A randomized n-of-1 study comparing blood pressure measured on a clothed arm and on an arm with a rolled-up sleeve.

BACKGROUND: Blood pressure [BP] should be measured using a bare upper arm with an appropriately sized cuff. In practice, it is more convenient to measure BP on a bare arm below a rolled-up sleeve or on a sleeved arm. AIM: A n-of-1 randomized controlled trial was performed to assess the difference between BP measurements over a sleeve or below a rolled-up sleeve. METHODS: The study subject was male, white, 72 years old, BMI 26 kg/m2, arm circumference 29 cm, and under stable antihypertensive treatment. The mean of three BP measurements over a thin sleeve was compared with measurements below a rolled-up sleeve. Additional measurements on a completely bare arm, with thicker sleeves and up to three layers were performed. The order of measurements was determined by chance and two oscillometric devices were used. Descriptive statistics, Bland-Altman test and 2-side T test were used for comparisons. RESULTS: 504 measurements were performed: 50 % over the sleeve and 50 % below the rolled-up sleeve. The mean systolic blood pressure (SBP) was respectively 116.9 ± 9. 2 [95% CI 115.7-118.0, range 96-135] and 122.8 ± 9.2 [95% CI 121.7-124.0, range 103-139, p = 0.001] mm Hg. The mean diastolic blood pressure [DBP] was respectively 67.6 ± 6.8 [95% CI 66.8-68.4, range 52-84] and 71.8 ± 6.8 [95% CI 71.0-72.7, range 55-85, p = 0.001] mm Hg. There was no significant difference between the measurements over the sleeve and on the completely bare arm [n = 94, p = 0.97]. Sleeve thickness with 2 layers up to 3 mm thick did not affect the results. CONCLUSIONS: Blood pressure measurements over a thin sleeve were significantly lower than measurements below a rolled-up sleeve and match measurements on a completely bare arm.

Economic evaluation of different treatment modalities in acute kidney injury.

BACKGROUND: Major controversy exists regarding the preferred treatment option for acute kidney injury (AKI). The purpose of this study was to assess the incremental cost-effectiveness of continuous renal replacement therapy (CRRT) versus intermittent renal replacement therapy (IRRT) and conservative (CONS) AKI treatment in Belgium. METHODS: An area-under-the-curve model based on survival analysis was used to estimate costs and health outcomes using a 2-year time horizon. Input data were derived from the multi-centre Stuivenberg Hospital Acute Renal Failure 4 study. RESULTS: Analyses indicated that in-hospital mortality, hospitalization costs and hospital length of stay differed significantly between treatment modes. Follow-up mortality rates and follow-up cost per day showed no significant difference between the treatment modes. Utility values, which improved gradually after admission to the hospital, revealed no significant differences between the three treatment strategies. CONS treatment was associated with a 2-year cost of 33,802€ and 0.54 quality-adjusted life years (QALYs). The CRRT was the most expensive therapy with a cost of 51,365€ leading to 0.57 QALYs. The cost and QALYs associated with IRRT were 43,445€ and 0.50, respectively. One-way sensitivity analyses indicated the 'in-hospital mortality' as the variable with the greatest influence on the results. Probabilistic sensitivity analysis resulted in a significant difference in treatment costs but no significant difference in QALY gain. CONCLUSIONS: This study has indicated that the most expensive treatment (CRRT) associated with an incremental cost of approximately €7920 generates only a minor non-significant increase in QALYs of 0.07 compared with IRRT. Additionally, the results revealed that the RRTs did not result in a significant increase in QALYs despite their higher cost compared with the CONS treatment. From a health economic perspective, the latter seems to be the preferred treatment strategy.

Renal replacement therapy is an independent risk factor for mortality in critically ill patients with acute kidney injury.

INTRODUCTION: Outcome studies in patients with acute kidney injury (AKI) have focused on differences between modalities of renal replacement therapy (RRT). The outcome of conservative treatment, however, has never been compared with RRT. METHODS: Nine Belgian intensive care units (ICUs) included all adult patients consecutively admitted with serum creatinine >2 mg/dl. Included treatment options were conservative treatment and intermittent or continuous RRT. Disease severity was determined using the Stuivenberg Hospital Acute Renal Failure (SHARF) score. Outcome parameters studied were mortality, hospital length of stay and renal recovery at hospital discharge. RESULTS: Out of 1,303 included patients, 650 required RRT (58% intermittent, 42% continuous RRT). Overall results showed a higher mortality (43% versus 58%) as well as a longer ICU and hospital stay in RRT patients compared to conservative treatment. Using the SHARF score for adjustment of disease severity, an increased risk of death for RRT compared to conservative treatment of RR = 1.75 (95% CI: 1.4 to 2.3) was found. Additional correction for other severity parameters (Acute Physiology And Chronic Health Evaluation II (APACHE II), Sequential Organ Failure Assessment (SOFA)), age, type of AKI and clinical conditions confirmed the higher mortality in the RRT group. CONCLUSIONS: The SHARF study showed that the higher mortality expected in AKI patients receiving RRT versus conservative treatment can not only be explained by a higher disease severity in the RRT group, even after multiple corrections. A more critical approach to the need for RRT in AKI patients seems to be warranted.

Outcome of acute kidney injury with different treatment options: long-term follow-up.

BACKGROUND AND OBJECTIVES: The multicenter Stuivenberg Hospital Acute Renal Failure 4 study investigated outcome in patients with acute kidney injury (AKI) stratified according to disease severity by the Stuivenberg Hospital Acute Renal Failure score. Patients in need of renal replacement therapy (RRT) received intermittent RRT or continuous RRT. This study investigated long-term mortality, renal function, comorbidity, and quality of life. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: All AKI hospital survivors were included. Mortality at 1 and 2 years of follow-up was traced for all patients. Between 1 and 2 years after hospital discharge, survivors were visited at home to determine morbidity (renal function), comorbidity (Charlson comorbidity index [CCI]), and quality of life (Medical Outcome Survey SF-36). RESULTS: The baseline population consisted of 595 AKI patients. Mortality rates were 23.0 and 7.6%, respectively, during the first and second year after discharge. Total mortality increased from 50.7% at discharge to 65.7% 2 years after AKI and was not related to disease severity or treatment modality offered during hospitalization. Two hundred four survivors could be visited at home. Mean serum creatinine did not differ between discharge and follow-up. CCI was only related with age. SF-36 scores were negatively correlated with CCI, age, and body mass index, but not with disease severity, renal function, or dialysis modality. CONCLUSIONS: Long-term outcome of AKI consists of a high additional mortality unrelated to treatment modality offered during hospitalization, varying evolution of renal recovery, and many comorbidities, but a mental health at the same level as the general population.

Intermittent versus continuous renal replacement therapy for acute kidney injury patients admitted to the intensive care unit: results of a randomized clinical trial.

BACKGROUND: There is uncertainty on the effect of different dialysis modalities for the treatment of patients with acute kidney injury (AKI), admitted to the intensive care unit (ICU). This controlled clinical trial performed in the framework of the multicentre SHARF 4 study (Stuivenberg Hospital Acute Renal Failure) aimed to investigate the outcome in patients with AKI, stratified according to severity of disease and randomized to different treatment options. METHODS: This was a multicentre prospective randomized controlled trial with stratification according to severity of disease expressed by the SHARF score. ICU patients were eligible for inclusion when serum creatinine was >2 mg/dL, and RRT was initiated. The selected patients were randomized to intermittent (IRRT) or continuous renal replacement therapy (CRRT). RESULTS: A total of 316 AKI patients were randomly assigned to IRRT (n = 144) or CRRT (n = 172). The mean age was 66 (range 18-96); 59% were male. Intention-to-treat analysis revealed a mortality of 62.5% in IRRT compared to 58.1% in CRRT (P = 0.430). No difference between IRRT and CRRT could be observed in the duration of ICU stay or hospital stay. In survivors, renal recovery at hospital discharge was comparable between both groups. Multivariate analysis, including the SHARF score, APACHE II and SOFA scores for correction of disease severity, showed no difference in mortality between both treatment modalities. This result was confirmed in pre-specified subgroup analysis (elderly, patients with sepsis, heart failure, ventilation) and after exclusion of possible confounders (early mortality, delayed ICU admission). CONCLUSIONS: Modality of RRT, either CRRT or IRRT, had no impact on the outcome in ICU patients with AKI. Both modalities need to be considered as complementary in the treatment of AKI (Clinical Trial: SHARF 4, NCT00322933, http://ClinicalTrials.gov).

Aliskiren, a novel orally effective renin inhibitor, provides dose-dependent antihypertensive efficacy and placebo-like tolerability in hypertensive patients.

BACKGROUND: Stopping the detrimental effects of the renin-angiotensin system at the most upstream point of the cascade offers theoretical advantages for cardiovascular protection. This study compares the antihypertensive efficacy and safety of the novel oral renin inhibitor aliskiren with placebo and an active comparator. METHODS AND RESULTS: The study was a randomized, multicenter, double-blind, placebo-controlled, active-comparator 8-week trial in patients with mild-to-moderate hypertension (mean sitting diastolic blood pressure [DBP] > or =95 and <110 mm Hg). After a 2-week, single-blind placebo run-in, 652 patients were randomized to receive double-blind treatment with once-daily oral doses of aliskiren (150, 300, or 600 mg), irbesartan 150 mg, or placebo. Aliskiren 150, 300, and 600 mg effectively lowered both trough mean sitting DBP and systolic blood pressure (SBP) (P<0.001 versus placebo for both variables). The least-squares mean reductions in trough DBP were 9.3+/-0.8, 11.8+/-0.8, and 11.5+/-0.8 mm Hg, respectively, versus 6.3+/-0.8 mm Hg for placebo, and the least-squares mean reductions in trough SBP were 11.4+/-1.3, 15.8+/-1.2, and 15.7+/-1.2 mm Hg, respectively, versus 5.3+/-1.2 mm Hg for placebo. The antihypertensive effect of aliskiren 150 mg was comparable to that of irbesartan 150 mg (8.9+/-0.7 and 12.5+/-1.2 mm Hg, least-squares reduction in mean sitting DBP and SBP, respectively, for irbesartan). Aliskiren 300 and 600 mg lowered mean sitting DBP significantly more than irbesartan 150 mg (P<0.05). Aliskiren showed safety and tolerability comparable to those of placebo and irbesartan; the incidence of adverse events and number of patients discontinuing therapy were similar in all groups. CONCLUSIONS: Once-daily oral treatment with aliskiren lowers blood pressure effectively, with a safety and tolerability profile comparable to that of irbesartan and placebo, in patients with mild-to-moderate hypertension. Aliskiren 150 mg is as effective as irbesartan 150 mg in lowering blood pressure.

Pharmacokinetics of atorvastatin and its metabolites after single and multiple dosing in hypercholesterolaemic haemodialysis patients.

BACKGROUND: Patients with chronic renal failure commonly suffer from a secondary form of complex dyslipidaemia, and may benefit from lipid-lowering treatment. Atorvastatin has been shown to reduce efficiently the levels of atherogenic lipoproteins also in patients with renal failure, but pharmacokinetic data in haemodialysis patients are lacking. METHODS: In this study, hypercholesterolaemic haemodialysis patients received 40 mg (n=12) or 80 mg (n=11) atorvastatin once daily, first as a single dose and then continuously for 2 weeks. Plasma levels of atorvastatin and its active and inactive metabolites were measured by LC/MS/MS, and pharmacokinetic parameters (C(max), t(max), AUC, t(1/2)) compared between single and multiple dosing, and between the different doses. RESULTS: The pharmacokinetic parameters of the parent drug atorvastatin acid were not significantly different after single and 2-week multiple dosing; they showed dose-proportionality between the 40 and 80 mg dose, and were comparable to findings in healthy volunteers. Dose-proportionality and absence of accumulation was also observed for the major active metabolite ortho-hydroxy-atorvastatin and the inactive metabolites atorvastatin lactone and ortho-hydroxy-atorvastatin lactone, but the levels of the active metabolite were relatively lower, and the inactive metabolites higher, compared with healthy volunteers. The para-hydroxy-metabolites constituted only a minor pathway in atorvastatin's metabolic elimination. Haemodialysis did not cause enhanced clearance of atorvastatin or its metabolites, the drug was well tolerated and there were no serious adverse events. CONCLUSION: While subtle differences may exist in the metabolic processing of atorvastatin in haemodialysis patients, active drug did not accumulate nor did it show enhanced elimination, and levels were comparable to those measured in healthy volunteers. Therefore there is no need to adapt atorvastatin dosage in this particular patient population.