BACKGROUND. There is considerable variability in COVID-19 outcomes among younger adults, and some of this variation may be due to genetic predisposition. METHODS. We combined individual level data ...from 13,888 COVID-19 patients (n = 7185 hospitalized) from 17 cohorts in 9 countries to assess the association of the major common COVID-19 genetic risk factor (chromosome 3 locus tagged by rs10490770) with mortality, COVID-19-related complications, and laboratory values. We next performed metaanalyses using FinnGen and the Columbia University COVID-19 Biobank. RESULTS. We found that rs10490770 risk allele carriers experienced an increased risk of all-cause mortality (HR, 1.4; 95% CI, 1.2-1.7). Risk allele carriers had increased odds of several COVID-19 complications: severe respiratory failure (OR, 2.1; 95% CI, 1.6-2.6), venous thromboembolism (OR, 1.7; 95% CI, 1.2-2.4), and hepatic injury (OR, 1.5; 95% CI, 1.2-2.0). Risk allele carriers age 60 years and younger had higher odds of death or severe respiratory failure (OR, 2.7; 95% CI, 1.8-3.9) compared with those of more than 60 years (OR, 1.5; 95% CI, 1.2-1.8; interaction, P = 0.038). Among individuals 60 years and younger who died or experienced severe respiratory failure, 32.3% were risk-variant carriers compared with 13.9% of those not experiencing these outcomes. This risk variant improved the prediction of death or severe respiratory failure similarly to, or better than, most established clinical risk factors. CONCLUSIONS. The major common COVID-19 genetic risk factor is associated with increased risks of morbidity and mortality, which are more pronounced among individuals 60 years or younger. The effect was similar in magnitude and more common than most established clinical risk factors, suggesting potential implications for future clinical risk management.
Late presentation for HIV care is a major issue and the cause of higher morbidity, mortality and transmission. In this regard, we analyzed the characteristics of patients presenting for care at our ...center from January 2006 to July 2017 (n = 687). The majority of the studied population was of African origin (54.3%) with heterosexual women representing the main group (n = 292; 42.5%). 44% of the patients were late presenters (LP) (presenting for care with CD4 T cells <350/mm
or an AIDS defining event) and 24% were late presenters with advanced disease (LP-AD) (presenting for care with CD4 T cells <200/mm
or an AIDS defining event). A very high risk of being LP and LP-AD was associated with Sub-Saharan origin (OR 3.4 and 2.6 respectively). Other factors independently associated with LP or LP-AD were age (OR 1.3), male gender (OR 2.0 and 1.5 respectively) and heterosexual route of transmission (OR 2.4 and 2.3 respectively). A significant increase in HIV screening without forgetting those groups would contribute to earlier HIV diagnosis, a key element to end the HIV epidemic. To achieve this goal, addressing the specific hurdles to HIV testing in the migrant population is critical.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
OBJECTIVES:To test the usefulness of procalcitonin serum level for the reduction of antibiotic consumption in intensive care unit patients.
DESIGN:Single-center, prospective, randomized controlled ...study.
SETTING:Five intensive care units from a tertiary teaching hospital.
PATIENTS:All consecutive adult patients hospitalized for > 48 hrs in the intensive care unit during a 9-month period.
INTERVENTIONS:Procalcitonin serum level was obtained for all consecutive patients suspected of developing infection either on admission or during intensive care unit stay. The use of antibiotics was more or less strongly discouraged or recommended according to the Muller classification. Patients were randomized into two groupsone using the procalcitonin results (procalcitonin group) and one being blinded to the procalcitonin results (control group). The primary end point was the reduction of antibiotic use expressed as a proportion of treatment days and of daily defined dose per 100 intensive care unit days using a procalcitonin-guided approach. Secondary end points includeda posteriori assessment of the accuracy of the infectious diagnosis when using procalcitonin in the intensive care unit and of the diagnostic concordance between the intensive care unit physician and the infectious-disease specialist.
MEASUREMENTS AND MAIN RESULTS:There were 258 patients in the procalcitonin group and 251 patients in the control group. A significantly higher amount of withheld treatment was observed in the procalcitonin group of patients classified by the intensive care unit clinicians as having possible infection. This, however, did not result in a reduction of antibiotic consumption. The treatment days represented 62.6 ± 34.4% and 57.7 ± 34.4% of the intensive care unit stays in the procalcitonin and control groups, respectively (p = .11). According to the infectious-disease specialist, 33.8% of the cases in which no infection was confirmed, had a procalcitonin value >1µg/L and 14.9% of the cases with confirmed infection had procalcitonin levels <0.25 µg/L. The ability of procalcitonin to differentiate between certain or probable infection and possible or no infection, upon initiation of antibiotic treatment was low, as confirmed by the receiving operating curve analysis (area under the curve = 0.69). Finally, procalcitonin did not help improve concordance between the diagnostic confidence of the infectious-disease specialist and the ICU physician.
CONCLUSIONS:Procalcitonin measuring for the initiation of antimicrobials did not appear to be helpful in a strategy aiming at decreasing the antibiotic consumption in intensive care unit patients.
HIV persistence despite therapy contributes to chronic immune activation and inflammation, increasing the risk of aging-associated events in HIV-infected individuals. We sought here to better ...understand the complex link between clinical and treatment features and HIV persistence despite therapy. A total of 11,045 samples from 1,160 individuals under combination antiretroviral therapy (cART) with an unquantifiable viral load (VL; limit of quantification, 20 copies/ml) were categorized as detectable or undetectable depending on the detection of a PCR signal using a commercially available assay. Generalized estimating equation (GEE) regression was used to model viral load detectability and to assess the determinants of residual viremia (RV; VL detected below 20 copies/ml) despite therapy. A high VL zenith was associated with a higher probability to have a detectable viremia under cART. Conversely, the probability to have a detectable viral load below 20 copies/ml decreased with time under therapy. Of therapy regimens, protease inhibitor (PI)-based cART was associated with a significantly higher probability of detectable RV compared to nonnucleoside transcriptase inhibitor- or integrase inhibitor-based cART. We found that a PI-based treatment regimen is highly associated with an increased frequency of RV, supporting previous evidence suggesting that PI-based cART regimens could favor ongoing viral replication in some individuals.
Listeria monocytogenes is a rare cause of potentially lethal infection and sepsis in transplant recipients. Listeriosis is usually described after kidney or bone marrow transplant, and has been less ...frequently reported after liver transplantation. Here, the authors present two cases of severe Listeria infection occurring within 4 months after complicated liver transplantation in patients still recovering on the ward. The patients were successfully treated by intravenous ampicillin. These cases should remind transplant physicians that listeriosis may develop in liver transplant recipients, that food safety advice should be provided, and that intravenous ampicillin might be an effective treatment for systemic listeriosis in solid organ recipients. It is likely that trimethoprim‐sulfamethoxazole prophylaxis might help prevent early listeriosis after solid organ transplantation.
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BFBNIB, DOBA, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UILJ, UKNU, UL, UM, UPUK
Acute acalculous cholecystitis (AAC) can occur without gallstones in critically ill or injured patients and has also been associated with various infectious agents.(1-4) We report here a case of AAC ...in a patient with Plasmodium falciparum malaria.
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BFBNIB, FZAB, GIS, IJS, KILJ, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Abstract
Background
Polypharmacy and drug interactions are important issues for HIV-infected individuals. The number and nature of those interactions are continuously evolving with the use of new ...antiretroviral drugs and the aging of HIV-infected individuals. We aimed to analyze this evolution over time.
Methods
This retrospective cohort study was conducted in the University Hospital of Liège (Belgium). Treatments of HIV-infected outpatients attending Liège University Hospital were collected and analyzed in 2012 and 2016. The University of Liverpool HIV drug interactions database was used to determine drug interactions.
Results
We included 1038 patients in 2016, of whom 78% had 1 comedication. Polypharmacy was seen in 20% of the cohort. Four percent of the patients presented red flag interactions, and 38% had orange flag interactions. Nonantiretroviral (non-ARV) therapeutic classes involved in drug interactions were mostly cardiovascular and central nervous system drugs. They were followed by hormone drugs and dietary supplements for orange flag interactions. Two factors significantly contributed to both red and orange flag interactions: the number of non-ARV comedications and protease inhibitor–based ARV regimens. The proportion of patients with red or orange flag interactions remained stable from 2012 to 2016.
Conclusions
This study highlights the persistence of an alarming number of contraindicated drug interactions and a high prevalence of potential drug interactions over time. Identification, prevention, and management of drug interactions remain a key priority in HIV care.
In an era of evolving in the use of antiretroviral drugs and polymedication, this retrospective cohort study highlights the persistence of an alarming number of contraindicated drug interactions and a high prevalence of potential drug interactions involving antiretroviral therapies in HIV-infected patients overtime.
We report a case of louse-borne relapsing fever (LBRF) in a refugee from Somalia who had arrived in Belgium a few days earlier. He complained of myalgia and secondarily presented fever. Blood smears ...revealed spirochetes later identified as Borrelia recurrentis. LBRF should be considered in countries hosting refugees, particularly those who transit through endemic regions.