Postradioiodine Graves' management: The PRAGMA study.

OBJECTIVE: Thyroid status in the months following radioiodine (RI) treatment for Graves' disease can be unstable. Our objective was to quantify frequency of abnormal thyroid function post-RI and compare effectiveness of common management strategies. DESIGN: Retrospective, multicentre and observational study. PATIENTS: Adult patients with Graves' disease treated with RI with 12 months' follow-up. MEASUREMENTS: Euthyroidism was defined as both serum thyrotropin (thyroid-stimulating hormone [TSH]) and free thyroxine (FT4) within their reference ranges or, when only one was available, it was within its reference range; hypothyroidism as TSH ≥ 10 mU/L, or subnormal FT4 regardless of TSH; hyperthyroidism as TSH below and FT4 above their reference ranges; dysthyroidism as the sum of hypo- and hyperthyroidism; subclinical hypothyroidism as normal FT4 and TSH between the upper limit of normal and <10 mU/L; and subclinical hyperthyroidism as low TSH and normal FT4. RESULTS: Of 812 patients studied post-RI, hypothyroidism occurred in 80.7% and hyperthyroidism in 48.6% of patients. Three principal post-RI management strategies were employed: (a) antithyroid drugs alone, (b) levothyroxine alone, and (c) combination of the two. Differences among these were small. Adherence to national guidelines regarding monitoring thyroid function in the first 6 months was low (21.4%-28.7%). No negative outcomes (new-onset/exacerbation of Graves' orbitopathy, weight gain, and cardiovascular events) were associated with dysthyroidism. There were significant differences in demographics, clinical practice, and thyroid status postradioiodine between centres. CONCLUSIONS: Dysthyroidism in the 12 months post-RI was common. Differences between post-RI strategies were small, suggesting these interventions alone are unlikely to address the high frequency of dysthyroidism.

Cost and Cost Savings of Navigation Services to Avoid Rehospitalization for a Comorbid Substance Use Disorder Population.

BACKGROUND: A randomized clinical trial found that patient navigation for hospital patients with comorbid substance use disorders (SUDs) reduced emergency department (ED) and inpatient hospital utilization compared with treatment-as-usual. OBJECTIVE: To compare the cost and calculate any cost savings from the Navigation Services to Avoid Rehospitalization (NavSTAR) intervention over treatment-as-usual. RESEARCH DESIGN: This study calculates activity-based costs from the health care providers and uses a net benefits approach to calculate the cost savings generated from NavSTAR. NavSTAR provided patient navigation focused on engagement in SUD treatment, starting before hospital discharge and continuing for up to 3 months postdischarge. SUBJECTS: Adult hospitalized medical/surgical patients with comorbid SUD for opioids, cocaine, and/or alcohol. COST MEASURES: Cost of the 3-month NavSTAR patient navigation intervention and the cost of all inpatient days and ED visits over a 12-month period. RESULTS OF BASE CASE ANALYSIS: NavSTAR generated $17,780 per participant in cost savings. Ninety-seven percent of bootstrapped samples generated positive cost savings, and our sensitivity analyses did not change our results. LIMITATIONS: Participants were recruited at one hospital in Baltimore, MD through the hospital's addiction consultation service. Findings may not generalize to the broader population. Outpatient health care cost data was not available through administrative records. CONCLUSION: Our findings show that patient navigation interventions should be considered by payors and policy makers to reduce the high hospital costs associated with comorbid SUD patients.

Cost and Cost-Effectiveness of Incentives for Viral Suppression in People Living with HIV.

Only 63% of people living with HIV in the United States are achieving viral suppression. Structural and social barriers limit adherence to antiretroviral therapy which furthers the HIV epidemic while increasing health care costs. This study calculated the cost and cost-effectiveness of a contingency management intervention with cash incentives. People with HIV and detectable viral loads were randomized to usual care or an incentive group. Individuals could earn up to $3650 per year if they achieved and maintained an undetectable viral load. The average 1-year intervention cost, including incentives, was $4105 per patient. The average health care costs were $27,189 per patient in usual care and $35,853 per patient in the incentive group. We estimated a cost of $28,888 per quality-adjusted life-year (QALY) gained, which is well below accepted cost-per-QALY thresholds. Contingency management with cash incentives is a cost-effective intervention for significantly increasing viral suppression.

Increased Population Risk of AIP-Related Acromegaly and Gigantism in Ireland.

The aryl hydrocarbon receptor interacting protein (AIP) founder mutation R304* (or p.R304* ; NM_003977.3:c.910C>T, p.Arg304Ter) identified in Northern Ireland (NI) predisposes to acromegaly/gigantism; its population health impact remains unexplored. We measured R304* carrier frequency in 936 Mid Ulster, 1,000 Greater Belfast (both in NI) and 2,094 Republic of Ireland (ROI) volunteers and in 116 NI or ROI acromegaly/gigantism patients. Carrier frequencies were 0.0064 in Mid Ulster (95%CI = 0.0027-0.013; P = 0.0005 vs. ROI), 0.001 in Greater Belfast (0.00011-0.0047) and zero in ROI (0-0.0014). R304* prevalence was elevated in acromegaly/gigantism patients in NI (11/87, 12.6%, P < 0.05), but not in ROI (2/29, 6.8%) versus non-Irish patients (0-2.41%). Haploblock conservation supported a common ancestor for all the 18 identified Irish pedigrees (81 carriers, 30 affected). Time to most recent common ancestor (tMRCA) was 2550 (1,275-5,000) years. tMRCA-based simulations predicted 432 (90-5,175) current carriers, including 86 affected (18-1,035) for 20% penetrance. In conclusion, R304* is frequent in Mid Ulster, resulting in numerous acromegaly/gigantism cases. tMRCA is consistent with historical/folklore accounts of Irish giants. Forward simulations predict many undetected carriers; geographically targeted population screening improves asymptomatic carrier identification, complementing clinical testing of patients/relatives. We generated disease awareness locally, necessary for early diagnosis and improved outcomes of AIP-related disease.

Cost of start-up activities to implement a community-level opioid overdose reduction intervention in the HEALing Communities Study.

BACKGROUND: Communities That HEAL (CTH) is a novel, data-driven community-engaged intervention designed to reduce opioid overdose deaths by increasing community engagement, adoption of an integrated set of evidence-based practices, and delivering a communications campaign across healthcare, behavioral-health, criminal-legal, and other community-based settings. The implementation of such a complex initiative requires up-front investments of time and other expenditures (i.e., start-up costs). Despite the importance of these start-up costs in investment decisions to stakeholders, they are typically excluded from cost-effectiveness analyses. The objective of this study is to report a detailed analysis of CTH start-up costs pre-intervention implementation and to describe the relevance of these data for stakeholders to determine implementation feasibility. METHODS: This study is guided by the community perspective, reflecting the investments that a real-world community would need to incur to implement the CTH intervention. We adopted an activity-based costing approach, in which resources related to hiring, training, purchasing, and community dashboard creation were identified through macro- and micro-costing techniques from 34 communities with high rates of fatal opioid overdoses, across four states-Kentucky, Massachusetts, New York, and Ohio. Resources were identified and assigned a unit cost using administrative and semi-structured-interview data. All cost estimates were reported in 2019 dollars. RESULTS: State-level average and median start-up cost (representing 8-10 communities per state) were $268,657 and $175,683, respectively. Hiring and training represented 40%, equipment and infrastructure costs represented 24%, and dashboard creation represented 36% of the total average start-up cost. Comparatively, hiring and training represented 49%, purchasing costs represented 18%, and dashboard creation represented 34% of the total median start-up cost. CONCLUSION: We identified three distinct CTH hiring models that affected start-up costs: hospital-academic (Massachusetts), university-academic (Kentucky and Ohio), and community-leveraged (New York). Hiring, training, and purchasing start-up costs were lowest in New York due to existing local infrastructure. Community-based implementation similar to the New York model may have lower start-up costs due to leveraging of existing infrastructure, relationships, and support from local health departments.

Cost and cost-effectiveness of abstinence contingent wage supplements.

BACKGROUND: Substance use disorders are correlated with unemployment and poverty. However, few interventions aim to improve substance use, unemployment, and, distally, poverty. The Abstinence-Contingent Wage Supplement (ACWS) randomized controlled trial combined a therapeutic workplace with abstinence-contingent wage supplements to address substance use and unemployment. The ACWS study found that abstinence-contingent wage supplements increased the percentage of participants who had negative drug tests, who were employed, and who were above the poverty line during the intervention period. This study presents the cost of ACWS and calculates the cost-effectiveness of ACWS compared with usual care. METHODS: To calculate the cost and cost-effectiveness of ACWS, we used activity-based costing methods to cost the intervention and calculated the costs from the provider and healthcare sector perspective. We calculated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves for negative drug tests and employment. RESULTS: ACWS cost $11,310 per participant over the 12-month intervention period. Total intervention and healthcare costs per participant over the intervention period were $20,625 for usual care and $30,686 for ACWS. At the end of the intervention period an additional participant with a negative drug test cost $1437 while an additional participant employed cost $915. CONCLUSIONS: ACWS increases drug abstinence and employment and may be cost-effective at the end of the 12-month intervention period if decision makers are willing to pay the incremental cost associated with the intervention.

Systems analysis and improvement approach to improve naloxone distribution within syringe service programs: study protocol of a randomized controlled trial.

BACKGROUND: More than half a million Americans died of an opioid-related overdose between 1999 and 2020, the majority occurring between 2015 and 2020. The opioid overdose mortality epidemic disproportionately impacts Black, Indigenous, and people of color (BIPOC): since 2015, overdose mortality rates have increased substantially more among Black (114%) and Latinx (97%) populations compared with White populations (32%). This is in part due to disparities in access to naloxone, an opioid antagonist that can effectively reverse opioid overdose to prevent death. Our recent pilot work determined that many barriers to naloxone access can be identified and addressed by syringe service programs (SSPs) using the Systems Analysis and Improvement Approach to Naloxone distribution (SAIA-Naloxone). This randomized controlled trial will test SAIA-Naloxone's ability to improve naloxone distribution in general and among BIPOC specifically. METHODS: We will conduct a trial with 32 SSPs across California, randomly assigning 16 to the SAIA-Naloxone arm and 16 to receive implementation as usual. SAIA-Naloxone is a multifaceted, multilevel implementation strategy through which trained facilitators work closely with SSPs to (1) assess organization-level barriers, (2) prioritize barriers for improvement, and (3) test solutions through iterative change cycles until achieving and sustaining improvements. SSPs receiving SAIA-Naloxone will work with a trained facilitator for a period of 12 months. We will test SAIA-Naloxone's ability to improve SSPs' naloxone distribution using an interrupted time series approach. Data collection will take place during a 3-month lead-in period, the 12-month active period, and for an additional 6 months afterward to determine whether impacts are sustained. We will use a structured approach to specify SAIA-Naloxone to ensure strategy activities are clearly defined and to assess SAIA-Naloxone fidelity to aid in interpreting study results. We will also assess the costs associated with SAIA-Naloxone and its cost-effectiveness. DISCUSSION: This trial takes a novel approach to improving equitable distribution of naloxone amid the ongoing epidemic and associated racial disparities. If successful, SAIA-Naloxone represents an important organizational-level solution to the multifaceted and multilevel barriers to equitable naloxone distribution.

Health care use and cost of treatment for adolescents and young adults with opioid use disorder.

BACKGROUND: Few studies have examined the cost of medication for opioid use disorder (MOUD) with counseling for the adolescent and young adult population. This study calculated the health care utilization and cost of MOUD treatment, other substance use disorder treatment, and general health care for adolescents and young adults receiving treatment for opioid use disorder. METHODS: The study randomized youth ages 15 to 21 (N = 288) equally into the two study conditions: extended-release naltrexone (XR-NTX) or treatment as usual (TAU). While participants committed to treatment based on randomization the study observed considerable nonadherence to both randomized conditions. Instead of using the randomly assigned study conditions, we present descriptive costs by the type of MOUD treatment received: XR-NTX only, buprenorphine only, any other combination of MOUD treatments, and no MOUD. Health care use was aggregated over the 6-month period for each participant, and we calculated average/participant utilization for each treatment group. To determine participant costs, we multiplied the unit costs of health care services obtained from the literature by the reported amount of health care utilization for each participant. We then calculated the mean, standard error, median and IQR for MOUD costs, other substance use disorder treatment costs and general healthcare cost from the health care sector perspective. RESULTS: On average, participants in the XR-NTX only group received 2.6 doses of XR-NTX (equivalent to approximately 78 days of treatment). The buprenorphine only group had an average of 97 days of buprenorphine treatment. The XR-NTX only group had higher/patient costs compared to participants in the buprenorphine only group ($10,491 vs. $8765) and higher XR-NTX utilization would further increase costs. Participants in the any other MOUD combination group had the highest total costs ($14,627) while participants in the no MOUD group at the lowest ($3453). DISCUSSION: Our cost analysis calculates the real-world cost of MOUD treatment and, while not generalizable, provides policy makers an estimate of costs for adolescents and young adults. We found that participants in the XR-NTX only group received fewer days of medication compared to the buprenorphine only group, but their medication costs were higher due to the cost of XR-NTX injections. While the buprenorphine only group had the highest number of days of medication utilization of all the groups, the average number of days of medication utilization was considerably shorter than the six-month treatment period.

Cost and cost-effectiveness of interim methadone treatment and patient navigation initiated in jail.

BACKGROUND: Individuals with opioid use disorder (OUD) who are released from pre-trial detention in jail have a high risk of opioid relapse. While several interventions for OUD initiated during incarceration have been studied, few have had an economic evaluation. As part of a three-group randomized trial, we estimated the cost and cost-effectiveness of a negative urine opioid test. Detainees were assigned to interim methadone (IM) in jail with continued methadone treatment post-release with and without 3 months of post-release patient navigation (PN) compared to an enhanced treatment-as-usual group. METHODS: We implemented a micro-costing approach from the provider's perspective to estimate the cost per participant in jail and over the 12 months post-release from jail. Economic data included jail-based and community-based service utilization, self-reported healthcare utilization and justice system involvement, and administrative arrest records. Our outcome measure is the number of participants with a negative opioid urine test at their 12-month follow-up. We calculated incremental cost-effectiveness ratios (ICERs) for intervention costs only and costs from a societal perspective. RESULTS: The average cost of providing patient navigation services per individual beginning in jail and continuing in the community was $283. We find that IM is dominated by ETAU and IM + PN. Per additional participant with a negative opioid urine test, the ICER for IM + PN including intervention costs only is $91 and $305 including societal costs. CONCLUSIONS: IM + PN is almost certainly the cost-effective choice from both an intervention provider and societal perspective.

Group Versus Standard Behavioral Couples' Therapy for Alcohol Use Disorder Patients: Cost-Effectiveness.

OBJECTIVE: The purpose of this study was to evaluate the costs and cost-effectiveness of two treatments for 101 alcohol use disorder patients and their intimate partners--group behavioral couples' therapy plus individual-based treatment (G-BCT), or standard behavioral couples' therapy plus individual-based treatment (S-BCT). METHOD: We estimated the per-patient cost of each intervention using a microcosting approach that allowed us to estimate costs of specific components in each intervention as well as the overall total costs. Using simple means analysis and multiple regression models, we estimated the incremental effectiveness of G-BCT relative to S-BCT. Immediately after treatment and 12 months after treatment, we computed incremental cost-effectiveness ratios (ICER) and cost-effectiveness acceptability curves for percentage days abstinent, adverse consequences of alcohol and drugs, and overall relationship functioning. RESULTS: The average per-patient cost of delivering G-BCT was $674, significantly less than the cost of S-BCT ($831). However, 12 months after treatment, S-BCT participants performed better on all outcomes compared with those in G-BCT, and the calculated ICER moving from G-BCT to S-BCT ranged from $10 to $12 across these outcomes. The current findings indicated that, except at very low willingness-to-pay values, S-BCT is a cost-effective option relative to G-BCT when considering 12-month posttreatment outcomes. CONCLUSIONS: As expected, G-BCT was delivered at a lower cost per patient than S-BCT; however, S-BCT performed better over time on the clinical outcomes studied. These economic findings indicate that alcohol use disorder treatment providers should seriously consider S-BCT over G-BCT when deciding what format to use in behavioral couples' therapy.

Navigation Services to Avoid Rehospitalization among Medical/Surgical Patients with Comorbid Substance Use Disorder: Rationale and Design of a Randomized Controlled Trial.

Substance use disorders (SUDs) are associated with significant morbidity and mortality and contribute to inefficient use of healthcare services. Hospitalized medical/surgical patients with comorbid SUD are at elevated risk of hospital readmission and poor outcomes. Thus, effective interventions are needed to help such patients during hospitalization and post-discharge. This article reports the rationale, methodological design, and progress to date on a randomized trial comparing the effectiveness of Navigation Services to Avoid Rehospitalization (NavSTAR) vs Treatmentas-Usual (TAU) for hospital medical/surgical patients with comorbid SUD (N = 400). Applying Andersen's theoretical model of health service utilization, NavSTAR employed Patient Navigation and motivational interventions to promote entry into SUD treatment, facilitate adherence to recommendations for medical follow-up and self-care, address basic needs, and prevent the recurrent use of hospital services. As part of the NavSTAR service model, Patient Navigators embedded within the SUD consultation service at a large urban hospital delivered patient-centered, proactive navigation and motivational services initiated during the hospital stay and continued for up to 3 months post-discharge. Participants randomized to TAU received usual care from the hospital and the SUD consultation service, which included referral to SUD treatment but no continued contact post-hospital discharge. Hospital service utilization will be determined via review of electronic health records and the regional Health Information Exchange. Participants were assessed at baseline and again at 3-, 6-, and 12-month follow-up on various measures of healthcare utilization, substance use, and functioning. The primary outcome of interest is time-to-rehospitalization through 12 months. In addition, a range of secondary outcomes spanning the medical and SUD service areas will be assessed. The study will include a health economic evaluation of NavSTAR. If NavSTAR proves to be effective and cost-effective in this high-risk patient group, it would have important implications for addressing the needs of hospital patients with comorbid SUD, designing hospital discharge planning services, informing cost containment initiatives, and improving public health.

Screening and Intervention for Suicide Prevention: A Cost-Effectiveness Analysis of the ED-SAFE Interventions.

OBJECTIVE: Suicide screening followed by an intervention may identify suicidal individuals and prevent recurring self-harm, but few cost-effectiveness studies have been conducted. This study sought to determine whether the increased costs of implementing screening and intervention in hospital emergency departments (EDs) are justified by improvements in patient outcomes (decreased attempts and deaths by suicide). METHODS: The Emergency Department Safety Assessment and Follow-up Evaluation (ED-SAFE) study recruited participants in eight U.S. EDs between August 2010 and November 2013. The eight sites sequentially implemented two interventions: universal screening added to treatment as usual and universal screening plus a telephone-based intervention delivered over 12 months post-ED visit. This study calculated incremental cost-effectiveness ratios and cost-effectiveness acceptability curves to evaluate screening and suicide outcome measures and costs for the two interventions relative to treatment as usual. Costs were calculated from the provider perspective (e.g., wage and salary data and rental costs for hospital space) per patient and per site. RESULTS: Average per-patient costs to a participating ED of universal screening plus intervention were $1,063 per month, approximately $500 more than universal screening added to treatment as usual. Universal screening plus intervention was more effective in preventing suicides compared with universal screening added to treatment as usual and treatment as usual alone. CONCLUSIONS: Although the choice of universal screening plus intervention depends on the value placed on the outcome by decision makers, results suggest that implementing such suicide prevention measures can lead to significant cost savings.

Re-engineering methadone-Cost-effectiveness analysis of a patient-centered approach to methadone treatment.

Methadone maintenance treatment has proven effectiveness in the treatment of opioid use disorder, but significant barriers remain to treatment retention. In a randomized clinical trial, 300 newly-admitted methadone patients were randomly assigned to patient-centered methadone (PCM) v. treatment-as-usual (TAU). In PCM, participants were treated under revised program rules which permitted voluntary attendance at counseling and other changes focused on reducing involuntary discharge, and different staff roles which shifted disciplinary responsibility from the participant's counselor to the supervisor. The study found no significant differences in treatment retention, measures of opioid use, or other patient outcomes. This paper employs an activity-based costing approach to estimate the cost and cost-effectiveness of the two study conditions. We found that service use and costs were similar between PCM and TAU. Specifically, the average cost for PCM patients was $2396 compared to $2292 for standard methadone, while the average length of stay was 2 weeks longer for PCM patients. Incremental cost-effectiveness ratios (ICER) for self-reported heroin use, opioid positive urine screens, and meeting DSM-IV criteria for opioid dependence were mixed, with TAU achieving non-significantly better outcomes at lower treatment episode costs (i.e., economically dominating) for opioid positive urine screens. PCM patients reported slightly more days abstinent from heroin and fewer meet the opioid dependence criteria. While these differences are small and not statistically significant, we can still examine the cost-effectiveness implications. For days, abstinent from heroin, the ICER was $242 for one additional day of abstinence, however, there was notable uncertainty around this estimate. For opioid dependence criteria, the ICER was $1160 for a one-percentage point increase in the probability that a participant no longer met criteria for opioid dependence at follow-up. This economic study finds that patient choice concepts can be introduced into methadone treatment without significant impacts on costs or patient outcomes.

Clinical experience in the screening and management of a large kindred with familial isolated pituitary adenoma due to an aryl hydrocarbon receptor interacting protein (AIP) mutation.

CONTEXT: Germline AIP mutations usually cause young-onset acromegaly with low penetrance in a subset of familial isolated pituitary adenoma families. We describe our experience with a large family with R304* AIP mutation and discuss some of the diagnostic dilemmas and management issues. OBJECTIVE: The aim of the study was to identify and screen mutation carriers in the family. PATIENTS: Forty-three family members participated in the study. SETTING: The study was performed in university hospitals. OUTCOME: We conducted genetic and endocrine screening of family members. RESULTS: We identified 18 carriers of the R304* mutation, three family members with an AIP-variant A299V, and two family members who harbored both changes. One of the two index cases presented with gigantism and pituitary apoplexy, the other presented with young-onset acromegaly, and both had surgery and radiotherapy. After genetic and clinical screening of the family, two R304* carriers were diagnosed with acromegaly. They underwent transsphenoidal surgery after a short period of somatostatin analog treatment. One of these two patients is in remission; the other achieved successful pregnancy despite suboptimal control of acromegaly. One of the A299V carrier family members was previously diagnosed with a microprolactinoma; we consider this case to be a phenocopy. Height of the unaffected R304* carrier family members is not different compared to noncarrier relatives. CONCLUSIONS: Families with AIP mutations present particular problems such as the occurrence of large invasive tumors, poor response to medical treatment, difficulties with fertility and management of pregnancy, and the finding of AIP sequence variants of unknown significance. Because disease mostly develops at a younger age and penetrance is low, the timing and duration of the follow-up of carriers without overt disease requires further study. The psychological and financial impact of prolonged clinical screening must be considered. Excellent relationships between the family, endocrinologists, and geneticists are essential, and ideally these families should be managed in centers with specialist expertise.