Recent Publications by CFE Educators

BACKGROUND

Although untreated human immunodeficiency virus (HIV)-infected patients maintaining undetectable plasma HIV RNA levels (elite controllers) have high HIV-specific immune responses, it is unclear whether they experience abnormal levels of T cell activation, potentially contributing to immunodeficiency.

METHODS

We compared percentages of activated (CD38(+)HLA-DR(+)) T cells between 30 elite controllers, 47 HIV-uninfected individuals, 187 HIV-infected individuals with undetectable viremia receiving antiretroviral therapy (antiretroviral therapy suppressed), and 66 untreated HIV-infected individuals with detectable viremia. Because mucosal translocation of bacterial products may contribute to T cell activation in HIV infection, we also measured plasma lipopolysaccharide (LPS) levels.

RESULTS

Although the median CD4(+) cell count in controllers was 727 cells/mm(3), 3 (10%) had CD4(+) cell counts 350 cells/mm(3) and 2 (7%) had acquired immunodeficiency syndrome. Controllers had higher CD4(+) and CD8(+) cell activation levels (P .001 for both) than HIV-negative subjects and higher CD8(+) cell activation levels than the antiretroviral therapy suppressed (P = .048). In controllers, higher CD4(+) and CD8(+) T cell activation was associated with lower CD4(+) cell counts (P = .009 and P = .047). Controllers had higher LPS levels than HIV-negative subjects (P .001), and in controllers higher LPS level was associated with higher CD8(+) T cell activation (P = .039).

CONCLUSION

HIV controllers have abnormally high T cell activation levels, which may contribute to progressive CD4(+) T cell loss even without measurable viremia.

The oxidative DNA lesion, FaPydG rapidly anomerizes to form a mixture of the alpha and beta anomer. To investigate the mutagenic potential of both forms, we prepared stabilized bioisosteric analogues of both configurational isomers and incorporated them into oligonucleotides. These were subsequently used for thermodynamic melting-point studies and for primer-extension experiments. While the beta compound, in agreement with earlier data, prefers cytidine as the pairing partner, the alpha compound is not able form a stable base pair with any natural base. In primer-extension studies with the high-fidelity polymerase Bst Pol I, the polymerase was able to read through the lesion. The beta compound showed no strong mutagenic potential. The alpha compound, in contrast, strongly destabilized DNA duplexes and also blocked all of the tested DNA polymerases, including two low-fidelity polymerases of the Y-family.

CONTEXT

The expression of adipogenic genes in sc adipose tissue has been reported to be lower among patients with HIV-associated lipoatrophy than HIV-uninfected controls. It is unclear whether this is a result or cause of lipoatrophy.

OBJECTIVE

The objective of the study was to investigate the temporal relationships among changes in adipogenic gene expression in sc adipose tissue and changes in body fat distribution and metabolic complications in HIV-infected subjects on antiretroviral therapy.

DESIGN

This was a prospective longitudinal study.

SETTING

The study was conducted at HIV clinics in Seattle, Washington.

PARTICIPANTS

The study population included 31 HIV-infected and 12 control subjects.

INTERVENTIONS

Subjects were followed up for 12 months after they initiated or modified their existing antiretroviral regimen.

MAIN OUTCOME MEASURES

Changes in body composition, plasma lipids, insulin sensitivity, and gene expression in sc abdominal and thigh adipose tissue.

RESULTS

Subjects who developed lipoatrophy (n=10) had elevated fasting triglycerides [3.16 (sd 2.79) mmol/liter] and reduced insulin sensitivity as measured by frequently sampled iv glucose tolerance test [1.89 (sd 1.27)x10(-4) min(-1)/microU.ml] after 12 months, whereas those without lipoatrophy (n=21) did not show any metabolic complications [triglycerides 1.32 (sd 0.58) mmol/liter, P=0.01 vs. lipoatrophy; insulin sensitivity 3.52 (sd 1.91)x10(-4) min(-1)/microU.ml, P=0.01 vs. lipoatrophy]. In subjects developing lipoatrophy, the expression of genes involved in adipocyte differentiation, lipid uptake, and local cortisol production in thigh adipose tissue was significantly reduced already at the 2-month visit, several months before any loss of extremity fat mass was evident.

CONCLUSIONS

In HIV-infected subjects, lipoatrophy is associated with elevated fasting triglycerides and insulin resistance and might be caused by a direct or indirect effect of antiretroviral drugs on sc adipocyte differentiation.

INTRODUCTION

The incidence of premature ejaculation (PE) and other sexual problems in infertile couples is unknown.

AIMS

We attempted to determine the prevalence of PE in infertile couples.

METHODS

Infertile couples presenting for evaluation at our institutions were invited to participate in our study. Multiple regression analysis was conducted to assess for associations between partner responses.

MAIN OUTCOME MEASURE

Respondents completed a demographic survey, the Short Form-36 (SF-36), and the Center for Epidemiological Studies Depression (CES-D) scale. Both partners also completed a gender-specific survey instrument to detect PE and distress related to the condition. Male partners completed the International Index of Erectile Function (IIEF) and the Self-Esteem and Relationship Quality (SEAR) scale. Female partners completed the Female Sexual Function Index (FSFI) and a modified version of the SEAR.

RESULTS

Fifty percent of men reported that they ejaculated more rapidly than they wished. When men reported PE, their partners agreed with the diagnosis in 47% of cases. Female partners of men who did not report PE reported PE in 11% of cases. Partner frustration related to PE was reported by 30% of men. Partners agreed that they were frustrated in 43% of these cases. Among the 70% of men who did not report partner frustration from PE, 93% of the partners agreed that they were not frustrated. There was a statistically significant negative association between male and female report of PE and SEAR scores. There were no other statistically significant associations between PE responses and demographic variables, IIEF, FSFI, CES-D, and SF-36 scores.

CONCLUSIONS

PE is prevalent among infertile couples although the perceived incidence of the condition among men is higher than partner perceived incidence. Additionally, many men may overestimate the level of partner frustration related to PE. PE is associated with lower relationship satisfaction in both men and women. Further research is required.

OBJECTIVES

To examine factors associated with the prevalence of elevated anti-thyroid peroxidase antibodies (ATPO) among iodine-deficient adolescents and young adults and test whether associations vary according to the presence of diffuse goitre.

DESIGN

Subjects were members of the Ukrainian-American Cohort Study exposed to the Chornobyl accident whose (131)I thyroid dose estimates were below 0.2 Gy.

MEASUREMENTS

The odds ratios (ORs) for ATPO above 60 U/ml were estimated using logistic regression models for a number of factors in the total population (N = 5133), and separately for thyroid disease-free subjects (N = 3875), those with diffuse goitre (N = 921), and diffuse goitre without autoimmune thyroiditis (AIT; N = 883).

RESULTS

Elevated ATPO was found in 9.9% of the total population and ORs were significantly higher in females, older individuals, those examined in earlier calendar years, residents of Kyiv and Chernihiv oblasts, subjects with a family history of thyroid disease, higher thyroid ultrasound volume, suppressed or elevated TSH, blood collection in March to May, very low thyroglobulin (Tg), and shorter serum storage time. When thyroid disease-free subjects and those with diffuse goitre were compared, there were few differences in antibody prevalence, and after excluding individuals with AIT, the only difference was an increased prevalence of elevated ATPO at low urinary iodine in those with goitre alone.

CONCLUSIONS

Although a number of factors are associated with the prevalence of elevated ATPO in our study group, with the exception of urinary iodine these factors are independent of goitre, and differences between thyroid disease-free subjects and those with diffuse goitre are largely due to AIT.

BACKGROUND

Residents have primary responsibility for teaching medical students, yet many receive no formal teaching instruction. This study evaluated the impact of a longitudinal multidisciplinary teaching curriculum on resident participants' self-perceived teaching skills.

METHODS

Residents received instruction on teaching and leadership skills during a four-month longitudinal teaching course. Participants completed a validated pre-post self-assessment inventory for teaching and a teaching self-efficacy survey.

RESULTS

Participants' self-rated teaching skills significantly increased in all categories of the self-assessment inventory for teaching. Self-efficacy survey results revealed statistically significant increased participant confidence in all teaching skills. Residents were very satisfied with course content.

CONCLUSION

Residents are eager to improve their teaching skills and benefit from a multidisciplinary learning group. A successful teaching curriculum increases resident interest in teaching and impacts self-efficacy and self-assessed teaching skills.

CONTEXT

Thyroid disease is common, and thyroidectomy is a mainstay of treatment for many benign and malignant thyroid conditions. Overall, thyroidectomy is associated with favorable outcomes, particularly if experienced surgeons perform it.

OBJECTIVE

To examine racial differences in clinical and economic outcomes of patients undergoing thyroidectomy in the United States.

DESIGN, SETTING, PATIENTS

The nationwide inpatient sample was used to identify thyroidectomy admissions from 1999 to 2004, using ICD-9 procedure codes. Race and other clinical and demographic characteristics of patients were collected along with surgeon volume and hospital characteristics to predict outcomes.

MAIN OUTCOME MEASURES

Inpatient mortality, complication rates, length of stay (LOS), discharge status, and mean total costs by racial group.

RESULTS

In 2003-2004, 16,878 patients underwent thyroid procedures; 71% were white, 14% black, 9% Hispanic, and 6% other. Mean LOS was longer for blacks (2.5 days) than for whites (1.8 days, P 0.001); Hispanics had an intermediate LOS (2.2 days). Although rare, in-hospital mortality was higher for blacks (0.4%) compared with that for other races (0.1%, P 0.001). Blacks trended toward higher overall complication rates (4.9%) compared with whites (3.8%) and Hispanics (3.6%, P = 0.056). Mean total costs were significantly lower for whites ($5447/patient) compared with those for blacks ($6587) and Hispanics ($6294). The majority of Hispanics (55%) and blacks (52%) had surgery by the lowest-volume surgeons (1-9 cases per year), compared with only 44% of whites. Highest-volume surgeons (>100 cases per year) performed 5% of thyroidectomies, but 90% of their patients were white (P 0.001). Racial disparities in outcomes persist after adjustment for surgeon volume group.

CONCLUSIONS

These findings suggest that, although thyroidectomy is considered safe, significant racial disparities exist in clinical and economic outcomes. In part, inequalities result from racial differences in access to experienced surgeons; more data are needed with regard to racial differences in thyroid biology and surveillance to explain the balance of observed disparities.

OBJECTIVE

Most US medical schools conduct comprehensive clinical skills assessments during Years 3 and 4. This study explores strategies used to identify and remediate students who perform poorly on these assessments.

METHODS

In the academic year 2005-06, we conducted 33 semi-structured interviews with individuals responsible for standard setting in and remediation after their schools' comprehensive clinical skills assessments. We coded interviews to identify major themes.

RESULTS

Prior to remediation, some schools employed a 'verification' step to ensure the accuracy of the failing score or need for remediation. Participants described a remediation process that included some or all of 3 steps. Firstly, students' specific learning deficits were diagnosed. Next, students participated in remedial activities such as performance review sessions or practice with standardised or actual patients. Lastly, students were re-tested, usually with a shorter, more formative examination. All participants reported using a diagnostic step, most offered or required remedial activities and many re-tested, although schools varied in the emphasis placed on each step. Many participants cited the individualised attention students received from remediation faculty staff as a strength of their approach, although they raised concerns about the substantial time demands placed on remediation faculty. Most respondents reported some dissatisfaction with their school's remediation process, particularly uncertainty about efficacy or rigour.

CONCLUSIONS

Schools vary in the intensity and scope of remediation offered to students who perform poorly on clinical skills assessments. Although many schools invest significant resources in remediation, the effect of these efforts on students' subsequent clinical performance is unknown.

INTRODUCTION

Peyronie's disease (PD) is a poorly understood clinical entity. Aim. We endeavored to determine how contemporary urologists in the United States manage PD.

METHODS

A randomly generated mailing list of 996 practicing urologists was generated from the American Urologic Association member directory. A specifically designed survey was mailed with a cover letter and a postage-paid return envelope.

MAIN OUTCOME MEASURE

Our survey assessed several practice-related factors and asked questions of how the subject would manage various presentations of PD in their practice. Four cases were presented: case 1, a healthy 55-year-old man with painless 30 degrees dorsal curvature of 16 months duration; case 2, a 60-year-old man with 35 degrees dorsal curvature, 4/10 pain on visual analog scale, of 6 months duration; case 3, a 62-year-old man with painless 60 degrees dorsal curvature and erectile dysfunction responsive to alprostadil suppository of 2 years duration; and case 4, a 50-year-old man with mid-shaft waist deformity, foreshortening, no pain/curvature/erectile dysfunction.

RESULTS

Responses were received from 236 (24%) practicing urologists. Vitamin E was the preferred initial management for 70% of respondents, with observation, Potaba (Glenwood, Englewood, New Jersey, USA), colchicine, verapamil injections, and verapamil gel favored by 32, 20, 12, 7, and 10% of respondents, respectively. Fifty-seven percent of respondents performed surgery for PD, with penile prostheses, Nesbit procedure, grafting, and plication used by 76, 66, 55, and 51% of respondents, respectively. Medical therapy and/or observation was the preferred management for all of the cases except case 3, for which penile prosthesis placement and referral were the favored options by 39 and 30% of urologists, respectively.

CONCLUSIONS

Medical therapy is the initial treatment for PD among American urologists. Penile prosthesis is the treatment of choice in impotent patients. Most American urologists conform to recommended practice patterns in the management of PD.