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Introduction: Patients with triple-class-exposed relapsed/refractory multiple myeloma (TCE-RRMM) have a poor prognosis and limited treatment options. Teclistamab, a B-cell maturation antigen × CD3 bispecific antibody, was studied in patients with TCE-RRMM in the single-arm MajesTEC-1 study. To assess the relative effectiveness of teclistamab versus real-world physician’s choice of therapy (RWPC), adjusted comparisons were performed using individual patient data from MajesTEC-1 and LocoMMotion, a prospective study of patients with TCE-RRMM. Methods: An external control arm for MajesTEC-1 was created from patients in LocoMMotion (n = 248; clinical cut-off: November 2, 2021) and compared with treated patients (n = 165) from MajesTEC-1 (teclistamab 1.5 mg/kg weekly; clinical cut-off: March 16, 2022). Inverse probability weighting was used to adjust for imbalances in baseline covariates. For binary endpoints [overall response rate (ORR), very good partial response or better (≥ VGPR) rate, complete response or better (≥ CR)], relative effect of teclistamab versus RWPC was estimated with an odds ratio and relative response rate and 95% confidence interval (CI), derived from weighted logistic regression. Weighted Cox proportional hazards model was used to estimate hazard ratios (HR) and 95% CIs for time-to-event endpoints [duration of response (DOR), progression-free survival (PFS), and overall survival (OS)]. Results: After weighting, baseline characteristics were balanced across cohorts. In adjusted comparisons, teclistamab-treated patients were 2.3-fold, 5.2-fold and 148.3-fold, more likely to reach ORR [response-rate ratio (RR) = 2.31, 95% CI 1.77–2.85, p

Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy studied in patients with triple-class exposed multiple myeloma (TCE-MM) in the single arm CARTITUDE-1 study. To assess cilta-cel’s effectiveness compared to real-world clinical practice (RWCP), we performed adjusted comparisons using individual patient data from CARTITUDE-1 and LocoMMotion, a prospective, multinational study of patients with TCE-MM. Comparisons were performed using inverse probability weighting (IPW). In CARTITUDE-1, 113 patients were enrolled, and 97 patients were infused with cilta-cel. In LocoMMotion, 248 patients were enrolled, and 170 patients were included in comparisons vs. infused patients. 92 unique regimens were used in LocoMMotion, most frequently carfilzomib-dexamethasone (13.7%), pomalidomide-cyclophosphamide-dexamethasone (13.3%) and pomalidomide-dexamethasone (11.3%). Adjusted comparisons showed that patients treated with cilta-cel were 3.12-fold more likely to respond to treatment vs. RWCP (RR 3.12, 95% CI: 2.24, 4.00), had a reduced risk of progression or death by 85% (PFS HR 0.15, 95% CI: 0.08, 0.29), and a lower risk of death of 80% (OS HR 0.20, 95% CI: 0.09, 0.41). Incremental improvement vs. baseline in HRQOL for cilta-cel vs. RWCP at week 52 as measured by EORTC QLQ-C30 Global Health Status was 13.4 (95% CI: 3.5, 23.6) and increased to 30.8 (95% CI: 21.8, 39.8) when including death as additional information regarding patients’ health status. Patients treated with cilta-cel experienced more adverse events vs. RWCP (any grade:100% vs. 83.5%). Results from this study demonstrate improved efficacy outcomes of cilta-cel vs. RWCP and highlight its potential as a novel and effective treatment option for patients with TCE-MM.

8016 Background : Pts with TCE RRMM who have been exposed to ≥3 lines of therapy (LOT) have a poor prognosis and limited tx options. Tec is a B-cell maturation antigen × CD3 bispecific antibody being evaluated in MajesTEC-1 (NCT04557098), a single-arm, phase 1/2 study in pts with RRMM who were TCE to an immunomodulatory drug, a proteasome inhibitor, and an anti-CD38 antibody and received ≥3 LOT. Since MajesTEC-1 lacks a control arm, we assessed the comparative efficacy of tec vs tx currently used in real-world clinical practice (RWCP) by creating an external real-world control arm from LocoMMotion (NCT04035226), a prospective study of RWCP efficacy and safety outcomes in pts with TCE RRMM who received ≥3 LOT. Methods: An external control arm for MajesTEC-1 was created from pts in LocoMMotion (248 pts, clinical cutoff May 21, 2021) who met MajesTEC-1 eligibility criteria. Individual pt-level data from MajesTEC-1 were included from 150 pts treated with tec (1.5 mg/kg weekly) at a clinical cutoff of Sep 7, 2021. Inverse probability of tx weighting with average tx effect on the treated was used to adjust for imbalances in baseline covariates of prognostic significance (refractory status, International Staging System stage, time to progression on prior LOT, extramedullary disease, number of prior LOT, time since diagnosis, average duration of prior LOT, age, hemoglobin, lactate dehydrogenase, creatinine clearance, Eastern Cooperative Oncology Group performance status, gender, type of MM, and prior transplant). Comparative efficacy of tec vs RWCP was estimated for overall response rate (ORR), very good partial response (VGPR) rate, complete response or better (≥CR) rate, duration of response (DOR), progression-free survival (PFS), and overall survival (OS). For binary endpoints (ORR, VGPR rate, and ≥CR rate), relative effect of tec vs RWCP was estimated with an odds ratio, transformed into a response-rate ratio (RR) and 95% confidence interval (CI), derived from weighted logistic regression. A weighted Cox proportional hazards model was used to compute hazard ratios (HRs) and 95% CIs for time-to-event endpoints (DOR, PFS, and OS). Results: Baseline characteristics were well balanced between the 2 cohorts after reweighting the external RWCP cohort. Pts treated with tec had improved outcomes vs tx used in RWCP: ORR (RR 2.31; 95% CI 1.75–2.87; P< 0.0001), VGPR rate (RR 5.54; 95% CI 3.38–7.70; P< 0.0001), ≥CR rate (RR 91.50; 95% CI 12.66–661.43; P< 0.0001), DOR (HR 0.17; 95% CI 0.08–0.36; P< 0.0001), PFS (HR 0.47; 95% CI 0.34–0.67; P< 0.0001), and OS (HR 0.69; 95% CI 0.46–1.05; P= 0.08). Conclusions : Tec showed significantly improved efficacy over RWCP for almost all outcomes, highlighting its potential as a highly effective tx option for pts with TCE RRMM who have been exposed to ≥3 LOT.

Systemic inflammation is thought to mediate the link between sleep and cardiovascular outcomes, but previous studies on sleep habits and inflammation markers have found inconsistent results. This study investigated the relationship between sleep characteristics and C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor α (TNFα). A representative sample of 319 Swedish women was randomly selected from the general population for in-home polysomnography, sleep questionnaire and blood samples. As variables were highly correlated, principal component analysis was used to reduce the number of original variables. Linear regression with log-transformation of the outcomes (lnCRP, lnIL-6 and lnTNFα) and quantile regression were fitted to estimate cross-sectional relationships. Multivariable linear regression models suggested a significant association of insomnia symptoms (self-reported) with higher lnCRP levels (β=0.11; 95% confidence interval [CI]=0.02; 0.21), but not with lnIL-6 and lnTNFα. From quantile regression analysis we found that a high non-restorative index (subjective) and insomnia symptoms (self-reported) were associated with higher values of CRP, especially in the highest quantiles of the CRP distribution (90th percentile: β=0.71; 95% CI=0.17; 1.24. β=1.23; 95% CI=0.44; 2.02, respectively). Additionally, higher amounts of rapid eye movement (REM) sleep were associated with lower CRP values (90th percentile: β=−0.80; 95% CI=−0.14; −1.46). In conclusion, sleep disturbances (self-reported), specifically difficulties maintaining sleep and early morning awakenings, but not sleep duration (neither subjective nor objective), were associated with higher CRP levels. No association was found with IL-6 or TNFα. Elevated REM sleep was associated with lower CRP levels. The results suggest that inflammation might be an intermediate mechanism linking sleep and health in women.

Simple Summary There is an urgent need to develop new treatments for patients with relapsed/refractory multiple myeloma (RRMM) to address unmet medical needs. Chimeric antigen receptor T-cell (CAR-T) therapy is a novel approach with the potential for long-term disease control. Ciltacabtagene autoleucel (cilta-cel) is a CAR-T treatment studied in patients with RRMM in the CARTITUDE-1 clinical trial and has shown clinically important effects. However, CARTITUDE-1 was a single arm study. The current study compared outcomes for cilta-cel with an external cohort of German patients that are similar to the ones in CARTITUDE-1 to compare the effectiveness of cilta-cel versus established clinical practice. To overcome potential bias, individual patient data were used to adjust for the differences in patient characteristics between cohorts. The results showed substantially better outcomes for cilta-cel on both overall survival and the time to next treatment. These findings highlight cilta-cel’s potential as a novel, effective treatment to address unmet treatment needs. Abstract Ciltacabtagene autoleucel (cilta-cel) is a Chimeric antigen receptor T-cell therapy with the potential for long-term disease control in heavily pre-treated patients with relapsed/refractory multiple myeloma (RRMM). As cilta-cel was assessed in the single-arm CARTITUDE-1 clinical trial, we used an external cohort of patients from the Therapie Monitor registry fulfilling the CARTITUDE-1 inclusion criteria to evaluate the effectiveness of cilta-cel for overall survival (OS) and time to next treatment (TTNT) vs. real-world clinical practice. Individual patient data allowed us to adjust the comparisons between both cohorts, using the inverse probability of treatment weighting (IPW; average treatment effect in the treated population (ATT) and overlap population (ATO) weights) and multivariable Cox proportional hazards regression. Outcomes were compared in intention-to-treat (HR, IPW-ATT: TTNT: 0.13 (95% CI: 0.07, 0.24); OS: 0.14 (95% CI: 0.07, 0.25); IPW-ATO: TTNT: 0.24 (95% CI: 0.12, 0.49); OS: 0.26 (95% CI: 0.13, 0.54)) and modified intention-to-treat (HR, IPW-ATT: TTNT: 0.24 (95% CI: 0.09, 0.67); OS: 0.26 (95% CI: 0.08, 0.84); IPW-ATO: TTNT: 0.26 (95% CI: 0.11, 0.59); OS: 0.31 (95% CI: 0.12, 0.79)) populations. All the comparisons were statistically significant in favor of cilta-cel. These results highlight cilta-cel’s potential as a novel, effective treatment to address unmet needs in patients with RRMM.

ObjectivesPsychological stress may influence both susceptibility and severity of infections. Although work-related stress is a widespread concern among many employees, few studies have been conducted with the focus on work stressors and infections. We therefore aimed to investigate this association in a prospective cohort study.MethodsOur study included 25 029 employed individuals who filled-out a questionnaire in September 1997 and were followed through record linkages until retirement or December 2016. Work stress was assessed at baseline using a Swedish version of the Demand-Control Questionnaire, whereas hospital contacts related to infections were identified from the National Patient Register. We fitted extensions of the standard Cox model to account for recurrent infections.ResultsIn total, we observed 8257 infections. Individuals in the third tertile of job demand had a 13% higher hazard of infections (HR=1.13; 95% CI=1.03 to 1.24) compared with individuals in the first tertile, specifically an increased incidence of upper respiratory tract infections (HR=1.15; 95% CI=1.00 to 1.33) and urinary tract infections (HR=1.31; 95% CI=1.09 to 1.57) was found. Employees with the highest job control (third tertile) had no lower risk of infections than individuals in the lowest tertile (HR=1.02; 95% CI=0.92 to 1.13). When combining the demand and control dimensions into job strain scale, no association between high job strain and infections was observed (HR=1.08; 95% CI=0.97 to 1.21).ConclusionHigh job demand, but not low job control, is associated with an increased occurrence of infections. No difference was observed in workers with high strain jobs compared with those with low strain jobs.

Background: The evaluation of the proportional hazards (PH) assumption in survival analysis is an important issue when Hazard Ratio (HR) is chosen as summary measure. The aim is to assess the appropriateness of statistical methods based on the PH assumption in oncological trials. Methods: We selected 58 randomised controlled trials comparing at least two pharmacological treatments with a time-to-event as primary endpoint in advanced non-small-cell lung cancer. Data from Kaplan–Meier curves were used to calculate the relative hazard at each time point and the Restricted Mean Survival Time (RMST). The PH assumption was assessed with a fixed-effect meta-regression. Results: In 19% of the trials, there was evidence of non-PH. Comparison of treatments with different mechanisms of action was associated (P = 0.006) with violation of the PH assumption. In all the superiority trials where non-PH was detected, the conclusions using the RMST corresponded to that based on the Cox model, although the magnitude of the effect given by the HR was systematically greater than the one from the RMST ratio. Conclusion: As drugs with new mechanisms of action are being increasingly employed, particular attention should be paid on the statistical methods used to compare different types of agents.

Background: With the advent of immunomodulatory agents (IMiDs), proteasome inhibitors (PIs) and, more recently, anti-CD38 monoclonal antibodies (mAbs), prognosis of patients with multiple myeloma (MM) has improved considerably. Unfortunately, even with these 3 major MM drug classes, most patients ultimately relapse and require further therapy. There remains an incomplete understanding of how patients who have received extensive therapy and with relapsed/refractory multiple myeloma (RRMM) are treated in routine clinical practice, as no standard-of-care exists for these patients, and what the outcomes are in this real-world setting. Objective: This study aims to evaluate the outcomes of patients with triple-class (IMiD, PI and anti-CD38 mAb) and triple-line exposed RRMM using real-world data from patients in Belgium. Methods: A multicenter, observational study, involving 7 non-academic and academic Belgian centers, was conducted based on a retrospective chart review of adult RRMM patients who started subsequent treatment from March 2017 through May 2021 after having received ≥3 lines of therapy including at least an IMiD, a PI, and anti-CD38-directed therapy (tri-exposed). Data were captured in an electronic case report form (Castor EDC). Patients with an ECOG performance status of ≥2, who received prior CAR-T treatment or prior BCMA-targeted therapy, or with a known active or prior history of CNS involvement (or with clinical signs thereof), were excluded. All treatment lines initiated after becoming eligible were used in the analysis. Specifically, all treatment lines for patients meeting the eligibility criteria more than once in their entire follow-up were included as separate observations, with date of treatment initiation as specific baseline for each treatment line. Cox proportional hazards models were fitted to explore the prognostic value with Overall Survival (OS), Progression Free Survival (PFS), and Time to Next Therapy (TTNT). Results: A total of 112 patients with 237 eligible treatment lines were included in the analysis; median follow-up was 16.6 months. In 45% of the initiated treatment lines, patients were refractory to 4 or 5 therapies, 62% had received ≥5 prior lines, 22% had extramedullary disease and in 48% of observations the time to progression in prior line was shorter than 4 months. After patients became tri-exposed, more than 50 unique treatment regimens were initiated, with the following being the most common: carfilzomib + dexamethasone (14%), pomalidomide + dexamethasone + chemotherapy (8%), and ixazomib + lenalidomide + dexamethasone (6%). Additionally, 4% of included observations were exposed to anti-BCMA agents. Overall, the following treatment classes were the most frequently started: PI only (19%), PI + IMiD combinations (17%), and regimens including anti-CD38 antibodies (15%). Median OS was 9.79 months [95% CI: 7.79; 12.22], median PFS was 3.42 months [95% CI: 2.79; 4.27], median TTNT was 3.61 months [95% CI: 3.09; 4.57]. Higher refractory status (p Conclusions: This retrospective chart review of patients with tri-exposed RRMM in Belgium shows that real-world outcomes in terms of OS, PFS and TTNT are poor for these patients, with a median OS of MD and MCV contributed equally to this work. Figure 1 Figure 1. Disclosures Delforge: Amgen, Celgene, Janssen, Sanofi: Honoraria, Research Funding. Vekemans: Amgen: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; BMS-Celgene: Membership on an entity's Board of Directors or advisory committees, Research Funding; Janssen Pharmaceutica: Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Membership on an entity's Board of Directors or advisory committees. Depaus: Takeda: Consultancy; Novartis: Consultancy; Janssen: Consultancy; Celgene: Consultancy. Meuleman: iTeos Therapeutics: Consultancy. Strens: Realidad bvba: Consultancy. Van Hoorenbeeck: Janssen: Current Employment. Moorkens: Janssen-Cilag: Current Employment. Diels: Janssen: Current Employment. Ghilotti: Janssen-Cilag SpA, Cologno Monzese, Italy: Current Employment. Dalhuisen: Janssen: Current Employment. Vandervennet: Janssen: Current Employment.

Background: Patients with relapsed and refractory multiple myeloma (RRMM) who have triple class exposure to immunomodulatory drugs (IMiDs), proteasome inhibitors (PIs) and anti-CD38 monoclonal antibodies (MoABs) have a poor prognosis and high unmet medical need. Ciltacabtagene autoleucel (cilta-cel) is a chimeric antigen receptor T-cell therapy which may offer long-term disease control for these patients. CARTITUDE-1 is an open-label, single arm phase 1b/2 clinical trial conducted to characterize the safety and efficacy of cilta-cel in adult patients with triple-class exposed RRMM. Since CARTITUDE-1 is a single-arm study, adjusted comparisons to other currently available therapies can provide valuable information on relative efficacy and safety benefits of cilta-cel over current real-world clinical practice (RWCP). LocoMMotion is the first prospective study of RWCP efficacy and safety outcomes in triple-class exposed patients with RRMM. It was designed a priori to serve as an external control cohort for CARTITUDE-1, using aligned inclusion criteria and endpoint definitions, to enable robust, high quality indirect comparisons vs. cilta-cel. Objective: To compare patient outcomes of cilta-cel vs. RWCP, including overall response rate (ORR), complete response or better rate (≥CR rate), progression-free survival (PFS) as assessed by a review committee and overall survival (OS) in patients with triple-class exposed RRMM. Methods: Individual patient level data available from both CARTITUDE-1 (clinical cut-off February 2021) and LocoMMotion (clinical cut-off March 2021) were pooled to conduct the comparative analyses. Imbalances between both cohorts on key prognostic baseline characteristics, including refractory status, ISS stage, time to progression on prior line, number of prior lines, average duration of prior lines, age, creatinine clearance, ECOG PS and MM type were adjusted for using inverse probability weighting. Average treatment effect on the treated (ATT) weights derived from propensity scores estimated using multivariable logistic regression modeling were applied to the LocoMMotion patients to have the weighted RWCP cohort reflecting the CARTITUDE-1 patient population. Balance between the ATT weighted RWCP cohort versus the CARTITUDE-1 population was evaluated based on reduction of standardized mean differences and overlap of propensity score distributions. Weighted logistic and Cox proportional hazards regression were used to estimate the relative treatment effects for cilta-cel vs. RWCP on binary endpoints (Odds ratios (OR), transformed into Response-rate Ratios (RR) and time to event endpoints (Hazard ratios (HR)), respectively. The base case analyses included all enrolled (apheresed) patients from CARTITUDE-1, reflecting an intention to treat approach. Additional analyses were conducted including only patients who received cilta-cel infusion compared to an aligned population of LocoMMotion where patients that progressed or died within 52 days were excluded from the LocoMMotion cohort. Results: 113 patients were enrolled in CARTITUDE-1, of which 97 were infused with cilta-cel. 246 patients were enrolled in LocoMMotion receiving RWCP in Italy (24%), Germany (15%), France (14%), UK (11%), Spain (10%), USA (9%), Belgium (5%), Poland (5%), Netherlands (4%) and Russia (3%). Therapies within the RWCP cohort were diverse and >90 unique treatment regimens were used. The most frequent regimens were Kd (13.8%), PCd (12.6%) and Pd (11.0%). The weighted LocoMMotion population was well balanced with the CARTITUDE-1 cohort. Adjusted comparisons (Table 1) showed statistically significant improvements for cilta-cel vs. RWCP for ORR (RR=4.43), ≥CR (RR=568.92), PFS (HR=0.15) and OS (HR=0.38), all comparisons with p Conclusions: Outcomes for patients with triple-class exposed RRMM treated with RWPC observed in LocoMMotion are poor, illustrating the high unmet medical need. Adjusted comparisons vs. CARTITUDE-1 demonstrate significantly improved ORR, ≥CR, PFS and OS for cilta-cel compared to a diverse set of RWCP. These findings highlight cilta-cel's potential as a highly effective treatment option for patients with triple-class exposed RRMM. Figure 1 Figure 1. Disclosures Mateos: Regeneron: Honoraria, Membership on an entity's Board of Directors or advisory committees; GSK: Honoraria; Sea-Gen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Adaptive Biotechnologies: Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene - Bristol Myers Squibb: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria; Takeda: Honoraria, Membership on an entity's Board of Directors or advisory committees; AbbVie: Honoraria; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Oncopeptides: Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees; Sanofi: Honoraria, Membership on an entity's Board of Directors or advisory committees; Bluebird bio: Honoraria; Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees. Weisel: GSK: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Adaptive Biotechnologies: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bristol Myers Squibb: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Karyopharm: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria; Oncopeptides: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Sanofi: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Abbvie: Consultancy; Novartis: Honoraria; Pfizer: Honoraria. Martin: Sanofi: Research Funding; Oncopeptides: Consultancy; Janssen: Research Funding; GlaxoSmithKline: Consultancy; Amgen: Research Funding. Berdeja: Celularity, CRISPR Therapeutics: Research Funding; Abbvie, Acetylon, Amgen: Research Funding; Bluebird bio, BMS, Celgene, CRISPR Therapeutics, Janssen, Kite Pharma, Legend Biotech, SecuraBio, Takeda: Consultancy; EMD Sorono, Genentech: Research Funding; GSK, Ichnos Sciences, Incyte: Research Funding; Lilly, Novartis: Research Funding; Poseida, Sanofi, Teva: Research Funding. Jakubowiak: Karyopharm: Membership on an entity's Board of Directors or advisory committees; GSK: Membership on an entity's Board of Directors or advisory committees; Janssen: Membership on an entity's Board of Directors or advisory committees; Sanofi: Membership on an entity's Board of Directors or advisory committees; Amgen: Membership on an entity's Board of Directors or advisory committees; Abbvie: Membership on an entity's Board of Directors or advisory committees; BMS: Membership on an entity's Board of Directors or advisory committees; Gracell: Membership on an entity's Board of Directors or advisory committees; Celgene: Membership on an entity's Board of Directors or advisory committees. Stewart: Oncopeptides: Honoraria; Janssen: Honoraria; GSK: Honoraria; BMS: Honoraria; Amgen: Honoraria; Skyline diagnostics: Consultancy; Genomcs England: Membership on an entity's Board of Directors or advisory committees; Tempus Inc.: Current holder of individual stocks in a privately-held company, Membership on an entity's Board of Directors or advisory committees; PikSci Inc.: Current holder of individual stocks in a privately-held company, Patents & Royalties; Sanofi Aventis: Honoraria. Jagannath: Legend Biotech: Consultancy; Bristol Myers Squibb: Consultancy; Karyopharm Therapeutics: Consultancy; Janssen Pharmaceuticals: Consultancy; Takeda: Consultancy; Sanofi: Consultancy. Lin: Novartis: Consultancy; Bluebird Bio: Consultancy, Research Funding; Legend: Consultancy; Sorrento: Consultancy; Juno: Consultancy; Takeda: Research Funding; Celgene: Consultancy, Research Funding; Gamida Cell: Consultancy; Vineti: Consultancy; Merck: Research Funding; Janssen: Consultancy, Research Funding; Kite, a Gilead Company: Consultancy, Research Funding. Diels: Janssen: Current Employment. Ghilotti: Janssen-Cilag SpA, Cologno Monzese, Italy: Current Employment. Perualila: Janssen: Current Employment. Cabrieto: Janssen: Current Employment. Haefliger: Janssen-Cilag AG: Ended employment in the past 24 months; Cilag GmbH International: Current Employment. Erler-Yates: Janssen: Current Employment. Hague: Janssen: Current Employment, Current equity holder in publicly-traded company. Jackson: Janssen: Current Employment; Memorial Sloan Kettering Cancer Center: Consultancy. Strulev: Janssen Pharmaceutica NV: Current Employment. Nesheiwat: Legend Biotech USA: Current Employment. Pacaud: Legend Biotech: Current Employment. Moreau: Janssen: Honoraria; Celgene BMS: Honoraria; Amgen: Honoraria; Sanofi: Honoraria; Abbvie: Honoraria; Oncopeptides: Honoraria. Einsele: Janssen, Celgene/BMS, Amgen, GSK, Sanofi: Consultancy, Honoraria, Research Funding.

OBJECTIVES: This study aims to determine the effects of transurethral polyacrylamide hydrogel injection in patients considered ineligible for midurethral sling surgery. METHODS: In this prospective observational study, 81 patients received treatment with transurethral polyacrylamide hydrogel injection. Patients were considered ineligible for placement of a midurethral sling based on significant comorbidity (48%), 1 or more previously failed invasive treatments (16%), mixed urinary incontinence (27%), continuous incontinence (5%), or previous pelvic radiation therapy (4%). Longitudinal assessment of subjective treatment outcomes was performed using the validated Urinary Distress Inventory (UDI) and the Pelvic Floor Impact Questionnaire at baseline, 2, and 6 months. To deal with repeated measurements, mixed linear models were used to assess changes in the outcomes over time. RESULTS: There was a significant improvement in the overall UDI score from baseline to month 2 follow-up (FU) (P

Introduction Insomnia disorder has a very weak link to polysomnography (PSG) and so does sleep problems in the general population. The reason for this is not clear. One possibility is that the perception of disturbed sleep may be related to immune activation or anxiety/depression, without impairment of objective sleep. Methods 400 women participated, constituting a representative sample of the city of Uppsala with oversampling of snorers. Insomniacs (N=41) were compared with normal sleepers in terms of polysomnography (PSG), immune parameters, anxiety and depression Results The results (after adjustment for age and BMI) show that C-reactive protein (CRP) reached a higher level (4.4±.5) in insomniacs (vs 2.3±.2 for normal sleepers) (p=.003) and lower subjective health (p=.000), while anxiety (p=.000) and depression (p=.000) (Hospital Anxiety and Depression Scale (HAD)) showed higher levels. PSG sleep continuity variables lacked association with insomnia, as did all sleep stage variables except for REM%, with a lower level in the insomnia group (p=.021). Interleukin 6 and Tumor Necrosis Factor alpha were not related to insomnia. CRP levels did not correlate significantly with anxiety or depression, but with subjective health (r=-.21, p=.000). A logistic regression analysis (excluding the variable subjective health) with insomnia as outcome (0/1) yielded as predictors CRP (OR=1.14, Ci= 1.05; 1.24, p=.000), depression (OR=1.21, Ci=1.06;1.38, p=.000) and anxiety (OR=1.15, Ci=1.02;1.30, p=.021). Conclusion It was concluded that increased CRP levels may be part of the subjective experience of insomnia. Support No external funding

Background Previous studies have shown an association between body mass index (BMI) and infections, but the literature on type-specific community acquired infections is still limited. Methods We included 39 163 Swedish adults who completed a questionnaire in September 1997 and were followed through record-linkages until December 2016. Information on BMI was self-reported and infections were identified from the Swedish National Patient Register using International Classification of Diseases (ICD), Tenth Revision (ICD-10) codes. We fitted multivariable Cox proportional hazards models for time-to-first-event analysis, and we used extensions of the standard Cox model when repeated events were included. Results During a 19-year follow-up 32% of the subjects had at least one infection requiring health care contact, leading to a total of 27 675 events. We found an increased incidence of any infection in obese women [hazard ratio (HR) = 1.22; 95% confidence interval (CI) = 1.12; 1.33] and obese men (HR = 1.25; 95% CI = 1.09; 1.43) compared with normal weight subjects. For specific infections, higher incidences were observed for skin infections in both genders (HR = 1.76; 95% CI = 1.47; 2.12 for obese females and HR = 1.74; 95% CI = 1.33; 2.28 for obese males) and gastrointestinal tract infections (HR = 1.44; 95% CI = 1.19; 1.75), urinary tract infections (HR = 1.30; 95% CI = 1.08; 1.55) and sepsis (HR = 2.09; 95% CI = 1.46; 2.99) in obese females. When accounting for repeated events, estimates similar to the aforementioned ones were found. Conclusions Obesity was associated with an increased risk of infections in both genders. Results from multiple-failure survival analysis were consistent with those from classic Cox models.

The aim of this article is to provide a detailed description of the SWEDE-I cohort, a prospective study designed to investigate work-related risk factors for transmission of viral infections. A total of 2,237 subjects aged 25-64, working and residing in Eskilstuna (central Sweden), enrolled in the study in August 2011. They filled in five detailed questionnaires including information on demography, personal characteristics, work tasks, work place, contact patterns, family structure, health status, physical activity and diet. During a 9-month follow-up period, the participants self-reported-via internet or telephone-any onset of fever, upper respiratory tract infection, or gastroenteritis immediately as they occurred. For each disease episode, the participants were asked to submit a self-sampled nasal swab for viral diagnosis. In total, 1,733 disease reports were recorded and 1,843 nasal swabs were received, of which 48% tested positive for one or more of 14 analyzed viruses. The cohort has been used to date to study diet, sleep and physical activity as determinants for upper respiratory tract infections. Analyses of contact patterns and occupational circumstances as risk factors for the transmission of infections are ongoing. The SWEDE-I study should be seen as a first pioneering effort to provide new insight in the epidemiology and prevention of viral infections. Potential joint collaborations can be discussed with the principal investigators.

Previous studies have found a U-shaped relationship between mortality and (weekday) sleep duration. We here address the association of both weekday and weekend sleep duration with overall mortality. A cohort of 43,880 subjects was followed for 13years through record-linkages. Cox proportional hazards regression models with attained age as time-scale were fitted to estimate multivariable-adjusted hazard ratios and 95% confidence intervals for mortality; stratified analyses on age (

Objectives Previous studies found higher levels of physical activity to be protective against infections and that short and long sleep negatively affects the immune response. However, these relationships remain debatable. We aimed to investigate if physical activity and sleep habits affect incidence of upper respiratory tract infections (URTI) in a prospective cohort study. Methods A total of 2,038 adults aged 25-64 years served as a random sample of the gainfully employed population of an industrial town in Sweden. Physical activity and sleep habits were estimated through self-reported questionnaires. Physical activity was expressed as metabolic energy turnover hours per day. Sleep was assessed as number of hours slept per night and its perceived quality. URTI outcome was prospectively self-reported during a 9-month follow-up period. Associations of physical activity and sleep with URTI were estimated using hurdle regression models adjusted for potential confounders. Results During 1,583 person-years 1,597 URTI occurred, resulting in an incidence of 1.01 infections/person-year (95% CI 0.96-1.06). The fitted regression models did not provide support for an association with physical activity or sleep habits. Factors positively associated with experiencing URTI were having children ≤ 6 years, female gender, higher education and treatment for allergy, asthma or lung cancer. Having children ≤ 6 years and female gender were related to a higher number of URTI among those experiencing URTI. Conclusions We did not find any association between physical activity, sleep duration or sleep quality and the occurrence of upper respiratory tract infections in adult Swedish population.

Prior work has shown that both short and long sleep predict mortality. However, sleep duration decreases with age and this may affect the relationship of sleep duration with mortality. The purpose of the present study was to assess whether the association between sleep duration and mortality varies with age. Prospective cohort study. 43,863 individuals (64% women), recruited in September 1997 during the Swedish National March and followed through record-linkages for 13 years. Sleep duration was self-reported and measured using the Karolinska Sleep Questionnaire, and grouped into 4 categories: ≤5, 6, 7 (reference) and ≥8 h. Up to 2010 3548 deaths occurred. Multivariable Cox proportional hazards regression models with attained age as time scale were fitted to estimate mortality rate ratios. Among individuals

BACKGROUND Neuro-Behcet Syndrome (NBS) is a severe chronic inflammatory vascular disease involving the Central Nervous System (CNS), and it is an invalidating condition with disability and a huge impact on quality of life. Recommendations on treatments for NBS include the use of disease-modifying therapies in general, although they are not supported by a systematic review of the evidence. OBJECTIVES To assess the benefit and harms of available treatments for NBS, including biologics, colchicine, corticosteroids, immunosuppressants and interferon-alpha. SEARCH METHODS We searched the following databases up to 30 September 2014: Trials Specialised Register of The Cochrane Multiple Sclerosis and Rare Diseases of the Central Nervous System Group, CENTRAL, MEDLINE, EMBASE, CINAHL, LILACS, ORPHANET, Clinicaltrials.gov and World Health Organization (WHO) International Clinical Trials Registry Portal. SELECTION CRITERIA Randomised controlled trials (RCTs), controlled clinical trials (CCTs), prospective and retrospective controlled cohort studies were eligible to assess the benefit. Patients over 13 years of age with a diagnosis of NBS. For assessment of harms, open-label extension (OLE), case-control studies, population-based registries, case-series and case-reports were additionally planned to be evaluated. DATA COLLECTION AND ANALYSIS Selection of studies, data extraction and assessment of risk of bias were planned to be carried out independently by two review authors. Standard methodological procedures expected by The Cochrane Collaboration were followed. We planned to perform standard pair-wise meta-analyses for RCTs, and meta-analyses based on the adjusted estimates using the inverse-variance weighted average method for non-randomised studies (NRSs). We planned to present the main results of the review in a 'Summary of Findings' table using the GRADE approach. MAIN RESULTS No RCTs, CCTs or controlled cohort studies on the benefit of the treatments for NBS met the inclusion criteria of the review. Only one potentially eligible study was identified, but it did not report sufficient details on the patient characteristics. The author of this study did not provide additional data on request, and therefore it was excluded. Hence, no studies were included in the present review. Since no studies were included in the assessment of benefit, no further search was performed in order to collect data on harms. AUTHORS' CONCLUSIONS There is no evidence to support or refute the benefit of biologics, colchicine, corticosteroids, immunosuppressants and interferon-alpha for the treatment of patients with NBS. Thus, well-designed multicentre RCTs are needed in order to inform and guide clinical practice.