Marine heatwaves intensification, expansion and departure into the permanent state over the Tropical Indian Ocean: A regional earth system model assessment

This study employed a regional earth system model, namely ROM over the CORDEX-SA domain, to investigate the future changes in the Marine heatwaves (MHWs) with respect to the historical baseline period (1976–2005) in the three time-slices, explicitly, near future (NRF; 2010–2039), middle future (MDF;2040–2069), and far future (FRF; 2070–2099) under two emission scenarios, Representative Concentration Pathway (RCP4.5 and RCP8.5). For the historical period, ROM showed a reasonable agreement with observed MHWs metrics and their trends and outperformed the forcing General Circulation Model and Multi-Model Ensemble of CMIP5 models. The future MHWs are expected to increase in intensity and duration. The continuous lengthening of MHWs duration leads to a permanent MHW state condition with strong spatial variability in its appearance. The first permanent MHW will emerge in both RCPs, while the absolute permanent MHW state is mainly visible in RCP8.5. The genesis and augmentation in the MHWs intensity is associated with local air-sea fluxes, however, in the long term, the increase in the mean SST in the future led to the rise of MHWs activity. The diagnosis of El Niño Southern Oscillation teleconnection and Indian Ocean Dipole on the MHWs is investigated. During the El Niño regime, not only did the proportion of the Tropical Indian Ocean experiencing MHWs increase but also an increase in the intensity is evident. IOD controls the MHWs metrics in the proximity of the western box and eastern box during its positive and negative phases

Analyzing future marine cold spells in the tropical Indian Ocean: Insights from a regional Earth system model

In this study, a future projection of marine cold spells (MCSs) over the tropical Indian Ocean is made using a fully coupled regional Earth system model, namely ROM, under two representative concentration pathways (RCPs): RCP4.5 and RCP8.5. In both RCPs, the future MCS properties have been estimated across three distinct time intervals: the near future (NF; 2010–2039), the middle future (MF; 2040–2069), and the far future (FF; 2070–2099). The future MCS computations were examined with respect to fixed historical baseline periods and varying baseline periods. MCSs were frequent, intense, and prolonged during the historical period. ROM effectively simulated these historical MCS metrics and their trends and outperformed the forcing general circulation model as well as the multimodel ensemble mean of Coupled Model Intercomparison Project phase 5 models. In the future, MCSs will cease to occur in ∼13% (4%), ∼56% (66%) and ∼69% (93%) of the area of the tropical Indian Ocean in the NF, MF, and FF respectively under the RCP4.5 (RCP8.5) scenario using a fixed historical baseline period. This departure of MCSs led to the disappearance of events, first identified over the Arabian Sea in both RCPs. The decrease in net heat flux and increase in wind speed contribute to the genesis and severity of MCS events. Further, during the El Niño regime, the MCS events dramatically decrease due to the basin-wide warming, but during the La Niña phase, the MCS intensity and spatial range increase. This study further investigates the sensitivity of MCSs with the choice of baseline period. Adopting varying baseline periods over time does not result in the disappearance of MCSs but does produce declining trends in MCS activity, highlighting the need for careful consideration in choosing a baseline period

Poisoning deaths in Poland : types and frequencies reported in Łódź, Kraków, Sosnowiec, Gdańsk, Wrocław and Poznań during 2009-2013

Objectives: The aim of this study has been to assess the characteristics of acute poisoning deaths in Poland over a period of time 2009–2013. Material and Methods: The analysis was based on the data obtained from the patient records stored in toxicology departments in 6 cities – Łódź, Kraków, Sosnowiec, Gdańsk, Wrocław and Poznań. Toxicological analyses were routinely performed in blood and/or urine. Major toxic substances were classified to one of the following categories: pharmaceuticals, alcohol group poisonings (ethanol and other alcohols), gases, solvents, drugs of abuse, pesticides, metals, mushrooms, others. Cases were analyzed according to the following criteria: year, age and gender of analyzed patients, toxic substance category and type of poisoning. The recorded fatal poisonings were classified according to the International Classification of Diseases. Results: The record of 261 deaths were retrospectively reviewed. There were 187 males (71.64%) and 74 females (28.36%) and the male to female ratio was 2.52. Alcohol group poisonings were more frequently responsible for deaths in men compared to all poisonings, 91.1% vs. 71.6%, respectively (p < 0.05), and pharmaceutical agents were more frequently responsible for deaths in women, 47.4% vs. 28.4%, (p < 0.05). Methanol was the most common agent in the alcohol group poisonings, accounting for 43.75% (N = 49), followed by ethylene glycol, 39.29% (N = 44), and ethanol, 16.96% (N = 19). Conclusions: Epidemiological profile data from investigation of poisoning deaths in Poland may be very useful for the development of preventive programs. Int J Occup Med Environ Health 2017;30(6):897–90

Antiplatelet therapy with aspirin, clopidogrel, and dipyridamole versus clopidogrel alone or aspirin and dipyridamole in patients with acute cerebral ischaemia (TARDIS): a randomised, open-label, phase 3 superiority trial

Background: Intensive antiplatelet therapy with three agents might be more effective than guideline treatment for preventing recurrent events in patients with acute cerebral ischaemia. We aimed to compare the safety and efficacy of intensive antiplatelet therapy (combined aspirin, clopidogrel, and dipyridamole) with that of guideline-based antiplatelet therapy. Methods: We did an international, prospective, randomised, open-label, blinded-endpoint trial in adult participants with ischaemic stroke or transient ischaemic attack (TIA) within 48 h of onset. Participants were assigned in a 1:1 ratio using computer randomisation to receive loading doses and then 30 days of intensive antiplatelet therapy (combined aspirin 75 mg, clopidogrel 75 mg, and dipyridamole 200 mg twice daily) or guideline-based therapy (comprising either clopidogrel alone or combined aspirin and dipyridamole). Randomisation was stratified by country and index event, and minimised with prognostic baseline factors, medication use, time to randomisation, stroke-related factors, and thrombolysis. The ordinal primary outcome was the combined incidence and severity of any recurrent stroke (ischaemic or haemorrhagic; assessed using the modified Rankin Scale) or TIA within 90 days, as assessed by central telephone follow-up with masking to treatment assignment, and analysed by intention to treat. This trial is registered with the ISRCTN registry, number ISRCTN47823388. Findings: 3096 participants (1556 in the intensive antiplatelet therapy group, 1540 in the guideline antiplatelet therapy group) were recruited from 106 hospitals in four countries between April 7, 2009, and March 18, 2016. The trial was stopped early on the recommendation of the data monitoring committee. The incidence and severity of recurrent stroke or TIA did not differ between intensive and guideline therapy (93 [6%] participants vs 105 [7%]; adjusted common odds ratio [cOR] 0·90, 95% CI 0·67–1·20, p=0·47). By contrast, intensive antiplatelet therapy was associated with more, and more severe, bleeding (adjusted cOR 2·54, 95% CI 2·05–3·16, p<0·0001). Interpretation: Among patients with recent cerebral ischaemia, intensive antiplatelet therapy did not reduce the incidence and severity of recurrent stroke or TIA, but did significantly increase the risk of major bleeding. Triple antiplatelet therapy should not be used in routine clinical practice

Efficacy and Safety of Respiratory Syncytial Virus (RSV) Prefusion F Protein Vaccine (RSVPreF3 OA) in Older Adults Over 2 RSV Seasons

Background. The adjuvanted RSV prefusion F protein–based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD) in ≥60-years-olds over 1 RSV season. We evaluated efficacy and safety of 1 RSVPreF3 OA dose and of 2 RSVPreF3 OA doses given 1 year apart against RSV-LRTD over 2 RSV seasons post–dose 1. Methods. In this phase 3, blinded trial, ≥60-year-olds were randomized (1:1) to receive RSVPreF3 OA or placebo pre–season 1. RSVPreF3 OA recipients were re-randomized (1:1) to receive a second RSVPreF3 OA dose (RSV_revaccination group) or placebo (RSV_1dose group) pre–season 2; participants who received placebo pre–season 1 received placebo pre–season 2 (placebo group). Efficacy of both vaccine regimens against RSV-LRTD was evaluated over 2 seasons combined (confirmatory secondary objective, success criterion: lower limits of 2-sided CIs around efficacy estimates >20%). Results. The efficacy analysis comprised 24 967 participants (RSV_1dose: 6227; RSV_revaccination: 6242; placebo: 12 498). Median efficacy follow-up was 17.8 months. Efficacy over 2 seasons of 1 RSVPreF3 OA dose was 67.2% (97.5% CI: 48.2–80.0%) against RSV-LRTD and 78.8% (95% CI: 52.6–92.0%) against severe RSV-LRTD. Efficacy over 2 seasons of a first dose followed by revaccination was 67.1% (97.5% CI: 48.1–80.0%) against RSV-LRTD and 78.8% (95% CI: 52.5–92.0%) against severe RSV-LRTD. Reactogenicity/safety of the revaccination dose were similar to dose 1. Conclusions. One RSVPreF3 OA dose was efficacious against RSV-LRTD over 2 RSV seasons in ≥60-year-olds. Revaccination 1 year post–dose 1 was well tolerated but did not seem to provide additional efficacy benefit in the overall study population. Clinical Trials Registration. ClinicalTrials.gov: NCT04886596

The respiratory syncytial virus prefusion F protein vaccine attenuates the severity of respiratory syncytial virus‐associated disease in breakthrough infections in adults ≥60 years of age

Background: Respiratory syncytial virus (RSV) is a contagious pathogen causing acute respiratory infections (ARIs). Symptoms range from mild upper respiratory tract infections to potentially life-threatening lower respiratory tract disease (LRTD). In adults ≥60 years old, vaccine efficacy of a candidate vaccine for older adults (RSVPreF3 OA) was 71.7% against RSV-ARI and 82.6% against RSV-LRTD (AReSVi-006/NCT04886596). We present the patient-reported outcomes (PROs) from the same trial at the end of the first RSV season in the northern hemisphere (April 2022). Methods: In this phase 3 trial, adults aged ≥60 years were randomized (1:1) to receive one dose of RSVPreF3 OA vaccine or placebo. PROs were assessed using InFLUenza Patient-Reported Outcome (FLU-PRO), Short Form-12 (SF-12), and EuroQol-5 Dimension (EQ-5D) questionnaires. Peak FLU-PRO Chest/Respiratory scores during the first 7 days from ARI episode onset were compared using a Wilcoxon test. Least squares mean (LSMean) of SF-12 physical functioning (PF) and EQ-5D health utility scores were estimated using mixed effects models. Results: In the RSVPreF3 OA group (N = 12,466), 27 first RSV-ARI episodes were observed versus 95 in the Placebo group (N = 12,494). Median peak FLU-PRO Chest/Respiratory scores were lower in RSVPreF3 OA (1.07) versus Placebo group (1.86); p = 0.0258. LSMean group differences for the PF and EQ-5D health utility score were 7.00 (95% confidence interval [CI]: −9.86, 23.85; p = 0.4125) and 0.0786 (95% CI: −0.0340, 0.1913; p = 0.1695). Conclusions: The RSVPreF3 OA vaccine, in addition to preventing infection, attenuated the severity of RSV-associated symptoms in breakthrough infections, with trends of reduced impact on PF and health utility

Respiratory Syncytial Virus Prefusion F Protein Vaccine Is Efficacious in Older Adults With Underlying Medical Conditions

Background Older adults with chronic cardiorespiratory or endocrine/metabolic conditions are at increased risk of respiratory syncytial virus (RSV)-related acute respiratory illness (RSV-ARI) and severe respiratory disease. In an ongoing, randomized, placebo-controlled, multicountry, phase 3 trial in &amp; GE;60-year-old participants, an AS01E-adjuvanted RSV prefusion F protein-based vaccine (RSVPreF3 OA) was efficacious against RSV-related lower respiratory tract disease (RSV-LRTD), severe RSV-LRTD, and RSV-ARI. We evaluated efficacy and immunogenicity among participants with coexisting cardiorespiratory or endocrine/metabolic conditions that increase the risk of severe RSV disease ("conditions of interest").Methods Medically stable &amp; GE;60-year-old participants received 1 dose of RSVPreF3 OA or placebo. Efficacy against first RSV-LRTD and RSV-ARI episodes was assessed in subgroups with/without coexisting cardiorespiratory or endocrine/metabolic conditions of interest. Immunogenicity was analyzed post hoc in these subgroups.Results In total, 12 467 participants received RSVPreF3 OA and 12 499 received placebo. Of these, 39.6% (RSVPreF3 OA) and 38.9% (placebo) had &amp; GE;1 coexisting condition of interest. The median efficacy follow-up was 6.7 months. Efficacy against RSV-LRTD was high in participants with &amp; GE;1 condition of interest (94.6%), &amp; GE;1 cardiorespiratory (92.1%), &amp; GE;1 endocrine/metabolic (100%), and &amp; GE;2 conditions of interest (92.0%). Efficacy against RSV-ARI was 81.0% in participants with &amp; GE;1 condition of interest (88.1% for cardiorespiratory, 79.4% for endocrine/metabolic conditions) and 88.0% in participants with &amp; GE;2 conditions of interest. Postvaccination neutralizing titers were at least as high in participants with &amp; GE;1 condition of interest as in those without.Conclusions RSVPreF3 OA was efficacious against RSV-LRTD and RSV-ARI in older adults with coexisting medical conditions associated with an increased risk of severe RSV disease.Clinical Trials Registration ClinicalTrials.gov: NCT04886596.Graphical Abstrac

Cerebral malaria in children: using the retina to study the brain

Cerebral malaria is a dangerous complication of Plasmodium falciparum infection, which takes a devastating toll on children in sub-Saharan Africa. Although autopsy studies have improved understanding of cerebral malaria pathology in fatal cases, information about in vivo neurovascular pathogenesis is scarce because brain tissue is inaccessible in life. Surrogate markers may provide insight into pathogenesis and thereby facilitate clinical studies with the ultimate aim of improving the treatment and prognosis of cerebral malaria. The retina is an attractive source of potential surrogate markers for paediatric cerebral malaria because, in this condition, the retina seems to sustain microvascular damage similar to that of the brain. In paediatric cerebral malaria a combination of retinal signs correlates, in fatal cases, with the severity of brain pathology, and has diagnostic and prognostic significance. Unlike the brain, the retina is accessible to high-resolution, non-invasive imaging. We aimed to determine the extent to which paediatric malarial retinopathy reflects cerebrovascular damage by reviewing the literature to compare retinal and cerebral manifestations of retinopathy-positive paediatric cerebral malaria. We then compared retina and brain in terms of anatomical and physiological features that could help to account for similarities and differences in vascular pathology. These comparisons address the question of whether it is biologically plausible to draw conclusions about unseen cerebral vascular pathogenesis from the visible retinal vasculature in retinopathy-positive paediatric cerebral malaria. Our work addresses an important cause of death and neurodisability in sub-Saharan Africa. We critically appraise evidence for associations between retina and brain neurovasculature in health and disease, and in the process we develop new hypotheses about why these vascular beds are susceptible to sequestration of parasitized erythrocytes