Safe shortening of antibiotic treatment duration for complicated bacteraemia (SAFE trial): protocol for a randomised, controlled, open-label, non-inferiority trial comparing 4 and 6 weeks of antibiotic treatment.

Introduction: A major knowledge gap in the treatment of complicated bacteraemia (SAB) is the optimal duration of antibiotic therapy. Safe shortening of antibiotic therapy has the potential to reduce adverse drug events, length of hospital stay and costs. The objective of the SAFE trial is to evaluate whether 4 weeks of antibiotic therapy is non-inferior to 6 weeks in patients with complicated SAB.

Correction: Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study.

[This corrects the article DOI: 10.1371/journal.pmed.

Immunogenicity and reactogenicity of SARS-CoV-2 vaccines in people living with HIV in the Netherlands: A nationwide prospective cohort study.

Background: Vaccines can be less immunogenic in people living with HIV (PLWH), but for SARS-CoV-2 vaccinations this is unknown. In this study we set out to investigate, for the vaccines currently approved in the Netherlands, the immunogenicity and reactogenicity of SARS-CoV-2 vaccinations in PLWH.

Methods And Findings: We conducted a prospective cohort study to examine the immunogenicity of BNT162b2, mRNA-1273, ChAdOx1-S, and Ad26.

Timely administration of tocilizumab improves outcome of hospitalized COVID-19 patients.

Introduction: The aim of this study was to determine the efficacy of early tocilizumab treatment for hospitalized patients with COVID-19 disease.

Methods: Open-label randomized phase II clinical trial investigating tocilizumab in patients with proven COVID-19 admitted to the general ward and in need of supplemental oxygen. The primary endpoint of the study was 30-day mortality with a prespecified 2-sided significance level of α = 0.

Carotid Intima-Media Thickness Progression as Surrogate Marker for Cardiovascular Risk: Meta-Analysis of 119 Clinical Trials Involving 100 667 Patients.

Background: To quantify the association between effects of interventions on carotid intima-media thickness (cIMT) progression and their effects on cardiovascular disease (CVD) risk.

Methods: We systematically collated data from randomized, controlled trials. cIMT was assessed as the mean value at the common-carotid-artery; if unavailable, the maximum value at the common-carotid-artery or other cIMT measures were used.

Limited Generalizability of Registration Trials in Hepatitis C: A Nationwide Cohort Study.

Background: Approval of drugs in chronic hepatitis C is supported by registration trials. These trials might have limited generalizability through use of strict eligibility criteria. We compared effectiveness and safety of real world hepatitis C patients eligible and ineligible for registration trials.

Virological and Social Outcomes of HIV-Infected Adolescents and Young Adults in The Netherlands Before and After Transition to Adult Care.

Background: As a result of effective combination antiretroviral therapy (cART) and advanced supportive healthcare, a growing number of human immunodeficiency virus (HIV)-infected children survive into adulthood. The period of transition to adult care is often associated with impaired adherence to treatment and discontinuity of care. We aimed to evaluate virological and social outcomes of HIV-infected adolescents and young adults (AYAs) before and after transition, and explore which factors are associated with virological failure.

Zidovudine/lamivudine but not nevirapine in combination with lopinavir/ritonavir decreases subcutaneous adipose tissue mitochondrial DNA.

Objective: No randomized study has prospectively followed subcutaneous adipose tissue mitochondrial DNA (mtDNA) changes when starting thymidine nucleoside reverse transcriptase inhibitors (tNRTIs).

Design: The Metabolic Effects of DIfferent CLasses of AntiretroviralS study randomized HIV-positive, treatment-naive male participants to start lopinavir/ritonavir (LPVr) with either zidovudine/lamivudine (ZDV/3TC) or nevirapine (NVP).

Methods: Regional body fat was assessed by dual energy x-ray absorptiometry and abdominal computed tomography at months 0, 3, 12, 24 and 36.

Temporary antiretroviral treatment during primary HIV-1 infection has a positive impact on health-related quality of life: data from the Primo-SHM cohort study.

Objectives: The aim of the study was to compare health-related quality of life (HRQL) over 96 weeks in patients receiving no treatment or 24 or 60 weeks of combination antiretroviral therapy (cART) during primary HIV-1 infection (PHI).

Methods: A multicentre prospective cohort study of PHI patients, with an embedded randomized trial, was carried out. HRQL was assessed with the Medical Outcomes Study Health Survey for HIV (MOS-HIV) and a symptom checklist administered at weeks 0, 8, 24, 36, 48, 60, 72, 84 and 96.

The lopinavir/ritonavir-associated rise in lipids is not related to lopinavir or ritonavir plasma concentration.

Background: The relationship between lopinavir plasma concentration and the magnitude of lipid elevation after initiation of lopinavir/ritonavir-containing antiretroviral therapy is unclear. The aim of this study was to determine the relationship between drug concentration and lipid changes in two patient cohorts.

Methods: First, we analysed, in an outpatient cohort, the correlation between percentage lipid changes and lopinavir concentration, measured at least 2 weeks or more after initiation of lopinavir/ritonavir.

Brain abscess associated with Aggregatibacter actinomycetemcomitans: case report and review of literature.

Introduction: Aggregatibacter actinomycetemcomitans is considered a major pathogen in localized and generalized aggressive periodontitis. A. actinomycetemcomitans has been found in various extra oral infections and most frequently in endocarditis.

Insulin sensitivity in multiple pathways is differently affected during zidovudine/lamivudine-containing compared with NRTI-sparing combination antiretroviral therapy.

Objective: The extent and manner by which HIV nucleoside reverse transcriptase inhibitors contribute to insulin resistance is unclear. We evaluated the effect of zidovudine/lamivudine (ZDV/3TC) on glucose metabolism.

Methods: combination antiretroviral therapy-naive men were randomized to lopinavir/ritonavir (LPV/r, 400/100 mg twice a day) + ZDV/3TC or LPV/r (533/133 mg twice a day) + nevirapine (NVP).

Baseline lipid levels rather than the presence of reported body shape changes determine the degree of improvement in lipid levels after switching to atazanavir.

Purpose: To study factors influencing lipid changes after switching to atazanavir (ATV) and the effectiveness of ATV in maintaining virus suppression.

Methods: Retrospective cohort study in patients with viral suppression, comparing patients switching to ATV with those continuing combination antiretroviral therapy (cART). Outcome measures were 48-week total (TC), high-density (HDL) and low-density lipoprotein (LDL) cholesterol, and triglycerides (TG) changes, stratified for dyslipidemia and lipodystrophy and virological failure (time to first of two consecutive detectable HIV RNA).

Zidovudine/lamivudine for HIV-1 infection contributes to limb fat loss.

Background: Lipoatrophy is known to be associated with stavudine as part of the treatment for HIV infection, but it is less clear if this serious side effect is also related to other nucleoside reverse transcriptase inhibitors like zidovudine. We aimed to determine whether zidovudine-sparing first-line antiretroviral therapy would lead to less lipoatrophy and other metabolic changes than zidovudine-containing therapy.

Methodology/principal Findings: Fifty antiretroviral therapy-naïve HIV-1 infected men with an indication to start antiretroviral therapy were included in a randomized single blinded clinical trial.

First line zidovudine/lamivudine/lopinavir/ritonavir leads to greater bone loss compared to nevirapine/lopinavir/ritonavir.

Objective: We studied changes in bone mineral density (BMD) and bone turnover after initiation of combination antiretroviral therapy (cART) and the contribution of zidovudine/lamivudine (ZDV/3TC) in particular.

Design: Randomized clinical trial comparing lopinavir/ritonavir(LPV/r) + ZDV/3TC with LPV/r + nevirapine (NVP) in 50 cART-naive men.

Methods: Dual energy X-ray absorptiometry (DXA) and quantitative computed tomography scans (QCT) were performed at baseline and 3, 12, and 24 months after cART initiation.

Increase in carotid artery intima-media thickness and arterial stiffness but improvement in several markers of endothelial function after initiation of antiretroviral therapy.

Background: The risk of cardiovascular disease in human immunodeficiency virus (HIV)-infected patients is an increasing concern. We studied the changes in vascular properties after the initiation of combination antiretroviral therapy (cART) as well as the contribution of different drug classes.

Methods: cART-naive men were randomized to receive either lopinavir/ritonavir (LPV/r) plus zidovudine/lamivudine (ZDV/3TC) (n = 19) or LPV/r plus nevirapine (NVP) (n = 18).

Carotid intima-media thickness and arterial stiffness in HIV-infected patients: the role of HIV, antiretroviral therapy, and lipodystrophy.

Objectives: HIV-infected patients using combination antiretroviral therapy (ART) have an increased cardiovascular risk. We aimed to identify the effects of HIV, ART, and lipodystrophy (LD) on carotid artery intima-media thickness (C-IMT), a surrogate measure of atherosclerosis, and arterial stiffness, a marker of cardiovascular risk.

Design: Case-control study of 77 HIV-infected men (55 exposed to ART, 22 ART naive, and 23 with LD) and 52 controls.

Managing rural emergency department overcrowding.

Emergency department visits reached more than 115 million in 2005, a 30% increase over the past decade. Although much has been written regarding these numbers, little attention has been focused on the impact of overcrowding and volume increases on rural emergency departments. Rural emergency departments face challenges unlike their urban counterparts that make implementation of current overcrowding strategies difficult or impossible.

Zidovudine/lamivudine contributes to insulin resistance within 3 months of starting combination antiretroviral therapy.

Background: Patients with antiretroviral therapy (ART)-associated lipodystrophy frequently have disturbances in glucose metabolism associated with insulin resistance. It is not known whether changes in body composition are necessary for the development of these disturbances in ART-naive patients starting treatment with different combination ART regimens.

Methods: Glucose metabolism and body composition were assessed before and after 3 months of ART in a prospective randomized clinical trial of HIV-1-positive ART-naive men taking lopinavir/ritonavir within either a nucleoside reverse transcriptase inhibitor (NRTI)-containing regimen (zidovudine/lamivudine; n = 11) or a NRTI-sparing regimen (nevirapine; n = 9).

[Optimalisation of the antibiotic policy in The Netherlands. XI. The national electronic antibiotic guide'SWAB-ID' for use in hospitals].

The 'Stichting Werkgroep Antibioticabeleid' (Dutch Working Party on Antibiotic Policy) has developed an electronic national antibiotic guide for the antibiotic treatment and prophylaxis of common infectious diseases in hospitals. This guide also contains information on the most important characteristics of antimicrobial drugs. Advice on antibiotic treatment is based on existing national evidence-based guidelines, where available.

Cutting edge: Rapid recovery of NKT cells upon institution of highly active antiretroviral therapy for HIV-1 infection.

CD1d-restricted NKT cells play important regulatory roles in various immune responses and are rapidly and selectively depleted upon infection with HIV-1. The cause of this selective depletion is incompletely understood, although it is in part due to the high susceptibility of CD4+ NKT cells to direct infection and subsequent cell death by HIV-1. Here, we demonstrate that highly active antiretroviral therapy (HAART) results in the rapid recovery of predominantly CD4(-) NKT cells with kinetics that are strikingly similar to those of mainstream T cells.

[Hypoglycemia caused by oral hypoglycemic agents: risk of relapse after normalisation of blood glucose].

Three patients, two women aged 83 and 79 years, and one man aged 61 years, known with diabetes mellitus and using oral blood glucose-lowering drugs, presented with impaired consciousness due to hypoglycaemia. Two of them were admitted and recovered well after recurrence of hypoglycaemia in one and discontinuation of medication in both. The third patient had prolonged hypoglycaemia and died three weeks later, still unconscious, due to pneumonia.