Implant-related Adverse Events Research Articles

Safety and Effectiveness of a Bioabsorbable Steroid-Releasing Implant for the Paranasal Sinus Ostia

Suboptimal outcomes of endoscopic sinus surgery (ESS) are often associated with restenosis and inflammation of frontal sinus ostia. Steroid-releasing sinus implants have been shown to maintain sinus patency by minimizing inflammation and scar tissue formation. An hourglass-shaped, bioabsorbable, steroid-releasing implant was developed to provide mechanical support and optimize drug delivery to paranasal sinus ostia. To assess the safety and efficacy of the hourglass-shaped, bioabsorbable, steroid-releasing sinus implant in improving postoperative outcomes when placed in the frontal sinus ostia (FSO) following ESS in patients with chronic rhinosinusitis (CRS). In a prospective, multicenter, randomized clinical trial using an intrapatient control design (ESS followed by implant placement within 1 FSO vs ESS alone on the contralateral side) 80 adult patients, with a mean (SD) age of 49.5 (13.4) years and consisting of 53 (66%) men and 27 (34%) women, were enrolled and underwent bilateral frontal sinusotomies with 1 frontal sinus randomized to receive a steroid-releasing implant. The study was carried out in 12 US centers between July 2015 and March 2016. A bioabsorbable steroid-releasing implant with hourglass shape containing 370 µg of mometasone furoate. All patients received standardized postoperative care. The need for postoperative interventions, medical and surgical, in the FSO at day 30, as determined based on review of video endoscopic findings by an independent blinded surgeon. Also, endoscopic grading by the independent reviewer and clinical investigators at day 30 and day 90 and computed tomographic scan at day 90. The mean (SD) age of patients was 49.5 (13.4) years, 53 (66%) were men. Implants were successfully placed in all 80 randomized treatment sinuses. At day 30, steroid-releasing implants significantly reduced the need for postoperative interventions to 11.5% compared with 32.8% by surgery alone (mean difference, -21.3%; 95% CI, -35.1% to -7.6%), as assessed by the independent reviewer. Real-time endoscopic assessment by clinical investigators at day 30 demonstrated significant reduction in need for postoperative intervention (mean difference, -17.3%; 95% CI, -27.9% to -6.7%), significant reduction in inflammation score (mean difference, -12.3 mm; 95% CI, -18.3 to -6.4 mm), and significant reduction in rate of frontal restenosis or occlusion (mean difference, -22.7%; 95% CI, -33.5% to -11.9%) on treated compared with control sides. The results favoring the treatment sides were sustained through day 90: reduced need for postoperative interventions (mean difference, -11.7%; 95% CI, -21.0% to -2.4%) and reduction in restenosis and/or occlusion of the frontal ostium (mean difference, -17.4%; 95% CI, -28.6% to -6.1%). No implant-related adverse events were observed. The hourglass-shaped steroid-releasing sinus implant was safe and more effective in maintaining FSO patency and improving surgical outcomes compared with surgery alone in the setting where no other immediate postoperative corticosteroids were administered. ClinicalTrials.gov identifier: NCT02266810.

Hypersensitivity to biomedical implants: Prevention and diagnosis.

There has been growing interest in the potential for adverse immunologic reactions to metals in biomedical devices and increasing referrals for the evaluation and management of metal hypersensitivity reactions reported in orthopedic, cardiac, gynecologic, and dental implant devices. However, there are few studies that give evidence-based recommendations on how to evaluate this issue in our practices. We reviewed reasonable evidence and expert opinion on biomedical device hypersensitivity and published guidelines on pre- and postimplantation evaluation of delayed hypersensitivity reactions in patients suspected of possible metal hypersensitivity to biomedical devices. There is consensus that routine preimplantation evaluation in individuals with no history of adverse cutaneous reactions to metals or a history of implant-related adverse events is not necessary. However, patients with a history of metal hypersensitivity of a magnitude sufficient to cause concern for the patient or health care provider may benefit from evaluation by patch testing (PT) before device implantation. Patients after implantation and with chronic unexplained implant failure or with dermatitis may benefit from patch test evaluation after other causes, such as infection and biomechanical issues, are ruled out. However, a positive metal patch test result does not prove symptom causality, and the decision regarding implant revision can only be made after a thorough discussion among the patient, the allergist or dermatologist, and the orthopedic surgeon. Consensus guidelines for the evaluation of hypersensitivity to biomedical devices can be used by the practicing physician while awaiting for the results of further investigations.

Patch Testing for Evaluation of Hypersensitivity to Implanted Metal Devices: A Perspective From the American Contact Dermatitis Society

The American Contact Dermatitis Society recognizes the interest in the evaluation and management of metal hypersensitivity reactions. Given the paucity of robust evidence with which to guide our practices, we provide reasonable evidence and expert opinion-based guidelines for clinicians with regard to metal hypersensitivity reaction testing and patient management. Routine preoperative evaluation in individuals with no history of adverse cutaneous reactions to metals or history of previous implant-related adverse events is not necessary. Patients with a clear self-reported history of metal reactions should be evaluated by patch testing before device implant. Patch testing is only 1 element in the assessment of causation in those with postimplantation morbidity. Metal exposure from the implanted device can cause sensitization, but a positive metal test does not prove symptom causality. The decision to replace an implanted device must include an assessment of all clinical factors and a thorough risk-benefit analysis by the treating physician(s) and patient.

Effect of Buprenorphine Implants on Illicit Opioid Use Among Abstinent Adults With Opioid Dependence Treated With Sublingual Buprenorphine

The effectiveness of buprenorphine treatment of opioid dependence is limited by suboptimal medication adherence, abuse, and diversion. To determine whether 6-month buprenorphine implants are noninferior to daily sublingual buprenorphine as maintenance treatment for opioid-dependent patients with stable abstinence. Outpatient, randomized, active-controlled, 24-week, double-blind, double-dummy study conducted at 21 US sites from June 26, 2014, through May 18, 2015. Outpatients were prescribed daily sublingual buprenorphine for 6 months or more, were abstinent while taking 8 mg/d or less of sublingual buprenorphine for 90 days or longer, and were determined to be clinically stable by their physician. Participants were randomized to receive sublingual buprenorphine plus 4 placebo implants or sublingual placebo plus four 80-mg buprenorphine hydrochloride implants (expected efficacy, 24 weeks). The primary end point was between-group difference in proportion of responders (≥4 of 6 months without opioid-positive urine test result [monthly and 4 times randomly] and self-report). The noninferiority established for the lower bound of the 95% confidence interval was greater than -0.20 (P < .025). Secondary end points included cumulative percentage of negative opioid urine results, abstinence, and time to first illicit opioid use. Safety was assessed by adverse event reporting. Of 177 participants (mean age, 39 years; 40.9% female), 90 were randomized to sublingual buprenorphine with placebo implants and 87 to buprenorphine implants with sublingual placebo; 165 of 177 (93.2%) completed the trial. Eighty-one of 84 (96.4%) receiving buprenorphine implants and 78 of 89 (87.6%) receiving sublingual buprenorphine were responders, an 8.8% difference (1-sided 97.5% CI, 0.009 to ∞; P < .001 for noninferiority). Over 6 months, 72 of 84 (85.7%) receiving buprenorphine implants and 64 of 89 (71.9%) receiving sublingual buprenorphine maintained opioid abstinence (hazard ratio, 13.8; 95% CI, 0.018-0.258; P = .03). Non-implant-related and implant-related adverse events occurred in 48.3% and 23% of the buprenorphine implant group and in 52.8% and 13.5% of participants in the sublingual buprenorphine group, respectively. Among adults with opioid dependence maintaining abstinence with a stable dose of sublingual buprenorphine, the use of buprenorphine implants compared with continued sublingual buprenorphine did not result in an inferior likelihood of remaining a responder. However, the study population had an exceptionally high response rate in the control group, and further studies are needed in broader populations to assess the efficacy in other settings. clinicaltrials.gov Identifier: NCT02180659.

Randomized controlled trial of a bioabsorbable steroid-releasing implant in the frontal sinus opening.

To assess safety and efficacy of a steroid-releasing implant in improving surgical outcomes when placed in the frontal sinus opening (FSO) following endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). Prospective, multicenter, randomized, blinded trial using an intrapatient control design. Eighty adult (≥ 18 years) CRS patients who underwent successful bilateral frontal sinusotomy were randomized to receive a steroid-releasing implant in one FSO, whereas the contralateral control side received no implant. All patients received standard postoperative care. Endoscopic evaluations recorded at 30-days postendoscopic sinus surgery (ESS) were graded real time by clinical investigators and by an independent, blinded sinus surgeon to assess the need for postoperative interventions in the FSO. Implants were successfully placed in all 80 frontal sinuses, resulting in 100% implant delivery success. At 30-days post-ESS, steroid-releasing implants provided a statistically significant (P = 0.0070) reduction in the need for postoperative interventions compared to surgery alone by an independent reviewer, representing 38% relative reduction. Clinical investigators reported statistically significant reduction in this measure at 30 days (P < 0.0001) and 90 days (P = 0.0129). Clinical investigators also reported a 55.6% reduction in the need for oral steroid interventions (P = 0.0015), 75% reduction in the need for surgical interventions (P = 0.0225), 16.7% reduction in inflammation score, 54.3% reduction in restenosis rate (P = 0.0002), and 32.2% greater diameter of FSO (P < 0.0001) on treated sides compared to control at 30 days. No implant-related adverse events were reported. This study demonstrates the efficacy of steroid-releasing implants in improving outcomes of frontal sinus surgery. 1b. Laryngoscope, 126:2659-2664, 2016.

Volar Plate Fixation for the Treatment of Distal Radius Fractures

Determining the rate of specific adverse events after volar plating performed for distal radius fractures. Retrospective. University level I trauma center. We searched the electronic database of all surgical procedures performed in our department using the following keywords: distal radius fracture, wrist fracture, and plate fixation. We identified 315 patients, 12 of whom were lost at follow-up. Volar plate fixation for the treatment of distal radius fractures. At an average follow-up of 5 years, 303 patients were evaluated through medical records and clinical and radiographic assessment for specific adverse events after volar plate fixation. Adverse events were observed in 18 patients (5.9%). Implant-related adverse events, including tendon impairments, intra-articular screws, and screw loosening, were observed in 15 patients (5.0%). Extensor tendon impairments were represented by 5 cases of extensor tenosynovitis and 3 cases of rupture of the extensor pollicis longus due to screws protruding dorsally. Flexor impairments were represented by 2 cases of tenosynovitis and 2 cases of flexor pollicis longus rupture. Screw penetration into the radioulnar joint was observed in 1 case. Loss of reduction was identified in 3 cases. One patient had a deep postoperative infection treated with operative debridement. One patient experienced injury to the median nerve during routine implant removal unrelated to tendon issues. The majority of adverse events after volar plate fixation were due to technical errors in implant placement. In our cohort, tendon impairments were the most frequently observed; among these, extensor tendon impairments were the most represented (50% of all adverse events). All 12 tendon-related adverse events were due to technical shortcomings with implant placement. Therapeutic level IV.

The Role of Patch Testing in the Evaluation of Orthopedic Implant-Related Adverse Effects

In recent years, there has been a growing interest in the use of skin patch testing to evaluate patients for orthopedic, implant-related adverse effects. This may be done preoperatively to avoid implanting a material to which an individual may be allergic or postoperatively to implicate sensitivity as a cause for implant failure. There is emerging evidence that patch testing might have utility in the workup of implant-related adverse events; however, the level of evidence at the present time is weak and based only on a collection of case reports, series, and retrospective cohort studies (level IV evidence as per United States Department of Health and Human Services guidelines); there are no randomized controlled trials (level I evidence) with which to guide medical decision making. Recent reports have advocated that patch testing be broadly used in the preoperative evaluation of all patients self-reporting a history of metal sensitivity. In addition, several authors have advocated that patch test results should guide preoperative implant selection and postoperative implant removal. It is the opinion of this author that these recommendations are premature, lacking robust clinical evidence, and unfeasible given the broad-reaching logistical impact and societal costs involved. More robust clinical data are needed, and thorough cost-benefit analyses must be performed before such far-reaching and costly systematic practices should be broadly implemented.

Implant Experience with an Implantable Hemodynamic Monitor for the Management of Symptomatic Heart Failure

Management of congestive heart failure is a serious public health problem. The use of implantable hemodynamic monitors (IHMs) may assist in this management by providing continuous ambulatory filling pressure status for optimal volume management. The Chronicle system includes an implanted monitor, a pressure sensor lead with passive fixation, an external pressure reference (EPR), and data retrieval and viewing components. The tip of the lead is placed near the right ventricular outflow tract to minimize risk of sensor tissue encapsulation. Implant technique and lead placement is similar to that of a permanent pacemaker. After the system had been successfully implanted in 148 patients, the type and frequency of implant-related adverse events were similar to a single-chamber pacemaker implant. R-wave amplitude was 15.2 +/- 6.7 mV and the pressure waveform signal was acceptable in all but two patients in whom presence of artifacts required lead repositioning. Implant procedure time was not influenced by experience, remaining constant throughout the study. Based on this evaluation, permanent placement of an IHM in symptomatic heart failure patients is technically feasible. Further investigation is warranted to evaluate the use of the continuous hemodynamic data in management of heart failure patients.

781 Bilateral Intraputaminal Infusion of Liatermin (Glial Cell Line-derived Neurotrophic Factor r-metHuGDNF) in Subjects with Advanced Parkinson's Disease

INTRODUCTION: Liatermin consistently has demonstrated neuro-protective and neuroregenerative properties in rodent and nonhuman primate models of Parkinson’s disease (PD). A previous trial of intracerebroventricular infusions of glial cell line-derived neurotrophic factor (GDNF) did not yield the expected improvements noted in the animal models. However, direct targeted delivery of GDNF has resulted in marked clinical improvement in open-label pilot trials of continuous intraputaminal (IPu) infusion of liatermin in patients with advanced PD. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that evaluated safety and efficacy in 34 subjects with advanced idiopathic PD. The SynchroMed Infusion System (Medtronic, Inc., Minneapolis, MN) was used to administer liatermin (15 mg/putamen/d) or placebo bilaterally into the dorsal posterior putamen via stereotactically implanted bilateral IPu catheters. A blinded neuroradiologist independently evaluated catheter tip placement and the delivery of study material on magnetic resonance images. Other blinded individuals evaluated before- and after-treatment 18F-dopa positron emission tomographic (PET) scans. Subjects continued to receive oral anti-parkinsonian medications. The primary outcome was the percent change from baseline to 6 months in the Unified Parkinson’s Disease Rating Scale (UPDRS) motor score in the practically defined off condition. RESULTS: Thirty-four subjects received implants and were randomized into the trial. The most serious implant-related adverse events included one symptomatic intraparenchymal hemorrhage, one subdural hygroma, and one recurrent infection that required device removal and reimplantation. No deaths or permanent neurological worsening occurred. Because the blinded phase continues through May 2004, complete unblinded safety and efficacy results will be revealed during the presentation of the data at the meeting. Efficacy results include the percent change in the UPDRS motor score in the practically defined off period and the findings of the pretreatment and posttreatment 18F-dopa PET studies. CONCLUSION: Continuous infusion of liatermin into the dorsal posterior putamen is well tolerated and may result in improvement (to be clarified once results are available) of parkinsonian motor symptoms in patients with advanced PD.