Nyt fra tidsskrifterne

Objectives: To assess the impact of a combination HIV prevention intervention including universal testing and treatment (UTT) on HIV stigma among people living with HIV, and among community members and health workers not living with HIV. Design: This HIV stigma study was nested in the HPTN 071 (PopART) trial, a three-arm cluster randomised trial conducted between 2013–2018 in 21 urban/peri-urban communities (12 in Zambia and 9 in South Africa). Methods: Using an adjusted two-stage cluster-level analysis, controlling for baseline imbalances, we compared multiple domains of stigma between the trial arms at 36 months. Different domains of stigma were measured among three cohorts recruited across all study communities: 4,178 randomly sampled adults aged 18–44 who were living with HIV, and 3,487 randomly sampled adults and 1,224 health workers who did not self-report living with HIV. Results: Prevalence of any stigma reported by people living with HIV at 36 months was 20.2% in arm A, 26.1% in arm B, and 19.1% in arm C (adjusted prevalence ratio, A vs C 1.01 95% CI 0.49–2.08, B vs C 1.34 95% CI 0.65–2.75). There were no significant differences between arms in any other measures of stigma across all three cohorts. All measures of stigma reduced over time (0.2% to 4.1% reduction between rounds) with most reductions statistically significant. Conclusions: We found little evidence that UTT either increased or decreased HIV stigma measured among people living with HIV, or among community members or health workers not living with HIV. Stigma reduced over time, but slowly. ClinicalTrials.gov number, NCT01900977 Correspondence to Anne L. Stangl, PhD, MPH, 711 W 40th St Ste 153 #343, Baltimore, MD 21211. Tel: +1 833 437 2765; e-mail: alstangl@gmail.com Received 29 January, 2020 Revised 29 June, 2020 Accepted 6 July, 2020 Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Website (http://www.AIDSonline.com). This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0 Copyright © 2020 Wolters Kluwer Health, Inc.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

The abrupt appearance of SARS-CoV-2 as a novel lethal zoonotic pathogen causing COVID-19 disease in humans in late December, 2019 (WHO, 2020a, b), and its explosive global spread (Hui et al, 2020) caught health authorities worldwide by surprise and exposed the ill-preparedness of global public health systems worldwide to deal with the appearance of a new pathogen. Apart from generic prevention and control issues of public health and lockdown measures to limit epidemic spread, specific issues of Mass Gathering (MG) sporting and religious events came under specific spotlight (Alzahrani et al, 2020; Memish et al, 2020a, b; Baloch et al, 2020; McCloskey et al, 2020; Petersen et al, 2020a, b).

No abstract available…

AbstractIn May 2020 the Russian Ministry of Health granted fast-track marketing authorization to RNA polymerase inhibitor AVIFAVIR (favipiravir) for the treatment of COVID-19 patients. In the pilot stage of Phase II/III clinical trial, AVIFAVIR enabled SARS-CoV-2 viral clearance in 62.5% of patients within 4 days, and was safe and well-tolerated.

AbstractThis study analyzed the cerebrospinal fluid features of 31 COVID-19 patients with neurological complications. We observed neither SARS-CoV-2 RNA in the cerebrospinal fluid, nor intrathecal IgG synthesis, but did observe signs of blood-brain barrier disruption. These results might serve as a basis for a better understanding of SARS-CoV-2 related neuropathogenesis.

diagnosticsgolden standardconsensusmetagenomicscase definition…

AbstractBackgroundThere are large knowledge gaps on the transmission dynamics of Mycobacterium tuberculosis in settings where both tuberculosis and HIV are endemic. We aimed to assess the infectiousness of tuberculosis patients coinfected with HIV.MethodsWe systematically searched for studies of contacts of both HIV-positive and negative tuberculosis index cases. Our primary outcome was Mycobacterium tuberculosis infection in contacts. Data on sputum smear and lung cavitation status of index cases was extracted from each study to assess effect modification. Secondary outcomes included prevalent tuberculosis and HIV in contacts of HIV-positive and negative index cases.ResultsOf 5,255 original citations identified, 32 studies met inclusion criteria including 25 studies investigating M. tuberculosis infection (Nparticipants=36,893), 13 on tuberculosis (Nparticipants=18,853), and 12 on HIV positivity (Nparticipants=18,424). Risk of M. tuberculosis infection was lower in contacts of HIV-positive index cases (Odds Ratio [OR], 0.67, 95% CI, 0.58–0.77) but was heterogeneous (I2=75.1%). Two factors modified this relationship: the lung cavitary status of the index case and immunosuppression (measured through CD4 counts or HIV or AIDS diagnoses) among index patients living with HIV. Rates of HIV were consistently higher in contacts of coinfected index cases (OR, 4.9, 95% CI, 3.0–8.0). This was modified by whether the study was in sub-Saharan Africa (OR, 2.8, 1.6–4.9) or in another global region (OR, 9.8, 5.9–16.3).ConclusionsTuberculosis patients coinfected with HIV are less infectious than HIV-uninfected cases when they have severe immunosuppression or paucibacillary disease. Contacts of coinfected index cases are almost five times more likely to also have HIV.

Contact tracinginfectious disease transmissioninfectiousnesstuberculosisCOVID-19…

Technological advances have allowed peritoneal dialysis (PD) to be increasingly applied to end-stage renal disease (ESRD) patients, especially in developing countries 1. As a common and serious complication of peritoneal dialysis, peritonitis was estimated to be ranging from 0.06 to 1.66 episodes per patient-year over different countries 2,3. Severe or persistent peritonitis can result in peritoneal membrane injury, promoting the progress of encapsulating peritoneal sclerosis 4,5.

Multidrug and extensively drug resistant (MDR/XDR) gram negative infections have been increasing in India (Epelboin et al. 2015; Basak et al. 2016; Laxminarayan and Chaudhury 2016) and have been associated with longer hospitalizations, higher mortality and greater cost of care (Gómez-Zorrilla et al. 2015; Harris et al. 2016; Tseng et al. 2018). In recent years, a re-emergence in the use of “Polymyxin E” or Colistin to treat these MDR/XDR gram negative bacterial infections has occurred (Falagas et al.

The European Union (EU) has recently announced it will allocate over 9 billion EUR of funding to the EU4Health programme between 2021 and 2027 to focus on three primary aims: tackling cross-border health threats, making medicines available and affordable, and strengthening health systems (European Commission, 2020a). This is a twenty-fold increase in health spending from the 450 million EUR the EU spent on health priorities in the previous seven years (European Commission, 2020b), and represents a fundamental shift in the approach of the EU to member states’ health systems.

The novel Coronavirus Disease 2019 pandemic, caused by the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), has claimed the lives of more than 600 thousand people (Anon., 2020). Highly prevalent in urban centers of China, USA, and European countries, the disease has spread to Africa and Latin America, where rural populations are especially vulnerable because of multiple factors inherent to under-development (Zhao et al., 2020; Caicedo-Ochoa et al., 2020; Miller et al., 2020). Despite the vast information on SARS-CoV-2 published from urban centers, there is little or nil evidence about the mortality rate of individuals with SARS-CoV-2 in remote rural settings.

Abstract Background Estimating prevalence of Chlamydia trachomatis (CT) worldwide is necessary in designing control programs and allocating health resources. We performed a meta-analysis to calculate the prevalence of CT in the general population. Methods The Pubmed and Embase databases were searched for eligible population-based studies from its inception through June 5, 2019. Q test and I2 statistic were used to calculate the heterogeneity between studies. Random effects models were used to pool the prevalence of CT. Meta regression was performed to explore the possible sources of heterogeneity. Publication bias was evaluated using a funnel plot and “trim and fill” method. Results Twenty nine studies that reported prevalence of CT infection from 24 countries were identified, including a total population of 89,886 persons. The pooled prevalence of CT among the general population was 2.9% (95% CI, 2.4–3.5%), and females had a higher CT prevalence (3.1, 95% CI, 2.5–3.8%) than males (2.6, 95% CI, 2.0–3.2%) (χ2 = 10.38, P 

Abstract Background Scale-up of hepatitis C virus (HCV) treatment for HIV/HCV coinfected individuals is occurring in Spain, the vast majority (> 85%) with a reported history of injecting drug use and a smaller population of co-infected men who have sex with men (MSM). We assess impact of recent treatment scale-up to people living with HIV (PLWH) and implications for achieving the WHO HCV incidence elimination target (80% reduction 2015–2030) among PLWH and overall in Andalusia, Spain, using dynamic modeling. Methods A dynamic transmission model of HCV/HIV coinfection was developed. The model was stratified by people who inject drugs (PWID) and MSM. The PWID component included dynamic HCV transmission from the HCV-monoinfected population. The model was calibrated to Andalusia based on published data and the HERACLES cohort (prospective cohort of HIV/HCV coinfected individuals representing > 99% coinfected individuals in care in Andalusia). From HERACLES, we incorporated HCV treatment among diagnosed PLWH of 10.5%/year from 2004 to 2014, and DAAs at 33%/year from 2015 with 94.8% SVR. We project the impact of current and scaled-up HCV treatment for PLWH on HCV prevalence and incidence among PLWH and overall. Results Current treatment rates among PLWH (scaled-up since 2015) could substantially reduce the number of diagnosed coinfected individuals (mean 76% relative reduction from 2015 to 2030), but have little impact on new diagnosed coinfections (12% relative reduction). However, DAA scale-up to PWLH in 2015 would have minimal future impact on new diagnosed coinfections (mean 9% relative decrease from 2015 to 2030). Similarly, new cases of HCV would only reduce by a mean relative 29% among all PWID and MSM due to ongoing infection/reinfection. Diagnosing/treating all PLWH annually from 2020 would increase the number of new HCV infections among PWLH by 28% and reduce the number of new HCV infections by 39% among the broader population by 2030. Conclusion Targeted scale-up of HCV treatment to PLWH can dramatically reduce prevalence among this group but will likely have little impact on the annual number of newly diagnosed HIV/HCV coinfections. HCV microelimination efforts among PWLH in Andalusia and settings where a large proportion of PLWH have a history of injecting drug use will require scaled-up HCV diagnosis and treatment among PLWH and the broader population at risk.…

Abstract Background Tuberculosis (TB) is transmitted in bioaerosols containing Mycobacterium tuberculosis (Mtb). Despite being central to ongoing TB transmission, no routine diagnostic assay exists to measure Mtb in bioaerosols. Furthermore, published studies of Mtb in bioaerosol samples have been limited to individuals with sputum-positive pulmonary TB. Notably, TB diagnosis is based on clinical symptoms and sputum laboratory findings. This is despite the fact that approximately half of all patients commencing TB treatment are sputum-negative, resulting in a high proportion of presumptive treatments. Here, we propose to use a sensitive air sampling protocol to investigate the prevalence of Mtb-containing bioaerosols in both sputum-positive and sputum-negative TB suspects, at the same time evaluating the potential to identify unrecognized transmitters of TB. Methods Our parallel-group design will identify viable Mtb in bioaerosols produced by individuals attending a TB clinic in South Africa. Sampling will be performed on eligible individuals presenting with symptoms indicative of TB and repeated at 14 days if initially positive. Participants will be prospectively classified into three distinct groups based on National TB Control Program (NTBCP) criteria: Group A, TB notification with sputum-based laboratory confirmation; Group B, TB notification with empiric diagnosis; and Group C, individuals not notified. Group C individuals with detectable Mtb bioaerosol will be monitored until resolution of clinical and laboratory status. Collection of bioaerosol specimens will be via two consecutive sampling modalities: (1) direct sampling following a specific respiratory manoeuvre; and (2) indirect sampling during passive respiratory activity. Bioaerosol specimens will be analyzed for viable Mtb using DMN-trehalose staining and live-cell fluorescence microscopy. Mtb genomes and mycobacterial and host lipids will be detected using droplet digital PCR and mass spectrometry analyses, respectively. The primary objective is to determine the prevalence of Mtb bioaerosols in all TB clinic attendees and in each of the groups. Secondary objectives are to investigate differences in prevalence of Mtb bioaerosol by HIV status and current isoniazid preventive therapy (IPT) use; we will also determine the impact of anti-TB chemotherapy on Mtb-containing bioaerosol production. Discussion Respiratory bioaerosol has a potential role in non-invasive TB diagnosis, infectivity measurement and treatment monitoring. Trial registration ClinicalTrials.gov: NCT04241809. Date of Registration: 27/1/2020.…

In their Correspondence, Chad Wells and colleagues1 wrote about COVID-19 in the African continent, proposing more rigorous measures of prevention and lockdown and predicting a total death toll of greater than 300 000 for DR Congo alone. We question the appropriateness of the mathematical model used by the authors and of the conclusions drawn. A more accurate prediction must go beyond this model and encompass long-term health strategies of the country, as well as death tolls attributable to the prevention measures themselves.

Many predictions have been made regarding the slowing spread of COVID-19; it is not my intention to refute the epidemiological position of Johan Giesecke in his Correspondence.1 However, I will respond as a student doctor concerned about the broader implications.

We congratulate Daniel Sessler and colleagues1 for completing their large multicentre trial, but we have concerns regarding the methodology and results. The authors report that paravertebral block techniques varied per study site across the 13 hospitals in eight countries. Typically, five levels are blocked with long-acting local anaesthetic and supplementation with sevoflurane was permitted.1…

Based on hazard ratio (HR) analyses, Barbara Burtness and colleagues1 reported that pembrolizumab, alone or with chemotherapy, significantly improved overall survival versus cetuximab with chemotherapy. For example, among patients with a programmed cell death ligand 1 combined positive score of 20 or more, the HR comparing the combination of pembrolizumab and chemotherapy with the combination of cetuximab and chemotherapy was 0·60 (95% CI 0·45–0·82). However, the Kaplan-Meier curves for overall survival in figure 2F cross at least once during the study follow-up period, indicating that the assumption of proportional hazards was not met.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Journal of Medical Virology, Accepted Article.

Antimicrobial resistance (AMR) is an emerging global challenge that is thought to account for more than 700,000 deaths annually (O’neill, 2014). Certain practices that are common in resource-limited settings can fuel resistance. Inappropriate use of antibiotics is highly problematic, especially where they are availed over the counter without prescriptions. Similarly, the availability of falsified or substandard drugs is a significant issue (O’neill, 2014; Ayukekbong et al., 2017). In hospital settings, inappropriate use has been fuelled by lack of surveillance and diagnostic capabilities, poor antibiotic stewardship activities and lack of treatment guidelines (Petti et al., 2006; Elbireer et al., 2013; Doron and Davidson, 2011; Paterson, 2006).

Abstract Background Dermatomycoses are the most common fungal infections in the world affecting a significant part of the human and animal population. The majority of zoophilic infections in humans are caused by Trichophyton mentagrophytes. Currently, the first-line drug for both oral and topical therapy is terbinafine. However, an increasing number of cases that are difficult to be cured with this drug have been noted in Europe and Asia. Resistance to terbinafine and other allylamines is very rare and usually correlated with point mutations in the squalene epoxidase gene resulting in single amino acid substitutions in the enzyme, which is crucial in the ergosterol synthesis pathway. Purpose Here, we report terbinafine-resistant T. mentagrophytes isolates among which one was an etiological factor of tinea capitis in a man and three were obtained from asymptomatic foxes in Poland. Methods We used the CLSI protocol to determine antifungal susceptibility profiles of naftifine, amphotericin B, griseofulvin, ketoconazole, miconazole, itraconazole, voriconazole, and ciclopirox. Moreover, the squalene epoxidase gene of the terbinafine-resistant strains was sequenced and analysed. Results In the genomes of all four resistant strains exhibiting elevated MICs to terbinafine (16 to 32 µg/ml), single-point mutations leading to Leu393Phe substitution in the squalene epoxidase enzyme were revealed. Among the other tested substances, a MIC50 value of 1 µg/ml was shown only for griseofulvin. Conclusion Finally, our study revealed that the terbinafine resistance phenomenon might not be acquired by exposure to the drug but can be intrinsic. This is evidenced by the description of the terbinafine-resistant strains isolated from the asymptomatic animals.…

Objectives: Proprotein convertase subtilisin/kexin type 9 is a central regulator of lipid metabolism and has been implicated in regulating the host response to sepsis. Proprotein convertase subtilisin/kexin type 9 loss-of-function is associated with improved sepsis outcomes in the adult host through increased hepatic bacterial clearance. Thus, there is interest in leveraging proprotein convertase subtilisin/kexin type 9 inhibitors as a therapeutic strategy in adults with sepsis. We sought to validate this association in children with septic shock and in a juvenile murine model of sepsis. Design: Prospectively enrolled cohort of children with septic shock; experimental mice. Setting: Seventeen participating institutions; research laboratory. Patients and Subjects: Five-hundred twenty-two children with septic shock; juvenile (14 d old) and adult (10–14 wk) mice with constitutive proprotein convertase subtilisin/kexin type 9 null and wildtype control mice (C57BL/6). Interventions: Proprotein convertase subtilisin/kexin type 9 single-nucleotide polymorphisms, serum proprotein convertase subtilisin/kexin type 9, and lipid profiles in patients. Cecal slurry murine model of sepsis; survival studies in juvenile and adult mice, assessment of lipoprotein fractions, bacterial burden, and inflammation in juvenile mice. Measurements and Main Results: PCSK9 loss-of-function genetic variants were independently associated with increased odds of complicated course and mortality in children with septic shock. PCSK9, low-density lipoprotein, and high-density lipoprotein concentrations were lower among patients with complicated course relative to those without. PCSK9concentrations negatively correlated with proinflammatory cytokine interleukin-8. Proprotein convertase subtilisin/kexin type 9 loss-of-function decreased survival in juvenile mice, but increased survival in adult mice with sepsis. PCSK9 loss-of-function resulted in low lipoproteins and decreased hepatic bacterial burden in juvenile mice. Conclusions: In contrast to the adult host, proprotein convertase subtilisin/kexin type 9 loss-of-function is detrimental to the juvenile host with septic shock. PCSK9 loss-of-function, in the context of low lipoproteins, may result in reduced hepatic bacterial clearance in the juvenile host with septic shock. Our data indicate that children should be excluded in sepsis clinical trials involving proprotein convertase subtilisin/kexin type 9 inhibitors. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Dr. Atreya received funding from a “Research in Residency” grant awarded by the Cincinnati Children’s Research Foundation. Drs. Cvijanovich, Thomas, Fitzgerald, Allen, Lutfi, and Wong received support for article research from the National Institutes of Health (NIH). Dr. Cvijanovich’s institution received funding from Cincinnati Children’s Hospital Medical Center and Boston Children’s Hospital. Drs. Bigham’s and Thomas’s institutions received funding from a NIH subaward. Drs. Fitzgerald’s, Allen’s, and Lutfi’s institutions received funding from the NIH. Dr. Weiss’s institution received funding from National Institute of General Medical Sciences K23GM110496. Dr. Wong’s institution received funding from NIH R35 GM126943 and R21 HD092896. All authors discuss the off-label product use of proprotein convertase subtilisin/kexin type 9 inhibitors and their use in sepsis. This work was performed at Cincinnati Children’s Hospital Medical Center, Cincinnati, OH. For information regarding this article, E-mail: Mihir.Atreya@cchmc.org Copyright © by 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Objectives: The use of a videolaryngoscope in the ICU on the first endotracheal intubation attempt and intubation-related complications is controversial. The objective of this study was to evaluate the first intubation attempt success rate in the ICU with the McGrath MAC videolaryngoscope (Medtronic, Minneapolis, MN) according to the operators’ videolaryngoscope expertise and to describe its association with the occurrence of intubation-related complications. Design: Observational study. Setting: Medical ICU. Subjects: Consecutive endotracheal intubations in critically ill patients. Interventions: Systematic use of the videolaryngoscope. Measurements and Main Outcomes: We enrolled 202 consecutive endotracheal intubations. Overall first-attempt success rate was 126 of 202 (62%). Comorbidities, junior operator, cardiac arrest upon admission, and coma were associated with a lower first-attempt success rate. The first-attempt success rate was less than 50% in novice operators (1–5 previous experiences with videolaryngoscope, independently of airway expertise with direct laryngoscopies) and 87% in expert operators (> 15 previous experiences with videolaryngoscope). Multivariate analysis confirmed the association between specific skill training with videolaryngoscope and the first-attempt success rate. Severe hypoxemia and overall immediate intubation-related complications occurred more frequently in first-attempt failure intubations (24/76, 32%) than in first-attempt success intubations (14/126, 11%) (p < 0.001). Conclusions: We report for the first time in the critically ill that specific videolaryngoscopy skill training, assessed by the number of previous videolaryngoscopies performed, is an independent factor of first-attempt intubation success. Furthermore, we observed that specific skill training with the McGrath MAC videolaryngoscope was fast. Therefore, future trials evaluating videolaryngoscopy in ICUs should consider the specific skill training of operators in videolaryngoscopy. Dr. Amalric participated in the study design, collected data, analyzed results, and participated in article editing. Drs. Larcher and Brunot participated in resident training in airway management and in data collection. Dr. Garnier participated in data collection and in article editing. Dr. De Jong participated in the study design and performed the statistical analysis. Dr. Moulaire Rigollet and Corne participated in data collection and in article editing. Dr. Klouche participated in the study design, results analysis, and article editing. Dr. Jung designed the study, supervised data collection, results analysis, and article editing. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by grant from the department resources only. The authors have disclosed that they do not have any potential conflicts of interest. For information regarding this article, E-mail: b-jung@chu-montpellier.fr Copyright © by 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

Objectives: To assess the role of thromboprophylaxis regimens on the occurrence of pulmonary embolism in coronavirus disease 2019 patients. Design: Retrospective analysis of prospectively collected data on coronavirus disease 2019 patients, included between March 10, and April 30, 2020. Setting: ICU of an University Hospital in Belgium. Patients and Interventions: Critically ill adult mechanically ventilated coronavirus disease 2019 patients were eligible if they underwent a CT pulmonary angiography, as part of the routine management in case of persistent hypoxemia or respiratory deterioration. The primary endpoint of this study was the occurrence of pulmonary embolism according to the use of standard thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units once daily) or high regimen thromboprophylaxis (i.e. subcutaneous enoxaparin 4,000 international units bid or therapeutic unfractioned heparin). Measurements and Main Results: Of 49 mechanically ventilated coronavirus disease 2019, 40 underwent CT pulmonary angiography after a median of 7 days (4–8 d) since ICU admission and 12 days (9–16 d) days since the onset of symptoms. Thirteen patients (33%) were diagnosed of pulmonary embolism, which was bilateral in six patients and localized in the right lung in seven patients. D-dimers on the day of CT pulmonary angiography had a predictive accuracy of 0.90 (95% CIs: 0.78–1.00) for pulmonary embolism. The use of high-regimen thromboprophylaxis was associated with a lower occurrence of pulmonary embolism (2/18; 11%) than standard regimen (11/22, 50%—odds ratio 0.13 [0.02–0.69]; p = 0.02); this difference remained significant even after adjustment for confounders. Six patients with pulmonary embolism (46%) and 14 patients without pulmonary embolism (52%) died at ICU discharge (odds ratio 0.79 [0.24–3.26]; p = 0.99). Conclusions: In this study, one third of coronavirus disease 2019 mechanically ventilated patients have a pulmonary embolism visible on CT pulmonary angiography. High regimen thromboprophylaxis may decrease the occurrence of such complication. Drs. Taccone, Peluso, Grimaldi, and Creteur prepared this article; Drs. Gevenois, Brasseur, Motte, Nobile, and Vincent collaborated in the design of the trial and organized the initial ethics applications; Drs. Pletchette, Garufi, and Talamonti are responsible for study governance and roll out of the trial. Dr. Taccone is responsible for logistical support of the study. Drs. Peluso, Pletchette, Garufi, and Talamonti collected the data; Drs. Taccone, Creteur, and Vincent supervised data collection. All authors contributed substantially to the design and methodology of this study and to the writing of this article. All authors have read and approved the final article. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). The authors have disclosed that they do not have any potential conflicts of interest. The datasets used and/or analyzed during the current study are available from the corresponding author on reasonable request. For information regarding this article, E-mail: ftaccone@ulb.ac.be Copyright © by 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

No abstract available…

Objectives: Early detection of sepsis is critical in clinical practice since each hour of delayed treatment has been associated with an increase in mortality due to irreversible organ damage. This study aimed to develop an explainable artificial intelligence model for early predicting sepsis by analyzing the electronic health record data from ICU provided by the PhysioNet/Computing in Cardiology Challenge 2019. Design: Retrospective observational study. Setting: We developed our model on the shared ICUs publicly data and verified on the full hidden populations for challenge scoring. Patients: Public database included 40,336 patients’ electronic health records sourced from Beth Israel Deaconess Medical Center (hospital system A) and Emory University Hospital (hospital system B). A total of 24,819 patients from hospital systems A, B, and C (an unidentified hospital system) were sequestered as full hidden test sets. Interventions: None. Measurements and Main Results: A total of 168 features were extracted on hourly basis. Explainable artificial intelligence sepsis predictor model was trained to predict sepsis in real time. Impact of each feature on hourly sepsis prediction was explored in-depth to show the interpretability. The algorithm demonstrated the final clinical utility score of 0.364 in this challenge when tested on the full hidden test sets, and the scores on three separate test sets were 0.430, 0.422, and –0.048, respectively. Conclusions: Explainable artificial intelligence sepsis predictor model achieves superior performance for predicting sepsis risk in a real-time way and provides interpretable information for understanding sepsis risk in ICU. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s website (http://journals.lww.com/ccmjournal). Supported, in part, by the Distinguished Young Scholars of Jiangsu Province (BK20190014), the National Natural Science Foundation of China (81871444), the Key Research & Development Plan of Ministry of science and technology (2017YFB1303200), and the Primary Research & Development Plan of Jiangsu Province (BE2017735). Dr. Chengyu Liu received support from the Distinguished Young Scholars of Jiangsu Province (BK20190014), the National Natural Science Foundation of China (81871444). Dr. Li received support from the Key Research & Development Plan of Ministry of Science and Technology (2017YFB1303200) and the Primary Research & Development Plan of Jiangsu Province (BE2017735). The remaining authors have disclosed that they do not have any potential conflicts of interest. The content of this article is solely the responsibility of the authors. For information regarding this article, E-mail: chengyu@seu.edu.cn; ljq@seu.edu.cn Copyright © by 2020 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.

To investigate and explore temporal changes in risk factors of community-onset extended-spectrum β-lactamase (ESBL) Escherichia coli and Klebsiella pneumoniae bacteraemia in a region with low antibiotic resistance.

We aimed to develop and validate a risk score to predict severe respiratory failure (SRF) among patients hospitalized with coronavirus disease-2019 (COVID-19).

AbstractBackgroundPilot studies showed lower tenofovir plasma concentrations during PrEP use among transgender women (TGW) using feminizing hormones compared with cisgender men (CGM). Tenofovir diphosphate (TFV-DP) concentrations in TGW and transgender men (TGM) using gender affirming hormones and on directly observed dosing of PrEP have not been studied.MethodsTGM and TGW on at least 6 months of stable sex hormone therapy containing testosterone or estradiol (respectively) were enrolled in a 4-week study of directly observed dosing of daily oral co-formulated emtricitabine and tenofovir disoproxil fumarate (FTC/TDF). TFV-DP in dried blood spots and sex hormones in serum were measured at weekly intervals. TFV-DP was compared with 2 and 4 week samples from DOT-DBS (NCT02022657).ResultsFrom May 2017 to June 2018, 24 TGM and 24 TGW were enrolled; one TGM withdrew prior to 4 weeks of PrEP. Ethnicity (non-exclusive) was 27 (57%) white, 10 (21%) black, and 15 (32%) latinx. The median age was 31 (IQR 28 to 40). Of TGW, 9 (38%) took spironolactone in addition to estradiol. Testosterone (total and free) and estradiol concentrations were comparable before and after 4 weeks of PrEP use in TGM and TGW respectively. Historical controls comprised of 17 cisgender women (CGW) and 15 CGM. TFV-DP concentrations at week 4 were comparable between TGW and TGM (mean difference -6%; 95% CI -21% to 12%; P=0.47), comparable between TGW and CGM (mean difference -12%; 95% CI -27% to 7%; P=0.21) and were lower among TGM compared with CGW (mean difference -23%; 95% CI -36% to -7%; P=0.007). All persons in all groups were projected to reach the TFV-DP threshold that has been associated with high protection from HIV. There were no associations between serum estradiol or free testosterone concentrations and TFV-DP.ConclusionCGM, TGM, and TGW had comparable TFV-DP concentrations in DBS after 4 weeks of directly observed daily FTC/TDF PrEP use. Serum hormone concentrations were not affected by FTC/TDF PrEP use.

ABSTRACTBackgroundChronic lung disease (CLD) has been reported among African children with perinatally-acquired HIV infection (C-PHIV), despite combination antiretroviral therapy (cART). In adults, shorter telomere length (TL) has been reported in association with both CLD and HIV. As little is known in children, our objective was to compare TL in HIV+ (cART-naïve or treated) and HIV-negative children with and without CLD.MethodsParticipants included Zimbabwean C-PHIV, aged 6-16, who were either newly diagnosed and cART-naïve, or on cART for >6 months, and HIV-negative controls of similar age and sex. Packed blood cell (granulocyte) TL from 621 children were compared cross-sectionally between groups. For a subset of newly diagnosed C-PHIV, changes in TL following cART initiation was evaluated.ResultsC-PHIV had shorter granulocyte TL compared to uninfected peers, regardless of cART. Among 255 C-PHIV without CLD, TL was shorter in cART-naïve participants. In multivariable analyses adjusted for age, sex, CLD, and HIV/cART status, shorter TL was independently associated with older age, being HIV+, and having reduced forced vital capacity (FVC). Lastly, cART initiation increased TL.ConclusionsIn this cohort, C-PHIV and those with reduced FVC have shorter granulocyte TL, possibly the result of increased immune activation and cellular turnover due to long-standing HIV infection with delayed cART initiation.

AbstractBackgroundThe aim of this study was to assess the impact of HIV infection on the risk of developing hepatocellular carcinoma (HCC) in HCV-infected patients who achieve sustained virological response (SVR) with direct-acting antiviral (DAA).MethodsMultisite prospective cohort study, where HCV-monoinfected patients and HIV/HCV-coinfected individuals were included if they met: 1) SVR with DAA-based combination; 2) Liver stiffness (LS) ≥9.5 kPa previous to treatment; 3) LS measurement at the SVR time-point. The main endpoint was the occurrence of HCC. Propensity score (PS) was calculated to address potential confounders due to unbalanced distribution of baseline characteristics of HIV/HCV-coinfected and HCV-monoinfected patients.Results1035 HCV-infected patients were included, 667 (64%) coinfected with HIV. After a median (Q1-Q3) follow-up time of 43 (31-49) months, 19 (1.8%) patients developed HCC [11 (3.0%) HCV-monoinfected, 8(1.2%) HIV/HCV-coinfected individuals; p=0.013]. In the multivariable analysis, HIV co-infection was associated with a lower adjusted risk of developing HCC [sHR=0.27, 95% IC (0.08-0.90); p=0.034]. Predictors of HCC emergence were: HCV genotype 3 [sHR=7.9 (2.5-24.9); p10 [sHR=1.37 (1.01-1.86); p=0.043] and LS value at SVR [sHR=1.03 (1.01-1.06) for 1 kPa increase; p=0.011]. Using inverse probability weighting method on the PS, HIV-infected patients had a lower risk of HCC [powered HR=0.33 (0.11-0.85)].ConclusionsAmong HCV-infected patients with advanced fibrosis, who achieve SVR with DAA, HIV-coinfection seems to be associated with a lower risk of HCC occurrence. The underlying causes for this finding need to be investigated.

AbstractBackgroundPlasma chemokines are biomarkers of greater disease severity, higher bacterial burden and delayed sputum culture conversion in pulmonary tuberculosis (PTB). Whether plasma chemokines could also serve as biomarkers of unfavorable treatment outcomes in PTB is not known.MethodsA cohort of newly diagnosed, sputum smear and culture positive adult individuals with drug-sensitive PTB were recruited under the Effect of diabetes on Tuberculosis Severity study in Chennai, India. Plasma chemokine levels measured before treatment initiation were compared between 68 cases with unfavorable outcomes (treatment failure, death or recurrence) and 136 control individuals who had recurrence-free cure. A second validation cohort comprising of newly diagnosed, culture positive adults with drug-sensitive TB was used to measure plasma chemokine levels in 20 cases and 40 controls.FindingsSix chemokines (CCL2, CCL3, CCL4, CXCL8, CXCL10 and CX3CL1) were associated with increased risk, while CXCL1 was associated with decreased risk of unfavorable outcomes in unadjusted and adjusted analyses in the test cohort. Similarly, CCL3, CXCL8 and CXCL10 were associated with increased risk of unfavorable treatment outcomes in the validation cohort. Receiver operating characteristic analysis revealed combinations of CCL3, CXCL8 and CXCL10 exhibited very high sensitivity and specificity in differentiating cases versus controls.ConclusionsOur study reveals a plasma chemokine signature that can be used as a novel biomarker for predicting adverse treatment outcomes in PTB.

AbstractChlorhexidine gluconate (CHG) is an antiseptic that is widely used in healthcare due to its excellent safety profile and wide spectrum of activity. Daily bathing with CHG has proven to be effective in the prevention of healthcare-associated infections and multi-drug resistant pathogen decolonization. Despite the proven benefits of CHG use, there remain concerns and unanswered questions about the potential for unintended microbial consequences of routine CHG bathing. This review aims to explore some of these questions.

AbstractBackgroundThe diversity of individuals at risk for Trypanosoma cruzi infection in the U.S. poses challenges for diagnosis. We evaluated the diagnostic accuracy of FDA-cleared tests in the Washington Metropolitan area (WMA).Methods1514 individuals living were evaluated (1078 from Mexico, Central and northern South America [TcI-predominant areas], and 436 from southern South America [TcII/V/VI-predominant areas]). OD values from the Hemagen EIA and Chagatest v.3 Wiener, and categorical results of the IgG-TESA-blot (Western Blot with Trypomastigote Excretory-Secretory Antigen), and the Chagas Detect Plus (CDP), as well as information of area of origin were used to determine T. cruzi serostatus using Latent Class Analysis.ResultsWe detected two latent class (LC) of seropositives with low (LC1) and high (LC2) antibody levels. A significantly lower number of seropositives were detected by the Wiener, IgG-TESA-blot, and CDP in LC1 (60.6%, p

AbstractBackgroundBlastomycosis has been reported from countries in Africa and the Middle East, but a decades-long debate has persisted regarding whether this is the same disease known in North America and caused by Blastomyces dermatitidis and B. gilchristii.MethodsWe reviewed published cases of human and veterinary blastomycosis from Africa and the Middle East. We abstracted epidemiological and clinical features of cases, including sites of disease, diagnosis, management, and outcomes, and, where available, genetic and antigenic typing of case isolates. In addition, we sequenced nucleic acids from 9 clinical isolates from Africa deposited in global collections as B. dermatitidis; for 5, we sequenced the internal transcribed spacer regions, and for 4 others the whole genomes.ResultsWe identified 172 unique human patients with blastomycosis, including 159 patients from 25 African countries and 12 patients from 5 Middle Eastern countries, and 7 reports of veterinary blastomycosis. In humans, cutaneous disease predominated (n=100/137, 73%), followed by pulmonary (n=73/129, 57%) and osteoarticular involvement (n=61/128, 48%). Unusual direct microscopy/histopathological presentations included short hyphal fragments in tissues (n=23/129, 18%). Thirty-four genotyped case isolates comprised 4 species: B. percursus, (n=22, 65%) from 8 countries throughout all regions; B. emzantsi (n=9, 26%) from South Africa; B. dermatitidis (n=1, 3%) from Democratic Republic of Congo; and B. gilchristii (n=2, 6%) from South Africa and Zimbabwe.ConclusionBlastomycosis occurs throughout Africa and the Middle East and is caused predominantly by B. percursus and, at least in South Africa, B. emzantsi, resulting in distinct clinical and pathological patterns of disease.

AbstractBackgroundThe COVID-19 pandemic has led to significant reductions in transplantation, motivated in part by concerns of disproportionately more severe disease among solid organ transplant (SOT) recipients. However, clinical features, outcomes, and predictors of mortality in SOT recipients are not well-described.MethodsWe performed a multi-center cohort study of SOT recipients with laboratory-confirmed COVID-19. Data were collected using standardized intake and 28-day follow-up electronic case report forms. Multivariable logistic regression was used to identify risk factors for the primary endpoint, 28-day mortality, among hospitalized patients.ResultsFour hundred eighty-two SOT recipients from >50 transplant centers were included: 318 (66%) kidney or kidney/pancreas, 73 (15.1%) liver, 57 (11.8%) heart, and 30 (6.2%) lung. Median age was 58 (IQR 46-57), median time post-transplant was 5 years (IQR 2-10), 61% were male, and 92% had ≥1 underlying comorbidity. Among those hospitalized (376 [78%]), 117 (31%) required mechanical ventilation, and 77 (20.5%) died by 28 days after diagnosis. Specific underlying comorbidities (age >65 [aOR 3.0, 95%CI 1.7-5.5, p