Early termination of ISRCTN45828668, a phase 1/2 prospective, randomized study of Sulfasalazine for the treatment of progressing malignant gliomas in adults

BACKGROUND: Sulfasalazine, a NF-kappaB and x(c)-cystine/glutamate antiport inhibitor, has demonstrated a strong antitumoral potential in preclinical models of malignant gliomas. As it presents an excellent safety profile, we initiated a phase 1/2 clinical study of this anti-inflammatory drug for the treatment of recurrent WHO grade 3 and 4 astrocytic gliomas in adults. METHODS: 10 patients with advanced recurrent anaplastic astrocytoma (n = 2) or glioblastoma (n = 8) aged 32-62 years were recruited prior to the planned interim analysis of the study. Subjects were randomly assigned to daily doses of 1.5, 3, 4.5, or 6 grams of oral sulfasalazine, and treated until clinical or radiological evidence of disease progression or the development of serious or unbearable side effects. Primary endpoints were the evaluation of toxicities according to the CTCAE v.3.0, and the observation of radiological tumor responses based on MacDonald criteria. RESULTS: No clinical response was observed. One tumor remained stable for 2 months with sulfasalazine treatment, at the lowest daily dose of the drug. The median progression-free survival was 32 days. Side effects were common, as all patients developed grade 1-3 adverse events (mean: 7.2/patient), four patients developed grade 4 toxicity. Two patients died while on treatment or shortly after its discontinuation. CONCLUSION: Although the proper influence of sulfasalazine treatment on patient outcome was difficult to ascertain in these debilitated patients with a large tumor burden (median KPS = 50), ISRCTN45828668 was terminated after its interim analysis. This study urges to exert cautiousness in future trials of Sulfasalazine for the treatment of malignant gliomas. TRIAL REGISTRATION: Current Controlled Trials ISRCTN45828668

Challenges to the surveillance of non-communicable diseases – a review of selected approaches

Background: The rising global burden of non-communicable diseases (NCDs) necessitates the institutionalization of surveillance systems to track trends and evaluate interventions. However, NCD surveillance capacities vary across high- and low- and middle-income countries. The objective of the review was to analyse existing literature with respect to structures of health facility-based NCD surveillance systems and the lessons low- and middle-income countries can learn in setting up and running these systems. Methods: A literature review was conducted using Pub Med, Web of Knowledge and WHOLIS databases to identify citations published in English language between 1993 and 2013. In total, 20 manuscripts met inclusion criteria: 12 studies were analysed in respect to the surveillance approach, eight supporting documents in respect to general and regional challenges in NCD surveillance. Results: Eleven of the 12 studies identified were conducted in high-income countries. Five studies had a single disease focus, three a multiple NCD focus and three covered communicable as well as non-communicable diseases. Nine studies were passive assisted sentinel surveillance systems, of which six focused on the primary care level and three had additional active surveillance components, i.e., population-based surveys. The supporting documents reveal that NCD surveillance is rather limited in most low- and middle-income countries despite the increasing disease burden and its socioeconomic impact. Major barriers include institutional surveillance capacities and hence data availability. Conclusions: The review suggests that given the complex system requirements, multiple surveillance approaches are necessary to collect comprehensive information for effective NCD surveillance. Sentinel augmented facility-based surveillance, preferably supported by population-based surveys, can provide improved evidence and help budget scarce resources. Electronic supplementary material: The online version of this article (doi:10.1186/s12889-015-2570-z) contains supplementary material, which is available to authorized users

Meiofauna in the Gollum Channels and the Whittard Canyon, Celtic Margin—How Local Environmental Conditions Shape Nematode Structure and Function

The Gollum Channels and Whittard Canyon (NE Atlantic) are two areas that receive high input of organic matter and phytodetritus from euphotic layers, but they are typified by different trophic and hydrodynamic conditions. Sediment biogeochemistry was analysed in conjunction with structure and diversity of the nematode community and differences were tested between study areas, water depths (700 m vs 1000 m), stations, and sediment layers. The Gollum Channels and Whittard Canyon harboured high meiofauna abundances (1054–1426 ind. 10 cm−2) and high nematode diversity (total of 181 genera). Next to enhanced meiofauna abundance and nematode biomass, there were signs of high levels of organic matter deposition leading to reduced sedimentary conditions, which in turn structured the nematode community. Striking in this respect was the presence of large numbers of ‘chemosynthetic’ Astomonema nematodes (Astomonema southwardorum, Order Monhysterida, Family Siphonolaimidae). This genus lacks a mouth, buccal cavity and pharynx and possesses a rudimentary gut containing internal, symbiotic prokaryotes which have been recognised as sulphur-oxidising bacteria. Dominance of Astomonema may indicate the presence of reduced environments in the study areas, which is partially confirmed by the local biogeochemical environment. The nematode communities were mostly affected by sediment layer differences and concomitant trophic conditions rather than other spatial gradients related to study area, water depth or station differences, pointing to small-scale heterogeneity as the main source of variation in nematode structure and function. Furthermore, the positive relation between nematode standing stocks, and quantity and quality of the organic matter was stronger when hydrodynamic disturbance was greater. Analogically, this study also suggests that structural diversity can be positively correlated with trophic conditions and that this relation is tighter when hydrodynamic disturbance is greater

Seasonal Changes in Physical Qualities of Elite Youth Soccer Players according to Maturity Status: Comparisons with Aged Matched Controls.

Purpose: Longitudinal studies assessing the seasonal development of strength, speed and power qualities are limited in youth soccer players. The purpose of this study was to evaluate the seasonal changes in the physical development of elite youth soccer players across Pre-, Circa- and Post-Peak Height Velocity (PHV), against a similar age and maturity matched control groups. Methods: One-hundred and twelve male elite youth soccer players (Pre-PHV n = 55; Circa-PHV n = 21; Post-PHV n = 36) and 38 controls consisting of non-elite active participants (Pre-PHV n = 18; Circa-PHV n = 10; Post-PHV n = 10) all undertook isometric mid-thigh pull strength, 10–30 m sprints, change of direction speed (CODs) and countermovement jump (CMJ) tests pre- and post-season. Results: The elite Circa-PHV improved greater than the control group for all physical qualities between pre- and post-season. The elite Pre-PHV improved greater in sprints, CODs, CMJ jump height and strength while the elite Post-PHV group improved more in CODs and strength than their respective control groups. Conclusion: Findings suggest that systematic academy soccer training enhances the development of physical qualities in youth soccer players but maturity status may impact upon such adaptations

Evidence-based guidelines for the pharmacological treatment of postmenopausal osteoporosis: a consensus document by the Belgian Bone Club

Several drugs are available for the management of postmenopausal osteoporosis. This may, in daily practice, confuse the clinician. This manuscript offers an evidence-based update of previous treatment guidelines, with a critical assessment of the currently available efficacy data on all new chemical entities which were granted a marketing authorization. Osteoporosis is widely recognized as a major public health concern. The availability of new therapeutic agents makes clinical decision-making in osteoporosis more complex. Nation-specific guidelines are needed to take into consideration the specificities of each and every health care environment. The present manuscript is the result of a National Consensus, based on a systematic review and a critical appraisal of the currently available literature. It offers an evidence-based update of previous treatment guidelines, with the aim of providing clinicians with an unbiased assessment of osteoporosis treatment effect