Objective To summarise the long term efficacy of antiobesity drugs in reducing weight and improving health status.Design Updated meta-analysis of randomised trials. Data sources Medline, Embase, the Cochrane controlled trials register, the Current Science meta-register of controlled trials, and reference lists of identified articles. All data sources were searched from December 2002 (end date of last search) to December 2006. Studies reviewed Double blind randomised placebo controlled trials of approved anti-obesity dugs used in adults (age over 18) for one year or longer.

Studies evaluating the long-term efficacy of anti-obesity agents are limited to orlistat and sibutramine. Both drugs appear modestly effective in promoting weight loss; however, interpretation is limited by high attrition rates. Longer and more methodologically rigorous studies of anti-obesity drugs that are powered to examine endpoints such as mortality and cardiovascular morbidity are required to fully evaluate any potential benefit of such agents.

Many patients with non-dialysis dependent chronic kidney disease (CKD) live far from the closest nephrologist; although reversible, this might constitute a barrier to optimal care. In order to evaluate outcomes, we selected 31,452 outpatients older than 18 years with an estimated glomerular filtration rate (eGFR) less than 45 ml/min per 1.73 m² who had serum creatinine measured at least once during 2005 in Alberta, Canada. We then used logistic regression to examine the association between outcomes of 6545 patients who lived more than 50 km from the nearest nephrologist. Over a median follow-up of 27 months, 7684 participants died and 15,075 were hospitalized at least once. Compared with those living within 50 km, those further away were significantly less likely to visit a nephrologist or a multidisciplinary CKD clinic within 18 months of the index measurement of the eGFR. Similarly, remote dwellers with diabetes were significantly less likely to have hemoglobin A1c evaluated within 1 year of the index eGFR measurement, to have urinary albumin assessed biannually, or to receive an angiotensin converting enzyme inhibitor or receptor blocker in the setting of diabetes or proteinuria. Remote-dwelling participants were also significantly more likely to die or be hospitalized during follow-up than those living closer. Thus, among people with CKD, remote dwellers were less likely to receive specialist care, recommended laboratory testing, and appropriate medications, and were more likely to die or be hospitalized compared with those living closer to a nephrologist.

Patients with chronic kidney disease undergoing hemodialysis (HD) are potentially at risk of deficiency and excess of trace elements. HD exposes patients to large volumes of water (>120 l/week) in the form of dialysate. Although levels of certain ions (such as potassium and calcium) are carefully regulated in dialysate, many others are measured infrequently, if ever. As a result, substances in lower concentrations in the dialysis may be leached from the body. Conversely, toxic trace elements present in water but not in blood may accumulate and cause toxicity. Given that essential trace elements play key roles in multiple biological systems including immunological defense against oxidation and infection, it has been hypothesized that the increased morbidity and mortality seen in HD patients may in part be due to the imbalance of trace elements that has not been recognized. A recent systematic review has shown that compared with healthy controls, HD patients have significantly lower blood levels of zinc, manganese, and selenium, while blood levels of lead are likely to accumulate. Other trace elements, such as mercury and arsenic, are biologically plausible causes of excess mortality in dialysis patients, but available evidence is inconclusive as to whether they consistently accumulate in this population. Whether altered trace element levels are potentially reversible causes of adverse clinical outcomes in dialysis patients remains to be determined. This review highlights key issues related to this hypothesis, with special emphasis on zinc, manganese, selenium, lead, mercury, and arsenic.

Osteoarthritis is the most common joint disorder with aging, but its cause is unknown. Mice lose joint afferents with aging, and this loss precedes development of osteoarthritis. We hypothesized a loss of joint afferents is involved in the pathogenesis of osteoarthritis.To test this hypothesis, we denervated knee joints of 16 rats at age 2 months, by intra-articular injection o f an immunotoxin. The imrnunotoxin killed neurons after retrograde axonal transport to the cell body. At 16 or 24 months follow-up, each joint was histologically assessed and assigned an osteoarthritis score.At follow-up, the number of joint afferents had spontaneously decreased by 42% in control knees and 69%~ in denervated knees. We found that control knees developed osteoarthritic changes with aging. However, denervated knees had far more severe changes, as evidenced by a 54% higher average osteoarthritis score than control knees ( P = 0.0016, both groups 16 knees).These results suggest a loss of afferents predisposes a joint to osteoarthritis. We propose the spontaneous loss o f neurons with aging may be a normal developmental process. To explain the mechanism causing osteoarthritis, we suggest denervation permits aberrant joint loading, either by disturbing neuromuscular joint control, or by inducing joint laxity after neurogenic loss of tissue homeostasis.

Chronic kidney disease (CKD) is associated with accelerated progression of cardiovascular disease, perhaps because patients with CKD have a high burden of traditional cardiovascular risk factors in addition to a range of nontraditional risk factors such as inflammation and abnormal metabolism of calcium and phosphate. Although the cardiovascular burden of CKD is well documented, potentially beneficial therapies are sometimes underused in patients with stage 3-4 CKD and are rarely studied in patients on dialysis. In this Review, we describe the epidemiology of cardiovascular disease in patients with stage 3-5 CKD (excluding kidney transplant recipients) and outline cardiovascular risk factors that are relevant in this population; we then discuss the implications of this knowledge for the optimal management of cardiovascular risk in this setting. Finally, we highlight opportunities for further research.

These data support the hypothesis that the age-related decline in bone mass in men is associated with declining levels of IGF-I and testosterone.

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