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.

Breast Cancer Care Pathways for Women with Preexisting Severe Mental Disorders: Evidence of Disparities in France?

The excess cancer mortality in persons with severe mental illness (SMI) has been well documented, and research suggests that it may be influenced by care-related factors. Our objective was to assess breast cancer care pathways in women with SMI in France, using an exhaustive population-based data-linkage study with a matched case-control design. The cases were 1346 women with incident breast cancer in 2013/2014 and preexisting SMI who were matched with three controls without SMI presenting similar demographics, initial breast cancer type, and year of incidence. We compared cancer care pathways and their quality for cases and controls, using a consensual set of indicators covering diagnosis, treatment, follow-up, and mortality (until 2017). After adjusting for covariates, cases had lower odds to undergo the main diagnostic tests, lumpectomy, adjuvant chemotherapy, and radiotherapy, as well as hormone therapy, but higher odds for mastectomy. Suboptimal quality in cancer pathways was observed for both groups, but to a higher extent for cases, especially for not receiving timely care after diagnosis and post-treatment follow-up. Breast cancer mortality, considering competing risks of deaths, was significantly elevated in women with SMI. These findings highlight disparities in cancer care pathways for individuals with SMI, as well as specific aspects of the care continuum which could benefit from targeted actions to reach equity of outcomes.

Hypoparathyroidism-related health care utilization and expenditure during the first postoperative year after total thyroidectomy for cancer: a comprehensive national cohort study.

Objectives: Hypoparathyroidism is the most common complication of total thyroidectomy for cancer, and requires calcium and/or vitamin D supplementation for an unpredictable period of time. The additional cost associated with this complication has not hitherto been assessed. The aim of this study was to assess the economic burden of postoperative hypoparathyroidism after total thyroidectomy for cancer in France. Methods: Based on the French national cancer cohort, which extracts data from the French National Health Data System (SNDS), all adult patients who underwent a total thyroidectomy for cancer in France between 2011 and 2015 were identified, and their healthcare resource use during the first postoperative year was compared according to whether they were treated postoperatively with calcium and/or vitamin D or not. Univariate and multivariate cost analyses were performed with the non-parametric Wilcoxon test and generalized linear model (gamma distribution and log link), respectively. Results: Among the 31,175 patients analyzed (75% female, median age: 52y), 13,247 (42%) started calcium and/or vitamin D supplementation within the first postoperative month, and 2,855 patients (9.1%) were still treated at 1 year. Over the first postoperative year, mean overall and specific health expenditures were significantly higher for treated patients than for untreated patients: €7,233 vs €6,934 per patient (p<0.0001) and €478.6 vs €332.7 per patient (p<0.0001), respectively. After adjusting for age, gender, Charlson Comorbidity index, ecological deprivation index, types of thyroid resection, lymph node dissection and complications, year and region, the incremental cost of overall health care utilization was €142 (p<0.004). Conclusion: Our study found a significant additional cost in respect of health expenditures for patients who had hypoparathyroidism after thyroidectomy for cancer, over the first postoperative year. Five-year follow-up is planned to assess the impact of more severe long-term complications on costs.

Access to palliative care for cancer patients between diagnosis and death: a national cohort study.

Background and purpose: Introducing palliative care earlier in the disease trajectory has been found to provide better management of physical and psychological suffering. In France, the proportion of cancer patients who receive palliative care is unclear. This study aimed primarily to measure the prevalence of access to inpatient palliative care and associated patient-level factors, and to identify the time between access to palliative care and death. Patients and methods: A nationwide retrospective cohort study using data from the French national health system database (SNDS). All those diagnosed with cancer in 2013 who died between 2013 and 2015 were included. Access to inpatient palliative care was the main outcome. Results: Of the 313,059 patients diagnosed with cancer in 2013 in France, 72,315 (23%) died between 2013 and 2015. Overall, 57% had access to inpatient palliative care. The following groups were the most likely to have access to palliative care: women (adjusted odds ratio, aOR: 1.15; 95% CI: 1.11-1.20), people aged 18-49 (aOR: 1.38; 95% CI: 1.26-1.51), individuals with metastatic cancer (aOR: 2.04; 95% CI: 1.96-2.13), and patients with cancer of the nervous system (aOR: 1.80; 95% CI: 1.62-2.01). The median time between palliative care and death was 29 (interquartile range: 13-67) days. Conclusion: More than half of cancer patients who died within 2 years after diagnosis had access to inpatient palliative care. Access to palliative care occurs late in the disease trajectory, often during the final month of life. Further research and guidelines are warranted to optimize access to early, standardized palliative care.

Study of the impact of liver transplantation on the outcome of intestinal grafts in children.

BACKGROUND: Successful small bowel transplantation remains a challenge due to the septic and immune content of the gut. The possible beneficial role of the liver was assessed in pediatric recipients of isolated intestinal and liver intestinal combined transplantation, receiving the same immunosuppressive therapy. METHODS: Fifteen children who underwent small bowel transplantation (seven SbTx) or combined liver-small bowel transplantation (eight LSbTx) at a single center between 1994 and 1998 were retrospectively reviewed and compared with fifteen controls (eight normal and seven appendicitis as inflammatory control). Transplant and patient survival, acute rejection episodes were analyzed and compared. Epithelial apoptotic body counts (ABC) and NF-kB (p65), Caspase-3 and Bax intestinal immunostaining from days 0 to 20 after transplantation were assessed. RESULTS: Graft and patient survivals at 5 years were respectively 75% and 75% in LSbTx; 43% and 57% in SbTx (NS). Histological analysis showed higher ABC in LSbTx intestinal mucosa (P = 0.05 on day 5, P < 0.01 thereafter). Immunostaining of biopsies on day 0 after reperfusion showed different expression of NF-kB, Caspase-3 and Bax on endothelial (P < 0.05 for NF-kB and Bax), mononuclear (P < 0.05 for Bax) and epithelial cells in LSbTx and SbTx. CONCLUSIONS: Our results suggest a protective role of the liver toward intestinal transplantation even in absence of significative difference, probably due to the small number of children. Early changes in NF-kB immunostaining in the biopsies sampled on day 0, pointed to a possible beneficial effect of the liver in the very early phase following transplantation, perhaps through the differential control of ischemia-reperfusion.

Log files analysis to assess the use and workload of a dynamic web server dedicated to end-stage renal disease.

A Multi-Source Information System (MSIS), has been designed for the Renal Epidemiology and Information Network (REIN) dedicated to End-Stage Renal Disease (ESRD). MSIS aims at providing reliable follow-up data for ESRD patients. It is based on an n-tier architecture, made out of a universal client, a dynamic Web server connected to a production database and to a data warehouse. MSIS is operational since 2002 and progressively deployed in 9 regions in France. It includes 16,677 patients. We show that the analysis of MSIS web log files allows evaluating the use of the system and the workload in a public-health perspective.

Perforation of the atretic pulmonary valve. Long-term follow-up.

OBJECTIVES: We evaluated the long-term results of perforation of the pulmonary valve in patients with pulmonary atresia with an intact ventricular septum (PA-IVS). BACKGROUND: Interventional perforation of the pulmonary valve is considered the elective first stage treatment for PA-IVS, particularly in patients with a tripartite right ventricle (RV) and normal coronary circulation. However, the long-term results of this procedure are lacking. METHODS: Between January 1991 and December 2001, 39 newborns with a favorable form of PA-IVS underwent attempted perforation of the pulmonary valve. We evaluated the early and long-term outcomes. RESULTS: Median tricuspid and pulmonary z values were -1.2 and -2.4, respectively. Perforation was successful in 33 patients. Among them, 17 needed neonatal surgery, 13 did not need any surgery, and 3 had elective surgery after the first month of life. There were two procedure-related deaths, seven nonfatal procedural complications, and four postsurgical deaths. Compared with patients needing neonatal surgery, those having no or elective surgery had a higher incidence of a tripartite RV and a higher median tricuspid z value (92% vs. 53%, p = 0.04 and -1.7 vs. -0.5, p = 0.03). At a median follow-up of 5.5 years (range 0.5 to 11.5), survival was 85% and freedom from surgery was 35%. Five patients, four of whom had neonatal surgery, underwent a partial cavo-pulmonary connection. CONCLUSIONS: Our results show that this technique, although burdened by non-negligible mortality and morbidity, is effective in selected patients with a normal-sized RV. Preselection of patients allows interventional or surgical biventricular correction in the majority of cases.

Long-term social outcome of children after kidney transplantation.

BACKGROUND: There are few data concerning the social outcome at adult age of children who received a kidney transplant. The aim of this study was to collect information on this outcome in a cohort of 366 children who underwent transplantation between 1973 and 1985. METHODS: Information was obtained through a simple questionnaire in 244 patients. The mean age of the patients was 31.7 years, and they had undergone grafting at a mean age of 11.9 years. RESULTS: As of December 2000 or at last visit, 77% had a functioning graft. The mean height was 156.6 cm for male patients and 147.4 cm for female patients. The distribution of educational level was lower than national averages: 27.4% were at the lowest level versus 3% of the general population, 41.4% were at the middle level, 31.2% had reached the baccalaureate level, and 11% had followed a university cursus. Activity was similar to the general population: 73% had paid employment versus 72%, 6.5% were unemployed versus 10.5%, and 18.7% received a disablement pension. Among the 149 male patients, 39 (27%) had a marital life and 12 (8.3%) had children, whereas among the 95 female patients, 48 (50%) had a marital life and 26 (27%) had at least one child. Lodging was the parent's home in 46% and independent in 54%. Multivariate analysis showed a significant correlation between educational level, paid activity, marital life, and independent housing with final height. CONCLUSIONS: The long-term social outcome of patients who underwent grafting in childhood more than 15 years previously is encouraging. The importance of reaching a normal height is stressed.

Incidence and cost of osteoporotic fractures in France during 2001. A methodological approach by the national hospital database.

The objective of this study was to describe the hospital incidence rate and the in-patient costs of three peripheral "osteoporotic" fractures (proximal humerus and hip, distal radius and/or ulna) in women and men aged over 45 in France during 2001. Each stay for fracture was selected from the dataset of the French national hospital database in 2001. The incidence rate (CI 95%) was standardized by age and gender according to the last census of the French population (1999). The effect of age and existence of geographical difference in incidence rates has been studied. For each fracture, we described the number of stays, rate of surgical procedure and in-patient costs according to the 2004 French list of cost per diagnosis-related group (2004 Euros); 118,839 fractures were registered during 2001 (61% hip, 28% distal radius and 11% proximal humerus; sex ratio 0.26). The incidence rate for all fracture was 7,567 (7,519-7,615) and 2,312 (2,283-2,341) for 10(6) inhabitants in women and men aged over 45 years, respectively. The incidence increased significantly whatever type of fracture and gender. There were more fracture incidents in the east of France compared to the west and in the south compared to the north, whatever type of fracture in women and only for hip fracture in men. Surgical procedures were performed in 91% of proximal hip fractures, 83% of distal radius fractures and 53% of proximal humerus fractures. The median in-patient costs were 3,786 Euros for the humerus, from 2,363 to 2,574 Euros for the radius and from 8,048 to 8,727 Euros for the hip. The evaluation of the burden of peripheral fractures is possible using national hospital data in France. The incidence of fractures increased with age and is more common in women. Hip fracture with its higher occurrence, rate of procedure and in-patient costs could be used as a marker of osteoporosis for evaluating strategies of management.

Complications of paediatric interventional catheterisation: an analysis of risk factors.

OBJECTIVES: To identify predictive factors of complications occurring during paediatric interventional catheterisation. BACKGROUND: Interventional paediatric catheterisation is still burdened by a substantial risk. Risk factors, however, have rarely been investigated. METHODS: We analysed prospectively 1,022 interventional procedures performed over a period of 8 years, excluding 260 procedures for atrial septostomy. We considered several patient-related variables, specifically age, weight, and gender, type of procedure, times required for fluoroscopy and the overall procedure, technical challenge, and the severity of the clinical condition. We also analysed variables linked to the environment, specifically the date of the examination, whether the operator remained in training, the novelty of the material, any breakdown in the installation, and errors made by the operator. We classified complications as those without clinical consequence, those which proved lethal, those requiring cardiopulmonary resuscitation, elective or emergency surgery, hospitalisation in the intensive care unit, and those leading to recatheterisation. RESULTS: Our average incidence of complications was 4.1 per cent, which did not change significantly during the period of study. Of the patients, 4 died, 7 needed urgent surgery, 5 elective surgery, 3 hospitalisation in intensive care unit, and 8 recatheterisation. Independent risk factors for complications were technical challenge, critical clinical condition, operator in training, operator error, and breakdown of the installation. Young age was not associated with a higher risk of complications. Patients in whom no cause for complication could be found, either related to their own features or the environment, had a risk of complication of 1.4 per cent (95 per cent confidence intervals from 0.7 to 2.5 per cent). CONCLUSIONS: Our data show that variables relating either to the patient or the environment of catheterisation are associated with an increased risk of procedural complications. Knowledge of the risk factors can improve the odds of paediatric interventional catheterisation.

Olfactory evaluation in children: application to the CHARGE syndrome.

OBJECTIVE: To find an efficient tool for testing olfactory function in children and use it to investigate a group of children with CHARGE (coloboma, congenital heart disease, choanal atresia, mental and growth retardation, genital anomalies, and ear malformations and hearing loss) syndrome. METHODS: We adapted for children an olfaction test that had just been validated in an adult French population and investigated a control group of 25 healthy children aged 6 to 13 years. We then tested the olfactory capacity of a group of 14 children with CHARGE syndrome, aged 6 to 18 years. A questionnaire was completed with the parents about their children's feeding difficulties and their ability to recognize odors in everyday life. We recorded and scored the histories of feeding behavior anomalies, the visual and auditory status, and current intellectual levels. MRI of the olfactory tracts and bulbs was analyzed for 9 of 14 children. RESULTS: We showed that healthy children have similar olfactory function to that of the adult control group, which was representative of the general population, without any difference for either gender or age. We also showed that all children with CHARGE syndrome had olfactory deficiency. Half of them were anosmic, and the others had olfactory residual function (hyposmic). We found no association between olfactory deficiency and feeding behavior, visual or auditory impairment, or intellectual level. Parental subjective evaluations were accurate for only half of the group. All of the MRIs showed anomalies of the olfactory tracts and bulbs varying from moderate hypoplasia to complete aplasia, without any relation between the radiologic and the functional results. CONCLUSIONS: Olfaction can be assessed in children, even the young and disabled. Our results support the proposition that rhinencephalon anomalies should be included as a major criterion for the diagnosis of CHARGE syndrome.

Glucocorticoid pharmacokinetics and growth retardation in children with renal transplants.

Long-term glucocorticoid treatment contributes to the growth retardation in children after renal transplantation. We investigated whether determination of prednisone (PN) and prednisolone (PL) in plasma and PN, PL, and 6-beta-hydroxyprednisolone (betaOH-PL) in urine could help to predict growth. PN and PL pharmacokinetics were studied in 36 children, from 5 to 15 years of age, receiving daily (D) or alternate-day (AD) oral PN treatment. Statural growth velocity was evaluated over a 1-year period. We compared three groups of children according to the growth kinetics during the study year (catch-up, stable, or decline) for clinical and pharmacokinetic parameters. A multiple linear regression analysis was performed in order to determine pharmacokinetic parameters able to explain height 1 year after inclusion. Height at the beginning of the study, creatinine clearance, and type of D or AD treatment explained 94.2% of height variance 1 year after inclusion. Only PL clearance was associated with growth evolution, but introduction of PL clearance in the multivariate model did not improve the variance of height accounted for by the previous model. We, therefore, do not recommend using glucocorticoid pharmacokinetics to predict growth retardation in children with renal transplantation.