Search

Background Risk of infection with SARS-CoV-2 has remained high among health care personnel (HCP) throughout the pandemic, due to both exposure in the community and occupational settings. While vaccine uptake among health care workers is high, real-world continual monitoring of vaccine effectiveness (VE) among this population is crucial for informing future vaccination and prevention efforts. Methods Data for this analysis came from a test-negative case-control study conducted among HCP working at two acute care hospitals in Monroe County, NY from December 2020 through March 2022, performed as part of the CDC Emerging Infections Program. Case participants were identified as HCP who had at least one COVID-19 like symptom, and a positive polymerase-chain-reaction (PCR) SARS-CoV-2 test during the study time period. Control participants had a negative SARS-CoV-2 PCR test, regardless of presence of COVID-19 like symptoms. Cases and controls were matched based on the study week of their test date. Conditional logistic regression was used to assess vaccine effectiveness against symptomatic infection. Effectiveness was assessed between December 2020-May 2021, May 2021-October 2021, and October 2021-March 2022. Results From December 28th, 2020 through March 12th, 2022, 881 cases and 1794 controls were enrolled. Vaccine effectiveness against symptomatic infection was greatest from December 2020 through May 2021, with mRNA complete series effectiveness at 93.1% (95% CI: 86.9%-96.3%) with complete series VE falling to 25.1% (95% CI: 0.0%-50.9%) during May 2021-October 2021. Waning immunity following receipt of second dose was observed across all time periods. Vaccine effectiveness following receipt of one booster vaccine was found to be 59.2% (95% CI: 43.5-70.6), with evidence of waning immunity two months from receipt of the booster (VE: 46.6%; 95% CI: 14.6%-66.7%). Conclusion Protection provided by the COVID-19 mRNA vaccines against symptomatic infection is highly variable among HCP, based on the circulating dominant variant and the time since receipt of each dose. Monitoring of vaccine effectiveness, as well as waning immunity, among this high-risk population is essential to guide future vaccine policies. Disclosures christopher J. Myers, MS, Infectious diseases, Pfizer: Grant/Research Support Ghinwa Dumyati, MD, Pfizer: Grant/Research Support.

Background: The incidence of cardiovascular disease is higher in HIV-positive (HIV + ) patients than it is in the average population, and combination antiretroviral therapy (cART) is a recognized risk factor for cardiovascular disease. However, the molecular mechanisms that link cART and cardiovascular disease are currently unknown. Our study explores the role of the activation of p90RSK, a reactive oxygen species-sensitive kinase, in engendering senescent phenotype in macrophages and accelerating atherogenesis in patients undergoing cART. Methods: Peripheral whole blood from cART-treated HIV + individuals and nontreated HIV-negative individuals was treated with H 2 O 2 (200 µmol/L) for 4 minutes, and p90RSK activity in CD14 + monocytes was measured. Plaque formation in the carotids was also analyzed in these individuals. Macrophage senescence was determined by evaluating their efferocytotic ability, antioxidation-related molecule expression, telomere length, and inflammatory gene expression. The involvement of p90RSK-NRF2 signaling in cART-induced senescence was assessed by p90RSK-specific inhibitor (FMK-MEA) or dominant-negative p90RSK (DN-p90RSK) and NRF2 activator (NRF2A). Further, the severity of atherosclerosis was determined in myeloid cell-specific wild-type and DN-p90RSK transgenic mice. Results: Monocytes from HIV + patients exhibited higher levels of p90RSK activity and were also more sensitive to reactive oxygen species than monocytes from HIV-negative individuals. A multiple linear regression analysis involving cART, Reynolds cardiovascular risk score, and basal p90RSK activity revealed that cART and basal p90RSK activity were the 2 significant determinants of plaque formation. Many of the antiretroviral drugs individually activated p90RSK, which simultaneously triggered all components of the macrophage senescent phenotype. cART inhibited antioxidant response element reporter activity via ERK5 S496 phosphorylation. NRF2A reversed the H 2 O 2 -induced overactivation of p90RSK in cART-treated macrophages by countering the induction of senescent phenotype. Last, the data obtained from our gain- or loss-of-function mice conclusively showed the crucial role of p90RSK in inducing senescent phenotype in macrophages and atherogenesis. Conclusions: cART increased monocyte/macrophage sensitivity to reactive oxygen species- in HIV + individuals by suppressing NRF2-ARE activity via p90RSK-mediated ERK5 S496 phosphorylation, which coordinately elicited senescent phenotypes and proinflammatory responses. As such, our report underscores the importance of p90RSK regulation in monocytes/macrophages as a viable biomarker and therapeutic target for preventing cardiovascular disease, especially in HIV + patients treated with cART.

AIDS Clinical Trial Group study A5202 (ClinicalTrials.gov identifier {"type":"clinical-trial","attrs":{"text":"NCT00118898","term_id":"NCT00118898"}}NCT00118898) was a phase 3b, randomized, partially blinded equivalence study of open-label atazanavir/ritonavir or efavirenz, plus either placebo-controlled tenofovir disoproxil fumarate/emtricitabine or abacavir/lamivudine, in treatment-naive adults living with HIV-1, evaluating efficacy, safety, and tolerability. We report an analysis of the contribution of participant characteristics to the disposition of tenofovir plasma concentrations. Tenofovir concentration data from a total of 817 individuals (88% of the total number of eligible patients randomly assigned to receive treatment in the TDF-containing arms of A5202) were available for analysis. Pharmacokinetic analysis was performed using nonlinear mixed-effects modeling. One- and two-compartment models with first-order absorption and first-order elimination were evaluated. An exponential error model was used for examination of interindividual variability (IIV), and a proportional and mixed-error model was assessed for residual variability. The final structural model contained two compartments with first-order absorption and elimination. IIV was estimated for apparent clearance (CL/F) and the first-order absorption rate constant (ka), and a proportional residual variability model was selected. The final mean parameter estimates were as follows: ka = 2.87 h−1, CL/F = 37.2 liters/h, apparent volumes of the central and peripheral compartments = 127 and 646 liters, respectively, and apparent intercompartmental clearance = 107 liters/h. In addition to race/ethnicity, creatinine clearance and assignment to atazanavir/ritonavir or efavirenz were significantly associated with CL/F (P < 0.001). In conclusion, race/ethnicity is associated with tenofovir oral CL in HIV-1 positive, treatment-naive adults. This covariate relationship raises questions about the possibility of differences in efficacy and risk of adverse events in different patient populations and suggests that examining preexposure prophylaxis regimens and tenofovir exposure in different race/ethnicity groups be considered.

We report on the use of the faecal egg count reduction test to evaluate the performance of ivermectin in treating gastrointestinal nematode infections in first grazing season (FGS) calves on four dairy farms in Co. Kilkenny, Ireland. On each farm, FGS calves were injected subcutaneously with ivermectin in accordance with their live weight (day 0). Calves were individually faecal sampled on both day 0 and day 14. Faecal egg counts were determined using the Mini-FLOTAC technique. Composite faecal cultures for each farm were performed on each sampling occasion. The faecal egg count reductions (mode) ranged from 17.3–80.2% with the lower 95% confidence limit ranging from 3.1–72.3% on the four farms, respectively. Ivermectin-resistant nematodes were detected on all farms, with evidence of Ostertagia resistance on one farm. This study highlights the urgent need for Irish producers to reappraise their parasite control practices. Electronic supplementary material The online version of this article (10.1186/s13620-019-0142-8) contains supplementary material, which is available to authorized users.

Background. There is a need to prevent or minimize bone loss associated with antiretroviral treatment (ART) initiation. We compared maraviroc (MVC)- to tenofovir disoproxil fumarate (TDF)–containing ART. Methods. This was a double-blind, placebo-controlled trial. ART-naive subjects with human immunodeficiency virus type 1 RNA load (viral load [VL]) >1000 copies/mL and R5 tropism were randomized to MVC 150 mg or TDF 300 mg once daily (1:1), stratified by VL

The objective of the present study was to determine the combined effects of dietary protein and carbohydrate sources on total body energy and protein and fat gains as well as on plasma insulin and glucose and tissue lipoprotein lipase activity in male Sprague-Dawley rats fed semipurified diets for 28 days. The diets varied in both protein and carbohydrate sources, namely, casein-cornstarch, casein-sucrose, soy protein isolate (SPI) - cornstarch, SPI-sucrose, cod protein - cornstarch, and cod protein - sucrose. When SPI was combined with cornstarch, lower total body energy and fat gains were observed compared with the combination of either casein and sucrose, casein and cornstarch, or SPI and sucrose. Plasma glucose and insulin concentrations in addition to total and metabolizable energy intake and body weight gain were lower in rats fed the SPI-cornstarch diet than in those fed the casein-sucrose diet. Feeding the SPI-cornstarch diet compared with feeding either the casein-cornstarch or the SPI-sucrose diet also caused lower plasma glucose concentrations and a concomitant trend ( p = 0.06) to reduced energy intake and body weight gain. Therefore, the reducing effects of the SPI-cornstarch diet compared with the casein-cornstarch, the casein-sucrose, and the SPI-sucrose diets on body energy and fat gains may result from reductions in energy intake and in plasma glucose concentrations.Key words: dietary proteins, soy protein, dietary carbohydrates, body fat, plasma glucose, plasma insulin.

Background: In 2013 a Technology Adoption Program for sheep farmers was established to encourage the implementation of best management practices on sheep farms in Ireland. There were 4,500 participants in this programme in 2013. As part of this programme, farmers had the option to carry out a drench test to establish the efficacy of their anthelmintic treatment. Results: Flock faecal samples were collected before and after treatment administration and gastrointestinal nematode eggs enumerated. In total there were 1,893 participants in the task, however only 1,585 included both a pre- and post-treatment faecal sample. Of those, 1,308 provided information on the anthelmintic product that they used with 46%, 23% and 28% using a benzimidazole (BZ), levamisole (LEV) and macrocyclic lactone (ML) product respectively. The remaining farmers used a product inapplicable for inclusion in the task such as a flukicide or BZ/LEV combination product. Samples were included for analysis of drench efficacy if the pre-treatment flock egg count was >= 200 eggs per gram and the interval post-sampling was 10-14 days for BZ products, 4-7 days for LEV products and 14-18 days for ML products. These criteria reduced the number of valid tests to 369, 19.5% of all tests conducted. If the reduction post-treatment was >= 95% the treatment was considered effective. Only 51% of treatments were considered effective using this criterion. There was a significant difference in efficacy between the anthelmintic drug classes with BZ effective in only 30% of treatments, LEV effective in 52% of cases and ML effective in 76% of cases. Conclusions: Gastrointestinal nematode anthelmintic treatments, as practiced on Irish farms, have a high failure rate. There was a significant difference between the efficacies of the anthelmintic classes with BZ the least effective and ML the most effective.

The purpose of this study was to verify the respective and interactive effects of dietary proteins and carbohydrates on lipid and glucose metabolisms. In order to do so, 120 male Sprague-Dawley rats were fed low-fat high-carbohydrate purified diets varying in both protein (20%) and carbohydrate (60%) sources consisting of either casein-cornstarch, casein-sucrose, soy protein-cornstarch, soy protein-sucrose, cod protein-cornstarch, or cod protein-sucrose for 28 days. In fasted and fed rats, casein induced a hypercholesterolemic effect compared with soy or cod protein. However, on hepatic lipids, cod protein responded similarly to casein, being more elevated than soy protein. The independent carbohydrate effect was seen by decreased levels of liver cholesterol and triglycerides with sucrose diets compared with cornstarch diets. An interaction was also observed between dietary proteins and carbohydrates, which produced higher postprandial insulin levels with cod protein-cornstarch and casein-sucrose diets, suggesting that different mechanisms are involved in the insulin secretion of rats fed cod protein and casein. It is therefore possible that dietary proteins and carbohydrates may influence fasting and postprandial lipid and glucose metabolisms through plasma insulin levels.

To determine the respective and interactive effects of dietary protein source and calcium level on serum, hepatic, and fecal lipid levels, 48 male New Zealand rabbits were fed purified diets varying in the source of dietary protein, namely casein, cod protein, or soy protein, at an adequate (7 mg Ca/g diet) or a high (14 mg Ca/g diet) concentration of calcium in a 3 × 2 factorial design for 28 days. Dietary proteins interacted with dietary calcium to modulate serum and low density lipoprotein (LDL) cholesterol. When combined with the adequate-calcium diet, cod protein induced higher levels of serum and LDL cholesterol than casein and soy protein. When calcium was increased in the diet, cod protein, in contrast to casein and soy protein, induced lower serum and LDL cholesterol than when associated with an adequate concentration of calcium. These results indicate that the hypercholesterolemic effect of cod protein is reduced in the presence of high dietary calcium. Moreover, fecal lipid content was inversely correlated with serum total (p = 0.06) and LDL (p = 0.04) cholesterol in rabbits fed cod protein diets only. An increased formation of insoluble calcium phosphate in the intestine, which may result in lower fat intestinal absorption and serum cholesterol levels, may have been responsible for the decrease in serum and LDL cholesterol in rabbits fed cod protein with high dietary calcium.Key words: dietary protein, dietary calcium, serum cholesterol, lipoproteins, fat excretion.

An educational program to promote screening through primary health care for the squamous cell cancers of the buccal cavity, pharynx, and larynx as developed and implemented, and its impact on screening was documented. Providers of care for high‐risk patients at seven inner‐city health care sites in Boston were identified and targeted for training. Of the 327 providers who were targeted for training from December 1986 through June 1989, 261 (80%) attended educational sessions. Screening exams were documented on an average of 14.7 patients per targeted provider through December 1989. The educational program was associated with a large increase in documented screening for these cancers, compared with baseline rates. Several adaptations in the program were required, including a demonstration of efficient screening to address the concerns of these providers about time constraints. Variations in the quantity and quality of documented screening among health care sites were noted.

One hundred thirty incident cases of head and neck cancer in Boston between September 1, 1985, and March 31, 1988, provided interview or medical record review data on the use of health services in the 24 months preceding the diagnosis of cancer. One hundred twenty-four subjects were able to recall whether and how often they visited health care sites in this period, reporting a median number of 10.5 visits; 94% recalled at least one visit. Eighty-nine medical record reviews indicated a median of seven visits. For the most part, these visits were to providers whom subjects considered their regular source of care--sources that provided care in a broad range of locations. These data support a strategy of integrating screening for head and neck cancers into existing health care services.

BackgroundAntiretroviral regimens with simplified dosing and better safety are needed to maximize the efficiency of antiretroviral delivery in resource-limited settings. We investigated the efficacy and safety of antiretroviral regimens with once-daily compared to twice-daily dosing in diverse areas of the world.Methods and findings1,571 HIV-1-infected persons (47% women) from nine countries in four continents were assigned with equal probability to open-label antiretroviral therapy with efavirenz plus lamivudine-zidovudine (EFV+3TC-ZDV), atazanavir plus didanosine-EC plus emtricitabine (ATV+DDI+FTC), or efavirenz plus emtricitabine-tenofovir-disoproxil fumarate (DF) (EFV+FTC-TDF). ATV+DDI+FTC and EFV+FTC-TDF were hypothesized to be non-inferior to EFV+3TC-ZDV if the upper one-sided 95% confidence bound for the hazard ratio (HR) was ≤1.35 when 30% of participants had treatment failure. An independent monitoring board recommended stopping study follow-up prior to accumulation of 472 treatment failures. Comparing EFV+FTC-TDF to EFV+3TC-ZDV, during a median 184 wk of follow-up there were 95 treatment failures (18%) among 526 participants versus 98 failures among 519 participants (19%; HR 0.95, 95% CI 0.72-1.27; p = 0.74). Safety endpoints occurred in 243 (46%) participants assigned to EFV+FTC-TDF versus 313 (60%) assigned to EFV+3TC-ZDV (HR 0.64, CI 0.54-0.76; pConclusionEFV+FTC-TDF had similar high efficacy compared to EFV+3TC-ZDV in this trial population, recruited in diverse multinational settings. Superior safety, especially in HIV-1-infected women, and once-daily dosing of EFV+FTC-TDF are advantageous for use of this regimen for initial treatment of HIV-1 infection in resource-limited countries. ATV+DDI+FTC had inferior efficacy and is not recommended as an initial antiretroviral regimen.Trial registrationwww.ClinicalTrials.gov NCT00084136. Please see later in the article for the Editors' Summary.

The use of autologous fat transplantation has seen renewed popularity with the recent advent of liposuction as a body recontouring technique. However, clinicians are still faced with uncertainty concerning the ultimate volume maintenance of the transplanted fat graft at its recipient site. This study was initiated to examine and evaluate the changes in volume of suctioned versus surgically excised fat grafts over a 9-month period in the New Zealand White rabbit. Fat grafts of equal volume were harvested from the groin using standard suction and surgical techniques and transferred into isolated pockets in the ear. Results demonstrate that both suctioned and surgically removed fat grafts undergo significant volume reduction. However, surgically excised fat maintains its volume (42.2 percent; n = 16) better than suction-assisted fat grafts (31.6 percent; n = 16; p0.05). Histologic examination showed that fibrous connective tissue was more prevalent in the suctioned fat grafts than in the surgically removed fat grafts.

The literature suggests that children with autism typically are unresponsive to verbal initiations from others in community settings, and that such unresponsiveness can lead to problematic social interactions and severely disruptive behavior. The present study assessed whether self-management could be used as a technique to produce extended improvements in responsiveness to verbal initiations from others in community, home, and school settings without the presence of a treatment provider. The results showed that children with autism who displayed severe deficits in social skills could learn to self-manage responsivity to others in multiple community settings, and that such improvements were associated with concomitant reductions in disruptive behavior without the need for special intervention. The results are discussed in terms of their significance for improved development of social skills in children with autism.