Treatment of pituitary-dependent Cushing's disease with the multireceptor ligand somatostatin analog pasireotide (SOM230): a multicenter, phase II trial.

CONTEXT: There is currently no medical therapy for Cushing's disease that targets the pituitary adenoma. Availability of such a medical therapy would be a valuable therapeutic option for the management of this disorder. OBJECTIVE: Our objective was to evaluate the short-term efficacy of the novel multireceptor ligand somatostatin analog pasireotide in patients with de novo, persistent, or recurrent Cushing's disease. DESIGN: We conducted a phase II, proof-of-concept, open-label, single-arm, 15-d multicenter study. PATIENTS: Thirty-nine patients with either de novo Cushing's disease who were candidates for pituitary surgery or with persistent or recurrent Cushing's disease after surgery without having received prior pituitary irradiation. INTERVENTION: Patients self-administered sc pasireotide 600 microg twice daily for 15 d. MAIN OUTCOME MEASURE: Normalization of urinary free cortisol (UFC) levels after 15 d treatment was the main outcome measure. RESULTS: Of the 29 patients in the primary efficacy analysis, 22 (76%) showed a reduction in UFC levels, of whom five (17%) had normal UFC levels (responders), after 15 d of treatment with pasireotide. Serum cortisol levels and plasma ACTH levels were also reduced. Steady-state plasma concentrations of pasireotide were achieved within 5 d of treatment. Responders appeared to have higher pasireotide exposure than nonresponders. CONCLUSIONS: Pasireotide produced a decrease in UFC levels in 76% of patients with Cushing's disease during the treatment period of 15 d, with direct effects on ACTH release. These results suggest that pasireotide holds promise as an effective medical treatment for this disorder.

Plasma exchange for severe attacks of CNS demyelination: predictors of response.

The authors reviewed 59 consecutive patients treated with plasma exchange (PE) for acute, severe attacks of CNS demyelination at Mayo Clinic from January 1984 through June 2000. Most patients had relapsing-remitting MS (n = 22, 37.3%), neuromyelitis optica (NMO) (n = 10, 16.9%), and acute disseminated encephalomyelitis (n = 10, 16.9%). PE was followed by moderate or marked functional improvement in 44.1% of treated patients. Male sex (p = 0.021), preserved reflexes (p = 0.019), and early initiation of treatment (p = 0.009) were associated with moderate or marked improvement. Successfully treated patients improved rapidly following PE, and improvement was sustained.

Potential effect of authorization bias on medical record research.

OBJECTIVE: To analyze the influence of recent changes in Minnesota statutes that generally require prior authorization for use of medical records for research from patients who received medical care after Jan. 1, 1997. MATERIAL AND METHODS: In this Mayo Clinic Institutional Review Board-approved study, we obtained a stratified random sample of patients encountered at Mayo Clinic Rochester during the period 1994 through 1996 and estimated the proportion willing to provide the general authorization. On the basis of data from administrative files, we then compared demographic, diagnostic, and utilization characteristics for patients who provided authorization and those who did not. RESULTS: Overall, 3.2% (95% confidence interval, 2.4 to 4.0%) of the study subjects declined authorization. If patients not responding to requests for authorization were also considered to have refused, the overall refusal rate would be 20.7% (95% confidence interval, 18.5 to 22.9%). Women were somewhat more likely to refuse authorization than were men (4.0% versus 2.4%; P = 0.067), and patients younger than 60 years were more likely to refuse than were older patients (5.4% versus 1.2%; P<0.001). Patients residing more than 120 miles from Rochester were much less likely to decline authorization than were local residents (2.1% versus 5.8%; P = 0.001). Patients with prior diagnoses that might be considered more sensitive such as mental disorders, infectious diseases, and reproductive problems also were more likely to refuse authorization. CONCLUSION: These data demonstrate that laws requiring written authorization for research use of the medical record could result in substantial biases in etiologic and outcome studies, the direction and magnitude of which may vary from topic to topic. Clinicians should be prepared to enter the discussion to help inform patients and legislators of the potential hazards of laws that restrict access to medical records for research purposes.

Screening digital rectal examination and prostate cancer mortality: a population-based case-control study.

OBJECTIVES: Although digital rectal examination (DRE) for the detection of prostate cancer has been recommended by many professional groups and has become part of the general physical examination, no randomized clinical trial has demonstrated the efficacy or effectiveness of this practice. We conducted a population-based case-control study to evaluate the association between DRE and prostate cancer mortality. METHODS: With the resources of the Rochester Epidemiology Project, all 173 men who died of prostate cancer in Olmsted County from 1976 to 1991, who were resident at the time of diagnosis, were identified. For each case, two control patients were drawn from the population, matched for residence at the time of diagnosis in the case, birth date, and duration of medical record in Olmsted County. Trained nurse abstractors reviewed the community medical records for up to 10 years before the date of diagnosis in the case for mention of DRE and specific findings associated with each mention. RESULTS: Case subjects were less likely than control subjects to have had any DRE in the 10 years before diagnosis (matched odds ratio [OR] = 0.51; 95% confidence interval [CI] = 0.31, 0.84). When limited to DREs without mention of signs or symptoms that might raise suspicion of prostate cancer, the association was even stronger (OR = 0.31; 95% CI = 0.19, 0.49). Adjustment for educational attainment, marital status, and comorbid conditions did little to alter the associations. CONCLUSIONS: These results demonstrate a strong inverse association between DRE and prostate cancer mortality. If further research concludes this association to be causal, screening DREs may have prevented as many as 50% to 70% of deaths due to prostate cancer that might have occurred in the absence of screening.