 3.9 years, IQR 1.7-6.6). During the follow-up, 6312 (3%) patients were diagnosed with dementia. Dementia was more common in individuals diagnosed with sepsis during their ICU stay (log-rank p < 0.001), however diagnosis of sepsis during critical care was not an independent risk factor for a later dementia diagnosis in an extended Cox model: hazard ratio (HR) 1.01 (95% confidence interval 0.91-1.11, p = 0.873). Renal replacement therapy and ventilator therapy during the ICU stay were protective. High age was a strong risk factor for later dementia, as was increasing severity of acute illness, although to a lesser extent. However, the severity of comorbidities and the length of ICU and hospital stay were not independent risk factors in the model., Conclusion: Although dementia is more common among patients treated with sepsis in the ICU, sepsis was not an independent risk factor for later dementia in the Swedish national critical care cohort., Trial Registration: This study was registered a priori with the Australian and New Zeeland Clinical Trials Registry (registration no. ACTRN12618000533291 ).

Aim: This reports some of the first incidence rate (IR) estimates of second primary malignancies (SPMs) in men with metastatic castration-resistant prostate cancer (mCRPC) in three countries. Patients & methods: Claims data from the German Pharmacoepidemiological Research Database; registry data from the Prostate Cancer Data Base Sweden; and combined registry-claims data from the US Surveillance, Epidemiology and End Results-Medicare database were analyzed to obtain overall survival and incidence of SPMs in men with mCRPC. Results: SPMs occurred in 308 German (n = 2360), 273 Swedish (n = 2849) and 172 US (n = 2234) men with mCRPC. IRs of SPMs were 79.0 (95% CI: 70.4-88.4), 101.7 (95% CI: 90.3-114.5) and 59 (95% CI: 50-68) per 1000 person-years in German, Swedish and US cohorts, respectively. Conclusion: These studies report some of the first IR estimates of SPMs in men with mCRPC, providing a historical risk estimate of SPM in this patient population.

Objective: Colon cancer surgery remains associated with substantial postoperative morbidity and mortality despite advances in surgical techniques and care. The trauma of surgery triggers adrenergic hyperactivation which drives adverse stress responses. We hypothesised that outcome benefits are gained by reducing the effects of hyperadrenergic activity with beta-blocker therapy in patients undergoing colon cancer surgery. This study aims to test this hypothesis., Design: Retrospective cohort study., Setting and Participants: This is a nationwide study which includes all adult patients undergoing elective colon cancer surgery in Sweden over 10 years. Patient data were collected from the Swedish Colorectal Cancer Registry. The national drugs registry was used to obtain information about beta-blocker use. Patients were subdivided into exposed and unexposed groups. The association between beta-blockade, short-term and long-term mortality was evaluated using Poisson regression, Kaplan-Meier curves and Cox regression., Primary and Secondary Outcomes: Primary outcome of interest was 1-year all-cause mortality. Secondary outcomes included 90-day all-cause and 5-year cancer-specific mortality., Results: The study included 22 337 patients of whom 36.1% were prescribed preoperative beta-blockers. Survival was higher in patients on beta-blockers up to 1 year after surgery despite this group being significantly older and of higher comorbidity. Regression analysis demonstrated significant reductions in 90-day deaths (IRR 0.29, 95% CI 0.24 to 0.35, p<0.001) and a 43% risk reduction in 1-year all-cause mortality (adjusted HR 0.57, 95% CI 0.52 to 0.63, p<0.001) in beta-blocked patients. In addition, cancer-specific mortality up to 5 years after surgery was reduced in beta-blocked patients (adjusted HR 0.80, 95% CI 0.73 to 0.88, p<0.001)., Conclusion: Preoperative beta-blockade is associated with significant reductions in postoperative short-term and long-term mortality following elective colon cancer surgery. Its potential prophylactic effect warrants further interventional studies to determine whether beta-blockade can be used as a way of improving outcomes for this patient group., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The androgen metabolism plays an important role in the progression of prostate cancer. Contradictory to what one might assume given the androgenic potency of dihydrotestosterone (DHT) there are indications that high DHT levels protect from prostate cancer. We want to determine whether there is a long-term association between baseline levels of DHT and death from prostate cancer., Method: During the years 1988 and 1989, 1782 men out of 2400 invited were screened for prostate cancer. The invited men were randomly selected from a background population of more than 27 000 men. Serum levels of DHT were analyzed for all 65 men diagnosed in the trial and 130 controls from the same cohort without any signs of prostate cancer. In this study we evaluate outcomes for the whole cohort (n = 195), the men without clinical signs of prostate cancer at beginning of follow up (n = 130) and men with screening detected cancer (n = 65). The cohort was followed up after 30 years and data from the Swedish Cause of Death Registry and the Swedish Cancer Registry were extracted. Hazard ratios (HRs) were calculated using Cox regression models., Result: High DHT levels were positively correlated to a lower risk for prostate cancer death in the entire cohort: HR = 0.44 (0.25-0.77 95% confidence interval [CI]). The positive correlation remained significant for the subgroup analysis. HR for the men enrolled in the study without any clinical signs of prostate cancer was 0.25 (0.07-0.88 95% CI) and for the men with a prostate cancer diagnosis at time of inclusion: HR = 0.50 (0.26-0.94 95% CI)., Conclusion: DHT is negatively associated with long-term prostate cancer death regardless of clinical presentation at time of inclusion., (© 2020 Wiley Periodicals, Inc.)

The increased survival in malignant cutaneous melanoma (melanoma) is probably due to early diagnosis combined with improved treatment most recently. National health campaigns and screening programs for melanoma detection were started in Sweden several decades ago. We want to assess the influence of tumor characteristics, based on the TNM classification, and of second primary cancers on overall survival in melanoma. We used the Swedish Cancer Registry to assess all-cause survival in melanoma from 2003 to 2015. Hazard ratios (HRs) were estimated using multivariable Cox regression models. A total of 19,773 melanoma patients were diagnosed with TNM data. Survival showed a strong improving trend over time (p-trend <.001). T1a was the most common classification (48.0% of all), while higher T class was associated systematically with worse survival (p-trend <.001). For distant metastases, the HR was 3.17, accounting for 0.9% of the patients. Any types of second primary cancers, other than melanoma, were associated with an HR of 2.00, accounted for 6.7% of all cases. Even if melanoma survival in Sweden ranks among the best national rates, the large percentage of patients with advanced tumors (T3b, T4a, and T4b, 17%) and 21% of deaths with T1a call for improved preventive and follow-up strategies., (© 2020 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Importance: Psoriasis is a complex systemic disease with skin involvement, somatic comorbidity, and psychiatric illness (PI). Although this view of psoriasis is widely accepted, potential synergies within this triad of symptoms have not been adequately investigated., Objectives: To investigate the independent association of skin psoriasis and somatic comorbidity with the development of PI and to assess whether skin psoriasis and somatic comorbidity act synergistically to produce a risk of PI that is greater than the additive associations., Design, Setting, and Participants: Participants were enrolled between January 2005 and December 2010, in this retrospective matched case-control study using secondary (ie, administrative), population-based registry data from Swedish patients in routine clinical care. The dates of analysis were March 2017 to December 2019. Participants were patients with skin psoriasis and control participants without psoriasis matched on age, sex, and municipality, who were all free of preexisting PI., Exposures: Presence of skin psoriasis and somatic comorbidity (captured through the Charlson Comorbidity Index and the Elixhauser Comorbidity Index)., Main Outcomes and Measures: Risk of PI onset (composite of depression, anxiety, and suicidality) is shown using Kaplan-Meier curves stratified by the presence of skin psoriasis and somatic comorbidity. Adjusted associations of skin psoriasis and somatic comorbidity with the development of PI were analyzed using Cox proportional hazards regression models, including interactions to assess synergistic associations. The 3 components of PI were also assessed individually., Results: A total of 93 239 patients with skin psoriasis (mean [SD] age, 54 [17] years; 47 475 men [51%]) and 1 387 495 control participants (mean [SD] age, 54 [16] years; 702 332 men [51%]) were included in the study. As expected, patients with skin psoriasis were more likely to have somatic comorbidity and PI than control participants. Compared with those without skin psoriasis or somatic comorbidity, patients with psoriasis without somatic comorbidity had a 1.32 times higher risk of PI onset (hazard ratio [HR], 1.32; 95% CI, 1.27-1.36; P < .001), whereas patients with psoriasis with somatic comorbidity had a 2.56 times higher risk of PI onset (HR, 2.56; 95% CI, 2.46-2.66; P < .001). No synergistic associations of skin psoriasis and somatic comorbidity with the development of PI were found (HR, 0.93; 95% CI, 0.81-1.04; P = .21)., Conclusions and Relevance: This study found that somatic comorbidity appeared to alter PI onset even more than skin psoriasis. The observed association of skin psoriasis and somatic comorbidity with the development of PI reinforces the need for proactive, holistic treatment of patients with psoriasis.

Midregional Pro-enkephalin A (MR-PENK A) and N-terminal Protachykinin A (NT-PTA) have been associated with vascular dementia. However, the longitudinal relationship between these biomarkers and incident dementia has not been fully investigated. In the population-based Malmö Preventive Project, circulating levels of MR-PENK A and NT-PTA were determined in a random sample of 5,323 study participants (mean age: 69 ± 6 years) who were followed-up over a period of 4.6 ± 1.6 years. The study sample included 369 patients (7%) who were diagnosed in the same period with dementia. We analyzed relationship of MR-PENK A and NT-PTA with the risk of developing dementia by using multivariable-adjusted Cox regression models adjusted for traditional risk factors. Increased plasma levels of MR-PENK A were associated with higher risk of incident vascular dementia whereas no associations were found with all-cause or Alzheimer dementia. The risk of vascular dementia was mainly conferred by the highest quartile of MR-PENK as compared with lower quartiles. Elevated levels of NT-PTA yielded significant association with all-cause dementia or dementia subtypes. Elevated plasma concentration of MR-PENK A independently predicts vascular dementia in the general population. MR-PENK A may be used as an additional tool for identifying vascular subtype in ambiguous dementia cases.

Introduction: Radiotherapy is an established treatment option for prostate cancer (PCa), both as primary treatment and secondary treatment after radical prostatectomy (RP). Since 1998, detailed data on radiotherapy delivered to Swedish men with PCa (e.g. treatment modalities, absorbed doses, fractionation) have been collated within PCa data Base Sweden (PCBaSe). This study reports patterns of radical radiotherapy for PCa in Sweden over the past two decades. Materials and methods: All men with non-metastatic PCa (1998-2016) who received external beam radiotherapy (EBRT) or high or low dose-rate brachytherapy (HDR-BT/LDR-BT) were identified in PCBaSe. Analyses included: trends in radiation techniques, fractionation patterns and total doses over time; PCa-specific survival comparing treatment in 2007-2017 with 1998-2006; and regional variation in type of primary radiotherapy. Results: About 20,876 men underwent primary radiotherapy. The main treatment modalities include conventionally fractionated (2.0 Gy/fraction) EBRT (51%), EBRT with HDR-BT boost (27%) and hypofractionated (>2.4 Gy/fraction) EBRT (11%). EBRT with photon or proton boost and HDR-BT and LDR-BT monotherapies were each used minimally. Use of dose-escalated EBRT (>74 Gy) and moderate hypofractionation increased over time, while use of HDR-BT declined. Considerable regional variation in treatment modalities was apparent. Risk of PCa death following primary radiotherapy had declined for intermediate-risk (HR: 0.60; 95%CI 0.47-0.87) and high-risk PCa (HR: 0.72; 95%CI 0.61-0.86). Discussion: Increased use of dose escalation and hypofractionated EBRT has occurred in Sweden over the past two decades, reflecting current evidence and practice guidelines. Disease-specific outcomes have also improved. Data collected in PCBaSe provide an excellent resource for further research into RT use in PCa management.

Background: Previous studies have reported an increased fracture risk after bariatric surgery., Objective: To investigate the association between different bariatric surgery procedures and fracture risk., Methods: Incidence rates and hazard ratios for fracture events were analysed in the Swedish Obese Subjects study; an ongoing, nonrandomized, prospective, controlled intervention study. Hazard ratios were adjusted for risk factors for osteoporosis and year of inclusion. Information on fracture events were captured from the Swedish National Patient Register. The current analysis includes 2007 patients treated with bariatric surgery (13.3% gastric bypass, 18.7% gastric banding, and 68.0% vertical banded gastroplasty) and 2040 control patients with obesity matched on group level based on 18 variables. Median follow-up was between 15.1 and 17.9 years for the different treatment groups., Results: During follow-up, the highest incidence rate for first-time fracture was observed in the gastric bypass group (22.9 per 1000 person-years). The corresponding incidence rates were 10.4, 10.7 and 9.3 per 1000 person-years for the vertical banded gastroplasty, gastric banding and control groups, respectively. The risk of fracture was increased in the gastric bypass group compared with the control group (adjusted hazard ratio [adjHR] 2.58; 95% confidence interval [CI] 2.02-3.31; P < 0.001), the gastric banding group (adjHR 1.99; 95%CI 1.41-2.82; P < 0.001), and the vertical banded gastroplasty group (adjHR 2.15; 95% CI 1.66-2.79; P < 0.001)., Conclusions: The risk of fracture is increased after gastric bypass surgery. Our findings highlight the need for long-term follow-up of bone health for patients undergoing this treatment., (© 2020 The Association for the Publication of the Journal of Internal Medicine.)