Cost-effectiveness of the top 100 drugs by public spending in Canada, 2015-2021: a repeated cross-sectional study.

OBJECTIVES: To assess the distribution and spending by cost-effectiveness category among those drugs with the highest public spending levels in Canada. DESIGN: Repeated cross-sectional study. SETTING: The Canadian provinces of Manitoba, Ontario, New Brunswick, Nova Scotia, Prince Edward Island and Newfoundland. MAIN OUTCOMES AND MEASURES: Cost-effectiveness assessments by the Canadian Agency for Drugs and Technologies in Health (CADTH) for top-100 brand-name outpatient drugs by gross public plan spending in any year between 2015 and 2021 in Canada Institute for Health Information's National Prescription Drug Utilization Information System data. Gross public plan spending by cost-effectiveness category. RESULTS: From 2015 to 2021, 152 brand-name drugs occupied a top-100 rank and were included in the analysis. Of those, 117 had been assessed by CADTH. During the 7-year period, there was an increase in both top-100 drugs with cost-effective (from 18 to 24) and cost-ineffective (from 29 to 41) assessments, while drugs not assessed or with an unclear assessment declined (from 31 to 19 and from 22 to 16, respectively). As a share of spending on top-100 drugs with an assessment, spending on cost-effective drugs was mostly stable at 40%-46% from 2015 to 2021, while spending on cost-ineffective drugs increased from 30% to 45%. CONCLUSION: A large and growing share of public drug spending has been allocated to cost-ineffective drugs in Canada. Dedicating large budgets to such treatments prevents spending with greater health impact elsewhere in the healthcare system and could restrain the capacity to pay for groundbreaking pharmaceutical innovation in the future.

Early observations of Tier-3 drug shortages on purchasing trends across Canada: A cross-sectional analysis of 3 case-example drugs.

BACKGROUND: To curb the growing impact of drug shortages, Health Canada developed the Tiered Notification and Communication Framework which assigns potential shortages a corresponding tiered status. Tier-3 is assigned to shortages with the greatest potential impact on the healthcare system. This study aims to describe drug purchasing trends in response to Tier-3 shortages using three case-examples. METHODS: We conducted a time-series analysis of monthly purchasing data for three out of 17 Tier-3 drug shortages (hydralazine, sarilumab, and medroxyprogesterone acetate) with publicly available reports in July 2021 and available IQVIA MIDAS data from January 2016 to December 2021. We assessed percent changes in purchasing at 1-, 3-, and 6-months after the onset of each Tier-3 drug shortage and interventional ARIMA modelling was used to assess the statistical significance. RESULTS: Medroxyprogesterone acetate experienced a significant shift (p = 0.0370) in purchasing following its shortage, and the 1-, 3-, and 6-month percent changes were +14.9%, +6.8% and -3.1%, respectively. Hydralazine and sarilumab did not show a significant shift. The 1-, 3-, and 6-month percent changes for hydralazine were +15.5%, +10.2%, and +9.6% respectively and +25.2%, +45.1% and +39.2 for sarilumab. CONCLUSIONS: These results indicate that drugs assigned a Tier-3 status may not show declines in purchasing in the months following status assignment, which may be due to policy responses following the assignment. However, more insight is needed into the mechanisms through which these policy measures impact shortages and whether they are functioning as intended.

California Hospitals' Rapidly Declining Traditional Medicare Operating Margins.

In recent years, Medicare margins of U.S. short-term acute care hospitals participating in the inpatient prospective payment system (IPPS) have declined nationally by over 10 percentage points, from 2.2% in 2002 to -8.7% in 2019. This trend conceals critical regional variations, with recent studies documenting particularly low and negative margins in metropolitan areas with higher labor costs despite geographic adjustments by the Centers for Medicare & Medicaid Services (CMS). In this article, we describe recent trends in California hospitals' traditional fee-for-service Medicare operating margins compared to hospital operating margins across payers and changes in the CMS hospital wage index (HWI) used to adjust Medicare payments. We conduct an observational study of audited financial reports of IPPS-participating California hospitals using California Department of Health Care Access and Information and CMS data for years 2005-2020 (n = 4429 reports included in the analysis). We describe trends in financial measures by payer and investigate associations between HWI and traditional Medicare margins, focusing on the pre-COVID period of 2005 through 2019. During that period, California hospitals' statewide traditional Medicare operating margin declined from -27 to -40%, and financial shortfalls in caring for fee-for-service Medicare patients more than doubled ($4.1 billion in 2005 to $8.5 billion in 2019, both values in 2019 dollars). Meanwhile, operating margins from commercial managed care patients increased from 21% in 2005 to 38% in 2019. There was a stable negative association between HWI and traditional Medicare operating margins throughout the period (p = 0.000 in 2005; p < 0.0001 in 2006-2020), indicating that areas of California with higher health care wages had persistently worse traditional Medicare operating margins than areas with lower wages.

Employment and Economic Outcomes of Participants With Mild Traumatic Brain Injury in the TRACK-TBI Study.

Importance: Mild traumatic brain injury (mTBI) may impair the ability to work. Strategies to facilitate return to work are understudied. Objective: To assess employment and economic outcomes for employed, working-age adults with mTBI in the 12 months after injury and the association between return to work and employer assistance. Design, Setting, and Participants: Using data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, a cohort study of patients with mTBI presenting to emergency departments of 11 level I US trauma centers was performed. Patients with mTBI enrolled in the TRACK-TBI cohort study from February 26, 2014, to May 4, 2016, were followed up at 2 weeks and 3, 6, and 12 months after injury. Work status and income decline of participants were documented in the first year after injury. Associations between work status, injury characteristics, and offer of employer assistance and associations between follow-up care and employer assistance were investigated. Results were adjusted for unobserved outcomes using inverse probability weighting. Data were extracted July 12, 2020; analyses were completed March 24, 2021. Analyses included 435 participants aged 18 to 64 years who were working before the injury, had a Glasgow Coma Scale score of 13 to 15, and completed all postinjury follow-up surveys. Main Outcomes and Measures: Primary outcomes were work status (working or not working) at each study follow-up milestone. Employer assistance included sick leave, reduced hours, modified schedule, transfer to different tasks, assistive technology, and coaching offered during the first 3 months after injury. Results: Of 435 participants (147 [34%] female; 320 [74%] White; mean [SD] age 37.3 [12.9] years), 258 (59%) reported not working at 2 weeks after injury and 74 (17%) reported not working at 12 months after injury. More than one-fifth (92 [21%]) experienced a decline in annual income. Work status at 12 months was significantly associated with postconcussion symptoms experienced at 3 months after injury (73% of patients with 3 or more symptoms reported working at 12 months after injury vs 89% of patients with 2 or fewer symptoms; P < .001) but not with other injury characteristics. Participants offered employer assistance in the first 3 months after injury were more likely to report working after injury than those not offered such assistance (at 6 months: 88% vs 78%; P = .02; at 12 months: 86% vs 72%; P = .005). Conclusions and Relevance: In this cohort study, mTBI was associated with substantial employment and economic consequences for some patients. Clinicians should systematically follow up with patients with mTBI and coordinate with employers to promote successful return to work.

Association of Posttraumatic Epilepsy With 1-Year Outcomes After Traumatic Brain Injury.

Importance: Posttraumatic epilepsy (PTE) is a recognized sequela of traumatic brain injury (TBI), but the long-term outcomes associated with PTE independent of injury severity are not precisely known. Objective: To determine the incidence, risk factors, and association with functional outcomes and self-reported somatic, cognitive, and psychological concerns of self-reported PTE in a large, prospectively collected TBI cohort. Design, Setting, and Participants: This multicenter, prospective cohort study was conducted as part of the Transforming Research and Clinical Knowledge in Traumatic Brain Injury study and identified patients presenting with TBI to 1 of 18 participating level 1 US trauma centers from February 2014 to July 2018. Patients with TBI, extracranial orthopedic injuries (orthopedic controls), and individuals without reported injuries (eg, friends and family of participants; hereafter friend controls) were prospectively followed for 12 months. Data were analyzed from January 2020 to April 2021. Exposure: Demographic, imaging, and clinical information was collected according to TBI Common Data Elements. Incidence of self-reported PTE was assessed using the National Institute of Neurological Disorders and Stroke Epilepsy Screening Questionnaire (NINDS-ESQ). Main Outcomes and Measures: Primary outcomes included Glasgow Outcome Scale Extended, Rivermead Cognitive Metric (RCM; derived from the Rivermead Post Concussion Symptoms Questionnaire), and the Brief Symptom Inventory-18 (BSI). Results: Of 3296 participants identified as part of the study, 3044 met inclusion criteria, and 1885 participants (mean [SD] age, 41.3 [17.1] years; 1241 [65.8%] men and 644 [34.2%] women) had follow-up information at 12 months, including 1493 patients with TBI; 182 orthopedic controls, 210 uninjured friend controls; 41 patients with TBI (2.8%) and no controls had positive screening results for PTE. Compared with a negative screening result for PTE, having a positive screening result for PTE was associated with presenting Glasgow Coma Scale score (8.1 [4.8] vs.13.5 [3.3]; P < .001) as well as with anomalous acute head imaging findings (risk ratio, 6.42 [95% CI, 2.71-15.22]). After controlling for age, initial Glasgow Coma Scale score, and imaging findings, compared with patients with TBI and without PTE, patients with TBI and with positive PTE screening results had significantly lower Glasgow Outcome Scale Extended scores (mean [SD], 6.1 [1.7] vs 4.7 [1.5]; P < .001), higher BSI scores (mean [SD], 50.2 [10.7] vs 58.6 [10.8]; P = .02), and higher RCM scores (mean [SD], 3.1 [2.6] vs 5.3 [1.9]; P = .002) at 12 months. Conclusions and Relevance: In this cohort study, the incidence of self-reported PTE after TBI was found to be 2.8% and was independently associated with unfavorable outcomes. These findings highlight the need for effective antiepileptogenic therapies after TBI.

Pathological Computed Tomography Features Associated With Adverse Outcomes After Mild Traumatic Brain Injury: A TRACK-TBI Study With External Validation in CENTER-TBI.

Importance: A head computed tomography (CT) with positive results for acute intracranial hemorrhage is the gold-standard diagnostic biomarker for acute traumatic brain injury (TBI). In moderate to severe TBI (Glasgow Coma Scale [GCS] scores 3-12), some CT features have been shown to be associated with outcomes. In mild TBI (mTBI; GCS scores 13-15), distribution and co-occurrence of pathological CT features and their prognostic importance are not well understood. Objective: To identify pathological CT features associated with adverse outcomes after mTBI. Design, Setting, and Participants: The longitudinal, observational Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study enrolled patients with TBI, including those 17 years and older with GCS scores of 13 to 15 who presented to emergency departments at 18 US level 1 trauma centers between February 26, 2014, and August 8, 2018, and underwent head CT imaging within 24 hours of TBI. Evaluations of CT imaging used TBI Common Data Elements. Glasgow Outcome Scale-Extended (GOSE) scores were assessed at 2 weeks and 3, 6, and 12 months postinjury. External validation of results was performed via the Collaborative European NeuroTrauma Effectiveness Research in Traumatic Brain Injury (CENTER-TBI) study. Data analyses were completed from February 2020 to February 2021. Exposures: Acute nonpenetrating head trauma. Main Outcomes and Measures: Frequency, co-occurrence, and clustering of CT features; incomplete recovery (GOSE scores <8 vs 8); and an unfavorable outcome (GOSE scores <5 vs ≥5) at 2 weeks and 3, 6, and 12 months. Results: In 1935 patients with mTBI (mean [SD] age, 41.5 [17.6] years; 1286 men [66.5%]) in the TRACK-TBI cohort and 2594 patients with mTBI (mean [SD] age, 51.8 [20.3] years; 1658 men [63.9%]) in an external validation cohort, hierarchical cluster analysis identified 3 major clusters of CT features: contusion, subarachnoid hemorrhage, and/or subdural hematoma; intraventricular and/or petechial hemorrhage; and epidural hematoma. Contusion, subarachnoid hemorrhage, and/or subdural hematoma features were associated with incomplete recovery (odds ratios [ORs] for GOSE scores <8 at 1 year: TRACK-TBI, 1.80 [95% CI, 1.39-2.33]; CENTER-TBI, 2.73 [95% CI, 2.18-3.41]) and greater degrees of unfavorable outcomes (ORs for GOSE scores <5 at 1 year: TRACK-TBI, 3.23 [95% CI, 1.59-6.58]; CENTER-TBI, 1.68 [95% CI, 1.13-2.49]) out to 12 months after injury, but epidural hematoma was not. Intraventricular and/or petechial hemorrhage was associated with greater degrees of unfavorable outcomes up to 12 months after injury (eg, OR for GOSE scores <5 at 1 year in TRACK-TBI: 3.47 [95% CI, 1.66-7.26]). Some CT features were more strongly associated with outcomes than previously validated variables (eg, ORs for GOSE scores <5 at 1 year in TRACK-TBI: neuropsychiatric history, 1.43 [95% CI .98-2.10] vs contusion, subarachnoid hemorrhage, and/or subdural hematoma, 3.23 [95% CI 1.59-6.58]). Findings were externally validated in 2594 patients with mTBI enrolled in the CENTER-TBI study. Conclusions and Relevance: In this study, pathological CT features carried different prognostic implications after mTBI to 1 year postinjury. Some patterns of injury were associated with worse outcomes than others. These results support that patients with mTBI and these CT features need TBI-specific education and systematic follow-up.

Functional Outcomes Over the First Year After Moderate to Severe Traumatic Brain Injury in the Prospective, Longitudinal TRACK-TBI Study.

Importance: Moderate to severe traumatic brain injury (msTBI) is a major cause of death and disability in the US and worldwide. Few studies have enabled prospective, longitudinal outcome data collection from the acute to chronic phases of recovery after msTBI. Objective: To prospectively assess outcomes in major areas of life function at 2 weeks and 3, 6, and 12 months after msTBI. Design, Setting, and Participants: This cohort study, as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study, was conducted at 18 level 1 trauma centers in the US from February 2014 to August 2018 and prospectively assessed longitudinal outcomes, with follow-up to 12 months postinjury. Participants were patients with msTBI (Glasgow Coma Scale scores 3-12) extracted from a larger group of patients with mild, moderate, or severe TBI who were enrolled in TRACK-TBI. Data analysis took place from October 2019 to April 2021. Exposures: Moderate or severe TBI. Main Outcomes and Measures: The Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS) were used to assess global functional status 2 weeks and 3, 6, and 12 months postinjury. Scores on the GOSE were dichotomized to determine favorable (scores 4-8) vs unfavorable (scores 1-3) outcomes. Neurocognitive testing and patient reported outcomes at 12 months postinjury were analyzed. Results: A total of 484 eligible patients were included from the 2679 individuals in the TRACK-TBI study. Participants with severe TBI (n = 362; 283 men [78.2%]; median [interquartile range] age, 35.5 [25-53] years) and moderate TBI (n = 122; 98 men [80.3%]; median [interquartile range] age, 38 [25-53] years) were comparable on demographic and premorbid variables. At 2 weeks postinjury, 36 of 290 participants with severe TBI (12.4%) and 38 of 93 participants with moderate TBI (41%) had favorable outcomes (GOSE scores 4-8); 301 of 322 in the severe TBI group (93.5%) and 81 of 103 in the moderate TBI group (78.6%) had moderate disability or worse on the DRS (total score ≥4). By 12 months postinjury, 142 of 271 with severe TBI (52.4%) and 54 of 72 with moderate TBI (75%) achieved favorable outcomes. Nearly 1 in 5 participants with severe TBI (52 of 270 [19.3%]) and 1 in 3 with moderate TBI (23 of 71 [32%]) reported no disability (DRS score 0) at 12 months. Among participants in a vegetative state at 2 weeks, 62 of 79 (78%) regained consciousness and 14 of 56 with available data (25%) regained orientation by 12 months. Conclusions and Relevance: In this study, patients with msTBI frequently demonstrated major functional gains, including recovery of independence, between 2 weeks and 12 months postinjury. Severe impairment in the short term did not portend poor outcomes in a substantial minority of patients with msTBI. When discussing prognosis during the first 2 weeks after injury, clinicians should be particularly cautious about making early, definitive prognostic statements suggesting poor outcomes and withdrawal of life-sustaining treatment in patients with msTBI.

Association of Sex and Age With Mild Traumatic Brain Injury-Related Symptoms: A TRACK-TBI Study.

Importance: Knowledge of differences in mild traumatic brain injury (mTBI) recovery by sex and age may inform individualized treatment of these patients. Objective: To identify sex-related differences in symptom recovery from mTBI; secondarily, to explore age differences within women, who demonstrate poorer outcomes after TBI. Design, Setting, and Participants: The prospective cohort study Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) recruited 2000 patients with mTBI from February 26, 2014, to July 3, 2018, and 299 patients with orthopedic trauma (who served as controls) from January 26, 2016, to July 27, 2018. Patients were recruited from 18 level I trauma centers and followed up for 12 months. Data were analyzed from August 19, 2020, to March 3, 2021. Exposures: Patients with mTBI (defined by a Glasgow Coma Scale score of 13-15) triaged to head computed tomography in 24 hours or less; patients with orthopedic trauma served as controls. Main Outcomes and Measures: Measured outcomes included (1) the Rivermead Post Concussion Symptoms Questionnaire (RPQ), a 16-item self-report scale that assesses postconcussion symptom severity over the past 7 days relative to preinjury; (2) the Posttraumatic Stress Disorder Checklist for the Diagnostic and Statistical Manual of Mental Disorders (Fifth Edition) (PCL-5), a 20-item test that measures the severity of posttraumatic stress disorder symptoms; (3) the Patient Health Questionnaire-9 (PHQ-9), a 9-item scale that measures depression based on symptom frequency over the past 2 weeks; and (4) the Brief Symptom Inventory-18 (BSI-18), an 18-item scale of psychological distress (split into Depression and Anxiety subscales). Results: A total of 2000 patients with mTBI (1331 men [67%; mean (SD) age, 41.0 (17.3) years; 1026 White (78%)] and 669 women [33%; mean (SD) age, 43.0 (18.5) years; 505 (76%) White]). After adjustment of multiple comparisons, significant TBI × sex interactions were observed for cognitive symptoms (B = 0.76; 5% false discovery rate-corrected P = .02) and somatic RPQ symptoms (B = 0.80; 5% false discovery rate-corrected P = .02), with worse symptoms in women with mTBI than men, but no sex difference in symptoms in control patients with orthopedic trauma. Within the female patients evaluated, there was a significant TBI × age interaction for somatic RPQ symptoms, which were worse in female patients with mTBI aged 35 to 49 years compared with those aged 17 to 34 years (B = 1.65; P = .02) or older than 50 years (B = 1.66; P = .02). Conclusions and Relevance: This study found that women were more vulnerable than men to persistent mTBI-related cognitive and somatic symptoms, whereas no sex difference in symptom burden was seen after orthopedic injury. Postconcussion symptoms were also worse in women aged 35 to 49 years than in younger and older women, but further investigation is needed to corroborate these findings and to identify the mechanisms involved. Results suggest that individualized clinical management of mTBI should consider sex and age, as some women are especially predisposed to chronic postconcussion symptoms even 12 months after injury.

Latent Profile Analysis of Neuropsychiatric Symptoms and Cognitive Function of Adults 2 Weeks After Traumatic Brain Injury: Findings From the TRACK-TBI Study.

Importance: Heterogeneity across patients with traumatic brain injury (TBI) presents challenges for clinical care and intervention design. Identifying distinct clinical phenotypes of TBI soon after injury may inform patient selection for precision medicine clinical trials. Objective: To investigate whether distinct neurobehavioral phenotypes can be identified 2 weeks after TBI and to characterize the degree to which early neurobehavioral phenotypes are associated with 6-month outcomes. Design, Setting, and Participants: This prospective cohort study included patients presenting to 18 US level 1 trauma centers within 24 hours of TBI from 2014 to 2019 as part of the Transforming Research and Clinical Knowledge in TBI (TRACK-TBI) study. Data were analyzed from January 28, 2020, to January 11, 2021. Exposures: TBI. Main Outcomes and Measures: Latent profiles (LPs) were derived from common dimensions of neurobehavioral functioning at 2 weeks after injury, assessed through National Institutes of Health TBI Common Data Elements (ie, Brief Symptom Inventory-18, Patient Health Questionnaire-9 Depression checklist, Posttraumatic Stress Disorder Checklist for DSM-5, PROMIS Pain Intensity scale, Insomnia Severity Index, Rey Auditory Verbal Learning Test, Wechsler Adult Intelligence Scale-Fourth Edition Coding and Symbol Search subtests, Trail Making Test, and NIH Toolbox Cognitive Battery Pattern Comparison Processing Speed, Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, and Picture Sequence Memory subtests). Six-month outcomes were the Satisfaction With Life Scale (SWLS), Quality of Life after Brain Injury-Overall Scale (QOLIBRI-OS), Glasgow Outcome Scale-Extended (GOSE), and Rivermead Post-Concussion Symptoms Questionnaire (RPQ). Results: Among 1757 patients with TBI included, 1184 (67.4%) were men, and the mean (SD) age was 39.9 (17.0) years. LP analysis revealed 4 distinct neurobehavioral phenotypes at 2 weeks after injury: emotionally resilient (419 individuals [23.8%]), cognitively impaired (368 individuals [20.9%]), cognitively resilient (620 individuals [35.3%]), and neuropsychiatrically distressed (with cognitive weaknesses; 350 individuals [19.9%]). Adding LP group to models including demographic characteristics, medical history, Glasgow Coma Scale score, and other injury characteristics was associated with significantly improved estimation of association with 6-month outcome (GOSE R2 increase = 0.09-0.19; SWLS R2 increase = 0.12-0.22; QOLIBRI-OS R2 increase = 0.14-0.32; RPQ R2 = 0.13-0.34). Conclusions and Relevance: In this cohort study of patients with TBI presenting to US level-1 trauma centers, qualitatively distinct profiles of symptoms and cognitive functioning were identified at 2 weeks after TBI. These distinct phenotypes may help optimize clinical decision-making regarding prognosis, as well as selection and stratification for randomized clinical trials.

COVID-19's Limited Impact on Drug Shortages in Canada.

Using data from the Drug Shortages Canada website, we ask whether the first months of the coronavirus disease 2019 (COVID-19) pandemic were associated with a significant increase in drug shortages in Canada. We find an increase of 147 shortages (32 percent) reported by manufacturers during March and April 2020 relative to the same months in previous years. The upsurge was concentrated during the two-week period from 25 March to 7 April 2020, after which report counts returned to usual levels. Excess reports cite both supply-side and demand-side causes for shortages. Increases were noted in therapeutic classes associated with COVID-19 care.

Analysant les données du site Web Pénuries de médicaments Canada, l'auteur se demande si les premiers mois de la pandémie causée par le coronavirus 2019 (COVID­19) ont été associés à une hausse importante des pénuries de médicaments au Canada. La hausse qu'il observe dans le nombre de pénuries signalées par les fabricants au cours des mois de mars et avril 2020, par rapport aux mêmes mois des années précédentes, s'établit à 147 (soit 32 pour cent). Cette hausse est concentrée dans la période de deux semaines se situant entre le 25 mars et le 7 avril 2020, après quoi le nombre des pénuries signalées revient aux niveaux habituels. Cette disproportion des pénuries signalées est attribuable à des causes liées tant à l'offre qu'à la demande. Des hausses sont constatées dans les classes thérapeutiques associées aux soins exigés par la COVID­19.

Recovery After Mild Traumatic Brain Injury in Patients Presenting to US Level I Trauma Centers: A Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) Study.

IMPORTANCE: Most traumatic brain injuries (TBIs) are classified as mild (mTBI) based on admission Glasgow Coma Scale (GCS) scores of 13 to 15. The prevalence of persistent functional limitations for these patients is unclear. OBJECTIVES: To characterize the natural history of recovery of daily function following mTBI vs peripheral orthopedic traumatic injury in the first 12 months postinjury using data from the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study, and, using clinical computed tomographic (CT) scans, examine whether the presence (CT+) or absence (CT-) of acute intracranial findings in the mTBI group was associated with outcomes. DESIGN, SETTING, AND PARTICIPANTS: TRACK-TBI, a cohort study of patients with mTBI presenting to US level I trauma centers, enrolled patients from February 26, 2014, to August 8, 2018, and followed up for 12 months. A total of 1453 patients at 11 level I trauma center emergency departments or inpatient units met inclusion criteria (ie, mTBI [n = 1154] or peripheral orthopedic traumatic injury [n = 299]) and were enrolled within 24 hours of injury; mTBI participants had admission GCS scores of 13 to 15 and clinical head CT scans. Patients with peripheral orthopedic trauma injury served as the control (OTC) group. EXPOSURES: Participants with mTBI or OTC. MAIN OUTCOMES AND MEASURES: The Glasgow Outcome Scale Extended (GOSE) scale score, reflecting injury-related functional limitations across broad life domains at 2 weeks and 3, 6, and 12 months postinjury was the primary outcome. The possible score range of the GOSE score is 1 (dead) to 8 (upper good recovery), with a score less than 8 indicating some degree of functional impairment. RESULTS: Of the 1453 participants, 953 (65.6%) were men; mean (SD) age was 40.9 (17.1) years in the mTBI group and 40.9 (15.4) years in the OTC group. Most participants (mTBI, 87%; OTC, 93%) reported functional limitations (GOSE <8) at 2 weeks postinjury. At 12 months, the percentage of mTBI participants reporting functional limitations was 53% (95% CI, 49%-56%) vs 38% (95% CI, 30%-45%) for OTCs. A higher percentage of CT+ patients reported impairment (61%) compared with the mTBI CT- group (49%; relative risk [RR], 1.24; 95% CI, 1.08-1.43) and a higher percentage in the mTBI CT-group compared with the OTC group (RR, 1.28; 95% CI, 1.02-1.60). CONCLUSIONS AND RELEVANCE: Most patients with mTBI presenting to US level I trauma centers report persistent, injury-related life difficulties at 1 year postinjury, suggesting the need for more systematic follow-up of patients with mTBI to provide treatments and reduce the risk of chronic problems after mTBI.

Risk of Posttraumatic Stress Disorder and Major Depression in Civilian Patients After Mild Traumatic Brain Injury: A TRACK-TBI Study.

Importance: Traumatic brain injury (TBI) has been associated with adverse mental health outcomes, such as posttraumatic stress disorder (PTSD) and major depressive disorder (MDD), but little is known about factors that modify risk for these psychiatric sequelae, particularly in the civilian sector. Objective: To ascertain prevalence of and risk factors for PTSD and MDD among patients evaluated in the emergency department for mild TBI (mTBI). Design, Setting, and Participants: Prospective longitudinal cohort study (February 2014 to May 2018). Posttraumatic stress disorder and MDD symptoms were assessed using the PTSD Checklist for DSM-5 and the Patient Health Questionnaire-9 Item. Risk factors evaluated included preinjury and injury characteristics. Propensity score weights-adjusted multivariable logistic regression models were performed to assess associations with PTSD and MDD. A total of 1155 patients with mTBI (Glasgow Coma Scale score, 13-15) and 230 patients with nonhead orthopedic trauma injuries 17 years and older seen in 11 US hospitals with level 1 trauma centers were included in this study. Main Outcomes and Measures: Probable PTSD (PTSD Checklist for DSM-5 score, ≥33) and MDD (Patient Health Questionnaire-9 Item score, ≥15) at 3, 6, and 12 months postinjury. Results: Participants were 1155 patients (752 men [65.1%]; mean [SD] age, 40.5 [17.2] years) with mTBI and 230 patients (155 men [67.4%]; mean [SD] age, 40.4 [15.6] years) with nonhead orthopedic trauma injuries. Weights-adjusted prevalence of PTSD and/or MDD in the mTBI vs orthopedic trauma comparison groups at 3 months was 20.0% (SE, 1.4%) vs 8.7% (SE, 2.2%) (P < .001) and at 6 months was 21.2% (SE, 1.5%) vs 12.1% (SE, 3.2%) (P = .03). Risk factors for probable PTSD at 6 months after mTBI included less education (adjusted odds ratio, 0.89; 95% CI, 0.82-0.97 per year), being black (adjusted odds ratio, 5.11; 95% CI, 2.89-9.05), self-reported psychiatric history (adjusted odds ratio, 3.57; 95% CI, 2.09-6.09), and injury resulting from assault or other violence (adjusted odds ratio, 3.43; 95% CI, 1.56-7.54). Risk factors for probable MDD after mTBI were similar with the exception that cause of injury was not associated with increased risk. Conclusions and Relevance: After mTBI, some individuals, on the basis of education, race/ethnicity, history of mental health problems, and cause of injury were at substantially increased risk of PTSD and/or MDD. These findings should influence recognition of at-risk individuals and inform efforts at surveillance, follow-up, and intervention.

Lifetime Consequences of Early-Life and Midlife Access to Health Insurance: A Review.

Over the past decade, the number of studies examining the effects of health insurance has grown rapidly, along with the breadth of outcomes considered. In light of growing research in this area and the intense policy focus on coverage expansions in the United States, there is need for an up-to-date and comprehensive literature review and synthesis of lessons learned. We reviewed 112 experimental or quasi-experimental studies on the effects of health insurance prior to people becoming eligible for Medicare on a broad set of outcomes. Over the past decade, evidence related to the effect of increased access to health insurance has strengthened, illuminating that children and vulnerable adults are most likely to see health and economic benefits. We identified promising areas for future study in this active and burgeoning research area, noting benefit design of health insurance and outcomes such as government program participation and self-reported health status as targets.

Assessment of Follow-up Care After Emergency Department Presentation for Mild Traumatic Brain Injury and Concussion: Results From the TRACK-TBI Study.

Importance: Mild traumatic brain injury (mTBI) affects millions of Americans each year. Lack of consistent clinical practice raises concern that many patients with mTBI may not receive adequate follow-up care. Objective: To characterize the provision of follow-up care to patients with mTBI during the first 3 months after injury. Design, Setting, and Participants: This cohort study used data on patients with mTBI enrolled in the Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study between February 26, 2014, and August 25, 2016. We examined site-specific variations in follow-up care, the types of clinicians seen by patients receiving follow-up care, and patient and injury characteristics associated with a higher likelihood of receiving follow-up care. The TRACK-TBI study is a prospective, multicenter, longitudinal observational study of patients with TBI presenting to the emergency department of 1 of 11 level I US trauma centers. Study data included patients with head trauma who underwent a computed tomography (CT) scan within 24 hours of injury, had a Glasgow Coma Scale score of 13 to 15, were aged 17 years or older, and completed follow-up care surveys at 2 weeks and 3 months after injury (N = 831). Main Outcomes and Measures: Follow-up care was defined as hospitals providing TBI educational material at discharge, hospitals calling patients to follow up, and patients seeing a physician or other medical practitioner within 3 months after the injury. Unfavorable outcomes were assessed with the Rivermead Post Concussion Symptoms Questionnaire. Results: Of 831 patients (289 [35%] female; 483 [58%] non-Hispanic white; mean [SD] age, 40.3 [16.9] years), less than half self-reported receiving TBI educational material at discharge (353 patients [42%]) or seeing a physician or other health care practitioner within 3 months after injury (367 patients [44%]). Follow-up care varied by study site; adjusting for patient characteristics, the provision of educational material varied from 19% to 72% across sites. Of 236 patients with a positive finding on a CT scan, 92 (39%) had not seen a medical practitioner 3 months after the injury. Adjusting for injury severity and demographics, patient admission to the hospital ward or intensive care unit, patient income, and insurance status were not associated with the probability of seeing a medical practitioner. Among the patients with 3 or more moderate to severe postconcussive symptoms, only 145 of 279 (52%) reported having seen a medical practitioner by 3 months. Conclusions and Relevance: There are gaps in follow-up care for patients with mTBI after hospital discharge, even those with a positive finding on CT or who continue to experience postconcussive symptoms.

PCSK9 Inhibitors Show Value for Patients and the US Health Care System.

BACKGROUND: Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors were approved by the US Food and Drug Administration (FDA) as cholesterol-lowering therapies for patients with familial hypercholesterolemia or atherosclerotic cardiovascular disease. OBJECTIVES: To estimate the long-term health and economic value of PCSK9 inhibitors for Americans (51 years and older). METHODS: We conducted simulations using the Future Elderly Model, an established dynamic microsimulation model to project the lifetime outcomes for the US population aged 51 years and older. Health effects estimates and confidence intervals from published meta-analysis studies were used to project changes in life expectancy, quality-adjusted life-years, and lifetime medical spending resulting from the use of PCSK9 inhibitors. We considered two treatment scenarios: 1) current FDA eligibility and 2) an extended eligibility scenario that includes patients with no pre-existing cardiovascular disease but at high risk. We assumed that the price of PCSK9 inhibitors was discounted by 35% in the first 12 years and by 57% thereafter, with gradual uptake of the drug in eligible populations. RESULTS: Use of PCSK9 inhibitors by individuals covered by current FDA approval would extend life expectancy at the age of 51 years by an estimated 1.1 years and would yield a lifetime net value of $5800 per person. If use was extended to those at high risk for cardiovascular disease, PCSK9 inhibitors would generate a lifetime net benefit of $14,100 per person. CONCLUSIONS: Expanded access to PCSK9 inhibitors would offer positive long-term net value for patients and the US health care system at the current discounted prices.

Using Self-reports or Claims to Assess Disease Prevalence: It's Complicated.

BACKGROUND: Two common ways of measuring disease prevalence include: (1) using self-reported disease diagnosis from survey responses; and (2) using disease-specific diagnosis codes found in administrative data. Because they do not suffer from self-report biases, claims are often assumed to be more objective. However, it is not clear that claims always produce better prevalence estimates. OBJECTIVE: Conduct an assessment of discrepancies between self-report and claims-based measures for 2 diseases in the US elderly to investigate definition, selection, and measurement error issues which may help explain divergence between claims and self-report estimates of prevalence. DATA: Self-reported data from 3 sources are included: the Health and Retirement Study, the Medicare Current Beneficiary Survey, and the National Health and Nutrition Examination Survey. Claims-based disease measurements are provided from Medicare claims linked to Health and Retirement Study and Medicare Current Beneficiary Survey participants, comprehensive claims data from a 20% random sample of Medicare enrollees, and private health insurance claims from Humana Inc. METHODS: Prevalence of diagnosed disease in the US elderly are computed and compared across sources. Two medical conditions are considered: diabetes and heart attack. RESULTS: Comparisons of diagnosed diabetes and heart attack prevalence show similar trends by source, but claims differ from self-reports with regard to levels. Selection into insurance plans, disease definitions, and the reference period used by algorithms are identified as sources contributing to differences. CONCLUSIONS: Claims and self-reports both have strengths and weaknesses, which researchers need to consider when interpreting estimates of prevalence from these 2 sources.

The Long-Term Benefits of Increased Aspirin Use by At-Risk Americans Aged 50 and Older.

BACKGROUND: The usefulness of aspirin to defend against cardiovascular disease in both primary and secondary settings is well recognized by the medical profession. Multiple studies also have found that daily aspirin significantly reduces cancer incidence and mortality. Despite these proven health benefits, aspirin use remains low among populations targeted by cardiovascular prevention guidelines. This article seeks to determine the long-term economic and population-health impact of broader use of aspirin by older Americans at higher risk for cardiovascular disease. METHODS AND FINDINGS: We employ the Future Elderly Model, a dynamic microsimulation that follows Americans aged 50 and older, to project their lifetime health and spending under the status quo and in various scenarios of expanded aspirin use. The model is based primarily on data from the Health and Retirement Study, a large, representative, national survey that has been ongoing for more than two decades. Outcomes are chosen to provide a broad perspective of the individual and societal impacts of the interventions and include: heart disease, stroke, cancer, life expectancy, quality-adjusted life expectancy, disability-free life expectancy, and medical costs. Eligibility for increased aspirin use in simulations is based on the 2011-2012 questionnaire on preventive aspirin use of the National Health and Nutrition Examination Survey. These data reveal a large unmet need for daily aspirin, with over 40% of men and 10% of women aged 50 to 79 presenting high cardiovascular risk but not taking aspirin. We estimate that increased use by high-risk older Americans would improve national life expectancy at age 50 by 0.28 years (95% CI 0.08-0.50) and would add 900,000 people (95% CI 300,000-1,400,000) to the American population by 2036. After valuing the quality-adjusted life-years appropriately, Americans could expect $692 billion (95% CI 345-975) in net health benefits over that period. CONCLUSIONS: Expanded use of aspirin by older Americans with elevated risk of cardiovascular disease could generate substantial population health benefits over the next twenty years and do so very cost-effectively.