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Trust in science is crucial and concerns about the credibility of scientists may undermine evidence-based policy making. During the COVID-19 pandemic, scientific credibility was challenged by a lack of scientific evidence to back up policy decisions at the start of the pandemic, followed by a huge and overwhelming increase of scientific publications, often of poor quality [1]. However, concerns about the trust that the general public has in science are not new. In 1999, researchers stated that the scientific community has a credibility problem because of scientific involvement in genetic modification of crops [2].

Over 95% of humans have been infected with Epstein-Barr virus (EBV) and develop anti-EBV IgG antibodies conferring immunity. However, in specific populations, EBV may induce a range of B-cell lymphoproliferative disorders (LPDs). EBV may also contribute to T cell and NK Cell lymphoproliferation. The immune system is essential to prevent infection and development of cancer. Inborn errors of immunity (IEI) are a heterogenous group of over 450 genetic disorders predisposing to severe and/or recurrent infection, autoimmunity, autoinflammation or early-onset/severe neoplasia or lymphoproliferation.

Abstract

Background

Burkholderia cepacia (BC) has been detected more and more in infected patients in recent years. However, as a high-risk population, the clinical characteristics and prognosis of BC infection in hematopoietic stem cell transplantation (HSCT) patients have not been reported. The purpose of this study is to obtain data that will help fill in the gaps in this field, provide evidence for reducing the mortality rate of BC infection in HSCT patients, and guide the use of antibiotics in the future.

Methods

Electronic medical records of patients with BC infection who underwent HSCT in Xiangya Hospital of Central South University from September 1, 2015 to August 31, 2021 were collected. At the same time, 1:1 case–control matching was conducted according to gender, age and disease type. Comparisons between patients with/without BC infection and respiratory failure were made respectively, and the sensitivity of BC to five clinically commonly used antibiotics was also evaluated. Univariate and multivariate analyses were performed to identify independent risk factors for death.

Results

The most common site of BC infection in HSCT patients was the lung (75%). Although BC infection rate (3.74%) and antibiotic resistance were not significant, it was closely associated with a higher risk of death (P = 0.022), which even further increased to 90.9% when combined with respiratory failure (P = 0.008). Procalcitonin > 10 µg/L (HR = 40.88, 95% CI 6.51–256.63, P = 0.000) and septic shock (HR = 4.08, 95% CI 1.02–16.33, P = 0.047) were two independent risk factors for death.

Conclusion

HSCT patients with BC infection are in critical condition, and the management of respiratory infection should be especially strengthened to improve the prognosis of these patients.

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Abstract

Introduction

Randomised controlled trials have shown that steroids reduce the risk of dying in patients with severe Coronavirus disease 2019 (COVID-19), whilst many real-world studies have failed to replicate this result. We aim to investigate real-world effectiveness of steroids in severe COVID-19.

Methods

Clinical, demographic, and viral genome data extracted from electronic patient record (EPR) was analysed from all SARS-CoV-2 RNA positive patients admitted with severe COVID-19, defined by hypoxia at presentation, between March 13th 2020 and May 27th 2021. Steroid treatment was measured by the number of prescription-days with dexamethasone, hydrocortisone, prednisolone or methylprednisolone. The association between steroid > 3 days treatment and disease outcome was explored using multivariable cox proportional hazards models with adjustment for confounders (including age, gender, ethnicity, co-morbidities and SARS-CoV-2 variant). The outcome was in-hospital mortality.

Results

1100 severe COVID-19 cases were identified having crude hospital mortality of 15.3%. 793/1100 (72.1%) individuals were treated with steroids and 513/1100 (46.6%) received steroid ≤ 3 days. From the multivariate model, steroid > 3 days was associated with decreased hazard of in-hospital mortality (HR: 0.47 (95% CI: 0.31–0.72)).

Conclusion

The protective effect of steroid treatment for severe COVID-19 reported in randomised clinical trials was replicated in this retrospective study of a large real-world cohort.

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Antimicrobial Agents and Chemotherapy, Ahead of Print. …

Nature Medicine, Published online: 06 October 2022; doi:10.1038/s41591-022-02048-yEmerging evidence shows that boosting with updated mRNA vaccines that target SARS-CoV-2 variants stimulates better neutralizing antibody responses than homologous boosters.

Nature Medicine, Published online: 06 October 2022; doi:10.1038/s41591-022-02031-7A bivalent vaccine encoding the ancestral and Beta variant SARS-CoV-2 spike proteins boosts neutralizing antibody responses against multiple viral variants, suggesting that a bivalent approach is an effective strategy to broadly enhance protection against COVID-19.

Introduction

WHO has generated standardised clinical and epidemiological research protocols to address key public health questions for SARS-CoV-2 (COVID-19) pandemic. We present a standardised protocol with the aim to fill a gap in understanding the needs, attitudes and practices related to sexual and reproductive health in the context of COVID-19 pandemic, focusing on pregnancy, pregnancy prevention and abortion.

Methods and analysis plan

This protocol is a prospective qualitative research, using semi-structured interviews with at least 15 pregnant women at different gestational ages and after delivery, 6 months apart from the first interview. At least 10 partners, 10 non-pregnant women and 5 healthcare professionals will be interviewed once during the course of the research. Higher number of subjects may be needed if a saturation is not achieved with these numbers. Data collection will be performed in a standardised way by skilled trained interviewers using written notes or audio-record of the interview. The data will be explored using the thematic content analysis and the researchers will look for broad patterns, generalisations or theories from these categories.

Ethics and dissemination

The current protocol was first technically assessed and approved by the WHO scientific committee and then approved by its ethics review committee as a guidance document. It is expected that each country/setting implementing such a generic protocol adapted to their conditions also obtain local ethical approval. Comments for the user’s consideration are provided the document, as the user may need to modify methods slightly because of the local context in which this study will be carried out.

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Objective

This study aimed to assess factors associated with poor medication adherence during the COVID-19 pandemic among hypertensive patients visiting public hospitals in Eastern Ethiopia.

Setting

Hospital-based cross-sectional study was conducted in Harari regional state and Dire Dawa Administration from 1 January to 30 February 2022. Both settings are found in Eastern Ethiopia.

Participants

A total of 402 adult hypertensive patients who visited the chronic diseases clinic for follow-up were included in the study.

Main outcome measures

The main outcome measure was poor medication adherence during the COVID-19 pandemic.

Results

The level of poor antihypetensive medication adherence was 63% (95% CI 48.1 to 67.9). Patients who had no formal education (adjusted OR (AOR)=1.56, 95% CI 1.03 to 4.30), existing comorbid conditions (AOR=1.98, 95% CI 1.35 to 4.35), self-funded for medication cost (AOR=2.05, 95% CI 1.34 to 4.73), poor knowledge about hypertension (HTN) and its treatment (AOR=2.67, 95% CI 1.45 to 3.99), poor patient–physician relationship (AOR=1.22, 95% CI 1.02 to 4.34) and unavailability of medication (AOR=5.05, 95% CI 2.78 to 12.04) showed significant association with poor medication adherence during the pandemic of COVID-19.

Conclusion

The level of poor antihypertensive medication adherence was high in this study. No formal education, comorbidity, self-funded medication cost, poor knowledge about HTN and its treatment, poor patient–physician relationship, and unavailability of medication during the COVID-19 pandemic were factors significantly associated with poor adherence to antihypertensive medication. All stakeholders should take into account and create strategies to reduce the impact of the COVID-19 pandemic on medication adherence of chronic diseases.

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Clinical Microbiology Reviews, Ahead of Print. …

Mycobacterium kansasii (M. kansasii) pulmonary disease is frequently misdiagnosed and treated as tuberculosis, especially in countries with high tuberculosis burden. This study aimed to investigate the drug resistance profile of M. kansasii in patients with M. kansasii pulmonary disease in Shanghai, and to determine the variations in drug resistance after the 2-month antimycobacterial treatment.

The objective of this study was to compare the incidence rate for complications to upper respiratory tract infections, including acute bronchitis (URTI) and lower urinary tract infections (UTI) for untreated compared with those treated with antibiotics.

Chlamydia are Gram-negative, obligate intracellular pathogens, which currently comprise 13 species and 3 candidate species (Bommana and Polkinghorne 2019). Most of them have significant impacts on the health of humans or animals. Chlamydia trachomatis, Chlamydia pneumoniae, and Chlamydia psittaci are the major species that infect humans and can cause a variety of diseases (Elwell et al. 2016).

Patients with genetic and acquired humoral immunodeficiency present with an atypical COVID-19 course. Persistent viral shedding with multiple viral relapses continue in these patients for weeks. [1] Lymphopenia, recent anti-CD20 therapy, chimeric antigen receptor T cell therapy (CAR-T), hypogammaglobulinemia and hematopoietic stem cell transplantation are associated with virological persistence. [2] These patients have low seroconversion rates following SARS-CoV-2 vaccination, and are predisposed to SARS-CoV-2 infection and severe disease.

New England Journal of Medicine, Volume 387, Issue 14, October 2022. …

New England Journal of Medicine, Ahead of Print. …

Dendritic cells (DCs) play a key role to modulate anti-cancer immunity in the tumor microenvironment (TME). They link innate to adaptive immunity by processing and presenting tumor antigens to T cells thereby initiating an anti-tumor response. However, subsets of DCs also induce immune-tolerance, leading to tumor immune escape. In this regard, the TME plays a major role in adversely affecting DC function. Better understanding of DC impairment mechanisms in the TME will lead to more efficient DC-targeting immunotherapy. Here, we review the different subtypes and functions of DCs in the TME, including conventional DCs, plasmacytoid DC and the newly proposed subset, mregDC. We further focus on how cancer cells modulate DCs to escape from the host’s immune-surveillance. Immune checkpoint expression, small molecule mediators, metabolites, deprivation of pro-immunogenic and release of pro-tumorigenic cytokine secretion by tumors and tumor-attracted immuno-suppressive cells inhibit DC differentiation and function. Finally, we discuss the impact of established therapies on DCs, such as immune checkpoint blockade. Creative DC-targeted therapeutic strategies will be highlighted, including cancer vaccines and cell-based therapies.…

Proof-of-concept studies demonstrate that antimalarial drugs designed for human treatment can also be applied to mosquitoes to interrupt malaria transmission. Deploying a new control tool is ideally undertaken within a stewardship programme that maximises a drug's lifespan by minimising the risk of resistance evolution and slowing its spread once emerged. We ask: what are the epidemiological and evolutionary consequences of targeting parasites within mosquitoes? Our synthesis argues that targeting parasites inside mosquitoes (i) can be modelled by readily expanding existing epidemiological frameworks; (ii) provides a functionally novel control method that has potential to be more robust to resistance evolution than targeting parasites in humans; and (iii) could extend the lifespan and clinical benefit of antimalarials used exclusively to treat humans.

Science Advances, Volume 8, Issue 40, October 2022. …

Science Advances, Volume 8, Issue 40, October 2022. …

Science Advances, Volume 8, Issue 40, October 2022. …

Science Advances, Volume 8, Issue 40, October 2022. …

Objectives:

Sepsis causes significant mortality. However, most patients who die of sepsis do not present with severe infection, hampering efforts to deliver early, aggressive therapy. It is also known that the host gene expression response to infection precedes clinical illness. This study seeks to develop transcriptomic models to predict progression to sepsis or shock within 72 hours of hospitalization and to validate previously identified transcriptomic signatures in the prediction of 28-day mortality.

Design:

Retrospective differential gene expression analysis and predictive modeling using RNA sequencing data.

Patients:

Two-hundred seventy-seven patients enrolled at four large academic medical centers; all with clinically adjudicated infection were considered for inclusion in this study.

Measurements and Main Results:

Sepsis progression was defined as an increase in Sepsis 3 category within 72 hours. Transcriptomic data were generated using RNAseq of whole blood. Least absolute shrinkage and selection operator modeling was used to identify predictive signatures for various measures of disease progression. Four previously identified gene signatures were tested for their ability to predict 28-day mortality. There were no significant differentially expressed genes in 136 subjects with worsened Sepsis 3 category compared with 141 nonprogressor controls. There were 1,178 differentially expressed genes identified when sepsis progression was defined as ICU admission or 28-day mortality. A model based on these genes predicted progression with an area under the curve of 0.71. Validation of previously identified gene signatures to predict sepsis mortality revealed area under the receiver operating characteristic values of 0.70–0.75 and no significant difference between signatures.

Conclusions:

Host gene expression was unable to predict sepsis progression when defined by an increase in Sepsis-3 category, suggesting this definition is not a useful framework for transcriptomic prediction methods. However, there was a differential response when progression was defined as ICU admission or death. Validation of previously described signatures predicted 28-day mortality with insufficient accuracy to offer meaningful clinical utility.

Objectives:

Bloodstream infections (BSIs) acquired in the ICU represent a detrimental yet potentially preventable condition. We determined the prevalence of BSI acquired in the ICU (ICU-onset BSI), pathogen profile, and associated risk factors.

Design:

Retrospective cohort study.

DATA SOURCES:

Eighty-five U.S. hospitals in the Cerner Healthfacts Database.

PATIENT SELECTION:

Adult hospitalizations between January 2009 and December 2015 including a (≥ 3 d) ICU stay.

DATA EXTRACTION AND DATA SYNTHESIS:

Prevalence of ICU-onset BSI (between ICU Day 3 and ICU discharge) and associated pathogen and antibiotic resistance distributions were compared with BSI present on (ICU) admission (ICU-BSIPOA); and BSI present on ICU admission day or Day 2. Cox models identified risk factors for ICU-onset BSI among host, care setting, and treatment-related factors. Among 150,948 ICU patients, 5,600 (3.7%) had ICU-BSIPOA and 1,306 (0.9%) had ICU-onset BSI. Of those with ICU-BSIPOA, 4,359 (77.8%) were admitted to ICU at hospital admission day. Patients with ICU-onset BSI (vs ICU-BSIPOA) displayed higher crude mortality of 37.9% (vs 20.4%) (p < 0.001) and longer median (interquartile range) length of stay of 13 days (8–23 d) (vs 5 d [3–8 d]) (p < 0.001) (considering all ICU stay). Compared with ICU-BSIPOA, ICU-onset BSI displayed more Pseudomonas, Acinetobacter, Enterococcus, Candida, and Coagulase-negative Staphylococcus species, and more methicillin-resistant staphylococci, vancomycin-resistant enterococci, ceftriaxone-resistant Enterobacter, and carbapenem-resistant Enterobacterales and Acinetobacter species, respectively. Being younger, male, Black, Hispanic, having greater comorbidity burden, sepsis, trauma, acute pulmonary or gastrointestinal presentations, and pre-ICU exposure to antibacterial and antifungal agents was associated with greater ICU-onset BSI risk after adjusted analysis. Mixed ICUs (vs medical or surgical ICUs) and urban and small/medium rural hospitals were also associated with greater ICU-onset BSI risk. The associated risk of acquiring ICU-onset BSI manifested with any duration of mechanical ventilation and 7 days after insertion of central venous or arterial catheters.

Conclusions:

ICU-onset BSI is a serious condition that displays a unique pathogen and resistance profile compared with ICU-BSIPOA. Further scrutiny of modifiable risk factors for ICU-onset BSI may inform control strategies.

Antimicrobial Agents and Chemotherapy, Ahead of Print. …

Antimicrobial Agents and Chemotherapy, Ahead of Print. …