Preventing Unintentional Drug Overdose in North Carolina by Advocating for Policies that Support Overdose Prevention

The main purpose of this Capstone project was to develop and promote a policy, which became the 911 Good Samaritan and Naloxone Access bill, to reduce unintentional drug overdose deaths in North Carolina (NC). The team's partner organization, North Carolina Harm Reduction Coalition (NCHRC), solicited the Capstone team's help in raising awareness about NC's overdose problem, developing a policy solution, and advocating for state-level policy change. The Capstone project increased NCHRC's capacity to advocate for the 911 Good Samaritan and Naloxone Access bill, strengthened NCHRC's relationship with the North Carolina General Assembly (NCGA) and community stakeholders, raised awareness of the problem of drug overdose, and resulted in the passage of the policy into law. In 2010, unintentional poisoning, which typically involves drugs, became the second leading cause of injury death for all ages in the United States. Between 1997 and 2001, drug overdose deaths more than doubled in NC. Opioid pain relievers (OPR) accounted for 88% of the increase in drug-related deaths. Many overdose prevention efforts have focused on the supply side, with policies dictating prescribing practice or drug abuse screening and prevention. Although these efforts can prevent an overdose from happening, overdoses will still occur even with the best prevention efforts. Achieving a broader reduction in fatal overdose requires a more targeted policy-level intervention. For this Capstone project, the team produced five deliverables. Deliverable 1 was a literature review of the impact of drug overdose in NC and a fact sheet for distribution to stakeholders. Deliverable 2 consisted of policy recommendations, based on the literature review, intended to guide legislative sponsors in drafting a bill. Deliverable 3 was a presentation to the John Locke Foundation (JLF), a policy think tank, to educate their members and elicit support for the policy. Deliverable 4 was a drug overdose prevention summit in Raleigh to raise awareness and support among various stakeholders, including legislators, for the 911 Good Samaritan and Naloxone Access bill. Lastly, Deliverable 5 included the development of educational materials to raise awareness about the new law.Master of Public Healt

Effects of a Family-Implemented Treatment on the Repetitive Behaviors of Children with Autism

The restricted and repetitive behaviors of children with autism can interfere with family functioning as well as learning and socialization opportunities for the child. To date, neither pharmacological nor comprehensive behavioral treatments have been found to be consistently effective at significantly reducing children’s engagement in repetitive behaviors. We developed Family-Implemented Treatment for Behavioral Inflexibility (FITBI) to target the full variety of repetitive behaviors found in autism. For the current study, a therapist and parents of five children with autism (mean age = 48 months) co-implemented FITBI in a clinic setting over a 12-week treatment period. Using single case design methodology, significant reductions in repetitive behaviors were found for all participants and maintenance of treatment effects for 4 of 5 participants

The Bulletin, School of Nursing Alumnae Association, 1977

A Letter from the President Progress - The New Jefferson Hospital/Clinical Teaching Facility 1977 School of Nursing A Comprehensive Approach to Hand Rehabilitation Parking Garage Your Sesquicentennial Campaign Social Report Scholarship Report Sick and Welfare Committee Program Committee Resource Committee of the Board of Trustees Bulletin Administration Ways and Means Committee Report Resume of Minutes of Alumnae Association Meetings Duke University Distinguished Alumna Award to Col. Catherine T. Betz (Ret.) Patient Representatives The Joys and Sorrows of a Director of Geriatric Nursing Highlights 1976 P.N.A Convention Class News Marriages Births In Memoriam A Letter from the Former President Help Us - Help Yo

A randomized, controlled trial of Social Cognition and Interaction Training (SCIT) for outpatients with schizophrenia spectrum disorders

Objectives In schizophrenia, the ability to adaptively infer the thoughts and feelings of others (i.e., social cognition) is strongly associated with community functioning. Researchers have designed psychosocial interventions to improve social cognition with the aim of improving downstream social functioning. Social Cognition and Interaction Training (SCIT) is one such intervention. Previous research on SCIT has been promising, but has consisted largely of smaller trials with insufficient experimental control. Design Randomized, controlled trial. Methods The current article reports on a controlled trial of 66 adults with schizophrenia randomized to receive either SCIT (n = 33), delivered in weekly group sessions, or treatment as usual (n = 33) for 6 months. Participants completed assessments of social cognition, social functioning, neurocognition and symptoms at baseline, post‐treatment, and 3‐month follow‐up. Results Primary analyses suggest that SCIT may improve social functioning, negative symptoms, and possibly hostile attributional bias. Post‐hoc analyses suggest a dose–response effect. Conclusions Findings are discussed in the context of continuing to refine and improve social cognitive interventions for schizophrenia. Practitioner points - Social cognitive intervention is a feasible and promising approach to improving social functioning among individuals with schizophrenia‐spectrum disorders. - Dose–response findings suggest that delivering social cognitive interventions with greater frequency may maximize their benefit to patients. - Research on social cognitive interventions is still young and effects from well‐controlled trials have been inconsistent. - It is not yet clear which components of social cognitive training may be the key active ingredients.

Development of the Contextual Assessment of Social Skills (CASS): A Role Play Measure of Social Skill for Individuals with High-Functioning Autism

This study piloted a role play assessment of conversational skills for adolescents and young adults with high-functioning autism/Asperger syndrome (HFA/AS). Participants completed two semi-structured role plays, in which social context was manipulated by changing the confederate’s level of interest in the conversation. Participants’ social behavior was rated via a behavioral coding system, and performance was compared across contexts and groups. An interaction effect was found for several items, whereby control participants showed significant change across context, while participants with HFA/AS showed little or no change. Total change across contexts was significantly correlated with related social constructs and significantly predicted ASD. The findings are discussed in terms of the potential utility of the CASS in the evaluation of social skill

“A secret club”: focus groups about women’s toileting behaviors

Abstract Background Understanding reasons for and impact of women’s toileting behaviors on bladder health is important to prevent and manage urinary incontinence (UI) and overactive bladder (OAB). Methods Women, regardless of urinary incontinence (UI) and overactive bladder (OAB) status, were recruited in Pennsylvania and North Carolina. Focus groups were conducted by trained female moderators and sessions were audiotaped. Participants completed an anonymous questionnaire containing validated items to determine the presence of UI and OAB. Audiotapes were transcribed and content was analyzed by two investigators to identify themes. Results Twenty-four women participated (mean age 68 ± 13.4 years); most had UI (75%) or OAB (87.5%). Many women had difficulty in describing bladder health, and talked about bladder function, diseases or conditions, and control over the bladder. Four themes about toileting emerged: 1) cues/triggers/alerts women used to find and use toilets, 2) toilet cleanliness away from and at home, 3) toileting as a nuisance, and 4) situational awareness. Women described internal (e.g., sensation of heaviness) and external cues/triggers/alerts (e.g., walking by restrooms), and the trade-off between their concerns about public toilet cleanliness and the need to urinate. Some women expressed being irritated or annoyed about having to stop activities to urinate. Most women reported sitting on their home toilets, whereas, many hovered or stood over the toilet in public places. Conclusions The information gained from this study will facilitate the development of relevant public health messaging and interventions to raise public awareness about UI, OAB, and bladder health with the aim to encourage women to seek help when symptoms are present

Comparison of Very Low-Dose Decitabine to Standard-Dose Hypomethylating Agents in Myelodysplastic Syndromes (MDS)

Abstract Background: Aberrant epigenetic modifications, fundamental to the pathogenesis of MDS, provide rationale for the use of the so-called hypomethylating agents, decitabine (DAC) and azacitidine (AZA). As depletion of DNA methyltransferase 1 (DNMT1) by these agents is S-phase dependent, episodic dosing used in common practice (SD-DAC; 20 mg/m2 x 5 days, every 28 days, SD-AZA; 75 mg/m2 x 5-7 days, every 28 days) affects only a fraction of the malignant clones. Alternative dosing schedules of decitabine with lower doses given more frequently (LD-DAC; .1-.2 mg/kg SC once/twice weekly) may decrease toxicity and increase response rates by improved hematopoietic differentiation and DNMT1 depletion while avoiding cytotoxicity. Data comparing use of very low and standard-dose DAC or AZA are lacking. Methods: We compared response, survival, and toxicities of 242 MDS patients (pts) treated at our institution from 9/06-10/13 with LD-DAC (n=39), SD-DAC (n=17), or SD-AZA (n=186). Response was assessed per International Working Group 2006 (IWG) criteria, progression-free (PFS) from date of response, and overall survival (OS) from diagnosis. Results: There were no significant differences in baseline characteristics, including median age (70 vs. 74 years, P=.93), proportion of patients with ≥5% bone marrow blasts (27% vs. 35%, P=.54), high/very high cytogenetic risk by the Revised International Prognostic Scoring System (IPSS-R, 25% vs. 40%, P=.31), number of pts with comorbidities (44% vs. 29%, P=.38), median time from diagnosis to treatment (14.6 vs. 6.4 months, P=.25) or prior MDS treatment (AZA and/or lenalidomide, 46% vs. 53%, P=.17), between the LD-DAC and SD-DAC groups, respectively. Likewise, the LA-DAC and SD-AZA groups were similar with respect to median age (70 vs. 68 years, P=.15), proportion of patients with ≥5% bone marrow blasts (27% vs. 39%, P=.19), and high/very high cytogenetic risk by the IPSS-R (25% vs. 27%, P=.83). However, pts in the SD-AZA group had a shorter median time from diagnosis to treatment (2.9 vs. 14.6 months, P=.009) compared to LD-DAC. Median treatment duration was longer in LD-DAC pts compared to SD-DAC (9.1 vs. 3.1 months, P=.0008) with a median cumulative dose of 8.4 mg/kg (range 1.2-41.2) and 350 mg/m2 (range 175-975) for LD-DAC and SD-DAC, respectively. Compared to SD-DAC, the LD-DAC group required more frequent dose reductions/delays (67% vs. 20%, P=.004) and experienced more hematologic toxicity (85% vs. 29%, P< .0001), respectively. While median time to best response was similar for LD-DAC and SD-DAC (3 vs. 4.1 months, P=.52) there was a trend for higher IWG response rates (30% vs. 18%, P=.06) and lower disease progression rates (18% vs. 41%, P=.06) for LD-DAC compared to SD-DAC. However, this did not translate into a difference in median PFS (11 vs. 7.6 months, P= .34) or OS (23.9 vs. 18.2 months, P=.64, Figure 1). Comparing these results to SD-AZA, while LD-DAC had a longer median treatment duration (9.1 vs. 5.1 months, P=.052) and shorter median time to best response (3 vs. 5.3 months, P=.005) than SD-AZA, response rates were similar (30% vs. 31%, P=.5) and there were no significant differences with respect to median PFS (11 vs. 7.1 months, P=.059) or OS (23.9 vs. 21.1 months, P=.5, Figure 1). Conclusion: Pts treated with the LD-DAC strategy have a response rate at least equivalent to SD-DAC and SD-AZA, though they required more dose adjustments and receive treatment for a longer time period. Survival was similar for all dosing strategies. Very low-dose DAC is an active treatment approach and will be compared to standard-dose DAC and AZA in an upcoming randomized, prospective trial conducted through the MDS Clinical Research Consortium. Figure 1 Figure 1. Disclosures Off Label Use: Subcutaneous administration of very low-dose decitabine in treatment of MDS

Inhibition Of JAK-STAT Pathway As a Therapeutic Option For Myelofibrosis Associated Pulmonary Hypertension

Abstract Pulmonary hypertension (PH) is an under-recognized complication of myelofibrosis (MF) occurring in 30% of MF patients and associated with poor survival. Echocardiographic diagnostic findings include; elevated right ventricular systolic pressure (RVSP)>35 mmHg, right atrial (RA) enlargement and increased tricuspid regurgitation velocity (TRV) ≥2.5 m/sec. The pathophysiology of PH in MF has not been elucidated, although in idiopathic PH, the proliferation of pulmonary artery endothelial cells has been linked to activation of STAT3 pathway. Dysregulation of JAK-STAT pathway has been implicated in the pathogenesis of MF. Ruxolitinib, a JAK1/2 inhibitor, was approved for management of splenomegaly and cytokine-mediated symptoms in MF. Furthermore, no specific therapy in the management of MF-associated PH has been established. Given the association between MF and PH and the possible pathophysiologic link mediated by JAK signaling, we prospectively followed 19 patients with MF-associated PH and compared their echocardiographic findings and PH relevant serum biomarker levels (nitric oxide [NO], NT-pro brain natriuretic peptide [NT-proBNP], von Willebrand antigen (vWB), ristocetin co-factor (RCA), and uric acid (UA) pre- and post-ruxolitinib therapy. All categorical data were summarized for frequency, counts and percentages, and the comparison between two groups was performed by two-sample Wilcoxon signed rank test. Among 19 patients (pts), 9 had PMF, 5 post-ET MF, 4 post-PV MF and one CMML-1. In this cohort, 11 were females and 8 were males. The median age of the cohort was 68 years (range, 50-81 years). Fifteen pts were JAK2 V617F positive and 4 were wild-type, 8 were intermediate-1, 4 intermediate-2 and 6 high risk per Dynamic International Prognostic Scoring System-Plus risk grouping. The mean ruxolitinib dose was 10 mg BID (range: 5 mg QOD-20 mg BID]. Median duration of disease was 32 mos (6-164 mos), ruxolitinib duration of treatment was 10 mos (4 -17 mos) and follow-up was 11 mos (6-22 mos). Prior to the initiation of ruxolitinib treatment, NT-pro BNP levels, were measured and found to be elevated in 90% (17/19) of pts. In addition, UA, vWB, and RCA levels were all elevated in 47% (9/19), 24% (4/17), and 12% (2/17) of pts respectively. The strongest correlation among serum biomarkers was between plasma vWB and RCA levels (r2=-0.89, P=<.001). The biomarker most closely associated with elevated NT-pro BNP was UA both in the pre- (r2=-0.53, P=.065) and post-treatment (r2=-0.64, P=.019) settings. Echocardiographic findings by TTE pre- and post ruxolitinib therapy were available for 12 pts (63%). All 12 had documented PH with a mean RVSP of 47.5 mm Hg (42-68) [normal pressure ≤30 mmHg]. Echocardiographic evidence correlated with RCA (r2=-0.64, P= .045) and plasma NT-pro BNP levels (r2=-0.8, P=.013). Ruxolitinib resulted in reductions in NT-pro BNP level (88%) (p=.013), plasma UA levels in (71%), vWB (71%), and RCA (71%) (P=.045). Nitric oxide, a primary regulator of vascular endothelial function is reduced in MF patients with PH compared to normal individuals (median NO, 36 vs 65 pM). Treatment with ruxolitinib resulted in marked increase in NO levels compared to baseline (68 pM vs 36 pM; P=0.04) while no changes in NO levels were observed after treatment with hydroxyurea and lenalidomide (N=10). Treatment with ruxolitinib also resulted in reduction of key cytokines (TNF-α, IL-4, IL-10) that inhibit NO production and induction of cytokines (IFN-γ) that lead to increase in NO synthesis supporting the role of cytokines in PH pathogenesis in MF. Murine studies further supported the role of ruxolitinib in induction of NO levels. Eight normal CD-1 mice were treated with ruxolitinib (50 mg/kg p.o. daily for 5 days for three consecutive cycles with 14 day intervals between each cycle). After the first cycle, NO levels were significantly higher compared to baseline followed by significant increase compared to baseline at cycle 3 (P=.04). In addition, PH mice (Caveoline-1 mice) have been bred and undergoing treatment with ruxolitinib to assess changes in NO levels and its impact in improving of PH. In conclusion, aberrant JAK-STAT signaling in MF mediates PH by dysregulation of NO and cytokines levels which can be restored by therapy with JAK inhibitors. This suggests that inhibition of the JAK-STAT signaling pathway is a novel and viable target for the management of patients with MF-associated PH. Disclosures: No relevant conflicts of interest to declare