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Key Points: Question: Does 100 mg of fluvoxamine twice daily for 13 days, compared with placebo, shorten symptom duration among outpatient adults (aged ≥30 years) with symptomatic mild to moderate COVID-19? Findings: In this platform randomized clinical trial with 1175 US participants enrolled during the time that Omicron COVID-19 subvariants were circulating, there was no reportable difference in the time to sustained recovery between fluvoxamine and placebo groups (adjusted hazard ratio, 0.99 [95% credible interval, 0.89-1.09]; P for efficacy =.40). Median time to sustained recovery was 10 days (95% CI, 10-11) in both the intervention and placebo group. Meaning: Fluvoxamine, 100 mg twice daily, does not shorten the duration of symptoms in outpatient adults with mild to moderate COVID-19. Importance: The effect of higher-dose fluvoxamine in reducing symptom duration among outpatients with mild to moderate COVID-19 remains uncertain. Objective: To assess the effectiveness of fluvoxamine, 100 mg twice daily, compared with placebo, for treating mild to moderate COVID-19. Design, Setting, and Participants: The ACTIV-6 platform randomized clinical trial aims to evaluate repurposed medications for mild to moderate COVID-19. Between August 25, 2022, and January 20, 2023, a total of 1175 participants were enrolled at 103 US sites for evaluating fluvoxamine; participants were 30 years or older with confirmed SARS-CoV-2 infection and at least 2 acute COVID-19 symptoms for 7 days or less. Interventions: Participants were randomized to receive fluvoxamine, 50 mg twice daily on day 1 followed by 100 mg twice daily for 12 additional days (n = 601), or placebo (n = 607). Main Outcomes and Measures: The primary outcome was time to sustained recovery (defined as at least 3 consecutive days without symptoms). Secondary outcomes included time to death; time to hospitalization or death; a composite of hospitalization, urgent care visit, emergency department visit, or death; COVID-19 clinical progression scale score; and difference in mean time unwell. Follow-up occurred through day 28. Results: Among 1208 participants who were randomized and received the study drug, the median (IQR) age was 50 (40-60) years, 65.8% were women, 45.5% identified as Hispanic/Latino, and 76.8% reported receiving at least 2 doses of a SARS-CoV-2 vaccine. Among 589 participants who received fluvoxamine and 586 who received placebo included in the primary analysis, differences in time to sustained recovery were not observed (adjusted hazard ratio [HR], 0.99 [95% credible interval, 0.89-1.09]; P for efficacy =.40]). Additionally, unadjusted median time to sustained recovery was 10 (95% CI, 10-11) days in both the intervention and placebo groups. No deaths were reported. Thirty-five participants reported health care use events (a priori defined as death, hospitalization, or emergency department/urgent care visit): 14 in the fluvoxamine group compared with 21 in the placebo group (HR, 0.69 [95% credible interval, 0.27-1.21]; P for efficacy =.86) There were 7 serious adverse events in 6 participants (2 with fluvoxamine and 4 with placebo) but no deaths. Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with fluvoxamine does not reduce duration of COVID-19 symptoms. Trial Registration: ClinicalTrials.gov Identifier: NCT04885530 This randomized study examines the effect of higher-dose fluvoxamine on time to sustained recovery from mild to moderate COVID-19 or progression to severe disease in nonhospitalized adults. [ABSTRACT FROM AUTHOR]

Importance: The effectiveness of ivermectin to shorten symptom duration or prevent hospitalization among outpatients in the US with mild to moderate symptomatic COVID-19 is unknown.Objective: To evaluate the efficacy of ivermectin, 400 μg/kg, daily for 3 days compared with placebo for the treatment of early mild to moderate COVID-19.Design, Setting, and Participants: ACTIV-6, an ongoing, decentralized, double-blind, randomized, placebo-controlled platform trial, was designed to evaluate repurposed therapies in outpatients with mild to moderate COVID-19. A total of 1591 participants aged 30 years and older with confirmed COVID-19, experiencing 2 or more symptoms of acute infection for 7 days or less, were enrolled from June 23, 2021, through February 4, 2022, with follow-up data through May 31, 2022, at 93 sites in the US.Interventions: Participants were randomized to receive ivermectin, 400 μg/kg (n = 817), daily for 3 days or placebo (n = 774).Main Outcomes and Measures: Time to sustained recovery, defined as at least 3 consecutive days without symptoms. There were 7 secondary outcomes, including a composite of hospitalization or death by day 28.Results: Among 1800 participants who were randomized (mean [SD] age, 48 [12] years; 932 women [58.6%]; 753 [47.3%] reported receiving at least 2 doses of a SARS-CoV-2 vaccine), 1591 completed the trial. The hazard ratio (HR) for improvement in time to recovery was 1.07 (95% credible interval [CrI], 0.96-1.17; posterior P value [HR >1] = .91). The median time to recovery was 12 days (IQR, 11-13) in the ivermectin group and 13 days (IQR, 12-14) in the placebo group. There were 10 hospitalizations or deaths in the ivermectin group and 9 in the placebo group (1.2% vs 1.2%; HR, 1.1 [95% CrI, 0.4-2.6]). The most common serious adverse events were COVID-19 pneumonia (ivermectin [n = 5]; placebo [n = 7]) and venous thromboembolism (ivermectin [n = 1]; placebo [n = 5]).Conclusions and Relevance: Among outpatients with mild to moderate COVID-19, treatment with ivermectin, compared with placebo, did not significantly improve time to recovery. These findings do not support the use of ivermectin in patients with mild to moderate COVID-19.Trial Registration: ClinicalTrials.gov Identifier: NCT04885530. [ABSTRACT FROM AUTHOR]

The study aims to investigate the potential survival benefit of anterior temporal lobe resection for patients with pharmacoresistant temporary lobe epilepsy as compared with conventional medication. The results indicate that anterior temporal lobe resection showed substantial gains in life expectancy.

HMOs may be better at reducing the level of inappropriate care given to critically ill patients who are dying. This was the conclusion of a study that evaluated potentially ineffective care (PIC) in all critically ill Medicare patients in intensive care units in California in 1994. PIC is defined as extensive provision of health care resources to a patient who dies shortly thereafter. About 5% of the patients received PIC and they used 22% of the total ICU resources in the state that year. HMO members were less likely to receive PIC compared to fee-for-service patients., Context. -- The worst outcome of critical care may not be death itself; rather, the worst may be an extended death process in which a patient's and his or her family's suffering has been prolonged by services that are ultimately impotent. We have previously used potentially ineffective care (PIC) as a proxy measure for this type of care. Objective. -- To determine if PIC is delivered less often to Medicare patients enrolled in health maintenance organizations (HMOs) than those in traditional fee-for-service health plans. Patients. -- All Medicare patients hospitalized in intensive care units in California during fiscal year 1994. Outcome. -- Potentially ineffective care was defined as the concurrence of in-hospital death or death within 100 days of hospital discharge and resource use (total hospital costs) above the 90th percentile. Methods. -- Hospital costs were adjusted for institution-specific cost-to-charge ratios and local wage indices derived from Health Care Financing Administration cost reports. A multivariate regression model adjusted PIC rates for age, sex, race, elective admission to the hospital, Charlson index diseases, the 15 most common diagnosis related groups for death by 100 days, intensive care unit size, and number of residents at the hospital. Results. -- A total of 3914 (4.8%) of 81 494 patients experienced PIC and used 21.6% of total intensive care unit resources. The occurrence of PIC was less common among HMO members (adjusted odds ratio, 0.75; 95% confidence interval, 0.65-0.87). However, HMO members were not more likely to experience in-hospital death (adjusted odds ratio, 0.99; 95% confidence interval, 0.91-1.07) and only slightly more likely to experience death by 100 days after hospital discharge (adjusted odds ratio, 1.08; 95% confidence interval, 1.01-1.15). Conclusions. -- Patients who experience PIC outcomes are not uncommon in the Medicare population, and patients experiencing this outcome consume a disproportionate amount of medical resources. Medicare beneficiaries in HMO practice settings had a lower risk of experiencing PIC outcomes after adjusting for age, sex, diagnosis, comorbid conditions, and characteristics of the treating hospital. This suggests that HMO practices may be better at limiting or avoiding injudicious use of critical care near the end of life.

A newly proposed outcome measurement called potentially ineffective care (PIC) may help doctors identify critical care patients who are unlikely to benefit from treatment. Researchers studied mortality rates and hospital expenditures for 402 patients who had been admitted to an intensive care unit between Jun 1988 and Jan 1989. These patients incurred $22 million in hospital charges during their stay in the ICU. PIC was defined as resource use in the upper 25th percentile by patients who died within 100 days of discharge from the ICU. Thirteen percent of the patients fell into this category and used 32% of the total resources. The most appropriate determination of PIC involved multiplying the APACHE-predicted mortality (APM) on the first day of admission by the APM on the 5th day. A PIC value of 0.35 or more was 98% effective in identifying patients who could benefit from treatment., Objective.--To examine the limits of the effectiveness of critical care through the study of patients for whom it was ineffective. Design.--We studied the relationship between resource use and long-term outcome (2-year follow-up) in 402 consecutively admitted critical care patients to develop a benchmark for ineffective applications of critical care. We defined an outcome called potentially ineffective care (PIC), developed and evaluated a model with an independent data set to predict PIC from a patient's response to treatment, and estimated the economic effects of limiting care after a prediction of PIC. Setting.--The combined medical and surgical intensive care unit at a 600-bed university teaching hospital. Patients.--Two groups of 402 consecutively admitted critical care patients, one from 1989, the other from 1991. Main Outcome Measures and Results.--Based on observations from a two-dimensional plot of resource use vs benefit for 402 critical care patients, PIC was defined as resource use in the upper 25th percentile and survival for less than 1 00 days after discharge. Thirteen percent of the patients fell into the PIC category and used 32% of the resources. A product of the APACHE risk estimates on days 1 and 5 of at least 0.35 predicted 37% of PIC outcomes with a specificity of 98%. In a second data set, PIC outcome prediction had a sensitivity of 43% and a specificity of 94%, and a positive predictive value of 80%. For the hospital studied, reduction of intensity of treatment after a prediction of a PIC outcome would result in a reduction of hospital charges in the range of $1.8 million to $5 million per year. Conclusion.--Patients in the PIC category consumed a large portion of the resources devoted to critical care at an academic teaching hospital. We suggest a change in focus from assessment of the quality of critical care and risk-adjusted mortality to an assessment of ineffective care based on outcome and resource use and a patient's response to treatment over time. (JAMA. 1995;274:1544-1551)

Context: Patients with pharmacoresistant epilepsy have increased mortality compared with the general population, but patients with pharmacoresistant temporal lobe epilepsy who meet criteria for surgery and who become seizure-free after anterior temporal lobe resection have reduced excess mortality vs those with persistent seizures.Objective: To quantify the potential survival benefit of anterior temporal lobe resection for patients with pharmacoresistant temporal lobe epilepsy vs continued medical management.Design: Monte Carlo simulation model that incorporates possible surgical complications and seizure status, with 10,000 runs. The model was populated with health-related quality-of-life data obtained directly from patients and data from the medical literature. Insufficient data were available to assess gamma-knife radiosurgery or vagal nerve stimulation.Main Outcome Measures: Life expectancy and quality-adjusted life expectancy.Results: Compared with medical management, anterior temporal lobe resection for a 35-year-old patient with an epileptogenic zone identified in the anterior temporal lobe would increase survival by 5.0 years (95% CI, 2.1-9.2) with surgery preferred in 100% of the simulations. Anterior temporal lobe resection would increase quality-adjusted life expectancy by 7.5 quality-adjusted life-years (95%, CI, -0.8 to 17.4) with surgery preferred in 96.5% of the simulations, primarily due to increased years spent without disabling seizures, thereby reducing seizure-related excess mortality and improving quality of life. The results were robust to sensitivity analyses.Conclusion: The decision analysis model suggests that on average anterior temporal lobe resection should provide substantial gains in life expectancy and quality-adjusted life expectancy for surgically eligible patients with pharmacoresistant temporal lobe epilepsy compared with medical management. [ABSTRACT FROM AUTHOR]