Since acute hepatitis C virus (HCV) infection is often asymptomatic, it is difficult to examine the rate and determinants of spontaneous clearance. Consequently, these studies are subject to bias, ...which can potentially lead to biased rates of viral clearance and risk estimates. We evaluated determinants of spontaneous HCV clearance among HCV seroconverters identified in a unique community-based cohort.
Subjects were 106 drug users with documented dates of HCV seroconversion from the Amsterdam Cohort Study. Logistic regression was used to examine sociodemographic, behavioral, clinical, viral and host determinants, measured around acute infection, of HCV clearance.
The spontaneous viral clearance rate was 33.0% (95% confidence interval (CI) 24.2-42.8). In univariate analyses female sex and fever were significantly associated with spontaneous clearance. The favorable genotypes for rs12979860 (CC) and rs8099917 (TT) were associated with spontaneous clearance, although borderline significant. In multivariate analysis, females with the favorable genotype for rs12979860 (CC) had an increased odds to spontaneously clear HCV infection (adjusted OR 6.62, 95% 2.69-26.13), whereas females with the unfavorable genotype were as likely as men with the favorable and unfavorable genotype to clear HCV. Chronic Hepatitis B infection and absence of HIV coinfection around HCV seroconversion also favor HCV clearance.
This study shows that co-infection with HIV and HBV and genetic variation in the IL28B region play an important role in spontaneous clearance of HCV. Our findings suggest a possible synergistic interaction between female sex and IL28B in spontaneous clearance of HCV.
The objective of this study was to assess the cumulative incidence of invasive candidiasis (IC) in intensive care units (ICUs) in Europe.
A multinational, multicenter, retrospective study was ...conducted in 23 ICUs in 9 European countries, representing the first phase of the candidemia/intra-abdominal candidiasis in European ICU project (EUCANDICU).
During the study period, 570 episodes of ICU-acquired IC were observed, with a cumulative incidence of 7.07 episodes per 1000 ICU admissions, with important between-center variability. Separated, non-mutually exclusive cumulative incidences of candidemia and IAC were 5.52 and 1.84 episodes per 1000 ICU admissions, respectively. Crude 30-day mortality was 42%. Age (odds ratio OR 1.04 per year, 95% CI 1.02-1.06, p < 0.001), severe hepatic failure (OR 3.25, 95% 1.31-8.08, p 0.011), SOFA score at the onset of IC (OR 1.11 per point, 95% CI 1.04-1.17, p 0.001), and septic shock (OR 2.12, 95% CI 1.24-3.63, p 0.006) were associated with increased 30-day mortality in a secondary, exploratory analysis.
The cumulative incidence of IC in 23 European ICUs was 7.07 episodes per 1000 ICU admissions. Future in-depth analyses will allow explaining part of the observed between-center variability, with the ultimate aim of helping to improve local infection control and antifungal stewardship projects and interventions.
COVID-19 associated pulmonary aspergillosis (CAPA) is associated with increased morbidity and mortality in ICU patients. We investigated the incidence of, risk factors for and potential benefit of a ...pre-emptive screening strategy for CAPA in ICUs in the Netherlands/Belgium during immunosuppressive COVID-19 treatment.
A retrospective, observational, multicentre study was performed from September 2020–April 2021 including patients admitted to the ICU who had undergone diagnostics for CAPA. Patients were classified based on 2020 ECMM/ISHAM consensus criteria.
CAPA was diagnosed in 295/1977 (14.9%) patients. Corticosteroids were administered to 97.1% of patients and interleukin-6 inhibitors (anti-IL-6) to 23.5%. EORTC/MSGERC host factors or treatment with anti-IL-6 with or without corticosteroids were not risk factors for CAPA. Ninety-day mortality was 65.3% (145/222) in patients with CAPA compared to 53.7% (176/328) without CAPA (p = 0.008). Median time from ICU admission to CAPA diagnosis was 12 days. Pre-emptive screening for CAPA was not associated with earlier diagnosis or reduced mortality compared to a reactive diagnostic strategy.
CAPA is an indicator of a protracted course of a COVID-19 infection. No benefit of pre-emptive screening was observed, but prospective studies comparing pre-defined strategies would be required to confirm this observation.
•Incidence of COVID-19 associated pulmonary aspergillosis (CAPA) was 14.9%.•Treatment with interleukin-6 inhibitors was not a risk factor for CAPA.•Ninety-day mortality was higher in patients with CAPA than in patients without CAPA.•Median time from ICU admission to CAPA diagnosis was 12 days.•No benefit of a pre-emptive screening strategy for CAPA was observed.
Infections with hypervirulent
Klebsiella pneumoniae
(hvKp) commonly presents with primary liver infection, bacteremia, and metastatic abscesses. Here, we present 2 cases of severe community-acquired ...pulmonary infections by hvKp in patients in the Netherlands without recent travel history. Both bacterial isolates are closely related to an archetype ST23 hvKp reference isolate. Based on these findings, surveillance programs on hvKp may consider to include isolates from community-acquired pneumonia by
K. pneumoniae
.
Injecting drug users (DU) are at high risk for hepatitis C virus (HCV) and HIV infections. To examine the prevalence and incidence of these infections over a 20-year period (1985-005), the authors ...evaluated 1276 DU from the Amsterdam Cohort Studies who had been tested prospectively for HIV infection and retrospectively for HCV infection. To compare HCV and HIV incidences, a smooth trend was assumed for both curves over calendar time. Risk factors for HCV seroconversion were determined using Poisson regression. Among ever-injecting DU, the prevalence of HCV antibodies was 84.5% at study entry, and 30.9% were co-infected with HIV. Their yearly HCV incidence dropped from 27.5/100 person years (PY) in the 1980s to 2/100 PY in recent years. In multivariate analyses, ever-injecting DU who currently injected and borrowed needles were at increased risk of HCV seroconversion (incidence rate ratio 29.9, 95% CI 12.6, 70.9) compared to ever-injecting DU who did not currently inject. The risk of HCV seroconversion decreased over calendar time. The HCV incidence in ever-injecting DU was on average 4.4 times the HIV incidence, a pattern seen over the entire study period. The simultaneous decline of both HCV and HIV incidence probably results from reduced risk behavior at the population level.
Although hepatitis C virus (HCV) treatment has shown to be effective, uptake of treatment among active drug users is still low. The Drug Users Treatment for Chronic Hepatitis-C project aims to offer ...active drug users in Amsterdam HCV testing and treatment using a multidisciplinary approach.
The study population comprises drug users participating in the Amsterdam Cohort Studies and drug users referred to the Drug Users Treatment for Chronic Hepatitis-C unit. Drug users were offered HCV testing and, if chronically infected, medical and psychiatric screening and HCV treatment. Various specialists collaborated to provide optimal care. We assessed test-uptake and treatment-uptake and outcomes.
Four hundred and ninety-seven Amsterdam Cohort Studies drug users were offered HCV testing: 449 out of 497 (90%) accepted. HCV antibodies were found in 267 out of 449 (60%): 183 out of 267 (69%) were HCV-viremic and 49 out of 183 (27%) were HIV-co-infected. Of the 134 HCV-monoinfected patients, 102 (76%) initiated additional medical screening and 44 started treatment by 1 July 2009. Sixty-two drug users referred from methadone clinics were also HCV-monoinfected, of whom 14 started treatment by 1 July 2009. In total 58 persons were treated: 16 (27%) with genotype 1 or 4, 42 (72%) with genotype 2 or 3. Eighty-four percent used methadone, 97% used drugs (heroin, cocaine or amphetamine) at least once in the 6 months before treatment, 19% were active injectors. Sixty-two percent used alcohol, 41% had psychiatric disease other than substance abuse. Of the 57 individuals with sufficient follow-up, 37 (65%) achieved sustained virological response.
In a multidisciplinary setting, HIV-negative drug users with chronic HCV infection can be treated successfully despite active drug or alcohol use and psychiatric diseases. Therefore, access to HCV therapy using an integrated approach should be increased for this population.
Effective screening programs are urgently needed to provide undiagnosed hepatitis C virus (HCV)-infected individuals with therapy. This systematic review of characteristics and outcomes of screening ...programs for HCV focuses on strategies to identify HCV risk groups hidden in the general population.
We conducted a comprehensive search of MEDLINE and EMBASE databases for articles published between 1991-2010, including studies that screened the general population using either a newly developed (nonintegrated) screening program or one integrated in existing health care facilities. Look-back studies, prevalence studies, and programs targeting high-risk groups in care (e.g., current drug users) were excluded.
After reviewing 7052 studies, we identified 67 screening programs: 24 nonintegrated; 41 programs integrated in a variety of health care facilities (e.g., general practitioner); and 2 programs with both integrated and nonintegrated strategies. Together, these programs identified approximately 25,700 HCV-infected individuals. In general, higher HCV prevalence was found in programs in countries with intermediate to high HCV prevalence, in psychiatric clinics, and in programs that used a prescreening selection based on HCV risk factors. Only 6 programs used a comparison group for evaluation purposes, and 1 program used theory about effective promotion for screening. Comparison of the programs and their effectiveness was hampered by lack of reported data on program characteristics, clinical follow-up, and type of diagnostic test.
A prescreening selection based on risk factors can increase the efficiency of screening in low-prevalence populations, and we need programs with comparison groups to evaluate effectiveness. Also, program characteristics such as type of diagnostic test, screening uptake, and clinical outcomes should be reported systematically.
Introduction
Intra-abdominal infections represent the second most frequently acquired infection in the intensive care unit (ICU), with mortality rates ranging from 20% to 50%.
Candida
spp. may be ...responsible for up to 10–30% of cases. This study assesses risk factors for development of intra-abdominal candidiasis (IAC) among patients admitted to ICU.
Methods
We performed a case–control study in 26 European ICUs during the period January 2015–December 2016. Patients at least 18 years old who developed an episode of microbiologically documented IAC during their stay in the ICU (at least 48 h after admission) served as the case cohort. The control group consisted of adult patients who did not develop episodes of IAC during ICU admission. Matching was performed at a ratio of 1:1 according to time at risk (i.e. controls had to have at least the same length of ICU stay as their matched cases prior to IAC onset), ICU ward and period of study.
Results
During the study period, 101 case patients with a diagnosis of IAC were included in the study. On univariate analysis, severe hepatic failure, prior receipt of antibiotics, prior receipt of parenteral nutrition, abdominal drain, prior bacterial infection, anastomotic leakage, recurrent gastrointestinal perforation, prior receipt of antifungal drugs and higher median number of abdominal surgical interventions were associated with IAC development. On multivariate analysis, recurrent gastrointestinal perforation (OR 13.90; 95% CI 2.65–72.82,
p
= 0.002), anastomotic leakage (OR 6.61; 95% CI 1.98–21.99,
p
= 0.002), abdominal drain (OR 6.58; 95% CI 1.73–25.06,
p
= 0.006), prior receipt of antifungal drugs (OR 4.26; 95% CI 1.04–17.46,
p
= 0.04) or antibiotics (OR 3.78; 95% CI 1.32–10.52,
p
= 0.01) were independently associated with IAC.
Conclusions
Gastrointestinal perforation, anastomotic leakage, abdominal drain and prior receipt of antifungals or antibiotics may help to identify critically ill patients with higher probability of developing IAC. Prospective studies are needed to identify which patients will benefit from early antifungal treatment.
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