Early referral and planned initiation of dialysis: what impact on quality of life?

BACKGROUND: Early patient referral correlates with improved patient survival on dialysis. We examine whether early referral and a planned first dialysis affect quality of life (QoL). METHODS: All patients commencing dialysis in nine centres in seven European countries between 1 July 1998 and 31 October 1999 were recruited. Definitions: early referral=followed by a nephrologist >1 month before first dialysis (<1 month=late referral); planned=early referral and previous serum creatinine >300 micro mol/l and non-urgent first dialysis (early referral and no creatinine >300 micro mol/l or urgent first dialysis=unplanned). QoL was measured at 8 weeks using a visual analogue scale (VAS) and Short Form 36 (SF-36). RESULTS: VAS was significantly higher in early referral patients [mean (SD) 58.4 (20) vs 50.4 (19), P=0.005], particularly if the first dialysis was planned [60.7 (20) vs 54.2 (20), P=0.03]. Planned patients also had higher SF-36 mental summary scores [45.4 (12) vs 39.7 (11), P=0.003], role emotional scores [58.0 (43) vs 30.9 (38), P=0.003], and mental health scores [63.7 (24) vs 54.6 (22), P=0.01] than unplanned patients. Adjusting for centre and other confounding variables showed that having a planned first dialysis had an independent effect on QoL (VAS, and the SF-36's mental summary score, physical functioning, role physical, general health, role emotional and mental health). Early referral had no independent effect on QoL. Socio-economic status had an important positive effect on physical QoL. CONCLUSIONS: While the effect of early referral to a nephrologist on QoL appeared centre dependent, a smooth transition onto dialysis was associated with significantly better early QoL, independent of other variables.     

Relationship between low depressiveness and domain specific physical activity in women

In this study we investigated how different domains of physical activity are associated with depressiveness among women, and how individual variables moderate this relationship. Participants were 956 women, and the data were collected by mail-out survey using the Global Physical Activity Questionnaire, Beck Depression Inventory, and International Personality Item Pool. Lower depressiveness was related to higher leisure time physical activity and to lower occupational physical activity. Income, health problems, level of neuroticism, and extraversion had strong effects on depressiveness, and mediated the link between the leisure and occupational activities and depression.     

GSK-3 inhibition by an orally active small molecule increases bone mass in rats

Glycogen synthase kinase 3β (GSK-3β) actions are central in the canonical Wnt pathway, important in many biological processes and a potential drug target for treating several diseases. It is appreciated that a balanced Wnt canonical signaling is crucial for the maintenance of normal bone mass. In this study we investigated the effects of a potent orally active GSK-3 inhibitor, AZD2858, on bone mass in rats. Treatment (1 μM) of human osteoblast cells with AZD2858 in vitro increased β-catenin levels after a short period of time. In rats, oral AZD2858 treatment caused a dose-dependent increase in trabecular bone mass compared to control after a two-week treatment with a maximum effect at a dose of 20 mg/kg once daily (total BMC: 172% of control; p<0.001). A small but significant effect was also seen at cortical sites (total BMC: 111% of control; p<0.001). Biomechanical testing demonstrated an increase in both vertebral compression strength at a dose of 20 mg/kg once daily (Load at failure: 370% of control, p<0.001) and diaphyseal strength of femora subjected to a three point bending test (Load at failure: 115% of control; p<0.01). Furthermore, histomorphometry showed a dramatic increase in bone formation indices, and serum markers of both bone formation (Osteocalcin, 146% of control; p<0.001) and resorption (CTX, 189% of control; p<0.001) were elevated. Our conclusion is that a GSK-3 inhibitor drug may prove effective as an anabolic strategy in the treatment of diseases characterized by low bone mass, since AZD2858 has extensive bone building effects at predominantly trabecular sites.     

Health inequality among Estonian women

In Eastern Europe, in post-Communist countries, transformations during the past 10 years have considerably affected the life of women. Our aims were to (a) examine health status and socioeconomic inequalities among Estonian women, and (b) study the relationships between women's social roles and health. A group of 659 women, aged 18-45, completed the Health Questionnaire for Adults (HQA) and the General Health Questionnaire (GHQ). Income had the largest effect on self-related health and psychoemotional health ratings. The second important indicator was education. Women's additional social roles (marital status, parental role) were not detrimental to their health in our study.     

Recovery of Swedish Equine arteritis viruses from semen by cell culture isolation and RNA transfection

Recovery of infectious Equine arteritis virus (EAV) from the semen of persistently infected Swedish stallions was attempted by classical cell culture isolation and by transfection of extracted total RNA. Whereas virus from semen samples stored for several months at -20 degrees C or from extended semen could only be recovered by transfection of extracted RNA, isolation in cell culture was achieved readily with fresh, unextended semen stored at -70 degrees C or directly used after sampling. In parallel, the viruses were examined in the variable region of the large glycoprotein GP5 by nested RT-PCR and direct nucleotide sequencing. The resulting sequences were placed into a large phylogenetic tree from this region, demonstrating that Swedish strains belonged to very diverse phylogenetic groups. This represents the first report of recovery of infectious EAV from archived semen samples by RNA transfection.     

Optical Method and Biochemical Source for the Assessment of the Middle-Molecule Uremic Toxin β2-Microglobulin in Spent Dialysate

Optical monitoring of spent dialysate has been used to estimate the removal of water-soluble low molecular weight as well as protein-bound uremic toxins from the blood of end stage kidney disease (ESKD) patients. The aim of this work was to develop an optical method to estimate the removal of β2-microglobulin (β2M), a marker of middle molecule (MM) uremic toxins, during hemodialysis (HD) treatment. Ultraviolet (UV) and fluorescence spectra of dialysate samples were recorded from 88 dialysis sessions of 22 ESKD patients, receiving four different settings of dialysis treatments. Stepwise regression was used to obtain the best model for the assessment of β2M concentration in the spent dialysate. The correlation coefficient 0.958 and an accuracy of 0.000 ± 0.304 mg/L was achieved between laboratory and optically estimated β2M concentrations in spent dialysate for the entire cohort. Optically and laboratory estimated reduction ratio (RR) and total removed solute (TRS) of β2M were not statistically different (p > 0.35). Dialytic elimination of MM uremic toxin β2M can be followed optically during dialysis treatment of ESKD patients. The main contributors to the optical signal of the MM fraction in the spent dialysate were provisionally identified as tryptophan (Trp) in small peptides and proteins, and advanced glycation end-products.