The following represent additions to UpToDate since the last version of What’s New that were considered by the authors and editors to be of particular interest.
BACK AND NECK PAIN
Spinal manipulation for neck pain — Few data exist on the effects of spinal manipulation in patients with acute neck pain. One trial randomly assigned patients with acute or subacute neck pain to spinal manipulation, pharmacotherapy, or home exercise [1]. Spinal manipulation led to decreased self-reported neck pain up to 52 weeks of follow-up, compared with medications (non-steroidal antiinflammatory drugs, acetaminophen, narcotics, and/or muscle relaxants). Home exercise led to similar improvements in pain compared with spinal manipulation. This trial was limited by lack of blinding of participants and providers. Due to limitations of current evidence and the small risk for serious adverse outcomes, including permanent impairment or death, manipulation of the cervical spine is not recommended as first-line treatment for acute neck pain. Spinal manipulation may be appropriate for those not responding to conservative measures. (See "Treatment of neck pain", section on 'Spinal manipulation'.)
Tai chi for low back pain — Tai chi is a Chinese martial art that involves slow movements, breathing exercises, and meditation. In a randomized trial in 160 adults with nonspecific low back pain, those assigned to a tai chi program reported improved pain and disability after 10 weeks of treatment, compared with usual care [2]. Further trials are needed to determine long-term efficacy of tai chi in the treatment of low back pain. (See "Exercise-based therapy for low back pain", section on 'Mind body exercise'.)
CRYSTAL DISEASE
Urate-lowering therapies with pegloticase — Treatment with pegloticase, a pegylated form of recombinant uricase, should be discontinued if there is loss of urate-lowering effectiveness, as indicated (during monitoring of each pre-infusion serum uric acid concentration) by a rise in serum uric acid values to >6 mg/dL (>357 micromol/L) after an initial response to treatment. Other urate-lowering therapies, such as allopurinol and febuxostat, should not be given to patients receiving pegloticase, because they may mask recognition of rising serum uric acid levels, which are associated with an increased risk for infusion-related reactions and loss of benefit resulting from the effects of high titer anti-pegloticase antibodies [3]. This precaution was highlighted in recent notices from the manufacturer and from the American College of Rheumatology due to the frequency of concomitant therapy with these agents recognized during postmarketing surveillance [3]. (See "Prevention of recurrent gout", section on 'Pegloticase'.)
FIBROMYALGIA
Cognitive-behavioral therapy for chronic pain — In a randomized trial of patients with chronic widespread pain, symptom improvement at six months was reported in 8 percent of patients assigned to usual care, 35 percent assigned to cognitive-behavioral therapy (CBT) delivered via telephone, and 37 percent assigned to a combination of telephone CBT and exercise [4]. (See "Overview of the treatment of chronic pain", section on 'Cognitive-behavioral therapy'.)
MUSCLE DISEASE
Drugs causing nocturnal leg cramps — An increased risk of nocturnal leg cramps has been attributed to numerous medications in case reports and small series. A recent large observational study provides the strongest evidence for several of these associations [5]. Analysis of a population-derived pharmacy database involving over 24,000 individuals found that patients initiating use of inhaled long-acting beta agonists, potassium-sparing diuretics and thiazide-like diuretics were more likely to receive a quinine prescription for nocturnal leg cramps during the year after starting a drug from one of these classes, compared with their likelihood during the year preceding such use. Only small increased risks were seen for loop diuretics and statins. (See "Nocturnal leg cramps", section on 'Etiology'.)
ORTHOPEDICS
No benefit from metal-on-metal hip arthroplasty — Metal-on-metal bearing surfaces for hip implants were thought to potentially offer advantages over other materials, including a reduced need for revision, but concerns have arisen regarding the safety and effectiveness of some of these prostheses. A systematic review of clinical trials and observational studies involving over 3100 patients and 3400 hips, and of data from nearly 900,000 patients in five national registries and the US Medicare database, found no advantage for metal-on-metal or ceramic-on-ceramic implants compared with use of metal-on-polyethylene or ceramic-on-polyethylene bearing surfaces [6]. In the national registries, the revision rate was higher in patients who received metal–on-metal implants compared with those who received metal–on–polyethylene. Functional outcomes did not differ between patients receiving different types of prostheses. (See "Total hip arthroplasty", section on 'Bearing surface'.)
Bisphosphonates and prosthetic loosening — Prosthetic loosening due to osteolysis is a concern in joint arthroplasty. The use of oral bisphosphonates has been proposed as a way to inhibit osteoclast activity and prevent osteolysis secondary to wear debris. In a population based study of nearly 42,000 patients undergoing initial hip or knee joint arthroplasty, rates of subsequent revision arthroplasty were reduced in patients who had received oral bisphosphonates [7]. Among over 1900 patients in the population cohort who underwent initial joint arthroplasty and had used oral bisphosphonates for at least six months at some time prior to their surgery, there was a significantly lower rate of revision at five years, compared with patients who did not use bisphosphonates (0.9 versus 2.0 percent). Confirmation in other cohorts and randomized trials with adequate follow-up will be needed to establish the role of bisphosphonates in this setting. (See "Complications of total hip arthroplasty", section on 'Prevention'.)
Thromboembolism after joint replacement — Venous thromboembolism (VTE) and pulmonary embolism (PE), sometimes fatal, are potential complications of knee or hip joint arthroplasty. The frequency of events may be reported as a safety or quality indicator and disclosed as part of the informed consent process for surgery, but benchmarks have not been well-defined. The rates of inpatient VTE and PE among patients receiving prophylaxis following total or partial knee or hip arthroplasty were estimated in a meta-analysis involving over 44,000 patients in 26 randomized trials and observational studies [8]. VTE and PE occurred following knee arthroplasty in approximately 1 in 100 and 1 in 300 patients, respectively. Rates following hip arthroplasty were approximately 1 in 200 and 1 in 1000. (See "Complications of total knee arthroplasty", section on 'Thromboembolism' and "Complications of total hip arthroplasty", section on 'Thromboembolic disease'.)
OSTEOARTHRITIS
Increased symptomatic OA and knee pain — The prevalence of symptomatic osteoarthritis (OA) of the knee was evaluated among patients with radiographic OA in a study involving approximately 700 to 1100 patients from the Framingham Osteoarthritis Study cohort at each of three time periods; the rate approximately doubled in women and nearly tripled in men, over a period of 20 years, after adjustment for both age and body mass index [9]. Knee pain and obesity also increased over the same interval in this cohort and in national US survey data. However, increased obesity only explained a portion of the change (about 10 to 25 percent), and the prevalence of radiographic knee OA did not increase during this interval. The precise factors responsible for these increases in symptom prevalence and an increased rate of knee joint replacement surgery during this period are uncertain. (See "Risk factors for and possible causes of osteoarthritis", section on 'Knee'.)
OSTEOPOROSIS AND FRACTURE RISK
Repeat screening for bone mineral density — Data regarding the frequency of follow-up bone mineral density (BMD) testing in women who have had an initial screening test are limited. Two studies provide new related data:
These data suggest that healthy women 65 years of age and older at baseline screening, with normal or slightly low bone mass (T-score -1.01 to -1.49) and with no risk factors for accelerated bone loss, do not require repeat testing for 17 years. These results are not applicable to women with osteoporosis (T-scores below -2.5) at baseline, women already receiving osteoporosis treatment, or women younger than 65 years of age at time of first bone density screening. Women younger than 65 years of age with clinical risk factors for fracture (table 1) may require more frequent monitoring of bone density, depending upon risk factors. (See "Screening for osteoporosis", section on 'Repeat BMD measurements'.)
Vitamin D and fractures — A meta-analysis of five trials comparing vitamin D (400 to 1370 units/day) with placebo in over 14,500 older men and women showed that vitamin D supplementation alone did not reduce fracture risk [12]. However, a meta-analysis of 11 trials comparing combined supplementation with calcium (500 to 1200 mg/d) plus vitamin D (300 to 1100 units/day) with placebo showed a reduction in fracture risk [12]. In a subgroup analysis, the risk reduction was larger among institutionalized than community dwelling older individuals. These findings suggest that supplementation with both calcium and vitamin D is required to reduce the risk of fracture. (See "Calcium and vitamin D supplementation in osteoporosis", section on 'Calcium versus vitamin D'.)
Exercise in postmenopausal women — A meta-analysis of 43 randomized trials (4320 participants) of exercise and bone mineral density (BMD) in postmenopausal women showed a small but significant positive effect of exercise on BMD at the lumbar spine and trochanter compared with controls [13]. Various exercise types, including resistance training, jogging, jumping, and walking, were effective. The most effective type of exercise for BMD of the femoral neck was non-weight bearing high force exercise (eg, progressive resistance strength training), whereas a combined program (mixture of more than one exercise type) was most effective for lumbar spine BMD. (See "Overview of the management of osteoporosis in postmenopausal women", section on 'Exercise'.)
PEDIATRIC RHEUMATOLOGY
Glucocorticoids in initial therapy for Kawasaki disease — A meta-analysis of clinical trials found that initial therapy for Kawasaki disease (KD) with glucocorticoids in addition to intravenous immune globulin (IVIG) reduced the duration of fever and the rate of initial treatment failure compared with IVIG alone [14]. However, the addition of glucocorticoids did not significantly reduce the incidence of coronary artery aneurysms. Thus, we do not recommend routine use of glucocorticoids for initial therapy of KD. (See "Kawasaki disease: Initial treatment and prognosis", section on 'Glucocorticoids'.)
RHEUMATOID ARTHRITIS
Glucocorticoid addition to tight control with DMARDs — Evidence is conflicting regarding the benefits of chronic glucocorticoid therapy for patients with rheumatoid arthritis (RA). In one of the largest trials to date, low-dose glucocorticoid showed clinical and radiologic benefit even in the context of a tight control treatment strategy using methotrexate (MTX) and additional disease-modifying antirheumatic drug (DMARD) therapy [15]. In this trial, over 230 patients with early RA who had not received either DMARDs or glucocorticoids were randomly assigned to receive MTX plus either prednisone (10 mg/day) or placebo. Disease activity was assessed monthly for MTX dose adjustment, and a second DMARD was added if control was inadequate at a maximum MTX dose of 30 mg/week. After two years, radiologic scores for the patients in the prednisone group showed less disease progression compared with those in the placebo group; the difference was statistically significant although the absolute difference was small. (See "Use of glucocorticoids in the treatment of rheumatoid arthritis", section on 'Efficacy of chronic use'.)
NSAID use with methotrexate — Nonsteroidal antiinflammatory drugs (NSAIDs) may decrease the renal excretion of MTX; however, a systematic review of randomized trials and large studies involving patients with RA found that NSAIDs could be safely given together with MTX, assuming that appropriate monitoring for drug toxicity is performed [16]. The use of antiinflammatory doses of salicylates with MTX should be avoided. (See "Use of methotrexate in the treatment of rheumatoid arthritis", section on 'Pharmacology'.)
SYSTEMIC LUPUS ERYTHEMATOSUS
Mycophenolate mofetil versus azathioprine for lupus nephritis — The ALMS Maintenance Trial was a multinational study in which 227 patients who had achieved remission with either mycophenolate mofetil (MMF) or cyclophosphamide were randomly assigned to MMF (1 g twice daily) or azathioprine (2 mg/kg per day) as maintenance therapy for 36 months [17]. Among patients who responded to induction therapy with either MMF or cyclophosphamide, treatment failure at 36 months (defined by renal relapse, the need to intensify therapy, doubling of the serum creatinine, or death) was significantly lower with MMF compared with azathioprine groups. (See "Therapy of diffuse or focal proliferative lupus nephritis", section on 'Azathioprine versus mycophenolate mofetil'.)
VASCULITIS
Cocaine and levamisole in ANCA-associated vasculitis — Approximately 70 percent of cocaine bought illicitly in the United States is contaminated or “cut” with levamisole, an immunomodulatory agent. In the largest published series, 30 patients with cocaine and levamisole-related ANCA-associated vasculitis are described [18]. The most common clinical manifestations included arthralgias (83 percent) and skin lesions (61 percent). All patients had a positive MPO-ANCA, and 50 percent had positive PR3-ANCA. An abnormal urinalysis (including proteinuria, hematuria, or cellular casts) was present in 8 patients. (See "Clinical spectrum of antineutrophil cytoplasmic antibodies", section on 'Cocaine and levamisole'.)
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