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This study assessed the position of apremilast in the treatment pathway of psoriasis (PsO) and psoriatic arthritis (PsA) in Finnish clinical practice, compared the characteristics of apremilast and biologic therapy users, evaluated persistence with apremilast and identified factors influencing treatment discontinuation. This retrospective study used data from Finnish national health registries. The target group was identified based on L40* diagnosis and medication records between 2015 and 2018. Treatment persistence was analysed using Kaplan–Meier curves and Cox regression. Of eligible patients (PsO 31 202; PsA 12 386), 1% (n = 471) used apremilast and 10% (n = 4214) biologics, apremilast users being older (mean age 55.9 vs 52.4 years, p < 0.001) with a higher Charlson comorbidity score (0.71 vs 0.54, p < 0.001). Most patients switched to apremilast from conventional synthetic therapy (PsO 75%; PsA 76%); 47% of patients remained on apremilast during the observation period (PsO 58%; PsA 42%). Most patients discontinuing apremilast switched to biologics (PsO 51%; PsA 51%). Apremilast persistence increased with age (p = 0.042) and was higher in PsO than in PsA (median 14 vs 11 months; p = 0.005). Compared to prior conventional synthetic therapy, prior biologic therapy decreased persistence (hazard ratio for discontinuation 2.15, 95% confidence interval 1.42–3.25). In Finnish clinical practice, apremilast is mainly used between conventional synthetic therapy and biologics, with at least as high treatment persistence as reported in previous studies. Apremilast users were older with higher comorbidity burden than biologics users. [ABSTRACT FROM AUTHOR]

Purpose: Tumor inflammatory response was evaluated as a prognostic feature in triple-negative breast cancer (TNBC) and compared with the clinical prognosticators of breast cancer and selected biomarkers of cancer cell proliferation. Methods: TNBC patients (n = 179) with complete clinical data and up to 18-year follow-up were obtained from Auria biobank, Turku University Hospital, Turku, Finland. Tumor-infiltrating lymphocytes (TILs) and several subtypes of inflammatory cells detected with immunohistochemistry were evaluated in different tumor compartments in full tissue sections and tissue microarrays. Results: Deficiency of stromal TILs and low number of CD8+ T cells independently predicted mortality in TNBC (HR 2.4, p 0.02 and HR 2.1, p 0.02, respectively). Each 10% decrease in stromal TILs resulted in 20% increased risk of mortality. An average of 13.2-year survival difference was observed between the majority (> 75%) of patients with low (< 14% of TILs) vs high (≥ 14% of TILs) frequency of CD8+ T cells. The prognostic value of TILs and CD8+ T cells varied when evaluated in different tumor compartments. TILs and CD8+ T cells were significantly associated with Securin and Separase, essential regulators of metaphase–anaphase transition of the cell cycle. Discussion: TILs and CD8+ T cells provide additional prognostic value to the established clinical prognostic markers in TNBC. However, possible clinical applications would still benefit from systematic guidelines for evaluating tumor inflammatory response. Increasing understanding on the interactions between the regulation of cancer cell proliferation and inflammatory response may in future advance treatment of TNBC. [ABSTRACT FROM AUTHOR]

Objectives Increased risk of osteoporotic fractures in multiple sclerosis ( MS) patients compared with general population has been reported. The purpose of this study was to assess the risk of osteoporotic and other low-energy fractures in an MS cohort from a large hospital district in southwest Finland. Age-adjusted total and gender-specific prevalence for definite MS per 100 000 in a population of 472 139 was calculated as a point prevalence in December 31, 2012. Materials and Methods Patients with MS and comorbid fractures were identified by searching for ICD-9 and ICD-10 codes during a period from 2004 to 2012 from hospital administrative data in Turku University Hospital ( TYKS) in southwest Finland Case ascertainment was performed by review of medical records. Osteoporotic fracture was defined as a low-energy fracture of the pelvis, hip, femur, tibia, humerus, collar bone, ulna/radius, vertebrae, or rib. The control population was a 10-fold age- and gender-matched population. Results The point prevalence (N 1004) of MS was 212.6/105 ( CI 199.5-225.8) in December 31, 2012. A total of 100 (9.9%) of 1004 confirmed MS cases experienced at least one fracture during the study period. Relative risks ( RRs) for all fractures (1.33, 95% CI 1.10-1.60) and osteoporotic fractures (1.50, 95% CI 1.18-1.90) were significantly increased in patients with MS compared with controls. In particular, RRs for hip fractures (5.00, 95% CI 2.96-8.43) and fractures of humerus (2.36, 95% CI 1.32-4.42) were elevated in patients with MS vs controls. Conclusions We observed high prevalence of MS in southwest Finland and confirmed increased age-adjusted comorbid risk for osteoporotic fractures and other low-energy fractures compared with individually matched controls. [ABSTRACT FROM AUTHOR]

We studied the spatial covariation of breeding success of black grouse and capercaillie and densities of mammalian generalist predators in Finland. Our study was based on six years' data from the Finnish wildlife triangle censuses (1989--1994). At the nation-wide level (100 x 100 km grids), the proportion of hens with a brood in August covaried regionally in the two species and decreased towards southern Finland, whereas the brood sizes were not related to latitude. The relative densities of red fox and pine marten correlated negatively with theproportion of grouse hens with a brood and were two- to three-fold higher in southernmost Finland than elsewhere in the country. The relative density of stoat, however, increased with latitude. The results support the hypothesis that higher generalist predator densities are responsible for lower breeding success of forest dwelling grouse moving southwards in Fennoscandia. The results also suggest that the stoat is of minor importance as nest and brood predator compared to red fox and pine marten. In northern Finland, on a smaller spatial scale (about 25 km2), the increasing red fox density decreased the probability of an observed grouse hen being with a brood in low vole years, whereas in years of high vole densities no effect was detected in logistic regression analysis. In contrast to northern results, the red fox density in southern Finland, although generally higher, did not predict the spatial variation in breeding success of grouse either in high or in low vole years. The brood size of grouse was not related to red fox density. Our results agree with the alternative prey hypothesis in northern, but not in southern Finland. In addition tohigher amplitude of vole cycles in northern than in southern Finland, this inconsistency can probably be related to regional differences in both prey and predator communities. [ABSTRACT FROM AUTHOR]

Combination therapies in metastatic hormone-sensitive prostate cancer (mHSPC), which include the addition of an androgen receptor signaling inhibitor and/or docetaxel to androgen deprivation therapy, have been a game changer in the management of this disease stage. However, these therapies come with their fair share of toxicities and side effects. The goal of this observational study is to report drug-related adverse events (AEs), which are correlated with systemic combination therapies for mHSPC. Determining the optimal treatment option requires large cohorts to estimate the tolerability and AEs of these combination therapies in "real-life" patients with mHSPC, as provided in this study. We use a network of databases that includes population-based registries, electronic health records, and insurance claims, containing the overall target population and subgroups of patients defined by unique certain characteristics, demographics, and comorbidities, to compute the incidence of common AEs associated with systemic therapies in the setting of mHSPC. These data sources are standardised using the Observational Medical Outcomes Partnership Common Data Model. We perform the descriptive statistics as well as calculate the AE incidence rate separately for each treatment group, stratified by age groups and index year. The time until the first event is estimated using the Kaplan-Meier method within each age group. In the case of episodic events, the anticipated mean cumulative counts of events are calculated. Our study will allow clinicians to tailor optimal therapies for mHSPC patients, and they will serve as a basis for comparative method studies., (© 2024 The Authors.)

A growing body of research is focusing on real-world data (RWD) to supplement or replace randomized controlled trials (RCTs). However, due to the disparities in data generation mechanisms, differences are likely and necessitate scrutiny to validate the merging of these datasets. We compared the characteristics of RCT data from 5734 diabetic kidney disease patients with corresponding RWD from electronic health records (EHRs) of 23,523 patients. Demographics, diagnoses, medications, laboratory measurements, and vital signs were analyzed using visualization, statistical comparison, and cluster analysis. RCT and RWD sets exhibited significant differences in prevalence, longitudinality, completeness, and sampling density. The cluster analysis revealed distinct patient subgroups within both RCT and RWD sets, as well as clusters containing patients from both sets. We stress the importance of validation to verify the feasibility of combining RCT and RWD, for instance, in building an external control arm. Our results highlight general differences between RCT and RWD sets, which should be considered during the planning stages of an RCT-RWD study. If they are, RWD has the potential to enrich RCT data by providing first-hand baseline data, filling in missing data or by subgrouping or matching individuals, which calls for advanced methods to mitigate the differences between datasets., (© 2024. The Author(s).)

Background: Subject-level real-world data (RWD) collected during daily healthcare practices are increasingly used in medical research to assess questions that cannot be addressed in the context of a randomized controlled trial (RCT). A novel application of RWD arises from the need to create external control arms (ECAs) for single-arm RCTs. In the analysis of ECAs against RCT data, there is an evident need to manage and analyze RCT data and RWD in the same technical environment. In the Nordic countries, legal requirements may require that the original subject-level data be anonymized, i.e., modified so that the risk to identify any individual is minimal. The aim of this study was to conduct initial exploration on how well pseudonymized and anonymized RWD perform in the creation of an ECA for an RCT., Methods: This was a hybrid observational cohort study using clinical data from the control arm of the completed randomized phase II clinical trial (PACIFIC-AF) and RWD cohort from Finnish healthcare data sources. The initial pseudonymized RWD were anonymized within the (k, ε)-anonymity framework (a model for protecting individuals against identification). Propensity score matching and weighting methods were applied to the anonymized and pseudonymized RWD, to balance potential confounders against the RCT data. Descriptive statistics for the potential confounders and overall survival analyses were conducted prior to and after matching and weighting, using both the pseudonymized and anonymized RWD sets., Results: Anonymization affected the baseline characteristics of potential confounders only marginally. The greatest difference was in the prevalence of chronic obstructive pulmonary disease (4.6% vs. 5.4% in the pseudonymized compared to the anonymized data, respectively). Moreover, the overall survival changed in anonymization by only 8% (95% CI 4-22%). Both the pseudonymized and anonymized RWD were able to produce matched ECAs for the RCT data. Anonymization after matching impacted overall survival analysis by 22% (95% CI -21-87%)., Conclusions: Anonymization may be a viable technique for cases where flexible data transfer and sharing are required. As anonymization necessarily affects some aspects of the original data, further research and careful consideration of anonymization strategies are needed., (© 2023. The Author(s).)

Objective: To assess whether electronic health record (EHR) data text mining can be used to improve register-based heart failure (HF) subtyping. EHR data of 43,405 individuals from two Finnish hospital biobanks were mined for unstructured text mentions of ejection fraction (EF) and validated against clinical assessment in two sets of 100 randomly selected individuals. Structured laboratory data was then incorporated for a categorization by HF subtype (HF with mildly reduced EF, HFmrEF; HF with preserved EF, HFpEF; HF with reduced EF, HFrEF; and no HF)., Results: In 86% of the cases, the algorithm-identified EF belonged to the correct HF subtype range. Sensitivity, specificity, PPV and NPV of the algorithm were 94-100% for HFrEF, 85-100% for HFmrEF, and 96%, 67%, 53% and 98% for HFpEF. Survival analyses using the traditional diagnosis of HF were in concordance with the algorithm-based ones. Compared to healthy individuals, mortality increased from HFmrEF (hazard ratio [HR], 1.91; 95% confidence interval [CI], 1.24-2.95) to HFpEF (2.28; 1.80-2.88) to HFrEF group (2.63; 1.97-3.50) over a follow-up of 1.5 years. We conclude that quantitative EF data can be efficiently extracted from EHRs and used with laboratory data to subtype HF with reasonable accuracy, especially for HFrEF., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: In the inflammatory bowel diseases, chronic inflammation predisposes to dysplasia and colorectal carcinoma, leading to the need of surveillance colonoscopies. The most-used marker of colonic inflammation is faecal calprotectin. Its correlation with endoscopic and histological findings is well-documented. In this study, we evaluated the role of sequential faecal calprotectin measurements in predicting colorectal dysplasia, to identify patients with increased risk of dysplasia or colonic malignancy in ulcerative colitis. Methods: We collected the faecal calprotectin measurements and colorectal histology reports of patients with ulcerative colitis treated in Helsinki University Hospital (Helsinki, Finland) between 2007 and 2017, with a focus on IBD-associated neoplasia, inflammatory activity, and sporadic adenomas. Using the time-weighted AUC of faecal calprotectin as a marker of inflammatory burden, we tested the performance of faecal calprotectin to predict the risk for colorectal neoplasia. Results: In total, 982 patients with ulcerative colitis were included. Of them, 845 had pancolitis and 127 concomitant primary sclerosing cholangitis. Forty-one patients (4%) had IBD-associated colorectal dysplasia and seven (0.7%) developed adenocarcinoma. In patients with constantly elevated faecal calprotectin level (>500 µg/g), colorectal neoplasia was more frequent compared to those with low (<200 µg/g) calprotectin (13% and 4%, p  < 0.05). Histological inflammatory activity was also related to more frequent dysplastic changes. Conclusions: Colon dysplasia and adenocarcinoma are more common among ulcerative colitis patients with constantly elevated faecal calprotectin than in patients in remission. The role of inflammatory activity in inducing neoplastic changes in colon is further supported by histology, as histological inflammatory activity correlates with dysplasia.

Introduction: The prevalence of migraine is highest among working age individuals, and this disease is associated with an increased number of sick leaves and health care visits, as well as lost productivity. Erenumab, the first monoclonal antibody targeting the calcitonin gene-related peptide (CGRP) pathway, is effective in decreasing the monthly number of migraine days, but evidence of its impact on the number of sick leave days and health care visits in patients with migraine is limited., Methods: This retrospective registry study focused on occupationally active patients with migraine treated with erenumab at a Finnish private health care provider, Terveystalo. Erenumab responders, defined as patients who had at least two unique prescriptions of erenumab and no prescription of other CGRP inhibitor (CGRPi), were followed for 12 months prior to and after erenumab treatment initiation (index), and the change in the number of headache-related and all-cause sick leave days, health care visits and prescriptions for other medications during this period were assessed from the registry data. The same outcomes were assessed in an age- and sex-matched control group of migraine patients not receiving CGRPi to control for potential changes in patient behavior and health care practices during the COVID-19 pandemic., Results: Altogether, 162 patients who were entitled to employer-sponsored health care received erenumab and met the 12-month follow-up requirements. In the responder group (n = 82; 50.1%) headache-related sick leave days were reduced by 73.9% (p = 0.035) and health care visits by 44.6% (p < 0.001) in the 12 months following treatment initiation compared to the period of 12 months prior to treatment. All-cause sick leave days were reduced by 19.4% and all-cause health care visits by 13.5%, but these changes were not statistically significant. Triptan prescriptions decreased by 30.4% (p = 0.012) and other prophylactic treatments by 31.5% (p = 0.004). No significant changes were observed in the corresponding outcomes in the migraine control group during the same period., Conclusions: The results of this registry study suggest that in addition to the effect on the monthly number of migraine days documented in clinical trials, erenumab can significantly reduce the number of headache-related sick leave days and health care visits in employed patients with migraine managed in routine clinical practice., (© 2021. The Author(s).)