Sputum tumour necrosis factor-alpha and leukotriene concentrations in cystic fibrosis

It is postulated that a vigorous host inflammatory response in the cystic fibrosis lung contributes to lung injury. Tumour necrosis factor-alpha (TNF-alpha) may play a part in that process and in the generation of leukotrienes. Therefore, the relationships between sputum TNF-alpha, leukotriene concentration, and lung function abnormalities in 16 children with cystic fibrosis were investigated. Each subject provided sputum samples and performed spirometry. TNF-alpha was measured by enzyme linked immunosorbent assay; individual leukotrienes were separated using high performance liquid chromatography and quantified by radioimmunoassay. The geometric mean concentration of TNF-alpha was 129.7 pg/ml and 95% confidence interval 48.2 to 348.3. Mean (SEM) leukotriene B4 (LTB4) was 97.8 (22.9) pmol/g and total cysteinyl leukotrienes were 60.9 (14.8) pmol/g. Mean (SD) forced expiratory volume in one second (FEV1) of the group was 53 (15)% of predicted and forced vital capacity (FVC) was 65 (14)% of predicted. There was a significant positive correlation between TNF-alpha and both LTB4 and the total cysteinyl leukotriene sputum content. An inverse relationship existed between TNF-alpha and FEV1 and FVC. Moreover, a negative correlation was observed between sputum LTB4 and FEV1 and FVC. These results suggest that TNF-alpha and the leukotrienes may participate in the airways inflammation and airflow obstruction observed in cystic fibrosis subjects and support the hypothesis that TNF-alpha upregulates the 5-lipoxygenase pathway in vivo.     

A BPA survey of recently appointed consultants

A postal survey of recently appointed consultant paediatricians was undertaken to determine whether they perceived their training had adequately equipped them for their current job. The response rate was 69% (207/299). After excluding replies from consultants trained outside the UK the analysis was carried out on 167 replies. Trainees held a mean 5.2 posts during general and higher professional training, necessitating a mean 1.8 house moves. Altogether 82% felt moves were beneficial to training but 46% found moves 'very disruptive' to family life. Only 12% of district general hospital and 22% of teaching hospital senior registrars took two research sessions a week. Supervision and training in research was absent or poor for more than 60%; 24% felt major changes and 55% moderate changes were needed to current training. Training in non-clinical skills was particularly in demand and a curriculum for both trainers and trainees with regular appraisals is required. Research at senior registrar level needs review and educational methods improved to achieve better training in a shorter period.     

Thermal balance and metabolic rate during upper respiratory tract infection in infants

Sequential recordings were made in the first five months after birth of metabolic rate, environmental temperature, and body temperature during sleep at home in 17 infants, each with an older sibling. Further recordings were made whenever an older sibling developed an upper respiratory tract infection (URTI), again four to six days later, and again two weeks later, aiming to achieve recordings before, during, and after an URTI in the infant. The temperature of the room and wrapping of the infant were determined according to their usual practice by the parents. Parents added appropriate wrapping to achieve thermal neutrality based on our calculated values and the measured oxygen consumption. In five of the six infants who developed an URTI in the first three months after birth there was no change or a decrease in metabolic rate at the time of the infection; for infants older than 3 months the metabolic rate increased in three of the five episodes recorded. Peripheral skin temperature decreased at the time of URTI at all ages, though in the older infants it usually increased in parallel with rectal temperature during the latter part of the night, when pyrexia was most common. Infants thus respond to URTI by heat conservation. In the younger infants the lower metabolic rate and the further decrease in this rate with URTI means that fever is rare, and their temperature may decrease on infection. In the older infants the increase in metabolic rate (from an already higher baseline) may result in fever. These differences may contribute to the increased vulnerability of the older infants to heat stress, particularly at the time of acute viral infections.     

Neonatal subgaleal haematoma: Associated risk factors, complications and outcome

Objective : To describe the obstetric and perinatal factors, in particular the method of delivery, associated with development of a subgaleal haematoma (SGH) and to determine the outcome of survivors with this type of birth trauma. Methodology : Perinatal and obstetric data were retrospectively reviewed for 37 infants admitted to the neonatal unit of the sole tertiary paediatric referral hospital in Western Australia with an SGH, over a 24 year period from 1970 to 1993. These data were compared to data for all Western Australian births. The long-term outcome was obtained through medical and private paediatric records for 26 of these infants. Results : All except one of the neonates had instrumental deliveries; 89% had a vacuum extractor applied to the head at some stage of delivery compared to 10% of the general population of births in Western Australia. There was also a significantly increased risk of failure of attempted vacuum extraction. Of the cases where a vacuum extraction was attempted, 45% also had forceps applied to the head. Coagulopathy was associated with the severity of the SGH. There was also a high frequency of occurrence (40%) of associated head trauma such as intracranial haemorrhage, skull fracture and cerebral oedema, as well as neonatal encephalopathy (73%). The occurrence of these associated features did not correlate significantly with the severity of SGH. Minor complications of SGH included jaundice and facial bruising. There was an excess mortality associated with SGH; however, the long-term outcome for neonatal survivors with this disorder was good. None of the cases studied subsequently developed cerebral palsy or intellectual disability, and minor neurological sequelae only were documented in four infants. Conclusions : SGH is an uncommon type of birth trauma, and is associated with delivery or attempted delivery by vacuum extraction. The most commonly associated clinical problems were hypovolaemia and coagulopathy. The long-term outcome for neonates with this condition is good.     

Prospective decision analysis modeling indicates that clinical decisions in vascular surgery often fail to maximize patient expected utility

BACKGROUND: Applied prospectively to patients with peripheral arterial disease, individualized decision analysis has the potential to improve the surgeon's ability to optimize patient outcome. METHODS: A prospective, randomized trial comparing Markov surgical decision analysis to standard decision-making was performed in 206 patients with symptomatic lower extremity arterial disease. Utility assessment and quality of life were determined from individual patients prior to treatment. Vascular surgeons provided estimates of probability of treatment outcome, intended and actual treatment plans, and assessment of comfort with the decision (PDPI). Treatment plans and PDPI evaluations were repeated after each surgeon was made aware of model predictions for half of the patients in a randomized manner. RESULTS: Optimal treatments predicted by decision analysis differed significantly from the surgeon's initial plan and consisted of bypass for 30 versus 29%, respectively, angioplasty for 28 versus 11%, amputation for 31 versus 6%, and medical management for 34 versus 54% (agreement 50%, kappa 0.28). Surgeon awareness of the decision model results did not alter the verbalized final plan, but did trend toward less frequent use of bypass. Patients for whom the model agreed with the surgeon's initial plan were less likely to undergo bypass (13 versus 30%, P < 0.01). Greater surgeon comfort was present when the initial plan and model agreed (PDPI score 47.5 versus 45.6, P < 0.005). CONCLUSIONS: Individualized application of a decision model to patients with peripheral arterial disease suggests that arterial bypass is frequently recommended even when it may not maximize patient expected utility.     

Comparison of changes in blood pressure measurements and antihypertensive therapy in older, hypertensive, ambulatory care patients prescribed celecoxib or rofecoxib

STUDY OBJECTIVE: To determine if changes in blood pressure and changes in class or dosing of antihypertensive drugs were significantly different in patients treated with celecoxib versus rofecoxib, two cyclooxygenase (COX)-2 inhibitors. DESIGN: Retrospective cohort study. SETTING: Thirty-one ambulatory care practices that shared an electronic medical record. PATIENTS: Nine hundred sixty men and women over age 55 years with stable hypertension. INTERVENTION: Patients had to have at least a 30-day supply of celecoxib or rofecoxib (any dose) prescribed between July 1, 1999, and June 30, 2000. MEASUREMENTS AND MAIN RESULTS: Patients were followed for 6 months, and logistic regression and survival models were used to compare outcomes between groups while adjusting for confounders. Baseline characteristics of 517 patients receiving celecoxib and 443 receiving rofecoxib were similar. No significant differences were observed, regardless of the COX-2 inhibitor prescribed, in the proportion of patients whose systolic blood pressure increased by 20 mm Hg, whose diastolic blood pressure increased by 15 mm Hg, or who were prescribed a new class of antihypertensive drug. Compared with patients taking celecoxib, those taking rofecoxib were significantly more likely (odds ratio 1.68, 95% confidence interval 1.09-2.60) to have had the dosage of their antihypertensive drug increased and also the dosage increased sooner (p<0.05). New-onset cardiac and renal comorbidity, number of physician visits, and changes in body weight and laboratory values were not significantly different between the groups. CONCLUSION: No significant differences in blood pressure changes or in the proportion of patients who were prescribed a new class of antihypertensive drug were found between rofecoxib- and celecoxib-treated patients. However, significantly more rofecoxib-treated patients had the dosage of their existing antihypertensive drug increased compared with those receiving celecoxib.     

An interactive voice response system to enhance antidepressant medication compliance

Advances in technology can have direct and indirect benefits to clinical practice. The challenge that clinicians face is to properly match resources and outcomes, along with patient preferences. This article explores the use of an innovative interactive voice response system to increase patient compliance with antidepressant medication prescribed in primary care settings. The development of the interactive voice response system, its implementation, and clinical outcomes are described. The findings underscore the need to carefully match intervention strategies with the needs of specific patient populations, and the importance of human dialog in the context of healing.     

Paediatric trainees and the transportation of critically ill neonates: experience, training and confidence

AIM: To study the experience of, training in, and confidence in the transportation of critically ill neonates amongst paediatric trainees in one UK region. DESIGN: An anonymized questionnaire was sent to all middle grades with paediatrics National Training Numbers from the Trent region. RESULTS: The response rate was 78%. Less than half (45%) of the respondents reported receiving any training in the transportation of neonates, either in the UK or abroad; 45% (30/66) of the trainees reported having performed 10 or fewer neonatal transfers. The self-perceived confidence for transporting neonates was scored on a 10-point scale, to produce a "confidence score", the median score being 7 (IQ range 5, 8). Both as a group and individually, the trainee paediatricians were more confident in transporting neonates than older infants or children (p < 0.0001). Using multiple analysis of covariance, it was found that the most important and significant variables affecting the "confidence scores" for the inter-hospital transportation of critically ill neonates were receipt of any relevant transport training, and the current frequency of transports performed. CONCLUSIONS: Many training-grade paediatricians lack both the experience and training in transporting critically ill neonates, factors that were found to affect their confidence in transferring sick neonates. As the overwhelming majority of neonatal transports in the UK are still arranged by individual units and performed by training-grade paediatricians, concerns regarding both the safety and effectiveness of the current service provision for the inter-hospital transfer of critically ill neonates remain valid.