Using the specificity and overload principles to prevent sarcopenia, falls and fractures with exercise.

The aim of this narrative review is to discuss the evidence on exercise for fall, fracture and sarcopenia prevention, including evidence that aligns with the specificity and progressive overload principles used in exercise physiology, implementation strategies and future research priorities. We also provide a brief discussion of the influence of protein intake and creatine supplementation as potential effect modifiers. We prioritized evidence from randomized controlled trials and systematic reviews. Resistance training can improve muscle mass, muscle strength and a variety of physical performance measures in older adults. Resistance training may also prevent bone loss or increase bone mass, although whether it needs to be done in combination with impact exercise to be effective is less clear, because many studies use multicomponent interventions. Exercise programs prevent falls, and subgroup and network meta-analyses suggest an emphasis on balance and functional training, or specifically, anticipatory control, dynamic stability, functional stability limits, reactive control and flexibility, to maximize efficacy. Resistance training for major muscle groups at a 6-12 repetitions maximum intensity, and challenging balance exercises should be performed at least twice weekly. Choose resistance training exercises aligned with patient goals or movements done during daily activities (task specificity), alongside balance exercises tailored to ability and aspects of balance that need improvement. Progress the volume, level of difficulty or other aspects to see continuous improvement (progressive overload). A critical future priority will be to address implementation barriers and facilitators to enhance uptake and adherence.

Muscle Disuse as a Pivotal Problem in Sarcopenia-related Muscle Loss and Dysfunction.

An age-associated loss of muscle mass and strength--sarcopenia--begins at around the fifth decade of life, with mass being lost at ~0.5-1.2% per year and strength at ~3% per year. Sarcopenia can contribute to a variety of negative health outcomes, including an increased risk for falls and fractures, the development of metabolic diseases like type 2 diabetes mellitus, and increase the chance of requiring assisted living. Linear sarcopenic declines in muscle mass and strength are, however, punctuated by transient periods of muscle disuse that can accelerate losses of muscle and strength, which could result in increased risk for the aforementioned conditions. Muscle disuse is recognizable with bed rest or immobilization (for example, due to surgery or acute illness requiring hospitalization); however, recent work has shown that even a relative reduction in ambulation (reduced daily steps) results in significant reductions in muscle mass, strength and possibly an increase in disease risk. Although reduced ambulation is a seemingly "benign" form of disuse, compared to bed rest and immobilization, reports have documented that 2-3 weeks of reduced daily steps may induce: negative changes in body composition, reductions in muscle strength and quality, anabolic resistance, and decrements in glycemic control in older adults. Importantly, periods of reduced ambulation likely occur fairly frequently and appear more difficult to fully recover from, in older adults. Here we explore the consequences of muscle disuse due to reduced ambulatory activity in older adults, with frequent comparisons to established models of disuse: bed rest and immobilization.

Epidermal growth factor receptor targeted therapy in stages III and IV head and neck cancer.

QUESTION: What are the benefits associated with the use of anti-epidermal growth factor receptor (anti-EGFR) therapies in squamous cell carcinoma of the head and neck (HNSCC)? Anti-EGFR therapies of interest included cetuximab, gefitinib, lapatinib, zalutumumab, erlotinib, and panitumumab. PERSPECTIVES: Head-and-neck cancer includes malignant tumours arising from a variety of sites in the upper aerodigestive tract. The most common histologic type is squamous cell carcinoma, and most common sites are the oral cavity, the oropharynx, the hypopharynx, and the larynx. Worldwide, HNSCC is the sixth most common neoplasm, and despite advances in therapy, long-term survival in HNSCC patients is poor. Primary surgery followed by chemoradiation, or primary chemoradiation, are the standard treatment options for patients with locally advanced (stages III-IVB) HNSCC; however, meta-analytic data indicate that the benefit of concurrent platinum-based chemotherapy disappears in patients over the age of 70 years. Cetuximab is a monoclonal antibody approved for use in combination with radiation in the treatment of patients with untreated locally advanced HNSCC and as monotherapy for patients with recurrent or metastatic (stage IVC) HNSCC who have progressed on platinum-based therapy. Given the interest in anti-EGFR agents in advanced HNSCC, the Head and Neck Cancer Disease Site Group (DSG) of Cancer Care Ontario's Program in Evidence-Based Care (PEBC) chose to systematically review the literature pertaining to this topic so as to develop evidence-based recommendations for treatment. OUTCOMES: Outcomes of interest included overall and progression-free survival, quality of life, tumour response rate and duration, and the toxicity associated with the use of anti-EGFR therapies. METHODOLOGY: The medline, embase, and Cochrane Library databases, the American Society of Clinical Oncology online conference proceedings, the Canadian Medical Association InfoBase, and the National Guidelines Clearinghouse were systematically searched to locate primary articles and practice guidelines. The reference lists from relevant review articles were searched for additional trials. All evidence was reviewed, and that evidence informed the development of the clinical practice guideline. The resulting recommendations were approved by the Report Approval Panel of the PEBC, and by the Head and Neck Cancer DSG. An external review by Ontario practitioners completed the final phase of the review process. Feedback from all parties was incorporated to create the final practice guideline. RESULTS: The electronic search identified seventy-four references that were reviewed for inclusion. Only four phase iii trials met the inclusion criteria for the present guideline. No practice guidelines, systematic reviews, or meta-analyses were found during the course of the literature search. The randomized controlled trials (RCTS) involved three distinct patient populations: those with locally advanced HNSCC being treated for cure, those with incurable advanced recurrent or metastatic HNSCC being treated with first-line platinum-based chemotherapy, and those with incurable advanced recurrent or metastatic HNSCC who had disease progression despite, or who were unsuitable for, first-line platinum-based chemotherapy. PRACTICE GUIDELINE: These recommendations apply to adult patients with locally advanced (nonmetastatic stages iii-ivb) or recurrent or metastatic (stage IVC) HNSCC. Platinum-based chemoradiation remains the current standard of care for treatment of locally advanced HNSCC. In patients with locally advanced HNSCC who are medically unsuitable for concurrent platinum based chemotherapy or who are over the age of 70 years (because concurrent chemotherapy does not appear to improve overall survival in this patient population), the addition of cetuximab to radical radiotherapy should be considered to improve overall survival, progression-free survival, and time to local recurrence.Cetuximab in combination with platinum-based combination chemotherapy is superior to chemotherapy alone in patients with recurrent or metastatic HNSCC, and is recommended to improve overall survival, progression-free survival, and response rate.The role of anti-EGFR therapies in the treatment of locally advanced HNSCC is currently under study in large randomized trials, and patients with HNSCC should continue to be offered clinical trials of novel agents aimed at improving outcomes. QUALIFYING STATEMENTS: Chemoradiation is the current standard of care for patients with locally advanced HNSCC, and to date, there is no evidence that compares cetuximab plus radiotherapy with chemoradiation, or that examines whether the addition of cetuximab to chemoradiation is of benefit in these patients. However, five ongoing trials are investigating the effect of the addition of EGFR inhibitors concurrently with, before, or after chemoradiotherapy; those trials should provide direction about the best integration of cetuximab into standard treatment. In patients with recurrent or metastatic HNSCC who experience progressive disease despite, or who are unsuitable for, first-line platinum-based chemotherapy, gefitinib at doses of 250 mg or 500 mg daily, compared with weekly methotrexate, did not increase median overall survival [hazard ratio (hr): 1.22; 96% confidence interval (ci): 0.95 to 1.57; p = 0.12 (for 250 mg daily vs. weekly methotrexate); hr: 1.12; 95% ci: 0.87 to 1.43; p = 0.39 (for 500 mg daily vs. weekly methotrexate)] or objective response rate (2.7% for 250 mg and 7.6% for 500 mg daily vs. 3.9% for weekly methotrexate, p > 0.05). As compared with methotrexate, gefitinib was associated with an increased incidence of tumour hemorrhage (8.9% for 250 mg and 11.4% for 500 mg daily vs. 1.9% for weekly methotrexate).