[Evolution of the costs and management of lung cancer between 2004 and 2014]. / Évolution des coûts et de la prise en charge du cancer pulmonaire entre 2004 et 2014.

BACKGROUND: Given its morbidity and mortality, lung cancer is a major public health issue. In recent years, it has benefited from several therapeutic innovations. The objective of this study was to compare, over two distinct periods of ten years, the impact on survival and the costs of lung cancer management. METHODS: The monocentric study assessed survival and the direct costs of lung cancer management of patients diagnosed in Brest University hospital in 2004 and in 2014. RESULTS: The analysis included 142 patients in 2004 and 156 in 2014. Most patients were smokers (72%), metastatic at diagnosis (60%) both in 2004 and in 2014. Median survival was not significantly improved between the 2 periods (9.7 versus 10.9 months), but there was a significant increase in the average cost of care per patient (€ 17,063 vs. € 29,264, P=<0.0001) between 2004 and 2014. CONCLUSION: The significant increase in treatment costs did not translate into an improvement in the survival of patients with lung cancer between 2004 and 2014.

Quantification of CFTR splice variants in adults with disseminated bronchiectasis, using the TaqMan fluorogenic detection system.

Mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene are associated with different related disorders such as congenital bilateral absence of the vas deferens, chronic idiopathic pancreatitis, or disseminated bronchiectasis (DB). Many different disease-causing mutations are associated with DB, particularly the 5T allele (IVS 8 polyT tract), a variant of the splice acceptor site at the end of intron 8 that affects the efficiency with which the site is used. It therefore affects the accuracy of exon 9 splicing and hence expression of the functional CFTR protein. In this study we quantified transcripts from nasal biopsies of patients with DB compared to normal controls. We developed a real-time quantitative reverse transcription polymerase chain reaction assay (using the TaqMan system) to evaluate the relative amounts of accurately spliced transcript, and transcript lacking exon 9. Patients with the 5T allele had increased amounts of aberrant transcript: in genotypes 5T/7T, 7T/7T and 9T/7T, mean fractions of 38.4%, 3.5% and 0.6%, respectively, of transcripts had been spliced incorrectly. There was also some evidence that nasal biopsies can provide similar information on transcripts to bronchial biopsies. This functional test is of interest for monitoring the amount of CFTR transcript in different clinical situations or to monitor the effect of drugs on CFTR transcription.

Evaluation of sedation in quail induced by use of midazolam and reversed by use of flumazenil.

OBJECTIVE: To evaluate the sedative properties of 3 dosages of the benzodiazepine tranquilizer midazolam as a means of chemical restraint in quail (Colinus virginianus) and to evaluate the ability of the benzodiazepine antagonist flumazenil to reverse the sedative effects of midazolam. DESIGN: Prospective randomized controlled trial. ANIMALS: Study 1, 30 birds; study 2, 10 birds. PROCEDURE: 2 studies were performed. In the first study, 30 birds were randomly assigned to receive midazolam at a dosage of 2, 4, or 6 mg/kg of body weight (10 birds/dosage). Degree of sedation was evaluated by use of a numerical scale, and the peak time of adequate chemical restraint was determined. The dosage in study 1 that produced the highest degree of sedation was administered to 10 birds in study 2. Flumazenil was administered at a dosage of 0.1 mg/ kg at the peak time of sedation that had been determined in study 1. RESULTS: Administration of 6 mg of midazolam/kg induced the highest degree of chemical restraint without causing alterations in cardiopulmonary function. Peak time of sedation was 10 minutes after administration; however, administration of 4 mg of midazolam/ kg also induced a high degree of sedation, but for a shorter period. Administration of flumazenil caused complete recovery from sedation induced with midazolam. CLINICAL IMPLICATIONS: Administration of midazolam to wild birds induced adequate sedation. Results of the study reported here may be extrapolated to other species of wild birds, including raptors and, possibly, pet birds.

Cardiovascular-radical outcome method is effective in complex congenital cardiac lesions.

BACKGROUND: The cardiovascular-radical outcome method is a proactive process of patient care that uses standard critical pathway methodology to reduce negative variation while encouraging positive variation to accelerate recovery. Its effectiveness in patients with complex congenital heart disease is explored. METHODS: Two hundred fourteen consecutive patients with congenital heart disease were cared for using the cardiovascular radical outcome method. Age ranged from 2 days to 19 years (median age, 3 years). Cardiovascular radical outcome method data were compared with the pathway plan data for each patient. RESULTS: Survival was 99% (211 patients) with an overall reduction in stay of 156 days (0.74 day/patient) (p < 0.0001). Only 10 patients (5%) exceeded the pathway plan; 201 (95%) reached the planned length of stay (critical pathway method), and 127 patients (60%) had a shorter length of stay than expected by the critical pathway method. One hundred forty-eight patients (70%), including 95 (64%) with more complex conditions, had a length of stay of 3 days and 18% achieved a 2-day length of stay, the maximal response. The process was most effective in the most complex groups, although preoperative comorbidities influenced outcomes. Outcome assessment demonstrated minimal morbidity and excellent family satisfaction. CONCLUSIONS: The radical outcome method is effective in reducing the length of stay of patients with complex congenital heart disease. The power is in the process rather than the plan, and the method provides optimal patient care and family satisfaction.

Fetal echocardiography: retrospective review of clinical experience and an evaluation of indications.

OBJECTIVE: To assess the indications, use, and yield of fetal echocardiography. METHODS: We reviewed our 8-year experience with fetal echocardiography at a large health maintenance organization in northern California to assess the yield of abnormal findings for each indication and the accuracy of prenatal cardiac diagnosis. The study included 915 fetuses undergoing fetal echocardiography between 18-38 weeks' gestation because of accepted indications. All live-born infants had the presence or absence of congenital heart disease (CHD) confirmed postnatally. RESULTS: Family history of CHD led to 34% of all fetal echocardiography studies, with a detection rate of 0.7%. Maternal diabetes mellitus accounted for 28% of all studies, with a detection rate of 1.2%. Exposure of mothers to a potential teratogen led to 48 studies, but no abnormalities were detected. Only 4% of fetal echocardiograms were obtained because of a suspected heart defect noted on a screening obstetric sonogram; this indication had a detection rate of 68% and yielded by far the most cases of severe CHD. Based on the expected occurrence rate of severe CHD in our closed referral system, only about 15% were referred for fetal echocardiography and detected prenatally. CONCLUSION: Basing fetal echocardiography referral on risk factors misses most clinically significant detectable CHD.

Critical pathway methodology: effectiveness in congenital heart surgery.

Critical pathway methodology has been demonstrated to provide producible reduction in average length of stay (ALOS) in adults in certain diagnostic-related groups and operations such as coronary artery bypass grafting. The efficacy of this approach in congenital heart surgery was explored. Two hundred eighty-six consecutive patients from a health maintenance organization treated by a single surgeon since the institution of diagnostic-related group coding at that health maintenance organization constituted the study group. One hundred fourteen patients were treated at a university hospital without critical pathway methodology (group 1) and 172, subsequently at the health maintenance organization institution using the methodology (group 2). Operation/lesion, age, and diagnostic-related group matching was possible in 61 pairs. Examination of the ALOS Hospital (operative and postoperative days) for the entire cohort revealed a 43.8% reduction in ALOS Hospital (p < 0.0001) and a 39.0% reduction in ALOS Intensive Care Unit (p < 0.0001). There was also significant reduction in ALOS Hospital and ALOS Intensive Care Unit in the operation/lesion-matched subsets. Outcome measures including operative and late mortality, readmission, unscheduled emergency room and clinic visits, and health maintenance organization family assessment survey demonstrated no improvement in outcome with increased hospital stay. Thus, critical pathway methodology when used in patients undergoing a congenital heart operation produces a significant reduction in hospital stay and intensive care unit stay as well as quality patient care with uniformity of outcome.

Alpha 1-antitrypsin genetic polymorphism in ANCA-positive systemic vasculitis.

Alpha 1-antitrypsin (alpha 1-AT) is the major inhibitor of proteinase 3 (PR3), the main target antigen of antineutrophil cytoplasm antibodies (ANCA) in Wegener's granulomatosis. alpha 1-AT is encoded by a polymorphic gene, with over 75 alleles, defining severely, medium and non-deficient protease inhibitor (PI) phenotypes. We describe the association of severely and medium deficient PI phenotypes with anti-PR3 positive systemic vasculitis, and postulate a pathogenetic role for alpha 1-AT deficiency and the occurrence of ANCA, with specificity for PR3 in a subgroup of patients with Wegener's granulomatosis.

Asymmetric septal hypertrophy in infants of diabetic mothers. Fetal echocardiography and the impact of maternal diabetic control.

Maternal hyperglycemia may result in fetal hyperinsulinemia and asymmetric septal hypertrophy, macrosomia, and hypoglycemia in infants of diabetic mothers. We monitored glycosylated hemoglobin levels in 61 pregnant diabetic women each trimester as an index of maternal glycemic control and did serial fetal echocardiograms starting at 18 weeks of gestation. At delivery, cord blood C-peptide levels were obtained as an index of fetal hyperinsulinemia. Infants were assessed for hypoglycemia, macrosomia and septal thickening by echocardiography. Nineteen of the 61 infants (31%) had septal hypertrophy, were heavier, and had higher cord blood C-peptide levels and lower serum glucose levels than unaffected infants. Maternal glycosylated hemoglobin levels were higher during the third trimester in mothers of affected infants. Our data support a possible relationship between third-trimester maternal hyperglycemia and neonatal asymmetric septal hypertrophy, macrosomia, and hypoglycemia.

Persistent functional atrioventricular block in two patients with prolonged QT intervals: elucidation of the mechanism of block.

This article describes two infants with prolonged QT interval and intermittent second-degree atrioventricular block. An asymptomatic 14-month-old child with persistent 2:1 atrioventricular conduction since birth underwent electrophysiology study including measurements with a contact monophasic action potential catheter. During 2:1 conduction, atrioventricular block occurred distal to the site of the His-bundle recording. Monophasic action potential duration was closely related to prior RR intervals. Single premature atrial or ventricular depolarizations during 1:1 conduction followed by a pause, lead to monophasic action potential prolongation and subsequent 2:1 atrioventricular conduction, which was perpetuated by the resulting long RR intervals. Paired premature ventricular contractions or short bursts of ventricular pacing elicited monophasic action potential shortening and subsequent 1:1 atrioventricular conduction that was perpetuated by the resulting short RR intervals. A second infant presented at birth with a prolonged QT interval, ventricular tachycardia, and episodes of second-degree atrioventricular block with persistent 2:1 atrioventricular conduction. The atrioventricular block was repeatedly elicited by single premature ventricular contractions and terminated by ventricular couplets. We conclude that the atrioventricular block in both patients is functional in nature and results from the interrelationships between ventricular rate, action potential duration, and His-Purkinje system refractoriness.

Congenital left ventricular inflow obstruction evaluated by two-dimensional echocardiography.

Several forms of congenital heart disease that cause left ventricular inflow obstruction have similar M-mode findings, and frequently the exact anatomic diagnosis cannot be made by M-mode echocardiography alone. We examined five children with various forms of left ventricular inflow obstruction using two-dimensional echocardiography. The diagnosis was confirmed by cardiac catheterization and surgery in all five patients. In one patient with congenital mitral valve stenosis, a thick mitral valve with two papillary muscles was imaged. This patient was easily distinguished from a second child with parachute deformity of the mitral valve in whom a single papillary muscle arising from the left ventricular apex was seen. These two patients with mitral valve stenosis were easily differentiated from the three patients in whom the left ventricular inflow obstruction was caused by a membrane within the left atrium. The membrane could be seen in several spatial planes; however, we could not distinguish by two-dimensional echocardiography one child who had cor triatriatum from the other two patients who had a supravalvar mitral ring. Because of its spatial anatomic display, the two-dimensional echocardiogram provides information for a more detailed anatomic diagnosis in children with congenital left ventricular inflow obstruction.

Cardiac structure growth pattern determined by echocardiography.

Using M-mode echocardiography, we measured dimensions of the ventricular walls and cavities, great vessels, and left atrium and atrioventricular valve excursions on 93 infants and children without heart disease. The data were analyzed by relating each dimension in mm to body surface area in m2 and the 90% tolerance limits for the data were calculated. The tolerance lines of the data were wider than previously recorded. At birth and maturity they were similar to the range defined as normal by studies in neonates and adults. We suggest that the tolerance lines of these normal data may be used for quantitative echocardiography in childhood.