Circumcision and Risk of Febrile Urinary Tract Infection in Boys with Posterior Urethral Valves: Result of the CIRCUP Randomized Trial.

BACKGROUND: Boys with posterior urethral valves (PUVs) have an increased risk of febrile urinary tract infections (fUTIs). Circumcision is believed to reduce the risk of fUTIs in boys, although there are no randomized trials demonstrating this. OBJECTIVE: To determine the effect of circumcision on the risk of fUTIs in boys with PUVs. DESIGN, SETTING, AND PARTICIPANTS: A clinical randomized trial that ran between August 2012 and July 2017 was conducted. The trial was multicentric, including 13 referral centers for pediatric urology. Male boys, aged 1-28 d, diagnosed with posterior urethral valves, confirmed by voiding cystogram, were included. The exclusion criteria included presence of a genital malformation contraindicating performing a circumcision. INTERVENTION: Participants were randomized to neonatal circumcision + antibiotic prophylaxis (CATB) or antibiotic prophylaxis alone (ATB), and followed for 2 yr. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was a risk of presenting fUTIs in each group. An fUTI was defined as fever (>38.5 °C) with evidence of pyuria and culture-proven infection on urinalysis, obtained by urethral catheterization or suprapubic aspiration. A bivariate analysis of the primary outcome was performed using the Kaplan-Meier method. RESULTS AND LIMITATIONS: In total, 91 patients were included: 49 in group CATB and 42 in group ATB. The probability of presenting an fUTI was 20% in group ATB versus 3% in group CATB. The hazard ratio of presenting an fUTI within 2 yr in the ATB group compared with that in the CATB group was 10.3 (95% confidence interval: 1.3-82.5). Sixty-four children (70.3%) had a complete follow-up at 2 yr of age. CONCLUSIONS: Circumcision significantly decreases the risk of presenting an fUTI in boys with PUVs. PATIENT SUMMARY: In this report, we compared, in a multicentric trial, the number of febrile urinary tract infections (UTIs) in boys with posterior urethral valves who had either antibiotic prophylaxis alone or antibiotic prophylaxis and circumcision. We found that those who had a circumcision had a significantly lower risk of febrile UTIs.

[Technical improvement of cohort constitution in administrative health databases: Providing a tool for integration and standardization of data applicable in the French National Health Insurance Database (SNIIRAM)]. / Optimisation de la constitution de cohortes issues de bases de données médico-administratives : mise à disposition d'un algorithme pour l'intégration et la normalisation des données adapté au Système national d'information inter-régimes de l'assurance maladie (SNIIRAM).

AIM: Administrative health databases such as the French National Heath Insurance Database - SNIIRAM - are a major tool to answer numerous public health research questions. However the use of such data requires complex and time-consuming data management. Our objective was to develop and make available a tool to optimize cohort constitution within administrative health databases. METHODS: We developed a process to extract, transform and load (ETL) data from various heterogeneous sources in a standardized data warehouse. This data warehouse is architected as a star schema corresponding to an i2b2 star schema model. We then evaluated the performance of this ETL using data from a pharmacoepidemiology research project conducted in the SNIIRAM database. RESULTS: The ETL we developed comprises a set of functionalities for creating SAS scripts. Data can be integrated into a standardized data warehouse. As part of the performance assessment of this ETL, we achieved integration of a dataset from the SNIIRAM comprising more than 900 million lines in less than three hours using a desktop computer. This enables patient selection from the standardized data warehouse within seconds of the request. CONCLUSION: The ETL described in this paper provides a tool which is effective and compatible with all administrative health databases, without requiring complex database servers. This tool should simplify cohort constitution in health databases; the standardization of warehouse data facilitates collaborative work between research teams.

Male infants with hypospadias and/or cryptorchidism show a lower 2D/4D digit ratio than normal boys.

BACKGROUND: In humans the ratio of the index finger to the ring finger is sexually dimorphic, with the mean ratio being larger in women than in men. It has been suggested that this difference is related to prenatal androgen exposure. This has been further demonstrated in children with congenital adrenal hyperplasia. Normal development of the male external genitalia is linked to androgen-mediated events during gestation. We therefore wanted to determine if the 2D:4D digit ratio was normal in boys with cryptorchidism or hypospadias. METHODS: We prospectively enrolled all prepubertal patients seen in the outpatient clinic for cryptorchidism or hypospadias between September and December 2012. We then compared their 2D:4D digit ratio with two control groups made up of normal boys and normal girls. Interobserver and intraobserver variability was evaluated. RESULTS: We included 57 boys with hypospadias and/or cryptorchidism, 79 boys without genital abnormalities and 25 girls without genital abnormalities. The mean 2D:4D ratio for both hands was significantly different between the three groups, with the digit ratio for boys with genital anomalies being lower than for normal boys and normal girls (p<0.0001). CONCLUSIONS: It appears that boys with genital abnormalities (cryptorchidism and/or hypospadias) have a lower 2D:4D digit ratio than boys without genital anomalies.

Adjuvant endocrine therapy with tamoxifen in young women with breast cancer: determinants of interruptions vary over time.

BACKGROUND: In premenopausal women with hormone receptor-positive breast cancer (BC), 5 years of tamoxifen is recommended. Little is known about reasons for interruption in this population. The aim was to estimate the incidence of tamoxifen interruption and its correlates among younger women. PATIENTS AND METHODS: Using a prospective cohort Elippse 40 of women with BC aged ≤ 40 diagnosed between 2005 and 2008, we studied 196 women. Tamoxifen interruption was defined as two or more consecutive months without dispensed prescription of tamoxifen, based on pharmacy refill database. Two periods were studied: between tamoxifen initiation and 16 months after BC diagnosis, and between 16 and 28 months. RESULTS: Among women treated with tamoxifen, 42% interrupted within the first 2 years of treatment. During the first period, treatment interruptions were associated with a lack of understandable information about endocrine treatment and insufficient social support. During the second period, another set of factors were associated with interruption: treatment side-effects, no longer fearing cancer relapse, lack of social support, no opportunity to ask questions at the time of diagnosis, and fewer treatment modalities. CONCLUSIONS: Improving information and patient-provider relationship might prevent interruption. Particular attention should be paid to women with little social support.

Use of tamoxifen and aromatase inhibitors in a large population-based cohort of women with breast cancer.

BACKGROUND: Non-compliance with oral treatment in oncology is an emerging health issue. For breast cancer (BC) patients, few data are available on compliance and persistence to tamoxifen in younger women and to aromatase inhibitors (AIs) as compared with tamoxifen in older women. METHODS: We constituted a cohort of 13,479 women with BC who received at least one prescription of tamoxifen or AI between 1998 and 2008, in the United Kingdom General Practice Research Database. Days covered by medication and treatment discontinuation were studied. Time to treatment discontinuation was calculated using Kaplan-Meier estimates. RESULTS: Overall, 18.9% (95% CI: 15.1-23.0) of women on AIs as compared with 31.0% (95% CI: 29.6-32.2) of women on tamoxifen had discontinued their treatments within the first 5 years (P<0.001). This rate raised to 50.7% (95% CI: 43.0-57.9) among the 416 women under 40 years receiving tamoxifen as initial hormonal therapy. Among older women, treatment discontinuation was less frequent for AIs as compared with tamoxifen (P<0.001). Among women on AI therapy, 14% of them (n=374) had switched treatments. CONCLUSION: Among older women, the real-life patterns of use of AI show high rates of compliance. In younger women, tamoxifen is prematurely discontinued for half of patients.

Molecular study of CEBPA in familial hematological malignancies.

Familial aggregation in patients with several haematological malignancies has been described, but the genetic basis for this familial clustering is not known. Few genes predisposing to familial haematological malignancies have been identified, among which RUNX1 and CEBPA have been described as predisposing genes to acute myeloid leukemia (AML). Recent studies on RUNX1 suggest that germline mutations in this gene predispose to a larger panel of familial haematological malignancies than AML. In order to strengthen this hypothesis, we have screened CEBPA for germline mutations in several families presenting aggregation of hematological malignancies (including chronic or acute, lymphoid or myeloid leukemias, Hodgkin's or non Hodgkin's lymphomas, and myeloproliferative or myelodysplastic syndromes) with or without solid tumours. Although no deleterious mutations were found, we report two novel and rare variants of uncertain significance. In addition, we confirm that the in frame insertion c.1175_1180dup (p.P194_H195dup) is a germline polymorphism.

Subjective interpretation of inconclusive BRCA1/2 cancer genetic test results and transmission of information to the relatives.

OBJECTIVE: BRCA1/2 gene mutations are not frequently identified in breast or ovarian cancer patients who are the first members of their family to be tested. Little is known about how probands interpret and cope with these results, which are generally referred to as 'inconclusive'. The aim of this study was to describe subjective understanding by women with cancer in response to an inconclusive BRCA1/2 test, describing the difficulties or non-difficulties they encountered about the transmission of information to their family. METHODS: A cohort of 30 women with breast/ovarian cancer were followed for a period of up to 2 years after delivery of their inconclusive genetic test results. Self-administered questionnaires with closed and open questions were distributed. A qualitative analysis of open-ended questions is presented here. RESULTS: These women's reactions to inconclusive results were of three kinds. The majority (n=14) were still uncertain about their carrier status, which is an adequate medical interpretation of the results, while others (n=9) took their inconclusive results to mean that they were definitely not carriers, and the women in the last group (n=7) were convinced that they were actually carriers. There was some overlap between these perceptions and actual genetic risk. CONCLUSIONS: The transmission of information to the family was found to differ qualitatively across the three groups and more difficulties in this respect were expressed by those who were uncertain about their carrier status.

A reappraisal of preoperative chemoradiation for localized pancreatic head ductal adenocarcinoma in a 5-year single-institution experience.

Resection of localized pancreatic head ductal adenocarcinoma (LPHDA) has a limited impact on survival. Mechanisms of improvement provided by preoperative chemoradiation therapy (CRT) remain under debate. This study analyzes the outcome of patients treated for LPHDA to delineate the benefits of CRT. Among 87 patients with LPHDA, 17 had a pancreaticoduodenectomy alone (group I). Thirty-nine with initially resectable cancers received CRT with 5-fluorouracil-based chemotherapy (group II). Thirty-one with initially unresectable cancers were similarly treated by CRT (group III). Patients in groups II and III were restaged after completion of CRT. In patients with resectable disease, resection was planned. Patients in groups I and II were statistically comparable in terms of age, sex, and pretherapeutic stage. Median survival and 2-year overall survival in group I were 13.7 months and 31%, respectively. In group II, 23 patients (59%) had a pancreaticoduodenectomy (group IIa) and 16 patients (41%) did not have resection (group IIb). Median survival and 2-year overall survival were as follows: group IIa, 26.6 months and 51%; and group IIb, 6.1 months and 0%, respectively. In group IIa, pathologic examination revealed eight major responses (35%) including two sterilized specimens, and none of the patients had locoregional recurrence. In group III, none of the patients had resection, and median survival was 8 months with one 2-year survivor. Patient selection appears to play a major role with regard to results achieved with preoperative CRT followed by pancreaticoduodenectomy. However, a high histologic response rate and excellent local control can also be achieved.