Time course of risk factors associated with mortality of 1260 critically ill patients with COVID-19 admitted to 24 Italian intensive care units

94noopenPurpose: To evaluate the daily values and trends over time of relevant clinical, ventilatory and laboratory parameters during the intensive care unit (ICU) stay and their association with outcome in critically ill patients with coronavirus disease 19 (COVID-19). Methods: In this retrospective–prospective multicentric study, we enrolled COVID-19 patients admitted to Italian ICUs from February 22 to May 31, 2020. Clinical data were daily recorded. The time course of 18 clinical parameters was evaluated by a polynomial maximum likelihood multilevel linear regression model, while a full joint modeling was fit to study the association with ICU outcome. Results: 1260 consecutive critically ill patients with COVID-19 admitted in 24 ICUs were enrolled. 78% were male with a median age of 63 [55–69] years. At ICU admission, the median ratio of arterial oxygen partial pressure to fractional inspired oxygen (PaO2/FiO2) was 122 [89–175] mmHg. 79% of patients underwent invasive mechanical ventilation. The overall mortality was 34%. Both the daily values and trends of respiratory system compliance, PaO2/FiO2, driving pressure, arterial carbon dioxide partial pressure, creatinine, C-reactive protein, ferritin, neutrophil, neutrophil–lymphocyte ratio, and platelets were associated with survival, while for lactate, pH, bilirubin, lymphocyte, and urea only the daily values were associated with survival. The trends of PaO2/FiO2, respiratory system compliance, driving pressure, creatinine, ferritin, and C-reactive protein showed a higher association with survival compared to the daily values. Conclusion: Daily values or trends over time of parameters associated with acute organ dysfunction, acid–base derangement, coagulation impairment, or systemic inflammation were associated with patient survival.openZanella A.; Florio G.; Antonelli M.; Bellani G.; Berselli A.; Bove T.; Cabrini L.; Carlesso E.; Castelli G.P.; Cecconi M.; Citerio G.; Coloretti I.; Corti D.; Dalla Corte F.; De Robertis E.; Foti G.; Fumagalli R.; Girardis M.; Giudici R.; Guiotto L.; Langer T.; Mirabella L.; Pasero D.; Protti A.; Ranieri M.V.; Rona R.; Scudeller L.; Severgnini P.; Spadaro S.; Stocchetti N.; Vigano M.; Pesenti A.; Grasselli G.; Aspesi M.; Baccanelli F.; Bassi F.; Bet A.; Biagioni E.; Biondo A.; Bonenti C.; Bottino N.; Brazzi L.; Buquicchio I.; Busani S.; Calini A.; Calligaro P.; Cantatore L.P.; Carelli S.; Carsetti A.; Cavallini S.; Cimicchi G.; Coppadoro A.; Dall'Ara L.; Di Gravio V.; Erba M.; Evasi G.; Facchini A.; Fanelli V.; Feliciotti G.; Fusarini C.F.; Ferraro G.; Gagliardi G.; Garberi R.; Gay H.; Giacche L.; Grieco D.; Guzzardella A.; Longhini F.; Manzan A.; Maraggia D.; Milani A.; Mischi A.; Montalto C.; Mormina S.; Noseda V.; Paleari C.; Pedeferri M.; Pezzi A.; Pizzilli G.; Pozzi M.; Properzi P.; Rauseo M.; Russotto V.; Saccarelli L.; Servillo G.; Spano S.; Tagliabue P.; Tonetti T.; Tullo L.; Vetrugno L.; Vivona L.; Volta C.A.; Zambelli V.; Zanoni A.Zanella, A.; Florio, G.; Antonelli, M.; Bellani, G.; Berselli, A.; Bove, T.; Cabrini, L.; Carlesso, E.; Castelli, G. P.; Cecconi, M.; Citerio, G.; Coloretti, I.; Corti, D.; Dalla Corte, F.; De Robertis, E.; Foti, G.; Fumagalli, R.; Girardis, M.; Giudici, R.; Guiotto, L.; Langer, T.; Mirabella, L.; Pasero, D.; Protti, A.; Ranieri, M. V.; Rona, R.; Scudeller, L.; Severgnini, P.; Spadaro, S.; Stocchetti, N.; Vigano, M.; Pesenti, A.; Grasselli, G.; Aspesi, M.; Baccanelli, F.; Bassi, F.; Bet, A.; Biagioni, E.; Biondo, A.; Bonenti, C.; Bottino, N.; Brazzi, L.; Buquicchio, I.; Busani, S.; Calini, A.; Calligaro, P.; Cantatore, L. P.; Carelli, S.; Carsetti, A.; Cavallini, S.; Cimicchi, G.; Coppadoro, A.; Dall'Ara, L.; Di Gravio, V.; Erba, M.; Evasi, G.; Facchini, A.; Fanelli, V.; Feliciotti, G.; Fusarini, C. F.; Ferraro, G.; Gagliardi, G.; Garberi, R.; Gay, H.; Giacche, L.; Grieco, D.; Guzzardella, A.; Longhini, F.; Manzan, A.; Maraggia, D.; Milani, A.; Mischi, A.; Montalto, C.; Mormina, S.; Noseda, V.; Paleari, C.; Pedeferri, M.; Pezzi, A.; Pizzilli, G.; Pozzi, M.; Properzi, P.; Rauseo, M.; Russotto, V.; Saccarelli, L.; Servillo, G.; Spano, S.; Tagliabue, P.; Tonetti, T.; Tullo, L.; Vetrugno, L.; Vivona, L.; Volta, C. A.; Zambelli, V.; Zanoni, A

Off–label long acting injectable antipsychotics in real–world clinical practice: a cross-sectional analysis of prescriptive patterns from the STAR Network DEPOT study

Introduction: Information on the off–label use of Long–Acting Injectable (LAI) antipsychotics in the real world is lacking. In this study, we aimed to identify the sociodemographic and clinical features of patients treated with on– vs off–label LAIs and predictors of off–label First– or Second–Generation Antipsychotic (FGA vs. SGA) LAI choice in everyday clinical practice. Method: In a naturalistic national cohort of 449 patients who initiated LAI treatment in the STAR Network Depot Study, two groups were identified based on off– or on–label prescriptions. A multivariate logistic regression analysis was used to test several clinically relevant variables and identify those associated with the choice of FGA vs SGA prescription in the off–label group. Results: SGA LAIs were more commonly prescribed in everyday practice, without significant differences in their on– and off–label use. Approximately 1 in 4 patients received an off–label prescription. In the off–label group, the most frequent diagnoses were bipolar disorder (67.5%) or any personality disorder (23.7%). FGA vs SGA LAI choice was significantly associated with BPRS thought disorder (OR = 1.22, CI95% 1.04 to 1.43, p = 0.015) and hostility/suspiciousness (OR = 0.83, CI95% 0.71 to 0.97, p = 0.017) dimensions. The likelihood of receiving an SGA LAI grew steadily with the increase of the BPRS thought disturbance score. Conversely, a preference towards prescribing an FGA was observed with higher scores at the BPRS hostility/suspiciousness subscale. Conclusion: Our study is the first to identify predictors of FGA vs SGA choice in patients treated with off–label LAI antipsychotics. Demographic characteristics, i.e. age, sex, and substance/alcohol use co–morbidities did not appear to influence the choice towards FGAs or SGAs. Despite a lack of evidence, clinicians tend to favour FGA over SGA LAIs in bipolar or personality disorder patients with relevant hostility. Further research is needed to evaluate treatment adherence and clinical effectiveness of these prescriptive patterns

Comparing Long-Acting Antipsychotic Discontinuation Rates Under Ordinary Clinical Circumstances: A Survival Analysis from an Observational, Pragmatic Study

Background: Recent guidelines suggested a wider use of long-acting injectable antipsychotics (LAI) than previously, but naturalistic data on the consequences of LAI use in terms of discontinuation rates and associated factors are still sparse, making it hard for clinicians to be informed on plausible treatment courses. Objective: Our objective was to assess, under real-world clinical circumstances, LAI discontinuation rates over a period of 12 months after a first prescription, reasons for discontinuation, and associated factors. Methods: The STAR Network ‘Depot Study’ was a naturalistic, multicentre, observational prospective study that enrolled subjects initiating a LAI without restrictions on diagnosis, clinical severity or setting. Participants from 32 Italian centres were assessed at baseline and at 6 and 12 months of follow-up. Psychopathology, drug attitude and treatment adherence were measured using the Brief Psychiatric Rating Scale, the Drug Attitude Inventory and the Kemp scale, respectively. Results: The study followed 394 participants for 12 months. The overall discontinuation rate at 12 months was 39.3% (95% confidence interval [CI] 34.4–44.3), with paliperidone LAI being the least discontinued LAI (33.9%; 95% CI 25.3–43.5) and olanzapine LAI the most discontinued (62.5%; 95% CI 35.4–84.8). The most frequent reason for discontinuation was onset of adverse events (32.9%; 95% CI 25.6–40.9) followed by participant refusal of the medication (20.6%; 95% CI 14.6–27.9). Medication adherence at baseline was negatively associated with discontinuation risk (hazard ratio [HR] 0.853; 95% CI 0.742–0.981; p = 0.026), whereas being prescribed olanzapine LAI was associated with increased discontinuation risk compared with being prescribed paliperidone LAI (HR 2.156; 95% CI 1.003–4.634; p = 0.049). Conclusions: Clinicians should be aware that LAI discontinuation is a frequent occurrence. LAI choice should be carefully discussed with the patient, taking into account individual characteristics and possible obstacles related to the practicalities of each formulation

[Mechanical ventilation in acute respiratory distress syndrome. New Trends]

Adult Respiratory Distress Syndrome (ARDS) is characterized by an inflammatory process affecting endothelial and epithelial lung tissue, with occurrence of hypoxemia, bilateral X-ray infiltrates, in absence of cardiogenic edema. The introduction of Computerized Tomography brought some improvements in understanding the ARDS lung, leading to a pulmonary model made up of three zones: 1) normally inflated, 2) recruitable and 3) consolidated. It has now been well established that mechanical ventilation of ARDS lung presents some iatrogenic effects that may affect mortality. Several mechanisms are considered responsible of ventilator-associated lung injury (VALI): high inspired oxygen fraction, high inspiratory plateau pressure and large tidal volume, and intratidal collapse and reinflation of alveolar units. In these years, different ventilatory strategies in the treatment of ARDS patients have been suggested to decrease and to prevent VALI. The most important one seems to be the application of an appropriate value of tidal volume and positive end-expiratory pressure (PEEP). Several randomized studies, which compared low versus high tidal volumes, have recently been finished. Despite some differences, it seems that a ventilatory management limiting inspiratory plateau pressure to 35 cmH2O or lower may be useful to reduce VALI and mortality, also in association with a PEEP level sufficient to decrease the end-expiratory collapse. Another useful ventilatory tool for improving gas exchange and decreasing VALI in ARDS patients is likely the prone positioning, even if further studies are necessary to understand how this maneuver may really affect mortality. Another therapeutic instrument for improving oxygenation in ARDS patients is the inhalation of NO. Unfortunately, this pharmacological agent does not seem to affect the outcome of these patients