Exposure to oestrogen and risk of anastomotic leakage after colorectal cancer surgery - A clue to the different leak rates in men and women.

BACKGROUND: Colorectal anastomotic leakage is consistently more common in men, regardless of tumour location. This fact is largely unexplained but might be a consequence of biological differences including hormonal exposure and not only related to anatomy. METHODS: This was a retrospective, nationwide registry-based observational study of post-menopausal women operated for colorectal cancer with an anastomosis between 2007 and 2016. Hormonal exposure before surgery, as defined by prescribed drugs affecting oestrogen levels, was related to postoperative anastomotic leakage, using mixed-effects logistic regression models with adjustment for confounding. Odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were derived. In addition, separate estimates according to tumour location were computed, and a sensitivity analysis excluding topical oestrogen hormone exposure was conducted. RESULTS: Some 16,535 post-menopausal women were included, of which 16.2% were exposed to drugs increasing oestrogen levels before surgery. In this exposed group compared to the unexposed, leak rates were 3.1 and 3.8%, respectively. After adjustment, a reduction of anastomotic leakage in the exposed group was detected (OR: 0.77; 95% CI: 0.59-0.99). This finding was largely attributed to the rectal cancer subgroup (OR: 0.55; 95% CI: 0.36-0.85), while the exclusion of topical oestrogen drugs further reduced the estimates of the main analysis (OR: 0.63; 95% CI: 0.38-1.02). CONCLUSIONS: Anastomotic leakage rates are lower in women exposed to hormone replacement therapy before surgery for colorectal cancer, which might explain some of the difference in leak rates between men and women, especially regarding rectal cancer.

Estimating Potential for Drug Budget Reallocation Following Expiration of Exclusivity of Pharmaceutical Products.

Background: The prioritization of public funds in an equitable and ethically sound manner along with efficient budget allocation are key challenges for governments and budget holders. Following the introduction of generics/biosimilars, the potential total budget made available for reallocation resulting from the loss of exclusivity (LOE) in a given market has not been estimated. Objectives: This study investigated the impact of generic/biosimilar entry on drug budget in 4 countries. Methods: Pharmaceutical sales data, drug costs and LOE dates were modeled and forecast using an analytical framework (Affordability by ReallocaTing Funds model [ART]) to estimate future incremental budget availability using scenario analyses in Greece (GR), the Netherlands (NL), Norway (NO) and Sweden (SW). Results: During 2020-2022, 166 (GR), 222 (NL), 145 (NO) and 93 (SW) products facing LOE were identified. This equated to release of an estimated cumulative budget during 2020-2024 of €218 million (GR), €1319 million (NL), €340 million (NO) and €876 million (SW). The estimated average budget released per year during 2020-2024 was 1.8% (GR), 4.6% (NL), 3.4% (NO) and 3.9% (SW) of each country's total annual drug budget. Discussion: These analyses showed that LOE for pharmaceutical products between 2020 and 2022 can result in significant increase in budget availability. LOE in the retail channel was the main driver of budget availability in GR and SW, compared to LOE in the hospital channel in the NL and NO. Conclusion: Estimation of future release of budget capacity using the Affordability by ReallocaTing Funds model supports discussion on resource allocation to fund innovation and may help inform policy changes.

Incidence and prevalence of systemic sclerosis in Sweden, 2004-2015, a register-based study.

OBJECTIVES: we aim to present an in-depth report of the incidence and prevalence of systemic sclerosis (SSc) in Sweden in a nation-wide register-based study covering the entire Swedish population METHODS: each individual residing in Sweden is given a unique personal identity number. We linked the National Patient Register and the Total Population Register to identify 1) patients with prevalent SSc on 2015-12-31 and 2) patients with incident SSc during the time period 2004-2015 based on ICD-10 codes. We estimated prevalence and incidence overall and stratified on age, sex, and county. RESULTS: we identified 1774 prevalent cases, median age was 65 years (IQR 19.2) and 84% were women. The point prevalence estimate was 22.7 per 100,000 (95%CI 13.3-32.0). 1139 individuals were newly diagnosed with SSc during 2004-2015 with a median age of 60 years (IQR 20.6) and 80% were women. The mean standardized incidence was 11.9 per 1,000,000 person-years (95%CI 5.1-18.7). The annual incidence remained stable over the study period. Women had five times higher incidence and prevalence than men. The highest prevalence stratified by age strata was observed in the group aged 70-79. CONCLUSION: SSc incidence and prevalence in Sweden are comparable to estimates from southern Europe, as opposed to the previous assumption of lower occurrence in northern Europe. We further observe that SSc incidence has been rather constant throughout recent years in Sweden with no obvious increase.

Distribution and trajectory of direct and indirect costs of idiopathic inflammatory myopathies.

OBJECTIVES: To estimate the annual direct and indirect costs associated with Idiopathic Inflammatory Myopathies (IIM) over time, including the pre-diagnostic period. METHODS: A cohort of incident adult IIM patients (n = 673) was identified from the Swedish National Patient Register from 2010 to 2016 and matched with general population comparators (n = 3343). Follow-up started at IIM diagnosis and corresponding date in the general population. International Classification of Diseases codes (ICD-10) were used for IIM case definition. Costs were calculated using national register data. RESULTS: The costs related to IIM started to increase 2 years before diagnosis. In the year following diagnosis, the mean annual IIM cost was €21 639 compared to €4816 in the general population. Five years after diagnosis, the mean annual cost in the IIM cohort was €12 796. Outpatient visits, hospitalizations and productivity loss were the components driving the increment in overall annual disease-related expenditures. Indirect costs accounted for a significant portion of IIM long-term societal costs. The highest costs were found in individuals of working age with cancer-associated IIM. CONCLUSIONS: The mean annual costs in IIM were 3 to 5 times higher than in the general population in the 5-year period following diagnosis. These costs started to increase long before diagnosis, were at their peak in the year post-diagnosis and remained elevated thereafter. Indirect costs contributed to a substantial portion of this increment. Early in the IIM disease course, clinicians and allied health professionals should aim to improve function, reduce damage and address barriers to return-to-work to mitigate these costs.

Treatment of NAFLD with intermittent calorie restriction or low-carb high-fat diet - a randomised controlled trial.

BACKGROUND & AIMS: The first-line treatment for non-alcoholic fatty liver disease (NAFLD) is weight reduction. Several diets have been proposed, with various effects specifically on liver steatosis. This trial compared the effects of intermittent calorie restriction (the 5:2 diet) and a low-carb high-fat diet (LCHF) on reduction of hepatic steatosis. METHODS: We conducted an open-label randomised controlled trial that included 74 patients with NAFLD randomised in a 1:1:1 ratio to 12 weeks' treatment with either a LCHF or 5:2 diet, or general lifestyle advice from a hepatologist (standard of care; SoC). The primary outcome was reduction of hepatic steatosis as measured by magnetic resonance spectroscopy. Secondary outcomes included transient elastography, insulin resistance, blood lipids, and anthropometrics. RESULTS: The LCHF and 5:2 diets were both superior to SoC treatment in reducing steatosis (absolute reduction: LCHF: -7.2% [95% CI = -9.3 to -5.1], 5:2: -6.1% [95% CI = -8.1 to -4.2], SoC: -3.6% [95% CI = -5.8 to -1.5]) and body weight (LCHF: -7.3 kg [95% CI = -9.6 to -5.0]; 5:2: -7.4 kg [95% CI = -8.7 to -6.0]; SoC: -2.5 kg [95% CI =-3.5 to -1.5]. There was no difference between 5:2 and LCHF (p = 0.41 for steatosis and 0.78 for weight). Liver stiffness improved in the 5:2 and SoC but not in the LCHF group. The 5:2 diet was associated with reduced LDL levels and was tolerated to a higher degree than LCHF. CONCLUSIONS: The LCHF and 5:2 diets were more effective in reducing steatosis and body weight in patients with NAFLD than SoC, suggesting dietary advice can be tailored to meet individual preferences. LAY SUMMARY: For a person with obesity who suffers from fatty liver, weight loss through diet can be an effective treatment to improve the condition of the liver. Many popular diets that are recommended for weight reduction, such as high-fat diets and diets based on intermittent fasting, have not had their effects on the liver directly evaluated. This study shows that both a low-carb high-fat and the 5:2 diet are effective in treating fatty liver caused by obesity. CLINICAL TRIALS REGISTRATION: This study is registered at Clinicaltrials.gov (NCT03118310).

Anti-transcriptional intermediary factor 1 gamma antibodies in cancer-associated myositis: a longitudinal study.

OBJECTIVES: To investigate anti-TIF1-γ antibodies in longitudinally followed patients with myositis and cancer. METHODS: Serum levels of anti-TIF1-γ antibodies at different time-points in relation to myositis and cancer diagnosis were analysed by ELISA in 79 patients from a Swedish cohort with polymyositis (PM) and dermatomyositis (DM) and a Spanish cohort restricted to DM patients. Anti-TIF1-γ positive and negative patients were compared with Fisher's exact test, student t-tests and Wilcoxon test. RESULTS: Thirty-six patients (17 from cohort 1 and 19 from cohort 2) with myositis and cancer were anti-TIF1-γ antibody positive; all had DM. In 88% of anti-TIF1-γ positive patients, cancer was diagnosed within 3 years from DM diagnosis compared to 63% in anti-TIF1-γ negative. Four DM patients, anti-TIF1-γ positive at cancer diagnosis had positive serum samples even antedating cancer diagnosis up to five years. In cohort 1 the median (interquartile range) antibody level was higher, 2.13 au (1.82-2.15), in the seven patients who died <1 year after cancer diagnosis, compared to the seven that died >1 year after cancer diagnosis, 1.34 au (0.92-1.59), (p=0.004). Three patients were still alive and in remission from cancer and DM 14-16 years after cancer treatment of whom two became negative for anti-TIF1-γ antibodies. In the second cohort remission of cancer coincided with remission of DM and low or negative serum levels of autoantibodies. CONCLUSIONS: Anti-TIF1-γ antibodies may be detected before clinical symptoms of cancer and may disappear after successful treatment of cancer with remission of DM supporting DM being a paramalignant phenomenon.

Acute Coronary Syndrome in Idiopathic Inflammatory Myopathies: A Population-based Study.

OBJECTIVE: Evidence suggests an increased risk of cardiovascular (CV) diseases, including acute coronary syndrome (ACS), in idiopathic inflammatory myopathies (IIM). The aim of this study was to investigate the risk of ACS in an incident IIM cohort compared to the general Swedish population. METHODS: A cohort of 655 individuals with incident IIM and 6813 general population comparators were identified from national registries. IIM subjects were diagnosed from 2002 to 2011. Followup started at IIM diagnosis and corresponding date in the general population. ACS, CV comorbidities, and CV risk factors were defined using International Classification of Diseases codes. Incidence rates including 95% CI were calculated. Cox proportional hazards models were used to compare the risk of ACS in patients with IIM and the general population. The competing risk of death was accounted for using competing risk regression models. RESULTS: The incidence rate of ACS in IIM was higher than in the general population, particularly within the first year of diagnosis and in older individuals. The overall ACS incidence rate in IIM was 15.6 (95% CI 11.7-20.4) per 1000 person-years, with an HR of 2.4 (95% CI 1.8-3.2) compared with the general population. When accounting for the competing risk of death, the risk of ACS in IIM remained increased with a cumulative incidence of 7% at 5 years compared to 3.3% in the general population. CONCLUSION: IIM individuals are at higher risk of ACS, particularly within the first year after diagnosis.

The Risk of Ischemic and Hemorrhagic Stroke in Patients With Idiopathic Inflammatory Myopathies: A Swedish Population-Based Cohort Study.

OBJECTIVE: To study the occurrence of ischemic stroke and hemorrhagic stroke in patients with idiopathic inflammatory myopathies (IIMs) compared to that in the general population and to investigate how it varies by sex, age, clinical subdiagnosis, and time since IIM diagnosis. METHODS: All patients in Sweden with newly diagnosed IIM were identified from the National Patient Register, and general population comparators were identified from the Total Population Register. The study population was followed prospectively until death, emigration, December 2013, or first incident stroke. Incidence rates, rate differences, and hazard ratios (HRs) comparing patients with IIMs to the general population were estimated and stratified by age, sex, type of IIM, and time since diagnosis. To account for the competing risk of death, the subdistribution HR was estimated using Fine and Gray models. RESULTS: We observed 34 and 229 stroke events in 663 IIM patients and 6,673 comparators, respectively. The HR was elevated for ischemic stroke (HR 2.1 [95% confidence interval (95% CI) 1.4, 3.0]). Few hemorrhagic stroke events were identified, but an increased risk was observed (HR 1.9 (95% CI 0.7, 5.5]). The association remained elevated for both outcomes when taking the competing risk of death into account. For ischemic stroke, the rate difference was highest in the oldest age group (≥68 years), while the HR was highest in the youngest age group (<56 years). CONCLUSION: Our findings indicate that the risk of both ischemic stroke and hemorrhagic stroke is increased in patients with IIMs, but it should be kept in mind that stroke is a rare event. Focus on prevention should be directed toward groups with the highest absolute risk, especially older patients.

Venous Thromboembolic Events in Idiopathic Inflammatory Myopathy: Occurrence and Relation to Disease Onset.

OBJECTIVE: To assess the incidence of venous thromboembolic events (VTEs) in patients with idiopathic inflammatory myopathies (IIMs), to compare the incidence of VTEs in IIM to the incidence in the general population, and to identify patient categories at high risk and investigate the development of risk in relation to a diagnosis of IIM. METHODS: Using nationwide registers, we identified a cohort of 440 individuals with newly diagnosed IIM and 4,459 individuals from the general population. Patients with IIM were diagnosed between 2005 and 2011. The start of follow-up was the date of IIM diagnosis and the corresponding date in the general population. VTE was defined as hospital care with an International Statistical Classification of Diseases and Related Health Problems, Tenth Revision code indicating VTE, with a filled prescription for anticoagulant medication. Incidence rates including 95% confidence intervals (95% CIs) were calculated, and Cox proportional hazards models were used to compare the risk of VTE in patients with IIM to the risk in the general population. RESULTS: The incidence of VTEs was higher in patients with IIM than in the general population and was highest in patients who previously had cancer, who were ages >71 years when diagnosed with IIM, or who had dermatomyositis. The overall hazard ratio (HR) of VTE comparing the IIM cohort to the general population was 7.81 (95% CI 4.74, 12.85). The HR was highest the first year after IIM diagnosis, with HR 26.6 (95% CI 10.4, 68.0). CONCLUSION: Patients with IIM are at increased risk of VTE compared to the general population, especially during the first year after the diagnosis. Preventive measures should be focused on patients who previously have had cancer, who are ages >71 years when diagnosed, or who have dermatomyositis.

Mortality in idiopathic inflammatory myopathy: results from a Swedish nationwide population-based cohort study.

Patients with idiopathic inflammatory myopathies (IIMs) suffer an increased burden of comorbidities, but data on mortality in recently diagnosed IIM are conflicting. Also, little is known when, if ever, in relation to IIM diagnosis, mortality is increased. METHODS: A population-based IIM cohort of patients diagnosed between 2002 and 2011 and general population comparators were identified using healthcare registers. They were linked to the cause of death register for follow-up. RESULTS: 224 (31%) of the 716 patients with IIM and 870 (12%) of the 7100 general population died during follow-up. This corresponded to a mortality rate of 60/1000 person-years in IIM and 20/1000 person-years in the general population. The cumulative mortality at 1 year after diagnosis was 9% in IIM and 1% in the general population, and increased in both IIM and the general population with time. The overall hazard ratio (HR) 95%CI of death comparing IIM with the general population was 3.7 (3.2 to 4.4). When we stratified on time since diagnosis, we noted an increase in mortality already within the first year of diagnosis compared with the general population, HR 9.6 (95% CI 6.9 to 13.5). This HR then plateaued around 2 after >10 years with the disease, although the estimates were not statistically significant. Malignancies, diseases of the circulatory and respiratory system were common causes of death. CONCLUSION: Mortality is increased in patients with contemporary IIM. The increased mortality was noted within a year of diagnosis, which calls for extra vigilance during the first year of IIM diagnosis.

Infections and respiratory tract disease as risk factors for idiopathic inflammatory myopathies: a population-based case-control study.

OBJECTIVES: To investigate the association between infection or respiratory tract disease and future risk of developing idiopathic inflammatory myopathy (IIM). METHODS: A case-control study was performed using Swedish nationwide registers. Adults with newly diagnosed IIM were identified (2002-2011) from the National Patient Register (NPR) and the Swedish Rheumatology Register (n=957). Controls were matched by age, sex and place of residence (n=9476). Outpatient visits and hospitalisations preceding IIM diagnosis indicating infection or respiratory disease were identified from NPR. Conditional logistic regression models were used to calculate OR and 95% CI. Sensitivity analyses were performed by varying the exposure definition, adjusting for previous healthcare consumption and excluding individuals with connective tissue disease, IIM lung phenotype or IIM-associated cancer. RESULTS: Preceding infections were more common in IIM cases compared with controls (13% vs 9%) and were associated with an increased risk of IIM (OR 1.5, 95% CI 1.2 to 1.9). Gastrointestinal and respiratory tract infections were associated with an increased risk of IIM while cutaneous infections were not.Preceding respiratory tract disease was present in 10% of IIM cases and 4% of controls (OR 2.3, 95% CI 1.8 to 3.0). Both upper and lower respiratory tract diseases were associated with an increased risk of IIM.Variations in exposure and outcome definitions did not greatly affect the results. CONCLUSIONS: Infections and respiratory tract diseases are associated with an increased risk of IIM which suggests that the triggering of the immune system may take place outside the skeletal muscle.

Incidence and prevalence of idiopathic inflammatory myopathies in Sweden: a nationwide population-based study.

Objectives: To estimate the incidence rate and prevalence of idiopathic inflammatory myopathies (IIMs) in Sweden across clinical subgroups, age, sex, educational level and place of residence and to assess the robustness of register-based case definitions. Methods: IIM was identified from the Swedish National Patient Register and the Swedish Rheumatology Quality Register. The base case definition required ⩾2 visits indicating IIM (first ever with a consecutive visit within 1-12 months for incident cases) and the robustness was tested by applying a more liberal and a stricter definition. Results: Using the base case definition, 558 incident IIM patients were identified between 2007 and 2011. The incidence was estimated to 11 (13 for women and 9.7 for men) per 1 000 000 person years and was stable across case definitions. Incidence increased with age and peaked at the 50-79 years age groups. No differences were observed between different levels of education and place of residence. We identified 1267 IIM patients on 1 January 2012 corresponding to a prevalence of 14 per 100 000. Conclusion: We present nationwide register-based incidence and prevalence estimates for IIM, robust across three different case definitions. In contrast to many other reports, we did not find incidence by age to be bimodal and we found no explanation of incidence variation across education and residency. These register-based case definitions can be included in future population-based studies to better understand disease aetiology, risk factors and comorbidities.

Use of biologic agents in idiopathic inflammatory myopathies in Sweden: a descriptive study of real life treatment.

OBJECTIVES: Biologic treatment has revolutionised treatment in rheumatology in the last decades. Patients with idiopathic inflammatory myopathies (IIM) have so far only been treated with biologics off-label, with little published follow-up on those who are treated and how they are treated. We therefore set out to characterise the Swedish IIM patients who have been treated with biologics. METHODS: By linking Swedish registers we identified 95 patients with IIM who were treated with biologics between 2000 and 2011. Via chart review the diagnoses were validated and clinical characteristics extracted. RESULTS: In total, 95 individuals with IIM and biologic treatment were identified. Median disease duration was 5.5 years at start of biologics. All patients had been treated with prednisolone and failed at least one previous DMARD before the start of first biologic. Rituximab was the most common biologic drug, followed by anakinra and TNFinhibitors. Median overall treatment length was 10 months and varied between 5 and 12.5 months or the different therapies. CONCLUSIONS: Off-label treatment of IIMs is often tried and seldom successful. This study shows a large unmet need for novel treatments and therapies in IIM. It is therefore important to follow these patients in a structured way to learn about effects and potential risks for different subgroups of IIM associated with different therapies.

Health Care Utilization and Complications Rates among Users Of Hydrophilic-Coated Catheters.

This article presents results from an electronic survey completed by intermittent catheterization users who were registered members of a global web-based database. The results provide data on complication rates, health care utilization, and benefits from using hydrophilic-coated urinary catheters isotonic to urine.

Registries in idiopathic inflammatory myopathies.

PURPOSE OF REVIEW: The idiopathic inflammatory myopathies myositis are rare diseases with limited information on risk factors for disease and prognosis. The aim of this review is to give an overview of how registries can be used in myositis research. RECENT FINDINGS: Population-based registries have been used in a number of incidence and prevalence studies in the review period and have shown myositis to be more common than previously reported. Disease-specific registries have been used for detailed studies on subphenotypes and longitudinal studies to identify prognostic markers and treatment outcomes. SUMMARY: Registries, both national healthcare and health insurance registries, as well as disease-specific clinical registries, are useful sources to investigate a rare disease like myositis. To achieve increased understanding of whether different subphenotypes differ in treatment outcome and prognosis, a large number of patients need to be followed longitudinally in a systematic way. A novel international, multidisciplinary registry, EUROMYOSITIS, has been developed. This is an open source registry with to date 20 centers and more than 2500 patients with myositis, many of whom are followed longitudinally. This registry has clear potentials for clinical and epidemiological research, as well as for clinical trial in myositis, and welcomes investigators from all over the world.