Goals of Care 101

Hospice and Palliative Medicine - Alexandra Evans, DO Approaching Goals of Care in the Outpatient World - Elham Siddiqui, MD Inpatient Goals of Care Discussion - Adam Pennarola, M

Bringing Global Health Home: The Case of Global to Local in King County, Washington

The article describes the experience of testing successful global health interventions in the cities of SeaTac and Tukwila, Washington—2 very diverse, underserved communities outside of Seattle that experience significant health disparities compared with surrounding areas in King County. Topics covered include an overview of the partnership that established Global to Local, the process of engaging Seattle-based global health institutions in identifying global health strategies to test, identifying communities experiencing health disparities that might benefit from global health–inspired interventions, engaging those local communities to understand the perceived drivers of poor health outcomes, tailoring global interventions to the local context, launching programs, and the successes and challenges that have emerged throughout this process. Global health strategies that were tested and are reported on in the article include the use of community health workers to support chronic disease prevention and management, partnering with and building the capacity of local organizations and institutions, linking public health and primary care by addressing the social determinants of health in a primary care and community setting, and using mobile phones to transform practices for managing type 2 diabetes. The paper concludes that based on the early learnings of this approach, there is value in looking to tested and proven global health strategies to address health disparities in underserved communities in the United States and calls for further exploration of this approach by other actors

Pharmacotherapy for Chronic Insomnia: A Brief Survey of PCP Attitudes and Preferences

Purpose: To examine primary care professionals (PCP) attitudes and prescribing preferences toward hypnotic medications to treat chronic insomnia. Methods: An online survey was sent to members of the Dartmouth CO-OP, a practice-based primary care research network in Maine, Vermont, and New Hampshire. The survey begins with a case vignette of a 64-year old woman suffering from chronic insomnia. Clinicians were then presented with eight questions about management of the patient and their attitudes toward prescribing medications, focusing on benzodiazepines/benzodiazepine receptor agonists (BDZ/BZRAs). Results: 103 of 198 clinicians (52%) responded. Regarding choice of medication for the case vignette, 80% of respondents preferred the off-label use of hypnotics such as trazodone or melatonin; 11% stated they would choose BDZs and 21% would choose BZRAs. Strong majorities expressed that negative consequences would occur with use of BDZ/BZRAs, including tolerance (77%), dependence (68%), other side effects (53%), and addiction (51%). PCP preference for off- label prescribing was correlated to levels of concern about harms (addiction, dependence, tolerance, side effects) of BDZ/BZRAs as measured on a global medication risk score in this survey. In addition, 14% of respondents felt that pharmacotherapy was not an appropriate therapeutic option for chronic insomnia in the case vignette. Conclusion: Most of the clinicians surveyed acknowledged a legitimate role for hypnotic medications in chronic insomnia but expressed reservations toward BDZ/BZRAs despite their FDA approval and proven efficacy. There appears to be a gap between published guidelines for selection of sedative-hypnotic medications and PCP preferences

Field performance of bio-primed seeds to suppress Colletotrichum truncatum causing damping-off and seedling stand of soybean.

The soybean is prone to be attacked by Colletotrichum truncatum at seed and seedling stages, resulting in pre- and post-emergence damping-off. The efficacy of bio-priming for the control of damping-off of soybean caused by C. truncatum and the final seedling stand using two fungal biocontrol agents (BCAs) Trichoderma harzianum and T. virens and one bacterial BCA Pseudomonas aeruginosa was evaluated under field conditions. Treatments consisted of chemo-primed with Benlate® as a positive control; bio-primed with P. aeruginosa; bio-primed with T. harzianum; bio-primed with T. virens; bio-primed with the mixture of T. virens and T. harzianum and the controls as hydro-primed and non-primed seeds. Trichoderma isolates used singly or as a mixture established on the seed surface with germinating hyphae, whereas the strain P. aeruginosa colonized profusely as determined by increased colony forming units (CFU) from 1.2 × 109 to 5.1 × 109 seed−1 after 12 h of bio-priming. All bio-priming treatments significantly reduced pre- and post-emergence damping-off relative to hydro- and non-primed seed controls. In general, bio-priming with P. aeruginosa was the most effective treatment for controlling pre and post-emergence damping-off, with reductions in disease incidence with increases ranging from 48.6% to 51.9% and 65.0% to 97.2%, respectively. Moreover, P. aeruginosa resulted in enhancement of seed germination and healthy seedling stand ranging from 32.4% to 60.0% and 56.0% to 73.9%, respectively. Bio-priming with T. harzianum reduced pre- and post-emergence damping-off by 42.8–46.8% and 35.0–85.1%, respectively. However, P. aeruginosa was generally comparable to T. harzianum and the fungicide Benlate®. The combination treatment of T. harzianum and T. virens produced compareable results to T. harzianum alone, and T. virens was the least effective of the bio-primed treatments. Bio-priming with P. aeruginosa or T. harzianum offered an effective biological seed treatment system and an alternative to the fungicide Benlate® for control of damping-off of soybean caused by C. truncatum of soybean

Polymorphic segmental duplications at 8p23.1 challenge the determination of individual defensin gene repertoires and the assembly of a contiguous human reference sequence

BACKGROUND: Defensins are important components of innate immunity to combat bacterial and viral infections, and can even elicit antitumor responses. Clusters of defensin (DEF) genes are located in a 2 Mb range of the human chromosome 8p23.1. This DEF locus, however, represents one of the regions in the euchromatic part of the final human genome sequence which contains segmental duplications, and recalcitrant gaps indicating high structural dynamics. RESULTS: We find that inter- and intraindividual genetic variations within this locus prevent a correct automatic assembly of the human reference genome (NCBI Build 34) which currently even contains misassemblies. Manual clone-by-clone alignment and gene annotation as well as repeat and SNP/haplotype analyses result in an alternative alignment significantly improving the DEF locus representation. Our assembly better reflects the experimentally verified variability of DEF gene and DEF cluster copy numbers. It contains an additional DEF cluster which we propose to reside between two already known clusters. Furthermore, manual annotation revealed a novel DEF gene and several pseudogenes expanding the hitherto known DEF repertoire. Analyses of BAC and working draft sequences of the chimpanzee indicates that its DEF region is also complex as in humans and DEF genes and a cluster are multiplied. Comparative analysis of human and chimpanzee DEF genes identified differences affecting the protein structure. Whether this might contribute to differences in disease susceptibility between man and ape remains to be solved. For the determination of individual DEF gene repertoires we provide a molecular approach based on DEF haplotypes. CONCLUSIONS: Complexity and variability seem to be essential genomic features of the human DEF locus at 8p23.1 and provides an ongoing challenge for the best possible representation in the human reference sequence. Dissection of paralogous sequence variations, duplicon SNPs ans multisite variations as well as haplotypes by sequencing based methods is the way for future studies of interindividual DEF locus variability and its disease association

Effect of Covered Metallic Stents Compared With Plastic Stents on Benign Biliary Stricture Resolution A Randomized Clinical Trial

Importance Endoscopic placement of multiple plastic stents in parallel is the first-line treatment for most benign biliary strictures; it is possible that fully covered, self-expandable metallic stents (cSEMS) may require fewer endoscopic retrograde cholangiopancreatography procedures (ERCPs) to achieve resolution. Objective To assess whether use of cSEMS is noninferior to plastic stents with respect to stricture resolution. Design, Setting, and Participants Multicenter (8 endoscopic referral centers), open-label, parallel, randomized clinical trial involving patients with treatment-naive, benign biliary strictures (N = 112) due to orthotopic liver transplant (n = 73), chronic pancreatitis (n = 35), or postoperative injury (n = 4), who were enrolled between April 2011 and September 2014 (with follow-up ending October 2015). Patients with a bile duct diameter less than 6 mm and those with an intact gallbladder in whom the cystic duct would be overlapped by a cSEMS were excluded. Interventions Patients (N = 112) were randomized to receive multiple plastic stents or a single cSEMS, stratified by stricture etiology and with endoscopic reassessment for resolution every 3 months (plastic stents) or every 6 months (cSEMS). Patients were followed up for 12 months after stricture resolution to assess for recurrence. Main Outcomes and Measures Primary outcome was stricture resolution after no more than 12 months of endoscopic therapy. The sample size was estimated based on the noninferiority of cSEMS to plastic stents, with a noninferiority margin of −15%. Results There were 55 patients in the plastic stent group (mean [SD] age, 57 [11] years; 17 women [31%]) and 57 patients in the cSEMS group (mean [SD] age, 55 [10] years; 19 women [33%]). Compared with plastic stents (41/48, 85.4%), the cSEMS resolution rate was 50 of 54 patients (92.6%), with a rate difference of 7.2% (1-sided 95% CI, −3.0% to ∞; P < .001). Given the prespecified noninferiority margin of −15%, the null hypothesis that cSEMS is less effective than plastic stents was rejected. The mean number of ERCPs to achieve resolution was lower for cSEMS (2.14) vs plastic (3.24; mean difference, 1.10; 95% CI, 0.74 to 1.46; P < .001). Conclusions and Relevance Among patients with benign biliary strictures and a bile duct diameter 6 mm or more in whom the covered metallic stent would not overlap the cystic duct, cSEMS were not inferior to multiple plastic stents after 12 months in achieving stricture resolution. Metallic stents should be considered an appropriate option in patients such as these

Adaptive Radiation Therapy (ART) Strategies and Technical Considerations: A State of the ART Review From NRG Oncology

The integration of adaptive radiation therapy (ART), or modifying the treatment plan during the treatment course, is becoming more widely available in clinical practice. ART offers strong potential for minimizing treatment-related toxicity while escalating or de-escalating target doses based on the dose to organs at risk. Yet, ART workflows add complexity into the radiation therapy planning and delivery process that may introduce additional uncertainties. This work sought to review presently available ART workflows and technological considerations such as image quality, deformable image registration, and dose accumulation. Quality assurance considerations for ART components and minimum recommendations are described. Personnel and workflow efficiency recommendations are provided, as is a summary of currently available clinical evidence supporting the implementation of ART. Finally, to guide future clinical trial protocols, an example ART physician directive and a physics template following standard NRG Oncology protocol is provided

Hydrogen Sulfide and Silicon Together Alleviate Chromium (VI) Toxicity by Modulating Morpho-Physiological and Key Antioxidant Defense Systems in Chickpea (Cicer arietinum L.) Varieties

Extensive use of chromium (Cr) in anthropogenic activities leads to Cr toxicity in plants causing serious threat to the environment. Cr toxicity impairs plant growth, development, and metabolism. In the present study, we explored the effect of NaHS [a hydrogen sulfide; (H2S), donor] and silicon (Si), alone or in combination, on two chickpea (Cicer arietinum) varieties (Pusa 2085 and Pusa Green 112), in pot conditions under Cr stress. Cr stress increased accumulation of Cr reduction of the plasma membrane (PM) H+-ATPase activity and decreased in photosynthetic pigments, essential minerals, relative water contents (RWC), and enzymatic and non-enzymatic antioxidants in both the varieties. Exogenous application of NaHS and Si on plants exposed to Cr stress mitigated the effect of Cr and enhanced the physiological and biochemical parameters by reducing Cr accumulation and oxidative stress in roots and leaves. The interactive effects of NaHS and Si showed a highly significant and positive correlation with PM H+-ATPase activity, photosynthetic pigments, essential minerals, RWC, proline content, and enzymatic antioxidant activities (catalase, peroxidase, ascorbate peroxidase, dehydroascorbate reductase, superoxide dismutase, and monodehydroascorbate reductase). A similar trend was observed for non-enzymatic antioxidant activities (ascorbic acid, glutathione, oxidized glutathione, and dehydroascorbic acid level) in leaves while oxidative damage in roots and leaves showed a negative correlation. Exogenous application of NaHS + Si could enhance Cr stress tolerance in chickpea and field studies are warranted for assessing crop yield under Cr-affected area