El resurgimiento del metoxiflurano en México / The resurgence of methoxyflurane in Mexico

Resumen: El metoxiflurano es un anestésico halogenado que se utilizó hace varias décadas para anestesia general balanceada y que actualmente está indicado para otorgar sedación controlada por el paciente. Este medicamento se encuentra actualmente a la venta en la República Mexicana, por lo que recordar las características que lo hacen diferente a otros halogenados, su farmacocinética y su utilidad para distintos escenarios proporciona el conocimiento adecuado para su uso en la práctica clínica.

Abstract: Methoxyflurane is a halogenated anesthetic that was used decades ago for a balanced general anesthesia and is currently indicated for patient-controlled sedation. This drug is currently on sale in the Mexican Republic, so remembering the characteristics that make it different from other halogenated drugs, its pharmacokinetics and its usefulness for different scenarios provides knowledge for use in clinical practice.

Effectiveness of COVID-19 Vaccines at Preventing Emergency Department or Urgent Care Encounters and Hospitalizations Among Immunocompromised Adults: An Observational Study of Real-World Data Across 10 US States from August-December 2021

BackgroundImmunocompromised (IC) persons are at increased risk for severe COVID-19 outcomes and are less protected by 1-2 COVID-19 vaccine doses than are immunocompetent (non-IC) persons. We compared vaccine effectiveness (VE) against medically attended COVID-19 of 2-3 mRNA and 1-2 viral-vector vaccine doses between IC and non-IC adults. MethodsUsing a test-negative design among eight VISION Network sites, VE against laboratory-confirmed COVID-19-associated emergency department (ED) or urgent care (UC) events and hospitalizations from 26 August-25 December 2021 was estimated separately among IC and non-IC adults and among specific IC condition subgroups. Vaccination status was defined using number and timing of doses. VE for each status (versus unvaccinated) was adjusted for age, geography, time, prior positive test result, and local SARS-CoV-2 circulation. ResultsWe analyzed 8,848 ED/UC events and 18,843 hospitalizations among IC patients and 200,071 ED/UC events and 70,882 hospitalizations among non-IC patients. Among IC patients, 3-dose mRNA VE against ED/UC (73% [95% CI: 64-80]) and hospitalization (81% [95% CI: 76-86]) was lower than that among non-IC patients (ED/UC: 94% [95% CI: 93-94]; hospitalization: 96% [95% CI: 95-97]). Similar patterns were observed for viral-vector vaccines. Transplant recipients had lower VE than other IC subgroups. ConclusionsDuring B.1.617.2 (Delta) variant predominance, IC adults received moderate protection against COVID-19-associated medical events from three mRNA doses, or one viral-vector dose plus a second dose of any product. However, protection was lower in IC versus non-IC patients, especially among transplant recipients, underscoring the need for additional protection among IC adults. Key pointsDuring Delta variant predominance, immunocompromised (IC) adults received moderate protection against COVID-19-associated medical events from three mRNA doses, but IC patients, especially transplant recipients, were less protected than non-IC patients, underscoring the need for additional protection beyond the primary series.

Association between COVID-19 mRNA vaccination and COVID-19 illness and severity during Omicron BA.4 and BA.5 sublineage periods

ImportanceRecent sublineages of the SARS-CoV-2 Omicron variant, including BA.4 and BA.5, may be associated with greater immune evasion and less protection against COVID-19 following vaccination. ObjectiveTo evaluate the association between COVID-19 mRNA vaccination with 2, 3, or 4 doses among immunocompetent adults and the risk of medically attended COVID-19 illness during a period of BA.4/BA.5 predominant circulation; to evaluate the relative severity of COVID-19 in hospitalized cases across Omicron BA.1, BA.2/BA.2.12.1, and BA.4/BA.5 sublineage periods. Setting, Design and ParticipantsTest-negative study of adults with COVID-19-like illness (CLI) and molecular testing for SARS-CoV-2 conducted in 10 states from December 16, 2021, to August 20, 2022. ExposuremRNA COVID-19 vaccination. Main Outcomes and MeasuresEmergency department/urgent care encounters, hospitalizations, and admission to the intensive care unit (ICU) or in-hospital death. The adjusted odds ratio (OR) for the association between prior vaccination and medically attended COVID-19 was used to estimate VE, stratified by care setting and vaccine doses (2, 3, or 4 doses vs 0 doses as reference group). Among hospitalized case-patients, demographic and clinical characteristics and in-hospital outcomes including ICU admission and death were compared across sublineage periods. ResultsBetween June 19 - August 20, 2022, 82,229 ED/UC and 21,007 hospital encounters were included for the BA.4/BA.5 vaccine effectiveness analysis. Among adults hospitalized with CLI, the adjusted odds ratio (OR) was 0.75 (95% CI: 0.68-0.83) for receipt of 2 vaccine doses at [≥]150 days after receipt, 0.32 (95% CI: 0.20-0.50) for a third dose 7-119 days after receipt, and 0.64 (95% CI: 0.58-0.71) for a third dose [≥]120 days (median 235 days) after receipt for cases vs controls. For COVID-19-associated hospitalization, among patients ages [≥]65 years 7-59 and [≥]60 days (median 88 days) after a fourth dose, ORs were 0.34 (95% CI: 0.25-0.47) and 0.43 (95% CI: 0.34-0.56), respectively. Among hospitalized cases, ICU admission and/or in-hospital death occurred in 21.4% during the BA.1 vs 14.7% during the BA.4/BA.5 period (standardized mean difference: 0.17). ConclusionVE against medically attended COVID-19 illness decreased over time since last dose; receipt of one or two booster doses increased effectiveness over a primary series alone. KEY POINTS QuestionWhat is the association between receipt of first-generation COVID-19 mRNA vaccines and medically attended COVID-19 during Omicron BA.4/BA.5 sublineage predominance? FindingsThis test-negative analysis included 82,229 emergency department or urgent care encounters and 21,007 hospitalizations for COVID-19-like illness. Among hospitalized patients, the likelihood of recent vaccination (7-119 days) with 3 mRNA vaccine doses (vs unvaccinated) was significantly lower (odds ratio, 0.32) in cases than SARS-CoV-2-negative controls, but with lower associated protection [≥]120 days post-vaccination (odds ratio, 0.64). MeaningFirst-generation COVID-19 vaccines were associated with protection against COVID-19 during the Omicron BA.4/BA.5 sublineage-predominant periods but this declined over time.

Real-World Effectiveness and Tolerability of Monoclonal Antibodies for Ambulatory Patients with Early COVID-19

ImportanceInterventions to reduce hospitalization of patients with COVID-19 are urgently needed. Randomized trials for efficacy suggest that anti-SARS-CoV2 neutralizing monoclonal antibodies (MAb) may reduce medically-attended visits and hospitalization but effectiveness has not been confirmed in a real-world setting. ObjectiveEstimate the effectiveness of MAb infusion in a real-world cohort of ambulatory patients with early symptomatic COVID-19 at high risk for hospitalization. DesignQuasi-experimental observational cohort study using target trial emulation and causal inference methodology in pre-and post-implementation groups. SettingInfusion centers and urgent care clinics within an integrated healthcare system in the United States Participants13,534 high-risk adult outpatients with symptomatic, laboratory-confirmed COVID-19 within 7 days of symptom onset. ExposuresA single intravenous infusion of either bamlanivimab 700 mg or casirivimab/imdevimab 1200 mg/1200 mg. Main Outcomes and MeasuresThe primary outcome was emergency department visit or hospitalization within 14 days of positive test. Patients who received MAb infusion were compared to contemporaneous controls using inverse probability of treatment weighting, and to a pre-implementation cohort using propensity-weighted interrupted time series analysis. An exploratory analysis compared effectiveness of casirivimab/imdevimab and bamlanivimab. Results7404 patients who would have been MAb-eligible were identified in a pre-implementation cohort (July 1-November 27, 2020). In the post-implementation period (November 28, 2020-January 28, 2021), 594 received MAb treatment and 5536 MAb-eligible patients did not. Among Mab recipients, 479 (80.6%) received bamlanivimab and 115 (19.4%) casirivimab/imdevimab. The primary outcome occurred in 75 (12.6%) MAb recipients, 1018 (18.4%) contemporaneous controls, and 1525 (20.6%) patients in the pre-implementation cohort. MAb treatment was associated with fewer subsequent emergency department visits and hospitalizations (odds ratio estimating the average treatment effect 0.69, 95% CI 0.60-0.79). After implementation, propensity-weighted probability of emergency department visit or hospitalization decreased by 0.7% per day (95% CI 0.03-0.10%, p<0.001). Overall, 7 (1.2%) MAb patients experienced an adverse event; two (0.3%) were considered serious. In the exploratory analysis, the effect of casirivimab/imdevimab versus bamlanivimab was not significant (OR 0.52, 95% CI 0.17-1.63, p=0.26). Conclusions and RelevanceMAb treatment of high-risk ambulatory patients with early COVID-19 was well-tolerated and effective at preventing the need for subsequent medically-attended care. Key Points SectionO_ST_ABSQuestionC_ST_ABSWhat is the real-world effectiveness of COVID-19 monoclonal neutralizing antibody (MAb) infusions in high-risk, ambulatory patients? Findings594 high-risk, early-symptomatic adults with COVID-19 treated with MAb infusion were compared to 5536 contemporaneous controls using inverse probability of treatment weighting, and to 7404 patients in a pre-implementation cohort using propensity-weighted interrupted time series analysis. MAb treatment was associated with fewer subsequent emergency department visits and hospitalizations (odds ratio 0.69 (95% CI 0.60-0.79). After MAb implementation the probability of emergency department visit or hospitalization decreased by 0.7% per day, 95% CI 0.03-0.10%, p<0.001). MeaningMonoclonal antibody infusion within seven days of symptom onset in high-risk ambulatory adults with COVID-19 appears to prevent subsequent emergency department visits and hospitalization. Further evaluation of the differences between specific Mab products is warranted.

Simple Scoring Tool to Estimate Risk of Hospitalization and Mortality in Ambulatory and Emergency Department Patients with COVID-19

BackgroundAccurate methods of identifying patients with COVID-19 who are at high risk of poor outcomes has become especially important with the advent of limited-availability therapies such as monoclonal antibodies. Here we describe development and validation of a simple but accurate scoring tool to classify risk of hospitalization and mortality. MethodsAll consecutive patients testing positive for SARS-CoV-2 from March 25-October 1, 2020 within the Intermountain Healthcare system were included. The cohort was randomly divided into 70% derivation and 30% validation cohorts. A multivariable logistic regression model was fitted for 14-day hospitalization. The optimal model was then adapted to a simple, probabilistic score and applied to the validation cohort and evaluated for prediction of hospitalization and 28-day mortality. Results22,816 patients were included; mean age was 40 years, 50.1% were female and 44% identified as non-white race or Hispanic/Latinx ethnicity. 6.2% required hospitalization and 0.4% died. Criteria in the simple model included: age (0.5 points per decade); high-risk comorbidities (2 points each): diabetes mellitus, severe immunocompromised status and obesity (body mass index[≥]30); non-white race/Hispanic or Latinx ethnicity (2 points), and 1 point each for: male sex, dyspnea, hypertension, coronary artery disease, cardiac arrythmia, congestive heart failure, chronic kidney disease, chronic pulmonary disease, chronic liver disease, cerebrovascular disease, and chronic neurologic disease. In the derivation cohort (n=16,030) area under the receiver-operator characteristic curve (AUROC) was 0.82 (95% CI 0.81-0.84) for hospitalization and 0.91 (0.83-0.94) for 28-day mortality; in the validation cohort (n=6,786) AUROC for hospitalization was 0.8 (CI 0.78-0.82) and for mortality 0.8 (CI 0.69-0.9). ConclusionA prediction score based on widely available patient attributes accurately risk stratifies patients with COVID-19 at the time of testing. Applications include patient selection for therapies targeted at preventing disease progression in non-hospitalized patients, including monoclonal antibodies. External validation in independent healthcare environments is needed.