BACKGROUND: The prevalence of diabetes and coexisting multimorbidity rises worldwide. Treatment of this patient group can be complex. Providing an evidence-based, coherent, and patient-centred treatment of patients with multimorbidity poses a challenge in healthcare systems, which are typically designed to deliver disease-specific care. We propose an intervention comprising multidisciplinary team conferences (MDTs) to address this issue. The MDT consists of medical specialists in five different specialities meeting to discuss multimorbid diabetes patients. This protocol describes a feasibility test of MDTs designed to coordinate care and improve quality of life for people with diabetes and multimorbidity.
METHODS: A mixed-methods one-arm feasibility test of the MDT. Feasibility will be assessed through prospectively collected data. We will explore patient perspectives through patient-reported outcomes (PROs) and assess the feasibility of electronic questionnaires. Feasibility outcomes are recruitment, PRO completion, technical difficulties, impact of MDT, and doctor preparation time. During 17 months, up to 112 participants will be recruited. We will report results narratively and by the use of descriptive statistics. The collected data will form the basis for a future large-scale randomised trial.
CONCLUSIONS: A multidisciplinary approach focusing on better management of diabetic patients suffering from multimorbidity may improve functional status, quality of life, and health outcomes. Multimorbidity and diabetes are highly prevalent in our healthcare system, but we lack a solid evidence-based approach to patient-centred care for these patients. This study represents the initial steps towards building such evidence. The concept can be efficiency tested in a randomised setting, if found feasible to intervention providers and receivers. If not, we will have gained experience on how to manage diabetes and multimorbidity as well as organisational aspects, which together may generate hypotheses for research on how to handle multimorbidity in the future.
UNASSIGNED: Protocol version: 01 TRIAL REGISTRATION: NCT05913726 - registration date: 21 June 2023.

BACKGROUND: Total Knee Arthroplasty (TKA) is frequently performed for advanced osteoarthritis, with patient-reported outcome measures (PROMs) traditionally reporting on efficacy. These subjective evaluations, although useful, may inaccurately reflect post-TKA activity levels. With technological advancements, smart implantable devices (SIDs) offer objective, real-time gait metrics, potentially providing a more accurate postoperative recovery assessment. This study compares these objective metrics with PROMs to evaluate TKA success more effectively.
METHODS: We conducted a retrospective cohort study with 88 participants undergoing TKA using a SID. Eligible patients were aged 18 years or older and had advanced osteoarthritis. We excluded those who had bilateral TKAs, joint infections, or neuromuscular disease. The SID system collected daily gait metrics, including step count, distance traveled, walking speed, stride length, cadence, and functional knee range of motion. The PROMs, including Knee Injury and Osteoarthritis Outcome Score-Joint Replacement, Veterans Rand 12 Physical Component Summary, and Veterans Rand 12 Mental Component Summary, were analyzed against SID gait metrics. Among the 88 patients, 80 provided continuous data over 12 weeks.
RESULTS: All gait metrics, except stride length, significantly increased at the 12-week point (P < .05). The PROMs also significantly improved postoperatively (P < .05). Initial low positive correlations between 12-week PROMs and SID metrics decreased after adjusting for demographic variables, leaving only weak correlations between the Veterans Rand 12 Physical Component Summary and Knee Injury and Osteoarthritis Outcome Score-Joint Replacement with functional knee range of motion (r = 0.389, P = .002; r = 0.311, P = .014, respectively), and Veterans Rand 12 Mental Component Summary with step count (r = 0.406, P = .001) and distance traveled (r = 0.376, P = .003).
CONCLUSIONS: This study indicates that both PROMs and SID gait metrics show significant improvements post-TKA, though they correlate weakly with each other, suggesting a possible discrepancy between perceived recovery and actual functional improvement. The SID gait metrics might provide a valuable addition to traditional PROMs by offering an objective representation of physical capabilities unaffected by patient compliance or subjective perceptions of recovery. Further research is needed to validate these findings in larger populations and to explore whether integrating SID metrics can enhance long-term functional outcomes.

OBJECTIVE: Evaluate patterns of stringent disease control with 2 years of guselkumab across key disease-identified domains and patient-reported outcomes (PROs) in subgroups of patients with psoriatic arthritis (PsA) defined by baseline characteristics.
METHODS: This post hoc analysis of DISCOVER-2 (Clinicaltrials.gov NCT03158285) evaluated biologic-naïve PsA patients (≥ 5 swollen/ ≥ 5 tender joints, C-reactive protein [CRP] ≥ 0.6 mg/dL) randomized to guselkumab every 4 weeks (Q4W); guselkumab at Weeks 0 and 4, then Q8W; or placebo with crossover to guselkumab Q4W at Week 24. Achievement of American College of Rheumatology 50/70% improvement (ACR50/70), Investigator\'s Global Assessment (IGA) 0, dactylitis/enthesitis resolution, Functional Assessment of Chronic Illness Therapy (FACIT)-Fatigue response (≥ 4-point improvement), HAQ-Disability Index (HAQ-DI) response (≥ 0.35-point improvement), PsA Disease Activity Score (PASDAS) low disease activity (LDA), and minimal disease activity (MDA) was assessed at Weeks 24, 52, and 100 in subgroups defined by sex and baseline medication use, body mass index, PsA duration, swollen/tender joints, CRP, and psoriasis severity/extent. Patients with missing categorical response data were considered nonresponders.
RESULTS: 442/493 (90%) guselkumab-randomized patients completed treatment through Week 100. Significant multi-domain efficacy of guselkumab versus placebo was shown across adequately sized patient subgroups. A pattern of continuous improvement was observed across key PsA domains and PROs within patient subgroups: 65%-85% of guselkumab-randomized patients had enthesitis/dactylitis resolution, 50%-70% achieved complete skin clearance, 60%-80% reported meaningful improvements in function/fatigue, 40%-65% achieved PASDAS LDA, and 35%-50% achieved MDA at Week 100.
CONCLUSIONS: Patients with active PsA receiving guselkumab demonstrated durable achievement of stringent endpoints associated with disease control across key PsA domains and PROs, regardless of baseline characteristics. Key Points • Among biologic-naïve patients with highly active psoriatic arthritis (PsA), efficacy of guselkumab across stringent disease endpoints and patient-reported outcomes (PROs) at Week 24 was consistent regardless of baseline demographics and disease characteristics. • Within guselkumab-randomized PsA patient subgroups, major improvements in joint disease activity, complete skin clearance, dactylitis/enthesitis resolution, clinically meaningful improvements in PROs, and achievement of low overall disease activity were maintained through Week 100. • Durable stringent endpoint achievement indicating disease control was observed with guselkumab, regardless of baseline patient or disease characteristics.

UNASSIGNED: There is still debate regarding the association between arthrometric knee laxity measurements and subjective knee outcome and revision surgery after primary anterior cruciate ligament reconstruction (ACLR).
UNASSIGNED: To assess whether arthrometric knee laxity (measured with the KT-1000 arthrometer) 6 months after primary ACLR was associated with the 1-, 2-, and 5-year subjective knee outcomes or revision ACLR at a 5-year follow-up.
UNASSIGNED: Cohort study, Level of evidence 3.
UNASSIGNED: Patients who underwent primary ACLR with a hamstring tendon autograft at the authors\' institution between January 1, 2005, and December 31, 2017, with no concomitant ligamentous injuries, were identified. Anterior knee laxity (KT-1000 arthrometer, 134 N) was assessed 6 months postoperatively. The Knee injury and Osteoarthritis Outcome Score (KOOS) was collected preoperatively and 1, 2, and 5 years postoperatively. Patients who underwent revision ACLR at any institution in the country within 5 years of primary surgery were identified through the Swedish National Knee Ligament Registry.
UNASSIGNED: A total of 4697 patients (54.3% male) with available KT-1000 arthrometer measurements were included (normal: side-to-side [STS] ≤2 mm, 3015 [64.2%]; nearly normal: STS 3-5 mm, 1446 [30.8%]; abnormal: STS >5 mm, 236 [5.0%]). The only significant difference in subjective knee outcome between the groups was for the KOOS Symptoms subscale at the 1-year follow-up (STS ≤2 mm, 79.9 ± 16.2; STS 3-5 mm, 82.5 ± 14.8; STS >5 mm, 85.1 ± 14.2; P < .001). No other significant differences between the groups were found preoperatively or at 1, 2, or 5 years postoperatively for any of the KOOS subscales. The hazard for revision ACLR within 5 years of the primary surgery was significantly higher for the groups with an STS of 3 to 5 mm (6.6%; 95/1446) (hazard ratio [HR], 1.42; 95% CI, 1.07-1.87; P = .01) and an STS >5 mm (11.4%; 27/236) (HR, 2.61; 95% CI, 1.69-4.03; P < .001) compared with the group with an STS ≤2 mm (3.8%; 116/3015).
UNASSIGNED: A high grade of postoperative knee laxity (STS 3-5 mm and STS >5 mm) 6 months after primary ACLR was associated with an increased hazard of revision ACLR within 5 years, but it was not associated with an inferior subjective knee outcome.

BACKGROUND: The use of continuous passive motion therapy (CPM) has led to promising results in the early phase of rehabilitation after surgical treatment of rotator cuff tears and arthrolysis of the elbow. However, its use has not been proven in other pathologies of the upper extremity. Therefore, the aim of the underlying study was to evaluate the use of CPM therapy after plate osteosynthesis of proximal humeral fractures.
METHODS: 95 patients with isolated proximal humerus fractures were enrolled in a prospective, randomized study. Patients were assigned to a treatment group with (n = 48, CPM) or without CPM therapy (n = 47, CG). Four patients (2 of each cohort) violated the study protocol and were excluded. CPM therapy was used for 6 weeks after surgery 2-3 times daily. Functional (range of motion) and patient reported outcomes (PROM, Constant Score [CSS], QuickDASH, subjective shoulder value [SSV], pain on visual analogue scale [VAS]) were evaluated at 6 weeks, 3 and 12months. 60 patients completed the 1-year follow-up.
RESULTS: The average patient age was 65.3 years (min: 27, max: 88, SD: ± 14.7). Seventy-two patients were female (79%). There was no difference regarding injury severity (2/3/4 part-fracture: 6/32/7 vs. 9/26/11, p = 0.867) and sex (p = 0.08). However, patients in the CPM group were significantly younger (CPM: 67 [min: 34, max: 82], CG: 74 [min: 27, max: 88], p = 0.032). After 6 weeks we observed a better range of motion for forward flexion (CPM: 90° [min: 50°, max: 180°] vs. CG: 80° [min: 20°, max: 170°] p = 0.035) and abduction (CPM: 80° [min: 40°, max: 180°] vs. CG: 70° [min: 20°, max: 180°], p = 0.048) in the CPM group. There was no difference regarding the further planes of motion or the assessed PROMs at 6 weeks. At 3 and 12 months the results between the treatment groups equalized with no further significant differences.
CONCLUSIONS: The treatment with CPM increases the range of motion after plate osteosynthesis of proximal humerus fractures in the first 6 weeks after surgery. This effect is not sustained after 3 and 12months. The evaluated PROMs are not being influenced by CPM therapy. Hence the results of this prospective randomized study suggest that CPM can be a beneficial asset in the early period of rehabilitation after proximal humerus plate osteosynthesis.
BACKGROUND: The study protocol was registered in the US National Institutes of Health\'s database ( http://www.
RESULTS: gov ) registry under NCT05952622.

BACKGROUND: Spasticity is common after a stroke and is an independent risk factor for developing pain. BotulinumtoxinA injection is the treatment of choice for focal spasticity. We examined the effect of intramuscular botulinumtoxinA on pain relief in patients in routine clinical practice who were experiencing pain as a primary complaint associated with post-stroke lower limb spasticity.
METHODS: Prospective, multicentre, post-marketing observational study. The study period was 16 months. The primary effectiveness variable was the mean change from baseline on the pain 0-10 Numerical Rating Scale after four botulinumtoxinA injection cycles. Secondary endpoints included changes from baseline on the pain 0-100 Visual Analogue Scale, Goal Attainment Scale, modified Ashworth Scale, 10-Meter Walk Test, Penn Spasm Frequency Scale, and 36-item Short-Form Health Survey.
RESULTS: Of 186 enrolled patients, 180 (96.8%) received botulinumtoxinA at least once. The mean (standard deviation) pain 0-10 Numerical Rating Scale score decreased significantly (p<0.0001) from 4.9 (2.2) at baseline to 2.5 (2.1) at study end, representing a 50% decrease in pain severity. Relief of pain due to spasticity was supported by improvement from baseline in all secondary variables except the 10-Meter Walk Test. Two adverse events (erysipelas and phlebitis) in one patient were considered likely to be related to botulinumtoxinA injection.
CONCLUSIONS: BotulinumtoxinA appears to provide pain relief as an additional benefit of local treatment in patients with post-stroke lower limb spasticity for whom pain relief is a primary therapeutic goal (a Lay Abstract has been provided as Appendix A).

BACKGROUND: Chemotherapy (CT) remains a backbone treatment of epithelial ovarian cancer (EOC) inducing persistent peripheral neuropathy (CIPN). Using a dedicated patient-reported outcome tool, this study investigated persistent CIPN and its pharmacogenetic predictors in a cohort of long-term EOC survivors.
METHODS: Vivrovaire was a French multicenter cohort of patients with EOC free of disease 3 years after CT completion. Persistent CIPN was assessed using the FACT/GOG-Ntx4 self-questionnaire. The association of homozygous (hom) or heterozygous (het) single nucleotide polymorphisms (SNPs) in selected genes was evaluated.
RESULTS: 130 patients were included with a median time from CT completion of 63 [35-180] months. The median CIPN score was 37 [18-44], with 35 (26.9%) patients reporting severe CIPN (<33). SNPs were identified as follows: CYP2C8 [hom, n = 32 (24.6%)/het, n = 99, (76.2%)]; CYP3A4 [hom, n = 0 (0%)/het, n = 8 (6.2%)], ERCC1 [hom, n = 21 (16.2%)/het, n = 57 (43.8%)], and XPC [hom, n = 45 (34.6%)/het, n = 66 (50.8%)]. In univariate analysis, the identification of ≥1 hom SNP was associated with a lower CIPN score (continuous variable; p = 0.045). Patients harboring hom or het CYP2C8_rs1934951 SNP reported more likely severe CIPN (threshold <33) score (OR 2.482; 95% CI [1.126-5.47], p = 0.024). In the multivariate analyses, age, interval from CT completion, type and number of CT courses were not significantly associated with CIPN score (OR 5.165, 95% CI [0.478-55.83], p = 0.176).
CONCLUSIONS: Persistent CIPN is common among ovarian cancer long-term survivors. CYP2C8_rs1934951 SNP may be associated with severe residual CIPN in EOC survivors. More studies are warranted to identify predictive factors of CIPN.

Objective: Determine the validity and reliability of the LIMB-Q scales, Function, and Symptoms in patients with chronic lower extremity wounds. Approach: Cognitive debriefing interviews with people with current or previous wounds were conducted to examine content validity. Scales were field-tested in an international sample of people with chronic lower extremity wounds sourced from an online platform (i.e., Prolific). Psychometric properties were examined using the Rasch Measurement Theory analysis. A test-retest reproducibility study was performed, and construct validity was examined. Results: Content validity was established after 10 cognitive interviews. A total of 233 people with lower extremity wounds (age 19-80 years, mean 39.3) participated in the field test. All 25 items tested demonstrated good fit to the Rasch model with ordered thresholds. One item had a fit residual outside ±2.5, but no items had significant χ2 values after Bonferroni adjustment. Reliability was high with the person separation index, Cronbach alpha, and intraclass correlation coefficient values >0.8. Strong correlations were found between the Function and Symptoms scales and EQ-5D dimensions measuring similar constructs as well as the EQ-5D global score. All hypotheses for construct validity were confirmed. Innovation: Patient-reported outcome measures are an important component of patient-centered care, as they capture the patient\'s perspective in a rigorous and reproducible way. Adding these two scales to the WOUND-Q provides a means to measure function and symptoms associated with lower extremity wounds. Conclusion: These new WOUND-Q scales can be used to measure outcomes important to patients with lower extremity wounds in clinical settings and research studies.

BACKGROUND: Abemaciclib-induced diarrhea is a relevant concern in clinical practice. Postbiotics have emerged as a promising option for managing it.
METHODS: We conducted a retrospective-prospective, 2-group, observational study to assess the impact of the postbiotic PostbiotiX-Restore, derived by Lactobacillus paracasei CNCM I-5220, on abemaciclib-induced diarrhea in patients with hormone receptor-positive HER2-negative breast cancer. The prospective population (Postbio group) received postbiotic during the first cycle of abemaciclib, while the retrospective one received standard care (Standard group). Diarrhea grading was defined according to the National Cancer Institute\'s Common Terminology Criteria for Adverse Events.
RESULTS: During the first cycle, diarrhea occurred in 78.9% of patients in the Standard cohort and 97.1% in the Postbio one, with most cases being G1-G2. Severe (G3) diarrhea was significantly less frequent in the Postbio group (0%) compared to the Standard one (7.9%; P = .029). Over the entire study period, while the grading difference was not statistically significant, G3 events were less frequent in the Postbio population (5.9%) than the Standard one (15.4%). Moreover, Postbio patients required fewer dose reductions due to diarrhea compared to the Standard group (P = .002). Notably, in the Postbio population, G1 and G2 events had short median durations (3 and 1 days, respectively) and, for the 2 patients experiencing G3 events during the second abemaciclib cycle (off postbiotic), diarrhea lasted only 1 day.
CONCLUSIONS: Our study demonstrates the effect of PostbiotiX-Restore in mitigating abemaciclib-induced diarrhea, resulting in reduced severity, fewer dose reductions, and shorter duration. Further exploration and validation in larger cohorts are needed.

UNASSIGNED: Health-related quality of life (HRQoL), along with overall survival (OS), is a critical study endpoint for measuring the clinical benefits of cancer drugs. Previous studies have examined the OS benefit of new cancer drugs approved in China. However, their HRQoL benefits have not been systematically evaluated. We aimed to characterise the measurement and improvement of HRQoL associated with cancer drugs approved in China.
UNASSIGNED: This mixed-methods study comprises of a literature review and a cross-sectional study, including all antineoplastic agents approved in China between January 1, 2005 and December 31, 2020. A systematic search was conducted on December 31, 2023 to extract HRQoL information of identified drugs. We extracted information on the characteristics of HRQoL assessment and statistically significant HRQoL gains compared with the control treatment.
UNASSIGNED: A total of 64 novel cancer drugs, corresponding to 115 cancer indications, supported by randomised clinical trials were approved in China between 2005 and 2020. Among the indications, 78 (67.8%) used HRQoL as an endpoint in the pivotal trial. By December 31, 2023, after a median follow-up of 5.3 (range, 3.0-18.8) years from approval, HRQoL information was available for more than half of the indications (75, 65.2%). Thirty-three indications (28.7%) reported statistically significant improvement in HRQoL, with 22 (19.1%) also having documented OS benefit. Approximately one-third of the indications (39, 33.9%) showed no difference in HRQoL, with 21 (18.3%) having documented OS gains. Three indications (2.6%) reported worsening HRQoL. The most commonly used HRQoL measurements were individual disease-specific instruments (62 of 75, 82.7%) while the most frequently employed analysis metric was the mean change scores from baseline (56 of 75, 74.7%).
UNASSIGNED: Fewer than one-third of cancer indications approved in China had shown HRQoL improvements. There was considerable heterogeneity in the analysis and reporting of HRQoL benefits associated with new cancer drugs approved in China. These findings emphasise the important role of HRQoL evaluation and analysis in clinical research and the necessity of improving the standardization of HRQoL assessment.
UNASSIGNED: National Natural Science Foundation of China (72274004).