Compliance With Federal Price Transparency Rules and Cost Estimation at United States Hospitals With Neurosurgical Training Programs.

BACKGROUND AND OBJECTIVES: The Centers for Medicare & Medicaid Services implemented federal requirements on January 1, 2021, under the Public Health Service Act that require hospitals to provide a list of payer-negotiated prices or "standard charges" in a machine-readable file and in a patient-friendly online estimator for standard services. We sought to assess compliance by United States hospitals associated with neurosurgical training programs with these federal requirements for 11 common neurosurgical procedures. METHODS: We performed a cross-sectional analysis in March 2023 of 116 United States hospitals associated with a neurosurgical training program to assess compliance with the new federal requirements to have a machine-readable, downloadable file with standard charges and a patient-friendly online estimator for two spinal procedures. RESULTS: A total of 110/114 (96.5%) hospitals were compliant with the requirement for a machine-readable file with payer-negotiated prices. A total of 47/110 hospitals (42.7%) were compliant with downloadable machine-readable files and reported at least one payer-negotiated price for 1 of the 11 common neurosurgical procedures. A total of 45/110 (40.9%) used bundled Diagnosis-Related Group codes, and 18/110 (16.4%) did not contain any price information for neurosurgical procedures. For neurosurgical procedures, the percent difference between the average negotiated private insurance and Medicare price per procedure ranged from 17.5% to 77.6%. Medicare and private insurance data for each procedure were available on average for 10.3 states (SD = 3.8) and 15.6 states (SD = 4.8), respectively. CONCLUSION: While hospital compliance with federal requirements for machine-readable files with payer-negotiated prices was high, availability of payer-negotiated prices for 4 major insurance types across 11 common neurosurgical procedures based on Current Procedural Terminology codes was sparce. Consequently, meaningful conclusions on procedure-related charges for elective procedures are difficult for patients to make because of the unintelligible format of data and a lack of reporting of charges per Current Procedural Terminology code in a comprehensive manner.

The NOMS approach to metastatic tumors: Integrating new technologies to improve outcomes. / El enfoque de NOMS para los tumores metastásicos: integración de nuevas tecnologías para mejorar los resultados.

Treatment paradigms for patients with spine metastases have evolved significantly over the past two decades. The most transformative change to these paradigms has been the integration of spinal stereotactic radiosurgery (sSRS). sSRS allows for the delivery of tumoricidal radiation doses with sparing of nearby organs at risk, particularly the spinal cord. Evidence supports the safety and efficacy of radiosurgery as it currently offers durable local tumor control with low complication rates even for tumors previously considered radioresistant to conventional external beam radiation therapy. The role for surgical intervention remains consistent, but a trend has been observed toward less aggressive, often minimally invasive techniques. Using modern technologies and improved instrumentation, surgical outcomes continue to improve with reduced morbidity. Additionally, targeted agents such as biologics and checkpoint inhibitors have revolutionized cancer care by improving both local control and patient survival. These advances have brought forth a need for new prognostication tools and a more critical review of long-term outcomes. The complex nature of current treatment schemes necessitates a multidisciplinary approach including surgeons, medical oncologists, radiation oncologists, interventionalists and pain specialists. This review recapitulates the current state-of-the-art, evidence-based data on the treatment of spinal metastases and integrates these data into a decision framework, NOMS, which is based on four sentinel pillars of decision making in metastatic spine tumors: neurological status, Oocologic tumor behavior, mechanical stability and systemic disease burden and medical co-morbidities.

The NOMS approach to metastatic tumors: Integrating new technologies to improve outcomes.

Treatment paradigms for patients with spine metastases have evolved significantly over the past two decades. The most transformative change to these paradigms has been the integration of spinal stereotactic radiosurgery (sSRS). sSRS allows for the delivery of tumoricidal radiation doses with sparing of nearby organs at risk, particularly the spinal cord. Evidence supports the safety and efficacy of radiosurgery as it currently offers durable local tumor control with low complication rates even for tumors previously considered radioresistant to conventional external beam radiation therapy. The role for surgical intervention remains consistent, but a trend has been observed toward less aggressive, often minimally invasive techniques. Using modern technologies and improved instrumentation, surgical outcomes continue to improve with reduced morbidity. Additionally, targeted agents such as biologics and checkpoint inhibitors have revolutionized cancer care by improving both local control and patient survival. These advances have brought forth a need for new prognostication tools and a more critical review of long-term outcomes. The complex nature of current treatment schemes necessitates a multidisciplinary approach including surgeons, medical oncologists, radiation oncologists, interventionalists and pain specialists. This review recapitulates the current state-of-the-art, evidence-based data on the treatment of spinal metastases and integrates these data into a decision framework, NOMS, which is based on four sentinel pillars of decision making in metastatic spine tumors: Neurological status, Oncologic tumor behavior, Mechanical stability, and Systemic disease burden and medical co-morbidities.

Fifty-year history of the evolution of spinal metastatic disease management.

Spine metastases are a significant source of morbidity in oncology. Treatment of these spine metastases largely remains palliative, but advances over the past 50 years have improved the effectiveness of interventions for preserving functional status and obtaining local control while minimizing morbidity. While the field began with conventional external beam radiation as the primary treatment modality, a series of paradigm shifts and technological advances in the 2000s led to a change in treatment patterns. These advances allowed for an increased role of surgical decompression of neural elements, a shift in the stereotactic capabilities of radiation oncologists, and an improved understanding of the radiobiology of metastatic disease. The result was improved local control while minimizing treatment morbidity. These advances fit within the larger framework of metastatic spine tumor management known as the Neurologic, Oncologic, Mechanical, and Systemic disease decision framework. This dynamic framework takes into account the neurological function of the patient, the radiobiology of their tumor, their degree of mechanical instability, and their systemic disease control and treatment options to help determine appropriate interventions based on the individual patient. Herein, we describe the 50-year evolution of metastatic spine tumor management and the impact of various advances on the field.

A blockchain-based framework to support pharmacogenetic data sharing.

The successful implementation of pharmacogenetics (PGx) into clinical practice requires patient genomic data to be shared between stakeholders in multiple settings. This creates a number of barriers to widespread adoption of PGx, including privacy concerns related to the storage and movement of identifiable genomic data. Informatic solutions that support secure and equitable data access for genomic data are therefore important to PGx. Here we propose a methodology that uses smart contracts implemented on a blockchain-based framework, PGxChain, to address this issue. The design requirements for PGxChain were identified through a systematic literature review, identifying technical challenges and barriers impeding the clinical implementation of pharmacogenomics. These requirements included security and privacy, accessibility, interoperability, traceability and legal compliance. A proof-of-concept implementation based on Ethereum was then developed that met the design requirements. PGxChain's performance was examined using Hyperledger Caliper for latency, throughput, and transaction success rate. The findings clearly indicate that blockchain technology offers considerable potential to advance pharmacogenetic data sharing, particularly with regard to PGx data security and privacy, large-scale accessibility of PGx data, PGx data interoperability between multiple health care providers and compliance with data-sharing laws and regulations.

The transformation of a gold standard in-person substance use assessment to a web-based, REDCap integrated data capture tool.

The adoption of computer systems for gathering, managing, and analyzing health data is resulting in the replacement of pen-and-paper methods for collecting data and managing health records by computerized methods. One classic "pen-and-paper" assessment in health and substance use research is the Timeline Follow-Back (TLFB), the gold standard in self-reported substance use developed in 1996 by Sobell et al. to assess alcohol consumption patterns and later other substances such as marijuana or tobacco over discreet timeframes [1-7]. The TLFB has been modified by some research groups for use as a web-based assessment [8-10], but not without significant limitations. As such, this paper describes the team-oriented, interdisciplinary process by which a new online TLFB (O-TLFB) was conceptualized, the technical details of development towards a dynamic data capture tool fully integrated with REDCap via application programming interface (API), and the potential for this optimized O-TLFB to be leveraged broadly across the domains of substance use, health, and behavioral research.

Stereotactic-Guided Dilatable Endoscopic Port Surgery for Deep-Seated Brain Tumors: Technical Report with Comparative Case Series Analysis.

OBJECTIVE: Deep-seated brain tumors are often best treated by primary surgical excision. Traditional microsurgical techniques can cause retraction injury and require extensive brain dissection. To mitigate this risk, stereotactic-guided tubular retractors were developed; however, the risk of shear injury remains. We created a stereotactic-guided dilatable port system to create a corridor for deep brain tumor surgery along the trajectory of a brain needle to minimize iatrogenic brain injury. METHODS: Of the 8 included patients (6 colloid cysts, 1 metastasis, 1 intraventricular meningioma), 5 had undergone frameless and 3 frame-based stereotactic targeting. We used a tans-sulcal trajectory and a 2.6-mm stereotactic needle. At the target depth, the cannula was removed and the balloon inflated to 14 mm. The balloon was deflated and removed before placing the port. Pre- and 3-month postoperative magnetic resonance imaging scans were used to measure the T2-weighted signal change and residual cannulation defect. These patients were compared with a case-matched standard endoscopic port surgery cohort. RESULTS: All patients had undergone total lesional resection without new neurologic deficits. Patients undergoing dilatable endoscopic port surgery (DEPS) had significantly smaller residual cannulation defects (P < 0.05) but no significant differences in postoperative T2-weighted signal changes or diffusion restriction volumes at 3 months postoperatively (P > 0.05). CONCLUSIONS: DEPS might be a safe alternative to standard endoscopic port surgery or microsurgery for deep-seated brain tumors. The degree of iatrogenic injury using DEPS, as determined by magnetic resonance imaging analysis, might be equivalent to or less than that with standard port surgery techniques, although larger sample sizes are needed for validation.

Expanding the genotypic spectrum of Perrault syndrome.

Perrault syndrome is a rare autosomal recessive disorder characterized by sensorineural hearing loss (SNHL) in both sexes and primary ovarian insufficiency in 46, XX karyotype females. Biallelic variants in five genes are reported to be causative: HSD17B4, HARS2, LARS2, CLPP and C10orf2. Here we present eight families affected by Perrault syndrome. In five families we identified novel or previously reported variants in HSD17B4, LARS2, CLPP and C10orf2. The proband from each family was whole exome sequenced and variants confirmed by Sanger sequencing. A female was compound heterozygous for a known, p.(Gly16Ser) and novel, p.(Val82Phe) variant in D-bifunctional protein (HSD17B4). A family was homozygous for mitochondrial leucyl aminocyl tRNA synthetase (mtLeuRS) (LARS2) p.(Thr522Asn), previously associated with Perrault syndrome. A further family was compound heterozygous for mtLeuRS, p.(Thr522Asn) and a novel variant, p.(Met117Ile). Affected individuals with LARS2 variants had low frequency SNHL, a feature previously described in Perrault syndrome. A female with significant neurological disability was compound heterozygous for p.(Arg323Gln) and p.(Asn399Ser) variants in Twinkle (C10orf2). A male was homozygous for a novel variant in CLPP, p.(Cys144Arg). In three families there were no putative pathogenic variants in these genes confirming additional disease-causing genes remain unidentified. We have expanded the spectrum of disease-causing variants associated with Perrault syndrome.

Genetics of mitochondrial dysfunction and infertility.

Increasingly, mitochondria are being recognized as having an important role in fertility. Indeed in assisted reproductive technologies mitochondrial function is a key indicator of sperm and oocyte quality. Here, we review the literature regarding mitochondrial genetics and infertility. In many multisystem disorders caused by mitochondrial dysfunction death occurs prior to sexual maturity, or the clinical features are so severe that infertility may be underreported. Interestingly, many of the genes linked to mitochondrial dysfunction and infertility have roles in the maintenance of mitochondrial DNA or in mitochondrial translation. Studies on populations with genetically uncharacterized infertility have highlighted an association with mitochondrial DNA deletions, whether this is causative or indicative of poor functioning mitochondria requires further examination. Studies on the impact of mitochondrial DNA variants present conflicting data but highlight POLG as a particularly interesting candidate gene for both male and female infertility.

Mutations of SGO2 and CLDN14 collectively cause coincidental Perrault syndrome.

Perrault syndrome (PS) is a genetically heterogeneous disorder characterized by primary ovarian insufficiency (POI) in females and sensorineural hearing loss in males and females. In many PS subjects, causative variants have not been found in the five reported PS genes. The objective of this study was to identify the genetic cause of PS in an extended consanguineous family with six deaf individuals. Whole exome sequencing (WES) was completed on four affected members of a large family, and variants and co-segregation was confirmed by Sanger sequencing. All hearing impaired individuals, including the proband, are homozygous for a pathogenic variant of CLDN14, but this only explains the deafness. The PS proband is also homozygous for a frameshift variant (c.1453_1454delGA, p.(Glu485Lysfs*5)) in exon 7 of SGO2 encoding shugoshin 2, which is the likely cause of her concurrent ovarian insufficiency. In mouse, Sgol2a encoding shugoshin-like 2a is necessary during meiosis in both sexes to maintain the integrity of the cohesin complex that tethers sister chromatids. Human SGO2 has not previously been implicated in any disorder, but in this case of POI and perhaps others, it is a candidate for unexplained infertility.

Comprehensive RNA Analysis of the NF1 Gene in Classically Affected NF1 Affected Individuals Meeting NIH Criteria has High Sensitivity and Mutation Negative Testing is Reassuring in Isolated Cases With Pigmentary Features Only.

BACKGROUND: The detection rate for identifying the underlying mutation in neurocutaneous syndromes is affected by the sensitivity of the mutation test and the heterogeneity of the disease based on the diagnostic criteria. Neurofibromatosis type (NF1) has been defined for 29years by the National Institutes for Health (NIH) criteria which include ≥6 Café au Lait macules (CAL) as a defining criterion. The discovery of SPRED1 as a cause of Legius syndrome which is manifested by CAL, freckling and learning difficulties has introduced substantial heterogeneity to the NIH criteria. METHODS: We have defined the sensitivity of comprehensive RNA analysis on blood of presumed NF1 patients meeting NIH criteria with at least one nonpigmentary criterion and determined the proportion of children with ≥6 CAL and no family history that has an NF1 or SPRED1 genetic variant. RNA analysis was carried out from 04/2009-12/2015 on 361 NF1 patients. FINDINGS: A presumed causative NF1 mutation was found in 166/171 (97.08%-95% CI 94.56-99.6%) of familial cases and 182/190 (95.8%-95% CI 92.93-98.65%) sporadic de novo cases. Two of thirteen (15%) mutation negative individuals had dysembryoplastic neuroepithelial tumour (DNET) compared to 2/348 (0.6%) with an NF1 variant (p=0.007). No SPRED1 variants were found in the thirteen individuals with no NF1 variant. Of seventy-one individuals with ≥6 CAL and no non-pigmentary criterion aged 0-20years, 47 (66.2%) had an NF1 variant six (8.5%) a SPRED1 variant and 18 (25.3%) no disease causing variant. Using the 95.8% detection rate the likelihood of a child with ≥6 CAL having constitutional NF1 drops from 2/3 to 1/9 after negative RNA analysis. INTERPRETATION: RNA analysis in individuals with presumed NF1 has high sensitivity and includes a small subset with DNET without an NF1 variant. Furthermore negative analysis for NF1/SPRED1 provides strong reassurance to children with ≥6 CAL that they are unlikely to have NF1.