Similar Rates Of Adverse Events Research Articles

The effectiveness of buprenorphine for treating cancer pain: an abridged Cochrane review

ObjectivesTo assess the effectiveness and tolerability of buprenorphine for cancer pain in adults and children.MethodsWe searched CENTRAL, MEDLINE, EMBASE, ISI Web of Science, ISI BIOSIS, ClinicalTrials.gov, metaRegister of Controlled Trials,...

Omega-3 fatty acids for depression in adults.

Omega-3 fatty acids for depression in adults.

Piloting PrePex for Adult and Adolescent Male Circumcision in South Africa--Pain Is an Issue.

BackgroundThe World Health Organisation and the Joint United Nations Programme on HIV/AIDS have recommended the scale-up of Medical Male Circumcision (MMC) in countries with high HIV and low MMC prevalence. PrePex device circumcision is proposed as an alternate method for scaling up MMC.ObjectiveEvaluate safety and feasibility of PrePex in South Africa.DesignA multisite prospective cohort PrePex study in adults and adolescents at three MMC clinics. Participants were followed-up 8 times, up to 56 days after PrePex placement.ResultsIn total, 398 PrePex circumcisions were performed (315 adults and 83 adolescents) their median ages were 26 (IQR: 22–30) and 16 years (IQR: 15–17), respectively. The median time for device placement across both groups was 6 minutes (IQR: 5–9) with the leading PrePex sizes being B (30%) and C (35%) for adults (18–45 years), and A (31%) and B (38%) for adolescents (14–17 years). Additional sizes (size 12–20) were rarely used, even in the younger age group. Pain of device application was minimal but that of removal was severe. However, described pain abated rapidly and almost no pain was reported 1 hour after removal. The Adverse Events rate were experienced by 2.7% (11/398) of all participants, three of which were serious (2 displacements and 1 self-removal requiring prompt surgery). None of the Adverse Events required hospitalization. The majority of participants returned to work within a day of device placement.ConclusionOur study shows that PrePex is a safe MMC method, for males 14 years and above. PrePex circumcision had a similar adverse event rate to that reported for surgical MMC, but device removal caused high levels of pain, which subsided rapidly.

Association Between Anesthesia Techniques and Postoperative Complications in Older Adults with Dementia Undergoing Hip Fracture Surgery

To the Editor: The recent article by Seitz et al.1 assessing the association between anesthetic techniques and postoperative complications in older adults with dementia undergoing hip fracture surgery was of great interest. The authors found that general anesthesia and regional anesthesia were associated with similar rates of most perioperative adverse events. The power of this study is its use of several administrative databases containing most of the known preoperative factors that can affect perioperative adverse events in such individuals. To account for systematic differences in observed baseline confounders between individuals receiving general anesthesia and those receiving regional anesthesia, the authors used propensity-score matching to estimate the effects of anesthesia techniques on study endpoints. Nevertheless, this study was a retrospective analysis, which is inevitably subject to uncontrolled and unmeasured confounding. In our view, several important things were not well addressed in this study. First, perioperative hemoglobin levels and transfusion were not included in the data analysis. Perioperative anemia is common in individuals undergoing hip fracture surgery, and anemia at admission and postoperative anemia needing a transfusion are independent risk factors for worse postoperative outcomes in individuals with hip fracture.2 Second, information on mobility and functional status before surgery were not provided and analyzed. Preoperative impaired functional status and mobility disability are common problems of individuals with hip fracture, and more than half of individuals with hip fracture do not regain mobility in the first postoperative year.3 Such conditions can not only impair survival, but may also adversely affect recovery and clinical outcomes in the early postoperative period. Specifically, complete functional dependence has been found to be associated independently with short-term morbidity and mortality after hip fracture surgery.4 Thus, the possibility cannot be excluded that mobility disability was a serious health problem in the participants that confoiunded their data analysis for postoperative adverse events. Third, most importantly, detailed information about the anesthesia and intraoperative management is not provided. Thus, it is difficult to estimate how much influence anesthesiologists’ interventions might have on postoperative outcomes. It has been shown that intraoperative blood loss, hypoxemia, and hemodynamic instability are independently associated with morbidity and mortality after noncardiac surgery.5 Furthermore, short durations of intraoperative mean arterial pressure less than 55 mmHg can result in postoperative myocardial and kidney injuries, with an independent graded relationship between duration of intraoperative hypotension and postoperative myocardial and kidney injuries.6 Typically, based on estimated blood loss, lowest heart rate, and lowest mean arterial pressure during surgery, the Surgical Apgar Score, which was originally developed in individuals undergoing noncardiac surgery, has been shown to be a good predictor of postoperative 30-day major complications.7 Finally, approximately 10% of the participants had chronic kidney disease before surgery, but postoperative kidney complications were not included in the major adverse events. Acute kidney injury is a frequent adverse event in elderly adults after hip fracture surgery. In a study of 90 individuals aged 65 and older undergoing hip fracture surgery, 24% developed acute kidney injury, as defined according to risk, injury, failure, loss, and end-stage renal disease criteria.8 In a study of 165 elderly adults undergoing hip fracture surgery, 15.3% developed acute kidney injury within the first 48 postoperative hours, and preoperative baseline renal function was an independent risk factor for postoperative acute kidney injury.9 In a study of 1,511 individuals undergoing hip fracture surgery, 69 of 730 (9%) with normal renal function before surgery developed renal dysfunction after surgery, and 364 of 545 (67%) with a low glomerular filtration rate upon admission had evidence of postoperative renal dysfunction.10 Furthermore, acute kidney injury is associated with longer hospital stay and greater morbidity.9 We believe that addressing the above factors would increase the transparency of this study. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. None of the authors received financial support and there are no potential conflicts of interest for this work. Author Contributions: All authors have seen and approved the manuscript. Xue carefully read the manuscript of Seitz et al., analyzed their methods and data, suggested comment points, drafted this manuscript, and is responsible for this manuscript. Liu read the manuscript of Seitz et al. and helped to write and revise this manuscript. Sun read the manuscript of Seitz et al. and helped analyze their methods and data, review this manuscript. Sponsor's Role: None.

Aortic and right ventricular rupture in a patient after transcatheter aortic valve implantation; The direction of the calcification predicts aortic annulus rupture

Severe aortic valve stenosis (AS) is related significantly to morbidity and mortality, if untreated. The recent reports showed that TAVI for severe AS is feasible, associated with similar rate of major adverse events with surgery, and results in improved functional status in these patients. Transcatheter aortic valve implantation (TAVI) procedure has been applied in increasing amounts as a novel alternative choice of treatment in patients with aortic valve disease in case of high risk of cardiac surgery. But, there are possible dangerous and life-threatening complications at any moment during the TAVI procedure [ 1 Seiffert M. Conradi L. Baldus S. Schirmer J. Blankenberg S. Reichenspurner H. Diemert P. Treede H. Severe intraprocedural complications after transcatheter aortic valve implantation: calling for a heart team approach. Eur. J. Cardiothorac. Surg. Sep 2013; 44: 478-484 Crossref PubMed Scopus (37) Google Scholar , 2 Sgroi C. Gulino S. Attizzani G.F. Immè S. Patanè M. Ohno Y. Cannata S. Giarratana A. Aruta P. Bottari V. Barbanti M. Deste W. Giannazzo D. Tamburino C. Valve rupture after balloon aortic valvuloplasty successfully managed with emergency transcatheter aortic valve implantation. Int. J. Cardiol. Sep 20 2013; 168: e13-e14 Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar , 3 Griese D.P. Reents W. Kerber S. Diegeler A. Babin-Ebell J. Emergency cardiac surgery during transfemoral and transapical transcatheter aortic valve implantation: incidence, reasons, management, and outcome of 411 patients from a single center. Catheter. Cardiovasc. Interv. Nov 1 2013; 82: E726-E733 Crossref PubMed Scopus (27) Google Scholar , 4 Pavicevic J. Nguyen T.D. Caliskan E. Reser D. Frauenfelder T. Plass A. Stähli B.E. Maier W. Seifert B. Maisano F. Falk V. Corti R. Grünenfelder J. Emmert M.Y. Aortic valve calcium score is a significant predictor for the occurrence of post-interventional paravalvular leakage after transcatheter aortic valve implantation — results from a single center analysis of 260 consecutive patients. Int. J. Cardiol. Feb 15 2015; 181: 185-187 Abstract Full Text Full Text PDF PubMed Scopus (7) Google Scholar , 5 Montarello N. Copus B. Prakash R. Worthley S.G. Peripheral embolization of aortic valve calcium following trans-femoral Sapien XT valve implantation requiring emergency surgical embolectomy. Int. J. Cardiol. Feb 15 2015; 181: 17-18 Abstract Full Text Full Text PDF PubMed Scopus (3) Google Scholar ]. The aortic annulus and other structures of the aortic root may be damaged iatrogenically at various levels during the balloon inflation and valve implantation. Rupture of the aortic root during and after percutaneous valve implantation is a rare and potentially lethal complication. So, the landing zone of the valve and the direction of the annular calcification are very important to predict the aortic annulus rupture. Although there is enough time to repair of the aortic annulus during standard surgical procedure, it is very difficult to control this complication during TAVİ procedure. For this reason, it is very important to recognize and be aware of this event and take all preventive actions to prevent the complications on time. The treatment of the aortic annulus rupture is difficult or even mostly untreatable and the only treatment option for this complication is surgical replacement of the aortic root. Herein, we report a case of a 74-year-old woman with aortic annulus and right ventricular rupture after successful TAVI procedure.

Capsule Commentary for Tsilimingras et al., Post-Discharge Adverse Events Among Urban and Rural Patients of an Urban Community Hospital: A Prospective Cohort Study.

Tsilimingras et al. 1 investigate whether patients from urban and rural areas have similar rates of adverse events. They carefully consider a sample in one urban community hospital and track rates of adverse events using a rigorous, independently adjudicated method of detecting and classifying adverse events. There was little difference between the two patient groups; both had high rates of adverse events, with the majority being either preventable or ameliorable. The focus on patients discharged from one hospital is important to consider and is a study strength, as it holds constant the quality and practices of the specific facility. But it raises an additional element to consider: if rural patients “bypassing” their local hospital have better insurance (e.g., commercial), and are more likely to be admitted for complex conditions,2 the patients may differ in their baseline risk of adverse events. Curiously, the patient populations appear to exhibit some of these differences (e.g., slightly more secondary discharge diagnoses in rural) but not others (rural have lower income and are more likely to be on public insurance). Naturally, this reflects the difference in the underlying prevalence of conditions within the two patient groups. In this case, the urban patients of the hospital tend to live much closer to the study hospital: 90 % of the urban Medicare beneficiaries admitted to the hospital lived within 20 miles of Tallahassee Memorial Hospital (TMH), compared to 10 % of the rural Medicare beneficiaries.3 Although this suggests potential barriers to timely post-acute care—combined with more complex conditions and poorer socioeconomic status among the rural group—there seemed to be little difference in risk. Understanding the pathway to these similar rates of adverse events in the face of multiple risk factors would help improve transitions to post-acute care, something from which all acute patients would benefit.

Tu1500 Safety of Per-Oral Endoscopic Myotomy (POEM) in Patients With Severe Co-Morbidities

Per-oral endoscopic myotomy (POEM) is an upcoming treatment modality for achalasia cardia. Results of POEM have been encouraging and are comparable to those after laparoscopic Heller's myotomy (LHM) or endoscopic balloon dilatation (EBD). The patients with severe cardio-respiratory diseases are relative contraindications for LHM or EBD. In this multi-center study, we analyzed safety and efficacy of POEM in sub-group of patients with severe co-morbid conditions.

Tu1499 Optical Coherence Tomography (OCT) Prior to PerOral Endoscopic Myotomy (POEM): a New Standard?

Tu1499 Optical Coherence Tomography (OCT) Prior to PerOral Endoscopic Myotomy (POEM): a New Standard? Amit P. Desai*, Amy Tyberg, Prashant Kedia, Nikhil A. Kumta, Sanjay Salgado, Monica Gaidhane, Arnon Lambroza, Reem Z. Sharaiha, Amrita Sethi, Michel Kahaleh Interventional Endoscopy, Methodist Dallas Medical Center, Dallas, TX; Division of Gastroenterology & Hepatology, Weill Cornell Medical College, New York, NY; Digestive and Liver Diseases Columbia University Medical Center, Columbia University Medical Center, New York, NY Background & Aims: POEM has emerged as an endoscopic option for the treatment of achalasia. There are currently no pre-procedural imaging modalities to predict the safest and most efficacious approach. Our aim is to evaluate the use of OCT in providing a pre-procedural, in-vivo assessment of the esophagus to determine the optimal approach. Methods: All patients undergoing POEM from July 2013 to November 2014 were prospectively captured in a dedicated POEM registry. Demographics, esophageal motility studies, prior treatment, Eckardt scores, compliance and OCT were included. Patients who underwent OCT pre-POEM (“OCT arm”) were compared to patients without pre-POEM OCT (“control arm”). OCT images were assessed for the degree of vascularity and the thickness of the circular muscular layer (Figure 1). An approach was determined based on these findings in the OCT group. Procedural times, adverse events and clinical follow up data were compared. Technical success was defined as completion of adequate pre-POEM OCT. Clinical success was defined as lack of further re-intervention post-POEM. Results: 27 patients were captured in the registry. 15 patients underwent pre-POEM OCT. The average age in the OCT arm was higher than the control group (63.6 vs. 47.4 years, pZ0.03). The Charlson Co-Morbidity Index (CCI) was higher in the OCT arm than the control group (3.2 vs 1.3, pZ0.0316). The average baseline Eckardt scores in the OCT arm was similar to the control group (6.53 vs 6.54, p Z 0.77). More patients in the OCT arm were previously treated with Botox compared to the control group (7 vs. 2, pZ0.10) (Table 1). OCT demonstrated thick anterior or posterior muscle in 66% (nZ10) of patients and large palisading vessels in 60% (nZ9) of patients. Using OCT as a guide, 60% (nZ9) of patients underwent anterior POEM while 40% (nZ6) underwent posterior POEM. There was 100% technical success in completing adequate OCT prior to POEM. Clinical success was achieved in all patients except 1 (4%) in the control group who underwent repeat POEM due to refractory symptoms. In follow up, there was significant improvement in Eckardt scores in both OCT (6.53 vs 1.6, pZ0.0004) and control (6.54 vs. 1.5, pZ0.005) groups. The procedural time was similar among OCT and control groups (103 vs. 109 mins). Significantly less bleeding occurred in the OCT arm when compared to the control group (7% vs. 58%, pZ0.025) with similar rates of adverse non-bleeding events (6% vs. 8%, pZ0.41). Conclusion: OCT provides an in-vivo anatomic assessment of the esophagus prior to POEM. Although the OCT group was older, had higher CCI scores and underwent more Botox injections, the risk of peri-procedure bleeding was significantly lower due to avoidance of vessels seen on OCT. Therefore, OCT should be performed in the evaluation of all patients prior to POEM.

Impact of prior coronary bypass graft surgery on the outcomes of patients undergoing primary percutaneous coronary intervention

BackgroundHistorically, patients with prior coronary artery bypass graft (CABG) surgery undergoing primary percutaneous coronary intervention (PCI) have a worse prognosis than patients without prior CABG. However, more contemporary analyses have contested these findings. This study's aim was to evaluate the 30-day clinical outcomes in patients with and without prior CABG submitted to primary PCI. MethodsProspective cohort study, extracted from the database of Instituto de Cardiologia do Rio Grande do Sul, containing 1,854 patients undergoing primary PCI. ResultsPatients with prior CABG (3.8%) showed, in general, a more severe clinical profile. The time of symptom onset until arrival at the hospital was shorter in this group (2.50hours [1.46 to 3.66] vs. 3.99hours [1.99 to 6.50]; p<0.001), while the door-to-balloon time was similar (1.33 hour [0.85 to 2.07] vs. 1.16 hour [0.88 to 1.58]; p=0.12). Femoral access was more often used in the group with prior CABG (91.5% vs. 62.5%; p<0.001). Manual thrombus aspiration was less often performed in this group (16.9% vs. 31.1%; p=0.007), but there was no difference regarding the use of glycoprotein IIb/IIIa inhibitors (28.2% vs. 32.4%, p=0.28). Angiographic success was lower in the group with prior CABG (80.3% vs. 93.3%; p=0.009). At 30 days, patients with prior CABG had similar rates of major adverse cardiac events (14.1% vs. 11.2%; p=0.28), and mortality, although numerically higher, was not statistically significant (13.2% vs. 7.0%, p=0.07). ConclusionsIn this contemporary analysis, patients with prior CABG undergoing primary PCI had a more severe clinical profile and lower angiographic success, but showed no differences regarding 30-day clinical outcomes.

Impacto da cirurgia de revascularização miocárdica prévia em desfechos clínicos de pacientes submetidos à intervenção coronária percutânea primária

BackgroundHistorically, patients with prior coronary artery bypass graft (CABG) surgery undergoing primary percutaneous coronary intervention (PCI) have a worse prognosis than patients without prior CABG. However, more contemporary analyses have contested these findings. This study's aim was to evaluate the 30‐day clinical outcomes in patients with and without prior CABG submitted to primary PCI. MethodsProspective cohort study, extracted from the database of Instituto de Cardiologia do Rio Grande do Sul, containing 1,854 patients undergoing primary PCI. ResultsPatients with prior CABG (3.8%) showed, in general, a more severe clinical profile. The time of symptom onset until arrival at the hospital was shorter in this group (2.50hours [1.46 to 3.66] vs. 3.99 hour [1.99 to 6.50]; p < 0.001), while the door‐to‐balloon time was similar (1.33 hour [0.85 to 2.07] vs. 1.16 hour [0.88 to 1.58]; p = 0.12). Femoral access was more often used in the group with prior CABG (91.5% vs. 62.5%; p < 0.001). Manual thrombus aspiration was less often performed in this group (16.9% vs. 31.1%; p = 0.007), but there was no difference regarding the use of glycoprotein IIb/IIIa inhibitors (28.2% vs. 32.4%, p = 0.28). Angiographic success was lower in the group with prior CABG (80.3% vs. 93.3%; p = 0.009). At 30 days, patients with prior CABG had similar rates of major adverse cardiac events (14.1% vs. 11.2%; p = 0.28), and mortality, although numerically higher, was not statistically significant (13.2% vs. 7.0%, p = 0.07). ConclusionsIn this contemporary analysis, patients with prior CABG undergoing primary PCI had a more severe clinical profile and lower angiographic success, but showed no differences regarding 30‐day clinical outcomes.

Efficacy and safety of nebulized glycopyrrolate for administration using a high efficiency nebulizer in patients with chronic obstructive pulmonary disease.

AimsTo establish the dose−response for pharmacodynamics (bronchodilatation), safety and pharmacokinetics for a nebulized formulation of the long acting muscarinic antagonist glycopyrrolate (EP-101) with a high efficiency nebulizer in patients with chronic obstructive pulmonary disease (COPD).MethodsPatients with moderate to severe COPD (GOLD II/III), with reversible lung function, were enrolled into this randomized, double-blind, placebo-controlled, six period crossover study (n = 42). Patients received single doses of EP-101 (12.5–400 μg) and placebo via a high efficiency nebulizer (eFlow® PARI nebulizer), with washout between treatments. Plasma pharmacokinetics were assessed in a subset of patients (n = 11).ResultsAll treatments were well tolerated with similar adverse event rates reported with placebo and at all doses. There were no clinically relevant changes in heart rate, systolic and diastolic blood pressure or in ECG parameters including QTc interval. Following treatment with EP-101 at all doses there was a rapid bronchodilator response within 5 min. Significant improvements in mean change from baseline FEV1 at 24 h were reported at doses ≥50 μg compared with placebo, with a clear dose−response relationship. Mean changes in FEV1 were 0.10 l (95% CI 0.06, 0.14) and 0.12 l (95% CI 0.08, 0.16) for 100 μg and 200 μg, respectively.ConclusionSingle doses of EP-101 ranging from 12.5 μg to 400 μg were well tolerated. EP-101 delivered by high efficiency nebulizer device produced a rapid onset of bronchodilatation with clinically meaningful improvements in lung function maintained over a 24 h period at all doses >50 μg.

Is Long-Term Therapy With Thiopurines Effective for Maintaining Remission in Patients With Moderate-To-Severe Ulcerative Colitis?

The thiopurines, azathioprine and 6-mercaptopurine, have been in clinical use for 50 years. Prospective studies and meta-analyses suggest that thiopurines are effective for the maintenance of remission in UC.1,2 By maintaining remission, hospitalization and colectomy rates can be reduced, and long-term complications prevented. However, in the biologic era, the long-term efficacy of thiopurine needs to be better understood. In this issue of Intestinal Research, Yamada et al. tried to assess the long-term efficacy and safety of maintenance treatment with thiopurines in UC.3 They enrolled a total of 59 bio-naive patients who maintained remission by treatment with thiopurine and 5-aminosalicylate after induction. The cumulative remission-maintenance rates at 24, 48, and 84 months were reported as approximately 69%, 55%, and 44%, respectively. Recent meta-analyses of trial data revealed remission maintenance rates of 56-76% during thiopurine treatment.1,2 The remission maintenance rate of Yamada et al. was similar to that of meta-analyses, considering that the mean follow-up period of these studies was shorter. Yamada et al. also demonstrated that high-dose corticosteroid treatment (≥40 mg/day) was a negative predictive factor for maintenance treatment with thiopurine. This could be inferred from the fact that other maintenance treatments such as biologics should be considered in refractory UC patients treated with high-dose corticosteroids. Mucosal healing (MH) is becoming more widely accepted as a relevant outcome marker for UC. In a Norwegian population-based cohort study examining effects between the presence or absence of MH and long-term outcomes, MH at 1 year was confirmed in 50% of UC patients, and the colectomy rate at 5 years was 1.7%. MH at 1 year significantly decreased the need for colectomy at 5 years,4 and this association was significant after adjusting for factors that may influence colectomy, such as age, smoking, education level, and disease extent. Therefore, the previous study provides evidence that MH is strongly associated with the clinical outcomes of UC. Yamada et al. reported MH rates of >60% at 26.8 months, and a colectomy rate of 3.6%. Compared to that of Western studies, this result was not significantly different. However, only two-thirds of study patients underwent colonoscopy to evaluate MH and the time interval between initiating thiopurine therapy and performing the colonoscopy to assess MH was different in each patient due to the retrospective design of the study. Therefore, the results of Yamada et al. should be interpreted while considering the limitations of the study, such as the small number of patients included and the lack of adjustment for potential confounding factors. Efficacy must be balanced against safety and tolerability. In the Yamada et al. study, the median dose of thiopurine was 50 mg. Traditionally, the dose-escalating approach is used in East Asian patients.5,6 Several trials, including this study, have suggested that lower doses of azathioprine or 6-mercaptopurine may be effective and safe for the treatment of UC patients,7,8 contrary to the results of Western studies. According to previous studies, approximately 10-28% of patients reported adverse events (AEs), and 25.6% of patients had to discontinue thiopurine therapy due to AEs.9,10 A similar rate of AEs (28.8%) was reported in the study by Yamada et al. In this study, the discontinuation rate due to AEs was reported as low as 10.2%, probably due to low thiopurine dose they used. Although there were no severe AEs such as lymphoma and non-melanoma skin cancer in the Yamada et al. study, and the absolute risks of these malignancies remain low, the risks and benefits of continuing or ceasing thiopurine therapy should be weighed for each individual patient. Despite the fact that clinical trials (including the Yamada et al. study) concerning the use of thiopurines for UC have been heterogeneous in design, the evidence is sufficient to conclude that thiopurines are effective for maintenance of remission.

Current role of non-anesthesiologist administered propofol sedation in advanced interventional endoscopy.

Complex and lengthy endoscopic examinations like endoscopic ultrasonography and/or endoscopic retrograde cholangiopancreatography benefit from deep sedation, due to an enhanced quality of examinations, reduced discomfort and anxiety of patients, as well as increased satisfaction for both the patients and medical personnel. Current guidelines support the use of propofol sedation, which has the same rate of adverse effects as traditional sedation with benzodiazepines and/or opioids, but decreases the procedural and recovery time. Non-anesthesiologist administered propofol sedation has become an option in most of the countries, due to limited anesthesiology resources and the increasing evidence from prospective studies and meta-analyses that the procedure is safe with a similar rate of adverse events with traditional sedation. The advantages include a high quality of endoscopic examination, improved satisfaction for patients and doctors, as well as decreased recovery and discharge time. Despite the advantages of non-anesthesiologist administered propofol, there is still a continuous debate related to the successful generalization of the procedures.

An update on enzalutamide in the treatment of prostate cancer.

Enzalutamide is an oral androgen receptor inhibitor that targets multiple steps in the androgen receptor signaling pathway. In the randomized phase III AFFIRM study, significant improvements in survival versus placebo were observed when enzalutamide was used as a treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) following prior treatment with docetaxel. Additional benefits included significant delay in time to first skeletal-related event, and improvement in several measures of pain and health-related quality of life. Treatment effects were consistent across all prespecified subgroups. The phase III PREVAIL study evaluated enzalutamide versus placebo in patients with mCRPC who had not received chemotherapy. Enzalutamide significantly decreased the risk of radiographic progression and death. There were also significant improvements in all secondary and prespecified exploratory endpoints, including delayed initiation of chemotherapy, reduction in risk of first skeletal-related event and a high percentage of patients with objective response compared with placebo. Enzalutamide was also studied in hormone naïve patients (as monotherapy) in a small, open-label phase II study in patients with prostate cancer who were eligible for androgen-deprivation therapy. A prostate-specific antigen (PSA) response, defined as ⩾80% decline in PSA level from baseline at week 25, was achieved in 92.5% of patients. Long-term follow up is ongoing. Despite differences between these three trials, enzalutamide displayed a favorable safety profile in all three patient populations. Similar rates of adverse events between the enzalutamide and placebo groups were observed in AFFIRM and PREVAIL, with fatigue, diarrhea, back pain and hot flashes being more common with enzalutamide than with placebo. Hypertension was reported at a higher rate in the enzalutamide group than in the placebo group in PREVAIL. Breast-related disorders associated with enzalutamide treatment were also reported in the Monotherapy trial. Few seizures were reported in any trial. Enzalutamide is being studied in several early disease state populations.

FFR- and Angiography-Guided Provisional Side Branch Stenting Offer Similar Benefits

Results of the Comparison of FFR-guided and Angiography-guided Provisional Stenting for True Coronary Bifurcation Lesions: A Randomized, Multi-center Clinical Trial [DKCRUSH-VI] show that fractional flow reserve (FFR)-guided and angiography-guided provisional side branch stenting of true coronary bifurcation lesions are associated with similar rates of 1-year major adverse cardiac events.

Interleukin-1 inhibitors for acute gout.

Interleukin-1 inhibitors for acute gout.

Abstract 308: Percutaneous Coronary Intervention Outcomes in HIV+ and HIV- Patients

Background: Studies suggest HIV infected (HIV+) people have similar rates of major adverse cardiovascular events (MACE) after AMI and/or after percutaneous coronary interventions (PCI) compared to uninfected (HIV-) people. However, these studies were limited by a lack of CD4 cell count and/or stent type data. Low CD4 cell count and bare metal stents (BMS) are associated with higher MACE rates than high CD4 cell count and drug eluding stents (DES), respectively. Our study compared the rates and risk of MACE and mortality after PCI between HIV+ and HIV- stratified by stent type and CD4 cell count. Methods: We included 611 HIV+ and 1,564 HIV- from the Veterans Aging Cohort Study Virtual Cohort, a prospective, longitudinal, observational study of HIV+ and 1:2 matched HIV- who underwent PCI with stent placement between 1/2002-1/2010. 1-year incidence rates (IR) per 1000 person years and 95% confidence intervals (CI) for MACE and mortality were calculated by HIV and CD4 (&lt;200/≥200 cells/mm3) status and stent type (BMS vs. DES). To compare 1-year MACE and mortality between HIV+ with CD4 &lt;200 and ≥200 to HIV-, hazard ratios (HR) were generated from multivariate Cox proportional hazards models adjusted for age, gender, race/ethnicity, hypertension, diabetes, dyslipidemia, smoking, hepatitis C, renal disease, anemia, and substance use. MACE was defined as a composite of repeat PCI, CABG, AMI using ICD9 and ICD10 codes and all-cause mortality. Results: There were 594 MACE including 108 deaths after PCI. Percent receiving DES was similar by HIV status (57% in HIV+ vs. 56% in HIV-). MACE rates were higher among those who received BMS (429.0, 95% CI 383.8-479.5) compared to DES (318.7, 95% CI 285.5-355.9), p=0.004 and the pattern is similar by HIV status. MACE rates were similar between HIV+ with CD4≥200 and HIV- (p=0.8), but higher for HIV+ with CD4&lt;200 (p&lt;0.001 compared to both HIV+ with CD4≥200 and HIV-). Mortality was also similar between HIV+ with CD4≥200 and HIV- (p=0.2), but higher for HIV+ with CD4&lt;200 (p&lt;0.01 compared to both HIV+ with CD4≥200 and HIV-). Adjusted HRs are shown in the table. Conclusion: Stent type received did not vary by HIV status. HIV+ with CD4&lt;200 have worse outcomes post PCI with stent placement than both HIV- and HIV+ with CD4≥200. Management of HIV may be important for decreasing MACE and mortality after PCI.

Outcome of appendicectomy in children performed in paediatric surgery units compared with general surgery units

Appendicectomy for acute appendicitis in children may be performed in specialist centres by paediatric surgeons or in general surgery units. Service provision and outcome of appendicectomy in children may differ between such units. This multicentre observational study included all children (aged less than 16 years) who had an appendicectomy at either a paediatric surgery unit or general surgery unit. The primary outcome was normal appendicectomy rate (NAR). Secondary outcomes included 30-day adverse events, use of ultrasound imaging and laparoscopy, and consultant involvement in procedures. Appendicectomies performed in 19 paediatric surgery units (242 children) and 54 general surgery units (461 children) were included. Children treated in paediatric surgery units were younger and more likely to have a preoperative ultrasound examination, a laparoscopic procedure, a consultant present at the procedure, and histologically advanced appendicitis than children treated in general surgery units. The unadjusted NAR was significantly lower in paediatric surgery units (odds ratio (OR) 0.37, 95 per cent confidence interval 0.23 to 0.59; P < 0.001), and the difference persisted after adjusting for age, sex and use of preoperative ultrasound imaging (OR 0.34, 0.21 to 0.57; P < 0.001). Female sex and preoperative ultrasonography, but not age, were significantly associated with normal appendicectomy in general surgery units but not in paediatric surgery units in this adjusted model. The unadjusted 30-day adverse event rate was higher in paediatric surgery units than in general surgery units (OR 1.90, 1.18 to 3.06; P = 0.011). When adjusted for case mix and consultant presence at surgery, no statistically significant relationship between centre type and 30-day adverse event rate existed (OR 1.59, 0.93 to 2.73; P = 0.091). The NAR in general surgery units was over twice that in paediatric surgery units. Despite a more severe case mix, paediatric surgery units had a similar 30-day adverse event rate to general surgery units. Service provision differs between paediatric and general surgery units.

Clinical outcomes after hybrid coronary revascularization versus coronary artery bypass surgery: a meta-analysis of 1,190 patients

Hybrid coronary revascularization (HCR) represents a minimally invasive revascularization strategy in which the durability of the internal mammary artery to left anterior descending artery graft is combined with percutaneous coronary intervention to treat remaining lesions. We performed a systematic review and meta-analysis to compare clinical outcomes after HCR with conventional coronary artery bypass graft (CABG) surgery. A comprehensive EMBASE and PUBMED search was performed for comparative studies evaluating in-hospital and 1-year death, myocardial infarction (MI), stroke, and repeat revascularization. Six observational studies (1 case control, 5 propensity adjusted) comprising 1,190 patients were included; 366 (30.8%) patients underwent HCR (185 staged and 181 concurrent), and 824 (69.2%) were treated with CABG (786 off-pump, 38 on-pump). Drug-eluting stents were used in 328 (89.6%) patients undergoing HCR. Hybrid coronary revascularization was associated with lower in-hospital need for blood transfusions, shorter length of stay, and faster return to work. No significant differences were found for the composite of death, MI, stroke, or repeat revascularization during hospitalization (odds ratio 0.63, 95% CI 0.25-1.58, P = .33) and at 1-year follow-up (odds ratio 0.49, 95% CI 0.20-1.24, P = .13). Comparisons of individual components showed no difference in all-cause mortality, MI, or stroke, but higher repeat revascularization among patients treated with HCR. Hybrid coronary revascularization is associated with lower morbidity and similar in-hospital and 1-year major adverse cerebrovascular or cardiac events rates, but greater requirement for repeat revascularization compared with CABG. Further exploration of this strategy with adequately powered randomized trials is warranted.

Liver biopsy: Analysis of results of two specialist teams.

To analyze the safety and the adequacy of a sample of liver biopsies (LB) obtained by gastroenterologist (G) and interventional radiologist (IR) teams. Medical records of consecutive patients evaluated at our GI unit from 01/01/2004 to 31/12/2010 for whom LB was considered necessary to diagnose and/or stage liver disease, both in the setting of day hospital and regular admission (RA) care, were retrieved and the data entered in a database. Patients were divided into two groups: one undergoing an ultrasonography (US)-assisted procedure by the G team and one undergoing US-guided biopsy by the IR team. For the first group, an intercostal approach (US-assisted) and a Menghini modified type needle 16 G (length 90 mm) were used. The IR team used a subcostal approach (US-guided) and a semiautomatic modified Menghini type needle 18 G (length 150 mm). All the biopsies were evaluated for appropriateness according to the current guidelines. The number of portal tracts present in each biopsy was assessed by a revision performed by a single pathologist unaware of the previous pathology report. Clinical, laboratory and demographic patient characteristics, the adverse events rate and the diagnostic adequacy of LB were analyzed. During the study period, 226 patients, 126 males (56%) and 100 females (44%), underwent LB: 167 (74%) were carried out by the G team, whereas 59 (26%) by the IR team. LB was mostly performed in a day hospital setting by the G team, while IR completed more procedures on inpatients (P < 0.0001). The groups did not differ in median age, body mass index (BMI), presence of comorbidities and coagulation parameters. Complications occurred in 26 patients (16 G team vs 10 IR team, P = 0.15). Most gross samples obtained were considered suitable for basal histological evaluation, with no difference among the two teams (96.4% G team vs 91.5% IR, P = 0.16). However, the samples obtained by the G team had a higher mean number of portal tracts (G team 9.5 ± 4.8; range 1-29 vs IR team 7.8 ± 4.1; range 1-20) (P = 0.0192) and a longer mean length (G team 22 mm ± 8.8 vs IR team 15 ± 6.5 mm) (P = 0.0001). LB can be performed with similar outcomes both by G and IR. Use of larger dimension needles allows obtaining better samples, with a similar rate of adverse events.