The International Registry of Werner syndrome (www.wernersyndrome.org) has been providing molecular diagnosis of the Werner syndrome (WS) for the past decade. The present communication summarizes, from among 99 WS subjects, the spectrum of 50 distinct mutations discovered by our group and by others since the WRN gene (also called RECQL2 or REQ3) was first cloned in 1996; 25 of these have not previously been published. All WRN mutations reported thus far have resulted in the elimination of the nuclear localization signal at the C-terminus of the protein, precluding functional interactions in the nucleus; thus, all could be classified as null mutations. We now report two new mutations in the N-terminus that result in instability of the WRN protein. Clinical data confirm that the most penetrant phenotype is bilateral ocular cataracts. Other cardinal signs were seen in more than 95% of the cases. The median age of death, previously reported to be in the range of 46-48 years, is 54 years. Lymphoblastoid cell lines (LCLs) have been cryopreserved from the majority of our index cases, including material from nuclear pedigrees. These, as well as inducible and complemented hTERT (catalytic subunit of human telomerase) immortalized skin fibroblast cell lines are available to qualified investigators.

The medical management of infants with the trisomy 13 and trisomy 18 syndromes is challenging and controversial. Both conditions have high neonatal and infant mortality, and surviving children display significant cognitive and motor disabilities. Currently, there exists a tension in the neonatal and perinatal communities regarding care. One view holds that management should consist solely of comfort care, while another opinion recommends offering medical and surgical intervention in appropriate situations. The purpose of this manuscript is to present a model for the care of fetuses and infants with trisomy 13 and 18 during the prenatal, perinatal, and postnatal periods. Adopting the pathways approach as a framework, we have identified several pertinent decision points, characterizing the goals of care and the resources needed for the decision points at various times. Additionally, we identified themes surrounding parental and professional experiences. The authors propose a care model for trisomy 13 and 18 that uses shared decision making as its foundational principle and the pathways approach as the method. Our model requires further investigation as a strategy for care in order to render it useful in other complex medical situations. © 2016 Wiley Periodicals, Inc.

People leaving incarceration are at high risk of opioid-related overdose. Overdose fatalities are preventable with administration of naloxone. In response to this risk, overdose education and naloxone distribution (OEND) programs have been implemented in a handful of jails and prisons in the United States. We document the history, structure, and data from the San Francisco County Jail OEND program. During 4 years of operation, 637 people participated; 67% received naloxone upon release, of whom only 3.5% had been previously trained in community-based OEND programs. Of those who received naloxone, 32% reported reversing an overdose and 44% received refills from community-based programs after reentry. This confirms that implementation of OEND in criminal justice settings is feasible and reaches people who have not previously been trained as well as those willing to act as overdose responders.

Background Hub and spoke systems (HSS) are increasingly promoted as a systems-level intervention to expand access to medication for opioid use disorders (MOUD), particularly in rural areas with limited treatment options. The HSS model consists of sub-systems in which “hubs” deliver specialized expertise to a regional network of office-based opioid treatment (OBOT) providers in “spokes,” who together create a continuum of acute and chronic care. Yet, little is known about system-level factors (e.g., system structure, financing) that influence HSS implementation and sustainability in rural areas. Methods For this case study, we conducted semi-structured interviews with substance use disorder treatment providers ( N = 26) and system-level stakeholders ( N = 16) in five rural HSS sub-systems throughout one state. We undertook iterative textual analysis of interview transcripts, identifying and coding themes related to key implementation constructs associated with the Exploration, Preparation, Implementation and Sustainability (EPIS) framework. Results California policy-makers adopted HSS to expand rural access to opioid treatment programs (OTPs, i.e., providers of methadone and other medications for opioid use disorder). However, stakeholders questioned the model's fit for rural regions featuring few established OTPs that could function as hubs and critiqued its treatment-focused approach, felt to sideline harm reduction service providers. Contracts to serve rural regions were awarded entirely to for-profit methadone providers, contributing to stigma and distrust among many buprenorphine providers whose organizations were later recruited as spokes. While hubs offered financial resources enabling some spokes to expand MOUD, the needs of spokes varied considerably. Relationships between hubs and spokes to facilitate the care continuum under HSS were restricted by limited behavioral health resources and the large distances characterizing rural California. Conclusions This case study reveals how rural contextual factors such as geography and behavioral healthcare resource availability can dramatically influence differential HSS implementation.

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