ABSTRACT
Background: Nirmatrelvir/ritonavir (NMV/r) was granted Emergency Use Authorization in December 2021 for treatment of early symptomatic patients with mild to moderate COVID-19 at high risk of progression. However, its benefit is specific population subgroups remains unclear. Method(s): We used a matched cohort design to emulate a target trial within the VA COVID-19 Shared Data Resource database. Eligible individuals were those with at least two episodes of care in the VA in the last 2 years, who had a first confirmed SARS-CoV-2 infection between January 1 and August 31, 2022 and were free of hospitalization or death within 3 days of testing positive. Those hospitalized in the previous 60-days and those who received Molnupiravir after diagnosis were ineligible. Among the eligible individuals, we matched those prescribed NMV/r with those not prescribed NMV/r within 3 days of diagnosis. Controls were matched 1:1 on age (5-year blocks), race, sex, body mass index, Charlson Comorbidity Index, VA facility where NMV/r was prescribed, and vaccination status. Our primary outcome measure was hospitalization or death within 30 days of the index COVID-19 diagnosis date. Result(s): Among 90,432 persons with a confirmed first SARS-CoV-2 positive test, 68,236 persons met the eligibility criteria. Of those, 4,886 were prescribed NMV/r. Final primary analysis dataset included 4,148 matched pairs of NMV/r treated cases and controls. The incidence of hospitalization or death was significantly lower among those who were prescribed NMV/r overall (73 vs. 109 events;ARD [95% CI] -0.87 [-1.49 to -0.25]), for those older than 60 years (60 vs. 88 events;ARD [95% CI] -1.05 [-1.93 to -0.18]), for unvaccinated/incomplete primary series (ARD -1.88 [-3.54 to -0.22]), and those asymptomatic at baseline (ARD -1.96 [-3.00 to -0.92]). Those who were <60 years old, vaccinated with or without a booster, and those symptomatic at baseline did not experience a significant benefit. Conclusion(s): NMV/r use is associated with a modest but statistically significant reduction in hospitalization or death among previously uninfected, nonhospitalized population with COVID-19 who are at a high risk of progression to severe disease. The benefit is evident in older, unvaccinated, asymptomatic persons and those with certain comorbidities. But not in younger, vaccinated, and symptomatic persons.
ABSTRACT
Background: Clinical benefit of Molnupiravir (MPV) in COVID-19 infected subpopulations is unclear. Method(s): We used a matched cohort design emulating a target trial to analyze the VA COVID-19 Shared Resource database to determine the association of MPV with hospitalization or death within 30 days compared with untreated controls in previously uninfected non-hospitalized persons. Incidence of hospitalization/ death and absolute risk difference (ARD) with 95% confidence intervals were calculated for the treated and untreated groups. Result(s): Among 1,459 matched pairs, the incidence of hospitalization/death was not different among MPV treated vs. untreated controls (48 vs. 44 cases;ARD [95% CI] 0.27 [-0.94,1.49]). No benefit was observed among those >60 or <60 years old (ARD 0.27 [-1.25,1.79] vs. -0.29 [-1.22,1.80]), those with specific comorbidities, or by vaccination status. A significant benefit was observed in asymptomatic but not in symptomatic persons (ARD -2.80 [-4.74,-0.87] vs. 1.12 [-0.31,2.55]). Kaplan-Meier curves did not show a significant reduction in proportion of persons who were hospitalized or died among those treated with MPV compared with untreated controls (logrank P=0.7). Conclusion(s): MPV was not associated with a significant reduction in hospitalization or death within 30 days of COVID-19 diagnosis overall. A subgroup of patients presenting without symptoms experienced a benefit.
ABSTRACT
Background: The role of remdesivir in hospitalized patients with COVID-19 is not clear. Some studies have demonstrated improved clinical outcomes and reduced mortality, while others have failed to show a benefit. Method(s): We used the Department of Veterans Affairs' (VA) national COVID-19 Shared Data Resource database to identify confirmed SARS-CoV-2 infected Veterans between July 1, 2020 and December 31, 2021 who were hospitalized and received remdesivir and propensity-score matched controls who had not received remdesivir. Variables for propensity-score matching included demographics, comorbidities, time and location of diagnosis/admission, severity of illness, and use of other potential COVID-19 therapeutics. Primary outcome of interest was 28-day mortality in the entire matched cohort, and among subgroups stratified by use of supplemental oxygen. Result(s): Among 238,298 SARS-CoV-2 infected Veterans, 31,632 were hospitalized, and 13,147 received remdesivir. Our final dataset included 3,583 remdesivir recipients and 3,583 propensity-score matched controls. Probability of survival at 28 days overall was higher in those who had received remdesivir (P=0.032). Remdesivir recipients had better survival among the group who received supplemental oxygen but did not require mechanical ventilation (P=0.005). Conclusion(s): Remdesivir demonstrated a survival benefit among hospitalized patients with COVID-19 which was limited to those who received supplemental oxygen but did not require mechanical ventilation.
ABSTRACT
Background: Multimodal rheumatologic complex treatment (MRCT) is a treatment concept for patients with rheumatologic diseases requiring acute inpatient care suffering from exacerbated pain and/or functional impairment. A rheumatol-ogist directs the treatment program including multimodal assessments and treatment from three of the following: ergotherapy, physiotherapy, pain medicine and cognitive behavioural treatment. Most studies evaluated data from a two-week inpatient MRCT program.1 Available data on the effectiveness of a one-week inpatient multimodal treatment program are scarce. However, whether a shorter program might also be effective has not been studied so far. Objectives: To evaluate the effectiveness of a one-week inpatient multimodal and interprofessional treatment program on musculoskeletal pain and function of patients with rheumatologic disorders. Methods: 59 consecutive patients were entered into a program of multimodal treatment courses (MRCT) from January 2021 until December 2021. All patients completed a total of 11 hours of therapy in one week. Two patients were excluded for evaluation (one patient acquired COVID 19 during hospitalization and one patient was excluded due to missing data). Pain was assessed via visual analogue scale (VAS) and functional impairment via the 'Funktionsfragebogen Hanover (FFbH)' and the 'Health Assessment Questionnaire (HAQ)' at admission, at discharge and at 12 weeks of follow up. Paired t-test analyses for all treatment episodes were performed. Results: The mean treatment duration (days, ±SD) was 8.1 ± 0.8. Mean age (years, ±SD) of the 57 patients treated in the MRCT program was 57.2 ± 12.5, with 72% female and 28% male patients. Of all patients, 40% had an underlying infammatory disorder, 60% a non-infammatory rheumatic disease. 23% of all patients had 'back pain', 14% 'spondyloarthritis' and 11 % 'rheumatoid arthritis'. Overall, VAS (pain) mean at admission was 6.9 ± 1.0 (SD), HAQ mean 0.57 ± 0.23 (SD) and FFbH mean 81.44 ± 7.95 (SD), respectively. Signifcant improvements in VAS, HAQ and FFbH were demonstrated at discharge (day 8), with a mean improvement of VAS of-2.86 (95% CI:-3.07 to-2.64, P value: <0.0001), a mean improvement of HAQ of-0.24 (95% CI:-0.28 to-0.20, P value: <0.0001) and a mean improvement of FFbH of 5.38 (95% CI: 3.78 to 6.98, P value: <0.0001). Follow up assessment at week 12 was recorded in 22 patients (39%) with a signifcant mean improvement in VAS of-2.23 (95% CI:-2.98 to-1.48), P value < 0.0001) (Table 1 and Figure 1). Conclusion: Signifcant improvement of pain and function was demonstrated at discharge and at week 12 in patients with rheumatologic diseases and mus-culoskeletal pain completing a one-week inpatient multimodal interprofessional treatment program. A multimodal therapeutic approach may provide an effective treatment strategy superior to unimodal standard management.