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Background Despite known clinical risk factors, predicting anthracycline cardiotoxicity remains challenging. Objectives This study sought to develop a clinical and genetic risk prediction model for anthracycline cardiotoxicity in childhood cancer survivors. Methods We performed exome sequencing in 289 childhood cancer survivors at least 3 years from anthracycline exposure. In a nested case-control design, 183 case patients with reduced left ventricular ejection fraction despite low-dose doxorubicin (≤250 mg/m2), and 106 control patients with preserved left ventricular ejection fraction despite doxorubicin >250 mg/m2 were selected as extreme phenotypes. Rare/low-frequency variants were collapsed to identify genes differentially enriched for variants between case patients and control patients. The expression levels of 5 top-ranked genes were evaluated in human induced pluripotent stem cell–derived cardiomyocytes, and variant enrichment was confirmed in a replication cohort. Using random forest, a risk prediction model that included genetic and clinical predictors was developed. Results Thirty-one genes were differentially enriched for variants between case patients and control patients (p < 0.001). Only 42.6% case patients harbored a variant in these genes compared to 89.6% control patients (odds ratio: 0.09; 95% confidence interval: 0.04 to 0.17; p = 3.98 × 10–15). A risk prediction model for cardiotoxicity that included clinical and genetic factors had a higher prediction accuracy and lower misclassification rate compared to the clinical-only model. In vitro inhibition of gene-associated pathways (PI3KR2, ZNF827) provided protection from cardiotoxicity in cardiomyocytes. Conclusions Our study identified variants in cardiac injury pathway genes that protect against cardiotoxicity and informed the development of a prediction model for delayed anthracycline cardiotoxicity, and it also provided new targets in autophagy genes for the development of cardio-protective drugs. (Preventing Cardiac Sequelae in Pediatric Cancer Survivors [PCS2]; NCT01805778), Central Illustration

Background To tailor physical activity treatment programs for patients with osteoarthritis, clinicians need valid and feasible measurement tools to evaluate habitual physical activity. The widely used International Physical Activity Questionnaire-Short Form (IPAQ-SF) is not previously validated in patients with osteoarthritis. Purpose To assess the concurrent criterion validity of the IPAQ-SF in patients with osteoarthritis, using an accelerometer as a criterion-method. Method Patients with osteoarthritis (n = 115) were recruited at The Division of Rheumatology and Research at Diakonhjemmet Hospital (Oslo, Norway). Physical activity was measured by patients wearing an accelerometer (ActiGraph wGT3X-BT) for seven consecutive days, followed by reporting their physical activity for the past 7 days using the IPAQ-SF. Comparison of proportions that fulfilled physical activity recommendations as measured by the two methods were tested by Pearson Chi-Square analysis. Differences in physical activity levels between the IPAQ-SF and the accelerometer were analyzed with Wilcoxon Signed-Rank Test and Spearman rank correlation test. Bland-Altman plots were used to visualize the concurrent criterion validity for total- and intensity-specific physical activity levels. Results In total, 93 patients provided complete physical activity data, mean (SD) age was 65 (8.7) years, 87% were women. According to the IPAQ-SF, 57% of the patients fulfilled the minimum physical activity recommendations compared to 31% according to the accelerometer (p = 0.043). When comparing the IPAQ-SF to the accelerometer we found significant under-reporting of total physical activity MET-minutes (p = p Conclusion Physical activity is a core treatment of osteoarthritis. Our finding that patients tend to over-report activity of higher intensity and under-report low-intensity activity and sitting-time is of clinical importance. We conclude that the concurrent criterion validity of the IPAQ-SF was weak in patients with osteoarthritis.

Objective The present study assessed the prevalence of depressive disorders and associated factors in a sample of elderly persons in the south of Santa Catarina. Methods A cross-sectional study based on population data was performed, evaluating 1021 elderly individuals aged between 60 and 79 years. Home interviews were carried out using the Portuguese version of the Mini International Neuropsychiatric Interview (MINI), in order to collect demographic data, information on hypertension and reports of acute myocardial infarction. The disorders studied were current depressive episode, dysthymia and a comorbidity of a depressive episode and dysthymia, representing double depression. The comparison of mean age and prevalence was made with the t-test and other associations were analyzed using the Chi-squared test. Results The prevalence of depression was 26.2%, while 5.5% of the sample suffered from dysthymia and 2.7% experienced double depression. Risk factors for depression were: nine or more years of schooling [PR = 1.44 (1.17 to 1.77); p

It is frequently claimed that fatigue reflects pain and that strategies for alleviating fatigue in patients with ankylosing spondylitis (AS) should focus on pain management. The aim of this study was twofold: to investigate the correlation between fatigue and pain over time and to investigate the temporal relationship between fatigue and pain in patients with AS. Fatigue and pain were assessed twice a week for 35 weeks in 23 patients with AS. Data were reported with text messages on mobile phones, constituting around 70 repeated measurements per patient. To estimate correlation over time, the correlation coefficient within individuals was estimated. When estimating the temporal relationship, we lagged the independent variable and performed individual linear regression. In 16 (70 %) of the patients, ≤ 36 % of the variance in fatigue was explained by pain. The association between fatigue and pain was synchronous in time in 13 (57 %) patients, while 5 (22 %) patients reported that fatigue precedes pain by 1 week and 5 (22 %) that pain precedes fatigue by 1 week. Fatigue and pain may be two separate and independent symptoms in some patients with AS. The clinical implication is that the two symptoms should be targeted separately because it cannot always be expected that an improvement in one is followed by an improvement in the other.

Patients with osteoarthritis of the knee are commonly treated by physical therapists. Practice should be informed by updated evidence from systematic reviews. The purpose of this article is to summarize the evidence from systematic reviews on the effectiveness of physical therapy for patients with knee osteoarthritis. Systematic reviews published between 2000 and 2007 were identified by a comprehensive literature search. We graded the quality of evidence across reviews for each comparison and outcome. Twenty-three systematic reviews on physical therapy interventions for patients with knee osteoarthritis were included. There is high-quality evidence that exercise and weight reduction reduce pain and improve physical function in patients with osteoarthritis of the knee. There is moderate-quality evidence that acupuncture, transcutaneous electrical nerve stimulation, and low-level laser therapy reduce pain and that psychoeducational interventions improve psychological outcomes. For other interventions and outcomes, the quality of evidence is low or there is no evidence from systematic reviews.

The objective of the study was to analyze the relationships between Pain Readiness to Change, weekly measures of positive and negative affect and pain over eight subsequent weeks in patients with rheumatoid arthritis (RA). Factor analysis based on data from three different samples of patients with rheumatic diseases and other chronic pain conditions suggested a three factor solution for the Norwegian version of the Pain Stages of Change questionnaire (PSOCQ) representing Precontemplation, Contemplation, and Action/Maintenance (ACT) stages from the original Transtheoretical Model. Multilevel analyses on the weekly assessed data from a sub sample of 40 patients with RA revealed that higher levels of Pain Readiness to Change represented by high ACT scores were associated with more positive affect from week to week while no association was found between Readiness to Change and weekly pain. However, there was an interaction effect between Pain Readiness to Change and weekly positive affect on weekly pain, indicating that those persons having a higher level of Readiness to Change reported less pain in weeks when they also experienced increased positive affect. This may imply that a combination of cognitive factors and positive affect is most effective in relation to pain reduction. Results encourage continued investigation of apparent interactions between chronic pain, affect, and pain self-management.

Objective To assess beneficial and harmful effects of arthroplasty in the shoulder joint in patients with RA. Methods A systematic review within the framework of the Cochrane Collaboration identified randomized controlled trials (RCTs), controlled clinical trials and case series (included for assessment of complications) published between 1995 and 2008. Articles considered potentially relevant were retrieved in full text and assessed independently by two authors. Risk of bias and level of evidence were assessed according to the established criteria. Results One RCT (26 shoulders) compared cemented and uncemented humeral stem fixation during arthroplasty, reporting no significant differences between groups at 2-year follow-up (low-quality evidence). Nineteen case series (1155 shoulders) reported component loosening requiring revision at 5%, infections at 2% and minor complications at 7% (very low-quality evidence). The retrospective case series had several limitations related to methodological quality and standards of reporting. Conclusion At present, there is very little research evidence supporting decisions about shoulder joint arthroplasty in patients with RA.

BACKGROUND Involvment of the shoulder joint in patients with rheumatoid arthritis (RA) leads to severe destruction of the glenohumeral joint. When conservative treatment does not result in sufficient improvement, surgical procedures may be considered as the only beneficial treatment option. OBJECTIVES To assess beneficial and harmful effects of all forms of surgical treatment in the management of the shoulder in people with rheumatoid arthritis. SEARCH STRATEGY Articles were identified by searches in The Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, SCISEARCH and reference lists of relevant articles (January 1995 to May 2008). SELECTION CRITERIA Randomised Controlled Trials, and Controlled Clinical Trials reporting on effects of shoulder surgery. In addition case-series were included for the assessment of complications. DATA COLLECTION AND ANALYSIS Two review authors independently selected trials for inclusion, assessed trial quality and extracted the data. MAIN RESULTS One RCT, one CCT and 21 case-series were included. The RCT compared cemented versus uncemented humeral stem fixation in arthroplasty and found no significant differences between the two groups after two years (low quality evidence). The CCT compared rotator cuff repair with augmented subscapularis transposition versus subscapularis transposition alone and reported significant differences in favour of the augmented subscapularis transposition after 2 years in function, mean difference (MD) 4.00 on a 0 to 30 scale (95% CI 1.11 to 6.89) and pain, MD 4.00 on a 0 to 20 scale (95% CI 0.84 to 7.16) (low quality evidence). Based on 11 case series (mean follow up 4.5 to 12 years) complications were reported in 11% (95% CI: 9.9% to 12.1%) of the total shoulder arthroplasties, while 10 case-series (mean follow-up 2.7 to 11.3 years) reported complications in 9.9% (95% CI: 8.4% to 11.4%) of the hemiarthroplasties (very low quality evidence). AUTHORS' CONCLUSIONS The effects of surgical treatment in the management of the shoulder in people with rheumatoid arthritis are largely unknown due to the paucity of randomised controlled trials.

An increasing number of systematic reviews are available regarding nonpharmacological and nonsurgical interventions for hip osteoarthritis (OA). The objectives of this article are to identify high-quality systematic reviews on the effect of nonpharmacological and nonsurgical interventions for hip OA and to summarize available high-quality evidence for these treatment approaches. The authors identified and screened 204 reviews. Two independent reviewers using a previously pilot-tested quality assessment form assessed the full text of 58 reviews. Six reviews were of sufficient high quality and could be included for further analyses. There was moderate-quality evidence that acupuncture and diacerein have no effect on pain and function. There was low-quality evidence that strengthening exercises and avocado/soybean unsaponifiables reduce pain and that diacerein decreases radiographic OA progression. There was insufficient high-quality evidence regarding nonpharmacological and nonsurgical interventions for hip OA, and further primary studies and reviews are needed.

Question To compare the efficacy of aerobic walking and home based quadriceps strengthening exercises in reducing pain and disability in knee osteoarthritis. Design Systematic review of randomised controlled trials. Setting/population People with knee osteoarthritis. Interventions Comparison of aerobic walking or home based quadriceps strengthening exercise with a non-exercise control group. Strengthening exercise was considered to be ‘home based' where it was undertaken exclusively in the subject's home environment or, where exercise was partly supervised, the regimen was intended to be continued at home unsupervised. Outcomes Pain and disability. Results 13 studies were included. One study provided a direct comparison between aerobic walking and home based strengthening exercises and control. Nine RCTs evaluated quadriceps strengthening exercises, and in three studies the exercise intervention was predominantly aerobic walking. Control interventions included education and lifestyle advice, support by telephone calls, and no intervention. When comparing aerobic walking with no exercise interventions, the pooled effect sizes for pain and disability were 0.52 (95% CI 0.34 to 0.70) and 0.46 (95% CI 0.25 to 0.67) respectively. Corresponding effect size for quadriceps strengthening was 0.32 (95% CI 0.23 to 0.42) for both pain and disability. Conclusion Both aerobic walking and home based quadriceps strengthening exercises are effective at reducing pain and disability in subjects with knee osteoarthritis. No advantage of one form of exercise over the other was found on indirect comparison.

Background Rheumatoid arthritis (RA) is a chronic, inflammatory and systemic disease which affects the musculoskeletal system. Exercise programmes are reported to improve physical functioning in patients with RA. Tai Chi is a traditional Chinese martial art which combines slow and gentle movements with mental focus. The purpose of this study was to study in which way Tai Chi group exercise impacted on disease activity, physical function, health status and experience in RA patients, applying quantitative and qualitative methods. Methods Fifteen patients with RA (13 females, age 33-70 years) were recruited from a rheumatology department into a single group study. The patients were instructed in Tai Chi exercise twice weekly for 12 weeks. Assessments at baseline, 12 weeks, and 12 weeks follow-up were performed with a wide range of measures, including disease activity, self-reported health status, physical performance tests (Walking in Figure of Eight, Timed-Stands Test, and Shoulder Movement Impairment Scale). Qualitative data were obtained from a focus group interview conducted after completed intervention with taping and verbatim transcription. Review of the transcripts identified themes important to patients practicing Tai Chi. Results Within the group, Tai Chi practice lead to improved lower-limb muscle function at the end of intervention and at 12 weeks follow-up. Qualitative analyses showed that patients experienced improved physical condition, confidence in moving, balance and less pain during exercise and in daily life. Other experience included stress reduction, increased body awareness, confidence in moving and indicated that Tai Chi was a feasible exercise modality in RA. Conclusions Improved muscle function in lower limbs was also reflected when patient experiences with Tai Chi were studied in depth in this explorative study. The combination of qualitative and quantitative research methods shows that Tai Chi has beneficial effects on health not related to disease activity and standardised health status assessment, and may contribute to an understanding of how Tai Chi exerts its effects. Trial registration NCT00522054

Question Is Tai Chi effective and safe as a treatment for people with rheumatoid arthritis (RA)? Design Systematic review of randomised controlled trials (RCT) or controlled trials (CCT). Setting/population Ambulatory adults with a diagnosis of RA. Interventions Exercise programs with Tai Chi instruction or incorporating principles of Tai Chi philosophy. Control groups received no therapy, sham therapy, or another type of therapy. Outcomes Outcome measures from OMERACT 1993 and safety assessed as withdrawals. Results Three RCTs and one CCT including 206 participants were included in the review. On a scale from 0 (worst) to 5 (best) the methodological quality of the studies were assessed as 0 in three studies and 1 in one study. Tai Chi-based exercise programs had no clinically important or statistically significant effect on most outcomes of disease activity, which included activities of daily living, patient global overall rating, tenderness or number of swollen joints (WMD 2.45 joints, 95% CI –0.45 to 5.36). For range of motion, Tai Chi participants had statistically significant and clinically important improvements in ankle plantar flexion (WMD 24.00 degrees, 95% CI 3.34 to 44.66). There were statistically greater withdrawals from the control groups than from the Tai Chi groups (RR 0.97, 95% CI 0.19 to 0.72). One study found that compared to people who participated in traditional ROM exercise/rest programs those in a Tai Chi dance program reported a significantly higher level of participation in and enjoyment of exercise both immediately and four months after completion of the Tai Chi program. Conclusion The results suggest Tai Chi does not exacerbate symptoms of rheumatoid arthritis. In addition, Tai Chi has statistically significant benefits on lower extremity range of motion, in particular ankle range of motion, for people with RA. However, four studies of low methodological quality do not provide strong evidence and the results should be interpreted with caution.