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STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a treatment target for many patients with obstructive sleep apnea (OSA). We aimed to understand the prevalence, risk factors, and quality of life associated with EDS in a nonclinical, “real world” sample of patients with OSA. METHODS: Cross-sectional survey of patients with OSA participating in an online peer support community, assessing demographics, comorbidities, treatment, and quality of life. Differences in those with and without EDS (Epworth Sleepiness Scale > and ≤ 10) were assessed. RESULTS: The sample (n = 422) was 54.2% male, 65.9% were ≥ 55 years, and 43.3% reported sleeping ≤ 6 hours/night. EDS was identified among 31.0% of respondents and 51.7% reported sleepiness as a precipitating factor for seeking initial OSA treatment. EDS was more prevalent in individuals reporting asthma, insomnia symptoms, positive airway pressure (PAP) use less than 6 hours/night on ≥ 5 nights/week, or sleep duration < 6 hours/night. After adjusting for demographics and comorbidities, patients with EDS reported poorer mental and physical health and well-being, lower disease-specific functional status, more activity and work impairment, and more driving impairment (P values < .05). In the subsample (n = 265) with high PAP adherence, 26.0% reported EDS, and similar associations between EDS and outcomes were observed. CONCLUSIONS: These “real world” data suggest that patients seeking online OSA support experience a high prevalence of EDS, which was associated with poorer quality of life and worse functional status. Associations persisted among respondents with high self-reported PAP-therapy adherence, potentially driving these individuals to seek online support for sleepiness-related symptoms. CITATION: Wanberg LJ, Rottapel RE, Reid ML, et al. Prevalence of sleepiness and associations with quality of life in patients with sleep apnea in an online cohort. J Clin Sleep Med. 2021;17(12):2363–2372.

BACKGROUND The aim of this study was to evaluate the impact of different therapy regimens, including sodium oxybate (SXB)-containing regimens, on patient-reported outcomes (PROs) in people with narcolepsy. METHODS Online surveys were used to collect information from persons with narcolepsy in the Nexus Narcolepsy Registry. Surveys contained questionnaires assessing self-reported sleep quality (SQ; via single question), daytime sleepiness and function (Epworth Sleepiness Scale and Functional Outcomes of Sleep Questionnaire), health-related quality of life (HRQoL; 36-Item Short Form Health Survey [SF-36]), work productivity and impairment (Work Productivity and Activity Impairment: Specific Health Problem), and history of injuries or motor vehicle accidents. Treatment with SXB (including monotherapy or combination therapy; SXB group) was compared with non-SXB therapy (No SXB group). The P values presented are nominal, as there are no adjustments for multiplicity. RESULTS From June 2015 through December 2017, 983 participants completed 1760 surveys. SQ and daytime functioning scores were better in the SXB group compared with the No SXB group (all P

Background Obstructive sleep apnea (OSA) is associated with excessive daytime sleepiness (EDS), which may go undiagnosed and can significantly impair a patient’s health-related quality of life (HRQOL). This qualitative research examined timing and reasons patients sought medical care for their EDS and OSA symptoms, and the impact of EDS on HRQOL. Methods Focus groups were conducted in 3 US cities with 42 participants currently experiencing EDS with OSA. Transcripts were coded and analyzed using an adapted grounded theory approach common to qualitative research. Results Over three-fifths of study participants (n = 26, 62%) were currently using a positive airway pressure (PAP) or dental device; one-third (n = 14, 33%) had previously used a positive airway pressure (PAP) or dental device, and the remainder had either used another treatment (n = 1, 2%) or were treatment naïve (n = 1, 2%). Twenty-two participants (52%) reported experiencing OSA symptoms for ≥1 year, with an average duration of 11.4 (median 8.0, range 1–37) years before seeking medical attention. Several (n = 7, 32%) considered their symptoms to be “normal,” rather than signaling a serious medical condition. Thirty participants (71%) discussed their reasons for ultimately seeking medical attention, which included: input from spouse/partner, another family member, or friend (n = 20, 67%); their own concern about particular symptoms (n = 7, 23%); and/or falling asleep while driving (n = 5, 17%). For all 42 participants, HRQOL domains impacted by EDS included: physical health and functioning (n = 40, 95%); work productivity (n = 38, 90%); daily life functioning (n = 39, 93%); cognition (n = 38, 90%); social life/relationships (n = 37, 88%); and emotions (n = 30, 71%). Conclusions Findings suggest that patients may be unaware that their symptoms could indicate OSA requiring evaluation and treatment. Even following diagnosis, EDS associated with OSA can continue to substantially affect HRQOL and daily functioning. Further research is needed to address diagnostic delays and unmet treatment needs for patients with EDS associated with OSA.

This study analyzed a privately insured pediatric population with and without narcolepsy to determine the impact of pediatric narcolepsy on comorbidities, health care utilization, and cost. Additional analyses compared narcolepsy type 1 and type 2.This retrospective cross-sectional study identified US patients with narcolepsy18 years of age with ≥2 claims with a diagnosis code of narcolepsy using Truven MarketScan® data 2011 to 2015. Patients were matched to controls without narcolepsy. Comorbid conditions, health care utilization, and costs were measured by calendar year. P values are nominal, and no adjustments for multiplicity or multiple comparisons were made.A total of 1427 pediatric patients with narcolepsy were identified and matched with 4281 controls from 2011 to 2015. Patients with narcolepsy had more comorbid conditions (mean 5.8 vs 2.4, nominal P 0.001). Respiratory diseases and mood disorders were more common in patients with narcolepsy than controls (57% vs 32% and 56% vs 14%, respectively; both nominal P 0.001). Compared to controls, patients with narcolepsy underwent more diagnostic tests (electroencephalogram, EEG [0.13 vs 0.0053]) and brain computed tomography, CT/magnetic resonance imaging, MRI (0.26 vs 0.022; both nominal P 0.001). Mean annual inpatient days (0.71 vs 0.15), emergency department visits (0.51 vs 0.15), and outpatient office visits (8.6 vs 2.3) were higher for patients with narcolepsy than controls (all nominal P 0.001). Annual mean health care costs were higher for patients with narcolepsy versus controls ($15,797 vs $2449, nominal P 0.001).Pediatric patients with narcolepsy had greater comorbidity, higher health care utilization, and higher costs than patients without narcolepsy.

Veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) conditioning or high-dose nontransplant chemotherapy. VOD/SOS with multi-organ dysfunction (MOD) is associated with a mortality rate of > 80%. Defibrotide (25 mg/kg/day) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post HSCT in the United States and to treat severe hepatic VOD/SOS in patients > 1 month of age in the European Union. A random effects model was used for pooling data from 17 systematically chosen defibrotide studies. For patients in these reports (n = 2598), and those in the subset of 10 reports of patients treated with ~ 25 mg/kg/day (n = 1691), estimated Day + 100 survival rates were 54% and 56%, respectively. Among those patients treated with ~ 25 mg/kg/day, estimated Day + 100 survival was 44% among patients with MOD and 71% in patients without MOD; survival was 41% and 70%, respectively, for the population of patients receiving any dose of defibrotide. Safety results were not pooled owing to differences in reporting methodology but were generally consistent with the known tolerability profile of defibrotide. This analysis provides the largest assessment of survival in patients treated with defibrotide for VOD/SOS with or without MOD.

This study examined the correlation between improvements in excessive daytime sleepiness in participants with obstructive sleep apnea or narcolepsy and changes in functional status, work productivity and health‐related quality of life. Data from two 12‐week randomized controlled trials of solriamfetol were analyzed. Participants completed the Epworth Sleepiness Scale, 10‐item Functional Outcomes of Sleep Questionnaire, Work Productivity and Activity Impairment questionnaire and 36‐Item Short Form Health Survey and performed the Maintenance of Wakefulness Test at baseline and weeks 4, 8 and 12. Patient Global Impression of Change was assessed at weeks 4, 8 and 12. Pearson correlations were calculated for change in scores from baseline to week 12. For both studies, changes in the 10‐item Functional Outcomes of Sleep Questionnaire were highly correlated (absolute value >0.5) with changes in Epworth Sleepiness Scale scores; changes in multiple domain scores of the 36‐Item Short Form Health Survey and Work Productivity and Activity Impairment questionnaire were moderately correlated (0.3–0.5) with changes in Epworth Sleepiness Scale scores in both studies and highly correlated for participants with narcolepsy. Changes in Maintenance of Wakefulness Test scores correlated moderately with changes in Epworth Sleepiness Scale scores in both studies. At week 12, Patient Global Impression of Change ratings correlated highly with Epworth Sleepiness Scale and 10‐item Functional Outcomes of Sleep Questionnaire scores for both disorders. Other correlations were low. Self‐reported assessments of sleepiness and global improvement appear to be more strongly correlated with measures of functioning and health‐related quality of life than objectively assessed sleepiness.

Aims: Treatment of acute myeloid leukemia (AML) requires significant healthcare resource utilization (HRU), including lengthy hospitalizations. In a phase 3 study (NCT01696084), CPX-351 (Vyxeos) sh...

A risk score identifying patients at high risk for veno-occlusive disease (VOD) may aid efforts to study preventive strategies for this uncommon complication of hematopoietic cell transplantation (HCT). Patients receiving a first allogeneic HCT between 2008 and 2013 as reported to the Center for International Blood and Marrow Transplant Research (N = 13,097) were randomly divided into training and validation sets. Independent prognostic factors for development of VOD by day +100 after HCT were identified with a multivariate logistic regression model. A risk score was constructed in the training set using the significant factors and confirmed in the validation set. Baseline characteristics of the training and validation sets were balanced. In total, 637 patients (4.9%) developed VOD by day +100. Younger age, positive hepatitis B/C serology, lower Karnofsky performance scale score, use of sirolimus, disease, disease status at transplant, and conditioning regimen were independent prognostic factors. Myeloablative conditioning regimens were associated with higher risk of VOD. Busulfan-based myeloablative conditioning regimens guided by pharmacokinetic monitoring were associated with higher risk than those without pharmacokinetic monitoring. Patients were stratified into 4 distinct, statistically significantly different groups by their risk score percentile. This pretransplant risk score successfully stratified allogeneic HCT patients by risk of developing VOD, was validated in an independent set, and demonstrated strong discriminatory ability to identify a high-risk cohort.

Veno-occlusive disease (VOD), also called sinusoidal obstruction syndrome (SOS), is a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT) conditioning or high-dose nontransplant chemotherapy. VOD/SOS with multi-organ dysfunction (MOD) is associated with a mortality rate of 80%. Defibrotide (25 mg/kg/day) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post HSCT in the United States and to treat severe hepatic VOD/SOS in patients 1 month of age in the European Union. A random effects model was used for pooling data from 17 systematically chosen defibrotide studies. For patients in these reports (n = 2598), and those in the subset of 10 reports of patients treated with ~ 25 mg/kg/day (n = 1691), estimated Day + 100 survival rates were 54% and 56%, respectively. Among those patients treated with ~ 25 mg/kg/day, estimated Day + 100 survival was 44% among patients with MOD and 71% in patients without MOD; survival was 41% and 70%, respectively, for the population of patients receiving any dose of defibrotide. Safety results were not pooled owing to differences in reporting methodology but were generally consistent with the known tolerability profile of defibrotide. This analysis provides the largest assessment of survival in patients treated with defibrotide for VOD/SOS with or without MOD.

Introduction Narcolepsy patients report lower health-related quality of life (HRQoL) than the general population, as measured by the Short Form-36 Health Survey (SF-36). This analysis evaluated whether changes in SF-36 correlated with physician-rated Clinical Global Impression of Change (CGI-C). Methods Data were from 209 of 228 narcolepsy patients participating in an 8-week clinical trial of sodium oxybate. Changes from baseline for SF-36 subscales (Physical Functioning, Role Physical, Bodily Pain, General Health, Vitality, Social Functioning, Role Emotional, and Mental Health) and the summary scores were evaluated for correlation with CGI-C overall and by treatment group. Correlations were calculated using the Pearson product-moment correlation coefficient (r). Results Correlations described an inverse relationship in scores, but a direct relationship in improvement; lower CGI-C scores (i.e., better) were associated with higher SF-36 subscale scores (i.e., improved HRQoL). Moderate and significant correlations were observed for Vitality (r = −0.464; P

A Phase-3 study of defibrotide compared with historical controls demonstrated a 23% improvement in 100-day survival post-hematopoietic stem cell transplantation (HSCT) among patients with veno-occlusive disease with multi-organ dysfunction (VOD with MOD).To estimate the budget impact and cost-effectiveness of introducing defibrotide to a transplant center.The authors developed a budget impact model from the perspective of a bone-marrow transplant center. It was estimated that 2.3% of adults and 4.2% of children would develop VOD with MOD following HSCT based on a retrospective hospital database analysis and the effect that treating patients with defibrotide would have on costs for adult and pediatric centers was estimated. A cost-utility analysis (CUA) was also developed to capture the long-term cost-effectiveness of defibrotide. Projected life expectancies in the two groups were estimated based on trial data, transplant registry data, studies of long-term survival among HSCT patients, and US population life-tables.There was an estimated 3% increase ($330,706) per year in total adult transplantation center costs associated with adopting defibrotide, and a1% increase ($106,385) for pediatric transplant centers, assuming 100 transplants per year. In the CUA, the lifetime increase in cost per patient was $106,928, life expectancy increased by 3.74 years, and quality-adjusted life-years (QALYs) increased by 2.24. The incremental cost-effectiveness ratio (ICER) was $47,736 per QALY gained; 88% probability defibrotide was cost-effective at a $100,000/QALY threshold.The budget impact of defibrotide for a transplant center is relatively modest compared to the overall cost of transplantation. Defibrotide provides an important survival advantage for VOD with MOD patients, and the life years gained lead to defibrotide being highly cost-effective.

OBJECTIVE/BACKGROUND The real-world experience of people with narcolepsy is not well understood. PATIENTS/METHODS The Nexus Narcolepsy Registry (NCT02769780) is a longitudinal, web-based patient registry of self-reported data from adults with physician-diagnosed narcolepsy. Surveys were electronically distributed every 6 months; the current analysis reports registry population demographics, narcolepsy diagnosis journey, and predictors of diagnostic delays. RESULTS The registry population included in this analysis (N = 1024) was predominantly female (85%) and White (92%), with a mean age of 37.7 years. Most participants had education/training beyond high school (93%). Mean (median) reported ages at narcolepsy symptom onset, first consultation for symptoms, and narcolepsy diagnosis were 18.1 (16), 26.4 (24), and 30.1 (28) years, respectively. A majority (59%) of participants reported ≥1 misdiagnosis, and 29% reported consulting ≥5 physicians before narcolepsy diagnosis. More than half (56%) of participants' first consultations for narcolepsy symptoms were with a general practitioner, whereas the diagnosing clinician was usually a sleep specialist (64%) or neurologist (27%). Pediatric symptom onset was associated with a longer mean interval to first consultation than adult symptom onset (10.7 and 4.6 years, respectively; P

CPX-351 is a dual-drug liposomal encapsulation of cytarabine/daunorubicin. In a phase 3 study (ClinicalTrials.gov Identifier: NCT01696084), patients aged 60-75 years with newly diagnosed, high-risk/secondary AML received 1-2 induction cycles with CPX-351 or 7 + 3 chemotherapy; those achieving complete remission (including with incomplete platelet or neutrophil recovery) could receive up to 2 consolidation cycles with CPX-351 or 5 + 2 chemotherapy, respectively. In this exploratory analysis of the subgroup of patients who received consolidation, median overall survival was prolonged among patients receiving CPX-351 induction/consolidation versus 7 + 3/5 + 2 (25.43 vs. 8.53 months; HR = 0.44 [95% CI: 0.25-0.77]). The safety profile of CPX-351 consolidation was consistent with that of the overall study. Outpatient administration of CPX-351 consolidation occurred in 51%-61% of patients and did not diminish overall survival. These findings suggest consolidation with CPX-351 in this patient population contributed to the prolonged overall survival versus 7 + 3/5 + 2, building upon findings from the overall study population, and provide evidence that, with careful monitoring, some patients can successfully receive CPX-351 as outpatients.

Objective Solriamfetol (formerly JZP-110), a dopamine/norepinephrine reuptake inhibitor, is approved in the US to improve wakefulness in adults with excessive daytime sleepiness associated with narcolepsy (75–150 mg/d) or obstructive sleep apnea (37.5–150 mg/d). In a randomized, double-blind, placebo-controlled trial in participants with narcolepsy, effects of solriamfetol on functional status, health-related quality of life (HRQoL), and work productivity were evaluated. Methods Participants with narcolepsy (N = 239) were randomized to solriamfetol 75, 150, or 300 mg, or placebo for 12 weeks. Outcome measures included the Functional Outcomes of Sleep Questionnaire short version (FOSQ-10), 36-Item Short Form Health Survey version 2 (SF-36v2), and Work Productivity and Activity Impairment questionnaire for Specific Health Problem (WPAI:SHP). A mixed-effects model with repeated measures was used for comparisons vs placebo. Results At week 12, solriamfetol increased FOSQ-10 total score, with greatest mean difference from placebo (95% CI) at 300 mg (1.45 [0.31, 2.59]). On SF-36v2, improvements vs placebo were observed in physical component summary scores (300 mg: 2.22 [0.04, 4.41]) and subscales of role physical, general health, and vitality. On WPAI:SHP, solriamfetol 150 mg reduced overall work impairment vs placebo (−15.5 [−29.52, −1.47]), and 150 and 300 mg reduced activity impairment vs placebo (−10.05 [−19.48, −0.62] and −13.49 [−23.19, −3.78], respectively). Most treatment-emergent adverse events (TEAEs) were mild or moderate in severity. Common TEAEs were headache, nausea, decreased appetite, nasopharyngitis, dry mouth, and anxiety. Conclusions Solriamfetol improved measures of functional status, HRQoL, and work productivity, particularly at the 150- and 300-mg doses. Most TEAEs were mild to moderate. Trial registration ClinicalTrials.gov identifier NCT02348593, EudraCT number 2014-005487-15.

Background: Obstructive sleep apnea (OSA) with excessive daytime sleepiness (EDS) can impair quality of life (QOL) and may go undiagnosed. Objectives: To examine the diagnosis experience and impacts of EDS with OSA on QOL in the US. Methods: Focus groups in 3 US cities with 42 patients experiencing EDS with OSA; coded transcripts qualitatively analysed using adapted grounded theory approach. Results: Prior to diagnosis, 40% (n=17) of patients were aware of their EDS and 74% (n=31) were informed of their other OSA symptoms by a spouse/partner, family or friends. About half (n=22, 52%) waited an average of 11.4 (range 1-37) years to seek medical care for OSA; 32% (n=7/22) had thought their symptoms were normal rather than a sign of OSA. Reasons for seeking care were: input from a loved one (n=21, 50%); self-concern about symptoms (n=7, 17%); and impaired driving (n=5, 12%). Twenty-seven patients discussed referral pathways: 15/27 (56%) first saw a primary care physician and 12/27 (44%) a specialist. Although 74% (n=31) were currently on OSA treatment, the majority reported EDS impacts on physical functioning (n=40, 95%); daily life (n=39, 93%); cognition (n=38, 90%); social life (n=37, 88%); and work (n=29, 69%). Conclusions: In the US, OSA diagnosis is often delayed, with many patients unaware of the need to seek medical care. Following OSA diagnosis, EDS may continue to impair QOL. Future research should address diagnostic delays and unmet treatment needs for this population.

STUDY OBJECTIVES: Few population-based studies have explored how excessive sleepiness (ES) contributes to burden of illness among patients with obstructive sleep apnea (OSA). METHODS: This study utilized data from the annual, cross-sectional 2016 US National Health and Wellness Survey. Respondents self-reporting an OSA diagnosis were categorized as having ES (Epworth Sleepiness Scale [ESS] score ≥ 11) or not having ES (ESS score < 11). Comorbidities, health-related quality of life (HRQoL), and productivity were examined in three groups: OSA with ES (n = 731), OSA without ES (n = 1,452), and non-OSA controls (n = 86,961). RESULTS: The OSA with ES group had significantly higher proportions of respondents reporting depression (62.4% versus 48.0%), gastroesophageal reflux disease (39.0% versus 29.4%), asthma (26.3% versus 20.7%), and angina (7.8% versus 6.7%) compared to the OSA without ES group (P < .05). After controlling for covariates, the OSA with ES group had significantly lower (worse) scores for mental component score (41.81 versus 45.65 versus 47.81), physical component score (46.62 versus 48.68 versus 51.36), and SF-6D (0.65 versus 0.69 versus 0.73) compared with OSA without ES and non-OSA controls (all P < .001). The OSA with ES group had significantly higher (greater burden) mean rates of presenteeism (25.98% impairment versus 19.24% versus 14.75%), work impairment (29.41% versus 21.82% versus 16.85%), and activity impairment (31.09% versus 25.46% versus 19.93%) compared with OSA without ES and non-OSA controls (all P < .01) after controlling for covariates. CONCLUSIONS: OSA with ES is associated with higher prevalence of comorbidities, reduced HRQoL, and greater impairment in productivity compared to OSA without ES and compared to non-OSA controls. CITATION: Stepnowsky C, Sarmiento KF, Bujanover S, Villa KF, Li VW, Flores NM. Comorbidities, health-related quality of life, and work productivity among people with obstructive sleep apnea with excessive sleepiness: findings from the 2016 US National Health and Wellness Survey. J Clin Sleep Med. 2019;15(2):235–243.

Background: Schizophrenia is a debilitating disorder that often requires the affected individual to receive part- or full-time care from a caregiver. Aims: The purpose of this study was to examine the humanistic and economic burden of caring for an individual with Schizophrenia with regard to the measures of quality of life (QoL), work productivity, healthcare resource use and estimated economic costs. Methods: Data for this study came from the 2012 US National Health and Wellness Survey (NHWS; n = 71,149). Specifically, this analysis focused on those individuals in the survey who indicated that they were currently the primary caregiver for an individual with Schizophrenia (C-SCZ; n = 174). These individuals were matched via two separate 1:2 propensity score matches with both caregivers of other disorders (C-Other; n = 294) and non-caregivers (Non-C; n = 294) on significant covariates. Individuals were then compared across the outcomes of QoL, work productivity, healthcare resource use and estimated economic costs. Results: C-SCZ respondents had worse outcomes on all outcomes measured than C-Other respondents and Non-C respondents even when controlling for significant differences between the groups on sociodemographic characteristics. However, due to the small sample sizes, these comparisons were only significant in most cases for the C-SCZ to Non-C comparisons. Conclusion: Results indicate that caregivers of those with Schizophrenia experience a heightened humanistic and economic burden, especially relative to the burden experienced by non-caregivers. The fact that Schizophrenia not only affects the individual but also those who care for that individual is underscored by these results.

Background Understanding the longitudinal course of negative symptoms, especially in relationship to functioning, in the early phase of schizophrenia is crucial to developing intervention approaches. The course of negative symptoms and daily functioning was examined over a 1-year period following a recent onset of schizophrenia and at an 8-year follow-up point. Methods The study included 149 recent-onset schizophrenia patients who had a mean age of 23.7 (SD = 4.4) years and mean education of 12.9 (SD = 2.2) years. Negative symptom (BPRS and SANS) and functional outcome (SCORS) assessments were conducted frequently by trained raters. Results After antipsychotic medication stabilization, negative symptoms during the first outpatient year were moderately stable (BPRS ICC = 0.64 and SANS ICC = 0.66). Despite this overall moderate stability, 24% of patients experienced at least one period of negative symptoms exacerbation. Furthermore, entry level of negative symptoms was significantly associated with poor social functioning ( r = − .34, p r = − .25, p r = .29, p Discussion Early negative symptoms are fairly stable during the first outpatient year, are predictors of daily functioning at 12 months, and predict negative symptoms 8 years later. Despite the high levels of stability, negative symptoms did fluctuate in a subsample of patients. These findings suggest that negative symptoms may be an important early course target for intervention aimed at promoting recovery.

Hematopoietic stem-cell transplantation (HSCT) requires highly specialized, resource-intensive care. Myeloablative conditioning regimens used before HSCT generally require inpatient stays and are more intensive than other preparative regimens, and may therefore be more costly.To estimate the costs associated with inpatient HSCT according to the type of the conditioning regimen used and other potential contributors to the overall cost of the procedure.We used data from the Truven Health MarketScan insurance claims database to analyze healthcare costs for pediatric (age18 years) and adult (age ≥18 years) patients who had autologous or allogeneic inpatient HSCT between January 1, 2010, and September 23, 2013. We developed an algorithm to determine whether conditioning regimens were myeloablative or nonmyeloablative/reduced intensity.We identified a sample of 1562 patients who had inpatient HSCT during the study period for whom the transplant type and the conditioning regimen were determinable: 398 patients had myeloablative allogeneic HSCT; 195 patients had nonmyeloablative/reduced-intensity allogeneic HSCT; and 969 patients had myeloablative autologous HSCT. The median total healthcare cost at 100 days was $289,283 for the myeloablative allogeneic regimen cohort compared with $253,467 for the nonmyeloablative/reduced-intensity allogeneic regimen cohort, and $140,792 for the myeloablative autologous regimen cohort. The mean hospital length of stay for the index (first claim of) HSCT was 35.6 days in the myeloablative allogeneic regimen cohort, 26.6 days in the nonmyeloablative/reduced-intensity allogeneic cohort, and 21.8 days in the myeloablative autologous regimen cohort.Allogeneic HSCT was more expensive than autologous HSCT, regardless of the regimen used. Myeloablative conditioning regimens led to higher overall costs than nonmyeloablative/reduced-intensity regimens in the allogeneic HSCT cohort, indicating a greater cost burden associated with inpatient services for higher-intensity preparative conditioning regimens. Pediatric patients had higher costs than adult patients. Future research should involve validating the algorithm for identifying conditioning regimens using clinical data.

Sinusoidal obstruction syndrome (SOS) is a life-threatening complication of hematopoietic stem cell transplantation (HSCT) associated with significant morbidity and mortality. Healthcare utilization, costs, and mortality were assessed in HSCT patients diagnosed with SOS, with and without multi-organ dysfunction (MOD).This retrospective observational study identified real-world patients undergoing HSCT between January 1, 2009 and May 31, 2014 using the Premier Healthcare Database. In absence of a formal ICD-9-CM diagnostic code, SOS patients were identified using a pre-specified definition adapted from Baltimore and Seattle criteria and clinical practice. Severe SOS (SOS/MOD) and non-severe SOS (SOS/no-MOD) were classified according to clinical evidence for MOD in the database.Of the 5,418 patients with a discharge diagnosis of HSCT, 291 had SOS, with 134 categorized as SOS/MOD and 157 as SOS/no-MOD. The remaining 5,127 patients had HSCT without SOS. Overall SOS incidence was 5.4%, with 46% having evidence of MOD. Distribution of age, gender, and race were similar between the SOS cohorts and non-SOS patients. After controlling for hospital profile and admission characteristics, demographics, and clinical characteristics, the adjusted mean LOS was 31.0 days in SOS/MOD compared to 23.9 days in the non-SOS cohort (medians = 26.9 days vs 20.8 days, p .001). The adjusted mean cost of SOS/MOD patients was $140,653, which was $41,702 higher than the non-SOS cohort (medians = $105,749 vs $74,395, p .001). An almost 6-fold increased odds of inpatient mortality was associated with SOS/MOD compared to the non-SOS cohort (odds ratio = 5.88; 95% CI = 3.45-10.33).Limitations of retrospective observational studies apply, since the study was not randomized. Definition for SOS was based on ICD-9 diagnosis codes from a hospital administrative database and reliant on completeness and accuracy of coding.Analysis of real-world data shows that SOS/MOD is associated with significant increases in healthcare utilization, costs, and inpatient mortality.

Rationale, aims and objectives We describe catheter complications and outcomes in patients who received home parenteral nutrition (HPN) therapy. Methods Retrospective chart data were obtained from Boston Home Infusion agency that provided HPN therapy to 212 patients [International Classification of Diseases, 9th revision (ICD-9) codes: gastrointestinal (GI)-related disorders and oncology] between 1 January 2005 and 30 September 2011. Results Of the 163 patients who represented 19 104 home-catheter days, 19 (11.7%) patients experienced 25 catheter complications (CCs; 12 occlusions, 11 central line-associated bloodstream infections, one thrombosis and one line dislodgment). The overall CC rate was 1.30 per 1000 peripherally inserted central catheter (PICC)-line days. The mean number of PICC-line days (278.7 ± 335.0 vs. 95.9 ± 154.0) and patients with at least one hospital admission were significantly higher for patients with one or more CCs compared with patients with no CCs (P

Introduction Hepatic VOD/SOS is a progressive, potentially life-threatening complication of HSCT conditioning or of nontransplant chemotherapy. Without treatment, VOD/SOS with MOD (renal and/or pulmonary dysfunction) may be associated with >80% mortality. Defibrotide (DF) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States and Canada, and to treat severe hepatic VOD/SOS post-HSCT in patients aged >1 month in the European Union. The current analysis evaluates the cost-effectiveness of DF vs best supportive care (BSC) in Canada in patients with VOD/SOS with MOD post-HSCT. Methods A Markov cost-utility model, with an acute phase and a long-term phase, with a lifetime horizon, was adapted to reflect Canadian experience regarding epidemiology, management costs, and survival expectancy; only direct medical costs were included. In the acute phase, transition probabilities were based on endpoints of Day +100 survival and complete response (CR) from a phase 3 trial. The model included 4 health states: severe VOD/SOS, CR, survival, and death. Survival in the long-term phase was extrapolated using data from the literature. Hospital costs were calculated by taking the difference in time to CR in each arm in order to estimate the expected difference in hospital days between the BSC and DF arms. The severe VOD/SOS utility value was assumed to be the same as acute liver failure and end-stage liver disease scores (0.208), and the utility for CR was set to the age-matched general population. Costs and outcomes were discounted at 1.5% per year according to government guidance. Health effects were primarily expressed in terms of quality adjusted life years (QALYs). Results The difference in estimated costs between DF and BSC was $27,396 Canadian (Table). There was a 1.5 QALY increase for DF vs BSC. The incremental cost-effectiveness ratio (ICER; cost per QALY gained) was $17,724. In the probabilistic sensitivity analysis, for willingness to pay of $30,000 and $50,000 per QALY gained, the probabilities of DF being cost-effective were 85.6% and 100%, respectively, (Figure). Conclusions These results suggest that DF treatment for VOD/SOS with MOD is a cost-effective use of health resources in Canada, with an estimated ICER vs BSC below the accepted threshold for willingness to pay. Limitations include longer-term extrapolation of clinical trial data and assumptions about resource utilization patterns. Results were driven by estimates of more rapid recovery, reduced length of stay, and improved Day +100 survival in DF-treated patients. Results were supported by the sensitivity analysis. Support Jazz Pharmaceuticals.

Purpose: To estimate the risk–benefit trade-off of a pediatric-inspired regimen versus hyperfractionated cyclophosphamide, vincristine, doxorubicin, and dexamethasone (hyper-CVAD) for first-line treatment of adolescents/young adult (AYA; ages 16–39 years) patients with Philadelphia-negative acute lymphoblastic leukemia. Methods: Patient outcomes were simulated using a 6-state Markov model, including complete response (CR), no CR, first relapse, second CR, second relapse, and death. A Weibull distribution was fit to the progression-free survival curve of hyper-CVAD–treated AYA patients from a single-center study, and comparable patient data from a retrospective study of pediatric regimen–treated AYA patients were utilized to estimate a relative progression difference (hazard ratio = 0.51) and model survival differences. Health-state utilities were estimated based on treatment stage, with an assumption that the pediatric protocol had 0.10 disutility compared with hyper-CVAD before the maintenance phase of treatment. Total life-years and quality-adjusted life-years (QALYs) were compared between treatment protocols at 1, 5, and 10 years, with additional probabilistic sensitivity analyses. Results: Treatment with the pediatric-inspired protocol was associated with a 0.04 increase in life-years, but a 0.01 decrease in QALYs at 1 year. By years 5 and 10, the pediatric-inspired protocol resulted in 0.18 and 0.24 increase in life-years and 0.25 and 0.32 increase in QALYs, respectively, relative to hyper-CVAD. The lower quality of life associated with the induction and intensification phases of pediatric treatment was offset by more favorable progression-free survival and overall survival relative to hyper-CVAD. Conclusions: Our exploratory analysis suggests that, compared with hyper-CVAD, pediatric-inspired protocols may increase life-years throughout treatment stages and QALYs in the long term.

Introduction The present post hoc analysis was designed to evaluate health-related quality of life (HRQoL) using the 36-item Short Form Health Status Survey (SF-36) during an 8-week trial of sodium oxybate (SXB). Methods SF-36 was assessed in a phase 3 placebo-controlled trial in patients with narcolepsy (N = 228) randomized to placebo or SXB in doses of 4.5, 6, or 9 g nightly for 8 weeks. Changes from baseline in SF-36 (last observation carried forward) were compared between SXB and placebo, and effect sizes (ES) were estimated. Results Baseline SF-36 values were lower than normative values for the US general population. After 8 weeks of treatment, mean (±standard deviation) improvement from baseline on the Physical Component Summary (PCS) was significantly greater with SXB 9 g/night than placebo (6.3 ± 9.1 vs. 1.5 ± 6.2; p = 0.005), with moderate ES; no significant difference was found between the SXB and placebo groups on the Mental Component Summary. SXB 9 g/night resulted in significantly (p

To evaluate the burden of narcolepsy--with respect to psychiatric comorbidities, Health-Related Quality of Life (HRQoL), direct costs for healthcare resource utilization, and indirect costs for reported work loss-through comparison of patients to matched controls.This analysis was conducted on data from the 2011, 2012, and 2013 US National Health and Wellness Survey (NHWS; 2011 NHWS n = 75,000, 2012 NHWS n = 71,157, and 2013 NHWS n = 75,000). Patients who reported a narcolepsy diagnosis (n = 437) were matched 1:2 with controls (n = 874) on age, sex, race/ethnicity, marital status, education, household income, body mass index, smoking status, alcohol use, exercise, and physical comorbidity. Chi-square tests and one-way analyses of variance were used to assess whether the narcolepsy and control groups differed on psychiatric comorbidities, HRQoL, labor force participation, work productivity, and healthcare resource utilization.Patients with narcolepsy, in comparison to matched controls, reported substantially (two to four times) greater psychiatric comorbidity, HRQoL impairment, prevalence of long-term disability, absenteeism, and presenteeism, and greater resource use in the past 6 mo as indicated by higher mean number of hospitalizations, emergency department visits, traditional healthcare professional visits, neurologist visits, and psychiatrist visits (each p0.05).These population-based data suggest that a narcolepsy diagnosis is associated with substantial adverse impact on mental health, HRQoL, and key economic burdens that include work impairment, resource use, and both direct and indirect costs. Although this study is cross-sectional, the results highlight the magnitude of the potential opportunity to improve mental health, lower costs, and augment work-related productivity through effective assessment and treatment of narcolepsy.

Background and Purpose— Primary stroke centers (PSC) have demonstrated improved survival in patients with acute ischemic stroke (AIS). The objective of this study was to evaluate the cost-effectiveness of treating AIS patients in a PSC compared with a nonPSC hospital setting. Methods— We developed a decision analytic model to project the lifetime outcomes and costs of 2 hypothetical cohorts of 75 AIS patients. Clinical data were derived from a recent observational study comparing PSC- and nonPSC-admitted patients, clinical trials, longitudinal cohort studies, and health state preference studies. Cost data were based on Medicare reimbursement and other published sources. We used a healthcare payer perspective, and the primary outcomes were incremental life expectancy, quality-adjusted life years, and healthcare costs. We performed sensitivity and scenario analyses to evaluate uncertainty in the results. Results— Admission to a PSC resulted in a gain of 0.22 years of life (95% credible range [CR], 0.12–0.33) and 0.15 quality-adjusted life years (95% CR, 0.08–0.23) per patient, at a cost of $3600 (95% CR, $2400–$5000) per patient, compared with admission to a nonPSC hospital. The incremental cost/quality-adjusted life year gained was $24 000, and all probabilistic simulation results were below the $100 000/quality-adjusted life year threshold. In scenario analyses accounting for as few as 7 and as many as 500 AIS patients/year per PSC, cost-effectiveness improved as the number of AIS patients admitted per year increased. Conclusions— Our study indicates that care at a PSC for patients with AIS is cost-effective and improves outcomes across a wide range of possible scenarios.

Background: A central goal of treatment for high-risk AML is enabling patients to receive HCT. CPX-351 is a dual-drug liposomal encapsulation of cytarabine and daunorubicin at a synergistic ratio. A large randomized, open-label, multicenter, phase 3 trial demonstrated superior outcomes, including significantly longer overall survival and a larger fraction of patients reaching HCT, for CPX-351 versus conventional cytarabine/daunorubicin (7+3 regimen) in patients aged 60 to 75 years with newly diagnosed therapy-related AML (tAML) or AML with myelodysplasia-related changes (AML-MRC; Lancet JE, et al. J Clin Oncol. 2018). In order to estimate the cost-effectiveness of treatments for AML, and for CPX-351 in particular, it is necessary to extrapolate survival of patients undergoing HCT to the long-term. The objective of this analysis was to assess the impact of different estimates of post-HCT mortality on cost-effectiveness of CPX-351. Methods: An existing economic model of CPX-351 versus 7+3 for the treatment of tAML or AML-MRC was used to project lifetime health and cost outcomes. The modeled population included 30% patients Results: In the base case with different SMR values by age, the model yielded a predicted ICER value of $111,841/QALY in the overall cohort, which compares favorably to the typical $150,000/QALY threshold (Bae 2014) for good value care in the United States. Using the same estimates of SMR in all patients yielded ICER values of $125,280/QALY and $151,793/QALY for SMR values of 2.25 and 4.0, respectively. Assuming no excess mortality post-HCT relative to the general population, using an SMR of 1.0, resulted in modest improvements in cost-effectiveness (ICER = $102,298/QALY). Conclusions: CPX-351 is a cost-effective option for the treatment of patients with tAML or AML-MRC when accounting for potentially increased mortality following HCT. Disclosures Kansal: Jazz Pharmaceuticals: Consultancy. Reifsnider:Jazz Pharmaceuticals: Consultancy. Todorova:Jazz Pharmaceuticals: Employment, Equity Ownership. Coughlan:Jazz Pharmaceuticals: Consultancy. Villa:Jazz Pharmaceuticals: Employment, Equity Ownership, Other: Stock and stock options.

Introduction Hepatic VOD/SOS is a progressive, potentially life-threatening complication of conditioning for HSCT or of nontransplant-associated chemotherapy. Without treatment VOD/SOS with MOD (eg, renal and/or pulmonary dysfunction) may be associated with >80% mortality. Defibrotide (DF) is approved to treat hepatic VOD/SOS with renal and/or pulmonary dysfunction post-HSCT in the United States and Canada, and to treat severe hepatic VOD/SOS post-HSCT in patients aged >1 month in the European Union. The current analysis evaluates the cost-effectiveness of DF vs best supportive care (BSC) in Canada in patients with VOD/SOS with MOD post-HSCT. Methods A previously reported global Markov cost-utility model was adapted to reflect Canadian sources of care with regard to epidemiology, management costs, and survival expectancy; only direct medical costs were included. The model included an acute phase and a long-term phase, with a lifetime horizon. Transition probabilities in the acute phase were based on Phase 3 (Richardson et al, 2016) endpoints of Day +100 survival and complete response (CR). The model included 4 health states: severe VOD/SOS, CR, survival, and death. Survival in the long-term phase was extrapolated using Remberger et al (2011) and Ashton et al (2014). Hospital costs were calculated by taking the difference in time to CR in each arm in order to estimate the expected difference in hospital days between the BSC and DF arms. The severe VOD/SOS utility value was assumed to be the same as acute liver failure and end-stage liver disease scores (0.208), and the utility for CR was set to the age-matched general population. Costs and outcomes were discounted at 1.5% per year according to government guidance. Health effects were primarily expressed in terms of quality adjusted life years (QALYs). Results The difference in estimated costs between DF and BSC was $27,396 (Canadian dollars; Table). DF showed an increase in 1.5 QALYs versus BSC. The incremental cost-effectiveness ratio (ICER; cost per QALY gained) was $17,724. In the probabilistic sensitivity analysis, for willingness to pay of $30,000 and $50,000 per QALY gained, the probabilities of DF being cost-effective were 85.6% and 100%, respectively (Figure). Conclusion These results suggest that DF treatment for VOD/SOS with MOD represents cost-effective use of health resources in Canada, with an ICER estimate compared with BSC that was below the accepted willingness to pay threshold. Limitations of the analysis include longer-term extrapolation of clinical trial data and assumptions about resource utilization patterns. Results were driven by estimates of more rapid recovery, reduced length of stay, and improved Day +100 survival in DF-treated patients. Results were supported by the sensitivity analysis. Support: Jazz Pharmaceuticals. Disclosures Belsey: Jazz Pharmaceuticals: Consultancy. Kemadjou:Jazz Pharmaceuticals: Consultancy. Isaila:Jazz Pharmaceuticals: Employment, Other: Stock and stock options. Villa:Jazz Pharmaceuticals: Employment, Equity Ownership, Other: Stock and stock options.

Background VOD/SOS is an unpredictable, potentially life-threatening complication of conditioning regimens for HSCT or of chemotherapy without HSCT. VOD/SOS with multi-organ dysfunction (MOD; typically defined as renal and/or pulmonary dysfunction) may be associated with survival of 20%-30% (Coppell et al. Biol Blood Marrow Transplant. 2010;16[2]:157-168. Richardson et al. Blood. 2016;127[13]:1656-1665. Strouse et al. Biol Blood Marrow Transplant . 2016;22[7]:1306-1312). For adult and pediatric patients, defibrotide (25 mg/kg/day in 4 divided doses) is approved to treat hepatic VOD/SOS with renal or pulmonary dysfunction post-HSCT in the United States, and to treat severe hepatic VOD/SOS post-HSCT in patients over 1 month of age in the European Union. The overall efficacy and safety of defibrotide treatment in adult and pediatric patients with VOD/SOS have been reported in controlled and uncontrolled studies, including a large expanded-access study and a historically controlled phase 3 trial. Reported here is a pooled Day +100 survival analysis of available data from defibrotide studies in patients with VOD/SOS with or without MOD. Methods A title or abstract search of PubMed, Embase, and relevant 2017 congresses was performed for "defibrotide" in the treatment of VOD/SOS. Prospective and retrospective studies, post-HSCT and post-chemotherapy without HSCT, were included in the analysis, but case reports of fewer than 10 patients were excluded. Citations were reviewed for relevance to this analysis, and the resulting studies were divided into subgroups to analyze data for patients with and without MOD. A random effects model was used for pooling data for efficacy. Interstudy heterogeneity was assessed with Cochran9s Q-test. The percentage of total variation across studies due to heterogeneity was evaluated by the I2 measure. Safety was also evaluated. Results The literature review identified 606 publications and abstracts; 581 were excluded for relevance. This yielded 25 records (16 manuscripts, 9 abstracts), which were further refined by exclusion of 8 reports that were post hoc analyses, reviews, duplicates, case reports, or a prevention trial. Of the remaining 17, 10 records included data for 2239 patients, nearly all of whom were treated with ~25 mg/kg/day, including 6 that specified patients with MOD (1177 patients), 2 of which also specified patients without MOD (495 patients), and 4 where MOD status was not reported (Table). The other 7/17 studies included off-label dosages or the dosage was not reported. Estimated Day +100 survival for patients receiving defibrotide ~25 mg/kg/day across all studies was 56% (95% confidence interval [CI], 49%-62%; Figure). Pooled subgroup results showed estimated Day +100 survival rates of 42% (95% CI, 34%-49%) in the MOD subgroup; and 66% (95% CI, 61%-70%) in the no MOD subgroup (Figure). Safety results were not pooled for these studies due to differences in safety reporting methodology, but results of individual studies were generally consistent with the safety profile found in the phase 3 historically controlled trial in VOD/SOS patients with MOD (Richardson et al. Blood. 2016;127[13]:1656-1665). The trial reported that all but 1 of the 102 defibrotide treated patients and all 32 HC patients experienced ≥1 AE. Hypotension was the most frequent AE (39% for defibrotide, 50% for controls), and common hemorrhagic AEs, which included pulmonary alveolar and gastrointestinal hemorrhage, occurred in 64% of defibrotide-treated patients and 75% of controls. Related AEs in the defibrotide arm included hemorrhagic events and hypotension. Conclusion In this pooled analysis of studies of defibrotide given primarily at the approved dose of 25 mg/kg/day for the treatment of VOD/SOS, estimated Day +100 survival was 56% in the 2239 patients with or without MOD. As expected, survival in patients with VOD/SOS without MOD was greater at Day +100 (66%) than in patients with VOD/SOS with MOD (42%). Safety results in the individual studies were generally consistent with the known safety profile of defibrotide. Support: Jazz Pharmaceuticals. Disclosures Richardson: Takeda: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Jazz Pharmaceuticals: Consultancy, Membership on an entity9s Board of Directors or advisory committees, Research Funding; Oncopeptides AB: Membership on an entity9s Board of Directors or advisory committees. Aggarwal: Novel Health Strategies: Employment, Other: Funding from Jazz Pharmaceuticals. Topaloglu: Novel Health Strategies: Employment, Other: Funding from Jazz Pharmaceuticals. Villa: Jazz Pharmaceuticals: Employment, Other: stock options. Corbacioglu: Jazz Pharmaceuticals: Consultancy, Honoraria.