High rate of breakthrough invasive aspergillosis among patients receiving caspofungin for persistent fever and neutropenia.

A number of agents are now available for empirical antifungal treatment (EAFT) of patients with persistent fever and neutropenia. We carried out a study of efficacy of antifungal drugs to prevent breakthrough invasive aspergillosis by reviewing the medical records of all consecutive patients who received EAFT from November 2005 to February 2006. Patients' characteristics and the type, dose and duration of antifungal therapy were recorded. Breakthrough invasive fungal infections were documented according to the European Organization for Research and Treatment of Cancer/Invasive Fungal Infections Cooperative Group and the National Institute of Allergy and Infectious Diseases Mycoses Study Group (EORTC/MSG) definition. Fifty-six episodes of persistent fever with neutropenia requiring EAFT were recorded among 49 patients. All patients received high-dose chemotherapy for acute myeloid leukaemia (51%), acute lymphoid leukaemia (12%), lymphoma (14%) or other haematologic conditions (22%). Fourteen (29%) and five (10%) patients were allogeneic and autologous haematopoietic stem cell transplant recipients, respectively. Caspofungin was prescribed initially in 40 episodes (71%), amphotericin B (AmB) desoxycholate and liposomal AmB being prescribed in six (10%) and ten (18%) episodes, respectively. Six patients were switched from liposomal AmB to caspofungin because of adverse events. The median duration of antifungal therapy was 9 days. During follow-up, six patients (12%) were diagnosed with invasive aspergillosis after a median of 8 days (range 3-16 days) of EAFT. Invasive aspergillosis breakthrough occurred in 6/46 (13%) caspofungin recipients and in 0/16 (0%) AmB recipients (OR 3.1, p 0.32). The observed high rate of invasive aspergillosis among caspofungin recipients requires further evaluation.

Comparison of the learning curves of digital examination and transabdominal sonography for the determination of fetal head position during labor.

OBJECTIVES: To evaluate the learning curve of transabdominal sonography for the determination of fetal head position in labor and to compare it with that of digital vaginal examination. METHODS: A student midwife who had never performed digital vaginal examination or ultrasound examination was recruited for this study. Instructions on how to perform digital vaginal examination and ultrasound examination were given before and after completing the first vaginal and ultrasound examinations, and repeated for each subsequent examination for as long as necessary. Digital and ultrasound diagnoses of the fetal head position were always performed first by the student midwife, and repeated by an experienced midwife or physician. The learning curve for identification of the fetal head position by either one of the two methods was analyzed using the cumulative sums (CUSUM) method for measurement errors. RESULTS: One hundred patients underwent digital vaginal examination and 99 had transabdominal sonography for the determination of fetal head position. An error rate of around 50% for vaginal examination was nearly constant during the first 50 examinations. It decreased subsequently, to stabilize at a low level from the 82(nd) patient. Errors of +/- 180 degrees were the most frequent. The learning curve for ultrasound imaging stabilized earlier than that of vaginal examination, after the 32(nd) patient. The most frequent errors with ultrasound examination were the inability to conclude on a diagnosis, particularly at the beginning of training, followed by errors of +/- 45 degrees. CONCLUSIONS: Based on our findings for the student tested, learning and accuracy of the determination of fetal head position in labor were easier and higher, respectively, with transabdominal sonography than with digital examination. This should encourage physicians to introduce clinical ultrasound examination into their practice. CUSUM charts provide a reliable representation of the learning curve, by accumulating evidence of performance.

Increase in bone mineral density of patients with spondyloarthropathy treated with anti-tumour necrosis factor alpha.

OBJECTIVE: To determine the changes in bone mineral density (BMD) in patients with spondyloarthropathy (SpA) treated with infliximab. PATIENTS AND METHODS: 29 patients (six women; 23 men) aged 22-68 years, with persistently active SpA despite a high dose of non-steroidal anti-inflammatory drug and/or treatment with methotrexate or sulfasalazine, were studied. Median duration of disease was 13 years (range 3-30). Twenty five patients were treated with 5 mg/kg and four with 3 mg/kg of infliximab at weeks 0, 2, 6 and then received either no infusion (n=3), or additional infusion of infliximab every other month (n=6), and the remainder received one infusion only in the case of a relapse. Lumbar and femoral BMD was measured by dual energy x ray absorptiometry at baseline and six months later. Serum osteocalcin and urinary deoxypyridinoline were measured in 19 patients at weeks 0, 2, 24, and in 13 patients at all visits. RESULTS: In six months there was a significant increase in BMD at the spine (3.6%, p=0.001), total hip (2.2%, p=0.0012), and trochanter (2.3%, p=0.0012). A trend for increase (1.1%) was observed at the femoral neck. There was an increase in osteocalcin between baseline and week 6 (third infusion)-median 1.45 micro g/l (p=0.013). No change in marker of bone resorption was observed at the same time. There was no change in biochemical markers between baseline and final visits. There was a trend for a correlation between the decrease at six months in erythrocyte sedimentation rate, and lumbar spine BMD change (r(s)=-0.35, p=0.06). CONCLUSION: These data suggest that a benefit of anti-tumour necrosis factor alpha therapy on BMD in patients with SpA may be through an uncoupling effect on bone cells.