Nevirapine and Efavirenz Elicit Different Changes in Lipid Profiles in Antiretroviral- Therapy-Naive Patients Infected with HIV-1

BACKGROUND: Patients infected with HIV-1 initiating antiretroviral therapy (ART) containing a non-nucleoside reverse transcriptase inhibitor (NNRTI) show presumably fewer atherogenic lipid changes than those initiating most ARTs containing a protease inhibitor. We analysed whether lipid changes differed between the two most commonly used NNRTIs, nevirapine (NVP) and efavirenz (EFV). METHODS AND FINDINGS: Prospective analysis of lipids and lipoproteins was performed in patients enrolled in the NVP and EFV treatment groups of the 2NN study who remained on allocated treatment during 48 wk of follow-up. Patients were allocated to NVP (n = 417), or EFV (n = 289) in combination with stavudine and lamivudine. The primary endpoint was percentage change over 48 wk in high-density lipoprotein cholesterol (HDL-c), total cholesterol (TC), TC:HDL-c ratio, non-HDL-c, low-density lipoprotein cholesterol, and triglycerides. The increase of HDL-c was significantly larger for patients receiving NVP (42.5%) than for patients receiving EFV (33.7%; p = 0.036), while the increase in TC was lower (26.9% and 31.1%, respectively; p = 0.073), resulting in a decrease of the TC:HDL-c ratio for patients receiving NVP (−4.1%) and an increase for patients receiving EFV (+5.9%; p < 0.001). The increase of non-HDL-c was smaller for patients receiving NVP (24.7%) than for patients receiving EFV (33.6%; p = 0.007), as were the increases of triglycerides (20.1% and 49.0%, respectively; p < 0.001) and low-density lipoprotein cholesterol (35.0% and 40.0%, respectively; p = 0.378). These differences remained, or even increased, after adjusting for changes in HIV-1 RNA and CD4+ cell levels, indicating an effect of the drugs on lipids over and above that which may be explained by suppression of HIV-1 infection. The increases in HDL-c were of the same order of magnitude as those seen with the use of the investigational HDL-c-increasing drugs. CONCLUSION: NVP-containing ART shows larger increases in HDL-c and decreases in TC:HDL-c ratio than an EFV-containing regimen. Based on these findings, protease-inhibitor-sparing regimens based on non-nucleoside reverse transcriptase inhibitor, particularly those containing NVP, may be expected to result in a reduced risk of coronary heart disease

Feeding mice with diets containing mercury-contaminated fish flesh from French Guiana: a model for the mercurial intoxication of the Wayana Amerindians

International audienc

Sickle Cell Disease Treatment with Arginine Therapy (STArT): study protocol for a phase 3 randomized controlled trial.

BACKGROUND: Despite substantial illness burden and healthcare utilization conferred by pain from vaso-occlusive episodes (VOE) in children with sickle cell disease (SCD), disease-modifying therapies to effectively treat SCD-VOE are lacking. The aim of the Sickle Cell Disease Treatment with Arginine Therapy (STArT) Trial is to provide definitive evidence regarding the efficacy of intravenous arginine as a treatment for acute SCD-VOE among children, adolescents, and young adults. METHODS: STArT is a double-blind, placebo-controlled, randomized, phase 3, multicenter trial of intravenous arginine therapy in 360 children, adolescents, and young adults who present with SCD-VOE. The STArT Trial is being conducted at 10 sites in the USA through the Pediatric Emergency Care Applied Research Network (PECARN). Enrollment began in 2021 and will continue for 5 years. Within 12 h of receiving their first dose of intravenous opioids, enrolled participants are randomized 1:1 to receive either (1) a one-time loading dose of L-arginine (200 mg/kg with a maximum of 20 g) administered intravenously followed by a standard dose of 100 mg/kg (maximum 10 g) three times a day or (2) a one-time placebo loading dose of normal saline followed by normal saline three times per day at equivalent volumes and duration as the study drug. Participants, research staff, and investigators are blinded to the participant\u27s randomization. All clinical care is provided in accordance with the institution-specific standard of care for SCD-VOE based on the 2014 National Heart, Lung, and Blood Institute guidelines. The primary outcome is time to SCD-VOE pain crisis resolution, defined as the time (in hours) from study drug delivery to the last dose of parenteral opioid delivery. Secondary outcomes include total parental opioid use and patient-reported outcomes. In addition, the trial will characterize alterations in the arginine metabolome and mitochondrial function in children with SCD-VOE. DISCUSSION: Building on the foundation of established relationships between emergency medicine providers and hematologists in a multicenter research network to ensure adequate participant accrual, the STArT Trial will provide definitive information about the efficacy of intravenous arginine for the treatment of SCD-VOE for children. TRIAL REGISTRATION: The STArT Trial was registered in ClinicalTrials.gov on April 9, 2021, and enrollment began on June 21, 2021 (NCT04839354)

Nanosecond Yb fibre laser milling of aluminium: effect of process parameters on the achievable surface finish and machining efficiency

Pulsed ytterbium-doped fibre lasers based on a master oscillator power amplifier (MOPA) architecture possess attractive characteristics over their Q-switched diode-pumped solid-state counterparts. These include a relatively low cost of ownership and a flexible operating window with respect to the pulse duration, shape and repetition rate. For micro machining applications, given this inherent large processing window available with respect to the pulse characteristics, the effect of process parameters on particular machining outcomes needs to be investigated systematically. In this context, this paper considers the effect of a number of factors on the achievable material removal rate and surface roughness when processing aluminium with such fibre laser system operating at 1,064-nm wavelength and having built-in capabilities for selecting the duration of the delivered pulses in the nanosecond regime. The process parameters under investigation in this study were the pulse duration and repetition frequency, the pulse overlap, the scanning strategy and the distance between linear machined tracks. Initial results showed that, for pulse durations comprised between 25 and 140 ns, the specific frequency at which both the highest energy and average power are delivered leads to the maximum material removal rate (MRR) achievable and to high values of surface roughness. Following this, a design of experiments was conducted for a given pulse length with the aim of identifying an optimum combination of parameters with respect to the attained surface finish while operating at the frequency resulting in the highest MRR. This optimisation study resulted in a 60-% decrease in the achieved surface roughness and also showed that the distance between machined tracks had the highest influence on the surface finish

Development of surface roughness optimisation and prediction for the process of wire electro-discharge grinding

This paper investigates the technological capabilities of a hybrid micro machining process for performing wire electro-discharge grinding (WEDG). In particular, micro wire electrical discharge machining (μWEDM) is employed in combination with a rotating submergible spindle to perform WEDG. In this research, first a machining strategy for workpiece preparation is presented. Then, the effects of different machining setup parameters on the achievable surface finish after WEDG are investigated. In particular, an experimental study was conducted to identify the most statistically significant setup parameters for performing the main cut that affect the resulting surface quality. A signal-to-noise (S/N) ratio analysis was conducted to optimise the technological parameters for performing WEDG. By modifying the discharge energy for main cuts when performing WEDG surface finish comparable to that of μWEDM can be achieved. In addition, a simple and cost-effective method for on-the-machine estimation of resulting surface roughness is proposed. Especially, by applying inductive learning a surface roughness prediction model for WEDG can be generate based on data acquired by monitoring on-line the process

Racial and Ethnic Disparities in Nontraumatic Dental-Condition Visits to Emergency Departments and Physician Offices in the Wisconsin Medicaid Program

Background Nontraumatic dental condition (NTDC) visits occur in emergency departments (EDs) and physician offices (POs), but little is known about factors associated with NTDC visit rates to EDs and POs. Methods The authors analyzed all Medicaid dental claims in Wisconsin from 2001 through 2003 to examine factors associated with NTDC visits to EDs and POs. They performed bivariate and multivariable analyses. The independent variables they examined included race/ethnicity, age, sex, dental health professional shortage area (DHPSA) designation and urban influence code for county of residence. Results The authors evaluated 956,774 NTDC visits made during 1,718,006 person-years; 4.3 percent of visits occurred in EDs or POs. Native Americans, African-Americans and enrollees of unknown race/ethnicity had the highest unadjusted ED and PO visit rates for NTDCs. African-Americans, Native Americans, adults and residents in partial or entire DHPSAs had significantly higher adjusted rates of NTDC visits to EDs. The authors observed significantly higher adjusted NTDC visit rates to POs for Native Americans, adults and enrollees residing in entire DHPSAs, and a significantly lower adjusted rate among African-Americans. Conclusions Native Americans, those residing in entire DHPSAs and adults have significantly higher risks of NTDC visits to EDs and POs. African-Americans are at increased risk of making visits to EDs for NTDCs but at decreased risk of making visits to POs for NTDCs. Clinical Implications Reductions in Medicaid visits to EDs and POs and the associated costs might be achieved by improving dental care access and targeted educational strategies among minorities, DHPSA residents and adults