A Dwindling Matter: An Analysis of Medicare Reimbursement for Endocrine Surgery Procedures from 2000-23.

OBJECTIVE: To evaluate Medicare reimbursement trends for endocrine surgeries from 2000-23. BACKGROUND: As the population ages, demand for endocrine surgeries is expected to increase. Understanding reimbursement trends is essential to ensure the financial sustainability of endocrine surgery. METHODS: Data were extracted from Medicare Inpatient and Outpatient Hospital datasets, National Summary, and Physician Fee Look-up Files for nine common thyroid, parathyroid and adrenal surgeries. Data were adjusted for inflation. Descriptive statistics, compound annual growth rate (CAGR), and linear regression models were built to evaluate practice and reimbursement trends. RESULTS: From 2000-23, there was a 63.8% increase in endocrine surgery volume. However, inflation-adjusted average procedure reimbursements decreased by 43.2% from $1709 to $972 (CAGR -2.4%), which is the largest decrease for any surgical subspecialty reported in the published literature. At the current CAGR, the average estimated reimbursement is projected to decrease to $868 by 2030 (P<0.001). Average facility reimbursements for inpatient and outpatient hospitalizations increased. However, substantial practice pattern shifts in the study period led to decreased overall facility reimbursements, with a $17.9 million decrease in total inpatient reimbursements between 2016-21 that was only partially offset by a $3.2 million increase in outpatient hospital reimbursements. CONCLUSION: Medicare procedure reimbursements for endocrine surgeries have been outpaced by inflation, with large decreases since 2000. Concurrent changes in practice patterns have also resulted in markedly fewer inpatient stays leading to lower total facility reimbursements. Our data raise concern over the financial sustainability of the endocrine surgery field as the demand for endocrine surgery procedures increases.

A Novel Machine Learning Algorithm for Creating Risk-Adjusted Payment Formulas.

Importance: Models predicting health care spending and other outcomes from administrative records are widely used to manage and pay for health care, despite well-documented deficiencies. New methods are needed that can incorporate more than 70 000 diagnoses without creating undesirable coding incentives. Objective: To develop a machine learning (ML) algorithm, building on Diagnostic Item (DXI) categories and Diagnostic Cost Group (DCG) methods, that automates development of clinically credible and transparent predictive models for policymakers and clinicians. Design, Setting, and Participants: DXIs were organized into disease hierarchies and assigned an Appropriateness to Include (ATI) score to reflect vagueness and gameability concerns. A novel automated DCG algorithm iteratively assigned DXIs in 1 or more disease hierarchies to DCGs, identifying sets of DXIs with the largest regression coefficient as dominant; presence of a previously identified dominating DXI removed lower-ranked ones before the next iteration. The Merative MarketScan Commercial Claims and Encounters Database for commercial health insurance enrollees 64 years and younger was used. Data from January 2016 through December 2018 were randomly split 90% to 10% for model development and validation, respectively. Deidentified claims and enrollment data were delivered by Merative the following November in each calendar year and analyzed from November 2020 to January 2024. Main Outcome and Measures: Concurrent top-coded total health care cost. Model performance was assessed using validation sample weighted least-squares regression, mean absolute errors, and mean errors for rare and common diagnoses. Results: This study included 35 245 586 commercial health insurance enrollees 64 years and younger (65 901 460 person-years) and relied on 19 clinicians who provided reviews in the base model. The algorithm implemented 218 clinician-specified hierarchies compared with the US Department of Health and Human Services (HHS) hierarchical condition category (HCC) model's 64 hierarchies. The base model that dropped vague and gameable DXIs reduced the number of parameters by 80% (1624 of 3150), achieved an R2 of 0.535, and kept mean predicted spending within 12% ($3843 of $31 313) of actual spending for the 3% of people with rare diseases. In contrast, the HHS HCC model had an R2 of 0.428 and underpaid this group by 33% ($10 354 of $31 313). Conclusions and Relevance: In this study, by automating DXI clustering within clinically specified hierarchies, this algorithm built clinically interpretable risk models in large datasets while addressing diagnostic vagueness and gameability concerns.

Managed competition in the United States: How well is it promoting equity and efficiency?

Managed competition frameworks aim to control healthcare costs and promote access to high-quality health insurance and services through a combination of public policies and market forces. In the United States, managed competition delivery systems are varied and diffused across a patchwork of divided markets and populations. This, coupled with extremely high national health spending per capita, makes a more unified managed competition strategy an appealing alternative to a currently struggling healthcare system. We examine the relative effectiveness of three existing programmes in the U.S. that each rely upon some principles of managed competition: health insurance exchanges instituted by the Affordable Care Act, Medicaid managed care organisations, and Medicare Advantage plans. Although each programme leverages some competitive features, each faces significant hurdles as a candidate for expansion. We highlight these challenges with a survey of academic health economists, and find that provider and insurer consolidation, highly segmented markets, and failing to incentivise competitive efficiencies all dampen the success of existing programmes. Although managed competition for all is a potentially desirable framework for future health reform in the U.S., successful expansion relies on addressing fundamental issues revealed by imperfect existing programmes.

Scope and Incentives for Risk Selection in Health Insurance Markets With Regulated Competition: A Conceptual Framework and International Comparison.

In health insurance markets with regulated competition, regulators face the challenge of preventing risk selection. This paper provides a framework for analyzing the scope (i.e., potential actions by insurers and consumers) and incentives for risk selection in such markets. Our approach consists of three steps. First, we describe four types of risk selection: (a) selection by consumers in and out of the market, (b) selection by consumers between high- and low-value plans, (c) selection by insurers via plan design, and (d) selection by insurers via other channels such as marketing, customer service, and supplementary insurance. In a second step, we develop a conceptual framework of how regulation and features of health insurance markets affect the scope and incentives for risk selection along these four dimensions. In a third step, we use this framework to compare nine health insurance markets with regulated competition in Australia, Europe, Israel, and the United States.

Evaluation of Vibration as an Extrinsic Variable in In Vivo Research.

Vibration is inherent in research animal facilities due to the mechanical systems and practices required for animal care and use. Ample evidence indicates that vibration can change behavior and physiology in multiple species, potentially altering the results of research studies. Although one cannot eliminate environmental vibration, its control is important in research animal environments to decrease the possibility of introducing a research variable due to vibration effects. To assess the potential for a vibration source to alter experimental results and variability, one must understand the principles of vibration, its likely sources, and control methods. The literature regarding the effects of vibration, as it applies in a practical sense, can be challenging to interpret because the vibration frequencies tested to date have often not been within or near the most sensitive ranges of the species being tested. Some previous studies have used unrealistic vibration magnitudes and provided insufficient detail to duplicate or build upon conclusions. Standardization is essential for research examining the effects of vibration on animals to validate knowledge of this extrinsic variable in animal research and identify ways to mitigate the variable in research facilities.

Improving citrus bud grafting efficiency.

Commercial citrus trees are composed of a scion grafted onto a rootstock. Because grafting is one of the most expensive methods of plant propagation, grafting efficiency is of large practical importance. The purpose of this study was to improve citrus bud-grafting efficiency. The effects of six factors that included BA, Tween-20, DMSO, type of solvent (water or EtOH), cardinal orientation of grafted bud, and type of supplemental light (LED, metal halide, none) on forty-four bud-grafting measures were determined using a multifactor design of experiment approach. Four measures useful for identifying treatments of practical value included the number of rootstock axial buds that formed shoots, the percentage of grafted buds that formed shoots, the length of the longest shoot formed from the grafted buds, and the total leaf area of the grafted bud shoots. The factors that most affected these responses were no supplemental light to minimize the number of shoots from rootstock axial buds, a south orientation and 5 mM BA to maximize the percentage of grafted buds that formed shoots, a north orientation and 5 mM BA to maximize the length of the longest grafted bud shoot, and 5 mM BA to maximize the leaf area of the grafted bud shoots.

The histotripsy spectrum: differences and similarities in techniques and instrumentation.

Since its inception about two decades ago, histotripsy - a non-thermal mechanical tissue ablation technique - has evolved into a spectrum of methods, each with distinct potentiating physical mechanisms: intrinsic threshold histotripsy, shock-scattering histotripsy, hybrid histotripsy, and boiling histotripsy. All methods utilize short, high-amplitude pulses of focused ultrasound delivered at a low duty cycle, and all involve excitation of violent bubble activity and acoustic streaming at the focus to fractionate tissue down to the subcellular level. The main differences are in pulse duration, which spans microseconds to milliseconds, and ultrasound waveform shape and corresponding peak acoustic pressures required to achieve the desired type of bubble activity. In addition, most types of histotripsy rely on the presence of high-amplitude shocks that develop in the pressure profile at the focus due to nonlinear propagation effects. Those requirements, in turn, dictate aspects of the instrument design, both in terms of driving electronics, transducer dimensions and intensity limitations at surface, shape (primarily, the F-number) and frequency. The combination of the optimized instrumentation and the bio-effects from bubble activity and streaming on different tissues, lead to target clinical applications for each histotripsy method. Here, the differences and similarities in the physical mechanisms and resulting bioeffects of each method are reviewed and tied to optimal instrumentation and clinical applications.

Direct Infusion Device for Molecule Delivery in Plants.

Testing the function of therapeutic compounds in plants is an important component of agricultural research. Foliar and soil-drench methods are routine but have drawbacks, including variable uptake and the environmental breakdown of tested molecules. Trunk injection of trees is well-established, but most methods for this require expensive, proprietary equipment. To screen various treatments for Huanglongbing, a simple, low-cost method to deliver these compounds to the vascular tissue of small greenhouse-grown citrus trees infected with the phloem-limited bacterium Candidatus Liberibacter asiaticus (CLas) or infested with the phloem-feeding CLas insect vector Diaphorina citri Kuwayama (D. citri) is needed. To meet these screening requirements, a direct plant infusion (DPI) device was designed that connects to the plant's trunk. The device is made using a nylon-based 3D-printing system and easily obtainable auxiliary components. The compound uptake efficacy of this device was tested in citrus plants using the fluorescent marker 5,6-carboxyfluorescein-diacetate. Uniform compound distribution of the marker throughout the plants was routinely observed. Furthermore, this device was used to deliver antimicrobial and insecticidal molecules to determine their effects on CLas and D. citri respectively. The aminoglycoside antibiotic streptomycin was delivered into CLas-infected citrus plants using the device, which resulted in a reduction in the CLas titer from 2 weeks to 4 weeks post treatment. Delivering the neonicotinoid insecticide imidacloprid into D. citri-infested citrus plants resulted in a significant increase in psyllid mortality after 7 days. These results suggest that this DPI device represents a useful system for delivering molecules into plants for testing and facilitate research and screening purposes.

Patient preference for commonly-used, head and neck cancer-specific quality of life questionnaires in the follow-up setting (Determin): A multi-centre randomised controlled trial and mixed methods study.

BACKGROUND: Quality of life (QoL) assessment forms an integral part of modern cancer care and research. The aim of this study is to determine patients' preferences and willingness to complete commonly used head-and-neck cancer (HNC) QoL questionnaires (QLQs) in routine follow-up clinics. METHODS: This is a randomised control trial of 583 subjects from 17 centres during follow-up after treatment for oral, oropharyngeal or laryngeal cancer. Subjects completed three structured validated questionnaires: EORTC QLQ-HN35; FACT-HN and UW-QOL, and an unstructured patient-generated list. The order of questionnaire presentation was randomised, and subjects were stratified by disease site and stage. Patients self-rated the questionnaires they found most helpful to communicate their health concerns to their clinicians. RESULTS: Of the 558 respondents, 82% (457) found QLQs useful to communicate their health concerns to their clinician (OR = 15.76; 95% CI 10.83-22.94). Patients preferred the structured disease-specific instruments (OR 8.79; 95% CI 5.99-12.91), while the open list was the most disliked (OR = 4.25; 95% CI 3.04-5.94). There was no difference in preference by treatment modality. More women preferred the FACT-HN (OR = 3.01, 95% CI 1.05-8.62), and patients under 70 preferred EORTC QLQ-HN35 (OR = 3.14, 95% CI 1.3-7.59). However, only 55% of patients expressed preference to complete questionnaires routinely at the clinic. CONCLUSIONS: Most patients found QLQs helpful during their follow-up and 55% supported routine questionnaires in follow-up clinics. Males and people over 70 years old were the least willing to complete the routine questionnaires and preferred shorter questionnaires (e.g., UW-QOL). Women preferred FACT-HN, and younger patients preferred EORTC QLQ-HN35. Reasons for the reluctance to complete questionnaires require elucidation.

Dual-Mode 1-D Linear Ultrasound Array for Image-Guided Drug Delivery Enhancement Without Ultrasound Contrast Agents.

Pulsed high-intensity focused ultrasound (pHIFU) uses nonlinearly distorted millisecond-long ultrasound pulses of moderate intensity to induce inertial cavitation in tissue without administration of contrast agents. The resulting mechanical disruption permeabilizes the tissue and enhances the diffusion of systemically administered drugs. This is especially beneficial for tissues with poor perfusion such as pancreatic tumors. Here, we characterize the performance of a dual-mode ultrasound array designed for image-guided pHIFU therapies in producing inertial cavitation and ultrasound imaging. The 64-element linear array (1.071 MHz, an aperture of 14.8×51.2 mm, and a pitch of 0.8 mm) with an elevational focal length of 50 mm was driven by the Verasonics V-1 ultrasound system with extended burst option. The attainable focal pressures and electronic steering range in linear and nonlinear operating regimes (relevant to pHIFU treatments) were characterized through hydrophone measurements, acoustic holography, and numerical simulations. The steering range at ±10% from the nominal focal pressure was found to be ±6 mm axially and ±11 mm azimuthally. Focal waveforms with shock fronts of up to 45 MPa and peak negative pressures up to 9 MPa were achieved at focusing distances of 38-75 mm from the array. Cavitation behaviors induced by isolated 1-ms pHIFU pulses in optically transparent agarose gel phantoms were observed by high-speed photography across a range of excitation amplitudes and focal distances. For all focusing configurations, the appearance of sparse, stationary cavitation bubbles occurred at the same P- threshold of 2 MPa. As the output level increased, a qualitative change in cavitation behavior occurred, to pairs and sets of proliferating bubbles. The pressure P- at which this transition was observed corresponded to substantial nonlinear distortion and shock formation in the focal region and was thus dependent on the focal distance of the beam ranging within 3-4 MPa for azimuthal F -numbers of 0.74-1.5. The array was capable of B-mode imaging at 1.5 MHz of centimeter-sized targets in phantoms and in vivo pig tissues at depths of 3-7 cm, relevant to pHIFU applications in abdominal targets.

Delivery of CRISPR-Cas12a Ribonucleoprotein Complex for Genome Editing in an Embryogenic Citrus Cell Line.

Clustered regularly interspaced short palindromic repeats (CRISPR) technology is a powerful genome editing tool. Recently developed CRISPR-Cas12a system confers several advantages over CRISPR-Cas9, making it ideal for use in plant genome editing and crop improvement. While traditional transformation methods based on plasmid delivery pose concerns associated with transgene integration and off-target effects, CRISPR-Cas12a delivered as ribonucleoproteins (RNPs) can effectively alleviate these potential issues. Here we present a detailed protocol for LbCas12a-mediated genome editing using RNP delivery in Citrus protoplasts. This protocol provides a comprehensive guideline for RNP component preparation, RNP complex assembly and delivery, and editing efficiency assessment.

Safety, pharmacokinetics and CNS distribution of tralesinidase alfa administered via intracerebroventricular infusion to juvenile cynomolgus monkeys.

Mucopolysaccharidosis Type IIIB (MPS IIIB) is an ultrarare, fatal pediatric disease with no approved therapy. It is caused by mutations in the gene encoding for lysosomal enzyme alpha-N-acetylglucosaminidase (NAGLU). Tralesinidase alfa (TA) is a fusion protein comprised of recombinant NAGLU and a modified human insulin-like growth factor 2 that is being developed as an enzyme replacement therapy for MPS IIIB. Since MPS IIIB is a pediatric disease the safety/toxicity, pharmacokinetics and biodistribution of TA were evaluated in juvenile non-human primates that were administered up to 5 weekly intracerebroventricular (ICV) or single intravenous (IV) infusions of TA. TA administered by ICV slow-, ICV isovolumetric bolus- or IV-infusion was well-tolerated, and no effects were observed on clinical observations, electrocardiographic or ophthalmologic parameters, or respiratory rates. The drug-related changes observed were limited to increased cell infiltrates in the CSF and along the ICV catheter track after ICV administration. These findings were not associated with functional changes and are associated with the use of ICV catheters. The CSF PK profiles were consistent across all conditions tested and TA distributed widely in the CNS after ICV administration. Anti-drug antibodies were observed but did not appear to significantly affect the exposure to TA. Correlations between TA concentrations in plasma and brain regions in direct contact with the cisterna magna suggest glymphatic drainage may be responsible for clearance of TA from the CNS. The data support the administration of TA by isovolumetric bolus ICV infusion to pediatric patients with MPS IIIB.

Management of Recurrent Well-Differentiated Thyroid Carcinoma in the Neck: A Comprehensive Review.

Surgery has been historically the preferred primary treatment for patients with well-differentiated thyroid carcinoma and for selected locoregional recurrences. Adjuvant therapy with radioactive iodine is typically recommended for patients with an intermediate to high risk of recurrence. Despite these treatments, locally advanced disease and locoregional relapses are not infrequent. These patients have a prolonged overall survival that may result in long periods of active disease and the possibility of requiring subsequent treatments. Recently, many new options have emerged as salvage therapies. This review offers a comprehensive discussion and considerations regarding surgery, active surveillance, radioactive iodine therapy, ultrasonography-guided percutaneous ablation, external beam radiotherapy, and systemic therapy for well-differentiated thyroid cancer based on relevant publications and current reference guidelines. We feel that the surgical member of the thyroid cancer management team is empowered by being aware and facile with all management options.

Amylase as a Diagnostic Tool for Plunging Ranula: Clinical Series and Description of the Technique.

OBJECTIVES: This study describes a technique of measurement for neck cyst amylase content and reviews the experience of a tertiary referral center for cases of suspected plunging ranula. METHODS: A retrospective study was performed at the Manukau Surgical Center in Auckland, New Zealand. Patients with a possible diagnosis of plunging ranula based on clinical presentation and diagnostic aspiration of the cyst contents were included. Demographic data, imaging and laboratory findings were collected, along with findings from surgery and histology. The technique for measuring the amylase of the aspirated cyst contents was also carefully recorded. RESULTS: The 37 cases of confirmed plunging ranula included in this study had a submandibular cystic swelling that was aspirated. Imaging features consistent with a plunging ranula were seen in 89% of the study group. All cases had detectable levels of amylase of ≥3 U/L in the ranula contents. There was large variability (range: 5-560 U/L) in the concentration of amylase, with 70% of the cases demonstrating an amylase concentration below 200 U/L. Aspirates were typically described as viscous (87.5%) and yellow or straw-colored. CONCLUSION: The combination of clinical presentation, imaging and the presence of amylase in the cyst contents is diagnostic for plunging ranula. LEVEL OF EVIDENCE: 4 Laryngoscope, 133:535-538, 2023.

Medullary thyroid cancer with RET V804M mutation: more indolent than expected?

BACKGROUND: Significant genotype-phenotype variability among multiple endocrine neoplasia type 2A patients with a RET V804M mutation has been reported. METHODS: Patients with a RET V804M mutation treated at a single center were identified (January 1996-December 2020). The baseline characteristics, operative details, pathology, biochemical, and long-term data were analyzed. RESULTS: There were 79 patients; none developed pheochromocytoma or hyperparathyroidism or died in the study period. The mean age was 41.5 years (range = 1.0-81.0 years); 46.8% were men. Of 68 surgical patients, 53 (77.9%) underwent total thyroidectomy and 15 (22.1%) underwent total thyroidectomy with central neck dissection with or without lateral neck dissection. Twenty-four patients had elevated preoperative calcitonin, of whom 12 underwent total thyroidectomy (median = 7.5; range = 5.0-237.0 pg/mL), 10 underwent total thyroidectomy + central neck dissection (median = 27.6; range = 5.1-147.0 pg/mL), and 2 underwent total thyroidectomy + central neck dissection + lateral neck dissection (median = 3182.0; range = 361.0-6003.0 pg/mL). Pathology was benign (27.9%), papillary thyroid cancer alone (1.5%), C-cell hyperplasia (23.5%), and medullary thyroid cancer (47.1%; median tumor size = 3.0 mm). Three patients had elevated calcitonin postoperatively (median follow-up time = 60.0 months). In adjusted modeling, a preoperative calcitonin >5 pg/mL was associated with having medullary thyroid cancer on final pathology (odds ratio = 13.3; 95% confidence interval, 3.2-56.3; P < .001). CONCLUSION: In this large United States cohort of surgical patients with a RET V804M mutation, most had indolent disease and were without classic multiple endocrine neoplasia type 2A features. Calcitonin >5 pg/mL may serve as a meaningful value to guide surveillance and timing of surgery.

Salvage Cryoablation for Local Recurrences of Thyroid Cancer Inseparable from the Trachea and Neurovascular Structures.

PURPOSE: To demonstrate safety, feasibility, and effectiveness of cryoablation of recurrent papillary thyroid cancer ineligible for reoperation because of scarring, eligible for focal ablation as defined within 2015 American Thyroid Association guideline sections C16 and C17. MATERIALS AND METHODS: With multidisciplinary consensus, cryoablation was performed with curative intent for 15 tumors in 10 patients between January 2019 and July 2021. Demographics, procedural details, and serial postprocedural imaging findings were analyzed. RESULTS: The mean age was 72.5 years (range, 57-88 years), and 80% of the patients were women. The tumors (mean size, 16 mm ± 6; range, 9-29 mm) received 1 session of cryoablation with 100% technical success. The mean and median postcryoablation tumor volumetric involution rates were 88% and 99%, respectively, with 9 (60%) of 15 tumors involuting completely or down to the scar and 6 (40%) involuting partially at the end of the study period. Tumor size did not increase after cryoablation (0% local progression rate). All tumors abutted the trachea, skin, and/or vascular structures, and hydrodissection failed in all cases because of scarring. The major adverse event rate was 20% (3/15), with 2 cases of voice change and 1 case of Horner syndrome; all resolved at 6 months with no permanent sequelae. No vascular, tracheal, dermal, or infectious adverse events occurred during a mean follow-up of 242 days (range, 114-627 days). One patient died at 386 days after cryoablation because of unrelated cholangiocarcinoma. CONCLUSIONS: Cryoablation of local recurrences of papillary thyroid cancer abutting the trachea and/or neurovascular structures in the setting of hydrodissection failure because of scarring yielded a mean volumetric involution of 88%, primary efficacy of 60%, and objective response rate of 100% with no local recurrences or permanent complications during a mean follow-up of 242 days. The secondary efficacy and longer-term outcomes remain forthcoming.

Guideline Adherence and Practice Patterns in the Management of Medullary Thyroid Cancer.

INTRODUCTION: Little is known about nationwide practice patterns for the management medullary thyroid cancer (MTC) in relation to the 2015 American Thyroid Association guidelines and their impact on survival. METHODS: Using the Surveillance, Epidemiology, and End Results Program database (2000-2018), MTC treatment patterns were evaluated in terms of adherence to the 2015 American Thyroid Association guidelines across three time periods (2000-2009, 2010-2015, and 2016-2018). Outcomes of interest were guideline concordance, treatment utilization trends, disease-specific survival (DSS), and overall survival (OS). RESULTS: A total of 3332 patients with MTC were identified. Of which, 53.8%, 33.2%, and 11.4% of patients had localized, regional, and distant disease, respectively. In patients with locoregional disease, the rate of guideline-concordant surgery improved over time from 63.0% in 2000-2009 to 76.0% in 2016-2018 (P < 0.001). Guideline-concordant care was associated with increased OS (HR = 1.85, 95% CI: 1.42-2.43, P < 0.001) in patients with localized disease and increased DSS (HR = 1.65, 95% CI: 1.01-2.54, P < 0.001) and OS (HR = 1.89, 95% CI: 1.35-2.58, P < 0.001) in patients with regional disease. The median OS and DSS in patients with distant disease were 31 and 55 mo, respectively, and the rate of chemotherapy use rose from 21.6% to 39.2% (P = 0.003). CONCLUSIONS: The rate of guideline-concordant surgery for locoregional MTC increased after guideline publication in 2015, with an observed prolongment in OS and DSS. Chemotherapy use among patients with distant disease has increased over time, but their prognosis remains variable.