Effect of a stabilization exercise program versus standard treatment for thumb carpometacarpal osteoarthritis: A randomized trial.

STUDY DESIGN: Randomized, interventional trial with 1 year follow-up. INTRODUCTION: Though recommended, evidence is lacking to support specific exercises to stabilize and strengthen the first carpometacarpal (CMC) joint for cases of osteoarthritis (OA). PURPOSE OF THE STUDY: To determine in a naturalistic setting, whether standard treatment plus a home exercise program (ST+HEP) is more effective than standard treatment (ST) alone in improving Quick Disabilities of Arm, Shoulder and Hand (qDASH) scores, and secondarily, in other patient-centered (pain, function) and clinical outcomes (range of motion, strength). METHODS: A total of 190 patients from a hand therapy practice in northwestern PA were enrolled by informed consent and randomized into ST or ST+HEP groups. Average age was 60 years, most were female (78%) with sedentary occupations most common (36%). ST group received orthotic interventions, modalities, joint protection education and adaptive equipment recommendations, while the ST+HEP group received a home exercise program in addition to ST for 6-12 months. Follow-up occurred at 3, 6, and 12 months. Outcomes included grip strength, pinch strength, range of motion (ROM), qDASH, Patient Specific Functional Scale (PSFS) and pain ratings. At the 6 month mark, all subjects could change groups if desired. Efficacy data analysis included both parametric and non-parametric tests. The threshold for statistical significance was 0.05 and adjusted for multiple comparisons. RESULTS: Repeated measures ANOVA failed to show a statistically significant difference in strength and ROM assessments between treatment groups over the 12 month follow-up (P ≥ .398). Differences between groups did not exceed 13%. Both the ST and ST+HEP groups evidenced improvement over time in most patient-focused assessments (P ≤ .011), including improvements exceeding reported clinically important differences in pain with activity and PSFS scores. Scores for these measures were similar at each follow-up period (P ≥ .080) in each group. The presence of CTS exerted no effect on outcomes; longer treatment time was weakly related to poorer qDASH and PSFS scores initially. Of those enrolled, 48% of subjects completed the study. CONCLUSIONS: The addition of a high-frequency home exercise program did not improve clinical or patient-centered outcomes more so than standard care in our sample however, study limitations are numerous. Both groups had decreased pain with activity and improved PSFS scores, meeting the established minimally clinically important difference (MCID) of each at 6 and 12 months. Adherence with the home program was poor and/or unknown.

Dynamic stabilization of the painful thumb: A historical and evidence-informed synthesis.

STUDY DESIGN: Expert opinion INTRODUCTION: Thumb carpometacarpal joint (CMC) osteoarthritis is a common condition seen in the hand therapy clinic. Prevalence is generally higher in females, and the percentage rises for post-menopausal females. Patients typically present with pain and functional difficulties. Conservative management is recommended before a surgical consult. Evidence is mounting that a dynamic stability modeled approach has a significant effect on pain and improving function. PURPOSE: The purpose of this paper is two-fold: first, to present the history and development of a dynamic stabilization model for treatment of the patient with thumb CMC osteoarthritis (OA), and second, to provide expert clinical commentary and recommendations for the treatment of thumb CMC OA in light of the best available evidence. METHODS: Expert clinical commentary is based on an extensive review of relevant literature. RESULTS: The current literature and expert opinion supports an evidence-informed multimodal intervention: modalities, pain relief techniques, manual release, joint mobilizations as deemed necessary, neuromuscular re-education through proprioceptive exercises, and education in joint protection principles. CONCLUSION: A rationale for a dynamic stabilization approach is presented. The unique anatomy of the thumb deserves finely tuned care based on high quality research. To advance our knowledge and clinical skills we must not become stagnant, but continue to generate high level evidence. The standard for future thumb CMC OA studies should be well-defined intervention parameters, consistent documentation, and the use of appropriate patient-rated outcome measures.

A phase II study of the dual mTOR inhibitor MLN0128 in patients with metastatic castration resistant prostate cancer.

Background MLN0128 is a first-in-class, dual mTOR inhibitor with potential to outperform standard rapalogs through inhibition of TORC1 and TORC2. This phase II study was designed to assess antitumor activity of MLN0128 in metastatic castration-resistant prostate cancer (mCRPC). Methods Eligible patients had mCRPC previously treated with abiraterone acetate and/or enzalutamide. Five patients started MLN0128 at 5 mg once daily, subsequently dose reduced to 4 mg because of toxicity. Four subsequent patients started MLN0128 at 4 mg daily. Primary endpoint was progression-free survival at 6 months. Results Nine patients were enrolled and median time on treatment was 11 weeks (range: 3-30). Best response was stable disease. All patients had a rise in PSA on treatment, with a median 159% increase from baseline (range: 12-620%). Median baseline circulating tumor cell count was 1 cell/mL (range: 0-40); none had a decrease in cell count posttreatment. Grade ≤ 2 adverse events included fatigue, anorexia, and rash. The most common serious adverse events were grade 3 dyspnea and maculopapular rash. Eight patients discontinued treatment early because of radiographic progression (n = 1), grade 3 toxicity (n = 5), or investigator discretion (n = 2). Four patients had immediate PSA decline following drug discontinuation, suggesting MLN0128 could cause compensatory increase of androgen receptor (AR) activity. Correlative studies of pretreatment and posttreatment biopsy specimens revealed limited inhibition of AKT phosphorylation, 4EBP1 phosphorylation, and eIF4E activity. Conclusions Clinical efficacy of MLN0128 in mCRPC was limited likely due to dose reductions secondary to toxicity, PSA kinetics suggesting AR activation resulting from mTOR inhibition, and poor inhibition of mTOR signaling targets.