OBJECTIVE: Physicians tend to focus on biomedical targets while little is known about issues important to patients. We aimed to identify critical concepts impacting patients with inflammatory bowel disease (IBD).

DESIGN: We performed a survey of patients with IBD in biologic therapy (n=172) and used a validated qualitative method called group concept mapping (GCM) in patient workshops. The survey included 13 questions on attitudes toward symptoms and issues related to IBD. In the eight workshops, patients (n=26) generated statements later clustered into concepts identifying issues impacting a patient's life. Patients ranked the statements.

RESULTS: In the survey, patients' mean age were 40 years (SD 13), 53% were women, and 38% had ulcerative colitis. They identified fatigue (57%) and stool frequency (46%) as the most critical symptoms impacting their daily lives regardless of disease activity. In the GCM workshops with Crohn's disease (n=13) (median age 42 years (IQR 39-51) and 62% were women), 335 statements divided among 10 concepts were generated, and the three most important concepts were 'Positive attitudes', 'Accept and recognition', and 'Sharing knowledge and experiences in life with Crohn's disease'. In the workshops with ulcerative colitis (n=13) (median age 43 years (IQR 36-49) and 69% were women), 408 statements divided into 11 concepts were generated; the most important concepts were 'Take responsibility and control over your life', 'Medication', and 'Everyday life with ulcerative colitis'.

CONCLUSION: Focusing solely on IBD symptoms, patients identified fatigue and stool frequency to impact daily life the most. However, when investigating the disease burden in a broader perspective beyond classic IBD symptoms, patients identified concepts with focus on emotional health to be most important.

TRIAL REGISTRATION: The Copenhagen University Hospital, Herlev and Gentofte approved the questionnaire and methodology (work-zone no: 18015429).

OBJECTIVE: Patients with inflammatory arthritis have a high risk of sleep disturbances and disorders. The objective was to evaluate the evidence of nonpharmacologic interventions targeting sleep disturbances or disorders in patients with inflammatory arthritis.

METHODS: A systematic search was undertaken from inception to September 8, 2020. We included randomized trials concerning nonpharmacologic interventions applied in adults with inflammatory arthritis and concomitant sleep disturbances or disorders. The primary outcome was the sleep domain, while secondary outcomes were core outcome domains for inflammatory arthritis trials and harms. The Cochrane Risk of Bias tool was applied, and the overall quality of the evidence was assessed using Grading of Recommendations Assessment, Development and Evaluation criteria. Effect sizes for continuous outcomes were based on the standardized mean difference, combined using random-effects meta-analysis.

RESULTS: Six trials (308 patients) were included in the quantitative synthesis; 3 of these reported improvement in sleep in favor of the nonpharmacologic interventions. The meta-analysis of the sleep domains indicated a large clinical effect of -0.80 (95% confidence interval -1.33, -0.28) in favor of nonpharmacologic interventions targeting sleep disturbances or disorders. The estimate was rated down twice for risk of bias and unexplained inconsistency; this risk was assessed as corresponding to low-quality evidence. None of the secondary core outcomes used in contemporary inflammatory arthritis trials indicated a clinical benefit in favor of nonpharmacologic interventions targeting sleep.

CONCLUSION: Nonpharmacologic interventions targeting sleep disturbances/disorders in patients with inflammatory arthritis indicated a promising effect on sleep outcomes, but not yet with convincing evidence.

BACKGROUND: Ankle sprain is the most common type of sports injury, especially in team sports. Standing and dynamic landing balance, as an indicator of ankle instability, were investigated using varying experimental approaches.

METHODS: In the present cross-sectional study, 81 adolescent female elite handball and football players were divided into two groups based on previous ankle sprain injury (PI) or not (C). At time of test, all players were fully returned to elite-level sport. Subjects were tested during a one-legged landing (OLL) and in a one-legged static standing balance test (OLBT). In the OLL CoP trajectory displacement was calculated in 200 ms time epochs for evaluation of the initial stages of dynamic landing balance. OLBT was evaluated by calculating total displacement of the CoP trajectory.

RESULTS: CoP displacement was greater in PI than C during the first 200 milliseconds epoch after landing (P=0.001, 252 mm [44], vs. 223 mm [28]), respectively) and in the subsequent 200 ms epoch (P=0.021, 72 mm [20], vs. 61 mm [16], respectively). No significant differences between PI and C were observed in time epochs from 400 to 1000 milliseconds or in OLBT.

CONCLUSIONS: Adolescent elite athletes with a history of previous ankle sprain demonstrate impaired OLL balance in the first 400 milliseconds following jump landing compared to non-injured controls. Consequently, although athletes with previous ankle sprain may return to sport, dynamic postural control may not be fully restored. Future prospective studies are needed to decide, if the OLL test could be considered a relevant criterion tool for safe return-to-sport.

OBJECTIVES: To evaluate the efficacy of intensive smoking cessation interventions (ISCIs) directly compared with shorter interventions (SIs), measured as successful quitting.

METHOD: Medline, Embase, the Cochrane Library and CINAHL were searched on 15 October 2021. Peer-reviewed randomised controlled trials (RCTs) of adult, daily smokers undergoing an ISCI were included. No setting, time or language restrictions were imposed. Risk of bias and quality of evidence was assessed using the Cochrane tool and Grading of Recommendations, Assessment, Development and Evaluation, respectively. Meta-analyses were conducted using a random-effects model.

RESULTS: 17 550 unique articles were identified and 17 RCTs evaluating 9812 smokers were included. 14 studies were conducted in Europe or the USA. The quality of the evidence was assessed as low or moderate. Continuous abstinence was significantly higher in ISCIs in the long term (risk ratio 2.60, 95% CI 1.71-3.97). Direction and magnitude were similar in the short term; however, they were not statistically significant (risk ratio 2.49, 95% CI: 0.94-6.56). When measured as point prevalence, successful quitting was still statistically significant in favour of ISCIs, but lower (long term: 1.64, 1.08-2.47; short term: 1.68, 1.10-2.56). Sensitivity analysis confirmed the robustness of the results.

CONCLUSION: ISCIs are highly effective compared to SIs. This important knowledge should be used to avoid additional morbidity and mortality caused by smoking.

No effective therapy exists for the most common long-term side effect of radiation therapy for head and neck cancer (HNC)-xerostomia. The objective was to evaluate safety and provide proof of concept for efficacy of allogeneic adipose tissue-derived mesenchymal stem/stromal cells (AT-MSCs) injected into the major salivary glands of irradiated patients. This open-label, first-in-human, phase 1b, and single-center trial was conducted with repeated measurements days 0, 1, 5, and 30 and 4 months. Eligible patients with objective and subjective signs of radiation-induced salivary gland damage after treatment of oropharyngeal squamous cell carcinoma stages I-II (UICC 8) were enrolled. Twenty-five million cryopreserved AT-MSCs were injected into each submandibular and 50 million AT-MSCs into each parotid gland. Data were collected on adverse events, unstimulated and stimulated whole saliva (UWS and SWS) flow rates and saliva composition, patient-reported outcomes (EORTC QLQ-H&N35 and Xerostomia Questionnaire [XQ]), blood samples and salivary gland scintigraphy. Data were analyzed using repeated measures linear mixed models. Ten patients (7 men, 3 women, 59.5 years [range: 45-70]) were treated in 4 glands. No treatment-related serious adverse events occurred. During 4 months, UWS flow rate increased from 0.13 mL/minute at baseline to 0.18 mL/minute with a change of 0.06 (P = .0009) mL/minute. SWS flow rate increased from 0.66 mL/minute at baseline to 0.75 mL/minute with a change of 0.09 (P = .017) mL/minute. XQ summary score decreased by 22.6 units (P = .0004), EORTC QLQ-H&N35 dry mouth domains decreased by 26.7 (P = .0013), sticky saliva 23.3 (P = .0015), and swallowing 10.0 (P = .0016). Our trial suggests treatment of the major salivary glands with allogenic AT-MSCs is safe, warranting confirmation in larger trials.

INTRODUCTION: Ixekizumab, a selective interleukin-17A antagonist, was compared with adalimumab in the SPIRIT-H2H study (NCT03151551) in patients with psoriatic arthritis (PsA) and concomitant psoriasis. This post hoc analysis reports outcomes to week 52 in patients from SPIRIT-H2H, stratified by baseline psoriasis severity.

METHODS: SPIRIT-H2H was a 52-week, multicenter, randomized, open-label, rater-blinded, parallel-group study of biologic disease-modifying antirheumatic drug (DMARD)-naïve patients (N = 566) with PsA and active psoriasis (≥ 3% body surface area involvement). Patients were randomized to ixekizumab or adalimumab (1:1) with stratification by baseline concomitant use of conventional synthetic DMARDs and psoriasis severity (with/without moderate-to-severe psoriasis). Patients received on-label dosing according to psoriasis severity. The primary endpoint was the proportion of patients simultaneously achieving ≥ 50% improvement in American College of Rheumatology criteria (ACR50) and 100% improvement in Psoriasis Area Severity Index (PASI100) at week 24. Secondary endpoints included musculoskeletal, disease activity (defined by composite indices), skin and nail, quality of life and safety outcomes. In this post hoc analysis, primary and secondary endpoints of SPIRIT-H2H were analyzed by baseline psoriasis severity.

RESULTS: A greater proportion of patients achieved the combined endpoint of ACR50 + PASI100 and PASI100 with ixekizumab compared with adalimumab at weeks 24 and 52, regardless of baseline psoriasis severity. ACR response rates were similar for ixekizumab and adalimumab across both patient subgroups. For musculoskeletal outcomes, similar efficacy was seen for ixekizumab and adalimumab, but ixekizumab showed greater responses for skin outcomes regardless of psoriasis severity. The safety profiles of ixekizumab and adalimumab were consistent between subgroups.

CONCLUSIONS: Regardless of baseline psoriasis severity, ixekizumab demonstrated greater efficacy than adalimumab with respect to simultaneous achievement of ACR50 + PASI100, and showed consistent and sustained efficacy across PsA-related domains. It also demonstrated higher response rates for skin outcomes. These subgroup analyses highlight the efficacy of ixekizumab in patients with PsA irrespective of the severity of concomitant psoriasis.

PURPOSE: Mesenchymal stem/stromal cell therapy may reduce radiation-induced xerostomia. We investigated the long-term safety of autologous adipose tissue-derived mesenchymal stem/stromal cell (ASC) injections into the submandibular glands.

EXPERIMENTAL DESIGN: An investigator-initiated, randomized, single-center, placebo-controlled trial. Previous patients with oropharyngeal squamous cell carcinoma with radiation-induced xerostomia were randomly (1:1) allocated to receive a 2.8 million ASCs/cm3 injection or placebo in both submandibular glands and followed for a minimum of 2 years. The primary endpoint was number of serious adverse events (SAE). Secondary endpoints included whole saliva flow rates and xerostomia-related symptoms. Data analysis was based on the intention-to-treat population using repeated measures mixed-effects linear models.

RESULTS: Thirty-three patients were randomized; 30 patients were treated (ASC group, n = 15; placebo group, n = 15). Long-term safety data were collected from all 30 patients. During follow-up, 6 of 15 (40%) of the ASC-treated patients versus 5 of 15 (33%) of the placebo patients experienced an SAE; no SAEs appeared to be treatment related. Unstimulated whole saliva flow rate increased to 0.20 and 0.16 mL/minute in the ASC and placebo group, respectively, yielding a 0.05 mL/minute (95% confidence interval: 0.00-0.10; P = 0.051) difference between groups. Patient-reported xerostomia symptoms diminished according to a decreased xerostomia questionnaire summary score of 35.0 and 45.1, respectively [-10.1 (-18.1 to -2.2); P = 0.013]. Three of the visual analog scale xerostomia measures indicated clinical benefit following use of ASC.

CONCLUSIONS: Our data show that ASC therapy is safe with a clinically relevant effect on xerostomia-related symptoms. Confirmation in larger randomized controlled trials is warranted.

Objectives: The aim of this mixed-method study was to explore maintenance of physical activity and health effects one year after completion of exercise interventions in transport and leisure-time domains of everyday life. We hypothesised that routinisation of active commuting would lead to better maintenance of physical activity and health effects compared with leisure-time exercise. Study design: Mixed-methods follow-up study. Methods: Individuals with overweight/obesity, who completed a 6-month exercise intervention (active commuting by bike (BIKE), moderate (MOD) or vigorous intensity leisure-time exercise (VIG)), were after one year invited to participate in a follow-up visit which included measurements of cardiorespiratory fitness during an incremental bicycle test and body composition using dual-energy X-ray absorptiometry. Variability in maintenance practices was assessed in a sub-sample of participants who experienced the greatest improvements (‘VO₂peak improvers’) and reductions (‘VO₂peak reducers’), respectively, in cardiorespiratory fitness. Semi-structured interviews were conducted (15–30 min) and analysed using systematic text condensation to identify barriers and facilitators associated with maintenance of physical activity. Results: Out of the 74 participants completing an exercise intervention, 46 (62%) completed follow-up (BIKE: n = 14; MOD: n = 14; VIG: n = 18). Improvements in VO₂peak and reductions in fat mass were maintained in BIKE and VIG. Body weight decreased in BIKE and fat free mass increased in VIG. Changes in VO₂peak and anthropometry at follow-up did not differ between BIKE and MOD + VIG. Fat mass decreased and recreational physical activity increased in ‘VO₂peak improvers’. Findings from the interviews suggested that self-monitoring, collective exercising, and new personal exercise challenges facilitate maintenance of a physically active lifestyle. Conclusion: Completion of a structured exercise intervention consisting of 6 months of active commuting or vigorous intensity leisure-time exercise was associated with long-term maintenance of improvements in VO₂peak and body composition, whereas moderate intensity leisure-time exercise was not. In contrast to our hypothesis, active commuting was not associated with better maintenance of physical activity and health effects after the intervention compared with leisure-time exercise.