A novel scale based on biomarkers associated with COVID-19 severity can predict the need for hospitalization and intensive care, as well as enhanced probabilities for mortality.

Prognostic scales may help to optimize the use of hospital resources, which may be of prime interest in the context of a fast spreading pandemics. Nonetheless, such tools are underdeveloped in the context of COVID-19. In the present article we asked whether accurate prognostic scales could be developed to optimize the use of hospital resources. We retrospectively studied 467 files of hospitalized patients after COVID-19. The odds ratios for 16 different biomarkers were calculated, those that were significantly associated were screened by a Pearson's correlation, and such index was used to establish the mathematical function for each marker. The scales to predict the need for hospitalization, intensive-care requirement and mortality had enhanced sensitivities (0.91 CI 0.87-0.94; 0.96 CI 0.94-0.98; 0.96 CI 0.94-0.98; all with p < 0.0001) and specificities (0.74 CI 0.62-0.83; 0.92 CI 0.87-0.96 and 0.91 CI 0.86-0.94; all with p < 0.0001). Interestingly, when a different population was assayed, these parameters did not change considerably. These results show a novel approach to establish the mathematical function of a marker in the development of highly sensitive prognostic tools, which in this case, may aid in the optimization of hospital resources. An online version of the three algorithms can be found at: http://benepachuca.no-ip.org/covid/index.php.

Survey of Barriers and Facilitators to Prescribing Buprenorphine and Clinician Perceptions on the Drug Addiction Treatment Act of 2000 Waiver.

Importance: As opioid-related deaths continue to climb, methods to reduce barriers to prescribing buprenorphine for individuals with opioid use disorder (OUD) are needed. Recent conversations by state and federal authorities targeting low-threshold buprenorphine aim to reduce some barriers to prescribing buprenorphine; however, what remains unclear is whether removal of the requirement to obtain a waiver for prescribing buprenorphine through the Drug Addiction Treatment Act of 2000 (an X-waiver) will be enough to increase access to buprenorphine. Objective: To assess barriers and facilitators of obtaining an X-waiver and prescribing buprenorphine. Design, Setting, and Participants: This mixed-method survey study was conducted between September and December 2020; 607 office-based Texas clinicians were surveyed after they attended a buprenorphine X-waiver training course. All attendees between March 2, 2019, and February 28, 2020, were eligible to receive this survey; 126 responses were received (20% response rate: 81 physicians, 37 nurse practitioners, and 8 physician assistants). Data analysis was performed October 2021. Main Outcomes and Measures: Surveys measured the extent to which clinicians experienced 9 previously identified barriers during the waiver process and in prescribing buprenorphine. The survey included open-ended items assessing facilitating factors to obtaining a waiver and to prescribing buprenorphine for OUD. The barriers were analyzed using χ2 tests of homogeneity. Qualitative data were analyzed using a constant comparative method. Results: Among 126 clinicians who responded, 61 (48.4%) had received an X-waiver; of these waivered clinicians, 22 (36%) were prescribing buprenorphine and 39 (64%) were not. "Complexity of X-waiver process," "Perceived lack of professional support and referral network," and "Getting started" were significantly different barriers among waivered and nonwaivered clinicians. Significant differences in barriers experienced between prescribers and nonprescribers were "Getting started" and "Accessing reimbursement for treatment." The most frequently mentioned facilitators involved changes to the waiver training and the need for networks connecting experienced clinicians with those in the initial stages of readiness for prescribing buprenorphine for OUD. Conclusions and Relevance: This survey study's results contribute new understanding of facilitators to obtaining the X-waiver and to prescribing buprenorphine. Furthermore, these findings suggest that to increase access to compassionate evidence-based treatment for OUD, clinicians need ongoing support and mentorship from experienced and knowledgeable clinicians. Interventions aimed at improving access to buprenorphine should focus on facilitating such networks to increase the number of clinicians who obtain an X-waiver and prescribe buprenorphine for OUD.

Tocilizumab reduces COVID-19 mortality and pathology in a dose and timing-dependent fashion: a multi-centric study.

Life-threatening COVID-19 is associated with strong inflammation, where an IL-6-driven cytokine storm appears to be a cornerstone for enhanced pathology. Nonetheless, the specific inhibition of such pathway has shown mixed outcomes. This could be due to variations in the dose of tocilizumab used, the stage in which the drug is administered or the severity of disease presentation. Thus, we performed a retrospective multicentric study in 140 patients with moderate to critical COVID-19, 79 of which received tocilizumab in variable standard doses (< 400 mg, 400-800 mg or > 800 mg), either at the viral (1-7 days post-symptom onset), early inflammatory (8-15) or late inflammatory (16 or more) stages, and compared it with standard treated patients. Mortality, reduced respiratory support requirements and pathology markers were measured. Tocilizumab significantly reduced the respiratory support requirements (OR 2.71, CI 1.37-4.85 at 95%) and inflammatory markers (OR 4.82, CI 1.4-15.8) of all patients, but mortality was only reduced (4.1% vs 25.7%, p = 0.03) when the drug was administered at the early inflammatory stage and in doses ranging 400-800 mg in severely-ill patients. Despite the apparent inability of Tocilizumab to prevent the progression of COVID-19 into a critical presentation, severely-ill patients may be benefited by its use in the early inflammatory stage and moderate doses.

Consensus for the management of analgesia, sedation and delirium in adults with COVID-19-associated acute respiratory distress syndrome. / Consenso para el manejo de la analgesia, sedación y delirium en adultos con síndrome de distrés respiratorio agudo por COVID-19.

OBJECTIVE: To propose agile strategies for a comprehensive approach to analgesia, sedation, delirium, early mobility and family engagement for patients with COVID-19-associated acute respiratory distress syndrome, considering the high risk of infection among health workers, the humanitarian treatment that we must provide to patients and the inclusion of patients' families, in a context lacking specific therapeutic strategies against the virus globally available to date and a potential lack of health resources. METHODS: A nonsystematic review of the scientific evidence in the main bibliographic databases was carried out, together with national and international clinical experience and judgment. Finally, a consensus of recommendations was made among the members of the Committee for Analgesia, Sedation and Delirium of the Sociedad Argentina de Terapia Intensiva. RESULTS: Recommendations were agreed upon, and tools were developed to ensure a comprehensive approach to analgesia, sedation, delirium, early mobility and family engagement for adult patients with acute respiratory distress syndrome due to COVID-19. DISCUSSION: Given the new order generated in intensive therapies due to the advancing COVID-19 pandemic, we propose to not leave aside the usual good practices but to adapt them to the particular context generated. Our consensus is supported by scientific evidence and national and international experience and will be an attractive consultation tool in intensive therapies.

OBJETIVO: Proponer estrategias agile para este abordaje integral de la analgesia, sedación, delirium, implementación de movilidad temprana e inclusión familiar del paciente con síndrome de dificultad respiratoria aguda por COVID-19, considerando el alto riesgo de infección que existe entre los trabajadores de salud, el tratamiento humanitario que debemos brindar al paciente y su familia, en un contexto de falta estrategias terapéuticas específicas contra el virus globalmente disponibles a la fecha y una potencial falta de recursos sanitarios. METODOS: Se llevó a cabo una revision no sistemática de la evidencia científica en las principales bases de datos bibliográficos, sumada a la experiencia y juicio clínico nacional e internacional. Finalmente, se realizó un consenso de recomendaciones entre los integrantes del Comité de Analgesia, Sedación y Delirium de la Sociedad Argentina de Terapia Intensiva. RESULTADOS: Se acordaron recomendaciones y se desarrollaron herramientas para asegurar un abordaje integral de analgesia, sedación, delirium, implementación de movilidad temprana e inclusión familiar del paciente adulto con síndrome de dificultad respiratoria aguda por COVID-19. DISCUSIÓN: Ante el nuevo orden generado en las terapias intensivas por la progresión de la pandemia de COVID-19, proponemos no dejar atrás las buenas prácticas habituales, sino adaptarlas al contexto particular generado. Nuestro consenso está respaldado en la evidencia científica, la experiencia nacional e internacional, y será una herramienta de consulta atractiva en las terapias intensivas.

Both Chloroquine and Lopinavir/Ritonavir Are Ineffective for COVID-19 Treatment and Combined Worsen the Pathology: A Single-Center Experience with Severely Ill Patients.

The off-label use of antiviral and antimalarial drugs has been considered by many researchers as a fast and relatively safe alternative to provide therapeutic options to treat COVID-19, but the assessment of such drug-specific effectiveness in this regard is far from complete. Especially, the current body of knowledge about COVID-19 therapeutics needs more data regarding drug effectiveness and safety in the severely ill patients with comorbidities. In the present article, we retrospectively analyze data from 61 patients that received treatment with chloroquine, lopinavir/ritonavir, both drugs administered together, or a standard treatment with no antiviral drugs, and the study was carried in severely ill patients. We found that either drug is ineffective at treating COVID-19, as they are not able to reduce hospitalization length, mortality, C-reactive protein (CRP), lactate dehydrogenase (LDH), d-Dimer, or ferritin, or to enhance gasometric parameters, lymphocytes, total leukocytes, and neutrophil levels, whereas both drugs administered together decrease circulating lymphocytes, increase LDH and ferritin levels, and more importantly, enhance mortality. In this way, our results show that both drugs are ineffective and even potentially harmful alternatives against SARS-CoV-2.

Consenso para el manejo de la analgesia, sedación y delirium en adultos con síndrome de distrés respiratorio agudo por COVID-19 / Consensus for the management of analgesia, sedation and delirium in adults with COVID-19-associated acute respiratory distress syndrome

RESUMEN Objetivo: Proponer estrategias agile para este abordaje integral de la analgesia, sedación, delirium, implementación de movilidad temprana e inclusión familiar del paciente con síndrome de dificultad respiratoria aguda por COVID-19, considerando el alto riesgo de infección que existe entre los trabajadores de salud, el tratamiento humanitario que debemos brindar al paciente y su familia, en un contexto de falta estrategias terapéuticas específicas contra el virus globalmente disponibles a la fecha y una potencial falta de recursos sanitarios. Metodos: Se llevó a cabo una revision no sistemática de la evidencia científica en las principales bases de datos bibliográficos, sumada a la experiencia y juicio clínico nacional e internacional. Finalmente, se realizó un consenso de recomendaciones entre los integrantes del Comité de Analgesia, Sedación y Delirium de la Sociedad Argentina de Terapia Intensiva. Resultados: Se acordaron recomendaciones y se desarrollaron herramientas para asegurar un abordaje integral de analgesia, sedación, delirium, implementación de movilidad temprana e inclusión familiar del paciente adulto con síndrome de dificultad respiratoria aguda por COVID-19. Discusión: Ante el nuevo orden generado en las terapias intensivas por la progresión de la pandemia de COVID-19, proponemos no dejar atrás las buenas prácticas habituales, sino adaptarlas al contexto particular generado. Nuestro consenso está respaldado en la evidencia científica, la experiencia nacional e internacional, y será una herramienta de consulta atractiva en las terapias intensivas.

ABSTRACT Objective: To propose agile strategies for a comprehensive approach to analgesia, sedation, delirium, early mobility and family engagement for patients with COVID-19-associated acute respiratory distress syndrome, considering the high risk of infection among health workers, the humanitarian treatment that we must provide to patients and the inclusion of patients' families, in a context lacking specific therapeutic strategies against the virus globally available to date and a potential lack of health resources. Methods: A nonsystematic review of the scientific evidence in the main bibliographic databases was carried out, together with national and international clinical experience and judgment. Finally, a consensus of recommendations was made among the members of the Committee for Analgesia, Sedation and Delirium of the Sociedad Argentina de Terapia Intensiva. Results: Recommendations were agreed upon, and tools were developed to ensure a comprehensive approach to analgesia, sedation, delirium, early mobility and family engagement for adult patients with acute respiratory distress syndrome due to COVID-19. Discussion: Given the new order generated in intensive therapies due to the advancing COVID-19 pandemic, we propose to not leave aside the usual good practices but to adapt them to the particular context generated. Our consensus is supported by scientific evidence and national and international experience and will be an attractive consultation tool in intensive therapies.

Central venous to mixed venous blood oxygen and lactate gradients are associated with outcome in critically ill patients.

OBJECTIVE: Blood O(2) saturation and lactate concentration gradients from superior vena cava (SVC) to pulmonary artery (PA) occur in critically ill patients. These gradients (DeltaSO(2) and Delta[Lac]) may be positive or negative. We tested the hypothesis that positive DeltaSO(2) and Delta[Lac] are associated with improved survival in critically ill patients. DESIGN AND SETTING: Multinational, prospective observational study conducted in six medical and surgical ICUs. PATIENTS: Consecutive sample of 106 adults requiring insertion of a pulmonary artery catheter (PAC). Average age was 59.5 +/- 15.5 years, APACHE II score was 15.5 +/- 6.7 (mean +/- SD). Main outcome measure was 28-day mortality. INTERVENTIONS: None. MEASUREMENTS AND RESULTS: We drew blood samples from the proximal and distal ports of PACs every 6 h from the time of PAC insertion (Initial measurement) until its removal (Final measurement). Samples were analyzed for SO(2), [Lac], glucose concentration and blood gases. Hemodynamic measurements were obtained after blood samples. We monitored patients for 30.9 +/- 11.0 h. Overall mortality rate was 25.5%. More survivors had mean and final DeltaSO(2) > or = 0 and Delta[Lac] > or = 0 than decedents (p < 0.01; p < 0.05 respectively). On the average, DeltaSO(2) and Delta[Lac] were positive in survivors and negative in decedents. Survival odds ratios for final measurements of DeltaSO(2) > or = 0 and Delta[Lac] > or = 0 were 19.22 and 7.70, respectively (p < 0.05). CONCLUSIONS: A strong association exists between positive DeltaSO(2) and Delta[Lac] and survival in critically ill patients. Whether therapy aimed at increasing DeltaSO(2) and Delta[Lac] results in improved ICU survival remains to be determined.