Relative survival: a useful tool to assess generalisability in longitudinal studies of health in older persons

Generalisability of longitudinal studies is threatened by issues such as choice of sampling frame, representativeness of the initial sample, and attrition. To determine representativeness, cohorts are often compared with the population of interest at baseline on demographic and health characteristics. This study illustrates the use of relative survival as a tool for assessing generalisability of results from a cohort of older people among whom death is a potential threat to generalisability.The authors used data from the 1921-26 cohort (n = 12,416, aged 70-75 in 1996) of the Australian Longitudinal Study on Women's Health (ALSWH). Vital status was determined by linkage to the National Death Index, and expected deaths were derived using Australian life tables. Relative survival was estimated using observed survival in the cohort divided by expected survival among women of the same age and State or Territory.Overall, the ALSWH women showed relative survival 9.5% above the general population. Within States and Territories, the relative survival advantage varied from 6% to 23%. The interval-specific relative survival remained relatively constant over the 12 years (1996-2008) under review, indicating that the survival advantage of the cohort has not diminished over time.This study demonstrates that relative survival can be a useful measure of generalisability in a longitudinal study of the health of the general population, particularly when participants are older

Comparison of digital and conventional impression techniques: evaluation of patients’ perception, treatment comfort, effectiveness and clinical outcomes

Background: The purpose of this study was to compare two impression techniques from the perspective of patient preferences and treatment comfort.Methods: Twenty-four (12 male, 12 female) subjects who had no previous experience with either conventional or digital impression participated in this study. Conventional impressions of maxillary and mandibular dental arches were taken with a polyether impression material (Impregum, 3 M ESPE), and bite registrations were made with polysiloxane bite registration material (Futar D, Kettenbach). Two weeks later, digital impressions and bite scans were performed using an intra-oral scanner (CEREC Omnicam, Sirona). Immediately after the impressions were made, the subjects' attitudes, preferences and perceptions towards impression techniques were evaluated using a standardized questionnaire. The perceived source of stress was evaluated using the State-Trait Anxiety Scale. Processing steps of the impression techniques (tray selection, working time etc.) were recorded in seconds. Statistical analyses were performed with the Wilcoxon Rank test, and p < 0.05 was considered significant.Results: There were significant differences among the groups (p < 0.05) in terms of total working time and processing steps. Patients stated that digital impressions were more comfortable than conventional techniques.Conclusions: Digital impressions resulted in a more time-efficient technique than conventional impressions. Patients preferred the digital impression technique rather than conventional techniques

Brown-Vialetto-Van Laere and Fazio Londe syndrome is associated with a riboflavin transporter defect mimicking mild MADD: a new inborn error of metabolism with potential treatment

We report on three patients (two siblings and one unrelated) presenting in infancy with progressive muscle weakness and paralysis of the diaphragm. Metabolic studies revealed a profile of plasma acylcarnitines and urine organic acids suggestive of a mild form of the multiple acyl-CoA dehydrogenation defect (MADD, ethylmalonic/adipic acid syndrome). Subsequently, a profound flavin deficiency in spite of a normal dietary riboflavin intake was established in the plasma of all three children, suggesting a riboflavin transporter defect. Genetic analysis of these patients demonstrated mutations in the C20orf54 gene which encodes the human homolog of a rat riboflavin transporter. This gene was recently implicated in the Brown-Vialetto-Van Laere syndrome, a rare neurological disorder which may either present in infancy with neurological deterioration with hypotonia, respiratory insufficiency and early death, or later in life with deafness and progressive ponto-bulbar palsy. Supplementation of riboflavin rapidly improved the clinical symptoms as well as the biochemical abnormalities in our patients, demonstrating that high dose riboflavin is a potential treatment for the Brown-Vialetto-Van Laere syndrome as well as for the Fazio Londe syndrome which is considered to be the same disease entity without the deafnes

Biochemical Effects of Carbohydrate Supplementation in a Simulated Competition of Short Terrestrial Duathlon

The purpose of the present study was to investigate the biochemical effects of carbohydrate supplementation in a simulated competition of short terrestrial duathlon. Ten duathletes participated in a simulated competition of short terrestrial duathlon 30 minutes after the ingestion of a 6% (30 g/500 ml) maltodextrin solution (MALT) or a placebo (PLA). This solution was also ingested every 15 minutes during the competition (12 g/200 ml); and immediately after the competition (18 g/300 ml). Samples of blood were collected at 3 time points: 1) at rest 1 hour before the beginning of the competition; 2) during the competition (approximately 1 hour and 45 minutes after the 1st collection); 3) immediately after the competition. Blood was analyzed for blood glucose, lactate, insulin and cortisol. Significant differences were observed in relation to blood glucose levels between MALT and PLA in the post-competition phase. There was also a significant difference in the lactate levels observed between MALT and PLA during the competition phase. Similarly, a significant difference in the cortisol concentrations during and after the competition phases (MALT and PLA) were observed. We conclude that maltodextrin supplementation appears to be beneficial during short terrestrial duathlon competition as evidenced by biochemical markers

Edge restenosis: impact of low dose irradiation on cell proliferation and ICAM-1 expression

BACKGROUND: Low dose irradiation (LDI) of uninjured segments is the consequence of the suggestion of many authors to extend the irradiation area in vascular brachytherapy to minimize the edge effect. Atherosclerosis is a general disease and the uninjured segment close to the intervention area is often atherosclerotic as well, consisting of neointimal smooth muscle cells (SMC) and quiescent monocytes (MC). The current study imitates this complex situation in vitro and investigates the effect of LDI on proliferation of SMC and expression of intercellular adhesion molecule-1 (ICAM-1) in MC. METHODS: Plaque tissue from advanced primary stenosing lesions of human coronary arteries (9 patients, age: 61 ± 7 years) was extracted by local or extensive thrombendarterectomy. SMC were isolated and identified by positive reaction with smooth muscle α-actin. MC were isolated from buffy coat leukocytes using the MACS cell isolation kit. For identification of MC flow-cytometry analysis of FITC-conjugated CD68 and CD14 (FACScan) was applied. SMC and MC were irradiated using megavoltage photon irradiation (CLINAC2300 C/D, VARIAN, USA) of 6 mV at a focus-surface distance of 100 cm and a dose rate of 6 Gy min(-1 )with single doses of 1 Gy, 4 Gy, and 10 Gy. The effect on proliferation of SMC was analysed at day 10, 15, and 20. Secondly, total RNA of MC was isolated 1 h, 2 h, 3 h, and 4 h after irradiation and 5 μg of RNA was used in standard Northern blot analysis with ICAM-1 cDNA-probes. RESULTS: Both inhibitory and stimulatory effects were detected after irradiation of SMC with a dose of 1 Gy. At day 10 and 15 a significant antiproliferative effect was found; at day 20 after irradiation cell proliferation was significantly stimulated. Irradiation with 4 Gy and 10 Gy caused dose dependent inhibitory effects at day 10, 15, and 20. Expression of ICAM-1 in human MC was neihter inhibited nor stimulated by LDI. CONCLUSION: Thus, the stimulatory effect of LDI on SMC proliferation at day 20 days after irradiation may be the in vitro equivalent of a beginning edge effect. Extending the irradiation area in vascular brachytherapy in vivo may therefore merely postpone and not inhibit the edge effect. The data do not indicate that expression of ICAM-1 in quiescent MC is involved in the process

Some considerations in the design and interpretation of antimalarial drug trials in uncomplicated falciparum malaria

BACKGROUND: Treatments for uncomplicated falciparum malaria should have high cure rates. The World Health Organization has recently set a target cure rate of 95% assessed at 28 days. The use of more effective drugs, with longer periods of patient follow-up, and parasite genotyping to distinguish recrudescence from reinfection raise issues related to the design and interpretation of antimalarial treatment trials in uncomplicated falciparum malaria which are discussed here. METHODS: The importance of adequate follow-up is presented and the advantages and disadvantages of non-inferiority trials are discussed. The different methods of interpreting trial results are described, and the difficulties created by loss to follow-up and missing or indeterminate genotyping results are reviewed. CONCLUSION: To characterize cure rates adequately assessment of antimalarial drug efficacy in uncomplicated malaria requires a minimum of 28 days and as much as 63 days follow-up after starting treatment. The longer the duration of follow-up in community-based assessments, the greater is the risk that this will be incomplete, and in endemic areas, the greater is the probability of reinfection. Recrudescence can be distinguished from reinfection using PCR genotyping but there are commonly missing or indeterminate results. There is no consensus on how these data should be analysed, and so a variety of approaches have been employed. It is argued that the correct approach to analysing antimalarial drug efficacy assessments is survival analysis, and patients with missing or indeterminate PCR results should either be censored from the analysis, or if there are sufficient data, results should be adjusted based on the identified ratio of new infections to recrudescences at the time of recurrent parasitaemia. Where the estimated cure rates with currently recommended treatments exceed 95%, individual comparisons with new regimens should generally be designed as non-inferiority trials with sample sizes sufficient to determine adequate precision of cure rate estimates (such that the lower 95% confidence interval bound exceeds 90%)

FUS/TLS Is a Co-Activator of Androgen Receptor in Prostate Cancer Cells

Androgen receptor (AR) is a member of the nuclear receptor family of transcription factors. Upon binding to androgens, AR becomes transcriptionally active to regulate the expression of target genes that harbor androgen response elements (AREs) in their promoters and/or enhancers. AR is essential for the growth and survival of prostate cancer cells and is therefore a target for current and next-generation therapeutic modalities against prostate cancer. Pathophysiologically relevant protein-protein interaction networks involving AR are, however, poorly understood. In this study, we identified the protein FUsed/Translocated in LipoSarcoma (FUS/TLS) as an AR-interacting protein by co-immunoprecipitation of endogenous proteins in LNCaP human prostate cancer cells. The hormonal response of FUS expression in LNCaP cells was shown to resemble that of other AR co-activators. FUS displayed a strong intrinsic transactivation capacity in prostate cancer cells when tethered to basal promoters using the GAL4 system. Chromatin immunoprecipitation experiments showed that FUS was recruited to ARE III of the enhancer region of the PSA gene. Data from ectopic overexpression and “knock-down” approaches demonstrated that AR transcriptional activity was enhanced by FUS. Depletion of FUS reduced androgen-dependent proliferation of LNCaP cells. Thus, FUS is a novel co-activator of AR in prostate cancer cells