Primary ciliary dyskinesia gene contribution in Tunisia: Identification of a major Mediterranean allele

Primary ciliary dyskinesia (PCD) is a genetically heterogeneous disease of motile cilia. Even though PCD is widely studied, North‐African patients have been rarely explored. In this study, we aim at confirming the clinical diagnosis and explore the genetic spectrum of PCD in a cohort of Tunisian patients. Forty clinically diagnosed patients with PCD belonging to 34 families were recruited from Tunisian pediatric departments. In each proband, targeted capture PCD panel sequencing of the 40 PCD genes was performed. PCD panel sequencing identified bi‐allelic mutations in 82% of the families in eight PCD genes. Remarkably, 23.5% of patients carried the same c.2190del CCDC39 mutation. Single nucleotide polymorphism profiling in six unrelated patients carrying this mutation has revealed a founder effect in North‐African patients. This mutation is estimated to date back at least 1,400–1,750 years ago. The identification of this major allele allowed us to suggest a cost‐effective genetic diagnostic strategy in North‐African patients with PCD.     

Antinuclear antibodies in children: clinical signification and diagnosis utility

Background: Antinuclear antibodies (ANA) test is used to screen adults as well as children for connective tissue diseases (CTD) and autoimmune hepatitis. However, interpretation of ANA positivity can be delicate. Aim: to determine clinical significance and diagnosis utility of ANA positivity in children. Methods: Patients from a general pediatric department with ANA positive results were included (follow-up period of 2 years). ANA screening was performed by indirect immunofluorescence (IIF) on HEp-2 cells substrate (BioSystems^®). In case of ANA positivity (cut-off: 1:80), the specificity was determined by IIF on Crithidia luciliea substrate (BioSystems^®) and immunodot (Euroimmun^®). Results: Among 102 ANA tests, 55 (53,9%) were positive. We recorded the data of 38 patients (age average: 9,5 years - sex ratio: 0.72). The most frequent signs were join pain (55,3%). ANA titer varied between 1:80 (39,5% of cases) and 1:1280 (2,6% of cases). Typing was negative in 89,5% of cases. The majority (42,1%) of children with positive ANA test had musculoskeletal diseases. The others (57,9%) had systemic lupus erythematosus(n=2), overlap syndrome(n=1), rheumatoid purpura(n=2), idiopathic thrombocytopenic purpura(n=1), coeliac disease(n=1) or non-autoimmune diseases/no confirmed diagnosis(n=15). Conclusions: ANA prevalence in children was relatively high. When the pretest probability is low, the positive predictive value for CTD or autoimmune hepatitis is low. However, depending on the clinical context, ANA detection can represent a supplement diagnostic tool for these diseases and/or can lead to a clinico-biological monitoring.     

Stability and change in family psychosocial risk over 6 months in pediatric cancer and its association with medical and psychosocial healthcare utilization

Purpose: Family psychosocial risk in pediatric oncology can be assessed using the Psychosocial Assessment Tool (PAT), a brief parent report screener based on the Pediatric Psychosocial Preventative Health Model (PPPHM; universal, targeted, and clinical). However, little is known about risk over the course of treatment and its association with medical and psychosocial healthcare utilization. Methods: Primary caregivers of children with cancer participated in this prospective multisite investigation, completing the PAT at diagnosis (T1; n = 396) and 6 months later (T2; n = 304). Healthcare utilization data were extracted from electronic health records. Results: The distribution of PPPHM risk levels at T1 and T2 was highly consistent for the samples. Two‐thirds of families remained at the same level of risk, 18% decreased and 16% increased risk level. Risk was not related to sociodemographic or treatment variables. The PAT risk score correlated with psychosocial contacts over the 6‐month period. Conclusions: Although the majority of families reported universal (low) risk on the PAT and were stable in their risk level over 6 months, reassessing risk is helpful in identifying those families who report higher level of risk during treatment than at diagnosis. PAT scores were related to psychosocial services that are provided to most but not all families and could be tailored more specifically to match risk and delivery of evidence‐based care.     

Evaluation of <i>MGMT</i> Gene Methylation in Neuroendocrine Neoplasms

Unresectable neuroendocrine neoplasms (NENs) often poorly respond to standard therapeutic approaches. Alkylating agents, in particular temozolomide, commonly used to treat high-grade brain tumors including glioblastomas, have recently been tested in advanced or metastatic NENs, where they showed promising response rates. In glioblastomas, prediction of response to temozolomide is based on the assessment of the methylation status of the MGMT gene, as its product, O6 -methylguanine-DNA methyltransferase, may counteract the damaging effects of the alkylating agent. However, in NENs, such a biomarker has not been validated yet. Thus, we have investigated MGMT methylation in 42 NENs of different grades and from various sites of origin by two different approaches: in contrast to methylation-specific PCR (MSP), which is commonly used in glioblastoma management, amplicon bisulfite sequencing (ABS) is based on high-resolution, next-generation sequencing and interrogates several additional CpG sites compared to those covered by MSP. Overall, we found MGMT methylation in 74% (31/42) of the NENs investigated. A higher methylation degree was observed in welldifferentiated tumors and in tumors originating in the gastrointestinal tract. Comparing MSP and ABS results, we demonstrate that the region analyzed by the MSP test is sufficiently informative of the MGMT methylation status in NENs, suggesting that this predictive parameter could routinely be interrogated also in NENs.     

Single-dose miconazole nitrate vaginal ovule in the treatment of vulvovaginal candidiasis: two single-blind, controlled studies versus miconazole nitrate 100 mg cream for 7 days

To determine the efficacy and safety of a single-dose (1200 mg) soft gel insert (vaginal ovule) with miconazole nitrate (2%) topical cream compared with Monistat 7 (miconazole nitrate 2%) Vaginal Cream (Advanced Care Products, North Brunswick NJ) in treating vulvovaginal candidiasis (VVC), two randomized, single-blind, multicenter, controlled, comparative phase III studies were performed. Five hundred fifty-eight patients received either a single-dose miconazole nitrate (1200 mg) ovule or seven consecutive doses of Monistat 7. Ovule arm patients also received miconazole nitrate 2% cream for symptom relief, as needed, up to twice daily. The primary end point was a therapeutic cure. Also evaluated were time to complete symptom relief, safety, and patient preference. The ovule had overall cure rates of 71.7% (71 of 99 patients) and 61.5% (64 of 104 patients). Monistat 7 had overall cure rates of 70.1% (68 of 97 patients) and 61.1% (55 of 90 patients). A significantly greater proportion of patients experienced complete symptom relief by day 3 with the ovule (p = 0.008 and p = 0.025), and time to complete relief was significantly faster (median 4 versus 5 days and 3 versus 4 days). Overall safety results were consistent between groups in both studies. Miconazole nitrate vaginal ovule is as safe and efficacious in curing VVC as Monistat 7 while providing complete symptom relief significantly faster. Patients preferred the ovule to prior therapy.     

Value of reagent strips in screening urinary infection in children

The aim of this study is to specify the role of rapid tests in the screening of childhood urinary tract infection. During the period between july to december 1998, 572 urinary samples were collected from pediatric out-patient in H?pital d'Enfants de Tunis and aged from 1 month to 15 years. Only 75 samples (12.5%) were culture positive. The predictive value of leucocytes or nitrites test was 97.2%. These results allowed the use of rapid test in the screening of urinary tract infection in children. However, if clinical symptoms are present, the culture of urine must be associated to the rapid test.