Outcomes at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults in the USA: a follow-up surveillance study.

BACKGROUND: Data on medium-term outcomes in indivduals with myocarditis after mRNA COVID-19 vaccination are scarce. We aimed to assess clinical outcomes and quality of life at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination in adolescents and young adults. METHODS: In this follow-up surveillance study, we conducted surveys in US individuals aged 12-29 years with myocarditis after mRNA COVID-19 vaccination, for whom a report had been filed to the Vaccine Adverse Event Reporting System between Jan 12 and Nov 5, 2021. A two-component survey was administered, one component to patients (or parents or guardians) and one component to health-care providers, to assess patient outcomes at least 90 days since myocarditis onset. Data collected were recovery status, cardiac testing, and functional status, and EuroQol health-related quality-of-life measures (dichotomised as no problems or any problems), and a weighted quality-of-life measure, ranging from 0 to 1 (full health). The EuroQol results were compared with published results in US populations (aged 18-24 years) from before and early on in the COVID-19 pandemic. FINDINGS: Between Aug 24, 2021, and Jan 12, 2022, we collected data for 519 (62%) of 836 eligible patients who were at least 90 days post-myocarditis onset: 126 patients via patient survey only, 162 patients via health-care provider survey only, and 231 patients via both surveys. Median patient age was 17 years (IQR 15-22); 457 (88%) patients were male and 61 (12%) were female. 320 (81%) of 393 patients with a health-care provider assessment were considered recovered from myocarditis by their health-care provider, although at the last health-care provider follow-up, 104 (26%) of 393 patients were prescribed daily medication related to myocarditis. Of 249 individuals who completed the quality-of-life portion of the patient survey, four (2%) reported problems with self-care, 13 (5%) with mobility, 49 (20%) with performing usual activities, 74 (30%) with pain, and 114 (46%) with depression. Mean weighted quality-of-life measure (0·91 [SD 0·13]) was similar to a pre-pandemic US population value (0·92 [0·13]) and significantly higher than an early pandemic US population value (0·75 [0·28]; p<0·0001). Most patients had improvements in cardiac diagnostic marker and testing data at follow-up, including normal or back-to-baseline troponin concentrations (181 [91%] of 200 patients with available data), echocardiograms (262 [94%] of 279 patients), electrocardiograms (240 [77%] of 311 patients), exercise stress testing (94 [90%] of 104 patients), and ambulatory rhythm monitoring (86 [90%] of 96 patients). An abnormality was noted among 81 (54%) of 151 patients with follow-up cardiac MRI; however, evidence of myocarditis suggested by the presence of both late gadolinium enhancement and oedema on cardiac MRI was uncommon (20 [13%] of 151 patients). At follow-up, most patients were cleared for all physical activity (268 [68%] of 393 patients). INTERPRETATION: After at least 90 days since onset of myocarditis after mRNA COVID-19 vaccination, most individuals in our cohort were considered recovered by health-care providers, and quality of life measures were comparable to those in pre-pandemic and early pandemic populations of a similar age. These findings might not be generalisable given the small sample size and further follow-up is needed for the subset of patients with atypical test results or not considered recovered. FUNDING: US Centers for Disease Control and Prevention.

Reproducibility of Transcranial Doppler ultrasound in the middle cerebral artery.

BACKGROUND: Transcranial Doppler ultrasound remains the only imaging modality that is capable of real-time measurements of blood flow velocity and microembolic signals in the cerebral circulation. We here assessed the repeatability and reproducibility of transcranial Doppler ultrasound in healthy volunteers and patients with symptomatic carotid artery stenosis. METHODS: Between March and August 2017, we recruited 20 healthy volunteers and 20 patients with symptomatic carotid artery stenosis. In a quiet temperature-controlled room, two 1-h transcranial Doppler measurements of blood flow velocities and microembolic signals were performed sequentially on the same day (within-day repeatability) and a third 7-14 days later (between-day reproducibility). Levels of agreement were assessed by interclass correlation co-efficient. RESULTS: In healthy volunteers (31±9 years, 11 male), within-day repeatability of Doppler measurements were 0.880 (95% CI 0.726-0.950) for peak velocity, 0.867 (95% CI 0.700-0.945) for mean velocity, and 0.887 (95% CI 0.741-0.953) for end-diastolic velocity. Between-day reproducibility was similar but lower: 0.777 (95% CI 0.526-0.905), 0.795 (95% CI 0.558-0.913), and 0.674 (95% CI 0.349-0.856) respectively. In patients (72±11 years, 11 male), within-day repeatability of Doppler measurements were higher: 0.926 (95% CI 0.826-0.970) for peak velocity, 0.922 (95% CI 0.817-0.968) for mean velocity, and 0.868 (95% CI 0.701-0.945) for end-diastolic velocity. Similarly, between-day reproducibility revealed lower values: 0.800 (95% CI 0.567-0.915), 0.786 (95% CI 0.542-0.909), and 0.778 (95% CI 0.527-0.905) respectively. In both cohorts, the intra-observer Bland Altman analysis demonstrated acceptable mean measurement differences and limits of agreement between series of middle cerebral artery velocity measurements with very few outliers. In patients, the carotid stenoses were 30-40% (n = 9), 40-50% (n = 6), 50-70% (n = 3) and > 70% (n = 2). No spontaneous embolisation was detected in either of the groups. CONCLUSIONS: Transcranial Doppler generates reproducible data regarding the middle cerebral artery velocities. However, larger studies are needed to validate its clinical applicability. TRIAL REGISTRATION: ClinicalTrial.gov (ID NCT 03050567), retrospectively registered on 15/05/2017.

Measuring hospital efficiency with Data Envelopment Analysis: nonsubstitutable vs. substitutable inputs and outputs.

There is a conflict between Data Envelopment Analysis (DEA) theory's requirement that inputs (outputs) be substitutable, and the ubiquitous use of nonsubstitutable inputs and outputs in DEA applications to hospitals. This paper develops efficiency indicators valid for nonsubstitutable variables. Then, using a sample of 87 community hospitals, it compares the new measures' efficiency estimates with those of conventional DEA measures. DEA substantially overestimated the hospitals' efficiency on the average, and reported many inefficient hospitals to be efficient. Further, it greatly overestimated the efficiency of some hospitals but only slightly overestimated the efficiency of others, thus making any comparisons among hospitals questionable. These results suggest that conventional DEA models should not be used to estimate the efficiency of hospitals unless there is empirical evidence that the inputs (outputs) are substitutable. If inputs (outputs) are not substitutes, efficiency indicators valid for nonsubstitutability should be employed, or, before applying DEA, the nonsubstitutable variables should be combined using an appropriate weighting scheme or statistical methodology.

Improving the efficiency of distributive and clinical services in hospital pharmacy.

Three problems impede the assessment of hospital pharmacy efficiency. First, although multiple efficiency indicators are utilized to measure a large variety of activities, it has not been possible to validly measure overall efficiency. Second, there have been no widely-used clinical activity indicators, so key outputs often have not been accounted for. Third, there has been no effective methodology for identifying when declines in efficiency are normal random variations and when they represent true decreases in performance. This paper presents a procedure that simultaneously addresses these three problems. It analyzes data from a group of U.S. hospital pharmacies that collect an inclusive set of clinical and distributional indicators. It employs Data Envelopment Analysis to develop comprehensive efficiency measures from the numerous outputs and inputs. It applies statistical Panel Data Analysis to estimate confidence intervals within which each pharmacy's true efficiency resides, and to develop control charts for signaling when a pharmacy's efficiency has declined by more than can be attributed to random variation. This integrated efficiency evaluation system is transferable to other hospital pharmacy systems, thereby offering decision makers a better way of measuring, controlling and improving hospital pharmacy efficiency.

Association between hospital size and pharmacy department productivity.

PURPOSE: The purposes of this study were to characterize and quantify workload and productivity in hospitals according to their size, to establish comparative statistics useful for pharmacy administrators as a means to contrast their efficiency to that of other hospitals of similar sizes, and to provide data to enable policymakers to better assess staffing and resource needs. METHODS: A 50-item Web-based survey designed to illicit information about pharmacy department staffing, workload, and productivity was sent electronically to 242 members of Consorta, Inc., a group-purchasing organization. Responses were received from 110 organizations, a response rate of 45.5%. The responses were categorized into three groups according to the number of staffed beds and were profiled and compared using descriptive and inferential statistics. RESULTS: Pharmacy department workload and expenditures were primarily a function of hospital size: Hospital volume statistics, pharmacy expenditures, hours of operation, pharmacy full-time equivalents (FTEs), and dispensing workload all are highly dependent on the size of the facility. The range of clinical services provided by small, medium, and large hospitals did not differ with the exception of a few services provided more often in larger hospitals. Overall productivity ratios demonstrated greater efficiency among larger hospitals. In terms of costs, pharmacy and hospital expenditures per occupied bed and per admission generally decreased as hospital size increased. CONCLUSION: Results of a survey suggested consistency in clinical services provided by hospitals of varying size and increased productivity with increasing hospital size. Respondents employed fewer FTEs than those in other national surveys.

Monitoring of pharmacy staffing, workload, and productivity in community hospitals.

PURPOSE: The purpose of this survey was to identify and characterize pharmacy productivity monitoring systems used in community hospitals that were part of a national group purchasing organization (GPO). METHODS: A 50-item questionnaire was developed, pretested, and sent electronically to the directors of pharmacy at 242 member hospitals of Consorta, Inc., a national GPO. The questionnaire was designed to elicit information on (1) hospital pharmacy demographics, (2) systems used to measure hospital pharmacy productivity, and (3) staffing levels and workload. Hospital demographic data were also obtained for respondent and nonrespondent hospitals from the American Hospital Association's AHA Guide. Descriptive statistics, Student's t tests, and chi-square tests were used to characterize the data and compare respondents with nonrespondents. RESULTS: Responses were received from 110 hospitals (45.5%). No clinically significant differences were found when respondent and nonrespondent hospitals were compared based on AHA Guide data. The productivity workload ratios monitored most often by respondent hospitals were full-time equivalents (FTEs) per adjusted patient day, FTEs per dose dispensed, and FTEs per dose billed. Respondents reported a mean +/- S.D. of 21.90 +/- 18.83 actual FTEs and total doses dispensed, billed, or administered per year of 111,391.4 +/- 111,538.0. A major limitation of the productivity systems used in the hospitals was the inability of the systems to account for clinical services performed by the pharmacy staff. CONCLUSION: A survey of community hospitals indicated that although most engaged in productivity monitoring, systems for such measurement often failed to capture all relevant clinical workload data.

Dose-finding and pharmacokinetic profiles of prophylactic doses of a low molecular weight heparin (reviparin-sodium) in pediatric patients.

INTRODUCTION: The low molecular weight heparin (LMWH), reviparin-sodium was studied in dose-finding and pharmacokinetic studies in children with central venous lines (CVLs). MATERIALS AND METHODS: The dose-finding study was performed in 24 patients aged 3 days to 16 years. Dose adjustments were made using a nomogram based on anti-factor Xa levels (units (U)/ml) (target of 0.1-0.3 U/ml). The pharmacokinetic study was performed in 19 patients, 9 less than or equal to 5 kg (7 of whom were less than 3 months) and 10 greater than 5 kg (all more than 3 months). RESULTS: The dose-finding study demonstrated that children over 5 kg required 30 International Units (IU)/kilogram (kg), subcutaneous (SC) twice daily (BID), and children less than or equal to 5 kg required 50 IU/kg, SC BID, to achieve target levels. The pharmacokinetic study demonstrated that 80% of anti-factor Xa levels were within the target range with both patient groups having similar peak (average=0.26 U/ml) and trough (average=0.13 U/ml) levels. CONCLUSIONS: Peak anti-factor Xa levels (0.1-0.3 U/ml) using reviparin-sodium are achieved by administering 50 IU/kg in children greater than 3 months of age and 30 U/kg in children less than 3 months of age.

An open-label randomized controlled trial of low molecular weight heparin compared to heparin and coumadin for the treatment of venous thromboembolic events in children: the REVIVE trial.

OBJECTIVE(S): Venous thromboembolic events (VTE) are serious complications in children and for which the standard of care, unfractionated heparin followed by oral anticoagulation (UFH/OA), is problematic. The objective of REVIVE was to compare the efficacy and safety of a low molecular weight heparin (reviparin-sodium) to UFH/OA for the treatment of VTE in children. STUDY DESIGN: This multicenter, open-label study, with blinded central outcome adjudication, randomized patients with objectively confirmed VTE to receive either reviparin-sodium or UFH/OA. Dose adjustments were made using nomograms. The efficacy outcome was based on recurrent VTE and death due to VTE during the 3-month treatment period. The safety outcomes were major bleeding, minor bleeding and death. Due to slow patient accrual, REVIVE was closed prematurely. RESULTS: At 3 months, with reviparin-sodium, 2/36 patients (5.6%) had recurrent VTE or death compared to 4/40 patients (10.0%) receiving UFH/OA (odds ratio=0.53; 95% CI=(0.05, 4.00); Fisher's exact test: 2P=0.677). There were 7 major bleeds, 2/36 (5.6%) in the reviparin-sodium group and 5/40 (12.5%) in UFH/OA group (odds ratio=0.41; 95% confidence interval 0.04, 2.76); Fisher's exact test: P=0.435). There were 5 deaths during the study period, 1 (2.8%) in the reviparin-sodium group and 4 (10.0%) in the UFH/OA group. All five deaths were unrelated to VTE but one was due to an intracranial hemorrhage in the UFH/OA group. CONCLUSIONS: Although limited by small sample size, REVIVE provides valuable information on the incidence of recurrent VTE, major bleeding and problematic issues associated with therapy of VTE in children.

An open-label randomized controlled trial of low molecular weight heparin for the prevention of central venous line-related thrombotic complications in children: the PROTEKT trial.

OBJECTIVE(S): Central venous lines (CVLs) are major risk factors for venous thromboembolism (VTE) in children. The objective of PROTEKT was to determine if a low molecular weight heparin (reviparin-sodium) safely prevents CVL-related VTE. STUDY DESIGN: This multi-center, open-label study, with blinded central outcome adjudication, randomized patients with new CVLs to twice-daily reviparin-sodium or standard care. The efficacy outcome was based on an exit venogram at Day 30 (+14 days), or earlier in case of CVL removal, or confirmed symptomatic VTE. The safety outcomes were major bleeding and death. Due to slow and restricted patient accrual, PROTEKT was closed prematurely. RESULTS: With reviparin-sodium, 14.1% (11:78) of patients had VTE compared to 12.5% (10:80) of control patients (odds ratio=1.15; 95% confidence interval 0.42, 3.23); 2P=0.82). One patient had a major bleed and there were two deaths, all three events occurring in the standard care group. CONCLUSIONS: The use of reviparin-sodium for short-term prophylaxis of CVL-related VTE in children was safe but its efficacy remains unclear. Although underpowered, PROTEKT provided valuable information on event rates and predictors of CVL-related VTE.