Predialysis therapeutic care and health-related quality of life at dialysis onset (The pharmacoepidemiologic AVENIR study)

Background  

To determine the impact of the quality of pre-dialysis nephrological care on health-related quality of life (HRQoL) at dialysis onset, which has not been well evaluated.     

The rat gut micronucleus assay: A good choice for alternative in vivo genetic toxicology testing strategies

The in vivo bone marrow (BM) micronucleus assay is one of the three tests in the standard test battery to assess the genotoxic potential of a pharmaceutical candidate. In some cases, depending on results of in vitro studies, the route of administration or the degree of systemic exposure, in vivo assessment of genotoxicity in the BM alone may not be sufficient. Based on the potential for high gut exposures to orally administered compounds with low systemic exposures as well as the potential susceptibility of rapidly dividing cells of the intestinal tissues, we have developed a modified technique for evaluating micronuclei formation in both the duodenum and colon of rats based on earlier publications. Adult male Sprague Dawley rats were treated once daily for 2 days with either vehicle control or with the test articles acetyl salicylic acid (ASA), carbendazim (CAR), cyclophosphamide (CP), dimethylhydrazine (DMH), mitomycin C (MMC) or vinblastine sulfate (VIN). The duodenum, colon, and BM were harvested, processed, and analyzed for micronucleus induction. Results from these studies demonstrated differences in the susceptibility for different test compounds in the three tissues tested. When MMC and VIN were dosed by different routes at the same dose levels both compounds produced positive results in all three tissues by intraperitoneal injection but not oral administration. These studies suggest that overall the GI micronucleus assay might be a useful tool for clastogenic and aneugenic compounds that are expected to produce high sustained concentrations in the gastrointestinal tract with little systemic exposure. Environ. Mol. Mutagen., 2011. © 2010 Wiley‐Liss, Inc.     

Developmental dyscalculia: a dysconnection syndrome?

Numerical understanding is important for everyday life. For children with developmental dyscalculia (DD), numbers and magnitudes present profound problems which are thought to be based upon neuronal impairments of key regions for numerical understanding. The aim of the present study was to investigate possible differences in white matter fibre integrity between children with DD and controls using diffusion tensor imaging. White matter integrity and behavioural measures were evaluated in 15 children with developmental dyscalculia aged around 10 years and 15 matched controls. The main finding, obtained by a whole brain group comparison, revealed reduced fractional anisotropy in the superior longitudinal fasciculus in children with developmental dyscalculia. In addition, a region of interest analysis exhibited prominent deficits in fibres of the superior longitudinal fasciculus adjacent to the intraparietal sulcus, which is thought to be the core region for number processing. To conclude, our results outline deficient fibre projection between parietal, temporal and frontal regions in children with developmental dyscalculia, and therefore raise the question of whether dyscalculia can be seen as a dysconnection syndrome. Since the superior longitudinal fasciculus is involved in the integration and control of distributed brain processes, the present results highlight the importance of considering broader domain-general mechanisms in the diagnosis and therapy of dyscalculia.     

Microflora associated with successful and failed orthodontic mini-implants

Objectives: Mini-implants are used for orthodontic bone anchorage. The reasons for a potential instability or loss of the mini-implants during treatment are multiple. Among other factors, colonization of implants with pathogenic bacteria is discussed. Therefore, the microflora associated with successful and failed mini-implants has been screened.
Material and methods: A total of 76 mini-implants collected from 25 patients were observed during regular orthodontic treatment. Bacterial samples of eight failed and – exemplarily – four successful (control) cases were subjected to a universal Bacteria -directed real-time quantitative polymerase chain reaction for quantification in combination with a microarray-based identification of 20 selected species.
Results: The failure rate in the present investigation was 10.5%. The bacterial analysis did not reveal any major difference in the total amount or species composition between control and failed mini-implants. However, Actinomyces viscosus was found in four (100%) and Campylobacter gracilis in three (75%) stable controls, whereas both species were rarely found (12.5%) in failed implants.
Conclusions: In the present study, the peri-implant sulcus surrounding failed orthodontic mini-implants did not show a specific aggressive bacterial flora.     

An exploratory study of systemic administration of the toll-like receptor-7 agonist 852A in patients with refractory metastatic melanoma.

PURPOSE: A topical Toll-like receptor 7 (TLR7) agonist induces regression of cutaneous melanocytic neoplasms. We explored antitumor activity of a systemically administered TLR7 agonist, 852A, in patients with metastatic melanoma. EXPERIMENTAL DESIGN: We undertook a phase II, multicenter, open-label study in patients with chemotherapy-refractory metastatic melanoma. Patients received i.v. 852A, starting at 0.6 mg/m(2) and increasing to 0.9 mg/m(2) based on tolerance, thrice per week for 12 weeks. Clinical response was determined by Response Evaluation Criteria in Solid Tumors. Immune effects of 852A were monitored by measuring serum type I IFN and IP-10 together with assessment of immune cell markers in peripheral blood. RESULTS: Twenty-one patients were enrolled. Thirteen patients completed the initial 12-week treatment cycle, with two discontinuing for adverse events considered to be possibly related to study drug. Four (19%) patients had disease stabilization for >100 days. One patient had a partial remission after two treatment cycles, but progressed during the third. Dose-limiting toxicity was observed in two patients. Serum type I IFN and IP-10 increased in most patients on 852A administration. Serum type I IFN increases were greater after dosing with 852A 0.9 mg/m(2) than after 0.6 mg/m(2) (P = 0.009). The maximal increase in IP-10 compared with baseline correlated with the maximal increase in type I IFN (P = 0.003). In the eight patients with immune cell marker data, CD86 expression on monocytes increased significantly post-first dose (P = 0.007). CONCLUSION: Intravenous 852A was well tolerated and induced systemic immune activation that eventually resulted in prolonged disease stabilization in some patients with stage IV metastatic melanoma who had failed chemotherapy.     

Randomised trial of standard 2D radiotherapy (RT) versus intensity modulated radiotherapy (IMRT) in patients prescribed breast radiotherapy.

BACKGROUND: Radiation dose distributions created by two dimensional (2D) treatment planning are responsible for partial volumes receiving >107% of the prescribed dose in a proportion of patients prescribed whole breast radiotherapy after tumour excision of early breast cancer. These may contribute to clinically significant late radiation adverse effects. AIM: To test three dimensional (3D) intensity modulated radiotherapy (IMRT) against 2D dosimetry using standard wedge compensators in terms of late adverse effects after whole breast radiotherapy. METHODS: Three hundred and six women prescribed whole breast radiotherapy after tumour excision for early stage cancer were randomised to 3D IMRT (test arm) or 2D radiotherapy delivered using standard wedge compensators (control arm). All patients were treated with 6 or 10MV photons to a dose of 50Gy in 25 fractions to 100% in 5 weeks followed by an electron boost to the tumour bed of 11.1Gy in 5 fractions to 100%. The primary endpoint was change in breast appearance scored from serial photographs taken before radiotherapy and at 1, 2 and 5 years follow up. Secondary endpoints included patient self-assessments of breast discomfort, breast hardness, quality of life and physician assessments of breast induration. Analysis was by intention to treat. RESULTS: 240 (79%) patients with 5-year photographs were available for analysis. Change in breast appearance was identified in 71/122 (58%) allocated standard 2D treatment compared to only 47/118 (40%) patients allocated 3D IMRT. The control arm patients were 1.7 times more likely to have a change in breast appearance than the IMRT arm patients after adjustment for year of photographic assessment (95% confidence interval 1.2-2.5, p=0.008). Significantly fewer patients in the 3D IMRT group developed palpable induration assessed clinically in the centre of the breast, pectoral fold, infra-mammary fold and at the boost site. No significant differences between treatment groups were found in patient reported breast discomfort, breast hardness or quality of life. CONCLUSION: This analysis suggests that minimisation of unwanted radiation dose inhomogeneity in the breast reduces late adverse effects. Incidence of change in breast appearance was statistically significantly higher in patients in the standard 2D treatment arm compared with the IMRT arm. A beneficial effect on quality of life remains to be demonstrated.     

Positive Impact of a Shelter-based Hepatitis B Vaccine Program in Homeless Baltimore Children and Adolescents

Homeless youth are at increased risk for hepatitis B virus (HBV) infection and HBV vaccine coverage is poor in this group. The purpose of our study was to determine if a shelter-based HBV vaccine program in children and adolescents 2–18 years of age with a randomized controlled trial using a culturally appropriate HBV video could increase HBV vaccine coverage rates. Subjects were randomized to an 8 min HBV video or a control, smoking prevention video. Before exposure to the videos, HBV knowledge, and demographics were assessed in caregivers and adolescents. HBV vaccine no. 1 was offered to all subjects who did not produce a vaccine record; subsequently, an accurate HBV vaccine history was obtained from medical providers. Subjects were asked to return 1 and 3 months after visit 1, HBV vaccine was offered to all with incomplete coverage, and HBV knowledge was reassessed. There were 328 children and adolescents cared for by 170 caregivers enrolled in the study. One hundred and four had incomplete HBV vaccine coverage. Data are reported for all family units with at least one subject needing vaccine. There were 53 children and adolescents randomized to the HBV video vs. 51 to the smoking video. HBV knowledge scores of caregivers improved at Visit no. 2 vs. no. 1 in the HBV video group (p = 0.01) but not in the smoking group (p = 0.82). Similar results were observed for adolescents in the HBV video group (p = 0.05) but not in the smoking group (p = 0.40). Exposure to the HBV video vs the smoking video had a significant effect on return rates for vaccine at Visit no. 2 (59 vs. 31%; p = 0.05) but not at Visit no. 3 (47 vs. 18%, p = 0.06). The shelter-based vaccine program was very effective in increasing HBV coverage rates in the entire group of 328 children and adolescents enrolled in the study, from 68% coverage at baseline to 85% at the conclusion of the study. We conclude that shelter-based HBV vaccine programs can be highly effective in increasing vaccine coverage rates in older children and adolescents. A brief exposure to a culturally appropriate HBV video improves HBV knowledge and may improve return rates for vaccine.