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BackgroundThe magnitude of infant antiretroviral (ARV) exposure from breast milk is unknown MethodsWe measured concentrations of nevirapine, lamivudine, and zidovudine in serum and whole breast milk from human immunodeficiency virus type 1 (HIV-1)–infected women in Botswana receiving ARV treatment and serum from their uninfected, breast-feeding infants ResultsTwenty mother-infant pairs were enrolled. Maternal serum concentrations of nevirapine were high (median, 9534 ng/mL at a median of 4 h after nevirapine ingestion). Median breast-milk concentrations of nevirapine, lamivudine, and zidovudine were 0.67, 3.34, and 3.21 times, respectively, those in maternal serum. The median infant serum concentration of nevirapine was 971 ng/mL, at least 40 times the 50% inhibitory concentration and similar to peak concentrations after a single 2-mg/kg dose of nevirapine. The median infant serum concentration of lamivudine was 28 ng/mL, and the median infant serum concentration of zidovudine was 123 ng/mL, but infants were also receiving zidovudine prophylaxis ConclusionsHIV-1 inhibitory concentrations of nevirapine are achieved in breast-feeding infants of mothers receiving these ARVs, exposing infants to the potential for beneficial and adverse effects of nevirapine ingestion. Further study is needed to understand the impact of maternal ARV treatment on breast-feeding HIV-1 transmission, infant toxicity, and HIV-1 resistance mutations among infected infants

Cities are concentrated areas of CO₂ emissions and have become the foci of policies for mitigation actions. However, atmospheric measurement networks suitable for evaluating urban emissions over time are scarce. Here we present a unique long-term (decadal) record of CO₂ mole fractions from five sites across Utah’s metropolitan Salt Lake Valley. We examine “excess” CO₂ above background conditions resulting from local emissions and meteorological conditions. We ascribe CO₂ trends to changes in emissions, since we did not find longterm trends in atmospheric mixing proxies. Three contrasting CO₂ trends emerged across urban types: negative trends at a residential-industrial site, positive trends at a site surrounded by rapid suburban growth, and relatively constant CO₂ over time at multiple sites in the established, residential, and commercial urban core. Analysis of population within the atmospheric footprints of the different sites reveals approximately equal increases in population influencing the observed CO₂, implying a nonlinear relationship with CO₂ emissions: Population growth in rural areas that experienced suburban development was associated with increasing emissions while population growth in the developed urban core was associated with stable emissions. Four state-of-the-art global-scale emission inventories also have a nonlinear relationship with population density across the city; however, in contrast to our observations, they all have nearly constant emissions over time. Our results indicate that decadal scale changes in urban CO₂ emissions are detectable through monitoring networks and constitute a valuable approach to evaluate emission inventories and studies of urban carbon cycles.

Nearly all microbial communities are dynamic in time. Understanding how temporal dynamics in microbial community structure affect soil biogeochemistry and fertility are key to being able to predict the responses of the soil microbiome to environmental perturbations. Here, we explain the effects of soil spatial structure and relic DNA on the determination of microbial community fluctuations over time. We found that intensive spatial sampling was required to identify temporal effects in microbial communities because of the high degree of spatial heterogeneity in soil and that DNA from nonliving sources masks important temporal patterns. We identified groups of microbes with shared temporal responses and show that these patterns were predictable from changes in soil characteristics. These results provide insight into the environmental preferences and temporal relationships between individual microbial taxa and highlight the importance of considering relic DNA when trying to detect temporal dynamics in belowground communities. Few studies have comprehensively investigated the temporal variability in soil microbial communities despite widespread recognition that the belowground environment is dynamic. In part, this stems from the challenges associated with the high degree of spatial heterogeneity in soil microbial communities and because the presence of relic DNA (DNA from dead cells or secreted extracellular DNA) may dampen temporal signals. Here, we disentangle the relationships among spatial, temporal, and relic DNA effects on prokaryotic and fungal communities in soils collected from contrasting hillslopes in Colorado, USA. We intensively sampled plots on each hillslope over 6 months to discriminate between temporal variability, intraplot spatial heterogeneity, and relic DNA effects on the soil prokaryotic and fungal communities. We show that the intraplot spatial variability in microbial community composition was strong and independent of relic DNA effects and that these spatial patterns persisted throughout the study. When controlling for intraplot spatial variability, we identified significant temporal variability in both plots over the 6-month study. These microbial communities were more dissimilar over time after relic DNA was removed, suggesting that relic DNA hinders the detection of important temporal dynamics in belowground microbial communities. We identified microbial taxa that exhibited shared temporal responses and show that these responses were often predictable from temporal changes in soil conditions. Our findings highlight approaches that can be used to better characterize temporal shifts in soil microbial communities, information that is critical for predicting the environmental preferences of individual soil microbial taxa and identifying linkages between soil microbial community composition and belowground processes. IMPORTANCE Nearly all microbial communities are dynamic in time. Understanding how temporal dynamics in microbial community structure affect soil biogeochemistry and fertility are key to being able to predict the responses of the soil microbiome to environmental perturbations. Here, we explain the effects of soil spatial structure and relic DNA on the determination of microbial community fluctuations over time. We found that intensive spatial sampling was required to identify temporal effects in microbial communities because of the high degree of spatial heterogeneity in soil and that DNA from nonliving sources masks important temporal patterns. We identified groups of microbes with shared temporal responses and show that these patterns were predictable from changes in soil characteristics. These results provide insight into the environmental preferences and temporal relationships between individual microbial taxa and highlight the importance of considering relic DNA when trying to detect temporal dynamics in belowground communities.

Challenges to recruitment of family caregivers exist and are amplified when consent must occur in the context of chaotic healthcare circumstances, such as the transition from hospital to home. The onset of the COVID-19 pandemic during our randomized controlled trial provided an opportunity for a natural experiment exploring and examining different consent processes for caregiver recruitment. The purpose of this publication is to describe different recruitment processes (in-person versus virtual) and compare diversity in recruitment rates in the context of a care recipient’s hospitalization. We found rates of family caregiver recruitment for in-person versus virtual were 28% and 23%, respectively ( p  = 0.01). Differences existed across groups with family caregivers recruited virtually being more likely to be younger, white, have greater than high school education, and not be a spouse or significant other to the care recipient, such as a child. Future work is still needed to identify the modality and timing of family caregiver recruitment to maximize rates and enhance the representativeness of the population for equitable impact.

Background Transitioning care from hospital to home is associated with risks of adverse events and poor continuity of care. These transitions are even more challenging when new approaches to care, such as palliative care, are introduced before discharge. Family caregivers (FCGs) are expected to navigate these transitions while also managing care. In addition to extensive caregiving responsibilities, FCGs often have their own health needs that can inhibit their ability to provide care. Those living in rural areas have even fewer resources to meet their self-care and caregiving needs. The purpose of this study is to test the efficacy and cost-effectiveness of an intervention to improve FCGs’ health and well-being. The intervention uses video visits to teach, guide, and counsel FCGs in rural areas during hospital-to-home transitions. The intervention is based on evidence of transitional and palliative care principles, which are individualized to improve continuity of care, provide caregiver support, enhance knowledge and skills, and attend to caregivers’ health needs. It aims to test whether usual care practices are similar to this technology-enhanced intervention in (1) caregiving skills (e.g., caregiving preparedness, communication with clinicians, and satisfaction with care), (2) FCG health outcomes (e.g., quality of life, burden, coping skills, depression), and (3) cost. We describe the rationale for targeting rural caregivers, the methods for the study and intervention, and the analysis plan to test the intervention’s effect. Methods The study uses a randomized controlled trial design, with FCGs assigned to the control condition or the caregiver intervention by computer-generated lists. The intervention period continues for 8 weeks after care recipients are discharged from the hospital. Data are collected at baseline, 2 weeks, 8 weeks, and 6 months. Time and monetary costs from a societal perspective are captured monthly. Discussion This study addresses 2 independent yet interrelated health care foci—transitional care and palliative care—by testing an intervention to extend palliative care practice and improve transition management for caregivers of seriously ill patients in rural areas. The comprehensive cost assessment will quantify the commitment and financial burden of FCGs. Trial registration ClinicalTrials.gov NCT03339271 . Registered on 13 November 2017. Protocol version: 11.

Background Patients with multiple chronic conditions represent a growing segment for healthcare. The Chronic Care Model (CCM) supports leveraging community programs to support patients and their caregivers overwhelmed by their treatment plans, but this component has lagged behind the adoption of other model elements. Community Care Teams (CCTs) leverage partnerships between healthcare delivery systems and existing community programs to address this deficiency. There remains a gap in moving CCTs from pilot phase to sustainable full-scale programs. Therefore, the purpose of this study was to identify the cognitive and structural needs of clinicians, social workers, and nurse care coordinators to effectively refer appropriate patients to the CCT and the value these stakeholders derived from referring to and receiving feedback from the CCT. We then sought to translate this knowledge into an implementation toolkit to bridge implementation gaps. Methods Our research process was guided by the Assess, Innovate, Develop, Engage, and Devolve (AIDED) implementation science framework. During the Assess process we conducted chart reviews, interviews, and observations and in Innovate and Develop phases, we worked with stakeholders to develop an implementation toolkit. The Engage and Devolve phases disseminate the toolkit through social networks of clinical champions and are ongoing. Results We completed 14 chart reviews, 11 interviews, and 2 observations. From these, facilitators and barriers to CCT referrals and patient re-integration into primary care were identified. These insights informed the development of a toolkit with seven components to address implementation gaps identified by the researchers and stakeholders. Conclusion We identified implementation gaps to sustaining the CCT program, a community-healthcare partnership, and used this information to build an implementation toolkit. We established liaisons with clinical champions to diffuse this information. The AIDED Model, not previously used in high-income countries’ primary care settings, proved adaptable and useful.

Development of Preventive and Treatment Strategies Will Require a More In-Depth Understanding of Host-Pathogen Interactions Host and pathogen factors are known to contribute to NTM PD. Certain body morphotypes and sex (4), structural lung abnormalities, genetic disorders affecting mucociliary clearance, and the use of immunosuppressive drugs, such as steroids and tumor necrosis factor (TNF)-a blockers, are associated with a higher risk of NTM PD (5). Distinct immune pathways may be relevant to NTM infection in cystic fibrosis (CF); the high prevalence of NTM PD among persons with CF (8) may facilitate studies of host factors that vary between those who do and do not have NTM PD. Interestingly, patients receiving TNF-a inhibitors (5) for inflammatory conditions have an elevated risk of NTM infection. M. avium subsp. hominissuis (15) biofilm appears to be important for invasion and infection (15-18). [...]we need a better understanding of biofilms, including their structure, physiology, and how concomitant pathogens interact with each other. Examples from TB (CDC Tuberculosis Trials Consortium) and HIV (NIH/National Institute of Allergy and Infectious Diseases AIDS Clinical Trial Group) clearly demonstrate the importance of clinical trial consortia for providing the necessary expertise, patient population, and data management infrastructure to conduct high-quality trials.

Purpose The purpose of this study was to evaluate engraftment and adverse events with a conditioning and prophylactic regimen intended to achieve high rates of engraftment with minimal graft-versus-host disease (GVHD) in allogeneic transplantation for chronic granulomatous disease in a single center. Methods Forty patients, 37 male, with chronic granulomatous disease were transplanted. Transplant products were matched sibling peripheral blood stem cells (PBSCs) in four and matched unrelated donor (MUD) bone marrow in three, and one patient received mismatched unrelated PBSCs. Thirty-two patients received MUD PBSCs. All patients received a conditioning regimen of busulfan/alemtuzumab (with low-dose total body irradiation for MUD recipients) with sirolimus graft-versus-host disease prophylaxis. Results Engraftment occured in 38/40 recipients (95%). Acute or chronic GVHD occurred in 18 (45%) and 5 (12.5%), respectively, with 6 episodes of grades III–IV and/or steroid refractory GVHD. Overall survival was 33/40 (82.5%) and event-free survival was 30/40 (80%). Successful engraftment was associated with myeloid and NK cell, but not CD3+ chimerism. Myeloid engraftment was greater than 70% in 30/32 recipients at mean follow-up of 3.4 years. Evidence of persistent immunodeficiency was not seen in successful transplants. Attempts to rescue failed or poorly functioning grafts were associated with unacceptable morbidity and mortality. Conclusions A reduced-intensity allogeneic transplant protocol based on alemtuzumab and busulfan with sirolimus GVHD prophylaxis produced high rates of successful engraftment and minimal regimen-related toxicity. Prolonged clinical follow-up has confirmed its efficacy in ameliorating CGD-related disease. Outcomes were not acceptable with donor cell infusion rescue of cause with poor graft function.

There has been a proliferation of initiatives to improve discharge processes and outcomes for the transition from hospital to home and community-based care. Operationalization of these processes has varied widely as hospitals have customized discharge care into innovative roles and functions. This article presents a model for conceptualizing the components of hospital discharge preparation to ensure attention to the full range of processes needed for a comprehensive strategy for hospital discharge.