Cystic Fibrosis Screen Positive, Inconclusive Diagnosis (CFSPID): A new designation and management recommendations for infants with an inconclusive diagnosis following newborn screening.

BACKGROUND: Newborn screening (NBS) for cystic fibrosis (CF) results in the recognition of a number of infants with a positive NBS result, but an inconclusive diagnosis. Varied practice exists with respect to the management of these infants. METHODS: A Delphi consensus approach was used to determine agreement on statements generated by a core group of specialists. A designation (naming) exercise was required after Round 1 and further expert opinion was sought to guide that process. After Round 2, a sensitivity analysis was undertaken to assess the impact of attrition on subsequent agreement levels. RESULTS: Infants were divided into group A (normal sweat chloride and two CFTR mutations, at least one of which has unclear phenotypic consequences) and group B (intermediate sweat chloride and one or no CFTR mutations). 32 statements were produced for Round 1 and 24 achieved consensus. After Round 1, a designation exercise was undertaken and the term "CF Screen Positive, Inconclusive Diagnosis (CFSPID)" was suggested for Round 2. Agreement was achieved for this statement and for all other statements aside from the need for routine respiratory culture, on which there was divided opinion. The core group advocated local practice for this issue. A sensitivity analysis demonstrated that consensus for Round 2 was achieved by change in opinion rather than attrition. CONCLUSION: We have generated a new designation and statements to guide the management of infants with CFSPID through a robust international Delphi process. These statements will be a valuable tool for CF teams and will improve the consistency of management of these infants.

A European consensus for the evaluation and management of infants with an equivocal diagnosis following newborn screening for cystic fibrosis.

Screening newborns for cystic fibrosis (CF) is considered to be an ethical undertaking in regions with a significant incidence of the condition. Current screening protocols result in recognition of infants with an equivocal diagnosis. A survey of European practice suggested inconsistencies in the evaluation and management of these infants. We have undertaken a consensus process using a modified Delphi method. This has enabled input of CF specialists from a wide geographical area to a rigorous process that has provided a clear pathway to a consensus statement. A core group produced 21 statements, which were modified over a series of three rounds (including a meeting arranged at the European CF Conference). A final document of 19 statements was produced, all of which achieved a satisfactory level of consensus. The statements cover four themes; sweat testing, further assessments and investigations, review arrangements and database. This consensus document will provide guidance to CF specialists with established screening programmes and those who are in the process of implementing newborn screening in their region.

Assessing senior house officers' perceptions of learning.

OBJECTIVE: To identify trainers', senior house officers' (SHOs) and their nursing colleagues' perceptions of learning in a neonatal unit. DESIGN: Three questionnaires were administered to staff of the neonatal intensive care unit. The first one asked consultants about activities that trainees are exposed to, a second explored the views of other permanent staff regarding the value of the educational activities available for trainees and a third explored the perception of the SHOs of their learning experiences. SETTING: Regional neonatal intensive care unit. RESULTS: Permanent clinical staff felt that the consultant ward round, emergency management, protected teaching, practical procedures and informal discussion were the most valuable learning experiences. Trainees felt that consultant and handover ward rounds were important and formal protected teaching less so. CONCLUSION: A mismatch of perception of learning experiences was identified in the department. These mismatches can be addressed by acknowledging the importance of when the trainees perceive they learn best and improving the learning experience in situations where they do not.

Late presentation of medium-chain acyl-CoA dehydrogenase deficiency.

Medium-chain acyl-CoA dehydrogenase (MCAD) deficiency is the commonest disorder of fatty acid metabolism, with a high incidence of morbidity and mortality at presentation. We report a 16 year old girl with first presentation of MCAD deficiency following an alcoholic binge and subsequent period of starvation. Presentation was as acute encephalopathy progressing to coma. Renal, cardiac and hepatic failures were managed with intensive supportive care including mechanical ventilation, inotropic support, blood products and renal replacement therapy. Diagnosis of MCAD deficiency was confirmed on day 6. The patient was discharged from hospital on day 20 with a mild proximal myopathy, which subsequently resolved. The diagnosis of MCAD deficiency requires a high index of suspicion at all ages. Precipitating factors in later life may include alcohol.

Prior test experience compromises the anxiolytic efficacy of chlordiazepoxide in the mouse light/dark exploration test.

It is now well established that prior test experience can alter behavioural baselines and attenuate/abolish the anxiolytic efficacy of benzodiazepines in the elevated plus-maze paradigm. In view of evidence that different models of anxiety measure qualitatively distinct forms of anxiety-like behaviour, it is important to establish whether the effects of prior experience extend to other widely-used tests. The present study assessed the behavioural and pharmacological sequelae of a single undrugged prior exposure to the light/dark exploration (L/D) test in mice, using ethological scoring methods. One group of adult male Swiss-Webster mice was given a single undrugged exposure to the L/D test 24 h prior to drug testing, while another group was completely naïve to the apparatus. On test day, half the animals in each experiential condition were treated with saline and half with an anxiolytic dose (10 mg/kg) of chlordiazepoxide (CDP). When administered to test-naïve animals, CDP induced a clear reduction in anxiety-like behaviour as evidenced by significant increases in exploration of the light compartment (line crossings, % line crossings, and % time) as well as reductions in stretched attend postures (SAPs) and the proportion of SAPs displayed toward the light compartment. The behavioural specificity of these effects was confirmed by the absence of a drug effect on line crossings in the dark compartment, total rearing and grooming. In complete contrast, with the sole exception of a decrease in total SAPs, CDP was without significant behavioural effect in test-experienced mice. As prior test experience did not significantly alter behavioural baselines in the L/D test, a second experiment was designed to investigate the possibility that handling/intraperitoneal injection may have precluded detection of experientially-induced changes in baseline behaviour. Results showed that handling/injection had no effect upon L/D behavioural profiles in either test-naïve or test-experienced subjects, and confirmed that prior experience itself did not modify the primary indices of anxiety in this test. Present data indicate that prior test experience seriously compromises the anxiolytic efficacy of CDP (10 mg/kg) in the mouse L/D test and, together with recent findings in the four-plate test, appear to confirm that an experientially-induced reduction in sensitivity to the anxiolytic effects of benzodiazepines is by no means unique to the elevated plus-maze.