Nonpharmacologic and pharmacologic management of acute pain from non­low back, musculoskeletal injuries in adults: a clinical guideline from the American College of Physicians and American Academy of Family Physicians

The American College of Physicians (ACP) and American Academy of Family Physicians (AAFP) developed this guideline to provide clinical recommendations on nonpharmacologic and pharmacologic management of acute pain from non­low back, musculoskeletal injuries in adults in the outpatient setting. The guidance is based on current best available evidence about benefits and harms, taken in the context of costs and patient values and preferences. This guideline does not address noninvasive treatment of low back pain, which is covered by a separate ACP guideline that has also been endorsed by AAFP.

Treatment of low bone density or osteoporosis to prevent fractures in men and women: a clinical practice guideline update from the American College of Physicians

DESCRIPTION: This guideline updates the 2008 American College of Physicians (ACP) recommendations on treatment of low bone density and osteoporosis to prevent fractures in men and women. This guideline is endorsed by the American Academy of Family Physicians. METHODS: The ACP Clinical Guidelines Committee based these recommendations on a systematic review of randomized controlled trials; systematic reviews; large observational studies (for adverse events); and case reports (for rare events) that were published between 2 January 2005 and 3 June 2011. The review was updated to July 2016 by using a machine-learning method, and a limited update to October 2016 was done. Clinical outcomes evaluated were fractures and adverse events. This guideline focuses on the comparative benefits and risks of short- and long-term pharmacologic treatments for low bone density, including pharmaceutical prescriptions, calcium, vitamin D, and estrogen. Evidence was graded according to the GRADE (Grading of Recommendations Assessment, Development and Evaluation) system. TARGET AUDIENCE AND PATIENT POPULATION: The target audience for this guideline includes all clinicians. The target patient population includes men and women with low bone density and osteoporosis. RECOMMENDATION 1: ACP recommends that clinicians offer pharmacologic treatment with alendronate, risedronate, zoledronic acid, or denosumab to reduce the risk for hip and vertebral fractures in women who have known osteoporosis. (Grade: strong recommendation; high-quality evidence). RECOMMENDATION 2: ACP recommends that clinicians treat osteoporotic women with pharmacologic therapy for 5 years. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 3: ACP recommends that clinicians offer pharmacologic treatment with bisphosphonates to reduce the risk for vertebral fracture in men who have clinically recognized osteoporosis. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 4: ACP recommends against bone density monitoring during the 5-year pharmacologic treatment period for osteoporosis in women. (Grade: weak recommendation; low-quality evidence). RECOMMENDATION 5: ACP recommends against using menopausal estrogen therapy or menopausal estrogen plus progestogen therapy or raloxifene for the treatment of osteoporosis in women. (Grade: strong recommendation; moderate-quality evidence). RECOMMENDATION 6: ACP recommends that clinicians should make the decision whether to treat osteopenic women 65 years of age or older who are at a high risk for fracture based on a discussion of patient preferences, fracture risk profile, and benefits, harms, and costs of medications. (Grade: weak recommendation; low-quality evidence).

Noninvasive treatments for acute, subacute, and chronic low back pain: a clinical practice guideline from the American College of Physicians

DESCRIPTION: The American College of Physicians (ACP) developed this guideline to present the evidence and provide clinical recommendations on noninvasive treatment of low back pain. METHODS: Using the ACP grading system, the committee based these recommendations on a systematic review of randomized, controlled trials and systematic reviews published through April 2015 on noninvasive pharmacologic and nonpharmacologic treatments for low back pain. Updated searches were performed through November 2016. Clinical outcomes evaluated included reduction or elimination of low back pain, improvement in back-specific and overall function, improvement in health-related quality of life, reduction in work disability and return to work, global improvement, number of back pain episodes or time between episodes, patient satisfaction, and adverse effects. TARGET AUDIENCE AND PATIENT POPULATION: The target audience for this guideline includes all clinicians, and the target patient population includes adults with acute, subacute, or chronic low back pain. RECOMMENDATION 1: Given that most patients with acute or subacute low back pain improve over time regardless of treatment, clinicians and patients should select nonpharmacologic treatment with superficial heat (moderate-quality evidence), massage, acupuncture, or spinal manipulation (low-quality evidence). If pharmacologic treatment is desired, clinicians and patients should select nonsteroidal anti-inflammatory drugs or skeletal muscle relaxants (moderate-quality evidence). (Grade: strong recommendation). RECOMMENDATION 2: For patients with chronic low back pain, clinicians and patients should initially select nonpharmacologic treatment with exercise, multidisciplinary rehabilitation, acupuncture, mindfulness-based stress reduction (moderate-quality evidence), tai chi, yoga, motor control exercise, progressive relaxation, electromyography biofeedback, low-level laser therapy, operant therapy, cognitive behavioral therapy, or spinal manipulation (low-quality evidence). (Grade: strong recommendation). RECOMMENDATION 3: In patients with chronic low back pain who have had an inadequate response to nonpharmacologic therapy, clinicians and patients should consider pharmacologic treatment with nonsteroidal anti-inflammatory drugs as first-line therapy, or tramadol or duloxetine as second-line therapy. Clinicians should only consider opioids as an option in patients who have failed the aforementioned treatments and only if the potential benefits outweigh the risks for individual patients and after a discussion of known risks and realistic benefits with patients. (Grade: weak recommendation, moderate-quality evidence).

Anticardiolipin antibodies in the polymyalgia rheumatica-temporal arteritis syndromes.

A series of seven patients with the polymyalgia rheumatica-temporal arteritis (PMR-TA) complex is presented, each of whom during the clinical course demonstrated the presence of anticardiolipin antibodies (ACLs). Presenting symptoms consisted of proximal myalgias and stiffness characteristic of PMR in five patients and of visual symptoms and headache suspicious for TA in two patients. Two of the five PMR patients later developed jaw claudication characteristic of TA. Six of the seven cases demonstrated clinical evidence of a vasculopathic process such as a cerebrovascular infarct or a vasculitic syndrome. Previous studies have suggested an association between ACLs and PMR-TA, and this series of patients appears to provide more supporting evidence. Even patients who only manifested PMR symptoms without suggestion of accompanying TA developed vascular complications. An increasing range of symptoms have been recognized in association with ACLs, and the vasculitic syndromes of PMR-TA should be included as a possible association. While this series together with previous studies may suggest that the presence of ACLs in patients with PMR-TA symptoms may serve as a marker for the development of vascular complications, larger longitudinal studies will be necessary in the future.

Bone and joint manifestations of hypothyroidism.

Hypothyroidism is frequently accompanied by musculoskeletal manifestations ranging from myalgias and arthralgias to true myopathy and arthritis. A case is presented in which an arthropathic process in the hip was the isolated finding in a young man who was severely hypothyroid. Previous literature on bone and joint manifestations of hypothyroidism is reviewed, with emphasis on cases where such manifestations were the presenting symptoms of thyroid dysfunction. Most cases of arthropathic changes in adult-recognized hypothyroidism involved the knees and hands, while the hip and the epiphysis of the femoral head appear more commonly involved in children. Thyroid hormones have known effects at the cellular level on proliferation and differentiation of bone and cartilage. The hypothyroid state appears to induce abnormalities in these tissues, which result in such clinical manifestations as epiphyseal dysgenesis, aseptic necrosis, possibly crystal-induced arthritis, and an arthropathy characterized by highly viscous noninflammatory joint effusions primarily affecting the knees, wrists, and hands. Neuropathic and myopathic symptoms accompanying hypothyroidism may manifest as joint region abnormalities when in fact there is no underlying arthropathy.

Leukemic synovitis as the cause of arthritis in myelodysplastic syndrome.

Up to 10% of patients with myelodysplastic syndrome (MDS) may have arthralgias as a feature of their disease. All patients with MDS have the potential to progress into acute leukemia. We describe the case of a 59-year-old male with MDS who presented with synovitis due to leukemic infiltration of the synovium as the first symptom heralding the conversion of MDS into acute leukemia.

Magnesium and its therapeutic uses: a review.

Magnesium has been reported as an effective medical therapy in an expanding array of conditions. Evidence investigating magnesium's use is presented, with a number of studies suggesting it should be seriously considered in such conditions as ischemic heart disease, cardiac arrhythmias, and asthma. Magnesium balance and metabolism are briefly reviewed, and then various hypotheses are presented that may explain magnesium's physiologic mechanisms of action, most likely involving calcium and potassium flux across cellular membranes in smooth muscle. In a number of the conditions to be discussed, it has been uncertain whether magnesium administration serves the purpose of merely correcting an underlying deficiency state or of utilizing a specific pharmacologic effect of magnesium. Magnesium deficiency is a relatively common condition, and predisposing factors as well as recent methods for assessing total body stores of magnesium are discussed. Physicians should be familiar with the numerous conditions and therapeutics that are risk factors for an underlying magnesium deficiency and in which empiric magnesium replacement should be considered. Guidelines for administration of parenteral magnesium are presented with specific focus on the low risk of adverse effects, as suggested by the large and rapid dosing regimens used in many of the clinical studies discussed here.

Investigations on the origin and metabolism of the carbon skeleton of ornithine, arginine and proline in selected animals.

The origin and metabolism of the carbon skeletons of the amino acids ornithine and arginine have been investigated in selected animals--an earthworm, an edible mollusc, a starfish, a sea-squirt, a freshwater crustacean and a rat. Only in the rat and microorganisms of sea water was any evidence obtained for the conversion of glutamate (or N-acetylglutamate) to ornithine. Apart from the crustacean, the other animals were able to synthesise the amidine moiety of arginine. All animals were able to hydrolyse (arginase) the amidine moiety from arginine and had the enzymic capacity to convert ornithine to proline. All the animals had some enzymic ability to oxidise proline to pyrroline-5-carboxylic acid. The crustacean (Cherax destructor) was able to conserve the high concentrations of arginine in its tail muscles during fasting. The hypothesis is put forward that, as arginine appears to be an essential amino acid in the diet of this animal, its demonstrated cannibalism is, among other things, a way of supplementing dietary arginine. The results are discussed in relation to the evolution of different phosphagens derived from arginine.

Synthesis of phosphocreatine and phosphoarginine by mitochondria from various sources.

Mitochondria from heart, skeletal muscle and the liver of the rat have been shown to synthesise phosphoarginine through ATP if supplied with arginine and lobster arginine kinase. Liver mitochondria have been shown to synthesise phosphocreatine through ATP with the aid of the cytosolic isomer of creatine kinase. Mitochondria prepared from muscles of a crustacean, a fish and a bird have been shown oxidatively to synthesise phosphocreatine (crustacean) and phosphoarginine (fish and bird) provided they are supplied with the appropriate kinase and catalytic amounts of ATP. Within one second of the addition of either cytosolic kinases, mitochondria from skeletal muscle and liver begin a steady state synthesis of phosphoarginine or phosphocreatine. The results suggest that, with respect to phosphagen synthesis, the addition of the cytosolic enzymes can substitute for the mitochondrial enzyme. It is difficult therefore to accept a special vectorial function for the bound mitochondrial enzyme at the biological concentrations of ATP and the cytosolic enzymes normally associated with phosphagen synthesis.

On the possible significance of the transamidination reaction in evolution.

The origin of the various muscle phosphagens during evolution is considered in the context of the need to conserve ornithine for the synthesis of proline for connective tissue necessary for structural strength and flexibility and/or a complicated musculature. In each phosphagen, arginine is known to have contributed its amidine moiety thus maintaining the function of the phosphagen and setting free the proline precursor ornithine. Tissues from an earthworm, a starfish and a sea-squirt have been found to contain the enzymes arginase, ornithine aminotransferase and pyrroline-5-carboxylate reductase which are necessary to convert arginine to proline. For each of the animals studied analysis for the relevant free amino acids and for the characteristic amino acids (Pro, Oh-Pro, Oh-Lys, Gly) of collagen are presented. The amino acid composition of the diet of the sea-squirt Pyura stolonifera and of the starfish Coscinasterias calamaria is presented along with the level of the phosphagen kinases of the animals studied. The significance of the experimental results is discussed in connection with the importance of the transamidination reaction.

A study of the plasma lipoproteins and the tissue lipids of the migrating lamprey, Mordacia mordax.

Sea lampreys, Mordacia mordax, were collected in spring from the Yarra River, Victoria, during their upstream spawning migration, to study the lipid composition in their tissues and plasma and their lipid transport system. Plasma lipoproteins were isolated by preparative ultracentrifugation and their chemical compositions were analyzed. The major classes of lipoproteins were found to be similar to those of man and higher animals. Lipids from the muscle and liver were analyzed for fatty acids. The striking feature of the lipids in the migrating lamprey is the presence of very high levels of cholesterol in both plasma and muscle. The possible metabolic roles of cholesterol have been discussed.