Pediatric Device Innovation: An Analysis of Food and Drug Administration Authorizations Over Time.

BACKGROUND: Despite a tremendous increase in the number of orthopaedic devices authorized by the U.S. Food and Drug Administration (FDA), novel devices designed specifically for the pediatric population remain sparse. Surgeons frequently repurpose adult implants for "off-label" use in pediatric patients, with both legal and technical ramifications. This study seeks to objectively quantify and characterize the nature of pediatric device innovation over time. METHODS: The FDA employs 4 pathways for assessing safety and effectiveness of novel devices prior to authorization. Perceived device risk and novelty determine the pathway. Orthopaedic devices were identified from the FDA's online database. All devices approved since inception via the Humanitarian Device Exemption, Pre-Market Approval, and De Novo regulatory pathways were included and grouped as "highly innovative." Because of their number and the rapidity of their development, the evaluation of 510(k) devices was limited to those cleared from January 1, 2018, to December 31, 2022. Such 510(k) devices make up ∼97% of devices and by definition are less risky and less novel. Approval statements were assessed for pediatric indications within the approved labeling. As a secondary analysis, the impact of company size on developing a product with a pediatric indication was analyzed. RESULTS: Of the 1,925 devices cleared via the 510(k) pathway, 9 (0.5%) were designed exclusively for pediatrics and 160 (8.3%) included pediatric indications. Five of the 9 pediatrics-only devices were for spine and 4 were for trauma indications. Of the 97 highly innovative devices, only 2 (2%) were exclusively pediatric and another 2 (2%) included pediatric indications. The 2 pediatrics-only devices were for the spine. Large and medium-sized companies were 1.9 times and 1.6 times more likely to bring to market a device with pediatric indications than a small company, respectively. CONCLUSIONS: Innovation for pediatric orthopaedic devices lags substantially behind that for adult orthopaedic devices. These findings are consistent with clinical experience and the common practice of modifying adult implants for "off-label" use in pediatric patients. Despite long-standing efforts to stimulate innovation for this vulnerable population, our results suggest little progress.

Ten-year Risk of Recall of Novel Spine Devices.

STUDY DESIGN: Observational epidemiological study. OBJECTIVE: This study's primary objective was to examine the risk of recall for novel spine devices over time. Secondarily, we sought to analyze interbody fusion and vertebral body replacement (VBR) devices (corpectomy cages) as a risk factor for recall. SUMMARY OF BACKGROUND DATA: The recall risk of a novel spine device over time has not been reported. Additionally, FDA regulations were lowered for interbody fusion devices to enter the market in 2007. As well, VBR implants were recently approved by the FDA for use in the cervical spine in 2015. METHODS: Spine devices cleared between January 1, 2008 and December 31, 2018 were identified from the FDA's 510(k) database. All recall data was collected from the database in January of 2021 to provide a 2-year minimum follow-up for a recall to occur. Product labels were used to classify interbody fusion and VBR devices. Cumulative incidence function was conducted to compare the overall risk of recall for FDA cleared spine devices, and the hazard ratio determined for VBR and all other devices vs interbody implants during the study period. RESULTS: 2,384 spine devices were cleared via 510(k) in the study period. The hazard of recall at 5 years was 5.3% (95% CI: 4.4%-6.2%) and 6.5% (95% CI: 5.4-7.7%) at 10 years. No significant difference in recall risk was identified for interbody fusion and VBR devices. CONCLUSION: The risk of recall at 5 and 10 years of a novel spine device is about half the 12% rate reported for orthopedic devices in general. Despite lowered FDA regulations for interbody fusion devices and recent approval for VBR device use in the cervical spine, no increased risk of recall was detected. Further research is necessary to explain the reason for the lower risk of recall with spine devices. LEVEL OF EVIDENCE: V.

American Academy of Orthopaedic Surgeons Technology Overview Summary: Platelet-Rich Plasma (PRP) for Knee Osteoarthritis.

The Platelet-Rich Plasma (PRP) for Knee Osteoarthritis Technology Overview is based on a systematic review of current scientific and clinical research. Through analysis of the current best evidence, this technology overview seeks to evaluate the efficacy of PRP for patients with knee osteoarthritis. The systematic literature review resulted in 54 articles: 36 high-quality and 18 moderate-quality. The findings of these studies were summarized to present findings on PRP versus control/placebo, acetaminophen, non-steroidal anti-inflammatory drugs, corticosteroids, exercise, prolotherapy, autologous conditioned serum, bone marrow aspirate concentrate, hyaluronic acid, and ozone therapy. In addition, the work group highlighted areas that needed additional research when evidence proved lacking on the topic and carefully noted the potential harms associated with an intervention, required resource utilization, acceptability, and feasibility.

A Case Report of U-Type Sacral Fracture After Chiropractic Adjustment.

CASE: A U-type sacral fracture, or spinopelvic dissociation, resulting from chiropractic manipulation has not been described in the medical literature. This report presents the case of a 74-year-old male patient who sustained a U-type sacral fracture after drop-table chiropractic manipulation. CONCLUSION: Our case demonstrates that chiropractic manipulative therapy involving the commonly used drop-table can cause severe injury. The patient's course was complicated by a delay in diagnosis and a prolonged hospital stay. Orthopaedic surgeons should have a high degree of suspicion for spinopelvic dissociation in the setting of bilateral sacral fractures. One year after injury, with conservative management, the patient returned to baseline function with mild residual neuropathy.

Risk of Recall Associated With Modifications to High-risk Medical Devices Approved Through US Food and Drug Administration Supplements.

Importance: High-risk medical devices approved by the US Food and Drug Administration (FDA) can undergo modifications to their original premarket approval (PMA) via 1 of 5 types of supplements. Only panel track supplements (approximately 1%) require clinical data for approval. The association between device modifications and risk to patient safety has not previously been analyzed. Objective: To determine the association between PMA supplements and the risk of any device recall and high-risk (class 1) recall. Design, Setting, and Participants: In this cohort study, the FDA database was queried for original devices approved via PMA from January 1, 2008, through December 31, 2019. Supplement and recall data were obtained for these devices from January 1, 2008, through December 31, 2021, giving a minimum 2-year follow-up after initial approval. Data were analyzed from July 6 to August 6, 2022. Retrospective, time-to-event analysis investigated the association between the number and type of supplements and risk of recall. Exposures: Supplements submitted by manufacturers for FDA approval to modify devices. Main Outcomes and Measures: A mixed-effects Cox proportional hazards regression model with frailty terms was used, modeling device recall as an outcome variable during the observation period. A second model was performed for class 1 (high-risk) recall. Explanatory variables are the number of supplements, number of panel track supplements, and cardiovascular devices. Multivariable analysis was performed to identify independent risk factors for recall with hazard ratios (HRs) as the main end point. Results: A total of 373 original PMA devices with 10 776 associated supplements were included in the analysis. A median 2.5 (IQR, 1.2-5.0) supplements per device were approved annually. Cardiovascular devices contributed 138 supplements (37.0%), followed by microbiology with 45 (12.1%). No other specialty contributed more than 10%. Multivariable analysis demonstrated that each increase of 1 supplement per year was associated with increased risk of recall (HR, 1.28 [95% CI, 1.15-1.44]; P < .001). For class 1 recall, increased number of supplements (HR, 1.32 [95% CI, 1.06-1.64]; P = .01) and cardiovascular vsnoncardiovascular classification of devices (HR, 3.51 [95% CI, 1.15-10.72]; P = .03) were significantly associated with an increased risk of recall. Conclusions and Relevance: The findings of this cohort study suggest that PMA supplements are associated with an approximately 30% increased risk of any recall and class 1 recall. The FDA processes for approving modifications to high-risk medical devices should be reevaluated to optimize patient safety and public health.

Risk of Recall for Total Joint Arthroplasty Devices Over 10 Years.

BACKGROUND: Orthopaedic devices comprise nearly 20% of devices on the market and 12% to 20% of these devices undergo a recall within 10 years. More than 95% of these devices are approved without supporting clinical data through the Food and Drug Administration's 510(k) pathway. The risk of recall of orthopaedic arthroplasty devices approved through the 510(k) pathway has not been previously studied. METHODS: The FDA 510(k) database was queried for orthopaedic devices approved between January 01, 2008 and December 31, 2018 and subsequently codified to hip and knee arthroplasty devices using product codes. The database included 904 arthroplasty devices during the study period, with hip and knee making up 53.7% (485) and 46.3% (419) of devices, respectively. Information regarding numbers, dates, and reasons for recall were recorded. Cumulative incidence function was conducted to compare the risk of recall between hip and knee arthroplasty. RESULTS: In total, 94 (19.4%) hip and 85 (20.3%) knee devices were recalled. The hazard of recall by 10 years for hip and knee arthroplasty devices was approximately 24%, with no statistical differences between each region. The most common causes of recall were process control and device design, accounting for 29.6% and 26.3% of recalls, respectively, with no significant difference between study groups. CONCLUSION: The risk of recall for arthroplasty devices is more than that previously understood. Improved postmarket surveillance strategies along with increased physician participation in detecting and reporting device safety issues are necessary to strengthen patient safety.

Use of calcium phosphate cement after removal of a cephalomedullary nail: A case report.

Femoral neck fracture in the absence of trauma is a rare, but known complication after hardware removal. This complication may be due to the boney defect created by the hardware removal itself, or the increase in femoral neck strain that occurs after removal of the hardware. Previous biomechanical studies have suggested that filling the defect with calcium phosphate cement after removal of hardware may prevent the development of a femoral neck fracture. However, there are no reports on the use of calcium phosphate cement after removal of hardware in the clinical setting. The purpose of this case discussion is to present the first reported case, to our knowledge, of the use of calcium phosphate cement augmentation of the boney defect after lag screw removal, and the subsequent failure resulting in atraumatic femoral neck fracture.

The FDA and Ensuring Safety and Effectiveness of Devices, Biologics, and Technology.

Orthopaedic devices account for nearly 20% of all devices on the market, with more than 600 novel orthopaedic devices cleared or approved by the FDA for marketing in the United States annually. Advances in technology and biologic therapies offer tremendous potential for patients with musculoskeletal ailments; however, it is important that the safety and effectiveness of these products be assessed to safeguard the public health. The FDA uses multiple different premarket pathways for devices, biologics, and combination products based on perceived risk of the novel product. More than 97% of orthopaedic devices go through the FDA's 510(k) pathway, which does not require clinical trials. The remaining high-risk devices must receive premarket approval and submit clinical trial data demonstrating safety and effectiveness. Similarly, high-risk biologics must obtain a biologics license application by submitting clinical trial data. Postmarketing surveillance strategies, including extended clinical trials or real-world evidence from registries, are increasingly being relied on by the FDA to expedite approval while also improving its capacity to identify problematic products.

Risk of Recall Among Medical Devices Undergoing US Food and Drug Administration 510(k) Clearance and Premarket Approval, 2008-2017.

Importance: The US Food and Drug Administration (FDA) uses 510(k) clearance and premarket approval (PMA) pathways to ensure device safety before marketing. Premarket approval evaluates high-risk medical devices and requires clinical trials, whereas 510(k) clearance evaluates moderate-risk devices and relies on benchtop (nonclinical and biomechanical) and descriptive data. Existing literature suggests that the clinical trials required by PMA are associated with reduced risk of recall compared with devices granted 510(k) clearance. Several investigators have found weaknesses in pivotal PMA trials, raising safety concerns. Furthermore, methodological factors may have led to a previous underestimation of recall risk for devices with PMA. Objectives: To compare risk of recall and high-risk recall between devices that received 510(k) clearance and those that received PMA and to compare the risk of recall between devices for medical specialties. Design, Setting, and Participants: This cohort study compared devices with 510(k) clearance vs those with PMA that reached the market between January 1, 2008, and December 31, 2017. Two- to 12-year follow-up was obtained from the FDA's 510(k) and PMA medical device database. Orthopedic surgery was chosen arbitrarily as the reference category for analysis between specialties because no baseline exists. Statistical analysis was performed from February 1 to November 1, 2020. Main Outcomes and Measures: The FDA issues recalls for safety concerns. These recalls are stratified into class I, II, and III, with class I representing high-risk issues for serious harm or death. The main outcome was the hazard ratio of any recall and class I recall between devices with PMA and those with 510(k) clearance. The secondary outcome was the recall hazard ratio between specialties with respect to the reference category. A single Cox proportional hazards regression model evaluating the association of medical specialty and FDA approval pathway with the risk of recall was performed. Results: During the study period, 28 246 devices received 510(k) clearance and 310 devices (10.7%) received PMA; 3012 devices (10.7%) with 510(k) clearance and 84 devices (27.1%) with PMA were recalled. A total of 216 devices (0.8%) with 510(k) clearance and 16 devices (5.2%) with PMA had class I recalls. Devices with PMA compared with those with 510(k) clearance had a hazard ratio for recall of 2.74 (95% CI, 2.19-3.44; P < .001) and a hazard ratio for high-risk recall of 7.30 (95% CI, 4.39-12.13; P < .001). Only radiologic devices were associated with an increased risk of recall (hazard ratio, 1.57; 95% CI, 1.32-1.87; P < .001), whereas 6 specialties were assocated with a decreased risk compared with the orthopedic reference category: general and plastic surgery, otolaryngology, obstetrics and gynecology, physical medicine, hematology, and general hospital. Conclusions and Relevance: This study suggests that high-risk medical devices approved via PMA are associated with a greater risk of recall than previously reported. Most recalls are for devices with 510(k) clearance, also raising safety concerns. Strengthening postmarketing surveillance strategies and pivotal trials may improve device safety.

Intramedullary Antibiotic Delivery for Emphysematous Osteomyelitis of the Femur.

The authors present a case of bilateral femoral emphysematous osteomyelitis caused by Escherichia coli in a 60-year-old woman with rheumatoid arthritis who was receiving long-term prednisone therapy. The infection in both femoral shafts was eradicated with surgical debridement, followed by insertion of intramedullary rods composed of culture-specific antibiotic cement into the femoral canals in conjunction with 6 weeks of intravenous antibiotics. The rods were subsequently removed, and no signs of further osteomyelitis were recognized at follow-up. To the authors' knowledge, this is the first case of its kind reported in the orthopedic literature. Emphysematous osteomyelitis, a rare and dangerous entity, can be successfully managed by intramedullary antibiotic delivery in the subacute setting. [Orthopedics. 2019; 42(1):e128-e130.].

A trivalent gC2/gD2/gE2 vaccine for herpes simplex virus generates antibody responses that block immune evasion domains on gC2 better than natural infection.

Vaccines for prevention and treatment of genital herpes are high public health priorities. Our approach towards vaccine development is to focus on blocking virus entry mediated by herpes simplex virus type 2 (HSV-2) glycoprotein D (gD2) and to prevent the virus from evading complement and antibody attack by blocking the immune evasion domains on HSV-2 glycoproteins C (gC2) and E (gE2), respectively. HSV-2 gC2 and gE2 are expressed on the virion envelope and infected cell surface where they are potential targets of antibodies that bind and block their immune evasion activities. We demonstrate that antibodies produced during natural infection in humans or intravaginal inoculation in guinea pigs bind to gC2 but generally fail to block the immune evasion domains on this glycoprotein. In contrast, immunization of naïve or previously HSV-2-infected guinea pigs with gC2 subunit antigen administered with CpG and alum as adjuvants produces antibodies that block domains involved in immune evasion. These results indicate that immune evasion domains on gC2 are weak antigens during infection, yet when used as vaccine immunogens with adjuvants the antigens produce antibodies that block immune evasion domains.

Wound Closure With Acute Dermatotraction.

Many described techniques take advantage of the viscoelasticity of the human integument to assist in primary closure of fasciotomy wounds. A retrospective chart review was performed on eight patients with a total of 17 incisions who underwent fasciotomy for acute compartment syndrome. Wounds were closed with delayed primary closure (DPC). Patients were males with a mean age of 40 years (range, 21-64). Fasciotomy mean wound length and width at attempted closure was 16.1 s 6 cm and 6.3 s 2 cm, respectively. Mean time to closure after fasciotomy was 3.9 days (range, 2-8). All wounds healed, at a mean of 18.3 s 2.6 days. Patients were followed for a mean of 21 weeks (range, 3-52). The described novel sequential suturing technique can achieve closure with low risk of major complications; 100% wound healing was achieved. When used judiciously, the technique presented can achieve reliable results in selected fasciotomy wound healing. (Journal of Surgical Orthopaedic Advances 27(2):155-159, 2018).

The Methodology of Clinical Studies Used by the FDA for Approval of High-Risk Orthopaedic Devices.

BACKGROUND: The purpose of this investigation was to examine the methodology of clinical trials used by the U.S. Food and Drug Administration (FDA) to determine the safety and effectiveness of high-risk orthopaedic devices approved between 2001 and 2015. METHODS: Utilizing the FDA's online public database, this systematic review audited study design and methodological variables intended to minimize bias and confounding. An additional analysis of blinding as well as the Checklist to Evaluate a Report of a Nonpharmacological Trial (CLEAR NPT) was applied to the randomized controlled trials (RCTs). RESULTS: Of the 49 studies, 46 (94%) were prospective and 37 (76%) were randomized. Forty-seven (96%) of the studies were controlled in some form. Of 35 studies that reported it, blinding was utilized in 21 (60%), of which 8 (38%) were reported as single-blinded and 13 (62%) were reported as double-blinded. Of the 37 RCTs, outcome assessors were clearly blinded in 6 (16%), whereas 15 (41%) were deemed impossible to blind as implants could be readily discerned on imaging. When the CLEAR NPT was applied to the 37 RCTs, >70% of studies were deemed "unclear" in describing generation of allocation sequences, treatment allocation concealment, and adequate blinding of participants and outcome assessors. CONCLUSIONS: This study manifests the highly variable reporting and strength of clinical research methodology accepted by the FDA to approve high-risk orthopaedic devices.

The Role of the Fracture Liaison Service in Osteoporosis Care.

Osteoporosis is a disease classified by the alteration of bony microarchitecture predisposing a person to fragility fractures. This costs the US $19 billion per year and is expected to rise as our population ages. Only 20% of patients with fragility fractures receive treatment for osteoporosis. A Fracture Liaison Service is a cost-effective way to follow patients and improve appropriate work up and management from multiple medical disciplines.

The Age of OrthoInfo: A Randomized Controlled Trial Evaluating Patient Comprehension of Informed Consent.

BACKGROUND: Integral to an orthopaedic surgeon-patient informed consent discussion is the assessment of patient comprehension of their medical care. However, little is known about how to optimize patient comprehension of an informed consent discussion. The purpose of our study was to evaluate three time-controlled informed consent discussion methods to determine which optimized patient comprehension immediately after the discussion. METHODS: Sixty-seven consecutive patients with knee osteoarthritis who were considered medically appropriate for a knee corticosteroid injection were enrolled in our trial. Participants were randomized and were allocated into one of three groups in a parallel fashion and 1:1:1 ratio. Our three groups varied by sensory input and included verbal (hearing), verbal and video (hearing and sight), and verbal and model (hearing, sight, and touch). Each participant listened to a 10-minute scripted lecture given by a researcher; this lecture was based on content from the American Academy of Orthopaedic Surgeons patient education web site OrthoInfo. Patient comprehension was assessed after the lecture using a validated questionnaire called the Nkem test. Our primary outcome evaluated patient comprehension utilizing a pairwise comparison of mean comprehension scores between the groups. The primary outcome was analyzed using a one-way analysis of variance with the least significant difference calculated post hoc and a 95% confidence interval (95% CI). The health-care staff, study participants, and outcome assessor were each blinded to group assignments. RESULTS: The mean comprehension scores were 84% (95% CI, 79% to 88%) for the verbal and model group, 74% (95% CI, 63% to 80%) for the verbal and video group, and 71% (95% CI, 61% to 80%) for the verbal group. The omnibus analysis of variance was significant and showed a difference among the groups (p = 0.019). The pairwise comparison of the groups using the least significant difference calculated post hoc showed that the verbal and model group outperformed the verbal group (p = 0.01) and the verbal and video group (p = 0.023). CONCLUSIONS: Multisensory patient education incorporating OrthoInfo and an anatomic model optimized patient comprehension immediately after a time-controlled informed consent discussion. This finding could play an important role in improving surgeon-patient communication in the field of orthopaedic surgery.

Novel Technique for Femoral Head Reconstruction using Allograft following Obturator Hip Dislocation.

INTRODUCTION: Obturator hip dislocations with an associated osteochondral fracture of the femoral head are uncommon. The treatment of these injuries is challenging and the functional outcomes are poor. Though the injury pattern has been described previously in literature, there are few published reports regarding treatment options. This case report illustrates a novel technique for fixation and stabilization for an unusual injury involving an obturator hip dislocation and an osteochondral impaction fracture of the femoral head. CASE PRESENTATION: A 30-years old African American male, involved in a motor vehicle collision, sustained an obturator dislocation of the left hip with a large posterior osteochondral fracture of the femoral head. An emergency closed reduction procedure was performed followed by a computed tomography (CT) scan of the hip joint which demonstrated a large osteochondral defect (25 x 10 mm, depth: 5 mm) of the femoral head, visualized within the weight-bearing area. Surgical intervention was planned as a fracture of the femoral head with a defect deeper than four millimeters has been shown to be a risk factor for the development of post-traumatic arthritis, often with onset of symptoms within 5 years of the date of injury. Following surgical hip dislocation, the defect of the femoral head was reconstructed with implantation of a femoral head allograft and internal fixation. At the six months follow-up, the patient could ambulate with minimal pain and without assistive devices. Radiographs demonstrated maintenance of articular congruity with no evidence of implant failure, post-traumatic arthritis or avascular necrosis. CONCLUSION: Surgical hip dislocation and reconstruction using femoral head allograft used to treat obturator hip dislocations with concomitant femoral head impaction fractures can lead to satisfactory short term functional outcomes.

Second Place Award Immediate versus delayed operative treatment of low-energy tibial plateau fractures.

BACKGROUND: Current management of tibial plateau fractures requires careful soft-tissue management. Often a staged approach with temporary external fixation followed by delayed internal fixation is recommended. While proven in high-energy injuries, its relevance in treating low-energy fractures has not been investigated. The goal of the current study was to assess the short-term complication rates in low-energy tibial plateau fractures treated early (<48 hr). As a secondary aim, we investigated whether surgical approach would affect rates of wound complications. METHODS: This is a retrospective analysis of patients treated operatively for low-energy tibial plateau fractures at a level-1 urban trauma center between January 1, 2000 and January 1, 2010. Schatzker type 1-3 fractures were considered "low-energy," despite stated mechanism. Statistical analysis was performed using chi-square and Fischer's exact tests. RESULTS: We analyzed 49 patients. From these, 29 received early (<48 hr) definitive surgery, while 20 had surgery delayed (>48 hr). The early treatment group had an infection rate of 3.4% and total complication rate of 20.6%. The delayed treatment group had an infection rate of 5.0% and total complication rate of 25%. There was no significant difference with respect to superficial infection (P=1.0), deep infection (P=0.48), or total complications (P=0.74) Additionally, infection rates did not differ between surgical approaches (P=1.0, 1.0). CONCLUSIONS: Early surgical fixation (<48 hr) of low-energy tibial plateau fractures can be performed safely. Additionally, a midline approach did not increase soft-tissue complications and could be utilized in a patient with a prior midline incision, or one who will soon require a knee arthroplasty.