Preferences for Long-Acting PrEP Products Among Women and Girls: A Quantitative Survey and Discrete Choice Experiment in Eswatini, Kenya, and South Africa.

While oral pre-exposure prophylaxis (PrEP) can substantially reduce HIV risk, there are important barriers to uptake and adherence. We explored preferences for long-acting injectable and implantable PrEP among women and girls in Eswatini, Kenya, and South Africa. We conducted an online quantitative survey and discrete choice experiment (DCE) among adolescent girls (15-17), young women (18-29), and adult women (30-49). Participants completed a survey about their demographics and behavior and a DCE with 5 attributes (format, insertion location, number of insertions, dual-protection, and palpability). We recruited 1236 respondents (Eswatini = 420; Kenya = 350; South Africa = 493) in May 2022. Most participants were sexually active (72%), nearly 29% of whom reported recently engaging in transactional sex. 46% had heard of oral PrEP, but of those, only 16% reported having ever used it. Product format and dual-protection were significant predictors of product choice. Relative to a 2-month injection, participants had 1.76 times the odds (95% CI 1.08-2.04) of choosing a 6-month injectable, and 1.70 the odds (95% CI 1.06-1.92) of choosing a 12-month removable implant. Compared to a single-indication product, respondents had 2.46 times the odds (95% CI 1.04-2.68) of preferring a product also protecting against pregnancy, and 2.81 the odds (95% CI 1.04-3.05) of choosing a product that also protected against STIs. Adolescent girls and women in these countries showed strong preferences for longer-acting PrEP product formats, as well as those offering dual-protection. Introduction of long-acting options could improve PrEP uptake and reduce HIV burdens in east and southern African settings.

Cervical and systemic innate immunity predictors of HIV risk linked to genital herpes acquisition and time from HSV-2 seroconversion.

OBJECTIVES: To examine innate immunity predictors of HIV-1 acquisition as biomarkers of HSV-2 risk and biological basis for epidemiologically established HIV-1 predisposition in HSV-2 infected women. METHODS: We analysed longitudinal samples from HIV-1 negative visits of 1019 women before and after HSV-2 acquisition. We measured cervical and serum biomarkers of inflammation and immune activation previously linked to HIV-1 risk. Protein levels were Box-Cox transformed and ORs for HSV-2 acquisition were calculated based on top quartile or below/above median levels for all HSV-2 negative visits. Bivariate analysis determined the likelihood of HSV-2 acquisition by biomarker levels preceding infection. Linear mixed-effects models evaluated if biomarkers differed by HSV-2 status defined as negative, incident or established infections with an established infection cut-off starting at 6 months. RESULTS: In the cervical compartment, two biomarkers of HIV-1 risk (low SLPI and high BD-2) also predicted HSV-2 acquisition. In addition, HSV-2 acquisition was associated with IL-1ß, IL-6, IL-8, MIP-3α, ICAM-1 and VEGF when below median levels. Systemic immunity predictors of HSV-2 acquisition were high sCD14 and IL-6, with highest odds when concomitantly increased (OR=2.23, 1.49-3.35). Concomitant systemic and mucosal predictors of HSV-2 acquisition risk included (1) serum top quartile sCD14 with cervical low SLPI, VEGF and ICAM-1, or high BD-2; (2) serum high IL-6 with cervical low VEGF and ICAM-1, SLPI, IL-1ß and IL-6; and (3) serum low C reactive protein with cervical high BD-2 (the only combination also predictive of HIV-1 acquisition). Most cervical biomarkers were decreased after HSV-2 acquisition compared with the HSV-2 negative visits, with incident infections associated with a larger number of suppressed cervical biomarkers and lower serum IL-6 levels compared with established infections. CONCLUSIONS: A combination of systemic immunoinflammatory and cervical immunosuppressed states predicts HSV-2 acquisition. A persistently suppressed innate immunity during incident HSV-2 infection may add to the increased HIV-1 susceptibility.

Single-Administration Long-Acting Microarray Patch with Ultrahigh Loading Capacity and Multiple Releases of Thermally Stable Antibodies.

Current antibody (Ab) therapies require development of stable formulations and an optimal delivery system. Here, we present a new strategy to create a single-administration long-lasting Ab-delivery microarray (MA) patch, which can carry high doses of thermally stabilized Abs. The MA fabricated by an additive three-dimensional manufacturing technology can be fully embedded into the skin via a single application to deliver doses of Abs at multiple programmable time points, thus sustaining Ab concentrations in systemic circulation. We developed an MA formulation that stabilized and delivered human immunoglobulins (hIg) in a time-controlled manner while maintaining their structure and functionality. As an example, the b12 Ab─a broadly neutralizing Ab against HIV-1─maintained antiviral activity in vitro after MA manufacturing and heat exposure. Pharmacokinetic studies of MA patch-delivered hIg in rats successfully provided a proof of concept for concurrent and time-delayed Ab delivery. These MA patches codeliver different Abs, providing a tool for expanded protection against viral infections or combination HIV therapy and prevention.

The potential impact of implementation of expanded carrier screening on pediatric patient diagnoses: A retrospective chart review of patients who receive care in an outpatient genetics clinic in the northeast.

The use of expanded carrier screening (ECS) to assess reproductive risk for autosomal recessive (AR) or X-linked recessive (XLR) conditions has been increasingly integrated into obstetrical care. The aim of this study was to determine what proportion of pediatric patients seen by a medical genetics practice could have had their diagnosis predicted if the parent(s) had undergone currently available ECS at the time of data collection in 2021. A retrospective chart review of patients seen for a medical genetic evaluation at a large academic institution was performed from June 1, 2017, through June 1, 2020. At this institution, 8% of patients were diagnosed with an AR or XLR condition. Of these patients, 61% of the diagnoses could have been predicted in advance if the parent(s) had undergone ECS via the panel referenced in this study. The results of this study highlight the broad range of conditions currently seen in a clinical setting that could be identified as a risk prior to or during pregnancy via ECS. In the prenatal setting, ascertainment of reproductive risk via ECS enables prospective parents to undertake interventions such as prenatal and preimplantation genetic diagnosis. For parents who decline reproductive risk-reducing measures, knowledge about neonatal risk allows for prompt confirmatory testing. In the pediatric setting, the option of early and focused testing can benefit affected individuals and their families.

HIV Pre-exposure Prophylaxis Implant Stated Preferences and Priorities: Results of a Discrete Choice Experiment Among Women and Adolescent Girls in Gauteng Province, South Africa.

For adolescent girls (AG) and young women (YW), adherence barriers may limit the effectiveness of daily oral HIV pre-exposure prophylaxis (PrEP). Due to its low-burden and long-lasting product attributes, PrEP implants could remove some of the critical adherence barriers of oral PrEP products for individuals at risk of HIV. To explore stated preferences for a long-acting PrEP implant, we conducted a quantitative survey and discrete choice experiment with AG (ages 15-17), YW (18-34), and female sex workers (FSW; ≥ 18) in Gauteng Province, South Africa. We completed 600 quantitative surveys across the three subgroups of women. Respondents stated preference for an implant that provided longer HIV protection (24 months versus 6 months) and required a single insertion. They stated that they preferred a biodegradable implant that could be removed within 1 month of insertion. Respondents had no preference for a particular insertion location. Overall, 78% of respondents said they would be likely (33%) or very likely (45%) to use a PrEP implant were one available, with the majority (82%) stating preference for a product that would provide dual protection against HIV and unintended pregnancies. To reduce their risk of HIV, AG, YW, and FSW in our survey reported a strong willingness to use long-acting, highly-effective, dissolvable PrEP implants.

RESUMEN: Las niñas adolescentes (NA) y mujeres jóvenes (MJ), pueden enfrentar barreras de adherencia que limitan la eficacia de la profilaxis oral previa a la exposición al VIH (PrEP). Ya que el implante de PrEP es un producto que requiere de poca intervención de la usuaria y es de larga duración, podría eliminar algunas de las barreras de adherencia más importantes en el uso de los productos orales de PrEP para aquellas personas en riesgo de infección de VIH. Para explorar las preferencias declaradas en cuanto al implante de PrEP de acción prolongada, llevamos a cabo una encuesta cuantitativa y un experimento de elección discreta (DCE) con NA (de 15 a 17 años), MJ (de 18 a 34 años) y mujeres trabajadoras del sexo (MTS; ≥ 18 años) en la provincia de Gauteng, Sudáfrica. Administramos 600 encuestas cuantitativas en los tres subgrupos de mujeres. Los resultados indican la preferencia por un implante que proporciona una protección contra el VIH más prolongada (24 meses a comparación con 6 meses) y que requiere de una única inserción. Las participantes afirmaron que prefieren un implante biodegradable que puede retirarse un mes después de su inserción. Las participantes no tenían preferencia por un sitio específico de inserción. En general, el 78% de las participantes indicaron que probablemente (33%) o muy probablemente (45%) utilizarían un implante de PrEP si estuviera disponible, y la mayoría (82%) manifestó su preferencia por un producto que proporcionaba una doble protección contra el VIH y el embarazo no deseado. Para reducir el riesgo de contraer el VIH, las NA, MJ y MTS participantes se mostraron muy dispuestas a utilizar implantes de PrEP de larga duración, altamente eficaces y disolubles.

Optimizing the integration of family caregivers in the delivery of person-centered care: evaluation of an educational program for the healthcare workforce.

BACKGROUND: While family caregivers provide 70-90% of care for people living in the community and assist with 10-30% of the care in congregate living, most healthcare providers do not meaningfully involve family caregivers as partners in care. Recent research recommends that the healthcare workforce receive competency-based education to identify, assess, support, and partner with family caregivers across the care trajectory. OBJECTIVE: This paper reports a mixed-methods evaluation of a person-centered competency-based education program on Caregiver-Centered Care for the healthcare workforce. METHODS: This foundational education was designed for all healthcare providers and trainees who work with family caregivers and is offered free online (caregivercare.ca). Healthcare providers from five healthcare settings (primary, acute, home, supportive living, long-term care) and trainees in medicine, nursing, and allied health were recruited via email and social media. We used the Kirkpatrick-Barr health workforce training evaluation framework to evaluate the education program, measuring various healthcare providers' learner satisfaction with the content (Level 1), pre-post changes in knowledge and confidence when working with family caregivers (Level 2), and changes in behaviors in practice (Level 3). RESULTS: Participants were primarily healthcare employees (68.9%) and trainees (21.7%) and represented 5 healthcare settings. Evaluation of the first 161 learners completing the program indicated that on a 5-point Likert scale, the majority were satisfied with the overall quality of the education (Mean(M) = 4.69; SD = .60). Paired T-tests indicated that out of a score of 50, post-education changes in knowledge and confidence to work with family caregivers was significantly higher than pre-education scores (pre M = 38.90, SD = 6.90; post M = 46.60, SD = 4.10; t(150) = - 16.75, p < .0001). Qualitative results derived from open responses echoed the quantitative findings in satisfaction with the education delivery as well as improvements in learners' knowledge and confidence. CONCLUSION: Health workforce education to provide person-centered care to all family caregivers is an innovative approach to addressing the current inconsistent system of supports for family caregivers. The education program evaluated here was effective at increasing self-reported knowledge and confidence to work with family caregivers.

Tailored, Community-Based Programs for People Living With Dementia and Their Family Caregiver.

People living with dementia (PLWD) have voiced a desire to remain in their home environment as long as possible; unfortunately, there is limited integrated person-and family-centered community support. To examine the need for tailored supports for PLWD and their family caregivers (caregiving dyad), a meeting was conducted in Spring 2020. Thirty key provincial stakeholders with diversity in geographic location, employer and/or organization, range of roles, and family representatives participated in the meeting. Stakeholders identified a series of gaps, including: (a) systemic gaps; (b) gaps between communities of practice; (c) underserved populations; (d) program content and delivery gaps; and (e) PLWD and family caregiver support gaps. With input from stakeholders, we highlighted the need for consistent resources for the caregiving dyad that are flexible, timely, and accessible, which are embedded in the community and led by qualified and trained staff. [Journal of Gerontological Nursing, 48(4), 26-32.].

Congenital Nephrotic Syndrome of the Finnish Type in a Dominican Newborn: An Overview and Case Report.

Congenital nephrotic syndrome of the Finnish type (CNS-FT) is a rare genetic condition that causes massive proteinuria, hypoproteinemia, hypercholesterolemia, and edema that progresses to end-stage renal disease. Symptoms may manifest in utero as fetal hydrops or during the first few days to months of life. This article shares the case of a Dominican infant who presented with CNS-FT. It provides a comprehensive overview of CNS-FT including the underlying genetic cause, prenatal and postnatal diagnostic testing options, and treatment recommendations. It walks the reader through the diagnostic and initial and longer-term management of this infant and provides patient outcome at 10 months of age.

Decreasing Chlamydial Reinfections in a Female Urban Population.

BACKGROUND: Chlamydia is the most reported bacterial sexually transmitted infection (STI). The rates of chlamydia rose by 19% between 2011 and 2018. The STI National Strategic Plan (2021-2025), encourages coordinated solutions to address STIs and reduce disparities in disadvantaged populations. METHODS: We implemented institutional policy changes, clinical decision support, including a Best Practice Advisory, and defaulted SmartSet with provider and patient education for women's health clinics at a large county health system. The advisory prompted providers to follow best practices when treating Chlamydia trachomatis infections. New C. trachomatis diagnosis cohorts were compared preintervention and postintervention for 6-month reinfection rates and patient and expedited partner treatment (EPT) practices. RESULTS: Five hundred and nineteen women were included in the final analysis. Six-month chlamydia reinfection was lower in the postintervention cohort after adjusting for age (12.3% [26/211] vs 6.5% [20/308], P = 0.02). There was an increase in directly observed therapy of primary patients (17.5% [37/211] vs 77.3% [238/308], P < 0.001), an increase in EPT prescriptions written (4.3% [9/211] vs 79.5% [245/308], P < 0.0001), and a decrease of partners referred out for treatment (61.6% [130/211] vs 5.2% [16/308], P < 0.001) when compared with the control group. The majority of EPT was patient-delivered partner therapy postintervention (3.3% [7/211] vs 69.2% [213/308], P < 0.001). CONCLUSIONS: A multifaceted, streamlined approach was effective in changing provider practices in the treatment of C. trachomatis. Increased rates of directly observed therapy for primary patient treatment and increased rates of patient-delivered partner therapy were observed postimplementation in addition to lower 6-month reinfection rates in a public women's health clinic setting.

Person-centered care for family caregivers of people living with dementia: Co-designing an education program for the healthcare workforce.

BACKGROUND: Recent research recommends the healthcare workforce receive competency-based education to identify, assess, support and partner with family-caregivers [FCGs} across the care trajectory.[1 2] Although the risk of FCG anxiety, burden, and loneliness to FCG's wellbeing is widely documented, typically education has been targeted towards FCG's to increase their care skills rather to educate healthcare providers to support FCG's caregiving and wellbeing.[3] OBJECTIVES: We will present the co-design process used to create a competency-based education program for the healthcare workforce that ensures a person-centered focus on FCGs and introduce our Health Workforce Caregiver-Centered Care Education focused on dementia. Co-design is the act of creating with stakeholders to ensure the results meet their needs and are usable. PROJECT DESCRIPTION: We began by coining the concept "caregiver-centered care," defining it as: a collaborative working relationship between families and healthcare providers aimed at supporting FCGs in their caregiving role, decisions about services, care management, and advocacy [4 5] . From this definition, and working with multi-level interdisciplinary stakeholders we designed[6] and validated[7] a Caregiver-Centered Care Competency Framework in a Modified Delphi Process. Stakeholders (n= 101) including FCGs, health providers, policy makers, community organizations, research team, script writer, and educational designers then used effective practices for dementia education for the health workforce [8-11] to co-design the first or 'foundational' level of a Caregiver Centered Care education program. RESULTS: Teaching and learning resources include six competency-aligned educational modules with videos and interactive exercises that encourage reflection. With the COVID-19 pandemic, we moved the education online (caregivercare.ca). In the first two months online, November 9, 2020-January 9, 2021, 352 healthcare providers completed the education. To date, learners' qualitative evaluations have been positive, "Very good information for professionals working with caregivers; especially relevant to homecare, geriatricians, allied health, and others working within the Seniors' Health realm. Engaging format that really evokes empathy for caregivers." DISCUSSION: We continue to use mixed methods to evaluate the Caregiver-Centered Care Education, for acceptability and effectiveness, in five care contexts (primary, acute, home, supportive living, long-term care). CONCLUSION: We expect that our education will support caregiver-centered care in all settings providing dementia-related care.

Seminal exosomes and HIV-1 transmission.

Exosomes are endosomal-derived membrane-confined nanovesicles secreted by many (if not all) cell types and isolated from every human bodily fluid examined up to now including plasma, semen, vaginal secretions and breast milk. Exosomes are thought to represent a new player in cell-to-cell communication pathways and immune regulation, and be involved in many physiological and pathological processes. Susceptibility to HIV-1 infection can be impacted by exosomes, while HIV-1 pathogenesis can alter exosomal function and composition. Exosomes isolated from semen and vaginal fluid of healthy individuals can inhibit HIV-1 infection and/or potently block viral transfer in vitro. However, the role of exosomes in HIV-1 transmission and progression is not fully understood yet and some studies show conflicting results, mainly for exosomes isolated from plasma and breast milk. Determining the composition of exosomes from infected donors and studying their interaction with HIV-1 in vitro compared to exosomes isolated from uninfected donors will provide insights into the role exosomes play in HIV-1 transmission during sexual intercourse and breastfeeding.

Respirometric reserve capacity of cumulus cell mitochondria correlates with oocyte maturity.

PURPOSE: Oocyte competence is critical in success of assisted reproduction. Metabolic signaling between oocyte and cumulus cells within the cumulus-oocyte complex procure oocyte development. This study evaluated the relationship between respirometric activity of cumulus cells and maturity of corresponding oocytes. METHODS: In prospective cohort study, 20 women of age 28-42 undergoing IVF procedure were involved. To evaluate oocyte maturity, the cumulus cells from individual oocytes were assessed flow cytometrically by double labeling of cells with mitochondria specific dyes. The respirometric stress analysis using ATPase inhibitor oligomycin was applied to assess mitochondria metabolic abnormalities. RESULTS: The cumulus cells from each of 327 oocytes were analyzed. The respirometric index of cumulus cells (O'R) strongly correlates with maternal ovarian reserve, showing to be higher in patients with higher AMH (p < 0.0017). Cumulus cells from immature oocytes had severe mitochondria deficiency, i.e., low O'R, than those from mature oocytes (p < 0.02). No significant difference in respirometric capacity was found between cumulus cells associated with good vs poor-quality embryos. CONCLUSIONS: The oocyte maturity is potentially related to the mitochondria activity of cumulus cells.

Determination of renal function and injury using near-infrared fluorimetry in experimental cardiorenal syndrome.

Cardiorenal syndrome type 1 causes acute kidney injury but is poorly understood; animal models and diagnostic aids are lacking. Robust noninvasive measurements of glomerular filtration rate are required for injury models and clinical use. Several have been described but are untested in translational models and suffer from biologic interference. We developed a mouse model of cardiorenal syndrome and tested the novel near-infrared fluorophore ZW800-1 to assess renal and cardiac function. We performed murine cardiac arrest and cardiopulmonary resuscitation followed by transthoracic echocardiography, 2 and 24 h later. Transcutaneous fluorescence of ZW800-1 bolus dispersion and clearance was assessed with whole animal imaging and compared with glomerular filtration rate (GFR; inulin clearance), tubular cell death (using unbiased stereology), and serum creatinine. Correlation, Bland-Altman, and polar analyses were used to compare GFR with ZW800-1 clearance. Cardiac arrest and cardiopulmonary resuscitation caused reversible cardiac failure, halving fractional shortening of the left ventricle (n = 12, P = 0.03). Acute kidney injury resulted with near-zero GFR and sixfold increase in serum creatinine 24 h later (n = 16, P < 0.01). ZW800-1 biodistribution and clearance were exclusively renal. ZW800-1 t1/2 and clearance correlated with GFR (r = 0.92, n = 31, P < 0.0001). ZW800-1 fluorescence was reduced in cardiac arrest, and cardiopulmonary resuscitation-treated mice compared with sham animals 810 s after injection (P < 0.01) and bolus time-dispersion curves demonstrated that ZW800-1 fluorescence dispersion correlated with left ventricular function (r = 0.74, P < 0.01). Cardiac arrest and cardiopulmonary resuscitation lead to experimental cardiorenal syndrome type 1. ZW800-1, a small near-infrared fluorophore being developed for clinical intraoperative imaging, is favorable for evaluating cardiac and renal function noninvasively.

Innovative Information Technology-Powered Population Health Care Management Improves Outcomes and Reduces Hospital Readmissions and Emergency Department Visits.

BACKGROUND: Patients with chronic conditions are often the most frequent users of health care. Moreover, adapting to developments in one's illness, understanding how to self-manage a chronic illness, and sharing information between primary care and specialty providers, can be a full-time job for someone with a chronic illness. In response to these challenges, Christiana Care Health System (Wilmington, Delaware) developed Care Link, an information technology (IT)-enhanced care management support to enable populations of patients to achieve better clinical outcomes at lower cost. METHODS: In 2012 Christiana Care received a grant to design a generalizable, scalable, and replicable IT-driven care model that would integrate disparate clinical and registry data generated from routine care to support longitudinal care management for patients with ischemic heart disease. The single-disease care management program was expanded beginning in mid-2015 to serve risk-based models for many diseases and chronic conditions. RESULTS: More than 8,600 patients in several surgical and medical populations, including joint replacement, cervical spine surgery, and congestive heart failure, have been supported by Care Link. For example, preoperative assessment of patients with elective joint replacement to predict post-acute care needs led to an increase in the volume of patients discharged to home with self-care or with home health care by 30%-from 61% to 80%. CONCLUSION: Care Link IT functions can be replicated to address the unique longitudinal care needs of any population. Care Link's next steps are to continue to increase the number of patients served throughout the region and to expand the scope of care management programming.

Translating Knowledge: Promoting Health Through Intergenerational Community Arts Programming.

INTRODUCTION: Intergenerational programs have been touted to address the generation gaps and isolation of older adults. Mutual contact alone has produced mixed results, but attention to the intergenerational program content demonstrates well-being benefits. This practice-based article examines the benefits of creating and performing ensemble-created plays to older adults' and university students' well-being and the key processes that promote well-being. METHOD: This community participatory research project involved older adults as researchers as well as research subjects. Individual semistructured interviews were conducted by two trained interviewers with older adults (n = 15) and university students (n = 17). RESULTS: Professional dramaturgical processes of storytelling, reminiscence, and playfulness were key elements in participants' generative learning. They augmented older adults' and university students' ability to understand their situations and try innovative solutions. Skills such as openness, flexibility, and adaptation transferred into students' and older adults' daily lives. CONCLUSION: Participating in this intergenerational theatre group reduced ageism and improved intergenerational relationships. It increased older adults' and university students' well-being by building social networks, confidence, and self-esteem and developed a sense of social justice, empathy, and support for others.

Bleeding 'downhill' esophageal varices associated with benign superior vena cava obstruction: case report and literature review.

BACKGROUND: Proximal or 'downhill' esophageal varices are a rare cause of upper gastrointestinal hemorrhage. Unlike the much more common distal esophageal varices, which are most commonly a result of portal hypertension, downhill esophageal varices result from vascular obstruction of the superior vena cava (SVC). While SVC obstruction is most commonly secondary to malignant causes, our review of the literature suggests that benign causes of SVC obstruction are the most common cause actual bleeding from downhill varices. Given the alternative pathophysiology of downhill varices, they require a unique approach to management. Variceal band ligation may be used to temporize acute variceal bleeding, and should be applied on the proximal end of the varix. Relief of the underlying SVC obstruction is the cornerstone of definitive treatment of downhill varices. CASE PRESENTATION: A young woman with a benign superior vena cava stenosis due to a tunneled internal jugular vein dialysis catheter presented with hematemesis and melena. Urgent upper endoscopy revealed multiple 'downhill' esophageal varices with stigmata of recent hemorrhage. As there was no active bleeding, no endoscopic intervention was performed. CT angiography demonstrated stenosis of the SVC surrounding the distal tip of her indwelling hemodialysis catheter. The patient underwent balloon angioplasty of the stenotic SVC segment with resolution of her bleeding and clinical stabilization. CONCLUSION: Downhill esophageal varices are a distinct entity from the more common distal esophageal varices. Endoscopic therapies have a role in temporizing active variceal bleeding, but relief of the underlying SVC obstruction is the cornerstone of treatment and should be pursued as rapidly as possible. It is unknown why benign, as opposed to malignant, causes of SVC obstruction result in bleeding from downhill varices at such a high rate, despite being a less common etiology of SVC obstruction.

Barriers to Knowledge Translation Regarding the Use of Probiotics as a Risk-Reduction Strategy for Necrotizing Enterocolitis.

BACKGROUND: Increasingly, evidence supports enteral probiotics are an important risk-reduction strategy for necrotizing enterocolitis (NEC) among very low birth-weight and extremely low birth-weight preterm infants. Yet, the majority of providers remain reluctant to implement practice changes. PURPOSE: The aim of this study was to better understand the discrepancy between the available evidence and clinical practice regarding the use of probiotics and other NEC prevention strategies in New Jersey. METHODS: Using an exploratory descriptive design, a multimodal interprofessional survey was developed and executed to elicit intensive care nursery provider knowledge, views, and current practice. RESULTS: Although the sample size was small (N = 29), approximately one-half of respondents familiar with the literature rated the quality of the evidence regarding probiotics as "above average" to "excellent." These respondents were "very likely" to "extremely likely" to recommend probiotics as an NEC prevention strategy; however, none actually prescribed this intervention. The most important reason respondents did not prescribe probiotics was the focus on providing exclusive maternal and donor breast milk feedings. Other confounding factors included provision of oral colostrum care, standardized feeding protocols, and withholding feedings during blood transfusion. IMPLICATIONS FOR PRACTICE: Study results suggested that some providers (primarily nurses) were not familiar with probiotic literature, which may contribute to deficits in knowledge translation to practice. IMPLICATIONS FOR RESEARCH: Areas for future study include identifying improved mechanisms for knowledge dissemination, recognizing and addressing barriers and facilitators to knowledge translation, and understanding how probiotics fit and/or contrast with other NEC risk-reduction strategies in the research and clinical settings.

An Extremely Rare Disorder of Somatic Mosaicism: CLOVES Syndrome.

BACKGROUND: CLOVES (Congenital Lipomatous Overgrowth, Vascular malformations, Epidermal nevi Scoliosis, Skeletal, Spinal) syndrome is an extremely rare, complex, non-Mendelian genetic condition with clinical overlap to several other overgrowth syndromes. PURPOSE: This article shares an interesting case report of the prenatal to postnatal diagnostic course for an infant with this condition. CASE FINDINGS/RESULTS: It shares prenatal and postnatal images and imaging studies which helped confirm the diagnosis. In addition, the unusual genetic causes of the condition as well as recommended patient-specific management and treatment therapies for this complex condition are discussed. IMPLICATIONS FOR PRACTICE: Practice implications include honing of physical examination skills and facilitating diagnostic testing required to differentiate CLOVES syndrome from similar conditions. Providers must provide ongoing information and ensure support to families during this diagnostic process. In addition, the majority of care will likely be provided beyond the newborn period. As such, providers must facilitate outpatient follow-up with a number of consultants after hospital discharge. IMPLICATIONS FOR RESEARCH: Because CLOVES syndrome is so rare, research in this area is limited to a small number of field experts. These experts, however, are well-suited to continue research surrounding disease management and lesion treatment (whether surgical, procedural, or medical) moving forward.

Estrogen administered after cardiac arrest and cardiopulmonary resuscitation ameliorates acute kidney injury in a sex- and age-specific manner.

INTRODUCTION: There is a sex difference in the risk of ischemic acute kidney injury (AKI), and estrogen mediates the protective effect of female sex. We previously demonstrated that preprocedural chronic restoration of physiologic estrogen to ovariectomized female mice ameliorated AKI after cardiac arrest and cardiopulmonary resuscitation (CA/CPR). In the present study, we hypothesized that male mice and aged female mice would benefit from estrogen administration after CA/CPR. We tested the effect of estrogen in a clinically relevant manner by administrating it after CA/CPR. METHODS: CA/CPR was performed in young (10-15 weeks), middle-aged (43-48 weeks), and aged (78-87 weeks) C57BL/6 male and female mice. Mice received intravenous 17ß-estradiol or vehicle 15 min after resuscitation. Serum chemistries and unbiased stereological assessment of renal injury were completed 24 h after CA. Regional renal cortical blood flow was measured by a laser Doppler, and renal levels of estrogen receptor alpha (ERα) and G protein-coupled estrogen receptor (GPER) were evaluated with immunoblotting. RESULTS: Post-arrest estrogen administration reduced injury in young males without significant changes in renal blood flow (percentage reduction compared with vehicle: serum urea nitrogen, 30 %; serum creatinine (sCr), 41 %; volume of necrotic tubules (VNT), 31 %; P < 0.05). In contrast, estrogen did not affect any outcomes in young females. In aged mice, estrogen significantly reduced sCr (80 %) and VNT (73 %) in males and VNT (51 %) in females. Serum estrogen levels in aged female mice after CA/CPR were the same as levels in male mice. With age, renal ERα was upregulated in females. CONCLUSIONS: Estrogen administration after resuscitation from CA ameliorates renal injury in young males and aged mice in both sexes. Because injury was small, young females were not affected. The protective effect of exogenous estrogen may be detectable with loss of endogenous estrogen in aged females and could be mediated by differences in renal ERs. Post-arrest estrogen administration is renoprotective in a sex- and age-dependent manner.

Getting on with the rest of your life following stroke: a randomized trial of a complex intervention aimed at enhancing life participation post stroke.

OBJECTIVE: To enhance participation post stroke through a structured, community-based program. DESIGN: A controlled trial with random allocation to immediate or four-month delayed entry. SETTING: Eleven community sites in seven Canadian cities. SUBJECTS: Community dwelling persons within five years of stroke onset, cognitively intact, able to toilet independently. INTERVENTIONS: Evidence-based program delivered in three 12-week sessions including exercise and project-based activities, done as individuals and in groups. MAIN MEASURES: Hours spent per week in meaningful activities outside of the home and Reintegration to Normal Living Index; Stroke-Specific Geriatric Depression Scale, Apathy Scale, gait speed, EuroQuol EQ-5D, and Preference-Based Stroke Index. All measures were transformed to a scale from 0 to 100. Assessments prior to randomization, after the first session at three months, six months, 12 months, and 15 months. RESULTS: A total of 186 persons were randomized. The between-group analysis showed no disadvantage to waiting and so groups were combined and a within-person analysis was carried out at three time points. There were statistically significant increases in all study outcomes on average over all persons. Over 45% of people met or exceeded the pre-specified target of a three hour per week increase in meaningful activity and this most often took a full year of intervention to achieve. Greatest gains were in satisfaction with community integration (mean 4.78; 95% CI: 2.01 to 7.55) and stroke-specific health-related quality of life (mean 4.14; 95% CI: 2.31 to 5.97). CONCLUSIONS: Community-based programs targeting participation are feasible and effective, but stroke survivors require time to achieve meaningful gains.