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BACKGROUND: Adherence to antihypertensive drugs (AHDs) is crucial for controlling blood pressure (BP). We aimed to determine the effectiveness of measuring AHD concentrations using a dried blood spot (DBS) sampling method to identify nonadherence, combined with personalized feedback, in reducing resistant hypertension. METHODS: We conducted a multicenter, randomized, controlled trial (RHYME-RCT, ICTRP NTR6914) in patients with established resistant hypertension. Patients were randomized to receive either an intervention with standard of care (SoC) or SoC alone. SoC consisted of BP measurement and DBS sampling at baseline, 3 months (t3), 6 months (t6), and 12 months (t12); AHD concentrations were measured but not reported in this arm. In the intervention arm, results on AHD concentrations were discussed during a personalized feedback conversation at baseline and t3. Study endpoints included the proportion of patients with RH and AHD adherence at t12. RESULTS: Forty-nine patients were randomized to receive the intervention+SoC, and 51 were randomized to receive SoC alone. The proportion of adherent patients improved from 70.0 to 92.5% in the intervention+SoC arm ( P  = 0.008, n  = 40) and remained the same in the SoC arm (71.4%, n  = 42). The difference in adherence between the arms was statistically significant ( P  = 0.014). The prevalence of resistant hypertension decreased to 75.0% in the intervention+SoC arm ( P  < 0.001, n  = 40) and 59.5% in the SoC arm ( P  < 0.001, n  = 42) at t12; the difference between the arms was statistically nonsignificant ( P  = 0.14). CONCLUSION: Personalized feedback conversations based on DBS-derived AHD concentrations improved AHD adherence but did not reduce the prevalence of RH.

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BACKGROUND AND OBJECTIVES: A geriatric assessment (GA) is a structural method for identifying frail patients. The relation of GA findings and risk of death in end-stage kidney disease (ESKD) is not known. The objective of the GA in OLder patients starting Dialysis Study was to assess the association of GA at dialysis initiation with early mortality and hospitalization. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: Patients ≥65 years old were included just prior to dialysis initiation. All participants underwent a GA, including assessment of (instrumental) activities of daily living (ADL), mobility, cognition, mood, nutrition, and comorbidity. In addition, a frailty screening (Fried Frailty Index, [FFI]) was applied. Outcome measures were 6- and 12-month mortality, and 6-month hospitalization. Associations with mortality were assessed with cox-regression adjusting for age, sex, comorbidity burden, smoking, residual kidney function and dialysis modality. Associations with hospitalization were assessed with logistic regression, adjusting for relevant confounders. RESULTS: In all, 192 patients were included, mean age 75 ± 7 years, of whom 48% had ≥3 geriatric impairments and were considered frail. The FFI screening resulted in 46% frail patients. Mortality rate was 8 and 15% at 6- and 12-months after enrolment, and transplantation rate was 2 and 4% respectively. Twelve-month mortality risk was higher in patients with ≥3 impairments (hazard ratio [HR] 2.97 [95% CI 1.19-7.45]) compared to less impaired patients. FFI frail patients had a higher risk of 12-month mortality (HR 7.22 [95% CI 2.47-21.13]) and hospitalization (OR 1.93 [95% CI 1.00-3.72]) compared to fit patients. Malnutrition was associated with 12-month mortality, while impaired ADL and depressive symptoms were associated with 12-month mortality and hospitalization. CONCLUSIONS: Frailty as assessed by a GA is related to mortality in elderly patients with ESKD. Individual components of the GA are related to both mortality and hospitalization. As the GA allows for distinguishing between frail and fit patients initiating dialysis, it is potentially of added value in the decision-making process concerning dialysis initiation.

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OBJECTIVE: To compare the brachiocephalic (BC) and basilic vein transposition (BVT) arteriovenous fistula (AVF) with regard to maturation, patency, blood flow and complication rates. DESIGN: A retrospective chart review. MATERIALS AND METHOD: Between January 2000 and December 2010, consecutive patients undergoing BC or BVT AVF were included. Patient characteristics were collected retrospectively from digital patient files and a prospective database of haemodialysis patients. RESULTS: A total of 173 autologous upper arm AVFs (87 BC and 86 BVT) were created in 151 patients. Mean (±SEM) follow-up was 19 ± 1.4 months (range 0-100). There were no differences between the groups in respect to brachial artery and cubital fossa vein diameters, time to first use, flow and the number of secondary interventions. Operative time was significantly longer (P < 0.001) and the mid upper arm vein diameter before bifurcation greater (P = 0.038) in BVT patients. The 1- and 2-year primary patency rates for the whole cohort was 40.8% and 30.2% with secondary patency rates of 78.0% and 72.4%. There was no difference between the groups for these outcomes (P = 0.951, P = 0.516, respectively). CONCLUSION: With the exception of the efferent vein diameter in the mid upper arm and operative time, there was no difference between a BC and BVT AVF.

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BACKGROUND: Chronic kidney disease (CKD) is associated with increased cardiovascular risk. Here we evaluate whether strict implementation of guidelines aimed at multiple targets with the aid of nurse practitioners (NP) improves management in patients with CKD. METHODS: MASTER PLAN is a randomised controlled clinical trial, performed in nine Dutch hospitals. Patients with CKD (estimated glomerular filtration rate (eGFR) 20-70 ml÷min) were randomised to receive NP support (intervention group (IG)) or physician care (control group (CG)). Patients were followed for a median of five years. Presented data are an interim analysis on risk factor control at two-year follow-up. RESULTS: We included 788 patients (532 M, 256 F), (393 CG, 395 IG), mean (±SD ) age 59 (±13) years, eGFR 38 (±15) ml÷min÷1.73m(2), blood pressure (BP) 138 (±21)÷80 (±11) mmHg. At two years 698 patients (352 IG, 346 CG) could be analysed. IG as compared with CG had lower systolic (133 vs 135 mmHg; p= 0.04) and diastolic BP (77 vs 80 mmHg; p=0.007), LDL cholesterol (2.30 vs 2.45 mmol(-l); p= 0.03), and increased use of ACE inhibitors, statins, aspirin and vitamin D. The intervention had no effect on smoking cessation, body weight, physical activity or sodium excretion. CONCLUSION: In both groups, risk factor management improved. However, changes in BP control, lipid management and medication use were more pronounced in IG than in CG. Lifestyle interventions were not effective. Coaching by NPs thus benefits everyday care of CKD patients. Whether these changes translate into improvement in clinical endpoints remains to be established.

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BACKGROUND: Blood pressure (BP) is the most important modifiable risk factor for cardiovascular (CV) disease and progression of kidney dysfunction in patients with chronic kidney disease. Despite extensive antihypertensive treatment possibilities, adequate control is notoriously hard to achieve. Several determinants have been identified which affect BP control. In the current analysis we evaluated differences in achieved BP and achievement of the BP goal between hospitals and explored possible explanations. METHODS: At baseline, BP was measured in a supine position with an oscillometric device in 788 patients participating in the MASTER PLAN study. We also retrieved the last measured office BP from the patient records. Additional baseline characteristics were derived from the study database. Univariate and multivariate analyses were performed with general linear modelling using hospital as a random factor. RESULTS: In univariate analysis, hospital was a determinant of the level of systolic and diastolic BP at baseline. Adjustment for patient, kidney disease, treatment or hospital characteristics affected the relation. Yet, in a fully adjusted model, differences between centres persisted with a range of 15 mmHg for systolic BP and 11 mmHg for diastolic BP. CONCLUSION: Despite extensive adjustments, a clinically relevant, statistically significant difference between hospitals was found in standardised BP measurements at baseline of a randomised controlled study. We hypothesise that differences in the approach towards BP control exist at the physician level and that these explain the differences between hospitals.

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BACKGROUND: Atherosclerotic renal artery stenosis (ARAS) is associated with progressive loss of renal function and is one of the most important causes of renal failure in the elderly. Current treatment includes restoration of the renal arterial lumen by endovascular stent placement. However, this treatment only affects damage caused by ARAS due to the stenosis and ensuing post-stenotic ischemia. ARAS patients have severe general vascular disease. Atherosclerosis and hypertension can also damage the kidney parenchyma causing renal failure. Medical treatment focuses on the latter. Lipid-lowering drugs (statins) could reduce renal failure progression and could reduce the overall high cardiovascular risk. The additional effect on preserving renal function of stent placement as compared to medical therapy alone is unknown. Therefore, the STAR-study aims to compare the effects of renal artery stent placement together with medication vs. medication alone on renal function in ARAS patients. METHOD: Patients with an ARAS of > or = 50% and renal failure (creatinine (Cr) clearance < 80 mL/min/1.73 m2) are randomly assigned to stent placement with medication or to medication alone. Medication consists of statins, anti-hypertensive drugs and antiplatelet therapy. Patients are followed for 2 yrs with extended follow-up to 5 yrs. The primary outcome of this study is a reduction in Cr clearance > 20% compared to baseline. This trial will include 140 patients.

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UNLABELLED: Preliminary data suggest that aspirin renography is more sensitive than captopril renography for indicating renal artery stenosis (RAS). Considering that aspirin, compared with captopril, reduces renal blood flow and, thus, tubular tracer delivery in poststenotic kidneys, aspirin renography is expected to be more useful, particularly if tubular tracers are used. METHODS: We prospectively compared aspirin renography (20 mg/kg orally) and captopril renography (25 mg orally) with 99mTc-mercaptoacetyltriglycine in 75 consecutive patients suspected of having RAS. RESULTS: RAS, diagnosed as stenosis of more than 50% on angiography, was found unilaterally in 34 patients and bilaterally in 17 patients. RAS was absent in 24 patients. The sensitivities for unilateral RAS or bilateral RAS (i.e., stenosis that was at least unilateral) were, respectively, 88% and 88% for captopril renography and 82% and 94% for aspirin renography (not significant). The overall specificity was 75% for captopril renography and 83% for aspirin renography (not significant). Tracer uptake ratios, time to peak activity, and percentage of 20-min tracer retention were also not significantly different for captopril and aspirin renography. Subgroup analysis of modest (50-75%) and severe (> or =75%) RAS, or of plasma creatinine greater than 120 micromol/L, also showed no difference between captopril and aspirin renography. CONCLUSION: We conclude that for identification of RAS, the usefulness of aspirin renography equals, but does not surpass, that of captopril renography.

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BACKGROUND: Percutaneous transluminal angioplasty (PTA) for ostial atherosclerotic renal-artery stenosis has poor results. Angioplasty with stent placement (PTAS) may be more effective. We undertook a randomised prospective study to compare PTA with PTAS in patients with ostial atherosclerotic renal-artery stenosis. METHODS: Patients with ostial atherosclerotic renal-artery stenosis were assigned to receive PTA or PTAS. Secondary PTAS was allowed if PTA failed immediately or during 6 months' follow-up. Analysis was by intention to treat. FINDINGS: 42 patients were assigned PTA and 43 were assigned PTAS, but one patient in the PTAS group was excluded from the study. Primary success rate (<50% residual stenosis) of PTA was 57% (24 patients) compared with 88% (37 patients) for PTAS (difference between groups 31% [95% CI 12-50]). Complications were similar. At 6 months, the primary patency rate was 29% (12 patients) for PTA, and 75% (30 patients) for PTAS (46% [24-68]). Restenosis after a successful primary procedure occurred in 48% of patients for PTA and 14% for PTAS (34% [11-58]). 12 patients underwent secondary stenting for primary or late failure of PTA within the follow-up period: success was similar to that of primary PTAS. Evaluation based on intention to treat showed no difference in clinical results at six months for PTA or PTAS. INTERPRETATION: PTAS is a better technique than PTA to achieve vessel patency in ostial atherosclerotic renal-artery stenosis. Primary PTAS and primary PTA plus PTAS as rescue therapy have similar outcomes. However, the burden of reintervention after PTA outweighs the potential saving in stents, so primary PTAS is a better approach to use.

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In some patients with hypertension or renal insufficiency, renal artery stenosis can play a causative part. If fibromuscular dysplasia is the pathology of the stenosis, treatment of the stenosis by transluminal percutaneous renal angioplasty (TPRA) results in improvement of the concomitant hypertension in 80-90% of the patients. In case of atherosclerotic lesions 50% of the patients benefit by such treatment. In renal insufficiency TPRA of atherosclerotic lesions results in improvement of renal function in only one third of the patients. As restenosis and elastic recoil are seen as the prime determinants of this lack of success in atherosclerosis, intravascular stents were developed with the aim to accomplish a permanent dilation of the arterial lumen. In recent studies stent placement resulted in cure of high blood pressure in 0-16% of the patients and in improvement in 35-70%. The percentage of improvement must be viewed with caution because of the open design of these studies. Improvement of renal function was reported in 7-36% of the patients and worsening in 8-18%. Based on these outcomes stent placement in stenosed renal arteries should not be regarded as a routine clinical treatment.

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Ischemic nephropathy due to bilateral renovascular disease (RVD) is increasingly recognized as cause of end-stage renal failure in the elderly, but a reliable non-invasive method of detection is nor available. Angiotensin converting enzyme inhibition (ACEi) may impair renal function in such patients, but a prospective study of its diagnostic validity has not been undertaken. We studied the effects of controlled exposure to ACEi on plasma creatinine in 108 patients at risk for severe bilateral atherosclerotic RVD, and compared the findings with subsequent angiography. ACEi was given for two weeks, or, to avoid acute renal failure, for four days if plasma creatinine had increased by 20% or more. If after two weeks of ACEi plasma creatinine had not increased by > or = 20%, while blood pressure was still elevated, plasma creatinine was remeasured after blood pressure control by addition of diuretics. The severity of RVD was scored by the stenosis grade of the best perfused kidney. Fifty-two patients had severe bilateral RVD, defined as > or = 50% stenosis to both kidneys (N = 23) or a solitary functioning kidney (N = 29). Of the others, 21 had less severe bilateral RVD, 20 unilateral RVD, and 15 no apparent RVD. Basal plasma creatinine was higher in severe bilateral RVD (median 170 mumol/liter, range 85 to 654 mumol/liter) than in the others (122 mumol/liter, 62 to 675 mumol/liter; P < 0.01), but not discriminative due to a large variability. The increase during ACEi was correlated with the degree of RVD (r = 0.53, P < 0.001). In 69 patients ACEi caused at least a 20% increase in plasma creatinine, in 26 cases by four days, in 31 after two weeks, and in 12 only after blood pressure control by diuretics. Among these were all 52 patients with severe bilateral RVD, 15 of the 41 patients with lesser forms of RVD, and two with normal renal arteries. Thus, in this selected population the criterion of > or = 20% rise in plasma creatinine upon ACEi was 100% sensitive to detect severe bilateral RVD, while its specificity was 70%. No case of acute renal failure was encountered, and plasma creatinine always recovered after stopping ACEi. In conclusion, controlled exposure to ACEi in these patients is safe, and ACEi-induced increase in plasma creatinine is a very sensitive detector of severe bilateral RVD in a high risk population.

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In two patients, women of 54 and 46 years old, with metastatic carcinoma of the breast, multiple microscopic tumour emboli in the lungs were found at autopsy. Ante mortem, unexplained respiratory distress in the former and an atypical thrombotic thrombocytopenic purpura-like syndrome in the latter were the most characteristic clinical features. Pulmonary microscopic tumour embolism is a rare diagnosis but it may occur in all types of cancer. Clinically, thrombotic pulmonary emboli are difficult to distinguish from microscopic tumour embolism. Special attention is to be paid to typical findings on radionuclide perfusion lung scanning (multiple subsegmental perfusion defects at the periphery of the bronchopulmonary segments with a normal ventilation named "segmental contour pattern'). Microangiopathic haemolytic anaemia and consumption coagulopathy are associated disorders. Tumour-directed therapy is the treatment of choice.

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In external beam radiotherapy, conventional analysis of portal images in two dimensions (2D) is limited to verification of in-plane rotations and translations of the patient. We developed and clinically tested a new method for automatic quantification of the patient setup in three dimensions (3D) using one set of computed tomography (CT) data and two transmission images. These transmission images can be either a pair of simulator images or a pair of portal images. Our procedure adjusts the position and orientation of the CT data in order to maximize the distance through bone in the CT data along lines between the focus of the irradiation unit and bony structures in the transmission images. For this purpose, bony features are either automatically detected or manually delineated in the transmission images. The performance of the method was quantified by aligning randomly displaced CT data with transmission images simulated from digitally reconstructed radiographs. In addition, the clinical performance were assessed in a limited number of images of prostate cancer and parotid gland tumor treatments. The complete procedure takes less than 2 min on a 90-MHz Pentium PC. The alignment time is 50 s for portal images and 80 s for simulator images. The accuracy is about 1 mm and 1 degrees. Application to clinical cases demonstrated that the procedure provides essential information for the correction of setup errors in case of large rotations (typically larger than 2 degrees) in the setup. The 3D procedure was found to be robust for imperfections in the delineation of bony structures in the transmission images. Visual verification of the results remains, however, necessary. It can be concluded that our strategy for automatic analysis of patient setup in 3D is accurate and robust. The procedure is relatively fast and reduces the human workload compared with existing techniques for the quantification of patient setup in 3D. In addition, the procedure improves the accuracy of treatment verification in 2D in some cases where rotational deviations in the setup occur.

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PURPOSE: Presently, the majority of clinical tools to quantify deviations in patient setup during external beam radiotherapy is based on two-dimensional (2D) analysis of portal images. The purpose of this study is to develop a tool for the inspection of the patient setup in three dimensions (3D) and to validate its clinical advantage over methods based on 2D analysis in the presence of out-of-plane rotations. METHODS AND MATERIALS: We developed an interactive procedure to quantify the setup deviation of the patient in 3D. The procedure is based on fast computation of digitally reconstructed radiographs (DRRs) in two beam directions and comparison of these DRRs with corresponding portal images. The potential of the tool is demonstrated on three selected cases of prostate and parotid gland treatment where conventional 2D analysis produced inconsistent results. The measurements from 3D analysis are compared with those obtained from the 2D analysis. RESULTS: Despite application of an immobilization cast, two investigated parotid gland setups showed rotational deviations in 3D up to 3 degrees. Two-dimensional analysis of these deviations produced inconsistent results. Analysis of the selected prostate setup in 3D showed a rotational deviation of 7 degrees around the left-right axis, possibly causing displacement of the seminal vesicles toward the borders of the conformal boost fields. Using 2D analysis, this out-of-plane rotation was misinterpreted as a translation resulting in the failure to trigger the decision protocol to correct the setup after the first fraction. Using the 3D patient setup analysis procedure, an accuracy of the order of 1 mm and 1 degree (SD) could be obtained. The computation time of the interactive DRRs is of the order of 1 s on a 60 MHz PC. The complete interactive 3D analysis requires about 10 min. CONCLUSIONS: Quantification of the patient setup in 3D provides essential additional information in cases where conventional 2D analysis is inconsistent, e.g., in the presence of out-of-plane rotations or geometrical degeneracies. The speed and accuracy of the interactive 3D patient setup inspection are acceptable for use in offline clinical studies and analysis of problem cases.

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We implanted transluminal stents in 24 hypertensive patients with a critical atherosclerotic ostial renal artery stenosis (28 arteries). Immediate revascularisation was successful in all. Follow-up angiography at 6 months, available in 18 patients, revealed restenosis twice. In another patient restenosis was suspected and confirmed by angiography at 2 months. Hence, the total restenosis rate was 3 of 19 patients (16%) and 3 of 23 arteries (13%). Two patients developed renal insufficiency due to cholesterol embolism. In the remaining 22 patients renal function improved (n = 8) or stabilised (n = 14). Although all had to resume antihypertensive treatment, blood pressure normalised in 15 patients, improved in one, remained unchanged in five and worsened in one.

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Two men aged 33 and 31 years suffered a fatal heat stroke on a warm summer day. One of them used pimozide and clomipramine, the other zuclopenthixol, dexetimide, droperidol, promethazine and propranolol as psychiatric medication. Both of them had a body temperature > 42.3 degrees C, without perspiring. At first only a comatose situation with practically normal laboratory values existed; this was rapidly followed by massive liver damage, disseminated intravascular coagulation, anaemia, thrombopenia and acute renal failure. In spite of adequate and rapid treatment these complications were fatal. Both patients used medication with an antidopaminergic and anticholinergic (side) effect. The set point of the temperature regulation centre can be elevated by the antidopaminergic activity of antipsychotics. Use of anticholinergic medication can disturb the thermoregulation via inhibition of the parasympathicomimetically mediated sweat secretion. It is recommended to point out the danger of unusually high outdoor temperatures to patients using this medication.

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