Implementation of AZD7442 (Tixagevimab/Cilgavimab) COVID-19 Pre-exposure Prophylaxis (PrEP) in the Largest Health Maintenance Organization in Israel: Real-world Uptake and Sociodemographic and Clinical Characteristics Across Immunocompromised Patient Groups.

INTRODUCTION: AZD7442 is a combination of two neutralizing antibodies (tixagevimab/cilgavimab) with demonstrated efficacy in reducing the risk of symptomatic coronavirus disease 2019 (COVID-19) among individuals at high risk of severe COVID-19 ≤ 6 months after administration. On February 15, 2022, the Israeli Ministry of Health (IMoH) authorized the administration of 300 mg AZD7442 as pre-exposure prophylaxis (PrEP) against severe acute respiratory syndrome coronavirus 2 infection among immunocompromised individuals aged ≥ 12 years. This study describes the real-world uptake of AZD7442 in Israel. METHODS: This descriptive, observational study analyzed data from Israel's largest health maintenance organization, Clalit Health Services (CHS). Individuals were assessed for AZD7442 eligibility between February 13 and December 11, 2022, and were included if they were aged ≥ 12 years, had ≥ 1 year of continuous CHS membership, had ≥ 1 moderate or severe immunocompromising condition, and were eligible for AZD7442 per IMoH recommendations during this time frame. RESULTS: Overall, 19,161 AZD7442-eligible individuals with immunocompromising conditions were identified during the study period; 2829 (14.8%) received AZD7442. A higher proportion of individuals receiving AZD7442 were older (aged ≥ 65 years), male, not current smokers and residents in large cities; required more physician visits (> 50 visits); and had ≥ 1 COVID-19 hospitalization over 12 months, while uptake was lowest among ultra-orthodox Jewish individuals. AZD7442 uptake was also higher among individuals with multiple comorbidities (Charlson Comorbidity Index ≥ 5), including hypertension, diabetes and chronic kidney disease. In specific immunocompromised types, AZD7442 uptake was highest among individuals with lung transplantation (41%), primary immunodeficiency (32%), bone marrow transplantation (29%) and multiple myeloma (25%) or those receiving anti-CD20 therapy (26%) and was lowest in individuals with lymphoma (8%). CONCLUSION: These results show AZD7442 uptake among the eligible population of Israel in 2022 was relatively low, at 14.8%. Uptake was generally higher among immunocompromised individuals who may be perceived to be frail or at highest risk of COVID-19 infection and complications, although at 25-41%, further improvements in uptake would be more impactful. These results also indicate there is opportunity to expand AZD7442 uptake across immunocompromised groups and ensure more equitable uptake among some other sociodemographic groups. Overall, this study will help inform and reassess future implementation strategies for vulnerable populations.

Trends in Telerehabilitation Utilization in the United States 2020-2021.

OBJECTIVE: To examine telerehabilitation utilization in the United States (US) during the first 2 years of the pandemic. DESIGN: We performed a retrospective analysis of outpatient insurance claims from the IBM MarketScan Commercial Claims and Encounters Database to identify the number and proportion of patients using telerehabilitation from 2020 to 2021. Telerehabilitation was identified based on the presence of specific code modifiers and place of service. SETTING: Retrospective claims analysis. PARTICIPANTS: Individuals living in the United States with employer-sponsored insurance plans using outpatient physical or occupational therapy (PT/OT) (N=2,007,524). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Number and proportion of outpatient PT/OT visits completed via telerehabilitation. RESULTS: We identified 21,026,608 PT/OT visits among 2,007,524 patients. Overall, 49,974 (2.5%) patients received ≥1 telerehabilitation visit during the specified timeframe. We observed trends in utilization over time, with utilization peaking in April 2020 when 10.9% of all PT/OT visits were conducted by telerehabilitation. We also observed geographic trends with lower rates of utilization identified in rural areas. State-by-state utilization rates ranged from 10.4% (California) to 0.3% (Wyoming). CONCLUSION: Telerehabilitation may be underutilized as a means of improving access to PT/OT, especially in rural areas of the country. Further research is needed to examine contributing factors to low observed utilization rates, such as provider and patient perceptions of telerehabilitation.

Effect of Aspirin Versus Low-Molecular-Weight Heparin Thromboprophylaxis on Medication Satisfaction and Out-of-Pocket Costs: A Secondary Analysis of a Randomized Clinical Trial.

BACKGROUND: Current guidelines recommend low-molecular-weight heparin for thromboprophylaxis after orthopaedic trauma. However, recent evidence suggests that aspirin is similar in efficacy and safety. To understand patients' experiences with these medications, we compared patients' satisfaction and out-of-pocket costs after thromboprophylaxis with aspirin versus low-molecular-weight heparin. METHODS: This study was a secondary analysis of the PREVENTion of CLots in Orthopaedic Trauma (PREVENT CLOT) trial, conducted at 21 trauma centers in the U.S. and Canada. We included adult patients with an operatively treated extremity fracture or a pelvic or acetabular fracture. Patients were randomly assigned to receive 30 mg of low-molecular-weight heparin (enoxaparin) twice daily or 81 mg of aspirin twice daily for thromboprophylaxis. The duration of the thromboprophylaxis, including post-discharge prescription, was based on hospital protocols. The study outcomes included patient satisfaction with and out-of-pocket costs for their thromboprophylactic medication measured on ordinal scales. RESULTS: The trial enrolled 12,211 patients (mean age and standard deviation [SD], 45 ± 18 years; 62% male), 9725 of whom completed the question regarding their satisfaction with the medication and 6723 of whom reported their out-of-pocket costs. The odds of greater satisfaction were 2.6 times higher for patients assigned to aspirin than those assigned to low-molecular-weight heparin (odds ratio [OR]: 2.59; 95% confidence interval [CI]: 2.39 to 2.80; p < 0.001). Overall, the odds of incurring any out-of-pocket costs for thromboprophylaxis medication were 51% higher for patients assigned to aspirin compared with low-molecular-weight heparin (OR: 1.51; 95% CI: 1.37 to 1.66; p < 0.001). However, patients assigned to aspirin had substantially lower odds of out-of-pocket costs of at least $25 (OR: 0.15; 95% CI: 0.12 to 0.18; p < 0.001). CONCLUSIONS: Use of aspirin substantially improved patients' satisfaction with their medication after orthopaedic trauma. While aspirin use increased the odds of incurring any out-of-pocket costs, it protected against costs of ≥$25, potentially improving health equity for thromboprophylaxis. LEVEL OF EVIDENCE: Therapeutic Level II . See Instructions for Authors for a complete description of levels of evidence.

Lumbar Decompression With and Without Fusion for Lumbar Stenosis With Spondylolisthesis: A Cost Utility Analysis.

STUDY DESIGN: Markov model. OBJECTIVE: To compare the cost-effectiveness of lumbar decompression alone (DA) with lumbar decompression with fusion (DF) for the management of adults undergoing surgery for lumbar stenosis with associated degenerative spondylolisthesis. SUMMARY OF BACKGROUND DATA: Rates of lumbar fusion have increased for all indications in the United States over the last 20 years. Recent randomized controlled trial data, however, have suggested comparable functional outcomes and lower reoperation rates for lumbar decompression and fusion as compared with DA in the treatment of lumbar stenosis with degenerative spondylolisthesis. MATERIALS AND METHODS: A multistate Markov model was constructed from the US payer perspective of a hypothetical cohort of patients with lumbar stenosis with associated spondylolisthesis requiring surgery. Data regarding clinical improvement, costs, and reoperation were generated from contemporary randomized trial evidence, meta-analyses of recent prospective studies, and large retrospective cohorts. Base case, one-way sensitivity analysis, and probabilistic sensitivity analyses were conducted, and the results were compared with a WTP threshold of $100,000 (in 2022 USD) over a two-year time horizon. A discount rate of 3% was utilized. RESULTS: The incremental cost and utility of DF relative to DA were $12,778 and 0.00529 aggregated quality adjusted life years. The corresponding incremental cost-effectiveness ratio of $2,416,281 far exceeded the willingness to pay threshold of $100,000. In sensitivity analysis, the results varied the most with respect to rate of improvement after DA, rate of improvement after lumbar decompression and fusion, and odds ratio of reoperation between the two groups. Zero percent of one-way and probabilistic sensitivity analyses achieved cost-effectiveness at the willingness-to-pay threshold. CONCLUSIONS: Within the context of contemporary surgical data, DF is not cost-effective compared with DA in the surgical management of lumbar stenosis with associated spondylolisthesis over a two-year time horizon.

Cost of U.S emergency department and inpatient visits for fall injuries in older adults.

BACKGROUND: Falls are a leading cause of injury and hospital readmissions in older adults. Understanding the distribution of acute treatment costs across inpatient and emergency department settings is critical for informed investment and evaluation of fall prevention efforts. METHODS: This study used the 2016-2018 National Inpatient Sample and National Emergency Department Sample. Annual treatment cost of fall injury among adults 65 years and older was estimated from charges, applying cost-to-charge and professional fee ratios. Weighted multivariable generalized linear models were used to separately estimate cost for inpatient and emergency department (ED) setting by injury type and individual demographic and health characteristics after adjusting for payer and hospital level characteristics. RESULTS: Older adults incurred an estimated 922,428 inpatient and 2.3 million ED visits annually due to falls with combined annual costs of $19.8 billion. Over half of inpatient visits for fall injury were for fracture. Notably, 23% of inpatient visits were for fractures other than hip fracture and 14% of inpatient visits were for multiple fractures with costs totaling $3.4 billion and $2.5 billion, respectively. Annual ED costs were driven by superficial injury totaling $1.5 billion. Cost of ED visits were higher for adults 85 years and older (adjusted cost ratio (aCR): 1.11, 95% Confidence Interval (CI)I: 1.11-1.12) and those with dementia (aCR: 1.14, 95% CI: 1.13-1.15). Higher inpatient and ED visit cost was also associated with high-energy falls and discharge to post-acute care. CONCLUSION: The study found that more than 3 million older adults in the United States seek hospital care for fall injuries annually, a major concern given increasing capacity strain on hospitals and EDs. The $20 billion in annual acute treatment costs attributed to fall injury indicate an urgent need to implement evidence-based fall prevention interventions and underscores the importance of newly launched ED-based fall prevention efforts and investments in geriatric emergency departments.

Cost-Effectiveness Analysis of Trastuzumab Deruxtecan Versus Trastuzumab Emtansine for Patients With Human Epidermal Growth Factor Receptor 2 Positive Metastatic Breast Cancer in the United States.

OBJECTIVES: To assess the cost-effectiveness of trastuzumab deruxtecan compared with trastuzumab emtansine as second-line therapy for patients with human epidermal growth factor receptor 2 positive metastatic breast cancer from a US healthcare sector perspective. METHODS: A 3-state partitioned survival model was developed to estimate the cost-effectiveness of trastuzumab deruxtecan compared with trastuzumab emtansine. For both treatments, modeled patients were administered treatment intravenously every 3 weeks indefinitely or until disease progression. Transition parameters were principally derived from the updated DESTINY-Breast03 phase III randomized clinical trial. Costs include drug costs extracted from Centers for Medicare and Medicaid Services average sales price and administrative, adverse event, and third-line therapy costs derived from published literature, measured in 2022 US dollars. Health utilities for health states and disutilities for adverse events were sourced from published literature. Effects were measured in quality-adjusted life years (QALYs). We conducted both probabilistic sensitivity analysis and comprehensive scenario analysis to test model assumptions and robustness, while utilizing a lifetime horizon. RESULTS: In our base-case analysis, total costs for trastuzumab deruxtecan were $1 266 945, compared with $820 082 for trastuzumab emtansine. Total QALYs for trastuzumab deruxtecan were 5.09, compared with 3.15 for trastuzumab emtansine. The base-case incremental cost-effectiveness ratio was $230 285/QALY. Probabilistic sensitivity analysis indicated that trastuzumab deruxtecan had an 11.1% probability of being cost-effective at a $100 000 per QALY willingness-to-pay threshold. CONCLUSIONS: Despite the higher efficacy of trastuzumab deruxtecan in patients with human epidermal growth factor receptor 2 positive metastatic breast cancer, our findings raise concern regarding its value at current prices.

Work Productivity Loss After Minimally Displaced Complete Lateral Compression Pelvis Fractures.

OBJECTIVE: To quantify work impairment and economic losses due to lost employment, lost work time (absenteeism), and lost productivity while working (presenteeism) after a lateral compression pelvic ring fracture. Secondarily, productivity loss of patients treated with surgical fixation versus nonoperative management was compared. DESIGN: Secondary analysis of a prospective, multicenter trial. SETTING: Two level I academic trauma centers. PATIENT SELECTION CRITERIA: Adult patients with a lateral compression pelvic fracture (OTA/AO 61-B1/B2) with a complete posterior pelvic ring fracture and less than 10 mm of initial displacement. Excluded were patients who were not working or non-ambulatory before their pelvis fracture or who had a concomitant spinal cord injury. OUTCOME MEASURES AND COMPARISONS: Work impairment, including hours lost to unemployment, absenteeism, and presenteeism, measured by Work Productivity and Activity Impairment assessments in the year after injury. Results after non-operative and operative treatment were compared. RESULTS: Of the 64 included patients, forty-seven percent (30/64) were treated with surgical fixation, and 53% (30/64) with nonoperative management. 63% returned to work within 1 year of injury. Workers lost an average of 67% of a 2080-hour average work year, corresponding with $56,276 in lost economic productivity. Of the 1395 total hours lost, 87% was due to unemployment, 3% to absenteeism, and 10% to presenteeism. Surgical fixation was associated with 27% fewer lost hours (1155 vs. 1583, P = 0.005) and prevented $17,266 in average lost economic productivity per patient compared with nonoperative management. CONCLUSIONS: Lateral compression pelvic fractures are associated with a substantial economic impact on patients and society. Surgical fixation reduces work impairment and the corresponding economic burden. LEVEL OF EVIDENCE: Economic Level IV. See Instructions for Authors for a complete description of levels of evidence.

Estimated Savings From Using Added Therapeutic Benefit and Therapeutic Reference Pricing in United States Medicare Drug Price Negotiations.

OBJECTIVES: US Medicare will begin negotiating prices for top-selling drugs in 2023. This study describes and estimates potential savings from a therapeutic reference pricing approach, linking comparative effectiveness with the costs of existing therapeutic alternatives, that Medicare could use to adjust the starting point for price negotiations. METHODS: First, we identified target drugs likely to be selected for Medicare negotiation. Second, we identified comparative effectiveness ratings for target drugs based on French Haute Autorité de Santé reports. For target drugs with minor or no added benefit, we identified therapeutic alternatives based on the French reports and US clinical guidelines. For each target drug with minor or no added benefit, we computed the difference between spending based on the drug's estimated statutory ceiling price and spending based on the weighted average cost of therapeutic alternatives or the lowest cost therapeutic alternative. Finally, we calculated potential annual savings from using a starting point in negotiations based on costs of therapeutic alternatives. RESULTS: Potential drug-level savings to Medicare from using a starting point in negotiations based on average spending across therapeutic alternatives, compared with using the statutory ceiling price alone, ranged from $186 541 340 to $2 173 441 197. Potential savings from using a starting point based on the lowest cost alternative ranged from $199 872 163 to $3 605 904 765. CONCLUSIONS: Although we do not expect Medicare to rely on French comparative effectiveness assessments, this study demonstrates the potential for additional savings when using comparative effectiveness and costs of therapeutic alternatives to inform the starting price for negotiations.

Mediators of change in online mindfulness-based cognitive therapy: A secondary analysis of a randomized trial of mindful mood balance.

OBJECTIVE: Digital delivery of mindfulness-based cognitive therapy through the Mindful Mood Balance (MMB) program is clinically effective (Segal et al., 2020); however, the mechanisms through which this program delivers its benefits have not been established. METHOD: This study investigates the differential impact of the MMB program paired with usual depression care (UDC) compared to UDC alone on the putative targets of self-reported mindfulness, decentering, and rumination and the extent to which change in these targets mediates subsequent depressive relapse among a sample of predominantly White, female participants, with residual depressive symptoms. RESULTS: The MMB program relative to UDC was associated with a significantly greater rate of change in decentering (t = 4.94, p < .0001, d = 0.46), mindfulness (t = 6.04, p < .0001, d = 0.56), and rumination (t = 3.82, p < .0001, d = 0.36). Subsequent depressive relapse also was mediated by prior change in these putative targets, with a significant natural indirect effect for decentering, χ2(1) = 7.25, p < .008, OR = 0.57; mindfulness, χ2(1) = 9.99, p < .002, OR = 0.50; and rumination, χ2(1) = 12.95, p < .001, OR = 0.35. CONCLUSIONS: These findings suggest the mechanisms of MMB are consistent with the conceptual model for mindfulness-based cognitive therapy and depressive relapse risk and that such processes can be modified through digital delivery. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Comparison of Price Index Methods and Drug Price Inflation Estimates for Hepatitis C Virus Medications.

Importance: Measuring drug price inflation is challenging because new drugs continually enter the market, some drugs transition from branded to generic, and current inflation indexes do not account for these market basket changes. Instead, they measure the price increases after new drugs have been launched. Therefore, the public pays the higher costs of newer and usually more expensive drugs, but the inflation indexes do not reflect the increases over existing drugs previously used to treat the same conditions. Objective: To assess how price index methods can affect estimates of drug price inflation using a case study of hepatitis C virus (HCV) medication and to explore other approaches for constructing a price index. Design, Setting, and Participants: This cross-sectional study used data from outpatient pharmacies to compile a list of all HCV medications that were ever on the market (brand and generic) from 2013 to 2020. Using National Drug Codes of HCV drugs, a 20% nationally representative sample of Medicare Part D claims from 2013 to 2020 was queried. Alternative drug price indexes, including product-level vs class-level product and quantity definitions were developed in which gross vs net price definitions were used and an adjustment was created and applied to capture treatment duration because newer drugs often required a shorter duration. Main Outcomes and Measures: Price index value and rate of inflation from 2013 to 2020 for each methodologic approach to constructing a drug pricing index. Results: In all, 27 different HCV drug regimens were identified in Medicare Part D claims in 2013 to 2020. A product-level approach for measuring inflation estimated a 10% gross drug price increase from 2013 to 2020 for HCV drugs, whereas a class-level approach including the higher prices of the new drugs showed a 31% gross price increase. After adjusting for manufacturer rebates to estimate net prices, the findings showed that HCV drug prices fell by 31% from 2013 to 2020. Conclusions and Relevance: The findings of this cross-sectional study indicate that the current product-level methods to estimate drug price inflation underestimated price increases for HCV drugs by failing to include the high launch prices of new market entrants. Using a class-level approach, the index captured higher spending on new products at launch. Prescription-level analyses, which did not consider shorter durations of treatment, overestimated price increases.

The cost burden of hospital-treated tap water scald burns in the United States.

OBJECTIVE: We aimed to determine the cost burden and epidemiology of hospital-treated, tap water scald burns in the United States to inform consideration of policy proposals to require thermostatic mixing valves with all new water heaters. METHODS: A retrospective, cross-sectional study was performed using the 2016-2018 National Inpatient Sample (NIS) and Nationwide Emergency Department Sample (NEDS) from the Healthcare Cost and Utilisation Project (HCUP). We queried the samples to examine the prevalence, cost, and epidemiology of hospital-treated, tap water scald burns. RESULTS: The NIS and NEDS identified 52 088 (weighted) emergency department (ED) visits, 7270 (weighted) hospitalisations and 110 hospital-based deaths attributable to tap water scald burns in 2016-2018. The average cost for each encounter was $572 per ED visit and $28 431 per hospitalisation. In aggregate, the direct healthcare cost of these initial encounters was $206.69 million for inpatient (IP) visits and $29.79 million for ED visits. Medicare paid $109.54 million of these costs and Medicaid paid $18.3 million. Multiple body surfaces were involved in 35.4% of IP visits and 16.1% of ED visits. CONCLUSIONS: NIS and NEDS are valuable tools to examine the cost burden and epidemiology of hospital-treated, tap water scald burns. The high injuries, deaths, and overall cost of these scald burns suggest policy proposals are needed to require the use of thermostatic mixing valves.The additional detail provided by using the International Classification of Diseases (ICD)-10 External Cause of Morbidity Code allows for a better understanding of the size and scope of tap water scald injuries than was possible with ICD-9.

The influence of Medicare Part D on the list pricing of brand drugs.

OBJECTIVE: To compare the Medicare Part D market share of brand drugs with their net-to-list price ratio. DATA SOURCES AND STUDY SETTING: SSR Health Brand Net Price Tool and Medical Expenditure Panel Survey, 2007-2019. STUDY DESIGN: For each drug, we calculated the ratio of net to list price and the percent of users that were Medicare-eligible. We compared these cross-sectionally in each year and estimated a difference-in-differences model comparing drugs with high or low Medicare market shares (MMS) after following changes to program incentives in 2010. DATA COLLECTION/EXTRACTION METHODS: The sample included brand drugs without generic competitors appearing in both datasets. PRINCIPAL FINDINGS: Net-to-list price ratios were negatively correlated with MMS in the later years of our sample. In 2019, a 10% increase in MMS was associated with a significant 4.6% [95% CI: 2.1%, 7.1%] decrease in net-to-list ratio. Difference-in-differences showed net-to-list price ratios of drugs with above median MMS fell relative to those with below median MMS. By 2019, we observe an absolute reduction of -0.2 [95% CI: -0.29, -0.11], representing 28% reduction relative to the average ratio in 2010. CONCLUSIONS: Greater exposure to the Medicare Part D market was associated with larger differences between net and list prices of drugs.

Gastrointestinal bleeding in children with familial dysautonomia: a case-control study.

OBJECTIVE: Familial dysautonomia (FD) is a rare inherited autosomal recessive disorder with abnormal somatosensory, enteric, and afferent autonomic neurons. We aimed to define the incidence of gastrointestinal bleeding and its associated risk factors in patients with FD. METHODS: In this retrospective case-control study, we identified all episodes of gastrointestinal bleeding in patients with FD, occurring over four decades (January 1980-December 2017), using the New York University FD registry. RESULTS: We identified 104 episodes of gastrointestinal bleeding occurring in 60 patients with FD. The estimated incidence rate of gastrointestinal bleeds in the FD population rate was 4.20 episodes per 1000 person-years. We compared the 60 cases with 94 age-matched controls. Bleeding in the upper gastrointestinal tract from gastric and duodenal ulcers occurred most frequently (64 bleeds, 75.6%). Patients were more likely to have a gastrostomy (G)-tube and a Nissen fundoplication [odds ratio (OR) 3.73, 95% confidence interval (CI) 1.303-13.565] than controls. The mean time from G-tube placement to first gastrointestinal bleed was 7.01 years. The mean time from Nissen fundoplication to bleed was 7.01 years. Cases and controls had similar frequency of intake of nonsteroidal antiinflammatory drugs (NSAID) and selective serotonin reuptake inhibitors (SSRI). CONCLUSION: The incidence of gastrointestinal bleeding in the pediatric FD population was estimated to be 4.20 per 1000 person-years, 21 times higher than in the general pediatric population (0.2 per 1000 person-years). Patients with FD with a G-tube and a Nissen fundoplication had a higher risk of a subsequent gastrointestinal bleeding.

The Role of Latina Peer Mentors in the Implementation of the Alma Program for Women With Perinatal Depression.

This study examines the role that compañeras (peer mentors) play in the implementation of a program, Alma, which was designed to support Latina mothers who are experiencing depression during pregnancy or early parenting and implemented in the rural mountain West of the United States. Drawing from the fields of dissemination and implementation and Latina mujerista (feminist) scholarship, this ethnographic analysis demonstrates how the Alma compañeras facilitate the delivery of Alma by creating and inhabiting intimate mujerista spaces with other mothers and create relationships of mutual and collective healing in the context of relationships de confianza (of trust and confidence). We argue that these Latina women, in their capacity as compañeras, draw upon their cultural funds of knowledge to bring Alma to life in ways that prioritizes flexibility and responsiveness to the community. Shedding light on contextualized processes by which Latina women facilitate the implementation of Alma illustrates how the task-sharing model is well suited to the delivery of mental health services for Latina immigrant mothers and how lay mental health providers can be agents of healing.

Gene-Folic Acid Interactions and Risk of Conotruncal Heart Defects: Results from the National Birth Defects Prevention Study.

Conotruncal heart defects (CTDs) are heart malformations that affect the cardiac outflow tract and typically cause significant morbidity and mortality. Evidence from epidemiological studies suggests that maternal folate intake is associated with a reduced risk of heart defects, including CTD. However, it is unclear if folate-related gene variants and maternal folate intake have an interactive effect on the risk of CTDs. In this study, we performed targeted sequencing of folate-related genes on DNA from 436 case families with CTDs who are enrolled in the National Birth Defects Prevention Study and then tested for common and rare variants associated with CTD. We identified risk alleles in maternal MTHFS (ORmeta = 1.34; 95% CI 1.07 to 1.67), maternal NOS2 (ORmeta = 1.34; 95% CI 1.05 to 1.72), fetal MTHFS (ORmeta = 1.35; 95% CI 1.09 to 1.66), and fetal TCN2 (ORmeta = 1.38; 95% CI 1.12 to 1.70) that are associated with an increased risk of CTD among cases without folic acid supplementation. We detected putative de novo mutations in genes from the folate, homocysteine, and transsulfuration pathways and identified a significant association between rare variants in MGST1 and CTD risk. Results suggest that periconceptional folic acid supplementation is associated with decreased risk of CTD among individuals with susceptible genotypes.

Incorporating Dynamic Pricing in Cost-Effectiveness Analysis: Are Known Unknowns Valuable?

BACKGROUND: Current practice in health technology assessment (HTA) of pharmaceuticals conducts cost-effectiveness analyses (CEAs) based on a static price or the estimated price at market launch. Recent publications suggest incorporating dynamic pricing. To test the feasibility and importance of including dynamic pricing, we compared the standard static approach to four dynamic scenarios by replicating US-based HTA evaluations with dynamic pricing inputs. METHODS: The four case examples included omalizumab (Xolair®) for the treatment of allergic asthma, elagolix (Orilissa®) for the treatment of endometriosis, ocrelizumab (Ocrevus®) for the treatment of primary progressive multiple sclerosis (PPMS), and dupilumab (Dupixent®) for the treatment of atopic dermatitis (AD). The primary outcome was the relative percentage change in incremental cost-effectiveness ratios (ICERs) per quality-adjusted life-year (QALY) for two dynamic pricing scenarios versus static pricing. Secondary outcomes included the absolute difference in ICERs versus base-case and an assessment of decision uncertainty. RESULTS: Base-case ICERs were $327,000, $102,000, $700,000, and $102,000 for allergic asthma, endometriosis, PPMS, and AD, respectively. Across scenarios and case examples, the range of ICERs versus base-case varied from decreases of 56% to increases of 232%. The absolute difference in ICERs versus base-case ranged from decreases of $120,000 to increases of $758,000. Conclusions on cost effectiveness were altered in 2/16 scenarios across the four case examples. CONCLUSIONS: Given the decision context that US payers face, with prices varying over time, findings suggest further research to reduce uncertainty around price trajectories, as well as conducting or updating multiple assessments over the lifecycle of pharmaceutical products.

The price paradox of biosimilar-like long-acting insulin.

OBJECTIVES: To describe the uptake and out-of-pocket (OOP) costs of Basaglar, the first long-acting insulin biosimilar, in a commercially insured population in the United States. STUDY DESIGN: Retrospective analysis of commercial pharmacy claims and pharmacy co-payment offsets. METHODS: We assessed Basaglar uptake by examining trends in the composition of the long-acting insulin market in the United States from 2014 to 2018. As patient demographics and plan type may be important determinants of biosimilar uptake, we also assessed characteristics of all long-acting insulin users by drug. We examined Basaglar OOP costs by assessing mean OOP costs per claim for users of Basaglar and other long-acting insulins, overall and by plan type, and the number and source of co-payment offsets for Basaglar and other insulin glargine products from Basaglar market entry through 2018. We used multivariate linear models to examine the relationship between Basaglar OOP expenditures and insurer-negotiated amounts, overall and by plan type. RESULTS: Basaglar experienced a rapid uptake. However, there was no evidence that Basaglar users had lower OOP costs than reference product (Lantus) users. CONCLUSIONS: Given our results and the approval of the first interchangeable biosimilar, we recommend the empirical evaluation of biosimilar cost savings to patients and insurers prior to promoting their automatic substitution.

Statin Medications and Amyotrophic Lateral Sclerosis Incidence and Mortality.

Studies of statins and amyotrophic lateral sclerosis (ALS) incidence and survival have had conflicting findings possibly related to difficulties with confounding by indication. We considered potency of statins used and duration of use to explore confounding by indication. Within the Clalit Health Services in Israel, we identified 948 ALS case patients from 2004 through 2017 and matched them with 1,000 control subjects each. Any statin use up to 3 years before ALS onset was not associated with ALS incidence but was associated with a reduced hazard ratio (HR) for death. Odds of ALS did not vary by statin potency, but use of only lower-potency statins was associated with longer survival (HR = 0.82, 95% CI: 0.68, 0.98), whereas the association with higher-potency statins was null compared with those case patients who did not use statins. However, duration of statin use appeared to account for these findings. Those who used statins only up to 3 years had longer survival (HR = 0.77, 95% CI: 0.61, 0.96) than did case patients who did not use statins, but those who used statins for >3 years did not. Although other explanations are possible, these findings could suggest a protective effect of statins on ALS survival that is partially masked by a worse prognosis from underlying reasons for taking statins that deserves further exploration.

Sieved mass and shape data from simulated fluvial transport of icy clasts in the Titan Tumbler.

Data in this article are related to the research article "Rapid rounding of icy clasts during simulated fluvial transport in the Titan Tumbler". Whereas that research focused on low-temperature ice abrasion in the context of Saturn's moon Titan, the full dataset on experiments testing the breakdown of water ice under a variety of tested conditions is reported in this article. Following the work of previous terrestrial studies, these experiments utilize tumblers that produce collisions to simulate some aspects of mechanical weathering during fluvial transport. Data files publicly available on Mendeley Data include measures of mass and roundness of clasts of specific grain sizes as well as raw images, videos, and the MATLAB script used for analysis. In this article, the varying conditions of temperature, initial clast size, shape, ice type, number of clasts for each of the 42 experiments are reported, along with best-fit models of abrasion typically applied in terrestrial tumbler studies. This text describes the methodology, including the development of icy clasts, operation of the tumblers, measurement of clast properties, calculation of derived parameters, and application of abrasion models. Exploration of various approaches to tumbler development and data acquisition are reported to benefit future researchers in this area. Experiments on the abrasion of different materials benefit from cross-comparison, which is also a fundamental aspect of planetary science.

Ambulatory Surgery Centers Versus Hospital Outpatient Departments for Orthopaedic Surgeries.

BACKGROUND: The goals of this study were to compare the utilization and costs of ambulatory surgery centers (ASCs) versus hospital outpatient department (HOPD) for commonly performed outpatient orthopaedic surgical procedures. METHODS: Commercially insured patients undergoing elective, outpatient orthopaedic surgery were queried using an administrative claims database. We queried the following surgeries: carpal tunnel release, lumbar microdiskectomy, anterior cruciate ligament reconstruction, knee arthroscopy, arthroscopic rotator cuff repair, and bunion repair. Total costs were defined as the sum of all payments for a surgical episode. Professional fees were defined as payments to the primary orthopaedic surgeon and technical fees as all other payments. Comparisons between ASC and HOPD reimbursements were conducted using bivariate statistics and generalized linear models controlling for patient age, sex, and Elixhauser comorbidity index. RESULTS: Among 990,980 cases of outpatient orthopaedic surgery done from 2013 to 2018, the utilization rate of ASCs increased from 31% to 34% across all procedures assessed: compound annual growth rate of 3.3% for lumbar microdiscectomy, 1.8% for knee arthroscopy, 1.4% for anterior cruciate ligament, 1.4% for carpal tunnel release, 1.2% for arthroscopic rotator cuff repair, and 0.5% for bunion repair (P < 0.001 for all). The average total costs were 26% lower at ASCs than HOPDs (P < 0.001 for each procedure). The average technical fees were 33% lower at ASCs than HOPDs (P < 0.001 for each procedure). Both total costs and technical fees were less for ASCs than HOPDs after controlling for patient age, sex, and Elixhauser comorbidity index (P < 0.001 for each procedure). Over the study period, the mean total costs at HOPDs increased by 2.5% yearly, whereas the mean total costs at ASCs decreased by 0.1% yearly. The average surgeon professional fees declined in both care settings over time. CONCLUSION: From 2013 to 2018, there was an increase in ASC utilization for common outpatient orthopaedic surgeries. ASCs were overall less costly than HOPDs for outpatient orthopaedic surgeries. LEVEL OF EVIDENCE: IV.