Up-front rituximab maintenance improves outcome in patients with follicular lymphoma: a collaborative Nordic study.

The introduction of the anti-CD20 antibody rituximab in combination with chemotherapy (R-chemo) has improved the prognosis of patients with follicular lymphoma (FL). During the last decade, the addition of a maintenance treatment with rituximab (MR) after R-chemo has been tested with the hope of further improving the outcome of these patients. Using 2 independent population-based cohorts, we investigated the effect of up-front MR on time related end points as well as the risk of histological transformation (HT). FL patients were included if they: (1) completed first-line induction treatment with R-chemo, (2) were alive after induction treatment and eligible for MR, and (3) had no evidence of HT at this time point. The training cohort consisted of 733 Danish patients of whom 364 were consolidated with MR; 369 were not. Patients receiving MR more often had advanced clinical stage (90% vs 78%), high Follicular Lymphoma International Prognostic Index (FLIPI) score (64% vs 55%), and bone marrow infiltration (49% vs 40%). Those consolidated with MR had an improved 5-year overall survival (OS; 89% vs 81%; P = .001) and progression-free survival (PFS; 72% vs 60%; P < .001). In the training cohort, MR was associated with a reduction of HT risk (P = .049). Analyses of an independent validation cohort of 190 Finnish patients confirmed the favorable impact of MR on 5-year OS (89% vs 81%; P = .046) and PFS (70% vs 57%; P = .005) but did not find a reduced risk of HT. The present population-based data suggest that the outcome of patients with FL has improved after consolidation of R-chemo with MR.

Cushing's syndrome due to pharmacological interaction in a cystic fibrosis patient.

UNLABELLED: Treatment of allergic bronchopulmonary aspergillosis with itraconazole is becoming more widespread in chronic lung diseases. A considerable number of patients is concomitantly treated with topical or systemic glucocorticoids for anti-inflammatory effect. As azole compounds inhibit cytochrome P450 enzymes such as CYP3A isoforms, they may compromise the metabolic clearance of glucocorticoids, thereby causing serious adverse effects. A patient with cystic fibrosis is reported who developed iatrogenic Cushing's syndrome after long-term treatment with daily doses of 800 mg itraconazole and 1,600 microg budesonide. The patient experienced symptoms of striae, moon-face, increased facial hair growth, mood swings, headaches, weight gain, irregular menstruation despite oral contraceptives and increasing insulin requirement for diabetes mellitus. Endocrine investigations revealed total suppression of spontaneous and stimulated plasma cortisol and adrenocorticotropin. Discontinuation of both drugs led to an improvement in clinical symptoms and recovery of the pituitary-adrenal axis after 3 mo. CONCLUSION: This observation suggests that the metabolic clearance of buDesonide was compromised by itraconazole's inhibition of cytochrome P450 enzymes, especially the CYP3A isoforms, causing an elevation in systemic budesonide concentration. This provoked a complete suppression of the endogenous adrenal function, as well as iatrogenic Cushing's syndrome. Patients on combination therapy of itraconazole and budesonide inhalation should be monitored regularly for adrenal insufficiency. This may be the first indicator of increased systemic exogenous steroid concentration, before clinical signs of Cushing's syndrome emerge.

Iatrogenic adrenal insufficiency as a side-effect of combined treatment of itraconazole and budesonide.

A recent case of iatrogenic Cushing's syndrome and complete suppression of the pituitary-adrenal-axis in a patient with cystic fibrosis (CF) and allergic bronchopulmonary aspergillosis treated with itraconazole as an antifungal agent, and budesonide as an anti-inflammatory agent led to a systematic assessment of this axis and gonadal function in all patients treated with itraconazole in the authors' CF centre. Itraconazole can inhibit CYP3A, thus interfering with synthesis of gluco- and mineralocorticoids, androgens and oestradiol as well as the metabolism of budesonide. The aim of this study was to evaluate adrenal and gonadal function in patients treated with itraconazole with or without budesonide. An adrenocorticotrophic hormone (ACTH) test (250 microg tetracosactid) was performed in 25 CF patients treated with both itraconazole and budesonide, and in 12 patients treated with itraconazole alone (six patients with CF and six with chronic granulomateous disease). Mineralocorticoid and gonadal steroid function were evaluated by measurements of plasma-renin, follicle stimulating hormone, luteinising hormone, progesterone, oestradiol, testosterone, serum-inhibin A and B. ACTH tests performed as part of a pretransplantation programme in an additional 30 CF patients were used as controls. Eleven of the 25 patients treated with both itraconazole and budesonide had adrenal insufficiency. None of the patients on itraconazole therapy alone nor the control CF patients had a pathological ACTH test. Mineralocorticoid and gonadal insufficiency was not observed in any of the patients. Only one patient with an initial pathological ACTH-test subsequently normalised, the other 10 patients improved but had not achieved normalised adrenal function 2-10 months after itraconazole treatment had been discontinued. Suppression of the adrenal glucocorticoid synthesis was observed in 11 of 25 cystic fibrosis patients treated with both itraconazole and budesonide. The pathogenesis is most likely an itraconazole caused increase in systemic budesonide concentration through a reduced/inhibited metabolism leading to inhibition of adrenocorticotrophic hormone secretion along with a direct inhibition of steroidogenesis. In patients treated with this combination, screening for adrenal insufficiency at regular intervals is suggested.

[Relevance of the 112-emergency calls among the clientele of the emergency department of the Herlev hospital admitting office]. / Relevansen af alarm 112-opkald blandt skadestueklientel i amtssygehuset i herlevs optagelsesområde.

It is a common view, shared by Emergency Department staff and ambulance crews, that a large number of patients unnecessarily use Emergency Service ambulances instead of transporting themselves to the hospital by other, more appropriate means. In this retrospective study, 528 consecutive Emergency Service calls to the Herlev Hospital Casualty/Emergency Department during a six week period were reviewed for relevance. Attention was solely aimed at the relevance of the use of Emergency Service ambulances in each case, but not on patient or health care providers' perception of urgency. All calls resulting in admission to hospital were pre-defined as being relevant. Seventeen point six percent of all calls were deemed irrelevant. Thirty-three percent of all calls not resulting in admission were deemed irrelevant. The results confirm Emergency Department health care providers' and ambulance crews' view that Emergency Service ambulances are used inappropriately by the public.