A clone-directed approach may improve diagnosis and treatment of proliferative glomerulonephritis with monoclonal immunoglobulin deposits.

The optimal treatment for the monoclonal gammopathies of renal significance is not known, but there is consensus among experts that treatment should be specific for the underlying clone. The majority of patients with proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID) do not have an identifiable clone, and prior studies have found poor renal outcomes for patients with PGNMID treated with a variety of regimens. Here we present a retrospective case series of 19 patients with PGNMID with a more uniform, clone-directed approach. A circulating paraprotein was detected in 37% of patients, and the overall clone detection rate was 32%. Treatment was directed at the underlying clone or, for patients without a detectable clone, empirically prescribed to target the hypothesized underlying clone. Of the 16 patients who underwent treatment, the overall renal response rate was 88%, and 38% of patients experienced complete renal response (proteinuria reduction to under 0.5 gm/24 hours) with initial treatment. All patients were End Stage Renal Disease-free at last follow-up (median 693 days after diagnosis), and treatment was well tolerated. Thus, a clone-directed approach may lead to novel, targeted treatment strategies that could significantly improve outcomes for patients with PGNMID.

L-carnitine supplementation in dialysis: treatment in quest of disease.

L-Carnitine (LC) administration has been recommended for specific indications in dialysis patients, including epoetin-resistant anemia, intradialytic hypotension, cardiomyopathy, fatigue, muscle weakness, and exercise performance; it may ameliorate insulin resistance, inflammation, and protein wasting. Use of LC for anemia and intradialytic hypotension has been approved for reimbursement by the Centers for Medicare and Medicaid Services. Yet, the data to support these recommendations are inadequate and have not been bolstered over several decades. LC administration continues to appeal to nephrologists because its use in dialysis patients has an attractive rationale, it addresses problems that persist despite dialysis, it is safe, and the existing literature does not refute its use. Nevertheless, definitive trials to justify LC administration have not been conducted and are increasingly unlikely to be funded. In an era of shrinking resources and bundling of dialysis services, the use of LC in dialysis patients will, appropriately, diminish.

Institutional leadership and faculty response: fostering professionalism at the University of Pennsylvania School of Medicine.

Fostering professionalism requires institutional leadership and faculty buy-in. At the University of Pennsylvania School of Medicine, policies and educational programs were developed to enhance professionalism in three areas: conduct of clinical trials, relations with pharmaceutical manufacturers, and the clinical and teaching environment. Responsible conduct of clinical trials has been addressed with mandatory online education and certification for clinical investigators, but some still fail to recognize conflicts of interest. Activity of pharmaceutical representatives has been strictly regulated, meals and gifts from pharmaceutical companies prohibited, and the role of the pharmaceutical industry in the formulary process and in continuing medical education curtailed. Some faculty members have resented such restrictions, particularly in regard to their opportunity to give paid lectures. Professionalism in the clinical and teaching environment has been addressed with interdisciplinary rounding, experiential learning for medical students and residents in small groups, increased recognition of role models of professionalism, and active management of disruptive physicians. Leadership has been exerted through policy development, open communications, and moral suasion and example. Faculty members have expressed both their support and their reservations. Development of communication strategies continues, including town hall meetings, small groups and critical incident narratives, and individual feedback. The understanding and endorsement of faculty, staff, and trainees are an essential element of the professionalism effort.

Lessons in medical humanism: the case of Montaigne.

Michel de Montaigne, the great French humanist and inventor of the personal essay, suffered from frequent and severe renal colic. He wrote about his illness in his travel journal and in his last and greatest essay, "Of Experience." In his illness narratives, Montaigne integrated disease and suffering into his life and art. He humanized rather than conquered his disease. A mature humanism replaced his youthful Stoic philosophy of detachment and disengagement and provides a worthy model for our own medical humanism.

Mentoring at the University of Pennsylvania: results of a faculty survey.

BACKGROUND: Research suggests mentoring is related to career satisfaction and success. Most studies have focused on junior faculty. OBJECTIVE: To explore multiple aspects of mentoring at an academic medical center in relation to faculty rank, track, and gender. DESIGN: Cross-sectional mail survey in mid-2003. PARTICIPANTS: Faculty members, 1,432, at the University of Pennsylvania School of Medicine MEASUREMENTS: Self-administered survey developed from existing instruments and stakeholders. RESULTS: Response rate was 73% (n = 1,046). Most (92%) assistant and half (48%) of associate professors had a mentor. Assistant professors in the tenure track were most likely to have a mentor (98%). At both ranks, the faculty was given more types of advice than types of opportunities. Satisfaction with mentoring was correlated with the number of types of mentoring received (r = .48 and .53, P < .0001), job satisfaction (r = .44 and .31, P < .0001), meeting frequency (r = .53 and .61, P < .0001), and expectation of leaving the University within 5 years (Spearman r = -.19 and -.18, P < .0001), at the assistant and associate rank, respectively. Significant predictors of higher overall job satisfaction were associate rank [Odds ratio (OR) = 2.04, CI = 1.29-3.21], the 10-point mentoring satisfaction rating (OR = 1.27, CI = 1.17-1.35), and number of mentors (OR = 1.60, CI = 1.20-2.07). CONCLUSIONS: Having a mentor, or preferably, multiple mentors is strongly related to satisfaction with mentoring and overall job satisfaction. Surprisingly, few differences were related to gender. Mentoring of clinician-educators, research track faculty, and senior faculty, and the use of multiple mentors require specific attention of academic leadership and further study.

Effectiveness of a two-part educational intervention to improve hypertension control: a cluster-randomized trial.

STUDY OBJECTIVE: To measure the effectiveness of a multifaceted educational intervention to improve ambulatory hypertension control. DESIGN: Cluster-randomized trial. SETTING: Academic health system using an ambulatory electronic medical record. SUBJECTS: A total of 10,696 patients with a diagnosis of hypertension cared for by 93 primary care providers. INTERVENTION: Academic detailing, provision of provider-specific data about hypertension control, provision of educational materials to the provider, and provision of educational and motivational materials to patients. MEASUREMENTS AND MAIN RESULTS: The primary outcome was blood pressure control, defined as a blood pressure measurement below 140/90 mm Hg, and was ascertained from electronic medical records over 6 months of follow-up. We determined the adjusted odds ratio for the association between the intervention and the achievement of controlled blood pressure. When we accounted for clustering by provider, this adjusted odds ratio was 1.13 (95% confidence interval 0.87-1.47). Adjusted odds ratios were 1.03 (95% confidence interval 0.78-1.36) in patients whose blood pressure was controlled at baseline and 1.25 (95% confidence interval 0.94-1.65) in those whose blood pressure was not. These odds ratios were not significantly different (p=0.11). CONCLUSIONS: These results were consistent with no effect or, at best, a relatively modest effect of the intervention among patients with hypertension. Had we not included a concurrent control group, the data would have provided an unduly optimistic view of the effectiveness of the program. The effectiveness of future interventions may be improved by focusing on patients whose blood pressure is uncontrolled at baseline.

Pulmonary hypertension among end-stage renal failure patients following hemodialysis access thrombectomy.

PURPOSE: Percutaneous hemodialysis thrombectomy causes subclinical pulmonary emboli without short-term clinical consequence; the long-term effects on the pulmonary arterial vasculature are unknown. We compared the prevalence of pulmonary hypertension between patients who underwent one or more hemodialysis access thrombectomy procedures with controls without prior thrombectomy. METHODS: A retrospective case-control study was performed. Cases (n = 88) had undergone one or more hemodialysis graft thrombectomy procedures, with subsequent echocardiography during routine investigation of comorbid cardiovascular disease. Cases were compared with controls without end-stage renal disease (ESRD) (n = 100, group 1), and controls with ESRD but no prior thrombectomy procedures (n = 117, group 2). The presence and velocity of tricuspid regurgitation on echocardiography was used to determine the prevalence and grade of pulmonary hypertension; these were compared between cases and controls using the chi-square test and logistic regression. RESULTS: The prevalence of pulmonary hypertension among cases was 52% (46/88), consisting of mild, moderate and severe in 26% (n = 23), 10% (n = 9) and 16% (n = 14), respectively. Prevalence of pulmonary hypertension among group 1 controls was 26% (26/100), consisting of mild, moderate and severe pulmonary hypertension in 14%, 5% and 7%, respectively. Cases had 2.7 times greater odds of having pulmonary hypertension than group 1 controls (p = 0.002). The prevalence of pulmonary hypertension among group 2 controls was 42% (49/117), consisting of mild, moderate and severe pulmonary arterial hypertension in 25% (n = 49), 10% (n = 12) and 4% (n = 5), respectively. Cases were slightly more likely to have pulmonary hypertension than group 2 controls (OR = 1.5), although this failed to reach statistical significance (p = 0.14). CONCLUSION: Prior hemodialysis access thrombectomy does not appear to be a risk factor for pulmonary arterial hypertension. Patients with ESRD are more likely to have pulmonary hypertension.

Recombinant human erythropoietin usage in a large academic medical center.

OBJECTIVE: Recombinant human erythropoeitin (rhEPO) is a highly effective but expensive drug used for the treatment of certain anemias. We considered opportunities to curtail inpatient rhEPO utilization in light of therapeutic alternatives, the drug's delayed onset of action, and the available literature. STUDY DESIGN: A retrospective review of rhEPO administration in a large academic medical center between February and June 2000 was conducted by using administrative databases. METHODS: The computerized inpatient pharmacy transaction file of the Hospital of the University of Pennsylvania was queried to determine trends for rhEPO administration. We then employed CaduCIS (CareScience, Philadelphia, PA) to determine the clinical diagnoses and resources used for each inpatient receiving rhEPO. RESULTS: In the study period, 248 inpatients received at least 1 rhEPO dose. More than 100 different physicians, representing 20 departments and divisions, ordered approximately 17 million units of rhEPO. Hematology/Oncology accounted for 33% of all units ordered, and Surgery and General Medicine ordered 16% and 14%, respectively. The usual length of stay for patients receiving rhEPO varied considerably: 34% of patients remained in hospital for < or = 7 days, while 31% remained > or = 3 weeks. As many as 34% of patients began rhEPO therapy as inpatients. Of inpatients receiving rhEPO, only 49% met labeled indications for rhEPO administration. CONCLUSIONS: At our institution, approximately one half of all inpatient rhEPO usage is for an off-label indication. Utilization patterns may suggest strategies for conserving this scarce resource.