Incidence rates of thrombosis with thrombocytopenia syndrome (TTS) among adults in United States commercial and Medicare claims databases, 2017-2020.

BACKGROUND: Increased risk of thrombosis with thrombocytopenia syndrome (TTS) following adenovirus vector-based COVID-19 vaccinations has been identified in passive surveillance systems. TTS incidence rates (IRs) in the United States (U.S.) are needed to contextualize reports following COVID-19 vaccination. METHODS: We estimated annual and monthly IRs of overall TTS, common site TTS, and unusual site TTS for adults aged 18-64 years in Carelon Research and MarketScan commercial claims (2017-Oct 2020), CVS Health and Optum commercial claims (2019-Oct 2020), and adults aged ≥ 65 years using CMS Medicare claims (2019-Oct 2020); IRs were stratified by age, sex, and race/ethnicity (CMS Medicare). RESULTS: Across data sources, annual IRs for overall TTS were similar between Jan-Dec 2019 and Jan-Oct 2020. Rates were higher in Medicare (IRs: 370.72 and 365.63 per 100,000 person-years for 2019 and 2020, respectively) than commercial data sources (MarketScan IRs: 24.21 and 24.06 per 100,000 person-years; Optum IRs: 32.60 and 31.29 per 100,000 person-years; Carelon Research IRs: 24.46 and 26.16 per 100,000 person-years; CVS Health IRs: 30.31 and 30.25 per 100,000 person-years). Across years and databases, common site TTS IRs increased with age and were higher among males. Among adults aged ≥ 65 years, the common site TTS IR was highest among non-Hispanic black adults. Annual unusual site TTS IRs ranged between 2.02 and 3.04 (commercial) and 12.49 (Medicare) per 100,000 person-years for Jan-Dec 2019; IRs ranged between 1.53 and 2.67 (commercial) and 11.57 (Medicare) per 100,000 person-years for Jan-Oct 2020. Unusual site TTS IRs were higher in males and increased with age in commercial data sources; among adults aged ≥ 65 years, IRs decreased with age and were highest among non-Hispanic American Indian/Alaska native adults. CONCLUSION: TTS IRs were generally similar across years, higher for males, and increased with age. These rates may contribute to surveillance of post-vaccination TTS.

Background rates of adverse events of special interest for COVID-19 vaccine safety monitoring in the United States, 2019-2020.

BACKGROUND: The U.S. Food and Drug Administration (FDA) Biologics Effectiveness and Safety (BEST) Initiative conducts active surveillance of adverse events of special interest (AESI) after COVID-19 vaccination. Historical incidence rates (IRs) of AESI are comparators to evaluate safety. METHODS: We estimated IRs of 17 AESI in six administrative claims databases from January 1, 2019, to December 11, 2020: Medicare claims for adults ≥ 65 years and commercial claims (Blue Health Intelligence®, CVS Health, HealthCore Integrated Research Database, IBM® MarketScan® Commercial Database, Optum pre-adjudicated claims) for adults < 65 years. IRs were estimated by sex, age, race/ethnicity (Medicare), and nursing home residency (Medicare) in 2019 and for specific periods in 2020. RESULTS: The study included >100 million enrollees annually. In 2019, rates of most AESI increased with age. However, compared with commercially insured adults, Medicare enrollees had lower IRs of anaphylaxis (11 vs 12-19 per 100,000 person-years), appendicitis (80 vs 117-155), and narcolepsy (38 vs 41-53). Rates were higher in males than females for most AESI across databases and varied by race/ethnicity and nursing home status (Medicare). Acute myocardial infarction (Medicare) and anaphylaxis (all databases) IRs varied by season. IRs of most AESI were lower during March-May 2020 compared with March-May 2019 but returned to pre-pandemic levels after May 2020. However, rates of Bell's palsy, Guillain-Barré syndrome, narcolepsy, and hemorrhagic/non-hemorrhagic stroke remained lower in multiple databases after May 2020, whereas some AESI (e.g., disseminated intravascular coagulation) exhibited higher rates after May 2020 compared with 2019. CONCLUSION: AESI background rates varied by database and demographics and fluctuated in March-December 2020, but most returned to pre-pandemic levels after May 2020. It is critical to standardize demographics and consider seasonal and other trends when comparing historical rates with post-vaccination AESI rates in the same database to evaluate COVID-19 vaccine safety.

Validating Claims-Based Algorithms Determining Pregnancy Outcomes and Gestational Age Using a Linked Claims-Electronic Medical Record Database.

INTRODUCTION: Pregnancy outcome identification and precise estimates of gestational age (GA) are critical in drug safety studies of pregnant women. Validated pregnancy outcome algorithms based on the International Classification of Diseases, Tenth Revision, Clinical Modification/Procedure Coding System (ICD-10-CM/PCS) have not previously been published. METHODS: We developed algorithms to classify pregnancy outcomes and estimate GA using ICD-10-CM/PCS and service codes on claims in the 2016-2018 IBM® MarketScan® Explorys® Claims-EMR Data Set and compared the results with ob-gyn adjudication of electronic medical records (EMRs). Obstetric services were grouped into episodes using hierarchical and spacing requirements. GA was based on evidence with the highest clinical accuracy. Among pregnancies with obstetric EMRs, 100 full-term live births (FTBs), 100 preterm live births (PTBs), 100 spontaneous abortions (SAs), and 24 stillbirths were selected for review. Physicians adjudicated cases using Global Alignment of Immunization safety Assessment in pregnancy (GAIA) definitions applied to structured EMRs. RESULTS: The claims-based algorithms identified 34,204 pregnancies, of which 9.9% had obstetric EMRs. Of sampled pregnancies, 92 FTBs, 93 PTBs, 75 SAs, and 24 stillbirths were adjudicated. Among these pregnancies, the percent agreement was 97.8%, 62.4%, 100.0%, and 70.8% for FTBs, PTBs, SAs, and stillbirths, respectively. The percent agreement on GA within 7 and 28 days, respectively, was 85.9% and 100.0% for FTBs, 81.7% and 98.9% for PTBs, 61.3% and 94.7% for SAs, and 66.7% and 79.2% for stillbirths. CONCLUSIONS: The pregnancy outcome algorithms had high agreement with physician adjudication of EMRs and may inform post-market maternal safety surveillance.

Outcomes of lower extremity orthopedic surgery in ambulatory children with cerebral palsy with and without gait analysis: results of a randomized controlled trial.

This study examined the impact of gait analysis on surgical outcomes in ambulatory children with cerebral palsy (CP) through a randomized controlled trial. 156 children with CP (94 male; age 10.2 ± 3.7 years) underwent gait analysis and were randomized to two groups: Gait Report group (N = 83), where the referring surgeon received the patient's gait analysis report, and Control group (N = 73), where the surgeon did not receive the gait report. Outcomes were assessed pre- and 1.3 ± 0.5 years post-operatively. An intent-to-treat analysis compared outcomes between the two groups. Outcome measures included the Gillette Functional Activity Questionnaire (FAQ), Gait Deviation Index (GDI), oxygen cost, gross motor function measure, Child Health Questionnaire (CHQ), Pediatric Outcomes Data Collection Instrument (PODCI), and Pediatric Evaluation and Disability Inventory. The outcomes that differed significantly between groups were change in health from the CHQ, which was rated as much better for 56% (46/82) of children in the Gait Report group compared with 38% (28/73) in the Control group (p = 0.04), and upper extremity physical function from the PODCI. Gait outcomes (FAQ and GDI) improved more when over half of the recommendations for a patient were followed or the recommended extent of surgery (none, single, or multi-level) was done (p ≤ 0.04). On average, however, only 42% of the recommendations were followed in the Gait Report group, compared with 35% in the Control group (p = 0.23). This is much less than the >85% reported in previous studies and may account for the lack of differences between groups for some of the outcome measures.

Influence of gait analysis on decision-making for lower extremity orthopaedic surgery: Baseline data from a randomized controlled trial.

Previous studies examining the influence of gait analysis on surgical decision-making have been limited by the lack of a control group. The aim of this study was to use data from a randomized controlled trial to determine the effects of gait analysis on surgical decision-making in children with cerebral palsy (CP). 178 ambulatory children with CP (110 male; age 10.3±3.8 years) being considered for lower extremity orthopaedic surgery underwent gait analysis and were randomized into one of two groups: gait report group (N=90), where the orthopaedic surgeon received the gait analysis report, and control group (N=88), where the surgeon did not receive the gait report. Data regarding specific surgeries were recorded by the treating surgeon before gait analysis, by the gait laboratory surgeon after gait analysis, and after surgery. Agreement between the treatment done and the gait analysis recommendations was compared between groups using the 2-sided Fisher's Exact test. When a procedure was planned initially and also recommended by gait analysis, it was performed more often in the gait report group (91% vs. 70%, p<0.001). When the gait laboratory recommended against a planned procedure, the plan was changed more frequently in the gait report group (48% vs. 27%, p=0.009). When the gait laboratory recommended adding a procedure, it was added more frequently in the gait report group (12% vs. 7%, p=0.037). These results provide a stronger level of evidence demonstrating that gait analysis changes treatment decision-making and also reinforces decision-making when it agrees with the surgeon's original plan.

Effects of preoperative gait analysis on costs and amount of surgery.

BACKGROUND: The purpose of this study was to determine the effects of clinical gait analysis (GA) on the costs of care in ambulatory children with cerebral palsy (CP) and the amount of surgery these children undergo. METHODS: A retrospective review identified all ambulatory patients with CP who had undergone lower extremity orthopaedic surgery at our hospital from 1991 to 2005 with at least a 6-month follow-up. The patients were grouped into those who had undergone GA before their index surgery (GA group, N=313) and those who had not (NGA group, N=149). The groups were compared in terms of the number of procedures during index surgery and subsequent surgeries and the direct costs associated with these surgeries. Costs were calculated in US dollars by using a standardized protocol including fees for the surgeon, anesthesia, operating room, hospital stay, physical therapy, and GA. RESULTS: Patients in the GA group were significantly older and less functionally involved, had their first surgery in later years, and had a shorter follow-up than patients in the NGA group (P<0.001). Adjusting for these differences, patients in the GA group had more procedures (GA: 5.8, NGA: 4.2; P<0.001) and higher cost (GA: $43,006, NGA: $35,215; P<0.001) during index surgery, but less subsequent surgery. A higher proportion of patients went on to additional surgery in the NGA group (NGA: 32%, GA: 11%; P<0.001), with more additional surgeries per person-year (NGA: 0.3/person-year, GA: 0.1/person-year; P<0.001) resulting in higher additional costs (NGA: $3009/person-year, GA: $916/person-year; P<0.001). The total number of procedures (GA: 2.6/person-year, NGA: 2.3/person-year; P=0.22) and cost (GA: $20,448/person-year, NGA: $19,535/person-year; P=0.58) did not differ significantly between the 2 groups. CONCLUSIONS: Clinical GA is associated with a lower incidence of additional surgery, resulting in lesser disruption to patients' lives. This finding has not been shown before and may assist patients, physicians, policy makers, and insurance companies in assessing the role of GA in the care of ambulatory children with CP. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Concurrent and discriminant validity of Spanish language instruments for measuring functional health status.

BACKGROUND: Questionnaires translated into languages other than English are often not validated to the same extent as the English versions. This study examined the concurrent and discriminant validity of selected domains related to physical function from Spanish language versions of the Child Health Questionnaire (CHQ), Pediatric Outcomes Data Collection Instrument (PODCI), and Pediatric Evaluation and Disability Inventory (PEDI). METHODS: Concurrent validity was examined in 93 children with cerebral palsy by correlating questionnaire domain scores with Gross Motor Function Measure and Gillette Functional Assessment Questionnaire walking scale scores. Discriminant validity with respect to Gross Motor Function Classification System (GMFCS) level was examined using analysis of variance and nonparametric discriminant analysis. RESULTS: Concurrent validity was demonstrated for 3 domains from the PEDI (Mobility functional skills, tau = 0.62; Mobility caregiver assistance, tau = 0.46-0.55; and Self-care functional skills, tau = 0.30-0.36), 3 domains from the PODCI (Sports and physical function, tau = 0.48-0.51; Transfer and basic mobility, tau = 0.48-0.51; and Upper extremity physical function, tau = 0.28), and 1 domain from the CHQ (Physical function, tau = 0.31-0.36). Discriminant validity was demonstrated for the same domains based on significant decreases in domain scores with increasing GMFCS level. Discriminant validity was highest for the PODCI, which correctly classified 98% (91/93) of subjects into the correct GMFCS level when all 3 domains were considered. CONCLUSIONS: For the first time, concurrent validity and discriminant validity have been demonstrated for the physical function domains of Spanish language versions of the PODCI, PEDI, and CHQ questionnaires. PODCI and PEDI had the highest concurrent validity, and PODCI had the best discriminant ability. CLINICAL RELEVANCE: It is important to examine the validity of instruments when they have been translated from English into other languages. This importance will only increase as the population of non-English-speaking patients expands.

The challenges of assessing fidelity to physician-driven HIV prevention interventions: lessons learned implementing Partnership for Health in a Los Angeles HIV clinic.

Documenting fidelity to HIV prevention interventions is critical to ensure consistency in intervention implementation and necessary for measuring intervention exposure and, ultimately, outcomes. Significant variation from prescribed protocols or inconsistent implementation can jeopardize the integrity of evaluation research and render outcomes uninterpretable. There is increasing support for HIV prevention models targeting seropositive individuals designed to be delivered by physicians during clinic visits. Assessing fidelity to physician-delivered interventions that occur during clinical exams present unique challenges. This paper presents findings from various data sources designed to track intervention fidelity and exposure to the Partnership for Health intervention, a physician-delivered HIV prevention intervention implemented in an urban community HIV clinic. We present findings from chart abstraction data, patient surveys and exit interviews, and provider qualitative interviews. Lessons learned and recommendations for maximizing the accuracy and validity of fidelity assessment in future evaluations of HIV prevention interventions in primary care settings are considered.

Agreement among three instruments for measuring functional health status and quality of life in pediatric orthopaedics.

The Child Health Questionnaire (CHQ), Pediatric Outcomes Data Collection Instrument (PODCI), and Pediatric Evaluation and Disability Inventory (PEDI) are the 3 instruments commonly used to measure function and quality of life in pediatric orthopaedics. This study compared answers to specific questions on the CHQ, PODCI, and PEDI given by the parents of 66 children with cerebral palsy, who completed all 3 questionnaires. Both Spanish- and English-speaking subjects were included. No overlapping questions were found between the CHQ and PEDI. Of the 8 questions that overlapped between the CHQ and PODCI, 2 questions (general health and change in health) had weighted kappa greater than 0.70, with responses within +/-1 point for more than 95% of respondents. These 2 questions had almost exactly the same wording on both questionnaires. The other 6 questions had fair to poor agreement between questionnaires (kappa, 0.10-0.55). All 5 questions that were addressed by both the PODCI and PEDI also had poor agreement (kappa < 0.40). There was little correspondence between the preconceived match quality and the actual matching results (r=0.41; P=0.16). These results suggest that differences in wording have a significant and unpredictable effect on parents' responses; this should be considered when selecting from among different instruments. Of the instruments used in this study, the CHQ is the easiest to administer and is a good general quality of life measure; however, the PODCI or PEDI may be preferred if information about more specific functional activities is desired.