Recent Publications by CFE Educators

BACKGROUND

The Ukrainian American Cohort Study was established to evaluate the risk of thyroid disorders in a group exposed as children and adolescents to 131I by the Chernobyl accident (arithmetic mean thyroid dose, 0.79 grays). Individuals are screened by palpation and ultrasound and are referred to surgery according to fine-needle aspiration biopsy (FNA). However, the accuracy of FNA cytology for detecting histopathologically confirmed malignancy after this level of internal exposure to radioiodines is unknown.

METHODS

During the first screening cycle (1998-2000), 13,243 individuals were examined, 356 individuals with thyroid nodules were referred for FNA, 288 individuals completed the procedure, 85 individuals were referred to surgery, 82 individuals underwent surgery, and preoperative cytology was available for review in 78 individuals. Cytologic interpretation for the nodule that resulted in surgical referral was correlated with final pathomorphology; discrepancies were reviewed retrospectively; and the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of FNA cytology were calculated.

RESULTS

All 24 cytologic interpretations that were definite for papillary thyroid cancer (PTC) were confirmed histopathologically (PPV, 100%); and, of 11 cytologic interpretations that were suspicious for PTC, 10 were confirmed (PPV, 90.9%). Ten of 41 FNAs that were interpreted as either definite or suspect for follicular neoplasm were confirmed as malignant (PPV, 24.4%), including 2 follicular thyroid cancers and 8 PTCs (all but 1 of the follicular or mixed subtypes). Depending on whether a cytologic interpretation of follicular neoplasm was considered "positive" or "negative," the sensitivity was 100% and 77.3%, respectively; similarly, the respective specificity was 17.6% and 97.1%, the respective PPV was 61.1% and 97.1%, and the respective NPV was 100% and 76.7%.

CONCLUSIONS

Among children and adolescents who were exposed to 131I after the Chernobyl accident and were evaluated 12 to 14 years later, thyroid cytology had a sensitivity and a predictive value similar to those reported in unexposed populations.

OBJECTIVE

The objective of the study was to examine risk factors for postterm (gestational age >or= 42 weeks) or prolonged (gestational age >or= 41 weeks) pregnancy.

STUDY DESIGN

We conducted a retrospective cohort study of all term, singleton pregnancies delivered at a mature, managed care organization. The primary outcome measures were the rates of pregnancies greater than 41 or 42 weeks' gestation. Multivariable logistic regression models were used to control for potential confounding and interaction.

RESULTS

Specific risk factors for pregnancy beyond 41 weeks of gestation include obesity (adjusted odds ratio [aOR], 1.26; 95% confidence interval [CI], 1.16-1.37), nulliparity (aOR, 1.46; 95% CI 1.42-1.51), and maternal age 30-39 years (aOR, 1.06; 95% CI, 1.02-1.10) and 40 years or older (aOR, 1.07; 95% CI, 1.02-1.12). Additionally, African American, Latina, and Asian race/ethnicity were all associated with a lower risk of reaching 41 or 42 weeks of gestation.

CONCLUSION

Our findings suggest that there may be biological differences that underlie the risk for women to progress to 41 or 42 weeks of gestation. In particular, obesity is a modifiable risk factor and could potentially be prevented with prepregnancy or interpregnancy interventions.

OBJECTIVES

To determine whether obesity increases the risk of urethroplasty failure.

METHODS

A total of 381 patients underwent urethroplasty and had complete body mass index (BMI) data. Stricture recurrence-free survival was defined as subjective and objective improvement in urinary flow, an absence of radiographic evidence of stricture, and no further need for urethral instrumentation. Cox proportional hazards regression analysis was used to identify both univariate and multivariate predictors of urethroplasty outcome.

RESULTS

The median patient age was 40 years (range 18-90). The median follow-up was 5.9 years (range 1 month to 10 years). Of the 381 patients, 60 developed recurrent stricture (15.7%). Overweight (BMI 25-30 kg/m(2)) and obese (BMI 30-35 kg/m(2)) patients were more likely to have urethroplasty failure, reaching significance and near significance on univariate and multivariate analysis, respectively (P = .03 and P = .07, respectively). Patients who were severely (BMI 35-40 kg/m(2)) or morbidly obese (BMI >40 kg/m(2)) did not have an increased risk of urethroplasty failure.

CONCLUSIONS

Although obesity's relationship with urethroplasty failure is not linear, it does appear to affect outcomes after urethroplasty.

BACKGROUND

Endoscopic necrosectomy is now an established minimally invasive method for treatment of organized pancreatic necrosis.

METHODS

Review of methods and results of endoscopic treatment of pancreatic necrosis.

RESULTS

Reports by multiple groups have demonstrated favorable results of endoscopic necrosectomy. The mortality of critically ill patients undergoing endoscopic treatment in several series is approximately 10%. Some patients will eventually also require surgery for situations such as complete pancreatic duct disruption, but even in these cases endoscopic necrosectomy is useful because pancreatic surgery can often be delayed until the patient is stable.

CONCLUSIONS

Endoscopic necrosectomy will likely assume an increasing role in the treatment of pancreatic necrosis. This should result in reduced morbidity and mortality in these critically ill patients.

Candida krusei is an uncommon cause of vaginitis and cystitis but is unique because of the management challenge it poses due to intrinsic resistance to fluconazole and flucytosine. We report a case of C. krusei vaginitis and cystitis successfully managed with topical vaginal and intravesical amphotericin B. The challenges in managing C. krusei cystitis and the role of amphotericin B bladder irrigation in the management of fungal urinary tract infections are discussed.

PURPOSE

The basic concepts of pharmacogenetics, pharmacogenetic study approaches, factors to consider when applying pharmacogenetic discoveries to patient care, and potential roles for pharmacists in pharmacogenetics are discussed.

SUMMARY

The Food and Drug Administration (FDA) has recognized pharmacogenomics as an opportunity to identify new biomarkers that may expedite the drug development process. Currently, there are over 50 drugs with pharmacogenetic discoveries on their labeling. Sequence variations in drug disposition genes can alter the pharmacokinetics of a drug, while sequence variations in drug target genes can change the pharmacodynamics of the drug. The two most common strategies to test a pharmacogenetic question are the candidate-gene approach and genomewide association study. Given the complex interplay among the many factors that influence a drug dose, determination of an appropriate dose of a particular drug for a given patient will eventually require knowledge about both genetic and nongenetic factors that affect drug disposition and pharmacodynamics. Many factors can influence the application of pharmacogenetic discoveries to patient care. Before these discoveries find widespread application in clinical practice, additional work is needed, including randomized clinical trials to evaluate the clinical utility of a pharmacogenetic test, the development of guidelines for the clinical use of various pharmacogenetic tests, and provider education on pharmacogenetics.

CONCLUSION

Pharmacogenetics has made significant progress in the past decade, and many pharmacogenetic discoveries have now been included on FDA-approved drug labeling. Pharmacogenetic discoveries may further promote safe and effective use of medications by more accurately predicting an individual's drug response.

OBJECTIVES

Possessing the epsilon4 allele of apolipoprotein E (APOE-epsilon4) genotype is associated with cognitive impairment in nondemented older adults. The authors hypothesized that they might find a subtype of depression related to impaired cognitive performance associated with the APOE-epsilon4 allele.

DESIGN

A survey conducted between 2001 and 2003 with APOE genotyping.

SETTING

Primary care offices in the Baltimore area.

PARTICIPANTS

The study sample consisted of 305 adults aged 65 or older with complete information on APOE genotyping and covariates.

MEASUREMENTS

The authors used the latent class model to classify respondents according to symptom criteria of American Psychiatric Association's Diagnostic and Statistical Manual as assessed in the Composite International Diagnostic Interview and the following four measures of cognitive function: the Mini-Mental State Exam, Hopkins Verbal Learning Test, Controlled Oral Word Association Test, and the Brief Test of Attention. The authors examined the relationship between class membership and APOE genotype.

RESULTS

The latent class model yielded three classes: a nondepressed class, a class with depressive symptoms and average cognitive functioning, and a class with depressive symptoms (particularly thoughts of death and suicide) and impaired cognitive functioning. Possessing at least one APOE-epsilon4 allele was not predictive of class membership.

CONCLUSION

A subgroup of elderly patients with depressive symptoms, cognitive impairment, and a high likelihood of experiencing thoughts of death or suicide may exist that may not be related to APOE-epsilon4. Subgroups of older patients with depressive symptoms may be important to identify because of the association with thoughts of death or suicide and cognitive impairment.

OBJECTIVES

Despite a recognised need to prepare future faculty members, little research has been conducted on how best to accomplish this task, especially among learners and faculty members within research-intensive medical schools.

METHODS

We interviewed 40 medical students, residents and faculty members from a single institution in the USA and asked questions about which careers the school does and should prepare individuals for, and the strengths of the institution for doing so. Interviews were conducted in person at a location chosen by the participant. All interviews were transcribed and coded using qualitative methods and software. The coding and themes were reviewed and discussed among members of the research team and verified by external reviewers.

RESULTS

We identified five themes related to becoming an academic doctor: early exposure to research; role models and mentoring; career pathways; interplay of personal and social factors, and career support for junior faculty members.

CONCLUSIONS

Results suggest that opportunities should be structured within undergraduate and graduate medical education to stimulate interest in careers as academic doctors and to aid junior faculty members to act as role models who can encourage learners to pursue careers in academic medicine.

INTRODUCTION

Bladder exstrophy is a rare urogenital abnormality. Other urogenital malformations have been associated with exposure to hormonal pesticide disruptors during critical developmental periods. This is the first report in the literature to associate household exposure to pesticides with bladder exstrophy.

CASE PRESENTATION

We describe the pediatric environmental history of a newborn baby boy with isolated bladder exstrophy. In this case the pediatric environmental history includes the constitutional, genealogical, genetic and environmental factors related to bladder exstrophy, which revealed a cockroach infestation in the parents' home and the daily use of bug spray to kill them. The mother used one bottle of spray every 2 days (1000cc) and more in the summer, when the problem was worse. During gestational weeks 0-12, the mother intensively used a domestic pesticide consisting of a mixture of pyrethroids (cyfenothrin 0.5%, and tetramethrin 0.31%) and pyriproxyfen (0.01%). She described repeated episodes of mild to moderate poisoning that are associated with the use of household pesticides. The mother is a housewife and the father works as a fumigator of fruit fields and he reported gastrointestinal symptoms associated with the use of occupational pesticides. However, he did not believe he carried traces of these products into the home and his wife washed his work clothes separately. The pyrethroids and pyriproxyfen were detected in a urine sample obtained from the child 4 months after he was born. No other risk factors were identified.

CONCLUSIONS

A detailed and carefully conducted pediatric environmental history, which includes information about home pesticide use, should be carried out for all children with bladder exstrophy. Domestic exposure to pesticides during critical developmental periods may have deleterious effects for the fetus.