Recent Publications by CFE Educators

Solid organ transplantation in human immunodeficiency virus 1 (HIV)-infected individuals requiring the concomitant use of immunosuppressants (IS) [e.g. cyclosporine (CsA) or tacrolimus (TAC)] and antiretrovirals (ARVs) [e.g. protease inhibitors (PIs) and/or non-nucleoside reverse transcriptase inhibitors (NNRTIs)] is complicated by significant drug interactions. This paper describes the pharmacokinetics of CsA and TAC in 52 patients on both IS and NNRTIs, PIs or combined NNRTIs + PIs, in studies conducted at 2 weeks, 3, 6, 12 and 24 months after transplantation. Cyclosporine and TAC blood concentrations were measured by LC/MS/MS. This multisubject, varied ARV-IS drug combination, longitudinal observational patient study provided a unique opportunity to examine the effect of different ARV drugs on IS pharmacokinetics (PK) by comparing the ratios of parameters over time and between PK parameters. Subjects taking concomitant PIs exhibited increases in CsA and TAC exposure (AUC/dose) due to the increased apparent oral bioavailability and decreased apparent oral clearance. Those subjects taking CsA and concomitant efavirenz (EFV) showed time dependent increases in exposure due to ~30% increases in the apparent oral bioavailability over time as well as a decreased apparent oral clearance, while subjects on TAC and EFV showed time-dependent changes in all PK parameters. The increased bioavailability was not observed in patients on CsA and nevirapine (NVP). These differences between IS drugs and the changes in PK parameters are not easily predicted, illustrating the importance of continued therapeutic drug monitoring in patients on these complex medication regimens. Published 2013. This article is a U.S. Government work and is in the public domain in the USA.

BACKGROUND

Periodontitis is the most common chronic inflammatory condition worldwide and is associated with incident coronary disease.

HYPOTHESIS

We hypothesized that periodontal disease would also be associated with cardiac calcification, a condition which shares many risk factors with atherosclerosis and is considered a marker of subclinical atherosclerosis.

METHODS

Cross-sectional study at two sites (USA and Japan) involving subjects with both clinical echocardiograms and detailed dental examinations. Semiquantitative scoring systems were used to assess severity of periodontal disease and echocardiographic calcification.

RESULTS

Fifty-six of 73 subjects (77%) had cardiac calcifications, and 51% had moderate to severe periodontal disease (score > 2). In unadjusted analysis, a significant relationship between periodontal score and cardiac calcification (Spearman rho = 0.4, P = 0.001) was noted, with increases in mean calcification score seen across increasing levels of periodontal disease. On multivariate logistic regression, adjusted for age, gender, race, glomerular filtration rate, and traditional risk factors, this association remained significant (P = 0.024). There was no significant interaction by study site, race, or gender.

CONCLUSIONS

In a multiracial population, we found a significant association between the degree of periodontal disease, a chronic inflammatory condition, and cardiac calcification. Further, higher periodontal scores were associated with greater degrees of calcification.

BACKGROUND

Experts can accurately characterize the histology of diminutive polyps with narrow-band imaging (NBI). There are limited data on the performance of non-experts.

OBJECTIVE

To assess the impact of a computer-based teaching module on the accuracy of predicting polyp histology with NBI by non-experts (in academics and community practice) by using video clips.

DESIGN

Prospective, observational study.

SETTING

Academic and community practice.

PARTICIPANTS

A total of 15 gastroenterologists participated-5 experts in NBI, 5 non-experts in academic practice, and 5 non-experts in community practice.

INTERVENTION

Participants reviewed a 20-minute, computer-based teaching module outlining the different NBI features for hyperplastic and adenomatous polyps.

MAIN OUTCOME MEASUREMENTS

Performance characteristics in characterizing the histology of diminutive polyps with NBI by using short video clips before (pretest) and after (posttest) reviewing the teaching module.

RESULTS

Non-experts in academic practice showed a significant improvement in the sensitivity (54% vs 79%; P  .001), accuracy (64% vs 81%; P  .001), and proportion of high-confidence diagnoses (49% vs 69%; P  .001) in the posttest. Non-experts in community practice had significantly higher sensitivity (58% vs 75%; P = .004), specificity (76% vs 90%; P = .04), accuracy (64% vs 81%; P  .001), and proportion of high-confidence diagnoses (49% vs 72%; P  .001) in the posttest. Performance of experts in NBI was significantly better than non-experts in both academic and community practice.

LIMITATIONS

Selection bias in selecting good quality videos. Performance not assessed during live colonoscopy.

CONCLUSION

Academic and community gastroenterologists without prior experience in NBI can achieve significant improvements in characterizing diminutive polyp histology after a brief computer-based training. The durability of these results and applicability in everyday practice are uncertain.

BACKGROUND

The tall cell variant of papillary thyroid carcinoma is an aggressive subtype that generally presents as a large tumor in the advanced stage; however, little is known about the tall cell variant of microcarcinoma (tumors measuring 1 cm). In this study, we compare the tall cell variant of microcarcinoma (microTCV) with classic papillary microcarcinomas to examine the hypothesis that, despite the small size, the microTCV may be more aggressive than the classic papillary microcarcinoma.

METHODS

We identified 27 microTCV patients and compared their clinicopathologic features and BRAF(V600E) mutational status with classic papillary microcarcinomas matched by age and size. The patients with microTCV included 22 women and 5 men aged 33 to 74 years (median age, 56 years). All patients underwent total thyroidectomy; 20 patients had lymph node dissection.

RESULTS

Tumor size in microTCV patients ranged from 2 mm to 10 mm (median, 7 mm). Extrathyroidal extension and lymphovascular invasion were seen in 9 (33%) and 4 (15%) tumors, respectively. Thirteen patients (48%) harbored multifocal papillary carcinomas. Metastasis to central compartment lymph nodes was seen in 8 patients and to lateral cervical nodes in 3 patients. Nine of the 25 patients (36%) presented at an advanced stage (stage III/IVA). The BRAF(V600E) mutation was detected in 25 of 27 tumors (92.6%). In contrast, age- and size-matched classic papillary microcarcinomas (n=26) showed no extrathyroidal extension (p=0.002), lymphovascular invasion in 1, central compartment lymph node metastasis in 2, lateral cervical node metastasis in 1, multifocal tumors in 10 (38.5%), the BRAF(V600E) mutation in 20 (76.9%), and it infrequently presented in stage III/IVA (7.7%, p=0.02).

CONCLUSIONS

The microTCV form is associated with aggressive features at presentation, and it should be differentiated from other papillary thyroid microcarcinomas.

OBJECTIVE

To assess readiness of general surgery graduate trainees entering accredited surgical subspecialty fellowships in North America.

METHODS

A multidomain, global assessment survey designed by the Fellowship Council research committee was electronically sent to all subspecialty program directors. Respondents spanned minimally invasive surgery, bariatric, colorectal, hepatobiliary, and thoracic specialties. There were 46 quantitative questions distributed across 5 domains and 1 or more reflective qualitative questions/domains.

RESULTS

There was a 63% response rate (n = 91/145). Of respondent program directors, 21% felt that new fellows arrived unprepared for the operating room, 38% demonstrated lack of patient ownership, 30% could not independently perform a laparoscopic cholecystectomy, and 66% were deemed unable to operate for 30 unsupervised minutes of a major procedure. With regard to laparoscopic skills, 30% could not atraumatically manipulate tissue, 26% could not recognize anatomical planes, and 56% could not suture. Furthermore, 28% of fellows were not familiar with therapeutic options and 24% were unable to recognize early signs of complications. Finally, it was felt that the majority of new fellows were unable to conceive, design, and conduct research/academic projects. Thematic clustering of qualitative data revealed deficits in domains of operative autonomy, progressive responsibility, longitudinal follow-up, and scholarly focus after general surgery education.

OBJECTIVES

Iliosacral fixation of unstable pelvic fractures does not produce enough stability to allow for immediate postoperative weight bearing. Triangular osteosynthesis creates additional resistance to vertical displacement and rotation. A disadvantage is the loss of the L5/S1 motion segment. We propose a modification of the standard triangular osteosynthesis construct in which the contralateral S1 pedicle is used. As the ipsilateral L5 pedicle is unavailable for fixation in a saw-bones composite pelvic model, we compared ipsilateral and contralateral S1 pedicle screw constructs. We hypothesized that ipsilateral and contralateral S1 pedicle screw constructs would demonstrate no difference in displacement or rotation.

METHODS

Seven saw bones pelvic models were tested. A 5-mm vertical fracture gap was created through the left sacrum while the pubic symphysis was completely dissociated. Each pelvis was tested sequentially in 4 triangular osteosynthesis configurations: ipsilateral S1 screw with anterior plate, contralateral S1 screw with anterior plate, contralateral S1 screw without anterior plate, and ipsilateral S1 screw without anterior plate. Specimens were cyclically loaded from 100-200 N at 0.25 Hz for 25 cycles and then loaded up to 300 N at 10 mm/min while displacement and rotation at the sacral and pubic fracture sites were measured.

RESULTS

There was no difference in any of the displacement measures between ipsilateral and contralateral constructs. When comparing rotation, the contralateral configuration experienced significantly less rotation than the ipsilateral configuration with and without the anterior plate applied.

CONCLUSIONS

Within the limitations of the current model, contralateral S1 constructs for modified triangular osteosynthesis were biomechanically equal to ipsilateral constructs in preventing displacement and superior in preventing rotation.

BACKGROUND

Large randomized trials have reported mixed results regarding the risk of bradycardia between metoprolol and carvedilol. We compared the incidence of emergent bradycardia (measured by an emergency department visit or hospitalization due to bradycardia) for patients initiating metoprolol and carvedilol.

METHODS

Adult beneficiaries of Medi-Cal, the State of California Medicaid program, without a diagnosis of bradycardia who initiated metoprolol or carvedilol between May 1, 2004, and November 1, 2009, were included. Cox proportional hazard regression analysis was performed to model the time to first occurrence of emergent bradycardia after initiation of the study drugs as a dependent variable and the study drug (metoprolol vs carvedilol) as the primary predictor with adjustments for total daily metoprolol-equivalent dose, formulations, and use of nonstudy drugs as time-varying covariates, as well as demographics and comorbidities.

RESULTS

Among 38,186 subjects, 77.7% initiated metoprolol and 22.3% initiated carvedilol. The incidence of emergent bradycardia was low and comparable between the drugs (18.1 per 1000 person-years using metoprolol vs 17.7 per 100 person-years using carvedilol; unadjusted hazard ratio, 1.07; 95% confidence interval, 0.76-1.49). However, carvedilol users had substantially different population characteristics compared with metoprolol users. After adjustments for demographics, comorbidities, metoprolol-equivalent dose, formulations, and use of nonstudy drugs, initiation of metoprolol was associated with an increased risk of emergent bradycardia compared with that of carvedilol (adjusted hazard ratio, 1.64; 95% confidence interval, 1.14-2.36).

CONCLUSIONS

Initiation of metoprolol is associated with an increased risk of emergent bradycardia compared with carvedilol, although the overall incidence of emergent bradycardia is low in routine clinical practice.

OBJECTIVE

To determine the frequency and clinical predictors of seizures and markers of epileptiform activity in a noncritically ill general inpatient population.

PATIENTS AND METHODS

We performed a retrospective cohort study of patients 18 years and older who underwent inpatient electroencephalography (EEG) between January 1, 2005, and December 31, 2010, for an indication of spells or altered mental status. The EEGs and reports were reviewed for ictal activity, interictal epileptiform abnormalities, and nonepileptiform abnormalities. Demographic and clinical data were gathered from the electronic medical record to determine seizure predictors.

RESULTS

Of 2235 patients screened, 1048 met the inclusion criteria, of which 825 (78.7%) had an abnormal EEG finding. Seizures occurred in 78 of 1048 patients (7.4%), and interictal epileptiform discharges were noted in 194 of 1048 patients (18.5%). An intracranial mass and spells as the indication for the EEG were independently associated with the group of patients experiencing seizures in a multivariate logistic regression model (adjusted for age, sex, EEG indication, intracranial mass, stroke, and history of epilepsy). Ninety-seven percent of patients (69 of 71) experienced their first seizure within 24 hours of monitoring, and the presence of seizures was associated with a lower likelihood of being discharged (odds ratio, 0.45; 95% CI, 0.27-0.76).

CONCLUSION

Seizures occurred at a high frequency in hospitalized patients with spells and altered mental status. The EEG may be an underused investigative tool in the hospital with the potential to identify treatable causes of these common disorders.