Overall Rate Of Adverse Events Research Articles

875 Efficacy and Safety of Endoscopic Ultrasound (EUS) Guided Gastroenterostomy (GE): A Systematic Review and Meta-Analysis

INTRODUCTION: Endoscopic ultrasound (EUS) guided gastroenterostomy (GE) is emerging as an alternative to enteral stenting and surgical GE for management of malignant gastric outlet obstruction (GOO). With advances in EUS technology and availability of dedicated devices/stents for EUS scopes, the use of EUS-GE is expected to increase in the future. We performed a systematic review and meta-analysis to estimate the success rate and adverse events associated with EUS-GE. METHODS: We conducted a comprehensive search of multiple electronic databases and conference proceedings including PubMed, EMBASE, and Web of Science databases (from inception through May 2019) to identify studies that reported success rate and adverse events of EUS-GE. The primary outcome was to estimate the pooled rates of technical and clinical success of EUS-GE. The secondary outcome was to estimate the rate of adverse events. RESULTS: 9 studies with a total of 268 patients were included. The pooled rate of technical success of EUS-GE was 91.7 % (95% CI 87.5 – 94.5; I2 = 0). The pooled rate of clinical success of EUS-GJ was 87.8% (95% CI 83.1 – 91.3; I2 = 0). The pooled rate of overall adverse events was 12.6% (95% CI 9.0- 17.6; I2 = 0). The pooled rate of individual adverse events – perforation, bleeding, peritonitis and stent migration / misdeployment were 2% (95% CI 0.7 – 5.1), 3.2% (95% CI 1.5 – 6.5), 2.6% (95% CI 1.1-6.1) and 8.9 % (95% CI 4.3-17.5) respectively.The rate of surgical intervention for adverse events was 2%. CONCLUSION: While the rates of technical success (92%) and clinical success (88%) of EUS-GJ is promising, the risk of adverse events is considerable at 12.6%, with stent misdeployment (9%) being the most common adverse event. Hence, EUS-GJ should be performed at tertiary referral centers in a multidisciplinary (surgery, oncology, gastroenterology) team-based approach.

Meta-Analysis Comparing the Relative Risk of Adverse Events for Amiodarone Versus Placebo

Amiodarone has been associated with adverse events that may restrict its use. We performed a meta-analysis of placebo-controlled trials to assess the relative risk of adverse events of amiodarone compared with placebo. In total, 43 randomized trials were included. A total of 11,395 patients were included (5,792 patients randomized to amiodarone and 5,603 patients randomized to placebo). The incident rate of adverse events per 10,000 person-years was higher in the amiodarone group compared with placebo for pulmonary (129 vs 74; relative risk (RR) 1.77, p = 0.002), thyroid (201 vs 42; RR 4.44, p <0.001), hepatic (54 vs 25; RR 2.27, p = 0.01), cardiac (771 vs 450; RR 1.94, p <0.001), neurological (140 vs 76; RR 1.93, p <0.001), and skin (81 vs 23; RR 1.99, p = 0.04) adverse events. Low-dose amiodarone was not associated with statistically significant increase in pulmonary adverse events but was still associated with thyroid and liver adverse events. In conclusion, the likelihood of experiencing adverse events related to amiodarone was higher than that of placebo. The overall rate of adverse events however, was low, and severe adverse events were rare.

Delayed Restart of Antithrombotic Therapy and Rates of Adverse Events in Subdural Hematomas

Abstract INTRODUCTION The management of subdural hematoma (SDH) in the setting of antithrombotic (AT) therapy, which includes antiplatelet and anticoagulant therapy, is especially challenging. While there exists consensus that AT should be discontinued during initial workup and surgical treatment of SDH, guidance regarding whether and when to restart AT is lacking. This study aims to characterize the association between the timing of AT restart and rates of thrombotic and hemorrhagic adverse events among SDH patients previously on AT in order to inform future clinical decision making. METHODS A 10-yr retrospective analysis of SDH patients treated with antiplatelet or anticoagulant therapy was performed. Patients were grouped based on time to restart of AT therapy from admission (within 14, 15–29, 30–44, 45–59 d, and not within 60 d), and multivariable regression was used to compare the rates of adverse events between these groups. Adverse events included bleeding, thromboembolism, myocardial infarction, deep vein thrombosis, and stroke. RESULTS A total of 226 consecutive patients were included in this analysis. Groups based on AT restart time were similar in terms of demographics and rates of comorbidities. The rates of coronary artery disease, operative treatment, and chronicity of SDH differed significantly between groups. The 45 to 59 d group had significantly fewer total complications compared to the 60 + day group (P = .016) and trended towards fewer complications than the within 14 d group and the 15 to 29 d group (P = .062 and .065, respectively). CONCLUSION Evidence supports a lower rate of overall adverse events in patients restarted between 45 and 59 d postadmission. This restart window may be the optimal time point for potential future clinical trials.

Liraglutide in Children and Adolescents with Type 2 Diabetes

BackgroundMetformin is the regulatory-approved treatment of choice for most youth with type 2 diabetes early in the disease. However, early loss of glycemic control has been observed with metformin monotherapy. Whether liraglutide added to metformin (with or without basal insulin treatment) is safe and effective in youth with type 2 diabetes is unknown.MethodsPatients who were 10 to less than 17 years of age were randomly assigned, in a 1:1 ratio, to receive subcutaneous liraglutide (up to 1.8 mg per day) or placebo for a 26-week double-blind period, followed by a 26-week open-label extension period. Inclusion criteria were a body-mass index greater than the 85th percentile and a glycated hemoglobin level between 7.0 and 11.0% if the patients were being treated with diet and exercise alone or between 6.5 and 11.0% if they were being treated with metformin (with or without insulin). All the patients received metformin during the trial. The primary end point was the change from baseline in the glycated hemoglobin level after 26 weeks. Secondary end points included the change in fasting plasma glucose level. Safety was assessed throughout the course of the trial.ResultsOf 135 patients who underwent randomization, 134 received at least one dose of liraglutide (66 patients) or placebo (68 patients). Demographic characteristics were similar in the two groups (mean age, 14.6 years). At the 26-week analysis of the primary efficacy end point, the mean glycated hemoglobin level had decreased by 0.64 percentage points with liraglutide and increased by 0.42 percentage points with placebo, for an estimated treatment difference of −1.06 percentage points (P<0.001); the difference increased to −1.30 percentage points by 52 weeks. The fasting plasma glucose level had decreased at both time points in the liraglutide group but had increased in the placebo group. The number of patients who reported adverse events was similar in the two groups (56 [84.8%] with liraglutide and 55 [80.9%] with placebo), but the overall rates of adverse events and gastrointestinal adverse events were higher with liraglutide.ConclusionsIn children and adolescents with type 2 diabetes, liraglutide, at a dose of up to 1.8 mg per day (added to metformin, with or without basal insulin), was efficacious in improving glycemic control over 52 weeks. This efficacy came at the cost of an increased frequency of gastrointestinal adverse events. (Funded by Novo Nordisk; Ellipse ClinicalTrials.gov number, NCT01541215.)

A 15-Minute Incremental Increase in Operative Duration Is Associated With an Additional Risk of Complications Within 30 Days After Arthroscopic Rotator Cuff Repair.

Background:Operative time is a risk factor for short-term complications after orthopaedic procedures; however, it has yet to be investigated as an independent risk factor for postoperative complications after arthroscopic rotator cuff repair.Purpose:To determine whether operative time is an independent risk factor for complications, readmissions, and extended hospital stays within 30 days after arthroscopic rotator cuff repair.Study Design:Descriptive epidemiology study.Methods:The American College of Surgeons National Surgical Quality Improvement Program was queried for all hospital-based inpatient and outpatient arthroscopic rotator cuff repairs (Current Procedural Terminology code 29827) from 2005 to 2016. Concomitant procedures such as subacromial decompression, biceps tenodesis, superior labrum anterior and posterior (SLAP) repair, labral repair, and distal clavicle excision were also included, whereas patients undergoing arthroplasty were excluded from the study. Operative time was correlated with patient demographics, comorbidities, and concomitant procedures. All adverse events were correlated with operative time, while controlling for the above preoperative variables, using multivariate Poisson regression with a robust error variance.Results:A total of 27,524 procedures met inclusion and exclusion criteria. The mean age of patients was 58.4 ± 10.9 years, the mean operative time was 86.9 ± 37.4 minutes, and the mean body mass index was 30.4 ± 7.0 kg/m2. Concomitant biceps tenodesis, glenohumeral debridement, SLAP repair, labral repair, and distal clavicle excision significantly increased operative time (P < .001) but not the risk of adverse events (P > .05). The overall rate of adverse events was 0.88%. After adjusting for demographic and procedural characteristics, a 15-minute increase in operative duration was associated with an increased risk of anemia requiring transfusion (relative risk [RR], 1.27 [95% CI, 1.14-1.42]; P < .001), venous thromboembolism (RR, 1.17 [95% CI, 1.02-1.35]; P = .029), surgical site infection (RR, 1.13 [95% CI, 1.03-1.24]; P = .011), and extended length of hospital stay (RR, 1.07 [95% CI, 1.00-1.14]; P = .036).Conclusion:Although the rate of short-term complications after arthroscopic rotator cuff repair is low, incremental increases in operative time are associated with an increased risk of adverse events such as surgical site infection, pulmonary embolism, transfusion, and extended length of hospital stay. Efforts should be made to maximize surgical efficiency in the operating room through optimal coordination of the staff or increased preoperative planning.

IL-12/23 in IBD: Making the Best Use of Available Evidence

Prof Ghosh presented data from the UNITI studies exploring ustekinumab in primary or secondary nonresponders to TNF agonists (UNITI-1) and conventional therapy failures (UNITI-2). The data demonstrate that ustekinumab shows higher efficacy in patients who have failed conventional therapy compared to those who have failed anti-TNF therapy. Further sub-studies showed similar efficacy for ustekinumab 90 mg every 8 weeks (q8w) and ustekinumab 90 mg every 12 weeks (q12w) subcutaneous (SC) regimens, except for in patients with high inflammatory burdens, who did better with q8w regimens. No new safety signals were identified for ustekinumab between Week 96 and Week 156, with overall rates of adverse events and serious adverse events being comparable to placebo. Rates of antibody formation remained low. Dr Raine described two case studies involving Crohn’s disease patients treated with ustekinumab. The first case described a female patient with luminal Crohn’s disease who had secondary nonresponse to an anti-TNF with signs of intestinal and systemic inflammation. The second case considered a patient with bio-naïve luminal Crohn’s disease who had a previous history of opportunistic infections (coughs, colds, and recurrent herpes simplex). Prof Armuzzi presented the results of the induction part of the UNIFI study, which randomised patients with moderate-to-severe ulcerative colitis (UC) to placebo, ustekinumab 130 mg, or a weight-tiered ustekinumab dose (˜6 mg/kg). Results showed clinical remission at Week 8 was 5.3% for placebo, 15.6% for ustekinumab 130 mg intravenous (IV) (p&lt;0.001), and 15.5% for ustekinumab at ˜6 mg/kg IV (p&lt;0.001). Furthermore, ustekinumab IV induced clinical response and endoscopic and mucosal healing, improved health related quality of life, and had an adverse event profile consistent with known safety profiles.

Operative Time as an Independent and Modifiable Risk Factor for Short-Term Complications After Knee Arthroscopy

To determine whether operative time is an independent risk factor for 30-day complications after arthroscopic surgical procedures on the knee. The American College of Surgeons National Surgical Quality Improvement Program database was queried between 2005 and 2016 for all arthroscopic knee procedures including lateral release, loose body removal, synovectomy, chondroplasty, microfracture, and meniscectomy. Cases with concomitant procedures were excluded. Correlations between operative time and adverse events were controlled for variables such as age, sex, body mass index, patient comorbidities, and procedure using a multivariate Poisson regression with robust error variance. A total of 78,864 procedures met our inclusion and exclusion criteria. The mean age of patients was 51.0 ± 14.3years; mean operative time, 31.2 ± 18.1minutes; and mean body mass index, 31.0 ± 7.8. Arthroscopic lateral release (coefficient, 5.8; 95% confidence interval [CI], 4.8-6.8; P < .001), removal of loose bodies (coefficient, 4.2; 95% CI, 3.2-5.3; P < .001), synovectomy (coefficient, 1.8; 95% CI, 1.2-2.3; P < .001), and microfracture (coefficient, 6.5; 95% CI, 5.8-7.2; P < .001) had significantly greater durations of surgery in comparison with meniscectomy. The overall rate of adverse events was 1.24%. After we adjusted for demographic characteristics and the procedure, a 15-minute increase in operative duration was associated with an increased risk of transfusion (relative risk [RR], 1.5; 95% CI, 1.3-1.8; P < .001), death (RR, 1.6; 95% CI, 1.2-2.1; P= .005), dehiscence (RR, 1.6; 95% CI, 1.2-2.2; P= .002), surgical-site infection (RR, 1.3; 95% CI, 1.2-1.3; P=.001), sepsis (RR, 1.3; 95% CI, 1.2-1.4; P < .001), readmission (RR, 1.1; 95% CI, 1.1-1.2; P<.001), and extended length of stay (RR, 1.4; 95% CI, 1.3-1.4; P < .001). Marginal increases in operative time are associated with an increased risk of adverse events such as surgical-site infection, sepsis, extended length of stay, and readmission. Efforts should be made to maximize surgical efficiency. Level IV, retrospective database study.

Long-term adverse event profile from four completed trials of oral eliglustat in adults with Gaucher disease type 1

BackgroundEliglustat is a first-line oral treatment for adults with Gaucher disease type 1 who have an extensive, intermediate or poor CYP2D6 metabolizer phenotype (> 90% of patients). Whereas enzyme replacement therapy for Gaucher disease has been widely used for more than two decades, eliglustat has only been in commercial use since 2014. Clinicians and patients want to better understand which adverse events are most commonly associated with eliglustat, as well as their severity, frequency, and duration.MethodsThis pooled analysis of treatment-emergent adverse events combines data from four completed eliglustat clinical trials involving 393 Gaucher disease type 1 patients. It represents 1400 patient-years of eliglustat exposure and a mean treatment duration of 3.6 years (maximum: 9.3 years).ResultsEighty-one percent of patients remained in their respective trial until commercial availability of eliglustat (US patients only) or until trial completion. Nine patients (2.3%) withdrew from their respective trial due to one or more adverse events reported as eliglustat treatment-related; all but one of these events were mild or moderate. Overall, 97% of adverse events were mild or moderate and 86% were reported by the investigator as unrelated to eliglustat treatment. The overall rate of adverse events decreased over time and did not increase with increasing eliglustat dose. We evaluated frequency, duration, and severity of 14 adverse event terms reported at least once as treatment-related in 2% or more of all patients: dyspepsia (5.9%), headache (5.3%), abdominal pain upper (5.1%), dizziness (5.1%), diarrhea (4.6%), nausea (4.6%), arthralgia (3.6%), constipation (3.3%), abdominal pain (2.8%), gastroesophageal reflux disease (2.8%), fatigue (2.8%), palpitations (2.8%), abdominal distension (2.5%), and gastritis (2.3%). For abdominal pain upper, diarrhea, nausea, abdominal pain, and headache events, median duration was less than 14 days. All 14 adverse event terms, except for arthralgia and headache, were reported only once per patient in more than 70% of patients experiencing the event.ConclusionsThis final pooled analysis of treatment-emergent adverse events reinforces the favorable safety profile of eliglustat. The majority of the most frequently reported treatment-related adverse events were mild or moderate, transient, and occurred only once per patient.

Higher adalimumab serum levels do not increase the risk of adverse events in patients with inflammatory bowel disease

Background: The relationship between serum adalimumab concentrations and adverse events in patients with inflammatory bowel disease (IBD) is unknown. We aimed to determine whether patients with IBD using adalimumab are at increased risk of adverse events if they have higher adalimumab serum levels compared to those with lower adalimumab levels.Methods: This was a retrospective study of 191 IBD patients with at least one serum adalimumab level measurement available. The cohort was divided using a cutoff level of 10 mcg/mL. The primary outcome was the rate of overall adverse events between the two groups. Secondary outcomes included rate of infections, dermatologic reactions, injection-site reactions and other adverse events in both groups. Rates of discontinuation of adalimumab due to adverse events were evaluated. Multivariate logistic regression analysis was performed to evaluate the relationship between adalimumab levels and adverse events.Results: A total of 41 adverse events were reported in 191 patients in the overall cohort. Among 86 patients with higher adalimumab levels, 22 adverse events were reported, vs. 19 adverse events among 105 patients with lower adalimumab levels (25.6% vs. 18.1%, p = .21). Analysis according to adalimumab level tertiles also did not show significant differences in the rates of adverse events. A multivariate forward selection model also did not find higher odds of an adverse event in IBD patients with higher adalimumab levels compared to lower levels (OR 1.54, 95% CI 0.77–3.08).Conclusions: There does not appear to be a relationship between adalimumab exposure and risk of adverse events in IBD patients.

45 Long-term Treatment with Deutetrabenazine Is Associated with Continued Improvement in Tardive Dyskinesia: Results from an Open-label Extension Study

AbstractStudy ObjectiveTo evaluate long-term efficacy of deutetrabenazine in patients with tardive dyskinesia (TD) by examining response rates from baseline in Abnormal Involuntary Movement Scale (AIMS) scores. Preliminary results of the responder analysis are reported in this analysis.BackgroundIn the 12-week ARM-TD and AIM-TD studies, the odds of response to deutetrabenazine treatment were higher than the odds of response to placebo at all response levels, and there were low rates of overall adverse events and discontinuations associated with deutetrabenazine.MethodPatients with TD who completed ARM-TD or AIM-TD were included in this open-label, single-arm extension study, in which all patients restarted/started deutetrabenazine 12mg/day, titrating up to a maximum total daily dose of 48mg/day based on dyskinesia control and tolerability. The study comprised a 6-week titration and a long-term maintenance phase. The cumulative proportion of AIMS responders from baseline was assessed. Response was defined as a percent improvement from baseline for each patient from 10% to 90% in 10% increments. AlMS score was assessed by local site ratings for this analysis.Results343 patients enrolled in the extension study (111 patients received placebo in the parent study and 232 patients received deutetrabenazine). At Week 54 (n=145; total daily dose [mean±standard error]: 38.1±0.9mg), 63% of patients receiving deutetrabenazine achieved ≥30% response, 48% of patients achieved ≥50% response, and 26% achieved ≥70% response. At Week 80 (n=66; total daily dose: 38.6±1.1mg), 76% of patients achieved ≥30% response, 59% of patients achieved ≥50% response, and 36% achieved ≥70% response. Treatment was generally well tolerated.ConclusionsPatients who received long-term treatment with deutetrabenazine achieved response rates higher than those observed in positive short-term studies, indicating clinically meaningful long-term treatment benefit.Presented at: American Academy of Neurology Annual Meeting; April 21–27, 2018, Los Angeles, California, USA.Funding Acknowledgements: This study was supported by Teva Pharmaceuticals, Petach Tikva, Israel.

Patient- and Nurse-Controlled Analgesia: 22-Year Experience in a Pediatric Hospital

Pediatric pain management has rapidly changed over the last 2 decades. In this study, we describe the changing practices and adverse events (AEs) related to patient-controlled analgesia (PCA) and/or nurse-controlled analgesia (NCA) over a 22-year period. After institutional review board approval, retrospective data from a single tertiary-care pediatric hospital were collected between 1994 and 2016. Subgroup analyses were done for surgical and medical case patients. We reported the number of times that PCA and/or NCA was ordered annually, the median and interquartile ranges for age, PCA and/or NCA duration and length of stay, and AE frequencies. Over 22 years, 32 338 PCAs and/or NCAs were ordered in this institution. Morphine and hydromorphone were used most commonly. Between 1994 and 2006, initial orders for PCA and/or NCA increased 2.5-fold. After 2007, initial orders for PCA and/or NCA rapidly decreased; after 2013, the decrease continued at a slower rate, with a total of 1007 orders in 2016. This decrease occurred despite increased hospital admissions and surgeries. Between 2007 and 2012, peripheral nerve blocks rapidly increased (10-fold). After 2002, 146 AEs were reported (1.0%). Of those, 50.5% were nonintercepted, and 20.6% were intercepted AEs; 5.5% and 6.2% were preventable and nonpreventable AEs, respectively. PCA and/or NCA usage continues to be common in pediatric patients, although usage has declined and stabilized in the setting of other emerging methods of analgesia and increases in the number of minimally invasive surgical procedures. The overall rate of AEs was extremely low. However, improvements to eliminate all errors are needed, especially with medications with a great risk of harm (such as opioids).

New Medications for the Treatment of Diabetes.

New Medications for the Treatment of Diabetes.

Efficacy and safety of therapeutic endoscopic retrograde cholangiopancreatography in patients with native papillae with a performance status score of 3 or 4: A single-center retrospective study.

Objective: This study aimed to assess the efficacy and safety of therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in patients with an Eastern Cooperative Oncology Group performance status (ECOG-PS) score of 3 or 4.Patients and Methods: We reviewed the data of 287 patients with native papillae who underwent therapeutic ERCP for biliary disease at our hospital between October 2016 and October 2018. The patients were divided into two groups; those with an ECOG-PS score of 3 or 4 (group A; n=78) and those with an ECOG-PS score of 0–2 (group B; n=209).Results: The rate of technical success was not significantly different between the two groups (95% versus 89%, P=0.13). Although the occurrence rate of overall adverse events (10% versus 11%, P=0.95) was not significantly different between the groups, the occurrence rates of aspiration pneumonia (3.8% versus 0%, P=0.0044) and heart failure (2.6% versus 0%, P=0.020) were significantly higher in group A.Conclusion: The rates of technical success and overall adverse events did not significantly differ between patients with an ECOG-PS score of 3 or 4 and those with a score of 0–2; however, aspiration pneumonia and heart failure were more likely to occur among patients with an ECOG-PS score of 3 or 4.

Adverse Events and Acute Chronic Liver Failure in Patients With Cirrhosis Undergoing Endoscopic Retrograde Cholangiopancreatography: A Multicenter Matched-Cohort Study.

Data on the outcome of adverse events (AEs) and the risk of developing acute-on-chronic liver failure (ACLF) after ERCP in patients with cirrhosis are unknown. We examined the incidence and risk factors of post-ERCP AEs in patients with cirrhosis and the appearance of ACLF after ERCP. In this multicenter, retrospective, matched-cohort study, we evaluated ERCPs performed from January 2002 to 2015. A group of patients with cirrhosis with non-ERCP interventions and one without interventions was also analyzed for the development of ACLF. A total of 441 ERCPs were analyzed; 158 in patients with cirrhosis (cases) and 283 in patients without cirrhosis (controls). The overall rate of AEs after all ERCPs was significantly higher in cases compared to controls (17% vs 9.5, p = 0.02). Cholangitis developed more in cases compared to controls (6.3% vs 1.8%; p = 0.01). In a subanalysis of those with sphincterotomy, the rate of bleeding was higher in those with cirrhosis (9.4% vs 3.4%; p = 0.03). Logistic regression identified cirrhosis (OR, 2.48; 95% CI, 1.36-4.53; p = 0.003) and sphincterotomy (OR, 2.66; 95% CI, 1.23-5.72; p = 0.01) as risk factors of AEs. A total of 18/158 (11.4%) cases developed ACLF after ERCP. ACLF occurred in 7/27 cases with post-ERCP AEs and in 11/131 without post-ERCP AEs (25.9% vs 8.3%; p = 0.01). A total of 3.2% (13/406) patients without interventions developed ACLF compared to 17.5% (102/580) who developed ACLF after non-ERCP interventions. Patients with decompensated cirrhosis at ERCP had a higher risk of developing ACLF (17% vs 6.8%; p = 0.04). Patients with a MELD score ≥ 15 were 3.1 times more likely (95% CI: 1.14-8.6; p = 0.027) to develop ACLF after ERCP. The rate of AEs after ERCP is higher in patients with cirrhosis compared to the non-cirrhotic population. The incidence of ACLF is higher in those with AEs after ERCP compared to those without AEs, especially cholangitis. The development of ACLF is common after ERCP and other invasive procedures. ACLF can be precipitated by numerous factors which include preceding events before the procedure, including manipulation of the bile duct, and AEs after an ERCP.

EUS-specific stents: Available designs and probable lacunae.

Interventional EUS has seen exponential growth in its indications and applications in the last decade.[1,2,3] Dedicated endoscopic devices for EUS-guided interventions are still limited. Up until recently, the tools used have been borrowed from other procedures such as ERCP. In interventional EUS, the linear-array echoendoscope allows a needle to be advanced under EUS-guidance from the upper gastrointestinal lumen to the biliary, pancreatic, or another adjacent intestinal lumen. Real-time puncture can be performed and provide the possibility of EUS-guided transluminal drainage (EUS-TLD). Plastic stents and conventional self-expandable metallic stents (SEMSs) were initially used but present several limitations due to their design.[1,4,5] They lack lumen-to-lumen anchorage and present migratory risks in the absence of stricture to hold them in place. Plastic stents are associated with potential pneumoperitoneum and bile peritonitis, whereas fully-covered SEMS (FCSEMS), despite preventing bile leak, will not maintain secure apposition between two nonadherent organs. Furthermore, their length often exceeds the anatomical requirement of a shorter transluminal anastomosis and predisposes them to obstruction as well as difficult positioning. With the rise in new EUS-guided interventional techniques, new tools, in particular, new stent designs have evolved to facilitate the various applications. A few EUS-specific stents have now become available for EUS-TLD.[4,5] We hereby review the stent designs and discuss lacunae to be addressed to improve the efficacy, safety, and ease of procedures.

Resident Involvement in Shoulder Arthroscopy Is Not Associated With Short-term Risk to Patients.

Background:Shoulder arthroscopy is a commonly performed, critical component of orthopaedic residency training. However, it is unclear whether there are additional risks to patients in cases associated with resident involvement.Purpose:To compare shoulder arthroscopy cases with and without resident involvement via a large, prospectively maintained national surgical registry to characterize perioperative risks.Study Design:Cohort study; Level of evidence, 3.Methods:The prospectively maintained American College of Surgeons National Surgical Quality Improvement Program registry was queried to identify patients who underwent 1 of 12 shoulder arthroscopy procedures from 2005 through 2012. Multivariate Poisson regression with robust error variance was used to compare the rates of postoperative adverse events and readmission within 30 days between cases with and without resident involvement. Multivariate linear regression was used to compare operative time between cohorts.Results:A total of 15,774 patients with shoulder arthroscopy were included in the study, and 12.3% of these had a resident involved with the case. The overall rate of adverse events was 1.09%. On multivariate analysis, resident involvement was not associated with increased rates of any aggregate or individual adverse event. There was also no association between resident involvement and risk of readmission within 30 days. Resident involvement was not associated with any difference in operative time (P = .219).Conclusion:Resident involvement in shoulder arthroscopy was not associated with increased risk of adverse events, increased operative time, or readmission within 30 days. The results of this study suggest that resident involvement in shoulder arthroscopy cases is a safe method for trainees to learn these procedures.

A Prospective, Multicenter Surveillance Study for Adverse Events Associated with Hematopoietic Stem Cell Infusion: Analysis of Pediatric and Low Body-Weight Recipients

Adverse events (AEs) associated with blood component transfusion have been widely surveyed. In contrast, surveillance of AEs associated with hematopoietic stem cell (HSC) infusion in HSC transplant (HSCT),including bone marrow transplant (BMT), peripheral blood stem cell transplant (PBSCT), and cord blood transplant (CBT),has been less rigorous, even though HSC products contain cells of diverse maturity and viability,plasma with various antigens, cytokines and antibodies, and dimethyl sulfoxide (DMSO) in the case of cryopreserved products. In fact, HSC infusion is associated with several AEs, e.g., allergic reactions, flushing, hypo- or hypertension, and respiratory distress, which have been attributed to toxicity of dead cells and DMSO (Otrock et al, Transfusion, 2017). However, our recent prospective surveillance revealed that HSC infusion-related AEs often occurred in each HSC type and the overall rates of AEs were greater in allo-BMT with no DMSO, compared with auto-PBSCT, allo-PBSCT, and allo-CBT typically cryopreserved with DMSO. Hypertension was the most common AE in each HSC source, with the highest rate in BMT, while allergic reactions were the most frequent in allo-PBSCT. A multivariate analysis identified a history of transfusion reactions as a risk factor of HSC infusion-related AEs (Ikeda et al, Transfus Med Rev, 2018). These findings suggest that some DMSO-independent factor(s), such as plasma components, may contribute to HSC infusion-related AEs.Thus, we asked if HSC volume and component effects were more substantial in small recipients, and if age-related factors alter susceptibility to HSC infusion-related AEs in pediatric patients. So far, data on HSC infusion-related AEs in pediatric and low body-weight recipients are lacking. Here, to address these issues, we investigated AEs due to HSC infusions in 219 recipients of <45 kg body weight, including 90 recipients 15 years old or younger, versus data from 1,125 recipients in general (general recipients)in the prospective study described above.The rates of overall HSC infusion-related AEs were quite similar among HSC sources among low body-weight/pediatric recipients (Table 1) andexclusivepediatric recipients (P= .158 in auto-/allo-HSCT and .867 in allo-HSCT), in contrast to general recipientswhose rate of AEs was highest in BMT. In addition, bradycardia was more often reported in CBT compared with PBSCT and BMT (Table 1), especially in pediatric recipients (30.8% in CBT and 0% in others, P< .001). On the other hand, there were some similar trends between low body-weight/pediatric recipients and general recipients: PBSCT and CBT recipients, but not BMT recipients, complained of malodor, whereas the rate of hypertension was highest in BMT (Table 1).Next, we compared HSC infusion-related AEs between auto- and allo-HSCT using cryopreserved products (Table 2). This comparison showed higher overall rates of AEs in allo-HSCT compared with auto-HSCT, especially in pediatric recipients, suggesting that plasma componentsrather than DMSO contribute to HSC infusion-related AEs in low body-weight/pediatric recipients as well as in general recipients. Of note, pediatric recipients showed a 10-foldhigher incidence of nausea/vomiting in allo-HSCT versus auto-HSCT, instead of allergic reactions, for which the incidence was significantly higher in allo-HSCT than auto-HSCT in general recipients.Subsequently, we sought factors that correlate with HSC infusion-related AEs in allo-HSCT using multivariate analysis with logistic regression, which identified lymphoid neoplasms over myeloid neoplasms as a factor for overall AEs (OR 3.013, P= .026), while history of transfusion reactions did not reach statistical significance (OR 2.368, P= .066). Notably, in a multivariate analysis for any grade ≥2 AEs, there were some factors that did not correlate with general recipients but did with low body-weight/pediatric recipients, including complications before HSCT (OR 5.764, P= .019), without plasma or red blood cell removal for ABO mismatch (OR 3.815, P= .032), and >10 ml/kg infusion volume (OR 5.306, P= .027).In conclusion, our data quantifysome specific symptoms associated with HSC infusionin low body-weight and pediatric recipients. We should be mindful ofinfusion volume and preexisting complications when small recipients receive HSC infusion. [Display omitted] DisclosuresFujiwara:Astellas: Consultancy; Kyowa-Hakko: Consultancy; Kirin: Consultancy; Chugai: Consultancy; Pfizer: Consultancy; Shire: Consultancy. Muroi:JCR: Speakers Bureau; Becton: Speakers Bureau; Dickinson and Company: Speakers Bureau; Japanese Red Cross Society: Speakers Bureau. Mori:Astella Pharma: Honoraria; Kyowa Hakko Kirin: Honoraria; Japan Blood Products Organization: Honoraria; MSD: Research Funding; Ono: Honoraria; Novartis Pharma: Honoraria; Eisai: Honoraria; Janssen: Honoraria; Asahi Kasei: Research Funding; Novartis Pharma: Research Funding; Celgene: Honoraria; Taisho Toyama Pharmaceutical Co: Honoraria; Shire Japan: Honoraria; Pfizer: Honoraria; CHUGAI: Honoraria; MSD: Honoraria; SHIONOGI: Honoraria. Nagai:Ono Pharmaceutical Co.Ltd.: Consultancy; Kaneka Corporation: Research Funding; Kawasumi Laboratories Inc.: Research Funding.

The Associations Between CYP2D6 Metabolizer Status and Pharmacokinetics and Clinical Outcomes of Venlafaxine: A Systematic Review and Meta-Analysis.

The association between CYP2D6 metabolizer status and clinical outcomes of venlafaxine was extensively investigated previously, but no widely accepted conclusion has been reached so far. To obtain a more precise estimation of the association, a systematic review by meta-analysis was conducted in the present study. The PubMed, EMBASE, Cochrane Library, Chinese National Knowledge Infrastructure, Technology of Chongqing, and Wan Fang Database were searched for eligible studies up to August 2018. Fourteen related studies involving 1035 patients were finally included. Significant associations were found among 3 CYP2D6 phenotypes (NM, IM, and PM) and most pharmacokinetic parameters of venlafaxine. However, CYP2D6 phenotypes were not associated with Hamilton Depression Rating Scale response of venlafaxine. In addition, we also found no significant association between CYP2D6 phenotype and overall rate of adverse events. CYP2D6 metabolizer status had significant influence on venlafaxine pharmacokinetics, but insufficient evidence demonstrated that CYP2D6 metabolizer status was associated with its therapeutic effects and overall rate of adverse events, which provided further evidence regarding the relationship between CYP2D6 metabolizer status and venlafaxine.

OC80 THE ROLE OF SURGICAL TECHNIQUE ON LONG-TERM OUTCOMES OF TETRALOGY OF FALLOT REPAIR: A MULTICENTER STUDY

Abstract Background and Aim: to evaluate clinical outcomes of patients undergoing Tetralogy of Fallot (ToF) repair, focusing on the type of surgical strategy performed. Methods: a retrospective clinical review of patients undergoing ToF repair in six centers. Excluded were ToF with pulmonary atresia or aplasia, and double-outlet right ventricle. Results: between 1990 and 2015, 720 patients underwent ToF repair (M/F 57%/43%; median age 5,9months, IQ range 3,8–11,5); 132 (18%) had preoperative cyanotic spells; 111 (15%) received previous palliative surgery. Repair was achieved by transatrial approach (TA) in 433 patients (60,1%), and transventricular (TV) in the remaining ones. The pulmonary valve (PV) was saved in 249 (34,6%), while, in the remaining patients, RVOT reconstruction was performed by means of a transanular patch (60,8%), or a conduit (4,6%). Major postoperative complications occurred in 247 (34,0%). Early mortality was 3%. At 20-year follow-up (completeness 86%), 10 (2%) patients died, 39 (7%) required surgical reoperation, and 72 (12%) an interventional procedure. There were no significant differences between TA and TV approaches, in terms of early mortality and onset of adverse events (interventional procedures, surgical reoperations and mortality) at follow-up. When PV was saved, there was a lower rate of postoperative complications and early mortality, and a lower rate of overall adverse events (Figure 1, p &lt; 0,05). Conclusions: ToF repair in infancy is confirmed to be a safe procedure, with good late clinical outcomes. PV preservation at repair is associated with lower early morbidity and mortality, and a lower rate of adverse events at long-term follow up.

Outcomes in resident-performed cataract surgeries with iris challenges: Results from the Perioperative Care for Intraocular Lens study

To assess the outcomes of resident-performed cataract surgeries with iris challenges and to compare these outcomes with similar surgeries performed by attending surgeons. Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, Massachusetts, USA. Retrospective chart review. All cases of cataract extraction by phacoemulsification with intraocular lens implantation, performed by comprehensive ophthalmologists between January 1 and December 31, 2014, were reviewed. Cases with preoperative or intraoperative miosis, iris prolapse, and intraoperative floppy iris syndrome, were included for analysis. Visual outcomes and the rate of perioperative adverse events were compared between resident and attending surgeon cases. Factors predicting adverse events were also assessed. In total, 1931 eye cases of 1434 patients were reviewed, and 65 resident cases and 168 attending surgeon cases were included. The mean logarithm of the minimum angle of resolution corrected distance visual acuity was better in the resident group1month after surgery (0.051±0.10 [SD] versus 0.132±0.30, P=.03); however, the difference was eliminated when controlling for macular disease. The mean operative time was 43.8±26.5minutes and 30.9±12.6minutes for cases performed by resident surgeons and attending surgeons, respectively (P.0001). Residents utilized supplemental pharmacologic dilation or retraction more frequently than attending surgeons (98% versus 87% of cases, P=.008). The overall rate of adverse events was no different between residents and attending surgeons (P=0.16). Dense nuclear sclerosis predicted adverse events in cataract cases with iris challenges (adjusted odds ratio, 1.86; 95% confidence interval, 1.17-2.94; P=.001). Although requiring longer operative times and more surgical manipulation, residents who performed cataract surgeries with iris challenges achieved outcomes comparable to those performed by attending surgeons, and residents should be given the opportunity to operate on these eyes.