Pharmacokinetics and haemodynamics of candesartan cilexetil in hypertensive patients on regular haemodialysis

AIMS: The pharmacokinetic profile of candesartan cilexetil might be altered in patients with end-stage renal disease (ESRD). No data are available about the pharmacokinetics and haemodynamics of the angiotensin II receptor antagonist candesartan cilexetil in ESRD patients on regular haemodialysis (HD). METHODS: We performed a repeated dose study (8 mg candesartan cilexetil once daily) in eight male HD patients over a treatment period of 5 days with an additional observation period of 3 days. RESULTS: Pharmacokinetic analysis with nonlinear mixed effects modeling (NONMEM) over the whole treatment period revealed a dependency of the volume of distribution on body weight and of the metabolic clearance on age and body weight in the studied population. No significant drug elimination by HD was observed. The estimated metabolic and intercompartmental clearances were 83 ml min-1 (CV 39%) and 9.9 ml min-1, respectively. The unexplained random variability of the final two compartment model was 30%. In one patient with adult polycystic kidney disease oral clearance decreased during the observation period, attributable to a significant increase in bioavailability. Maximum observed changes in blood pressure were -50/-27+/-14/8 mmHg on day 5 with haemodialysis therapy as compared with changes in blood pressure of -14/-12+/-14/8 mmHg on day 1 without haemodialysis treatment. The observed maximum decrease in systolic blood pressure correlated with the amount of ultrafiltration during the HD session on day 5 (r=0.70, P<0.05). In two patients, one of whom was binephrectomized, severe hypotensive episodes were observed during this HD session. CONCLUSIONS: HD does not influence the elimination kinetics of candesartan. The observed inter- and intraindividual variability of oral clearance and the pronounced influence of HD-induced volume contraction on the haemodynamic effects of candesartan makes it mandatory to carefully monitor HD patients treated with candesartan cilexetil.     

Kompetent vernetzt – optimal versorgt!

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - Das Bayerische Staatsministerium für Gesundheit und Pflege (StMGP) fördert den Aufbau regionaler Hospiz- und...     

Randomized Nutrition Education Intervention to Improve Carbohydrate Counting in Adolescents with Type 1 Diabetes Study: Is More Intensive Education Needed?

BackgroundYouth with type 1 diabetes do not count carbohydrates accurately, yet it is an important strategy in blood glucose control.ObjectiveThe study objective was to determine whether a nutrition education intervention would improve carbohydrate counting accuracy and glycemic control.DesignWe conducted a randomized, controlled nutrition intervention trial that was recruited from February 2009 to February 2010.SubjectsYouth (12 to 18 years of age, n=101) with type 1 diabetes were screened to identify those with poor carbohydrate counting accuracy, using a previously developed carbohydrate counting accuracy test covering commonly consumed foods and beverage items presented in six mixed meals and two snacks. All participants (n=66, age=15±3 years, 41 male, diabetes duration=6±4 years, hemoglobin A1c [HbA1c]=8.3%±1.1%) were randomized to the control or intervention group at the baseline visit. The intervention group attended a 90-minute class with a registered dietitian/certified diabetes educator and twice kept 3-day food records, which were used to review carbohydrate counting progress.Main outcome measuresCarbohydrate counting accuracy (measured as described) and HbA1c were evaluated at baseline and 3 months to determine the effectiveness of the intervention.Statistical analyses performedt Tests, Spearman correlations, and repeated measures models were used.ResultsAt baseline, carbohydrate content was over- and underestimated in 16 and 5 of 29 food items, respectively. When foods were presented as mixed meals, participants either significantly over- or underestimated 10 of the 9 meals and 4 snacks. After 3 months of follow-up, HbA1c decreased in both the intervention and control groups by ?0.19%±0.12% (P=0.12) and ?0.08%±0.11% (P=0.51), respectively; however, the overall intervention effect was not statistically significant for change in HbA1c or carbohydrate counting accuracy.ConclusionsMore intensive intervention might be required to improve adolescents' carbohydrate counting accuracy and nutrition management of type 1 diabetes. Additional research is needed to translate nutrition education into improved health outcomes.     

Visceral artery aneurysms—follow-up of 23 patients with 31 aneurysms after surgical or interventional therapy

Purpose  

Visceral artery aneurysms (VAA) are rare forms of vascular pathology, with an incidence of 0.1% to 0.2% in routine autopsies [1–4]. They frequently present as a life-threatening, often fatal, emergency, if associated with rupture and intra- or retroperitoneal bleeding. The clinical symptoms, natural history, and mortality of VAAs vary depending on the vessels involved. The mortality rates range from 8.5% up to 25% and, in pregnant women, up to 75% [1, 4, 6, 7]. A retrospective analysis of all VAAs diagnosed at our institution from 1991 to 2006 was performed. The presentation, management, and outcome of therapy was evaluated for each patient.     

Association between vaginal bulge and anatomical pelvic organ prolapse during pregnancy and postpartum: an observational study

Introduction and hypothesis

Pelvic organ prolapse (POP) is defined as the coexistence of anatomical POP and relevant symptoms. Vaginal bulge is the symptom most closely associated with the anatomical condition in nonpregnant women. Even if childbearing is a major risk factor for the development of POP, there is scant knowledge on the prevalence of specific POP symptoms, and how these symptoms relate to anatomical POP during pregnancy and postpartum. The aim of this study was to explore whether vaginal bulge symptoms were associated with anatomical POP in pregnancy and postpartum, and to present the prevalence of vaginal bulge symptoms throughout this period.

Methods

A prospective observational study was carried out following 300 nulliparous pregnant women with repeat assessments from mid-pregnancy until 1 year postpartum. Symptoms of vaginal bulge defined as the sensation of a vaginal bulge inside and/or outside the vagina were assessed by electronic questionnaires. Anatomical POP defined as pelvic organ prolapse quantification system (POP-Q) stage ≥2 has been presented in a previous publication and showed a range of 1–9%. The association between the symptom vaginal bulge and anatomical POP at the various visits was analyzed using Fisher’s exact test.

Results

Prevalence of vaginal bulge ranged between 16 and 23%. At 6 weeks postpartum the symptom was associated with anatomical POP; otherwise, these two features were unrelated.

Conclusions

The symptom vaginal bulge was barely associated with anatomical POP, and cannot identify anatomical POP in pregnancy or postpartum.