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Context In the name of public safety, a general suspension on hospital visiting was imposed in the U.K., prohibiting family and friends to visit hospitalized patients, even if they were critically ill. Objectives we aimed to assess the impact of the FLT on the communication with patients' family and friends (PFF), especailly around end-of-life care, and their interaction with CC clinicians. Methods A retrospective, mixed-methods analysis of a family liaison team (FLT) formed by redeployed clinicians in critical care (CC) during the first surge of the 2020 COVID 19 pandemic. Results The FLT was constituted predominantly of non-ICU consultants (30/39, 77%). Following two one-hourly webinars around basic communication skills, the FLT facilitated over 12,000 video and telephone calls with 172 patients’ family and friends (PFF). The majority of the PFF interviewed were mostly, very or extremely satisfied with the frequency, ease, understanding, honesty, completeness, and consistency of the information provided. Approximately 5% of the interviewees reported to be slightly or very dissatisfied in one or more of the following 3 categories: frequency, consistency, and ease of getting the information. The thematic analysis identified 3 themes: 1) being there with/ for the patient; 2) breakdown in communication; 3) disbelief at the speed of deterioration. In 14.9% of cases there was documented discrepancy between the information transmitted by the CC team and that by the FLT, particularly around the severity of the patient's illness and their imminent death. Conclusion The formation of a dedicated FLT was feasible and associated with high levels of satisfaction by the PFF. Friction was created when communication was not consistent and did not convey the severity of the patient's condition, to prepare the PFF for a bad outcome.

We evaluated nucleic acid amplification testing (NAAT) for Zika virus on whole-blood specimens compared with NAAT on serum and urine specimens among asymptomatic pregnant women during the 2015–2016 Puerto Rico Zika outbreak. Using NAAT, more infections were detected in serum and urine than in whole blood specimens.

Background Influenza causes significant morbidity and mortality and stresses hospital resources during periods of increased circulation. We evaluated the effectiveness of the 2019–2020 influenza vaccine against influenza-associated hospitalization in the United States. Methods We included adults hospitalized with acute respiratory illness at 14 hospitals and tested for influenza viruses by reserve-transcription polymerase chain reaction. Vaccine effectiveness (VE) was estimated by comparing the odds of current-season influenza vaccination in test-positive influenza cases vs test-negative controls, adjusting for confounders. VE was stratified by age and major circulating influenza types along with A(H1N1)pdm09 genetic subgroups. Results A total of 3116 participants were included, including 18% (n = 553) influenza-positive cases. Median age was 63 years. Sixty-seven percent (n = 2079) received vaccination. Overall adjusted VE against influenza viruses was 41% (95% confidence interval [CI], 27%–52%). VE against A(H1N1)pdm09 viruses was 40% (95% CI, 24%–53%) and 33% against B viruses (95% CI, 0–56%). Of the 2 major A(H1N1)pdm09 subgroups (representing 90% of sequenced H1N1 viruses), VE against one group (5A + 187A,189E) was 59% (95% CI, 34%–75%) whereas no VE was observed against the other group (5A + 156K) (–1% [95% CI, –61% to 37%]). Conclusions In a primarily older population, influenza vaccination was associated with a 41% reduction in risk of hospitalized influenza illness.

We estimated vaccine effectiveness (VE) for prevention of influenza-associated hospitalizations among adults during the 2018–2019 influenza season. Adults admitted with acute respiratory illness to 14 hospitals of the US Hospitalized Adult Influenza Vaccine Effectiveness Network (HAIVEN) and testing positive for influenza were cases; patients testing negative were controls. VE was estimated using logistic regression and inverse probability of treatment weighting. We analyzed data from 2863 patients with a mean age of 63 years. Adjusted VE against influenza A(H1N1)pdm09–associated hospitalization was 51% (95% confidence interval [CI], 25%–68%). Adjusted VE against influenza A(H3N2) virus–associated hospitalization was −2% (95% CI, −65% to 37%) and differed significantly by age, with VE of −130% (95% CI, −374% to −27%) among adults 18 to ≤56 years of age. Although vaccination halved the risk of influenza A(H1N1)pdm09–associated hospitalizations, it conferred no protection against influenza A(H3N2)–associated hospitalizations. We observed negative VE for young and middle-aged adults but cannot exclude residual confounding as a potential explanation.

Extracranial internal carotid artery (ICA) aneurysms account for

Dengue is a potentially fatal acute febrile illness caused by any of four mosquito-transmitted dengue viruses (DENV-1 to DENV-4) belonging to the family Flaviviridae and endemic throughout the tropics. Competent mosquito vectors of DENV are present in approximately one half of all U.S. counties. To describe epidemiologic trends in travel-associated and locally acquired dengue cases in the United States, CDC analyzed cases reported from the 50 states and District of Columbia to the national arboviral surveillance system (ArboNET). Cases are confirmed by detection of 1) virus RNA by reverse transcription-polymerase chain reaction (RT-PCR) in any body fluid or tissue, 2) DENV antigen in tissue by a validated assay, 3) DENV nonstructural protein 1 (NS1) antigen, or 4) immunoglobulin M (IgM) anti-DENV antibody if the patient did not report travel to an area with other circulating flaviviruses. When travel to an area with other flaviviruses was reported, IgM-positive cases were defined as probable. During 2010-2017, totals of 5,009 (93%) travel-associated and 378 (7%) locally acquired confirmed or probable dengue cases were reported to ArboNET. Cases were equally distributed between males and females, and median age was 41 years. Eighteen (three per 1,000) fatal cases were reported, all among travelers. Travelers should review country-specific recommendations (https://wwwnc.cdc.gov/travel/notices/watch/dengue-asia) for reducing their risk for DENV infection, including using insect repellent and staying in residences with air conditioning or screens on windows and doors.

Hispanics are the majority ethnic population in Puerto Rico where we reviewed charts of 109 hospitalized COVID-19 patients to better understand demographic and clinical characteristics of COVID-19 and determine risk factors for poor outcomes. Eligible medical records of hospitalized patients with confirmed COVID-19 illnesses were reviewed at four participating hospitals in population centers across Puerto Rico and data were abstracted that described the clinical course, interventions, and outcomes. We found hospitalized patients had a median of 3 underlying conditions with obesity and diabetes as the most frequently reported conditions. Intensive care unit (ICU) admission occurred among 28% of patients and 18% of patients died during the hospitalization. Patients 65 or older or with immune deficiencies had a higher risk for death. Common symptoms included cough, dyspnea, and fatigue; less than half of patients in the study reported fever which was less frequent than reported elsewhere in the literature. It is important for interventions within Hispanic communities to protect high-risk groups.

BACKGROUND: Recommended testing for both infants with Zika-associated birth defects (i.e., microcephaly and selected brain or eye anomalies) and infants without birth defects whose mothers had laboratory evidence of possible Zika virus (ZIKV) infection during pregnancy includes nucleic acid amplification testing (NAAT) and immunoglobulin M (IgM) testing within days after birth. Brain and eye defects highly specific for congenital ZIKV infection have been described; sporadic reports have documented negative ZIKV testing in such infants. METHODS: Infants from the U.S. Zika Pregnancy and Infant Registry and Zika Birth Defects Surveillance with Zika-associated birth defects and maternal and infant laboratory testing for ZIKV and two congenital infections (i.e., cytomegalovirus [CMV] and toxoplasmosis) were reviewed for phenotype and laboratory results. Infants with at least one defect considered highly specific for congenital ZIKV infection were designated as having congenital Zika syndrome (CZS) clinical phenotype for this study. RESULTS: Of 325 liveborn infants with Zika-associated birth defects and laboratory evidence of maternal ZIKV infection, 33 (10%) had CZS clinical phenotype; 172 (53%) had ZIKV IgM testing with negative or no ZIKV NAAT. ZIKV IgM was negative in the remaining 121 infants, and for 90%, testing for CMV and toxoplasmosis was missing/incomplete. Among 11 infants testing negative for ZIKV IgM, CMV, and toxoplasmosis, 2 infants had CZS clinical phenotype. CONCLUSIONS: These data add support to previous reports of negative ZIKV IgM testing in infants with clear maternal and phenotypic evidence of congenital ZIKV infection. Follow-up care consistent with the diagnosis is recommended regardless of infant ZIKV test results.

Objective:The aim of this study was to describe individuals seeking care for injury at a major emergency department (ED) in southern Puerto Rico in the months after Hurricane Maria on September 20, 2017.Methods:After informed consent, we used a modified version of the Natural Disaster Morbidity Surveillance Form to determine why patients were visiting the ED during October 16, 2017–March 28, 2018. We analyzed visits where injury was reported as the primary reason for visit and whether it was hurricane-related.Results:Among 5 116 patients, 573 (11%) reported injury as the primary reason for a visit. Of these, 10% were hurricane-related visits. The most common types of injuries were abrasions, lacerations, and cuts (43% of all injury visits and 50% of hurricane-related visits). The most common mechanisms of injury were falls, slips, trips (268, 47%), and being hit by/or against an object (88, 15%). Most injury visits occurred during the first 3 months after the hurricane.Conclusions:Surveillance after Hurricane Maria identified injury as the reason for a visit for about 1 in 10 patients visiting the ED, providing evidence on the patterns of injuries in the months following a hurricane. Public health and emergency providers can use this information to anticipate health care needs after a disaster.

Background: Detection of local dengue transmission requires an aware and engaged medical community, as health care providers are the front line of public health surveillance. To assess the...

Visual Abstract, Highlights • The impact of breastfeeding on prolactin, cellular immune activation, and myocardial recovery was analyzed in 100 women with peripartum cardiomyopathy • Cardiac function was assessed by echocardiography at presentation and at serial intervals over the first year postpartum • The levels of circulating prolactin were assessed by ELISA, and cellular immunophenotyping by flow cytometry, and compared between breastfeeding and nonbreastfeeding women • Prolactin levels were higher in breastfeeding women and correlated with significant increases in CD8+ T cells • Despite significantly higher prolactin levels and increased CD8+ cells, myocardial recovery was similar in breastfeeding and nonbreastfeeding women, Summary The etiology of peripartum cardiomyopathy remains unknown. One hypothesis is that an increase in the 16-kDa form of prolactin is pathogenic and suggests that breastfeeding may worsen peripartum cardiomyopathy by increasing prolactin, while bromocriptine, which blocks prolactin release, may be therapeutic. An autoimmune etiology has also been proposed. The authors investigated the impact of breastfeeding on cellular immunity and myocardial recovery for women with peripartum cardiomyopathy in the IPAC (Investigations in Pregnancy Associated Cardiomyopathy) study. Women who breastfed had elevated prolactin, and prolactin levels correlated with elevations in CD8+ T cells. However, despite elevated prolactin and cytotoxic T cell subsets, myocardial recovery was not impaired in breastfeeding women.

Approximately 60 million persons in the United States live in rural counties, representing almost one fifth (19.3%) of the population.* In September 2020, COVID-19 incidence (cases per 100,000 population) in rural counties surpassed that in urban counties (1). Rural communities often have a higher proportion of residents who lack health insurance, live with comorbidities or disabilities, are aged ≥65 years, and have limited access to health care facilities with intensive care capabilities, which places these residents at increased risk for COVID-19-associated morbidity and mortality (2,3). To better understand COVID-19 vaccination disparities across the urban-rural continuum, CDC analyzed county-level vaccine administration data among adults aged ≥18 years who received their first dose of either the Pfizer-BioNTech or Moderna COVID-19 vaccine, or a single dose of the Janssen COVID-19 vaccine (Johnson & Johnson) during December 14, 2020-April 10, 2021 in 50 U.S. jurisdictions (49 states and the District of Columbia [DC]). Adult COVID-19 vaccination coverage was lower in rural counties (38.9%) than in urban counties (45.7%) overall and among adults aged 18-64 years (29.1% rural, 37.7% urban), those aged ≥65 years (67.6% rural, 76.1% urban), women (41.7% rural, 48.4% urban), and men (35.3% rural, 41.9% urban). Vaccination coverage varied among jurisdictions: 36 jurisdictions had higher coverage in urban counties, five had higher coverage in rural counties, and five had similar coverage (i.e., within 1%) in urban and rural counties; in four jurisdictions with no rural counties, the urban-rural comparison could not be assessed. A larger proportion of persons in the most rural counties (14.6%) traveled for vaccination to nonadjacent counties (i.e., farther from their county of residence) compared with persons in the most urban counties (10.3%). As availability of COVID-19 vaccines expands, public health practitioners should continue collaborating with health care providers, pharmacies, employers, faith leaders, and other community partners to identify and address barriers to COVID-19 vaccination in rural areas (2).

Long-standing systemic social, economic, and environmental inequities in the United States have put many communities of color (racial and ethnic minority groups) at increased risk for exposure to and infection with SARS-CoV-2, the virus that causes COVID-19, as well as more severe COVID-19-related outcomes (1-3). Because race and ethnicity are missing for a proportion of reported COVID-19 cases, counties with substantial missing information often are excluded from analyses of disparities (4). Thus, as a complement to these case-based analyses, population-based studies can help direct public health interventions. Using data from the 50 states and the District of Columbia (DC), CDC identified counties where five racial and ethnic minority groups (Hispanic or Latino [Hispanic], non-Hispanic Black or African American [Black], non-Hispanic Asian [Asian], non-Hispanic American Indian or Alaska Native [AI/AN], and non-Hispanic Native Hawaiian or other Pacific Islander [NH/PI]) might have experienced high COVID-19 impact during April 1-December 22, 2020. These counties had high 2-week COVID-19 incidences (>100 new cases per 100,000 persons in the total population) and percentages of persons in five racial and ethnic groups that were larger than the national percentages (denoted as "large"). During April 1-14, a total of 359 (11.4%) of 3,142 U.S. counties reported high COVID-19 incidence, including 28.7% of counties with large percentages of Asian persons and 27.9% of counties with large percentages of Black persons. During August 5-18, high COVID-19 incidence was reported by 2,034 (64.7%) counties, including 92.4% of counties with large percentages of Black persons and 74.5% of counties with large percentages of Hispanic persons. During December 9-22, high COVID-19 incidence was reported by 3,114 (99.1%) counties, including >95% of those with large percentages of persons in each of the five racial and ethnic minority groups. The findings of this population-based analysis complement those of case-based analyses. In jurisdictions with substantial missing race and ethnicity information, this method could be applied to smaller geographic areas, to identify communities of color that might be experiencing high potential COVID-19 impact. As areas with high rates of new infection change over time, public health efforts can be tailored to the needs of communities of color as the pandemic evolves and integrated with longer-term plans to improve health equity.

Background Rabies is a viral disease of animals and people causing fatal encephalomyelitis if left untreated. Although effective pre- and post-exposure vaccines exist, they are not widely available in many endemic countries within Africa. Since many individuals in these countries remain at risk of infection, post-exposure healthcare-seeking behaviors are crucial in preventing infection and warrant examination. Methodology A rabies knowledge, attitudes, and practices survey was conducted at 24 geographically diverse sites in Uganda during 2013 to capture information on knowledge concerning the disease, response to potential exposure events, and vaccination practices. Characteristics of the surveyed population and of the canine-bite victim sub-population were described. Post-exposure healthcare-seeking behaviors of canine-bite victims were examined and compared to the related healthcare-seeking attitudes of non-bite victim respondents. Wealth scores were calculated for each household, rabies knowledge was scored for each non-bitten survey respondent, and rabies exposure risk was scored for each bite victim. Logistic regression was used to determine the independent associations between different variables and healthcare-seeking behaviors among canine-bite victims as well as attitudes of non-bitten study respondents. Results A total of 798 households were interviewed, capturing 100 canine-bite victims and a bite incidence of 2.3 per 100 person-years. Over half of bite victims actively sought medical treatment (56%), though very few received rabies post-exposure prophylaxis (3%). Bite victims who did not know or report the closest location where PEP could be received were less likely to seek medical care (p = 0.05). Respondents who did not report having been bitten by a dog with higher knowledge scores were more likely to respond that they would both seek medical care (p = 0.00) and receive PEP (p = 0.06) after a potential rabies exposure event. Conclusions There was varying discordance between what respondents who did not report having been bitten by a dog said they would do if bitten by a dog when compared to the behaviors exhibited by canine-bite victims captured in the KAP survey. Bite victims seldom elected to wash their wound or receive PEP. Having lower rabies knowledge was a barrier to theoretically seeking care and receiving PEP among not bitten respondents, indicating a need for effective and robust educational programs in the country.

ObjectiveYoung people moving from child and adolescent mental health services (CAMHS) to adult mental health services (AMHS) are faced with significant challenges. To improve this state of affairs, there needs to be a recognition of the problem and initiatives and an urgent requirement for appropriate tools for measuring readiness and outcomes at the transfer boundary (16–18 years of age in Europe). The objective of this study was to develop and validate the Transition Readiness and Appropriateness Measure (TRAM) for assessing a young person’s readiness for transition, and their outcomes at the transfer boundary.DesignMILESTONE prospective study.SettingEight European Union (EU) countries participating in the EU-funded MILESTONE study.ParticipantsThe first phase (MILESTONE validation study) involved 100 adolescents (pre-transition), young adults (post-transition), parents/carers and both CAMHS and AMHS clinicians. The second phase (MILESTONE cohort study and nested cluster randomised trial) involved over 1000 young people.ResultsThe development of the TRAM began with a literature review on transitioning and a review of important items regarding transition by a panel of 34 mental health experts. A list of 64 items of potential importance were identified, which together comprised the TRAM. The psychometric properties of the different versions of the TRAM were evaluated and showed that the TRAM had good reliability for all versions and low-to-moderate correlations when compared with other established instruments and a well-defined factor structure. The main results of the cohort study with the nested cluster randomised trial are not reported.ConclusionThe TRAM is a reliable instrument for assessing transition readiness and appropriateness. It highlighted the barriers to a successful transition and informed clinicians, identifying areas which clinicians on both sides of the transfer boundary can work on to ease the transition for the young person.Trial registration numberISRCTN83240263 (Registered 23 July 2015), NCT03013595 (Registered 6 January 2017); Pre-results.

Background Mental health disorders in the child and adolescent population are a pressing public health concern. Despite the high prevalence of psychopathology in this vulnerable population, the transition from Child and Adolescent Mental Health Services (CAMHS) to Adult Mental Health Services (AMHS) has many obstacles such as deficiencies in planning, organisational readiness and policy gaps. All these factors contribute to an inadequate and suboptimal transition process. A suite of measures is required that would allow young people to be assessed in a structured and standardised way to determine the on-going need for care and to improve communication across clinicians at CAMHS and AMHS. This will have the potential to reduce the overall health economic burden and could also improve the quality of life for patients travelling across the transition boundary. The MILESTONE (Managing the Link and Strengthening Transition from Child to Adult Mental Health Care) project aims to address the significant socioeconomic and societal challenge related to the transition process. This protocol paper describes the development of two MILESTONE transition-related measures: The Transition Readiness and Appropriateness Measure (TRAM), designed to be a decision-making aide for clinicians, and the Transition Related Outcome Measure (TROM), for examining the outcome of transition. Methods The TRAM and TROM have been developed and were validated following the US FDA Guidance for Patient-reported Outcome Measures which follows an incremental stepwise framework. The study gathers information from service users, parents, families and mental health care professionals who have experience working with young people undergoing the transition process from eight European countries. Discussion There is an urgent need for comprehensive measures that can assess transition across the CAMHS/AMHS boundary. This study protocol describes the process of development of two new transition measures: the TRAM and TROM. The TRAM has the potential to nurture better transitions as the findings can be summarised and provided to clinicians as a clinician-decision making support tool for identifying cases who need to transition and the TROM can be used to examine the outcomes of the transition process. Trial registration MILESTONE study registration: ISRCTN83240263 Registered 23-July-2015 - ClinicalTrials.gov NCT03013595 Registered 6 January 2017.

Many applications have been developed for electronic data collection. However, offline field navigation tools incorporating secure electronic data capture and field visit tracking are currently scarce. We created an R-Shiny application, HTrack (Household Tracking), for use on encrypted Android devices in the field. The application was implemented in the Communities Organized to Prevent Arboviruses (COPA) project, a study beginning in 2018 to better understand arboviral disease incidence in 38 communities in Puerto Rico. The application was used to navigate to randomly selected structures and capture visit outcomes after conducting multiple visits for participant recruitment. It also served as a bridge to an alternate software, Epi Info, to collect participant-level questionnaire data. This application successfully captured each visit outcome and improved the logistics of field level activities for the COPA project, eliminating the use of paper maps for navigation. We show the development of HTrack and comment on the limitations and strengths of this application and further improvements.

Background Little is known about the prevalence or incidence of Zika virus (ZIKV) infection in settings affected by the 2015–2016 Zika pandemic and associated risk factors. We assessed these factors among household contacts of patients with ZIKV disease enrolled in a cohort study in Puerto Rico during 2016–2017. Methods Household contacts of index case patients completed a questionnaire and gave specimens for real-time polymerase chain reaction (RT-PCR) and immunoglobulin M enzyme-linked immunosorbent assay testing to detect ZIKV infection. We measured the prevalence of ZIKV infection among contacts and associated individual and household factors, examined sexual transmission using a sexual-networks approach, and assessed incident infection among initially uninfected household contacts 2–4 months later. Results Of 366 contacts, 34.4% had evidence of ZIKV infection at enrollment, including 11.2% by RT-PCR. Having open doors and windows that were either screened (prevalence ratio [PR], 2.1 [95% confidence interval {CI}, 1.2–3.6]) or unscreened (PR, 2.5 [95% CI, 1.5–4.1]) was associated with increased prevalence. Sexual partners were more likely to both be RT-PCR positive relative to other relationships (odds ratio, 2.2 [95% CI, 1.1–4.5]). At follow-up, 6.1% of contacts had evidence of incident infection. Conclusions This study identified sexual contact as a risk factor for ZIKV infection. Persons living with ZIKV-infected individuals should be a focus of public health efforts.

There has been increasing interest in nutraceutical augmentation strategies to boost the efficacy of antidepressants. This study assessed whether S-adenosylmethionine (SAMe), a methyl donor that occurs naturally in the body, may be of such benefit. We conducted an 8-week, double-blind RCT in which 107 treatment non-remittent outpatients with DSM-5 diagnosed Major Depressive Disorder (MDD) were randomized to either SAMe or placebo adjunctively to antidepressants. One-carbon cycle nutrients, pertinent single nucleotide polymorphisms (SNPs), and BDNF were also analysed as potential moderators of response. A linear mixed-effects model revealed a significant overall reduction in Montgomery-Asberg Depression Rating Scale (MADRS) score across time, however there was no significant between-group difference observed (p = 0.51). Response rates at Week 8 were 54.3% in the SAMe group and 50.0% in the placebo group, with remission rates 43.5% for SAMe and 38.3% for placebo (all results NS). No effect of SAMe was found on any secondary outcome. Differential response to SAMe was not modified by a range of key genotypes (e.g. COMT), nor reflected in a change of homocysteine, red cell folate, or BDNF. Use of SAMe elicited no significant adverse effects beyond placebo, however it was implicated in one case of serotonin syndrome-like symptoms. This study concludes that 800 mg/day of SAMe is not an effective adjunctive treatment in MDD, and no obvious biomarker reflected any differential response to treatment. Due to such a distinctly high placebo-response (despite rigorous screening), future studies should employ a placebo run-in period and other strategies to minimize placebo response.

Rabies postexposure prophylaxis (PEP) is administered for rabies prevention after a human exposure to a potentially rabid animal, such as a bite. Previous studies have reported that rabies PEP is often inappropriately administered. Health professional education was proposed as one potential solution to address inappropriate PEP use. We assessed baseline knowledge, knowledge gain, and knowledge retention among health professionals in Arizona of rabies epidemiology and appropriate PEP administration. Maricopa County Department of Public Health created an online rabies PEP continuing education module and measured knowledge before and after module completion using a 10-question test. The same test was administered three times (pretest, posttest, and retention test at ≥3 months). To assess knowledge gain and retention, we compared median scores using nonparametric methods. A total of 302 respondents completed the pretest (median score, 60%) and posttest (median score, 90%; p < .001); 98 respondents completed all three tests with median scores 60% (pretest), 90% (posttest, p < .01), and 80% (retention test and compared with pretest, p < .01). Sixty-nine (70%) respondents improved their pretest to retention test score by a mean of 2.4 points out of a total 10 points (median: 2 points; range: −5 to 7 points). Only 48% of pretest respondents correctly answered that PEP should not be administered immediately to anyone bitten by a healthy dog. However, 81% and 70% answered correctly on the posttest ( p < .0001) and retention test ( p = .002), respectively. Respondents demonstrated rabies epidemiology and PEP knowledge gain and ≥3-month knowledge retention after completing the online continuing education module.

BACKGROUND St. Louis encephalitis virus is a mosquito-borne flavivirus that infrequently causes epidemic central nervous system infections. In the United States, blood donors are not screened for St. Louis encephalitis virus infection, and transmission through blood transfusion has not been reported. During September 2015, St. Louis encephalitis virus infection was confirmed in an Arizona kidney transplant recipient. An investigation was initiated to determine the infection source. STUDY DESIGN AND METHODS The patient was interviewed, and medical records were reviewed. To determine the likelihood of mosquito-borne infection, mosquito surveillance data collected at patient and blood donor residences in timeframes consistent with their possible exposure periods were reviewed. To investigate other routes of exposure, organ and blood donor and recipient specimens were obtained and tested for evidence of St. Louis encephalitis virus infection. RESULTS The patient presented with symptoms of central nervous system infection. Recent St. Louis encephalitis virus infection was serologically confirmed. The organ donor and three other organ recipients showed no laboratory or clinical evidence of St. Louis encephalitis virus infection. Among four donors of blood products received by the patient via transfusion, one donor had a serologically confirmed, recent St. Louis encephalitis virus infection. Exposure to an infected mosquito was unlikely based on the patient's minimal outdoor exposure. In addition, no St. Louis encephalitis virus-infected mosquito pools were identified around the patient's residence. CONCLUSION This investigation provides evidence of the first reported possible case of St. Louis encephalitis virus transmission through blood product transfusion. Health care providers and public health professionals should maintain heightened awareness for St. Louis encephalitis virus transmission through blood transfusion in settings where outbreaks are identified.

Background Among various cardiac autoantibodies (AAbs), those recognizing the β 1 -adrenergic receptor (β 1 AR) demonstrate agonist-like effects and induce myocardial damage that can be reversed by β-blockers and immunoglobulin G3 (IgG3) immunoadsorption. Objectives The goal of this study was to investigate the role of β 1 AR-AAbs belonging to the IgG3 subclass in patients with recent-onset cardiomyopathy. Methods Peripheral blood samples were drawn at enrollment in patients with recent-onset cardiomyopathy (left ventricular ejection fraction [LVEF] ≤0.40; 1 AR-AAb was determined, and echocardiograms were assessed, at baseline and 6 months. Patients were followed up for ≤48 months. Results Among the 353 patients who had blood samples adequate for the analysis, 62 (18%) were positive for IgG3-β 1 AR-AAbs (IgG3 group), 58 (16%) were positive for IgG but not IgG3 (non-IgG3 group), and the remaining were negative. There were no significant differences in baseline systolic blood pressure, heart rate, or LVEF among the groups at baseline. Left ventricular end-diastolic and end-systolic diameters were significantly larger in the non-IgG3 group compared with the other groups (left ventricular end-diastolic diameter, p 1 AR-AAb was an independent predictor of LVEF at 6 months and change in LVEF over 6 months, even after multivariable adjustment (LVEF at 6 months, β = 0.20, p = 0.01; change in LVEF, β = 0.20, p = 0.008). In patients with high New York Heart Association functional class (III or IV) at baseline, the IgG3 group had a lower incidence of the composite endpoint of all-cause death, cardiac transplantation, and hospitalization due to heart failure, whereas the non-IgG3 group had the highest incidence of the composite endpoint. Conclusions IgG3-β 1 AR-AAbs were associated with more favorable myocardial recovery in patients with recent-onset cardiomyopathy.

Objectives: Hurricane Maria caused catastrophic damage in Puerto Rico, increasing the risk for morbidity and mortality in the post-impact period. We aimed to establish a syndromic surveillance system to describe the number and type of visits at 2 emergency health-care settings in the same hospital system in Ponce, Puerto Rico. Methods: We implemented a hurricane surveillance system by interviewing patients with a short questionnaire about the reason for visit at a hospital emergency department and associated urgent care clinic in the 6 mo after Hurricane Maria. We then evaluated the system by comparing findings with data from the electronic medical record (EMR) system for the same time period. Results: The hurricane surveillance system captured information from 5116 participants across the 2 sites, representing 17% of all visits captured in the EMR for the same period. Most visits were associated with acute illness/symptoms (79%), followed by injury (11%). The hurricane surveillance and EMR data were similar, proportionally, by sex, age, and visit category. Conclusions: The hurricane surveillance system provided timely and representative data about the number and type of visits at 2 sites. This system, or an adapted version using available electronic data, should be considered in future disaster settings.

Dysregulation of the one carbon cycle is documented in depression. Thereby, S-adenosylmethionine (SAMe), a one–carbon cycle nutraceutical compound with a favourable side effect profile, has a theoretical rationale for efficacy. However, further controlled studies are required to confirm SAMe’s efficacy. To test the efficacy of SAMe versus placebo in unmedicated DSM-5 diagnosed (major depressive disorder) (MDD) patients with mild-to-moderate levels of depressive symptoms. We conducted an 8-week, double-blind, randomised controlled trial testing 800 mg/day of SAMe monotherapy versus placebo in 49 patients with MDD (Montgomery-Asberg Depression Rating Scale [MADRS] score 14–25) who were not currently taking antidepressants. One–carbon cycle biomarkers, brain-derived neurotropic factor (BDNF), and relevant single nucleotide polymorphisms (SNPs) were analysed as potential treatment moderators. A clinically relevant differential reduction from baseline to week 8 of 3.76 points occurred on the primary outcome (MADRS) in favour of SAMe. This however was not significant (p = 0.13) on an adjusted linear mixed model, notwithstanding a medium to large effect size of 0.72. A high placebo response rate of 53% occurred (> 50% reduction on MADRS). Exploratory analyses showed that SAMe was however effective in reducing depression amongst participants with milder depression severity (MADRS ≤ 22, p = 0.045). Response was not moderated by BDNF, SNPs, or one–carbon cycle biomarkers, although increased folate concentrations were correlated with improved symptoms in the SAMe group (r = − 0.57, p = 0.026). The treatment was safe and well tolerated. Although a differential reduction in depression symptoms between groups was observed in favour of SAMe, the results of this pilot study were not statistically significant. ANZCTR—Australian New Zealand Clinical Trials Registry; No.: ACTRN12613001299796; URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364900

Dengue is an acute febrile illness caused by any of four dengue virus types (DENV-1-4). DENVs are transmitted by mosquitos of the genus Aedes (1) and are endemic throughout the tropics (2). In 2010, an estimated 390 million DENV infections occurred worldwide (2). During 2007-2013, a total of three to 10 dengue cases were reported annually in Arizona and all were travel-associated. During September-December 2014, coincident with a dengue outbreak in Sonora, Mexico, 93 travel-associated dengue cases were reported in Arizona residents; 70 (75%) cases were among residents of Yuma County, which borders San Luis Río Colorado, Sonora, Mexico. San Luis Río Colorado reported its first case of locally acquired dengue in September 2014. To investigate the temporal relationship of the dengue outbreaks in Yuma County and San Luis Río Colorado and compare patient characteristics and signs and symptoms, passive surveillance data from both locations were analyzed. In addition, household-based cluster investigations were conducted near the residences of reported dengue cases in Yuma County to identify unreported cases and assess risk for local transmission. Surveillance data identified 52 locally acquired cases (21% hospitalized) in San Luis Río Colorado and 70 travel-associated cases (66% hospitalized) in Yuma County with illness onset during September-December 2014. Among 194 persons who participated in the cluster investigations in Yuma County, 152 (78%) traveled to Mexico at least monthly during the preceding 3 months. Four (2%) of 161 Yuma County residents who provided serum samples for diagnostic testing during cluster investigations had detectable DENV immunoglobulin M (IgM); one reported a recent febrile illness, and all four had traveled to Mexico during the preceding 3 months. Entomologic assessments among 105 households revealed 24 water containers per 100 houses colonized by Ae. aegypti. Frequent travel to Mexico and Ae. aegypti colonization indicate risk for local transmission of DENV in Yuma County. Public health officials in Sonora and Arizona should continue to collaborate on dengue surveillance and educate the public regarding mosquito abatement and avoidance practices. Clinicians evaluating patients from the U.S.-Mexico border region should consider dengue in patients with acute febrile illness and report suspected cases to public health authorities.

BackgroundAfter Zika virus (ZIKV) emerged in the Americas, laboratory-based surveillance for arboviral diseases in Puerto Rico was adapted to include ZIKV disease.Methods and findingsSuspected cases of arboviral disease reported to Puerto Rico Department of Health were tested for evidence of infection with Zika, dengue, and chikungunya viruses by RT-PCR and IgM ELISA. To describe spatiotemporal trends among confirmed ZIKV disease cases, we analyzed the relationship between municipality-level socio-demographic, climatic, and spatial factors, and both time to detection of the first ZIKV disease case and the midpoint of the outbreak. During November 2015-December 2016, a total of 71,618 suspected arboviral disease cases were reported, of which 39,717 (55.5%; 1.1 cases per 100 residents) tested positive for ZIKV infection. The epidemic peaked in August 2016, when 71.5% of arboviral disease cases reported weekly tested positive for ZIKV infection. Incidence of ZIKV disease was highest among 20-29-year-olds (1.6 cases per 100 residents), and most (62.3%) cases were female. The most frequently reported symptoms were rash (83.0%), headache (64.6%), and myalgia (63.3%). Few patients were hospitalized (1.2%), and 13 (ConclusionsDuring the ZIKV epidemic in Puerto Rico, 1% of residents were reported to public health authorities and had laboratory evidence of ZIKV disease. Transmission was first detected in urban areas of eastern Puerto Rico, where transmission also peaked earlier. These trends suggest that ZIKV was first introduced to Puerto Rico in the east before disseminating throughout the island.

Background Zika virus (ZIKV) infection has been associated with severe thrombocytopenia. We describe the incidence, clinical manifestations, and outcomes of patients with ZIKV infection and thrombocytopenia. Methods We reviewed medical records of patients with ZIKV infection and thrombocytopenia (platelet count Results Of 37 878 patients with ZIKV infection, 47 (0.1%) had thrombocytopenia in the absence of an alternative etiology (1.4 cases/100 000 population), including 12 with severe thrombocytopenia. Most patients with thrombocytopenia were adult (77%) and male (53%). Platelet nadir occurred a median (range) of 6 (1–16) and 5 (0–34) days after symptom onset for patients with severe and nonsevere thrombocytopenia, respectively. Among patients with severe thrombocytopenia, all had bleeding, 33% were admitted to the intensive care unit, and 8% died; 50% were treated for ITP. Among 5 patients with severe thrombocytopenia who received intravenous immunoglobulin, the median platelet count increase (range) was 112 (65–202) ×109/L. In contrast, among 4 patients who received platelet transfusion, the median increase in platelet count (range) was 8.5 (–6 to 52) ×109/L. Conclusions Patients with severe thrombocytopenia and ZIKV infection experienced prominent acute morbidity. Consistent with recommended management, administration of ITP treatments to such patients may be more efficacious than platelet transfusion in resolving thrombocytopenia. Severe thrombocytopenia should be considered a rare outcome of ZIKV infection.

Veterinarians play a crucial role in zoonotic disease detection in animals and prevention of disease transmission; reporting these zoonoses to public health officials is an important first step to protect human and animal health. Evidence suggests veterinarians and their staff are at higher risk for exposure to zoonoses because of possible interactions with infected animals. We examined the knowledge, attitudes, and practices of veterinarians regarding zoonotic disease reporting to public health agencies and associated infection prevention (IP) practices such as personal protective equipment (PPE) use, and the need for targeted education and outreach for veterinarians in Arizona. An online questionnaire was developed and distributed by email in September 2015 and was available through November 2015 to all 1,100 members of the Arizona Veterinary Medical Association. Chi-square and logistic regression analyses were performed. In total, 298 (27%) veterinarians from all 15 Arizona counties completed the survey; the majority (70%) were female, practiced small animal medicine (84%), and reported practicing veterinary medicine for ≥10 years (75%). Only 57% reported they knew when to report a suspected zoonotic disease and 60% reported they knew how to make that type of report. The majority said they would report rabies (97%), plague (96%), and highly pathogenic avian influenza (91%) to a state agency. Most respondents reported using PPE (e.g., masks, face shields, and gloves) when performing a surgical procedure (96%) or necropsy (94%), although fewer reported using PPE for handling clinically ill animals (37%) or healthy animals (17%). Approximately 70% reported always using PPE when in contact with animal birthing fluids, urine, or feces, and 47% for contact with animal blood, saliva, or other body fluids. Veterinarians who agreed that they knew the appropriate actions to protect themselves from zoonotic disease exposures were more likely to report always washing their hands before eating or drinking at work (OR = 3.81, 95% confidence interval (CI) [1.97–7.35], P < 0.01). Responses for when to make a report and how to report were not significantly different by gender, years of practice, or holding additional degrees, but did differ by practice type, age, and number of veterinarians in the practice. Small animal veterinarians were less likely to report knowing when to make a report compared to other veterinarians (P < 0.01). Respondents demonstrated suboptimal zoonotic disease reporting and IP practices, including PPE use. Public health agencies should improve outreach and education to veterinarians to facilitate better zoonotic disease prevention practices and reporting.

Background One of the most pressing questions in “Nutritional Psychiatry” is whether using combinations of different nutraceuticals with putative antidepressant activity may provide an enhanced synergistic antidepressant effect. Methods A phase II/III, Australian multi-site, 8-week, double-blind, RCT involving 158 outpatients with a DSM-5 diagnosis of MDD. The intervention consisted of a nutraceutical combination: S-adenosyl methionine; Folinic acid; Omega-3 fatty acids; 5-HTP, Zinc picolinate, and relevant co-factors versus placebo. The primary outcome was change in MADRS score. Hypothesis-driven analyses of potential moderators of response involving key SNPs, and BDNF were also conducted. Results Placebo was superior to the nutraceutical combination in reducing MADRS score (differential reduction -1.75 points), however a mixed linear model revealed a non-significant Group X Time interaction (p = 0.33). Response rates were 40% for the active intervention and 51% for the placebo; remission rates were 34% and 43% for active and placebo groups, respectively. No significant differences were found between groups on any other secondary depression, anxiety, psychosocial, or sleep outcome measures. Key SNPs and BDNF did not significantly moderate response. No significant differences occurred between groups for total adverse effects, aside from more nausea in the active group. Limitations Very high placebo response rates suggest a placebo run-in design may have been valuable. Interpretation The adoption of a nutraceutical ‘shotgun’ approach to treating MDD was not supported, and appeared to be less effective than adding placebo to treatment as usual.

Background: Transient Ischaemic Attacks (TIA) should be treated as a medical emergency. While high-risk TIAs have higher stroke risks than low-risk patients, there is an inherent limitation to this risk stratification, as some low-risk patients may have undiagnosed high-risk conditions. Inequity of care for TIA patients was observed, such that high-risk patients received urgent assessment through acute admission, while low-risk patients faced long waits for clinical consultation. A redesign of the TIA service was planned to offer timely assessment for all patients and avoid acute admission for high-risk patients. Methods: Service reconfiguration was undertaken to set up a daily weekday rapid access TIA clinic where patients would be assessed, investigated, and treated. Results: A re-audit of clinic performance showed a significant increase in the number of patients seen in the ages of 18 to 52. The median time from referral to clinical consultation improved from 10 days to 1. There were similar significant improvements seen in median time to brain imaging (from 10.5 days to 1), and carotid ultrasound (from 10 days to all scans being performed on the same day). Conclusions: The redesigned service achieved the objective of offering urgent assessment and investigations for all TIA patients, including low-risk patients, while avoiding the acute admission for high-risk patients. We share our experience of establishing a successful rapid access ambulatory service without any additional resources.

Melanoma incidence continues to increase across many populations globally and there is significant mortality associated with advanced disease. However, if detected early, patients have a very promising prognosis. The methods that have been utilised for early detection include clinician and patient skin examinations, dermoscopy (static and sequential imaging) and total body photography via 2D imaging. Total body photography has recently witnessed an evolution from 2D imaging with the ability to now create a 3D representation of the patient linked with dermoscopy images of individual lesions. 3D total body photography is a particularly beneficial screening tool for patients at high risk due to their personal or family history or those with multiple dysplastic naevi – the latter can make monitoring especially difficult without the assistance of technology. In this perspective, we discuss clinical examples utilising 3D total body photography, associated advantages and limitations, and future directions of the technology. The optimal system for melanoma screening should improve diagnostic accuracy, be time and cost efficient, and accessible to patients across all demographic and socioeconomic groups. 3D total body photography has the potential to address these criteria and, most importantly, optimise crucial early detection.

A prospective cohort of women with reverse transcription polymerase chain reaction (RT-PCR) confirmed Zika virus infection aged 18–39 years in Puerto Rico found that pregnant women have about a 3-fold longer estimated median detection of Zika virus RNA in serum, which can increase definitive diagnosis of infection and facilitate timely and appropriate clinical management.

The authors investigated the second botulism outbreak to occur in a maximum security prison in Arizona within a 4-month period. Botulism was confirmed in eight men aged 20 to 35 years who reported sharing a single batch of pruno made with potatoes. Initial symptoms included blurred vision, slurred speech, muscle weakness, ptosis, and dysphagia. All patients received heptavalent botulinum antitoxin, seven required mechanical ventilation, and all survived. The median incubation period was 29 hours. Sera from all patients and leftover pruno tested positive for botulinum toxin type A. Botulism should be considered among prisoners with cranial nerve palsies and descending, symmetric flaccid paralysis. Prison-brewed alcohol, particularly when made with potatoes, can be a vehicle for botulism and is associated with outbreaks of botulism in prisons.

Immunotherapy using short immunogenic peptides of disease-related autoantigens restores immune tolerance in preclinical disease models. We studied safety and mechanistic effects of injecting human leukocyte antigen-DR4(DRB1*0401)-restricted immunodominant proinsulin peptide intradermally every 2 or 4 weeks for 6 months in newly diagnosed type 1 diabetes patients. Treatment was well tolerated with no systemic or local hypersensitivity. Placebo subjects showed a significant decline in stimulated C-peptide (measuring insulin reserve) at 3, 6, 9, and 12 months versus baseline, whereas no significant change was seen in the 4-weekly peptide group at these time points or the 2-weekly group at 3, 6, and 9 months. The placebo group's daily insulin use increased by 50% over 12 months but remained unchanged in the intervention groups. C-peptide retention in treated subjects was associated with proinsulin-stimulated interleukin-10 production, increased FoxP3 expression by regulatory T cells, low baseline levels of activated β cell-specific CD8 T cells, and favorable β cell stress markers (proinsulin/C-peptide ratio). Thus, proinsulin peptide immunotherapy is safe, does not accelerate decline in β cell function, and is associated with antigen-specific and nonspecific immune modulation.

Pregnant women living in or traveling to areas with local mosquito-borne Zika virus transmission are at risk for Zika virus infection, which can lead to severe fetal and infant brain abnormalities and microcephaly (1). In February 2016, CDC recommended 1) routine testing for Zika virus infection of asymptomatic pregnant women living in areas with ongoing local Zika virus transmission at the first prenatal care visit, 2) retesting during the second trimester for women who initially test negative, and 3) testing of pregnant women with signs or symptoms consistent with Zika virus disease (e.g., fever, rash, arthralgia, or conjunctivitis) at any time during pregnancy (2). To collect information about pregnant women with laboratory evidence of recent possible Zika virus infection* and outcomes in their fetuses and infants, CDC established pregnancy and infant registries (3). During January 1, 2016-April 25, 2017, U.S. territories† with local transmission of Zika virus reported 2,549 completed pregnancies§ (live births and pregnancy losses at any gestational age) with laboratory evidence of recent possible Zika virus infection; 5% of fetuses or infants resulting from these pregnancies had birth defects potentially associated with Zika virus infection¶ (4,5). Among completed pregnancies with positive nucleic acid tests confirming Zika infection identified in the first, second, and third trimesters, the percentage of fetuses or infants with possible Zika-associated birth defects was 8%, 5%, and 4%, respectively. Among liveborn infants, 59% had Zika laboratory testing results reported to the pregnancy and infant registries. Identification and follow-up of infants born to women with laboratory evidence of recent possible Zika virus infection during pregnancy permits timely and appropriate clinical intervention services (6).

OBJECTIVE: The aim of this work was to evaluate the hypothesis that the distribution of circulating immune cell subsets, or their activation state, is significantly different between peripartum cardiomyopathy (PPCM) and healthy postpartum (HP) women. BACKGROUND: PPCM is a major cause of maternal morbidity and mortality, and an immune-mediated etiology has been hypothesized. Cellular immunity, altered in pregnancy and the peripartum period, has been proposed to play a role in PPCM pathogenesis. METHODS: The Investigation of Pregnancy-Associated Cardiomyopathy (IPAC) study enrolled 100 women presenting with a left ventricular ejection fraction of

Zika virus is a flavivirus transmitted primarily by Aedes species mosquitoes; symptoms of infection include rash, arthralgia, fever, and conjunctivitis.*,† Zika virus infection during pregnancy can cause microcephaly and other serious brain anomalies (1), and in rare cases, Zika virus infection has been associated with Guillain-Barre syndrome (2) and severe thrombocytopenia (3). This report describes the incidence of reported symptomatic Zika virus disease in the U.S. territory of Puerto Rico by age and sex. During November 1, 2015-October 20, 2016, 62,500 suspected Zika virus disease cases were reported to the Puerto Rico Department of Health (PRDH); 29,345 (47%) were confirmed by reverse transcription-polymerase chain reaction (RT-PCR) testing, or were presumptively diagnosed based on serological testing. The highest incidence among confirmed or presumptive cases occurred among persons aged 20-29 years (1,150 cases per 100,000 residents). Among 28,219 (96.2%) nonpregnant patients with confirmed or presumptive Zika virus disease, incidence was higher among women (936 per 100,000 population) than men (576 per 100,000) for all age groups ≥20 years, and the majority (61%) of reported Zika virus disease cases occurred in females. Among suspected Zika virus disease cases in nonpregnant adults aged ≥40 years, the percentage that tested positive among females (52%) was higher than that among males (47%) (p

Zika virus is a flavivirus transmitted primarily by Aedes aegypti and Aedes albopictus mosquitoes, and infection can be asymptomatic or result in an acute febrile illness with rash (1). Zika virus infection during pregnancy is a cause of microcephaly and other severe birth defects (2). Infection has also been associated with Guillain-Barre syndrome (GBS) (3) and severe thrombocytopenia (4,5). In December 2015, the Puerto Rico Department of Health (PRDH) reported the first locally acquired case of Zika virus infection. This report provides an update to the epidemiology of and public health response to ongoing Zika virus transmission in Puerto Rico (6,7). A confirmed case of Zika virus infection is defined as a positive result for Zika virus testing by reverse transcription-polymerase chain reaction (RT-PCR) for Zika virus in a blood or urine specimen. A presumptive case is defined as a positive result by Zika virus immunoglobulin M (IgM) enzyme-linked immunosorbent assay (MAC-ELISA)* and a negative result by dengue virus IgM ELISA, or a positive test result by Zika IgM MAC-ELISA in a pregnant woman. An unspecified flavivirus case is defined as positive or equivocal results for both Zika and dengue virus by IgM ELISA. During November 1, 2015-July 7, 2016, a total of 23,487 persons were evaluated by PRDH and CDC Dengue Branch for Zika virus infection, including asymptomatic pregnant women and persons with signs or symptoms consistent with Zika virus disease or suspected GBS; 5,582 (24%) confirmed and presumptive Zika virus cases were identified. Persons with Zika virus infection were residents of 77 (99%) of Puerto Rico's 78 municipalities. During 2016, the percentage of positive Zika virus infection cases among symptomatic males and nonpregnant females who were tested increased from 14% in February to 64% in June. Among 9,343 pregnant women tested, 672 had confirmed or presumptive Zika virus infection, including 441 (66%) symptomatic women and 231 (34%) asymptomatic women. One patient died after developing severe thrombocytopenia (4). Evidence of Zika virus infection or recent unspecified flavivirus infection was detected in 21 patients with confirmed GBS. The widespread outbreak and accelerating increase in the number of cases in Puerto Rico warrants intensified vector control and personal protective behaviors to prevent new infections, particularly among pregnant women.

Strongyloides stercoralis is an intestinal nematode endemic in the tropics and subtropics. Infection is usually acquired through skin contact with contaminated soil, or less commonly, from person to person through fecal contamination of the immediate environment. Infections are often asymptomatic, but can result in a pruritic rash, respiratory symptoms (e.g., cough or wheeze), and gastrointestinal symptoms (e.g., diarrhea and vomiting). Immunosuppressed persons can develop strongyloides hyperinfection syndrome, which can be fatal (1). In June 2015, the Pinal County Public Health Services District in Arizona was notified of a suspected strongyloidiasis infection in a resident of a long-term-care facility for developmentally disabled persons. The patient had anemia and chronic eosinophilia. The patient's serum tested positive for S. stercoralis-specific immunoglobulin G (IgG) by a commercial enzyme-linked immunosorbent assay (ELISA) and at CDC by a crude antigen ELISA, a quantitative assay for detection of IgG against S. stercoralis. An investigation was conducted to determine the infection source and identify additional cases.

Patients with dementia often exhibit significant mental state disturbances including confusion, agitation and aggression and these may be provoked or exacerbated by many external factors. The research team hypothesised that optimising the sensory awareness of residents to their environment would reduce the number of documented aggressive episodes. During this four-month study the care team documented the number of aggressive episodes in a nursing home unit before, during and after the implementation of the following changes: residents had their hearing aids and glasses checked, cleaned and fitted on a daily basis to maximise the resident's sensory awareness. Living conditions were altered with improved lighting, signing and daily sensory stimulation in line with NICE guideline recommendations. Following the implementation of this intervention, the number of documented aggressive episodes reduced throughout the study period with an overall significant reduction of 25%. The research concluded that simple non-pharmaceutical measures aimed at maximising the ability of residents to sense their environment could indeed reduce aggressive episodes.

Background The aim of this study was to evaluate nocturia severity and nocturia-related differences in sleep, daytime symptoms and functional performance among patients with stable heart failure (HF). Methods and Results In this cross-sectional observational study, we recruited 173 patients [mean age 60.3 ± 16.8 years; female n = 60 (35%); mean left ventricular ejection fraction 32 ± 14.6%] with stable chronic HF from HF disease management programs in the northeastern United States. Participants reported nocturia and completed a 6-minute walk test (6MWT), 1 night of ambulatory polysomnography, and the SF-36 Medical Outcomes Study, Epworth Sleepiness, Pittsburgh Sleep Quality Index, Multidimensional Assessment of Fatigue, and Centers for the Epidemiological Studies of Depression scales. Participants reported 0 (n = 30; 17.3%), 1–2 (n = 87; 50.2%), and ≥3 (n = 56; 32.4%) nightly episodes of nocturia. There were decreases in sleep duration and efficiency, REM and stage 3–4 sleep, physical function, and 6MWT distance and increases in the percentage of wake time after sleep onset, insomnia symptoms, fatigue, and sleepiness across levels of nocturia severity. Conclusions Nocturia is common, severe, and closely associated with decrements in sleep and functional performance and increases in fatigue and sleepiness in patients with stable HF.

Pembrolizumab(®) , a first line immune checkpoint inhibitor, has shown good clinical activity with an acceptable safety profile, in the management of metastatic melanoma.(1, 2) We report a patient with metastatic melanoma, treated with anti-PD-1, who demonstrated metastatic disease regression, focal complete regression of a primary melanoma, partial regression of several solar lentigines, and a patch of poliosis superficial to a thigh metastatic deposit. This article is protected by copyright. All rights reserved.

Background Secondary dengue virus (DENV) infections are typically more severe than primary infections. It is not known whether previous DENV infection is associated with higher Zika virus (ZIKV) quantitative RT-PCR results (viral loads (VLs)) in areas endemic for DENV such as Puerto Rico. Our objective was to analyze the association between previous DENV infection (DENV IgG-positive) and ZIKV VL among children with symptomatic ZIKV infection enrolled in the Sentinel Enhanced Dengue and Acute Febrile Illness Surveillance System (SEDSS) in Puerto Rico. Methods The study population for this analysis comprised individuals Results Of the 319 individuals who met inclusion criteria, 163 have dengue IgG assays completed to date. Of these, 90/163 (55%) were DENV IgG-positive and 73/163 (45%) were DENV IgG-negative, and did not vary by sex (P = 1.00). However, the proportion of patients with DENV IgG-positivity increased with age (P < 0.001) (Figure). Overall, the median (interquartile range, IQR) ZIKV VL was 23,110 (7,452–84,003), and did not vary by age (P = 0.11) or sex (P = 0.33). However, the median ZIKV VL varied by DPO: 26,230 (DPO Conclusion DENV IgG-positivity increased with age among children with symptomatic ZIKV infection. ZIKV VLs did not vary by age, but decreased with increasing DPO. There was no association between DENV IgG and ZIKV VL. Disclosures All authors: No reported disclosures.

16 Background: Increased scrutiny over costs of cancer care has led to the introduction of episode-based payment by federal and commercial insurers. National average billed charges for autologous and allogeneic transplant episodes of care are approximately $375K and $925K, respectively. Through comprehensive analysis of claims data, we identified leading drivers of cost in BMT episodes (which span 30 days before transplant through 60-100 days post-transplant) and cost reduction opportunities. By redesigning care delivery, we can reduce post-transplant admissions and potentially improve the health and patient experience for this population. Methods: From September 1, 2013 – February 28, 2015, SHC performed 221 allogeneic and 241 autologous transplants. We analyzed internal claims data to map costs of BMT episodes, including pre-transplant, transplant (index), and post-transplant phases of care using standardized cost categories including room accommodations, medications, medical and surgical supplies, imaging, and labs. Results: 67% of episode cost was associated with pre-transplant and index phases. In both phases, patients’ treatment closely matched defined protocols. Imaging, medications, and blood utilization met clinical indications. The largest opportunity was seen in the post-transplant phase for patients with multiple myeloma who received autologous transplants. On average, episodes with post-transplant admissions were 35% more costly than episodes without post-transplant admissions. Many of these patients are admitted 5-9 days after transplant due to neutropenic fever, have short LOS, and receive empiric antibiotics. An estimated 37% of post-transplant admissions, totaling $790,000 in annualized cost, may be prevented with additional outpatient support. Conclusions: A multidisciplinary team proposed redesigning care to safely shift treatment from the inpatient to outpatient setting. Strategies include expanding Infusion Treatment Area and home pharmacy capacity and partnering with home health agencies.

Background Identifying factors associated with time-to-loss of Zika virus (ZIKV) RNA in serum and semen is important to inform diagnostic testing and prevention recommendations. CDC currently recommends RT-PCR testing of serum up to two weeks after symptom onset. We evaluated such associations among participants of the Zika virus Persistence (ZiPer) study in Puerto Rico. Methods Patients presenting for care with Zika-like illness and ZIKV RNA detected by RT-PCR in serum or urine (index cases) were offered study participation. Index cases’ household members were offered study participation, and those with detectable ZIKV RNA were eligible for the prospective cohort. Serum and semen were collected weekly for the first month, and biweekly thereafter for participants with detectable ZIKV RNA in any fluid and at 2, 4, and 6 months post-enrollment for all others. We used chi-squared and Fischer’s exact tests to assess if detecting ZIKV RNA in specific specimens at any point was associated with sex, age, Zika-like symptoms (rash, fever, arthralgia, or conjunctivitis), or pregnancy. We performed Weibull regression models to estimate time-to-loss of ZIKV RNA in days post symptom onset (DPO) and evaluated associations between covariates and duration of detection. Results Among 295 participants, 260 (88.1%) had ZIKV RNA detected in serum at any point. Participants aged ≥18 years (n = 244) had a significantly longer median time-to-loss of ZIKV RNA in serum than participants aged < 18 years (n = 50) (13.1 vs. 7.8 DPO, respectively; P = 0.003) (Figure 1). Among women aged 18–39 years (n = 60), pregnant women (n = 9) had a significantly longer median time-to-loss of ZIKV RNA in serum than non-pregnant women (n = 51) (37.4 vs. 15.5 DPO, respectively; P = 0.0005) (Figure 2). The proportion of men who had detectable ZIKV RNA in semen at any point was significantly higher among men with conjunctivitis (47 of 82) than among men without conjunctivitis (3 of 14) (P = 0.01). No other associations were significant. Conclusion Time-to-loss of ZIKV RNA in serum was longer among adults than children, and conjunctivitis was associated with detecting ZIKV RNA in semen. This study provides evidence that time-to-loss of ZIKV RNA is longer among pregnant women than non-pregnant women. Findings may inform the recommended period to test pregnant women for ZIKV using RT-PCR. Disclosures All authors: No reported disclosures.

Background— Cardiac transplantation, a procedure nearly abandoned in the 1970s, has evolved into the standard of care for appropriate patients with end-stage heart failure. Much of this success has been due to improvements in immunosuppression, including the introduction of a triple-drug regimen. Retrospective reports suggested that single-drug immunosuppression with tacrolimus was feasible. As such, a prospective, randomized trial was conducted to test this approach. Methods and Results— One hundred fifty adult de novo heart transplant recipients were enrolled in a prospective, randomized, controlled, open-label trial comparing tacrolimus monotherapy (MONO) with tacrolimus and mycophenolate mofetil therapy (COMBO). Corticosteroids were used in the early postoperative period but discontinued in all patients over 8 to 9 weeks. The primary end point was the composite biopsy score at 6 months after transplant. Patients were followed for 1 to 5 years. The composite biopsy score was similar between groups at 6 and 12 months: 6-month MONO, 0.70±0.44 (95% confidence interval, 0.60 to 0.80) versus COMBO, 0.65±0.40 (95% confidence interval, 0.55 to 0.74; P =0.44). Allograft vasculopathy was assessed by angiography and intravascular ultrasound, with no significant differences noted. Three-year survival was also similar (92.4% MONO versus 97% COMBO; P =0.58, log-rank). Conclusions— Addition of mycophenolate to single-agent immunosuppression did not provide an advantage over single-agent immunosuppression in terms of rejection, allograft vasculopathy, or 3-year survival. Corticosteroids, which have traditionally been a mainstay of therapy, were successfully discontinued in all patients. These conclusions are tempered by the limited statistical power associated with a sample size of only 150 patients. Clinical Trial Registration— URL: http://www.clinicaltrials.gov . Unique identifier: NCT00299221.

A well, 13 day old boy presented with indurated, violaceous nodules on the back (fig 1) and raised corrected calcium of 2.97 mmol/L (2.15-2.60 mmol/L). The rash was initially treated as cellulitis, and he required …