# Background Acute kidney injury (AKI) is a common complication after cardiac surgery and is associated with more infections, prolonged recovery, longer hospital stays, increased readmission rates, greater costs, and higher mortality. Patients with pre-existing chronic kidney disease (CKD) are at particularly high risk, with this risk increasing as renal function worsens. Damage caused by AKI may be irreversible, despite a return to baseline GFR, compounding stress on remaining nephrons. Understanding risk in these populations may ultimately help to improve prevention and outcomes. # Objective Evaluate the impact of AKI on outcomes and healthcare costs among adults with CKD undergoing cardiac surgery with cardiopulmonary bypass (CPB). # Methods Multi-institutional, retrospective, observational study using the Healthcare Cost and Utilization Project Nationwide Readmissions Database, 2016-2020 datasets. The total adult cardiac surgery population were those with CKD who underwent cardiac surgery requiring CPB (reporting incidence); from which a subpopulation of adults with severe CKD (stage 3 or 4; based on ICD-10-CM codes during index hospitalization) was assessed (impact of AKI). Patients were categorized as follows, based on AKI status during index hospitalization: no AKI, AKI, or AKI requiring dialysis (a subpopulation of AKI). # Results AKI incidence during initial hospitalization was 55.9% and 77.3% in patients with CKD stage 3 and 4, respectively. AKI requiring dialysis occurred in 3.4% and 14.5% of CKD 3 and 4 patients, respectively. One-third of all AKI cases and half of AKI requiring dialysis cases occurred in patients with CKD stage 3 or 4. In patients with CKD stage 3 or 4, multivariate analysis showed AKI was associated with increased inpatient days, increased risk of 180-day readmission, higher hospitalization costs, and greater odds of in-hospital mortality. Patients experienced the greatest burden when AKI required dialysis. # Conclusions Incidence of AKI is higher in patients with preexisting CKD stage 3 or 4 vs 1 or 2 and those without CKD. The burden of AKI is elevated in patients with CKD undergoing cardiac surgery with CPB; targeted interventions are needed to prevent poor outcomes.
# Background Congenital thrombotic thrombocytopenic purpura (cTTP) is an ultra-rare, life-threatening thrombotic disorder. The real-world clinical trajectory and management of cTTP are not well defined. # Objectives Describe patient characteristics, quantify the incidence and prevalence of clinical manifestations and disease-related complications, and describe treatment patterns and treatment-related outcomes of patients with cTTP. # Methods In this retrospective, multinational, longitudinal cohort study, data were abstracted from the medical records of patients with severe hereditary ADAMTS13 deficiency (<10% activity) at 9 participating sites across Europe and the United States. Eligible patients experienced an index event (cTTP diagnosis, an acute TTP event or TTP manifestation, a cTTP-related clinical event, or prophylaxis) between January 1, 2009, and December 31, 2017. Data collection was from January 1, 2009, to December 31, 2020. A post hoc analysis was conducted among patients who matched inclusion criteria for a phase 3 trial (NCT03393975), and who received plasma-based therapy (PBT) prophylaxis at least once per month, up to 3 times per week. # Results Medical records from 78 patients (61 [78.2%] female) were included in the study. The mean (SD) follow-up was 8.1 (3.1) years. Ninety-two acute TTP events were recorded in 55 (70.5%) patients (overall event rate, 0.145 events per person-year). Eighty (87.0%) acute TTP events occurred in the absence of prophylactic treatment, of which 16 (20.0%) resulted in organ damage (based on physicians’ assessment). Twelve (13.0%) acute TTP events occurred during prophylaxis; none resulted in organ damage. Sixty-four TTP manifestations were recorded in 29 (37.2%) patients (overall event rate, 0.101 events per person-year). Of the 25 patients in the post hoc analysis, 4 experienced 9 acute TTP events while receiving PBT prophylaxis. # Conclusions Our findings suggest that acute TTP events occurred less frequently during periods of prophylaxis but also highlight prophylaxis’ intrinsic limitations in preventing ongoing manifestations, cumulative organ damage, and the logistical and safety burdens associated with repeated plasma infusions. Patients with cTTP bear a substantial clinical and disease burden associated with acute TTP events and organ damage. Despite treatment with PBT prophylaxis, some patients still experienced acute TTP events, suggesting that more effective treatments may be needed.
# Background Systematic literature reviews (SLRs) are central to evidence generation in health economics and outcomes research, but traditional SLR workflows are labor-intensive. Artificial intelligence (AI) is increasingly being explored to support evidence synthesis tasks. # Objectives To describe methods used to assess AI performance in screening and data extraction in SLRs, and to provide recommendations on how to ensure appropriate use of AI in literature reviews. # Methods We conducted an AI-assisted SLR that mirrored a traditional SLR performed by humans only and assessed the performance of the AI tools employed. AI was used to screen titles/abstracts, screen full texts, and conduct data extraction. Using the traditional SLR as the benchmark, AI performance for title/abstract screening was evaluated in terms of accuracy, recall, and precision at predefined screening milestones, followed by the accuracy assessment of full-text screening by AI. Data items extracted by AI were verified by humans and categorized as correct, incomplete, missing, incorrect, or requiring human checks. The average accuracy rate calculated on the basis of correct data items extracted was used as an indicator of AI performance in data extraction. # Results During title/abstract screening, accuracy and recall remained high but precision was low, increasing false positives. Full-text screening identified a minority of studies included in the traditional SLR. Mean extraction accuracy was 72.93% (range, 57.69%-88.46%). No data were hallucinated by the AI model used.
# Background Adult T-cell leukemia/lymphoma (ATL) is a rare and aggressive type of peripheral T-cell malignancy caused by the human T-lymphotropic virus type 1 (HTLV-1). Approximately 5 to 10 million people are infected with HTLV-1 worldwide, with high prevalence in Japan. This observational study analyzed patient characteristics, treatment patterns, healthcare resource utilization (HRU), and costs of ATL in Japan. # Methods A retrospective analysis of ATL patients from the Medical Data Vision database, Sept. 1, 2012–Aug. 31, 2022, was conducted. # Results Among 1572 ATL patients, 384 received systemic therapy. The mean age at diagnosis was 66.4 years, with 63.7% being ≥65 years; 55.2% patients were females. Excluding cancer, 61% of patients had a Charlson Comorbidity Index score of 0. The most frequently observed comorbidities were congestive heart failure (15.8%), diabetes (14.8%), and peptic ulcer disease (14.6%). Among the treated patients, 37.5% received 1 line of therapy, 26% received 2 lines of therapy, and 36.5% received ≥3 lines. Mogamulizumab was most frequently utilized (60.4%), as monotherapy or in combination regimens. The most common combination regimen in all lines of therapy were cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP), utilized in 46.6% of patients. Additionally, use of combinations such as VCAP-AMP-VECP, which include vincristine, cyclophosphamide, doxorubicin, and prednisone; adriamycin, manimustine, and prednisone; and vindesine, etoposide, carboplatin, and prednisone, was observed in 33.3% of patients. Initial treatment was discontinued in 74.7% patients; only 3.4% received stem cell transplants. Most (96%) patients were hospitalized, 29.7% had emergency room visits, and 79.4% averaged 1.8 outpatient visits monthly. The mean all-cause healthcare cost per patient per month was $29 538 (¥4 647 300), mainly due to outpatient visits and hospitalizations. # Conclusion Although real-world studies based on MDV database have certain limitations, the findings of this study provide deeper understanding of the real-world patient characteristics, treatment patterns, HRU, and costs of ATL patients in Japan. The results indicate that patients often encounter high treatment costs and frequent hospitalizations, demonstrating the necessity for advanced regimens and highlighting the unmet need for more effective therapies in ATL patients that may reduce HRU and economic burden in this patient population.
# Background External beam radiation therapy (EBRT) and radical prostatectomy (RP) are definitive options for patients with localized or locally advanced prostate cancer (LPC). Limited evidence exists on the post-treatment economic burden in these patients. # Objective This real-world analysis investigated healthcare costs among Medicare beneficiaries with LPC who received EBRT or RP as initial definitive treatment. # Methods This is a retrospective, longitudinal cohort study using Surveillance, Epidemiology, and End Results (SEER)–Medicare database. Included were Medicare Fee-For-Service beneficiaries newly diagnosed with LPC at the age of ≥65 years during 2012-2019 and received either EBRT or RP as an initial definitive therapy. After the initial therapy, all-cause and prostate cancer–related costs were summarized and stratified by the earliest observed definitive therapy (RP vs EBRT) and the National Comprehensive Cancer Network risk classification (low/intermediate-risk [LIR-LPC] vs high-risk [HR-LPC]). # Results Of the 17 066 LPC patients treated with EBRT, 60% (N =10 321) had LIR-LPC and 40% (N = 6745) had HR-LPC. During the follow-up, the mean per-person-per-year all-cause cost was $9837 higher in the HR-LPC cohort than the LIR-LPC cohort ($34 441 vs $24 604; _P_ < .0001). Of the 9479 patients treated with RP, 43% (N = 4120) had LIR-LPC and 57% (N = 5359) had HR-LPC. The mean per-person-per-year all-cause cost during follow-up was $6829 higher in the HR-LPC cohort than the LIR-LPC cohort ($23 820 vs $16 991; _P_ < .0001). Across all cohorts, the largest all-cause healthcare cost category was outpatient, followed by inpatient and prescription drug. # Conclusions This real-world study on healthcare costs in patients with LPC treated with EBRT or RP showed HR-LPC is associated with significant incremental economic burden relative to LIR-LPC. The findings highlight the current unmet need for more cost-effective treatment strategies for HR-LPC.
Background: Ehlers-Danlos Syndrome (EDS) is a rare connective tissue disorder associated with substantial clinical complexity and healthcare utilization. Despite increasing recognition of EDS, little is known about its economic burden in the United States. Objective: To assess the all-cause healthcare costs for individuals with newly diagnosed EDS during the pre-diagnosis year and the first 2 years post-diagnosis. Methods: A retrospective cohort study was conducted using the Merative™ MarketScan® Commercial Claims and Encounters Database (2016-2022). Newly diagnosed patients were identified using ICD-10-CM codes, with the first observed diagnosis defined as the index date. Continuous enrollment for 12 months pre-index and 24 months post-index was required. Costs represented gross payments to providers, adjusted to 2022 US dollars. Outcomes included inpatient, outpatient, and pharmacy expenditures, with outpatient services further stratified. Two-part models were estimated: a logistic regression for the probability of incurring costs and a GLM gamma model with log link for cost intensity among users. Results: The study included 4765 patients (mean age, 28.8 years; 78% female). Total annual costs rose from $19 733 pre-index to $28 922 in the first year post-diagnosis, then declined to $21 804 in the second year, though remaining above baseline. Outpatient and pharmacy services were the largest contributors, while inpatient admissions, though less frequent, were resource intensive when they occurred. Two-part models showed that the likelihood of incurring any cost was significantly higher in Year 1 (β = 4.15, P < .001) but not in Year 2 (β = –0.03, P = .845). Among cost users, expenditures remained elevated in both Year 1 (β = 0.41, P < .001) and Year 2 (β = 0.13, P < .001). Female sex and higher Charlson Comorbidity Index scores were associated with significantly greater costs. Costs peaked immediately after diagnosis, driven by outpatient and pharmacy use, and remained elevated in Year 2. Patient characteristics, particularly comorbidities, strongly influenced expenditures. Conclusions: Healthcare costs for patients with EDS peaked during the first year following diagnosis and remained elevated in the second year relative to pre-diagnosis levels. These findings highlight the substantial and persistent economic impact of EDS on the healthcare system.
# Background Obesity is a chronic disease associated with substantial morbidity and healthcare costs. In Japan, the Optimal Use Promotion Guidelines (OUG) impose restrictions on patient eligibility for semaglutide 2.4 mg and limit treatment duration. This study evaluated the cost-effectiveness of semaglutide 2.4 mg in Japan under retreatment assumptions informed by OUG requirements. # Methods A Markov cohort model (Core Obesity Model) was used to evaluate lifetime clinical and economic outcomes from a Japanese public payer perspective. The Core Obesity Model assesses the associations between risk factors and the incidence of obesity-related complications. People with obesity disease and either a BMI ≥35 kg/m2 with at least 1 obesity-related comorbidity (hypertension, dyslipidemia, or type 2 diabetes), or a BMI ≥27 kg/m² with at least 2 obesity-related health disorders, were included. The intervention was semaglutide 2.4 mg plus diet and exercise vs diet and exercise alone. We modeled retreatment scenarios (0, 1, or 2 retreatments) with a fixed 1-year off-treatment period after each regimen. Complication costs were sourced from Japanese studies. The primary outcome was the incremental cost-effectiveness ratio (ICER) in Japanese yen per quality adjusted life year (QALY), discounted at 2%. # Results In the base case, semaglutide 2.4 mg reduced the incidence of obesity-related complications, such as type 2 diabetes (T2D), cardiovascular events, obstructive sleep apnea, and gout. The ICER was ¥5 300 580/QALY for patients with obesity disease without T2D, and ¥7 077 984/QALY for patients with obesity disease with T2D. Retreatment significantly improved QALY gains compared with limited or no retreatment, reflecting longer maintenance of treatment benefit. # Conclusions Accounting for OUG consistent retreatment in Japan improved the cost-effectiveness of semaglutide 2.4 mg and provided a more realistic representation of long-term obesity management than single course assumptions. Analyses that omit retreatment may underestimate its long-term value in Japanese clinical practice. Results were broadly robust, although uncertainty remains around retreatment efficacy and long-term discontinuation. Semaglutide 2.4 mg represents a clinically and economically valuable intervention for obesity disease in Japan. These findings emphasize the need for long‑term, clinically realistic assessments when evaluating obesity treatments in Japan.
# Background The optimal screening interval for fecal immunochemical testing (FIT) in Japan remains uncertain. # Objective This study aimed to evaluate the cost-effectiveness of biennial FIT screening compared with annual FIT screening to inform future national guidelines. # Methods We developed a microsimulation model of a cohort of 100 000 average-risk Japanese individuals aged 40 years and older followed over a 60-year horizon from a healthcare payer perspective. Two screening methods were compared: the current annual FIT and biennial FIT. Effectiveness was measured in quality-adjusted life-years (QALYs), and costs were measured in 2024 Japanese yen. # Results Annual FIT screening was dominant, resulting in lower total costs (¥408 058 vs. ¥451 407) and higher QALYs (26.483 vs 26.440) compared with biennial screening. Probabilistic sensitivity analysis indicated that annual screening was cost-effective in 92.7% of iterations at a WTP threshold of ¥5 million per QALY. # Conclusions The analysis indicated that annual FIT screening was dominant over biennial screening, because of its lower costs and higher QALY yield. These findings were supported by probabilistic sensitivity analysis. Although annual FIT screening is generally superior to biennial screening in Japan and provides greater health benefits at lower costs, future policies should aim to address endoscopic capacity constraints to ensure program sustainability.
# Background Type 2 diabetes (T2D) and obesity increase individuals’ risk of microvascular and macrovascular complications, which may increase healthcare costs. The RESET program combined low-calorie diet using diabetes-specific nutritional formula and a digital lifestyle behavior change program to target sustainable weight loss and improved diabetes management. # Objective To quantify projected changes in diabetes-related complication risks following the 12-week weight-loss phase of the RESET program and to relate these modeled risk reductions to program costs. # Methods Data from 157 adults with type 2 diabetes (mean age, 56 years; diabetes duration, 2.2 years; baseline body mass index (BMI), 35 kg/m²; HbA1c, 7.5%) completing the RESET weight-loss phase were analyzed. Observed mean changes in HbA1c, BMI, and systolic blood pressure were applied to the UK Prospective Diabetes Study Outcomes Model 2 (UKPDS-OM2) to estimate projected relative risk reductions in microvascular and macrovascular complications over a 3-month horizon. Program costs were derived using a microcosting approach from the healthcare payer perspective, and parameter uncertainty was evaluated through 20 000 Monte Carlo simulations. # Results Participants achieved mean reductions of 1.0% in HbA1c, 11.0 kg in body weight, and 4.5 mmHg in systolic blood pressure. The model projected an overall relative reduction in total complication risk of 15.4% (95% confidence interval [CI], 9.1-21.4), corresponding to an absolute reduction of 1.9 projected events per 1000 participants over 3 months, comprising a –13.2% mean reduction in macrovascular and –23.8% in microvascular complication risks. Mean program cost was £1236 per participant (95% CI, £1001-£1492), corresponding to an incremental cost of £84 per 1% relative risk reduction. # Conclusions Short-term, intensive weight loss achieved clinically meaningful improvements in HbA1c and body weight that were associated with favorable reductions in projected microvascular and macrovascular complications at modest cost. Absolute event reductions over 3 months were modest, and sustaining these improvements is essential to realize long-term clinical and economic benefit.
# Background Patient self-monitoring (PSM) is emerging as an innovative modality for chronic disease management. While PSM technologies are established in therapeutic areas including diabetes and cardiovascular diseases, current payer and health technology assessments (HTA) do not adequately evaluate the unique facets of their value. # Objectives This study developed a multi-country, stakeholder-informed framework that considers the value drivers of PSM technologies, mapping these to payer and HTA evaluation criteria to guide evidence generation and reimbursement decision making. # Methods A sequential mixed methodology study of an artificial intelligence-enabled targeted literature review using Nested Knowledge® and qualitative primary research with 10 payer and healthcare practitioner respondents in the United States, United Kingdom, and Germany was used to inform development of the framework. # Results The framework comprises three interconnected core components: value drivers, evaluation criteria, and evidence generation considerations. The value drivers component consists of four themes: clinical, economic, humanistic, and societal. Primary research respondents weighted the respective emphasis of decision making as 60% clinical, 20% economic, 10% humanistic, and 10% societal value. Key value drivers included treatment efficacy/clinical utility, diagnostic efficacy, and healthcare resource utilization. Evaluation criteria indicate the coverage/reimbursement requirements of key payer and HTA organizations. Evidence generation considerations comprise potential study types and evidence generation activities. # Conclusions This framework provides a conceptual foundation for stakeholders including payers, HTA bodies, physicians, and developers to align upon evidence requirements for PSM technologies. It can support streamlined strategic evidence generation and consistent evaluation to improve patient access to innovative chronic disease self-monitoring technologies.
# Background Colorectal cancer is a leading cause of cancer-related morbidity and mortality in the United States; however, a substantial proportion of eligible adults do not complete screening. # Objectives To evaluate real-world completion of multitarget stool DNA (mt-sDNA) testing for colorectal cancer screening among Medicare beneficiaries in Texas and to identify beneficiary-, provider-, and outreach-related factors associated with test completion. # Methods This retrospective cohort study included Texas beneficiaries aged 65 to 85 years with traditional Medicare or Medicare Advantage coverage who received an mt-sDNA kit between October 2014 and December 2024. Completion was defined as return of a valid test kit within 1 year of shipment. Multivariable logistic regression was used to identify factors associated with completion. Kaplan–Meier and Cox proportional hazards models were used to evaluate time to kit return. # Results Among 710 515 beneficiaries, 538 377 (75.8%) completed mt-sDNA testing within 1 year. Completion was higher among beneficiaries with traditional Medicare vs Medicare Advantage (81.7% vs 71.7%). In adjusted analyses, gastroenterologist ordering (odds ratio [OR], 2.66; 95% confidence interval [CI], 2.53-2.79), full digital outreach (OR, 1.73; 95% CI, 1.69-1.77), and prior mt-sDNA use (OR, 1.61; 95% CI, 1.59-1.64) were associated with higher odds of completion. Higher neighborhood income and lower social vulnerability were also associated with higher completion rates. Time-to-event analyses were consistent, with faster completion observed among patients receiving digital outreach, with prior mt-sDNA use, and those with gastroenterologist-ordered tests. # Discussion These findings suggest that both patient context and modifiable care delivery factors influence screening completion and may inform the design of more effective and equitable CRC screening programs. # Conclusions In this large real-world Medicare cohort, mt-sDNA completion was high overall but varied by payer type, provider specialty, outreach modality, and socioeconomic vulnerability.
Background:Peripheral T-cell lymphomas (PTCLs) are a rare and heterogeneous group of non-Hodgkin lymphomas associated with aggressive clinical course and suboptimal outcomes. PTCL accounts for a higher proportion of non-Hodgkin lymphoma cases in Japan compared with Western countries; however, real-world evidence on treatment patterns, healthcare resource utilization (HRU), and costs in Japan is limited. Objectives:To describe real-world patient characteristics, treatment patterns, HRU, and costs among patients with PTCL in Japan. Methods:This retrospective observational study used administrative claims data from the Medical Data Vision database in Japan. Adult patients diagnosed with PTCL between September 2012 and August 2022 were identified. Patients were categorized as receiving nonsystemic therapy or systemic therapy and stratified by lines of therapy. Patient demographics, comorbidities, treatment regimens, time on treatment, HRU, and healthcare costs, measured per patient per month, were analyzed descriptively. Results:Among 910 patients identified, 71.3% received systemic treatment and 28.7% received nonsystemic therapy, most receiving corticosteroids only. Mean age at diagnosis was 69.8 years; 70% of patients were at least 65 years old. Key comorbidities included peptic ulcer disease, congestive heart failure, and diabetes. PTCL-not otherwise specified and angioimmunoblastic T-cell lymphoma accounted for over 75% of subtypes. First-line therapy was mainly cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) or CHOP-like regimens; later lines were more heterogeneous and of shorter duration. Mogamulizumab and brentuximab vedotin were used in 4.16% and 10.48% of patients, respectively. Stem cell transplantation was infrequent (6.3%). Median per patient per month PTCL-related total healthcare cost was 9712 ; m e d i a n d r u g ( 7056.9) and hospitalization costs ($5177.7) were the main contributors. Discussion:These findings demonstrate substantial clinical and economic burden among PTCL patients in Japan. Treatment heterogeneity and short duration in later lines of therapy highlight ongoing therapeutic challenges. Conclusions:High economic burden of PTCL treatment underscores the need for more effective, tolerable, and less costly therapeutic strategies for treating PTCL patients in Japan.
# Background Trofinetide (TROF) became the first approved pharmacologic treatment for Rett syndrome (RTT) in the United States in March 2023; however, real-world evidence comparing TROF-treated and untreated individuals is limited. # Objective This study aimed to compare the baseline demographic and clinical profiles of those treated with TROF vs untreated in routine clinical practice. # Methods This retrospective cohort study used linked IQVIA Anonymized Patient Level Database medical claims and a specialty pharmacy database. Individuals with ≥1 medical claim for RTT between 01/01/2021 and 09/30/2024 (study period) were identified. Treated individuals had ≥1 TROF prescription during 04/01/2023 to 09/30/2023 (identification period), with first prescription set as index; untreated individuals had no TROF prescription. A risk-set sampling approach was used to assign proxy index dates to untreated individuals to improve comparability and reduce immortal time bias. Individuals with cerebrovascular disease or brain trauma before RTT diagnosis and those without 12 months pre-and post-index enrollment were excluded. Baseline characteristics were assessed during the 12 months pre-index. # Results Of 8047 individuals with RTT identified, 2950 met eligibility criteria; 766 (26.0%) were treated with TROF and 2184 (74.0%) remained untreated. Treated individuals were younger at index (15.4 vs 23.5 years), and a greater proportion were pediatric (≤17 years; 66.6% vs 38.3%). Females predominated in both groups, while males represented a smaller proportion of the treated (4.6% vs 10.8%). Treated individuals more frequently had documented nonspecific developmental delay (31.3% vs 21.6%), autism spectrum disorder (19.1% vs 15.7%), and core RTT-related neurodevelopmental features such as loss of acquired communication skills (23.8% vs 12.9%) and loss of acquired motor skills (11.1% vs 4.9%). Child neurology was the most common prescriber specialty in both groups and was more frequent among treated individuals (50.3% vs 26.8%). Overall comorbidity burden was broadly similar between groups. # Conclusion In this real-world analysis, only one-quarter of eligible individuals with RTT initiated TROF during the early post-approval period. TROF uptake appeared concentrated in younger, specialist-managed individuals with more clearly documented RTT-related features, while three-quarters remained untreated. These findings highlight the need to better understand treatment pathways and barriers to initiation in males and adults in routine RTT care.
# Background Real-world evidence studies increasingly rely on integrated data resources that combine Medicare fee-for-service claims with electronic medical records (EMRs), laboratory results, and patient-reported outcomes. The Medicare-Enhanced Laboratory and Demographics (MELD™) dataset, developed by Columbia Data Analytics, spans 2020 through 2024 and contains 60 million unique patients, roughly 1 billion visits, and more than 241 000 clinicians. Its data-quality properties must be characterized before regulatory-grade use. # Objective To provide a preregistered, multidomain validation of MELD, quantifying internal consistency, concurrent validity against Centers for Medicare & Medicaid Services (CMS) benchmarks, construct validity, record-linkage quality, missing-data mechanisms, temporal stability, and predictive validity across 20 indication cohorts. # Methods An analytic cohort of 32 118 604 patients with at least 12 months of continuous Medicare enrollment was derived. Internal consistency used Cronbach’s α and Kuder-Richardson KR-20. Concurrent validity compared MELD with CMS benchmarks using bias, mean absolute percentage error, Lin’s concordance correlation coefficient, and Bland-Altman limits of agreement. Construct validity used exploratory and confirmatory factor analysis. Record linkage used Fellegi-Sunter probabilistic matching. Predictive validity was assessed for 12-month mortality and 30-day readmission using the area under the receiver operating characteristic curve (AUROC), Brier score, and calibration slope/intercept. # Results Internal consistency was high (Cronbach’s α, 0.87; KR-20, 0.84). MELD replicated CMS prevalence with mean bias, −1.32 per 1000; Lin’s concordance correlation coefficient, 0.993 (95% confidence interval, 0.986-0.997); and mean absolute percentage error, 3.1%. The 3-factor confirmatory model achieved excellent fit (comparative fit index, 0.962; root mean square error of approximation, 0.041; standardized root mean square residual, 0.036). Fellegi-Sunter linkage produced a 94.7% match rate with false-match probability <0.3%. Weighted κ between International Classification of Diseases, Tenth Revision claims and EMR problem lists ranged 0.66 to 0.91. AUROC was 0.821 for mortality and 0.783 for readmission, with calibration slopes 0.97 and 0.94. # Conclusions MELD demonstrated strong psychometric, epidemiologic, and predictive properties, supporting use in health economics and outcomes research for Medicare-aged and adjacent populations. Limitations include residual missingness of race/ethnicity (26%) and EMR fragmentation outside networked provider groups.
# Background Ritlecitinib, a JAK3/TEC family kinase inhibitor, and baricitinib, a JAK1/2 inhibitor, are approved for treating severe alopecia areata (AA). # Objective Develop a cost-per-responder analysis for ritlecitinib and baricitinib for treating severe AA to estimate the budget impact based on clinical efficacy, available dosages, and pricing structure. # Methods A decision tree evaluated cost implications of once-daily ritlecitinib 50 mg, or baricitinib 2 mg and 4 mg treatment over 1 year from a US perspective. Drug costs were estimated using wholesale acquisition costs. Distribution across treatment and dosing options were based on real-world evidence. We defined shorter-term response as Severity of Alopecia Tool (SALT) score relative change from baseline ≥30% (SALT Δ≥30%; SALT~30~) at Weeks 18 and 24, and longer-term response as absolute SALT score ≤20 at Weeks 36 and 52. Patients initiating baricitinib 2 mg with no shorter-term response could uptitrate to 4 mg or discontinue therapy. Decision probabilities were derived from real-world evidence and clinical trial data. # Results At Week 24, 52.10% of ritlecitinib initiators and 36.28% of baricitinib initiators achieved SALT Δ ≥30%; at Week 52, 40.26% and 30.63% of ritlecitinib and baricitinib initiators, respectively, achieved SALT ≤20. Baricitinib had a higher cost per responder than ritlecitinib at Weeks 24 ($54 887 vs $45 577) and 52 ($107 217 vs $94 834). Cost-equivalence was reached at Week 52 ($38 180), with 42.72% of baricitinib patients initiating 2 mg treatment. Sensitivity analyses showed ritlecitinib cost per responder was lower at Week 24 (difference, −$1532) and higher at Week 52 (difference, $10 728) than only baricitinib 2 mg use, and lower at Weeks 24 and 52 (difference, −$20 001 and −$60 073) than only baricitinib 4 mg use. The lower cost per responder for ritlecitinib 50 mg vs baricitinib 2 or 4 mg at Weeks 24 and 52, and greater early efficacy and fewer discontinuations is consistent with the results of a prior indirect treatment comparison that supported favorable outcomes with ritlecitinib 50 mg vs baricitinib 2 mg. # Conclusions Ritlecitinib 50 mg demonstrated a lower cost per responder than baricitinib 2 or 4 mg at Weeks 24 and 52, which may inform reimbursement or formulary inclusion of ritlecitinib for treating AA.
# Background Discrete choice experiments (DCE) are commonly used for understanding patient preferences. However, their validity relies upon appropriate attribute selection and development. The present review aimed to identify reporting patterns and gaps to inform future reporting of patient preference studies. # Methods Ovid (MEDLINE and EMBASE) was used to search terms for "patients," "discrete choice experiments," and "attribute selection." Two independent reviewers screened studies against PICOS eligibility criteria, focusing on formative attribute development methods and reporting quality in patient preference DCEs up to 2024. Only full-text journal publications detailing attribute selection and development in patient preference DCEs were included. A coding form was developed and used to capture reporting on formative research used for attribute selection or development. Data synthesis employed a narrative approach following PRISMA guidelines. # Results Six categories of formative methods were identified across 28 studies: patient qualitative concept elicitation (n = 27; 96%), literature reviews (n = 21; 75%), expert consultation (n = 21; 75%), quantitative prioritization (n = 17, 61%), quantitative pilot DCE surveys (n = 13; 46%), and qualitative cognitive debriefing ( n =7; 25%). Most studies stated objectives (>85%), but methodological transparency decreased substantially for other elements, including rationale for choice of method, sample characteristics, sampling methods, data collection procedures data analysis, and results for formative research methods involving primary data collection. Most studies reported attribute lists following formative research (>75% across methods), but across formative methods fewer than half overall reported how formative findings informed attribute selection, level selection, or wording decisions. While 96% of studies included patients as research participants, only 7% reported engaging patients as research partners. # Conclusions The findings revealed inconsistent reporting of formative methods for attribute selection and development. Reporting of formative method details and results was mixed, with particularly low levels of reporting for how formative research results informed attribute selection, level selection, and wording. Furthermore, few studies engaged patients as research partners, suggesting another key area for development in the field of patient preference research. Improved reporting standards are needed to support methodological clarity and strengthen the validity of patient preference research. Patient engagement in the development of studies may further strengthen the patient relevance of patient preference studies.
# Background Early intervention for psychosis (EIP) is a multidisciplinary service that treats individuals experiencing early psychosis. Treatment often consists of pharmacotherapy and cognitive behavioral therapy for psychosis (CBTp). While EIP demonstrates clinical efficacy and cost-effectiveness as a comprehensive package, the incremental contribution of its individual components remains unclear. With mental health services facing sustained funding pressures, understanding which EIP elements offer value for money is crucial for resource allocation decisions. # Objectives To evaluate whether CBTp used in conjunction with pharmacotherapy in EIP is cost-effective compared with pharmacotherapy alone. # Methods A cost-effectiveness analysis was conducted using a cohort-based Markov model from the societal perspective over a 3-year time horizon. Model parameters were derived from a targeted literature review. The primary outcome was the incremental cost-effectiveness ratio (ICER), expressed as the cost per quality-adjusted life-year (QALY) gained. One-way sensitivity analysis identified influential parameters and probabilistic sensitivity analysis (PSA) quantified uncertainty around the ICER. # Results CBTp as an adjunct to pharmacotherapy resulted in a gain of 0.48 QALYs in the base case compared with pharmacotherapy alone. The corresponding ICER was £32 979 per QALY gained. This currently sits above the conventional upper willingness-to-pay threshold of £30 000 per QALY. One-way sensitivity analysis identified cost parameters and utility parameters for symptom-free status as the most influential variables on the ICER. PSA showed that CBTp had approximately a 50% probability of being cost-effective at the £30 000 threshold. # Conclusions Parameter uncertainty, particularly regarding costs and health utilities, drives the marginal cost-effectiveness case for CBTp. The intervention’s proximity to conventional thresholds suggests targeted improvements in service delivery or patient selection could enhance value. CBTp could potentially be a cost-effective adjunct to pharmacotherapy in EIP; however, there is uncertainty around the results of this modeling. These findings support the targeted implementation of CBTp within EIP. Further high-quality long-term studies are recommended to strengthen the evidence base.
# Background Sepsis is a leading cause of morbidity, mortality, and increased healthcare costs. Early recognition is critical, yet occult sepsis often evades standard screening, delaying care and worsening outcomes. Monocyte distribution width (MDW), a novel blood biomarker automatically reported with a routine complete blood cell count (CBC), has emerged as a promising tool for early detection of occult sepsis in adult patients in the emergency department (ED). # Objectives To evaluate the clinical and economic impact of incorporating MDW into standard ED sepsis screening vs standard of care (SoC). # Methods This study utilized a cost-consequence model to evaluate the clinical and economic impact of incorporating MDW into standard ED sepsis screening compared with standard screening (SoC) alone. Adults presenting to the ED and meeting sepsis criteria within 24 hours of CBC collection were stratified by sepsis suspicion level (no, low, high) and MDW values (normal, elevated). Outcomes, including time-to-antibiotics, hospital and intensive care unit (ICU) length of stay (LOS), ICU admission, mortality, and readmissions, were estimated using trial data and regression models from published literature. Costs were assessed from a US provider perspective in 2024 US dollars. # Results In the base case, SoC + MDW testing was associated with lower costs per patient than SoC ($36 340 vs $37 703; savings of $1363). Savings were driven by reduced ward and ICU LOS, particularly among patients with no or low suspicion of sepsis (eg, ICU LOS 0.30 vs 0.44 days; ward LOS 2.22 vs 2.75 days). Mortality was also reduced (0.03 vs 0.06 deaths per patient). While ED LOS increased in the MDW arm, inpatient savings offset these costs. Scenario analyses confirmed greater savings when unadjusted time-to-antibiotic data were applied. These findings are consistent with prior economic evaluations of early sepsis diagnostic tools and support the role of MDW in reducing downstream resource utilization, particularly among patients with occult presentations. # Conclusions MDW was found to be a low-cost tool that can strengthen sepsis screening by flagging cases earlier, especially in occult sepsis. Because it is reported with a routine CBC, MDW can be readily implemented and may improve outcomes while reducing costs.
# Background Progression rates in immunoglobulin A nephropathy (IgAN) are variable, making future healthcare needs in this patient population difficult to anticipate. # Objectives We sought to determine whether baseline patient characteristics at biopsy diagnosis are predictive of subsequent healthcare resource utilization (HCRU) in individuals affected by IgAN. # Methods This was a longitudinal, retrospective cohort study of members enrolled in Kaiser Permanente Southern California, a racially, ethnically, and socioeconomically diverse population. We extracted data on members diagnosed with primary IgAN based on kidney biopsies performed from 2000 to 2021. Statistical associations between indicators of disease severity at baseline and subsequent HCRU were evaluated. The baseline variables assessed were chronic kidney disease (CKD) stage, urine protein creatinine ratio (UPCR), and the individual burden of comorbidities expressed as Elixhauser Comorbidity Index. The HCRU outcomes were emergency department visits, inpatient visits, outpatient visits, radiology, laboratory, and medication dispensations within 2 years after biopsy, all expressed as utilization per patient per month (PPPM). # Results A total of 612 adults with primary IgAN were identified. Worse baseline CKD stage and UPCR exhibited statistically significant positive correlations with the PPPM for aggregate HCRU. Patients in CKD stage G4 had an overall PPPM of 2.94, which was significantly (P < .01) greater than for each milder CKD category (1.56-2.04). Patients with UPCR >2 g/g had an overall PPPM (2.38), which was significantly (P < .01) greater than each milder UPCR category (1.70-1.84). Aggregate PPPM showed a numerically increasing trend from the least (<0.5 g/g) to most severe UPCR category (>2 g/g). CKD stage, UPCR, and comorbidity score all correlated significantly with individual HCRU outcomes. # Discussion Easily assessed patient baseline variables including CKD stage, proteinuria, and comorbidities are predictive of HCRU in primary IgAN. Our findings are consistent with recent IgAN management guidelines designating proteinuria ≥0.5 g/g as indicative of elevated progression risk. # Conclusions Patient clinical characteristics can be used to estimate future HCRU in IgAN, facilitating cost-benefit analysis. The accurate estimation of anticipated HCRU is becoming increasingly important in IgAN as new, disease-specific therapies become available for this long-term, progressive condition.
**Background:** The economic burden associated with idiopathic pulmonary fibrosis (IPF) is not well understood, especially since the approval of antifibrotic medications to treat IPF in 2014. **Objective:** This study assessed healthcare resource utilization (HCRU) and costs for patients with and without IPF among insured patients in the United States. **Methods:** This retrospective study used claims data from the Optum Research Database from 01 January 2016 through 31 December 2023. The IPF cohort included patients with at least 2 claims for IPF within 365 days. A comparator cohort was exact matched to the IPF cohort in a 4:1 ratio on demographic characteristics. Follow-up all-cause and respiratory-related HCRU and costs were collected. Outcomes were presented as weighted per-patient per-month (wPPPM) to account for variable follow-up. Descriptive results were reported by cohort, overall, and stratified by insurance type. All-cause and respiratory-related wPPPM costs were modeled using generalized linear models and time to all-cause and respiratory-related inpatient visits were modeled using Cox proportional hazards regression models, adjusted for baseline comorbidities. **Results:** A total of 7582 patients were included in the IPF cohort; 10.4% were commercially insured and 89.6% insured by Medicare Advantage Prescription Drug (MAPD) plans. The comparator cohort included 30 328 demographically matched controls. Overall, mean all-cause wPPPM counts of HCRU during follow-up were significantly higher in the IPF cohort than the comparator cohort for all categories (all P < .001). Similarly, mean (SD) follow-up all-cause wPPPM total healthcare costs were higher for the IPF cohort than the comparator cohort ($4667 [$8252] vs $1196 [$2114], P < .001). After adjustment, the cost ratio for all-cause total healthcare costs between the IPF and comparator cohorts was 3.4 (95% confidence interval [CI], 3.10-3.64), and patients in the IPF cohort were 2.1 times (95% CI, 1.97-2.15) more likely to be hospitalized for all causes than the comparator cohort. For both HCRU and costs, similar patterns were observed in both the commercial and MAPD populations. Conclusion: Patients with IPF incurred substantially higher HCRU and costs than the demographically matched comparator cohort. Study results suggest the need for treatment options to improve management of IPF and reduce costly HCRU.
