Microscopic Colitis and Risk of Incident Psoriasis: A Nationwide Population-Based Matched Cohort Study.

Background: Microscopic colitis (MC) has been associated with several immune-mediated diseases including psoriasis, but earlier research has been limited to psoriasis occurring before MC. Data from large-scale cohort studies investigating MC and risk of future psoriasis are lacking. Objective: To examine the association between MC and psoriasis. Methods: In a nationwide, population-based, matched cohort study in Sweden from 2007 to 2021, we identified 8404 patients with biopsy-verified MC (diagnosed in 2007-2017), 37,033 matched reference individuals, and 8381 siblings without MC. Information on MC was obtained through the ESPRESSO cohort (a Swedish histopathology database with nationwide coverage). Using Cox regression, we calculated hazard ratios (HRs) and 95% confidence intervals (CIs) for psoriasis up until 2021. Results: During a median follow-up of 9.2 years (interquartile range = 6.7-11.7), 179 MC patients and 440 reference individuals were diagnosed with psoriasis (241.1 vs 131.8 events per 100,000 person-years), corresponding to one extra case of psoriasis in 91 patients with MC over 10 years. After adjustment for the matching variables (birth year, sex, county of residence, and calendar period) and level of education, we computed an adjusted hazard ratio (aHR) of 1.82 (95% CI = 1.53-2.17). Stratified by sex, estimates were similar and when examining the aHR across different lengths of follow-up, we found significantly elevated estimates up to 10 years after MC diagnosis. Compared to MC-free siblings, the aHR was 1.85 (95% CI = 1.36-2.51). Conclusion: Patients with MC are at an almost doubled risk of psoriasis compared to the general population. Clinicians need to consider psoriasis in MC patients with skin lesions.

Tumor-Stroma Proportion to Predict Chemoresistance in Patients With Ovarian Cancer.

IMPORTANCE: Platinum-based chemotherapy is the backbone of standard-of-care treatment for patients with advanced-stage, high-grade serous carcinoma (HGSC), the most common form of ovarian cancer; however, one-third of patients have or acquire chemoresistance toward platinum-based therapies. OBJECTIVE: To demonstrate the utility of tumor-stroma proportion (TSP) as a predictive biomarker of chemoresistance of HGSC, progression-free survival (PFS), and overall survival (OS). DESIGN, SETTING, AND PARTICIPANTS: This prognostic study leveraged tumors from patients with HGSC in The Cancer Genome Atlas (TCGA) cohort (1993-2013) and an independent cohort of resected clinical specimens from patients with HGSC (2004-2014) available in diagnostic and tissue microarray formats from the University of Tübingen in Germany. Data analysis was conducted from January 2021 to January 2024. EXPOSURE: Diagnosis of HGSC. MAIN OUTCOMES AND MEASURES: Principal outcome measures were the ability of TSP to predict platinum chemoresistance, PFS, and OS. Using hematoxylin and eosin-stained slides from the Tübingen cohort (used for routine diagnostic assessment from surgical specimens) as well as tissue microarrays, representative sections of tumors for scoring of TSP were identified using previously evaluated cutoffs of 50% stroma or greater (high TSP) and less than 50% stroma (low TSP). Digitized slides from the TCGA Cohort were analyzed and scored in a similar fashion. Kaplan-Meier time-to-event functions were fit to estimate PFS and OS. RESULTS: The study included 103 patients (mean [SD] age, 61.6 [11.1] years) from the TCGA cohort and 192 patients (mean [SD] age at diagnosis, 63.7 [11.1] years) from the Tübingen cohort. In the TCGA cohort, there was no significant association of TSP levels with chemoresistance, PFS, or OS. However, in the Tübingen cohort, high TSP was associated with significantly shorter PFS (HR, 1.586; 95% CI, 1.093-2.302; P = .02) and OS (hazard ratio [HR], 1.867; 1.249-2.789; P = .002). Patients with chemoresistant tumors were twice as likely to have high TSP as compared to patients with chemosensitive tumors (HR, 2.861; 95% CI, 1.256-6.515; P = .01). In tissue microarrays from 185 patients from the Tübingen cohort, high TSP was again associated with significantly shorter PFS (HR, 1.675; 95% CI, 1.012-2.772 P = .04) and OS (HR, 2.491; 95% CI, 1.585-3.912; P < .001). CONCLUSIONS AND RELEVANCE: In this prognostic study, TSP was a consistent and reproducible marker of clinical outcome measures of HGSC, including PFS, OS, and platinum chemoresistance. Accurate and cost-effective predictive biomarkers of platinum chemotherapy resistance are needed to identify patients most likely to benefit from standard treatments, and TSP can easily be implemented and integrated into prospective clinical trial design and adapted to identify patients who are least likely to benefit long-term from conventional platinum-based cytotoxic chemotherapy treatment at the time of initial diagnosis.

Identifying Predictors of First-Line Subcutaneous TNF-Inhibitor Persistence in Patients with Inflammatory Arthritis: A Decision Tree Analysis by Indication.

INTRODUCTION: Treatment persistence is a proxy for efficacy, safety and patient satisfaction, and a switch in treatment or treatment discontinuation has been associated with increased indirect and direct costs in inflammatory arthritis (IA). Hence, there are both clinical and economic incentives for the identification of factors associated with treatment persistence. Until now, studies have mainly leveraged traditional regression analysis, but it has been suggested that novel approaches, such as statistical learning techniques, may improve our understanding of factors related to treatment persistence. Therefore, we set up a study using nationwide Swedish high-coverage administrative register data with the objective to identify patient groups with distinct persistence of subcutaneous tumor necrosis factor inhibitor (SC-TNFi) treatment in IA, using recursive partitioning, a statistical learning algorithm. METHODS: IA was defined as a diagnosis of rheumatic arthritis (RA), ankylosing spondylitis/unspecified spondyloarthritis (AS/uSpA) or psoriatic arthritis (PsA). Adult swedish biologic-naïve patients with IA initiating biologic treatment with a SC-TNFi (adalimumab, etanercept, certolizumab or golimumab) between May 6, 2010, and December 31, 2017. Treatment persistence of SC-TNFi was derived based on prescription data and a defined standard daily dose. Patient characteristics, including age, sex, number of health care contacts, comorbidities and treatment, were collected at treatment initiation and 12 months before treatment initiation. Based on these characteristics, we used recursive partitioning in a conditional inference framework to identify patient groups with distinct SC-TNFi treatment persistence by IA diagnosis. RESULTS: A total of 13,913 patients were included. Approximately 50% had RA, while 27% and 23% had AS/uSpA and PsA, respectively. The recursive partitioning algorithm identified sex and treatment as factors associated with SC-TNFi treatment persistence in PsA and AS/uSpA. Time on treatment in the groups with the lowest treatment persistence was similar across all three indications (9.5-11.3 months), whereas there was more variation in time on treatment across the groups with the highest treatment persistence (18.4-48.9 months). CONCLUSIONS: Women have low SC-TNFi treatment persistence in PsA and AS/uSpA whereas male sex and golimumab are associated with high treatment persistence in these indications. The factors associated with treatment persistence in RA were less distinct but may comprise disease activity and concurrent conventional systemic disease-modifying anti-rheumatic drug (DMARD) treatment.

Clinical Significance of the Stromatic Component in Ovarian Cancer: Quantity Over Quality in Outcome Prediction.

Background: The tumor stroma is composed of a complex network of non-cancerous cells and extracellular matrix elements that collectively are crucial for cancer progression and treatment response. Within the realm of ovarian cancer, the expression of the stromal gene cluster has been linked to poorer progression-free and overall survival rates. However, in the age of precision medicine and genome sequencing, the notion that the simple measurement of tumor-stroma proportion alone can serve as a biomarker for clinical outcome is a topic that continues to generate controversy and provoke discussion. Our current study reveals that it is the quantity of stroma, rather than its quality, that serves as a clinically significant indicator of patient outcome in ovarian cancer. Methods: This study leveraged the High-Grade-Serous-Carcinoma (HGSC) cohort of the publicly accessible Cancer Genome Atlas Program (TCGA) along with an independent cohort comprising HGSC clinical specimens in diagnostic and Tissue Microarray formats. Our objective was to investigate the correlation between the Tumor-Stroma-Proportion (TSP) and progression-free survival (PFS), overall survival (OS), and response to chemotherapy. We assessed these associations using H&E-stained slides and tissue microarrays. Our analysis employed semi-parametric models that accounted for age, metastases, and residual disease as controlling factors. Results: We found that high TSP (>50% stroma) was associated with significantly shorter progression-free survival (PFS) (p=0.016) and overall survival (OS) (p=0.006). Tumors from patients with chemoresistant tumors were twice as likely to have high TSP as compared to tumors from chemosensitive patients (p=0.012). In tissue microarrays, high TSP was again associated with significantly shorter PFS (p=0.044) and OS (p=0.0001), further confirming our findings. The Area Under the ROC curve for the model predicting platinum was estimated at 0.7644. Conclusions: In HGSC, TSP was a consistent and reproducible marker of clinical outcome measures, including PFS, OS, and platinum chemoresistance. Assessment of TSP as a predictive biomarker that can be easily implemented and integrated into prospective clinical trial design and adapted to identify, at time of initial diagnosis, patients who are least likely to benefit long-term from conventional platinum-based cytotoxic chemotherapy treatment.

Establishment and Utility of SwedAD: A Nationwide Swedish Registry for Patients with Atopic Dermatitis Receiving Systemic Pharmacotherapy.

SwedAD, a Swedish nationwide registry for patients with atopic dermatitis receiving systemic pharmacotherapy, was launched on 1 September 2019. We describe here the establishment of a user-friendly registry to the benefit of patients with atopic dermatitis. By 5 November 2022, 38 clinics had recorded 931 treatment episodes in 850 patients with an approximate national coverage rate of 40%. Characteristics at enrolment included median Eczema Area and Severity Index (EASI) 10.2 (interquartile range 4.0, 19.4), Patient-Oriented Eczema Measure (POEM) 18.0 (10.0, 24.0), Dermatology Life Quality Index (DLQI) 11.0 (5.0, 19.0) and Peak Itch Numerical Rating Scale-11 (NRS-11) 6.0 (3.0, 8.0). At 3 months, median EASI was 3.2 (1.0, 7.3) and POEM, DLQI, and NRS-11 were improved. Regional coverage varied, reflecting the distribution of dermatologists, the ratio of public to private healthcare, and difficulties in recruiting certain clinics. This study highlights the importance of a nationwide registry when managing systemic pharmacotherapy of atopic dermatitis.

An experience- and preference-based EQ-5D-3L value set derived using 18 months of longitudinal data in patients who sustained a fracture: results from the ICUROS.

INTRODUCTION: EQ-5D-3L preference-based value sets are predominately based on hypothetical health states and derived in cross-sectional settings. Therefore, we derived an experience-based value set from a prospective observational study. METHODS: The International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS) was a multinational study on fragility fractures, prospectively collecting EQ-5D-3L and Time trade-off (TTO) within two weeks after fracture (including pre-fracture recall), and at 4, 12, and 18 months thereafter. We derived an EQ-5D-3L value set by regressing the TTO values on the ten impairment levels in the EQ-5D-3L. We explored the potential for response shift and whether preferences for domains vary systematically with prior impairment in that domain. Finally, we compared the value set to 25 other EQ-5D-3L preference-based value sets. RESULTS: TTO data were available for 12,954 EQ-5D-3L health states in 4683 patients. All coefficients in the value set had the expected sign, were statistically significant, and increased monotonically with severity of impairment. We found evidence for response shift in mobility, self-care, and usual activities. The value set had good agreement with the only other experience- and preference-based value set, but poor agreement with all hypothetical value sets. CONCLUSIONS: We present an experience- and preference-based value set with high face validity. The study indicates that response shift may be important to account for when deriving value sets. Furthermore, the study suggests that perspective (experienced versus hypothetical) is more important than country setting or demographics for valuation of EQ-5D-3L health states.

The Impact of Systemic Treatment of Atopic Dermatitis on Depressive Symptoms: A Prospective Clinical Cohort Study

Information on depressive symptoms among patients with atopic dermatitis (AD) undergoing systemic treatment in a real-world setting is scarce. This prospective real-world clinical cohort study analysed data from SwedAD, a Swedish national register comprising patients with AD undergoing systemic treatment. Data were collected at baseline (n = 120) and at follow-up at 6 months (range 3-9 months, n = 59), and 12 months (10 months or later, n = 36). Depression was assessed with the Montgomery-Åsberg Depression Rating Scale-Self-report (MADRS-S) and AD with the Eczema Area Severity Index, the Patient-Oriented Eczema Measure, the Dermatology Life Quality Index and evaluation of pruritus. More than half of patients with moderate-to-severe AD had depressive symptoms at baseline, 24% presented with moderate-to-severe depression and 3% had pronounced suicidal ideation. Systemic treatment of AD significantly reduced both depression and AD symptoms at 6 months, and this positive effect remained at 12 months. In conclusion, depressive symptoms are common among adults with moderate-to-severe AD. Systemic treatment of AD significantly reduced depressive symptoms in parallel with AD symptoms.

Costs of patient management over 18 months following a hip, clinical vertebral, distal forearm, or proximal humerus fragility fracture in France-results from the ICUROS study.

This observational study prospectively assessed direct and indirect costs related to patient management over 18 months following hip, clinical vertebral, humeral, or distal forearm fracture events in France. It appears that their levels were much higher than the previous estimates, raising the burden of osteoporosis-related fractures on public health expenditures. INTRODUCTION: This prospective observational study assessed the costs related to patient management over the 18-month period following the event of a hip, clinical vertebral, humeral, or distal forearm fracture in France. METHODS: Individuals aged ≥ 50 years old with the diagnosis of a fragility fracture in six French University Hospitals were enrolled in the International Costs and Utilities Related to Osteoporotic Fractures Study (ICUROS). All resources used over the defined period and related to fracture and the underlying osteoporosis management were collected by questionnaires at baseline, 4 months, 12 months, and 18 months. Information was collected by direct or phone contact completed by patients' records and interviews of partner, family, and general practitioners. Costs were estimated from a societal perspective, including direct and indirect costs. We implemented recursive partitioning analysis (RPA), a statistical learning algorithm to identify predictors of costs. RESULTS: Four hundred thirty-one patients (mean age 72.5 years; 84.6% women) were evaluated. Among them, 17.6% had a prior fracture in the last 5 years. Approximately half of the whole group lived alone in the community, and 56.8% were from a low- or middle-income category. Over the 18-month period of evaluation, total costs (including initial fracture-related and follow-up ones) were 23 926 €, 14 561 €, and 6 905 € for the hip, clinical vertebral, and distal forearm fracture, respectively. Over a year, costs related to a humeral fracture were 10 319 €. The RPA identified mobility impairment prior to fracture as a predictor of increase in costs related to fracture. CONCLUSIONS: Our study for the first time prospectively assessed total costs related to the four main osteoporotic fractures in France. It appears that their levels were much higher than previous estimates, raising the burden of osteoporosis-related fractures on public health expenditures.

Thirty years of hip fracture incidence in Austria: is the worst over?

Nationwide hip fracture incidence in the Austrian population was assessed over a period of 30 years (1989-2018), including 20 years data from a previous study and a recent 10 years follow-up. While absolute numbers in men continued to increase, absolute numbers in women and age-standardized incidences in both men and women decreased. PURPOSE: In the Austrian population ≥ 50 years, nationwide hip fracture incidences over a period of 20 years (1989-2008) have shown an initial steep increase, followed by a leveling-off during the last few years of observation. The purpose of the present study was to follow up on hip fracture incidences for another 10 years (2009-2018) and to analyze trends over the entire period of 30 years. METHODS: ICD-10 code classes S72.0, S72.1, and S72.2 were applied. All data were retrieved from the Statistics Austria database and its hospital discharge register. Annual absolute numbers, crude and age-standardized incidences, and incidence rate ratios (IRR) were stratified by sex and 5-year age intervals, and calculated by using a correction factor for multiple registrations. RESULTS: Total number of hip fracture cases increased from 13,984 (2009) to 14,640 (2015), and decreased thereafter to 14,457 (2018), despite a persistent increase in men. Age-standardized incidences peaked at 476/100,000 (2010), followed by a decrease to 408/100,000 (2018). The observed overall decrease was mainly driven by the female population. Incidence rate ratios (IRRs) yielded a statistically significant average annual decrease of age-standardized incidences in both women and men (∆IRR 0.984; 0.981-0.987). CONCLUSION: While absolute numbers of hip fracture in women showed a slight decrease during the last 10 years of observation, numbers in men continued to increase. Age-standardized incidences nevertheless decreased in both men and women, which may be interpreted as a trend in the right direction. However, due to the rapid aging of the population, it cannot be precluded that this trend will be compromised during the next few decades.

Health-Care and Societal Costs Associated with Non-Persistence with Subcutaneous TNF-α Inhibitors in the Treatment of Inflammatory Arthritis (IA): A Retrospective Observational Study.

OBJECTIVE: A few studies have suggested that patients with inflammatory arthritis (IA) who remain persistent with subcutaneous TNF-α inhibitors (SC-TNFi) incur lower health care costs than patients who discontinue treatment, whereas data on the impact of non-persistence on indirect costs are largely lacking. Furthermore, existing estimates are based on fixed follow-ups, in relation to treatment initiation, and therefore do not measure costs in direct relation to treatment discontinuation. Therefore, by capturing costs in direct relation to treatment discontinuation, this study aimed to estimate direct and indirect costs associated with non-persistence with SC-TNFis in IA. METHODS: Adult Swedish biologic-naïve IA patients initiating biologic treatment with a SC-TNFi (adalimumab, etanercept, certolizumab or golimumab) between May 6, 2010, and December 31, 2017, were identified in population-based registers with almost complete coverage. IA was defined as a diagnosis of rheumatic arthritis, ankylosing spondylitis/unspecified spondyloarthritis or psoriatic arthritis. Non-persistent patients were matched on propensity score to patients persistent with treatment by at least an additional 12 months. This enabled comparisons of direct healthcare costs and indirect costs for sick leave and disability pension, respectively, 12 months before and 12 months after treatment discontinuation. RESULTS: A balanced cohort of 486 matched pairs was generated. The total direct and indirect costs were significantly higher among non-persistent patients already during the 12 months before index ($20,802 [18,335-23,429] vs. $16,600 [14,331-18,696]). However, while non-persistent patients increased their total direct and indirect costs, persistent patients significantly decreased the same, further widening the difference in costs during the 12-month period after index date ($22,161 [19,754-24,556] vs. $13,465 [11,415-15,729]). CONCLUSIONS: Among biologic-naïve Swedish IA patients treated with SC-TNFis, persistent patients incurred about 40% lower aggregated direct and indirect costs compared to non-persistent patients the year following SC-TNFi discontinuation. This highlights the impact of treatment persistence from an economic viewpoint, adding further aspects to the clinical perspective.

Treatment Persistence in Patients Cycling on Subcutaneous Tumor Necrosis Factor-Alpha Inhibitors in Inflammatory Arthritis: A Retrospective Study.

INTRODUCTION: Biologic treatments including subcutaneous tumor necrosis factor-alpha inhibitors (SC-TNFis) have greatly improved disease management of rheumatoid arthritis (RA), psoriatic arthritis (PsA) and ankylosing spondylitis (AS) (collectively inflammatory arthritis, IA). Nevertheless, some patients discontinue their first-line treatment; for them, one option may be a subsequent line of the same treatment class (i.e., cycling). The aim of this study was to assess treatment persistence between first- and second-line therapy in Swedish IA patients cycling on SC-TNFis. METHODS: Using data from the Swedish Health Data Registers, adult IA patients filling prescriptions between May 1, 2010, and October 31, 2016, for a SC-TNFi (adalimumab, etanercept, certolizumab and golimumab) were included. Treatment persistence was derived based on information from filled prescriptions and a 60-day grace period. Unadjusted and adjusted marginal Cox proportional hazards models were fitted to estimate the relative risk of discontinuation across treatment lines, using robust sandwich covariance matrix estimates to account for intrapatient dependence (i.e., multiple treatment lines per patient). The analysis was restricted to the first two lines of treatment. RESULTS: Of the eligible patients, 3181 were identified as cyclers. Among these, most were female (68%), and 46%, 28% and 26% were diagnosed with RA, AS and PsA, respectively. Both the unadjusted and adjusted analyses showed that the relative risk of discontinuing SC-TNFi treatment was significantly lower in second compared to first line (hazard ratio; 0.60 [0.57, 0.63] and HR; 0.59 [0.56, 0.62]). This finding was also consistent across IA indications. CONCLUSIONS: In this study of patients cycling on SC-TNFis in IA, persistence was greater in second- compared to first-line treatment. The finding was consistent across all IA indications. Hence, patients who discontinue their first-line treatment may still benefit from treatment with an alternative SC-TNFi as a second-line therapy in IA.

Recovery of quality of life is associated with lower mortality 5-year post-fracture: the Australian arm of the International Costs and Utilities Related to Osteoporotic Fractures Study (AusICUROS).

Little is known about factors that lead to excess mortality post-fracture. This study demonstrated that 5-year mortality is lower in older adults who recovered to their pre-fracture health-related quality of life (HRQoL) at 12-months compared to those who did not recover. Our results highlight the importance of post-fracture interventions known to improve HRQoL. INTRODUCTION: Fragility fractures lead to increased mortality and decreased health-related quality of life (HRQoL) in older adults, although whether an association exists between these outcomes remains uncertain. The aim of this study was to determine whether recovery of HRQoL 12-month post-fracture is associated with lower 5-year mortality. METHODS: This data linkage study included 524 adults (mean age: 70.2 years; 79.2% women) with fragility fracture (150 hip, 261 distal forearm, 61 vertebral, 52 humerus) from the Australian arm of the International Costs and Utilities Related to Osteoporotic fractures Study (AusICUROS). HRQoL was measured using the EQ-5D-3L and all-cause mortality post-fracture was ascertained from the Australian National Death Index (NDI). Cox proportional hazards models were used to assess the association between HRQoL recovery (vs. non-recovery) and all-cause mortality within 5 years. RESULTS: Overall, 279 participants (53.2%) recovered to their pre-fracture HRQoL at 12-month follow-up. There were 70 deaths (13.4%) during the 5-year post-fracture. Mortality rate was the highest in hip fracture participants (24.7%), followed by vertebral (16.4%), humeral (13.5%), and distal forearm fracture participants (6.1%). After adjustment for age, pre-fracture HRQoL, and fracture site, mortality risk was lower in participants who recovered to their pre-fracture HRQoL at 12-months compared to those who did not recover (HR = 0.56, 95% CI: 0.33-0.96, p = 0.034). CONCLUSION: This study provides evidence that HRQoL recovery post-fracture is associated with improved 5-year survival in older adults. The extent to whether current interventions known to improve HRQoL post-fracture could prevent some of these deaths is unknown.

Long-term Outcomes and Prognosis in New-Onset Psoriasis.

IMPORTANCE: Psoriasis is a heterogeneous disease. Improved understanding of prognosis and long-term outcomes in new-onset psoriasis may improve care. OBJECTIVE: To describe the clinical course of psoriasis and identify possible indicators of long-term outcomes. DESIGN, SETTING, AND PARTICIPANTS: The Stockholm Psoriasis Cohort was a noninterventional inception cohort study enrolling patients between 2001 and 2005. The present study was conducted from January 15, 2019, to February 5, 2021. At enrollment and 10 years, patients were examined by dermatologists and rheumatologists. Data from examinations were complemented by questionnaires, medical records, and registers. A total of 721 patients with recent-onset psoriasis (<12 months duration), 15 years or older were recruited using advertising and referrals from a broad range of health care settings. MAIN OUTCOMES AND MEASURES: Disease severity and psoriatic arthritis (PsA). Recursive partitioning and regression models were implemented to identify probable indicators of long-term outcomes. RESULTS: A total of 721 patients (median [interquartile range] age, 39 [27-55] years; 405 [56%] women), including 542 (75%) with plaque-onset and 174 (24%) with guttate-onset psoriasis, were enrolled. The median follow-up was 9.6 years (interquartile range, 8.8-10.4 years). The cumulative incidence of severe psoriasis at 12 years from enrollment was 21%. Among 509 patients examined clinically after 10 years, 77 of 389 patients (20%) with plaque onset and 56 of 116 (48%) with guttate onset had minimal disease activity without treatment, and 120 of 509 (24%) had PsA. Recursive partitioning identified strata with distinct risks for severe skin disease and PsA: the cumulative incidence of severe disease in patients with plaque phenotype, above-median disease activity, and scalp lesions was 52% (95% CI, 41%-64%), compared with 11% (95% CI, 8%-14%) in patients with below-median disease activity at inclusion; and 48 of 82 patients (59%) with peripheral enthesitis had PsA after 10 years compared with 37 of 304 patients (12%) without initial joint pain (P < .001). Smoking (hazard ratio, 1.70; 95% CI, 1.10-2.63) and activating genes in the interleukin-23 (IL-23) pathway (odds ratio, 1.55; 95% CI, 1.14-2.11) were also significantly associated with a severe disease course. Systemic therapy at or before enrollment was associated with a lower risk for severe disease at 10 years compared with later initiation of systemic therapy (odds ratio, 0.24; 95% CI, 0.06-0.90). CONCLUSIONS AND RELEVANCE: The findings of this cohort study suggest that combinations of clinical characteristics at onset and activating genes in the IL-23 pathway are significantly associated with the clinical course of psoriasis, whereas joint pain and peripheral enthesitis may indicate the probability of PsA. Patients within those categories merit specialist referral and closer follow-up. The possibility of modifying the disease course with early systemic intervention should be tested.

Health service use pathways associated with recovery of quality of life at 12-months for individual fracture sites: Analyses of the International Costs and Utilities Related to Osteoporotic fractures Study (ICUROS).

PURPOSE: We aimed to identify combinations of health service use specific to each major osteoporotic fracture (MOF) site - hip, distal forearm, vertebrae and humerus - associated with recovery of health-related quality of life (HRQoL) 12-months post-MOF. METHODS: Patients were 4126 adults aged ≥50 years with a MOF (1657 hip, 1354 distal forearm, 681 vertebral, 434 humerus) from the International Costs and Utilities Related to Osteoporotic fractures Study (Australia, Austria, Estonia, France, Italy, Lithuania, Mexico, Russia, Spain and the UK). HRQoL (pre-fracture and 12-months post-fracture) was measured using the EQ-5D-3L. Health service use data were collected via interviews and medical record reviews and included in-hospital care, outpatient care, supported living, community health services, and medication use. Latent class analyses were undertaken to identify different combinations of health service use ("classes"); and logistic regression to assess associations between classes and HRQoL recovery. Fracture site-specific analyses were performed using pooled data from all 10 countries. RESULTS: The proportion of patients who recovered to their pre-fracture HRQoL at 12-month follow-up varied across fracture sites: 37.3%, 65.8%, 48.9% and 49.5% for hip, distal forearm, vertebrae, and humerus, respectively. We observed several site-specific classes associated with improved odds of HRQoL recovery. Generally, the combination of hospital presentations without admission; primary care center visits; use of osteoporosis-related medications; vitamin D/calcium supplementation; and non-opioid analgesic use was associated with greater likelihood of HRQoL recovery. CONCLUSION: The identified fracture site-specific health service use pathways associated with recovery of HRQoL could potentially improve the management and health outcomes of patients treated for a MOF.