Alzheimer's Disease Linkage to Real-World Evidence (AD-LINE) Study: Linking Claims Data to Phase 3 GRADUATE Study of Gantenerumab.

BACKGROUND: Linking data from clinical trials and real-world claims may improve the robustness of trial data and provide information on the health, economic, and societal impacts of a disease. OBJECTIVE: To report on the feasibility of linking trial data to Medicare claims data in early symptomatic Alzheimer's disease (AD) in the US. DESIGN AND SETTING: Alzheimer's Disease Linkage to Real-World Evidence (AD-LINE) was a noninterventional cohort study that included participants recruited from the GRADUATE program whose trial data were linked to their Medicare claims. PARTICIPANTS: AD-LINE participants were 66 years and older with early symptomatic AD (ie, mild cognitive impairment [MCI] due to AD or mild AD dementia) and were enrolled in the GRADUATE program and a Medicare fee-for-service or Medicare Advantage plan. MEASUREMENTS: The Centers for Medicare and Medicaid Services linked participants' clinical trial identifiers to their Medicare beneficiary identifiers using a deterministic, exact matching process. Demographics and clinical characteristics of the AD-LINE cohort at baseline were collected. Outcomes measured in this study included healthcare resource utilization derived from Medicare claims data. RESULTS: In total, 147 participants across 21 US sites were invited to participate and 111 provided informed consent. Of those, 61 patients had linkable data (ie, Medicare beneficiary identifier), Medicare Parts A/B enrollment, and no health maintenance organization (HMO) enrollment in the year before trial entry. Of the 61 participants whose data were analyzed in this study, 30 had MCI due to AD and 31 had mild AD dementia. Participants in the MCI due to AD group had more healthcare resource utilization on average in the baseline period than those in the mild AD dementia group (29.9 [SD, 20.9] vs 24.5 claims [SD, 12.3]). In an ad hoc analysis, a relatively high concordance (85.3%) was seen between the rates of clinically confirmed AD diagnosis and evidence of AD diagnosis in claims data. CONCLUSION: This linkage process may serve as a proof of concept for researchers interested in linking clinical trial and real-world claims data. The lessons learned from AD-LINE and innovation of data linkage approaches may encourage key stakeholders to link data in the future.

Healthcare resource utilization and associated costs in patients with chronic graft-versus-host disease post allogeneic hematopoietic stem cell transplantation in England: HCRU and associated costs in patients with cGvHD in England.

BACKGROUND: Limited evidence suggests chronic graft-versus-host disease (cGvHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) increases healthcare resource utilization (HCRU) and costs. However, this burden has not been well characterized in England. OBJECTIVE: This study assesses secondary care HCRU and costs for patients following allo HSCT in England with cGvHD and patients who did not develop graft versus-host disease (GvHD). Further stratification was performed among patients who did or did not subsequently receive high-cost therapies for the treatment of cGvHD. STUDY DESIGN: This descriptive, retrospective cohort study used Hospital Episode Statistics (HES) data from April 2017-March 2022. HES data captures information on reimbursed diagnoses and procedures from all National Health Service (NHS) secondary care admissions and attendances in England. High-cost drugs as defined by NHS England are recorded in HES, these drugs and other procedures including plasma exchange, were used to identify patients with cGvHD who were in receipt of high-cost therapies. HCRU and costs were described for patients with cGvHD following allo-HSCT (n=721) and were matched with patients with no evidence of GvHD following allo-HSCT (n=718). HCRU and costs were also described for the subset of patients with cGvHD (n=198) following receipt of high-cost therapies and patients with cGvHD prior to or without such therapies (n=523). RESULTS: A higher proportion of patients with cGvHD had at least one inpatient or intensive care unit (ICU) admission or emergency care attendance than patients without GvHD (inpatient: 74.6% vs 66.6%; emergency care: 39.3% vs 30.5%; ICU: 7.4% vs 4.7%; respectively); whilst the proportion of patients with an outpatient attendance were similar for both groups (outpatient: 80.3% vs 84.1%; respectively). The cost across all secondary care settings was higher for patients with cGvHD than patients without GvHD, with a mean cost of inpatient admissions of £17,339 ppy for those with cGvHD vs £8,548 ppy in patients without GvHD. A higher proportion of patients who received high-cost therapies for the treatment of cGvHD had at least one secondary care admission or attendance, than patients who did not (inpatient: 85.4% vs 66.4%; ICU: 7.1% vs 5.4%; outpatient: 87.9% vs 76.7%; emergency care: 44.4% vs 36.5%; respectively). Patients who were treated with high-cost therapies for the treatment of cGvHD had a greater mean number (14.6 vs 8.2 ppy, respectively) for all-cause inpatient admissions after treatment, than patients who did not. In all secondary care settings, the total cost ppy was higher for patients who received high-cost therapies for the treatment of cGvHD, than for those who did not. Patients who were treated with high-cost therapies for the treatment of cGvHD had a greater mean cost (£21,137 vs £15,956 ppy, respectively) for all-cause inpatient admissions than patients who did not. CONCLUSIONS: This study demonstrates that cGvHD and the use of associated high-cost therapies impacts healthcare activity and costs across various secondary care settings in England more than patients without GvHD and patients with cGvHD who received no high-cost therapies.

Real-world insights into the management of hemophilia A in Italy: treatment patterns and healthcare resource utilization.

PURPOSE: This real-world analysis described the Hemophilia A (HA) population in Italy, evaluating drug utilization and consumption of factor VIII (FVIII) products of patients under prophylaxis and on-demand therapy. METHODS: From Jan-2017 to Jun-2022, male patients with HA were identified through prescriptions of FVIII products [extended half-life FVIII, standard half-life recombinant FVIII, and plasma-derived FVIII (EHL FVIII, SHL rFVIII, and pdFVIII, respectively)], or emicizumab or FVIII plus von Willebrand factor or HA-related hospitalization using administrative flows of Italian healthcare entities. Patients on treatment with FVIII products during 2021-2022 were stratified by treatment regimen (prophylaxis/on-demand). The mean annual consumption expressed in International Units (IU) of EHL FVIII and SHL FVIII in patients treated during 2021-2022 having at least 12-month follow-up were assessed. RESULTS: Among included HA patients, 145 (39.5%) received EHL FVIII and 222 (60.5%) SHL FVIII. Of 165 patients on prophylaxis, 105 (64%) received an EHL FVIII and 60 (36%) an SHL FVIII. The mean annual consumption of FVIII was 336,700 IU (median 319,000 IU) for EHL FVIII and 440,267 IU (median 360,500 IU) for SHL FVIII. Specifically, for patients on EHL FVIII, the most common drugs were efmoroctocog alfa (N = 51) and damoctocog alfa pegol (N = 50), followed by turoctocog alfa pegol (N = 25) and rurioctocog alfa pegol (N = 19). Of 702 HA patients initially treated with FVIII products, 74 (10.5%) switched to emicizumab during follow-up. CONCLUSION: These findings revealed an extensive use of EHL FVIII products, suggesting growing efforts from clinicians to optimize prophylactic strategies and achieve better bleeding protection.

The economic burden of recurrence in elderly patients with completely resected, stage IIB/IIC or III melanoma: an analysis of the Surveillance, Epidemiology, and End Results-Medicare linked database.

AIMS: To compare healthcare resource utilization (HRU) and costs between patients with or without melanoma recurrence and between patients with distant or locoregional melanoma recurrence. METHODS: Patients aged ≥65 years with completely resected, stage IIB/IIC or III melanoma were identified from Surveillance, Epidemiology, and End Results-Medicare data and stratified based on whether they experienced a recurrence, and whether it was distant or locoregional (separately for each stage). The index date was the date of recurrence (recurrence group) or a randomly assigned date (non-recurrence group). Patients in the recurrence and non-recurrence groups were propensity score-matched 1:1 based on patient characteristics; HRU and healthcare costs were compared between the 2 groups and between patients with distant or locoregional recurrence during the ≤24 months following index. RESULTS: After matching, 507 pairs of patients with recurrent or non-recurrent stage IIB/IIC melanoma (236 patients with distant recurrence, 271 with locoregional) and 141 pairs of patients with recurrent or non-recurrent stage III melanoma (50 patients with distant recurrence, 91 with locoregional) were included. During the first year following recurrence, unadjusted HRU was generally higher in patients with versus without recurrence and patients with distant versus locoregional recurrence among both stage IIB/IIC and III cohorts. Patients who experienced recurrence incurred $6,474 (stage IIB/IIC) or $6,112 (stage III) per patient per month (PPPM) more in unadjusted, all-cause, total healthcare costs than patients without recurrence (both p < 0.001). Patients with distant recurrence incurred $7,292 (stage IIB/IIC) or $5,436 (stage III) PPPM more in unadjusted, all-cause, total healthcare costs than patients with locoregional recurrence (both p < 0.05). LIMITATIONS: Melanoma recurrence was identified using a claims-based algorithm. CONCLUSIONS: Economic burden is higher in patients with versus without melanoma recurrence and patients with distant versus locoregional recurrence. There is a high unmet need for adjuvant therapies that may help to prevent or delay recurrence.

The impact of diagnosing provider type on longitudinal care for patients with newly diagnosed Huntington's Disease.

AIMS: This study evaluated the association between provider types for patients with newly diagnosed Huntington's disease (HD) and healthcare resource utilization (HCRU), costs, and treatment patterns. MATERIALS AND METHODS: This retrospective analysis used MarketScan® databases (1/1/2017-12/31/21) to identify provider type who diagnosed and managed US adult patients with HD. Patients with continuous enrollment 6 months pre- and 12 months post-diagnosis were included. Outcomes evaluated over 12 months post-diagnosis included hospitalizations, outpatient visits, antipsychotic or vesicular monoamine transporter 2 (VMAT2) inhibitor use, and total healthcare costs. RESULTS: 340 eligible patients had a mean age at diagnosis of 49 years. 56.5% were female; 71.5% had a Charlson Comorbidity Index of 0. Patients were diagnosed by neurologists (48.5%), primary care providers (PCP) (35.6%), psychiatrists (3.5%), or other providers (12.4%). Patients diagnosed by PCPs or neurologists received significantly more follow-ups by the same diagnosing provider type (P < 0.05).All-cause and HD-related outpatient visits at 12-month follow-up had more patients diagnosed by PCPs (23.9, 5.1) than neurologists (18.0, 2.4), psychiatrists (16.7, 1.67), or others (15.3, 2.4). HD-related mean costs totaled $2,489 ($1,179 inpatient and $1,310 outpatient). Patients diagnosed by neurologists had significantly lower HD-related total non-medication costs vs those diagnosed by PCPs (-$2,256; P < 0.05).Among patients diagnosed by neurologists vs PCPs, similar proportions received antipsychotics within the first year (55% vs 52%, respectively); more patients managed by neurologists received VMAT2 inhibitors (12% vs 7%, respectively). LIMITATIONS: Our study includes limitations inherent to retrospective claims studies. CONCLUSIONS: Patients with HD are most often diagnosed by neurologists or PCPs; the same diagnosing provider type typically manages follow-up. Patients diagnosed by neurologists had significantly fewer HD-related outpatient visits, lower HD-related non-drug costs, and more frequently received VMAT2 inhibitors vs those diagnosed by PCPs. Our findings show an integrated care team may provide evidence-based, personalized care for patients with HD.

Huntington's disease is a rare disease that is caused by changes in genes. Symptoms of Huntington's disease are irritability, depression, loss of memory, and issues with movement. The symptoms are different for each person and can happen at different times during the disease. A team of doctors that can help with all the symptoms is important for treating Huntington's disease. In our study we looked at which type of doctor was diagnosing Huntington's disease and if the patient continued to see the same type of doctor. We also looked at whether the costs of the disease were related to the type of doctor that diagnosed the disease. We found that most patients were diagnosed by a primary care doctor or a neurologist (brain doctor), and they continued to see the same doctor. Patients who saw a neurologist had less doctor visits for their HD and also less costs for their HD. These results show having a team of doctors that can help with all symptoms of HD may make it easier for patients to receive the best care for their symptoms.

Healthcare resource utilization and costs of chronic lymphocytic leukemia/small lymphocytic lymphoma patients who relapse or are refractory to ibrutinib.

Aim: Evaluate healthcare resource utilization (HRU) and costs in chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) who relapsed or are refractory to (R/R) ibrutinib.Methods: All-cause and CLL/SLL-related HRU and healthcare costs were evaluated in adult patients with CLL/SLL who received ibrutinib (2/2014-3/2020) as single-agent or combination therapy and discontinued/switched to another antineoplastic agent (R/R) vs. all other (non-R/R) ibrutinib users.Results: Compared with the non-R/R patients (N = 919), R/R patients (N = 207) had higher all-cause HRU (inpatient, outpatient and emergency room visits; rate ratios [95% CIs]: 1.51 [1.38, 1.65]-1.92 [1.57, 2.37]; all P < 0.001) and healthcare costs ($81,645 vs. $34,717; cost difference [95% CI] = $50,170 [$40,555, $61,383]; P < 0.001).Conclusion: CLL/SLL patients who are R/R to ibrutinib bear a substantial economic burden.

Ibrutinib is a drug often prescribed for chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL)­two similar types of blood cancer-that returns/does not show improvement after a previous treatment (i.e., to patients who relapse after/are refractory to [R/R] the treatment). CLL/SLL that is R/R to ibrutinib can be costly because patients are left with fewer options for treatment and their cancer is likely to worsen. Knowing how much medical services are used and their cost when treating CLL/SLL that is R/R to ibrutinib can help patients, doctors and policy makers make informed decisions. In this study, the authors compared the use of healthcare resources-which included visits to the hospital, emergency room and doctor's office­and associated costs between patients with CLL/SLL in the United States who were R/R to ibrutinib and those who were not (non-R/R patients). The study showed that healthcare resource use and CLL/SLL-related medical costs were approximately two-times higher in R/R patients than in non-R/R patients. Thus, there is a substantial economic burden associated with R/R CLL/SLL.

Real world analysis of treatment change and response in adults with attention-deficit/hyperactivity disorder (ADHD) alone and with concomitant psychiatric comorbidities: results from an electronic health record database study is the United States.

BACKGROUND: The objectives of this study were to examine the association of psychiatric comorbidities and patient characteristics with treatment change and response as well as to assess the association between treatment change and healthcare resource utilization (HCRU) among adult patients with attention-deficit/hyperactivity disorder (ADHD) and psychiatric comorbidities. METHODS: De-identified electronic health records from the NeuroBlu Database (2002-2021) were used to select patients ≥ 18 years with ADHD who were prescribed ADHD-specific medication. The index date was set as the first prescription of ADHD medication. The outcomes were treatment change (discontinuation, switch, add-on, or drop) and HCRU (inpatient, outpatient, composite) within 12 months of follow-up. Cox proportional-hazard model was used to assess the association between clinical and demographic patient characteristics and treatment change, while generalized linear model with negative binomial distribution and log link function was used to assess the association between key risk factors linked to treatment change and HCRU rates. RESULTS: A total of 3,387 patients with ADHD were included (ADHD only: 1,261; ADHD + major depressive disorder (MDD): 755; ADHD + anxiety disorder: 467; ADHD + mood disorder: 164). Nearly half (44.8%) of the study cohort experienced a treatment change within the 12-month follow-up period. Treatment switch and add-on were more common in patients with ADHD and comorbid MDD and anxiety disorder (switch: 18.9%; add-on: 20.5%) compared to other cohorts (range for switch: 8.5-13.6%; range for add-on: 8.9-12.1%) Survival analysis demonstrated that the probability of treatment change within 12 months from treatment initiation in the study cohort was estimated to be 42.4%. Outpatient visit rates statistically significantly increased from baseline (mean [SD] 1.03 [1.84] visits/month) to 3 months post-index (mean [SD] 1.62 [1.91] visits/month; p < 0.001), followed by a gradual decline up to 12 months post-index. Being prescribed both a stimulant and a non-stimulant at index date was statistically significantly associated with increased risk of treatment change (adjusted hazard ratio: 1.64; 95% CI: 1.13, 2.38; p = 0.01). CONCLUSIONS: This real-world study found that treatment change was common among patients with ADHD and psychiatric comorbidities. These findings support the need for future studies to examine the unmet medical and treatment needs of this complex patient population.

Disease burden and healthcare utilization in pediatric low-grade glioma: A United States retrospective study of linked claims and electronic health records.

Background: Despite high long-term survival rates, pediatric low-grade gliomas (pLGGs) are linked with significant tumor- and treatment-associated morbidities that may persist throughout life. The aims of this descriptive cross-sectional pilot study were to characterize health conditions among a cohort of patients with pLGG and explore the feasibility of quantifying disease burden and healthcare resource utilization (HRU). Methods: Optum® Market Clarity Data were used to identify patients aged ≤18 years with an ICD-10 code for brain neoplasm, ≥1 physician notes, and with evidence of pLGG recorded between January 1, 2017 and June 30, 2018. Outcomes including health characteristics, HRU, medications, and procedures were assessed at 6-month intervals over 36 months. Results: One hundred and fifty-four patients were identified with pLGG and over half experienced headache/migraine, respiratory infection, pain, or behavioral issues during the 36-month study period. The most common comorbidities were ocular/visual (including blindness), mental health disorders, seizures, and behavioral/cognition disorders. Most symptoms and comorbidities persisted or increased during the study period, indicating long-term health deficits. HRU, including speciality care visits, filled prescriptions, and administered medications, was common; 74% of patients had prescriptions for anti-infectives, 56% antiemetics, and 52% required pain or fever relief. Sixty-five percent of patients underwent treatment to control their pLGG, the most common being brain surgery. Little decline was observed in medication use during the study period. Conclusions: Patients with pLGG have complex healthcare needs requiring high HRU, often over a long time. Patients need to be optimally managed to minimize disease- and treatment-related burden and HRU.

Comparison of healthcare resource use and cost between influenza and COVID-19 vaccine coadministration and influenza vaccination only.

OBJECTIVE: To compare healthcare resource utilization (HCRU) and all-cause medical costs among individuals aged ≥50 years who received influenza and COVID-19 vaccines on the same day and those who received influenza vaccine only. METHODS: We conducted a retrospective cohort study leveraging Optum's de-identified Clinformatics DataMart from 8/31/2021 to 7/31/2023. Individuals aged ≥50 years continuously enrolled in health plans for 1 year prior and until 7/31/2023 were included. Two cohorts were formed based on vaccination status between 8/31/2022 and 1/31/2023: co-administered influenza and COVID-19 vaccines (co-admin cohort) and influenza vaccine only (influenza cohort). Associations between vaccination status and all-cause, influenza-related, COVID-related, pneumonia-related, and cardiorespiratory-related hospitalization, outpatient or emergency room visits and all-cause medical costs were estimated by weighted generalized linear models, adjusting for confounding by stabilized inverse probability of treatment weighting. RESULTS: 613,156 (mean age: 71) and 1,340,011 (mean age: 72) individuals were included in the co-admin and influenza cohorts, respectively. After weighting, the baseline characteristics were balanced between cohorts. The co-admin cohort was at statistically significant lower risk of all-cause (RR: 0.95, 95% CI: 0.93-0.96), COVID-19-related (RR: 0.59, 95% CI: 0.56-0.63), cardiorespiratory-related (RR: 0.94, 95% CI: 0.93-0.96) and pneumonia-related (RR: 0.86, 95% CI: 0.83-0.90) hospitalization but not influenza-related hospitalizations (RR: 0.91, 95% CI: 0.81, 1.04) compared with the influenza cohort. Co-administration was associated with 3% lower all-cause medical cost (cost ratio: 0.974, 95% CI: 0.968, 0.979) during the follow-up period compared to receiving influenza vaccine only. LIMITATIONS: Limitations include the potential residual confounding bias in observational data, measurement errors from claims data, and that the cohort was followed for a single season. CONCLUSION: Receiving co-administered COVID-19 and influenza vaccines versus only receiving influenza vaccination reduced the risk of HCRU, especially COVID-19-related hospitalization and all-cause medical costs. Increasing vaccine coverage, particularly for COVID-19, might have public health and economic benefits.

Treatment patterns, healthcare resource utilization, and costs in Medicare patients with diffuse large B-cell lymphoma: a retrospective claims analysis (2015-2020).

AIMS: To understand treatment patterns, healthcare resource utilization (HCRU), and the economic burden of diffuse large B-cell lymphoma (DLBCL) in elderly adults in the US. MATERIALS AND METHODS: This retrospective database analysis utilized US Centers for Medicare and Medicaid Services Medicare fee-for-service administrative claims data from 2015 to 2020 to describe DLBCL patient characteristics, treatment patterns, HCRU, and costs among patients aged ≥66 years. Patients were indexed at DLBCL diagnosis and required to have continuous enrollment from 12 months pre-index until 3 months post-index. HCRU and costs (USD 2022) are reported as per-patient per-month (PPPM) estimates. RESULTS: A total of 11,893 patients received ≥1-line (L) therapy; 1,633 and 391 received ≥2 L and ≥3 L therapies, respectively. Median (Q1, Q3) age at 1 L, 2 L, and 3 L initiation, respectively, was 76 (71, 81), 77 (72, 82), and 77 (72, 82) years. The most common therapy was R-CHOP (70.9%) for 1 L and bendamustine ± rituximab for 2 L (18.7%) and 3 L (17.4%). CAR T was used by 14.8% of patients in 3 L. Overall, 39.6% (1 L), 42.1% (2 L), and 47.8% (3 L) of patients had all-cause hospitalizations. All-cause mean (median [Q1-Q3]) costs PPPM during each line were $22,060 ($20,121 [$16,676-$24,597]) in 1 L, $30,027 ($20,868 [$13,416-$31,016]) in 2 L, and $47,064 ($25,689 [$15,555-$44,149]) in 3 L, with increasing costs driven primarily by inpatient expenses. Total all-cause 3 L mean (median [Q1-Q3]) costs PPPM for patients with and without CAR T were $153,847 ($100,768 [$26,534-$253,630]) and $28,466 ($23,696 [$15,466-$39,107]), respectively. CONCLUSIONS: No clear standard of care exists in 3 L therapy for older adults with relapsed/refractory DLBCL. The economic burden of DLBCL intensifies with each progressing line of therapy, thus underscoring the need for additional therapeutic options.

Healthcare Utilization and Costs Among Patients with Acute Myeloid Leukemia Receiving Oral Azacitidine Maintenance Therapy Versus No Maintenance: A US Claims Database Study.

INTRODUCTION: The substantial economic burden of acute myeloid leukemia (AML) could be reduced with post-remission maintenance therapies that delay relapse. Real-world healthcare resource utilization (HCRU) data and costs among patients with AML receiving oral azacitidine (Oral-AZA) maintenance therapy or no maintenance are not well understood. We characterize HCRU and costs among these patients in clinical practice in the USA. METHODS: Data from IQVIA PharMetrics® Plus (January 1, 2016-June 30, 2022) were used. Patients ≥ 18 years who were newly diagnosed with AML, received first-line systemic induction therapy, and attained disease remission were eligible. Patients receiving Oral-AZA maintenance and those receiving no maintenance ("watch and wait" [W&W]) were matched 1:3 on baseline characteristics using propensity score matching (PSM) and followed until hematopoietic stem cell transplantation or end of continuous insurance enrollment, whichever occurred first. Outcomes included treatment patterns, inpatient and outpatient visits, and costs. RESULTS: After PSM, the Oral-AZA cohort included 43 patients and the W&W cohort 129. Of the 43 patients receiving Oral-AZA, 88.4% started at the recommended dose of 300 mg and 11.6% at 200 mg. The Oral-AZA cohort had significantly (p = 0.0025) longer median (95% CI) time to relapse from the index maintenance date (median not reached [NR; 9.0 months-NR] vs 3.3 months [0.8 months-NR]), and fewer per person per month (PPPM) hospitalizations (0.23 vs 0.61; p = 0.0005) and overall outpatient visits (5.77 vs 7.58; p = 0.0391) than the W&W cohort. Despite higher AML drug costs PPPM in the Oral-AZA cohort ($16,401 vs $10,651 for W&W), total healthcare costs PPPM were lower ($25,786 vs $38,530 for W&W; p < 0.0001). CONCLUSIONS: Patients with newly diagnosed AML treated with Oral-AZA maintenance in clinical practice had prolonged remission and lower HCRU and costs than patients receiving no maintenance therapy. These findings underscore the clinical and economic value of Oral-AZA in clinical practice.

Fusion versus decompression alone for lumbar degenerative spondylolisthesis and spinal stenosis: a target trial emulation with index trial benchmarking.

PURPOSE: The value of adding fusion to decompression surgery for lumbar degenerative spondylolisthesis and spinal canal stenosis remains debated. Therefore, the comparative effectiveness and selected healthcare resource utilization of patients undergoing decompression with or without fusion surgery at 3 years follow-up was assessed. METHODS: Using observational data from the Lumbar Stenosis Outcome Study and a target trial emulation with index trial benchmarking approach, our study assessed the comparative effectiveness of the two main surgical interventions for lumbar degenerative spondylolisthesis-fusion and decompression alone in patients with lumbar degenerative spondylolisthesis and spinal canal stenosis. The primary outcome-measure was change in health-related quality of life (EuroQol Health Related Quality of Life 5-Dimension 3-Level questionnaire [EQ-5D-3L]); secondary outcome measures were change in back/leg pain intensity (Numeric Rating Scale), change in satisfaction (Spinal Stenosis Measure satisfaction subscale), physical therapy and oral analgesic use (healthcare utilization). RESULTS: 153 patients underwent decompression alone and 62 had decompression plus fusion. After inverse probability weighting, 137 patients were included in the decompression alone group (mean age, 73.9 [7.5] years; 77 female [56%]) and 36 in the decompression plus fusion group (mean age, 70.1 [6.7] years; 18 female [50%]). Our findings were compatible with no standardized mean differences in EQ-5D-3L summary index change score at 3 years (EQ-5D-3L German: 0.07 [95% confidence interval (CI), - 0.25 to 0.39]; EQ-5D-3L French: 0.18 [95% CI, - 0.14 to 0.50]). No between-group differences in change in back/leg pain intensity or satisfaction were found. Decompression plus fusion was associated with greater physical therapy utilization at 3 years follow-up. CONCLUSION: Decompression alone should be considered the primary option for patients with lumbar degenerative spondylolisthesis and spinal stenosis.

Reasons for Hospitalizations and Emergency Department Visits Among Patients with Essential Tremor.

Background: Prior studies suggest that patients with essential tremor (ET) have increased rates of healthcare utilization, but the reason for this increased use is unknown. The objective of this study was to evaluate the reasons for healthcare use among ET patients. Methods: This was a retrospective cross-sectional study of ET patients with an admission or emergency department (ED) visit at a tertiary health system from 2018-2023. Patients were matched on an encounter level with control patients based on propensity scores incorporating age, sex, race, and co-morbid conditions. The primary outcome was the odds of an encounter for each diagnostic category comparing ET patients with matched controls. Results: Only inpatient admissions for neurologic diagnoses were more likely for ET compared to control patients (odds ratio (OR) 3.73, 95% confidence interval (CI) 2.54 - 5.49, p < 0.001). Once admissions related to the surgical treatment of tremor were excluded, admissions for neurologic diagnoses were equally likely among ET and control patients (OR 0.96, 95% CI 0.59 - 1.57, p = 0.88). Discussion: Surgical treatment of tremor appears to be a key driver of healthcare use among ET patients. Future investigations should examine the pattern of healthcare use of ET patients before and after surgery. Highlights: Prior studies have shown increased healthcare use among essential tremor (ET) patients. The objective of this study was to evaluate the reasons for healthcare use among ET patients compared to matched control patients. Surgical treatment of tremor was found to be a key driver of healthcare use among ET patients.

Clinicoeconomic burden among heart failure patients with severely reduced ejection fraction after hospital admission: HF-RESTORE.

BACKGROUND: An estimated two-thirds of heart failure (HF) patients with reduced ejection fraction (HFrEF) hospitalized in the United States have a severely reduced left ventricular ejection fraction (LVEF < 30%). Few studies have categorized patients according to their severity of left ventricular dysfunction beyond an LVEF of < 30%. METHODS: Intermountain Health patients (≥18 years), with a primary HF diagnosis, ≥1 inpatient hospitalization with a primary discharge diagnosis of HF, a documented LVEF of < 30%, and a BNP > 100 pg/mL within one year of hospitalization were studied. Patients were stratified by LVEF levels (≤15%, 16-25%, and 26-29%) and evaluated for death, HF hospitalization, healthcare resource utilization, and medical costs. RESULTS: Overall, 2 184 patients (mean age 64.2 ± 15.5 years, 72.5% male) were stratified by LVEF (≤15%, n = 468 [21.4%]; 16-25%, n = 1399 [64.1%]; and 26-29%, n = 317 [14.5%]). Lower LVEF was associated with younger age, male sex, and fewer comorbidities. Although one-year mortality differed significantly between LVEF stratifications, which remained after adjustment by risk factors (vs. LVEF 26-29% [referent]): ≤15%, hazard ratio (HR)=1.92, p < 0.0001; and 16-25%, HR = 1.42, p = 0.01), mortality was similar by 3-years. HF hospitalizations at 1- and 3-years were similar among LVEF groups. Total HF costs-driven by increased HF outpatient costs-were significantly higher among LVEF of ≤ 15%. CONCLUSIONS: Patients with an LVEF of ≤ 15% had a modestly increased risk of 1-year mortality, as well as significantly higher total HF costs. Patients with HFrEF and a severely reduced LVEF continue to face an increased clinicoeconomic burden, and novel therapies to treat this unmet medical need are warranted.

One-year budget impact of InTandem™: a novel neurorehabilitation system for individuals with chronic stroke walking impairment.

Aim: Chronic stroke walking impairment is associated with high healthcare resource utilization (HCRU) costs. InTandem™ is a neurorehabilitation system that autonomously delivers a rhythmic auditory stimulation (RAS)-based intervention for the at-home rehabilitation of walking impairment in adults in the chronic phase of stroke recovery. This study was conducted to estimate the budget impact of InTandem in comparison with currently available intervention strategies for improvement of gait/ambulation in individuals with chronic stroke walking impairment. Methods & materials: A budget impact analysis (BIA) for InTandem was conducted based on a 1-million-member US third-party payer perspective over a 1-year time horizon. Key inputs for the budget impact model were: costs for each intervention strategy (InTandem, physical therapy, self-directed walking and no treatment), HCRU costs for persons with chronic stroke and anticipated HCRU cost offsets due to improvements in gait/ambulatory status as measured by self-selected comfortable walking speed (based on functional ability). In addition to the reference case analysis, a sensitivity analysis was conducted. Results: Based on the reference case, introduction of InTandem was projected to result in overall cost savings of $439,954 in one year. Reduction of HCRU costs (-$2,411,778) resulting from improved walking speeds with InTandem offset an increase in intervention costs (+$1,971,824). Demonstrations of cost savings associated with InTandem were robust and were consistently evident in nearly all scenarios evaluated in the sensitivity analysis (e.g., with increased/decreased patient shares, increased HCRU cost or increased InTandem rental duration). Conclusion: The InTandem system is demonstrated to improve walking and ambulation in adults in the chronic phase of stroke recovery after a five-week intervention period. The BIA predicts that introduction of InTandem will be associated with overall cost savings to the payer.

Clinical manifestations, healthcare resource utilization, and costs among patients with long-chain fatty acid oxidation disorders: a retrospective claims database analysis.

OBJECTIVE: Long-chain fatty acid oxidation disorders (LC-FAOD) are a group of rare genetic inborn errors of metabolism. Clinical manifestations may result in frequent healthcare visits, hospitalizations, and early death. This retrospective cohort study assessed manifestations, healthcare resource use (HRU), direct medical costs, and the impact of COVID-19 on HRU among patients with LC-FAOD. METHODS: The IQVIA PharMetrics Plus database was searched for pediatric (0-17 years) and adult (≥18 years) patients with confirmed LC-FAOD (ICD-10-CM Diagnosis Code E71.310) and ≥12 months continuous enrollment (CE) between January 2016-February 2020. A non-LC-FAOD general population cohort was randomly selected and matched using 1:20 exact matching on age, gender, payer type, and CE start year. Manifestations were identified via ICD-10 diagnosis codes (any billing position). Overall HRU and attributable costs were stratified by care setting. Pre-COVID-19 (March 2019-February 2020) and during COVID-19 (March 2020-February 2021) HRU was assessed among a subgroup of patients and the general population. Outcomes were evaluated among children and adults, respectively. RESULTS: 423 patients with LC-FAOD (47% female; 79.7% children) were included. The mean enrollment duration was 2.6 ± 1.2 years. 22.6% of children with LC-FAOD had at least one major clinical event (MCE), consisting of rhabdomyolysis (10.1%), hypoglycemia (9.8%), or cardiomyopathy (8.6%) versus 1.5% overall occurrence in the general population. Adults with LC-FAOD had a higher incidence of MCEs (37.2%) than children with LC-FAOD. Annualized all-cause HRU in all care settings and mean total annualized medical costs (children: $17,082 vs $4144; adults: $43,602 vs $3949) were higher in patients with LC-FAOD versus the general population. Patients with LC-FAOD had substantially fewer healthcare visits during COVID-19 across care settings than during the pre-COVID-19 period. CONCLUSIONS: LC-FAOD impart a high burden on patients. Extended hospital stays and increased outpatient management were especially pronounced for adults and for patients with ≥1 MCE, resulting in substantially higher medical costs than the general population.

Assessing the Association of Healthcare Resource Utilization and Patient-Reported Outcomes on Shared Decision-Making among Multimorbid Individuals.

Shared decision-making (SDM) is an essential component of patient-centered healthcare and disease management. However, the association of SDM with healthcare resource utilization and patient-reported outcomes among multimorbid individuals is not well understood. This study sought to evaluate the association of SDM with healthcare resource utilization and patient-reported outcomes among United States (US) adults with multimorbidity. Data were collected from the 2020 Medical Expenditure Panel Survey (MEPS) for this cross-sectional study. Eligible participants were US adults with two or more comorbidities. The predictor variable was SDM (optimal versus not optimal). The outcome variables were healthcare resource utilization and patient-reported outcomes. Logistic regression models, adjusted for demographic characteristics, assessed associations with SDM for each healthcare resource utilization and patient-reported outcome variable. The analysis maintained the complex survey data and was weighted to produce nationally representative estimates. Individuals who reported optimal SDM in adjusted analyses utilized more healthcare resources compared to those who reported not optimal SDM. Individuals with optimal SDM had more than one outpatient visit (odds ratio OR = 1.23, 95% CI = 1.03-1.47), emergency room visit (OR = 1.55, 95% CI = 1.17-2.06), and inpatient discharge (OR = 1.44, 95% CI = 1.05-1.96). Additionally, these individuals had higher odds of reporting limitations in their ability to work or engage in other activities due to their physical health in the past four weeks (OR = 1.27, 95% CI = 1.01-1.60). This study indicated evidence of increased healthcare resource utilization among patients who participate in SDM with their providers, which should be explored in future studies.

Evaluating Real World Health System Resource Utilization and Costs for a Risk-Based Breast Cancer Screening Approach in the Canadian PERSPECTIVE Integration and Implementation Project.

BACKGROUND: A prospective cohort study was undertaken within the PERSPECTIVE I&I project to evaluate healthcare resource utilization and costs associated with breast cancer risk assessment and screening and overall costs stratified by risk level, in Ontario, Canada. METHODS: From July 2019 to December 2022, 1997 females aged 50 to 70 years consented to risk assessment and received their breast cancer risk level and personalized screening action plan in Ontario. The mean costs for risk-stratified screening-related activities included risk assessment, screening and diagnostic costs. The GETCOST macro from the Institute of Clinical Evaluative Sciences (ICES) assessed the mean overall healthcare system costs. RESULTS: For the 1997 participants, 83.3%, 14.4% and 2.3% were estimated to be average, higher than average, and high risk, respectively (median age (IQR): 60 [56-64] years). Stratification into the three risk levels was determined using the validated multifactorial CanRisk prediction tool that includes family history information, a polygenic risk score (PRS), breast density and established lifestyle/hormonal risk factors. The mean number of genetic counseling visits, mammograms and MRIs per individual increased with risk level. High-risk participants incurred the highest overall mean risk-stratified screening-related costs in 2022 CAD (±SD) at CAD 905 (±269) followed by CAD 580 (±192) and CAD 521 (±163) for higher-than-average and average-risk participants, respectively. Among the breast screening-related costs, the greatest cost burden across all risk groups was the risk assessment cost, followed by total diagnostic and screening costs. The mean overall healthcare cost per participant (±SD) was the highest for the average risk participants with CAD 6311 (±19,641), followed by higher than average risk with CAD 5391 (±8325) and high risk with CAD 5169 (±7676). CONCLUSION: Although high-risk participants incurred the highest risk-stratified screening-related costs, their costs for overall healthcare utilization costs were similar to other risk levels. Our study underscored the importance of integrating risk stratification as part of the screening pathway to support breast cancer detection at an earlier and more treatable stage, thereby reducing costs and the overall burden on the healthcare system.

Comparison of real-world healthcare resource utilization among advanced therapy-naïve and advanced therapy-experienced patients with ulcerative colitis initiated on ustekinumab or vedolizumab.

OBJECTIVES: To describe and compare healthcare resource utilization (HRU) among advanced therapy-naïve and advanced therapy-experienced patients with ulcerative colitis (UC) initiating ustekinumab or vedolizumab in the United States. METHODS: Claims data from IQVIA PharMetrics Plus de-identified database (01/01/2015-06/30/2022) were used to identify adult patients with UC initiating ustekinumab or vedolizumab (index date) after 10/21/2019. Baseline characteristics were balanced using inverse probability of treatment weighting. All-cause and UC-related HRU (number of inpatient admissions, inpatient days, emergency department visits, and outpatient visits) were described during the post-index period, and Poisson regression models were used to evaluate associations between index therapy and HRU outcomes. Analyses were performed separately among advanced therapy-naïve or advanced therapy-experienced patients. RESULTS: A total of 444 (ustekinumab) and 1,917 (vedolizumab) advanced therapy-naïve patients, and 647 (ustekinumab) and 1,152 (vedolizumab) advanced therapy-experienced patients were identified. In advanced therapy-naïve patients, higher rates of UC-related inpatient days (rate ratio [95% confidence interval] = 1.84 [1.15, 3.58]; p = 0.004), emergency department visits (1.39 [1.01, 2.17]; p = 0.044), and outpatient visits (1.81 [1.61, 2.04]; p < 0.001) were observed among patients initiating vedolizumab relative to ustekinumab. In advanced therapy-experienced patients, higher rates of UC-related inpatient admissions (1.47 [1.06, 2.12]; p = 0.012), inpatient days (2.18 (1.44, 3.71); p < 0.001), and outpatient visits (1.50 (1.19, 1.82); p < 0.001) were observed among patients initiating vedolizumab relative to ustekinumab. Results were similar when all-cause HRU was examined. CONCLUSIONS: Among patients with UC with and without advanced therapy experience, higher rates of all-cause and UC-related HRU were observed among those treated with vedolizumab relative to ustekinumab.

A global perspective of the changing epidemiology of invasive fungal disease and real-world experience with the use of isavuconazole.

Global epidemiological data show that the incidence of invasive fungal disease (IFD) has increased in recent decades, with the rising frequency of infections caused by Aspergillus and Mucorales order species. The number and variety of patients at risk of IFD has also expanded, owing in part to advances in the treatment of hematologic malignancies and other serious diseases, including hematopoietic stem cell transplantation (HCT) and other therapies causing immune suppression. Isavuconazonium sulfate (active moiety: isavuconazole) is an advanced-generation triazole antifungal approved for the treatment of invasive aspergillosis and mucormycosis that has demonstrated activity against a variety of yeasts, moulds, and dimorphic fungi. While real-world clinical experience with isavuconazole is sparse in some geographic regions, it has been shown to be effective and well tolerated in diverse patient populations, including those with multiple comorbidities who may have failed to respond to prior triazole antifungal therapy. Isavuconazole may be suitable for patients with IFD receiving concurrent QTc-prolonging therapy, as well as those on venetoclax or ruxolitinib. Data from clinical trials are not available to support the use of isavuconazole prophylactically for the prevention of IFD or for the treatment of endemic IFD, such as those caused by Histoplasma spp., but real-world evidence from case studies suggests that it has clinical utility in these settings. Isavuconazole is an option for patients at risk of IFD, particularly when the use of alternative antifungal therapies is not possible because of toxicities, pharmacokinetics, or drug interactions.

This article summarizes the epidemiology and risk factors for IFD, before focusing on the effectiveness and safety of the antifungal agent isavuconazole for treatment of invasive aspergillosis and mucormycosis, and its potential to prevent IFD in specific patient populations.