The role of cAMP dependent gene transcription in lupus pathophysiology.

T lymphocytes play a major role in the pathophysiology of systemic lupus erythematosus. T cellular dysregulation includes significant alterations in signal transduction, cytokine production and metabolic pathways. The cAMP dependent transcription factors like CREB and CREM exert pleiotropic functions as they are critically involved in epigenetic conformational changes and gene regulation of different key effector cytokines in CD4+ T cells including that of IL2, IL17 and IL21 genes. In the present review we review current knowledge on altered expression and function of these factors in T cells that promote autoimmunity in SLE patients.

Cost-effectiveness of the tandem t: Slim X2 with control-IQ technology automated insulin delivery system in children and adolescents with type 1 diabetes in Sweden.

AIMS: The present analysis estimated the cost-effectiveness of treatment with the Tandem t: slim X2 insulin pump with Control IQ technology (CIQ) in children with type 1 diabetes in Sweden. METHODS: A four-state Markov model and probabilistic sensitivity analyses (PSA) were used to assess the cost-effectiveness of CIQ use compared with treatment with multiple daily insulin injections (MDI) or continuous subcutaneous insulin infusion (CSII) in conjunction with CGM. Data sources included clinical input data from a recent retrospective, observational study, cost data from local diabetes supply companies and government agencies, and published literature. Outcomes measures were quality adjusted life years (QALYs) at 10, 20 and 30-year time horizons based on cost per QALY and incremental cost-effectiveness ratio (ICER). RESULTS: A total of 84 type 1 diabetes children were included (CIQ, n = 37; MDI, n = 19; CSII, n = 28). For all time horizons, the use of CIQ was a dominant strategy (e.g. more effective and less costly) compared with MDI or CSII use: 10-year ICER, SEK -88,010.37 and SEK -91,723.92; 20-year ICER, SEK -72,095.33 and SEK -87,707.79; and 30-year ICER, SEK -65,573.01 and SEK -85,495.68, respectively. PSA confirmed that CIQ use was less costly compared with MDI and CSII. CONCLUSIONS: Initiation of CIQ use in children with type 1 diabetes is cost-saving, besides previously shown improved glycaemic control, and increased quality of life. Further investigations are needed to more fully elucidate the cost-effectiveness of these technologies in different countries with existing differences in payment models.

"Will ICER's 'shared savings' approach decrease value-based prices most for the most severe diseases?"

OBJECTIVES: To identify the types of disease most likely to be impacted by the Institute for Clinical and Economic Review's (ICER) shared savings assumptions. METHODS: For diseases with treatments that were FDA-approved between 2019 and 2023, annual direct and indirect economic burden and characteristics of each disease were extracted from peer-reviewed literature. ICER's shared savings methodology was applied two ways: 50/50 shared savings and $150,000 cost-offset cap. The primary outcome was the difference in eligible cost savings provided by a hypothetical disease cure under ICER's 2 shared savings methods. Characteristics of diseases most impacted by these 2 methods were evaluated descriptively. RESULTS: FDA approved 260 therapies for 89 unique diseases between 2019 and 2023. Shared savings reduced value of a hypothetical cure for hemophilia A most (50/50 method: -$367,670 per year; cap method: -$585,340 per year), followed by acute hepatic porphyria (50/50 method: -$333,948; cap method: -$517,896) and paroxysmal nocturnal hemoglobinuria (50/50 method: -$291,997; cap method: -$433,993). Compared to diseases with annual burdens <$150,000, those ≥$150,000 had earlier disease onset by 22.0 years (age 12.3 vs. 34.3), lower life expectancy by 10.6 years (55.8 vs. 66.4 years), and lower disease prevalence (4.7 vs. 1981.5 per 100,000). Shared savings' impact on health benefit price benchmarks was projected to be larger for diseases with shorter life expectancy (ρ=-0.319; p=0.005), worse quality-of-life (ρ=-0.263; p=0.020), and lower prevalence (ρ=-0.418; p<0.001). CONCLUSIONS: ICER's shared savings assumptions would most likely have the largest negative impact on health benefit price benchmarks for rare, severe, and pediatric diseases.

Cost-effectiveness of mepolizumab for severe eosinophilic asthma in China.

OBJECTIVE: To evaluate the economic value of mepolizumab as an add-on therapy to the standard of care (SoC) for patients with severe eosinophilic asthma in China. METHODS: A Markov model with three health conditions was constructed to calculate the incremental cost per quality-adjusted life year (QALY) in mepolizumab with SoC and SoC only groups from the perspective of the Chinese healthcare system throughout an entire lifespan. The model was populated with local costs, while efficacy parameters were obtained from the global Phase III MENSA trial and mortality was derived from two surveys. One-way and probabilistic sensitivity analyses were conducted. Additional scenario analysis was used to estimate the cost-effectiveness impact of changes in the price of mepolizumab. RESULTS: Over the lifetime treatment horizon, the incremental cost-effectiveness ratio (ICER) of mepolizumab plus SoC compared to SoC alone was $170 648.73 per QALY. Sensitivity analyses focused on these results. Scenario analysis showed that mepolizumab would require a price reduction of at least 82% to reach the current willingness-to-pay (WTP=$38 223.34/QALY) threshold. CONCLUSION: Mepolizumab is not a cost-effective healthcare resource in China at its current pricing.

Outcome and Cost-Effectiveness Analysis of Long-acting G-CSF as Primary Prophylaxis of Neutropenia Induced by Chemotherapy in Breast Cancer Patients, From a Retrospective Study.

PURPOSE: This retrospective analysis aimed to evaluate the clinical outcomes and cost-effectiveness of long-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia caused by chemotherapy for breast cancer. METHODS: Patients with breast cancer who received long- or short-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia were enrolled in this study, and incidences of neutropenia were compared between two groups. A decision-analytic and a Markov model were used to compare the health benefits and costs of utilizing long- vs short-acting granulocyte-colony stimulating factor as the primary prophylaxis from the perspective of the Chinese health service system. Subsequently, one-way deterministic and probabilistic sensitivity analyses were conducted. The incremental cost-effectiveness ratios were calculated in baseline and sensitivity analyses. RESULTS: Patients receiving long-acting granulocyte-colony stimulating factor as the primary prophylaxis of chemotherapy-induced neutropenia experienced a significant lower incidence of this adverse event, compared with the short-acting one for 2 to 7 days. The outcomes of baseline analysis indicated that long-acting granulocyte-colony stimulating factor had a gain of 0.08 quality-adjusted life years and costed $149 more than the short-acting one, yielding an incremental cost-effectiveness ratio of $1792 per quality-adjusted life year. The sensitivity analysis proved the stability of our models and economic efficiency of long-acting granulocyte-colony stimulating factor. CONCLUSIONS: Patients receiving long-acting granulocyte-colony stimulating factor as primary prophylaxis of neutropenia experienced lower risk of this event compared with those underusing short-acting one. The long-acting granulocyte-colony stimulating factor may be a more cost-effective strategy for primary prophylaxis of neutropenia than short-acting one, considering the Chinese willingness-to-pay threshold of $12158.6 per quality-adjusted life year.

Cost-effectiveness of omalizumab for the treatment of severe pediatric allergic asthma-Results of a real-life study in Spain.

BACKGROUND: Severe pediatric allergic asthma (SPAA) induces a huge economic burden in terms of direct, indirect, and intangible costs. The use of omalizumab for the treatment of these patients has produced a significant improvement in several clinical outcomes, but at the same time, the cost for the management of the disease has also increased. The aim of this report was to evaluate whether the use of omalizumab is cost-effective. METHODS: A sample of 426 children with SPAA from the ANCHORS (Asthma iN CHildren: Omalizumab in Real-life in Spain) study was used to calculate the incremental cost-effectiveness ratio (ICER) for the avoidance of moderate-to-severe exacerbations (MSE) and also for the improvement in childhood Asthma Control Test (c-ACT) or the Asthma Control Questionnaire (ACQ5). We retrospectively collected data on health encounters and drug consumption before and up to 6 years after the beginning of the treatment with omalizumab. RESULTS: The ICER per avoided MSE was €2107 after 1 year, and it consistently decreased to €656 in those followed up to 6 years. Similarly, the ICER for the minimally important difference in control tests showed a decrease from €2059 to €380 per each 0.5 points of improvement in ACQ5 and from €3141 to €2322 per each 3 points improvement in c-ACT, at years 1 and 6, respectively. CONCLUSION: The use of OMZ is a cost-effective option for most children with uncontrolled SPAA, especially those who have frequent exacerbations; the costs are progressively reduced in successive years of treatment.

Evidence that the transcriptional repressor ICER is regulated via the N-end rule for ubiquitination.

ICER is a transcriptional repressor that is mono- or poly-ubiquitinated. This either causes ICER to be translocated from the nucleus, or degraded via the proteasome, respectively. In order to further studies the proteins involved in ICER regulation mass spectrometry analysis was performed to identify potential candidates. We identified twenty eight ICER-interacting proteins in human melanoma cells, Sk-Mel-24. In this study we focus on two proteins with potential roles in ICER proteasomal degradation in response to the N-end rule for ubiquitination: the N-alpha-acetyltransferase 15 (NAA15) and the E3 ubiquitin-protein ligase UBR4. Using an HA-tag on the N- or C-terminus of ICER (NHAICER or ICERCHA) it was found that the N-terminus of ICER is important for its interaction to UBR4, whereas NARG1 interaction is independent of HA-tag position. Silencing RNA experiments show that both NAA15 and UBR4 up-regulates ICER levels and that ICER's N-terminus is important for this regulation. The N-terminus of ICER was found to have dire consequences on its regulation by ubiquitination and cellular functions. The half-life of NHAICER was found to be about twice as long as ICERCHA. Polyubiquitination of ICER was found to be dependent on its N-terminus and mediated by UBR4. This data strongly suggests that ICER is ubiquitinated as a response to the N-end rule that governs protein degradation rate through recognition of the N-terminal residue of proteins. Furthermore, we found that NHAICER inhibits transcription two times more efficiently than ICERCHA, and causes apoptosis 5 times more efficiently than ICERCHA. As forced expression of ICER has been shown before to block cells in mitosis, our data represent a potentially novel mechanism for apoptosis of cells in mitotic arrest.

A nationwide multicenter study of the cost effectiveness of five leading drugs for pharmacological management of cervicobrachial symptoms.

BACKGROUND: Cervicobrachial pain frequently affects the quality of life (QOL) of the general public and has a significant economic impact on the health care systems of various countries. There are a number of treatment options for this disease, including widely-used drug therapy, but the effectiveness of each option is indeterminate, and there have been no published cost-effectiveness analysis studies so far. This prospective observational study aimed to examine the cost-effectiveness of drug treatment for cervicobrachial symptoms. METHODS: A 6-month medication regimen for each of five frequently-prescribed drugs for cervicobrachial symptoms was administered to 322 patients at 24 centers in Japan. Outcome measures, including of the EuroQol Group 5D, Short Form-8, and Visual Analog Scale (VAS), were investigated at baseline and every month thereafter. Incremental cost-effectiveness ratios (ICERs) of the drug cost to quality-adjusted life years (QALYs) were calculated. A stratified analysis of patient characteristics was also performed to identify baseline factors potentially affecting cost-effectiveness. RESULTS: The ICER of entire drug treatment for cervicobrachial symptoms was 7,491,640 yen. Compared with the reference willingness-to-pay, the ICER was assumed to not be cost-effective. A certain number of QALYs were gained during the first 3 months after the treatment intervention, but almost no QALYs were gained during the following 3 months. Stratified analysis showed that cost-effectiveness was extremely low for patients with high baseline VAS and high QOL. CONCLUSIONS: The available medications for cervicobrachial symptoms did not have excellent cost-effectiveness. Although a certain number of QALYs were gained during the first 3 months after medication, no QALYs were gained in the latter half of the study period, suggesting that it is not advisable to continue the medication needlessly. LEVEL OF EVIDENCE: II, prospective cohort study.

Comparing Costs and Outcomes of Treatments for Irritable Bowel Syndrome With Diarrhea: Cost-Benefit Analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is one of the most expensive gastroenterological conditions and is an ideal target for developing a value-based care model. We assessed the comparative cost-benefit of treatments for IBS with diarrhea (IBS-D), the most common IBS subtype from insurer and patient perspectives. METHODS: We constructed a decision analytic model assessing trade-offs among guideline-recommended and recently FDA-approved drugs, supplements, low FODMAP diet, cognitive behavioral therapy (CBT). Outcomes and costs were derived from systematic reviews of clinical trials and national databases. Health-gains were represented using quality-adjusted life years (QALY). RESULTS: From an insurer perspective, on-label prescription drugs (rifaximin, eluxadoline, alosetron) were significantly more expensive than off-label treatments, low FODMAP, or CBT. Insurer treatment preferences were driven by average wholesale prescription drug prices and were not affected by health gains in sensitivity analysis within standard willingness-to-pay ranges up to $150,000/QALY-gained. From a patient perspective, prescription drug therapies and neuromodulators appeared preferable due to a reduction in lost wages due to IBS with effective therapy, and also considering out-of-pocket costs of low FODMAP food and out-of-pocket costs to attend CBT appointments. Comparative health outcomes exerted influence on treatment preferences from a patient perspective in cost-benefit analysis depending on a patients' willingness-to-pay threshold for additional health-gains, but health outcomes were less important than out-of-pocket costs at lower willingness-to-pay thresholds. CONCLUSIONS: Costs are critical determinants of IBS treatment value to patients and insurers, but different costs drive patient and insurer treatment preferences. Divergent cost drivers appear to explain misalignment between patient and insurer IBS treatment preferences in practice.

Cost-Effectiveness of Dapagliflozin for Chronic Kidney Disease in Japan.

BACKGROUND: The cost-effectiveness of sodium-glucose cotransporter 2 (SGLT2) inhibitors for chronic kidney disease (CKD) has not been evaluated in Japan, so we analyzed the cost-effectiveness of dapagliflozin, an SGLT2 inhibitor, for CKD stages 3a and 3b.Methods and Results: We used the Markov model for CKD to assess the costs and benefits associated with and without dapagliflozin from a health system perspective. We estimated the incremental cost-effectiveness ratio (ICER), expressed as per quality-adjusted life-years (QALYs). An ICER <5 million Japanese yen (JPY)/QALY was judged to be cost-effective. The effect of dapagliflozin on renal and cardiovascular events was based on published clinical trials. In patients with CKD stage 3a, the ICER of dapagliflozin over standard treatment was 4.03 million JPY/QALY gained. With a cost-effectiveness threshold of 5 million JPY/QALY gained, the cost-effectiveness probability of dapagliflozin over standard treatment was 52.6%. In patients with CKD stage 3b, the ICER of dapagliflozin over standard treatment was 0.12 million JPY/QALY gained. The cost-effectiveness probability of dapagliflozin over standard treatment was 75.2%. CONCLUSIONS: The results seemed to show acceptable cost-effectiveness when dapagliflozin was used for CKD stage 3b. On the other hand, cost-effectiveness of dapagliflozin for CKD stage 3a was ambiguous, and further validation is needed.

The First Year of Noninvasive Remote Telemonitoring in Chronic Heart Failure Is not Cost Saving but Improves Quality of Life: The Randomized Controlled CardioBBEAT Trial.

Introduction: Remote telemonitoring (RTM) for patients with chronic heart failure (HF) holds promise to improve prognosis and well-being beyond the standard of care (SoC). The CardioBBEAT trial assessed the health economic and clinical impact of an interactive bidirectional RTM system (Motiva®) versus SoC for patients with HF and a reduced ejection fraction (HFrEF), in Germany. Methods: This multicenter, randomized controlled trial enrolled 621 patients with HFrEF (mean age 63.0 ± 11.5 years, 88% men). The primary endpoint was the integrated effect of the intervention on total costs and nonhospitalized days alive after 12 months, reported as incremental cost-effectiveness ratio (ICER). Costs (in k€) were based on actual charges of patients' statutory health insurance. Among secondary outcome measures were mortality and disease-specific quality of life. Results: We found a neutral effect on nonhospitalized days alive (RTM mean 341 ± 59 days, SoC 346 ± 45 days; p = 0.298) associated with increased total costs (RTM 18.5 ± 39.5 k€, SoC 12.8 ± 22.0 k€; p = 0.046). This yielded an ICER of -1.15 k€/day. RTM did not impact mortality risk. All quality of life scales were consistently and meaningfully improved in the RTM group at 12 months compared to SoC (all p < 0.01). Conclusions: The first 12 months of RTM were not cost-effective compared to SoC in patients with HFrEF, but associated with a relevant improvement in disease-specific quality of life. The balanced assessment of the potential benefit of RTM requires integration of both the societal and patient perspective. ClinTrials.gov (NCT02293252).

The cAMP responsive element modulator (CREM) is a regulator of CD4+ T cell function.

The cAMP responsive element modulator (CREM) is a transcriptional regulator of different effector cytokines in CD4+ T cells including IL-2, IL-17, IL-21 but also IL-4 and IL-13 and thus an important determinant of central T helper cell functions. Our review gives an overview over the regulation of CREM in T cells and the pleiotropic effects of CREM on CD4+ T cells in health and autoimmune diseases with a particular focus on systemic lupus erythematosus.

Minimal-Contact Versus Standard Cognitive Behavioral Therapy for Irritable Bowel Syndrome: Cost-Effectiveness Results of a Multisite Trial.

BACKGROUND: Irritable bowel syndrome (IBS) is a common, often disabling gastrointestinal (GI) disorder for which there is no satisfactory medical treatment but is responsive to cognitive behavior therapy (CBT). PURPOSE: To evaluate the costs and cost-effectiveness of a minimal contact version of CBT (MC-CBT) condition for N = 145 for IBS relative to a standard, clinic-based CBT (S-CBT; N = 146) and a nonspecific comparator emphasizing education/support (EDU; N = 145). METHOD: We estimated the per-patient cost of each treatment condition using an activity-based costing approach that allowed us to identify and estimate costs for specific components of each intervention as well as the overall total costs. Using simple means analysis and multiple regression models, we estimated the incremental effectiveness of MC-CBT relative to S-CBT and EDU. We then evaluated the cost-effectiveness of MC-CBT relative to these alternatives for selected outcomes at immediate posttreatment and 6 months posttreatment, using both an intent-to-treatment and per-protocol methodology. Key outcomes included scores on the Clinical Global Impressions-Improvement Scale and the percentage of patients who positively responded to treatment. RESULTS: The average per-patient cost of delivering MC-CBT was $348, which was significantly less than the cost of S-CBT ($644) and EDU ($457) (p < .01). Furthermore, MC-CBT produced better average patient outcomes at immediate and 6 months posttreatment relative to S-CBT and EDU (p < .01). The current findings indicated that MC-CBT is a cost-effective option relative to S-CBT and EDU. CONCLUSION: As predicted, MC-CBT was delivered at a lower cost per patient than S-CBT and performed better over time on the primary outcome of global IBS symptom improvement.

Cost-utility analysis of esketamine and electroconvulsive therapy in adults with treatment-resistant depression.

BACKGROUND: Electroconvulsive therapy (ECT) has long been used for treating individuals with treatment-resistant depression (TRD). Esketamine has recently emerged as a new treatment for TRD due to its rapid antidepressant effects. To further inform the decision regarding choice of treatment, this paper aims to evaluate whether ECT or esketamine is the more cost-effective option. METHODS: The cost-effectiveness was derived as cost per quality-adjusted life-year (QALY) using a Markov model from a societal and life-time perspective. The incremental cost-effectiveness ratio (ICER) was calculated. Health states included different depression and remission states and death. Data to populate the model was derived from randomised controlled trials and other research. Various sensitivity analyses were carried out to test the robustness of the model. RESULTS: The base case scenario shows that ECT is cost-effective compared to esketamine and yields more QALYs at a lower cost. The sensitivity analysis shows that ECT is cost-effective in all scenarios and ECT dominates esketamine in 12 scenarios. CONCLUSIONS: This study found that, from a cost-effectiveness point of view, ECT should be the first-hand option for individuals with TRD, when other first line treatments have failed. Considering the lack of economic evaluation of ECT and esketamine, this study is of great value to decision makers.

Pyruvate dehydrogenase phosphatase catalytic subunit 2 limits Th17 differentiation.

Th17 cells favor glycolytic metabolism, and pyruvate dehydrogenase (PDH) is the key bifurcation enzyme, which in its active dephosphorylated form advances the oxidative phosphorylation from glycolytic pathway. The transcriptional factor, inducible cAMP early repressor/cAMP response element modulator (ICER/CREM), has been shown to be induced in Th17 cells and to be overexpressed in CD4+ T cells from the patients with systemic lupus erythematosus (SLE). We found that glycolysis and lactate production in in vitro Th17-polarized T cells was reduced and that the expression of pyruvate dehydrogenase phosphatase catalytic subunit 2 (PDP2), an enzyme that converts the inactive PDH to its active form, and PDH enzyme activity were increased in Th17 cells from ICER/CREM-deficient animals. ICER was found to bind to the Pdp2 promoter and suppress its expression. Furthermore, forced expression of PDP2 in CD4+ cells reduced the in vitro Th17 differentiation, whereas shRNA-based suppression of PDP2 expression increased in vitro Th17 differentiation and augmented experimental autoimmune encephalomyelitis. At the translational level, PDP2 expression was decreased in memory Th17 cells from patients with SLE and forced expression of PDP2 in CD4+ T cells from lupus-prone MRL/lpr mice and patients with SLE suppressed Th17 differentiation. These data demonstrate the direct control of energy production during Th17 differentiation in health and disease by the transcription factor ICER/CREM at the PDH metabolism bifurcation level.

Transcriptional factor ICER promotes glutaminolysis and the generation of Th17 cells.

Glutaminolysis is a well-known source of energy for effector T cells but its contribution to each T cell subset and the mechanisms which are responsible for the control of involved metabolic enzymes are not fully understood. We report that Th17 but not Th1, Th2, or Treg cell induction in vitro depends on glutaminolysis and the up-regulation of glutaminase 1 (Gls1), the first enzyme in the glutaminolysis pathway. Both pharmacological and siRNA-based selective inhibition of Gls1 reduced in vitro Th17 differentiation and reduced the CD3/TCR-mediated increase of the mammalian target of rapamycin complex 1 activity. Treatment of mice with a Gls1 inhibitor ameliorated experimental autoimmune encephalomyelitis. Furthermore, RAG1-deficient mice that received Gls1-shRNA-transfected 2D2 T cells had reduced experimental autoimmune encephalomyelitis scores compared with those that received control-shRNA-treated cells. Next we found that T cells deficient in inducible cAMP early repressor (ICER), a transcriptional factor known to promote Th17 differentiation, display reduced activity of oxidative phosphorylation rates in the presence of glutamine and reduced Gls1 expression, both of which could be restored by ICER overexpression. Finally, we demonstrate that ICER binds to the gls1 promoter directly and increases its activity. These findings demonstrate the importance of glutaminolysis in the generation of Th17 and the direct control of Gls1 activity by the IL-17-promoting transcription factor ICER. Pharmaceutical modulation of the glutaminolysis pathway should be considered to control Th17-mediated pathology.

Vocational Rehabilitation for Patients with Chronic Musculoskeletal Pain With or Without a Work Module: An Economic Evaluation.

Purpose Vocational rehabilitation (VR) is a widely used intervention aimed to optimize work participation for patients on sick leave due to chronic musculoskeletal pain (CMP). Economic evaluations of care as usual VR are scarce, and may provide relevant information to guide clinical, reimbursement and policy decisions. The aim of this study was to evaluate the short-term cost-effectiveness and return on investment (ROI) of VR for patients on sick leave due to CMP with an additional work module (VR+) compared to VR without work module, from a societal and employers' perspective. Methods A retrospective longitudinal cohort study within a Dutch care as usual context was applied. Participants with CMP and decreased work participation originating from seven Dutch rehabilitation centers were included in this study. Participants underwent VR or VR+. Main data sources at baseline and discharge: Quality-adjusted life year (QALY) based on EQ-5D, intervention costs, self-reported productivity and health care utilization. Main analyses cost-effectiveness, including incremental cost-effectiveness ratio (ICER) and a cost-effectiveness acceptability curve (CEAC); and ROI analyses with use of the human capital method. Results N = 324 participants were analyzed. The results show that VR+ was cost-effective compared to VR: mean cost savings of €820 per 0.012 QALY gained. CEAC suggests probability of VR+ being cost-effective is > 0.91 for thresholds of €20.000 and higher. The mean ROI of VR+ for employers was 38%. Conclusion It was concluded that at discharge, VR+ was cost-effective compared to VR. ROI was positive for employers.

Pilot Study of the Cost-Effectiveness of Youth F-ACT in the Netherlands.

Mental healthcare costs are rising. Community-based interventions often are being implemented without sufficient evidence for the effectiveness in terms of care and cost. In this pilot study, we evaluated the cost-effectiveness of youth Flexible Assertive Community Treatment (F-ACT) compared to treatment as usual (TAU). In total 28 adolescents (12-18 years) participated in F-ACT (N = 13) and TAU (N = 15). The outcome measures were the percentage of adolescents with a significant improvement in quality of life and Quality Adjusted Life Years (QALYs). Costs were measured using a retrospective cost-questionnaire. Outcomes were assessed at the start and after three months of care. Compared to TAU, F-ACT resulted in a significantly higher quality of life as reported by adolescents. There was no significant difference in quality of life reported by the parents. The incremental cost-effectiveness ratio (ICER) demonstrated that youth F-ACT is more effective but with higher costs. This study may help to make evidence-based decisions in terms of who benefits the most from youth F-ACT interventions.

Optimizing Management of Patients With Barrett's Esophagus and Low-Grade or No Dysplasia Based on Comparative Modeling.

BACKGROUND & AIMS: Endoscopic treatment is recommended for patients with Barrett's esophagus (BE) with high-grade dysplasia, yet clinical management recommendations are inconsistent for patients with BE without dysplasia (NDBE) or with low-grade dysplasia (LGD). We used a comparative modeling analysis to identify optimal management strategies for these patients. METHODS: We used 3 independent population-based models to simulate cohorts of 60-year-old individuals with BE in the United States. We followed up each cohort until death without surveillance and treatment (natural disease progression), compared with 78 different strategies of management for patients with NDBE or LGD. We determined the optimal strategy using cost-effectiveness analyses, at a willingness-to-pay threshold of $100,000 per quality-adjusted life-year (QALY). RESULTS: In the 3 models, the average cumulative incidence of esophageal adenocarcinoma was 111 cases, with costs totaling $5.7 million per 1000 men with BE. Surveillance and treatment of men with BE prevented 23% to 75% of cases of esophageal adenocarcinoma, but increased costs to $6.2 to $17.3 million per 1000 men with BE. The optimal strategy was surveillance every 3 years for men with NDBE and treatment of LGD after confirmation by repeat endoscopy (incremental cost-effectiveness ratio, $53,044/QALY). The average results for women were consistent with the results for men for LGD management, but the optimal surveillance interval for women with NDBE was 5 years (incremental cost-effectiveness ratio, $36,045/QALY). CONCLUSIONS: Based on analyses from 3 population-based models, the optimal management strategy for patient with BE and LGD is endoscopic eradication, but only after LGD is confirmed by a repeat endoscopy. The optimal strategy for patients with NDBE is endoscopic surveillance, using a 3-year interval for men and a 5-year interval for women.

Cost-Effectiveness Analysis of Screening for Hepatitis B Virus Infection in Patients With Solid Tumors Before Initiating Chemotherapy.

BACKGROUND & AIMS: Patients with solid tumors who undergo chemotherapy have an increased risk of hepatitis B virus (HBV) reactivation, but a low proportion of these patients are screened for HBV infection and guidelines make conflicting recommendations. Further, the cost-effectiveness of newer treatments for HBV prophylaxis has not been examined for this population. We aimed to analyze the cost-effectiveness of HBV screening before chemotherapy for patients with solid tumors. METHODS: We compared 3 HBV screening strategies (screen all, screen only high-risk patients, or screen none) using a Markov model of a population of adults in the United States who initiated chemotherapy for a solid tumor. We modeled use of entecavir prophylaxis for HB surface antigen (HBsAg)-positive patients and surveillance for HBsAg-negative patients who are positive for HBV core antibody. The Markov cycle length was 1 year, with model simulation for up to 5 years. RESULTS: The screen all strategy was the most cost effective, with an incremental cost-effectiveness ratio of $42,761 compared to screening only high-risk patients. The screen none strategy was less effective and less costly than screening all patients or only high-risk patients. The screen-all strategy was the most cost effective for all estimates of prevalence of HBsAg-positive patients and estimates of HBV reactivation in HBsAg-positive patients. Screening only high-risk patients was the most cost-effective strategy when more than 25% of high-risk patients were screened for HBV infection. CONCLUSIONS: In a Markov model analysis, we found screening all patients with solid tumors for HBV infection before chemotherapy to be the most cost-effective strategy. Guidelines should consider recommending HBV tests for patients initiating chemotherapy.