Health Care Resource Utilization and Total Costs of Care for Adult Patients With Relapsed or Refractory Acute Lymphoblastic Leukemia in the United States: A Retrospective Claims Analysis.

PURPOSE: Although immunotherapies such as blinatumomab and inotuzumab have led to improved outcomes, financial burden and health resource utilization (HRU) have increased for adult patients with relapsed or refractory B-cell acute lymphoblastic leukemia (R/R B-ALL). This study assessed real-world HRU and costs of care among adult patients with R/R B-ALL by line of therapy (LoT) in the United States. METHODS: We selected patients from the MarketScanⓇ Database (January 1, 2016 through December 31, 2020) as follows: ≥1 claims of ALL-indicated first-line (1L) therapies, ≥1 diagnosis of ALL before the index date (1L initiation date), 6-month continuous enrollment before the index date, second-line (2L) therapy initiation, ≥18 years old at 2L, no clinical trial enrollment, no diagnosis of other forms of non-Hodgkin's lymphoma, and no claim for daratumumab or nelarabine during the study period. Outcome measures included claim-based time to next treatment (TTNT), all-cause and adverse event (AE)-related HRU, and all-cause and AE-related costs. FINDINGS: The R/R B-ALL cohort (N = 203) was 60% male, median age of 41 years, and median Charlson Comorbidity Index score of 3.0. Mean (SD) follow-up was 17.8 (11.8) months. Of those who received 2L, 55.7% (113/203) required 3L, and 15% (30/203) initiated 4L+. Patients relapsed quickly, with a median TTNT of 170 days, 169 days, and 205 days for 2L, 3L, and 4L+, respectively. Hospitalization rates were high across each LoT (2L, 88%; 3L, 73%; 4L+, 73%), and the mean (SD) inpatient length of stay increased by LoT as follows: 8.6 (6.8) days for 2L, 10.6 (13.3) for 3L, and 11.6 (13.6) for 4L+. Mean (SD) overall costs were substantial within each LoT at $513,279 ($599,209), $340,419 ($333,555), and $390,327 ($332,068) for 2L, 3L, and 4L+, respectively. The mean (SD) overall/per-patient-per-month AE-related costs were $358,676 ($497,998) for 2L, $202,621 ($272,788) for 3L, and $210,539 ($267,814) for 4L+. Among those receiving blinatumomab or inotuzumab within each LoT, the mean (SD) total costs were $566,373 ($621,179), $498,070 ($376,260), and $512,908 ($159,525) for 2L, 3L, and 4L+, respectively. IMPLICATIONS: These findings suggest that adult patients with R/R B-ALL relapse frequently with standard of care and incur a substantial HRU and cost burden with each LoT. Those treated with blinatumomab or inotuzumab incurred higher total costs within each LoT compared with the overall R/R B-ALL cohort. Alternative therapies with longer duration of remission are urgently needed, and HRU should be considered for future studies examining the optimal sequencing of therapy.

Health resource utilization and costs of care for adult patients with relapsed or refractory mantle cell lymphoma in the United States: a retrospective claims analysis.

OBJECTIVES: We assessed real-world healthcare resource utilization (HRU) and costs among US patients with relapsed or refractory mantle cell lymphoma (R/R MCL) by line of therapy (LoT). METHODS: We selected patients from MarketScan® (1/1/2016-12/31/2020): ≥1 claims of MCL-indicated first line (1L) therapies, ≥1 diagnoses of MCL pre-index date (1L initiation date), ≥6-month continuous enrollment pre-index date, second line (2L) therapy initiation, ≥18 years old at 2L, and no clinical trial enrollment. Outcomes included time to next treatment (TTNT), all-cause HRU, and costs. RESULTS: The cohort (N = 142) was 77.5% male, aged 62 years (median). Sixty-six percent and 23% advanced to 3L and 4L+, respectively. Mean (median) TTNT was 9.7 (5.9), 9.3 (5.0), and 6.3 (4.2) months for 2L, 3L, and 4L+, respectively. Mean (median) per patient per month (PPPM) costs were $29,999 ($21,313), $29,352 ($20,033), and $30,633 ($23,662) for 2L, 3L, and 4L+, respectively. Among those who received Bruton tyrosine kinase inhibitors, mean (median) PPPM costs were $24,702 ($17,203), $31,801 ($20,363), and $36,710 ($25,899) for 2L, 3L, and 4L+, respectively. CONCLUSIONS: During the period ending in 2020, patients relapsed frequently, incurring high HRU and costs across LoTs. More effective treatments with long-lasting remissions in R/R MCL may reduce healthcare burden.

Mantle cell lymphoma is a rare blood cancer of white blood cells. This type of cancer can be hard to treat, even with new treatments. In about 15% to 20% of people, the cancer will not get better or will come back within 2 years of starting treatment. When this happens, there are few good options for treatments that work. Using medical claims data, we looked at healthcare use and costs among US patients with mantle cell lymphoma that came back after treatment or did not respond to treatment. We found 142 patients who met the study criteria. Of these, 77.5% were men with a median age of 62 years. Sixty-six percent got a third of the treatment and 23% got a fourth treatment or more. The time until the next treatment was about 9­10 months for patients who got a second and third treatments.. It was about 6 months for people who got a fourth or more treatment. The average monthly cost of treatment was about $30,000 for those receiving a second or fourth or more treatment. It was slightly less for those who got a third treatment. For those who got Bruton's tyrosine kinase inhibitors, the monthly costs went up with each treatment they needed. Overall, we found that during the study period, patients with mantle cell lymphoma worsened quickly, received multiple treatments, and had high costs of care. Better treatments that work longer are needed.

Correlation between Echocardiographic Diastolic Parameters and Invasive Measurements of Left Ventricular Filling Pressure in Patients with Takotsubo Cardiomyopathy.

BACKGROUND: The extent of diastolic dysfunction is of clinical importance in the risk stratification and management of patients with Takotsubo cardiomyopathy (TC). Standard echocardiographic indices of diastolic dysfunction have robust predictive ability in assorted disease states, but have not been validated in TC. The aim of this study was to compare Doppler metrics of diastolic function against catheterization-measured filling pressures in TC. METHODS: Patients with TC who met inclusion and exclusion criteria were evaluated using echocardiography and catheterization performed within 24 hours. Both left ventricular (LV) end-diastolic pressure and LV pre-A diastolic pressure were obtained from catheterization tracings. The echocardiographic parameters for diastolic function were extracted using the American Society of Echocardiography recommendations and a previously validated regression equation for mean left atrial pressure (mLAP). RESULTS: A total of 51 patients with TC were included. Patients were predominantly women (72.5%), with a mean age of 58 ± 13 years and a mean ejection fraction of 24 ± 10 %. E/e' ratio (septal, average, and lateral) and calculated mLAP correlated positively with catheterization LV pre-A, with fair to moderate correlation (coefficient range, 0.38-0.44). The t-test mean difference between LV pre-A pressure and calculated mLAP was 0.77 ± 7.34 mm Hg (95% CI, ±14.68 mm Hg) suggesting inconsistent measures. mLAP also exhibited poor diagnostic ability to discriminate elevated LV pre-A diastolic pressure, with an area under the receiver operating characteristic curve of 0.69 (95% CI, 0.50-0.88). CONCLUSIONS: Commonly used echocardiographic parameters for diastolic function demonstrated less-than-optimal correlation, with poor sensitivity and specificity, compared with invasively measured LV end-diastolic pressure or LV pre-A wave diastolic pressure in patients with TC. Precise characterization of LV filling pressure in patients with TC using contemporary noninvasive echocardiographic parameters appears challenging. Invasive measurements of filling pressure should remain the gold standard for optimal risk stratification and management of patients with TC.

Real-world study of multiple naloxone administration for opioid overdose reversal among bystanders.

BACKGROUND: The increasing prevalence of highly potent, illicitly manufactured fentanyl and its analogues (IMF) in the USA is exacerbating the opioid epidemic which has worsened during the COVID-19 pandemic. Narcan® (naloxone HCl) Nasal Spray has been approved by the US Food and Drug Administration as a treatment for opioid-related overdoses. Due to the high potency of IMF, multiple naloxone administrations (MNA) may be needed per overdose event. It is essential to determine the patterns of naloxone use, including MNA, and preferences among bystanders who have used naloxone for opioid overdose reversal. METHODS: A cross-sectional web-based survey was administered to 125 adult US residents who administered 4 mg Narcan® Nasal Spray during an opioid overdose in the past year. The survey asked about the most recent overdose event, the use of Narcan® during the event and the associated withdrawal symptoms, and participant preferences regarding dosages of naloxone nasal spray. An open-ended voice survey was completed by 35 participants. RESULTS: Participants were mostly female (70%) and white (78%), while reported overdose events most frequently occurred in people who were males (54%) and white (86%). Most events (95%) were successfully reversed, with 78% using ≥ 2 doses and 30% using ≥ 3 doses of Narcan® Nasal Spray. Over 90% were worried that 1 Narcan® box may not be enough for a successful future reversal. Reported withdrawal symptoms were similar in overdose events where 1 versus ≥ 2 sprays were given. Eighty-six percent of participants reported more confidence in an 8 mg versus a 4 mg naloxone nasal spray and 77% reported a stronger preference for 8 mg over 4 mg. CONCLUSIONS: MNA occurred in most overdose events, often involving more sprays than are provided in one Narcan® nasal spray box, and participants predominantly expressed having a stronger preference for and confidence in an 8 mg compared to a 4 mg nasal spray. This suggests the need and desire for a higher dose naloxone nasal spray formulation option. Given that bystanders may be the first to administer naloxone to someone experiencing an opioid overdose, ensuring access to an adequate naloxone supply is critical in addressing the opioid overdose epidemic.

Real-world study of multiple naloxone administrations for opioid overdose reversal among emergency medical service providers.

Background: The increasing rates of highly potent, illicit synthetic opioids (i.e., fentanyl) in the US is exacerbating the ongoing opioid epidemic. Multiple naloxone administrations (MNA) may be required to successfully reverse opioid overdoses. We conducted a real-world study to assess the rate of MNA for opioid overdose and identify factors associated with MNA. Methods: Data from the 2015-2020 National Emergency Medical Services Information System was examined to determine trends in events requiring MNA. Logistic regression analysis was performed to determine factors associated with MNA. Results: The percentage of individuals receiving MNA increased from 18.4% in 2015 to 28.4% in 2020. The odds of an event requiring MNA significantly increased by 11% annually. The adjusted odds ratio (aOR) for MNA were greatest among males, when advanced life support (ALS) was provided, and when the dispatch complaint indicated there was a drug poisoning event. Conclusions: The 54% increase in MNA since 2015 parallels the rise in overdose deaths attributable to synthetic opioids. This growth is visible in all regions of the country, including the West, where the prevalence of illicitly manufactured synthetic opioids is intensifying. Given this phenomenon, higher naloxone formulations may fulfill an unmet need in addressing the opioid overdose crisis.

The need for multiple naloxone administrations for opioid overdose reversals: A review of the literature.

Background A growing challenge in the opioid epidemic is the rise of highly potent synthetic opioids, (i.e., illicitly manufactured fentanyl [IMF]) entering the US non-prescription opioid market. Successful reversal may require multiple doses of naloxone, the standard of care for opioid overdose. We conducted a narrative literature review to summarize the rates of multiple naloxone administrations (MNA) for opioid overdose reversal. Methods: A MEDLINE search was conducted for published articles using MESH search terms: opioid overdose, naloxone and multiple naloxone administration. Of the 2,101 studies identified, articles meeting inclusion/exclusion criteria were reviewed, categorized by primary and secondary outcomes of interest and summarized by data source and study design. Results: A total of 24 articles meeting eligibility criteria were included. Among EMS-based studies, MNA rates ranged from 9% to 53%; in general, bystander-reported studies were notably higher, from 16% to 89%. Variation in study design, data sources, year and geography, may have contributed to these ranges. Three studies that included longitudinal results reported a significant percent increase between 26% and 43% in annual MNA rates or a significant increase in mean naloxone doses over time (p < .001). Conclusions: This summary found that multiple naloxone administrations during opioid overdose encounters vary widely, have occurred in up to 89% of all opioid overdoses, and have significantly increased over time. Higher naloxone formulations may fulfill an unmet need in opioid overdose reversals, given the rising rates of overdoses involving IMF. Further studies are needed to gain a better understanding of MNA during opioid overdose encounters, particularly across a wider geographic region in the US in order to inform continuing efforts to combat the opioid epidemic.

Impact of an active hemostatic product treatment approach on bleeding-related complications and hospital costs among inpatient surgeries in the United States.

AIMS: To examine the impact of active only (A) vs. combined passive and active (PA) hemostatic products on bleeding-related complications and costs among inpatient surgeries. MATERIALS AND METHODS: This retrospective analysis of the US Premier Hospital Database included patients who had an inpatient procedure within a specialty of interest (cardiac, vascular, noncardiac thoracic, solid organ, general, reproductive organ, knee/hip replacement, spinal, or neurosurgery) that utilized a hemostatic product from January 1, 2017 to December 31, 2018. Patients were directly matched 1:1 on surgery code, age categories, and Charlson Comorbidity Index score categories into A or PA cohorts. Unadjusted and adjusted rates of bleeding-related complications, length of stay (LOS) and total hospital costs were compared between cohorts. RESULTS: A total of 5,934 cardiac, 7,986 vascular, 2,042 noncardiac thoracic, 8,260 solid organ, 9,502 general, 4,616 reproductive organ, 2,758 knee/hip replacement, 42,648 spinal, and 10,716 neuro surgeries were included. Higher unadjusted rates of bleeding-related complications and greater LOS and total hospital costs were observed in the PA cohort vs A cohort across all specialties. The adjusted odds of bleeding complications were significantly higher in solid organ, general, knee/hip replacement, reproductive organ, and spinal surgery (OR range = 1.17-2.48, all p <.01), while incremental costs per hospitalization associated with PA (vs A) controlling for covariates were higher across all specialties (ratio range = 1.04-1.22, all p <.05). LIMITATIONS: This analysis focused on patients who had a single surgery during the hospital encounter; results may not be generalizable to patients undergoing multiple surgeries. CONCLUSIONS: The use of A hemostatic products was associated with significantly lower rates of bleeding-related complications and total hospital costs compared to PA hemostatic products. A treatment approach which considers bleeding-related factors including severity, risk and variability based on surgery type may provide guidance in choosing the optimal hemostatic product to improve surgical outcomes and costs.

Fresh osteochondral allograft transplantation (FOCAT) for definitive management of a 198 square millimeter osteochondral lesion of the talus (OLT): A case report.

An osteochondral lesion of the talus (OLT) is an idiopathic acquired lesion of the subchondral bone that can lead to debilitating sequelae. The causes of OLT's are still debatable, however, most agree that the etiology is repetitive microtrauma associated with vascular impairment. OLTs are most commonly described in the medial portion of the talus, while lateral involvement is less frequent. If not properly recognized and treated, an OLT may lead to numerous secondary conditions including premature osteoarthritis and functional limitations of the ankle joint. Multiple surgical and non-surgical treatment modalities have been described with varying results. Treatments are usually guided by the patients age, onset of symptoms, severity, and the disease stage according to the Berndt and Harty classification. Recent literature recommends curettage, drilling, or microfracture techniques for lesions which are no larger than 15mm in diameter and no deeper than 7mm. On the other hand, for large lesions or lesions that failed from primary bone marrow stimulation, surgery should be considered for autologous chondrocyte implantation (ACI), osteochondral autograft transplantation (OATs or mosaicplasty), or osteochondral allograft transplantation [1]. This case study examines surgical treatment of an extensive OLT in a 53 year old man who suffered with continuous ankle pain for over 10 years, misdiagnosed as ankle joint arthritis. Level of clinical evidence: Level of evidence 4.

Cost savings with hemin versus givosiran for the treatment of patients with acute intermittent porphyria (AIP).

OBJECTIVE: Since 1983, hemin has been FDA-approved for acute intermittent porphyria (AIP) attacks. In 2019, FDA approved givosiran for the treatment of adults with acute hepatic porphyria. The objective of this research was to estimate and compare the total cost of AIP-related healthcare for patients treated with hemin or givosiran. METHODS: A microsimulation cost model was developed to estimate the annual economic impact of hemin versus givosiran treatment for patients with AIP from the U.S. healthcare payer perspective. Hemin treatment costs were calculated from the Hemin Shipment Data in which patients were defined as receiving acute attack treatment or prophylaxis treatment based on shipment patterns. Three separate hemin subpopulations were considered: one attack per year, multiple attacks per year, and hemin prophylaxis. Treatment costs for givosiran (with hemin for acute attacks) were simulated based on Phase III trial efficacy results applied to individual treatment histories in the Hemin Shipment Data. Other healthcare utilization was also considered. Outcomes were annualized and expenditures inflated to 2019. RESULTS: For all patients with AIP, the average annual total cost of care with hemin was 78% lower (difference = $482,113; 95% CI=$373,638-$594,778) than the average annual total cost of care with givosiran. Average annual total cost of care with hemin was between 46% and 92% lower than givosiran for the three hemin subpopulations: one attack per year (difference = $545,219; 95% CI=$436,584-$657,239), multiple attacks per year (difference = $459,366; 95% CI=$350,291-$574,403), and hemin prophylaxis (difference = $311,950; 95% CI=$191,898-$435,893). Cost savings with hemin were robust to one-way and probabilistic sensitivity as well as scenario analyses. CONCLUSIONS: Hemin is expected to provide cost savings compared to givosiran for all AIP patients and subpopulations. Lower annual total costs of care with hemin range from $311,950 to $545,219 less depending on whether the patient uses hemin prophylactically or for acute treatment attacks.

Real-world annualized healthcare utilization and expenditures among insured US patients with acute intermittent porphyria (AIP) treated with hemin.

Background and aims: Patients with acute intermittent porphyria (AIP) may suffer from acute non-specific attacks that often result in hospitalizations or emergency room (ER) visits. Prior to the recent approval of givosiran (November 2019), hemin was the only FDA-approved therapy for AIP attacks in the US. Our aim was to estimate the annual healthcare utilization and expenditures for AIP patients treated with hemin using real-world data.Methods: Patients with ≥1 hemin claim and confirmed AIP diagnosis - 1 inpatient claim or 2 outpatient claims ≥30 d apart for AIP (2015-2017) or acute porphyria (prior to 2015) - were identified in MarketScan administrative claims dataset between 2007 and 2017. Continuous enrolment for ≥6 months from confirmed diagnosis was required. A secondary analysis ("active disease population") limited the sample to adult patients with ≥3 attacks or 10 months of prophylactic use of hemin within a 12-month pre-index period. AIP-related care was defined by hemin use during an attack (daily glucose and/or hemin use) or prophylaxis (non-attack hemin use). Outcomes were annualized and expenditures were inflated to 2017.Results: Across 10 years, patients with a confirmed AIP diagnosis (N = 8,877) and ≥1 hemin claim (N = 164) were restricted by ≥6 months continuous follow-up (N = 139). AIP patients were mostly female (N = 112; 81%), had median age of 40 and 3 years average follow-up. Annualized average total expenditures for AIP-related care were $113,477. Annualized average all-cause (any diagnosis) hospitalizations were statistically significantly lower for patients treated with hemin prophylaxis vs. acute treatment (1.0 vs. 2.1; p < .001). In the secondary analysis (N = 27), annualized average total expenditures for AIP-related care were higher ($187,480).Conclusions: For AIP patients treated with hemin, patients treated for acute attacks may use a greater number of resources compared to patients treated prophylactically.

Cost-consequence analysis of a hemostatic matrix alone or in combination for spine surgery patients.

BACKGROUND: A five-year retrospective database analysis comparing the use of Floseal 1 flowable topical hemostat alone (F) and in combination with gelatin/thrombin (F + G/T) to achieve hemostasis and control surgical bleeding showed higher resource utilization for F + G/T cases relative to F matched pairs during spinal surgery. Lower resource use in the F group was characterized by shorter hospital length of stay and surgical time as well as fewer blood transfusions and less hemostat agent used per surgery. OBJECTIVE: To evaluate the cost-consequence of using F compared to F + G/T in minor, major and severe spinal surgery from the US hospital perspective. METHODS: A cost-consequence model was developed using the US hospital perspective. Model inputs include clinical inputs from the literature, cost inputs (hemostatic matrices, blood product transfusion, hospital stay and operating room time) from the literature, and an analysis of annual spine surgery volume (minor, major and severe) using the 2012 National Inpatient Sample (NIS) database. Costs are reported in 2017 US dollars. One-way and probabilistic sensitivity analyses address sources of variability in the results. RESULTS: A medium-volume hospital (130 spine surgeries per year) using F versus F + G/T for spine surgeries is expected to require 85 less hours of surgical time, 58 fewer hospital days and 7 fewer blood transfusions in addition to hemostat volume savings (F: 1 mL, thrombin: 1994 mL). The cost savings associated with the hospital resources for a medium-volume hospital are expected to be $317,959 (surgical hours = $154,746, hospital days = $125,237, blood transfusions = $19,023, hemostatic agents = $18,953) or $2445 per spine surgery. CONCLUSIONS: The use of F versus F + G/T could lead to annual cost savings for US hospitals performing a low to high volume of spinal surgeries per year.

Systematic literature review of health-related quality of life among aggressive non-Hodgkin lymphoma survivors.

OBJECTIVE: Studies have shown that a proportion of patients with aggressive non-Hodgkin lymphoma (NHL) treated with standard chemotherapy will have long-term life expectancy comparable to those in the age-adjusted general population. This systematic literature review summarizes current literature regarding health-related quality of life (HRQoL) of long-term (≥2 years) survivors of aggressive NHL. METHODS: Electronic databases (without restriction on years) and abstracts from four major oncology and HRQoL conferences from 2014 to 2017 were searched. Studies were included if HRQoL or health utility was assessed at least 2 years after NHL diagnosis. Studies focusing on central nervous system lymphoma, or indolent NHL, were excluded. Results were categorized relative to baseline (improvement, deterioration or no change) and compared to the general population (better, comparable or worse). RESULTS: Fourteen studies met the inclusion criteria. Twelve studies included ≥1 HRQoL instrument, and two measured health utilities using EQ-5D. Half of the studies showed improvement (5/10) and half no change (5/10) in overall HRQoL. Compared to the general population, overall HRQoL was more comparable when assessed at ≥3 years from baseline (3/3 better or comparable) versus assessment at <3 years (2/3 better or comparable). Six studies reported on the physical HRQoL domain with improvement in 4/6 studies and no change in 2/6 studies. CONCLUSIONS: HRQoL of NHL survivors may improve from baseline and becomes more comparable to general population HRQoL with longer survival. Overall HRQoL improvement is driven mostly by improvements in the physical domain.

Cost-effectiveness analysis of a sealing hemostat patch (HEMOPATCH) vs standard of care in cardiac surgery.

BACKGROUND: A recent randomized controlled trial showed that patients undergoing ascending aorta surgery treated with HEMOPATCH to control bleeding had a significantly better hemostasis success rate than with dry or wet gauze compression or similar standard of care (SOC). OBJECTIVE: To compare the cost-effectiveness using two different agents for hemostasis (HEMOPATCH vs dry or wet gauze compression or similar SOC) in cardiac surgery from the European hospital perspective. METHODS: A literature-based cost-effectiveness model estimating average cost per successful hemostasis event was developed based on the hemostasis efficacy difference (HEMOPATCH = 97.6%, SOC = 65.8%, p < .001). Additional clinically significant end-points studied in the trial (blood transfusions and surgical revisions) were also analyzed. It was assumed that each surgery utilized two units of HEMOPATCH (dimensions of 4.5 × 9 cm) and two units of SOC. Product acquisition costs for HEMOPATCH and SOC were included along with outcome-related costs derived from the literature and inflation-adjusted to 2017 EUR and GBP. Results are presented for an average hospital with an annual case load of 574 cardiac surgeries. One-way and probabilistic sensitivity analyses were performed. RESULTS: Considering only product acquisition cost, HEMOPATCH had an incremental cost-effectiveness ratio (ICER) of €1,659, €1,519, €1,623, and £1,725 per hemostasis success when compared to SOC for Italy, Spain, France, and the UK, respectively. However, when considering the cost and potential difference in the frequency of transfusions and revisions compared to SOC, the use of HEMOPATCH was associated with an annual reduction of six revisions and 60 transfusions, improving the ICER to €1,440, €1,222, €1,461, and £1,592, respectively. Sensitivity analysis demonstrated model robustness. CONCLUSIONS: This analysis supports the use of HEMOPATCH over SOC in cardiac surgery in European hospitals to improve hemostasis success rates and potential cost offsets from reduced transfusions, complications, and surgical revisions.