COVID-19: identifying the main outcome predictors. A retrospective cohort study in Northern Italy.

OBJECTIVE: The need for efficient drugs and early treatment of patients with SARS-CoV-2 infection developing COVID-19 symptoms is of primary importance in daily clinical practice and it is certainly among the most difficult medical challenges in the current century. Recognizing those patients who will need stronger clinical efforts could effectively help doctors anticipate the eventual need for intensification of care (IoC) and choose the best treatment in order to avoid worse outcomes. PATIENTS AND METHODS: We enrolled 501 patients, consecutively admitted to our two COVID hospitals, and collected their clinical, anamnestic and laboratory data on admission. The aim of this retrospective study was to identify those data that are strictly associated with COVID-19 outcomes (IoC and in-hospital death) and that could somehow be intended as predictors of these outcomes. This allowed us to provide a "sketch" of the patient who undergoes, more often than others, an intensification of care and/or in-hospital death. RESULTS: Males were found to have a double risk of needing an IoC (OR=2.11) and a significant role was played by both the PaO2/FiO2 ratio on admission (OR=0.99) and serum LDH (OR=1.01). The main predictors of in-hospital death were age (OR=1.08) and the PaO2/FiO2 ratio on admission (OR=0.99). CONCLUSIONS: Male patients with high serum LDH on admission are those who undergo more often an intensification of care among COVID-19 inpatients. Both age and respiratory performances on admission modify the prognosis within the hospitalization period.

Efficacy of non-invasive mechanical ventilation in the general ward in patients with chronic obstructive pulmonary disease admitted for hypercapnic acute respiratory failure and pH < 7.35: a feasibility pilot study.

AIM: To date non-invasive (NIV) mechanical ventilation use is not recommended in chronic obstructive pulmonary disease (COPD) patients with acute respiratory failure (ARF) and pH < 7.30 outside a 'protected environment'. We assessed NIV efficacy and feasibility in improving arterial blood gases (ABG) and in-hospital outcome in patients with ARF and severe respiratory acidosis (RA) admitted to an experienced rural medical ward. METHODS: This paper is a prospective pilot cohort study conducted in the General Medicine Ward of Budrio's District Hospital. Two hundred and seventy-two patients with ARF were admitted to our Department, 112, meeting predefined inclusion criteria (pH < 7.35, PaCO2 > 45 mmHg). Patients were divided according to the severity of acidosis into: group A (pH < 7.26), group B (7.26 ≤ pH < 7.30) and group C (7.30 ≤ pH < 7.35). ABG were assessed at admission, at 2-6 h, 24 h, 48 h and at discharge. RESULTS: Group A included 55 patients (24 men, mean age: 80.8 ± 8.3 years), group B 31 (12 men, mean age: 80.3 ± 9.4 years) and group C 26 (15 men, mean age: 78.6 ± 9.9 years). ABG improved within the first hours in 92/112 (82%) patients, who were all successfully discharged. Eighteen percent (20/112) of the patients died during the hospital stay, no significant difference emerged in mortality rate (MR) within the groups (23%, 16% and 8%, for groups A, B and C, respectively) and between patients with or without pneumonia: 8/29 (27%) versus 12/83 (14%). On multivariable analysis, only age and Glasgow Coma Scale had an impact on the clinical outcome. CONCLUSION: In a non-'highly protected' environment such as an experienced medical ward of a rural hospital, NIV is effective not only in patients with mild, but also with severe forms of RA. MR did not vary according to the level of initial pH.

Cognitive ability assessment by brain-computer interface validation of a new assessment method for cognitive abilities.

Brain-Computer Interfaces (BCIs) are systems which can provide communication and environmental control to people with severe neuromuscular diseases. The current study proposes a new BCI-based method for psychometric assessment when traditional or computerized testing cannot be used owing to the subject's output impairment. This administration protocol was based on, and validated against, a widely used clinical test (Raven Colored Progressive Matrix) in order to verify whether BCI affects the brain in terms of cognitive resource with a misstatement result. The operating protocol was structured into two phases: phase 1 was aimed at configuring the BCI system on the subject's features and train him/her to use it; during phase 2 the BCI system was reconfigured and the test performed. A step-by-step checking procedure was adopted to verify progressive inclusion/exclusion criteria and the underpinning variables. The protocol was validated on 19 healthy subjects and the BCI-based administration was compared with a paper-based administration. The results obtained by both methods were correlated as known for traditional assessment of a similarly culture free and reasoning based test. Although our findings need to be validated on pathological participants, in our healthy population the BCI-based administration did not affect performance and added a further control of the response due to the several variables included and analyzed by the computerized task.

An automated method for relevant frequency bands identification based on genetic algorithms and dedicated to the Motor Imagery BCI protocol.

This paper presents an automated method for relevant frequency bands identification to be used in a left/right hand motor imagery based Brain Computer Interface system. The adopted optimization method aimed at maximizing the ratio between the mutual information and the error rate obtained using a Regularized Linear Discriminant Analysis (RLDA) based classifier and band-specific amplitude modulated envelopes as features. The search problem was handled by a genetic algorithm starting from an initial population determined on the basis of a-priori mu and beta relevant frequency bands identified by means of a standard power spectral density analysis between the idle and the left/right imagery data subset.

A four command BCI system based on the SSVEP protocol.

This paper discusses the development of a four command BCI system. This system is composed of a wearable electroencephalogram acquisition unit interfaced to a computer by a wireless Bluetooth (BT) connection. The implemented system relies on the steady-state visual evoked potential (SSVEP) protocol applied to a four selection system. In order to achieve the maximum reliability against false positives a five class classifier was used considering the idle state as an independent class. In order to maximize the usability of the system a two channel solution was tested and adopted. The BCI algorithm was based on a supervised multi-class classifier implemented by combining different binary regularized linear discriminant analysis (RLDA) classifiers. The biofeedback was evaluated by combining the resultant time signed distance with quality index related to the number of coherent identification obtained with the one-vs-all approach.

A wearable device for continuous monitoring of heart mechanical function based on impedance cardiography.

In this study we explored the possibility to realize a low power device for Cardiac Output continuous monitoring based on impedance cardiography technique. We assessed the possibility to develop a system able to record data allow an intra-subjective analysis based on the daily variations of this measure. The device was able to acquire and to send signals using a wireless Bluetooth transmission. The electronic circuit was designed in order to minimize power consumption, dimension and weight. The reported results were interesting for what concerns the power consumption and then noise level. In this way was obtained a wearable device that will permit to define specific clinical protocols based on continuous monitoring of the Cardiac Output signal.

Chronic treatment with desipramine facilitates its effect on extracellular noradrenaline in the rat hippocampus: studies on the role of presynaptic alpha2-adrenoceptors.

Adaptive phenomena such as desensitization of autoreceptors are considered an important factor in the achievement of therapeutic efficacy of antidepressant drugs after chronic treatment. We have studied whether a chronic treatment with desipramine had a greater effect than a single dose on the extracellular concentrations of noradrenaline in the dorsal hippocampus. Administration of 10 mg/kg i.p. desipramine once daily for 14 days significantly raised the basal extracellular noradrenaline in the dorsal hippocampus 24 h but not 48 h after the last drug injection. A challenge dose of desipramine increased extracellular noradrenaline in rats treated chronically with vehicle and desipramine. The effect was significantly higher in rats treated chronically with desipramine 48 h but not 24 h after the last injection. An intraperitoneal administration of the alpha2-adrenoceptor agonist clonidine at the dose of 10 microg/kg significantly reduced extracellular noradrenaline in the control group but not in animals chronically treated with desipramine whereas 30 microg/kg clonidine produced a similar decrease in both groups. Three concentrations of clonidine (0.05, 0.5 and 1 microM) infused into the hippocampus significantly reduced extracellular noradrenaline to a similar extent in rats chronically treated with saline or desipramine. Fourty-eight hours after the last injection of the chronic treatment, [3H]RX-821002 binding to alpha2-adrenoceptors in the rat locus coeruleus measured by autoradiography was not significantly modified. A slight (17%) but significant decrease of neuronal uptake of [3H]noradrenaline was found in synaptosome preparations from dorsal hippocampus of rats chronically treated with desipramine, but this was likely due to a decrease in affinity. The results suggest that a repeated treatment with desipramine (10 mg/kg i.p. once daily for 14 days) facilitates its effect on extracellular noradrenaline in the dorsal hippocampus and induces adaptive changes probably involving desensitization of alpha2-adrenoceptors, with no changes in their density, on noradrenergic neurons in the locus coeruleus.

Chronic treatment with reboxetine by osmotic pumps facilitates its effect on extracellular noradrenaline and may desensitize alpha(2)-adrenoceptors in the prefrontal cortex.

1. This study investigated the effect of acute (2 days) and chronic (14 days) treatment with a selective inhibitor of noradrenaline uptake, reboxetine (10 mg kg(-1) day(-1)) by osmotic pumps, on extracellular noradrenaline and the sensitivity of alpha(2)-adrenoceptors in the prefrontal cortex of rats. 2. The effect of continuous infusion of reboxetine for 14 days on cortical extracellular noradrenaline was significantly higher (599% of vehicle levels) than after 2 days (263% of vehicle levels). 3. Brain concentrations of reboxetine after 2 and 14 days of infusion were 37.9+/-17.8 and 37.1+/-7.7 ng g(-1), respectively. 4. Reboxetine infused for 2 and 14 days significantly increased extracellular dopamine in the prefrontal cortex, to a similar extent (257 and 342% of vehicle levels, respectively), whereas extracellular 5-HT was not modified by either treatment. 5. Clonidine (10 and 30 microg kg(-1) i.p.) reduced cortical extracellular noradrenaline similarly in animals treated with reboxetine or vehicle for 2 days whereas the effects in rats infused with reboxetine for 14 days were markedly less than in vehicle-treated animals. 6. Clonidine (0.05 and 0.2 microM), infused through the dialysis probe into the prefrontal cortex, reduced cortical extracellular noradrenaline much less in rats treated with reboxetine for 14 days than in vehicle-treated animals. 7. Reboxetine's effect on extracellular noradrenaline in the prefrontal cortex was greater after chronic treatment and could be associated with desensitization of terminal alpha(2)-adrenoceptors that normally serve to inhibit noradrenaline release.

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Studies on the acute and chronic effects of reboxetine on extracellular noradrenaline and other monoamines in the rat brain.

1 The effect of reboxetine, a novel antidepressant drug that potently and selectively inhibits neuronal noradrenaline (NA) uptake, on brain extracellular monoamines was studied by microdialysis. 2 Fifteen mg kg-1 i.p. reboxetine raised extracellular NA in the frontal cortex (by 242%) and dorsal hippocampus (by 240%). 3 Idazoxan (1 mg kg-1 s.c.), given 60 min after 15 mg kg-1 reboxetine, markedly potentiated the effect on extracellular NA in the frontal cortex (by 1580%) and dorsal hippocampus (by 1360%), but had no effect by itself. 4 Twenty-four hours after the last injection of a chronic schedule (15 mg kg-1 i.p. once daily for 14 days) reboxetine had no effect on basal extracellular concentrations of NA in the dorsal hippocampus and a challenge dose of reboxetine (15 mg kg-1) raised extracellular NA similarly in rats treated chronically with reboxetine (by 353%) and saline (by 425%). 5 Ten and 20 microg kg-1 i.p. clonidine dose-dependently reduced hippocampal extracellular NA similarly in rats given chronic reboxetine (by 32% and 57%) and saline (by 42% and 56%). 6 Extracellular concentrations of dopamine and 5-HT in the striatum were similar in rats treated chronically with reboxetine and saline. A challenge dose of reboxetine (15 mg kg-1) had no effect on striatal extracellular dopamine and slightly increased striatal extracellular 5-HT to a similar extent in rats treated chronically with reboxetine (by 137%) and saline (by 142%). 7 The results suggest that combining reboxetine with an alpha2-adrenoceptor antagonist may facilitate its antidepressant activity. Repeated treatment confirmed that reboxetine is fairly selective for the noradrenergic system but provided no evidence of adaptive changes in that system that could facilitate its effect on extracellular NA.