Objective To establish the significance of glucocerebrosidase gene (GBA) carrier status on motor impairment in a large cohort of patients with incident Parkinson disease (PD). Methods Three European population-based studies followed 528 patients with PD from diagnosis. A total of 440 with genomic DNA from baseline were assessed for GBA variants. We evaluated motor and functional impairment annually using the Unified Parkinson’s Disease Rating Scale (UPDRS) motor and activities of daily living (ADL) sections. Differential effects of classes of GBA variants on disease progression were evaluated using mixed random and fixed effects models. Results A total of 387 patients with idiopathic disease (age at baseline 70.3 ± 9.5 years; 60.2% male) and 53 GBA carriers (age at baseline 66.8 ± 10.1 years; 64.2% male) were included. The motor profile of the groups was clinically indistinguishable at diagnosis. GBA carriers showed faster annual increase in UPDRS scores measuring ADL (1.5 point per year, 95% confidence interval [CI] 1.1–2.0) and motor symptoms (2.2 points per year, 95% CI 1.3–3.1) compared to noncarriers (ADL, 1.0 point per year, 95% CI 0.9–1.1, p = 0.003; motor, 1.3 point per year, 95% CI 1.1–1.6, p = 0.007). Simulations of clinical trial designs showed that recruiting only GBA carriers can reduce trial size by up to 65% compared to a trial recruiting all patients with PD. Conclusion GBA variants are linked to a more aggressive motor disease course over 7 years from diagnosis in patients with PD. A better understanding of PD progression in genetic subpopulations may improve disease management and has direct implications for improving the design of clinical trials.

Background and Objectives Variations in the glucocerebrosidase gene (GBA) are common risk factors for Parkinson disease (PD) and dementia in PD (PDD) and cause a reduction in the activity of the lysosomal enzyme glucocerebrosidase (GCase). It is anticipated that GCase dysfunction might contribute to a more malignant disease course and predict cognitive impairment in PD, although evidence is lacking. We aimed to discover whether CSF GCase activity is altered in newly diagnosed patients with PD and associated with future development of dementia. Methods Patients with PD were participants of the ongoing population-based longitudinal ParkWest study in Southwestern Norway and were followed prospectively for up to 10 years. CSF was collected at diagnosis, and GBA carrier status was obtained. Control samples were from persons without neurodegenerative disorders. GCase activity was measured using a validated assay. PD dementia diagnosis was set according to the Movement Disorder Society criteria, and parametric accelerated failure time models were applied to analyze the association of GCase activity with dementia-free survival. Results This study enrolled 117 patients with PD (mean age 67.2 years, including 12 GBA non‐synonymous variant carriers) and 50 control participants (mean age 64 years). At the time of diagnosis, GCase activity was reduced in patients with PD with (mean ± SD, 0.92 ± 0.40 mU/mg, n = 12) or without GBA variations (1.00 ± 0.37 mU/mg, n = 105) compared with controls (1.20 ± 0.35, n = 50). GCase activity at the time of diagnosis was lower in patients with PD who developed dementia within 10 years (0.85 ± 0.27 mU/mg, n = 41) than in those who did not (1.07 ± 0.40 mU/mg, n = 76, p = 0.001). A 0.1-unit reduction in baseline GCase activity was associated with a faster development of PDD (hazard ratio 1.15, 95% CI 1.03–1.28, p = 0.014). Discussion The association of early CSF GCase activity with long-term progression to PD dementia will have important implications for the design of clinical trials for GCase targeting therapies and patient management. Classification of Evidence This study provides Class III evidence that reduced CSF GCase activity at the time of PD diagnosis is associated with an increased risk for later development of PDD.

Aim/s To explore next of kin satisfaction with cancer care, map next of kin suggestions for involvement and combine this information to create a basis for improving quality and safety in hospitals. Design Convergent parallel mixed-methods design applying the 20-item FAMCARE Scale survey instrument for quantitative measurement of satisfaction with care and with an open-ended question used for qualitative analysis. Data sources Responses from 238 next of kin (November 2016-November 2017). Methods Exploratory factor analysis, regression analysis and qualitative content analysis were combined. Results Both hospitals scored better in medical treatment (median, interquartile range: 1.5, 1.1-2.0), than in satisfaction with information and involvement of next of kin (1.9, 1.3-2.4), p < .001 (Wilcoxon signed ranks test). After adjusting for differences in demographical and clinical variables, the total FAMCARE scores were 13% higher (95% confidence interval: 1%-27%, Wald p = .029) at one of the hospitals. Qualitative findings support that the hospitals are not providing an equal offer to next of kin involvement in hospital cancer care that includes a proactive approach. Conclusion As a basis for quality and safety improvement, next of kin satisfaction and involvement in cancer care should be addressed in a two-sided perspective, balancing the next of kin's need for involvement in cancer treatment with the patient's perspective. Impact There is limited knowledge of next of kin satisfaction with hospital cancer care and how next of kin would like to be involved in this trajectory. Several aspects of satisfaction with cancer care can prompt change to improve service quality and safety (e.g. information, involvement, practical care), but this is an underused source of information. Next of kin are key in cancer care and our study demonstrates a potential large impact on future practical ways of improving cancer care service provision in an integrative perspective including next of kin.

Background and purpose: Intraoperative periprosthetic femoral fractures (IPFFs) can occur during primary total hip arthroplasty (THA). We describe the incidence of IPFFs during THA in Norway and estimate potential risk factors that could be associated with IPFFPatients and methods — Data from the Norwegian Arthoplasty Register (1987–2020) was used: 2,268 IPFFs from 218,423 primary THAs in 172,598 patients. The following factors were analyzed: sex, age, diagnosis, previous operation on the same hip, surgical approach, and stem fixation technique. Association of these factors with IPFF risk was assessed using multivariable Poisson regression. Results: IPFF occurred during 2,268 operations with an incidence of 1.0% among all primary THAs. The risk of IPFF was associated with female sex (relative risk 1.8; 99% CI 1.5–2.1), age 80–90 years and age over 90 years (compared with age 60–70 years: 1.3; CI 1.0–1.6 and 2.6; CI 1.6–4.3, respectively), non-osteoarthritis diagnoses (2.2; CI 1.9–2.6), previous surgery to the same hip (1.8; CI 1.5–2.2), lateral approach (compared with the posterior approach: 1.5; CI 1.1–2.0), and cementless stem fixation (2.7; CI 2.0–3.6). Interpretation: Surgeons should be aware of the factors associated with an increased risk of IPFF: female sex, age above 80 years, non-osteoarthritis diagnoses, and previous surgery to the same hip. Cemented stem fixation and posterior approach should be favored in high-risk patients, such as elderly women.

Background Fatigue is a frequent complaint in patients with inflammatory bowel disease. Biological drugs have demonstrated beneficial effects on some extraintestinal manifestations, but the effect on fatigue is not clear. Objective This study investigated the effects of biological and small molecule drugs approved for inflammatory bowel disease on fatigue. Methods We performed a systematic review and meta-analysis of randomized, placebo-controlled trials reporting Federal Drug Agency (FDA)-approved biological and small molecule drugs for use in ulcerative colitis and Crohn’s disease in which measures of fatigue were recorded before and after treatment. Only induction studies were included. Maintenance studies were excluded. We searched Embase (Ovid), Medline (Ovid), PsycINFO (Ovid), Cinahl (EBSCOhost), Web of Science Core Collection, Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov in May 2022. Risk of bias was analyzed using the Cochrane risk-of-bias tool. Standardized mean difference was used to measure the treatment effect. Results A total of seven randomized controlled trials composed of 3835 patients were included in the meta-analysis. All of the studies included patients with moderately to severely active ulcerative colitis or Crohn’s disease. The studies used three different generic fatigue instruments: the Functional Assessment of Chronic Illness Therapy-Fatigue and the Short Form 36 Health Survey Vitality Subscale versions 1 and 2. Overall treatment with biological or small molecule agents showed a beneficial effect compared with placebo, with a standardized mean difference of 0.25 (95% confidence interval 0.15–0.34, p < 0.001). The effect was independent of type of drug or subtype of inflammatory bowel disease. Discussion The risk of bias was considered to be low for all domains except for missing outcome data. Even though the included studies were of high methodological quality, the review is limited by the small number of studies included and that the available studies were not designed to evaluate fatigue specifically. Conclusion Biological and small molecule drugs used in inflammatory bowel disease have a consistent, though small, beneficial effect on fatigue.