Vaccine efficacy of ALVAC-HIV and bivalent subtype C gp120–MF59 in adults

BACKGROUND : A safe, effective vaccine is essential to eradicating human immunodeficiency virus (HIV) infection. A canarypox–protein HIV vaccine regimen (ALVAC-HIV plus AIDSVAX B/E) showed modest efficacy in reducing infection in Thailand. An analogous regimen using HIV-1 subtype C virus showed potent humoral and cellular responses in a phase 1–2a trial in South Africa. Efficacy data and additional safety data were needed for this regimen in a larger population in South Africa. METHODS : In this phase 2b–3 trial, we randomly assigned 5404 adults without HIV-1 infection to receive the vaccine (2704 participants) or placebo (2700 participants). The vaccine regimen consisted of injections of ALVAC-HIV at months 0 and 1, followed by four booster injections of ALVAC-HIV plus bivalent subtype C gp120–MF59 adjuvant at months 3, 6, 12, and 18. The primary efficacy outcome was the occurrence of HIV-1 infection from randomization to 24 months. RESULTS : In January 2020, prespecified criteria for non-efficacy were met at an interim analysis; further vaccinations were subsequently halted. The median age of the trial participants was 24 years; 70% of the participants were women. The incidence of adverse events was similar in the vaccine and placebo groups. During the 24-month followup, HIV-1 infection was diagnosed in 138 participants in the vaccine group and in 133 in the placebo group (hazard ratio, 1.02; 95% confidence interval, 0.81 to 1.30; P = 0.84). CONCLUSIONS : The ALVAC–gp120 regimen did not prevent HIV-1 infection among participants in South Africa despite previous evidence of immunogenicity.Supported by grants (HHSN272201300033C and HHSN272201600012C) to Novartis Vaccines and Diagnostics (now part of the GlaxoSmithKline [GSK] Biologicals) by the National Institute of Allergy and Infectious Diseases (NIAID) of the National Institutes of Health (NIH) for the selection and process development of the two gp120 envelope proteins TV1.C and 1086.C; by the Bill and Melinda Gates Foundation Global Health Grant (OPP1017604) and NIAID for the manufacture and release of the gp120 clinical grade material; and by U.S. Public Health Service Grants — UM1 AI068614 to the HIV Vaccine Trials Network (HVTN), UM1 AI068635 to the HVTN Statistical and Data Management Center, and UM1 AI068618 to the HVTN Laboratory Center — from the NIAID. GSK Biologicals contributed financially to the provision of preexposure prophylaxis to trial participants. The South African Medical Research Council supported its affiliated research sites.http://www.nejm.orgam2022School of Health Systems and Public Health (SHSPH

An electronic surveillance tool for catheter-associated urinary tract infection in intensive care units

Pod terminom nedonošče označavamo novorođenče koje je rođeno prije 37.tjedna gestacije, ili prije 259. dana od prvog dana ženine posljednje menstruacije. Unazad šezdeset godina termin nedonoščeta obuhvaćao je i djecu niske porođajne mase (< 2500 g),a u posljednja dva desetljeća za takvu djecu koristi se naziv nedostašče. Početak trudnoće se klinički određuje računanjem od datuma zadnje menstruacije te procijenjena na ovaj način prosječno iznosi 280 dana ili 40 tjedana, odnosno 10 lunarnih mjeseci. Prenatalni razvoj čovjeka se dijeli na embrionalno i fetalno razdoblje. Embrionalno razdoblje traje 8 tjedana i u to vrijeme formiraju se ljudski embrij i posteljica. Prema RonanuO'Rahillyu i Fabioli Muller embrionalno razdoblje ima 23 Carneige stadija. Na kraju te faze fetus je težak samo 2,8 grama. Fetalno razdoblje traje oko 30 tjedana i tad se u potpunosti počinju razvijati strukture i funkcije nezrelih organskih sustava formiranih tijekom embrionalnog razvoja. Uspješan prijelaz iz fetalnog u neonatalni život zahtijeva složenu interakciju između sljedećih sustava: respiratornog, kardiovaskularnog, imunološkog i termoregulacijskog. Zbog nerazvijenosti organskih sustava ta promjena je otežana nedonoščetu te se ono smješta na specijalizirani odjel neonatologije. Neonatologija je specijaliziran odjel za njegu naših najmanjih i najosjetljivijih pacijenata. Rad medicinske sestre na neonatologiji je vrlo odgovoran i zahtijeva timski i uigran rad kako bi se pružila najadekvatnija skrb.Premature born baby is defined as every newborn born before the 37th week of gestation or 259 days after the first day of woman's last menstruation. In the 1960's, term premature include dinfants with low birth weight (< 2500g) born around their estimated due date (born after 37 th week of gestation). Bythe 2000's term for low birth weight infants became separate term. Clinically, pregnancy starts from the last womans menstruation, estimated this way it lasts 280 days, or 40 weeks or 10 lunar months. Human prenatal development divides into embryonic and fetal periods. The duration of the embryonic period is 8 weeks, during which time a human embryo and placenta are formed. According to RonanO'Rahilly and Fabiola Muller, an embryonic period can be divided into 23 Carneige stages. At the end of the stage, the fetus weighs only 2.8 grams. Fetal period takes about 30 weeks during which time the body structures begin to fully form and function after the start of process. Successful transition from fetal to neonatal life requires a complex interaction between the following systems: respiratory, cardiovascular immune and thermoregulatory. Due to under developed organ systems, this change is difficult for preterm babies and therefore they are placed into neonatal intensive care also known as NICU. NICU specializes in the care of our smallest and most sensitive patients. Nurses workin neonatology unit is very responsible and seeks team work in order to provide the most appropriate care

Correlates of virulence in a frog-killing fungal pathogen: evidence from a California amphibian decline

The fungal pathogen Batrachochytrium dendrobatidis (Bd) has caused declines and extinctions in amphibians worldwide, and there is increasing evidence that some strains of this pathogen are more virulent than others. While a number of putative virulence factors have been identified, few studies link these factors to specific epizootic events. We documented a dramatic decline in juvenile frogs in a Bd-infected population of Cascades frogs (Rana cascadae) in the mountains of northern California and used a laboratory experiment to show that Bd isolated in the midst of this decline induced higher mortality than Bd isolated from a more stable population of the same species of frog. This highly virulent Bd isolate was more toxic to immune cells and attained higher density in liquid culture than comparable isolates. Genomic analyses revealed that this isolate is nested within the global panzootic lineage and exhibited unusual genomic patterns, including increased copy numbers of many chromosomal segments. This study integrates data from multiple sources to suggest specific phenotypic and genomic characteristics of the pathogen that may be linked to disease-related declines