Alternative strategies to evaluate the cost-effectiveness of peritoneal dialysis and hemodialysis

Background Dialysis treatment requires considerable resources and it is important to improve the efficiency of care. Methods Files of all adult end-stage renal disease (ESRD) patients who entered dialysis therapy between 1991 and 1996, were studied and all use of health care resources was recorded. A total of 138 patients started with in-center hemodialysis (HD) and 76 patients with continuous ambulatory peritoneal dialysis (CAPD). Four alternative perspectives were applied to assess effectiveness. An additional analysis of 68 matched CAPD-HD pairs with similar characteristics was completed. Results Cost-effectiveness ratios (CER; cost per life-year gained) were different in alternative observation strategies. If modality changes and cadaveric transplantations were ignored, annual first three years’ CERs varied between $41220–61465 on CAPD and $44540–85688 on HD. If CAPD-failure was considered as death, CERs were $34466–81197 on CAPD. When follow-up censored at transplantation but dialysis modality changes were ignored, CERs were $59409–95858 on CAPD and $70042–85546 on HD. If observation censored at any change of primarily selected modality, figures were $57731–66710 on CAPD and $74671–91942 on HD. There was a trend of lower costs and better survival on CAPD, the only exception was the strategy in which technical failure of modality was considered as death. Figures of the matched CAPD-HD pairs were very close to the figures of the entire study population. Conclusions Compared to HD, CERs were slightly lower on CAPD.     

Long-term outcome of intensive chemotherapy for adults with de novo acute myeloid leukaemia (AML): the nationwide AML-92 study by the Finnish Leukaemia Group

OBJECTIVE: To investigate the long-term outcome of idarubicin- and cytarabine-based intensive chemotherapy in adult acute myeloid leukaemia (AML). PATIENTS AND METHODS: A total of 327 consecutive patients with de novo AML (promyelocytic leukaemia excluded) aged 16-65 yr were recruited into the study between September 1992 and December 2001. The latest follow-up data were collected in October 2006. After remission achievement with the first (conventional cytarabine) or second (high-dose cytarabine) chemotherapy cycle, three intensive consolidation courses each containing high- or intermediate-dose cytarabine were given. RESULTS: A total of 268 patients (82%) achieved complete remission (CR). CR rate was 82% and 84% for patients <60 and > or =60 yr of age, respectively. CR rates in patients with favourable (93%) and intermediate/normal karyotypes (87%) were significantly (P < 0.01) higher than CR rate in patients with adverse karyotype (61%). Median relapse-free survival (RFS) for the patients not transplanted in the first CR (n = 195) was 1.7 yr (95% CI: 0.81-2.60). At 4 yr, a plateau of 70% in RFS was reached for patients with favourable karyotypes. The 5-yr survival was 71%, 47% and 37% for the non-transplanted patients (n = 202) with favourable, intermediate/normal and intermediate/abnormal karyotypes, respectively, while only 8% of the patients having adverse karyotype were alive at 5 yr (P < 0.01). Of the patients with favourable, intermediate/normal or intermediate/abnormal karyotypes, respectively, 58%, 41% and 31% were expected to be alive at 10 yr. CONCLUSIONS: Idarubicin- and cytarabine-based intensive chemotherapy regimen is very effective in de novo AML for adult patients up to 65 yr of age. New treatment strategies are needed, however, to improve the outcome of the patients with intermediate and adverse karyotypes.     

The effect of PPARgamma-agonism on LDL subclass profile in patients with type 2 diabetes and coronary artery disease

Patients with type 2 diabetes (T2DM) often present a preponderance of small, dense LDL particles (small-LDL), which are associated with a high risk of myocardial infarction. Some studies suggest that PPARgamma-agonists increase LDL cholesterol but have divergent effects on various LDL subclasses in T2DM patients. We studied the effect of rosiglitazone on the LDL subclass profile in T2DM patients with verified coronary artery disease (CAD). 58 patients with T2DM (HbA1c < 8.5%) and CAD were enrolled in a 16-week, randomized, double-blind and placebo-controlled trial with rosiglitazone 8 mg/day (n = 29) or placebo (n = 29). The LDL subclass profile was measured with gel electrophoresis. Rosiglitazone improved insulin sensitivity and glycemic control. Total cholesterol did not change after rosiglitazone treatment (p = 0.062, ANCOVA adjusted for gender and baseline values), whereas LDL (including IDL) cholesterol increased from 2.33 +/- 0.48 to 2.67 +/- 0.61 mmol/l (p = 0.002 vs. baseline, p = 0.0497 vs. placebo) and large buoyant LDL (large-LDL < 250A) increased from 1.31 +/- 0.36 to 1.46 +/- 0.42 mmol/l (p = 0.010 vs. baseline, p = 0.044 vs. placebo) in the rosiglitazone group. No significant changes occurred to the concentration of small-LDL (< 250A), the average LDL particle size, or HDL or triglyceride concentrations. Whole-body insulin sensitivity was associated with the average LDL particle size after intervention in the whole population (r = 0.40, p = 0.002) and in the rosiglitazone group (r = 0.43, p = 0.020). In conclusion, in T2DM patients with CAD, rosiglitazone treatment significantly increases the concentration of large (buoyant) LDL cholesterol, but not of small dense LDL cholesterol. The long term consequences of this divergent effect of rosiglitazone on LDL subfractions require further exploration.     

Haemodynamic and hormonal effects of short-term oestradiol treatment in postmenopausal women

Haemodynamic changes during a 3-wk treatment with oestradiol valerianate (2 mg/day orally) were studied in 12 postmenopausal women by isotope ¹¹³In^m radiocardiography.

Systolic blood pressure measured in the supine position decreased during oestradiol treatment by 3% (P < 0.05) and the diastolic blood pressure decreased by 4% (P < 0.01). The heart rate decreased by 15% (P < 0.001).

Blood volume increased during oestrogen treatment by 5% (P < 0.05) whereas cardiac output decreased by 9% (P < 0.05). Stroke volume increased by 13% (P < 0.001) due to concomitant decrease in heart rate.

Changes in plasma oestrone and oestradiol concentrations during oestradiol valerianate substitution showed a positive correlation with the changes of blood volume.     

Effects of Randomized Controlled Infancy-Onset Dietary Intervention on Leukocyte Telomere Length—The Special Turku Coronary Risk Factor Intervention Project (STRIP)

Reduced telomere length (TL) is a biological marker of aging. A high inter-individual variation in TL exists already in childhood, which is partly explained by genetics, but also by lifestyle factors. We examined the influence of a 20-year dietary/lifestyle intervention on TL attrition from childhood to early adulthood. The study comprised participants of the longitudinal randomized Special Turku Coronary Risk Factor Intervention Project (STRIP) conducted between 1990 and 2011. Healthy 7-month-old children were randomized to the intervention group (n = 540) receiving dietary counseling mainly focused on dietary fat quality and to the control group (n = 522). Leukocyte TL was measured using the Southern blot method from whole blood samples collected twice: at a mean age of 7.5 and 19.8 years (n = 232; intervention n = 108, control n = 124). Yearly TL attrition rate was calculated. The participants of the intervention group had slower yearly TL attrition rate compared to the controls (intervention: mean = −7.5 bp/year, SD = 24.4 vs. control: mean = −15.0 bp/year, SD = 30.3; age, sex and baseline TL adjusted β = 0.007, SE = 0.004, p = 0.040). The result became stronger after additional adjustments for dietary fat quality and fiber intake, serum lipid and insulin concentrations, systolic blood pressure, physical activity and smoking (β = 0.013, SE = 0.005, p = 0.009). A long-term intervention focused mainly on dietary fat quality may affect the yearly TL attrition rate in healthy children/adolescents.     

Empathizers and systemizers process social information differently

Using the empathizing-systemizing theory as our framework, we investigated how people with high self-reported empathizing (having good social skills and being interested in people) and systemizing (being interested in physical things and processes) differ in the social information processing of emotionally negative photographs of people during “spontaneous watching” and emotional and cognitive empathy tasks. Empathizers evaluated the pictures as more emotionally touching and the reactions in the photographs more understandable than the systemizers. Compared to the empathizers, systemizers had stronger activations in the posterior cingulate cortex, an area related to cognitive empathy, as well as in the left superior temporal gyrus and middle frontal gyrus when watching emotional photographs spontaneously. During guided emotional and cognitive empathy tasks, these differences disappeared. However, during the emotional empathy task, higher systemizing was associated with weaker activation of the right inferior frontal gyrus /insula. Furthermore, during emotional and cognitive empathy tasks, empathizing was related to increased activations of the amygdala which were in turn related to higher behavioral ratings of emotional and cognitive empathy. The results suggest that empathizers and systemizers engage in social information processing differently: systemizers in more cognitive terms and empathizers with stronger automatic emotional reactions.     

The role of organic cation transporters (OCTs) in the transfer of metformin in the dually perfused human placenta

ObjectivesOur aim was to investigate the mode of placental transfer of metformin in term human placenta with special reference to involvement of the organic cation transporters (OCTs).Study designTwenty-nine placentas were obtained after delivery and a 2-h non-recirculating perfusion of a single placental cotyledon was performed to study maternal-to-fetal and fetal-to-maternal transport of metformin, which is a substrate for OCTs by using antipyrine as a reference of passive diffusion transfer compound. Cimetidine was used as an inhibitor for OCT-dependent active transfer.ResultsMaternal-to-fetal transfer of metformin and antipyrine were 3.7% and 10.0%, respectively, and fetal-to-maternal transfers were 15.5% and 42.3%, respectively. Cimetidine did not have any effect on the transfer of metformin. Fetal-to-maternal transfer of metformin was significantly higher than maternal-to-fetal transfer (P < 0.05) in perfusions performed with or without cimetidine.ConclusionsA higher transfer rate of metformin was detected in fetal-to-maternal than maternal-to-fetal direction, but a similar difference was observed with antipyrine. Inhibition of OCTs did not have a significant effect on the placental transfer of metformin. Although the existence of other active transporting systems cannot be ruled out, the influence of OCT-dependent active transport system on the placental pharmacokinetics of metformin is unlikely significant.