Allegheny County Pennsylvania has the second highest HIV prevalence in the state. In the county, racial and ethnic minorities are disproportionately impacted by HIV.
In responses to HIV epidemic in ...the Allegheny County, AIDS Free Pittsburgh was created with the goals of reducing new HIV infections by 75% and declaring Allegheny County AIDS free (no new AIDS cases) by 2020. AIDS Free Pittsburgh uses a collective impact framework in which partners pledge to collect and share data uniformly across health systems, to co-organize events for provider and community education, and to enhance access to quality healthcare by developing resources and referral networks.
Since its inception, there has been nearly a 43% decrease in new HIV cases, a 23% decrease in new AIDS cases, and other promising trends related to HIV testing, preexposure prophylaxis, linkage to care, and viral load suppression for people living with HIV in Allegheny County.
This article provides a detailed description of the community-level project, the activities conducted by collective group, a summary of project outcomes, and lessons learned for replicating this project in other midsized, mid-HIV incidence jurisdictions.
Regression from prediabetes to normal glucose regulation (NGR) was associated with reduced incidence of diabetes by 56% over 10 years in participants in the Diabetes Prevention Program Outcomes Study ...(DPPOS). In an observational analysis, we examined whether regression to NGR also reduced risk for microvascular disease (MVD).
Generalized estimating equations were used to examine the prevalence of aggregate MVD at DPPOS year 11 in people who regressed to NGR at least once (vs. never) during the Diabetes Prevention Program (DPP). Logistic regression assessed the relationship of NGR with retinopathy, nephropathy, and neuropathy, individually. Generalized additive models fit smoothing splines to describe the relationship between average A1C during follow-up and MVD (and its subtypes) at the end of follow-up.
Regression to NGR was associated with lower prevalence of aggregate MVD in models adjusted for age, sex, race/ethnicity, baseline A1C, and treatment arm (odds ratio OR 0.78, 95% CI 0.65-0.78,
= 0.011). However, this association was lost in models that included average A1C during follow-up (OR 0.95, 95% CI 0.78-1.16,
= 0.63) or diabetes status at the end of follow-up (OR 0.92, 95% CI 0.75-1.12,
= 0.40). Similar results were observed in examination of the association between regression to NGR and prevalence of nephropathy and retinopathy, individually. Risk for aggregate MVD, nephropathy, and retinopathy increased across the A1C range.
Regression to NGR is associated with a lower prevalence of aggregate MVD, nephropathy, and retinopathy, primarily due to lower glycemic exposure over time. Differential risk for the MVD subtypes begins in the prediabetes A1C range.
-acetylcysteine (NAC) is a novel therapeutic agent with multiple mechanisms of action in the central nervous system and a favourable side effect profile. Clinical evidence indicates that adjunctive ...NAC may reduce the severity of depressive symptoms in individuals with major depressive disorder (MDD).
A 12-week randomised controlled trial of 2,000 mg/day adjunctive NAC for MDD found no significant improvement at the primary endpoint (week 12) but did see improvements at the post-discontinuation interview (week 16). Within the context of patient-centered treatment, mixed-methods qualitative analysis was also included to explore factors that may determine individual responses to adjunctive NAC treatment. These data were drawn, under blinded conditions, from clinician notes recorded in the case report form. Using the DSM-5 symptom profile for MDD as the initial framework, themes were developed and explored. Frequencies were compared between placebo and NAC groups.
Per protocol analysis of individual themes across the six interviews revealed group differences in favour of NAC for overall depressive affect, optimism, relationships and reduced functional impairment.
This study provides further evidence for the utility of the mixed methods approach complimenting the primary findings using traditional quantitative analyses, as well as being able to capture additional, often more subtle, evidence of individual symptom-level change that reflects improvement in functional abilities in response to NAC supplementation. The use of mixed methods to explore outcomes from psychiatric studies should be considered in future to work towards improved patient-centred care and both confirm quantitative findings and generate novel hypotheses.
Background and purpose
Mutations in the glucocerebrosidase (GBA) gene are known to be a risk factor for Parkinson's disease (PD). Data on clinicopathological correlation are limited. The purpose of ...this study was to determine the clinicopathological findings that might distinguish PD cases with and without mutations in the GBA gene.
Methods
Data from the Arizona Study of Aging and Neurodegenerative Disorders were used to identify autopsied PD cases that did or did not have a GBA gene mutation. Clinical and neuropathological data were compared.
Results
Twelve PD cases had a GBA mutation and 102 did not. The GBA mutation cases died younger (76 vs. 81 years of age) but there was no difference in disease duration or clinical examination findings. No neuropathological differences were found in total or regional semi‐quantitative scores for Lewy‐type synucleinopathy, senile plaques, neurofibrillary tangles, white matter rarefaction or cerebral amyloid angiopathy scores.
Conclusions
In longitudinally assessed, autopsied PD cases, those with GBA mutations had a younger age at death but there was no evidence for clinical or neuropathological differences compared to cases without GBA mutations. Due to the small GBA group size, small differences cannot be excluded.
Experimental and clinical data show that the oral bisphosphonate clodronate (Bonefos) can inhibit tumor-induced osteoclastic bone resorption. This randomized, double-blind, placebo-controlled, ...multicenter trial was designed to determine if the addition of oral clodronate to standard treatment for primary operable breast cancer could reduce the subsequent occurrence of bone metastases and thereby improve overall survival.
1,069 patients with primary operable stage I-III breast cancer were randomized to receive oral clodronate (1,600 mg/day) or placebo for 2 years, in conjunction with standard treatment for primary breast cancer including surgery, radiotherapy, adjuvant chemotherapy, and/or tamoxifen. All patients were assessed for bone metastases at two and five years and additionally when clinically indicated. Survival status was determined as of the close of the study on 30 June 2000 with a median follow up of 5.6 years. The treatment arms were compared using the unstratified log-rank test. Hazard ratios (HRs) with 95% confidence intervals were calculated.
Oral clodronate significantly reduced the risk of bone metastases in all patients over the 5 year study period (51 patients versus 73 patients with placebo; HR = 0.692, P = 0.043); the difference was also statistically significant over the 2 year medication period (19 patients versus 35 patients with placebo; HR = 0.546, P = 0.031). These differences were most pronounced in patients with stage II/III disease (39 patients versus 64 patients with placebo, HR = 0.592, P = 0.009 over 5 years; 16 patients versus 32 patients with placebo, HR= 0.496, P = 0.020 over 2 years). Survival data also favoured the clodronate arm (HR for all patients = 0.768, P = 0.048; HR for stage II/III disease = 0.743, P = 0.041), although this was not significant due to multiple analyses. Oral clodronate was well tolerated, with mild-to-moderate diarrhoea being the most frequently reported adverse event.
These results confirm that oral clodronate will significantly improve the 5 year bone relapse free survival when used as a supplementary adjuvant treatment for patients receiving standard treatment for primary operable breast cancer.
Despite rapid technical progress and demonstrable effectiveness for some types of diagnosis and therapy, much remains to be learned about clinical genome and exome sequencing (CGES) and its role ...within the practice of medicine. The Clinical Sequencing Exploratory Research (CSER) consortium includes 18 extramural research projects, one National Human Genome Research Institute (NHGRI) intramural project, and a coordinating center funded by the NHGRI and National Cancer Institute. The consortium is exploring analytic and clinical validity and utility, as well as the ethical, legal, and social implications of sequencing via multidisciplinary approaches; it has thus far recruited 5,577 participants across a spectrum of symptomatic and healthy children and adults by utilizing both germline and cancer sequencing. The CSER consortium is analyzing data and creating publically available procedures and tools related to participant preferences and consent, variant classification, disclosure and management of primary and secondary findings, health outcomes, and integration with electronic health records. Future research directions will refine measures of clinical utility of CGES in both germline and somatic testing, evaluate the use of CGES for screening in healthy individuals, explore the penetrance of pathogenic variants through extensive phenotyping, reduce discordances in public databases of genes and variants, examine social and ethnic disparities in the provision of genomics services, explore regulatory issues, and estimate the value and downstream costs of sequencing. The CSER consortium has established a shared community of research sites by using diverse approaches to pursue the evidence-based development of best practices in genomic medicine.
Most reported cases of coronavirus disease 2019 (COVID-19) in children aged <18 years appear to be asymptomatic or mild (1). Less is known about severe COVID-19 illness requiring hospitalization in ...children. During March 1-July 25, 2020, 576 pediatric COVID-19 cases were reported to the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET), a population-based surveillance system that collects data on laboratory-confirmed COVID-19-associated hospitalizations in 14 states (2,3). Based on these data, the cumulative COVID-19-associated hospitalization rate among children aged <18 years during March 1-July 25, 2020, was 8.0 per 100,000 population, with the highest rate among children aged <2 years (24.8). During March 21-July 25, weekly hospitalization rates steadily increased among children (from 0.1 to 0.4 per 100,000, with a weekly high of 0.7 per 100,000). Overall, Hispanic or Latino (Hispanic) and non-Hispanic black (black) children had higher cumulative rates of COVID-19-associated hospitalizations (16.4 and 10.5 per 100,000, respectively) than did non-Hispanic white (white) children (2.1). Among 208 (36.1%) hospitalized children with complete medical chart reviews, 69 (33.2%) were admitted to an intensive care unit (ICU); 12 of 207 (5.8%) required invasive mechanical ventilation, and one patient died during hospitalization. Although the cumulative rate of pediatric COVID-19-associated hospitalization remains low (8.0 per 100,000 population) compared with that among adults (164.5),* weekly rates increased during the surveillance period, and one in three hospitalized children were admitted to the ICU, similar to the proportion among adults. Continued tracking of SARS-CoV-2 infections among children is important to characterize morbidity and mortality. Reinforcement of prevention efforts is essential in congregate settings that serve children, including childcare centers and schools.
Many high-consequence human and animal pathogens persist in wildlife reservoirs. An understanding of the dynamics of these pathogens in their reservoir hosts is crucial to inform the risk of ...spill-over events, yet our understanding of these dynamics is frequently insufficient. Viral persistence in a wild bat population was investigated by combining empirical data and in-silico analyses to test hypotheses on mechanisms for viral persistence. A fatal zoonotic virus, European Bat lyssavirus type 2 (EBLV-2), in Daubenton's bats (Myotis daubentonii) was used as a model system. A total of 1839 M. daubentonii were sampled for evidence of virus exposure and excretion during a prospective nine year serial cross-sectional survey. Multivariable statistical models demonstrated age-related differences in seroprevalence, with significant variation in seropositivity over time and among roosts. An Approximate Bayesian Computation approach was used to model the infection dynamics incorporating the known host ecology. The results demonstrate that EBLV-2 is endemic in the study population, and suggest that mixing between roosts during seasonal swarming events is necessary to maintain EBLV-2 in the population. These findings contribute to understanding how bat viruses can persist despite low prevalence of infection, and why infection is constrained to certain bat species in multispecies roosts and ecosystems.
The genomes of most, if not all, flowering plants have undergone whole genome duplication events during their evolution. The impact of such polyploidy events is poorly understood, as is the fate of ...most duplicated genes. We sequenced an approximately 1 million-bp region in soybean (Glycine max) centered on the Rpg1-b disease resistance gene and compared this region with a region duplicated 10 to 14 million years ago. These two regions were also compared with homologous regions in several related legume species (a second soybean genotype, Glycine tomentella, Phaseolus vulgaris, and Medicago truncatula), which enabled us to determine how each of the duplicated regions (homoeologues) in soybean has changed following polyploidy. The biggest change was in retroelement content, with homoeologue 2 having expanded to 3-fold the size of homoeologue 1. Despite this accumulation of retroelements, over 77% of the duplicated low-copy genes have been retained in the same order and appear to be functional. This finding contrasts with recent analyses of the maize (Zea mays) genome, in which only about one-third of duplicated genes appear to have been retained over a similar time period. Fluorescent in situ hybridization revealed that the homoeologue 2 region is located very near a centromere. Thus, pericentromeric localization, per se, does not result in a high rate of gene inactivation, despite greatly accelerated retrotransposon accumulation. In contrast to low-copy genes, nucleotide-binding-leucine-rich repeat disease resistance gene clusters have undergone dramatic species/homoeologue-specific duplications and losses, with some evidence for partitioning of subfamilies between homoeologues.
Evidence that greenspaces are related to mental health and wellbeing mostly relies on residential exposure and few studies have considered actual use. We aimed to link the National Survey for Wales ...(NSW) to environmental metrics to determine whether there is an association between increased residential exposure to greenspace and subjective wellbeing, and whether this is mediated by visits to outdoor spaces.
In this cross-sectional data linkage study, we linked NSW data (2016–17 and 2018–19; repeat cross-sectional) to the Secure Anonymised Information Linkage (SAIL) Databank. Survey data included the Warwick and Edinburgh Mental Wellbeing Scale (WEMWBS), and self-reported time spent on leisure visits to open spaces in Wales (including bluespaces; derived from visit frequency in the past 4 weeks and duration of the main activity on the most recent visit). Linkage at individual level augmented this data with home neighbourhood greenspace data (Enhanced Vegetation Index EVI derived from satellite imagery). Using multivariate linear regression models, we estimated associations between home or visit exposures and WEMWBS, adjusting for various covariates including area level (via Welsh Index of Multiple Deprivation) and individual deprivation indicators. EVI, weekly time outdoors, and WEMWBS were standardised and both linear and quadratic terms were included in analyses. The e-cohort uses anonymised data and was approved by the SAIL Information Governance Review Panel.
Among NSW respondents providing outcome measures (n=5971), EVI was significantly related to both WEMWBS (U-shaped relationship, EVI beta −0·02, p=0·13; EVI2 beta 0·02, p= 0·0098), and weekly time outdoors (EVI beta 0·04, p=0·020). Time outdoors was also significantly related to WEMWBS (time outdoors beta 0·17, p<0·0001; time outdoors2 beta –0·04, p=0·018). Despite the conditions for potential mediation being met—i.e., EVI predicting both time outdoors and WEMWBS and time outdoors predicting WEMWBS—there was no evidence that time outdoors mediated the relationship between EVI and WEMWBS. EVI coefficients were not attenuated after including time outdoors (EVI beta –0·03, p=0·076; EVI2 beta 0·02, p=0·018).
Living near and time spent visiting greenspaces and bluespaces were both related to better subjective wellbeing. The absence of mediation suggests that better wellbeing associated with EVI occurs through a different mechanism than visiting.
National Institute for Health Research.
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