The Use of Incremental Peritoneal Dialysis in a Large Contemporary Peritoneal Dialysis Program

Background: The use of an incremental peritoneal dialysis (PD) strategy in a large contemporary patient population has not been described. Objective: We report the use of this strategy in clinical practice, the prescriptions required, and the clearances achieved in a large center which has routinely used this approach for more than 10 years. Design: This is a cross-sectional observational study. Setting: A single large Canadian academic center. Patients: This study collected data on 124 prevalent PD patients at a single Canadian academic center. Methods and Measurements: The proportion of patients who achieve the clearance target on a low clearance or incremental PD prescription; the actual PD prescriptions and consequent total, peritoneal, and renal urea clearances [Kt/V] achieved; and patient and technique survival and peritonitis rate in comparison with national and international reports. Results: Of the 124 prevalent PD patients in this PD unit, 106 (86%) were achieving the Kt/V target, and of these, 54 (44% of all patients) were doing so using incremental PD prescriptions. Fifty of these incremental PD patients were using automated PD (APD) with either no day dwell (68%) or less than 7 days a week treatment (12%) or both (20%). Patient survival in our PD unit was not different from that reported in Canada as a whole. Peritonitis rates were better than internationally recommended standards. Limitations: This is an observational study with no randomized control group. Conclusions: Incremental PD is feasible in a contemporary PD population treated mainly with APD. Almost half of the patients were able to achieve clearance targets while receiving less onerous and less costly low clearance prescriptions. We suggest that incremental PD should be widely used as a cost-effective strategy in PD

Nusinersen Versus Sham Control In Infantile-Onset Spinal Muscular Atrophy

BACKGROUND & para;& para;Spinal muscular atrophy is an autosomal recessive neuromuscular disorder that is caused by an insufficient level of survival motor neuron (SMN) protein. Nusinersen is an antisense oligonucleotide drug that modifies pre-messenger RNA splicing of the SMN2 gene and thus promotes increased production of full-length SMN protein.& para;& para;METHODS & para;& para;We conducted a randomized, double-blind, sham-controlled, phase 3 efficacy and safety trial of nusinersen in infants with spinal muscular atrophy. The primary end points were a motor-milestone response (defined according to results on the Hammersmith Infant Neurological Examination) and event-free survival (time to death or the use of permanent assisted ventilation). Secondary end points included over all survival and subgroup analyses of event-free survival according to disease duration at screening. Only the first primary end point was tested in a prespecified interim analysis. To control the overall type I error rate at 0.05, a hierarchical testing strategy was used for the second primary end point and the secondary end points in the final analysis.& para;& para;RESULTS & para;& para;In the interim analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (21 of 51 infants [41 %] vs. 0 of 27 [0%], P<0.001), and this result prompted early termination of the trial. In the final analysis, a significantly higher percentage of infants in the nusinersen group than in the control group had a motor-milestone response (37 of 73 infants [51%] vs. 0 of 37 [0%]), and the likelihood of event-free survival was higher in the nusinersen group than in the control group (hazard ratio for death or the use of permanent assisted ventilation, 0.53; P=0.005). The likelihood of overall survival was higher in the nusinersen group than in the control group (hazard ratio for death, 0.37; P=0.004), and infants with a shorter disease duration at screening were more likely than those with a longer disease duration to benefit from nusinersen. The incidence and severity of adverse events were similar in the two groups.& para;& para;CONCLUSIONS & para;& para;Among infants with spinal muscular atrophy, those who received nusinersen were more likely to be alive and have improvements in motor function than those in the control group. Early treatment may be necessary to maximize the benefit of the drug.Wo

The database of the PREDICTS (Projecting Responses of Ecological Diversity In Changing Terrestrial Systems) project

The PREDICTS project—Projecting Responses of Ecological Diversity In Changing Terrestrial Systems (www.predicts.org.uk)—has collated from published studies a large, reasonably representative database of comparable samples of biodiversity from multiple sites that differ in the nature or intensity of human impacts relating to land use. We have used this evidence base to develop global and regional statistical models of how local biodiversity responds to these measures. We describe and make freely available this 2016 release of the database, containing more than 3.2 million records sampled at over 26,000 locations and representing over 47,000 species. We outline how the database can help in answering a range of questions in ecology and conservation biology. To our knowledge, this is the largest and most geographically and taxonomically representative database of spatial comparisons of biodiversity that has been collated to date; it will be useful to researchers and international efforts wishing to model and understand the global status of biodiversity

Erratum to: Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition) (Autophagy, 12, 1, 1-222, 10.1080/15548627.2015.1100356

non present