Humanistic and Economic Burden of Conversion Therapy Among LGBTQ Youths in the United States.

IMPORTANCE: Sexual orientation and gender identity change efforts (SOGICE), also called conversion therapy, is a discredited practice attempting to convert lesbian, gay, bisexual, transgender, queer, or questioning (LGBTQ) individuals to be heterosexual and/or cisgender. OBJECTIVES: To identify and synthesize evidence on the humanistic and economic consequences of SOGICE among LGBTQ youths in the US. DESIGN, SETTING, AND PARTICIPANTS: This study, conducted from December 1, 2020, to February 15, 2021, included a systematic literature review and economic evaluation. The literature review analyzed published evidence on SOGICE among LGBTQ individuals of any age. The economic model evaluated the use of SOGICE vs no intervention, affirmative therapy vs no intervention, and affirmative therapy vs SOGICE to estimate the costs and adverse outcomes for each scenario and to assess the overall US economic burden of SOGICE. Published literature and public sources were used to estimate the number of LGBTQ youths exposed to SOGICE, the types of therapy received, and the associated adverse events (anxiety, severe psychological distress, depression, alcohol or substance abuse, suicide attempts, and fatalities). EXPOSURES: SOGICE (licensed or religion-based practitioners) or affirmative therapy (licensed practitioners). MAIN OUTCOMES AND MEASURES: Total incremental costs and quality-adjusted life-years (QALYs) vs no intervention and total economic burden of SOGICE. RESULTS: Among 28 published studies, which included 190 695 LGBTQ individuals, 12% (range, 7%-23%) of youths experienced SOGICE, initiated at a mean age of 25 years (range, 5-58 years), with a mean (SD) duration of 26 (29) months. At least 2 types of SOGICE were administered to 43% of recipients. Relative to LGBTQ individuals who did not undergo SOGICE, recipients experienced serious psychological distress (47% vs 34%), depression (65% vs 27%), substance abuse (67% vs 50%), and attempted suicide (58% vs 39%). In the economic analysis, over a lifetime horizon with a 3% annual discount rate, the base-case model estimated additional $97 985 lifetime costs per individual, with SOGICE associated with 1.61 QALYs lost vs no intervention; affirmative therapy yielded cost savings of $40 329 with 0.93 QALYs gained vs no intervention. With an estimated 508 892 youths at risk for SOGICE in 2021, the total annual cost of SOGICE is estimated at $650.16 million (2021 US dollars), with associated harms totaling an economic burden of $9.23 billion. CONCLUSIONS AND RELEVANCE: This economic evaluation study suggests that there is a high economic burden and high societal costs associated with SOGICE and identifies additional research questions regarding the roles of private and public funding in supporting this harmful practice.

What Does the Economic Burden of Acute Myeloid Leukemia Treatment Look Like for the Next Decade? An Analysis of Key Findings, Challenges and Recommendations.

Acute myeloid leukemia (AML) is conventionally treated with chemotherapy in eligible patients. Potentially curative regimens are associated with significant toxicity, and the major cost drivers in AML historically have been hospitalization and hematopoietic stem cell transplantation. The past several years have seen a dramatic increase in the number of treatment options, including oral therapies and drugs targeted to biological pathways implicated in AML. Major current and future drivers of cost in AML include hospitalization and medical costs, stem cell transplantation for eligible patients, and medication costs. It is likely that hospitalization and medical costs will decline as more AML treatment moves to the outpatient setting. Stem cell transplantation costs may increase, if more patients are eligible for improved procedures, although the overall cost of transplantation could decrease if new procedures reduce the need for hospitalization. Medication costs are likely to increase, with various branded drugs available and in development. From a broader perspective, another driver of cost is the proportion of patients with AML who can undergo treatment. Patients who may previously have been unable to tolerate chemotherapy are more likely to be treated with the range of less intensive, more tolerable options now available. The effectiveness of newer AML treatment options also suggests that, overall, there may be more patients staying alive and on treatment longer than in the past. While certain advances, such as increased use of oral and outpatient therapies, could potentially reduce costs, the overall economic impact of AML is likely to increase as more patients are eligible for novel therapies across several phases from induction to maintenance to relapsed/refractory disease. While these novel therapies have the potential to deliver value in the form of improved efficacy, safety, and convenience, payers will need to determine how to cover a longer, more complex AML treatment pathway.

Economic burden of acute steroid-refractory graft-versus-host disease in commercially insured pediatric patients.

BACKGROUND: Acute graft-versus-host disease (aGVHD), a potentially life-threatening complication of hematopoietic stem cell transplantation (HSCT), often occurs within 100 days of HSCT. While steroids are typically used as first-line treatment, there is no consensus on second-line steroid-refractory (SR) treatments. SR aGVHD is associated with significantly worse pediatric health outcomes, but less is known about its economic impact. OBJECTIVE: To evaluate the economic burden of SR pediatric aGVHD in a commercially insured US patient population. METHODS: Retrospective analyses were conducted using medical and pharmacy claims data from the HealthCore Integrated Research Database (study period January 1, 2006-May 31, 2019). Included patients had at least 1 claim for allogeneic HSCT (earliest HSCT claim set as index date), no claims for autologous HSCT, and no pre-index GVHD. Patients were aged less than 18 years with no minimum pre- or post-index continuous enrollment. The GVHD cohort included patients with at least 1 claim for aGVHD over 100 days from index with at least 1 claim for any steroid and at least 1 claim for second-line therapy, both on or after the date of the first aGVHD claim. Patients post-HSCT with no GVHD claims over follow-up formed the comparison cohort. Health care resource utilization and costs over 12 months from the index date were calculated and compared between cohorts using parametric testing. RESULTS: 38 patients with SR aGVHD and 184 controls were included. Mean age and sex were similar for aGVHD (8.6 years, 50% female) and control (8.2 years, 45% female). During the 12-month post-index follow-up, SR aGVHD patients had higher rates of complications vs controls (* for P < 0.05): anemia (79% vs 68%), drug-induced anemia* (53% vs 34%), neutropenia (63% vs 53%), thrombocytopenia (58% vs 42%), gastrointestinal complications* (95% vs 65%), and infections* (95% vs 79%). Mean inpatient length of stay was longer by 31.6 days (P < 0.01) with a total average of 96.0 days for those with SR aGVHD vs 64.3 days for the controls. More SR aGVHD patients required inpatient total parenteral nutrition (71% vs 58%), readmission within 12 months of discharge from index hospitalization* (89% vs 60%), ER visits (34% vs 24%), and outpatient visits (100% vs 86%). Total 12-month mean medical costs were higher in aGVHD patients: $1,212,944 vs $673,491 (P < 0.001), mostly because of complication-related costs: $868,966 vs $396,757 (P < 0.001). Among patients with SR aGVHD, mean total costs were higher by about $1.8 million ($2,609,445 vs $812,385; P = 0.014) for those who died compared with those who were alive within 12 months. CONCLUSIONS: SR aGVHD in pediatric patients following HSCT is associated with incremental 12-month medical costs of greater than $500,000, driven largely by complications. DISCLOSURES: This research was sponsored by Mesoblast, Inc. Grabner is an employee of HealthCore, Inc., which acted as consultants to Mesoblast, Inc., during the conduct of this research. Strati is an employee of Mesoblast, Inc. Sandman and Forsythe are employees of Purple Squirrel Economics, which acted as consultants to Mesoblast, Inc., during the conduct of this research. This work was presented at the AMCP Annual Meeting online in April 2020 and was an encore presentation at AMCP Nexus 2020 Virtual in October 2020.

Revised Escherichia coli selenocysteine insertion requirements determined by in vivo screening of combinatorial libraries of SECIS variants.

To investigate the stringency of the Escherichia coli selenocysteine insertion sequence (SECIS) requirements, libraries of SECIS variants were screened via a novel method in which suppression of the selenocysteine (Sec) opal codon was coupled to bacteriophage plaque formation. The SECIS variant libraries were designed with a mostly paired lower stem, so that randomization could be focused on the upper stem and loop regions. We identified 19 functional non-native SECIS sequences that violated the expected pairing requirements for the SECIS upper stem. All of the SECIS variants were shown to permit Sec insertion in phage (by chemical modification of the Sec residue) and fused to lacZalpha (by beta-galactosidase assay). The diminished pairing of the upper stem appears to be mitigated by the overall stem stability; a given upper stem variant has significantly higher readthrough in the context of a paired, rather than unpaired, lower stem. These results suggest an unexpected downstream sequence flexibility in prokaryotic selenoprotein expression.

Testis-specific HMG-domain protein alters the responses of cells to cisplatin.

Cisplatin is an effective agent for the treatment of testicular cancer. In the present study with mouse testicular teratocarcinoma cell extracts, we observed a deficiency in nucleotide excision repair (NER) of a DNA probe bearing a cisplatin 1,2-d(GpG) intrastrand cross-link. In contrast, repair of the cisplatin 1,3-d(GpTpG) intrastrand cross-link was still active in these cell extracts. A current working hypothesis is that complexes of HMG-domain proteins with the major cisplatin 1,2-intrastrand cross-links could enhance cisplatin cytotoxicity by blocking repair of these lesions on the genome. The family of HMG-domain proteins include a testis-specific protein, tsHMG, which might account for the altered NER in testicular cells. To test this possibility, a human cervical carcinoma cell line (HeLa) was constructed which ectopically expressed tsHMG under the control of an inducible promoter. Microscopic examination of tsHMG expression and cisplatin-induced apoptosis on a cellular level revealed that the nuclear protein did indeed modulate the cytotoxic consequences of cisplatin treatment. Also, tsHMG enhanced transcription inhibition by cisplatin. These results reveal that an HMG-domain protein can affect cellular responses to cisplatin and may be relevant to the clinical observation that cancer cells in specific tissues are particularly sensitive to cisplatin.