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.

Analysis of Polyethylene-Related Revisions After Total Ankle Replacements Reported in US Food and Drug Administration Medical Device Adverse Event Database.

BACKGROUND: There are 2 general types of total ankle replacement (TAR) designs with respect to the polyethylene insert, mobile-bearing (MB) and fixed-bearing (FB) TARs. The aim of this study is to compare polyethylene-related adverse events (AEs), particularly revisions, reported for MB TARs and FB TARs using the US Food and Drug Administration's (FDA's) Manufacturer and User Facility Device Experience (MAUDE) database. METHODS: A text mining method was applied to the medical device reporting (MDR) in the MAUDE database from 1991 to 2020, followed by manual reviews to identify, characterize, and describe all polyethylene-related AEs, including revisions, reported for MB and FB TARs. RESULTS: We found 1841 MDRs for MB (STAR Ankle only) and 1273 MDRs for 40+ FB TARs approved/cleared by the FDA. For the MB design, 33% (606/1841) of the AEs reported related to the polyethylene component, compared to 24% (291/1273) of the AEs reported for FB designs. Polyethylene fractures were reported in 11.3% (208/1841) for the MB designs compared to 0.2% (2/1273) for the FB designs. Half of the polyethylene-related revisions occurred within an average of 4.1 years after implantation for the MB design compared within an average of 5.2 years for FB designs. CONCLUSION: Analysis of this database revealed a higher proportion of reported polyethylene fractures and greater need for earlier revisions for polyethylene-related issues with use of the primary MB design in the database as compared with FB TAR designs. Further study of device-related complications with more recent designs for both MB and FB ankle replacement components are needed to improve the outcomes of total ankle replacement. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

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.

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.

Platelet adhesion to dengue-2 virus-infected endothelial cells.

Platelets in circulation normally do not adhere to resting endothelial cells. However, in response to vascular injury they adhere to stimulated endothelium and thereby play an essential role in hemostasis and thrombosis. Infection with dengue-2 virus can cause illness accompanied by thrombocytopenia and hemorrhage. Increased adherence of platelets to stimulated endothelial cells could contribute to the thrombocytopenia. In this study, adherence of radioisotopically labeled platelets to 1) unstimulated, 2) lipopolysaccharide (LPS)-stimulated, and 3) dengue-2 virus-infected human umbilical vein endothelial cells (HUVEC) was measured in an in vitro assay. Primary HUVEC were cultured in 96-well tissue culture plates in the presence or absence of LPS or dengue-2 virus. These cells were co-incubated with 3H-adenine-labeled fresh platelets for 30 min after which the cells were assayed for adherent platelets. Within 30 min there was maximum adherence of platelets to confluent LPS-stimulated HUVEC (36 +/- 4% over controls; P = 0.005). In comparison, there was a significant increase in adherence to dengue-2 infected HUVEC (78 +/- 7%; P < or = 0.001). Additionally, platelet adherence was visualized using fluorescent microscopy. Dengue-2 infection stimulated the HUVEC as monitored by expression of E-selectin. Platelets that adhered to dengue-2 or LPS-stimulated HUVEC were activated as visualized by dual fluorescent probes. These data demonstrate that human platelets adhere to dengue-2 virus-stimulated HUVEC and this interaction could contribute to the thrombocytopenia observed during infection.