Responsiveness of five condition-specific and generic outcome assessment instruments for chronic pain

<p>Abstract</p> <p>Background</p> <p>Changes of health and quality-of-life in chronic conditions are mostly small and require specific and sensitive instruments. The aim of this study was to determine and compare responsiveness, i.e. the sensitivity to change of five outcome instruments for effect measurement in chronic pain.</p> <p>Methods</p> <p>In a prospective cohort study, 273 chronic pain patients were assessed on the Numeric Rating Scale (NRS) for pain, the Short Form 36 (SF-36), the Multidimensional Pain Inventory (MPI), the Hospital Anxiety and Depression Scale (HADS), and the Coping Strategies Questionnaire (CSQ). Responsiveness was quantified by effect size (ES) and standardized response mean (SRM) before and after a four week in-patient interdisciplinary pain program and compared by the modified Jacknife test.</p> <p>Results</p> <p>The MPI measured pain more responsively than the SF-36 (ES: 0.85 vs 0.72, p = 0.053; SRM: 0.72 vs 0.60, p = 0.027) and the pain NRS (ES: 0.85 vs 0.62, p < 0.001; SRM: 0.72 vs 0.57, p = 0.001). Similar results were found for the dimensions of role and social interference with pain. Comparison in function was limited due to divergent constructs. The responsiveness of the MPI and the SF-36 was equal for affective health but both were better than the HADS (e.g. MPI vs HADS depression: ES: 0.61 vs 0.43, p = 0.001; SF-36 vs HADS depression: ES: 0.54 vs 0.43, p = 0.004). In the "ability to control pain" coping dimension, the MPI was more responsive than the CSQ (ES: 0.46 vs 0.30, p = 0.011).</p> <p>Conclusion</p> <p>The MPI was most responsive in all comparable domains followed by the SF-36. The pain-specific MPI and the generic SF-36 can be recommended for comprehensive and specific bio-psycho-social effect measurement of health and quality-of-life in chronic pain.</p

Effect of resistance training on muscle properties and function in women with generalized joint hypermobility: a single-blind pragmatic randomized controlled trial.

BACKGROUND Generalized joint hypermobility is defined as an excessive range of motion in several joints. Having joint hypermobility is not a pathology, but when associated with pain and other symptoms, it might affect health and function. Evidence for physiotherapy management is sparse and resistance training might be a possible intervention. Thus, the effects of 12-week resistance-training on muscle properties and function in women with generalized joint hypermobility were evaluated. METHODS In this single-blind randomized controlled trial women between 20 and 40 years with generalized joint hypermobility (Beighton score at least 6/9) were included. Participants were randomly allocated to 12-week resistance training twice weekly (experimental) or no lifestyle change (control). Resistance training focused on leg and trunk muscles. Primary outcome was muscle strength; additional outcomes included muscle properties, like muscle mass and density, functional activities, pain and disability. Training adherence and adverse events were recorded. RESULTS Of 51 participating women 27 were randomised to training and 24 into the control group. In each group 11 women had joint hypermobility syndrome, fulfilling the Brighton criteria, while 24 (89%) in the training group and 21 (88%) in the control group mentioned any pain. The mean strength of knee extensors varied in the training group from 0.63 (sd 0.16) N/bm before training to 0.64 (sd 0.17) N/bm after training and in the control group from 0.53 (sd 0.14) N/bm to 0.54 (sd 0.15) N/bm. For this and all other outcome measures, no significant differences between the groups due to the intervention were found, with many variables showing high standard deviations. Adherence to the training was good with 63% of participants performing more than 80% of sessions. One adverse event occurred during training, which was not clearly associated to the training. Four participants had to stop the training early. CONCLUSIONS No improvement in strength or muscle mass by self-guided resistance training was found. Low resistance levels, as well as the choice of outcome measures were possible reasons. A more individualized and better guided training might be important. However, program adherence was good with few side effects or problems triggered by the resistance training. TRIAL REGISTRATION This trial was prospectively registered in the ISRCTN registry ( www.isrctn.com , BMC, Springer Nature) on July 16, 2013 as ISRCTN90224545 . The first participant was enrolled at October 25, 2013

Exercise and other non-pharmaceutical interventions for cancer-related fatigue in patients during or after cancer treatment : a systematic review incorporating an indirect-comparisons meta-analysis

Aim: To assess the relative effects of different types of exercise and other non-pharmaceutical interventions on cancer-related fatigue (CRF) in patients during and after cancer treatment. Design: Systematic review and indirect-comparisons meta-analysis. Data sources: Articles were searched in PubMed, Cochrane CENTRAL and published meta-analyses. Eligibility criteria for selecting studies: Randomised studies published up to January 2017 evaluating different types of exercise or other non-pharmaceutical interventions to reduce CRF in any cancer type during or after treatment. Study appraisal and synthesis: Risk of bias assessment with PEDro criteria and random effects Bayesian network meta-analysis. Results: We included 245 studies. Comparing the treatments with usual care during cancer treatment, relaxation exercise was the highest ranked intervention with a standardised mean difference (SMD) of −0.77 (95% Credible Interval (CrI) −1.22 to −0.31), while massage (−0.78; −1.55 to −0.01), cognitive–behavioural therapy combined with physical activity (combined CBT, −0.72; −1.34 to −0.09), combined aerobic and resistance training (−0.67; −1.01 to −0.34), resistance training (−0.53; −1.02 to −0.03), aerobic (−0.53; −0.80 to −0.26) and yoga (−0.51; −1.01 to 0.00) all had moderate-to-large SMDs. After cancer treatment, yoga showed the highest effect (−0.68; −0.93 to −0.43). Combined aerobic and resistance training (−0.50; −0.66 to −0.34), combined CBT (−0.45; −0.70 to −0.21), Tai-Chi (−0.45; −0.84 to −0.06), CBT (−0.42; −0.58 to −0.25), resistance training (−0.35; −0.62 to −0.08) and aerobic (−0.33; −0.51 to −0.16) showed all small-to-moderate SMDs. Conclusions: Patients can choose among different effective types of exercise and non-pharmaceutical interventions to reduce CRF

Effect of goal-directed mobilisation intervention compared with standard care on physical activity among medical inpatients: protocol for the GoMob-in randomised controlled trial.

INTRODUCTION Despite the fact that immobilisation is a major contributor to morbidity and mortality, patients hospitalised in general internal medicine (GIM) wards spend up to 50% of time in bed. Previous studies in selected patient populations showed increased mobility after implementation of goal-directed mobilisation (GDM). Due to the study design used so far, the degree of evidence is generally low. The effect of GDM on clinical outcomes and economically relevant indicators in patients hospitalised in GIM wards is currently unknown. This study aims to evaluate a GDM intervention compared to standard care on physical activity (de Morton Mobility Index, DEMMI) in medical inpatients. METHODS AND ANALYSIS GoMob-in is a randomised, controlled, open-label study with blinded outcome assessment. We plan to enrol 160 inpatients with indication for physiotherapy on GIM wards of a tertiary hospital in Bern, Switzerland. Adult patients newly hospitalised on GIM wards will be included in the study. The primary outcome will be the change in the DEMMI score between baseline and 5 days. Secondary outcomes are change of DEMMI (inclusion to hospital discharge), mobilisation time (inclusion to day 5, inclusion to discharge), in-hospital delirium episodes, number of in-hospital falls, length of stay, number of falls within 3 months, number of re-hospitalisations and all-cause mortality within 3 months, change in independence during activities of daily living, concerns of falling, and quality of life within 3 months and destination after 3 months. Patients in the intervention group will be attributed a regularly updated individual mobility goal level made visible for all stakeholders and get a short educational intervention on GDM. ETHICS AND DISSEMINATION This study has been approved by the responsible Ethics Board (Ethikkommission Bern/2020-02305). Written informed consent will be obtained from participants before study inclusion. Results will be published in open access policy peer-reviewed journals. TRIAL REGISTRATION NUMBER NCT04760392

Effects of early, combined endurance and resistance training in mechanically ventilated, critically ill patients: a study protocol for a randomised controlled trial.

BACKGROUND Prolonged need for intensive care is associated with neuromuscular weakness, termed Intensive Care Unit Acquired Weakness. Those affected suffer from severe functional impairment that can persist for years. First studies suggest a positive effect of physiotherapy and early mobilisation. However, the ideal intervention for a preferential functional outcome is not known. So far no randomised controlled trial has been conducted to specifically evaluate an early endurance and resistance training in the mechanically ventilated, critically ill patient. METHODS/DESIGN A randomised controlled trial with blinded assessors and 6-month follow-up will be conducted in a tertiary, interdisciplinary intensive care unit in Switzerland. Participants (n = 115; expected dropouts: n = 15) will be randomised to a control group receiving standard physiotherapy and to an experimental group that undergoes early mobilisation combined with endurance and resistance training. The inclusion criteria are being aged 18 years or older, expected mechanical ventilation for more than 72 h and qualitative independence before the illness. Primary endpoints are functional capacity (6-Minute Walk Test) and the ability to perform activities of daily living (Functional Independence Measure) measured at hospital discharge. Secondary endpoints include muscle strength (Medical Research Council sum score, handgrip strength and handheld dynamometry for quadriceps muscle), joint contractures (range of motion), exercise capacity (Timed 'Up & Go' Test) and health-related quality of life (Short Form 36). Safety will be monitored during interventions by indirect calorimetry and continuous intensive care standard monitoring. All previously defined adverse events will be noted. The statistical analysis will be by intention-to-treat with the level of significance set at p < 0.05. DISCUSSION This prospective, single-centre, allocation-concealed and assessor-blinded randomised controlled trial will evaluate participant's function after an early endurance and resistance training compared to standard care. Limitations of this study are the heterogeneity of the critically ill and the discontinuity of the protocol after relocation to the ward. The strengths lie in the pragmatic design and the clinical significance of the chosen outcome measures. TRIAL REGISTRATION German Clinical Trials Register (DRKS): DRKS00004347 , registered on 10 September 2012

Outcomes after cardiac rehabilitation in patients following repair of thoracic aortic aneurysm or dissection: a protocol for a systematic review and meta-analysis.

BACKGROUND Patients receiving thoracic aortic repair suffer from long-term impairment in daily functioning and quality of life following intervention due to a combination of their life-threatening condition (i.e. aortic aneurysm or dissection), undergoing major surgery, as well as long-term exercise restrictions thereafter. Despite the known risks of exercise, it is vital that patients regain physical activity in order to recover their daily functioning and quality of life. Cardiac rehabilitation could be a safe and effective treatment to support patients to become physically active by providing exercise training, comprehensive rehabilitation services, and safety recommendations. Despite new insights in recent literature and clinical practice, international guidelines do not recommend cardiac rehabilitation due to limited evidence. We aim to fill this knowledge gap by performing a systematic review and meta-analysis on the effectiveness of cardiac rehabilitation in patients following thoracic aortic repair. METHODS This protocol has been developed following the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P). MEDLINE, Embase, and CINAHL will be searched for eligible observational and interventional studies from inception up to April 2022. Screening (title/abstract and full text), data extraction, risk of bias assessment, and therapeutic validity rating will be conducted by two independent reviewers. A random-effects model will be used to meta-analyse performance-based outcomes, patient-reported outcomes, clinician-reported outcomes, and researcher-reported outcomes. Subsequently, meta-bias and confidence in evidence will be analysed by two independent reviewers. DISCUSSION To exercise or not to exercise in patients following thoracic aortic repair has been a topic of discussion for years. The intended systematic review and meta-analysis will provide comprehensive evidence on the effectiveness of phase III outpatient exercise-based cardiac rehabilitation in patients following thoracic aortic repair. Findings from this review may inform future guidelines for the management of patients with thoracic aortic disease. SYSTEMATIC REVIEW REGISTRATION PROSPERO CRD42022301204

Differences in pain, function and coping in Multidimensional Pain Inventory subgroups of chronic back pain: a one-group pretest-posttest study

Contains fulltext : 97819.pdf (publisher's version ) (Open Access)BACKGROUND: Patients with non-specific back pain are not a homogeneous group but heterogeneous with regard to their bio-psycho-social impairments. This study examined a sample of 173 highly disabled patients with chronic back pain to find out how the three subgroups based on the Multidimensional Pain Inventory (MPI) differed in their response to an inpatient pain management program. METHODS: Subgroup classification was conducted by cluster analysis using MPI subscale scores at entry into the program. At program entry and at discharge after four weeks, participants completed the MPI, the MOS Short Form-36 (SF-36), the Hospital Anxiety and Depression Scale (HADS), and the Coping Strategies Questionnaire (CSQ). Pairwise analyses of the score changes of the mentioned outcomes of the three MPI subgroups were performed using the Mann-Whitney-U-test for significance. RESULTS: Cluster analysis identified three MPI subgroups in this highly disabled sample: a dysfunctional, interpersonally distressed and an adaptive copers subgroup. The dysfunctional subgroup (29% of the sample) showed the highest level of depression in SF-36 mental health (33.4 +/- 13.9), the interpersonally distressed subgroup (35% of the sample) a modest level of depression (46.8 +/- 20.4), and the adaptive copers subgroup (32% of the sample) the lowest level of depression (57.8 +/- 19.1). Significant differences in pain reduction and improvement of mental health and coping were observed across the three MPI subgroups, i.e. the effect sizes for MPI pain reduction were: 0.84 (0.44-1.24) for the dysfunctional subgroup, 1.22 (0.86-1.58) for the adaptive copers subgroup, and 0.53 (0.24-0.81) for the interpersonally distressed subgroup (p = 0.006 for pairwise comparison). Significant score changes between subgroups concerning activities and physical functioning could not be identified. CONCLUSIONS: MPI subgroup classification showed significant differences in score changes for pain, mental health and coping. These findings underscore the importance of assessing individual differences to understand how patients adjust to chronic back pain

Dendritic Cell Based Tumor Vaccination in Prostate and Renal Cell Cancer: A Systematic Review and Meta-Analysis

BACKGROUND: More than 200 clinical trials have been performed using dendritic cells (DC) as cellular adjuvants in cancer. Yet the key question whether there is a link between immune and clinical response remains unanswered. Prostate and renal cell cancer (RCC) have been extensively studied for DC-based immunotherapeutic interventions and were therefore chosen to address the above question by means of a systematic review and meta-analysis. METHODOLOGY/PRINCIPAL FINDINGS: Data was obtained after a systematic literature search from clinical trials that enrolled at least 6 patients. Individual patient data meta-analysis was performed by means of conditional logistic regression grouped by study. Twenty nine trials involving a total of 906 patients were identified in prostate cancer (17) and RCC (12). Objective response rates were 7.7% in prostate cancer and 12.7% in RCC. The combined percentages of objective responses and stable diseases (SD) amounted to a clinical benefit rate (CBR) of 54% in prostate cancer and 48% in RCC. Meta-analysis of individual patient data (n = 403) revealed the cellular immune response to have a significant influence on CBR, both in prostate cancer (OR 10.6, 95% CI 2.5-44.1) and in RCC (OR 8.4, 95% CI 1.3-53.0). Furthermore, DC dose was found to have a significant influence on CBR in both entities. Finally, for the larger cohort of prostate cancer patients, an influence of DC maturity and DC subtype (density enriched versus monocyte derived DC) as well as access to draining lymph nodes on clinical outcome could be demonstrated. CONCLUSIONS/SIGNIFICANCE: As a 'proof of principle' a statistically significant effect of DC-mediated cellular immune response and of DC dose on CBR could be demonstrated. Further findings concerning vaccine composition, quality control, and the effect of DC maturation status are relevant for the immunological development of DC-based vaccines

Whole exome re-sequencing implicates CCDC38 and cilia structure and function in resistance to smoking related airflow obstruction

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality and, whilst smoking remains the single most important risk factor, COPD risk is heritable. Of 26 independent genomic regions showing association with lung function in genome-wide association studies, eleven have been reported to show association with airflow obstruction. Although the main risk factor for COPD is smoking, some individuals are observed to have a high forced expired volume in 1 second (FEV1) despite many years of heavy smoking. We # hypothesised that these ‘‘resistant smokers’’ may harbour variants which protect against lung function decline caused by smoking and provide insight into the genetic determinants of lung health. We undertook whole exome re sequencing of 100 heavy smokers who had healthy lung function given their age, sex, height and smoking history and applied three complementary approaches to explore the genetic architecture of smoking resistance. Firstly, we identified novel functional variants in the ‘‘resistant smokers’’ and looked for enrichment of these novel variants within biological pathways. Secondly, we undertook association testing of all exonic variants individually with two independent control sets. Thirdly, we undertook gene-based association testing of all exonic variants. Our strongest signal of association with smoking resistance for a non-synonymous SNP was for rs10859974 (P = 2.3461024) in CCDC38, a gene which has previously been reported to show association with FEV1/FVC, and we demonstrate moderate expression of CCDC38 in bronchial epithelial cells. We identified an enrichment of novel putatively functional variants in genes related to cilia structure and function in resistant smokers. Ciliary function abnormalities are known to be associated with both smoking and reduced mucociliary clearance in patients with COPD. We suggest that genetic influences on the development or function of cilia in the bronchial epithelium may affect growth of cilia or the extent of damage caused by tobacco smoke

Adrenal function recovery after durable oral corticosteroid sparing with benralizumab in the PONENTE study

Background Oral corticosteroid (OCS) dependence among patients with severe eosinophilic asthma can cause adverse outcomes, including adrenal insufficiency. PONENTE's OCS reduction phase showed that, following benralizumab initiation, 91.5% of patients eliminated corticosteroids or achieved a final dosage ≤5 mg·day-1 (median (range) 0.0 (0.0-40.0) mg). Methods The maintenance phase assessed the durability of corticosteroid reduction and further adrenal function recovery. For ~6 months, patients continued benralizumab 30 mg every 8 weeks without corticosteroids or with the final dosage achieved during the reduction phase. Investigators could prescribe corticosteroids for asthma exacerbations or increase daily dosages for asthma control deteriorations. Outcomes included changes in daily OCS dosage, Asthma Control Questionnaire (ACQ)-6 and St George's Respiratory Questionnaire (SGRQ), as well as adrenal status, asthma exacerbations and adverse events. Results 598 patients entered PONENTE; 563 (94.1%) completed the reduction phase and entered the maintenance phase. From the end of reduction to the end of maintenance, the median (range) OCS dosage was unchanged (0.0 (0.0-40.0) mg), 3.2% (n=18/563) of patients experienced daily dosage increases, the mean ACQ-6 score decreased from 1.26 to 1.18 and 84.5% (n=476/563) of patients were exacerbation free. The mean SGRQ improvement (-19.65 points) from baseline to the end of maintenance indicated substantial quality-of-life improvements. Of patients entering the maintenance phase with adrenal insufficiency, 32.4% (n=104/321) demonstrated an improvement in adrenal function. Adverse events were consistent with previous reports. Conclusions Most patients successfully maintained maximal OCS reduction while achieving improved asthma control with few exacerbations and maintaining or recovering adrenal function