In three phase 3 trials involving patients with psoriasis, ixekizumab was effective through 60 weeks of treatment. As with any treatment, the benefits need to be weighed against the risks of adverse events. The efficacy and safety of ixekizumab beyond 60 weeks of treatment are not yet known. (Funded by Eli Lilly; UNCOVER-1, UNCOVER-2, and UNCOVER-3 ClinicalTrials.gov numbers NCT01474512, NCT01597245, and NCT01646177, respectively.).

Cystic fibrosis (CF) is the most common genetic disease within the Caucasian population and leads to premature respiratory failure. Approximately 60,000 individuals are currently living with CF in North America and Europe, 40% of whom are adults. The life span of these patients has increased from approximately 2 to 32 yr of age over the last three decades. Bone disease has emerged as a common complication in long-term survivors of CF. Some studies have observed that 50-75% of adults have low bone density and increased rates of fractures. Prevention and treatment of CF-related bone disease must address the myriad risk factors (decreased absorption of fat-soluble vitamins due to pancreatic insufficiency, altered sex hormone production, chronic lung infection with increased levels of bone-active cytokines, physical inactivity, and glucocorticoid therapy) for poor bone health. This review is a condensed and updated summary of the Guide to Bone Health and Disease in Cystic Fibrosis: A Consensus Conference, a statement that evolved from a meeting convened by the Cystic Fibrosis Foundation in May 2002 to address the pathogenesis, diagnosis, and treatment of bone disease in CF. The goal of this conference was to develop practice guidelines for optimizing bone health in patients with CF.

No abstract

Insulin resistance has recently been found to be a common feature of essential hypertension. We have tested the hypothesis that reduced skeletal muscle blood flow in response to insulin may at least partially account for the wide range of insulin sensitivity observed in normotensive subjects. To this end, we studied 19 lean (body mass index £27) subjects exhibiting basal mean arterial pressures ranging from 58 to 110 mm Hg. All subjects were normotensive with the exception of one. Each subject was studied at baseline and during a hyperinsulinemic (600 milliunits/m 2 per minute) euglycemic clamp to quantitate insulin sensitivity. Mean arterial pressure was monitored invasively, and both leg (muscle) blood flow and cardiac output were measured by indicator dilution techniques, allowing the determination of both systemic and leg (or muscle) vascular resistance. In response to hyperinsulinemia, both cardiac output and leg blood flow increased approximately 37% and 80% (p<0.01), respectively. Rates of insulin-mediated glucose uptake were inversely correlated with the baseline mean arterial pressure (r=-0.62, p<0.01). The individual increment in leg blood flow above baseline in response to insulin was inversely proportional to the height of the baseline mean arterial pressure (r=-0.59, p<0.01). Mean arterial pressure and insulin-mediated glucose uptake were not correlated with either age or body fat content. The femoral arteriovenous glucose difference during hyperinsulinemia was not correlated with either basal mean arterial pressure or the rate of insulin-mediated glucose uptake. In summary, among normotensive subjects, 1) the rate of insulin-mediated glucose uptake is inversely proportional to the basal mean arterial pressure, 2) the increase in insulin-mediated muscle blood flow is inversely related to the basal mean arterial pressure, and 3) muscle glucose extraction is not related to the basal mean arterial pressure or the rate of insulin-mediated glucose uptake. In conclusion, attenuated insulin-mediated skeletal muscle blood flow appears to be a major cause of insulin resistance in subjects with elevated mean arterial pressure. Our data in normotensive subjects do not exclude the coexistence of other defects in glucose uptake and metabolism; nevertheless, they strongly support a hemodynamic basis for the insulin resistance observed in patients with hypertension.