Structural and pharmacological profile of generic enoxaparins used in Brazil

Generic active pharmaceutical ingredients (APIs) have been commonly used in Brazil, since 1999, but most of them are synthetic and small molecules. Recently, a large number of generic enoxaparins were introduced into the market raising concerns related to product-to-product interchangeability, efficiency, and drug counterfeiting. These drugs are produced from biological sources and their production involves complex procedures and purification processes. The present article evaluates several generic enoxaparins, structurally and pharmacologically, and compares them with the branded products. Structural analysis showed that the generic products are, indeed, quite similar to the branded products, however, this similarity cannot be extended to their pharmacological activities. The results showed that generic products must go through extensive structural, pharmacological, and clinical evaluation in order to assess their quality, efficacy and, ultimately, avoid drug counterfeiting before clinical use. Variation was also observed between the branded products, showing that such drugs must be at constant surveillance.     

Ischemic stroke in the setting of chronic immune thrombocytopenia in an elderly patient--a therapeutic dilemma

Chronic immune thrombocytopenia (ITP) carries a poor prognosis in the elderly patients. Increasing evidence proposes that a subgroup of patients with chronic ITP may be more susceptible to ischemic stroke. An 84-year-old Caucasian man with multiple ischemic stroke risk factors presented with acute onset of slurred speech, confusion, and unsteady gait. Physical examination and neurologic imaging were consistent with a new left thalamic infarct. Platelet counts ranged between 40 000 × 10(9)/L and 65 000 × 10(9) /L. Antiplatelet therapy for his newly acquired stroke was not initiated considering his low platelet counts and for mildly symptomatic thrombocytopenia, and the patient was discharged home. Both hematologic and neurologic guidelines for the management of chronic ITP and stroke have contradictory goals. Although anticoagulation is mandated in acute stroke, ITP causes low platelet counts that increase bleeding complications.     

Assessment of levels of vascular endothelial growth factor in patients with ESRD and its possible role in cardiovascular morbidity and mortality

Patients with end-stage renal disease (ESRD) are known to have an elevation of a variety of abnormal thrombotic and inflammatory markers associated with high cardiovascular mortality. Vascular endothelial growth factor (VEGF) is also dysregulated in ESRD but not much is known about the serum levels of VEGF in patients with ESRD. Published reports suggest that elevated levels of VEGF may be protective to the kidney during periods of acute injury and may maintain local glomerular function. Impaired production of VEGF may lead to proteinuria, hypertension, and thrombotic microangiopathy. However, its role in chronic kidney disease or ESRD remains undefined. In our study, we analyzed blood samples of 52 patients with ESRD on stable hemodialysis regimen and measured predialysis serum levels of VEGF and compared these with blood samples obtained from 50 healthy volunteers in order to study differences between baseline levels of VEGF and also attempted to determine its role in ESRD-related cardiovascular mortality.     

Agreement and reproducibility of gray‐scale intravascular ultrasound and optical coherence tomography for the analysis of the bioresorbable vascular scaffold

Objective : To report the agreement between gray‐scale intravascular ultrasound (GS‐IVUS) and optical coherence tomography (OCT) in assessing the bioresorbable vascular scaffolds (BVS) structures and their respective reproducibility. Background : BVS are composed of an erodible polymer. Ultrasound and light signals backscattered from polymeric material differs from metallic stents using GS‐IVUS and OCT. Methods : Forty‐five patients included in the ABSORB trial were treated with a 3.0 × 18 mm BVS and imaged with GS‐IVUS 20 MHz and OCT post‐implantation. Qualitative (ISA, side‐branch struts, protrusion, and dissections) and quantitative (number of struts, lumen, and scaffold area) measurements were assessed by two investigators. The agreement and the inter‐ and intraobserver reproducibility were investigated using the kappa (κ) and the interclass correlation coefficient (ICC). Results : GS‐IVUS and OCT agreement was predominantly poor at a lesion, frame, and strut level analysis (κ and ICC <0.4) for qualitative measurements. GS‐IVUS demonstrated a reduced ability to detect cross‐sections with ISA (4.5% vs. 20.6%), side‐branch (SB) struts (6.3% vs. 7.8%), protrusions (3.2% vs. 9.6%), and dissections (0.2% vs. 9.0%) compared with OCT. GS‐IVUS reproducibility was poor–moderate (κ and ICC <0.6) except for ISA and SB‐struts (κ and ICC between 0.2 and 0.75). OCT showed an excellent reproducibility (κ and ICC > 0.75) except for the assessment of tissue protrusion (κ and ICC between 0.47 and 0.94). GS‐IVUS reproducibility was poor–moderate (ICC ≤ 0.5) in assessing the number of struts but excellent with OCT (ICC > 0.85). The reproducibility to assess lumen and scaffold areas was excellent using both techniques (ICC > 0.85). Conclusions : GS‐IVUS has a poor capacity to detect qualitative findings post‐BVS implantation and its reproducibility is low compared with OCT. The use of GS‐IVUS should be limited when assessing lumen and scaffold areas. © 2011 Wiley Periodicals, Inc.     

Optimal projection for transcatheter aortic valve implantation determined from the reference projection angles

Introduction : An optimal fluoroscopic working view projection (OP) with all three aortic sinuses aligned is crucial during trans‐catheter aortic valve implantation (TAVI). The aim of this study was to identify simple reference projection angles, which would act as a starting point for the operator to help determine OP for patients undergoing TAVI. Methods : During the period under consideration, 50 patients underwent TAVI. Procedural data and outcomes were collected prospectively on a dedicated database. Optimal angiographic deployment angles were achieved for all patients by starting in an anteroposterior caudal 15 degrees projection and then adjusting according to the initial image, with multiple small volume contrast injections undertaken to determine when all three aortic cusps were aligned (OP). Results : OP angles for the 50 cases were plotted on a graph. After normality testing confirmed that all angles were normally distributed, regression analysis enabled a regression line to be calculated. The equation for the regression line was defined as cranial/caudal intercept ?16.4 ± 1.5 (SE of the coefficient), P < 0.0001, slope of regression line LAO/RAO + 0.53 ± 0.1 (SE of the coefficient SE), P < 0.0001). Conclusions : As the regression line and its equation represents an acceptable estimate of the true relationship between Cranial/Caudal and LAO/RAO, to determine OP while remaining close to the regression line we suggest starting in LAO = 8.9, Caudal = ?11.4 (which represent the mean values of these two variables), and then increasing the caudal angle by approximately 0.5 degrees for every increase of 1 degree of the LAO angle or decreasing the caudal angle by 0.53 degrees for every decrease of 1 degree in LAO until all three aortic sinuses are in line which represents OP. © 2012 Wiley Periodicals, Inc.     

Managing scaphoid fractures. How we do it?

The scaphoid is the common carpal bone to be fractured. Proper clinical and radiological evaluation is required to establish it's diagnosis. The management of acute fractures includes conservative treatment with cast in minimally displaced to open reduction and internal fixation in case of displaced ones. The established nonunion requires open reduction, bone grafting and internal fixation.     

The effect of low concentrations versus high concentrations of local anesthetics for labour analgesia on obstetric and anesthetic outcomes: a meta-analysis

Introduction

The influence that different concentrations of labour epidural local anesthetic have on assisted vaginal delivery (AVD) and many obstetric outcomes and side effects is uncertain. The purpose of this meta-analysis was to determine whether local anesthetics utilized at low concentrations (LCs) during labour are associated with a decreased incidence of AVD when compared with high concentrations (HCs).

Methods

We searched PubMed, Ovid EMBASE, Ovid MEDLINE, CINAHL, Scopus, clinicaltrials.gov, and Cochrane databases for randomized controlled trials of labouring patients that compared LCs (defined as ≤ 0.1% epidural bupivacaine or ≤ 0.17% ropivacaine) of epidural local anesthetic with HCs for maintenance of analgesia. The primary outcome was AVD and secondary outcomes included Cesarean delivery, duration of labour, analgesia, side effects (nausea and vomiting, motor block, hypotension, pruritus, and urinary retention), and neonatal outcomes. The odds ratios (OR) or weighted mean differences (WMD) and 95% confidence intervals (CI) were calculated using random effects modelling. An OR < 1 or a WMD < 0 favoured LCs.

Results

Eleven studies met our criteria (eight bupivacaine and three ropivacaine studies), providing 1,145 patients in the LCs group and 852 patients in the HCs group for analysis of the primary outcome. Low concentrations were associated with a reduction in the incidence of AVD (OR = 0.70; 95% CI 0.56 to 0.86; P < 0.001). There was no difference in the incidence of Cesarean delivery (OR 1.05; 95% CI 0.82 to 1.33; P = 0.7). The LCs group had less motor block (OR 3.9; 95% CI 1.59 to 9.55; P = 0.003), greater ambulation (OR 2.8; 95% CI 1.1 to 7.14; P = 0.03), less urinary retention (OR 0.42; 95% CI 0.23 to 0.73; P = 0.002), and a shorter second stage of labour (WMD ?14.03; 95% CI ?27.52 to ?0.55; P = 0.04) compared with the HCs group. There were no differences between groups in pain scores, maternal nausea and vomiting, hypotension, fetal heart rate abnormalities, five-minute Apgar scores, and need for neonatal resuscitation. One-minute Apgar scores < 7 favoured the HCs group (OR 1.53; 95% CI 1.07 to 2.21; P = 0.02), and there was more pruritus in the LCs group (OR 3.36; 95% CI 1.00 to 11.31; P = 0.05).

Conclusion

When compared with HCs of local anesthetics, the use of LCs for labour epidural analgesia reduces the incidence of AVD. This may be due to a reduction in the amount of local anesthetic used and the subsequent decrease in motor blockade. We therefore recommend the use of LCs of local anesthetics for epidural analgesia to optimize obstetric outcome.     

“GIOSAT”: a tool to assess CanMEDS competencies during simulated crises

Purpose

Our objective was to develop and evaluate a Generic Integrated Objective Structured Assessment Tool (GIOSAT) to integrate Medical Expert and intrinsic (non-medical expert) CanMEDS competencies with non-technical skills for crisis simulation.

Methods

An assessment tool was designed and piloted using two pediatric anesthesia scenarios (laryngospasm and hyperkalemia). Following revision of the tool, we used previously recorded videos of anesthesia residents (n = 50) who managed one of two intraoperative advanced cardiac life support (ACLS) scenarios (ventricular tachycardia or ventricular fibrillation). Four independent trained raters, blinded to the residents’ level of training, analyzed the video recordings using the GIOSAT scale. Inter-rater reliability was calculated using intraclass correlations (ICCs) for single raters (single measure) and the average of the four raters (average measure), and construct validity was investigated by correlating GIOSAT scores with postgraduate year of residency (PGY).

Results

Total GIOSAT scores for the ACLS scenarios had single measure ICCs of 0.62 and average measure ICCs of 0.85. Inter-rater reliability was substantial for both Medical Expert and intrinsic competencies (single measure ICCs 0.69 and 0.62, respectively; average measure ICCs 0.90 and 0.82, respectively). We found significant correlations between PGY level and total GIOSAT score (r = 0.36; P = 0.011) and between PGY level and Medical Expert competencies (r = 0.42; P = 0.003); however, correlations were not found between PGY level and intrinsic CanMEDS competencies (r = 0.24; P = 0.09).

Conclusion

Inter-rater reliability of the total GIOSAT scores using four trained raters was substantial. Significant correlation between PGY and (i) total GIOSAT score and (ii) Medical Expert competencies supports construct validity. Evidence of validity was not obtained for intrinsic CanMEDS competencies.     

The difficult airway with recommendations for management – Part 1 – Difficult tracheal intubation encountered in an unconscious/induced patient

Background

Previously active in the mid-1990s, the Canadian Airway Focus Group (CAFG) studied the unanticipated difficult airway and made recommendations on management in a 1998 publication. The CAFG has since reconvened to examine more recent scientific literature on airway management. The Focus Group’s mandate for this article was to arrive at updated practice recommendations for management of the unconscious/induced patient in whom difficult or failed tracheal intubation is encountered.

Methods

Nineteen clinicians with backgrounds in anesthesia, emergency medicine, and intensive care joined this iteration of the CAFG. Each member was assigned topics and conducted reviews of Medline, EMBASE, and Cochrane databases. Results were presented and discussed during multiple teleconferences and two face-to-face meetings. When appropriate, evidence- or consensus-based recommendations were made together with assigned levels of evidence modelled after previously published criteria.

Conclusions

The clinician must be aware of the potential for harm to the patient that can occur with multiple attempts at tracheal intubation. This likelihood can be minimized by moving early from an unsuccessful primary intubation technique to an alternative “Plan B” technique if oxygenation by face mask or ventilation using a supraglottic device is non-problematic. Irrespective of the technique(s) used, failure to achieve successful tracheal intubation in a maximum of three attempts defines failed tracheal intubation and signals the need to engage an exit strategy. Failure to oxygenate by face mask or supraglottic device ventilation occurring in conjunction with failed tracheal intubation defines a failed oxygenation, “cannot intubate, cannot oxygenate” situation. Cricothyrotomy must then be undertaken without delay, although if not already tried, an expedited and concurrent attempt can be made to place a supraglottic device.     

Cytoreductive Surgery and Hyperthermic Intraperitoneal Chemotherapy in Asian Patients: 100 Consecutive Patients in a Single Institution

Background

Cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) have been shown to improve survival in selected patients with peritoneal carcinomatosis. We review our institutional experience with the procedure and evaluate the overall survival (OS) and disease-free survival (DFS) rates in 100 consecutive patients.

Methods

Data were prospectively collected from 100 consecutive patients with peritoneal carcinomatosis treated by CRS and HIPEC at the National Cancer Centre Singapore between April 2001 and May 2012. Our primary end points were OS and DFS.

Results

Of the 100 patients, 84 were of Chinese ethnicity, 3 were Malay, 6 were Indian, and 7 were of other ethnicities. Primary tumors were ovarian cancer (n = 39), colorectal cancer (n = 28), primary peritoneal (n = 6), appendiceal cancer (n = 20), and mesothelioma (n = 7). Median follow-up duration was 21 months. At 5 years, the DFS was 26.3 % and OS was 50.9 %. Factors influencing OS and DFS were cytoreductive score, primary cancer, and disease-free interval of more than 12 months on univariate analysis. The only factors that remained significant for prognosis after multivariate analysis were primary cancer and cytoreductive score. Thirty-day morbidity was 56 %, and there were no 30-day mortalities.

Conclusions

CRS and HIPEC can be safely carried out in Asian patients with peritoneal carcinomatosis from ovarian, colorectal, appendiceal, mesothelioma, and primary peritoneal origins. Overall, the ovarian, appendiceal, mesothelioma, and primary peritoneal cancer patients tended to do better than the colorectal patients, but careful patient selection ensuring that optimal cytoreduction can be achieved is essential for the success of this procedure.