Adjunctive Use of WATS-3D in Symptomatic GERD Patients Increases Detection of Barrett's Esophagus and Dysplasia.

BACKGROUND: Patients with gastroesophageal reflux (GERD) symptoms undergoing screening upper endoscopy for Barrett's esophagus (BE) frequently demonstrate columnar-lined epithelium (CLE), with forceps biopsies (FB) failing to yield intestinal metaplasia (IM). Repeat endoscopy is often necessary. AIM: Assess the yield of IM leading to a diagnosis of BE by the addition of Wide-Area Trans-epithelial Sampling (WATS-3D) to FB in the screening of GERD patients. METHODS: We performed a prospective registry study of GERD patients undergoing screening upper endoscopy. Patients had both WATS-3D and FB. Patients were classified by their Z line appearance: regular, irregular (<1 cm CLE), possible short-segment BE (1-<3cm), and possible long-segment BE (≥3cm). Demographics, IM yield, and dysplasia yield were calculated. Adjunctive yield was defined as cases identified by WATS-3D not detected by FB, divided by cases detected by FB. Clinicians were asked if WATS-3D results impacted patient management. RESULTS: Of 23,933 patients, 6,829(28.5%) met endoscopic criteria for BE. Of these, 2,878(42.1%) had IM identified by either FB or WATS-3D. Among patients fulfilling endoscopic criteria for BE, the adjunctive yield of WATS-3D was 76.5%, and absolute yield was 18.1%. 1,317 patients (19.3%) who fulfilled endoscopic BE criteria had IM detected solely by WATS-3D. Of 240 patients with dysplasia, 107(44.6%) were found solely by WATS-3D. Among patients with positive WATS-3D but negative FB, the care plan changed in 90.7%. CONCLUSION: The addition of WATS-3D to FB in GERD patients being screened for BE resulted in confirmation of BE in an additional 1/5 th of patients. Furthermore, dysplasia diagnoses approximately doubled.

WATS 3D : An Interobserver Study of Barrett's Esophagus-Associated Dysplasia Among Gastrointestinal Pathologists.

INTRODUCTION: Wide-area transepithelial sampling with 3-dimensional computer-assisted analysis (WATS 3D ) has been shown to increase the detection rate of dysplasia (and intestinal metaplasia) in patients with Barrett's esophagus (BE). The purpose of this study was to evaluate the interobserver variability and accuracy of diagnosing BE-associated dysplasia in WATS 3D specimens among gastrointestinal (GI) pathologists without prior experience with this technology. METHODS: Five GI pathologists underwent a 4-hour in-person (at microscope) and virtual training session and then evaluated digital images of discrete cellular foci from 60 WATS 3D cases with BE (20 nondysplastic BE [NDBE], 20 low-grade dysplasia [LGD], and 20 high-grade dysplasia/esophageal adenocarcinoma [HGD/EAC]). Each case consisted of 1 hematoxylin and eosin-stained image (cell block), and 1 liquid cytology or papanicolaou-stained smear image (120 images in total). RESULTS: The overall kappa value among the 5 study pathologists was excellent (overall kappa = 0.93; kappa = 0.93 and 0.97 for cell block and smear specimens, respectively). There were no significant differences noted in kappa values in interpretation of the cell block vs smear specimens or in any of the individual diagnostic categories when the latter were evaluated separately. Furthermore, agreement was perfect (100%) regarding detection of neoplasia (either LGD, HGD, or EAC). Diagnoses were made with complete confidence in 91% of instances. DISCUSSION: We conclude that GI pathologists, without any prior experience in interpretation of WATS 3D specimens, can undergo a short training session and then diagnose these specimens with a very high level of accuracy and reproducibility.

Increased Hazard Risk of First Malignancy in Adults with Undetectable Serum IgE: a Retrospective Cohort Study.

PURPOSE: The clinical relevance of IgE-deficiency is not established. Previous studies have postulated a relationship between absent serum IgE and the incidence of specific malignancies. We sought to examine the relationship between undetectable total serum IgE (< 3 IU/mL) and first malignancy, considering both general all-cause malignancy risk and risk of specific malignancy subtypes in adult subjects. METHODS: Retrospective cohort study at a single center of 39,965 adults aged 18 or older (median age 51, 65.1% female) with at least one serum total IgE measurement from 1998 to 2020. Analytics included chi2 table and logistic regression modeling of the main outcome measures, which include diagnosis of first malignancy and first diagnosis of specific malignancy subtype. RESULTS: Of the entire cohort, 2584 subjects (6.5%) developed a first malignancy and 2516 (6.3%) had an undetectable IgE. Of those with undetectable IgE levels, 8.9% developed a first malignancy versus 6.3% with detectable IgE measurements. After adjusting for risk factors, there was a significant association between undetectable IgE and risk/hazard of first malignancy (relative risk 1.49, 95% confidence interval (CI) 1.27-1.75) (hazard ratio 1.28, 95% CI 1.08-1.52). Results were similar in multiple sensitivity analyses. For type of malignancy developed, undetectable IgE was associated with increased risk of hematologic malignancy (relative risk 2.07, 95% CI 1.29-3.30) and skin malignancy (relative risk 1.52, 95% CI 1.13-2.05). CONCLUSION: Compared to individuals with detectable IgE levels, patients with undetectable total serum IgE had increased risk and hazard of first malignancy in general, and increased risk of hematologic malignancy in particular.

High rate of missed Barrett's esophagus when screening with forceps biopsies.

BACKGROUND: Screening for Barrett's esophagus (BE) with endoscopy plus forceps biopsy (FB) has poor compliance with the recommended Seattle protocol and fails to sample large areas of mucosa. This statistical modeling study estimates, for the first time, the actual frequency of missed BE cases by FB. METHODS: Published, calibrated models in the literature were combined to calculate the age-specific prevalence of BE in white males with gastroesophageal reflux disease (GERD). We started with estimates of the prevalence of BE and GERD, and applied the relative risk for BE in patients with GERD based on the literature. This created estimates of the true prevalence of BE in white males with GERD by decade of life. The proportion of BE missed was calculated as the difference between the prevalence and the proportion with a positive screen. RESULTS: The prevalence of BE in white males with GERD was 8.9%, 12.1%, 15.3%, 18.7% and 22.0% for the third through eighth decades of life. Even after assuming no false positives, missed cases of BE were about 50% when estimated for patients of ages 50 or 60 years, and over 60% for ages of 30, 40 or 70 years. Sensitivity analysis was done for all variables in the model calculations. For ages 50 and 60 years, this resulted in values from 30.3 to 57.3% and 36.4 to 60.9%. CONCLUSION: Screening for BE with endoscopy and FB misses approximately 50% of BE cases. More sensitive methods of BE detection or better adherence to the Seattle protocol are needed.

Wide Area Transepithelial Sampling with Computer-Assisted Analysis (WATS3D) Is Cost-Effective in Barrett's Esophagus Screening.

BACKGROUND: Wide area transepithelial sampling with three-dimensional computer-assisted analysis (WATS3D) is an adjunct to the standard random 4-quadrant forceps biopsies (FB, "Seattle protocol") that significantly increases the detection of Barrett's esophagus (BE) and associated neoplasia in patients undergoing screening or surveillance. AIMS: To examine the cost-effectiveness of adding WATS3D to the Seattle protocol in screening patients for BE. METHODS: A decision analytic model was used to compare the effectiveness and cost-effectiveness of two alternative BE screening strategies in chronic gastroesophageal reflux disease patients: FB with and without WATS3D. The reference case was a 60-year-old white male with gastroesophageal reflux disease (GERD). Effectiveness was measured by the number needed to screen to avert one cancer and one cancer-related death, and quality-adjusted life years (QALYs). Cost was measured in 2019 US$, and the incremental cost-effectiveness ratio (ICER) was measured in $/QALY using thresholds for cost-effectiveness of $100,000/QALY and $150,000/QALY. Cost was measured in 2019 US$. Cost and QALYs were discounted at 3% per year. RESULTS: Between 320 and 337 people would need to be screened with WATS3D in addition to FB to avert one additional cancer, and 328-367 people to avert one cancer-related death. Screening with WATS3D costs an additional $1219 and produced an additional 0.017 QALYs, for an ICER of $71,395/QALY. All one-way sensitivity analyses resulted in ICERs under $84,000/QALY. CONCLUSIONS: Screening for BE in 60-year-old white male GERD patients is more cost-effective when WATS3D is used adjunctively to the Seattle protocol than with the Seattle protocol alone.

Cost-effectiveness of surgery for drug-resistant temporal lobe epilepsy in the US.

OBJECTIVE: Surgery is an effective but costly treatment for many patients with drug-resistant temporal lobe epilepsy (DR-TLE). We aim to evaluate whether, in the United States, surgery is cost-effective compared to medical management for patients deemed surgical candidates and whether surgical evaluation is cost-effective for patients with DR-TLE in general. METHODS: We use a semi-Markov model to assess the cost-effectiveness of surgery and surgical evaluation over a lifetime horizon. We use second-order Monte Carlo simulations to conduct probabilistic sensitivity analyses to estimate variation in model output. We adopt both health care and societal perspectives, including direct health care costs (e.g., surgery, antiepileptic drugs) and indirect costs (e.g., lost earnings by patients and care providers.) We compare the incremental cost-effectiveness ratio to societal willingness to pay (∼$100,000 per quality-adjusted life-year [QALY]) to determine whether surgery is cost-effective. RESULTS: Epilepsy surgery is cost-effective compared to medical management in surgically eligible patients by virtue of being cost-saving ($328,000 vs $423,000) and more effective (16.6 vs 13.6 QALY) than medical management in the long run. Surgical evaluation is cost-effective in patients with DR-TLE even if the probability of being deemed a surgical candidate is only 5%. From a societal perspective, surgery becomes cost-effective within 3 years, and 89% of simulations favor surgery over the lifetime horizon. CONCLUSION: For surgically eligible patients with DR-TLE, surgery is cost-effective. For patients with DR-TLE in general, referral for surgical evaluation (and possible subsequent surgery) is cost-effective. Patients with DR-TLE should be referred for surgical evaluation without hesitation on cost-effectiveness grounds.

Cost and Cost-Effectiveness of Image Guided Partial Breast Irradiation in Comparison to Hypofractionated Whole Breast Irradiation.

PURPOSE: Hypofractionated whole breast irradiation (HWBI) and accelerated partial breast irradiation (APBI) represent two adjuvant radiation therapy options after breast-conserving surgery. We performed a cost and cost-effectiveness analysis of an external beam image guided APBI technique compared with HWBI. METHODS AND MATERIALS: HWBI was defined as 40 Gy in 15 fractions to the whole breast with or without a 10-Gy/5-fraction boost. APBI was 30 Gy in 5 fractions per Livi et al and was evaluated as both intensity modulated radiation therapy (IMRT) and stereotactic body radiation therapy. The decision analytical model measured effectiveness in quality-adjusted life years. Micro-costing was conducted to estimate the true cost of the different treatment regimens, and incremental cost-effectiveness analysis was performed. RESULTS: Based on micro-costing, the cost of HWBI was $4551 with boost and $3666 without boost, compared with $2966 for APBI. Including indirect costs, HWBI with boost cost $6160, HWBI without boost cost $4940, and APBI cost $3569. Cost savings for APBI compared with HWBI with and without boost was $1585 and $700 based on direct costs and $2591 and $1371 including indirect costs. APBI was also more effective, at 0.2300 quality-adjusted life years compared with 0.2289 for HWBI with or without boost. Thus, APBI was both less costly and more effective. Basing cost on Medicare reimbursement (IMRT) leads to APBI again dominating HWBI, but basing cost for APBI on reimbursement billed as stereotactic body radiation therapy leads to HWBI being far more cost-effective. CONCLUSIONS: Image guided partial breast irradiation is less costly to deliver and has slightly improved efficacy compared with HWBI, with or without a boost. IMRT APBI should be considered a standard-of-care option in appropriately selected patients based on efficacy and value.

Cost-effectiveness of nivolumab for recurrent or metastatic head and neck cancer☆.

OBJECTIVE: Nivolumab is the first drug to demonstrate a survival benefit for platinum-refractory recurrent or metastatic head and neck cancer. We performed a cost-utility analysis to assess the economic value of nivolumab as compared to alternative standard agents in this context. MATERIALS AND METHODS: Using data from the CheckMate 141 trial, we constructed a Markov simulation model from the US payer's perspective to evaluate the cost-effectiveness of nivolumab compared to physician choice of either cetuximab, methotrexate or docetaxel. Alternative strategies considered included: single-agent cetuximab, methotrexate or docetaxel, or first testing for PD-L1 to select for nivolumab. Costs were extracted from Medicare and utilities from the literature and CheckMate. Probabilistic sensitivity analysis (PSA) was used to evaluate parameter uncertainty. $100,000/QALY was the primary threshold for cost-effectiveness. RESULTS: When comparing nivolumab to the standard arm of CheckMate, nivolumab demonstrated an incremental cost-effectiveness ratio (ICER) of $140,672/QALY. When comparing standard therapies, methotrexate was the most cost-effective with similar results for docetaxel. Nivolumab was cost-effective compared to single-agent cetuximab (ICER $89,786/QALY). Treatment selection by PD-L1 immunohistochemistry did not markedly improve the cost-effectiveness of nivolumab. Factors likely to positively impact the cost-effectiveness of nivolumab include better baseline quality-of-life, poor tolerability of standard treatments and/or a lower cost of nivolumab. CONCLUSIONS: Nivolumab is preferred to single-agent cetuximab but requires a willingness-to-pay of at least $150,000/QALY to be considered cost-effective when compared to docetaxel or methotrexate. Selection by PD-L1 does not markedly improve the cost-effectiveness of nivolumab. This informs patient selection and clinical care-path development.

Using Claims Data to Examine Hospital Readmission Risk in Patients With Schizophrenia and Comorbid Marijuana Use Disorders.

OBJECTIVE: Few epidemiologic studies have examined marijuana use disorder and repeated hospitalizations related to schizophrenia. To address this gap, this study examines time to readmission by indicators for recent marijuana use disorder in the presence of alcohol use disorder (AUD) and other drug use disorder. METHOD: Our sample consisted of 4,349 patients with a primary diagnosis of schizophrenia spectrum disorder (SSD) in 2005 in individually linked California Health Care Cost and Utilization Project (CA HCUP) data. Readmissions were assessed from 2005 to 2011. Predictors for readmission were examined using a stratified, recurrent-event, Cox proportional hazards model. Sensitivity analyses were conducted on patients readmitted in 2010 or 2011. RESULTS: We found that having marijuana use disorder or AUD alone within 90 days of initial hospitalization was associated with longer times until first readmission. A lower risk of readmission for those with recent marijuana use disorder persisted through the fifth readmission (hazard ratio [HR] = 0.92, 95% CI [0.85, 0.99]) but was not significant in the sixth or greater readmission nor in sensitivity analyses. SSD patients with recent other drug use disorder had an increased risk for a second to fifth readmission (HR = 1.13, 95% CI [1.06, 1.20]). Those with recent AUD had an increased risk for a sixth or greater readmission (HR = 1.15, 95% CI [1.07, 1.23]). Both of these results remained significant in the sensitivity analysis. CONCLUSIONS: We found that AUD and other drug use disorder increase readmission risk in patients with SSD after a first hospitalization, whereas marijuana use disorder does not appear to be associated with an increased risk for readmission.

Long-term reduction of health care costs and utilization after epilepsy surgery.

OBJECTIVE: To assess long-term direct medical costs, health care utilization, and mortality following resective surgery in persons with uncontrolled epilepsy. METHODS: Retrospective longitudinal cohort study of Medicaid beneficiaries with epilepsy from 2000 to 2008. The study population included 7,835 persons with uncontrolled focal epilepsy ages 18-64 years, with an average follow-up time of 5 years. Of these, 135 received surgery during the study period. To account for selection bias, we used risk-set optimal pairwise matching on a time-varying propensity score, and inverse probability of treatment weighting. Repeated measures generalized linear models were used to model utilization and cost outcomes. Cox proportional hazard was used to model survival. RESULTS: The mean direct medical cost difference between the surgical group and control group was $6,806 after risk-set matching. The incidence rate ratio of inpatient, emergency room, and outpatient utilization was lower among the surgical group in both unadjusted and adjusted analyses. There was no significant difference in mortality after adjustment. Among surgical cases, mean annual costs per subject were on average $6,484 lower, and all utilization measures were lower after surgery compared to before. SIGNIFICANCE: Subjects that underwent epilepsy surgery had lower direct medical care costs and health care utilization. These findings support that epilepsy surgery yields substantial health care cost savings.

Disparities in access to specialized epilepsy care.

OBJECTIVE: To examine the impact of individual and community characteristics on access to specialized epilepsy care. METHODS: This retrospective cross-sectional study analyzed data from the California State Inpatient Sample, the State Ambulatory Surgery Database, and the State Emergency Department Database, that were linked with the 2009 Area Resource File and the location of the National Association of Epilepsy Center's epilepsy centers. The receipt of video-EEG monitoring was measured and used to indicate access to specialized epilepsy care in subjects with persistent seizures, identified as those who had frequent seizure-related hospital admissions and/or ER visits. A hierarchical logistic regression model was employed to assess barriers to high quality care at both individual and contextual levels. RESULTS: Among 115,632 persons with persistent seizures, individuals who routinely received care in an area where epilepsy centers were located were more likely to have access to specialized epilepsy care (OR: 1.81, 95% CI: 1.20, 2.72). Interestingly, the availability of epilepsy centers did not influence access to specialized epilepsy care in people who had private insurance. In contrast, uninsured individuals and those with public insurance programs including Medicaid and Medicare had significant gaps in access to specialized epilepsy care. Other individual characteristics such as age, race/ethnicity, and the presence of comorbid conditions were also associated with disparities in access to specialized care in PWE. CONCLUSION: Both individual and community characteristics play substantial roles in access to high quality epilepsy care. Policy interventions that incorporate strategies to address disparities at both levels are necessary to improve access to specialized care for PWE.

Utility of repeated praziquantel dosing in the treatment of schistosomiasis in high-risk communities in Africa: a systematic review.

BACKGROUND: Controversy persists about the optimal approach to drug-based control of schistosomiasis in high-risk communities. In a systematic review of published studies, we examined evidence for incremental benefits from repeated praziquantel dosing, given 2 to 8 weeks after an initial dose, in Schistosoma-endemic areas of Africa. METHODOLOGY/PRINCIPAL FINDINGS: We performed systematic searches of electronic databases PubMed and EMBASE for relevant data using search terms 'schistosomiasis', 'dosing' and 'praziquantel' and hand searches of personal collections and bibliographies of recovered articles. In 10 reports meeting study criteria, improvements in parasitological treatment outcomes after two doses of praziquantel were greater for S. mansoni infection than for S. haematobium infection. Observed cure rates (positive to negative conversion in egg detection assays) were, for S. mansoni, 69-91% cure after two doses vs. 42-79% after one dose and, for S. haematobium, 46-99% cure after two doses vs. 37-93% after a single dose. Treatment benefits in terms of reduction in intensity (mean egg count) were also different for the two species-for S. mansoni, the 2-dose regimen yielded an weighted average 89% reduction in standardized egg counts compared to a 83% reduction after one dose; for S. haematobium, two doses gave a 93% reduction compared to a 94% reduction with a single dose. Cost-effectiveness analysis was performed based on Markov life path modeling. CONCLUSIONS/SIGNIFICANCE: Although schedules for repeated treatment with praziquantel require greater inputs in terms of direct costs and community participation, there are incremental benefits to this approach at an estimated cost of $153 (S. mansoni)-$211 (S. haematobium) per additional lifetime QALY gained by double treatment in school-based programs. More rapid reduction of infection-related disease may improve program adherence, and if, as an externality of the program, transmission can be reduced through more effective coverage, significant additional benefits are expected to accrue in the targeted communities.

Preoperative predictors of returning to work following primary total knee arthroplasty.

BACKGROUND: There is little in the literature to guide clinicians in advising patients regarding their return to work following a primary total knee arthroplasty. In this study, we aimed to identify which factors are important in estimating a patient's time to return to work following primary total knee arthroplasty, how long patients can anticipate being off from work, and the types of jobs to which patients are able to return following primary total knee arthroplasty. METHODS: A prospective cohort study was performed in which patients scheduled for a primary total knee arthroplasty completed a validated questionnaire preoperatively and at four to six weeks, three months, and six months postoperatively. The questionnaire assessed the patient's occupational physical demands, ability to perform job responsibilities, physical status, and motivation to return to work as well as factors that may impact his or her recovery and other workplace characteristics. Two survival analysis models were constructed to evaluate the time to return to work either at least part-time or full-time. Acceleration factors were calculated to indicate the relative percentage of time until the patient returned to work. RESULTS: The median time to return to work was 8.9 weeks. Patients who reported a sense of urgency about returning to work were found to return in half the time taken by other employees (acceleration factor = 0.468; p < 0.001). Other preoperative factors associated with a faster return to work included being female (acceleration factor = 0.783), self-employment (acceleration factor = 0.792), higher mental health scores (acceleration factor = 0.891), higher physical function scores (acceleration factor = 0.809), higher Functional Comorbidity Index scores (acceleration factor = 0.914), and a handicap accessible workplace (acceleration factor = 0.736). A slower return to work was associated with having less pain preoperatively (acceleration factor = 1.132), having a more physically demanding job (acceleration factor = 1.116), and receiving Workers' Compensation (acceleration factor = 4.360). CONCLUSIONS: Although the physical demands of a patient's job have a moderate influence on the patient's ability to return to work following a primary total knee arthroplasty, the patient's characteristics, particularly motivation, play a more important role.

Development of the Occupational Activities Knee Scale.

A primary concern of many knee surgery patients is their ability to return to work following surgery, but it is often difficult to predict the practicality of returning due to a job's unclear knee demands. A cross-sectional study of employed patients and general population participants was conducted. Study participants were asked if their job required nine separate tasks and if their job had low, moderate, or high physical demands. The relative risk of each task placing high demands on the knee was calculated, and those risk ratios were summated to calculate a scaled score. The scaled score accurately distinguishes the levels of job demands with each reported level of job demands having a significantly higher mean scaled score than the level below it (p < 0.0001). The Occupational Activities Knee Scale offers occupational and health care providers greater precision in comparing the physical requirements of jobs for knee surgery patients.

Cost-effectiveness of hematologic growth factors for anemia occurring during hepatitis C combination therapy.

In hepatitis C virus (HCV)-infected patients who develop anemia during combination therapy, erythropoietic growth factors maintain higher drug treatment levels compared to ribavirin dose reduction, which may lead to an increase in treatment response rates. This study estimated the cost-effectiveness of growth factor therapy in maintaining anemic HCV-infected patients on target drug levels during combination therapy. A decision analysis using a Markov model was developed with 7 health states: Sustained viral response, chronic HCV, compensated cirrhosis, decompensated cirrhosis, hepatocellular carcinoma, liver transplantation, and death. Data sources included population-based studies of growth factor therapy, previously published estimates of costs and natural history of hepatitis C, and recent prospective studies. Our reference case was a 45-year-old Caucasian man with HCV infection (genotype 1, 2, or 3) who developed anemia while undergoing combination therapy with ribavirin and pegylated interferon. We compared growth factor injections (darbepoetin alpha or epoetin alpha) during combination therapy with standard ribavirin dose reduction. Compared to a ribavirin dose reduction strategy, the cost of darbepoetin per additional quality-adjusted life-year was 34,793 dollars for genotype 1 and 33,832 dollars for genotypes 2 or 3 versus 60,600 dollars and 64,311 dollars for epoetin. For all genotypes, the results were sensitive to changes in the cure rates of HCV therapy, the utility of chronic HCV, the costs of growth factors, and the age at which therapy is begun. In conclusion, use of erythropoietic growth factors, specifically darbepoetin, for patients with anemia occurring during HCV combination therapy appears to be cost-effective for genotypes 1, 2, or 3.

Cost-effectiveness of population screening for alpha-1 antitrypsin deficiency: a decision analysis.

The objective was to assess the cost-effectiveness of population screening for alpha-1 antitrypsin (AAT) deficiency. The design was a Markov-based decision analytic model. Hypothetical cohorts were analyzed from birth and followed over time until death using Monte Carlo simulation. The following strategies were compared: 1) screen all newborns, 2) screen all 10-year-old children, and 3) do not screen. Screenees found to have PI*ZZ AAT deficiency received the benefits of lower smoking rates and were offered augmentation therapy. In keeping with reported experience, most (96%) non-screened AAT deficient individuals remained undiagnosed and, therefore, missed these benefits. Under base conditions, screening all newborns cost nearly $422,000 per quality-adjusted life-year (QALY) gained; this estimate fell to $92,135 per QALY when the cost of screening was minimized to $6 in the model. Delaying screening until age 10 decreased the incremental cost-effectiveness ratio (ICER) to nearly $317,000. In sensitivity analysis, when the prevalence of PI*ZZ individuals increased from a baseline of 1.96 to 16 per 10,000, the ICER for newborn screening decreased below $100,000 per QALY. When the cost of screening and augmentation therapy were decreased simultaneously with increasing PI*ZZ prevalence, there were many scenarios in which the ICER decreased below $50,000. While population-based screening for AAT deficiency is not cost-effective under current conditions, cost-effectiveness criteria could be satisfied when case-finding in a high prevalence population is undertaken.

The potential impact on melanoma mortality of reducing rates of suboptimal excision margins.

We estimated the potential benefit of reducing rates of inadequate excision margins in the treatment of localized invasive melanoma. A computer-simulated Markov decision analytic model was created to follow until death a hypothetical cohort of 55 y old Caucasians, newly diagnosed in a community setting with localized invasive melanoma. We considered two scenarios: usual care, and a hypothetical intervention. Markov states included well without local recurrence, local recurrence, cured, and dead. Published population-based data were used for rates of optimal excision margins, local recurrence, and mortality. Two outcome measures were employed: melanoma-related mortality and life expectancy. Major assumptions included: local recurrence occurs within 10 y of diagnosis, and patients revert to general population mortality rates 10 y following melanoma excision or subsequent local recurrence. For usual care, the model estimated 8.17% melanoma-related mortality. Modeling intervention with 100% optimal excision margins reduced this rate to 6.15%, a 25% relative reduction in mortality. This increased average life expectancy by 0.437 y, which equates to approximately 11 additional years in the 4% who would not experience a local recurrence due to improved excision margins. Increasing the percentage of optimal excision margins to 80% would still yield substantial improvement, with 6.83% melanoma-related mortality, saving 0.29 life-years compared with baseline. Results were insensitive to moderate changes in the parameter values. Suboptimal excision margins may account for approximately one-fourth of all melanoma-related mortality for localized invasive melanoma. If intervention can achieve even modest adherence to optimal excision margins, it might substantially reduce mortality.

The cost-effectiveness of treatment strategies for achalasia.

Achalasia is a disorder characterized by abnormal motility of the esophageal body and the lower esophageal sphincter, resulting in dysphagia, regurgitation, and chest pain. Treatment options for achalasia include Botulinum toxin injection, pneumatic balloon dilation, and surgical esophagomyotomy. The aim of this study was to determine the cost-effectiveness of these three strategies in the treatment of achalasia in adults. We constructed a Markov cost-effectiveness model comparing Botox injection, pneumatic balloon dilation, and laparoscopic esophagomyotomy as initial treatments of achalasia. Costs and probabilities were derived from the published literature. The utility for symptomatic achalasia was derived from a sample of patients with achalasia. Sensitivity analyses were performed. Over a five-year time horizon, pneumatic dilation was the most cost-effective treatment strategy for achalasia, with an incremental cost-effectiveness ratio of $1348 per quality-adjusted life-year compared to Botox. Although laparoscopic esophagomyotomy was more effective than the other treatment options, it was not cost-effective because of its high initial cost. In conclusion, pneumatic dilation is the most cost-effective treatment option for adults with achalasia. Further studies should examine the long-term relapse rates following treatment with Botox and more precisely determine the quality of life of symptomatic achalasia.