Reasons for Long-term Opioid Prescriptions After Guideline-directed Opioid Prescribing and Excess Opioid Pill Disposal.

OBJECTIVES: The aim of this study was to determine the frequency and reasons for long-term opioid prescriptions (rxs) after surgery in the setting of guideline-directed prescribing and a high rate of excess opioid disposal. BACKGROUND: Although previous studies have demonstrated that 5% to 10% of opioid-naïve patients prescribed opioids after surgery will receive long-term (3-12 months after surgery) opioid rxs, little is known about the reasons why long-term opioids are prescribed. METHODS: We studied 221 opioid-naïve surgical patients enrolled in a previously reported prospective clinical trial which used a patient-centric guideline for discharge opioid prescribing and achieved a high rate of excess opioid disposal. Patients were treated on a wide variety of services; 88% of individuals underwent cancer-related surgery. Long-term opioid rxs were identified using a Prescription Drug Monitoring Program search and reasons for rxs and opioid adverse events were ascertained by medical record review. We used a consensus definition for persistent opioid use: opioid rx 3 to 12 months after surgery and >60day supply. RESULTS: 15.3% (34/221) filled an opioid rx 3 to 12 months after surgery, with 5.4% and 12.2% filling an rx 3 to 6 and 6 to 12 months after surgery, respectively. The median opioid rx days supply per patient was 7, interquartile range 5 to 27, range 1 to 447 days. The reasons for long-term opioid rxs were: 51% new painful medical condition, 40% new surgery, 6% related to the index operation; only 1 patient on 1 occasion was given an opioid rx for a nonspecific reason. Five patients (2.3%) developed persistent opioid use, 2 due to pain from recurrent cancer, 2 for new medical conditions, and 1 for a chronic abscess. CONCLUSIONS: In a group of prospectively studied opioid-naïve surgical patients discharged with guideline-directed opioid rxs and who achieved high rates of excess opioid disposal, no patients became persistent opioid users solely as a result of the opioid rx given after their index surgery. Long-term opioid use did occur for other, well-defined, medical or surgical reasons.

Test-Retest repeatability of automated threshold audiometry in Nicaraguan schoolchildren.

OBJECTIVE: Automated threshold audiometry (ATA) could increase access to paediatric hearing assessment in low- and middle-income countries, but few studies have evaluated test-retest repeatability of ATA in children. This study aims to analyse test-retest repeatability of ATA and to identify factors that affect the reliability of this method. DESIGN: ATA was performed twice in a cohort of Nicaraguan schoolchildren. During testing, the proportion of responses occurring in the absence of a stimulus was measured by calculating a stimulus response false positive rate (SRFP). Absolute test-retest repeatability was determined between the two trials, as well as the impact of age, gender, ambient noise, head circumference, and SRFP on these results. STUDY SAMPLE: 807 children were randomly selected from 35 schools in northern Nicaragua. RESULTS: Across all frequencies, the absolute value of the difference between measurements was 5.5 ± 7.8 dB. 89.6% of test-retest differences were within 10 dB. Intra-class correlation coefficients between the two measurements showed that lower SRFP was associated with improved repeatability. No effect of age, gender, or ambient noise was found. CONCLUSIONS: ATA produced moderate test-retest repeatability in Nicaraguan schoolchildren. Participant testing behaviours, such as delayed or otherwise inappropriate response patterns, significantly impacts the repeatability of these measurements.

Compassion, stigma, and professionalism among emergency personnel responding to the opioid crisis: An exploratory study in New Hampshire, USA.

OBJECTIVE: Drug overdoses are the leading cause of death in the United States for those under 50 years of age, and New Hampshire has been disproportionately affected, resulting in increased encounters with the emergency response system. The ensuing impact on emergency personnel has received little attention. The present study aimed to explore the experiences and perspectives of emergency personnel responding to the opioid crisis in NH, with a focus on their views toward people who use opioids. METHODS: Thirty-six emergency personnel (emergency department clinicians, n = 18; emergency medical service providers, n = 6; firefighters, n = 6; and police officers, n = 6) in 6 New Hampshire counties were interviewed about their experiences responding to overdoses and their perspectives on individuals who use opioids. Directed content analysis was used to identify themes in the transcribed, semistructured interviews. The results were reviewed for consensus. RESULTS: Several categories of themes were identified among emergency personnel's accounts of their overdose response experiences and perspectives, including varied degrees of compassion and stigma toward people who use opioids; associations between compassion or stigma and policy- and practice-related themes, such as prehospital emergency care and the role of emergency departments (EDs); and primarily among personnel expressing compassion, a sense of professional responsibility that outweighed personal biases. CONCLUSIONS: Despite the magnitude of the ongoing opioid crisis, some emergency personnel in New Hampshire have sustained or increased their compassion for people who use opioids. Others' perspectives remain or have become increasingly stigmatizing. The associations of compassion and stigma with various policy- and practice-related themes warrant further investigation.

Comparison of Social Media Utilization Among Vascular Surgeons, Interventional Cardiologists, and Interventional Radiologists at Academic Training Institutions.

BACKGROUND: Social media platforms, especially Twitter, are increasingly utilized across medical practice, education, and research. However, little is known about differences in social media use among physicians of varying specialties and its impact on recruitment of trainees. Our objective was to describe differences in social media use among vascular interventional proceduralists at academic training institutions. METHODS: We identified institutions with training programs in vascular surgery (VS), interventional radiology (IR), and interventional cardiology (IC). Faculty providers were identified in each specialty at these institutions. A standardized search was used to identify non-anonymous social media profiles on Facebook, Instagram, and Twitter in September 2019. Influencers were defined as physicians with more than 1,000 Twitter followers. Follow ratio was defined as the number of followers divided by the number of accounts followed. Between-specialty differences were analyzed. RESULTS: A total of 1,330 providers (n = 454 VS, n=451 IR, n = 425 IC) were identified across 47 institutions in 27 states. Across all physicians, a minority of providers utilize social media (Facebook: 24.9%, n = 331; Instagram: 10.8%, n = 143; Twitter: 18.0%, n = 240). VS were significantly more likely to use Instagram (P = 0.001) but there was not a significant difference in utilization of Facebook and Twitter. Among Twitter users, VS had fewer followers on average (median 178, inter-quartile range [IQR] 39-555) than IR (median 272, IQR 50-793, P = 0.26) and IC (median 286, IQR 71-1257, P = 0.052). IC were most likely to be influencers (30.9%, n = 25) followed by IR (17.9%, n = 15) and VS (10.7%, n = 8, P = 0.006). On average, interventional cardiologists had the highest follow ratio (mean 4.9 ± 7.1) compared to interventional radiologists (mean 3.2 ± 5.5) and vascular surgeons (mean 2.5 ± 3.3, P < 0.001). CONCLUSION: A minority of academic vascular interventional proceduralists utilize social media in a non-anonymous manner. On Twitter, interventional cardiologists are most likely to be influencers based on number of followers and, on average, have the highest follow ratio. Vascular surgeons could potentially benefit from pursuing greater influence and visibility on social media as a means to recruit trainees.

Trajectory of Recovery in PROMIS Global Physical Health After Surgical Fracture Fixation.

INTRODUCTION: Patient-reported outcomes (PROs) provide data on the effect of conditions and treatments on patients' lives without third party interpretation. Mounting evidence suggests that PROs may be useful in elective procedure decision making, but its utility in trauma remains unclear. Longitudinally collected PROs may prove effective in identifying patients recovering below the norm. We sought to document recovery trajectory in patients with and without complication and to evaluate the sources of variability in functional recovery after injury. METHODS: This retrospective study included 831 patients with trauma, identified via Current Procedural Terminology (CPT) codes for surgical extremity and/or pelvic/acetabular fracture management between 2014 and 2018. Global Physical Health (GPH) scores collected via the PROMIS Global Health in a 14-month window after injury were analyzed using mixed-effects modeling. RESULTS: A curvilinear GPH recovery trajectory was observed where patients demonstrated an initial positive recovery trajectory (B = 1.28, P < 0.001) gradually decelerating over time (B = -0.07, P < 0.001). Patients who experienced complications requiring revision surgery demonstrated markedly lower GPH scores. Several notable predictors of postoperative physical health recovery were identified, including both between-person (B = 0.52, 95% CI, 0.48 to 0.56) and within-person (B = 0.41, 95% CI, 0.36 to 0.46) Global Mental Health (GMH) score, Body Mass Index (BMI) (B = -0.07, 95% CI, -0.12 to -0.02), two or more psychiatric diagnoses (B = -0.97, 95% CI, -1.84 to 0.09), Injury Severity Score 10 to 15 and 16+ (B = -2.62, 95% CI, -4.81 to 0.42 and B = -2.17, 95% CI, -3.60 to 0.74, respectively), readmission for complication (B = -2.64, 95% CI, -3.60 to 1.68), and lower extremity or multiextremity fracture (relative to upper extremity) (B = -3.61, 95% CI, 4.45 to 2.78, B = -4.11, 95% CI, -5.77 to 2.44, respectively). Additional analysis suggests that GMH scores are related to the presence of psychiatric diagnoses. DISCUSSION: This study establishes a normal course of recovery as reflected by PROMIS GPH score to serve as an index for monitoring individual postoperative course. Patients who experienced a complication demonstrated markedly lower GPH across all time points, potentially allowing earlier identification of at-risk patients. Furthermore, GMH may represent a modifiable risk factor that could profoundly affect physical recovery. LEVEL OF EVIDENCE: Level III (Prognostic Study = Retrospective Cohort).

Perceptions of Sound Quality and Enjoyment After Cochlear Implantation.

OBJECTIVES: To characterize the quality and enjoyment of sound by cochlear implant (CI) recipients and identify predictors of these outcomes after cochlear implantation. STUDY DESIGN: Cross-sectional study. SETTING: A tertiary care hospital. METHODS: Surveys based on the Hearing Implant Sound Quality Index were sent to all patients who received a CI at a tertiary care hospital from 2000 to 2019. Survey questions prompted CI recipients to characterize enjoyment and quality of voices, music, and various sounds. RESULTS: Of the 339 surveys, 60 (17.7%) were returned with complete data. CI recipients had a mean ± SD age of 62.5 ± 17.4 years with a mean 8.0 ± 6.1 years since CI surgery. Older current age and age at implantation significantly predicted lower current sound quality (P < .05) and sound enjoyment (P < .05), as well as worsening of sound quality (P < .05) and sound enjoyment (P < .05) over time. Greater length of implantation was associated with higher reported quality and enjoyment (r = 0.4, P < .001; r = 0.4, P < .05), as well as improvement of sound quality (r = 0.3, P < .05) but not sound enjoyment over time. CONCLUSION: Recipients who had CIs for a longer period had improved quality of sound perception, suggesting a degree of adaptation. However, CI recipients with implantation at an older age reported poorer sound quality and enjoyment as well as worsening sound quality and enjoyment over time, indicating that age-related changes influence outcomes of cochlear implantation.

When is surgical resection alone appropriate treatment for pediatric nodular lymphocyte-predominant Hodgkin lymphoma?

The surgeon's role in the management of lymphoma is typically limited to performing biopsies for diagnosis. Most patients with lymphoma are treated with chemotherapy and/or radiation, but in rare cases, lymphoma can be primarily treated with surgery. We present a case of nodular lymphocyte-predominant Hodgkin lymphoma in a 4-year-old child with cervical adenopathy and discuss initial treatment with surgery alone. Surgery as primary treatment avoids the serious long-term sequelae of chemotherapy and radiation, and reserves those options for possible future recurrences; however, this approach should be reserved for patients with limited and low-risk disease. This case report reviews the pros and cons of treating early-stage nodular lymphocyte-predominant Hodgkin lymphoma in a pediatric patient with surgery alone.

Preoperative Criteria Predict Operative Time Variability Within Tympanoplasty Procedures.

OBJECTIVE: To identify preoperative patient and surgical parameters that predict operative time variability within tympanoplasty current procedural terminology (CPT) codes. STUDY DESIGN: Retrospective. SETTING: Tertiary referral center. PATIENTS: One hundred twenty eight patients who underwent tympanoplasty (CPT code 69631) or tympanoplasty with ossicular chain reconstruction (69633) by a single surgeon over 3 years. INTERVENTIONS: Procedures were preoperatively assigned a complexity modifier: Level 1 (small or posterior perforation able to be repaired via transcanal approach), Level 2 (large perforation or other factor requiring postauricular approach), or Level 3 (cholesteatoma or severe infection). MAIN OUTCOME MEASURES: Total in-room time (nonoperative time plus actual operative time). RESULTS: Consideration of preoperative parameters including surgical complexity, surgical facility, use of facial nerve monitoring, laser usage, resident involvement, revision surgery, and underlying patient characteristics (American Society of Anesthesiologists [ASA] score, body mass index [BMI]) accounted for up to 69% of surgical time variance. Across both CPT codes, surgical complexity levels accurately stratified operative times (p < 0.05). Total time was longer (by 30.0 min for 69631, 55.4 min for 69633) in Level 3 procedures compared with Level 2, while Level 1 cases were shorter (27.6, 33.9 min). Resident involvement added 25 and 32 minutes to total time (p < 0.02). Nonoperative preparation times were longer (22.1, 15.4 min) in the main hospital compared with ambulatory surgical center (p < 0.001). CONCLUSIONS: There is significant surgical time variability within tympanoplasty CPT codes, which can be accurately predicted by the preoperative assignment of complexity level modifiers and consideration of patient and surgical factors. Application of complexity modifiers can enable more efficient surgical scheduling.

Image-guided surgery in otolaryngology: A review of current applications and future directions in head and neck surgery.

Image-guided surgery (IGS) has become a widely adopted technology in otolaryngology. Since its introduction nearly three decades ago, IGS technology has developed rapidly and improved real-time intraoperative visualization for a diverse array of clinical indications. As usability, accessibility, and clinical experiences with IGS increase, its potential applications as an adjunct in many surgical procedures continue to expand. Here, we describe the basic components of IGS and review both the current state and future directions of IGS in otolaryngology, with attention to current challenges to its application in surgery of the nonrigid upper aerodigestive tract.

Guidelines for Patient-CenteredOpioid Prescribing and Optimal FDA-Compliant Disposal of Excess Pills after Inpatient Operation: Prospective Clinical Trial.

BACKGROUND: To optimize responsible opioid prescribing after inpatient operation, we implemented a clinical trial with the following objectives: prospectively validate patient-centered opioid prescription guidelines and increase the FDA-compliant disposal rate of leftover opioid pills to higher than currently reported rates of 20% to 30%. STUDY DESIGN: We prospectively enrolled 229 patients admitted for 48 hours or longer after elective general, colorectal, urologic, gynecologic, or thoracic operation. At discharge, patients received a prescription for both nonopioid analgesics and opioids based on their opioid usage the day before discharge: if 0 oral morphine milligram equivalents (MME) were used, then five 5-mg oxycodone pill-equivalents were prescribed; if 1 to 29 MME were used, then fifteen 5-mg oxycodone pill-equivalents were prescribed; if 30 or more MME were used, then thirty 5-mg oxycodone pill-equivalents were prescribed. We considered patients' opioid pain medication needs to be satisfied if no opioid refills were obtained. To improve FDA-compliant disposal of leftover pills, we implemented patient education, convenient drop-box, reminder phone call, and questionnaire. RESULTS: Our opioid guideline satisfied 93% (213 of 229) of patients. Satisfaction was significantly higher in lower opioid usage groups (p = 0.001): 99% (99 of 100) in the 0 MME group, 90% (91 of 101) in the 1 to 29 MME group, and 82% (23 of 28) in the 30 or more MME group. Overall, 95% (217 of 229) of patients used nonopioid analgesics. Sixty percent (138 of 229) had leftover pills; 83% (114 of 138) disposed of them using an FDA-compliant method and 51% (58 of 114) used the convenient drop-box. Of 2,604 prescribed pills, only 187 (7%) were kept by patients. CONCLUSIONS: This clinical trial prospectively validated a patient-centered opioid discharge prescription guideline that satisfied 93% of patients. FDA-compliant disposal of excess pills was achieved in 83% of patients with easily actionable interventions.

Evaluating the Effectiveness of a Web-Based Program (POP4Teens) to Prevent Prescription Opioid Misuse Among Adolescents: Randomized Controlled Trial.

BACKGROUND: Prescription opioid (PO) use is common among adolescents in the United States. Despite recent declines from unprecedented peaks in adolescent PO use (eg, in 2012-2013), there is seemingly paradoxical evidence that PO-related consequences (eg, opioid use disorder and overdoses) are increasing. These trends and their possible consequences emphasize the importance of prevention efforts targeting PO misuse. To our knowledge, we have developed the first interactive web-based program (POP4Teens [P4T]) focused specifically on the prevention of PO misuse among adolescents. OBJECTIVE: This study aimed to evaluate the effectiveness of P4T, a web-based program designed to prevent adolescent PO misuse, in comparison with JustThinkTwice (JTT), an active control website, on PO-related attitudes, knowledge, risk perception, and intentions to use. METHODS: We conducted a web-based randomized controlled trial in 2018. A total of 406 adolescents (aged 12-17 years) were randomly assigned to either P4T or JTT. The outcome variables were attitudes, knowledge, and risk perceptions associated with PO misuse, intentions to use POs, and program feedback. Data were collected at baseline and at 1, 3, and 6 months. RESULTS: Both programs resulted in significant and sustained improvements in intention to use POs, increased perceived risk, impacted expectancies consistent with prevention, and improved PO refusal skills. P4T produced significantly greater increases in PO-related knowledge than JTT did, and it was reportedly easier to use and more liked. Baseline scores for youth reporting past-year medical use of POs, friends who engage in nonmedical use of POs, and/or poor mental health underscored their at-risk status compared with youth from the other groups. CONCLUSIONS: P4T positively impacted all study variables that are known to prevent PO misuse among teens. Moreover, its web-based nature simplifies the dissemination and implementation of this novel tool designed to help meet the challenges of the evolving national opioid crisis. TRIAL REGISTRATION: ClinicalTrials.gov NCT02737696; https://clinicaltrials.gov/ct2/show/NCT02737696.

Online Ratings for Vascular Interventional Proceduralists Vary by Physician Specialty.

BACKGROUND: Multiple specialties offer vascular interventional care, creating potential competition for referrals and procedures. At the same time, patient/consumer ratings have become more impactful for physicians who perform vascular procedures. We hypothesized that there are differences in online ratings based on specialty. METHODS: We used official program lists from the Association for Graduate Medical Education to identify institutions with training programs in integrated vascular surgery (VS), integrated interventional radiology (IR), and interventional cardiology (IC). Faculty providers were identified in each specialty at these institutions. A standardized search was performed to collect online ratings from Vitals.com, Healthgrades.com, and Google.com as well as from online demographics. Between specialty differences were analyzed using chi-squared and analysis of variance tests as appropriate. Multivariable linear regression was used to identify factors associated with review volume and star rating. RESULTS: A total of 1,330 providers (n = 454 VS, n = 451 IR, n = 425 IC) were identified across 47 institutions in 27 states. VS (55.5%-69.4%) and IC (63.8%-71.1%) providers were significantly more likely to have reviews than IR (28.6%-48.8%) providers across all online platforms (P < 0.001 for all websites). Across all platforms, IC providers were rated significantly higher than VS and IR providers. Multivariable regression showed that provider specialty and additional time in practice were associated with higher review volume. In addition to specialty, review volume was associated with star rating as those physicians with more reviews tended to have a higher rating. CONCLUSIONS: On average, vascular surgeons have more reviews and are more highly rated than interventional radiologists but tend to have fewer reviews and lower ratings than interventional cardiologists. VS providers may benefit from encouraging patients to file online reviews, especially in competitive markets.

Outcomes of a novel alloplastic technique for external auditory canal repair in tympanomastoidectomy.

OBJECTIVE: To analyze surgical outcomes of a novel alloplastic reconstruction technique for partial external auditory canal (EAC) defects in tympanomastoidectomy. METHODS: Retrospective study of 51 patients with cholesteatoma who underwent repair of partial EAC defects during tympanomastoidectomy at a tertiary referral center over 8 years. Nineteen patients were treated with a novel alloplastic graft technique using hydroxyapatite cement and bone pâté for EAC repair. Thirty-two patients treated with traditional cartilage repair of the EAC served as a control group. The primary outcomes measured were postoperative cholesteatoma recurrence rates, infection rates, and mean air-bone gap (ABG). RESULTS: Twenty of the 51 cases (39.2%) were revision surgeries for cholesteatoma recidivism, with a greater proportion of revision surgeries in the alloplastic group (57.9% vs 28.1%, P = .04). There was no significant difference in postoperative cholesteatoma recurrence (P = 1.00) or infection rates (P = .64) between the two techniques, with the alloplastic group experiencing slightly lower rates of recurrence (36.8%) and infection (5.3%) than cartilage repair (37.5% recurrence, 12.5% infection). Mean postoperative ABGs were comparable between the alloplastic (21.5 dB) and cartilage group (26.0 dB, P = .10). CONCLUSIONS: Composite alloplastic and bone pâté reconstruction is an effective technique to repair partial EAC defects in tympanomastoidectomy, with comparable postoperative hearing outcomes and no increased risk of cholesteatoma recurrence or infection compared to traditional cartilage repair. Recidivism rates were relatively high in both groups, likely due to the high rate of revision surgeries and aggressive nature of cholesteatoma within the cohort. LEVEL OF EVIDENCE: Level 3B.

Translating coding lists in administrative claims-based research for cardiovascular procedures.

BACKGROUND: To effectively use administrative claims for healthcare research, clinical events must be inferred from coding data according to validated algorithms. In October 2015, the United States transitioned from the International Classification of Diseases Ninth Revision (ICD-9) to the Tenth Revision (ICD-10). We describe our method to derive new ICD-10 codes for outcomes after vascular procedures from our prior, validated ICD-9 codes. METHODS: We began with validated ICD-9 coding lists known to represent outcomes after lower extremity revascularization, thoracic aortic endograft placement, abdominal aortic aneurysm reintervention, and carotid revascularization. We used the publicly available general equivalence mapping tools to derive corresponding ICD-10 codes for each of the ICD-9 codes in our current lists. The resulting lists were then manually reviewed by multiple authors to ensure clinical relevance for appropriate event detection. Clinically nonrelevant and duplicated codes were removed. RESULTS: A total of 475 ICD-9 codes were translated to ICD-10 with a 98-fold increase (n = 46,630) in the total number of codes. Overall, we found that 77% of codes (n = 35,833) were either duplicated or not clinically relevant upon manual review. For example, for thoracic aortic endograft placement, 97 ICD-9 codes mapped to 14,661 ICD-10 codes in total. A total of 890 codes were removed as duplicates and 9035 codes were removed during manual clinical review. The resultant, reviewed list contained 4736 ICD-10 codes representing a 49-fold increase from the initial ICD-9 list. Findings were similar across the other procedures studied. CONCLUSIONS: ICD-10 has expanded the number of codes necessary to describe outcomes after vascular procedures. More than 75% of the codes obtained using the general equivalence mapping database were either duplicated or not clinically relevant. Manual review of codes by researchers with clinical knowledge of the procedures is imperative.

Client Desires and the Price of Seduction: Exploring the Relationship Between Independent Escorts' Marketing and Rates.

This article explores Web site content and differences in advertised rates among a sample of 839 independent female online escorts operating their own Web sites in major metropolitan areas in the United States. Statistical analyses of escorts' rates indicate pricing variation across cities in which escorts advertise; the number of cities and Websites in which they advertise; whether they travel to areas beyond their primary locality to meet clients; their age and stated racial/ethnic/sexual identity; the Internet platforms on which they advertise; and how they present themselves and their services on their Web pages. These relationships between business strategies of independent escorts and their published rates shed light on client preferences and market demand. Our findings provide important new insights into independent online escorts' business strategies and financial tactics and identify factors impacting perceived market value for escort services. This research supports emerging literature indicating that clients of independent online escorts will pay more for particular provider characteristics, dispositions, and services, and they most highly value erotic services that are seductive and mirror the qualities of nonremunerative sexual exchange, often described as the "girlfriend experience" (GFE).

Recapture and improved outcome of pegloticase response with methotrexate-A report of two cases and review of the literature.

INTRODUCTION: Pegloticase is a PEGylated uric acid specific enzyme indicated for the treatment of refractory gout. Anti-pegloticase antibodies contribute to high discontinuation rates, increased risk of infusion reactions, and early loss of drug efficacy. OBJECTIVE: To describe the use of methotrexate to recapture function of pegloticase after development of anti-drug antibodies while treating gout. METHODS: We report two cases of using methotrexate as an adjunct to treatment with pegloticase for refractory tophaceous gout. We also present the results of a literature review on the use of concomitant immunosuppressive therapy with pegloticase to prevent anti-pegloticase antibody development. RESULTS: Patient A, a 55-year-old man with a history of tophaceous gout, was treated with pegloticase but developed high serum urate(sUA) levels prior to his third infusion. Adjunctive treatment with methotrexate restored pegloticase response and the patient's sUA levels decreased, and remained low for the remainder of his treatment. Patient B, a 36-year-old man with a history of tophaceous gout, was treated with pegloticase. Oral methotrexate was initiated at the first infusion. Low sUA levels were achieved but increased after a lapse in methotrexate compliance. Re-initiation of methotrexate restored pegloticase response and the patient tolerated subsequent infusions. Literature review identified three reports of successful use of concomitant pegloticase and immunosuppressive therapy for refractory tophaceous gout, including an open label trial with a subset of 7 transplant recipients, an additional case study of pegloticase treatment with one transplant recipient, and a case study of pegloticase administered with low-dose azathioprine. CONCLUSION: Prophylactic use of immunosuppressive therapy with pegloticase may enable sustained treatment and improve outcomes. Additionally, immunosuppressive therapy seems to show the ability to recapture pegloticase response after development of anti-drug antibodies. The use of immunosuppressants to prevent anti-drug antibody formation, recapture pegloticase efficacy, and reduce discontinuation rates warrants further study.

A Meta-analysis of the Impact of Aspirin, Clopidogrel, and Dual Antiplatelet Therapy on Bleeding Complications in Noncardiac Surgery.

OBJECTIVE: The aim of this study was to determine the bleeding risks associated with single (aspirin) and dual (aspirin + clopidogrel) antiplatelet therapy (DAPT) versus placebo or no treatment in adults undergoing noncardiac surgery. SUMMARY OF BACKGROUND DATA: The impact of antiplatelet therapy on bleeding during noncardiac surgery remains controversial. A meta-analysis was performed to examine the risk associated with single and DAPT. METHODS: A systematic review of antiplatelet therapy, noncardiac surgery, and perioperative bleeding was performed. Peer-reviewed sources and meeting abstracts from relevant societies were queried. Studies without a control group, or those that only examined patients with coronary stents, were excluded. Primary endpoints were transfusion and reintervention for bleeding. RESULTS: Of 11,592 references, 46 studies met inclusion criteria. In a meta-analysis of >30,000 patients, the relative risk (RR) of transfusion versus control was 1.14 [95% confidence interval (CI) 1.03-1.26, P = 0.009] for aspirin, and 1.33 (1.15-1.55, P = 0.001) for DAPT. Clopidogrel had an elevated risk, but data were too heterogeneous to analyze. The RR of bleeding requiring reintervention was not significantly higher for any agent compared to control [RR 0.96 (0.76-1.22, P = 0.76) for aspirin, 1.84 (0.87-3.87, P = 0.11) for clopidogrel, and 1.51 (0.92-2.49, P = 0.1) for DAPT]. Subanalysis of thoracic and abdominal procedures was similar. There was no difference in RR for myocardial infarction [1.06 (0.79-1.43)], stroke [0.97 (0.71-1.33)], or mortality [0.97 (0.87-1.1)]. CONCLUSIONS: Antiplatelet therapy at the time of noncardiac surgery confers minimal bleeding risk with no difference in thrombotic complications. In many cases, it is safe to continue antiplatelet therapy in patients with important indications for their use.