Intensive renal support in critically ill patients with acute kidney injury did not decrease mortality, improve recovery of kidney function, or reduce the rate of nonrenal organ failure as compared with less-intensive therapy involving a defined dose of intermittent hemodialysis three times per week and continuous renal-replacement therapy at 20 ml per kilogram per hour. (ClinicalTrials.gov number, NCT00076219.)

Background & Aims The interferon-free regimen of simeprevir plus sofosbuvir was recommended by professional guidelines for certain patients with hepatitis C virus (HCV) genotype 1 infection based on the findings of a phase 2 trial. We aimed to evaluate the safety and efficacy of this regimen in clinical practice settings in North America. Methods We collected demographic, clinical, and virologic data, as well as reports of adverse outcomes, from sequential participants in HCV-TARGET—a prospective, observational cohort study of patients undergoing HCV treatment in routine clinical care settings. From January through October 2014, 836 patients with HCV genotype 1 infection began 12 weeks of treatment with simeprevir plus sofosbuvir (treatment duration of up to 16 weeks); 169 of these patients received ribavirin. Most patients were male (61%), Caucasian (76%), or black (13%); 59% had cirrhosis. Most had failed prior treatment with peginterferon and ribavirin without (46%) or with telaprevir or boceprevir (12%). The primary outcome was sustained virologic response (SVR), defined as level of HCV RNA below quantification at least 64 days after the end of treatment (beginning of week 12 after treatment—a 2 week window). Logistic regression models with inverse probability weights were constructed to adjust for baseline covariates and potential selection bias. Results The overall rate of SVR rate was 84% (675/802 patients, 95% CI: 81–87%). Model-adjusted estimates indicate patients with cirrhosis, prior decompensation, and previous protease inhibitor treatments were less likely to achieve an SVR. The addition of ribavirin had no detectable effects on SVR. The most common adverse events were fatigue, headache, nausea, rash, and insomnia. Serious adverse events and treatment discontinuation occurred in only 5% and 3% of participants, respectively. Conclusions In a large, prospective observational cohort study, a 12 week regimen of simeprevir plus sofosbuvir was associated with high rates of SVR and infrequent treatment discontinuation. ClinicalTrials.gov: NCT01474811

Background Recurrent infection with the hepatitis C virus (HCV) after liver transplantation is associated with decreased graft and patient survival. Achieving sustained virological response (SVR) with antiviral therapy improves survival. Because interferon-based therapy has limited efficacy and is poorly tolerated, there has been rapid transition to interferon-free direct-acting antiviral (DAA) regimens. Herein the experience with DAAs in the treatment of post-transplant genotype 1HCV from a consortium of community and academic centers (HCV TARGET) is described. Methods Twenty-one of the 54 centers contributing to the HCV TARGET consortium participated in this study. Enrollment criteria included positive post-transplant HCV RNA prior to treatment, HCV genotype 1, and documentation of use of a simeprevir/sofosbuvir (SMV/SOF) containing DAA regimen. Safety and efficacy were assessed. SVR was defined as undetectable HCV RNA 64 days or later after cessation of treatment. Results A total of 162 patients enrolled in HCV-TARGET started treatment with SMV/SOF with or without ribavirin following liver transplantation. The study population included 151 patients treated with these regimens for whom outcomes and safety data were available. The majority of the 151 patients were treated with sofosbuvir and simeprevir alone (n=119, 78%) or with ribavirin (n=32, 22%), The duration of therapy was 12 weeks for most patients, although 15 patients received 24 weeks of treatment. Of all patients receiving SOF/SIM +/− Ribavirin, 133/151 (88%) achieved SVR12 and 11 relapsed (7%). One patient had virologic breakthrough (n=1) and 6 patients were lost to post treatment follow up. Serious adverse events occurred in 12%; 3 patients (all cirrhotic) died due to aspiration pneumonia, suicide, and multi-organ failure. One experienced liver transplant rejection. Conclusions Interferon-free DAA treatment represents a major improvement over prior interferon-based therapy. Broader application of these and other emerging DAA regimens in the treatment of post-transplant hepatitis C is warranted.

JSTOR is a not-for-profit service that helps scholars, researchers, and students discover, use, and build upon a wide range of content in a trusted digital archive. We use information technology and tools to increase productivity and facilitate new forms of scholarship. For more information about JSTOR, please contact support@jstor.org.. INSTAAR, University of Colorado andThe Regents of the University of Colorado, a body corporate, contracting on behalf of the University of Colorado at Boulder for the benefit of INSTAAR are collaborating with JSTOR to digitize, preserve and extend access to Arctic and Alpine Research.ABSTRACT More than 70 samples of Holocene driftwood between present sea level and the marine limit are plotted on an emergence curve from Clements Markham Inlet (82?40'N). Three periods of driftwood abundance and sparsity are recognized. These are interpreted as indications of climatically induced changes in summer sea ice conditions. Period 1 extends from initial driftwood entry ca. 8900 BP until ca. BP. During this period driftwood penetration increases with greatest abundance (= reduced summer sea ice) ca. 6000 to BP. During Period 2 (ca. to 500 BP) driftwood penetration is sparse whereas in Period 3 (< 500 BP) driftwood bordering the present shoreline exceeds all the samples in the previous periods. Driftwood dates from elsewhere in the Canadian and Greenland High Arctic show similar periods.In Clements Markham Inlet the initiation of abundant driftwood penetration corresponds with the deposition in marine sediments of fossil bryophytes (25 species) dated 6400 BP. This increased plant productivity is also interpreted as indicating summer warmth/higher precipitation associated with the greater open water. Accompanying these bryophytes is the disjunct marine pelecypod Limatula (Lima) subauriculata which presently has a subarctic-boreal distribution. This paleoenvironmental information is discussed in relation to Holocene ice core records and the history of Arctic Ocean sea ice stability.

CKD is steadily increasing along with obesity worldwide. Furthermore, obesity is a proinflammatory risk factor for progression of CKD and cardiovascular disease. We tested the hypothesis that implementation of caloric restriction and aerobic exercise is feasible and can improve the proinflammatory metabolic milieu in patients with moderate to severe CKD through a pilot, randomized, 2×2 factorial design trial. Of 122 participants consented, 111 were randomized to receive caloric restriction and aerobic exercise, caloric restriction alone, aerobic exercise alone, or usual care. Of those randomized, 42% were women, 25% were diabetic, and 91% were hypertensive; 104 started intervention, and 92 completed the 4-month study. Primary outcomes were a change from baseline in absolute fat mass, body weight, plasma F-isoprostane concentrations, and peak oxygen uptake (VO). Compared with usual care, the combined intervention led to statistically significant decreases in body weight and body fat percentage. Caloric restriction alone also led to significant decreases in these measures, but aerobic exercise alone did not. The combined intervention and each independent intervention also led to significant decreases in F-isoprostane and IL-6 concentrations. No intervention produced significant changes in VO, kidney function, or urine albumin-to-creatinine ratio. In conclusion, 4-month dietary calorie restriction and aerobic exercise had significant, albeit clinically modest, benefits on body weight, fat mass, and markers of oxidative stress and inflammatory response in patients with moderate to severe CKD. These results suggest healthy lifestyle interventions as a nonpharmacologic strategy to improve markers of metabolic health in these patients.

Sea‐ice ice shelves, at the apex of North America (>80° N), constitute the oldest sea ice in the Northern Hemisphere. We document the establishment and subsequent stability of the Ward Hunt Ice Shelf, and multiyear landfast sea ice in adjacent fiords, using 69 radiocarbon dates obtained on Holocene driftwood deposited prior to coastal blockage. These dates (47 of which are new) record a hiatus in driftwood deposition beginning ∼5500 cal yr BP, marking the inception of widespread multiyear landfast sea ice across northern Ellesmere Island. This chronology, together with historical observations of ice shelf breakup (∼1950 to present), provides the only millennial‐scale record of Arctic Ocean sea ice variability to which the past three decades of satellite surveillance can be compared. Removal of the remaining ice shelves would be unprecedented in the last 5500 years. This highlights the impact of ongoing 20th and 21st century climate warming that continues to break up the remaining ice shelves and soon may cause historically ice‐filled fiords nearby to open seasonally.

Background Older adults with advanced CKD have significant pain, other symptoms, and disability. To help ensure that care is consistent with patients' values, nephrology providers should understand their patients' priorities when they make clinical recommendations.Methods Patients aged $60 years with advanced (stage 4 or 5) non-dialysis-dependent CKD receiving care at a CKD clinic completed a validated health outcome prioritization tool to ascertain their health outcome priorities. For each patient, the nephrology provider completed the same health outcome prioritization tool. Patients also answered questions to self-rate their health and completed an end-of-life scenarios instrument. We examined the associations between priorities and self-reported health status and between priorities and acceptance of common end-of-life scenarios, and also measured concordance between patients' priorities and providers' perceptions of priorities.Results Among 271 patients (median age 71 years), the top health outcome priority was maintaining independence (49%), followed by staying alive (35%), reducing pain (9%), and reducing other symptoms (6%). Nearly half of patients ranked staying alive as their third or fourth priority. There was no relationship between patients' self-rated health status and top priority, but acceptance of some end-of-life scenarios differed significantly between groups with different top priorities. Providers' perceptions about patients' top health outcome priorities were correct only 35% of the time. Patient-provider concordance for any individual health outcome ranking was similarly poor.Conclusions Nearly half of older adults with advanced CKD ranked maintaining independence as their top heath outcome priority. Almost as many ranked being alive as their last or second-to-last priority. Nephrology providers demonstrated limited knowledge of their patients' priorities.

Background & Aims The safety profiles of boceprevir and telaprevir in the treatment of chronic hepatitis C, administered in academic and community centres across the United States, were evaluated. Methods In 90 medical centres, patients with chronic HCV received pegylated interferon, ribavirin, and either telaprevir or boceprevir per local standard of care. Demographic, adverse event, clinical, and virological data were collected during treatment and follow-up. Results A total of 2084 patients (97% HCV genotype 1) received at least one dose of a protease inhibitor. At baseline, 38% of patients had cirrhosis, and 57% had received at least one prior treatment for hepatitis C. Serious adverse events occurred in 12% of patients receiving protease inhibitor therapy. Overall, 66% of patients experienced anaemia, leading to frequent ribavirin dose reductions (42%) and erythropoietin use (37%); 11% received blood transfusion. More than 90% of patients had adverse events that led to a prescription, treatment, or dosage change, and 39% of patients discontinued treatment early, most commonly because of adverse events (18%) or lack of efficacy (16%). Hepatic decompensation events occurred in 3% of all patients. Age, female gender, cirrhosis, HCV genotype 1 subtype, creatinine clearance, platelet levels, albumin levels and haemoglobin levels were independent predictors of anaemia. Five deaths occurred. Overall, 52% of all patients achieved a sustained virologic response. Conclusions In academic and community centres, where chronic hepatitis C patients commonly have advanced liver disease, triple therapy was associated with a high rate of adverse events and involved frequent treatment modifications and adverse event management.