Real-world effectiveness of molnupiravir and nirmatrelvir/ritonavir as treatments for COVID-19 in patients at high risk

Background Using a retrospective cohort study design, we aimed to evaluate the effectiveness of molnupiravir and nirmatrelvir/ritonavir in patients with SARS-CoV-2 who were highly vulnerable. Methods The impact of each drug was determined via comparisons with age-matched control groups of patients positive for SARS-CoV-2 who did not receive oral antiviral therapy. Results Administration of molnupiravir significantly reduced the risk of hospitalization (odds ratio [OR], 0.40; P < .001) and death (OR, 0.31; P < .001) among these patients based on data adjusted for age, previous SARS-CoV-2 infection, vaccination status, and time elapsed since the most recent vaccination. The reductions in risk were most profound among elderly patients (≥75 years old) and among those with high levels of drug adherence. Administration of nirmatrelvir/ritonavir also resulted in significant reductions in the risk of hospitalization (OR, 0.31; P < .001) and death (OR, 0.28; P < .001). Similar to molnupiravir, the impact of nirmatrelvir/ritonavir was more substantial among elderly patients and in those with high levels of drug adherence. Conclusions Collectively, these real-world findings suggest that although the risks of hospitalization and death due to COVID-19 have been reduced, antivirals can provide additional benefits to members of highly vulnerable patient populations

Tobacco Use, Exposure to Secondhand Smoke, and Cessation Counseling Among Health Professions Students: Greek Data from the Global Health Professions Student Survey (GHPSS).

We conducted the GHPSS (Global Health Professions Student Survey) to obtain information regarding health profession students’ smoking habits and perceptions, exposure to secondhand smoke (SHS) as well as level of knowledge and training on tobacco use and smoking cessation counseling. GHPSS is a survey for third-year students in the following fields: health visitors, dentistry, medicine, nursing and/or pharmacy. The highest tobacco use prevalence rate and exposure to SHS were recorded among health visitor students with 46.4% and 33.3% respectively. The majority of the respondents believed that their profession serves as a role model for their patients. Formal training on cessation counseling ranged between 10.7% for health visitor students to 22.4% for nursing students. The relatively high percentage of health profession students who currently smoke and the alarmingly high percentage of those exposed to SHS indicate lack of concerted efforts for implementation and effective enforcement of the anti-tobacco policy measures. Despite its significance, formal training on cessation counseling for students is strikingly low. These results indicate the urgent need to train health professional students on tobacco cessation counseling and educate them on the dangers of tobacco use, SHS and the positively influential role they can play to affect their patients’ smoking habits

No need for secondary Pneumocystis jirovecii pneumonia prophylaxis in adult people living with HIV from Europe on ART with suppressed viraemia and a CD4 cell count greater than 100 cells/µL

Introduction: Since the beginning of the HIV epidemic in resource-rich countries, Pneumocystis jirovecii pneumonia (PjP) is one of the most frequent opportunistic AIDS-defining infections. The Collaboration of Observational HIV Epidemiological Research Europe (COHERE) has shown that primary Pneumocystis jirovecii Pneumonia (PjP) prophylaxis can be safely withdrawn in patients with CD4 counts of 100 to 200 cells/µL if plasma HIV-RNA is suppressed on combination antiretroviral therapy. Whether this holds true for secondary prophylaxis is not known, and this has proved difficult to determine due to the much lower population at risk. Methods: We estimated the incidence of secondary PjP by including patient data collected from 1998 to 2015 from the COHERE cohort collaboration according to time-updated CD4 counts, HIV-RNA and use of PjP prophylaxis in persons >16 years of age. We fitted a Poisson generalized additive model in which the smoothed effect of CD4 was modelled by a restricted cubic spline, and HIV-RNA was stratified as low (10,000copies/mL). Results: There were 373 recurrences of PjP during 74,295 person-years (py) in 10,476 patients. The PjP incidence in the different plasma HIV-RNA strata differed significantly and was lowest in the low stratum. For patients off prophylaxis with CD4 counts between 100 and 200 cells/µL and HIV-RNA below 400 copies/mL, the incidence of recurrent PjP was 3.9 (95% CI: 2.0 to 5.8) per 1000 py, not significantly different from patients on prophylaxis in the same stratum (1.9, 95% CI: 0.1 to 3.7). Conclusions: HIV viraemia importantly affects the risk of recurrent PjP. In virologically suppressed patients on ART with CD4 counts of 100 to 200/µL, the incidence of PjP off prophylaxis is below 10/1000 py. Secondary PjP prophylaxis may be safely withheld in such patients. While European guidelines recommend discontinuing secondary PjP prophylaxis only if CD4 counts rise above 200 cells/mL, the latest US Guidelines consider secondary prophylaxis discontinuation even in patients with a CD4 count above 100 cells/µL and suppressed viral load. Our results strengthen and support this US recommendation. Keywords: opportunistic infections; Pneumocystis jirovecii pneumonia; prophylaxi

ClimateFish: A Collaborative Database to Track the Abundance of Selected Coastal Fish Species as Candidate Indicators of Climate Change in the Mediterranean Sea

Under the effects of global warming, many animals and plants are undergoing rapid distribution shifts. These changes can be particularly rapid in marine fishes, and many species have responded markedly to recent increases in sea temperature. ClimateFish is an open-access database, which collates abundance data for 7 Mediterranean indigenous and 8 non-indigenous fishes, proposed as candidate indicators of climate change. These species have been selected by a network of Mediterranean scientists based on their wide distribution, responsiveness to temperature conditions and easy identification. Data are periodically collected according to a standard visual census protocol in four different depth layers. At present, the database collates data on a total number of 101'771 observed individuals belonging to the 15 target species. Counts were realized along 3142 transects carried out in 7 Mediterranean countries between 2009 and 2021. This database, associated with climate data, offers new opportunities to investigate spatiotemporal effects of climate change and to test the effectiveness of each selected indicator. Data are available at https://doi.org/10.17882/86784.The Mediterranean ClimateFish initiative was initially conceived by the international basin wide monitoring program CIESM Tropical Signals (funded by the Albert II of Monaco Foundation) and subsequently supported by the Interreg Med Programme (Projects: MPA-ADAPT, grant number 1MED15_3.2_M2_337 and MPA Engage, grant number 5MED18_3.2_M23_007), 85% co funded by the European Regional Development Fund

Hyperimmune immunoglobulin for hospitalised patients with COVID-19 (ITAC): a double-blind, placebo-controlled, phase 3, randomised trial

BACKGROUND: Passive immunotherapy using hyperimmune intravenous immunoglobulin (hIVIG) to SARS-CoV-2, derived from recovered donors, is a potential rapidly available, specific therapy for an outbreak infection such as SARS-CoV-2. Findings from randomised clinical trials of hIVIG for the treatment of COVID-19 are limited. METHODS: In this international randomised, double-blind, placebo-controlled trial, hospitalised patients with COVID-19 who had been symptomatic for up to 12 days and did not have acute end-organ failure were randomly assigned (1:1) to receive either hIVIG or an equivalent volume of saline as placebo, in addition to remdesivir, when not contraindicated, and other standard clinical care. Randomisation was stratified by site pharmacy; schedules were prepared using a mass-weighted urn design. Infusions were prepared and masked by trial pharmacists; all other investigators, research staff, and trial participants were masked to group allocation. Follow-up was for 28 days. The primary outcome was measured at day 7 by a seven-category ordinal endpoint that considered pulmonary status and extrapulmonary complications and ranged from no limiting symptoms to death. Deaths and adverse events, including organ failure and serious infections, were used to define composite safety outcomes at days 7 and 28. Prespecified subgroup analyses were carried out for efficacy and safety outcomes by duration of symptoms, the presence of anti-spike neutralising antibodies, and other baseline factors. Analyses were done on a modified intention-to-treat (mITT) population, which included all randomly assigned participants who met eligibility criteria and received all or part of the assigned study product infusion. This study is registered with ClinicalTrials.gov, NCT04546581. FINDINGS: From Oct 8, 2020, to Feb 10, 2021, 593 participants (n=301 hIVIG, n=292 placebo) were enrolled at 63 sites in 11 countries; 579 patients were included in the mITT analysis. Compared with placebo, the hIVIG group did not have significantly greater odds of a more favourable outcome at day 7; the adjusted OR was 1·06 (95% CI 0·77–1·45; p=0·72). Infusions were well tolerated, although infusion reactions were more common in the hIVIG group (18·6% vs 9·5% for placebo; p=0·002). The percentage with the composite safety outcome at day 7 was similar for the hIVIG (24%) and placebo groups (25%; OR 0·98, 95% CI 0·66–1·46; p=0·91). The ORs for the day 7 ordinal outcome did not vary for subgroups considered, but there was evidence of heterogeneity of the treatment effect for the day 7 composite safety outcome: risk was greater for hIVIG compared with placebo for patients who were antibody positive (OR 2·21, 95% CI 1·14–4·29); for patients who were antibody negative, the OR was 0·51 (0·29–0·90; pinteraction=0·001). INTERPRETATION: When administered with standard of care including remdesivir, SARS-CoV-2 hIVIG did not demonstrate efficacy among patients hospitalised with COVID-19 without end-organ failure. The safety of hIVIG might vary by the presence of endogenous neutralising antibodies at entry. FUNDING: US National Institutes of Health

A Phylogenetic Analysis of Human Immunodeficiency Virus Type 1 Sequences in Kiev: Findings Among Key Populations

Background: The human immunodeficiency virus (HIV) epidemic in Ukraine has been driven by a rapid rise among people who inject drugs, but recent studies have shown an increase through sexual transmission. Methods: Protease and reverse transcriptase sequences from 876 new HIV diagnoses (April 2013–March 2015) in Kiev were linked to demographic data. We constructed phylogenetic trees for 794 subtype A1 and 64 subtype B sequences and identified factors associated with transmission clustering. Clusters were defined as ≥2 sequences, ≥80% local branch support, and maximum genetic distance of all sequence pairs in the cluster ≤2.5%. Recent infection was determined through the limiting antigen avidity enzyme immunoassay. Sequences were analyzed for transmitted drug resistance mutations. Results Thirty percent of subtype A1 and 66% of subtype B sequences clustered. Large clusters (maximum 11 sequences) contained mixed risk groups. In univariate analysis, clustering was significantly associated with subtype B compared to A1 (odds ratio [OR], 4.38 [95% confidence interval {CI}, 2.56–7.50]); risk group (OR, 5.65 [95% CI, 3.27–9.75]) for men who have sex with men compared to heterosexual males; recent, compared to long-standing, infection (OR, 2.72 [95% CI, 1.64–4.52]); reported sex work contact (OR, 1.93 [95% CI, 1.07–3.47]); and younger age groups compared with age ≥36 years (OR, 1.83 [95% CI, 1.10–3.05] for age ≤25 years). Females were associated with lower odds of clustering than heterosexual males (OR, 0.49 [95% CI, .31–.77]). In multivariate analysis, risk group, subtype, and age group were independently associated with clustering (P < .001, P = .007, and P = .033, respectively). Eighteen sequences (2.1%) indicated evidence of transmitted drug resistance. Conclusions Our findings suggest high levels of transmission and bridging between risk groups

Impact of an antibiotic restriction policy on the antibiotic resistance patterns of Gram-negative microorganisms in an Intensive Care Unit in Greece

The purpose of this study was to investigate the influence of an antibiotic policy programme based on restriction of the empirical use of fluoroquinolones and ceftazidime on the susceptibilities of Gram-negative microorganisms in a general Intensive Care Unit (ICU). The epidemiology of infections caused by the predominant ICU pathogens, i.e. Acinetobacter baumannii, Pseudomonas aeruginosa and Klebsiella pneumoniae, and their resistance patterns as well as antibiotic consumption were recorded for a 6-month period. An antibiotic restriction policy including ceftazidime and quinolones was applied. After an 18-month period of protocol application, the same parameters were recorded for another 6-month period. Consumption of restricted and overall antibiotics was reduced by 92.5% and 55.4%, respectively. Susceptibilities to ciprofloxacin of the three predominant infection-causing Gram-negative bacilli were significantly increased. Ceftazidime showed an increase in susceptibility only for P. aeruginosa. Similar rates of infectious episodes were recorded in the two periods and no differences were observed either in overall mortality or in ICU ecology as expressed by the type of microorganisms implicated in colonisation and/or infection. The reported data suggest that an antibiotic restriction policy can significantly reduce antimicrobial consumption and antimicrobial resistance rates, although the latter effect can be also influenced by the prevalent resistance mechanisms and the prevalence of imported resistance. (C) 2007 Elsevier B.V and the International Society of Chemotherapy. All rights reserved

Acute Generalized Exanthematous Pustulosis (AGEP) Triggered by a Spider Bite

Background: Acute generalized exanthematous pustulosis (AGEP) is a rare and severe cutaneous reaction usually triggered by drugs. Other causative factors such as viral infections are rarely involved. In this study, we report a case of AGEP caused by a spider bite. Case Summary: A 56-year-old woman was referred to the allergy unit after a spider bite at the left popliteal fossa, while gardening, 5 days earlier. The offending spider was captured and identified by an entomologist as belonging to the Loxosceles rufescens species. No acute reaction was observed; however, after 24 hours, due to the occurrence of typical dermonecrotic skin lesions associated with erythema and edema, Cefuroxime and Clindamycin were administered intramuscularly after medical advice was given. Almost 72 hours after the spider bite, an erythematous and partly edematous eruption appeared locally in the gluteus area bilaterally, which progressively expanded to the trunk, arms and femors. Within 24 hours dozens of small, pinhead sized, non- follicular pustules were present, mainly in the folds. The patient complained of a burning sensation of the skin in addition to pruritus; and simultaneously had a fever of 38-39 °C as the eruption expanded. Discussion: A spider bite may represent a possible causative factor of AGEP. A spider's venom contains sphingomyelinase that stimulates the release of IL8 and GM-CSF, which are involved in AGEP pathogenesis. Whether or not the con-current use of antibiotics has an effect in AGEP appearance when combined with a spider's venom, cannot be excluded

Evaluation of CHROMagar (TM) KPC for the detection of carbapenemase-producing Enterobacteriaceae in rectal surveillance cultures

In this study, the performance of the chromogenic medium CHROMagar (TM) KPC was evaluated and was compared with in-house-daily prepared McConkey agar plates supplemented with imipenem (1 mg/L) for the detection of carbapenemase-producing Enterobacteriaceae. In this surveillance study, rectal swabs were cultured on both media and polymerase chain reaction (PCR) for bla(KPC) and bla(VIM) was used to confirm the genotype of growing colonies of Enterobacteriaceae. CHROMagar KPC was also tested with 17 genotypically characterised carbapenemase-producing and non-producing Gram-negative bacteria. It was shown that CHROMagar allows rapid detection of carbapenemase-producing Enterobacteriaceae, although bla(KPC)- and bla(VIM)-harbouring isolates could not be differentiated by colour or colony morphology. The positive and negative predictive values of the tested methods for the detection of carbapenemase-producing Enterobacteriaceae were, respectively, 100% and 98.8% for CHROMagar KPC and 94.7% and 88.6% for imipenem-supplemented McConkey agar. CHROMagar KPC medium is a useful screening medium for carbapenemase-producing Enterobacteriaceae in stools in settings with a high proportion of patients colonised with a variety of carbapenemase-producers. (C) 2010 Elsevier B. V. and the International Society of Chemotherapy. All rights reserved