Challenges in the Clinical Recognition of Acute Flaccid Myelitis and its Implications.

OBJECTIVES: To explore the challenges in diagnosing acute flaccid myelitis (AFM) and evaluate clinical features and treatment paradigms associated with under recognition. STUDY DESIGN: This was a retrospective multicenter study of pediatric patients (≤18 years) who were diagnosed with AFM from 2014 to 2018 using the Centers for Disease Control and Prevention's case definition. RESULTS: In 72% of the cases (126 of 175), AFM was not considered in the initial differential diagnosis (n = 108; 61.7%) and/or the patient was not referred for acute care (n = 90; 51.4%) at the initial clinical encounter, and this did not improve over time. Although many features of the presentation were similar in those initially diagnosed with AFM and those who were not; preceding illness, constipation, and reflexes differed significantly between the 2 groups. Patients with a non-AFM initial diagnosis more often required ventilatory support (26.2% vs 12.2%; OR, 0.4; 95% CI, 0.2-1.0; P = .05). These patients received immunomodulatory treatment later (3 days vs 2 days after neurologic symptom onset; 95% CI, -2 to 0; P = .05), particularly intravenous immunoglobulin (5 days vs 2 days; 95% CI, -4 to -2; P < .001). CONCLUSIONS: Delayed recognition of AFM is concerning because of the risk for respiratory decompensation and need for intensive care monitoring. A non-AFM initial diagnosis was associated with delayed treatment that could have a clinical impact, particularly as new treatment options emerge.

Characteristics of pediatric patients with multiple sclerosis and related disorders infected with SARS-CoV-2.

BACKGROUND: Pediatric patients with multiple sclerosis (POMS) and related disorders, clinically isolated syndrome (CIS), myelin oligodendrocyte glycoprotein antibody disorder (MOGAD), and neuromyelitis optica spectrum disorder (NMOSD), are commonly treated with immunosuppressants. Understanding the impact of SARS-CoV-2 infection in patients may inform treatment decisions. OBJECTIVE: Characterize SARS-CoV-2 infection prevalence and severity among a cohort of patients with POMS and related disorders, as well as the impact of disease-modifying therapies (DMTs). METHODS: POMS and related disorders patients enrolled in a large, prospective registry were screened for COVID-19 during standard-of-care neurology visits. If confirmed positive of having infection, further analysis was undertaken. RESULTS: Six hundred and sixty-nine patients were surveyed between March 2020 and August 2021. There were 73 confirmed COVID-19 infections. Eight of nine hospitalized patients (89%), and all patients admitted to the ICU were treated with B cell depleting therapy. The unadjusted odds ratio of hospitalization among those who tested positive of having had COVID-19 was 15.27 among those on B-cell-depleting therapy (p = 0.016). CONCLUSIONS: B-cell-depleting treatment was associated with a higher risk of COVID-19, higher rates of hospitalization, and ICU admission, suggesting this therapy carries a higher risk of severe infection in POMS and related disorders.

Dietary Supplements for Athletic Performance in Women: Beta-Alanine, Caffeine, and Nitrate.

Beta-alanine, caffeine, and nitrate are dietary supplements generally recognized by the sport and exercise science community as evidence-based ergogenic performance aids. Evidence supporting the efficacy of these supplements, however, is greatly skewed due to research being conducted primarily in men. The physiological differences between men and women, most notably in sex hormones and menstrual cycle fluctuations, make generalizing male data to the female athlete inappropriate, and potentially harmful to women. This narrative review outlines the studies conducted in women regarding the efficacy of beta-alanine, caffeine, and nitrate supplementation for performance enhancement. Only nine studies on beta-alanine, 15 on caffeine, and 10 on nitrate in healthy women under the age of 40 years conducted in normoxia conditions were identified as relevant to this research question. Evidence suggests that beta-alanine may lower the rate of perceived exertion and extend training bouts in women, leading to greater functional adaptations. Studies of caffeine in women suggest the physiological responder status and caffeine habituation may contribute to caffeine's efficacy, with a potential plateau in the dose-response relationship of performance enhancement. Nitrate appears to vary in influence based on activity type and primary muscle group examined. However, the results summarized in the limited literature for each of these three supplements provide no consensus on dosage, timing, or efficacy for women. Furthermore, the literature lacks considerations for hormonal status and its role in metabolism. This gap in sex-based knowledge necessitates further research on these ergogenic supplements in women with greater considerations for the effects of hormonal status.

Differential Inhibition of LRRK2 in Parkinson's Disease Patient Blood by a G2019S Selective LRRK2 Inhibitor.

BACKGROUND: A common genetic mutation that causes Parkinson's disease (PD) is the G2019S LRRK2 mutation. A precision medicine approach that selectively blocks only excess kinase activity of the mutant allele could yield a safe and effective treatment for G2019S LRRK2 PD. OBJECTIVE: To determine the activity of a G2019S mutant selective leucine-rich repeat kinase 2 (LRRK2) kinase inhibitor as compared to a nonselective inhibitor in blood of subjects with genetic and idiopathic PD on two LRRK2 biomarkers, pSer935 LRRK2 and pThr73 Rab10. METHODS: Blood was collected from 13 subjects with or without a G2019S LRRK2 mutation with PD and one healthy control. Peripheral blood mononuclear cells were treated ex vivo with a novel G2019S LRRK2 inhibitor (EB-42168) or the nonselective inhibitor MLi-2. Quantitative western immunoblot analyses were performed. RESULTS: EB-42168 was 100 times more selective for G2019S LRRK2 when compared to wild-type (WT) LRRK2. Concentrations that inhibited phosphorylation of pSer935 LRRK2 by 90% in homozygous G2019S LRRK2 patients, inhibited pSer935 LRRK2 by 36% in heterozygous patients, and by only 5% in patients carrying only the WT allele. Similar selectivity was seen for pThr73 Rab10. MLi-2 showed an equivalent level of inhibition across all genotypes. CONCLUSIONS: These findings demonstrate that EB-42168, a G2019S LRRK2 selective inhibitor, lowers mutant G2019S LRRK2 phosphorylated biomarkers while simultaneously sparing WT LRRK2. Selective targeting of G2019S LRRK2 with a small molecule lays the foundation for a precision medicine treatment of G2019S LRRK2 PD. © 2021 ESCAPE Bio, Inc. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

A social systems analysis of implementation of El Salvador's national HIV combination prevention: a research agenda for evaluating Global Health Initiatives.

BACKGROUND: Global Health Initiatives (GHIs) have been instrumental in the rapid acceleration of HIV prevention, treatment access, and availability of care and support services for people living with HIV (PLH) in low and middle income countries (LMIC). These efforts have increasingly used combination prevention approaches that include biomedical, behavioral, social and structural interventions to reduce HIV incidence. However, little research has evaluated their implementation. We report results of qualitative research to examine the implementation of a national HIV combination prevention strategy in El Salvador funded by the Global Fund to Fight AIDS, Tuberculosis and Malaria. METHODS: We conducted in-depth interviews with principal recipients of the funding, members of the Country Coordinating Mechanism (CCM) and front line peer outreach workers and their clients. We analyzed the data using a dynamic systems framework. RESULTS: El Salvador's national HIV combination prevention strategy had three main goals: 1) to decrease the sexual risk behaviors of men who have sex with men (MSM), commercial sex workers (CSW) and transgender women (TW); 2) to increase HIV testing rates among members of these populations and the proportion of PLH who know their status; and 3) to improve linkage to HIV treatment and adherence to antiretroviral therapy (ART). Intervention components to achieve these goals included peer outreach, community prevention centers and specialized STI/HIV clinics, and new adherence and retention protocols for PLH. In each intervention component, we identified several factors which reinforced or diminished intervention efforts. Factors that negatively affected all intervention activities were an increase in violence in El Salvador during implementation of the strategy, resistance to decentralization, and budget constraints. Factors that affected peer outreach and sexual risk reduction were the human resource capacity of grassroots organizations and conflicts of the national HIV strategy with other organizational missions. CONCLUSIONS: Overall, the national strategy improved access to HIV prevention and care through efforts to improve capacity building of grass roots organizations, reduced stigma, and improved coordination among organizations. However, failure to respond to environmental and organizational factors limited the intervention's potential impact.

Development and Pilot Test of a Commercial Sexual Exploitation Prevention Tool: A Brief Report.

Commercial sexual exploitation of children (CSEC) is a persistent problem in the United States, yet few youth-oriented CSEC prevention tools exist. The objectives of this project were to develop an educational website about CSEC for adolescents and evaluate it through pre- and posttests of adolescents' knowledge and attitudes about CSEC. Results demonstrated increases in participants' CSEC knowledge and decreases in their tolerance of CSEC after navigating the website and viewing an embedded video. Qualitative and quantitative results suggest that CSEC is deemed an important issue by adolescents and web-based content is a relevant and useful mode through which to educate adolescents about CSEC. Consideration should be given to further exploration of this and other tools for CSEC prevention tailored to adolescents' needs and preferences.

Neuroinfectious Diseases in Children: Pathophysiology, Outcomes, and Global Challenges.

Pathogens with affinity for the central nervous system (CNS) in children are diverse in their mechanisms of infecting and attacking the brain. Infections can reach the CNS via hematogenous routes, transneurally thereby avoiding the blood-brain barrier, and across mucosal or skin surfaces. Once transmission occurs, pathogens can wreak havoc both by direct action on host cells and via an intricate interplay between the protective and pathologic actions of the host's immune system. Pathogen prevalence varies depending on region, and susceptibility differs based on epidemiologic factors such as age, immune status, and genetics. In addition, some infectious diseases are monophasic, whereas others may lie dormant for years, thereby causing a dynamic effect on outcomes. Outcomes in survivors are highly variable for each particular pathogen and depend on the vaccination and immune status of the patient as well as the speed by which the patient receives evidence-based treatments. Given pathogens cause communicable diseases that can cause morbidity and mortality on a population level when spread, the burden is often the greatest and the outcomes the worst in low-resource settings. Here we will focus on the most common infections with a propensity to affect a child's brain, the pathologic mechanisms by which they do so, and what is known about the developmental outcomes in children who are affected by these infections.

A comparison of cigarette smoking profiles in opioid-dependent pregnant patients receiving methadone or buprenorphine.

INTRODUCTION: Little is known about the relationship between cigarette smoking and agonist treatment in opioid-dependent pregnant patients. The objective of this study is to examine the extent to which cigarette smoking profiles differentially changed during the course of pregnancy in opioid-dependent patients receiving either double-blind methadone or buprenorphine. Patients were participants in the international, randomized controlled Maternal Opioid Treatment: Human Experimental Research (MOTHER) study. METHODS: A sample of opioid-maintained pregnant patients (18-41 years old) with available smoking data who completed a multisite, double-blind, double-dummy, randomized controlled trial of methadone (n = 67) and buprenorphine (n = 57) between 2005 and 2008. Participants were compared on smoking variables based on opioid agonist treatment condition. RESULTS: Overall, 95% of the sample reported cigarette smoking at treatment entry. Participants in the two medication conditions were similar on pretreatment characteristics including smoking rates and daily cigarette amounts. Over the course of the pregnancy, no meaningful changes in cigarette smoking were observed for either medication condition. The fitted difference in change in adjusted cigarettes per day between the two conditions was small and nonsignificant (ß = -0.08, SE = 0.05, p = .132). CONCLUSIONS: Results support high rates of smoking with little change during pregnancy among opioid-dependent patients, regardless of the type of agonist medication received. These findings are consistent with evidence that suggests nicotine effects, and interactions may be similar for buprenorphine compared with methadone. The outcomes further highlight that aggressive efforts are needed to reduce/eliminate smoking in opioid-dependent pregnant women.

The rod synapse in aging wildtype and Dscaml1 mutant mice.

The retina is an intricately organized neural tissue built on cone and rod pathways for color and night vision. Genetic mutations that disrupt the proper function of the rod circuit contribute to blinding diseases including retinitis pigmentosa and congenital stationary night blindness (CSNB). Down Syndrome cell adhesion molecule like 1 (Dscaml1) is expressed by rods, rod bipolar cells (RBCs), and sub-populations of amacrine cells, and has been linked to a middle age onset of CSNB in humans. However, how Dscaml1 contributes to this visual deficit remains unexplored. Here, we probed Dscaml1's role in the maintenance of the rod-to-RBC synapse using a loss of function mouse model. We used immunohistochemistry to investigate the anatomical formation and maintenance of the rod-to-RBC synapse in the young, adult, and aging retina. We generated 3D reconstructions, using serial electron micrographs, of rod spherules and RBCs to measure the number of invaginating neurites, RBC dendritic tip number, and RBC mitochondrial morphology. We find that while rod-to-RBC synapses form and are maintained, similar to wildtype, that there is an increase in the number of invaginating neurites in rod spherules, a reduction in RBC dendritic tips, and reduced mitochondrial volume and complexity in the Dscaml1 mutant retina compared to controls. We also observed precocious sprouting of RBC dendrites into the outer nuclear layer (ONL) of the Dscaml1 mutant retina compared to controls. These results contribute to our knowledge of Dscaml1's role in rod circuit development and maintenance and give additional insight into possible genetic therapy targets for blinding diseases and disorders like CSNB.

Student remote and distance research in neuroanatomy: Mapping Dscaml1 expression with a LacZ gene trap in mouse brain.

Undergraduate student engagement in research increases retention and degree completion, especially for students who are underrepresented in science. Several approaches have been adopted to increase research opportunities including curriculum based undergraduate research opportunities (CUREs), in which research is embedded into course content. Here we report on efforts to tackle a different challenge: providing research opportunities to students engaged in remote learning or who are learning at satellite campuses or community colleges with limited research infrastructure. In our project we engaged students learning remotely or at regional centers to map gene expression in the mouse brain. In this project we mapped expression of the Down syndrome cell adhesion molecule like 1 (Dscaml1) gene in mouse brain using a LacZ expression reporter line. Identifying where Dscaml1 is expressed in the brain is an important next step in determining if its roles in development and function in the retina are conserved in the rest of the brain. Students working remotely reconstruct brain montages and annotated Dscaml1 expression in the brain of mice carrying one or two copies of the gene trap. We built on these findings by further characterizing Dscaml1 expression in inhibitory neurons of the visual pathway. These results build on and extend previous findings and demonstrate the utility of including distance learners in an active research group for both the student learners and the research team. We conclude with best practices we have developed based on this and other distance learner focused projects.

Use of Lifesaving Medications by Athletic Trainers.

The athletic trainer's (AT's) emergency management skillset requires competency in the delivery of basic lifesaving medications. Some lifesaving medications have been a part of athletic training practice for decades, but that list has grown as ATs' practice settings have expanded, increasing the types of emergent conditions that the AT may have to treat. The 2020 Commission on Accreditation of Athletic Training Education (CAATE) curricular standards require that athletic training students be trained to administer the following: supplemental oxygen, nitroglycerine, low-dose aspirin, bronchodilators, epinephrine using an automated injection device, glucagon, and naloxone. Clinically, the conditions treated by these medications can be categorized as cardiac, respiratory, hypoglycemia, and anaphylaxis. All ATs should know the indications, contraindications, administration methods, and details of patient monitoring for each medication. Generally, these medications are safe and have clear indications for use and few contraindications. Although ATs are trained to administer these medications, they must consider state laws and local policies governing administration.

'Hybrid Survey' approach to non-communicable disease surveillance in the US-Affiliated Pacific Islands.

In 2010 the US-Affiliated Pacific Islands (USAPI) declared a regional state of health emergency due to the epidemic of non-communicable disease (NCD) and an NCD monitoring and surveillance framework was developed that includes adult NCD risk factor and disease prevalence indicators to be collected every 5 years using a population-based survey. On evaluation of existing data from adult population-based NCD surveys, it was found that there was a lack of valid, available and consistently collected data. Therefore, a new model was developed to combine various indicators and survey tools from different partner agencies into one survey. After the report was endorsed by local health leadership, a dissemination workshop was conducted. In 2015 (baseline for Hybrid Survey implementation), three out of nine jurisdictions (33.3%) had completed a population-based survey in the past 5 years. Four (44.4%) had no adult prevalence data at all, two (22.2%) had data sets from their surveys and four (44.4%) had at least two surveys ever collected that could be used for comparison. As of 2020, all nine jurisdictions have, or are in the process of completing an adult population-based survey. Eight (88.9%) have data sets from their surveys, and five (55.6%) have at least two surveys collected that can be used for comparison. This Hybrid Survey model has helped to improve adult NCD surveillance in the USAPI by more efficiently using limited resources. This model could be considered in other small island nations, or rural areas where adult NCD surveillance is challenging.

Stigma, isolation, and depression among older adults living with HIV in rural areas.

There is a growing population of ageing individuals living with acquired immunodeficiency syndrome (HIV). Older adults living with HIV often contend with intersecting stigmas including HIV stigma, ageism, and for some, homonegativity and/or racism. Although the HIV stigma literature is quite robust, research on the relationship between HIV stigma, social support, and mental well-being among older adults living with HIV is limited. This study begins to address this gap by examining how intersectional stigma affects social support and mental wellbeing among rural-dwelling older adults living with HIV. Qualitative interviews were conducted by phone with 29 older adults living with HIV, over the age of 50, living in rural areas of the United States. Interviews were transcribed verbatim and analyzed using thematic content analysis in MAXQDA qualitative analysis software. Analysis revealed three primary themes. The first had to do with gossip and non-disclosure of HIV status, which intersected with ageism and homonegativity to exacerbate experiences that fell within the remaining themes of experiences of physical and psychological isolation and loneliness, and shame and silence surrounding depression. The prevalence of social isolation and the effects of limited social support among older adults living with HIV are prominent and indicate a need for tailored interventions within the HIV care continuum for older adults living with HIV.

Safety, tolerability, and efficacy of fluoxetine as an antiviral for acute flaccid myelitis.

OBJECTIVE: To determine the safety, tolerability, and efficacy of fluoxetine for proven or presumptive enterovirus (EV) D68-associated acute flaccid myelitis (AFM). METHODS: A multicenter cohort study of US patients with AFM in 2015-2016 compared serious adverse events (SAEs), adverse effects, and outcomes between fluoxetine-treated patients and untreated controls. Fluoxetine was administered at the discretion of treating providers with data gathered retrospectively. The primary outcome was change in summative limb strength score (SLSS; sum of Medical Research Council strength in all 4 limbs, ranging from 20 [normal strength] to 0 [complete quadriparesis]) between initial examination and latest follow-up, with increased SLSS reflecting improvement and decreased SLSS reflecting worsened strength. RESULTS: Fifty-six patients with AFM from 12 centers met study criteria. Among 30 patients exposed to fluoxetine, no SAEs were reported and adverse effect rates were similar to unexposed patients (47% vs 65%, p = 0.16). The 28 patients treated with >1 dose of fluoxetine were more likely to have EV-D68 identified (57.1% vs 14.3%, p < 0.001). Their SLSS was similar at initial examination (mean SLSS 12.9 vs 14.3, p = 0.31) but lower at nadir (mean SLSS 9.25 vs 12.82, p = 0.02) and latest follow-up (mean SLSS 12.5 vs 16.4, p = 0.005) compared with the 28 patients receiving 1 (n = 2) or no (n = 26) doses. In propensity-adjusted analysis, SLSS from initial examination to latest follow-up decreased by 0.2 (95% confidence interval [CI] -1.8 to +1.4) in fluoxetine-treated patients and increased by 2.5 (95% CI +0.7 to +4.4) in untreated patients (p = 0.015). CONCLUSION: Fluoxetine was well-tolerated. Fluoxetine was preferentially given to patients with AFM with EV-D68 identified and more severe paralysis at nadir, who ultimately had poorer long-term outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with EV-D68-associated AFM, fluoxetine is well-tolerated and not associated with improved neurologic outcomes.

Rabies in Alaska, from the past to an uncertain future.

Rabies is a serious zoonotic disease with significant public health consequences in the circumpolar North. Recent studies have advanced our understanding of the disease ecology in Alaska. In this paper, we review historical records of rabies in Alaska ranging from the late nineteenth century to the present, analyse the public health impact in the state and review studies on disease ecology before assessing challenges and anticipated altered disease dynamics in the face of a rapidly changing North. Rabies is a disease that has been present in Alaska continuously for over 100 years. It is maintained in bats and foxes with the arctic fox likely playing a bigger role in maintaining the virus, although a multi-host system with both red and arctic foxes cannot be excluded. Some modelling evidence suggest a possible decrease in rabies due to a changing climate, although uncertainty is high around these predictions for rabies distribution in Alaska into the future.

Polyglutamine binding protein 1 (PQBP1) inhibits innate immune responses to cytosolic DNA.

Recent studies have highlighted the importance of immune sensing of cytosolic DNA of both pathogen and host origin. We aimed to examine the role of DNA sensors interferon-γ-inducible protein 16 (IFI16) and cyclic GMP-AMP synthase (cGAS) in responding to cytosolic DNA. We show IFI16 and cGAS can synergistically induce IFNb transcriptional activity in response to cytoplasmic DNA. We also examined the role of polyglutamine binding protein 1 (PQBP1), a protein predominantly expressed in lymphoid and myeloid cells that has been shown to lead to type I interferon production in response to retroviral infection. We show PQBP1 associates with cGAS and IFI16 in THP-1 cells. Unexpectedly, knockout of PQBP1 in THP-1 cells causes significantly increased type I IFN production in response to transfected cytosolic nucleic acids or DNA damage, unlike what is seen in response to retroviral infection. Overexpression of PQBP1 in HEK293 T cells impairs IFI16/cGAS-induced IFNb transcriptional activity. In human cancer patients, low expression of PQBP1 is correlated with improved survival, the opposite correlation of that seen with cGAS or IFI16 expression. Our findings suggest that PQBP1 inhibits IFI16/cGAS-induced signaling in response to cytosolic DNA, in contrast to the role of this protein in response to retroviral infection.

A Qualitative Application of Diffusion of Innovations to Adolescents' Perceptions of Long-Acting Reversible Contraception's Attributes.

STUDY OBJECTIVE: Long-acting reversible contraceptive (LARC) methods are the most effective forms of reversible contraception but adolescents often opt for other, less effective methods. In this study we explored how adolescents viewed LARC as an innovation to be adopted or rejected, and how their assessment of innovation attributes affected their decisions about LARC. DESIGN, SETTING, PARTICIPANTS, INTERVENTIONS, AND MAIN OUTCOME MEASURES: Sexually active adolescents between 15 and 22 years old (n = 22) participated in semistructured qualitative interviews. The data underwent a content analysis informed by constructs of the diffusion of innovations and emergent interview themes. RESULTS: Data analysis indicated 3 subgroups of participants on the basis of their inclination to use LARC and the mutability of that position: positive/persuaded (n = 7), negative/low knowledge (n = 10), and negative/adamant (n = 5). Participants' perceptions of the relative advantage, compatibility, complexity, trialability, and observability of LARC cohered around subgroup membership. Perceived complexity entailed in obtaining LARC and fears about LARC were observed across all participants. All participants believed that one has to try LARC to know how it will work for her, personally. This led the positive/persuaded group to be undeterred by others' negative experiences with LARC and the negative/low knowledge and negative/adamant groups to decide LARC was too risky to try. CONCLUSION: Adolescents engage in nuanced evaluations of LARC, weighing competing information about LARC while receiving anecdotal and empirical information about LARC from various valid sources. To reduce the uncertainty about LARC that prohibits trying these methods, adolescents require straightforward information about LARC that directly addresses the advantages of LARC over other methods coupled with candid acknowledgement of the potential disadvantages of LARC.

Investigation of a Canine Parvovirus Outbreak using Next Generation Sequencing.

Canine parvovirus (CPV) outbreaks can have a devastating effect in communities with dense dog populations. The interior region of Alaska experienced a CPV outbreak in the winter of 2016 leading to the further investigation of the virus due to reports of increased morbidity and mortality occurring at dog mushing kennels in the area. Twelve rectal-swab specimens from dogs displaying clinical signs consistent with parvoviral-associated disease were processed using next-generation sequencing (NGS) methodologies by targeting RNA transcripts, and therefore detecting only replicating virus. All twelve specimens demonstrated the presence of the CPV transcriptome, with read depths ranging from 2.2X - 12,381X, genome coverage ranging from 44.8-96.5%, and representation of CPV sequencing reads to those of the metagenome background ranging from 0.0015-6.7%. Using the data generated by NGS, the presence of newly evolved, yet known, strains of both CPV-2a and CPV-2b were identified and grouped geographically. Deep-sequencing data provided additional diagnostic information in terms of investigating novel CPV in this outbreak. NGS data in addition to limited serological data provided strong diagnostic evidence that this outbreak most likely arose from unvaccinated or under-vaccinated canines, not from a novel CPV strain incapable of being neutralized by current vaccination efforts.

Molecular characterization of epizootic hemorrhagic disease virus serotype 1 associated with a 1999 epizootic in white-tailed deer in the eastern United States.

During the autumn of 1999 (mid-August-late September), an outbreak of hemorrhagic disease in white-tailed deer (Odocoileus virginianus) caused by epizootic hemorrhagic disease virus serotype 1 (EHDV-1) occurred along the east coast of the United States from Georgia to New Jersey. An EHDV-1 epizootic of such magnitude had not been described in this region since 1975. To determine the genetic relatedness among the 1999 viruses, as well as among additional EHDV-1 isolates from the eastern and western United States, portions of the S10 and L2 gene segments were sequenced and compared utilizing phylogenetic analyses. Nearly all of the 1999 eastern isolates were identical in nucleotide sequence at one or both loci. Additionally, confirmed cases of EHDV-1 in white-tailed deer occurred in a south (Georgia)-to-north (New Jersey/Virginia) progression over a short period of approximately six weeks. Taken together, these results indicate that this outbreak resulted from the spread of a single viral strain. The phylograms derived from analysis of the entire sample set displayed eastern and western region-specific clusterings (topotypes), as well as an eastern versus western difference in branch lengths, which may reflect the influence of epizootic versus enzootic transmission patterns on viral genetic diversity.

Interdependent Barriers to Providing Adolescents with Long-Acting Reversible Contraception: Qualitative Insights from Providers.

STUDY OBJECTIVE: Long-acting reversible contraceptive (LARC) methods are the most effective form of reversible contraception but are underutilized by adolescents. The purpose of this study was to identify the context-specific barriers to providing adolescents with LARC that are experienced by pediatricians, family medicine physicians, and advanced practice nurses (APNs). DESIGN, SETTING, PARTICIPANTS, AND INTERVENTIONS: Pediatricians, family medicine providers, and APNs (n = 16) who care for adolescents participated in semistructured qualitative interviews. Interview data were analyzed using a modified grounded theory approach. MAIN OUTCOME MEASURES: Pediatricians, family medicine physicians, and APNs self-reported attitudes and practices regarding LARC provision to adolescents. RESULTS: Provider confidence in LARC, patient-centered counseling on LARC, and instrumental supports for LARC all work interdependently either in support of or in opposition to provision of LARC to adolescents. Low provider confidence in LARC for adolescents was characterized by confusion about LARC eligibility criteria and perceptions of LARC insertion as traumatic for adolescents. Patient-centered counseling on LARC required providers' ability to elicit patient priorities, highlight the advantages of LARC over other methods, and address patients' concerns about these methods. Instrumental support for LARC included provider training on LARC, access to and financial support for LARC devices, and opportunity to practice LARC insertion and counseling skills. CONCLUSION: Although none of the identified essential components of LARC provision to adolescents exist in isolation, instrumental support like provider training on LARC and access to LARC devices have the most fundamental effect on the other components and on providers' attitudes and practices regarding LARC for adolescents.