Enhancing Quality of Care Through Evidence-Based Practice: Training and Supervision Experiences.

OBJECTIVE: Evidence-based practice (EBP) is the preferred approach to treatment in mental health settings because it involves the integration of the best available research, clinical expertise, and patient values to optimize patient outcomes. Training on empirically supported treatments (ESTs) in mental health settings is an important component of EBP, and supervision of therapists' implementation of ESTs is critical for therapists to develop and maintain a strong EBP skill set. This study aimed to evaluate training and supervision histories of therapists in outpatient and inpatient psychiatric care settings as an essential first step in improving patient outcomes. METHODS: Electronic surveys were completed by 69 therapists, most of whom had a master's degree, within a psychiatry and behavioral sciences department at an academic institution. Participating therapists were recruited from several outpatient and inpatient mental health settings serving children, adolescents, and adults. RESULTS: Although most therapists reported completing some form of EST-related coursework, a majority did not receive any supervision related to implementation of ESTs (51% for cognitive-behavioral therapy cases, 76% for dialectical behavior therapy cases, and 52% for other EST cases) during graduate and postgraduate training. CONCLUSIONS: Although research from the past decade has supported the need for improvements in training on ESTs, and especially in supervision, problems related to limited exposure to training and supervision among therapists still exist. These findings have implications for how mental health centers can evaluate staff members' EST training and supervision experiences, training needs, and associated training targets to improve the quality of routine care.

Clinical excellence in child and adolescent psychiatry: examples from the published literature.

There has been growing interest in the past century in improving understanding of the development and treatment of psychopathology of children, with increasing government funding of research in the past two decades. However, child and adolescent psychiatry excellence in clinical care has not been well-documented in the existing literature. This article provides examples of clinical excellence in paediatric mental health to supplement existing guidelines for the clinical practice of paediatric psychiatry. A review of the literature identified 204 unique peer-reviewed articles that were then further evaluated for applicability and relevance to the definition of clinical excellence as outlined by the Miller-Coulson Academy of Clinical Excellence (MCACE). Cases were then identified and selected for each domain of clinical excellence as they apply to child and adolescent psychiatry and to provide a model for patient care. KeypointsClinical excellence in child and adolescent psychiatry has not previously been defined or extensively documented.The Miller-Coulson Academy of Clinical Excellence (MCACE) has developed a systematic method to measuring excellence in clinical care and created a definition of clinical excellence.The MCACE defined the domains of clinical excellence as communication and interpersonal skills, professionalism and humanism, diagnostic acumen, skilful negotiation of the healthcare system, knowledge, scholarly approach to clinical practice, exhibiting a passion for patient care and modelling clinical excellence, and collaborating with investigators to advance science and discovery.There are numerous case examples in the literature that represent mastery in paediatric psychiatry in these areas.Clinicians in paediatric mental health will likely benefit from future research on evidence-based approaches to training and education in these domains of clinical excellence.

United Ostomy Associations of America's Ostomy and Continent Diversion Patient Bill of Rights: An Examination of Best-in-Practice Care for Ostomy Patients.

PURPOSE: The purpose of this study was to examine best practices through utilization of United Ostomy Associations of America's (UOAA's) Ostomy and Continent Diversion Patient Bill of Rights (PBOR) from the perspective of patients and clinicians. DESIGN: Cross-sectional, comparative design. SUBJECTS AND SETTING: The sample comprised 412 patients with ostomies (colostomy, ileostomy, urostomy) and continent diversions (such as J-pouch) and 195 clinicians (physicians, nurses, nurse assistants) residing in the United States. All patients underwent surgery within the United States. Almost half of participants (n = 196/412; 47.6%) had surgery within 5 years of data collection. METHODS: Participants were recruited between 2019 and 2020. Patient data were collected from UOAA's national conference and affiliated ostomy support groups. Clinician data were collected at the 2019 National WOCN Society Conference and through affiliated nursing and medical professional societies. Participants completed a self-administered online or printed survey; items focused on the Ostomy and Continent Diversion PBOR and standards of ostomy care. RESULTS: Among clinicians familiar with the PBOR, 54% (n = 58/106) reported UOAA's PBOR was being used to inform ostomy care. When analyzing the full sample of both clinicians and patients, we found that less than 13% (n = 25/195) of clinicians and 5% (n = 20/412) of patients reported that all 16 of the recommended standards of care outlined in the PBOR were incorporated into ostomy care. Analysis also revealed differences between patients' and clinicians' reports of provision of 14 of the 16 PBOR components. They include a discussion on emotional impact of the ostomy surgery, instructions on troubleshooting potential difficulties with the ostomy, provision of educational materials, and providing information for ordering supplies. CONCLUSIONS: Study findings showed discrepancies between the PBOR standards of care being provided by clinicians versus the care patients reported they received. Findings also indicated variability in the consistency of delivering all components of the PBOR. We assert that further awareness and wider utilization of the PBOR in every health care setting in the United States are needed to provide best care to patients living with an ostomy.

Use of Ventricular Assist Devices and Heart Transplantation for Advanced Heart Failure.

There are only 2 treatments for the thousands of patients who progress to the most advanced form of heart failure despite the application of guideline-based medical therapy, use of ventricular assist devices and heart transplantation. There has been a great deal of progress in both of these therapies that have led to improved outcomes including significant improvement in survival and functional capacity. Heart transplantation offers the best short- and long-term survival for patients with end-stage heart failure, and the majority of these recipients achieve relatively limitless functional capacity for their age. However, the chronic shortage of available donors limits the number of recipients in the United States to an only 2500 patients/y or only a fraction of potential candidates. The significant improvement in outcomes now possible with durable ventricular assist devices has led to a significant increase in their use, which now exceeds the volume of heart transplants in the United States, with the greatest growth in use for those not considered to be candidates for heart transplantation, previously referred to as destination therapy. This article will review the substantial progress that has taken place for both of these life-saving treatment options, as well as the future directions.

Patient electronic communication data in clinical care: what is known and what is needed.

The novel coronavirus (COVID-19) and physical distancing guidelines around the world have resulted in unprecedented changes to normal routine and increased smartphone use to maintain social relationships and support. Reports of depressive and anxiety symptom are on the rise, contributing to suffering among people-especially adolescents and young adults-with pre-existing mental health conditions. Psychiatric care has shifted primarily to telehealth limiting the important patient nonverbal communication that has been part of in-person clinical sessions. Supplementing clinical care with patient electronic communication (EC) data may provide valuable information and influence treatment decision making. Research in the impact of patient EC data on managing psychiatric symptoms is in its infancy. This review aims to identify how patient EC has been used in clinical care and its benefits in psychiatry and research. We discuss smartphone applications used to gather different types of EC data, how data have been integrated into clinical care, and implications for clinical care and research.

Interpersonal Counseling for College Students: Pilot Feasibility and Acceptability Study.

OBJECTIVE: University counseling centers struggle to meet the growing demand for mental health treatment by students in distress. More acutely distressed students typically receive priority, whereas those with mild to moderate depression often face longer wait times and fewer available therapy sessions. For this reason, interpersonal counseling for college students (IPC-C) was created as a brief manualized psychotherapy, suitable for students with mild to moderate depression, that maintains the core components of interpersonal counseling and integrates components from interpersonal psychotherapy for adolescents and other developmentally appropriate techniques. This article describes a pilot trial of IPC-C. METHODS: IPC-C is delivered in three to six psychotherapy sessions focused on alleviating depressive symptoms and increasing social support. Ten participants from two university counseling centers were recruited to receive IPC-C. The inclusion criterion was a Patient Health Questionnaire-9 (PHQ-9) score of 5-14, indicating mild to moderate depression. Participants completed the PHQ-9 at each session, the College Adjustment Test at baseline and termination, and the IPC Satisfaction Scale at termination. RESULTS: Nine of the 10 participants completed the study, attending an average of five therapy sessions each. Participants agreed that the number of sessions was appropriate and indicated satisfaction with the IPC-C intervention. Participants exhibited significantly reduced depression severity (Cohen's d=2.45) and significantly improved college adjustment (d=0.92). CONCLUSIONS: In this pilot trial, IPC-C was found to be a feasible and acceptable intervention for university-based treatment of young adults with mild to moderate depressive symptoms. IPC-C holds promise as a potentially effective intervention for this population and warrants further study in a randomized trial.

Interpersonal Counseling for College Students: Pilot Feasibility and Acceptability Study.

OBJECTIVE: University counseling centers struggle to meet the growing demand for mental health treatment by students in distress. More acutely distressed students typically receive priority, whereas those with mild to moderate depression often face longer wait times and fewer available therapy sessions. For this reason, interpersonal counseling for college students (IPC-C) was created as a brief manualized psychotherapy, suitable for students with mild to moderate depression, that maintains the core components of interpersonal counseling and integrates components from interpersonal psychotherapy for adolescents and other developmentally appropriate techniques. This article describes a pilot trial of IPC-C. METHODS: IPC-C is delivered in three to six psychotherapy sessions focused on alleviating depressive symptoms and increasing social support. Ten participants from two university counseling centers were recruited to receive IPC-C. The inclusion criterion was a Patient Health Questionnaire-9 (PHQ-9) score of 5-14, indicating mild to moderate depression. Participants completed the PHQ-9 at each session, the College Adjustment Test at baseline and termination, and the IPC Satisfaction Scale at termination. RESULTS: Nine of the 10 participants completed the study, attending an average of five therapy sessions each. Participants agreed that the number of sessions was appropriate and indicated satisfaction with the IPC-C intervention. Participants exhibited significantly reduced depression severity (Cohen's d=2.45) and significantly improved college adjustment (d=0.92). CONCLUSIONS: In this pilot trial, IPC-C was found to be a feasible and acceptable intervention for university-based treatment of young adults with mild to moderate depressive symptoms. IPC-C holds promise as a potentially effective intervention for this population and warrants further study in a randomized trial.

A Path Forward for Regenerative Medicine.

Although clinical trials of cell-based approaches to cardiovascular disease have yielded some promising results, no cell-based therapy has achieved regulatory approval for a cardiovascular indication. To broadly assess the challenges to regulatory approval and identify strategies to facilitate this goal, the Cardiac Safety Research Consortium sponsored a session during the Texas Heart Institute International Symposium on Cardiovascular Regenerative Medicine in September 2017. This session convened leaders in cardiovascular regenerative medicine, including participants from academia, the pharmaceutical industry, the US Food and Drug Administration, and the Cardiac Safety Research Consortium, with particular focus on treatments closest to regulatory approval. A goal of the session was to identify barriers to regulatory approval and potential pathways to overcome them. Barriers identified include manufacturing and therapeutic complexity, difficulties identifying an optimal comparator group, limited industry capacity for funding pivotal clinical trials, and challenges to demonstrating efficacy on clinical end points required for regulatory decisions. Strategies to overcome these barriers include precompetitive development of a cell therapy registry network to enable dual-purposing of clinical data as part of pragmatic clinical trial design, development of standardized terminology for product activity and end points to facilitate this registry, use of innovative statistical methods and quality of life or functional end points to supplement outcomes such as death or heart failure hospitalization and reduce sample size, involvement of patients in determining the research agenda, and use of the Food and Drug Administration's new Regenerative Medicine Advanced Therapy designation to facilitate early discussion with regulatory authorities when planning development pathways.

Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients With Peripheral Artery Disease (STOP-PAD) Trial: Six-Month Results.

Purpose: To present the 6-month results of the Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Peripheral Artery Disease (STOP-PAD) trial. The trial was an attempt to alter the course of chronic limb-threatening ischemia (CLTI) with a biological agent vs placebo after successful arterial revascularization at or below the knee. Materials and Methods: The multicenter, randomized, double-blinded, placebo-controlled, phase 2B STOP-PAD trial (ClinicalTrials.gov identifier NCT02544204) randomized 109 patients (mean age 71 years; 68 men) with Rutherford category 5 or 6 CLTI and evidence of persistent impaired forefoot perfusion following recent successful revascularization to 8- (n=34) or 16-mg (n=36) intramuscular injections of a non-viral DNA plasmid-based treatment vs placebo (n=34). The primary efficacy outcome was the 6-month wound healing score evaluated by an independent wound core laboratory; the primary safety endpoint was major adverse limb events (MALE), a composite of major amputation plus clinically-driven target lesion revascularization at 6 months. Results: Only one-third of the patients had complete wound healing at 6 months in the placebo (31%), 8-mg injection (33%), and 16-mg injection (33%) groups. In addition, the observed increase in the toe-brachial index from baseline to 6 months was statistically significant in each group; however, this did not result in lower rates of MALE at 6 months (24% in the placebo, 29% in the 8-mg injection, and 11% in the 16-mg injection groups). During the 6-month period, 6 patients (6%) died, and 24 patients (23%) had an amputation [only 4 (4%) major]. Conclusion: Combining revascularization and biological therapy failed to improve outcomes in CLTI at 6 months. STOP-PAD has provided insights for future trials to evaluate biological therapy.

A Brief Look at Urgent Care Visits for Migraine: The Care Received and Ideas to Guide Migraine Care in this Proliferating Medical Setting.

OBJECTIVE: There has been a rise in urgent care centers throughout the country over the past 10 years, leading to an increase in patients accessing medical care in these locations. These centers advertise an alternative to the Emergency Department (ED) for the evaluation and treatment of urgent medical conditions. The goal of this analysis was to examine the use of urgent care visits for migraine within 2 urgent care centers within a large academic medical system in New York City. We examined the trends in management and treatment of migraine in these urgent care settings, as well as prescriptions and instructions given to this patient population upon discharge. We paid particular attention to whether the medications administered and prescribed on discharge were those recommended by American Headache Society migraine management guidelines. METHODS: We conducted a retrospective chart review of patients with migraine diagnoses at 2 different urgent care locations within 1 large urban medical center. We determined baseline patient demographics, previous migraine characteristics, frequencies of reasons for urgent care visits as well as various medications administered, medications prescribed on discharge, and characteristics of patient outcomes post-discharge. RESULTS: Of the 78 patients who visited urgent care with a migraine diagnosis, 20 (25.6%) had a known primary care provider within the urgent care centers' healthcare system. More than three-fourths of all patients (78.2%) had a self-reported history of either recurrent headache or migraine prior to the urgent care visit. Of those with a documented frequency of prior headaches, 94.1% (32/34) had episodic migraine and 79.4% (27/34) experienced at most 1-2 headache days per month. Of those presenting to the urgent care during an episode of migraine, 12.3% (9/73) were given intravenous metoclopramide and none were given subcutaneous sumatriptan or intravenous prochlorperazine. Of those with reported nausea or vomiting with their migraine, 46.2% (18/39) received an anti-emetic at the visit and 33.3% (13/39) were given an anti-emetic prescription. Only 11.1% (6/54) of patients who did not have a record of previous triptan use were given a triptan prescription at the urgent care visit. CONCLUSIONS: The majority of patients in our study who sought medical treatment for migraine in these 2 urgent care centers were not established patients within the urgent care centers' healthcare system. While 93.6% (73/78) of patients were experiencing current pain upon presentation to the urgent care centers, only 12.3% (9/73) received administration of the medications with the highest level of evidence by the American Headache Society (Level B) for acute migraine treatment in an ED. In addition, the majority of patients with a migraine history presenting to the urgent care setting were not given triptans or anti-emetic prescriptions upon discharge from their urgent care visit. Having these migraine-specific prescriptions may improve self-treatment at home should a migraine attack recur.

Review of the clinical approach to the treatment of disruptive mood dysregulation disorder.

Though a decade of research led to the creation of disruptive mood dysregulation disorder (DMDD), it was not until the 2013 publication of the DSM-5 that DMDD became an official diagnosis. The conception of DMDD was largely due to increasing rates of paediatric bipolar disorder (PBD) diagnoses, which significantly impacted treatment for these youth. The core symptoms of DMDD include persistent irritability and recurrent outbursts; the absence of a previous diagnostic category for youth experiencing these symptoms may have led to the over diagnosis of PBD. Due to the chronicity of symptoms, these youth are impaired in multiple areas of functioning. This article will present background information about DMDD, discuss clinical assessment strategies including scales for measuring irritability and aggression, and review pharmacologic and psychosocial treatments for youth with DMDD and clinical phenotypes similar to DMDD.

Social media use and depression in adolescents: a scoping review.

There have been increases in adolescent depression and suicidal behaviour over the last two decades that coincide with the advent of social media (SM) (platforms that allow communication via digital media), which is widely used among adolescents. This scoping review examined the bi-directional association between the use of SM, specifically social networking sites (SNS), and depression and suicidality among adolescents. The studies reviewed yielded four main themes in SM use through thematic analysis: quantity of SM use, quality of SM use, social aspects associated with SM use, and disclosure of mental health symptoms. Research in this field would benefit from use of longitudinal designs, objective and timely measures of SM use, research on the mechanisms of the association between SM use and depression and suicidality, and research in clinical populations to inform clinical practice.

Ostomy Care During Hospital Stay for Ostomy Surgery and the United Ostomy Associations of America Patient Bill of Rights: A Cross-sectional Study.

PURPOSE: The purpose of this study was to determine whether ostomy patients are receiving ostomy care pre- and postoperatively in accordance with the United Ostomy Associations of America Ostomy and Continent Diversion Patient Bill of Rights. DESIGN: Descriptive, quantitative study. SUBJECTS AND SETTING: The sample comprised 325 participants with an ostomy living in the United States. All participants underwent ostomy surgery in the United States. METHODS: Participants were recruited through a purposive, nonprobability sampling method based on the presence of an ostomy and the ability to read and understand English. Data were collected between summer 2017 and fall 2018 from ostomy support groups (online and in-person support groups). Respondents completed a self-administered online questionnaire, which included closed-ended and open-ended questions. RESULTS: Forty percent (n = 127) of participants reported not being supervised changing their pouch before discharge. Forty-two percent (n = 137) reported receiving only hands-on instruction on how to care for their ostomy after surgery (no reading materials, nor video tutorial). Slightly more than half (52%; n = 170) reported not receiving support group information, and only 14% (n = 46) indicated participating in a discussion on intimacy concerns. CONCLUSIONS: The study demonstrates that ostomy care at the hospital can improve. Receiving an ostomy is a life-changing operation, and the first line of support for ostomy patients is their provider. Future research should examine ostomy care from providers' perspectives and, prospectively, in order to test care measures on patient health outcomes.

Multidisciplinary amyotrophic lateral sclerosis telemedicine care: The store and forward method.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) patients benefit from multidisciplinary care in an ALS clinic. We studied whether multidisciplinary care of ALS patients using the store and forward method of telemedicine was feasible and acceptable to patients and providers. METHODS: ALS patients seen in the University of Florida (UF) Jacksonville ALS clinic were eligible for our study. A trained telemedicine nurse performed and recorded a multidisciplinary assessment of the patient in their home. Clinic team members reviewed the assessments and provided recommendations, and the clinic director discussed the plan with the patient via videoconference. Patient and provider satisfaction was evaluated using surveys. RESULTS: Eighteen patients completed a total of 27 telemedicine visits. Patient satisfaction was excellent and provider satisfaction was very good. DISCUSSION: The store and forward method of telemedicine is an acceptable alternative to live telemedicine for the multidisciplinary care of ALS patients. This method of care may improve access to multidisciplinary care for this patient population. Muscle Nerve 59:34-39, 2019.

SDF-1 plasmid treatment for patients with peripheral artery disease (STOP-PAD): Randomized, double-blind, placebo-controlled clinical trial.

The efficacy of biologic therapies in critical limb ischemia (CLI) remains elusive, in part, due to limitations in trial design and patient selection. Using a novel design, we examined the impact of complementing revascularization therapy with intramuscular JVS-100 - a non-viral gene therapy that activates endogenous regenerative repair pathways. In this double-blind, placebo-controlled, Phase 2B trial, we randomized 109 patients with CLI (Rutherford class V or VI) to 8 mg or 16 mg intramuscular injections of placebo versus JVS-100. Patients were eligible if they persistently had reduced forefoot perfusion, by toe-brachial index (TBI) or skin perfusion pressure (SPP), following successful revascularization with angiographic demonstration of tibial arterial flow to the ankle. The primary efficacy end point was a 3-month wound healing score assessed by an independent wound core laboratory. The primary safety end point was major adverse limb events (MALE). Patients' mean age was 71 years, 33% were women, 79% had diabetes, and 8% had end-stage renal disease. TBI after revascularization was 0.26, 0.27, and 0.26 among the three groups (placebo, 8 mg, and 16 mg injections, respectively). Only 26% of wounds completely healed at 3 months, without any differences between the three groups (26.5%, 26.5%, and 25%, respectively). Similarly, there were no significant changes in TBI at 3 months. Three (2.8%) patients died and two (1.8%) had major amputations. Rates of MALE at 3 months were 8.8%, 20%, and 8.3%, respectively. While safe, JVS-100 failed to improve wound healing or hemodynamic measures at 3 months. Only one-quarter of CLI wounds healed at 3 months despite successful revascularization, highlighting the need for additional research in therapies that can improve microcirculation in these patients. ClinicalTrials.gov Identifier: NCT02544204.

Interpersonal psychotherapy for mood and behavior dysregulation: Pilot randomized trial.

BACKGROUND: Youth with chronic irritability and excessive reactivity, diagnosed as disruptive mood dysregulation disorder (DMDD), have social impairment in multiple settings (i.e., peers, school, and home). This paper presents a pilot randomized trial assessing the feasibility, acceptability, and preliminary efficacy of interpersonal psychotherapy (IPT) for mood and behavior dysregulation (IPT-MBD), an adapted version of IPT for depressed adolescents. IPT-MBD focuses on decreasing outbursts and irritability and improving interpersonal interactions. METHODS: Nineteen adolescents (aged 12-17) with DMDD or its research precursor, severe mood dysregulation, were randomly assigned to IPT-MBD (n = 10) or treatment-as-usual (TAU, n = 9) in a 24-week psychosocial intervention study. Assessments of mood symptoms and overall functioning were conducted by an independent evaluator, blinded to treatment, every 4 weeks. Parent and self-report irritability measures were collected every 4 weeks. RESULTS: Eighty percent of participants randomized to the IPT-MBD arm completed the study. Also, participants enrolled in the IPT-MBD arm attended >80% of therapy sessions. Parents and teens agreed that the frequency and duration of therapy were appropriate and were satisfied with IPT-MBD treatment. Clinical global impression scales for severity and improvement showed statistically greater improvement in the IPT-MBD group compared to TAU. CONCLUSIONS: In this small pilot randomized trial, IPT-MBD was feasible and acceptable to parents and teens. There was significantly more improvement in the IPT-MBD group compared to TAU. IPT-MBD holds promise as a potentially effective psychosocial intervention for clinically impaired youth with DMDD and warrants further investigation in a larger randomized trial.

School-Based Curriculum to Improve Depression Literacy Among US Secondary School Students: A Randomized Effectiveness Trial.

OBJECTIVES: To determine the effectiveness of a universal school-based depression education program. METHODS: In 2012-2015, we matched 6679 students from 66 secondary schools into pairs by state (Maryland, Delaware, Pennsylvania, Michigan, and Oklahoma) and randomized to the Adolescent Depression Awareness Program (ADAP; n = 3681) or to a waitlist control condition (n = 2998). Trained teachers delivered ADAP as part of the health education curriculum to students aged 14 to 15 years. The primary outcome was depression literacy. Secondary outcomes included mental health stigma and, in a subset of the sample, the receipt of mental health services. Follow-up was at 4 months. RESULTS: ADAP resulted in significantly higher levels of depression literacy among participating students than did waitlist controls, after adjusting for pretest assessment depression literacy (P < .001). Overall, ADAP did not significantly affect stigma (P = .1). After ADAP, students approached 46% of teachers with concerns about themselves or others. Of students who reported the need for depression treatment, 44% received treatment within 4 months of ADAP implementation. CONCLUSIONS: ADAP is an effective public health intervention for improving depression literacy among students. TRIAL REGISTRATION: Clinicaltrials.gov NCT02099305.

Clinical Variables Associated with Hydration Status in Acute Ischemic Stroke Patients with Dysphagia.

Acute stroke patients with dysphagia are at increased risk for poor hydration. Dysphagia management practices may directly impact hydration status. This study examined clinical factors that might impact hydration status in acute ischemic stroke patients with dysphagia. A retrospective chart review was completed on 67 ischemic stroke patients who participated in a prior study of nutrition and hydration status during acute care. Prior results indicated that patients with dysphagia demonstrated elevated BUN/Cr compared to non-dysphagia cases during acute care and that BUN/Cr increased selectively in dysphagic patients. This chart review evaluated clinical variables potentially impacting hydration status: diuretics, parenteral fluids, tube feeding, oral diet, and nonoral (NPO) status. Exposure to any variable and number of days of exposure to each variable were examined. Dysphagia cases demonstrated significantly more NPO days, tube fed days, and parenteral fluid days, but not oral fed days, or days on diuretics. BUN/Cr values at discharge were not associated with NPO days, parenteral fluid days, oral fed days, or days on diuretics. Patients on modified solid diets had significantly higher mean BUN/Cr values at discharge (27.12 vs. 17.23) as did tube fed patients (28.94 vs. 18.66). No difference was noted between these subgroups at baseline (regular diet vs. modified solids diets). Any modification of solid diets (31.11 vs. 17.23) or thickened liquids (28.50 vs. 17.81) resulted in significantly elevated BUN/Cr values at discharge. Liquid or diet modifications prescribed for acute stroke patients with dysphagia may impair hydration status in these patients.

Changes in ventricular remodelling and clinical status during the year following a single administration of stromal cell-derived factor-1 non-viral gene therapy in chronic ischaemic heart failure patients: the STOP-HF randomized Phase II trial.

BACKGROUND: Stromal cell-derived factor-1 (SDF-1) promotes tissue repair through mechanisms of cell survival, endogenous stem cell recruitment, and vasculogenesis. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure (STOP-HF) is a Phase II, double-blind, randomized, placebo-controlled trial to evaluate safety and efficacy of a single treatment of plasmid stromal cell-derived factor-1 (pSDF-1) delivered via endomyocardial injection to patients with ischaemic heart failure (IHF). METHODS: Ninety-three subjects with IHF on stable guideline-based medical therapy and left ventricular ejection fraction (LVEF) ≤40%, completed Minnesota Living with Heart Failure Questionnaire (MLWHFQ) and 6-min walk distance (6 MWD), were randomized 1 : 1 : 1 to receive a single treatment of either a 15 or 30 mg dose of pSDF-1 or placebo via endomyocardial injections. Safety and efficacy parameters were assessed at 4 and 12 months after injection. Left ventricular functional and structural measures were assessed by contrast echocardiography and quantified by a blinded independent core laboratory. Stromal Cell-Derived Factor-1 Plasmid Treatment for Patients with Heart Failure was powered based on change in 6 MWD and MLWHFQ at 4 months. RESULTS: Subject profiles at baseline were (mean ± SD): age 65 ± 9 years, LVEF 28 ± 7%, left ventricular end-systolic volume (LVESV) 167 ± 66 mL, N-terminal pro brain natriuretic peptide (BNP) (NTproBNP) 1120 ± 1084 pg/mL, MLWHFQ 50 ± 20 points, and 6 MWD 289 ± 99 m. Patients were 11 ± 9 years post most recent myocardial infarction. Study injections were delivered without serious adverse events in all subjects. Sixty-two patients received drug with no unanticipated serious product-related adverse events. The primary endpoint was a composite of change in 6 MWD and MLWHFQ from baseline to 4 months follow-up. The primary endpoint was not met (P = 0.89). For the patients treated with pSDF-1, there was a trend toward an improvement in LVEF at 12 months (placebo vs. 15 mg vs. 30 mg ΔLVEF: -2 vs. -0.5 vs. 1.5%, P = 0.20). A pre-specified analysis of the effects of pSDF-1 based on tertiles of LVEF at entry revealed improvements in EF and LVESV from lowest-to-highest LVEF. Patients in the first tertile of EF (<26%) that received 30 mg of pSDF-1 demonstrated a 7% increase in EF compared with a 4% decrease in placebo (ΔLVEF = 11%, P = 0.01) at 12 months. There was also a trend towards improvement in LVESV, with treated patients demonstrating an 18.5 mL decrease compared with a 15 mL increase for placebo at 12 months (ΔLVESV = 33.5 mL, P = 0.12). The change in end-diastolic and end-systolic volume equated to a 14 mL increase in stroke volume in the patients treated with 30 mg of pSDF-1 compared with a decrease of -11 mL in the placebo group (ΔSV = 25 mL, P = 0.09). In addition, the 30 mg-treated cohort exhibited a trend towards improvement in NTproBNP compared with placebo at 12 months (-784 pg/mL, P = 0.23). CONCLUSIONS: The blinded placebo-controlled STOP-HF trial demonstrated the safety of a single endocardial administration of pSDF-1 but failed to demonstrate its primary endpoint of improved composite score at 4 months after treatment. Through a pre-specified analysis the STOP-HF trial demonstrates the potential for attenuating LV remodelling and improving EF in high-risk ischaemic cardiomyopathy. The safety profile supports repeat dosing with pSDF-1 and the degree of left ventricular remodelling suggests the potential for improved outcomes in larger future trials.