Clinical presentation of young people (10–24 years old) with brain tumors: results from the international MOBI-Kids study

Journal of Neuro-Oncology - We used data from MOBI-Kids, a 14-country international collaborative case–control study of brain tumors (BTs), to study clinical characteristics of the tumors in...     

Incidence and time trends of childhood lymphomas: findings from 14 Southern and Eastern European cancer registries and the Surveillance,Epidemiology and End Results,USA

Purpose

To describe epidemiologic patterns of childhood (0–14 years) lymphomas in the Southern and Eastern European (SEE) region in comparison with the Surveillance, Epidemiology and End Results (SEER), USA, and explore tentative discrepancies.

Methods

Childhood lymphomas were retrieved from 14 SEE registries (n = 4,702) and SEER (n = 4,416), diagnosed during 1990–2014; incidence rates were estimated and time trends were evaluated.

Results

Overall age-adjusted incidence rate was higher in SEE (16.9/10⁶) compared to SEER (13.6/10⁶), because of a higher incidence of Hodgkin (HL, 7.5/10⁶ vs. 5.1/10⁶) and Burkitt lymphoma (BL, 3.1 vs. 2.3/10⁶), whereas the incidence of non-Hodgkin lymphoma (NHL) was overall identical (5.9/10⁶ vs. 5.8/10⁶), albeit variable among SEE. Incidence increased with age, except for BL which peaked at 4 years; HL in SEE also showed an early male-specific peak at 4 years. The male preponderance was more pronounced for BL and attenuated with increasing age for HL. Increasing trends were noted in SEER for total lymphomas and NHL, and was marginal for HL, as contrasted to the decreasing HL and NHL trends generally observed in SEE registries, with the exception of increasing HL incidence in Portugal; of note, BL incidence trend followed a male-specific increasing trend in SEE.

Conclusions

Registry-based data reveal variable patterns and time trends of childhood lymphomas in SEE and SEER during the last decades, possibly reflecting diverse levels of socioeconomic development of the populations in the respective areas; optimization of registration process may allow further exploration of molecular characteristics of disease subtypes.

     

Neuroblastoma among children in Southern and Eastern European cancer registries: Variations in incidence and temporal trends compared to US

Neuroblastoma comprises the most common neoplasm during infancy (first year of life). Our study describes incidence of neuroblastoma in Southern–Eastern Europe (SEE), including – for the first time – the Nationwide Registry for Childhood Hematological Malignancies and Solid Tumors (NARECHEM‐ST)/Greece, compared to the US population, while controlling for human development index (HDI). Age‐adjusted incidence rates (AIR) were calculated for 1,859 childhood (0–14 years) neuroblastoma cases, retrieved from 13 collaborating SEE registries (1990–2016), and were compared to those of SEER/US (N = 3,166; 1990–2012); temporal trends were assessed using Poisson regression and Joinpoint analyses. The overall AIR was significantly lower in SEE (10.1/million) compared to SEER (11.7 per million); the difference was maximum during infancy (43.7 vs. 53.3 per million, respectively), when approximately one‐third of cases were diagnosed. Incidence rates of neuroblastoma at ages <1 and 1–4 years were positively associated with HDI, whereas lower median age at diagnosis was correlated with higher overall AIR. Distribution of primary site and histology was similar in SEE and SEER. Neuroblastoma was slightly more common among males compared to females (male‐to‐female ratio: 1.1), mainly among SEE infants. Incidence trends decreased in infants in Slovenia, Cyprus and SEER and increased in Ukraine and Belarus. The lower incidence in SEE compared to SEER, especially in infants living in low HDI countries possibly indicates a lower level of overdiagnosis in SEE. Hence, increases in incidence rates in infancy noted in some subpopulations should be carefully monitored to avoid the unnecessary costs health impacts of tumors that could potentially spontaneously regress.     

Bioequivalence studies: biometrical concepts of alternative designs and pooled analysis.

A bioequivalence study compares the bioavailability between a test and a reference drug product in terms of the rate and extent of drug absorption. Area under the plasma concentration-time curve (AUC) and maximum plasma concentration (Cmax) are the pharmacokinetic parameters that serve as characteristics for the assessment of the extent and rate of absorption, respectively. The experimental design of a bioequivalence study is usually a crossover and rarely a parallel or a paired comparative. The statistical assessment of bioequivalence is based on the 90% confidence interval for the ratio of the test mean to the reference mean for AUC and Cmax The aims of this paper are to: (i) investigate alternative designs to a crossover design for conducting bioequivalence studies; (ii) propose the statistical analysis of different designs for bioequivalence studies on the same products; and (iii) discuss their usefulness for the approval of new generic drug products. For this purpose, three case studies are illustrated and analysed. The first case study concerns the investigation of the merits of a crossover design relative to a parallel group design for highly variable drugs using as an example a bioequivalence study of tamoxifen products. The second case study concerns the pooled statistical analysis of two bioequivalent studies of the same levodopa products. The analyses of the individual studies failed to meet the regulatory criteria for bioequivalence. The one study design was a paired comparative and the other one a crossover. Under some assumptions the crossover design may be considered as a paired comparative and the data from the two studies may be analysed together as a paired comparative design. The third case study concerns the statistical pooled analysis of two bioequivalent studies of the same clodronate products. The one study was a three-period crossover pilot study and it was used to identify the variability of the active substance. Then, this variability was used to determine the number of subjects for the main pivotal study which was a two-period crossover. The pilot study design was converted into a two-period crossover design and the data from the two studies were analysed together as a two-period crossover design. The original data of the studies were modified accordingly.     

Biometrical evaluation of bioequivalence trials using a bootstrap individual direct curve comparison method.

Bioequivalence of two medicinal, or veterinary, products is established by comparing the mean of bioavailability measures, such as AUC and Cmax, following administration of the test (T) and reference (R) products. However, the use of these parameters has several drawbacks, e.g. they do not take into consideration the overall pharmacokinetic profile shape. Therefore, concerns have been raised regarding their appropriateness for assessment of bioequivalence. To overcome the limitations of these bioequivalence parameters, direct curve comparison metrics methods were recently proposed on an average basis. In this paper, an individual based direct curve comparison method for assessing bioequivalence is proposed. The bioequivalence of T and R in each subject is evaluated by a new curve comparison metrics delta. The metrics delta is the absolute sum of the difference between two curves. The significance of the metrics for each subject is assessed by bootstrapping. An overall bioequivalence of T and R may be considered if less than 25% of the subjects show statistically different profiles.     

Heterotopic pregnancies: 8 cases

Heterotopic pregnancy is the combination of intra-uterine pregnancy and ectopic pregnancy in the same patient whatever is the localization of the ectopic pregnancy. The aim of this work was to summarize the epidemics and clinical factors, the diagnostic means and the therapeutic methods for the spontaneous heterotopic pregnancy in Moroccan context. In a period of 6 years (1993-1998), 8 patients were treated for heterotopic pregnancy in Lalla Meryem Maternity of Casablanca, with a rate of 0.2/1000. Patients' ages ranged from 19 to 37. The backgrounds were: abortions (4 cases), secondary sterility (2 cases) and genital infection (2 cases). Five patients consulted for metrorrhagia associated with pelvic pain. Two for pelvic pain and one for metrorrhagia. The diagnosis was confirmed before echography in 5 cases. All patients were operated on, 3 in a condition of haemorrhagic shock. Ectopic pregnancy lay at the level of the fallopian tube in 7 cases and at the level of the ovary in one. The treatment consisted of a salpingectomy in the 7 patients with tubal localisations, the ovary pregnancy benefited from ovariectomy. Evolution has been marked by expulsion of intra-uterine pregnancy in 6 cases. Two women were able to carry out their pregnancy. Heterotopic pregnancy is more and more frequent because of genital infection increase and especially the wide diffusion of the assisted medical procreation.     

Discrepancy between anthropometry and biochemistry in the assessment of the nutritional status of the elderly

Institutionalized aged subjects, considered free of evolutive disease and whose body weight was stable, were studied. They were divided into two groups depending on their body mass index: controls (BMI greater than or equal to 24) and depleted (BMI less than or equal to 21). The depleted group, as judged by anthropometric measurements, showed dramatically reduced body muscle and adipose masses. Usual blood parameters were normal in both groups. Biochemical markers of the protein and energy status, viz. albumin, transthyretin, transferrin, somatomedin-C, as well as serum levels of osteocalcin and apolipoproteins AI, AII, B, CII, CIII and E, were not affected in the depleted group. However, moderate iron deficiency and marked zinc deficiency were found in this group. It is concluded that in the elderly, biochemical markers of the protein and energy status are not related to the nutritional status assessed by anthropometry.