Long-term HIV care outcomes under universal HIV treatment guidelines: A retrospective cohort study in 25 countries.

BACKGROUND: While national adoption of universal HIV treatment guidelines has led to improved, timely uptake of antiretroviral therapy (ART), longer-term care outcomes are understudied. There is little data from real-world service delivery settings on patient attrition, viral load (VL) monitoring, and viral suppression (VS) at 24 and 36 months after HIV treatment initiation. METHODS AND FINDINGS: For this retrospective cohort analysis, we used observational data from 25 countries in the International epidemiology Databases to Evaluate AIDS (IeDEA) consortium's Asia-Pacific, Central Africa, East Africa, Central/South America, and North America regions for patients who were ART naïve and aged ≥15 years at care enrollment between 24 months before and 12 months after national adoption of universal treatment guidelines, occurring 2012 to 2018. We estimated crude cumulative incidence of loss-to-clinic (CI-LTC) at 12, 24, and 36 months after enrollment among patients enrolling in care before and after guideline adoption using competing risks regression. Guideline change-associated hazard ratios of LTC at each time point after enrollment were estimated via cause-specific Cox proportional hazards regression models. Modified Poisson regression was used to estimate relative risks of retention, VL monitoring, and VS at 12, 24, and 36 months after ART initiation. There were 66,963 patients enrolling in HIV care at 109 clinics with ≥12 months of follow-up time after enrollment (46,484 [69.4%] enrolling before guideline adoption and 20,479 [30.6%] enrolling afterwards). More than half (54.9%) were females, and median age was 34 years (interquartile range [IQR]: 27 to 43). Mean follow-up time was 51 months (standard deviation: 17 months; range: 12, 110 months). Among patients enrolling before guideline adoption, crude CI-LTC was 23.8% (95% confidence interval [95% CI] 23.4, 24.2) at 12 months, 31.0% (95% CI [30.6, 31.5]) at 24 months, and 37.2% (95% [CI 36.8, 37.7]) at 36 months after enrollment. Adjusting for sex, age group, enrollment CD4, clinic location and type, and country income level, enrolling in care and initiating ART after guideline adoption was associated with increased hazard of LTC at 12 months (adjusted hazard ratio [aHR] 1.25 [95% CI 1.08, 1.44]; p = 0.003); 24 months (aHR 1.38 [95% CI 1.19, 1.59]; p < .001); and 36 months (aHR 1.34 [95% CI 1.18, 1.53], p < .001) compared with enrollment before guideline adoption, with no before-after differences among patients with no record of ART initiation by end of follow-up. Among patients retained after ART initiation, VL monitoring was low, with marginal improvements associated with guideline adoption only at 12 months after ART initiation. Among those with VL monitoring, VS was high at each time point among patients enrolling before guideline adoption (86.0% to 88.8%) and afterwards (86.2% to 90.3%), with no substantive difference associated with guideline adoption. Study limitations include lags in and potential underascertainment of care outcomes in real-world service delivery data and potential lack of generalizability beyond IeDEA sites and regions included in this analysis. CONCLUSIONS: In this study, adoption of universal HIV treatment guidelines was associated with lower retention after ART initiation out to 36 months of follow-up, with little change in VL monitoring or VS among retained patients. Monitoring long-term HIV care outcomes remains critical to identify and address causes of attrition and gaps in HIV care quality.

CD4 Count at Entry into Care and at Antiretroviral Therapy Prescription among Adults with Human Immunodeficiency Virus in the United States, 2005-2018.

From 2005 to 2018, among 32013 adults with human immunodeficiency virus entering care, median time to antiretroviral therapy (ART) prescription declined from 69 to 6 days, CD4 count at entry into care increased from 300 to 362 cells/µL, and CD4 count at ART prescription increased from 160 to 364 cells/µL.

Effects of National Adoption of Treat-All Guidelines on Pre-Antiretroviral Therapy (ART) CD4 Testing and Viral Load Monitoring After ART initiation: A Regression Discontinuity Analysis.

BACKGROUND: The World Health Organization's Treat-All guidance recommends CD4 testing before initiating antiretroviral therapy (ART), and routine viral load (VL) monitoring (over CD4 monitoring) for patients on ART. METHODS: We used regression discontinuity analyses to estimate changes in CD4 testing and VL monitoring among 547 837 ART-naive patients enrolling in human immunodeficiency virus (HIV) care during 2006-2018 at 225 clinics in 26 countries where Treat-All policies were adopted. We examined CD4 testing within 12 months before and VL monitoring 6 months after ART initiation among adults (≥20 years), adolescents (10-19 years), and children (0-9 years) in low/lower-middle-income countries (L/LMICs) and high/upper-middle-income countries (H/UMICs). RESULTS: Treat-All adoption led to an immediate decrease in pre-ART CD4 testing among adults in L/LMICs, from 57.0% to 48.1% (-8.9 percentage points [pp]; 95% CI: -11.0, -6.8), and a small increase in H/UMICs, from 90.1% to 91.7% (+1.6pp; 95% CI: 0.2, 3.0), with no changes among adolescents or children; decreases in pre-ART CD4 testing accelerated after Treat-All adoption in L/LMICs. In L/LMICs, VL monitoring after ART initiation was low among all patients in L/LMICs before Treat-All; while there was no immediate change at Treat-All adoption, VL monitoring trends significantly increased afterwards. VL monitoring increased among adults immediately after Treat-All adoption, from 58.2% to 61.1% (+2.9pp; 95% CI: 0.5, 5.4), with no significant changes among adolescents/children. CONCLUSIONS: While on-ART VL monitoring has improved in L/LMICs, Treat-All adoption has accelerated and disparately worsened suboptimal pre-ART CD4 monitoring, which may compromise care outcomes for individuals with advanced HIV.

A statistical quality assessment method for longitudinal observations in electronic health record data with an application to the VA million veteran program.

BACKGROUND: To describe an automated method for assessment of the plausibility of continuous variables collected in the electronic health record (EHR) data for real world evidence research use. METHODS: The most widely used approach in quality assessment (QA) for continuous variables is to detect the implausible numbers using prespecified thresholds. In augmentation to the thresholding method, we developed a score-based method that leverages the longitudinal characteristics of EHR data for detection of the observations inconsistent with the history of a patient. The method was applied to the height and weight data in the EHR from the Million Veteran Program Data from the Veteran's Healthcare Administration (VHA). A validation study was also conducted. RESULTS: The receiver operating characteristic (ROC) metrics of the developed method outperforms the widely used thresholding method. It is also demonstrated that different quality assessment methods have a non-ignorable impact on the body mass index (BMI) classification calculated from height and weight data in the VHA's database. CONCLUSIONS: The score-based method enables automated and scaled detection of the problematic data points in health care big data while allowing the investigators to select the high-quality data based on their need. Leveraging the longitudinal characteristics in EHR will significantly improve the QA performance.

Association of APOL1 Risk Alleles With Cardiovascular Disease in Blacks in the Million Veteran Program.

BACKGROUND: Approximately 13% of black individuals carry 2 copies of the apolipoprotein L1 (APOL1) risk alleles G1 or G2, which are associated with 1.5- to 2.5-fold increased risk of chronic kidney disease. There have been conflicting reports as to whether an association exists between APOL1 risk alleles and cardiovascular disease (CVD) that is independent of the effects of APOL1 on kidney disease. We sought to test the association of APOL1 G1/G2 alleles with coronary artery disease, peripheral artery disease, and stroke among black individuals in the Million Veteran Program. METHODS: We performed a time-to-event analysis of retrospective electronic health record data using Cox proportional hazard and competing-risks Fine and Gray subdistribution hazard models. The primary exposure was APOL1 risk allele status. The primary outcome was incident coronary artery disease among individuals without chronic kidney disease during the 12.5-year follow-up period. We separately analyzed the cross-sectional association of APOL1 risk allele status with lipid traits and 115 cardiovascular diseases using phenome-wide association. RESULTS: Among 30 903 black Million Veteran Program participants, 3941 (13%) carried the 2 APOL1 risk allele high-risk genotype. Individuals with normal kidney function at baseline with 2 risk alleles had slightly higher risk of developing coronary artery disease compared with those with no risk alleles (hazard ratio, 1.11 [95% CI, 1.01-1.21]; P=0.039). Similarly, modest associations were identified with incident stroke (hazard ratio, 1.20 [95% CI, 1.05-1.36; P=0.007) and peripheral artery disease (hazard ratio, 1.15 [95% CI, 1.01-1.29l; P=0.031). When both cardiovascular and renal outcomes were modeled, APOL1 was strongly associated with incident renal disease, whereas no significant association with the CVD end points could be detected. Cardiovascular phenome-wide association analyses did not identify additional significant associations with CVD subsets. CONCLUSIONS: APOL1 risk variants display a modest association with CVD, and this association is likely mediated by the known APOL1 association with chronic kidney disease.

Unplanned Hospital Encounters After Endoscopic Retrograde Cholangiopancreatography in 3 Large North American States.

BACKGROUND & AIMS: We have few population-level data on the performance of endoscopic retrograde cholangiopancreatography (ERCP) in the United States. We investigated the numbers of unplanned hospital encounters (UHEs), patient and facility factors associated with UHEs, and variation in quality and outcomes in the performance of ERCP in 3 large American states. METHODS: We collected data on 68,642 ERCPs, performed at 635 facilities in California, Florida, and New York from 2009 through 2014. The primary endpoint was number of UHEs with an ERCP-related event within 7 days of ERCP; secondary endpoints included number of UHEs within 30 days and mortality within 30 days. Each facility was assigned a risk-standardized cohort, and variations in number of UHEs were analyzed with multivariable analysis. RESULTS: Among all ERCPs, 5.8% resulted in a UHE within 7 days and 10.2% within 30 days. Performance of sphincterotomy was significantly associated with a higher risk of UHE at 7 and 30 days (P < .001). Younger age, female sex, and more advanced comorbidity were associated with UHE. There was substantial heterogeneity in rates of UHE among facilities: 4.2% at facilities in the 5th percentile and 25.2% at facilities in the 95th percentile. Increasing facility volume and ability to perform endoscopic ultrasonography were associated inversely with risk. The median number of ERCPs performed each year was 68.7, but 69% of facilities performed 100 or fewer ERCPs per year. Risk for UHE after sphincterotomy decreased with increasing facility volume until an inflection point of 157 ERCPs per year was reached. CONCLUSIONS: In an analysis of outcomes of 68,642 ERCPs performed in 3 states, we found a higher-than-expected number of UHEs. There is substantial unexplained variation in risk for adverse events after ERCPs among facilities, and volume is the strongest predictor of risk. Annual facility volumes above approximately 150 ERCPs per year may protect against UHE.

Point-of-Care Ultrasound as Part of a Short-Term Medical Mission to Rural Nicaragua.

OBJECTIVES: The lack of access to diagnostic imaging in resource-limited settings (RLSs) poses a worldwide problem. Advances in ultrasound (US) imaging technology bridge this gap, particularly when examinations are performed by physicians and integrated into the patient encounter, termed point-of-care ultrasound (POCUS). Because the number of physicians participating in short-term medical missions (STMMs) is increasing, the authors sought to characterize how the use of POCUS would affect care delivered as part of a 1-week outreach trip in rural Nicaragua. METHODS: In February 2017, as part of an ongoing collaboration among the University of South Carolina, the Medical University of South Carolina, and OneWorld Health, the authors conducted an observational prospective study of all of the patients who received a POCUS examination as part of standard clinical practice during an STMM to Sébaco, Nicaragua. The goal was to determine how often POCUS changed medical management. In addition, the number and types of scans performed were recorded to assess the most common reasons for POCUS use. RESULTS: More than 1100 patients were seen, and a total of 79 POCUS examinations were performed on 59 patients by 2 physicians with extensive POCUS training. Eighty percent of the patients were women, with an average age of 40.5 years (range 1.6-87 years). The use of US changed management for 35.6% of total patients examined (N = 21), divided among changes in diagnosis, pharmacotherapy, new referral, or referral not needed. The average time to perform a POCUS examination was 6.0 minutes. A wide range of POCUS examinations were performed, with lung, gallbladder, obstetric/gynecologic, and cardiac examinations performed most often. CONCLUSIONS: Incorporating POCUS by trained physicians in an RLS as part of an STMM was successful and often changed management. As interest in nonemergency and noncritical care POCUS increases and proliferation of low-cost, accurate, handheld US devices continues, it is probable that more physicians traveling to RLSs will use POCUS as part of STMMs, positively affecting patient care.

Suicidal Ideation is Associated with Limited Engagement in HIV Care.

PHQ-9 data from persons living with HIV (PLWH, n = 4099) being screened for depression in three clinics in the southeastern USA were used to determine the prevalence of suicidal ideation (SI). SI was reported by 352 (8.6 %); associated with <3 years since HIV diagnosis (1.69; 95 %CI 1.35, 2.13), and HIV RNA >50 copies/ml (1.70, 95 %CI 1.35, 2.14). Data from PLWH enrolled in a depression treatment study were used to determine the association between moderate-to-high risk SI (severity) and SI frequency reported on PHQ-9 screening. Over forty percent of persons reporting that SI occurred on "more than half the days" (by the PHQ-9) were assessed as having a moderate-to-high risk for suicide completion during the Mini International Neuropsychiatric Interview. SI, including moderate-to-high risk SI, remains a significant comorbid problem for PLWH who are not fully stabilized in care (as indicated by detectable HIV RNA or HIV diagnosis for less than 3 years).

Predicting clinical outcomes of SARS-CoV-2 infection during the Omicron wave using machine learning.

The Omicron SARS-CoV-2 variant continues to strain healthcare systems. Developing tools that facilitate the identification of patients at highest risk of adverse outcomes is a priority. The study objectives are to develop population-scale predictive models that: 1) identify predictors of adverse outcomes with Omicron surge SARS-CoV-2 infections, and 2) predict the impact of prioritized vaccination of high-risk groups for said outcome. We prepared a retrospective longitudinal observational study of a national cohort of 172,814 patients in the U.S. Veteran Health Administration who tested positive for SARS-CoV-2 from January 15 to August 15, 2022. We utilized sociodemographic characteristics, comorbidities, and vaccination status, at time of testing positive for SARS-CoV-2 to predict hospitalization, escalation of care (high-flow oxygen, mechanical ventilation, vasopressor use, dialysis, or extracorporeal membrane oxygenation), and death within 30 days. Machine learning models demonstrated that advanced age, high comorbidity burden, lower body mass index, unvaccinated status, and oral anticoagulant use were the important predictors of hospitalization and escalation of care. Similar factors predicted death. However, anticoagulant use did not predict mortality risk. The all-cause death model showed the highest discrimination (Area Under the Curve (AUC) = 0.903, 95% Confidence Interval (CI): 0.895, 0.911) followed by hospitalization (AUC = 0.822, CI: 0.818, 0.826), then escalation of care (AUC = 0.793, CI: 0.784, 0.805). Assuming a vaccine efficacy range of 70.8 to 78.7%, our simulations projected that targeted prevention in the highest risk group may have reduced 30-day hospitalization and death in more than 2 of 5 unvaccinated patients.

Metformin prescription for U.S. veterans with prediabetes, 2010-2019.

Affecting an estimated 88 million Americans, prediabetes increases the risk for developing type 2 diabetes mellitus (T2DM), and independently, cardiovascular disease, retinopathy, nephropathy, and neuropathy. Nevertheless, little is known about the use of metformin for diabetes prevention among patients in the Veterans Health Administration, the largest integrated healthcare system in the U.S. This is a retrospective observational cohort study of the proportion of Veterans with incident prediabetes who were prescribed metformin at the Veterans Health Administration from October 2010 to September 2019. Among 1,059,605 Veterans with incident prediabetes, 12,009 (1.1%) were prescribed metformin during an average 3.4 years of observation after diagnosis. Metformin prescribing was marginally higher (1.6%) among those with body mass index (BMI) ≥35 kg/m2, age <60 years, HbA1c≥6.0%, or those with a history of gestational diabetes, all subgroups at a higher risk for progression to T2DM. In a multivariable model, metformin was more likely to be prescribed for those with BMI ≥35 kg/m2 incidence rate ratio [IRR] 2.6 [95% confidence intervals (CI): 2.1-3.3], female sex IRR, 2.4 [95% CI: 1.8-3.3], HbA1c≥6% IRR, 1.93 [95% CI: 1.5-2.4], age <60 years IRR, 1.7 [95% CI: 1.3-2.3], hypertriglyceridemia IRR, 1.5 [95% CI: 1.2-1.9], hypertension IRR, 1.5 [95% CI: 1.1-2.1], Major Depressive Disorder IRR, 1.5 [95% CI: 1.1-2.0], or schizophrenia IRR, 2.1 [95% CI: 1.2-3.8]. Over 20% of Veterans with prediabetes attended a comprehensive structured lifestyle modification clinic or program. Among Veterans with prediabetes, metformin was prescribed to 1.1% overall, a proportion that marginally increased to 1.6% in the subset of individuals at highest risk for progression to T2DM.

Factors related to age at natural menopause: longitudinal analyses from SWAN.

Early age at the natural final menstrual period (FMP) or menopause has been associated with numerous health outcomes and might be a marker of future ill health. However, potentially modifiable factors affecting age at menopause have not been examined longitudinally in large, diverse populations. The Study of Women's Health Across the Nation (SWAN) followed 3,302 initially premenopausal and early perimenopausal women from 7 US sites and 5 racial/ethnic groups, using annual data (1996-2007) and Cox proportional hazards models to assess the relation of time-invariant and time-varying sociodemographic, lifestyle, and health factors to age at natural FMP. Median age at the FMP was 52.54 years (n = 1,483 observed natural FMPs). Controlling for sociodemographic, lifestyle, and health factors, we found that racial/ethnic groups did not differ in age at the FMP. Higher educational level, prior oral contraceptive use, and higher weight at baseline, as well as being employed, not smoking, consuming alcohol, having less physical activity, and having better self-rated health over follow-up, were significantly associated with later age at the FMP. These results suggest that age at the natural FMP reflects a complex interrelation of health and socioeconomic factors, which could partially explain the relation of late age at FMP to reduced morbidity and mortality.

Anabolic and Antiresorptive Osteoporosis Treatment: Trends, Costs, and Sequence in a Commercially Insured Population, 2003-2021.

New anabolic medications (abaloparatide and romosozumab) were recently approved for osteoporosis, and data suggest that prescribing antiresorptive medications after a course of anabolic medications offers better outcomes. This study aimed to characterize prescription trends, demographics, geographical distributions, out-of-pocket costs, and treatment sequences for anabolic and antiresorptive osteoporosis medications. Using a commercial claims database (Clinformatics Data Mart), adult patients with osteoporosis from 2003 to 2021 were retrospectively reviewed and stratified based on osteoporosis medication class. Patient demographics and socioeconomic variables, provider types, and out-of-pocket costs were collected. Multivariable regression analyses were used to identify independent predictors of receiving osteoporosis treatment. A total of 2,988,826 patients with osteoporosis were identified; 616,635 (20.6%) received treatment. Patients who were female, Hispanic or Asian, in the Western US, had higher net worth, or had greater comorbidity burden were more likely to receive osteoporosis medications. Among patients who received medication, 31,112 (5.0%) received anabolic medication; these were more likely to be younger, White patients with higher education level, net worth, and greater comorbidity burden. Providers who prescribed the most anabolic medications were rheumatologists (18.5%), endocrinologists (16.8%), and general internists (15.3%). Osteoporosis medication prescriptions increased fourfold from 2003 to 2020, whereas anabolic medication prescriptions did not increase at this rate. Median out-of-pocket costs were $17 higher for anabolic than antiresorptive medications, though costs for anabolic medications decreased significantly from 2003 to 2020 (compound annual growth rate: -0.6%). A total of 8388 (1.4%) patients tried two or more osteoporosis medications, and 0.6% followed the optimal treatment sequence. Prescription of anabolic osteoporosis medications has not kept pace with overall osteoporosis treatment, and there are socioeconomic disparities in anabolic medication prescription, potentially driven by higher median out-of-pocket costs. Although prescribing antiresorptive medications after a course of anabolic medications offers better outcomes, this treatment sequence occurred in only 0.6% of the study cohort. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

Seneca Valley virus replicons are packaged in trans and have the capacity to overcome the limitations of viral transgene expression.

Oncolytic viruses (OVs) promote the anti-tumor immune response as their replication, and the subsequent lysis of tumor cells, triggers the activation of immune-sensing pathways. Arming OVs by expressing transgenes with the potential to promote immune cell recruitment and activation is an attractive strategy to enhance OVs' therapeutic benefit. For picornaviruses, a family of OVs with clinical experience, the expression of a transgene is limited by multiple factors: genome physical packaging limits, high rates of recombination, and viral-mediated inhibition of transgene secretion. Here, we evaluated strategies for arming Seneca Valley virus (SVV) with relevant immunomodulatory transgenes. Specificially in the contex of arming SVV, we evaluated transgene maximum size and stabiltity, transgene secretion, and the impact of transgene inclusion on viral fitness. We find that SVV is not capable of expressing secreted payloads and has a transgene packaging capacity of ∼10% of viral genome size. To enable transgene expression, we developed SVV replicons with greater transgene size capacity and secretion capabilities. SVV replicons can be packaged in trans by virus in co-infected cells to express immunomodulatory transgenes in surrounding cells, thus providing a means to enhance the potential of this therapeutic to augment the anti-tumor immune response.

The independent associations of anti-Müllerian hormone and estradiol levels over the menopause transition with lipids/lipoproteins: The Study of Women's health Across the Nation.

BACKGROUND: The menopause transition (MT) is linked to adverse changes in lipids/lipoproteins. However, the related contributions of anti-Müllerian hormone (AMH) and estradiol (E2) are not clear. OBJECTIVE: To evaluate the independent associations of premenopausal AMH and E2 levels and their changes with lipids/lipoproteins levels [total cholesterol (TC), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), apolipoprotein B (apoB) and apolipoprotein A-1 (apoA-1)] over the MT. METHODS: SWAN participants who transitioned to menopause without exogenous hormone use, hysterectomy, or bilateral oophorectomy with data available on both exposure and outcomes when they were premenopausal until the 1st visit postmenopausal were studied. RESULTS: The study included 1,440 women (baseline-age:mean±SD=47.4±2.6) with data available from up to 9 visits (1997-2013). Lower premenopausal levels and greater declines in AMH were independently associated with greater TC and HDL-C, whereas lower premenopausal levels and greater declines in E2 were independently associated with greater TG and apo B and lower HDL-C. Greater declines in AMH were independently associated with greater apoA-1, and greater declines in E2 were independently associated with greater TC and LDL-C. CONCLUSIONS: AMH and E2 and their changes over the MT relate differently to lipids/lipoproteins profile in women during midlife. Lower premenopausal and/or greater declines in E2 over the MT were associated with an atherogenic lipid/lipoprotein profile. On the other hand, lower premenopausal AMH and/or greater declines in AMH over the MT were linked to higher apo A-1 and HDL-C; the later found previously to be related to a greater atherosclerotic risk after menopause.

Major Publications in the Critical Care Pharmacotherapy Literature: 2022.

OBJECTIVES: A number of trials related to critical care pharmacotherapy were published in 2022. We aimed to summarize the most influential publications related to the pharmacotherapeutic care of critically ill patients in 2022. DATA SOURCES: PubMed/Medical Literature Analysis and Retrieval System Online and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update. STUDY SELECTION: Randomized controlled trials, prospective studies, or systematic review/meta-analyses of adult critically ill patients assessing a pharmacotherapeutic intervention and reporting clinical endpoints published between January 1, 2022, and December 31, 2022, were included in this article. DATA EXTRACTION: Articles from a systematic search and the Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update were included and stratified into clinical domains based upon consistent themes. Consensus was obtained on the most influential publication within each clinical domain utilizing an a priori defined three-round modified Delphi process with the following considerations: 1) overall contribution to scientific knowledge and 2) novelty to the literature. DATA SYNTHESIS: The systematic search and Clinical Pharmacy and Pharmacology Pharmacotherapy Literature Update yielded a total of 704 articles, of which 660 were excluded. The remaining 44 articles were stratified into the following clinical domains: emergency/neurology, cardiovascular, gastroenterology/fluids/nutrition, hematology, infectious diseases/immunomodulation, and endocrine/metabolic. The final article selected from each clinical domain was summarized following a three-round modified Delphi process and included three randomized controlled trials and three systematic review/meta-analyses. Article topics summarized included dexmedetomidine versus other sedatives during mechanical ventilation, beta-blocker treatment in the critically ill, restriction of IV fluids in septic shock, venous thromboembolism prophylaxis in critically ill adults, duration of antibiotic therapy for Pseudomonas aeruginosa ventilator-associated pneumonia, and low-dose methylprednisolone treatment in severe community-acquired pneumonia. CONCLUSIONS: This concise review provides a perspective on articles published in 2022 that are relevant to the pharmacotherapeutic care of critically ill patients and their potential impact on clinical practice.

Early Outcomes of SARS-CoV-2 Infection in a Multisite Prospective Cohort of Inpatient Veterans.

Background: Over 870 000 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections have occurred among Veterans Health Administration users, and 24 000 have resulted in death. We examined early outcomes of SARS-CoV-2 infection in hospitalized veterans. Methods: In an ongoing, prospective cohort study, we enrolled veterans age ≥18 tested for SARS-CoV-2 and hospitalized at 15 Department of Veterans Affairs medical centers between February 2021 and June 2022. We estimated adjusted odds ratios (aORs), adjusted incidence rate ratios (aIRRs), and adjusted hazard ratios (aHRs) for maximum illness severity within 30 days of study entry (defined using the 4-category VA Severity Index for coronavirus disease 2019 [COVID-19]), as well as length of hospitalization and rehospitalization within 60 days, in relationship with demographic characteristics, Charlson comorbidity index (CCI), COVID-19 vaccination, and calendar period of enrollment. Results: The 542 participants included 329 (61%) who completed a primary vaccine series (with or without booster; "vaccinated"), 292 (54%) enrolled as SARS-CoV-2-positive, and 503 (93%) men, with a mean age of 64.4 years. High CCI scores (≥5) occurred in 61 (44%) vaccinated and 29 (19%) unvaccinated SARS-CoV-2-positive participants. Severe illness or death occurred in 29 (21%; 6% died) vaccinated and 31 (20%; 2% died) unvaccinated SARS-CoV-2-positive participants. SARS-CoV-2-positive inpatients per unit increase in CCI had greater multivariable-adjusted odds of severe illness (aOR, 1.21; 95% CI, 1.01-1.45), more hospitalization days (aIRR, 1.06; 95% CI, 1.03-1.10), and rehospitalization (aHR, 1.07; 95% CI, 1.01-1.12). Conclusions: In a cohort of hospitalized US veterans with SARS-CoV-2 infection, those with a higher CCI had more severe COVID-19 illness, more hospital days, and rehospitalization, after adjusting for vaccination status, age, sex, and calendar period.

Vacuum-induced Suction Stimulates Increased Numbers of Blood Vessels in Healthy Dog Gingiva.

UNLABELLED:  This study was designed to determine if vacuum-induced suction increased the number of blood vessels in healthy dog gingiva as a prelude to future studies testing vacuum therapy for improving local blood supply and controlling periodontal disease. METHODS: The buccal gingiva of five dogs was treated with subatmospheric pressure for 5 days, with untreated tissues acting as controls. Biopsies were analyzed for vascular endothelial growth factors (VEGF) and blood vessels were counted. RESULTS: VEGF and vessel numbers were elevated in treatment groups compared to controls (P < 0.05). CONCLUSION: A single daily application of subatmospheric pressure might be beneficial for healing damaged or diseased gingival tissues. .

Observed CD4 counts at entry into HIV care and at antiretroviral therapy prescription by age in the USA, 2004-18: a cohort study.

BACKGROUND: Adults aged 50 years or older comprise a majority of people with HIV in the USA. Our objective was to describe observed differences by age in CD4 count at entry into HIV care, timing of antiretroviral therapy (ART) prescription, and CD4 count at time of ART prescription before (2004-11) and during (2012-18) the current era of universal treatment. METHODS: For this descriptive study, we calculated median (IQR) CD4 count at entry into care, days from entry into care to ART prescription, and CD4 count at time of ART prescription among patients enrolled in US-based clinical cohorts of the North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD; see appendix). We excluded participants with no CD4 count recorded at entry into care, medical records that suggested previous ART use, or previous AIDS diagnosis. All calculations were stratified by age (≥50 and 18-50 years) and calendar year. FINDINGS: Of 35 293 ART-naive adult participants entering care between Jan 1, 2004 and Dec 31, 2018, 5794 (16%) were women and 29 499 (84%) were men; 15817 (45%) were Black, 11566 (33%) were White, 5538 (16%) were Hispanic (any race), 737 (2%) were Asian or Pacific Islander, 152 (0.4%) were Indigenous, and 98 (0.3%) were multiracial. Median age at entry into care was 39 years (IQR 29-49); 8004 (23%) were aged 50 years or older. Of 29 141 participants initially prescribed ART, 7274 (25%) were aged 50 years or older. From 2004 to 2018, median CD4 count at entry into care increased from 228 cells per µL (IQR 80-422) to 295 cells per µL (134-489) among adults aged 50 years and older, and from 297 cells per µL (119-480) to 378 cells per µL (202-564) among adults younger than 50 years. Median days from entry into care to ART prescription declined from 56 (IQR 17-658) to 6 (0-15) among adults older than 50 years, and from 61 (17-509) to 6 (0-16) among adults younger than 50 years. Median CD4 count at time of ART prescription increased from 139 cells per µL (IQR 59-257) to 311 cells per µL (137-504) among adults aged 50 years or older, and from 166 cells per µL (49-287) to 377 cells per µL (198-564) among adults younger than 50 years. INTERPRETATION: Before the release of universal treatment guidelines by the US Department of Health and Human Services in 2012, median time to ART prescription was already falling, leading to increases in median CD4 count at ART prescription for both age groups; both measures continued to improve in the treat-all era. However, median CD4 counts, both at entry into care and at ART prescription, among adults aged 50 years and older were lower than those of adults younger than 50 years throughout the study period. Furthermore, even into the treat-all era, over half of adults aged 50 years and older entered care with CD4 counts of less than 350 cells per µL, potentially because of factors including immunosenescence, delayed HIV diagnosis, and late presentation to care. Given that age-related immunological changes might not be fully avoidable, targeted strategies for increasing HIV risk awareness, routine testing, and immediate linkage to HIV care at diagnosis are particularly essential for this population. FUNDING: US National Institutes of Health grant U01AI069918.

Anal cancer incidence in men with HIV who have sex with men: are black men at higher risk?

OBJECTIVE: To assess differences in anal cancer incidence between racial/ethnic groups among a clinical cohort of men with HIV who have sex with men. DESIGN: Clinical cohort study. METHODS: We studied men who have sex with men (MSM) in the Centers for AIDS Research Network of Integrated Clinical Systems (CNICS) who initiated antiretroviral therapy (ART) under HIV care in CNICS. We compared anal cancer incidence between Black and non-Black men and calculated hazard ratios controlling for demographic characteristics (age, CNICS site, year of ART initiation), HIV disease indicators (nadir CD4+, peak HIV RNA), and co-infection/behavioral factors including hepatitis B virus (HBV), hepatitis C virus (HCV), tobacco smoking and alcohol abuse. RESULTS: We studied 7473 MSM with HIV who contributed 41 810 person-years of follow-up after initiating ART between 1996 and 2014 in CNICS. Forty-one individuals had an incident diagnosis of anal cancer under observation. Crude rates of anal cancer were 204 versus 61 per 100 000 person-years among Black versus non-Black MSM. The weighted hazard ratio for anal cancer in Black MSM (adjusting for demographics, HIV disease factors, and co-infection/behavioral factors) was 2.37 (95% confidence interval: 1.17, 4.82) compared to non-Black MSM. CONCLUSIONS: In this large multicenter cohort, Black MSM were at significantly increased risk for anal cancer compared to non-Black MSM. Further detailed studies evaluating factors impacting anal cancer incidence and outcomes in Black men with HIV are necessary. Inclusion of more diverse study cohorts may elucidate modifiable factors associated with increased anal cancer risk experienced by Black MSM.