Lopinavir/Ritonavir and Darunavir/Cobicistat in Hospitalized COVID-19 Patients: Findings From the Multicenter Italian CORIST Study

Background: Protease inhibitors have been considered as possible therapeutic agents for COVID-19 patients. Objectives: To describe the association between lopinavir/ritonavir (LPV/r) or darunavir/cobicistat (DRV/c) use and in-hospital mortality in COVID-19 patients. Study Design: Multicenter observational study of COVID-19 patients admitted in 33 Italian hospitals. Medications, preexisting conditions, clinical measures, and outcomes were extracted from medical records. Patients were retrospectively divided in three groups, according to use of LPV/r, DRV/c or none of them. Primary outcome in a time-to event analysis was death. We used Cox proportional-hazards models with inverse probability of treatment weighting by multinomial propensity scores. Results: Out of 3,451 patients, 33.3% LPV/r and 13.9% received DRV/c. Patients receiving LPV/r or DRV/c were more likely younger, men, had higher C-reactive protein levels while less likely had hypertension, cardiovascular, pulmonary or kidney disease. After adjustment for propensity scores, LPV/r use was not associated with mortality (HR = 0.94, 95% CI 0.78 to 1.13), whereas treatment with DRV/c was associated with a higher death risk (HR = 1.89, 1.53 to 2.34, E-value = 2.43). This increased risk was more marked in women, in elderly, in patients with higher severity of COVID-19 and in patients receiving other COVID-19 drugs. Conclusions: In a large cohort of Italian patients hospitalized for COVID-19 in a real-life setting, the use of LPV/r treatment did not change death rate, while DRV/c was associated with increased mortality. Within the limits of an observational study, these data do not support the use of LPV/r or DRV/c in COVID-19 patients

A database of the coseismic effects following the 30 October 2016 Norcia earthquake in Central Italy

We provide a database of the coseismic geological surface effects following the Mw 6.5 Norcia earthquake that hit central Italy on 30 October 2016. This was one of the strongest seismic events to occur in Europe in the past thirty years, causing complex surface ruptures over an area of >400 km 2. The database originated from the collaboration of several European teams (Open EMERGEO Working Group; about 130 researchers) coordinated by the Istituto Nazionale di Geofisica e Vulcanologia. The observations were collected by performing detailed field surveys in the epicentral region in order to describe the geometry and kinematics of surface faulting, and subsequently of landslides and other secondary coseismic effects. The resulting database consists of homogeneous georeferenced records identifying 7323 observation points, each of which contains 18 numeric and string fields of relevant information. This database will impact future earthquake studies focused on modelling of the seismic processes in active extensional settings, updating probabilistic estimates of slip distribution, and assessing the hazard of surface faulting

Pneumonia and hospitalizations in the elderly

Pneumonia in the elderly is a common and severe problem. In this review we analyze the state of the art for pneumonia in the elderly. Several aspects are discussed: i) how common is the disease; signs and symptoms in the elderly; ii) the elderly must always be hospitalized and which is the best place - Intensive Care Unit or medical ward?; iii) the role of comorbidities; iv) etiology and pathogenesis; medical treatment - when and how to start; v) antibiotic resistance; vi) antibiotics in hospital acquired and ventilator related pneumonia; vii) assisted non-invasive ventilation; viii) the treatment in the terminally ill elderly patient

SLOPE ANALYSIS AND ROCK FALL ASSESSMENT IN THE KHINIS ARCHAEOLOGICAL AREA (KURDISTAN, NORTHERN IRAQ)

This work assesses the conditions of slope instability in the Khinis archaeological area (northern Iraq), which threaten the integrity and conservation of the local cultural heritage. The site preserves traces of sculpturing activity produced during the reign of the Assyrian king Sennacherib (VIII-VII centuries BCE, i.e. before common era). Bas-reliefs were created to celebrate the realization of canalization works built to transport waters from the Zagros Mountains to Nineveh. Multidisciplinary analysis of the local rock slope highlights active rock fall processes of varying magnitude. A few large rock pillars (hundreds of m) show different conditions of instability after a limit-equilibrium analysis. Meanwhile, potential falls of smaller rock blocks affect the entire Khinis slope as they can detach from mid-slope escarpments. Through probabilistic 3D modelling, the calculation of block trajectories, arrest areas and energy values involved allows the design of a remediation plan, in accordance with the preservation requirements of the landscape value of the site. Finally, some hypotheses are advanced concerning the possible relationships between rock fall processes and the accomplishment of some of the Assyrian sculptures. A reason for further interest in this archaeological site, that it will soon be proposed for inclusion in the UNESCO World Heritage List

A Rapid Antigen Detection Test to Diagnose SARS-CoV-2 Infection Using Exhaled Breath Condensate by A Modified Inflammacheck® Device

Background: The standard test that identifies the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is based on reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal (NP) swab specimens. We compared the accuracy of a rapid antigen detection test using exhaled breath condensate by a modified Inflammacheck® device with the standard RT-PCR to diagnose SARS-CoV-2 infection. Methods: We performed a manufacturer-independent, cross-sectional, diagnostic accuracy study involving two Italian hospitals. Sensitivity, specificity, positive (PLR) and negative likelihood ratio (NLR), positive (PPV) and negative predictive value (NPV) and diagnostic accuracy with 95% confidence intervals (95% CI) of Inflammacheck® were calculated using the RT-PCR results as the standard. Further RT-PCR tests were conducted on NP specimens from test positive subjects to obtain the Ct (cycle threshold) values as indicative evidence of the viral load. Results: A total of 105 individuals (41 females, 39.0%; 64 males, 61.0%; mean age: 58.4 years) were included in the final analysis, with the RT-PCR being positive in 13 (12.4%) and negative in 92 (87.6%). The agreement between the two methods was 98.1%, with a Cohen’s κ score of 0.91 (95% CI: 0.79–1.00). The overall sensitivity and specificity of the Inflammacheck® were 92.3% (95% CI: 64.0%–99.8%) and 98.9% (95% CI: 94.1%–100%), respectively, with a PLR of 84.9 (95% CI: 12.0–600.3) and a NLR of 0.08 (95% CI: 0.01–0.51). Considering a 12.4% disease prevalence in the study cohort, the PPV was 92.3% (95% CI: 62.9%–98.8%) and the NPV was 98.9% (95% CI: 93.3%–99.8%), with an overall accuracy of 98.1% (95% CI: 93.3%–99.8%). The Fagan’s nomogram substantially confirmed the clinical applicability of the test in a realistic scenario with a pre-test probability set at 4%. Ct values obtained for the positive test subjects by means of the RT-PCR were normally distributed between 26 and 38 cycles, corresponding to viral loads from light (38 cycles) to high (26 cycles). The single false negative record had a Ct value of 33, which was close to the mean of the cohort (32.5 cycles). Conclusions: The modified Inflammacheck® device may be a rapid, non-demanding and cost-effective method for SARS-CoV-2 detection. This device may be used for routine practice in different healthcare settings (community, hospital, rehabilitation)

Audit on the appropriateness of integrated COPD management: The "aLT-BPCO" project

Background: Non communicable chronic diseases (including respiratory ones) are the leading cause of death and disability. To cope with them we need to redesign the health system, improving primary prevention, screening, and outpatient services, while fully integrating different branches of the health service. The Italian Ministry of Health published extended guidelines on integrated COPD management (COPD-GL) in 2010. In 2011 a condensed version was produced. These documents define appropriateness of management regarding both the specialist and the health service. Methods: An internal audit on how clinical practice conforms to COPD-GL standards was implemented in one Italian region involving 29 respiratory units (RU) (65.8% of the total regional RU): data were collected from the clinical database at time zero and after 6 months. In the meantime, specialists of RU underwent education on COPD-GL. Results: At time zero, significant gaps between current practice and recommendations emerged both in medical practice (mean agreement 25%) and in the health organization (48%). At month 6 the gaps were reduced more in clinical practice (60.7%) than in organization (54.7%). Conclusions: It is easier to resolve the gaps in specialist clinical practice than the organizational gaps, changing which is the politicians' task. Correcting specialists' inappropriateness may be worthless if this is not accompanied by improvement of the organizational obstacles. The search for appropriateness should not be limited only to specialists or to a strict control of drug prescription but should include all the organizational aspects. Implementation of COPD-GL calls for actions on the part of both specialists and the health system

Coseismic effects of the 2016 Amatrice seismic sequence: first geological results

Since the beginning of the ongoing Amatrice seismic sequence on August 24, 2016, initiated by a Mw 6.0 normal faulting earthquake, the EMERGEO Working Group (an INGV team devoted to earthquake aftermath geological survey) set off to investigate any coseismic effects on the natural environment. Up to now, we surveyed about 750 km2 and collected more than 3200 geological observations as differently oriented tectonic fractures together with intermediate- to small- sized landslides, that were mapped in the whole area. The most impressive coseismic evidence was found along the known active Mt. Vettore fault system, where surface ruptures with clear vertical/horizontal offset were observed for more than 5 km, while unclear and discontinuous coseismic features were recorded along the Laga Mts. Fault systems

Disentangling the Association of Hydroxychloroquine Treatment with Mortality in Covid-19 Hospitalized Patients through Hierarchical Clustering

The efficacy of hydroxychloroquine (HCQ) in treating SARS-CoV-2 infection is harshly debated, with observational and experimental studies reporting contrasting results. To clarify the role of HCQ in Covid-19 patients, we carried out a retrospective observational study of 4,396 unselected patients hospitalized for Covid-19 in Italy (February-May 2020). Patients' characteristics were collected at entry, including age, sex, obesity, smoking status, blood parameters, history of diabetes, cancer, cardiovascular and chronic pulmonary diseases, and medications in use. These were used to identify subtypes of patients with similar characteristics through hierarchical clustering based on Gower distance. Using multivariable Cox regressions, these clusters were then tested for association with mortality and modification of effect by treatment with HCQ. We identified two clusters, one of 3,913 younger patients with lower circulating inflammation levels and better renal function, and one of 483 generally older and more comorbid subjects, more prevalently men and smokers. The latter group was at increased death risk adjusted by HCQ (HR[CI95%] = 3.80[3.08-4.67]), while HCQ showed an independent inverse association (0.51[0.43-0.61]), as well as a significant influence of cluster*HCQ interaction (p<0.001). This was driven by a differential association of HCQ with mortality between the high (0.89[0.65-1.22]) and the low risk cluster (0.46[0.39-0.54]). These effects survived adjustments for additional medications in use and were concordant with associations with disease severity and outcome. These findings suggest a particularly beneficial effect of HCQ within low risk Covid-19 patients and may contribute to clarifying the current controversy on HCQ efficacy in Covid-19 treatment