Search

Pancreatic beta-cells and gamma-aminobutyric acid (GABA)-secreting neurons both express the enzyme glutamic acid decarboxylase (GAD) which is a major target of autoantibodies associated with beta-cell destruction and impairment of GABA-ergic neurotransmitter pathways. The predominant form of GAD in pancreatic beta-cells, GAD65, is synthesized as a soluble hydrophilic molecule, which is modified to become firmly membrane anchored. Here we show by immunogold electron microscopy that GAD65 is localized to the membrane of small vesicles which are identical in size to small synaptic-like microvesicles in pancreatic beta-cells. The NH2-terminal domain of GAD65 is the site of a two-step modification, the last of which results in a firm membrane anchoring that involves posttranslational hydroxylamine sensitive palmitoylation. GAD65 can be released from the membrane by an apparent enzyme activity in islets, suggesting that the membrane anchoring step is reversible and potentially regulated. The hydrophobic modifications and consequent membrane anchoring of GAD65 to microvesicles that store its product GABA may be of functional importance and, moreover, significant for its selective role as an autoantigen.

Developing skills to critically evaluate and conduct research is central to psychology training programmes. The fundamental importance of scientific evidence to the practice and progression of psychology as a discipline is reflected in the "Scientist-Practitioner" model, to which psychologists adhere. However, to fully realise the potential benefits of the Scientist-Practitioner model for psychological practice and client outcomes, its implementation needs to occur in a bi-directional way. That is, psychologists need to be actively engaged in both a critical analysis of literature to inform clinical practice, as well as using their clinical expertise to develop, inform, and lead research activities to contribute to the evidence-base. Unfortunately, psychologists employed in public health settings are rarely able to utilise their research skills to contribute to the evidence-base. In this Commentary, we critically examine literature regarding barriers and facilitators to psychologists employed in clinical roles engaging in research activities. We argue that enabling more practising psychologists to lead research could facilitate significant benefits to individuals (both the psychologists and their clients) and organisations. We then describe the strategies developed and implemented by a local psychology research committee to drive improvements and address obstacles to psychology-led research in public health. [ABSTRACT FROM AUTHOR]

Norfolk Island is a human genetic isolate, possessing unique population characteristics that could be utilized for complex disease gene localization. Our intention was to evaluate the extent and strength of linkage disequilibrium (LD) in the Norfolk isolate by investigating markers within Xq13.3 and the NOS2A gene encoding the inducible nitric oxide synthase. A total of six microsatellite markers spanning ∼11 Mb were assessed on chromosome Xq13.3 in a group of 56 men from Norfolk Island. Additionally, three single nucleotide polymorphisms (SNPs) localizing to the NOS2A gene were analyzed in a subset of the complex Norfolk pedigree. With the exception of two of the marker pairs, one of which is the most distantly spaced marker, all the Xq13.3 marker pairs were found to be in significant LD indicating that LD extends up to 9.5–11.5 Mb in the Norfolk Island population. Also, all SNPs studied showed significant LD in both Norfolk Islanders and Australian Caucasians, with two of the marker pairs in complete LD in the Norfolk population only. The Norfolk Island study population possesses a unique set of characteristics including founder effect, geographical isolation, exhaustive genealogical information and phenotypic data of use to cardiovascular disease risk traits. With LD extending up to 9.5–11 Mb, the Norfolk isolate should be a powerful resource for the localization of complex disease genes.Heredity (2008) 100, 366–373; doi:10.1038/sj.hdy.6801083; published online 19 December 2007 [ABSTRACT FROM AUTHOR]

Bis(2-Methoxyethyl) Ether: Metabolism and Embryonic Disposition of a Developmental Toxicant in the Pregnant CD-I Mouse. DANIEL, F. B., CHEEVER, K. L., BEGLEY, K. B., RICHARDS, D. E., WEIGEL, W. W., AND EISENMANN C. J. (1991). . 16, 567–575. An embryotoxic oral dose of bis(2-methoxyethyl) ether (DGDME), 3.73 mmol/kg body wt (500 mg/kg), administered on the 11th day of gestation to pregnant CD-I mice was metabolized predominantly by -demethylation to 2-(2-methoxyethoxy)ethanol with subsequent oxidation to (2-methoxyethoxy)acetic acid. Urinary excretion of this metabolite over 48 hr amounted to 63 ± 2% of the dose. A smaller percentage of the administered dose was metabolized at the central ether linkage to produce 2-methoxyethanol, which was further metabolized by alcohol dehydrogenase to methoxyacetic acid. Urinary excretion of methoxyacetic acid, a potent developmental toxicant, amounted to 28 ± 1% of the administered dose by 48 hr and was the second most prominent urinary metabolite. Unchanged DGDME and methoxyacetic acid were detected in the embryonic tissues from these animals, and embryos harvested after the initial 6-hr period showed detectable amounts of only methoxyacetic acid. The average amount of methoxyacetic acid per embryo was calculated to be 1.5 ± 1.0 μmol (5.9 mmol/kg body wt) at the 6-hr termination time. This finding suggests that the reported teratogenic effects of DGDME are due to methoxyacetic acid formed, either in the fetus or by hepatic metabolism in the dam with subsequent distribution to the embryonic tissue. These results suggest that such developmental toxicity may occur with structurally similar aprotic ethylene glycol ethers in which metabolic -dearylation would yield 2-methoxyethanol. [ABSTRACT FROM PUBLISHER]

The Interprofessional Education Collaborative's (IPEC's) core competencies are accreditation standards of most, if not all, healthcare professions (Interprofessional Education Collaborative Expert Panel [2016, Core Competencies for Interprofessional Collaborative Practice: 2016 Update. Washington, DC: IPEC]). Limited literature exists on interprofessional (IP) learning outcomes in healthcare ethics; even fewer studies include debrief sessions. Interprofessional education (IPE) case discussion using web-based technology is a promising way to incorporate ethics content. This article summarizes a model for healthcare programs to create, conduct, and assess synchronous IPE ethics discussions and debrief sessions. Specifically, this article highlights debrief sessions that followed a standardized patient (SP) IP interaction with students from pharmacy and advanced practice nursing. Qualitative analysis of debrief comments identified four themes: the benefit of IP collaboration, the importance of patient-centered care, the need to adapt clinical recommendations with ethical challenges, and the importance of trust among team members. The findings indicate web-based, synchronous IP/SP ethics simulations and debrief sessions are an effective, albeit laborious, method for collaboration and reflection.

Background: Despite advances in the management and treatment of HIV, identifying risks for disengagement are essential to maximize positive outcomes. The current study investigated the validity of the Clinical Complexity Rating Scale for HIV (CCRS-HIV), a risk-prediction tool, by assessing agreement between patient and clinician scores of patient complexity., Methods: 207 patients completed the patient version of the CCRS-HIV (CCRS-HIV P ), and six Attending Medical Officers (AMOs) caring for those individuals completed the original clinician version (CCRS-HIV C ). Kappa statistics, sensitivity and specificity were used to assess patient-clinician agreement., Results: Patient-clinician agreement was highest for problematic crystal methamphetamine use (86%), polypharmacy (84%) and other physical health concerns (67%). Cut-offs of 40 and 45 for the total CCRS-HIV score were identified as most appropriate, with high sensitivity (79.31% and 76.0% respectively)., Conclusions: Overall agreement between the clinician and patient complexity scores was high. These findings provide further evidence of the validity of the scale. The study demonstrates that the unique role of AMOs at the center contributes to them knowing their patients well, allowing them to manage and refer when required for interdisciplinary care which likely contributes to their ongoing engagement in care and may account for the high level of agreement., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Despite viral suppression, people living with HIV (PLHIV) report lower quality of life (QoL) than the general population, negatively impacting treatment adherence and wellbeing. This qualitative study explored factors influencing QoL of PLHIV. Participants completed a QoL questionnaire, with cut-off scores used to allocate participants into Low-Moderate QoL ( n  = 11) or High-Very High QoL ( n  = 10) focus groups. Thematic analysis indicated convergence across factors perceived to impact QoL, with some notable discrepancies. Socioeconomic stability, social connection and support, maintaining good health, adaptive attitudes and reduced impact of stigma were perceived to improve QoL, while obstacles to connection, ageing and poor HIV literacy in the general population were perceived to worsen QoL in both groups. The Low-Moderate QoL group alone identified socioeconomic stressors and ongoing burden of negative life experiences worsened their QoL. Results are presented in the context of local and global HIV health strategies, with implications for clinical management noted., Competing Interests: Declaration of conflicting interestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Competing Interests: All authors have completed and submitted the International Committee of Medical Journal Editors form for disclosure of potential conflicts of interest. No potential conflicts of interest were disclosed.

HIV is a manageable chronic illness, due to advances in biomedical management. However, many people living with HIV (PLHIV) continue to experience psychosocial challenges, which have been associated with poorer quality of life (QoL). This study aimed to explore how psychosocial factors contributed to the QoL of PLHIV in Australia; specifically, the relationship between HIV-related stigma, social connectedness, mental health, and QoL. Participants were 122 PLHIV attending The Albion Centre (a tertiary HIV clinic in Sydney, Australia), who completed questionnaires which measured HIV-related stigma, social support, mental health symptomology and QoL. Results indicated that HIV-related stigma predicted poorer QoL, as did mental health symptomology. Conversely, social connectedness improved QoL. Additionally, social connectedness was found to mediate the relationship between HIV-related stigma and QoL, whereas the hypothesized moderating role of mental health symptomology on this model was not significant. These findings provide insight into the impact of psychosocial factors on QoL, offering practitioners various points of clinical intervention., (© 2022. The Author(s).)

People with focal epilepsies are known to under-document their seizures, but there is no data on self-documentation in adults with genetic (idiopathic) generalized epilepsy (GGE/IGE). We assessed the accuracy of self-evaluation of typical absences (TA) or myoclonic seizures (MS) in adults with IGE based on home video-EEG telemetry (HVET). Patients' own estimates were compared to the objective count of definite TA and MS, performed visually. We considered definite TA as generalized spike-wave discharges (GSWD) that met any of the following criteria: 1) coinciding with clear behavioural arrest on video, 2) followed after a few seconds by positive indication that an absence occurred, or 3) in the absence of video, consistently coinciding with clear motor arrest, as evidenced by interruption of continuous muscle activity. For each patient, we also classified probable TA as GSWDs that were longer than those corresponding to the shortest definite TA on HVET or based on the most recent sleep-deprived EEG (SDEEG). From the first 300 consecutive adults who had HVET, 24 had IGE with TA and / or MS; 23 were women. Only one patient had newly diagnosed IGE. Erroneous self-assessment of TA and MS was noted in 16/24 patients (66.7%). Seizures were overestimated in nine (37.5%) and underestimated in seven (29.2%). Only one patient (4.2%) documented all her TA and MS without false-positive estimates. Overestimation (but not underestimation) of TA on HVET could be predicted when patients reported daily or multiple weekly TA and a recent SDEEG was either normal or contained only subclinical GSWD (p=0.0095). Under- and over-self-documentation of TA and MS occurred in two thirds of adults with GGE/IGE, with substantial impact on their outpatient management and treatment. Diagnostic HVET is a useful tool for the detection of erroneous self-evaluation in these patients.

In recent years there has been an explosion of interest in Artificial Intelligence (AI) both in health care and academic philosophy. This has been due mainly to the rise of effective machine learning and deep learning algorithms, together with increases in data collection and processing power, which have made rapid progress in many areas. However, use of this technology has brought with it philosophical issues and practical problems, in particular, epistemic and ethical. In this paper the authors, with backgrounds in philosophy, maternity care practice and clinical research, draw upon and extend a recent framework for shared decision-making (SDM) that identified a duty of care to the client's knowledge as a necessary condition for SDM. This duty entails the responsibility to acknowledge and overcome epistemic defeaters. This framework is applied to the use of AI in maternity care, in particular, the use of machine learning and deep learning technology to attempt to enhance electronic fetal monitoring (EFM). In doing so, various sub-kinds of epistemic defeater, namely, transparent, opaque, underdetermined, and inherited defeaters are taxonomized and discussed. The authors argue that, although effective current or future AI-enhanced EFM may impose an epistemic obligation on the part of clinicians to rely on such systems' predictions or diagnoses as input to SDM, such obligations may be overridden by inherited defeaters, caused by a form of algorithmic bias. The existence of inherited defeaters implies that the duty of care to the client's knowledge extends to any situation in which a clinician (or anyone else) is involved in producing training data for a system that will be used in SDM. Any future AI must be capable of assessing women individually, taking into account a wide range of factors including women's preferences, to provide a holistic range of evidence for clinical decision-making., (© 2020 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Introduction: Limited literature exists regarding current practices in teaching and assessment of drug utilization review (DUR) skills in pharmacy schools. This manuscript aimed to: (1) examine how assessment is conducted for DUR activities using survey results and (2) summarize the assessment strategies of DUR activities via analysis of tools in colleges of pharmacy., Methods: A survey was administered to members of the American Association of Colleges of Pharmacy Laboratory Instructors Special Interest Group via Qualtrics. Descriptive statistics were used to evaluate survey results and the assessment tools (i.e. rubrics/checklists) collected were analyzed qualitatively to determine common content areas., Results: Out of the 113 institutions emailed, 48 (42.5%) responses were complete and represented individual colleges. Thirty-four of those 48 both implemented and assessed DUR activities. Fourteen institutions (41%) utilized one DUR assessment tool throughout the entire curriculum. The majority (62%) used the assessment tool in the first professional year, with a paper tool being the most frequently utilized (74%). "Identification of drug-related problems" (97%) and "determination of the pharmacist's action" (85%) were listed as important components of the assessment tool. Faculty noted that the assessment tool was easy to use (55%) and adequately assessed students' knowledge/skills (55%). A validated assessment tool (85%) and inclusion of technology (50%) would improve delivery of student feedback., Conclusions: Wide variability existed in how schools incorporated and assessed DUR activities. Developing a standardized method of teaching and assessing DUR is important to adequately prepare the next generation of pharmacists., Competing Interests: Declaration of Competing Interest None., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Objective. To define essential skills for Doctor of Pharmacy (PharmD) graduates that are needed in the four most common sectors of pharmacy practice as determined by expert faculty who instruct within pharmacy skills laboratories. Methods. A three-round Delphi method was used to establish consensus. In the first round, participants were asked what skills were needed by students at entry to practice in community, health-system, ambulatory care, and managed care pharmacy settings. In rounds two and three, participants were asked to rate each skill with a level of importance using a 10-point Likert scale (1=not important to 10=very important). Results. In round one, participants produced a collective list of 289 essential skills. These skill statements were sent to participants in rounds two and three to assign a level of importance. After the third round, participants reached consensus using a mean level of importance for a final list of 69 community pharmacy skills, 47 health-system, 60 ambulatory care, and 15 managed care skills. These skills were then mapped to entrustable professional activities domains for schools and colleges pharmacy to use as a resource when assessing core competency development in the curriculum. Conclusion. The Delphi technique was used successfully with expert pharmacy skills laboratory faculty to identify laboratory-focused essential skills that recent PharmD graduates should have prior to entering community, health-system, ambulatory care, or managed care pharmacy practice. These essential skills can be used to guide curriculum development, develop milestone markers, and help ensure students are practice ready., (© 2021 American Association of Colleges of Pharmacy.)

This commentary summarizes proceedings of a workshop on chronic pain in military personnel and veterans (released personnel) at the Annual Forum of the Canadian Institute for Military and Veteran Health Research in Gatineau and Ottawa on October 22, 2019. The extent and impact of chronic pain among Canadian Armed Forces (CAF) veterans and their families is significant and has been underappreciated, largely due to limited disclosure by serving and veteran military personnel, stemming from a fear of stigmatization. Living with pain is seen as a fact of life in military cultures, something to be endured and not discussed. Though progress is being made in reducing the stigma of mental illness, the discourse on chronic pain remains censored. This workshop's goal was to bring the discussion of chronic pain out of the shadows in the search for ways to help veterans and active service personnel living with chronic pain. Many points of view were brought forward at this first national Canadian multidisciplinary gathering of researchers, veterans with lived experience, clinicians, and policymakers. A CAF member described his lived experience with constant chronic pain. Clinicians described aspects of chronic pain in military personnel and veterans whom they treat in their clinics. Dr. Ramesh Zacharias described the new Chronic Pain Center of Excellence for Canadian Veterans that will be established with funding from Veterans Affairs Canada. Dr. Norman Buckley highlighted collaboration with the existing Chronic Pain Network funded by the Canadian Institute for Health Research. Audience members identified a diverse variety of issues., (© 2020 Crown Copyright. Published with license by Taylor & Francis Group, LLC.)

Systems biology has experienced dramatic growth in the number, size, and complexity of computational models. To reproduce simulation results and reuse models, researchers must exchange unambiguous model descriptions. We review the latest edition of the Systems Biology Markup Language (SBML), a format designed for this purpose. A community of modelers and software authors developed SBML Level 3 over the past decade. Its modular form consists of a core suited to representing reaction-based models and packages that extend the core with features suited to other model types including constraint-based models, reaction-diffusion models, logical network models, and rule-based models. The format leverages two decades of SBML and a rich software ecosystem that transformed how systems biologists build and interact with models. More recently, the rise of multiscale models of whole cells and organs, and new data sources such as single-cell measurements and live imaging, has precipitated new ways of integrating data with models. We provide our perspectives on the challenges presented by these developments and how SBML Level 3 provides the foundation needed to support this evolution., (© 2020 California Institute of Technology Published under the terms of the CC BY 4.0 license.)

Shared decision-making involves health professionals and patients/clients working together to achieve true person-centred health care. However, this goal is infrequently realized, and most barriers are unknown. Discussion between philosophers, clinicians, and researchers can assist in confronting the epistemic and moral basis of health care, with benefits to all. The aim of this paper is to describe what shared decision-making is, discuss its necessary conditions, and develop a definition that can be used in practice to support excellence in maternity care. Discussion between the authors, with backgrounds in philosophy, clinical maternity care, health care management, and maternity care research, assisted the team to confront established norms in maternity care and challenge the epistemic and moral basis of decision-making for caesarean section. The team concluded that shared decision-making must start in pregnancy and continue throughout labour and birth, with equality in discourse facilitated by the clinician. Clinicians have a duty of care for the adequacy of women's knowledge, which can only be fulfilled when relevant knowledge is offered freely and when personal beliefs and biases that may impinge on decision-making (defeaters) are disclosed. Informed consent is not shared decision-making. Key barriers include existing cultural norms of "the doctor knows best" and "patient acquiescence" that prevent defeaters being acknowledged and discussed and can lead to legal challenges, overuse of medical intervention and, in some areas, obstetric violence. Shared decision-making in maternity care can thus be defined as an enquiry by clinician and expectant woman aimed at deciding upon a course of care or none, which takes the form of a dialogue within which the clinician fulfils their duty of care to the client's knowledge by making available their complete knowledge (based on all types of evidence) and expertise, including an exposition of any relevant and recognized potential defeaters. Research to develop measurement tools is required., (© 2019 The Authors. Journal of Evaluation in Clinical Practice published by John Wiley & Sons Ltd.)

Objective. To describe the development, implementation, and assessment of simulated interprofessional education (IPE) telehealth case activities. Methods. Faculty from pharmacy and physician assistant schools developed interprofessional cases covering topics addressed in both curricula and designed for specific levels of learners. Using a telehealth format, pharmacy students were paired with physician assistant students and met at specified times in a virtual room. Faculty representing both professions assessed students as they discussed a patient case, determined a diagnosis, and collaborated to develop appropriate treatment options. Pre-experience and post-experience data and student reflections were collected. Results. Pharmacy students' responses to items on the Team Skills Scale (TSS) completed after participating in four IPE telehealth case activities indicated positive changes. Mean total TSS scores significantly improved from pre-experience 62.3 (SD 8.4) to post-experience 72.6 (SD 5.7). Quantitative evaluation of student teams' participation in an interprofessional activity was assessed using the Creighton Interprofessional Collaborative Evaluation (C-ICE) instrument and the average score was 90%. Theme analysis was performed on student reflections and the most prominent themes identified were satisfaction from interacting with other health care professionals, increased confidence in clinical decision-making ability, and affirmation that IPE telehealth cases should be included in each year of the curriculum. Conclusion. Implementation of interprofessional cases using telehealth technology is an effective way for pharmacy schools to incorporate IPE into their curriculum. Students reported improved self-perception of interprofessional competence and attitudes toward interprofessional collaboration after participating in IPE telehealth cases.

Healthcare institutions, accreditation agencies for higher learning, and organizations such as the National Academy of Medicine in the United States, support interprofessional education (IPE) opportunities. However, incorporating IPE opportunities into academic settings remains difficult. One challenge is assessing IPE learning and practice outcomes, especially at the level of student performance to ensure graduates are "collaboration-ready". The Creighton-Interprofessional Collaborative Evaluation (C-ICE) instrument was developed to address the need for a measurement tool for interprofessional student team performance. Four interprofessional competency domains provide the framework for the C-ICE instrument. Twenty-six items were identified as essential to include in the C-ICE instrument. This instrument was found to be both a reliable and a valid instrument to measure interprofessional interactions of student teams. Inter-rater reliability as measured by Krippendorff's nominal alpha (nKALPHA) ranged from .558 to .887; with four of the five independent assessments achieving nKALPHA greater than or equal to 0.796. The findings indicated that the instrument is understandable (Gwet's alpha coefficient (gAC) 0.63), comprehensive (gAC = 0.62), useful and applicable (gAC = 0.54) in a variety of educational settings. The C-ICE instrument provides educators a comprehensive evaluation tool for assessing student team behaviors, skills, and performance.

Purpose: Rural, tobacco-growing areas are disproportionately affected by tobacco use, secondhand smoke, and weak tobacco control policies. The purpose was to test the effects of a stage-specific, tailored policy-focused intervention on readiness for smoke-free policy, and policy outcomes in rural underserved communities., Methods: A controlled community-based trial including 37 rural counties. Data were collected annually with community advocates (n = 330) and elected officials (n = 158) in 19 intervention counties and 18 comparison counties over 5 years (average response rate = 68%). Intervention communities received policy development strategies from community advisors tailored to their stage of readiness and designed to build capacity, build demand, and translate and disseminate science. Policy outcomes were tracked over 5 years., Findings: Communities receiving the stage-specific, tailored intervention had higher overall community readiness scores and better policy outcomes than the comparison counties, controlling for county-level smoking rate, population size, and education. Nearly one-third of the intervention counties adopted smoke-free laws covering restaurants, bars, and all workplaces compared to none of the comparison counties., Conclusions: The stage-specific, tailored policy-focused intervention acted as a value-added resource to local smoke-free campaigns by promoting readiness for policy, as well as actual policy change in rural communities. Although actual policy change and percent covered by the policies were modest, these areas need additional resources and efforts to build capacity, build demand, and translate and disseminate science in order to accelerate smoke-free policy change and reduce the enormous toll from tobacco in these high-risk communities., (© 2014 National Rural Health Association.)

Objectives: Objectives were to (1) explore perceived effectiveness of existing smoke-free print advertisements in rural communities and (2) generate message content, characteristics, and media delivery channels that resonate with residents., Design and Sample: Qualitative methods design. Thirty-nine rural adults recruited by community partners., Measures: Content analysis of findings from individuals in four focus groups who participated in general discussion and reviewed eight print ads related to secondhand smoke (SHS) and smoke-free policy., Results: Six content themes were identified: smoking/SHS dangers, worker health, analogies, economic impact, rights, and nostalgia. Seven message characteristics were recognized: short/to the point, large enough to read, graphic images, poignant stories, statistics/charts/graphs, message sender, and messages targeting different groups. Four media delivery channels were considered most effective: local media, technology, billboard messages, and print materials., Conclusions: Seeking input from key informants is essential to reaching rural residents. Use of analogies in media messaging is a distinct contribution to the literature on effective smoke-free campaigns. Other findings support previous studies of effective messaging and delivery channels. Further research is needed to examine effectiveness of themes related to message content in smoke-free ads and delivery strategies. Effective media messaging can lead to policy change in rural communities to reduce exposure to SHS., (© 2015 Wiley Periodicals, Inc.)

Purpose: To compare the retail distribution and density per population of electronic and conventional cigarettes in smoke-free communities with and without e-cigarette restrictions., Design: A cross-sectional study with field observations of retail tobacco stores., Setting: Two Central Kentucky counties with 100% smoke-free workplace regulations; counties selected on the basis of whether e-cigarette use was restricted., Subjects: Fifty-seven tobacco retailers in two counties, including conventional retailers and stand-alone e-cigarette stores., Measures: Type and location of store and products sold; addresses of stores and schools geocoded with ArcGIS., Analysis: Bivariate comparisons between counties, rates and confidence intervals for frequency of tobacco retailers and e-cigarette stores per population., Results: Fifty-three percent of tobacco retailers sold e-cigarettes. E-cigarette availability did not differ by whether smoke-free regulation covered e-cigarettes. Rates of tobacco retailers and e-cigarette distributors per 10,000 were 8.29 and 4.40, respectively, in the two-county area. Of the 40 schools, 88% had a tobacco retailer and 68% had an e-cigarette distributor within 1 mile., Conclusion: In this exploratory study, e-cigarette use restriction was not related to store availability. For a relatively new product, e-cigarettes were readily available in retail outlets and close to schools.

Objective: The purpose of this report is to describe a 57-year-old man who was admitted to a nursing facility for physical therapy. His home medication list included sodium oxybate. This article will provide the pharmacist with a therapeutic overview of sodium oxybate as well as review the unique processes involved with drug acquisition, dosing, patient education, and monitoring., Setting: Community pharmacy, nursing facility pharmacy, consultant pharmacy practice., Practice Considerations: Sodium oxybate is the only medication in the United States that has approval for both treatment of cataplexy in narcolepsy and treatment of excessive daytime sleepiness in narcolepsy. Sodium oxybate has many unique properties that cause it to differ from past therapies for cataplexy and excessive daytime sleepiness associated with narcolepsy., Conclusion: It is important for pharmacists to understand the therapeutic uses of sodium oxybate and to review the processes for acquisition, dosing, and administration to better assist physicians and patients and improve therapeutic outcomes.

Promoting tobacco control policies in rural tobacco-growing communities presents unique challenges. The purpose of this study was to assess smoke-free coalition cohesiveness in rural communities and identify coalition members' perceived barriers or divisive issues that impede the development of smoke-free policies. A secondary aim was to evaluate differences in coalition cohesiveness between advocates in communities receiving stage-based, tailored policy advocacy assistance versus those without assistance. Tobacco control advocates from 40 rural Kentucky communities were interviewed by telephone during the final wave of a 5-year longitudinal study of community readiness for smoke-free policy. On average, five health advocates per county participated in the 45-min interview. Participants rated coalition cohesiveness as not at all cohesive, somewhat cohesive, or very cohesive, and answered one open-ended question about potentially divisive issues within their coalitions. The mean age of the 186 participants was 48.1 years (SD = 13.3). The sample was predominantly female (83.6%) and Caucasian (99.5%). Divisive concerns ranged from rights issues, member characteristics, type of law, and whether or not to allow certain exemptions. Three of the divisive concerns were significantly associated with their rankings of coalition cohesiveness: raising tobacco in the community, the belief that smoke-free would adversely affect the economy, and government control. Educating coalition members on the economics of smoke-free laws and the actual economic impact on tobacco-growing may promote smoke-free coalition cohesiveness. More resources are needed to support policy advocacy in rural tobacco-growing communities as well as efforts to reduce the divisive concerns reported in this study.

Objective: To teach drug utilization review (DUR) skills to pharmacy students and assess their abilities and confidence before and after training., Design: Profile reviews and online and live drug-utilization-review activities of increasing difficulty were incorporated into the first (P1), second (P2), and third (P3) years of the Pharmacy Skills Training Laboratory sequence in a doctor of pharmacy (PharmD) curriculum., Assessment: An online survey instrument was administered to gauge how comfortable students were with specific DUR skills before and after the activities. Students' confidence in performing specific DUR skills improved after completing the activities., Conclusion: Profile reviews, as well as online and live medication reviews, gave students numerous opportunities to practice drug utilization review skills throughout the first 3 years of the pharmacy curriculum. Students' confidence in performing specific drug utilization review skills improved after the activities. Students' ability to perform the skills also improved as measured with the developed checklist in section V and VI of the Pharmacy Skills Laboratory sequence.

Objective: To evaluate the impact of repeated simulations and testing on the pharmacy practice skills development of third-year doctor of pharmacy (PharmD) students., Design: A pharmacy practice skills laboratory was redesigned to reinforce skills development and enhance retention. Timed, repeated learning experiences that increased in complexity throughout the semester were used to test student knowledge, skills, and abilities., Assessment: Over a 5-year period, scores from skills-based activities deemed essential to professional practice and repeated 4 or more times in the course were analyzed. There was a significant improvement in scores on drug utilization reviews and patient counseling simulations despite the increasing difficulty and complexity of the medication problems presented (p <0.001). Students' scores on prescription verification and sterile product verification also improved significantly over 3 assessments (p <0.001), but then plateaued, with less improvement seen in performance on subsequent assessments., Conclusion: Providing multiple opportunities for students to conduct or simulate pharmacy practice activities and then test their knowledge and skills improves students' learning and performance.

Pancreatic cancer is a highly lethal malignancy with few effective therapies. We performed exome sequencing and copy number analysis to define genomic aberrations in a prospectively accrued clinical cohort (n = 142) of early (stage I and II) sporadic pancreatic ductal adenocarcinoma. Detailed analysis of 99 informative tumours identified substantial heterogeneity with 2,016 non-silent mutations and 1,628 copy-number variations. We define 16 significantly mutated genes, reaffirming known mutations (KRAS, TP53, CDKN2A, SMAD4, MLL3, TGFBR2, ARID1A and SF3B1), and uncover novel mutated genes including additional genes involved in chromatin modification (EPC1 and ARID2), DNA damage repair (ATM) and other mechanisms (ZIM2, MAP2K4, NALCN, SLC16A4 and MAGEA6). Integrative analysis with in vitro functional data and animal models provided supportive evidence for potential roles for these genetic aberrations in carcinogenesis. Pathway-based analysis of recurrently mutated genes recapitulated clustering in core signalling pathways in pancreatic ductal adenocarcinoma, and identified new mutated genes in each pathway. We also identified frequent and diverse somatic aberrations in genes described traditionally as embryonic regulators of axon guidance, particularly SLIT/ROBO signalling, which was also evident in murine Sleeping Beauty transposon-mediated somatic mutagenesis models of pancreatic cancer, providing further supportive evidence for the potential involvement of axon guidance genes in pancreatic carcinogenesis.