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In many countries, there is a large amount of public money spent on health care. Some patient tests and treatments are not only unnecessary but also may be harmful, leading health researchers to look for the most effective interventions to change physician behaviour. The purpose of this chapter is to describe some of the interventions used to modify physician behaviour and highlight their challenges observed in a Canadian provincial context. We begin with a brief description of the increasing interest in behaviour change interventions in recent years and their theoretical basis. We then describe several interventions used to change physician behaviour ranging from nudges to choice restriction and the available evidence on their effectiveness. We provide examples of interventions and their challenges as we've experienced them in our research program, Quality of Care NL. We conclude with a summary of what the evidence tells us about interventions to change physicians' behaviours.

Health-related behavior change refers to a body of behavior change strategies that aim to align people's behavior with advances in evidence-based knowledge and decision-making. However, human behavior is complex, and changing it often requires a combination of strategies to be effective. The challenge is in choosing the combination of strategies that will work best. Implementation science, the study of behavior change, has rapidly expanded in recent years and has pioneered work in providing more transparent and theory-based methods for choosing and evaluating behavior change strategies. There are several models and frameworks that underlie the science of implementation, the most recent and comprehensive of which include the Implementation of Change Model, the COM-B (capability, motivation, and behavior) Model, and the Theoretical Domains Framework, as well as the behavior change techniques (BCTs) taxonomy. These models and frameworks can be applied to help support the development and evaluation of behavior change interventions. In this chapter, we will review the latest advances and lessons learned from implementation science as it applies to health-related behavior change.

Objective: Local wound infections are a major challenge for patients and health professionals. Various diagnostic and therapeutic options are available. However, a generally accepted standard is still lacking in Europe. The aim was to develop an easy-to-use clinical score for the early detection of local wound infections, as a basis for decision-making on antiseptic therapy or decolonisation., Method: An interdisciplinary and interprofessional panel of experts from seven European countries was brought together to discuss the various aspects of diagnosing local wound infections., Results: The result was the adoption of the Therapeutic Index for Local Infections (TILI) score, developed in Germany by Initiative Chronische Wunden e.V., specifically for health professionals not specialised in wound care. Available in six European languages, the TILI score could also be adapted for different European countries, depending on their specific national healthcare requirements. The six clinical criteria for local wound infection are erythema to surrounding skin; heat; oedema, induration or swelling; spontaneous pain or pressure pain; stalled wound healing; and increase and/or change in colour or smell of exudate. Meeting all criteria indicates that antiseptic wound therapy could be started. Regardless of these unspecific clinical signs, there are also health conditions for the clinical situation which are a direct indication for antimicrobial wound therapy. These include the presence of wound pathogens, such as meticillin-resistant Staphylococcus aureus , septic surgical wound or the presence of free pus., Conclusion: The development of the new internationally adapted TILI score, which could also be used by any caregiver in daily practice to diagnose local infections in acute and hard-to-heal wounds, is the result of expert consensus. However, the score system has to be validated through a clinical evaluation. This is to be performed in expert centres throughout Europe.

Objective: A score to identify local wound infections was developed by a panel of experts from seven European countries. The Therapeutic Index for Local Infections (TILI) score was designed for health professionals who are not specialised in wound care. This study was carried out to test the validity of the TILI score in everyday practice., Method: Content validity was analysed by means of evaluation by a panel of experts, individually and face-to-face, followed by a European multicentred, retrospective, observational study. Participating clinicians sent anonymised copies of completed TILI scores for patients with leg ulcers along with a photograph of the wound for analysis by two blinded reviewers. Concordance (Kappa index) and convergent criterion validity (sensitivity, specificity, accuracy, Youden's J Index and receiver operator characteristic (ROC) or area under the curve (AUC) curve) were calculated to construct validity and reliability., Results: A total of 307 patients with leg ulcers from seven institutions in five European countries were included in this retrospective analysis. It was shown that the diagnosis of local wound infection could be documented well with five of the six clinical criteria included in the TILI score. By summing up these facultative criteria in comparison with any direct criteria that may be present, there would have been an indication for local antiseptic wound therapy in 22% of patients examined., Conclusions: The results show that the TILI score is concordant with the expert assessment of patients and with good diagnostic characteristics. Thus, the easy-to-use TILI score can now be used in the daily routine practice of health professionals to diagnose local wound infections.

Background: Postoperative analgesia is paramount to recovery after thoracic surgery, and opioids play an invaluable role in this process. However, current 1-size-fits-all prescribing practices produce large quantities of unused opioids, thereby increasing the risk of nonmedical use and overdose. This study hypothesized that patient and perioperative characteristics, including 24-hour before-discharge opioid intake, could inform more appropriate postdischarge prescriptions after thoracic surgery., Methods: This prospective observational cohort study was conducted in 200 adult thoracic surgical patients. The cohort was divided into 3 groups on the basis of 24-hour before-discharge opioid intake in morphine milligram equivalents (MME): (1) no (0 MME), (2) low (>0 to ≤22.5 MME), or (3) high (>22.5 MME) before-discharge opioid intake. Logistic regression was used to analyze the association of patient and perioperative characteristics with self-reported after-discharge opioid use., Results: Univariate analysis showed that preoperative opioid use, 24-hour before-discharge acetaminophen and gabapentinoid intake, and 24-hour before-discharge opioid intake were associated with higher after-discharge opioid use. Multivariable modeling demonstrated that 24-hour before-discharge opioid intake was most significantly associated with after-discharge opioid use. For example, compared with patients who took high amounts of opioids before discharge, patients who took no opioids before discharge were 99% less likely to take a high amount of opioids after discharge compared with taking none (odds ratio, 0.011; 95% confidence interval, 0.003 to 0.047; P < .001)., Conclusions: Assessment of 24-hour before-discharge opioid intake may inform patient requirements after discharge. Opioid prescriptions after thoracic surgery can thereby be targeted on the basis of anticipated needs., (Copyright © 2020 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Despite guidelines, best-practice statements and CQUIN targets, venous leg ulcers have been highlighted as an area that continues to demonstrate lack of evidence-based practice and variation in practice, which contribute to poor patient outcomes and escalating costs. Leg ulcer services that use a systematic and standardised approach to leg ulcer management are highly successful in improving healing rates, preventing recurrence and contributing to patients' wellbeing. This article seeks to explore the use of the plan-do-study-act (PDSA) cycle in clinical practice to improve and standardise leg ulcer management.

Introduction: Exercise modalities offered as part of traditional pulmonary rehabilitation (PR) do not always translate to successful performance of Activities of Daily Living (ADL) and may hinder gains in patient's sense of well-being. Data is lacking on the efficacy of incorporation of ADL-focused training in PR. The aim of this study was to determine the impact of incorporation of ADL simulation and energy-conservation training in PR as part of a quality-initiative on health-related-quality-of-life (HRQOL), dyspnea, fatigue, and six-minute-walk-test among PR patients., Methods: Retrospective study where medical records of consecutive patients with chronic respiratory diseases who completed PR from 2016 to 2018 were reviewed. ADL-focused energy-conservation training was added to traditional PR in September 2017 by replacing three monthly sessions of traditional PR with energy-conservation training as a quality-improvement-initiative. The change from baseline on HRQOL measured by COPD assessment test (CAT), six-minute-walk-test, MMRC dyspnea score and CRQ-dyspnea and CRQ-fatigue questionnaires, were compared between patients who received traditional PR versus energy-conservation PR. Within and between group differences were calculated via repeated-measures ANOVA., Results: The baseline characteristics of 91 patients who participated in traditional PR versus energy-conservation PR (n = 85) were similar (mean age = 68.6±10.4 years, 49% men). While improvement from baseline was similar and significant for both groups for MMRC, CRQ-dyspnea and CRQ-fatigue scores, and six-minute walk test, patients who participated in energy-conservation PR had significantly higher improvement in HRQOL CAT scores (p = 0.01) than those who completed traditional PR., Conclusion: Tailoring patient's training programs to include energy-conservation training exercises specific to ADL in PR improved HRQOL over traditional PR in patients with chronic respiratory diseases despite no significant change in functional status. Future randomized-controlled trials will be needed to confirm these initial findings., Competing Interests: The authors have declared that no competing interests exist.

Importance: One major advantage of developing large, federally funded networks for clinical research in neurology is the ability to have a trial-ready network that can efficiently conduct scientifically rigorous projects to improve the health of people with neurologic disorders., Observations: National Institute of Neurological Disorders and Stroke Network for Excellence in Neuroscience Clinical Trials (NeuroNEXT) was established in 2011 and renewed in 2018 with the goal of being an efficient network to test between 5 and 7 promising new agents in phase II clinical trials. A clinical coordinating center, data coordinating center, and 25 sites were competitively chosen. Common infrastructure was developed to accelerate timelines for clinical trials, including central institutional review board (a first for the National Institute of Neurological Disorders and Stroke), master clinical trial agreements, the use of common data elements, and experienced research sites and coordination centers. During the first 7 years, the network exceeded the goal of conducting 5 to 7 studies, with 9 funded. High interest was evident by receipt of 148 initial applications for potential studies in various neurologic disorders. Across the first 8 studies (the ninth study was funded at end of initial funding period), the central institutional review board approved the initial protocol in a mean (SD) of 59 (21) days, and additional sites were added a mean (SD) of 22 (18) days after submission. The median time from central institutional review board approval to first site activation was 47.5 days (mean, 102.1; range, 1-282) and from first site activation to first participant consent was 27 days (mean, 37.5; range, 0-96). The median time for database readiness was 3.5 months (mean, 4.0; range, 0-8) from funding receipt. In the 4 completed studies, enrollment met or exceeded expectations with 96% overall data accuracy across all sites. Nine peer-reviewed manuscripts were published, and 22 oral presentations or posters and 9 invited presentations were given at regional, national, and international meetings., Conclusions and Relevance: NeuroNEXT initiated 8 studies, successfully enrolled participants at or ahead of schedule, collected high-quality data, published primary results in high-impact journals, and provided mentorship, expert statistical, and trial management support to several new investigators. Partnerships were successfully created between government, academia, industry, foundations, and patient advocacy groups. Clinical trial consortia can efficiently and successfully address a range of important neurologic research and therapeutic questions.

Background: In March 2016, an Enhanced Recovery After Surgery (ERAS) initiative was implemented for all elective colorectal resections at an urban hospital in St. John's, Newfoundland and Labrador, Canada. An ERAS coordinator supervised and enforced guideline compliance for 6 months. The aim of this study was to evaluate the sustainability of the ERAS program after supervision of guideline compliance was eliminated., Methods: Patient outcomes and guideline compliance were compared between surgeries performed under standard practice (April 2014 to March 2015) and those performed during and after the implementation of the ERAS initiative (March 2016 to August 2016 was the implementation phase and September 2016 to February 2017 was the sustainability phase)., Results: Hospital length of stay decreased from 7.26 days at baseline to 5.44 days during the implementation phase of the ERAS program (p < 0.001). There was no significant difference between length of stay at baseline and during the 6-month sustainability phase of the ERAS program (7.10 d). There were no significant differences in rates of readmission or mortality during and after implementation. Rate of ileus decreased significantly from 13.8% during the implementation phase to 4.6% during the sustainability phase (p = 0.036). Total guideline compliance increased from 52.2% at baseline to 80.7% during the implementation phase (p < 0.001), and decreased to 74.7% during the sustainability phase (p < 0.001). Adherence to postoperative guidelines regressed: 79.2% in the implementation phase and 68.6% in the sustainability phase (p < 0.001)., Conclusion: La durée des séjours à l’hôpital a diminué après l’adoption du programme de RAAC, lorsque le coordonnateur du programme était présent. Les méthodes de maintien des lignes directrices après leur adoption seront cruciales au succès de programmes similaires à l’avenir., Competing Interests: None declared., (© 2020 Joule Inc. or its licensors.)

Introduction: Current evidence suggests that preoperative tests such as chest X-rays, electrocardiograms and baseline laboratory studies may not be useful for healthy patients undergoing low-risk surgical procedures. Routine preoperative testing for healthy patients having low-risk surgery is not a scientifically sound practice. In this study, we will interview healthcare providers working at medical facilities where low-risk surgical procedures are carried out. This will allow us to gain insight into the determinants of preoperative testing behaviours for healthy patients undergoing low-risk surgeries and their barriers and enablers to guideline adherence., Methods and Analysis: We will use semistructured interviews with anaesthesiologists, surgeons and preadmission clinic nurses to assess the determinants of preoperative testing behaviours. The interview guide was designed around the Theoretical Domains Framework (TDF), developed specifically to determine the barriers and enablers to implementing evidence-based guidelines. Interviews will be audio-recorded, transcribed verbatim and coded according to the TDF. Key themes will be generated for each of the identified domains., Ethics and Dissemination: We have received ethics approval from the Health Research Ethics Board in Newfoundland and Labrador (HREB #2018.190) for this study. The results of this work will be disseminated through a peer-reviewed publication, presentation at a healthcare forum and plain-language infographic summaries. Additionally, deidentified data collected and analysed for this study will be available for review from the corresponding author on reasonable request., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Purpose: Although cesarean delivery is the most common surgical procedure in the United States, postoperative opioid prescribing varies greatly. We hypothesized that patient characteristics, procedural characteristics, or both would be associated with high vs low opioid use after discharge. This information could help individualize prescriptions., Methods: In this prospective cohort study, we quantified opioid use for 4 weeks following hospital discharge after cesarean delivery. Predischarge characteristics were obtained from health records, and patients self-reported total opioid use postdischarge on weekly questionnaires. Opioid use was quantified in milligram morphine equivalents (MMEs). Binomial and Poisson regression analyses were performed to assess predictors of opioid use after discharge., Results: Of the 233 patients starting the study, 203 (87.1%) completed at least 1 questionnaire and were included in analyses (86.3% completed all 4 questionnaires). A total of 113 patients were high users (>75 MMEs) and 90 patients were low users (≤75 MMEs) of opioids postdischarge. The group reporting low opioid use received on average 44% fewer opioids in the 24 hours before discharge compared with the group reporting high opioid use (mean = 33.0 vs 59.3 MMEs, P <.001). Only a minority of patients (11.4% to 15.8%) stored leftover opioids in a locked location, and just 31 patients disposed of leftover opioids., Conclusions: Knowledge of predischarge opioid use can be useful as a tool to inform individualized opioid prescriptions, help optimize nonopioid analgesia, and reduce opioid use. Additional studies are needed to evaluate the impact of implementing such measures on prescribing practices, pain, and functional outcomes., (© 2020 Annals of Family Medicine, Inc.)

Objective : To conduct a phase-II trial using a ranking and selection paradigm where multiple treatments are compared with limited sample size and the best is chosen for a subsequent efficacy trial versus placebo. This strategy can find an effective treatment faster than traditional strategy of conducting larger trials against placebo. Methods : Sixty amyotrophic lateral sclerosis (ALS) participants were randomized 1:1:1 to creatine 30 g/day (CRE), tamoxifen 40 mg/day (T40), or tamoxifen 80 mg/day (T80), with matching placebo. The primary outcome was 38-week change in ALS Functional Rating Scale-Revised (ALSFRS-R), analyzed in a repeated-measures ANOVA. Secondary outcomes included slow vital capacity (SVC), quantitative muscle strength, early drug discontinuation (EDD), adverse events (AEs), and survival. Results : CRE participants experienced higher rates of drug-related AEs (82% vs. 43% T40, 47% T80) and EDD (50% vs. 24% T40, 29% T80). T80 participants experienced slower adjusted mean decline in ALSFRS-R in points/month (-0.80 vs. -0.84 T40, -0.85 CRE) and quantitative muscle strength but not in SVC and higher rates of mortality. Conclusion : Efficacy of T80 ranked numerically superior to CRE and T40 with respect to ALSFRS-R decline. Following the selection paradigm, T80 would be chosen to test against placebo. The approach was not designed to distinguish among treatments that are nearly equally effective or ineffective. If treatments are equivalent, then under the paradigm, it does not matter which treatment is selected. Newer approaches for increasing trial efficiency, including an adaptive platform trial design, may mitigate limitations of the selection design.

Background: Reducing computed tomography (CT) examinations of the lumbar spine is one of Choosing Wisely Canada's initial top 10 recommendations. This study's objective was to report the age- and-sex standardized rates of lumbar spine CT ordered by family physicians in 1 health region in Newfoundland and Labrador., Methods: We conducted a retrospective study using local health data from Meditech, an electronic health record system, from 2013 to 2016 for the Eastern Health Region of Newfoundland and Labrador, the largest health region in the province. Records were included if the referral was for an adult aged 20 years or more, and CT was ordered by a family physician. Lumbar spine CT rates were contextualized with age- and sex-stratified estimates. Population estimates were provided by the Newfoundland and Labrador Centre for Health Information to calculate age- and sex-standardized rates per 100 000 people. We calculated rate ratios to test for statistical significance in differences in rates between years., Results: A total of 14 370 records were examined. The age- and sex-standardized rates of lumbar spine CT per 100 000 were 1225 in 2013, 1393 in 2014, 1556 in 2015 and 1395 in 2016. The rate ratio was 1.137 (95% confidence interval [CI] 1.084-1.194) for the comparison between 2014 and 2013, 1.117 (95% CI 1.067-1.169) between 2015 and 2014, and 0.896 (95% CI 0.857-0.938) between 2016 and 2015., Interpretation: The age- and sex-standardized rates suggest that there was a steady rate of lumbar spine CT examinations being ordered by family physicians in Newfoundland and Labrador in 2013-2016. Although all rate ratios were statistically significant, the magnitude of the difference between years is likely not clinically relevant. These rates are important because they serve as a benchmark for future initiatives to reduce unnecessary referrals for lumbar spine CT., Competing Interests: Competing interests: None declared., (Copyright 2020, Joule Inc. or its licensors.)

Background: Overprescribing of opioid medications for patients to be used at home after surgery is common. We sought to ascertain important patient and procedural characteristics that are associated with low versus high rates of self-reported utilization of opioids at home, 1-4 weeks after discharge following gastrointestinal surgery., Methods: We developed a survey consisting of questions from NIH PROMIS tools for pain intensity/interference and queries on postoperative analgesic use. Adult patients completed the survey weekly during the first month after discharge. Using regression procedures we determined the patient and procedure characteristics that predicted high post-discharge opioid use operationalized as 75 mg oral morphine equivalents/50 mg oxycodone reported taken., Results: The survey response rate was 86% (201/233). High opioid use was reported by 52.7% of patients (106/201). Median reported intake of opioid pain pills was 7 for week #1 and 0 for weeks #2-4. Combinations of acetaminophen and non-steroidal and anti-inflammatory drugs were used by 8.9%-12.5% of patients after discharge. Following adjustment for significant variables of the univariate analysis, last 24-h in-hospital opioid intake remained as a significant co-variate for post-discharge opioid intake., Conclusions: After gastrointestinal surgery, the equivalent of each oxycodone 5 mg tablet taken in the last 24 h before discharge increases the likelihood of taking the equivalent of > 10 oxycodone 5 mg tablets by 5%. Non-opioid analgesia was utilized in less than half of the cases. Maximizing non-opioid analgesic therapy and basing opioid prescriptions on 24-h pre-discharge opioid intake may improve the quality of post-discharge pain management.

Introduction: Preventing a primary cesarean birth in nulliparous women with term, singleton, vertex pregnancies (NTSV) is recognized as an important strategy to reduce maternal morbidities and risks to the newborn. Multiple professional organizations are supporting approaches to safely reduce NTSV cesarean rates, including the American College of Obstetricians and Gynecologists; the Society for Maternal-Fetal Medicine; and the Association of Women's Health, Obstetric and Neonatal Nurses. The American College of Nurse-Midwives (ACNM) is leading one such effort as part of its Healthy Birth Initiative: the Reducing Primary Cesareans (RPC) Learning Collaborative. The objective of this study is to estimate the cost savings of a decrease in NTSV cesareans at one hospital participating in the RPC Learning Collaborative., Methods: All women giving birth at Baystate Medical Center from October 1, 2016, to March 31, 2017, and their newborns were identified by Medicare Severity Diagnosis Related Group (N = 1747). Total hospital costs were calculated using a resource consumption profile for each of 6 groups: women who had vaginal birth, primary cesarean, and repeat cesarean and their linked newborns. A model was developed to estimate cost differences for the first and second births and overall cost savings., Results: For the NTSV birth, total costs for primary cesarean and newborn care were $5989 higher compared with vaginal birth and newborn care. For the subsequent birth, repeat cesareans and newborn care were $4250 higher compared with vaginal birth. In 2016, 69 primary cesareans were prevented, for an actual cost savings of $413,241. Projecting the prevention of 66 subsequent repeat cesareans would result in additional savings of $280,500, for a total savings of $693,741. Apgar score at 5 minutes and length of stay remained unchanged., Discussion: Participation in ACNM's RPC Learning Collaborative led to significant savings in hospital costs during the first year without affecting quality metrics. This cost comparison model could be replicated by other hospitals involved in cesarean reduction endeavors., (© 2019 by the American College of Nurse-Midwives.)

Participation in secondary prevention programs such as cardiac rehabilitation (CR) reduces morbidity, mortality, and hospitalizations while improving quality of life. Executive function (EF) is a complex set of cognitive abilities that control and regulate behavior. EF predicts many health-related behaviors, but how EF interacts with interventions to improve treatment adherence is not well understood. The objective of this study is to examine if EF predicts CR treatment adherence and how EF interacts with an intervention to improve adherence. Data were collected from 2013 to 2018 in Vermont, USA. 130 Medicaid-enrolled individuals who had experienced a qualifying cardiac event were enrolled in a controlled clinical trial and randomized 1:1 to receive financial incentives for completing secondary prevention sessions or to usual care. In this secondary analysis, effects of EF on CR adherence (defined as completing ≥30/36 sessions) were examined in 112 participants (57 usual care, 55 intervention) who completed an EF battery. Delay-discounting, a measure of impulsivity, predicted CR adherence (p = 0.01) and interacted with the incentive intervention, such that those who exhibited greater discounting of future rewards benefitted more from the intervention than those who discounted less (F(1, 104) = 5.23, p = 0.02). Better cognitive flexibility, measured with the trail-making-task, also predicted CR adherence (p = 0.02). While EF has been associated with adherence to a variety of treatment regimens, this interaction between an incentive-based intervention to promote treatment adherence and EF is novel. This work illustrates the value of considering individual differences in EF when designing and implementing interventions to promote health-related behavior change., (Copyright © 2019 Elsevier Inc. All rights reserved.)

The growing opioid crisis in the United States affects childbearing women and their infants at an alarming rate. Substance use disorders in pregnancy have transitioned from a topic barely addressed to one that has become mainstream in the issue of pregnancy management. Opioid use can include appropriate use of a prescribed medication, the misuse of street drugs, and maintenance on an opioid agonist treatment such as methadone. Identifying this population of childbearing women is critical to be able to organize the appropriate resources and to provide a comprehensive multidisciplinary evidence-based plan of care. All clinicians need to be educated in identifying and caring for the growing population of women with substance use disorders. Each component of the continuum from prenatal care, labor and birth, and postpartum has challenges and issues that can have a positive or negative impact on the outcome of the pregnancy and the mother-infant relationship. Risk assessment, medication-assisted treatment, pain management, and fostering maternal-infant bonding are important considerations in the care of the woman with substance use disorder. Unbiased empathetic nurses are well positioned to strongly advocate and intervene on behalf of women with substance use disorder, which in turn will help to create positive outcomes for the mother and her baby.

Study Objective: Individuals increasingly use online rating platforms to rate and review hospitals. We seek to describe and compare publicly available online review content and ratings of emergency departments (EDs) and urgent care centers., Methods: We analyzed Yelp reviews of EDs and urgent care centers to identify topics most correlated with 1- and 5-star ratings. Latent Dirichlet Allocation, a method of identifying groups of co-occurring words in narrative text, was used to identify and label 25 topics across 1- and 5-star reviews of urgent care centers and EDs. Differential Language Analysis was then used to measure the correlation of these topics with 1- and 5-star reviews for urgent care centers and EDs., Results: We analyzed 100,949 Yelp reviews, 16,447 from 1,566 EDs and 84,502 from 5,601 urgent care centers. There were significantly more 5-star urgent care center reviews (n=43,487; 51%) than 5-star ED reviews (n=4,437; 27%). Themes associated with 5-star reviews among EDs and urgent care centers were similar for comfort, professionalism, facilities, pediatric care, and staff interactions. Themes associated with 1-star reviews among EDs and urgent care centers were similar for communication, telephone experience, waiting, billing, pain management, and diagnostic testing. Themes unique to 5-star ED reviews included bedside manner, care for family members, and access. Themes unique to 5-star urgent care center reviews were based on recommendation and prescription refills. Themes unique to 1-star ED reviews were service and speed of care. Themes unique to 1-star urgent care center reviews were lack of confidence and reception experience., Conclusion: Understanding drivers for high and low online ratings and what patients value in their ED and urgent care center experiences offers insights for health systems and providers to improve acute care delivery. Patients' perspectives may become increasingly important as they seek care in the expanding urgent care markets., (Copyright © 2018 American College of Emergency Physicians. Published by Elsevier Inc. All rights reserved.)

In the United States, under the Cash and Counseling or budget authority model of self-directed personal assistance where the participant manages his or her own services and supports, the Support Broker role was established to assist and coach the participant. The support broker role grew out of a person-centered planning process where focus groups and surveys helped ascertain what potential participants wanted to help them establish a self-directed alternative. But, despite this role being described in policy guidance from the Center for Medicare and Medicaid, little research has been conducted examining the functions, activities and usefulness of this position. This study draws on 76 ethnographic case studies with early Cash and Counseling participants, examines what participants and their caregivers actually saw the support broker doing, and looks at what the participants found helpful and less than helpful. Participants and family caregivers saw support broker duties as falling into four areas: Coaching, Problem Solving, Advocacy and Monitoring. Equally important was how the support broker performed these duties. Key aspects of quality included: Familiarity, Supportive Relationship, Proactive Engagement, Responsiveness, Knowledge and Cultural Friendliness. These findings can provide the basis for establishing quality indicators for self-direction.

Objective: The purpose of this study is to report our experience with interprofessional simulations, executed in a mock-up of a proposed perioperative space, that were designed to elicit valuable end-user feedback on the design of the perioperative space., Design: A styrofoam, life-sized model of a perioperative unit was constructed. Various medical professionals and support staff participated in interactive sessions, including workflow simulations, and provided feedback on the perioperative design. Based on participant feedback, the perioperative design was modified, and the styrofoam model was re-constructed. A second round of sessions was conducted, and the change in participant feedback was analyzed., Setting: This study took place under the auspices of the University of Pennsylvania in Philadelphia, Pennsylvania, within Penn Medicine., Participants: One-hundred and ninety-three medical professionals and front line operating room staff participated in the initial round of interactive sessions, and 134 participated in the second round (after re-construction)., Results: In the first round of simulations and interactive sessions, participants spent 560 hours engaging with the space. Modifications were then made to the perioperative design based on participant feedback, and a second round was conducted, in which participants spent 403 hours in the space. Floor plans for round 2 show significant changes compared with round 1, and mean design satisfaction scores for round 2 (3.78 ± 0.41) were significantly higher than for round 1 (3.61 ± 0.49) (p = 0.02). The quality of feedback was associated with the type of interactive session the user participated in., Conclusions: This study suggests that simulations and other interactive sessions, when executed in a mock-up of a proposed perioperative space, can elicit valuable end-user feedback that impacts the final design of the perioperative space and that would traditionally be difficult to obtain until after construction and move-in., (Copyright © 2018 Association of Program Directors in Surgery. All rights reserved.)

Objective: The aim of this study was to explore the relationship between resilience and coping in frontline nurses working in a healthcare system that has recently undergone a merger., Background: Hospital mergers are common in the current healthcare environment. Mergers can provide hospital nurses the opportunity to use and develop positive coping strategies to help remain resilient during times of change., Methods: An anonymous-survey, quantitative, exploratory, descriptive study design was used. Data were obtained from an electronic survey that was made available to all nurses working in a 3-hospital system located in the northeast., Results: Overall, the results showed that, when nurses reported using positive coping strategies, they report higher levels of resilience. The levels of resilience also varied from campus to campus. The campus that has been through 2 recent mergers reported the highest levels of resilience., Conclusion: This study suggests that, during times of change in the workplace, if nurses are encouraged to use positive coping strategies, they may have higher levels of resilience. This changing environment provides the clinical nurse specialists/clinical nurse educators the opportunity to foster and support frontline nurses in the use of healthy coping strategies and to help improve and maintain a high level of resilience, which is critical in today's healthcare environment.

Purpose: Programmed cell death ligand-1 (PD-L1)/programmed cell death-1 (PD-1) blockade has been unsuccessful in prostate cancer, with poor immunogenicity and subsequent low PD-L1 expression in prostate cancer being proposed as an explanation. However, recent studies indicate that a subset of prostate cancer may express significant levels of PD-L1. Furthermore, the androgen antagonist enzalutamide has been shown to upregulate PD-L1 expression in prostate cancer preclinical models. In this study, we evaluated the effect of neoadjuvant androgen deprivation therapy with abiraterone acetate plus prednisone and leuprolide (Neo-AAPL) on PD-L1 expression in prostate cancer. Experimental Design: Radical prostatectomy (RP) tissues were collected from 44 patients with intermediate- to high-risk prostate cancer who underwent RP after Neo-AAPL treatment. Untreated prostate cancer tissues were collected from 130 patients, including 44 matched controls for the Neo-AAPL cases. Tumor PD-L1 expression was detected by IHC using validated anti-PD-L1 antibodies. Tumor-infiltrating CD8 + cells were analyzed in trial cases and matched controls. Expression of DNA mismatch repair genes was examined in PD-L1-positive tumors. Results: Neo-AAPL-treated tumors showed a trend toward decreased PD-L1 positivity compared with matched controls (7% vs. 21% having ≥1% positive tumor cells; P = 0.062). Treated tumors also harbored significantly fewer tumor-infiltrating CD8 + cells ( P = 0.029). In 130 untreated prostate cancers, African American ethnicity, elevated serum PSA, and small prostate independently predicted tumor PD-L1 positivity. Loss of MSH2 expression was observed in 1 of 21 PD-L1-positive tumors. Conclusions: A subset of prostate cancer expresses PD-L1, which is not increased by Neo-AAPL treatment, indicating that combining Neo-AAPL treatment with PD-L1/PD-1 blockade may not be synergistic. Clin Cancer Res; 23(22); 6812-22. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Blood loss associated with lower-extremity total joint arthroplasty (TJA) often results in anemia and the need for red blood cell transfusions (RBCTs). This article reports on a quality improvement initiative aimed at improving blood management strategies in patients undergoing TJA. A multifaceted intervention (preoperative anemia assessment, use of tranexamic acid, discouragement of autologous preoperative blood collection, restrictive RBCT protocols) was implemented. The results were stratified into 3 intervention periods: 1, pre; 2, peri; and 3, post. Fractional logistic regression was used to describe differences between various intervention periods. During the study period, 2511 patients underwent TJA. Compared with the preintervention period, there was 81.8% decrease in total units of RBCT during the postintervention period. Using activity-based costing (~$1000/unit), the annualized saving in RBC expenditure was $480 000. A multidisciplinary approach can be successful and sustainable in reducing RBCT and its associated costs for patients undergoing TJA.

Objective: The Chief Nurse National Health Service Wales initiated a national survey of acute and community hospital patients in Wales to identify the prevalence of pressure ulcers and incontinence-associated dermatitis., Methods: Teams of two nurses working independently assessed the skin of each inpatient who consented to having their skin observed., Results: Over 28 September 2015 to 2nd October 2015, 8365 patients were assessed across 66 hospitals with 748 (8.9%) found to have pressure ulcers. Not all patients had their skin inspected with all mental health patients exempt from this part of the audit along with others who did not consent or were too ill. Of the patients with pressure ulcers, 593 (79.3%) had their skin inspected with 158 new pressure ulcers encountered that were not known to ward staff, while 152 pressure ulcers were incorrectly categorised by the ward teams. Incontinence-associated dermatitis was encountered in 360 patients (4.3%), while medical device-related pressure ulcers were rare (n=33). The support surfaces used while patients were in bed were also recorded to provide a baseline against which future changes in equipment procurement could be assessed. The presence of other wounds was also recorded with 2537 (30.3%) of all hospital patients having one or more skin wounds., Conclusions: This survey has demonstrated that although complex, it is feasible to undertake national surveys of pressure ulcers, incontinence-associated dermatitis and other wounds providing comprehensive and accurate data to help plan improvements in wound care across Wales., Competing Interests: Competing interests: None declared., (© Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.)

Objective: To create guidelines focused on the use of structured physical activity (PA) in the management of juvenile idiopathic arthritis (JIA)., Data Sources: A systematic literature search was conducted using the electronic databases Cochrane Central Register of Controlled Trials, MEDLINE (Ovid), EMBASE (Ovid), and Physiotherapy Evidence Database for all studies related to PA programs for JIA from January 1966 until December 2014, and was updated in May 2015., Study Selection: Study selection was completed independently by 2 reviewers. Studies were included if they involved individuals aged ≤21 years diagnosed with JIA who were taking part in therapeutic exercise or other PA interventions for which effects of various disease-related outcomes were compared with a control group (eg, no PA program or activity of lower intensity)., Data Extraction: Two reviewers independently extracted information on interventions, comparators, outcomes, time period, and study design. The statistical analysis was reported using the Cochrane Collaboration methods. The quality of the included studies was assessed according to the Physiotherapy Evidence Database Scale., Data Synthesis: Five randomized controlled trials (RCTs) fit the selection criteria; of these, 4 were high-quality RCTs. The following recommendations were developed: (1) Pilates for improving quality of life, pain, functional ability, and range of motion (ROM) (grade A); (2) home exercise program for improving quality of life and functional ability (grade A); (3) aquatic aerobic fitness for decreasing the number of active joints (grade A); and (4) and cardio-karate aerobic exercise for improving ROM and number of active joints (grade C+)., Conclusions: The Ottawa Panel recommends the following structured exercises and physical activities for the management of JIA: Pilates, cardio-karate, home and aquatic exercises. Pilates showed improvement in a higher number of outcomes., (Copyright © 2017. Published by Elsevier Inc.)

Objective This update of a 2008 guideline from the American Academy of Otolaryngology-Head and Neck Surgery Foundation provides evidence-based recommendations to benign paroxysmal positional vertigo (BPPV), defined as a disorder of the inner ear characterized by repeated episodes of positional vertigo. Changes from the prior guideline include a consumer advocate added to the update group; new evidence from 2 clinical practice guidelines, 20 systematic reviews, and 27 randomized controlled trials; enhanced emphasis on patient education and shared decision making; a new algorithm to clarify action statement relationships; and new and expanded recommendations for the diagnosis and management of BPPV. Purpose The primary purposes of this guideline are to improve the quality of care and outcomes for BPPV by improving the accurate and efficient diagnosis of BPPV, reducing the inappropriate use of vestibular suppressant medications, decreasing the inappropriate use of ancillary testing such as radiographic imaging, and increasing the use of appropriate therapeutic repositioning maneuvers. The guideline is intended for all clinicians who are likely to diagnose and manage patients with BPPV, and it applies to any setting in which BPPV would be identified, monitored, or managed. The target patient for the guideline is aged ≥18 years with a suspected or potential diagnosis of BPPV. The primary outcome considered in this guideline is the resolution of the symptoms associated with BPPV. Secondary outcomes considered include an increased rate of accurate diagnoses of BPPV, a more efficient return to regular activities and work, decreased use of inappropriate medications and unnecessary diagnostic tests, reduction in recurrence of BPPV, and reduction in adverse events associated with undiagnosed or untreated BPPV. Other outcomes considered include minimizing costs in the diagnosis and treatment of BPPV, minimizing potentially unnecessary return physician visits, and maximizing the health-related quality of life of individuals afflicted with BPPV. Action Statements The update group made strong recommendations that clinicians should (1) diagnose posterior semicircular canal BPPV when vertigo associated with torsional, upbeating nystagmus is provoked by the Dix-Hallpike maneuver, performed by bringing the patient from an upright to supine position with the head turned 45° to one side and neck extended 20° with the affected ear down, and (2) treat, or refer to a clinician who can treat, patients with posterior canal BPPV with a canalith repositioning procedure. The update group made a strong recommendation against postprocedural postural restrictions after canalith repositioning procedure for posterior canal BPPV. The update group made recommendations that the clinician should (1) perform, or refer to a clinician who can perform, a supine roll test to assess for lateral semicircular canal BPPV if the patient has a history compatible with BPPV and the Dix-Hallpike test exhibits horizontal or no nystagmus; (2) differentiate, or refer to a clinician who can differentiate, BPPV from other causes of imbalance, dizziness, and vertigo; (3) assess patients with BPPV for factors that modify management, including impaired mobility or balance, central nervous system disorders, a lack of home support, and/or increased risk for falling; (4) reassess patients within 1 month after an initial period of observation or treatment to document resolution or persistence of symptoms; (5) evaluate, or refer to a clinician who can evaluate, patients with persistent symptoms for unresolved BPPV and/or underlying peripheral vestibular or central nervous system disorders; and (6) educate patients regarding the impact of BPPV on their safety, the potential for disease recurrence, and the importance of follow-up. The update group made recommendations against (1) radiographic imaging for a patient who meets diagnostic criteria for BPPV in the absence of additional signs and/or symptoms inconsistent with BPPV that warrant imaging, (2) vestibular testing for a patient who meets diagnostic criteria for BPPV in the absence of additional vestibular signs and/or symptoms inconsistent with BPPV that warrant testing, and (3) routinely treating BPPV with vestibular suppressant medications such as antihistamines and/or benzodiazepines. The guideline update group provided the options that clinicians may offer (1) observation with follow-up as initial management for patients with BPPV and (2) vestibular rehabilitation, either self-administered or with a clinician, in the treatment of BPPV.

Objective: This plain language summary serves as an overview in explaining benign paroxysmal positional vertigo, abbreviated BPPV. This summary applies to patients ≥18 years old with a suspected or potential diagnosis of BPPV and is based on the 2017 "Clinical Practice Guideline: Benign Paroxysmal Positional Vertigo (Update)." The evidence-based guideline includes research to support more effective diagnosis and treatment of BPPV. The guideline was developed as a quality improvement opportunity for managing BPPV by creating clear recommendations to use in medical practice.

Self-direction has emerged worldwide as a promising practice for persons with serious mental health conditions and as a means toward creating more person-centered service systems. In self-direction, service users control an individualized budget, purchasing goods or services that can help them achieve personal recovery goals. This Open Forum describes an international learning exchange meeting, held in September 2015, in which experts in self-direction and mental health from seven nations convened for sharing best practices, discussing challenges, and laying the groundwork for a learning community to support the continued development of self-direction. Meeting participants identified three themes that represent next steps toward ensuring that the promise of self-direction is realized. First, self-direction involves creating a culture shift for value-based systems change. Second, people with lived experience must be involved and supported at every level, including direct support, leadership, and oversight. Third, stakeholder communication about self-direction's impact is critical.

Objective: To compare neurodevelopmental outcomes at 2-3 years in extremely premature outborn and inborn infants., Design: Population-based retrospective cohort study., Setting: Geographically defined area of New South Wales (NSW) and the Australian Capital Territory (ACT) served by a network of 10 neonatal intensive care units (NICUs)., Patients: All premature infants <29 weeks gestation born between 1998 and 2004 in the setting., Intervention: At 2-3 years, corrected age, 1473 children were assessed with either the Griffiths Mental Developmental Scales (GMDS) or the Bayley Scales of Infant Development (BSID-II)., Main Outcome Measure: Moderate/severe functional disability (FD) defined as: developmental delay (GMDS general quotient (GQ) or BSID-II mental developmental index (MDI)) > 2 standard deviations (SD) below the mean; cerebral palsy (CP) requiring aids; sensorineural or conductive deafness (requiring amplification); or bilateral blindness (visual acuity <6/60 in better eye)., Results: At 2-3 years, moderate/severe functional disability does not appear to be significantly different between outborn and inborn infants (adjusted OR 0.782; 95% CI 0.424-1.443). However, there were a significant number of outborn infants lost to follow up (23.3% versus 42.9%)., Conclusion: In this cohort, at 2-3 years follow up neurodevelopmental outcome does not appear to be significantly different between outborn and inborn infants. These results should be interpreted with caution given the limitation of this study.

This study set out to explore the saving behavior, barriers, and facilitators along with effects of participating in a consumer-directed care program among people with disabilities in the state of West Virginia (N = 29). Results suggest that respondents were able to save money through the program to enable them to purchase goods and services they needed to enhance their welfare and quality of life. Generally, items saved for fell into 3 broad categories: household equipment, individual functioning, and home modification. Facilitators and barriers to saving were also indicated and so were the benefits of program participation. Program and policy implications are presented.

White-tailed deer (Odocoileus virginianus) are commonly exposed to disease agents that affect livestock but environmental factors that predispose deer to exposure are unknown for many pathogens. We trapped deer during winter months on two study areas (Northern Forest and Eastern Farmland) in Wisconsin from 2010 to 2013. Deer were tested for exposure to six serovars of Leptospira interrogans (grippotyphosa, icterohaemorrhagiae, canicola, bratislava, pomona, and hardjo), bovine viral diarrhea virus (BVDV-1 and BVDV-2), infectious bovine rhinotracheitis virus (IBR), and parainfluenza 3 virus (PI3). We used logistic regression to model potential intrinsic (e.g., age, sex) and extrinsic (e.g., land type, study site, year, exposure to multiple pathogens) variables we considered biologically meaningful to exposure of deer to livestock pathogens. Deer sampled in 2010-2011 did not demonstrate exposure to BVDV, so we did not test for BVDV in subsequent years. Deer had evidence of exposure to PI3 (24.7%), IBR (7.9%), Leptospira interrogans serovar pomona (11.7%), L. i. bratislava (1.0%), L. i. grippotyphosa (2.5%) and L. i. hardjo (0.3%). Deer did not demonstrate exposure to L. interrogans serovars canicola and icterohaemorrhagiae. For PI3, we found that capture site and year influenced exposure. Fawns (n = 119) were not exposed to L. i. pomona, but land type was an important predictor of exposure to L. i. pomona for older deer. Our results serve as baseline exposure levels of Wisconsin white-tailed deer to livestock pathogens, and helped to identify important factors that explain deer exposure to livestock pathogens.

Introduction: Bariatric surgery has proven safe and effective for long-term weight loss in morbidly obese patients. Readmissions within 30 days of discharge have become an important metric for quality of care. Sleeve gastrectomy is a common bariatric procedure, but data regarding early readmission is sparse. The purpose of this study is to determine what, if any, demographic or technical factors influence returns to the hospital or readmission following sleeve gastrectomy., Methods: All laparoscopic sleeve gastrectomies (n = 200) performed at a single community hospital from February 2009 to November 2012 were retrospectively reviewed. Demographic, technical, length of stay, return to Emergency Department (ED) and readmission data were gathered for each patient. The data were analyzed to determine what factors were related to early return to the Emergency Department or readmission., Results: Demographics were similar to other studies, with a male to female ratio of 1:4. Patients returning to the ED or readmitted within 30 days were statistically younger than those not returning. None of the other demographic, social, technical, or comorbid conditions considered were associated with a statistically significant risk of readmission or return to the ED within 30 days., Conclusion: Although the only statistically significant difference among the groups studied was age, trends toward significance exist in minority ethnicity and comorbid asthma. These factors have been associated with increased complications in other types of surgery. Larger, multi-institutional studies are needed to further evaluate these and other risk factors for readmission following bariatric surgery.

Background: Use of social media has become widespread across the United States. Although businesses have invested in social media to engage consumers and promote products, less is known about the extent to which hospitals are using social media to interact with patients and promote health., Objective: The aim was to investigate the relationship between hospital social media extent of adoption and utilization relative to hospital characteristics., Methods: We conducted a cross-sectional review of hospital-related activity on 4 social media platforms: Facebook, Twitter, Yelp, and Foursquare. All US hospitals were included that reported complete data for the Centers for Medicare and Medicaid Services Hospital Consumer Assessment of Healthcare Providers and Systems survey and the American Hospital Association Annual Survey. We reviewed hospital social media webpages to determine the extent of adoption relative to hospital characteristics, including geographic region, urban designation, bed size, ownership type, and teaching status. Social media utilization was estimated from user activity specific to each social media platform, including number of Facebook likes, Twitter followers, Foursquare check-ins, and Yelp reviews., Results: Adoption of social media varied across hospitals with 94.41% (3351/3371) having a Facebook page and 50.82% (1713/3371) having a Twitter account. A majority of hospitals had a Yelp page (99.14%, 3342/3371) and almost all hospitals had check-ins on Foursquare (99.41%, 3351/3371). Large, urban, private nonprofit, and teaching hospitals were more likely to have higher utilization of these accounts., Conclusions: Although most hospitals adopted at least one social media platform, utilization of social media varied according to several hospital characteristics. This preliminary investigation of social media adoption and utilization among US hospitals provides the framework for future studies investigating the effect of social media on patient outcomes, including links between social media use and the quality of hospital care and services.

The literature supports family presence during cardiopulmonary resuscitation (CPR) and its many perceived benefits for patients and their families. It also suggests that, overall, health care professionals are supportive of this practice. There have not been any published studies to date that have looked at the perception of family presence from the multidisciplinary resuscitation or code team's perspective. The purpose of this study was to describe the multidisciplinary care provider's understanding and perceived barriers of family presence during CPR in an academic medical center. This study is a quantitative, exploratory, descriptive study that utilized survey methodology. The sample included all members of an urban academic medical center's resuscitation response team. The study findings reveal that, overall, code team members feel that family members should be allowed to remain at the bedside during CPR but that challenges exist including education deficits and mixed feelings that may result from family presence; the study participants caring for neonates and children were more favorable to family presence during CPR than their adult counterparts. Barriers remain related to family presence during resuscitation. Education is needed for all members of the health care team to facilitate collaborative changes in resuscitation practices. Education should include information regarding institutional policies, methods for incorporating family members into the code process, and interventions to support the psychosocial needs of family members.

Patients belonging to some racial, ethnic, and socioeconomic groups are at risk of receiving suboptimal pain management. This study identifies health care provider attitudes, knowledge, and practices regarding the treatment of chronic pain in vulnerable patient populations and assesses whether a certified continuing medical education (CME) intervention can improve knowledge in this area. Survey responses revealed several knowledge gaps, including a lack of knowledge that the undertreatment of pain is more common in minority patients than others. Respondents identified language barriers, miscommunication, fear of medication diversion, and financial barriers as major obstacles to optimal pain management for this patient population. Participants who completed a CME-certified activity on pain management disparities demonstrated increased confidence in caring for disadvantaged patients, but only 1 of 3 knowledge items improved. Understanding clinician factors that underlie suboptimal pain management is necessary to develop effective strategies to overcome disparities and improve quality of care for patients with chronic pain., (© 2013 by the American College of Medical Quality.)

Background: Amyotrophic lateral sclerosis is a fatal neurodegenerative disease with few therapeutic options. Mild obesity is associated with greater survival in patients with the disease, and calorie-dense diets increased survival in a mouse model. We aimed to assess the safety and tolerability of two hypercaloric diets in patients with amyotrophic lateral sclerosis receiving enteral nutrition., Methods: In this double-blind, placebo-controlled, randomised phase 2 clinical trial, we enrolled adults with amyotrophic lateral sclerosis from participating centres in the USA. Eligible participants were aged 18 years or older with no history of diabetes or liver or cardiovascular disease, and who were already receiving percutaneous enteral nutrition. We randomly assigned participants (1:1:1) using a computer-generated list of random numbers to one of three dietary interventions: replacement calories using an isocaloric tube-fed diet (control), a high-carbohydrate hypercaloric tube-fed diet (HC/HC), or a high-fat hypercaloric tube-fed diet (HF/HC). Participants received the intervention diets for 4 months and were followed up for 5 months. The primary outcomes were safety and tolerability, analysed in all patients who began their study diet. This trial is registered with ClinicalTrials.gov, number NCT00983983., Findings: Between Dec 14, 2009, and Nov 2, 2012, we enrolled 24 participants, of whom 20 started their study diet (six in the control group, eight in the HC/HC group, and six in the HF/HC group). One patient in the control group, one in the HC/HC group, and two in the HF/HC group withdrew consent before receiving the intervention. Participants who received the HC/HC diet had a smaller total number of adverse events than did those in the other groups (23 in the HC/HC group vs 42 in the control group vs 48 in the HF/HC group; overall, p=0.06; HC/HC vs control, p=0.06) and significantly fewer serious adverse events than did those on the control diet (none vs nine; p=0.0005). Fewer patients in the HC/HC group discontinued their study diet due to adverse events (none [0%] of eight in the HC/HC group vs three [50%] of six in the control group). During the 5 month follow-up, no deaths occurred in the nine patients assigned to the HC/HC diet compared with three deaths (43%) in the seven patients assigned to the control diet (log-rank p=0.03). Adverse events, tolerability, deaths, and disease progression did not differ significantly between the HF/HC group and the control group., Interpretation: Our results provide preliminary evidence that hypercaloric enteral nutrition is safe and tolerable in patients with amyotrophic lateral sclerosis, and support the study of nutritional interventions in larger randomised controlled trials at earlier stages of the disease., Funding: Muscular Dystrophy Association, National Center for Research Resources, National Institutes of Health, and Harvard NeuroDiscovery Center., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Objectives: A significant proportion of patients with juvenile spondyloarthritis (JSpA) are refractory to treatment with established medications. The objective of this study was to assess long-term efficacy of treatment with anti-TNF agents in patients with JSpA., Methods: An observational study of 16 patients with JSpA from 3 centres treated with infliximab (n=10) and etanercept (n=6) was performed, with a median follow-up period of 7.2 years. Prospective data was collected according to a standardized protocol. Outcomes examined were TEC, TAJC, markers of inflammation (ESR, CRP), functional assessments (C-HAQ, BASDAI, BASFI), and ongoing requirement for anti-TNF treatment., Results: 13/16 patients (83%) had achieved clinical remission 6 months into the treatment. Improvement was sustained over time, with a median TAJC and TEC of 0 at any time point after 6 weeks. 6/16 patients (38%) showed a flare of arthritis after a median of 3.5 years. Two patients with hip disease prior to treatment required an arthroplasty 3 and 8 years post anti-TNF initiation. Patients showed progression of sacroiliitis with median modified New York score of 1 (range 0-3) at time of diagnosis and 3 (range 0-4) at last follow-up (p=0.002). Median BASDAI at last follow up was 1.6, median BASFI 3.1. Two patients developed transient reactions (one generalised, one local); no patient developed other adverse effects during the study., Conclusions: Anti-TNF treatment in JSpA refractory to standard treatment results in good long-term disease control except for pre-existing hip disease. However, radiographic evidence suggests inferior efficacy for control of sacroiliac joint disease.

We hypothesized that next-generation sequencing could reveal actionable genomic alterations (GAs) and potentially expand treatment options for patients with advanced adenoid cystic carcinoma (ACC). Genomic profiling using next-generation sequencing was performed on hybridization-captured, adapter ligation libraries derived from 28 relapsed and metastatic formalin-fixed paraffin-embedded ACC. The 3230 exons of 182 cancer-related genes and 37 introns of 14 genes frequently rearranged in cancer were fully sequenced using the Illumina HiSeq 2000. All classes of GAs were evaluated. Actionable GAs were defined as those impacting targeted anticancer therapies on the market or in registered clinical trials. A total of 44 GAs were identified in the 28 ACC tumors, with 12 of 28 (42.9%) of tumors harboring at least 1 potentially actionable GA. The most common nonactionable GAs were identified in KD6MA (5 cases; 18%), ARID1A (4 cases; 14%), RUNX1 (2 cases; 7%), and MYC (2 cases; 7%). Actionable GAs included NOTCH1 (3 cases; 11%), MDM2 (2 cases; 7%), PDGFRA (2 cases; 7%), and CDKN2A/B (p16) (2 cases; 7%). Other potentially actionable GAs identified in a single case included: mutations in AKT1, BAP1, EGFR, and PIK3CA, homozygous deletion of FBXW7, and amplifications of CDK4, FGFR1, IGF1R, KDR, KIT, and MCL1. The frequency of GA in ACC is lower than that seen in the more common solid tumors. Comprehensive genomic profiling of ACC can identify actionable GAs in a subset of patients that could influence therapy for these difficult-to-treat progressive neoplasms.

Although urothelial carcinoma (UC) of the urinary bladder generally portends a favorable prognosis, metastatic tumors often follow an aggressive clinical course. DNA was extracted from 40 μm of formalin-fixed, paraffin-embedded (FFPE) sections from 35 stage IV UCs that had relapsed and progressed after primary surgery and conventional chemotherapy. Next-generation sequencing (NGS) was performed on hybridization-captured, adaptor ligation-based libraries for 3320 exons of 182 cancer-related genes plus 37 introns from 14 genes frequently rearranged in cancer to at an average sequencing depth of 1164 × and evaluated for all classes of genomic alterations (GAs). Actionable GAs were defined as those impacting the selection of targeted anticancer therapies on the market or in registered clinical trials. A total of 139 GAs were identified, with an average of 4.0 GAs per tumor (range 0-10), of which 78 (56%) were considered actionable, with an average of 2.2 per tumor (range 0-7). Twenty-nine (83%) cases harbored at least one actionable GA including: PIK3CA (9 cases; 26%); CDKN2A/B (8 cases; 23%); CCND1 (5 cases; 14%); FGFR1 (5 cases; 14%); CCND3 (4 cases; 11%); FGFR3 (4 cases; 11%); MCL1 (4 cases; 11%); MDM2 (4 cases; 11%); EGFR (2 cases, 6%); ERBB2 (HER2/neu) (2 cases, 6%); NF1 (2 cases, 6%) and TSC1 (2 cases, 6%). Notable additional alterations included TP53 (19 cases, 54%) and RB1 (6 cases; 17%). Genes involved in chromatin modification were altered by nonsense mutation, splice site mutation or frameshift indel in a mutually exclusive manner in nearly half of all cases including KDM6A (10 cases; 29%) and ARID1A (7 cases; 20%). Comprehensive NGS of 35 UCs of the bladder revealed a diverse spectrum of actionable GAs in 83% of cases, which has the potential to inform treatment decisions for patients with relapsed and metastatic disease.

As more clinically relevant cancer genes are identified, comprehensive diagnostic approaches are needed to match patients to therapies, raising the challenge of optimization and analytical validation of assays that interrogate millions of bases of cancer genomes altered by multiple mechanisms. Here we describe a test based on massively parallel DNA sequencing to characterize base substitutions, short insertions and deletions (indels), copy number alterations and selected fusions across 287 cancer-related genes from routine formalin-fixed and paraffin-embedded (FFPE) clinical specimens. We implemented a practical validation strategy with reference samples of pooled cell lines that model key determinants of accuracy, including mutant allele frequency, indel length and amplitude of copy change. Test sensitivity achieved was 95-99% across alteration types, with high specificity (positive predictive value >99%). We confirmed accuracy using 249 FFPE cancer specimens characterized by established assays. Application of the test to 2,221 clinical cases revealed clinically actionable alterations in 76% of tumors, three times the number of actionable alterations detected by current diagnostic tests.

The majority of lower leg ulceration has a venous component. Compression therapy is the "Gold Standard" to reverse venous hypertension and heal venous ulceration. Over recent years, new compression systems have evolved which means greater choice for patients. This describes venous disease and assessment and treatment choices. Case studies are also presented.

Background: Mutations in SOD1 cause 13% of familial amyotrophic lateral sclerosis. In the SOD1 Gly93Ala rat model of amyotrophic lateral sclerosis, the antisense oligonucleotide ISIS 333611 delivered to CSF decreased SOD1 mRNA and protein concentrations in spinal cord tissue and prolonged survival. We aimed to assess the safety, tolerability, and pharmacokinetics of ISIS 333611 after intrathecal administration in patients with SOD1-related familial amyotrophic lateral sclerosis., Methods: In this randomised, placebo-controlled, phase 1 trial, we delivered ISIS 333611 by intrathecal infusion using an external pump over 11·5 h at increasing doses (0·15 mg, 0·50 mg, 1·50 mg, 3·00 mg) to four cohorts of eight patients with SOD1-positive amyotrophic lateral sclerosis (six patients assigned to ISIS 333611, two to placebo in each cohort). We did the randomisation with a web-based system, assigning patients in blocks of four. Patients and investigators were masked to treatment assignment. Participants were allowed to re-enrol in subsequent cohorts. Our primary objective was to assess the safety and tolerability of ISIS 333611. Assessments were done during infusion and over 28 days after infusion. This study was registered with Clinicaltrials.gov, number NCT01041222., Findings: Seven of eight (88%) patients in the placebo group versus 20 of 24 (83%) in the ISIS 333611 group had adverse events. The most common events were post-lumbar puncture syndrome (3/8 [38%] vs 8/24 [33%]), back pain (4/8 [50%] vs 4/24 [17%]), and nausea (0/8 [0%] vs 3/24 [13%]). We recorded no dose-limiting toxic effects or any safety or tolerability concerns related to ISIS 333611. No serious adverse events occurred in patients given ISIS 333611. Re-enrolment and re-treatment were also well tolerated., Interpretation: This trial is the first clinical study of intrathecal delivery of an antisense oligonucleotide. ISIS 333611 was well tolerated when administered as an intrathecal infusion. Antisense oligonucleotides delivered to the CNS might be a feasible treatment for neurological disorders., Funding: The ALS Association, Muscular Dystrophy Association, Isis Pharmaceuticals., (Copyright © 2013 Elsevier Ltd. All rights reserved.)