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Kimmie K McLaurin,1 Sally W Wade,2 Amanda M Kong,3 David Diakun,3 Ifedapo R Olajide,1 Jane Germano4 1US Medical Affairs, AstraZeneca, Gaithersburg, MD, USA; 2Wade Outcomes Research and Consulting, Salt Lake City, UT, USA; 3IBM Watson Health, Cambridge, MA, USA; 4Department of Pediatrics, MedStar Georgetown University Hospital, Washington, DC, USA Purpose: This study examined health care utilization and costs during the first year of life for preterm and full-term infants in the US. Subjects and methods: Preterm (75%) of preterm infants were admitted to the neonatal intensive care unit during their birth hospitalization. Generally, mean length of stay and costs for birth hospitalizations increased with decreasing GA. The average cost of a birth hospitalization was US $62,931 (SD $134,347) for commercially insured preterm infants and $43,858 (SD $115,412) for Medicaid-insured preterm infants compared to $2,401 (SD $7,399) and $1,894 (SD $5,444) for commercially insured and Medicaid-insured full-term infants, respectively. Post-neonatal hospitalization rates increased as GA decreased (in full-term to

Background: Chronic cigarette smokers report withdrawal symptomology, including affective dysfunction and cognitive deficits. While there are studies demonstrating sex specific withdrawal symptomology in nicotine-dependent individuals, literature examining the underlying biological mediators of this is scant and not in complete agreement. Therefore, in this study, we evaluated the sex specific effects of nicotine and withdrawal on contextual fear memory, a hippocampally dependent aspect of cognition that is disrupted in nicotine withdrawal., Methods: Male and female B6/129F1 mice (8-13 weeks old) were used in all experiments. For the acute nicotine experiment, mice received intraperitoneal saline or nicotine (0.5 mg/kg) prior to contextual fear conditioning and test. For the chronic nicotine experiment, mice received nicotine (18 mg/kg/day) or saline for 11 days, then underwent contextual fear conditioning and test. Following the test, mice underwent minipump removal to elicit withdrawal or sham surgery, followed by the fear extinction assay. Bulk cortical tissue was used to determine nicotinic acetylcholine receptor levels via single point [ 3 H]Epibatidine binding assay. Gene expression levels in the dorsal and ventral hippocampus were quantified via RT-PCR., Results: We found that female mice had a stronger expression of contextual fear memory than their male counterparts. Further, following acute nicotine treatment, male, but not female, subjects demonstrated augmented contextual fear memory expression. In contrast, no significant effects of chronic nicotine treatment on fear conditioning were observed in either sex. When examining extinction of fear learning, we observed that female mice withdrawn from nicotine displayed impaired extinction learning, but no effect was observed in males. Nicotine withdrawal caused similar suppression of fosb, cfos, and bdnf, our proxy for neuronal activation and plasticity changes, in the dorsal and ventral hippocampus of both sexes. Additionally, we found that ventral hippocampus erbb4 expression, a gene implicated in smoking cessation outcomes, was elevated in both sexes following nicotine withdrawal., Conclusions: Despite the similar impacts of nicotine withdrawal on gene expression levels, fosb, cfos, bdnf and erbb4 levels in the ventral hippocampus were predictive of delays in female extinction learning alone. This suggests sex specific dysfunction in hippocampal circuitry may contribute to female specific nicotine withdrawal induced deficits in extinction learning., (© 2024. The Author(s).)

Introduction: Ovarian cancer (OC) is one of the leading causes of cancer mortality among women in the United States. With the approval of first-line maintenance therapies, patients with OC experienced prolonged first-line progression-free survival. While the literature addresses some costs associated with OC, further research is needed on the costs of progression that are potentially deferred or prevented by early maintenance. The objective of this study was to capture the health care resource utilization and costs of patients with advanced OC who never received poly(ADP ribose) polymerase (PARP) inhibitor maintenance., Methods: We conducted a descriptive retrospective analysis of treatment patterns and the consequences of progression through several lines of therapy (LOTs) in patients with OC, using claims from commercial and Medicare Advantage health plan members in the United States from the Optum Research Database between January 1, 2010, and April 30, 2019. Patients were required to have an index OC diagnosis (≥ 2 non-diagnostic claims). We examined up to 4 LOTs and the time between treatments., Results: A total of 5498 women met the eligibility criteria. As the number of LOTs increased, the median duration of each line decreased from 137 days in LOT1 to 94 days in LOT4, and the time between lines also decreased from 245 to 0 days. Ambulatory care visits were a major driver of health care resource utilization, with a median of about 6 monthly visits during active treatment. The mean total monthly health care costs for patients with at least 2 LOTs were US$8588 (SD: $8533) before LOT2 and increased to $15,358 (SD: $21,460) during or after LOT2., Conclusions: Prolonging progression-free survival after first-line treatment in patients with OC may provide the opportunity to delay or prevent later treatment, the financial toxicity felt by patients, and the economic burden to the health care system associated with progression., (© 2022. The Author(s).)

Aim: To evaluate which treatment attributes US patients and oncologists prioritize in HER2 negative advanced breast cancer (ABC). Methods: Preferences were assessed via a discrete choice experiment. Also, treatment goal statements were rated on an agreement scale. Results: Patients (n = 169) most valued improving overall survival (OS), followed by improving nausea and neuropathy. Oncologists (n = 117) most valued improving OS, followed by neuropathy and progression-free survival. Regarding treatment goals, oncologists (67%) perceived that patients are more focused on efficacy than quality of life; fewer patients (29%) agreed with this statement; 81% of oncologists and 51% of patients agreed that patients prefer oral treatment. Conclusion: Patients and oncologists were willing to accept increases in toxicities in exchange for efficacy improvements in HER2 negative ABC.

Aim: To understand the preferences of US patients and oncologists for PARP inhibitors as second-line maintenance (2LM) for epithelial ovarian cancer. Methods: A discrete choice experiment was conducted to assess the preferences of treatment attributes. Results: The most valued attributes were risk of grade 3/4 adverse events (AEs; patients, n = 204) and progression-free survival (PFS; oncologists, n = 151). To accept a 37% increased risk of grade 3/4 AEs, PFS would need to increase by 27.9 months (patients) and 6.3 months (oncologists). The least valued attributes were dosing form/frequency (patients) and grade 3/4 anemia risk (oncologists). Conclusion: Patients' and oncologists' willingness to make benefit-risk trade-offs in the 2LM setting suggests that the PFS gains observed in selected studies of poly (ADP-ribose) polymerase inhibitors in BRCA-mutated disease are worth the toxicity risk.

Introduction: We aimed to characterize real-world utilization of poly(ADP-ribose) polymerase (PARP) inhibitors (PARPi) in women with ovarian cancer (OC)., Methods: This retrospective observational study of claims data from US MarketScan ® Commercial/Medicare Supplemental databases included women with OC initiating olaparib, niraparib, or rucaparib from January 1, 2017, to May 31, 2019. Patients were observed from first outpatient prescription until at least 30 days' follow-up. Clinical events of interest (CEIs), based on adverse reactions in PARPi prescribing information, were identified from claims using ICD-9/10 codes. Other outcomes included dose modification, persistence, adherence, healthcare resource utilization (HCRU), and cost., Results: Overall, 303, 348, and 162 women with OC received olaparib, niraparib, and rucaparib, respectively. During follow-up, risk of any CEI was higher with niraparib versus olaparib (odds ratio 3.36 [95% confidence interval 2.00-5.65]) and niraparib versus rucaparib (2.09 [1.10-3.95]), with no significant difference between rucaparib and olaparib (1.61 [0.93-2.79]). PARPi dose decreases were observed in 21.1%, 35.1%, and 30.2% of olaparib-, niraparib-, and rucaparib-treated patients, respectively. Persistence (no treatment gaps of more than 90 days) was significantly higher (P < 0.05) with olaparib (62.2%) versus niraparib (35.9%) and rucaparib (48.7%); adherence (medication possession ratio, MPR ≥ 80%) was 80.2% versus 38.6% and 63.2%, respectively (P < 0.001). Inpatient admissions and outpatient service use were higher with niraparib and rucaparib versus olaparib, reflected in mean (± standard deviation) total medical costs (excluding pharmacy) of $5393 ± 8828 for olaparib, $7732 ± 14,054 for niraparib, and $6868 ± 7929 for rucaparib., Conclusion: Differences between the licensed PARPi were observed in the risk of experiencing a CEI, likelihood of dose modifications, ability to receive continuous PARPi therapy, HCRU, and costs., (© 2021. The Author(s).)

Background: Ovarian cancer is the fifth leading cause of cancer death in women in the US. With poly(ADP-ribose) polymerase (PARP) inhibitors having shown promising results in ongoing trials, there is interest in better understanding their economic value., Objective: This study aimed to review and evaluate the quality of published cost-effectiveness analyses (CEAs), and provide recommendations for CEAs in this setting., Methods: A systematic literature review of the MEDLINE and EMBASE databases was conducted in June 2019 to identify CEAs of PARP inhibitors in treating advanced ovarian cancer from peer-reviewed journals and conferences. Key information from the identified publications were extracted and reviewed. The quality of full-text studies was assessed using the Quality of Health Economic Studies instrument. Recommendations for future CEAs were developed based on the findings from the literature review., Results: Eighteen CEAs (five in full texts) met the inclusion criteria. Most adopted a US healthcare or societal perspective. The majority of the studies did not clearly display the economic model structure. No studies reported the validation of model projections based on internal or external data. Surrogate outcomes such as incremental costs per progression-free life-year gained were the most common outcomes reported. The majority of studies drew their conclusions based on surrogate outcomes, even with no theoretical or empirical threshold for cost effectiveness. All five full-text studies included some type of sensitivity or scenario analyses. The key drivers of the incremental cost-effectiveness ratio were treatment duration, effects, and costs, health utility, and prevalence of BRCA mutations., Conclusion: In the existing CEAs for PARP inhibitors, there were uncertainties and challenges leading to variation in quality. We provided recommendations to improve consistency and quality of CEAs in this setting, which will help to better understand the value of PARP inhibitors, improve decision making, and reduce potential misallocation of resources.

Aim: Describe rates of prespecified adverse events in patients who switched from olaparib capsules to tablets. Patients & methods: Retrospective, observational cohort analysis using self-controlled, pre-post design. Data on patients with ovarian cancer who switched from olaparib capsules to tablets between January 2015 and February 2019 were obtained from a US claims database. Results: Among all patients (n = 48), proportion with any prespecified adverse event was 45.8% (95% confidence interval: 31.4-60.8) during initial 90 days' capsule use and 35.4% (22.2-50.5) during initial 90 days' tablets use; difference -10.4% (-28.8-9.0). Conclusion: Switching from olaparib capsules to tablets was manageable with no evidence of increased toxicity. This real-world study supports the manageable tolerability of olaparib in women with ovarian cancer.

Objective: Respiratory syncytial virus (RSV) is a common pathogen during infancy, with the potential to cause serious disease and mortality in high-risk groups. The objective of this study was to characterize trends of RSV and bronchiolitis hospitalizations in the first year in a population-based cohort and assess differences in trends according to risk status., Methods: Using an observational retrospective cohort design, we examined a California population-based dataset of vital statistics linked to hospital discharge data for up to 1 year after birth from 1997-2011. Infants were categorized by medical condition and then by gestational age. Medical conditions of interest included chronic lung disease, certain congenital heart diseases, or others known to affect risk for developing severe bronchiolitis. The primary outcome was hospitalization due to RSV; secondary outcome was hospitalization for unspecified bronchiolitis (UB) not coded as RSV. Annual person-year rates were calculated for infants <12 months of age during January to December of each year., Results: Of 7,298,401 infants born during the study period, 121,230 (1.7%) had a medical condition associated with risk; these infants experienced 6853 RSV and 6568 UB hospitalizations in the first year. In infants without medical conditions, 96,694 RSV and 69,886 UB hospitalizations occurred. All-cause infant hospitalizations declined over time from 12.2 to 9.3 per 100 person-years. RSV hospitalization rates for infants with medical conditions decreased from 7.6 to 3.4 per 100 person-years, with the largest relative decline in infants with chronic lung disease (12.0 to 5.0 per 100 person-years). For infants without medical conditions, RSV hospitalizations declined from 1.4 to 0.8 per 100 person-years, with greater decreases among preterm infants with earlier gestational age. UB hospitalization rates remained relatively stable across the study years, from 6.2 to 5.4 and 1.0 to 0.8 per 100 person-years for infants with and without medical conditions., Conclusions: Various interventions may have contributed to observed decreases in RSV hospitalizations from 1998-2011, which were greater in high-risk populations recommended for RSV immunoprophylaxis and not observed with UB. Further efforts to promote evidence-based practice and optimal targeting of appropriate interventions will ensure continued improvement in care for vulnerable infants., Competing Interests: This study was supported by AstraZeneca (Gaithersburg, MD). KM and CSA are employed by AstraZeneca. HL received funding from AstraZeneca for research effort and travel expenses to present findings at a national conference. MB received research funding from AstraZeneca. There are no patents, products in development, or marketed products to declare. This does not alter our adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Background: The variability in cost of palivizumab treatment, indicated for prevention of respiratory syncytial virus (RSV) infections in high-risk infants, has not been robustly estimated in prior studies. This study aimed to determine the cost variations of palivizumab from a US payer perspective for otherwise healthy preterm infants born 29-35 weeks gestational age (wGA) using infant characteristics and applied dosing regimens., Methods: Fenton Growth Charts were merged with World Health Organization Child Growth Standards to estimate preterm infant growth patterns. The merged growth chart was applied to infants who received palivizumab from a prospective, observational registry to determine future body weight using each infant's wGA and birth weight. Using quarter 3 (Q3) 2016-Q2 2017 vial cost, treatment costs at monthly dosing intervals were estimated using expected weights and averaged by age to derive expected mean 2016-2017 RSV seasonal costs per infant under various dosing scenarios., Results: Given different dosing scenarios (two to five doses), birth month, and growth patterns for preterm infants 29-35 wGA, the estimated average 2016-2017 seasonal cost of palivizumab treatment ranged from $3221 to $12,568. Outpatient-only cost (excluding first dose at hospital discharge) ranged from $1733 to $11,862. The main drivers of costs were dosing regimen (74% of variance), dosing interacted with birth month (17%), and wGA (6%)., Conclusion: The considerable variability in the average cost of palivizumab treatment for preterm infants is driven by choice of dosing regimen, wGA, and birth month. Therefore, when estimating the cost of palivizumab, it is important to consider both infant characteristics at each dose and potential dosing regimens.

Background: Respiratory syncytial virus (RSV) causes significant pediatric morbidity and is the most common cause of bronchiolitis. Bronchiolitis hospitalizations declined among US infants from 2000‒2009; however, rates in infants at high risk for RSV have not been described. This study examined RSV and unspecified bronchiolitis (UB) hospitalization rates from 1997‒2012 among US high-risk infants., Methods: The Kids' Inpatient Database (KID) infant annual RSV (ICD-9 079.6, 466.11, 480.1) and UB (ICD-9 466.19, 466.1) hospitalization rates were estimated using weighted counts. Denominators were based on birth hospitalizations with conditions associated with high-risk for RSV: chronic perinatal respiratory disease (chronic lung disease [CLD]); congenital airway anomalies (CAA); congenital heart disease (CHD); Down syndrome (DS); and other genetic, metabolic, musculoskeletal, and immunodeficiency conditions. Preterm infants could not be identified. Hospitalizations were characterized by mechanical ventilation, inpatient mortality, length of stay, and total cost (2015$). Poisson and linear regression were used to test statistical significance of trends., Results: RSV and UB hospitalization rates were substantially elevated for infants with higher-risk CHD, CLD, CAA and DS without CHD compared with all infants. RSV rates declined by 47.0% in CLD and 49.7% in higher-risk CHD infants; no other declines in high-risk groups were observed. UB rates increased in all high-risk groups except for a 22.5% decrease among higher-risk CHD. Among high-risk infants, mechanical ventilation increased through 2012 to 20.4% and 13.5% of RSV and UB hospitalizations; geometric mean cost increased to $31,742 and $25,962, respectively, and RSV mortality declined to 0.9%., Conclusions: Among high-risk infants between 1997 and 2012, RSV hospitalization rates declined among CLD and higher-risk CHD infants, coincident with widespread RSV immunoprophylaxis use in these populations. UB hospitalization rates increased in all high-risk groups except higher-risk CHD, suggesting improvement in the health status of higher-risk CHD infants, potentially due to enhanced surgical interventions. Mechanical ventilation use and RSV and UB hospitalization costs increased while RSV mortality declined.

Background: Health care costs increase in patients with more severe asthma, but the effect of asthma exacerbations on costs among patients with more severe asthma has not been quantified., Objective: This study compared direct health care costs between patients with moderate/severe persistent asthma with and without exacerbations., Methods: Patients who had an asthma diagnosis (International Classification of Diseases-ninth revision-Clinical Modification code 493.x), were 12 to 64 years old, and were receiving controller therapy were identified from a large administrative claims database. Patients were categorized as having moderate/severe persistent asthma and were further evaluated for exacerbations during a 12-month exacerbation identification period. Patients with 1 or more exacerbations (asthma-related inpatient or emergency department visit or corticosteroid prescription) were matched to patients without exacerbations on demographic characteristics and asthma severity. Total and asthma-related health care costs during the 1-year study period after the exacerbation index date were calculated., Results: Patients with exacerbations had significantly higher total health care costs ($9223 vs $5011, P < .0001) and asthma-related costs ($1740 vs $847, P < .0001). The cost differences remained significant after controlling for patient differences by using multivariate models. Patients with exacerbations (n = 3830) had higher rates of sinusitis, allergy-related diagnoses or medications, pneumonia, and mental disorders and higher average Charlson Comorbidity Index scores at baseline. Patients with exacerbations filled their prescriptions for controllers more often and had higher asthma-related drug costs., Conclusions: Patients with moderate/severe persistent asthma who had exacerbations had higher total and asthma-related health care costs than those without exacerbations. Moreover, controller medication use was higher in patients with exacerbations., (Copyright © 2012 American Academy of Allergy, Asthma & Immunology. Published by Mosby, Inc. All rights reserved.)

In many countries, reproductive health services do not actively include post-abortion family planning services for women who are treated for complications of unsafe abortion. This greatly increases the risk of further unintended pregnancies and unsafe abortions. The authors, drawing on the recommendations of a meeting of experts, make a plea for bridging the gap and dealing more realistically with this urgent need.