Measuring biomarkers in wastewater as a new source of epidemiological information:Current state and future perspectives

The information obtained from the chemical analysis of specific human excretion products (biomarkers) in urban wastewater can be used to estimate the exposure or consumption of the population under investigation to a defined substance. A proper biomarker can provide relevant information about lifestyle habits, health and wellbeing, but its selection is not an easy task as it should fulfil several specific requirements in order to be successfully employed. This paper aims to summarize the current knowledge related to the most relevant biomarkers used so far. In addition, some potential wastewater biomarkers that could be used for future applications were evaluated. For this purpose, representative chemical classes have been chosen and grouped in four main categories: (i) those that provide estimates of lifestyle factors and substance use, (ii) those used to estimate the exposure to toxicants present in the environment and food, (iii) those that have the potential to provide information about public health and illness and (iv) those used to estimate the population size. To facilitate the evaluation of the eligibility of a compound as a biomarker, information, when available, on stability in urine and wastewater and pharmacokinetic data (i.e. metabolism and urinary excretion profile) has been reviewed. Finally, several needs and recommendations for future research are proposed.</p

Treatment of Community-Acquired Pneumonia in Immunocompromised Adults:A Consensus Statement Regarding Initial Strategies

Background Community-acquired pneumonia (CAP) guidelines have improved the treatment and outcomes of patients with CAP, primarily by standardization of initial empirical therapy. But current society-published guidelines exclude immunocompromised patients. Research Question There is no consensus regarding the initial treatment of immunocompromised patients with suspected CAP. Study Design and Methods This consensus document was created by a multidisciplinary panel of 45 physicians with experience in the treatment of CAP in immunocompromised patients. The Delphi survey methodology was used to reach consensus. Results The panel focused on 21 questions addressing initial management strategies. The panel achieved consensus in defining the population, site of care, likely pathogens, microbiologic workup, general principles of empirical therapy, and empirical therapy for specific pathogens. Interpretation This document offers general suggestions for the initial treatment of the immunocompromised patient who arrives at the hospital with pneumonia

Measuring biomarkers in wastewater as a new source of epidemiological information:Current state and future perspectives

The information obtained from the chemical analysis of specific human excretion products (biomarkers) in urban wastewater can be used to estimate the exposure or consumption of the population under investigation to a defined substance. A proper biomarker can provide relevant information about lifestyle habits, health and wellbeing, but its selection is not an easy task as it should fulfil several specific requirements in order to be successfully employed. This paper aims to summarize the current knowledge related to the most relevant biomarkers used so far. In addition, some potential wastewater biomarkers that could be used for future applications were evaluated. For this purpose, representative chemical classes have been chosen and grouped in four main categories: (i) those that provide estimates of lifestyle factors and substance use, (ii) those used to estimate the exposure to toxicants present in the environment and food, (iii) those that have the potential to provide information about public health and illness and (iv) those used to estimate the population size. To facilitate the evaluation of the eligibility of a compound as a biomarker, information, when available, on stability in urine and wastewater and pharmacokinetic data (i.e. metabolism and urinary excretion profile) has been reviewed. Finally, several needs and recommendations for future research are proposed.This work was supported by the COST Action ES1307 “SCORE – Sewage biomarker analysis for community health assessment”. Emma Gracia-Lor is very grateful to Generalitat Valenciana, Conselleria d'Educació, Investigació, Cultura i Esport (APOSTD/2015, Programa VALi + d) for her post-doctoral contract. Lubertus Bijlsma acknowledges NPS-Euronet (HOME/2014/JDRUG/AG/DRUG/7086), co-funded by the European Union, for his post-doctoral fellowship. Erika Castrignanò, Richard Bade, Juliet Kinyua, Pedram Ramin, Nikolaos I. Rousis, Yeonsuk Ryu would like to thank the SEWPROF MC ITN project, ‘A new paradigm in drug use and human health risk assessment: Sewage profiling at the community level’ [grant agreement 317205] supported by the European Union's Seventh Framework Programme for research, technological development and demonstration for the financial support. Iria González-Mariño extends her gratitude to the Galician Council of Culture, Education and Universities for her postdoctoral contract (Plan Galego de Investigación, Innovación e Crecemento 2011–2015). Foon Yin Lai acknowledges her postdoctoral fellowship from the University of Antwerp. Luigi Lopardo, Axel Rydevik and Barbara Kasprzyk-Hordern would like to acknowledge Leverhulme Trust for funding ‘TOX-EDC, Wastewater profiling for community-wide human exposure assessment from environmental endocrine disrupting chemicals in personal care and consumer products’ (Project No: RPG-2013-297). Frederic Been would like to thank the Swiss National Science Foundation (SNF, P2LAP2_164892) for his post-doctoral grant. This publication reflects the views only of the authors, and the European Commission cannot be held responsible for any use which may be made of the information contained therein

Effects of Intermittent IL-2 Alone or with Peri-Cycle Antiretroviral Therapy in Early HIV Infection: The STALWART Study

The Study of Aldesleukin with and without antiretroviral therapy (STALWART) evaluated whether intermittent interleukin-2 (IL-2) alone or with antiretroviral therapy (ART) around IL-2 cycles increased CD4+ counts compared to no therapy

Circulating microRNAs in sera correlate with soluble biomarkers of immune activation but do not predict mortality in ART treated individuals with HIV-1 infection: A case control study

Introduction: The use of anti-retroviral therapy (ART) has dramatically reduced HIV-1 associated morbidity and mortality. However, HIV-1 infected individuals have increased rates of morbidity and mortality compared to the non-HIV-1 infected population and this appears to be related to end-organ diseases collectively referred to as Serious Non-AIDS Events (SNAEs). Circulating miRNAs are reported as promising biomarkers for a number of human disease conditions including those that constitute SNAEs. Our study sought to investigate the potential of selected miRNAs in predicting mortality in HIV-1 infected ART treated individuals. Materials and Methods: A set of miRNAs was chosen based on published associations with human disease conditions that constitute SNAEs. This case: control study compared 126 cases (individuals who died whilst on therapy), and 247 matched controls (individuals who remained alive). Cases and controls were ART treated participants of two pivotal HIV-1 trials. The relative abundance of each miRNA in serum was measured, by RTqPCR. Associations with mortality (all-cause, cardiovascular and malignancy) were assessed by logistic regression analysis. Correlations between miRNAs and CD4+ T cell count, hs-CRP, IL-6 and D-dimer were also assessed. Results: None of the selected miRNAs was associated with all-cause, cardiovascular or malignancy mortality. The levels of three miRNAs (miRs -21, -122 and -200a) correlated with IL-6 while miR-21 also correlated with D-dimer. Additionally, the abundance of miRs -31, -150 and -223, correlated with baseline CD4+ T cell count while the same three miRNAs plus miR- 145 correlated with nadir CD4+ T cell count. Discussion: No associations with mortality were found with any circulating miRNA studied. These results cast doubt onto the effectiveness of circulating miRNA as early predictors of mortality or the major underlying diseases that contribute to mortality in participants treated for HIV-1 infection

Development and Validation of a Risk Score for Chronic Kidney Disease in HIV Infection Using Prospective Cohort Data from the D:A:D Study

Ristola M. on työryhmien DAD Study Grp ; Royal Free Hosp Clin Cohort ; INSIGHT Study Grp ; SMART Study Grp ; ESPRIT Study Grp jäsen.Background Chronic kidney disease (CKD) is a major health issue for HIV-positive individuals, associated with increased morbidity and mortality. Development and implementation of a risk score model for CKD would allow comparison of the risks and benefits of adding potentially nephrotoxic antiretrovirals to a treatment regimen and would identify those at greatest risk of CKD. The aims of this study were to develop a simple, externally validated, and widely applicable long-term risk score model for CKD in HIV-positive individuals that can guide decision making in clinical practice. Methods and Findings A total of 17,954 HIV-positive individuals from the Data Collection on Adverse Events of Anti-HIV Drugs (D:A:D) study with >= 3 estimated glomerular filtration rate (eGFR) values after 1 January 2004 were included. Baseline was defined as the first eGFR > 60 ml/min/1.73 m2 after 1 January 2004; individuals with exposure to tenofovir, atazanavir, atazanavir/ritonavir, lopinavir/ritonavir, other boosted protease inhibitors before baseline were excluded. CKD was defined as confirmed (>3 mo apart) eGFR In the D:A:D study, 641 individuals developed CKD during 103,185 person-years of follow-up (PYFU; incidence 6.2/1,000 PYFU, 95% CI 5.7-6.7; median follow-up 6.1 y, range 0.3-9.1 y). Older age, intravenous drug use, hepatitis C coinfection, lower baseline eGFR, female gender, lower CD4 count nadir, hypertension, diabetes, and cardiovascular disease (CVD) predicted CKD. The adjusted incidence rate ratios of these nine categorical variables were scaled and summed to create the risk score. The median risk score at baseline was -2 (interquartile range -4 to 2). There was a 1: 393 chance of developing CKD in the next 5 y in the low risk group (risk score = 5, 505 events), respectively. Number needed to harm (NNTH) at 5 y when starting unboosted atazanavir or lopinavir/ritonavir among those with a low risk score was 1,702 (95% CI 1,166-3,367); NNTH was 202 (95% CI 159-278) and 21 (95% CI 19-23), respectively, for those with a medium and high risk score. NNTH was 739 (95% CI 506-1462), 88 (95% CI 69-121), and 9 (95% CI 8-10) for those with a low, medium, and high risk score, respectively, starting tenofovir, atazanavir/ritonavir, or another boosted protease inhibitor. The Royal Free Hospital Clinic Cohort included 2,548 individuals, of whom 94 individuals developed CKD (3.7%) during 18,376 PYFU (median follow-up 7.4 y, range 0.3-12.7 y). Of 2,013 individuals included from the SMART/ESPRIT control arms, 32 individuals developed CKD (1.6%) during 8,452 PYFU (median follow-up 4.1 y, range 0.6-8.1 y). External validation showed that the risk score predicted well in these cohorts. Limitations of this study included limited data on race and no information on proteinuria. Conclusions Both traditional and HIV-related risk factors were predictive of CKD. These factors were used to develop a risk score for CKD in HIV infection, externally validated, that has direct clinical relevance for patients and clinicians to weigh the benefits of certain antiretrovirals against the risk of CKD and to identify those at greatest risk of CKD.Peer reviewe

A global perspective on improving patient care in uncomplicated urinary tract infection: expert consensus and practical guidance

•Diagnosis of uncomplicated urinary tract infection (uUTI) is typically symptom-based.•uUTI is treated empirically with antibiotics.•Antimicrobial resistance (AMR) is a growing concern with antibiotics used to treat uUTIs.•Risk factors for AMR can be identified without urine culture. Uncomplicated urinary tract infections (uUTIs) are a common problem in female patients. Management is mainly based on empirical prescribing, but there are concerns about overtreatment and antimicrobial resistance (AMR), especially in patients with recurrent uUTIs. A multidisciplinary panel of experts met to discuss diagnosis, treatment, prevention, guidelines, AMR, clinical trial design and the impact of COVID-19 on clinical practice. Symptoms remain the cornerstone of uUTI diagnosis, and urine culture is necessary only when empirical treatment fails or rapid recurrence of symptoms or AMR is suspected. Specific antimicrobials are first-line therapy (typically nitrofurantoin, fosfomycin, trimethoprim/sulfamethoxazole and pivmecillinam, dependent on availability and local resistance data). Fluoroquinolones are not first-line options for uUTIs primarily due to safety concerns but also rising resistance rates. High-quality data to support most non-antimicrobial approaches are lacking. Local AMR data specific to community-acquired uUTIs are needed, but representative information is difficult to obtain; instead, identification of risk factors for AMR can provide a basis to guide empirical antimicrobial prescribing. The COVID-19 pandemic has impacted the management of uUTIs in some countries and may have long-lasting implications for future models of care. Management of uUTIs in female patients can be improved without increasing complexity, including simplified diagnosis and empirical antimicrobial prescribing based on patient characteristics, including a review of recent antimicrobial use and past pathogen resistance profiles, drug availability and guidelines. Current data for non-antimicrobial approaches are limited. The influence of COVID-19 on telehealth could provide an opportunity to enhance patient care in the long term