Risk Factors for Mortality in COVID-19 Hospitalized Patients in Piedmont, Italy: Results from the Multicenter, Regional, CORACLE Registry.

BACKGROUND: CORACLE is a retrospective and prospective, regional multicenter registry, developed to evaluate risk factors for mortality in a cohort of patients admitted with SARS-CoV-2 infection within non-intensive wards. METHODS: The primary objective was to estimate the role of several prognostic factors on hospital mortality in terms of adjusted Odds Ratios (aOR) with multivariable logistic regression models. RESULTS: A total of 1538 patients were enrolled; 42% were female, and 58% were >70 years old. Deceased patients were 422 (27%), with a median age of 83 years (IQR (Inter Quartile Range) 76-87). Older age at admission (aOR 1.07 per year, 95%CI 1.06-1.09), diabetes (1.41, 1.02-1.94), cardiovascular disease (1.79, 1.31-2.44), immunosuppression (1.65, 1.04-2.62), estimated glomerular filtration rate (eGFR) <30 mL/min/1.73 m2 (3.53, 2.26-5.51), higher C-reactive protein values and a decreased PaO2/FiO2 ratio at admission were associated with a higher risk of hospital mortality. Amongst patients still alive on day 7, only hydroxychloroquine (HCQ) treatment was associated with reduced mortality (0.57, 0.36-0.90). CONCLUSIONS: Several risk factors were associated with mortality in SARS-CoV-2 positive patients. Although HCQ seems to be the only factor significantly associated with reduced mortality, this result is in contrast with evidence from randomized studies. These results should be interpreted in light of the study limitations.

Rifampicin and Isoniazid Maximal Concentrations are Below Efficacy-associated Thresholds in the Majority of Patients: Time to Increase the Doses?

BACKGROUND: The treatment of drug-sensitive tuberculosis (TB) is highly effective; however, many patients have suboptimal drug exposure, which possibly explains treatment failures and selection of resistance. This study aimed to describe the prevalence and determinants of suboptimal maximal concentrations (Cmax) for anti-TB drugs. METHODS: An observational study was conducted in patients receiving first-line anti-TB treatment. At two early time points (T1 and T2), blood samples were withdrawn 2 hours post-dose (Cmax) and drug concentrations were measured. Data were expressed as medians (interquartile ranges). RESULTS: The study included 199 participants: 72.9% were male and the median age was 39.8 years (27.5-51.4). The median Cmax at T1 and T2 were 7950 ng/mL and 7122 ng/mL (rifampicin), 3260 ng/mL and 3185 ng/mL (isoniazid), 4210 ng/mL and 5742 ng/mL (ethambutol), and 31 008 ng/mL and 30 352 ng/mL (pyrazinamide), respectively. Higher doses/kg and other variables (being born in Italy and female gender for rifampicin, older age and proton pump inhibitor use for isoniazid, female gender and older age for pyrazinamide) were identified by multivariate linear regression analysis. Participants with a higher body mass index received lower doses/kg of all anti-TB drugs. Suboptimal Cmax at T1 and T2 were observed in 60% and 66% (rifampicin), 54% and 55% (isoniazid), 33% and 39% (ethambutol), 20% and 11% (pyrazinamide) of patients. Despite 21% of patients at T1 and 24% at T2 showing two or more drugs with suboptimal exposure, no effect on treatment outcome was observed. DISCUSSION: The majority of patients receiving first-line anti-TB drugs had low isoniazid and rifampin Cmax. Increased doses or the use of therapeutic drug monitoring in selected patients may be advised.

Dual antiretroviral therapies are effective and safe regimens in the central nervous system of neurologically symptomatic people living with HIV.

OBJECTIVE: Aim of this study was to compare cerebrospinal fluid (CSF) virological control, biomarkers and neurocognition of neurologically symptomatic patients on dual antiretroviral therapies (dual therapy) vs. 2 nucleoside reverse transcriptase inhibitors-based three-drug regimens (triple therapy). DESIGN: Retrospective monocentric cross-sectional study. METHODS: We analysed data from people living with HIV undergoing lumbar puncture for clinical/research reasons with plasma HIV-RNA less than 200 copies/ml and neurological/neurocognitive symptoms without significant contributing comorbidities. We measured CSF HIV-RNA, inflammation, blood-brain barrier integrity, neuronal damage and astrocytosis biomarkers (five biomarkers by ELISA and five indices by immunoturbidimetry) and recorded the neurocognitive performance (14 tests). CSF escape was defined as any case of CSF HIV-RNA 0.5 Log10 higher than viraemia or any case of detectable CSF HIV-RNA coupled with undetectable viraemia. RESULTS: A total of 78 patients on triple therapy and 19 on dual therapy were included. Overall, 75.3% male, median age 51 years (46-58), current CD4 count 545 cells/µl (349-735), time on current regimens 18 months (8-29), but length of plasma suppression 32 months (14-94). The two groups did not differ in terms of HIV-associated neurological diagnoses, demographic and viro-immunological features. Undetectable CSF HIV-RNA (73.7% in dual therapy vs. 78.2% in triple therapy, p.67) and CSF escape (21.1% in dual therapy vs. 19.2% in triple therapy, p.86) did not differ. No difference was observed in depression, anxiety, neurocognition (in 63 participants) nor in any tested biomarker. CONCLUSION: In people living with HIV with neurological/neurocognitive symptoms, peripherally effective dual therapy can show CSF virosuppression, inflammation, neuronal and astrocyte integrity and neurocognition comparable to triple therapy.