Hydroxychloroquine no more effective than placebo for relieving osteoarthritis hand pain

1. Hydroxychloroquine no more effective than placebo for relieving osteoarthritis hand pain

These findings do not support off-label use of hydroxychloroquine in patients with hand osteoarthritis

Abstract: http://annals.org/aim/article/doi/10.7326/M17-1430

Editorial: http://annals.org/aim/article/doi/10.7326/M18-0035

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Hydroxychloroquine is no more effective than placebo for relieving moderate to severe hand pain and radiographic osteoarthritis. The findings of a randomized trial are published in Annals of Internal Medicine.

Symptomatic hand osteoarthritis affects up to 31 percent of adults over the age of 70 and up to 15 percent of those over the age of 60. The pain can be debilitating and few therapies are effective. As such physicians seek alternatives to improve quality of life for patient suffering from hand osteoarthritis. Hydroxychloroquine has been used as an off-label treatment, but data on its efficacy is sparse.

Researchers from the Leeds Institute of Rheumatic and Musculoskeletal Medicine and NIHR Leeds Biomedical Research Centre randomly assigned 248 participants with symptomatic and radiographic hand osteoarthritis to either hydroxychloroquine (200 to 400 mg) or placebo for 12 months with ongoing usual care. The goal was to determine the effectiveness of hydroxychloroquine versus placebo as an analgesic treatment. At 6 months, mean hand pain was 5.49 points in the placebo group and 5.66 points in the hydroxychloroquine group. The authors concluded that hydroxychloroquine was no more effective than placebo for pain relief. According to the researchers, these findings do not support the current practice of off-label use of hydroxychloroquine in patients with hand osteoarthritis. The researchers also noted that a lot of hand pain may be caused by tendon problems, rather than arthritis, which hydroxychloroquine would not have helped.

Note: For an embargoed PDF, please contact Angela Collom. To interview the lead author, Sarah R. Kingsbury, PhD, please contact David Lewis at D.Lewis@leeds.ac.uk.

2. New guidelines offer recommendations for diagnosis and treatment of CKD-MBD

Abstract: http://annals.org/aim/article/doi/10.7326/M17-2640

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The Kidney Disease: Improving Global Outcomes (KDIGO) 2017 Clinical Practice Guideline Update provides revisions to 15 recommendations for the diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder (CKD-MBD). A synopsis of the guidelines is published in Annals of Internal Medicine.

CKD is defined as abnormalities in kidney structure or function that are present for more than 3 months and have health implications. As kidney function decreases, marked changes in bone mineral metabolism occur, resulting in increased risk for fractures, cardiovascular disease, and overall mortality.

To assist clinicians in caring for patients with CKD-MBD, the 2017 guideline update provides recommendations for diagnosis of bone abnormalities in CKD-MBD, treatment of CKD-MBD by decreasing serum phosphate levels and maintaining serum calcium levels, treatment of parathyroid hormone abnormalities in CKD-MBD, treatment of bone abnormalities using antiresorptive agents and other osteoporosis therapies, and evaluation and treatment of kidney transplant bone disease. The target audience for the synopsis includes nephrologists, primary care physicians, and other health professionals caring for adults with CKD or those receiving dialysis.

Media contacts: For an embargoed PDF, please contact Angela Collom. To interview the lead author, Mary B. Leonard, MD, MSCE, please contact Ruthann Richter at richter1@stanford.edu.

3. Complex government-mandated hospital performance measure not supported by evidence

Abstract: http://annals.org/aim/article/doi/10.7326/M17-2947

Editorial: http://annals.org/aim/article/doi/10.7326/M18-0290

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Evidence supporting the use of a complex government-mandated hospital performance measure does not hold up to scientific rigor. Findings from a systematic evidence review are published in Annals of Internal Medicine.

The Severe Sepsis and Septic Shock Early Management Bundle (SEP-1) is a hospital performance measure introduced by the Centers for Medicare & Medicaid Services (CMS). It requires clinicians perform up to 7 interventions, and as many as 141 tasks and 3 hours to document for a single patient. Hospitals will be forced to fully adopt this complex performance measure or jeopardize reimbursement and accreditation. CMS uses published criteria to grade the evidence supporting its performance measures. To be considered high- or moderate-level evidence, studies must be free of confounders and have low risk of bias.

Researchers from the National Institutes of Health searched databases for all available scientific evidence and examined whether moderate- or high-level evidence shows that SEP-1 or five of its hemodynamic interventions improve survival in adults with sepsis. They found 20 published studies addressing this question. These were mostly observational studies (n=15) subject to selection bias and not randomized controlled trials. Only one single-center, observational study reported lower in-hospital mortality after implementation of the SEP-1 bundle. Sixteen studies, again mostly observational (n=14), reported increased survival with serial lactate measurements or 30-mL/kg fluid infusions, which are part of the mandate. None of these 17 studies were free of confounders or at low risk of bias. No studies showed that other investigated hemodynamic interventions improved survival.

According to the researchers, these findings suggest that CMS should examine its performance measure approval process to determine how it adopted interventions lacking evidence meeting the agency's own criteria and how it can improve this process in the future.

Media contacts: For an embargoed PDF, please contact Angela Collom. To interview the corresponding author, Peter Q. Eichacker, MD, please email Dr. Eichacker directly at peichacker@mail.cc.nih.gov or call 301-402-2914.

4. Treatment-free remission of chronic myeloid leukemia is possible following second-line nilotinib

Abstract: http://annals.org/aim/article/doi/10.7326/M17-1094

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Treatment-free remission seems to be achievable in patients with chronic myeloid leukemia (CML) who have achieved sustained deep molecular response (DMR) after discontinuation of second-line nilotinib therapy. Results from a Phase 2, open-label study are published in Annals of Internal Medicine.

Tyrosine kinase inhibitors (TKIs), such as imatinib, nilotinib, dasatinib, and bosutinib, have dramatically improved outcomes for patients with CML. Treatment-free remission, or stopping TKI therapy without loss of response, is an emerging treatment goal for patients with CML in chronic phase. Potential benefits of treatment-free remission include relief of treatment side effects, reduced risk for long-term TKI toxicity, and the ability to plan a family. In the STIM1 (Stop Imatinib 1) trial, 38 percent of patients with sustained DMR while receiving long-term imatinib treatment had molecular recurrence-free survival at 5 years. These results confirm the feasibility of treatment-free remission after sustained DMR in patients receiving TKI.

Researchers from South Australian Health and Medical Research Institute studied 163 patients who had achieved sustained DMR after switching from imatinib to nilotinib to determine if they could maintain remission without TKI. They found that most of those patients maintained treatment-free remission for 48 weeks or longer. In addition, for those who do not achieve sustained DMR with imatinib, switching to nilotinib may enable more patients to become eligible for treatment-free remission.

Media contacts: For an embargoed PDF or author contact information, please contact Angela Collom.

American College of Physicians