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PURPOSE: An advisory panel of experts was convened by the ASHP Foundation as a part of its Medication-Use Evaluation Resources initiative to provide commentary on an approach to antibiotic stewardship in the treatment of skin and soft tissue infections (SSTIs), with a focus on oral antibiotics in the emergency department (ED) setting for patients who will be treated as outpatients. Considerations include a need to update existing guidelines to reflect new antibiotics and susceptibility patterns, patient-specific criteria impacting antibiotic selection, and logistics unique to the ED setting. SUMMARY: While national guidelines serve as the gold standard on which to base SSTI treatment decisions, our advisory panel stressed that institutional guidelines must be regularly updated and grounded in local antimicrobial resistance patterns, patient-specific factors, and logistical considerations. Convening a team of experts locally to establish institution-specific guidelines as part of a comprehensive antibiotic stewardship program can ensure patients receive the most appropriate oral therapy for the outpatient treatment of SSTIs in patients visiting the ED. CONCLUSION: SSTI treatment considerations for antibiotic selection in the ED supported by current, evidence-based guidelines, including guidance on optimal oral antibiotic selection for patients discharged for outpatient treatment, are a useful tool to improve the quality and efficiency of care, enhance patient-centric outcomes and satisfaction, decrease healthcare costs, and reduce overuse of antibiotics.
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BACKGROUND: Nirmatrelvir-ritonavir is recommended for persons at risk for severe coronavirus disease 2019 (COVID-19) but remains underutilized. Information on which eligible groups are likely to benefit from treatment is needed. METHODS: We conducted a target trial emulation study in the Veterans Health Administration comparing nirmatrelvir-ritonavir treated versus matched untreated veterans at risk for severe COVID-19 who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from April 2022 through March 2023. We measured incidence of any hospitalization or all-cause mortality at 30 days. Outcomes were measured for the entire cohort, as well as among subgroups defined by 30-day risk of death or hospitalization, estimated using an ensemble risk prediction model. RESULTS: Participants were 87% male with median age 66 years and 16% unvaccinated. Compared with matched untreated participants, those treated with nirmatrelvir-ritonavir (n = 24 205) had a lower 30-day risk for hospitalization (1.80% vs 2.30%; risk difference [RD], -0.50% points [95% confidence interval {CI}: -.69 to -.35]) and death (0.11% vs 0.30%; RD, -0.20 [95% CI: -.24 to -.13]). The greatest reductions in combined hospitalization or death were observed in the highest risk quartile (RD -2.85 [95% CI: -3.94 to -1.76]), immunocompromised persons (RD -1.91 [95% CI: -3.09 to -.74]), and persons aged ≥75 years (RD -1.16 [95% CI: -1.73 to -.59]). No reductions were observed in the 2 lowest risk quartiles or persons younger than 65 years. CONCLUSIONS: Nirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and death in older veterans, those at highest predicted risk for severe outcomes, and immunocompromised groups. Benefit was not observed in younger veterans or groups at lower predicted risk for hospitalization and death.
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The U.S. COVID-19 vaccination program, which commenced in December 2020, has been instrumental in preventing morbidity and mortality from COVID-19 disease. Safety monitoring has been an essential component of the program. The federal government undertook a comprehensive and coordinated approach to implement complementary safety monitoring systems and to communicate findings in a timely and transparent way to healthcare providers, policymakers, and the public. Monitoring involved both well-established and newly developed systems that relied on both spontaneous (passive) and active surveillance methods. Clinical consultation for individual cases of adverse events following vaccination was performed, and monitoring of special populations, such as pregnant persons, was conducted. This report describes the U.S. government's COVID-19 vaccine safety monitoring systems and programs used by the Centers for Disease Control and Prevention, the U.S. Food and Drug Administration, the Department of Defense, the Department of Veterans Affairs, and the Indian Health Service. Using the adverse event of myocarditis following mRNA COVID-19 vaccination as a model, we demonstrate how the multiple, complementary monitoring systems worked to rapidly detect, assess, and verify a vaccine safety signal. In addition, longer-term follow-up was conducted to evaluate the recovery status of myocarditis cases following vaccination. Finally, the process for timely and transparent communication and dissemination of COVID-19 vaccine safety data is described, highlighting the responsiveness and robustness of the U.S. vaccine safety monitoring infrastructure during the national COVID-19 vaccination program.
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BACKGROUND: Vaccine hesitancy persists alongside concerns about the safety of coronavirus disease 2019 (COVID-19) vaccines. We aimed to examine the effect of COVID-19 vaccination on risk of death among US veterans. METHODS: We conducted a target trial emulation to estimate and compare risk of death up to 60 days under two COVID-19 vaccination strategies: vaccination within 7 days of enrollment versus no vaccination through follow-up. The study cohort included individuals aged ≥18 years enrolled in the Veterans Health Administration system and eligible to receive a COVID-19 vaccination according to guideline recommendations from 1 March 2021 through 1 July 2021. The outcomes of interest included deaths from any cause and excluding a COVID-19 diagnosis. Observations were cloned to both treatment strategies, censored, and weighted to estimate per-protocol effects. RESULTS: We included 3 158 507 veterans. Under the vaccination strategy, 364 993 received vaccine within 7 days. At 60 days, there were 156 deaths per 100 000 veterans under the vaccination strategy versus 185 deaths under the no vaccination strategy, corresponding to an absolute risk difference of -25.9 (95% confidence limit [CL], -59.5 to 2.7) and relative risk of 0.86 (95% CL, .7 to 1.0). When those with a COVID-19 infection in the first 60 days were censored, the absolute risk difference was -20.6 (95% CL, -53.4 to 16.0) with a relative risk of 0.88 (95% CL, .7 to 1.1). CONCLUSIONS: Vaccination against COVID-19 was associated with a lower but not statistically significantly different risk of death in the first 60 days. These results agree with prior scientific knowledge suggesting vaccination is safe with the potential for substantial health benefits.
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COVID-19 , Veteranos , Adolescente , Adulto , Humanos , COVID-19/prevenção & controle , Teste para COVID-19 , Vacinas contra COVID-19/efeitos adversos , VacinaçãoRESUMO
During the COVID-19 pandemic, candidate COVID-19 vaccines were being developed for potential use in the United States on an unprecedented, accelerated schedule. It was anticipated that once available, under U.S. Food and Drug Administration (FDA) Emergency Use Authorization (EUA) or FDA approval, COVID-19 vaccines would be broadly used and potentially administered to millions of individuals in a short period of time. Intensive monitoring in the post-EUA/licensure period would be necessary for timely detection and assessment of potential safety concerns. To address this, the Centers for Disease Control and Prevention (CDC) convened an Advisory Committee on Immunization Practices (ACIP) work group focused solely on COVID-19 vaccine safety, consisting of independent vaccine safety experts and representatives from federal agencies - the ACIP COVID-19 Vaccine Safety Technical Work Group (VaST). This report provides an overview of the organization and activities of VaST, summarizes data reviewed as part of the comprehensive effort to monitor vaccine safety during the COVID-19 pandemic, and highlights selected actions taken by CDC, ACIP, and FDA in response to accumulating post-authorization safety data. VaST convened regular meetings over the course of 29 months, from November 2020 through April 2023; through March 2023 FDA issued EUAs for six COVID-19 vaccines from four different manufacturers and subsequently licensed two of these COVID-19 vaccines. The independent vaccine safety experts collaborated with federal agencies to ensure timely assessment of vaccine safety data during this time. VaST worked closely with the ACIP COVID-19 Vaccines Work Group; that work group used safety data and VaST's assessments for benefit-risk assessments and guidance for COVID-19 vaccination policy. Safety topics reviewed by VaST included those identified in safety monitoring systems and other topics of scientific or public interest. VaST provided guidance to CDC's COVID-19 vaccine safety monitoring efforts, provided a forum for review of data from several U.S. government vaccine safety systems, and assured that a diverse group of scientists and clinicians, external to the federal government, promptly reviewed vaccine safety data. In the event of a future pandemic or other biological public health emergency, the VaST model could be used to strengthen vaccine safety monitoring, enhance public confidence, and increase transparency through incorporation of independent, non-government safety experts into the monitoring process, and through strong collaboration among federal and other partners.
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Pharmacogenetic (PGx) testing before initiation of thiopurine treatment and CBC monitoring post-initiation helps avoid adverse events and ensure patient safety. This study aims to evaluate trends in PGx testing and CBC monitoring among Veterans prescribed azathioprine, thioguanine, or mercaptopurine to demonstrate VA's efforts to improve medication safety after an adverse event. To assess testing patterns, we used VA electronic health report data to identify 20,524 Veterans who first began thiopurine treatment between January 1, 2010, to December 31, 2021. Aggregate monthly counts of thiopurine prescriptions and associated lab tests were tabulated, and the trend in the proportion of patients tested was analyzed using the Mann-Kendall test. The proportion of patients undergoing PGx testing rose from 30.0% in 2010 to 47.5% in late 2014 (July-December). However, PGx testing and overall testing only increased slightly after the sentinel event, and orders levelled off over time at slightly lower levels than before the sentinel event. Very little change was seen in the overall proportion of individuals receiving any testing across all patients with new prescriptions from the time of the sentinel event in 2014 to the end of 2021. A large portion of patients prescribed thiopurine drugs did not receive testing that could help prevent the development of potential adverse events, leading to a predominantly reactive approach. Increased PGx testing may result in a more proactive approach to the prevention of adverse events due to genetic interaction.
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BACKGROUND: COVID-19 has been linked to the development of many post-COVID-19 conditions (PCCs) after acute infection. Limited information is available on the effectiveness of oral antivirals used to treat acute COVID-19 in preventing the development of PCCs. OBJECTIVE: To measure the effectiveness of outpatient treatment of COVID-19 with nirmatrelvir-ritonavir in preventing PCCs. DESIGN: Retrospective target trial emulation study comparing matched cohorts receiving nirmatrelvir-ritonavir versus no treatment. SETTING: Veterans Health Administration (VHA). PARTICIPANTS: Nonhospitalized veterans in VHA care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022. INTERVENTION: Nirmatrelvir-ritonavir treatment for acute COVID-19. MEASUREMENTS: Cumulative incidence of 31 potential PCCs at 31 to 180 days after treatment or a matched index date, including cardiac, pulmonary, renal, thromboembolic, gastrointestinal, neurologic, mental health, musculoskeletal, endocrine, and general conditions and symptoms. RESULTS: Eighty-six percent of the participants were male, with a median age of 66 years, and 17.5% were unvaccinated. Baseline characteristics were well balanced between participants treated with nirmatrelvir-ritonavir and matched untreated comparators. No differences were observed between participants treated with nirmatrelvir-ritonavir (n = 9593) and their matched untreated comparators in the incidence of most PCCs examined individually or grouped by organ system, except for lower combined risk for venous thromboembolism and pulmonary embolism (subhazard ratio, 0.65 [95% CI, 0.44 to 0.97]; cumulative incidence difference, -0.29 percentage points [CI, -0.52 to -0.05 percentage points]). LIMITATIONS: Ascertainment of PCCs using International Classification of Diseases, 10th Revision, codes may be inaccurate. Evaluation of many outcomes could have resulted in spurious associations with combined thromboembolic events by chance. CONCLUSION: Out of 31 potential PCCs, only combined thromboembolic events seemed to be reduced by nirmatrelvir-ritonavir. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.
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COVID-19 , Tromboembolia , Veteranos , Estados Unidos/epidemiologia , Humanos , Masculino , Idoso , Feminino , Tratamento Farmacológico da COVID-19 , Estudos Retrospectivos , Ritonavir/uso terapêutico , SARS-CoV-2 , Antivirais/uso terapêuticoRESUMO
Importance: Several pharmacotherapies have been authorized to treat nonhospitalized persons with symptomatic COVID-19. Longitudinal information on the use of these therapies is needed. Objective: To analyze trends and factors associated with prescription of outpatient COVID-19 pharmacotherapies within the Veterans Health Administration (VHA). Design, Setting, and Participants: This cohort study evaluated nonhospitalized veterans in VHA care who tested positive for SARS-CoV-2 from January 2022 through January 2023 using VHA and linked Community Care and Medicare databases. Exposures: Demographic characteristics, underlying medical conditions, COVID-19 vaccination, and regional and local systems of care, including Veterans Integrated Services Networks (VISNs). Main Outcomes and Measures: Monthly receipt of any COVID-19 pharmacotherapy (nirmatrelvir-ritonavir, molnupiravir, sotrovimab, or bebtelovimab) was described. Multivariable logistic regression was used to identify factors independently associated with receipt of any vs no COVID-19 pharmacotherapy. Results: Among 285â¯710 veterans (median [IQR] age, 63.1 [49.9-73.7] years; 247â¯358 males [86.6%]; 28â¯444 Hispanic [10.0%]; 61â¯269 Black [21.4%] and 198â¯863 White [69.6%]) who tested positive for SARS-CoV-2 between January 2022 and January 2023, the proportion receiving any pharmacotherapy increased from 3285 of 102â¯343 veterans (3.2%) in January 2022 to 5180 of 21â¯688 veterans (23.9%) in August 2022. The proportion declined to 2194 of 10â¯551 veterans (20.8%) by January 2023. Across VISNs, the range in proportion of patients who tested positive who received nirmatrelvir-ritonavir or molnupiravir during January 2023 was 41 of 692 veterans (5.9%) to 106 of 494 veterans (21.4%) and 2.1% to 120 of 1074 veterans (11.1%), respectively. Veterans receiving any treatment were more likely to be older (adjusted odds ratio [aOR] for ages 65-74 vs 50-64 years, 1.18; 95% CI, 1.14-1.22; aOR for ages ≥75 vs 50-64 years, 1.19; 95% CI, 1.15-1.23) and have a higher Charlson Comorbidity Index score (aOR for CCI ≥6 vs 0, 1.52; 95% CI, 1.44-1.59). Compared with White veterans, Black veterans (aOR, 1.06; 95% CI, 1.02-1.09) were more likely to receive treatment, and compared with non-Hispanic veterans, Hispanic veterans (aOR 1.06; 95% CI, 1.01-1.11) were more likely to receive treatment. Conclusions And Relevance: This study found that prescription of outpatient COVID-19 pharmacotherapies in the VHA peaked in August 2022 and declined thereafter. There were large regional differences in patterns of nirmatrelvir-ritonavir and molnupiravir use.
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COVID-19 , Veteranos , Estados Unidos/epidemiologia , Masculino , Humanos , Idoso , Pessoa de Meia-Idade , SARS-CoV-2 , Ritonavir/uso terapêutico , COVID-19/epidemiologia , Vacinas contra COVID-19 , Estudos de Coortes , MedicareRESUMO
Background: Although the benefits outweigh the risks, COVID-19 vaccines have been associated with an increased risk of myocarditis and pericarditis. This report is based on a national US veteran population with confirmed myocarditis/pericarditis following mRNA COVID-19 vaccines according to the near real-time active surveillance program of Veterans Affairs. Methods: This study is based on a cohort evaluation of all adults administered ≥1 mRNA COVID-19 vaccine, including boosters, in the Veterans Health Administration between 14 December 2020 and 9 October 2022. ICD-10-CM diagnosis codes were used to identify potential safety signals in near real time through a database analysis. All potential cases of myocarditis/pericarditis identified in the database analysis underwent in-depth chart review and case validation by a team of pharmacists and expert clinicians. Our main outcome was the incidence rate of confirmed myocarditis/pericarditis among vaccine recipients (overall and those aged 18-39 years) within 21 days of a first, second, or booster dose of a mRNA COVID-19 vaccine. We calculated the ratio of observed events among COVID-19 vaccine recipients over expected events from historical vaccine recipient controls (2015-2020) in the Veterans Health Administration. We used confirmed cases to calculate incidence rates and 95% CIs. Results: Through 9 October 2022, 3 877 453 doses of BNT162b2 (Pfizer-BioNTech) and 4 221 397 doses of mRNA-1273 (Moderna) were administered as first or second dose across Veterans Affairs, and 1 012 561 BNT162b2 and 1 156 160 mRNA-1273 booster doses were administered. Among all doses, the rapid cycle analysis identified 178 potential cases of myocarditis/pericarditis among vaccinees of any age and 22 potential cases among those aged 18-39 years. Of these, 33 cases, including 6 among those 18-39 years old, were confirmed after in-depth chart review and validation, corresponding with an overall incidence rate per million ranging from 0.46 (95% CI, .01-2.55) for Moderna dose 1 to 6.91 (95% CI, 2.78-14.24) for Pfizer booster. Among those aged 18-39, incidence rates ranged from 7.1 (95% CI, .18-39.56) for Moderna dose 2 to 19.76 (95% CI, 5.38-50.58) for Pfizer dose 2. Patients with confirmed cases were hospitalized for a mean 4.1 days (range, 1-15). The final disposition for 32 (97%) of 33 cases was discharge to home. Conclusions: This report is a real-world demonstration of the Veterans Affairs' active surveillance system for vaccines. Although the rapid cycle analysis initially identified 178 potential cases of myocarditis/pericarditis, only 1 of 5 cases was confirmed to be related to a COVID-19 vaccine after chart review. These findings highlight the paramount importance of active surveillance and chart validation for rare but serious adverse events related to COVID-19 vaccines.
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BACKGROUND: Information about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes in the setting of Omicron variant transmission and COVID-19 vaccination is limited. OBJECTIVE: To measure the effectiveness of nirmatrelvir-ritonavir and molnupiravir for outpatient treatment of COVID-19. DESIGN: Three retrospective target trial emulation studies comparing matched cohorts of nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir-ritonavir versus molnupiravir. SETTING: Veterans Health Administration (VHA). PARTICIPANTS: Nonhospitalized veterans in VHA care who were at risk for severe COVID-19 and tested positive for SARS-CoV-2 during January through July 2022. INTERVENTION: Nirmatrelvir-ritonavir or molnupiravir pharmacotherapy. MEASUREMENTS: Incidence of any hospitalization or all-cause mortality at 30 days and from 31 to 180 days. RESULTS: Eighty-seven percent of participants were male; the median age was 66 years, and 18% were unvaccinated. Compared with matched untreated control participants, those treated with nirmatrelvir-ritonavir (n = 9607) had lower 30-day risk for hospitalization (22.07 vs. 30.32 per 1000 participants; risk difference [RD], -8.25 [95% CI, -12.27 to -4.23] per 1000 participants) and death (1.25 vs. 5.47 per 1000 participants; RD, -4.22 [CI, -5.45 to -3.00] per 1000 participants). Among persons alive at day 31, reductions were seen in 31- to 180-day incidence of death (hazard ratio, 0.66 [CI, 0.49 to 0.89]) but not hospitalization (subhazard ratio, 0.90 [CI, 0.79 to 1.02]). Molnupiravir-treated participants (n = 3504) had lower 30-day and 31- to 180-day risks for death (3.14 vs. 13.56 per 1000 participants at 30 days; RD, -10.42 [CI, -13.49 to -7.35] per 1000 participants; hazard ratio at 31 to 180 days, 0.67 [CI, 0.48 to 0.95]) but not hospitalization. A difference in 30-day or 31- to 180-day risk for hospitalization or death was not observed between matched nirmatrelvir- or molnupiravir-treated participants. LIMITATION: The date of COVID-19 symptom onset for most veterans was unknown. CONCLUSION: Nirmatrelvir-ritonavir was effective in reducing 30-day hospitalization and death. Molnupiravir was associated with a benefit for 30-day mortality but not hospitalization. Further reductions in mortality from 31 to 180 days were observed with both antivirals. PRIMARY FUNDING SOURCE: U.S. Department of Veterans Affairs.
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COVID-19 , Veteranos , Idoso , Feminino , Humanos , Masculino , Antivirais/uso terapêutico , Tratamento Farmacológico da COVID-19 , Vacinas contra COVID-19 , Estudos Retrospectivos , Ritonavir/uso terapêutico , SARS-CoV-2RESUMO
PURPOSE: To describe the implementation of clinical decision support tools for alerting prescribers of actionable drug-gene interactions in the Veterans Health Administration (VHA). SUMMARY: Drug-gene interactions have been the focus of clinicians for years. Interactions between SCLO1B1 genotype and statin medications are of particular interest as these can inform risk for statin-associated muscle symptoms (SAMS). VHA identified approximately 500,000 new users of statin medications prescribed in VHA in fiscal year 2021, some of whom could benefit from pharmacogenomic testing for the SCLO1B1 gene. In 2019, VHA implemented the Pharmacogenomic Testing for Veterans (PHASER) program to offer panel-based, preemptive pharmacogenomic testing and interpretation. The PHASER panel includes SLCO1B1, and VHA utilized Clinical Pharmacogenomics Implementation Consortium statin guidelines to build its clinical decision support tools. The program's overarching goal is to reduce the risk of adverse drug reactions such as SAMS and improve medication efficacy by alerting practitioners of actionable drug-gene interactions. We describe the development and implementation of decision support for the SLCO1B1 gene as an example of the approach being used for the nearly 40 drug-gene interactions screened for by the panel. CONCLUSION: The VHA PHASER program identifies and addresses drug-gene interactions as an application of precision medicine to reduce veterans' risks for adverse events. The PHASER program's implementation of statin pharmacogenomics utilizes a patient's SCLO1B1 phenotype to alert providers of the risk for SAMS with the statin being prescribed and how to lower that risk through a lower dose or alternative statin selection. The PHASER program may help reduce the number of veterans who experience SAMS and may improve their adherence to statin medications.
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Sistemas de Apoio a Decisões Clínicas , Inibidores de Hidroximetilglutaril-CoA Redutases , Farmacogenética , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Saúde dos Veteranos , Medicina de PrecisãoRESUMO
BACKGROUND: Retention of patients in buprenorphine medication treatment for opioid use disorder (B-MOUD) reduces harms associated with opioid use disorder (OUD). We sought to characterize the patients receiving B-MOUD and courses of B-MOUD in a large healthcare system. METHODS: We conducted a retrospective, open cohort study of patients with OUD who either did or did not receive B-MOUD courses within the Veterans Health Administration (VHA) from January 2006 through July 2019, using VHA clinical data. We compared patients receiving or not receiving B-MOUD, characterized B-MOUD courses (e.g., length and doses), and examined persistence, across patient characteristics, over time. We used analyses for normally or non-normally distributed continuous variables, categorical data, and persistence over time (Kaplan-Meier persistence curves). RESULTS: We identified 255,726 Veterans with OUD; 40,431 (15.8%) had received 63,929 B-MOUD courses. Compared to patients with OUD without B-MOUD, patients with B-MOUD were younger, more often of white race, and had more co-morbidities. The frequency of new B-MOUD starts and prevalent B-MOUD patients ranged from 1550 and 1989 in 2007 to 8146 and 16,505 in 2018, respectively. The median duration of B-MOUD was 157 (IQR: 37-537) days for all courses and 33.8% patients had more than one course. The average proportion days covered was 90% (SD: 0.15), and the average prescribed daily dose was 13.44 (SD: 6.5). CONCLUSIONS: Within a VHA B-MOUD cohort, courses increased more than 10-fold from 2006 to 2016 with nearly half of patients experiencing multiple courses. Patient demographics seem to dictate the length of courses.
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Buprenorfina , Transtornos Relacionados ao Uso de Opioides , Humanos , Estudos de Coortes , Estudos Retrospectivos , Saúde dos Veteranos , Buprenorfina/uso terapêutico , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológicoRESUMO
PURPOSE: Costs of hospitalization due to severe adverse drug reactions (ADRs) were previously estimated within the Veterans Health Administration (VHA), but additional analyses are needed to infer potential interventions to mitigate these negative outcomes. The objective of this study was to compare specific adverse reaction-related hospitalization costs between medications with similar indications. METHODS: Mean hospitalization costs associated with the same ADR symptom were compared for different drugs with similar indications using adjusted generalized linear models with a Bonferroni correction for multiple comparisons as well as a gamma distribution. RESULTS: Overall, hospitalization costs between medications with similar indications were not significantly different for specific adverse reactions. However, gastrointestinal hemorrhage-associated costs were higher for warfarin versus nonsteroidal anti-inflammatory drugs (model estimate of mean cost, $18,114 [range of lower and upper model estimates, $12,522-$26,202] vs $14,255 [estimate range, $9,710-$20,929]). Similarly, the estimated mean hospitalization cost associated with angioedema was higher for losartan versus lisinopril or lisinopril/hydrochlorothiazide: $14,591 (range, $9467-$22,488) versus $8,935 (range, $6,301-$12,669) and $8,022 (range, $5,424-$11,865), respectively. CONCLUSION: Although we found few differences in the cost of hospitalization when comparing drugs with similar indications and the same adverse reaction, there were specific drug-ADR pairs that merit attention and consideration of interventions to improve safe and appropriate medication use. Evaluation of the effect of those interventions on the incidence of ADRs is an area for future study.
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Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Lisinopril , Humanos , Preparações Farmacêuticas , Hospitalização , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , IncidênciaRESUMO
PURPOSE: The purpose of this project was to develop and optimize a dashboard and registry to manage the distribution, utilization, and monitoring of coronavirus disease 2019 (COVID-19) emergency use-authorized medications (CEUAMs). SUMMARY: CEUAMs have specific requirements that must be met for prescribing, monitoring, and compliance. When remdesivir, the first COVID-19 medication with emergency use authorization (EUA), was approved, it immediately became necessary for the Veterans Health Administration, a national integrated health system, to describe the requirements for EUA, to distribute the medication in a fair and equitable manner, and to ensure compliance with all EUA requirements. A dashboard was developed and iteratively updated as additional CEUAMs were approved. The dashboard tracked CEUAM distribution and monitoring at the national, regional, facility, and patient level. Par stock levels were initially determined at the national level. Facilities were also able to request an additional allotment of medication based on demand and allocated supplies from the Department of Health and Human Services. Providers completed a questionnaire for the CEUAM for each patient to ensure all requirements for the medication were met. If there were data integrity concerns, the entry was flagged for review at the facility level and, upon evaluation, corrections were made. CONCLUSION: Development of the dashboard was resource intensive but provided an excellent mechanism to share information among facilities and national offices. Other healthcare systems can develop similar dashboards to ensure appropriate use of CEUAMs for their patients while meeting all CEUAM requirements.
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COVID-19 , Prestação Integrada de Cuidados de Saúde , Humanos , Preparações FarmacêuticasRESUMO
Background: Real-world data on use of PCSK9 inhibitors (PCSK9-Is), with or without statins and/or ezetimibe, and associated outcomes, can inform more effective prescribing. The objective was to evaluate clinical effectiveness and safety of PCSK9-Is within the Veterans Health Administration (VHA). Methods: In this retrospective cohort study, we included Veterans who had at least one outpatient prescription for alirocumab and/or evolocumab filled within VHA between August 21, 2015, and September 30, 2020. Analyses included 4 mutually exclusive subgroups: PCSK9-I alone, PCSK9-I+statin, PCSK9-I+ezetimibe, and PCSK9-I+statin+ezetimibe subgroups. Primary outcomes included medication possession ratio, persistence, and low-density lipoprotein (LDL). Results: Among Veterans in the analytical cohort (n = 2428), 36.2% were on PCSK9-I monotherapy; 24.0% received a PCSK9-I+statin; 27.4% were on a PCSK9-I+ezetimibe; and 12.4% received triple therapy, that is, PCSK9-I+statin+ezetimibe. The mean medication possession ratio (standard deviation [SD]) for PCSK9-I monotherapy was 83.8% (13.3) compared to 84.3% (11.2) with PCSK9-I+statin therapy, 87.1% (10.1) with PCSK9-I+ezetimibe therapy, and 85.8% (11.7) with triple therapy. The percentage of patients who discontinued PCSK9-I in the monotherapy subgroup was 12.3% vs 9.5%, 6.6%, and 7.4% in the concomitant statin, ezetimibe, and triple-therapy subgroups, respectively (p = .002 among the groups). Mean LDL level was greater in the PCSK9-I monotherapy subgroup (85.6 mg/dL) compared with the concomitant statin (66.5 mg/dL), ezetimibe (65.7 mg/dL), and triple-therapy subgroups (68.1 mg/dL). Conclusions: Veterans showed good adherence and/or persistence with PCSK9-I regimens. On average, those receiving concomitant therapy with a statin and/or ezetimibe achieved significantly lower LDL levels.
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Background: The US Department of Veterans Affairs (VA) enterprise approach to research (VA Research) has built a data-sharing framework available to all research teams within VA. Combined with robust analytic systems and tools available for investigators, VA Research has produced actionable results during the COVID-19 pandemic. Big data science techniques applied to VA's health care data demonstrate that medical research can be performed quickly and judiciously during nationwide health care emergencies. Observations: We envision a common framework of data collection, management, and surveillance implemented in partnership with other health care agencies that would capture even broader, actionable, and timely observational data on populations, while providing opportunities for enhanced collaborative research across agencies. This model should be continued and expanded through the current COVID-19 and future pandemics. Conclusions: Extending the achievements of VA Research in the COVID-19 pandemic to date, we advocate national goals of open science by working toward a synergistic national framework of anonymized, synchronized, shared health data that would provide researchers with potent tools to combat future public health crises.
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Background: Information about the effectiveness of oral antivirals in preventing short- and long-term COVID-19-related outcomes during the Omicron surge is limited. We sought to determine the effectiveness of nirmatrelvir-ritonavir and molnupiravir for the outpatient treatment of COVID-19. Methods: We conducted three retrospective target trial emulation studies comparing matched patient cohorts who received nirmatrelvir-ritonavir versus no treatment, molnupiravir versus no treatment, and nirmatrelvir-ritonavir versus molnupiravir in the Veterans Health Administration (VHA). Participants were Veterans in VHA care at risk for severe COVID-19 who tested positive for SARS-CoV-2 in the outpatient setting during January and February 2022. Primary outcomes included all-cause 30-day hospitalization or death and 31-180-day incidence of acute or long-term care admission, death, or post-COVID-19 conditions. For 30-day outcomes, we calculated unadjusted risk rates, risk differences, and risk ratios. For 31-180-day outcomes, we used unadjusted time-to-event analyses. Results: Participants were 90% male with median age 67 years and 26% unvaccinated. Compared to matched untreated controls, nirmatrelvir-ritonavir-treated participants (N=1,587) had a lower 30-day risk of hospitalization (27.10/1000 versus 41.06/1000, risk difference [RD] - 13.97, 95% CI -23.85 to -4.09) and death (3.15/1000 versus 14.86/1000, RD -11.71, 95% CI - 16.07 to -7.35). Among persons who were alive at day 31, further significant reductions in 31-180-day incidence of hospitalization (sub-hazard ratio 1.07, 95% CI 0.83 to 1.37) or death (hazard ratio 0.61, 95% CI 0.35 to 1.08) were not observed. Molnupiravir-treated participants aged â¥65 years (n=543) had a lower combined 30-day risk of hospitalization or death (55.25/1000 versus 82.35/1000, RD -27.10, 95% CI -50.63 to -3.58). A statistically significant difference in 30-day or 31-180-day risk of hospitalization or death was not observed between matched nirmatrelvir- or molnupiravir-treated participants. Incidence of most post-COVID conditions was similar across comparison groups. Conclusions: Nirmatrelvir-ritonavir was highly effective in preventing 30-day hospitalization and death. Short-term benefit from molnupiravir was observed in older groups. Significant reductions in adverse outcomes from 31-180 days were not observed with either antiviral.
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Objective: To conduct a contemporary detailed assessment of outpatient antibiotic prescribing and outcomes for positive urine cultures in a mixed-sex cohort. Design: Multicenter retrospective cohort review. Setting: The study was conducted using data from 31 Veterans' Affairs medical centers. Patients: Outpatient adults with positive urine cultures. Methods: From 2016 to 2019, data were extracted through a nationwide database and manual chart review. Positive urine cultures were reviewed at the chart, clinician, and aggregate levels. Cases were classified as cystitis, pyelonephritis, or asymptomatic bacteriuria (ASB) based upon documented signs and symptoms. Preferred therapy definitions were applied for subdiagnoses: ASB (no antibiotics), cystitis (trimethoprim-sulfamethoxazole, nitrofurantoin, ß-lactams), and pyelonephritis (trimethoprim-sulfamethoxazole, fluoroquinolone). Outcomes included 30-day clinical failure or hospitalization. Odds ratios for outcomes between treatments were estimated using logistic regression. Results: Of 3,255 cases reviewed, ASB was identified in 1,628 cases (50%), cystitis was identified in 1,156 cases (36%), and pyelonephritis was identified in 471 cases (15%). Of all 2,831 cases, 1,298 (46%) received preferred therapy selection and duration for cases where it could be defined. The most common antibiotic class prescribed was a fluoroquinolone (34%). Patients prescribed preferred therapy had lower odds of clinical failure: preferred (8%) versus nonpreferred (10%) (unadjusted OR, 0.74; 95% confidence interval [CI], 0.58-0.95; P = .018). They also had lower odds of 30-day hospitalization: preferred therapy (3%) versus nonpreferred therapy (5%) (unadjusted OR, 0.55; 95% CI, 0.37-0.81; P = .002). Odds of clinical treatment failure or hospitalization was higher for ß-lactams relative to ciprofloxacin (unadjusted OR, 1.89; 95% CI, 1.23-2.90; P = .002). Conclusions: Clinicians prescribed preferred therapy 46% of the time. Those prescribed preferred therapy had lower odds of clinical failure and of being hospitalized.