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.

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.

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.

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).

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.