Dexamethasone in hospitalised COVID-19 patients not on intensive respiratory support.

BACKGROUND: Dexamethasone decreases mortality in coronavirus disease 2019 (COVID-19) patients on intensive respiratory support (IRS) but is of uncertain benefit if less severely ill. We determined whether early (within 48 h) dexamethasone was associated with mortality in patients hospitalised with COVID-19 not on IRS. METHODS: We included patients admitted to US Veterans Affairs hospitals between 7 June 2020 and 31 May 2021 within 14 days after a positive test for severe acute respiratory syndrome coronavirus 2. Exclusions included recent prior corticosteroids and IRS within 48 h. We used inverse probability of treatment weighting (IPTW) to balance exposed and unexposed groups, and Cox proportional hazards models to determine 90-day all-cause mortality. RESULTS: Of 19 973 total patients (95% men, median age 71 years, 27% black), 15 404 (77%) were without IRS within 48 h. Of these, 3514 out of 9450 (34%) patients on no oxygen received dexamethasone and 1042 (11%) died; 4472 out of 5954 (75%) patients on low-flow nasal cannula (NC) only received dexamethasone and 857 (14%) died. In IPTW stratified models, patients on no oxygen who received dexamethasone experienced 76% increased risk for 90-day mortality (hazard ratio (HR) 1.76, 95% CI 1.47-2.12); there was no association with mortality among patients on NC only (HR 1.08, 95% CI 0.86-1.36). CONCLUSIONS: In patients hospitalised with COVID-19, early initiation of dexamethasone was common and was associated with no mortality benefit among those on no oxygen or NC only in the first 48 h; instead, we found evidence of potential harm. These real-world findings do not support the use of early dexamethasone in hospitalised COVID-19 patients without IRS.

Discussion and Initiation of HIV Pre-exposure Prophylaxis Were Rare Following Diagnoses of Sexually Transmitted Infections Among Veterans.

BACKGROUND: Healthcare encounters for the diagnosis and treatment of sexually transmitted infections (STIs) are common and represent an opportunity to discuss and initiate HIV pre-exposure prophylaxis (PrEP). Little is known about how frequently PrEP is discussed and initiated in association with encounters for STIs. DESIGN: Retrospective cohort and nested case-control study, matched by STI date, in national Veterans Health Administration (VHA) facilities  from January 2013 to December 2018. PARTICIPANTS: Veterans with a first STI diagnosis (i.e., early syphilis, gonorrhea, or chlamydia) based on ICD codes, excluding those with prior HIV diagnosis, prior PrEP use, or STI diagnosed on screening during a visit to initiate PrEP. MAIN MEASURES: Frequency of PrEP initiation within 90 days of healthcare encounter for STIs. In the case-control study, we performed a structured chart review from the initial STI-related clinical encounter and quantified frequency of PrEP discussions among matched patients who did and did not initiate PrEP in the following 90 days. KEY RESULTS: We identified 23,312 patients with a first STI, of whom 90 (0.4%) started PrEP within 90 days. PrEP initiation was associated with urban residence (OR = 5.0, 95% CI 1.8-13.5), White compared to Black race (OR = 1.7, 95% CI 1.0-2.7), and syphilis diagnosis (OR = 5.7, 95% CI 3.7-8.6). Chart review revealed that discussion of PrEP was rare among people with STIs who did not subsequently start PrEP (1.1%, 95% CI 0.1-4.0). PrEP initiation was associated with documentation of sexual history (80.0% of initiators vs. 51.0% of non-initiators, p < 0.01) and discussion of PrEP (52.2% vs. 1.1%, p < 0.01) during the initial STI diagnosis encounter. CONCLUSIONS: Discussion and initiation of PrEP were rare following healthcare encounters for STIs. Interventions are needed to improve low rates of sexual history-taking and discussion of PrEP during healthcare encounters for STIs.

Testing Practices and Incidence of Chlamydial and Gonococcal Infection in the Veterans Health Administration, 2009-2019.

BACKGROUND: Chlamydia trachomatis and Neisseria gonorrhoeae cases reached a record high in the United States in 2018. Although active-duty military service members have high rates of chlamydia and gonorrhea infection, trends in chlamydia and gonorrhea in the Veterans Health Administration (VHA) system have not been previously described, including among patients living with human immunodeficiency virus (HIV) and young women. METHODS: We identified all veterans in VHA care from 2009 through 2019. Tests and cases of chlamydia and gonorrhea were defined based on laboratory results in the electronic health record. Chlamydia and gonorrhea incidence rates were calculated each year by demographic group and HIV status. RESULTS: In 2019, testing for chlamydia and gonorrhea occurred in 2.3% of patients, 22.6% of women aged 18-24 years, and 34.1% of persons living with HIV. The 2019 incidence of chlamydia and gonorrhea was 100.8 and 56.3 cases per 100 000 VHA users, an increase of 267% and 294%, respectively, since 2009. Veterans aged ≤34 years accounted for 9.5% of the VHA population but 66.9% of chlamydia and 42.9% of gonorrhea cases. Chlamydia and gonorrhea incidence rates in persons living with HIV were 1432 and 1687 per 100 000, respectively. CONCLUSIONS: The incidence of chlamydia and gonorrhea rose dramatically from 2009 to 2019. Among tested persons, those living with HIV had a 15.2-fold higher unadjusted incidence of chlamydia and 34.9-fold higher unadjusted incidence of gonorrhea compared with those not living with HIV. VHA-wide adherence to chlamydia and gonorrhea testing in high-risk groups merits improvement.

Antibiotic Stewardship Implementation and Antibiotic Use at Hospitals With and Without On-site Infectious Disease Specialists.

BACKGROUND: Many US hospitals lack infectious disease (ID) specialists, which may hinder antibiotic stewardship efforts. We sought to compare patient-level antibiotic exposure at Veterans Health Administration (VHA) hospitals with and without an on-site ID specialist, defined as an ID physician and/or ID pharmacist. METHODS: This retrospective VHA cohort included all acute-care patient admissions during 2016. A mandatory survey was used to identify hospitals' antibiotic stewardship processes and their access to an on-site ID specialist. Antibiotic use was quantified as days of therapy per days present and categorized based on National Healthcare Safety Network definitions. A negative binomial regression model with risk adjustment was used to determine the association between presence of an on-site ID specialist and antibiotic use at the level of patient admissions. RESULTS: Eighteen of 122 (14.8%) hospitals lacked an on-site ID specialist; there were 525 451 (95.8%) admissions at ID hospitals and 23 007 (4.2%) at non-ID sites. In the adjusted analysis, presence of an ID specialist was associated with lower total inpatient antibacterial use (odds ratio, 0.92; 95% confidence interval, .85-.99). Presence of an ID specialist was also associated with lower use of broad-spectrum antibacterials (0.61; .54-.70) and higher narrow-spectrum ß-lactam use (1.43; 1.22-1.67). Total antibacterial exposure (inpatient plus postdischarge) was lower among patients at ID versus non-ID sites (0.92; .86-.99). CONCLUSIONS: Patients at hospitals with an ID specialist received antibiotics in a way more consistent with stewardship principles. The presence of an ID specialist may be important to effective antibiotic stewardship.

How Should We Organize Care for Patients With Human Immunodeficiency Virus and Comorbidities? A Multisite Qualitative Study of Human Immunodeficiency Virus Care in the United States Department of Veterans Affairs.

BACKGROUND: With human immunodeficiency virus (HIV) now managed as a chronic disease, health care has had to change and expand to include management of other critical comorbidities. We sought to understand how variation in the organization, structure and processes of HIV and comorbidity care, based on patient-centered medical home (PCMH) principles, was related to care quality for Veterans with HIV. RESEARCH DESIGN: Qualitative site visits were conducted at a purposive sample of 8 Department of Veterans Affairs Medical Centers, varying in care quality and outcomes for HIV and common comorbidities. Site visits entailed conduct of patient interviews (n=60); HIV care team interviews (n=60); direct observation of clinic processes and team interactions (n=22); and direct observations of patient-provider clinical encounters (n=45). Data were analyzed using a priori and emergent codes, construction of site syntheses and comparing sites with varying levels of quality. RESULTS: Sites highest and lowest in both HIV and comorbidity care quality demonstrated clear differences in provision of PCMH-principled care. The highest site provided greater team-based, comprehensive, patient-centered, and data-driven care and engaged in continuous improvement. Sites with higher HIV care quality attended more to psychosocial needs. Sites that had consistent processes for comorbidity care, whether in HIV or primary care clinics, had higher quality of comorbidity care. CONCLUSIONS: Provision of high-quality HIV care and high-quality co-morbidity care require different care structures and processes. Provision of both requires a focus on providing care aligned with PCMH principles, integrating psychosocial needs into care, and establishing explicit consistent approaches to comorbidity management.

Mixed-Methods Evaluation of the Incorporation of Home Specimen Self-Collection Kits for Laboratory Testing in a Telehealth Program for HIV Pre-exposure Prophylaxis.

Home specimen self-collection kits with central laboratory testing may improve persistence with PrEP and enhance telehealth programs. We offered Iowa TelePrEP clients the choice of using a home kit or visiting a laboratory site for routine monitoring. Mixed-methods evaluation determined the proportion of clients who chose a kit, factors influencing choice, associations between kit use and completion of indicated laboratory monitoring, and user experience. About 46% (35/77) chose to use a kit. Compared to laboratory site use, kit use was associated with higher completion of extra-genital swabs (OR 6.33, 95% CI 1.20-33.51, for anorectal swabs), but lower completion of blood tests (OR 0.21, 95% CI 0.06-0.73 for creatinine). Factors influencing choice included self-efficacy to use kits, time/convenience, and privacy/confidentiality. Clients reported kit use was straight-forward but described challenges with finger prick blood collection. Telehealth PrEP programs should offer clients home kits and support clients with blood collection and kit completion.

RESUMEN: Los kits de pruebas caseras de auto-recolección junto con los ensayos de laboratorio central puedan mejorar la persistencia de PrEP y aumentar los programas de telesalud. Ofrecimos a los clientes de Iowa TelePrEP la opción de o utilizar un kit de pruebas caseras o visitar un sitio de laboratorio para seguimiento rutinario.La evaluación de métodos mixtos determinó la proporción de los clientes que eligieron un kit, los factores que influyen en la elección, las asociaciones entre el uso del kit y la realización del monitoreo de laboratorio indicado y la experiencia de los usuarios. Casi 46 % (35 de 77) eligió utilizar un kit. Comparado con el uso del sitio de laboratorio, el kit fue asociado con mayores tasas de terminación para los hisopos extragenitales (OR 6.33, 95% CI 1.20-33.51, para hisopos anorectales), pero menores tasas de terminación para los análisis de sangre (OR 0.21, 95% CI 0.06-0.73 para creatinina). Los factores que influyeron en la elección incluyeron la autoeficacia para usar los kits, el tiempo / la comodidad y la privacidad/ confidencialidad. Los clientes informaron que el uso del kit fue sencillo pero describieron desafíos con la recolección de sangre por un pinchazo. Los programas de PrEP de telesalud deben ofrecer a los clientes kits para el hogar y apoyarlos con la recolección de sangre y la terminación del kit.

Cretaceous diversity and disparity in a lacewing lineage of predators (Neuroptera: Mantispidae).

Mantidflies (Mantispidae) are an unusual and charismatic group of predatory lacewings (Neuroptera), whereby the adults represent a remarkable case of morphological and functional convergence with praying mantises (Mantodea). The evolutionary history of mantidflies remains largely unknown due to a scarcity of fossils. Here, we report the discovery of a highly diverse palaeofauna of mantidflies from the mid-Cretaceous (lowermost Cenomanian) of Myanmar. The raptorial forelegs of these mantidflies possess highly divergent morphological modifications, some of which are unknown among modern mantidflies, e.g. the presence of forked basal profemoral spines or even the complete loss of foreleg spine-like structures. A phylogenetic analysis of Mantispidae reveals a pattern of raptorial foreleg evolution across the family. The high species diversity and disparate foreleg characters might have been driven by diverse niches of predator-prey interplay in the complex tropical forest ecosystem of the mid-Cretaceous.

Co-nonsolvency in concentrated aqueous solutions of PNIPAM: effect of methanol on the collective and the chain dynamics.

The polymer dynamics in concentrated solutions of poly(N-isopropyl acrylamide) (PNIPAM) in D2O/CD3OD mixtures is investigated in the one-phase region. Two polymer concentrations (9 and 25 wt%) and CD3OD contents in the solvent mixture of 0, 10 and 15 vol% are chosen. Temperature-resolved dynamic light scattering (DLS) reveals the collective dynamics. Two modes are observed, namely the fast relaxation of polymer segments within the blobs and the slow collective relaxation of the blobs. As the cloud point is approached, the correlation length related to the fast mode increases with CD3OD content. It features critical scaling behavior, which is consistent with mean-field behavior for the 9 wt% PNIPAM solution in pure D2O and with 3D Ising behavior for all other solutions. While the slow mode is not very strong in the 9 wt% PNIPAM solution in pure D2O, it is significantly more prominent as CD3OD is added and at all CD3OD contents in the 25 wt% solution, which may be attributed to enhanced interaction between the polymers. Neutron spin-echo spectroscopy (NSE) reveals a decay in the intermediate structure factor which indicates a diffusive process. For the polymer concentration of 9 wt%, the diffusion coefficients from NSE are similar to the ones from the fast relaxation observed in DLS. In contrast, they are significantly lower for the solutions having a polymer concentration of 25 wt%, which is attributed to the influence of the dominant large-scale dynamic heterogeneities. To summarize, addition of cosolvent leads to enhanced large-scale heterogeneities, which are reflected in the dynamic behavior at small length scales.

Regional and Rural-Urban Differences in the Use of Direct-acting Antiviral Agents for Hepatitis C Virus: The Veteran Birth Cohort.

BACKGROUND: Veterans with hepatitis C virus (HCV) infection may face geographic obstacles to obtaining treatment. OBJECTIVE: We studied the influence of region and rural versus urban residence on receipt of direct-acting antiretroviral (DAA) medications for HCV. SUBJECTS: Veterans receiving care within Veterans Affairs Healthcare System born between 1945 and 1965. RESEARCH DESIGN: This is a observational study using national electronic health record data. MEASURES: Receipt of DAAs was defined as ≥1 filled prescription from January 1, 2014 to December 31, 2016. Region (South, Northeast, Midwest, and West) and residence (urban, rural-micropolitan, small rural towns, and isolated rural towns) variables were created using residential zone improvement plan codes and rural-urban commuting area (RUCA) codes. Multivariable models were adjusted for age, race, sex, severity of liver disease, comorbidities, and prior treatment experience. RESULTS: Among 166,353 eligible patients 64,854 received, DAAs. Variation by rural-urban residence depended on region. In unadjusted analyses, receipt varied by rural-urban designations within Midwest, and West regions (P<0.05) but did not vary within the South (P=0.12). Southern rural small town had the lowest incidence of DAA receipt (40.1%), whereas the incidence was 52.9% in Midwestern isolated rural towns. In adjusted logistic analyses, compared with southern urban residents (the largest single group), southern rural small town residents had the lowest odds ratio, 0.85 (95% confidence interval, 0.75-0.93), and Midwestern residents from isolated and small rural towns had the highest odds (odds ratio, both 1.27) to receive treatment. CONCLUSIONS: Substantial geographic variation exists in receipt of curative HCV treatment. Efforts are needed to provide more equitable access to DAAs.

Iowa TelePrEP: A Public-Health-Partnered Telehealth Model for Human Immunodeficiency Virus Preexposure Prophylaxis Delivery in a Rural State.

BACKGROUND: Access to human immunodeficiency virus (HIV) preexposure prophylaxis (PrEP) is often poor in small urban and rural areas because of stigma and long distances to providers. The Iowa Department of Public Health and The University of Iowa created a regional telehealth program to address these barriers ("Iowa TelePrEP"). We describe initial TelePrEP results and share lessons learned. METHODS: Iowa Department of Public Health personnel in sexually transmitted infection (STI) clinics, disease intervention specialist and partner services, and HIV testing programs referred clients to pharmacists at University of Iowa. Clients could also self-refer via a website. Pharmacists completed video visits with clients in the community on smartphones and other devices, arranged local laboratory studies, and mailed medications. We performed a retrospective record review to quantify rates of PrEP referral, initiation, retention, guideline-concordant laboratory monitoring, and STI identification and treatment. RESULTS: Between February 2017 and October 2018, TelePrEP received 186 referrals (37% from public health) and completed 127 (68%) initial video visits with clients. Median client age was 32; 91% were men who have sex with men. Most clients with video visits (91%) started PrEP. Retention in TelePrEP at 6 months was 61%, and 96% of indicated laboratory monitoring tests were completed. Screening identified 37 STIs (8 syphilis, 10 gonorrhea, 19 chlamydia). Disease intervention specialist and partner services linked all clients with STIs to local treatment within 14 days (80% in 3 days). CONCLUSIONS: Using widely available technology and infrastructure, public health departments and health care systems can collaborate to develop regional telehealth programs to deliver PrEP in small urban and rural settings.

Health Care Facility Characteristics are Associated with Variation in Human Immunodeficiency Virus Pre-exposure Prophylaxis Initiation in Veteran's Health Administration.

To quantify health care facility-level variation in pre-exposure prophylaxis (PrEP) use in the Veteran's Health Administration (VHA); to identify facility characteristics associated with PrEP use. Retrospective analysis of the health care facility-level rate of PrEP initiation in VHA through June 30, 2017. Standardized PrEP initiation rates were used to rank facilities. Characteristics of facilities, prescribers, and PrEP recipients were examined within quartiles. Multiple linear regression was used to identify associations between facility characteristics and PrEP use. We identified 1600 PrEP recipients. Mean PrEP initiation rate was 20.0/100,000 (SD 22.8), ranging from 3.0/100,000 (SD 2.0) in the lowest quartile to 48.1/100,000 (SD 29.1) in the highest. PrEP prescribing was positively associated with proportions of urban dwellers and individuals < 45, tertiary care status, and location. Variability in PrEP uptake across a national health care system highlights opportunities to expand access in non-tertiary care facilities and underserved areas.

Phylogenomic analysis of Apoidea sheds new light on the sister group of bees.

BACKGROUND: Apoid wasps and bees (Apoidea) are an ecologically and morphologically diverse group of Hymenoptera, with some species of bees having evolved eusocial societies. Major problems for our understanding of the evolutionary history of Apoidea have been the difficulty to trace the phylogenetic origin and to reliably estimate the geological age of bees. To address these issues, we compiled a comprehensive phylogenomic dataset by simultaneously analyzing target DNA enrichment and transcriptomic sequence data, comprising 195 single-copy protein-coding genes and covering all major lineages of apoid wasps and bee families. RESULTS: Our compiled data matrix comprised 284,607 nucleotide sites that we phylogenetically analyzed by applying a combination of domain- and codon-based partitioning schemes. The inferred results confirm the polyphyletic status of the former family "Crabronidae", which comprises nine major monophyletic lineages. We found the former subfamily Pemphredoninae to be polyphyletic, comprising three distantly related clades. One of them, Ammoplanina, constituted the sister group of bees in all our analyses. We estimate the origin of bees to be in the Early Cretaceous (ca. 128 million years ago), a time period during which angiosperms rapidly radiated. Finally, our phylogenetic analyses revealed that within the Apoidea, (eu)social societies evolved exclusively in a single clade that comprises pemphredonine and philanthine wasps as well as bees. CONCLUSION: By combining transcriptomic sequences with those obtained via target DNA enrichment, we were able to include an unprecedented large number of apoid wasps in a phylogenetic study for tracing the phylogenetic origin of bees. Our results confirm the polyphyletic nature of the former wasp family Crabonidae, which we here suggest splitting into eight families. Of these, the family Ammoplanidae possibly represents the extant sister lineage of bees. Species of Ammoplanidae are known to hunt thrips, of which some aggregate on flowers and feed on pollen. The specific biology of Ammoplanidae as predators indicates how the transition from a predatory to pollen-collecting life style could have taken place in the evolution of bees. This insight plus the finding that (eu)social societies evolved exclusively in a single subordinated lineage of apoid wasps provides new perspectives for future comparative studies.

Gaps in Preexposure Prophylaxis Uptake for HIV Prevention in the Veterans Health Administration.

OBJECTIVES: To report demographics, regional variations, and indications for preexposure prophylaxis (PrEP) use for HIV prevention in the Veterans Health Administration (VHA). METHODS: We identified persons initiating tenofovir/emtricitabine for the PrEP indication in the United States between July 2012 and April 2016 in a VHA national database. We stratified PrEP use by provider type and VHA region. We calculated PrEP initiation rate for each region with VHA population data. RESULTS: Of the 825 persons who initiated PrEP during the observation period, 67% were White and 76% were men who have sex with men. People who inject drugs and transgender persons represented less than 1% each of the cohort. The majority of PrEP initiations were clustered in 3 states, leading with California (28%) followed by Florida (9%) and Texas (8%). The Southeast had one of the lowest PrEP rates at 10 PrEP initiations per 100 000 persons in care. Infectious disease specialists issued more than two thirds of index PrEP prescriptions. CONCLUSIONS: Uptake of PrEP in the VHA is uneven along geographic and risk categories. Understanding the reasons behind these gaps will be key in expanding the use of this important prevention tool.

"Availability of healthcare providers for rural veterans eligible for purchased care under the veterans choice act".

BACKGROUND: Military Veterans in the United States are more likely than the general population to live in rural areas, and often have limited geographic access to Veterans Health Administration (VHA) facilities. In an effort to improve access for Veterans living far from VHA facilities, the recently-enacted Veterans Choice Act directed VHA to purchase care from non-VHA providers for Veterans who live more than 40 miles from the nearest VHA facility. To explore potential impacts of these reforms on Veterans and healthcare providers, we identified VHA-users who were eligible for purchased care based on distance to VHA facilities, and quantified the availability of various types of non-VHA healthcare providers in counties where these Veterans lived. METHODS: We combined 2013 administrative data on VHA-users with county-level data on rurality, non-VHA provider availability, population, household income, and population health status. RESULTS: Most (77.9%) of the 416,338 VHA-users who were eligible for purchased care based on distance lived in rural counties. Approximately 16% of these Veterans lived in primary care shortage areas, while the majority (70.2%) lived in mental health care shortage areas. Most lived in counties that lacked specialized health care providers (e.g. cardiologists, pulmonologists, and neurologists). Counterintuitively, VHA played a greater role in delivering healthcare for the overall adult population in counties that were farther from VHA facilities (30.7 VHA-users / 1000 adults in counties over 40 miles from VHA facilities, vs. 22.4 VHA-users / 1000 adults in counties within 20 miles of VHA facilities, p < 0.01). CONCLUSIONS: Initiatives to purchase care for Veterans living more than 40 miles from VHA facilities may not significantly improve their access to care, as these areas are underserved by non-VHA providers. Non-VHA providers in the predominantly rural areas more than 40 miles from VHA facilities may be asked to assume care for relatively large numbers of Veterans, because VHA has recently cared for a greater proportion of the population in these areas, and these Veterans are now eligible for purchased care.

Comparative Effectiveness of Cefazolin Versus Nafcillin or Oxacillin for Treatment of Methicillin-Susceptible Staphylococcus aureus Infections Complicated by Bacteremia: A Nationwide Cohort Study.

Background: To treat patients with methicillin-susceptible Staphylococcus aureus (MSSA) infections, ß-lactams are recommended for definitive therapy; however, the comparative effectiveness of individual ß-lactams is unknown. This study compared definitive therapy with cefazolin vs nafcillin or oxacillin among patients with MSSA infections complicated by bacteremia. Methods: This retrospective study included patients admitted to 119 Veterans Affairs hospitals from 2003 to 2010. Patients were included if they had a blood culture positive for MSSA and received definitive therapy with cefazolin, nafcillin, or oxacillin. Cox proportional hazards regression and ordinal logistic regression were used to identify associations between antibiotic therapy and mortality or recurrence. A recurrent infection was defined as a MSSA blood culture between 45 and 365 days after the first MSSA blood culture. Results: Of 3167 patients, 1163 (37%) patients received definitive therapy with cefazolin. Patients who received cefazolin had a 37% reduction in 30-day mortality (hazard ratio [HR], 0.63; 95% confidence interval [CI], .51-.78) and a 23% reduction in 90-day mortality (HR, 0.77; 95% CI, .66-.90) compared with patients receiving nafcillin or oxacillin, after controlling for other factors. The odds of recurrence (odds ratio, 1.13; 95% CI, .94-1.36) were similar among patients who received cefazolin compared with patients who received nafcillin or oxacillin, after controlling for other factors. Conclusions: In this large, multicenter study, patients who received cefazolin had a lower risk of mortality and similar odds of recurrent infections compared with nafcillin or oxacillin for MSSA infections complicated by bacteremia. Physicians might consider definitive therapy with cefazolin for these infections.

Antimicrobial Nonsusceptibility of Gram-Negative Bloodstream Isolates, Veterans Health Administration System, United States, 2003-20131.

Bacteremia caused by gram-negative bacteria is associated with serious illness and death, and emergence of antimicrobial drug resistance in these bacteria is a major concern. Using national microbiology and patient data for 2003-2013 from the US Veterans Health Administration, we characterized nonsusceptibility trends of community-acquired, community-onset; healthcare-associated, community-onset; and hospital-onset bacteremia for selected gram-negative bacteria (Escherichia coli, Klebsiella spp., Pseudomonas aeruginosa, and Acinetobacter spp.). For 47,746 episodes of bacteremia, the incidence rate was 6.37 episodes/10,000 person-years for community-onset bacteremia and 4.53 episodes/10,000 patient-days for hospital-onset bacteremia. For Klebsiella spp., P. aeruginosa, and Acinetobacter spp., we observed a decreasing proportion of nonsusceptibility across nearly all antimicrobial drug classes for patients with healthcare exposure; trends for community-acquired, community-onset isolates were stable or increasing. The role of infection control and antimicrobial stewardship efforts in inpatient settings in the decrease in drug resistance rates for hospital-onset isolates needs to be determined.

BaitFisher: A Software Package for Multispecies Target DNA Enrichment Probe Design.

Target DNA enrichment combined with high-throughput sequencing technologies is a powerful approach to probing a large number of loci in genomes of interest. However, software algorithms that explicitly consider nucleotide sequence information of target loci in multiple reference species for optimizing design of target enrichment baits to be applicable across a wide range of species have not been developed. Here we present an algorithm that infers target DNA enrichment baits from multiple nucleotide sequence alignments. By applying clustering methods and the combinatorial 1-center sequence optimization to bait design, we are able to minimize the total number of baits required to efficiently probe target loci in multiple species. Consequently, more loci can be probed across species with a given number of baits. Using transcript sequences of 24 apoid wasps (Hymenoptera: Crabronidae, Sphecidae) from the 1KITE project and the gene models of Nasonia vitripennis, we inferred 57,650, 120-bp-long baits for capturing 378 coding sequence sections of 282 genes in apoid wasps. Illumina reduced-representation library sequencing confirmed successful enrichment of the target DNA when applying these baits to DNA of various apoid wasps. The designed baits furthermore enriched a major fraction of the target DNA in distantly related Hymenoptera, such as Formicidae and Chalcidoidea, highlighting the baits' broad taxonomic applicability. The availability of baits with broad taxonomic applicability is of major interest in numerous disciplines, ranging from phylogenetics to biodiversity monitoring. We implemented our new approach in a software package, called BaitFisher, which is open source and freely available at https://github.com/cmayer/BaitFisher-package.git.

Description of poly(ethylenepropylene) confined in nanopores by a modified Rouse model.

A recent model for unentangled polymer chains in confinement [M. Dolgushev and M. Krutyeva, Macromol. Theory Simul. 21, 565 (2012)] is scrutinized by small-angle neutron scattering (SANS) with respect to its static prediction, the single-chain structure factor. We find a remarkable agreement although the model simplifies the effect of the confinement to a harmonic potential. The effective confinement size from fits of SANS data with the model agrees well with the actual pore size. Starting from this result we discuss the possibility of an experiment on the dynamic structure factor predicted by the model. It turns out that such an experiment would need a large ratio polymer dimension/pore size which is difficult but not impossible to achieve.

How Will New Guidelines Affect CD4 Testing in Veterans With HIV?

BACKGROUND: Guidelines now recommend limited use of routine CD4 cell count testing in human immunodeficiency virus (HIV)-infected patients with successful viral control who are not immunocompromised. METHODS: CD4 and viral load tests for patients receiving HIV care from the US Department of Veterans Affairs during 2009-2013 were evaluated to determine trends in CD4 testing frequency and the number, cost, and results of CD4 tests considered optional under the guidelines. RESULTS: There were 28 530 individuals with sufficient testing to be included. At the time of the last CD4 test, 19.8% of the cohort was eligible for optional monitoring and 15.6% for minimal monitoring. CD4 testing frequency declined by 10.8% over 4 years, reducing the direct cost of testing by US$196 000 per year. Full implementation of new treatment guidelines could reduce CD4 testing a further 28.9%, an additional annual savings of US$600 000. CD4 tests conducted during periods of potentially reduced monitoring were rarely <200 cells/µL: 1.1% of the tests conducted when minimal monitoring was recommended and just 0.3% of tests conducted when optional monitoring was recommended were less than this value. CONCLUSIONS: Reduced CD4 monitoring of HIV-infected patients would result in modest cost savings and likely reduce patient anxiety, with little or no impact on the quality of care. Veterans Affairs has made substantial progress in reducing the frequency of optional CD4 testing, but further reductions may still be warranted.

Quality of HIV Care and Mortality Rates in HIV-Infected Patients.

BACKGROUND: The Patient Protection and Affordable Care Act encourages healthcare systems to track quality-of-care measures; little is known about their impact on mortality rates. The objective of this study was to assess associations between HIV quality of care and mortality rates. METHODS: A longitudinal survival analysis of the Veterans Aging Cohort Study included 3038 human immunodeficiency virus (HIV)-infected patients enrolled between June 2002 and July 2008. The independent variable was receipt of ≥80% of 9 HIV quality indicators (QIs) abstracted from medical records in the 12 months after enrollment. Overall mortality rates through 2014 were assessed from the Veterans Health Administration, Medicare, and Social Security National Death Index records. We assessed associations between receiving ≥80% of HIV QIs and mortality rates using Kaplan-Meier survival analysis and adjusted Cox proportional hazards models. Results were stratified by unhealthy alcohol and illicit drug use. RESULTS: The majority of participants were male (97.5%) and black (66.8%), with a mean (standard deviation) age of 49.0 (8.8) years. Overall, 25.9% reported past-year unhealthy alcohol use and 28.4% reported past-year illicit drug use. During 24 805 person-years of follow-up (mean [standard deviation], 8.2 [3.3] years), those who received ≥80% of QIs experienced lower age-adjusted mortality rates (adjusted hazard ratio, 0.75; 95% confidence interval, .65-.86). Adjustment for disease severity attenuated the association. CONCLUSIONS: Receipt of ≥80% of select HIV QIs is associated with improved survival in a sample of predominantly male, black, HIV-infected patients but was insufficient to overcome adjustment for disease severity. Interventions to ensure high-quality care and address underlying chronic illness may improve survival in HIV-infected patients.