Techniques to assess reproductive status in adult female American alligators (Alligator mississippiensis) using laparoscopic examination.

This protocol describes a minimally invasive surgical technique and approach to successfully examine the gonads of live female American alligators as part of a reproductive examination used in conservation medicine and biology. Best practices are based on examination of over 80 American alligators in the last two years adapting principles derived from other reptilian megafauna species. This protocol is designed for appropriately qualified veterinarians and biologists working in the field. We show likely reproductive tract presentations with respect to breeding status and environmental cues to help guide interpretation of observations. The laparoscopic approach and findings presented here provide tools to safely clinically examine animals in a welfare-oriented way that will advance our understanding of crocodilian reproduction. This technique has not previously been described in this species.

Newly described nesting sites of the green sea turtle (Chelonia mydas) and the hawksbill sea turtle (Eretmochelys imbricata) in the central Red Sea.

Background: There is relatively little published information about sea turtle nesting distribution and seasonality in the Saudi Arabian Red Sea. Upcoming large-scale developments occurring along the Saudi Arabian Red Sea coast could negatively affect many sea turtle nesting beaches with potential impacts on the survival of local populations. Methods: In 2019, two coastal beaches and three near-shore islands were surveyed for turtle nesting in the central Red Sea. We recorded all emergences, examined beach morphology, and collected sand samples to determine grain size, moisture content and colour. Results: Sea turtle nesting was found at all surveyed sites, though emergence counts were often low. The limited occurrence of nesting at several previously undocumented sites suggests that nesting activity may be widespread, but sparsely distributed, in the central Red Sea region. In addition, nesting at novel sites appeared to favour the seaward side of islands, a pattern that was not observed in previously documented areas. The substrate of most surveyed sites was composed of calcium carbonate with Ras Baridi as the only exception; it was composed of dark quartz-rich sediment. This study highlights several important sea turtle rookeries while also demonstrating that low levels of nesting occur throughout the region, although inter-annual nesting patterns still need to be determined. Future developments should be steered away from key nesting areas and the seaward bias in marginal rookeries should be taken into account where possible.

Employer-perspective cost comparison of surgical treatments for abnormal uterine bleeding.

Aim: To estimate direct and indirect costs of surgical treatment of abnormal uterine bleeding (AUB) from a self-insured employer's perspective. Methods: Employer-sponsored insurance claims data were analyzed to estimate costs owing to absence and short-term disability 1 year following global endometrial ablation (GEA), outpatient hysterectomy (OPH) and inpatient hysterectomy (IPH). Results: Costs for women who had GEA are substantially less than costs for women who had either OPH or IPH, with the difference ranging from approximately $7700 to approximately $10,000 for direct costs and approximately $4200 to approximately $4600 for indirect costs. Women who had GEA missed 21.8-24.0 fewer works days. Conclusion: Study results suggest lower healthcare costs associated with GEA versus OPH or IPH from a self-insured employer perspective.

Breast, Cervical, and Colorectal Cancer Screening: Patterns Among Women With Medicaid and Commercial Insurance.

INTRODUCTION: Despite healthcare reforms mandating expanded insurance coverage and reduced out-of-pocket costs for preventive care, cancer screening rates remain relatively static. No study has measured cancer screening rates for multiple tests among non-Medicare patients. METHODS: This retrospective, population-based claims analysis, conducted in 2016-2017, of commercially insured and Medicaid-insured women aged 30-59 years enrolled in IBM MarketScan Commercial and Medicaid Databases (containing approximately 90 and 17 million enrollees, respectively) during 2010-2015 describes screening rates for breast, cervical, and colorectal cancer. Key outcomes were (1) proportion screened for breast, cervical, and colorectal cancer among the age-eligible population compared with accepted age-based recommendations and (2) proportion with longer-than-recommended intervals between tests. RESULTS: One half (54.7%) of commercially insured women aged 40-59 years (n=1,538,444) were screened three or more times during the 6-year study period for breast cancer; for Medicaid-insured women (n=78,897), the rates were lower (23.7%). One third (43.4%) of commercially insured and two thirds (68.9%) of Medicaid-insured women had a >2.5-year gap between mammograms. Among women aged 30-59 years, 59.3% of commercially insured women and 31.4% of Medicaid-insured women received two or more Pap tests. The proportion of patients with a >3.5-year gap between Pap tests was 33.9% (commercially insured) and 57.1% (Medicaid-insured). Among women aged 50-59 years, 63.3% of commercially insured women and 47.2% of Medicaid-insured women were screened at least one time for colorectal cancer. Almost all women aged 30-59 years (commercially insured, 99.1%; Medicaid-insured, 98.9%) had at least one healthcare encounter. CONCLUSIONS: Breast and cervical cancer screenings remain underutilized among both commercially insured and Medicaid-insured populations, with lower rates among the Medicaid-insured population. However, almost all women had at least one healthcare encounter, suggesting opportunities for better coordinated care.

The Role of Dust Mites in Allergy.

House dust mites are an unsurpassed cause of atopic sensitization and allergic illness throughout the world. The major allergenic dust mites Dermatophagoides pteronyssinus, Dermatophagoides farinae, Euroglyphus maynei, and Blomia tropicalis are eight-legged members of the Arachnid class. Their approximately 3-month lifespan comprises egg, larval, protonymph, tritonymph, and adult stages, with adults, about one fourth to one third of a millimeter in size, being at the threshold of visibility. The geographic and seasonal distributions of dust mites are determined by their need for adequate humidity, while their distribution within substrates is further determined by their avoidance of light. By contacting the epithelium of the eyes, nose, lower airways, skin, and gut, the allergen-containing particles of dust mites can induce sensitization and atopic symptoms in those organs. Various mite allergens, contained primarily in mite fecal particles but also in shed mite exoskeletons and decaying mite body fragments, have properties that include proteolytic activity, homology with the lipopolysaccharide-binding component of Toll-like receptor 4, homology with other invertebrate tropomyosins, and chitin-cleaving and chitin-binding activity. Mite proteases have direct epithelial effects including the breaching of tight junctions and the stimulation of protease-activated receptors, the latter inducing pruritus, epithelial dysfunction, and cytokine release. Other components, including chitin, unmethylated mite and bacterial DNA, and endotoxin, activate pattern recognition receptors of the innate immune system and act as adjuvants promoting sensitization to mite and other allergens. Clinical conditions resulting from mite sensitization and exposure include rhinitis, sinusitis, conjunctivitis, asthma, and atopic dermatitis. Systemic allergy symptoms can also occur from the ingestion of cross-reacting invertebrates, such as shrimp or snail, or from the accidental ingestion of mite-contaminated foods. Beyond their direct importance as a major allergen source, an understanding of dust mites leads to insights into the nature of atopy and of allergic sensitization in general.

Women with Newly Diagnosed Uterine Fibroids: Treatment Patterns and Cost Comparison for Select Treatment Options.

The primary objective of this study was to describe surgical treatment patterns among women with newly diagnosed uterine fibroids (UF). A secondary objective was to estimate the medical costs associated with other common surgical interventions for UF. Claims-based commercial and Medicare data (2011-2016) were used to identify women aged ≥30 years with continuous enrollment for at least 12 months before and after a new diagnosis of UF. Receipt of a surgical or radiologic procedure (hysterectomy, myomectomy, endometrial ablation, uterine artery embolization, and curettage) was the primary outcome. Health care resource utilization and costs were calculated for women with at least 12 months of continuous enrollment following a UF surgical procedure. Among women who met selection criteria, 31.7% of patients underwent a surgical procedure; 20.9% of these underwent hysterectomy. An increase was observed over time in the percentage of women undergoing outpatient hysterectomy (from 27.0% to 40.2%) and hysteroscopic myomectomy (from 8.0% to 11.5%). The cost analysis revealed that total health care costs for hysteroscopic myomectomy ($17,324) were significantly lower (P < 0.001) than those for women who underwent inpatient hysterectomy ($24,027) and those for women undergoing the 3 comparison procedures. Hysterectomy was the most common surgical intervention. Patients undergoing inpatient hysterectomy had the highest health care costs. Although less expensive, minimally invasive approaches are becoming more common; they are performed infrequently in patients with newly diagnosed UF. The results of this study may be useful in guiding decisions regarding the most appropriate and cost-effective surgical treatment for UF.

Economic Evaluation of Global Endometrial Ablation Versus Inpatient and Outpatient Hysterectomy for Treatment of Abnormal Uterine Bleeding: US Commercial and Medicaid Payer Perspectives.

Every year, abnormal uterine bleeding (AUB) exacts a heavy toll on women's health and leads to high costs for the US health care system. The literature shows that endometrial ablation results in fewer complications, shorter recovery and lower costs than more commonly performed hysterectomy procedures. The objective of this study was to model clinical-economic outcomes, budget impact, and cost-effectiveness of global endometrial ablation (GEA) versus outpatient hysterectomy (OPH) and inpatient hysterectomy (IPH) procedures. A decision tree, state-transition (semi-Markov) economic model was developed to simulate 3 hypothetical cohorts of women who received surgical treatment for AUB (GEA, OPH, and IPH) over 1, 2, and 3 years to evaluate clinical and economic outcomes for GEA vs. OPH and GEA vs. IPH. Two versions of the model were created to reflect both commercial health care payer and US Medicaid perspectives, and analyses were conducted for both payer types. Total health care costs in the first year after GEA were substantially lower compared with those for IPH and OPH. Budget impact analysis results showed that increasing GEA utilization yields total annual cost savings of about $906,000 for a million-member commercial health plan and about $152,000 in cost savings for a typical-sized state Medicaid plan with 1.4 million members. Cost-effectiveness analysis results for both perspectives showed GEA as economically dominant (conferring greater benefit at lower cost) over both OPH and IPH in the 1-year commercial scenario. This study demonstrates that, for some patients, GEA may prove to be a safe, uterus-sparing, cost-effective alternative to OPH and IPH for the surgical treatment of AUB.

Economic analysis and budget impact of clostridial collagenase ointment compared with medicinal honey for treatment of pressure ulcers in the US.

OBJECTIVES: Pressure ulcer (PU) treatment poses significant clinical and economic challenges to health-care systems. The aim of this study was to assess the cost-effectiveness and budget impact of enzymatic debridement with clostridial collagenase ointment (CCO) compared with autolytic debridement with medicinal honey (MH) for PU treatment from a US payer/Medicare perspective in the hospital outpatient department setting. METHODS: A cost-effectiveness analysis using a Markov model was developed using a 1-week cycle length across a 1-year time horizon. The three health states were inflammation/senescence, granulation/proliferation (ie, patients achieving 100% granulation), and epithelialization. Data sources included the US Wound Registry, Medicare fee schedules, and other published clinical and cost studies about PU treatment. RESULTS: In the base case analysis over a 1-year time horizon, CCO was the economically dominant strategy (ie, simultaneously conferring greater benefit at less cost). Patients treated with CCO experienced 22.7 quality-adjusted life weeks (QALWs) at a cost of $6,161 over 1 year, whereas MH patients experienced 21.9 QALWs at a cost of $7,149. Patients treated with CCO achieved 11.5 granulation weeks and 6.0 epithelization weeks compared with 10.6 and 4.4 weeks for MH, respectively. The number of clinic visits was 40.1 for CCO vs 43.4 for MH, and the number of debridements was 12.3 for CCO compared with 17.6 for MH. Probabilistic sensitivity analyses determined CCO dominant in 72% of 10,000 iterations and cost-effective in 91%, assuming a benchmark willingness-to-pay threshold of $50,000/quality-adjusted life year ($962/QALW). The budget impact analysis showed that for every 1% of patients shifted from MH to CCO, a cost savings of $9,883 over 1 year for a cohort of 1,000 patients was observed by the payer. CONCLUSION: The results of these economic analyses suggest that CCO is a cost-effective, economically dominant alternative to MH in the treatment of patients with PUs in the hospital outpatient department setting.

Value Analysis of Digital Breast Tomosynthesis for Breast Cancer Screening in a US Medicaid Population.

PURPOSE: Better understanding regarding the clinical-economic value of digital breast tomosynthesis (DBT) for breast cancer screening for Medicaid enrollees is needed to help inform sound, value-based decision making. The objective of this study was to conduct a clinical-economic value analysis of DBT for breast cancer screening among women enrolled in Medicaid to assess the potential clinical benefits, associated expenditures, and net budget impact of DBT. METHODS: Two annual screening mammography scenarios were evaluated with an economic model: (1) full-field digital mammography and (2) combined full-field digital mammography and DBT. The model focused on two main drivers of DBT value: (1) capacity for DBT to reduce the number of women recalled for additional follow-up imaging and diagnostic services and (2) capacity of DBT to facilitate earlier diagnosis of cancer at earlier stages, when treatment costs are lower. RESULTS: Model analysis results showed that the use of DBT as a mammographic screening modality by Medicaid enrollees potentially reduces the need for follow-up diagnostic services and improves the detection of invasive cancers, allowing earlier, less costly treatment. With the modest incremental reimbursement of $37 for DBT expected for a typical Medicaid claim, annual cost savings from DBT predicted by the model amounts to $8.14 per patient, potentially translating into more than $12,000 savings per year for an average-sized Medicaid plan and as much as $207,000 savings per year for a typical state Medicaid program. CONCLUSIONS: Wider adoption of DBT presents an opportunity to deliver value-based care to Medicaid programs and to help address disparities and barriers to accessing preventive care by some of the nation's most vulnerable citizens.

Economic impact of longer battery life of cardiac resynchronization therapy defibrillators in Sweden.

OBJECTIVE: The objective of this study was to quantify the impact that longer battery life of cardiac resynchronization therapy defibrillator (CRT-D) devices has on reducing the number of device replacements and associated costs of these replacements from a Swedish health care system perspective. METHODS: An economic model based on real-world published data was developed to estimate cost savings and avoided device replacements for CRT-Ds with longer battery life compared with devices with industry-standard battery life expectancy. Base-case comparisons were performed among CRT-Ds of three manufacturers - Boston Scientific Corporation, St. Jude Medical, and Medtronic - over a 6-year time horizon, as per the available clinical data. As a sensitivity analysis, we evaluated CRT-Ds as well as single-chamber implantable cardioverter defibrillator (ICD-VR) and dual-chamber implantable cardioverter defibrillator (ICD-DR) devices over a longer 10-year period. All costs were in 2015 Swedish Krona (SEK) discounted at 3% per annum. RESULTS: Base-case analysis results show that up to 603 replacements and up to SEK 60.4 million cumulative-associated costs could be avoided over 6 years by using devices with extended battery life. The pattern of savings over time suggests that savings are modest initially but increase rapidly beginning in the third year of follow-up with each year's cumulative savings two to three times the previous year. Evaluating CRT-D, ICD-VR, and ICD-DR devices together over a longer 10-year period, the sensitivity analysis showed 2,820 fewer replacement procedures and associated cost savings of SEK 249.3 million for all defibrillators with extended battery life. CONCLUSION: Extended battery life is likely to reduce device replacements and associated complications and costs, which may result in important cost savings and a more efficient use of health care resources as well as a better quality of life for heart failure patients in Sweden.

Cost-effectiveness of edoxaban versus rivaroxaban for stroke prevention in patients with nonvalvular atrial fibrillation (NVAF) in the US.

BACKGROUND: Understanding the value of new anticoagulation therapies compared with existing therapies is of paramount importance in today's cost-conscious and efficiency-driven health care environment. Edoxaban and rivaroxaban for stroke prevention in nonvalvular atrial fibrillation (NVAF) patients with CHADS2 scores ≥2 have been evaluated in pivotal trials versus warfarin. The relative value of edoxaban versus rivaroxaban would be of interest to health care stakeholders and patients who prefer a once-daily treatment option for long-term stroke prevention in NVAF. OBJECTIVE: To evaluate the relative cost-effectiveness of two once-daily regimens of novel oral anticoagulation therapy - edoxaban (60 mg/30 mg dose-reduced) versus rivaroxaban (20 mg/15 mg dose-reduced) - for stroke prevention in NVAF patients from a US health-plan perspective. MATERIALS AND METHODS: A Markov model simulated lifetime risk and treatment of stroke, systemic embolism, major bleeding, clinically relevant nonmajor bleeding, myocardial infarction, and death in NVAF patients treated with edoxaban or rivaroxaban. Efficacy and safety data were derived from a network meta-analysis that utilized data from patients enrolled in ENGAGE AF-TIMI 48 and ROCKET-AF. Health care cost and utility data were obtained from published sources. Incremental cost-effectiveness ratios of $150,000 per quality-adjusted life year (QALY) gained were used as thresholds for "highly cost-effective", "cost-effective", and "not cost-effective" treatment options, respectively, as per American Heart Association/American College of Cardiology guidelines. RESULTS: Edoxaban was dominant relative to rivaroxaban, such that it was associated with lower total health care costs and better effectiveness in terms of QALYs in the base-case analysis. Results were supported by probabilistic sensitivity analyses that showed edoxaban as either dominant or a highly cost-effective alternative (incremental cost-effectiveness ratio <$50,000) to rivaroxaban in 88.4% of 10,000 simulations. CONCLUSION: Results of this study showed that the once-daily edoxaban (60 mg/30 mg dose-reduced) regimen is a cost-saving or highly cost-effective treatment relative to rivaroxaban (20 mg/15 mg dose-reduced) for stroke prevention in NVAF patients with CHADS2 ≥2.

Differential Mobility Spectrometry Coupled with Multiple Ion Monitoring in Regulated LC-MS/MS Bioanalysis of a Therapeutic Cyclic Peptide in Human Plasma.

A differential mobility spectrometry (DMS) in combination with a multiple ion monitoring (MIM) method was developed and validated for quantitative LC-MS/MS bioanalysis of pasireotide (SOM230) in human plasma. Pasireotide, a therapeutic cyclic peptide, exhibits poor collision-induced dissociation (CID) efficiency for multiple reaction monitoring (MRM) detection. Therefore, in an effort to increase the overall sensitivity of the assay, a DMS-MIM approach was explored. By selecting the most abundant doubly charged precursor ion in both the Q1 and Q3 of the mass analyzer in MIM and combining the DMS capability to significantly reduce the high matrix/chemical background noise, this new LC-DMS-MIM method overcomes the sensitivity challenge in the typical MRM method due to poor CID fragmentation of the analyte. Human plasma was spiked with pasireotide with concentrations in the range 0.01-50 ng/mL. Weak cation-exchange solid-phase extraction was employed for sample preparation. The sample extracts were analyzed with a SCIEX QTRAP 6500 system equipped with an ESI source and DMS device. The separation voltage and compensation voltage of the DMS and other parameters of the MS system were optimized to maximize signal responses. The performance of the LC-DMS-MIM assay for quantitative analysis of pasireotide in human plasma was evaluated and compared to those obtained via LC-MRM and LC-MIM without DMS. Overall, the assay sensitivity with DMS-MIM was approximately 5-fold better than that observed in MRM or MIM without DMS. The assay was validated with accuracy (% bias) and precision (% CV) of the QC results at eight concentration levels (0.01, 0.02, 0.05, 0.15, 0.3, 1.5, 15, and 37.5 ng/mL) evaluated ranging from -4.8 to 5.0% bias and 0.7 to 8.6% CV for the intraday and interday runs. The current LC-DMS-MIM workflow can be expanded to quantitative analysis of other molecules that have poor fragmentation efficiency in CID.

The Clinical and Economic Benefits of Co-Testing Versus Primary HPV Testing for Cervical Cancer Screening: A Modeling Analysis.

BACKGROUND: Consensus United States cervical cancer screening guidelines recommend use of combination Pap plus human papillomavirus (HPV) testing for women aged 30 to 65 years. An HPV test was approved by the Food and Drug Administration in 2014 for primary cervical cancer screening in women age 25 years and older. Here, we present the results of clinical-economic comparisons of Pap plus HPV mRNA testing including genotyping for HPV 16/18 (co-testing) versus DNA-based primary HPV testing with HPV 16/18 genotyping and reflex cytology (HPV primary) for cervical cancer screening. METHODS: A health state transition (Markov) model with 1-year cycling was developed using epidemiologic, clinical, and economic data from healthcare databases and published literature. A hypothetical cohort of one million women receiving triennial cervical cancer screening was simulated from ages 30 to 70 years. Screening strategies compared HPV primary to co-testing. Outcomes included total and incremental differences in costs, invasive cervical cancer (ICC) cases, ICC deaths, number of colposcopies, and quality-adjusted life years for cost-effectiveness calculations. Comprehensive sensitivity analyses were performed. RESULTS: In a simulation cohort of one million 30-year-old women modeled up to age 70 years, the model predicted that screening with HPV primary testing instead of co-testing could lead to as many as 2,141 more ICC cases and 2,041 more ICC deaths. In the simulation, co-testing demonstrated a greater number of lifetime quality-adjusted life years (22,334) and yielded $39.0 million in savings compared with HPV primary, thereby conferring greater effectiveness at lower cost. CONCLUSIONS: Model results demonstrate that co-testing has the potential to provide improved clinical and economic outcomes when compared with HPV primary. While actual cost and outcome data are evaluated, these findings are relevant to U.S. healthcare payers and women's health policy advocates seeking cost-effective cervical cancer screening technologies.

Cost-Effectiveness of Global Endometrial Ablation vs. Hysterectomy for Treatment of Abnormal Uterine Bleeding: US Commercial and Medicaid Payer Perspectives.

Cost-effectiveness modeling studies of global endometrial ablation (GEA) for treatment of abnormal uterine bleeding (AUB) from a US perspective are lacking. The objective of this study was to model the cost-effectiveness of GEA vs. hysterectomy for treatment of AUB in the United States from both commercial and Medicaid payer perspectives. The study team developed a 1-, 3-, and 5-year semi-Markov decision-analytic model to simulate 2 hypothetical patient cohorts of women with AUB-1 treated with GEA and the other with hysterectomy. Clinical and economic data (including treatment patterns, health care resource utilization, direct costs, and productivity costs) came from analyses of commercial and Medicaid claims databases. Analysis results show that cost savings with simultaneous reduction in treatment complications and fewer days lost from work are achieved with GEA versus hysterectomy over almost all time horizons and under both the commercial payer and Medicaid perspectives. Cost-effectiveness metrics also favor GEA over hysterectomy from both the commercial payer and Medicaid payer perspectives-evidence strongly supporting the clinical-economic value about GEA versus hysterectomy. Results will interest clinicians, health care payers, and self-insured employers striving for cost-effective AUB treatments.