Systematic neonatal screening for severe combined immunodeficiency and severe T-cell lymphopenia: Analysis of cost-effectiveness based on French real field data.

BACKGROUND: The inclusion of severe combined immunodeficiency (SCID) in a Europe-wide screening program is currently debated. OBJECTIVE: In making a case for inclusion in the French newborn screening program, we explored the costs incurred and potentially saved by early management of SCID. METHODS: For test costs, a microcosting study documented the resources used in a laboratory piloting a newborn screening test on Guthrie cards using the T-cell receptor excision circle quantification method. For treatment costs, patients with SCID admitted to the national reference center for primary immunodeficiency in France between 2006 and 2010 were included. Costs of admission were estimated from actual national production costs. We estimated the costs for patients who underwent early versus delayed hematopoietic stem cell transplantation (HSCT; age, ≤3 vs. >3 months, respectively). RESULTS: The unit cost of the test varied between €4.69 and €6.79 for 33,800 samples per year, depending on equipment use and saturation. Of the 30 patients included, 27 underwent HSCT after age 3 months. At 1 year after HSCT, 10 of these had died, and all 3 patients undergoing early transplantation survived. The medical costs for HSCT after 3 months were €195,776 (interquartile range, €165,884-€257,160) versus €86,179 (range, €59,014-€272,577) when performed before 3 months of age. In patients undergoing late transplantation, active infection contributed to high cost and poor outcome. CONCLUSION: Early detection of SCID could reduce the cost of treatment by €50,000-100,000 per case. Assuming a €5 unit cost per test, the incidence required to break even is 1:20,000; however, if the survival advantage of HSCT before 3 months is confirmed, universal screening is likely to be cost-effective.

Characteristics and outcome of early-onset, severe forms of Wiskott-Aldrich syndrome.

On the basis of a nationwide database of 160 patients with Wiskott-Aldrich syndrome (WAS), we identified a subset of infants who were significantly more likely to be attributed with an Ochs score of 5 before the age of 2 (n = 26 of 47 [55%], P = 2.8 × 10(−7)). A retrospective analysis revealed that these patients often had severe refractory thrombocytopenia (n = 13), autoimmune hemolytic anemia (n = 15), and vasculitis (n = 6). One patient had developed 2 distinct cancers. Hemizygous mutations predictive of the absence of WAS protein were identified in 19 of the 24 tested patients, and the absence of WAS protein was confirmed in all 10 investigated cases. Allogeneic hematopoietic stem cell transplantation (HSCT) was found to be a curative treatment with a relatively good prognosis because it was successful in 17 of 22 patients. Nevertheless, 3 patients experienced significant disease sequelae and 4 patients died before HSCT. Therefore, the present study identifies a distinct subgroup of WAS patients with early-onset, life-threatening manifestations. We suggest that HSCT is a curative strategy in this subgroup of patients and should be performed as early in life as possible, even when a fully matched donor is lacking.

Does the radiographic transition zone correlate with the level of aganglionosis on the specimen in Hirschsprung's disease?

PURPOSE: The correlation between radiographic transition zone on contrast enema in Hirschsprung's disease and the total length of aganglionosis is known to be inaccurate. The aim of our study was to analyse this correlation more precisely to improve preoperative planning of the corrective surgery. METHODS: From 1998 to 2009, 79 patients were operated on for Hirschsprung's disease. All available preoperative contrast enemas (n = 61) had been single blind reviewed by the same radiologist who defined the radiographic transition zone when present in vertebral level. Four groups were determined (rectal, rectosigmoid, long segment, and absence of transition zone) and by Kappa coefficient of agreement correlated to the length of aganglionosis in the pathological report. RESULTS: Radiological findings were concordant with the specimen in pathology in 8 cases of 19 in rectal form (42 %), in 20 cases of 35 in rectosigmoid form (57 %), in all 6 cases of long-segment form (100 %), in the 2 cases of total colonic form (100 %) with a global agreement of 58.1 %, κ = 0.39 CI [0.24; 0.57]. CONCLUSION: Correlation between level of radiographic transition zone on contrast enema and length of aganglionosis remains low. Systematic preoperative biopsy by coelioscopy or ombilical incision is mandatory.

Retrospective analysis of surgery versus endovascular intervention in Takayasu arteritis: a multicenter experience.

BACKGROUND: With recent advances in endovascular treatment, percutaneous endoluminal angioplasty has become particularly attractive for arterial lesions of Takayasu arteritis. However, data came from case reports or small series, and the long-term outcome has not been reported. The incidence of potential vascular complications after surgery or endovascular treatment is still to be determined. METHODS AND RESULTS: This retrospective multicenter study analyzed the results and outcomes of 79 consecutive patients with Takayasu arteritis (median age, 39 years; interquartile range [IQR], 25-50 years; 63 women [79.7%]) who underwent 166 vascular procedures (surgery, 104 [62.7%]; endovascular repair, 62 [37.3%]) for the management of arterial complications. After a follow-up of 6.5 years (IQR, 2.2-11.5 years), 70 complications were observed, including restenosis (n=53), thrombosis (n=7), bleeding (n=6), and stroke (n=4). The overall 1-, 3-, 5-, and 10-year arterial complication-free survival rates were 78% (IQR, 69%-88%), 67% (IQR, 57%-78%), 56% (IQR, 46%-70%), and 45% (IQR, 34%-60%), respectively. Among the 104 surgical procedures, 39 (37.5%) presented a complication compared with 31 of the 62 (50%) with endovascular repair. In multivariate analysis, biological inflammation at the time of revascularization (odds ratio, 7.48; 95% confidence interval, 1.42-39.39; P=0.04) was independently associated with the occurrence of arterial complications after the vascular procedure. Patients who experienced complications had higher erythrocyte sedimentation rates (P<0.001) and C-reactive protein (P<0.001) and fibrinogen (P<0.005) serum levels compared with those without complications. CONCLUSIONS: The overall 5-year arterial complication rate was 44%. Biological inflammation increased the likelihood of complications after revascularization in patients with Takayasu arteritis.

Case-control study of respiratory dynamic compliance in mechanically ventilated near-term newborns in a pre-hospital setting.

PURPOSE: To determine the threshold value between normal or decreased dynamic compliance (Cdyn) in ventilated near-term newborns. METHODS: A case control study was performed during pediatric transport. Controls were newborns without pulmonary disease (group 1; n = 30) and cases were newborns with respiratory distress syndrome, the paradigm of decreased Cdyn (group 2; n = 30). All consecutive newborns of more than 34 weeks' gestation and less than 5 days of life, intubated and ventilated with Babylog 8,000 plus (Dräger, Lübeck, Germany) were included from February 2008 to June 2010. Newborns were assigned to groups 1, 2, or 3 (other patients with disease where the compliance is not easily predictable) by two physicians, using predefined criteria. Cdyn was as measured by the ventilator in spontaneous mandatory ventilation mode with less than 15% leaks. RESULTS: One hundred and twelve newborns were included in the study. In the multivariate analysis, the groups of diseases and height were statistically associated with Cdyn (p < 0.001). The receiver operating characteristic curve of Cdyn corrected for height constructed with group 1 and 2 newborns yielded a cutoff value of 2.02 mL/mbar/m with a sensitivity of 100% (95% confidence interval [100-100%]) and a specificity of 96% (95% confidence interval [90-100%]) to differentiate between group 1 and 2 newborns. CONCLUSION: Ventilator-measured dynamic compliance can differentiate normal and decreased compliance in near-term newborns of more than 34 weeks' gestation in the clinical setting.