Non-Fusion Versus Fusion Surgery in Pediatric Idiopathic Scoliosis: What Trade-Offs in Outcomes Are Acceptable for the Patient and Family?

BACKGROUND: Vertebral body tethering and other non-fusion techniques for the treatment of pediatric idiopathic scoliosis are increasing in popularity. There is limited physician consensus on this topic as the result of a paucity of published data regarding which patients most benefit from non-fusion strategies. Thus, much of the decision-making is left to patients and parents, who must select a treatment based on their goals and values and the information available from health-care providers, the internet, and social media. We sought to understand patient and family preferences regarding the attributes of fusion versus non-fusion surgery that drive these choices. METHODS: Patients and families were recruited from 7 pediatric spine centers and were asked to complete a survey-based choice experiment that had been jointly developed with the U.S. Food and Drug Administration (FDA) to evaluate patient preferences. Choices between experimentally designed alternatives were analyzed to estimate the relative importance of outcomes and requirements associated with the choice options (attributes). The attributes included appearance, confidence in the planned correction, spinal motion, device failure, reoperation, and recovery period. The inclusion criteria were (1) an age of 10 to 21 years and (2) a diagnosis of adolescent idiopathic scoliosis in patients who were considering, or who had already undergone, treatment with fusion or non-fusion surgery. Preference weights were estimated from the expected changes in choice given changes in the attributes. RESULTS: A total of 344 respondents (124 patients, 92 parents, and 128 parent/patient dyads) completed the survey. One hundred and seventy-three patients were enrolled prior to surgery, and 171 were enrolled after surgery. Appearance and motion were found to be the most important drivers of choice. For the entire cohort, fusion was preferred over non-fusion. For patients who were considering surgery, the most important attributes were preservation of spinal motion and appearance. CONCLUSIONS: Patients and families seeking treatment for idiopathic scoliosis value appearance and preservation of spinal motion and, to a lesser extent, reoperation rates when considering fusion versus non-fusion surgery.

Evidence-based objective performance criteria for the evaluation of hip and knee replacement devices and technologies.

BACKGROUND: Objective performance criteria (OPC) is a novel method to provide minimum performance standards and improve the regulated introduction of original or incremental device innovations in order to prevent patients from being exposed to potentially inferior designs whilst allowing timely access to improvements. We developed 2-year safety and effectiveness OPC for total hip and knee replacement (THR and TKR). METHODS: Analyses of large databases were conducted using various data sources: a systematic literature review; a direct data analysis from The Functional Outcomes Research for Comparative Effectiveness in Total Joint Replacement and Quality Improvement Registry (FORCE-TJR) and the Kaiser Permanente Implant Registry (KPIR); and claims data analyses from longitudinal discharge data in New York and California states. The literature review included U.S. patients (≥18 years) who received THR or TKR for primary end-stage osteoarthritis and prospectively collected data on patient-reported outcome measures (PROMs) from at least 100 subjects and/or 2-year implant survival for at least 250 implants. Random effects models were used for meta-analysis. RESULTS: Data were available from a total of 951 100 patients. After screening of 7979 abstracts, 294 studies underwent full-text review and 31 studies contributed to the evidence synthesis (333 995 implants). Direct data analysis of FORCE-TJR contributed 9223 joint replacement patients to the construction of OPC for effectiveness; KPIR contributed 262 044 patients for the construction of OPC for safety. Claims database analysis contributed 345 838 patients to the construction of safety OPC. OPC for safety were constructed for cumulative incidences of 2-year all-cause and septic revision (THR/TKR 2.0%/1.6% and 0.6%/0.7%), and OPC for effectiveness were constructed based on four disease-specific and three general health-related quality of life PROMs (HOOS/KOOS 87.1/80.6; HSS/KSS function 94.4/90.6; SF-12/SF-36, PCS 46.5/41.9, EQ-5D 0.88/0.84). CONCLUSION: This study is the first to construct a 2-year OPC for the safety and effectiveness of THR and TKR based on U.S. real-world data. Based on these OPC, potential benchmarks for (single-arm study) evaluation of new device innovations are suggested for a regulated and safe introduction to the (commercial) market.

Advancing the Real-World Evidence for Medical Devices through Coordinated Registry Networks.

Objectives: Generating and using real-world evidence (RWE) is a pragmatic solution for evaluating health technologies. RWE is recognized by regulators, health technology assessors, clinicians, and manufacturers as a valid source of information to support their decision-making. Well-designed registries can provide RWE and become more powerful when linked with electronic health records and administrative databases in coordinated registry networks (CRNs). Our objective was to create a framework of maturity of CRNs and registries, so guiding their development and the prioritization of funding. Design setting and participants: We invited 52 stakeholders from diverse backgrounds including patient advocacy groups, academic, clinical, industry and regulatory experts to participate on a Delphi survey. Of those invited, 42 participated in the survey to provide feedback on the maturity framework for CRNs and registries. An expert panel reviewed the responses to refine the framework until the target consensus of 80% was reached. Two rounds of the Delphi were distributed via Qualtrics online platform from July to August 2020 and from October to November 2020. Main outcome measures: Consensus on the maturity framework for CRNs and registries consisted of seven domains (unique device identification, efficient data collection, data quality, product life cycle approach, governance and sustainability, quality improvement, and patient-reported outcomes), each presented with five levels of maturity. Results: Of 52 invited experts, 41 (79.9%) responded to round 1; all 41 responded to round 2; and consensus was reached for most domains. The expert panel resolved the disagreements and final consensus estimates ranged from 80.5% to 92.7% for seven domains. Conclusions: We have developed a robust framework to assess the maturity of any CRN (or registry) to provide reliable RWE. This framework will promote harmonization of approaches to RWE generation across different disciplines and health systems. The domains and their levels may evolve over time as new solutions become available.

Two-Year Revision Rates in Total Ankle Replacement Versus Ankle Arthrodesis: A Population-Based Propensity-Score-Matched Comparison from New York State and California.

The aim of this study was to compare outcomes between total ankle replacement (TAR) and ankle arthrodesis (AA) for ankle osteoarthritis using real-world data. Methods: We used longitudinal claims data from New York State from October 2015 to December 2018, and from California from October 2015 to December 2017. The primary outcome was revision. Secondary outcomes were in-hospital complications and below-the-knee amputation. Propensity-score matching adjusted for differences in baseline characteristics. To determine predictors of the main outcome, each group was analyzed using multivariable Cox regressions. Results: There were 1,477 TAR procedures (50.2%) and 1,468 AA procedures (49.8%). Patients undergoing TAR were less likely to belong to a minority group and had fewer comorbidities compared with those undergoing AA. Crude analyses indicated that the TAR group had a lower risk of revision (5.4% versus 9.1%), in-hospital complications (<1% versus 1.8%), and below-the-knee amputation (<1% versus 4.9%) (p < 0.001 for all). However, in the propensity-score-matched analysis, the risk of revision was no longer significantly lower (TAR, 5.6% versus AA, 7.6%; p = 0.16). In the multivariable analyses, older age was predictive of a lower risk of revision after TAR (hazard ratio [HR], 0.96 [95% confidence interval (CI), 0.93 to 1.00]), but age was not predictive of revision after AA (HR, 0.99 [95% CI, 0.97 to 1.01]). Female patients were less likely to undergo revision after AA (HR, 0.61 [95% CI, 0.39 to 0.96]), but sex was not predictive of revision after TAR (HR, 0.90 [95% CI, 0.51 to 1.60]). Conclusions: The 2-year adjusted revision risk was 5.6% after TAR and 7.6% after AA. This difference did not reach significance. Older age was a predictor of lower revision risk after TAR. Men had a higher risk of revision than women after AA. The number of TAR procedures has now caught up with the number of AA procedures. Level of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence.

Summary of the FDA virtual public workshop on spinal device clinical review held on September 17, 2021.

The mission of Food and Drug Administration (FDA)'s Center for Devices and Radiological Health is to protect and promote public health. It assures that patients and providers have timely and continued access to safe, effective, and high-quality medical devices and safe radiation-emitting products by providing meaningful and timely information about the products we regulate and the decisions we make. On September 17, 2021, an FDA workshop was held to provide information to stakeholders, including members of the spine community, device manufacturers, regulatory affairs professionals, clinicians, patients, and the general public regarding FDA regulations, guidance and regulatory pathways related to spinal device clinical review. It was not intended to communicate any new policies, processes, or interpretations regarding medical device marketing authorizations. This workshop consisted of individual presentations, group discussions, question and answer sessions, and audience surveys. Information-sharing included discussions related to patient-reported outcomes, clinician-reported outcomes, observer-reported outcomes, and performance outcomes. Discussions involving external subject matter experts covered topics related to spinal device clinical studies including definition of a target population, enrollment criteria, strategies for inclusion of under-represented patient groups, reporting of adverse event and secondary surgical procedures, clinical study endpoints, and clinical outcome assessments. A meeting transcript and webcast workshop link are currently posted on the FDA website. Important related issues and challenges were discussed, and an exciting range of new ideas and concepts were shared which hold promise to advance regulatory science, patient care and future innovation related to spinal devices.

Navigating the Regulatory Pathway for Medical Devices-a Conversation with the FDA, Clinicians, Researchers, and Industry Experts.

Successful translation of new and innovative medical products from concept to clinical use is a complex endeavor that requires understanding and overcoming a variety of challenges. In particular, regulatory pathways and processes are often unfamiliar to academic researchers and start-ups, and even larger companies. Growing evidence suggests that the successful translation of ideas to products requires collaboration and cooperation between clinicians, researchers, industry, and regulators. A multi-stakeholder group developed this review to enhance regulatory knowledge and thereby improve translational success for medical devices. Communication between and among stakeholders is identified as a critical factor. Current regulatory programs and processes to facilitate communication and translation of innovative devices are described and discussed. Case studies are used to highlight the importance of flexibility when considering evidence requirements. We provide a review of emerging strategies, opportunities, and best practices to increase the regulatory knowledge base and facilitate medical device translation by all stakeholders. Clinicians, regulators, industry, and researchers require regulatory knowledge and collaboration for successful translation of innovative medical devices.

Association of Sex With Risk of 2-Year Revision Among Patients Undergoing Total Hip Arthroplasty.

Importance: The worldwide population is aging and includes more female individuals than male individuals, with higher rates of total hip arthroplasty (THA) among female individuals. Although research on this topic has been limited to date, several studies are currently under way. Objectives: To evaluate the association between sex and 2-year revision after THA. Design, Setting, and Participants: This cohort study used data from statewide databases in New York and California between October 1, 2015, and December 31, 2018. Patients 18 years or older with osteoarthritis who underwent THA and had sex recorded in the database were included in the analysis. Exposure: Total hip arthroplasty. Main Outcomes and Measures: The outcome of interest was the difference in early, all-cause revision surgery rates after primary THA between women and men. The association of sex with the revision rate was examined using Cox proportional hazards regression analysis. Results: Of 132 826 patients included in the study, 74 002 (55.7%) were women; the mean (SD) age was 65.9 (11.0) years, and the median follow-up time was 1.3 years (range, 0.0-3.0 years). The 2-year revision rate was 2.5% (95% CI, 2.4%-2.6%) among women and 2.1% (95% CI, 2.0%-2.2%) among men. After adjusting for demographic characteristics, comorbidities, and facility volume, a minimal clinically meaningful difference was observed in revision rates despite women having a higher risk of all-cause revision compared with men (hazard ratio, 1.16; 95% CI, 1.07-1.26; P < .001). The risk of revision was increased among women compared with men in the subgroup of patients who were younger than 55 years (hazard ratio, 1.47; 95% CI, 1.20-1.81; P < .001). Conclusions and Relevance: In this cohort study, no clinically meaningful difference in all-cause revision rates after primary THA was found between men and women at 2-year follow-up. The modest difference in the risk of revision between men and women in a small subgroup of patients younger than 55 years suggests that the risk of revision in this population should be studied further.

Regulation of orthopaedic devices: Future implications for research and innovation.

The conception-to-market development of orthopaedic devices occurs across the total product life cycle including device design and preclinical testing, clinical investigations to support marketing applications, and monitoring of device performance after market introduction. This process involves industry, regulatory agencies, health care providers, engineers, scientists, and patients. The Food and Drug Administration (FDA) is responsible for regulating medical devices in the United States, and uses a 3-tier classification system based on the level of control necessary to provide reasonable assurance of safety and effectiveness. Classification directs the required regulatory pathway and premarket submission type. Variations in global regulations, particularly between the United States, European Economic Area (EEA), and the United Kingdom (UK), may impact industry response to orthopaedic device development. Changing device innovation and reimbursement models have led to the consolidation of market share among larger companies. Although larger companies are better able to cope with more rigorous regulatory requirements, this leads to decreased competition and increased upward price pressure. To assist with the complex regulatory processes, the FDA offers pre-submission assistance as an opportunity for early collaboration and discussion about the medical device or device-led combination product submissions. Orthopaedic organizations, such as the Orthopaedic Trauma Association (OTA), may assist in postmarket device surveillance through the coordinated development and maintenance of clinical data registries. Such registries can longitudinally follow patients with a specific orthopaedic pathology or device usage, and monitor outcomes towards improvements in next-generation device development. As technology evolves, the nexus of regulation, industry, and patient outcome monitoring will continue to support safe and effective device innovation.

DOCK 8 Deficiency, EBV+ Lymphomatoid Granulomatosis, and Intrafamilial Variation in Presentation.

Dedicator of cytokinesis 8 (DOCK8) deficiency is an autosomal recessive, combined immunodeficiency within the spectrum of hyper-IgE syndromes. Epstein-Barr virus-positive lymphomatoid granulomatosis (LYG) (EBV + LYG) is a rare diagnosis and a previously unreported presentation of DOCK8 deficiency. A 10-year-old girl was initially evaluated for mild eczema and recurrent sinopulmonary infections. She had normal immunoglobulins with elevated IgE, poor polysaccharide response with low switched memory B cells, low CD4 count, and normal mitogen and antigen responses. Despite clinical improvement following immunoglobulin replacement, a prolonged cough prompted a CT scan, which showed nodules. Biopsy identified a Grade 2 EBV + LYG. Due to an inadequate response with chemotherapy, further workup for primary immunodeficiency was performed. With her symptoms of eczema and IgE elevation, along with her brother's history of recurrent sinopulmonary infections and warts, targeted sequencing of DOCK8 was performed revealing compound heterozygous mutations for the two siblings. Both patients were successfully transplanted with resolution of the LYG and warts, respectively. This is the first reported case of LYG in DOCK8 deficiency. The EBV-driven lymphoproliferative disease along with the infection history in the brother led to the diagnosis of DOCK8 deficiency and curative hematopoietic stem cell transplants.

Genome-wide association studies of cancer.

Knowledge of the inherited risk for cancer is an important component of preventive oncology. In addition to well-established syndromes of cancer predisposition, much remains to be discovered about the genetic variation underlying susceptibility to common malignancies. Increased knowledge about the human genome and advances in genotyping technology have made possible genome-wide association studies (GWAS) of human diseases. These studies have identified many important regions of genetic variation associated with an increased risk for human traits and diseases including cancer. Understanding the principles, major findings, and limitations of GWAS is becoming increasingly important for oncologists as dissemination of genomic risk tests directly to consumers is already occurring through commercial companies. GWAS have contributed to our understanding of the genetic basis of cancer and will shed light on biologic pathways and possible new strategies for targeted prevention. To date, however, the clinical utility of GWAS-derived risk markers remains limited.

Intraoperative neurophysiologic monitoring during spinal surgery.

Intraoperative neurophysiologic monitoring (IONM) is a battery of neurophysiologic tests used to assess the functional integrity of the spinal cord, nerve roots, and other peripheral nervous system structures (eg, brachial plexus) during spinal surgery. The underlying principle of IONM is to identify emerging insult to nervous system structures, pathways, and/or related vascular supply and to provide feedback regarding correlative changes in neural function before development of irreversible neural injury. IONM data provide an opportunity for intervention to prevent or minimize postoperative neurologic deficit. Current multimodality monitoring techniques permit intraoperative assessment of the functional integrity of afferent dorsal sensory spinal cord tracts, efferent ventral spinal cord motor tracts, and nerve roots. Combined use of these techniques is useful during complex spinal surgery because these monitoring modalities provide important complementary information to the surgery team.

Intraoperative neurophysiologic monitoring: focus on cervical myelopathy and related issues.

BACKGROUND CONTEXT: The use of neurophysiologic monitoring during surgical procedures for cervical spondylotic myelopathy (CSM) is controversial. PURPOSE: The aim of this article is to review the literature regarding various monitoring techniques as applied to the patient with CSM. STUDY DESIGN/METHODS: A systematic literature review. CONCLUSIONS: Neurophysiologic monitoring is a diagnostic tool for assessment of neurologic function during cervical spine surgery. Recording of somatosensory evoked potentials (SSEPs), transcranial electrical motor evoked potentials (tceMEPs), and electromyograms (EMGs) may be useful as these monitoring modalities provide complementary information.