Manual lymphatic drainage and quality of life in patients with lymphoedema and mixed oedema: a systematic review of randomised controlled trials.

PURPOSE: To assess the impact of manual lymphatic drainage (MLD) on the health-related quality of life (HRQoL) of adults with lymphoedema or mixed oedema, through a systematic review of randomised controlled trials (RCTs). METHODS: MEDLINE, EMBASE, PsycINFO, CENTRAL, the Cochrane Database of Systematic Reviews and ClinicalTrials.gov were searched to identify RCTs evaluating HRQoL after a MLD intervention compared to non-MLD interventions (PROSPERO 2016:CRD42016042255). We extracted the effect of the interventions on the HRQoL (primary outcome) as well as data on volume and functional changes, and adverse events when available (secondary outcomes). RESULTS: Eight studies were eligible. The studies were heterogeneous in the aetiology of oedema, schemes of MLD applied, additional treatments offered with MLD, length of follow-up, instruments used to assess HRQoL and interventions offered to the control group. Five studies included patients with breast cancer-related arm lymphoedema; one study reported increased HRQoL among patients randomised to the MLD group. The two RCTs that involved patients with leg mixed oedema due to chronic venous insufficiency did not find between-group differences in the overall HRQoL. One trial included patients with hand oedema from systemic sclerosis and showed higher HRQoL in the group that received MLD. No studies reported reductions in HRQoL, or severe adverse events after MLD. The small numbers of patients analysed in all studies may have resulted in lack of power to detect between-group differences in HRQoL. CONCLUSIONS: The effect of MLD on the HRQoL of patients with chronic oedema is unclear

Obesity is Associated with More Disability at Presentation and After Treatment in Low Back Pain but Not in Neck Pain: Findings from the OIOC Registry

Background: The influence on the treatment response in patients with low back pain (LBP) and neck pain (NP) is unknown. The aim of the study was to investigate the influence of body weight in patients with low back pain (LBP) and neck pain (NP) on baseline and end of treatment disability. Methods: Cross-sectional analysis of baseline factors. Longitudinal analysis of prospectively collected patient information at an outpatient physical therapy registry (data from June 2010 to December 2012). WHO-BMI classification was used: underweight, lean, overweight, obesity class I, obesity class II and III. The influence of body weight and a predefined set of confounders was analyzed by multiple regression models. Results: In LBP, disability increased with increasing BMI [lean = reference, obesity class I Beta 5.41 (95 % CI 0.75; 10.07), obesity class II-III Beta 7.58 (95 % CI 2.13; 13.03)]. Compared to lean patients, disability after treatment improved in overweight subjects [Beta −3.90 (95 % CI −7.4; −0.41)] but not in subjects with obesity class II–III [Beta 3.43 (95 % CI −3.81; 10.68)]. There were insufficient patients in the sample with severe obesity and therefore this trend has to be confirmed. The likelihood for meaningful important change (MID) was similar in all BMI subgroups. For patients with NP, BMI was not associated with baseline disability, and did not predict end of treatment disability or the likelihood of a MID. These findings must be interpreted with caution as BMI subgroups did not meet the required sample size. Conclusion: Overweight and obesity are associated with higher levels of disability before treatment in LBP patients, but not in NP. In severely obese patients class II–III with LBP the rate of MID was lowest indicating that these patients experienced the least treatment response compared to the other groups. Further studies should address the impact of severe obesity on the prognosis of LBP. In patients with LBP, severe obesity may be an important factor to consider during the physical therapy treatment. In particular, combined treatment strategies combining weight management, cardiovascular fitness, and low back pain rehabilitation should be investigated

The role of the bone in complex regional pain syndrome 1-A systematic review

OBJECTIVE: The aim of this systematic review was to appraise and analyse the knowledge on bone-related biochemical and histological biomarkers in complex regional pain syndrome 1 (CRPS 1). DATABASE: A total of 7 studies were included in the analysis (biochemical analyses n  = 3, animal study n  = 1, histological examination n  = 3). RESULTS: Two studies were classified as having a low risk of bias and five studies with a moderate risk of bias. Biochemical analysis indicated an increased bone turnover with increased bone resorption (elevated urinary levels of deoxypyridinoline) and bone formation (increased serum levels of calcitonin, osteoprotegerin and alkaline phosphatase). The animal study reported an increased signalling of proinflammatory tumour necrosis factor 4 weeks postfracture, which did, however, not contribute to local bone loss. Histological examination from biopsies revealed thinning and resorption of cortical bone, rarefication and reduction in trabecular bone and vascular modification in the bone marrow in acute CRPS 1, and replacement of the bone marrow by dystrophic vessels in chronic CRPS 1. CONCLUSION: The limited data reviewed revealed certain potential bone-related biomarkers in CRPS. Biomarkers hold the potential to identify patients who may benefit from treatments that influence bone turnover. Thus, this review identifies important areas for future research in CRPS1 patients

Effect of an interdisciplinary inpatient program for patients with complex regional pain syndrome in reducing disease activity-a single-center prospective cohort study

OBJECTIVE The aim of this study was to evaluate the benefit of inpatient treatment in reducing disease activity in patients with complex regional pain syndrome (CRPS) who have exhausted outpatient options. Furthermore, the study sought to identify patient-related outcome variables that predict a reduction in disease activity. METHODS The primary outcome was disease severity (CRPS Severity Score, range 0-16 points). Secondary outcomes included depression, anxiety, physical function, pain interference, fatigue, sleep disturbance, and the ability to participate in social roles and activities, all of which were assessed using the PROMIS-29. Furthermore, pain catastrophizing, neuropathic pain, quality of life, pain self-efficacy, medication intake, and the patient's global impression of change were examined in accordance with current international agreed recommendations, assessed at discharge, 3-month, and 6-month post-discharge. Mixed-effects models were conducted to identify baseline variables associated with CRPS severity. RESULTS Twenty-five patients completed the program (mean age 49.28 [SD 11.23] years, 92% females, mean symptom duration 8.5 [SD 6.5] months). Results showed a significant reduction between baseline and discharge of disease activity (CSS -2.36, P < .0001), pain (PROMIS-29 pain -0.88, P = .005), and emotional function (PROMIS-29 depression -5.05, P < .001; fatigue -4.63, P = .002). Moderate evidence for a reduction between baseline and discharge could be observed for pain interference (+2.27, P = .05), social participation (PROMIS-29 + 1.93, P = .05), anxiety (PROMIS-29 -3.32, P = .02) and physical function (PROMIS-29 + 1.3, P = .03). On discharge, 92% of patients (23 of 25) reported improvement in their overall condition. In the follow-up period, medication intake could be reduced after 3 (MQS -8.22, P = .002) and 6 months (MQS -8.69, P = .001), and there was further improvement in social participation after 3 months (PROMIS-29 + 1.72, 0.03) and sleep after 6 months (PROMIS-29 + 2.38, 0.008). In the mixed models, it was demonstrated that patients experiencing less pain at baseline also exhibited lower disease activity. CONCLUSION The results of this study confirm that inpatient interdisciplinary treatment of CRPS patients improves disease activity, pain, physical function, emotional function, and social participation. Most improvements were maintained for up to 6 months after discharge. The majority of patients reported that their overall condition had improved during the study period

Increased Use and Large Variation in Strong Opioids and Metamizole (Dipyrone) for Minor and Major Musculoskeletal Injuries Between 2008 and 2018: An Analysis of a Representative Sample of Swiss Workers.

PURPOSE Musculoskeletal (MSK) injuries are a major contributing factor for chronic pain. To date, little is known how pain medication use in MSK injuries has changed over time. We assessed pain medication prescription for MSK injuries in a representative sample of Swiss workers between 2008 and 2018. METHODS Retrospective analysis of the Swiss Accident Insurance Fund (Suva) data. We calculated annual pain medication use, treatment days, and costs associated with pain medication use in minor and major MSK injuries. RESULTS In total, 1,921,382 cases with MSK injuries with ≥ 1 pain medication were analyzed. Whereas MSK injuries with ≥ 1 pain medication increased by 9.4%, we observed a larger increase in metamizole (+ 254%), strong opioids (+ 88.4%), coxibs (+ 85.8%), and paracetamol (+ 28.1%). Strong opioids were increasingly used in minor (+ 91.4%) and major (+ 88.3%) injuries. The increase in metamizole (+ 390.6%) and coxibs (+ 115.5%) was larger in minor injuries compared to major injuries (+ 238.7% and + 80.6%, respectively). Medical expenses decreased in all medications except for strong opioids where a substantial increase was observed (+ 192.4% in minor; + 34% in major injuries). CONCLUSIONS We observed a disproportionate increase in metamizole, strong opioids, coxibs, and paracetamol prescriptions even in minor MSK injuries between 2008 and 2018. Whereas treatment costs decreased for all pain medications, there was a substantial increase in strong opioids. A more liberal prescription practice of opioids conflict with current evidence-based practice recommendations and need to be addressed by physicians and policy makers

Relevant baseline characteristics for describing patients with knee osteoarthritis: results from a Delphi survey

BACKGROUND: Inclusion/exclusion criteria and baseline characteristics are essential for assessing the applicability of trial results to a given patient and the comparability of study populations for meta-analyses. This Delphi survey aimed to generate a set of baseline characteristics for describing patients with knee osteoarthritis enrolled in clinical studies. METHODS: Survey participants comprised clinical experts (n = 23; mean age 54 y; from 4 continents) that had authored at least two randomized trials on knee osteoarthritis. First, given a prepared list of baseline patient characteristics, the experts were asked to add characteristics they considered important for assessing comparability of patient populations in different trials that evaluated the efficacy of non-surgical interventions for treating knee osteoarthritis. Next, they were asked to rate the importance of each characteristic, on a scale of 0 (not important) to 10 (highly important), according to three outcome categories: pain, function, and structure. RESULTS: Participants identified 121 baseline characteristics. A rating ≥7 points was assigned to 39 characteristics (e.g., age, depression, global knee pain, daily dose of pain killers, Kellgren-Lawrence grading); of these, 20 were related to pain, 15 to function, and 23 to structural outcomes. Global knee pain was the only baseline characteristic that fulfilled among experts the predefined consensus criteria. CONCLUSIONS: Experts identified a large number of characteristics for describing patients with knee osteoarthritis. Disagreement and uncertainty prevailed over the relevance of these characteristics. Our findings justified further efforts to define appropriate, broadly acceptable sets of baseline characteristics for describing patients with knee osteoarthritis

Development and internal validation of a prediction model for long-term opioid use-an analysis of insurance claims data

In the United States, a public-health crisis of opioid overuse has been observed, and in Europe, prescriptions of opioids are strongly increasing over time. The objective was to develop and validate a multivariable prognostic model to be used at the beginning of an opioid prescription episode, aiming to identify individual patients at high risk for long-term opioid use based on routinely collected data. Predictors including demographics, comorbid diseases, comedication, morphine dose at episode initiation, and prescription practice were collected. The primary outcome was long-term opioid use, defined as opioid use of either >90 days duration and ≥10 claims or >120 days, independent of the number of claims. Traditional generalized linear statistical regression models and machine learning approaches were applied. The area under the curve, calibration plots, and the scaled Brier score assessed model performance. More than four hundred thousand opioid episodes were included. The final risk prediction model had an area under the curve of 0.927 (95% confidence interval 0.924-0.931) in the validation set, and this model had a scaled Brier score of 48.5%. Using a threshold of 10% predicted probability to identify patients at high risk, the overall accuracy of this risk prediction model was 81.6% (95% confidence interval 81.2% to 82.0%). Our study demonstrated that long-term opioid use can be predicted at the initiation of an opioid prescription episode, with satisfactory accuracy using data routinely collected at a large health insurance company. Traditional statistical methods resulted in higher discriminative ability and similarly good calibration as compared with machine learning approaches

Development and internal validation of a prediction model for long-term opioid use-an analysis of insurance claims data.

In the United States, a public-health crisis of opioid overuse has been observed, and in Europe, prescriptions of opioids are strongly increasing over time. The objective was to develop and validate a multivariable prognostic model to be used at the beginning of an opioid prescription episode, aiming to identify individual patients at high risk for long-term opioid use based on routinely collected data. Predictors including demographics, comorbid diseases, comedication, morphine dose at episode initiation, and prescription practice were collected. The primary outcome was long-term opioid use, defined as opioid use of either >90 days duration and ≥10 claims or >120 days, independent of the number of claims. Traditional generalized linear statistical regression models and machine learning approaches were applied. The area under the curve, calibration plots, and the scaled Brier score assessed model performance. More than four hundred thousand opioid episodes were included. The final risk prediction model had an area under the curve of 0.927 (95% confidence interval 0.924-0.931) in the validation set, and this model had a scaled Brier score of 48.5%. Using a threshold of 10% predicted probability to identify patients at high risk, the overall accuracy of this risk prediction model was 81.6% (95% confidence interval 81.2% to 82.0%). Our study demonstrated that long-term opioid use can be predicted at the initiation of an opioid prescription episode, with satisfactory accuracy using data routinely collected at a large health insurance company. Traditional statistical methods resulted in higher discriminative ability and similarly good calibration as compared with machine learning approaches

Prescribing pattern insights from a longitudinal study of older adult inpatients with polypharmacy and chronic non-cancer pain.

BACKGROUND The present study sought to determine the prevalence of chronic non-cancer pain (CNCP) among older adult inpatients with polypharmacy. It also aimed to analyse prescription patterns and assess the therapy adequacy and patient complexity for those with and without CNCP. METHODS This 4-year longitudinal study examined data from an exhaustive acute care hospital register on home-dwelling older adult patients (≥65) with polypharmacy. Commonly known combinations of potentially inappropriate medications were used to estimate therapy adequacy. Patient complexity was evaluated by comparing number of comorbidities and investigating physical and cognitive deficits. RESULTS We determined a prevalence of CNCP of 9.7% among all older adult inpatients with polypharmacy, rising to 11.3% for those aged ≥85. Overall, CNCP patients were prescribed more drugs and had more comorbidities and physical and cognitive deficits than patients without CNCP. Older adult patients with CNCP received more analgesics, greater quantities of opioids, paracetamol and co-analgesics and elevated opioid dosages. Older adult patients with CNCP aged ≥85 received fewer analgesics, opioids, non-steroidal anti-inflammatory drugs and co-analgesics but more paracetamol. Older adult patients with CNCP were prescribed more potentially inappropriate medications involving opioids. In particular, 24.5% received an opioid and a hypnotic (benzodiazepine or Z-drug), and 8.6% received an opioid and a gabapentinoid. CONCLUSION Observed differences in medication use between older adult inpatients with or without CNCP may be relevant for clinical practice. Potentially inadequate co-prescribing (such as hypnotics and opioids) affects a higher proportion of patients with CNCP and may have serious unintended consequences. SIGNIFICANCE STATEMENT This study describes differences in prescription patterns between people with and without chronic non-cancer pain in a large dataset of 20,422 discharges. The differences found may be relevant to clinical practice. In particular, high co-prescribing of opioids and hypnotics may have serious unintended consequences. Greater physical and cognitive deficits may indicate greater patient complexity, and appropriate interventions need to be developed to improve the management of this vulnerable patient group

Prognostic factors, disease course, and treatment efficacy in Duchenne muscular dystrophy: A systematic review and meta‐analysis

Introduction/Aims: Prognostic factors in Duchenne muscular dystrophy (DMD) predict the disease course and may help individualize patient care. The aim was to summarize the evidence on prognostic factors that may support treatment decisions. Methods: We searched six databases for prospective studies that each included ≥50 DMD patients with a minimum follow-up of 1 y. Primary outcomes were age at loss of ambulation (LoA), pulmonary function (forced vital capacity percent of predicted, FVC%p), and heart failure. Results: Out of 5074 references, 59 studies were analyzed. Corticosteroid use was associated with a delayed LoA (pooled effect hazard ratio [HR] 0.42, 95% confidence interval [CI] 0.23–0.75, I2 94%), better pulmonary function tests (higher peak FVC%, prolonged time with FVC%p > 50%, and reduced need for assisted ventilation) and delayed cardiomyopathy. Longer corticosteroid treatment was associated with later LoA (>1 y compared to <1 y; pooled HR: 0.50, 95% CI 0.27–0.90) and early treatment start (aged <5 y) may be associated with early cardiomyopathy and higher fracture risk. Genotype appeared to be an independent driver of LoA in some studies. Higher baseline physical function tests (e.g., 6-minute walk test) were associated with delayed LoA. Left ventricular dysfunction and FVC <1 L increased and the use of angiotensin-converting enzyme (ACE) inhibitors reduced the risk of heart failure and death. Fusion surgery in scoliosis may potentially preserve pulmonary function. Discussion: Prognostic factors that may inform clinical decisions include age at corticosteroid treatment initiation and treatment duration, ACE-inhibitor use, baseline physical function tests, pulmonary function, and cardiac dysfunction