Does presenting with meconium ileus affect the prognosis of children with cystic fibrosis?

It is a matter of debate as to what extent the long-term outcome of cystic fibrosis (CF) is affected by presenting with meconium ileus (MI). We compared long-term clinical outcomes of CF children who presented with MI, to those presenting with other symptoms (non-MI) in an era of non new-born-screening (NBS).We collected annual lung function data between the ages of 8-15 years in terms of percent predicted first second forced expired volume (FEV1%pr), percent predicted forced vital capacity (FVC%pr), and between the ages of 2-15 years annual height and weight Z-scores (HtZ and WtZ respectively) for children attending the Royal Brompton Hospital CF clinic. To be included in the study, subjects had to have at least five pulmonary function tests and five anthropometric measurements recorded over this period.Thirty-eight MI and 76 non-MI subjects were compared. There were no significant differences in genotype, sex, chronic Pseudomonas infection, or pancreatic enzyme use between the two groups. The median age of diagnosis was 1 day (MI) versus 7 months (non-MI). There was a decline in spirometry and anthropometric variables over the study period for both MI and non-MI groups apart from WtZ score in the non-MI group. Mixed model analysis adjusting for potential confounders including genotype, pancreatic status, sex, chronic Pseudomonas aeruginosa lung infection, and age of diagnosis revealed no difference between the two groups in terms of lung function and growth during the time period of the study, however there was a non-significant trend for subjects presenting with MI to do better in all four parameters.We conclude that babies presenting with MI have no worse long-term outcome than those presenting symptomatically later in infancy, despite having undergone invasive procedures in the newborn period. This underscores the importance of early diagnosis and treatment in CF.

Mycoplasma pneumonia and pulmonary embolism in a child due to acquired prothrombotic factors.

We report on a child with Mycoplasma pneumonia, who developed an unexplained new oxygen requirement. He was found to have an ileo-femoral thrombosis and an acute pulmonary embolus, with positive anti-phospholipid antibodies and acquired activated protein C resistance. These are both acquired risk factors for venous thrombosis. He was successfully anti-coagulated and well at follow-up with disappearance of the anti-phospholipid antibodies, and normalization of his activated protein C activity. Children who present with Mycoplasma infections who run an atypical course should be monitored closely for signs of thrombosis. Thrombosis formation should also be considered in those children with deteriorating respiratory status, but little change in radiographical findings. Children found to have developed thrombi should be investigated with a full thrombophilia screen to elicit both congenital and acquired risk factors, and should be anti-coagulated appropriately.

Factors effecting impact of Aspergillus fumigatus sensitization in cystic fibrosis.

The clinical impact of Aspergillus fumigatus (Af) sensitization in cystic fibrosis (CF) is controversial. We examined the effect of Af sensitization (Afs) on pulmonary function and growth using a retrospective cohort analysis over two 5-year study periods: 1996-2000 (19 Afs cases and 19 controls) and 2001-2005 (24 Afs cases and 23 controls). Sensitization was defined as Af specific radioallergosorbent test (RAST) >or= 17.5 iu/ml and total serum IgE level >or=150 iu/ml. We examined the impact of changing treatment schedules over these periods. Afs cases had lower median FEV(1) %predicted (%PR) compared to matched controls 1996: 67 versus 80, P < 0.01; 2001: 78 versus 93, P < 0.01. Afs cases in the 2001 cohort had a higher FEV(1) %PR compared to Afs cases in the 1996 cohort: 78 versus 67, P < 0.01. For the 1996 Afs cohort FEV(1) %PR fell significantly over 5 years but not for the 2001 Afs cohort. Af RAST and total IgE reflected the changes in pulmonary function. Children in the 2001 Afs cohort were prescribed significantly more oral antifungal treatment (odds ratio 4.3, 95%CI 1.2-15.7, P = 0.03). Afs children continue to have poorer lung function compared to controls but this observational, hypothesis generating study, suggests that the use of antifungal treatment is associated with better lung function.

Diagnostic omission errors in acute paediatric practice: impact of a reminder system on decision-making.

BACKGROUND: Diagnostic error is a significant problem in specialities characterised by diagnostic uncertainty such as primary care, emergency medicine and paediatrics. Despite wide-spread availability, computerised aids have not been shown to significantly improve diagnostic decision-making in a real world environment, mainly due to the need for prolonged system consultation. In this study performed in the clinical environment, we used a Web-based diagnostic reminder system that provided rapid advice with free text data entry to examine its impact on clinicians' decisions in an acute paediatric setting during assessments characterised by diagnostic uncertainty. METHODS: Junior doctors working over a 5-month period at four paediatric ambulatory units consulted the Web-based diagnostic aid when they felt the need for diagnostic assistance. Subjects recorded their clinical decisions for patients (differential diagnosis, test-ordering and treatment) before and after system consultation. An expert panel of four paediatric consultants independently suggested clinically significant decisions indicating an appropriate and 'safe' assessment. The primary outcome measure was change in the proportion of 'unsafe' workups by subjects during patient assessment. A more sensitive evaluation of impact was performed using specific validated quality scores. Adverse effects of consultation on decision-making, as well as the additional time spent on system use were examined. RESULTS: Subjects attempted to access the diagnostic aid on 595 occasions during the study period (8.6% of all medical assessments); subjects examined diagnostic advice only in 177 episodes (30%). Senior House Officers at hospitals with greater number of available computer workstations in the clinical area were most likely to consult the system, especially out of working hours. Diagnostic workups construed as 'unsafe' occurred in 47/104 cases (45.2%); this reduced to 32.7% following system consultation (McNemar test, p < 0.001). Subjects' mean 'unsafe' workups per case decreased from 0.49 to 0.32 (p < 0.001). System advice prompted the clinician to consider the 'correct' diagnosis (established at discharge) during initial assessment in 3/104 patients. Median usage time was 1 min 38 sec (IQR 50 sec-3 min 21 sec). Despite a modest increase in the number of diagnostic possibilities entertained by the clinician, no adverse effects were demonstrable on patient management following system use. Numerous technical barriers prevented subjects from accessing the diagnostic aid in the majority of eligible patients in whom they sought diagnostic assistance. CONCLUSION: We have shown that junior doctors used a Web-based diagnostic reminder system during acute paediatric assessments to significantly improve the quality of their diagnostic workup and reduce diagnostic omission errors. These benefits were achieved without any adverse effects on patient management following a quick consultation.

Voriconazole therapy in children with cystic fibrosis.

BACKGROUND: There is increasing evidence for the efficacy of the antifungal voriconazole, particularly in immunosuppression. We describe our experience of using voriconazole in children with CF. METHODS: We performed a retrospective case note review of children with CF treated with voriconazole in a single centre over an 18 month period. RESULTS: A total of 21 children aged 5 to 16 years (median 11.3) received voriconazole for between 1 and 50 (22) weeks. Voriconazole was used as monotherapy in 2 children with recurrent allergic bronchopulmonary aspergillosis (ABPA); significant and sustained improvements in clinical and serological parameters for up to 13 months were observed, without recourse to oral steroids. Voriconazole was used in combination with an immunomodulatory agent in a further 11 children with ABPA, with significant improvement in pulmonary function and serology. 8 children without ABPA but who had recurrent Aspergillus fumigatus isolates and increased symptoms also received voriconazole; this group did not improve with treatment. Adverse effects occurred in 7 children (33%: photosensitivity reaction 3, nausea 2, rise in hepatic enzymes 1, hair loss 1). CONCLUSIONS: Voriconazole may be a useful adjunctive therapy for ABPA in CF. Voriconazole monotherapy appears to be an alternative treatment strategy when oral corticosteroids may not be suitable.

Is there still a gender gap in cystic fibrosis?

OBJECTIVES: Previous studies have shown that female patients with cystic fibrosis (CF) have a significantly poorer prognosis than male patients. Such studies investigating gender-related differences have generally combined data from several centers. The aim of this study was to determine whether with modern aggressive treatment of CF this is still true when care is standardized within a single center. DESIGN: Retrospective analysis of annual assessment data constructing two cross-sectional studies for the year 1993 (56 female patients, 49 male patients) and 2002 (115 female patients, 94 male patients) and two longitudinal studies, each lasting 5 years, starting in 1993 (21 female patients, 19 male patients) and 1998 (40 female patients, 41 male patients). Outcome measures included mortality, height, and weight SD scores (z scores), and percent predicted for lung function. RESULTS: In neither cross-sectional study were there significant differences between the sexes for median FEV(1) percent predicted (1993: female patients, 86%; male patients, 84%; 2002: female patients, 93%; male patients, 92%). Female height and weight z scores were at least as good as those of male scores. In the longitudinal studies, there were no clear trends toward declining lung function or growth, but the overall FEV1 percent predicted appeared to be better in female patients than male patients for both cohorts. This was statistically significant for the 1998 cohort (female median FEV1, 91.5% [range, 28 to 134%]; male median FEV1, 84.8% [range, 32 to 145%]; p < 0.05). Female nutritional status was at least as good as male nutritional status, other than the 1998 weight z scores (-0.54 vs -0.21, respectively; p < 0.02). Since 1993, there have been 13 deaths altogether (7 female patients). CONCLUSION: During childhood and adolescence, the lung function and nutrition of CF patients should be at least as good in female patients as in male patients. Individual clinic practice should be reviewed if a gender gap persists.