Pharmacokinetics and Pharmacodynamics of Bimagrumab (BYM338).

Background: Bimagrumab is a human monoclonal antibody binding to the activin type II receptor with therapeutic potential in conditions of muscle wasting and obesity. This phase I study evaluated the pharmacokinetics (PK), pharmacodynamics (PD), and safety of various dose regimens of bimagrumab and routes of administration in healthy older adults.

Methods: This was a randomized, double-blind, placebo-controlled, parallel-arm, multiple-dose study in older adult men and women (aged ≥ 70 years, body mass index [BMI] 18-34 kg/m) with stable health and diet.

Longitudinal Changes in MRI Muscle Morphometry and Composition in People With Inclusion Body Myositis.

Background And Objectives: Limited data suggest that quantitative MRI (qMRI) measures have potential to be used as trial outcome measures in sporadic inclusion body myositis (sIBM) and as a noninvasive assessment tool to study sIBM muscle pathologic processes. Our aim was to evaluate changes in muscle structure and composition using a comprehensive multiparameter set of qMRI measures and to assess construct validity and responsiveness of qMRI measures in people with sIBM.

Methods: This was a prospective observational cohort study with assessments at baseline (n = 30) and 1 year (n = 26).

Bimagrumab vs Optimized Standard of Care for Treatment of Sarcopenia in Community-Dwelling Older Adults: A Randomized Clinical Trial.

Importance: The potential benefit of novel skeletal muscle anabolic agents to improve physical function in people with sarcopenia and other muscle wasting diseases is unknown.

Objective: To confirm the safety and efficacy of bimagrumab plus the new standard of care on skeletal muscle mass, strength, and physical function compared with standard of care alone in community-dwelling older adults with sarcopenia.

Design, Setting, And Participants: This double-blind, placebo-controlled, randomized clinical trial was conducted at 38 sites in 13 countries among community-dwelling men and women aged 70 years and older meeting gait speed and skeletal muscle criteria for sarcopenia.

Safety and efficacy of intravenous bimagrumab in inclusion body myositis (RESILIENT): a randomised, double-blind, placebo-controlled phase 2b trial.

Background: Inclusion body myositis is an idiopathic inflammatory myopathy and the most common myopathy affecting people older than 50 years. To date, there are no effective drug treatments. We aimed to assess the safety, efficacy, and tolerability of bimagrumab-a fully human monoclonal antibody-in individuals with inclusion body myositis.

Effects of bimagrumab, an activin receptor type II inhibitor, on pituitary neurohormonal axes.

Background: Bimagrumab is a human monoclonal antibody inhibitor of activin type II receptors (ActRII), with anabolic action on skeletal muscle mass by blocking binding of myostatin and other negative regulators of muscle growth. Bimagrumab is under evaluation for muscle wasting and associated functional loss in hip fracture and sarcopenia, and in obesity. Bimagrumab also blocks other endogenous ActRII ligands, such as activins, which act on the neurohormonal axes, pituitary, gonads and adrenal glands.

Evaluation of etoricoxib in patients undergoing total knee replacement surgery in a double-blind, randomized controlled trial.

Background: Optimal postoperative pain management is important to ensure patient comfort and early mobilization.

Methods: In this double-blind, placebo- and active-controlled, randomized clinical trial, we evaluated postoperative pain following knee replacement in patients receiving placebo, etoricoxib (90 or 120 mg), or ibuprofen 1800 mg daily for 7 days. Patients ≥18 years of age who had pain at rest ≥5 (0-10 Numerical Rating Scale [NRS]) after unilateral total knee replacement were randomly assigned to placebo (N = 98), etoricoxib 90 mg (N = 224), etoricoxib 120 mg (N = 230), or ibuprofen 1800 mg (N = 224) postoperatively.

Perioperative use of etoricoxib reduces pain and opioid side-effects after total abdominal hysterectomy: a double-blind, randomized, placebo-controlled phase III study.

Objective: To evaluate the effects of two different doses of etoricoxib delivered perioperatively compared with placebo and standard pain management on pain at rest, pain with mobilization, and use of additional morphine/opioids postoperatively.

Research Design And Methods: In this double-blind, placebo-controlled, randomized clinical trial, we evaluated postoperative pain following total abdominal hysterectomy over 5 days in patients receiving placebo or etoricoxib administered 90 min prior to surgery and continuing postoperatively. Patients were randomly assigned to receive either placebo (n = 144), etoricoxib 90 mg/day (n = 142), or etoricoxib 120 mg/day (n = 144).

Sarcopenia: an undiagnosed condition in older adults. Current consensus definition: prevalence, etiology, and consequences. International working group on sarcopenia.

Sarcopenia, the age-associated loss of skeletal muscle mass and function, has considerable societal consequences for the development of frailty, disability, and health care planning. A group of geriatricians and scientists from academia and industry met in Rome, Italy, on November 18, 2009, to arrive at a consensus definition of sarcopenia. The current consensus definition was approved unanimously by the meeting participants and is as follows: Sarcopenia is defined as the age-associated loss of skeletal muscle mass and function.

MK-0677 (ibutamoren mesylate) for the treatment of patients recovering from hip fracture: a multicenter, randomized, placebo-controlled phase IIb study.

Most elderly patients admitted for hip fracture suffer functional decline. Previous studies with MK-0677 in hip fracture patients suggested possible benefits to functional recovery. This is a randomized, double-blind study of 123 elderly hip fracture patients assigned to receive 25mg/day of MK-0677 (n = 62) or placebo (n = 61).

Once-weekly dose of 8400 IU vitamin D(3) compared with placebo: effects on neuromuscular function and tolerability in older adults with vitamin D insufficiency.

Background: Vitamin D insufficiency, which is prevalent in older individuals, is associated with bone and muscle weakness and falls.

Objective: We examined the effects of a weekly dose of 8400 IU vitamin D(3) on postural stability, muscle strength, and safety.

Design: In this double-blind trial, subjects aged > or =70 y with serum 25-hydroxyvitamin D [25(OH)D] concentrations < or =20 but > or =6 ng/mL were randomly assigned to receive a weekly dose of 8400 IU vitamin D(3) (n = 114) or a placebo (n = 112).

Performance-based or self-report measures of physical function: which should be used in clinical trials of hip fracture patients?

Objectives: To assess the validity, sensitivity to change, and responsiveness of 3 self-report and 4 performance-based measures of physical function: activity measure for postacute care (AM-PAC) Physical Mobility and Personal Care scales, the Medical Outcomes Study 36-Item Short Form Health Survey Physical Function scale (SF-36 PF), the Physical Functional Performance test (PFP-10), the Short Physical Performance Battery (SPPB), a 4-meter gait speed, and the six-minute walk test (6MWT).

Design: A prospective observational study of patients after a hip fracture. Assessments were performed at baseline and 12 weeks postenrollment.

Human adrenal glands secrete vitamin C in response to adrenocorticotrophic hormone.

Background: When vitamin C intake is from foods, fasting plasma concentrations do not exceed 80 micromol/L. We postulated that such tight control permits a paracrine function of vitamin C.

Objective: The purpose of this study was to determine whether paracrine secretion of vitamin C from the adrenal glands occurs.

Early adverse experience and risk for chronic fatigue syndrome: results from a population-based study.

Context: Chronic fatigue syndrome (CFS) is an important public health problem. The causes of CFS are unknown and effective prevention strategies remain elusive. A growing literature suggests that early adverse experience increases the risk for a range of negative health outcomes, including fatiguing illnesses.

Increased plasma interleukin 6 concentrations and exaggerated adipose tissue interleukin 6 content in severely obese patients after operative trauma.

Background: The cytokine response to operative trauma may be altered in obesity. Thus, we monitored changes in systemic and adipose tissue content of interleukin 6 (IL-6) and in insulin resistance in nonobese versus severely obese patients before and immediately after abdominal operations.

Methods: At the beginning and the end of operation, blood samples and biopsies consisting of visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) were collected from 13 nonobese and 33 severely obese patients.

Coping styles in people with chronic fatigue syndrome identified from the general population of Wichita, KS.

Objective: Studies of primary and tertiary care patients suggest that maladaptive coping styles contribute to the pathogenesis and maintenance of chronic fatigue syndrome (CFS). We assessed coping styles in persons with unexplained fatigue and nonfatigued controls in a population-based study.

Methods: We enrolled 43 subjects meeting the 1994 Research Case Definition of CFS, matching them with 61 subjects with chronic unexplained fatigue who did not meet criteria for CFS [we term them insufficient symptoms or fatigue (ISF)] and 60 non-ill (NI) controls.

Cognitive dysfunction relates to subjective report of mental fatigue in patients with chronic fatigue syndrome.

Patients with chronic fatigue syndrome (CFS) frequently complain of cognitive dysfunction. However, evidence of cognitive impairment in CFS patients has been found in some, but not other, studies. This heterogeneity in findings may stem from the relative presence of mental fatigue in the patient populations examined.

Orthostatic instability in a population-based study of chronic fatigue syndrome.

Purpose: Autonomic nervous system dysfunction has been suggested as involved in the pathophysiology of chronic fatigue syndrome. This population-based case control study addressed the potential association between orthostatic instability (one sign of dysautonomia) and chronic fatigue syndrome.

Subjects And Methods: Fifty-eight subjects who fulfilled criteria of the 1994 chronic fatigue syndrome research case definition and 55 healthy controls participated in a 2-day inpatient evaluation.

Chronic fatigue syndrome--a clinically empirical approach to its definition and study.

Background: The lack of standardized criteria for defining chronic fatigue syndrome (CFS) has constrained research. The objective of this study was to apply the 1994 CFS criteria by standardized reproducible criteria.

Methods: This population-based case control study enrolled 227 adults identified from the population of Wichita with: (1) CFS (n = 58); (2) non-fatigued controls matched to CFS on sex, race, age and body mass index (n = 55); (3) persons with medically unexplained fatigue not CFS, which we term ISF (n = 59); (4) CFS accompanied by melancholic depression (n = 27); and (5) ISF plus melancholic depression (n = 28).

Changes in C-reactive protein predict insulin sensitivity in severely obese individuals after weight loss surgery.

The production of inflammatory mediators by abdominal adipose tissue may link obesity and insulin resistance. We determined the influence of systemic levels of interleukin-6 and C-reactive protein on insulin sensitivity after weight loss via Roux-en-Y gastric bypass surgery. Severely obese individuals (n = 15) were evaluated at baseline and at 6 months after surgery.

Immunologic aspects of chronic fatigue syndrome. Report on a Research Symposium convened by The CFIDS Association of America and co-sponsored by the US Centers for Disease Control and Prevention and the National Institutes of Health.

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800,000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the immune system. A symposium was organized in October 2001 to explore the possibility of an association between immune dysfunction and CFS, with special emphasis on the interactions between immune dysfunction and other abnormalities noted in the neuroendocrine and autonomic nervous systems of individuals with CFS.

The effects of gastric surgery on systemic ghrelin levels in the morbidly obese.

Hypothesis: Circulating ghrelin, produced primarily in the stomach, is a powerful orexigen. Ghrelin levels are elevated in states of hunger, but rapidly decline postprandially. Early alterations in ghrelin levels in morbidly obese patients undergoing weight reduction surgery may be attributed to gastric partitioning.

Neuroendocrine aspects of chronic fatigue syndrome.

Chronic fatigue syndrome (CFS) is a serious health concern affecting over 800000 Americans of all ages, races, socioeconomic groups and genders. The etiology and pathophysiology of CFS are unknown, yet studies have suggested an involvement of the neuroendocrine system. A symposium was organized in March 2001 to explore the possibility of an association between neuroendocrine dysfunction and CFS, with special emphasis on the interactions between neuroendocrine dysfunction and other abnormalities noted in the immune and autonomic nervous systems of individuals with CFS.

Functional status of persons with chronic fatigue syndrome in the Wichita, Kansas, population.

Background: Scant research has adequately addressed the impact of chronic fatigue syndrome on patients' daily activities and quality of life. Enumerating specific problems related to quality of life in chronic fatigue syndrome patients can help us to better understand and manage this illness. This study addresses issues of functional status in persons with chronic fatigue syndrome and other fatiguing illnesses in a population based sample, which can be generalized to all persons with chronic fatigue.