Cost-utility of exercise therapy in patients with hip osteoarthritis in primary care.

OBJECTIVE: To determine the cost-effectiveness (CE) of exercise therapy (intervention group) compared to 'general practitioner (GP) care' (control group) in patients with hip osteoarthritis (OA) in primary care. METHOD: This cost-utility analysis was conducted with 120 GPs in the Netherlands from the societal and healthcare perspective. Data on direct medical costs, productivity costs and quality of life (QoL) was collected using standardised questionnaires which were sent to the patients at baseline and at 6, 13, 26, 39 and 52 weeks follow-up. All costs were based on Euro 2011 cost data. RESULTS: A total of 203 patients were included. The annual direct medical costs per patient were significantly lower for the intervention group (€ 1233) compared to the control group (€ 1331). The average annual societal costs per patient were lower in the intervention group (€ 2634 vs € 3241). Productivity costs were higher than direct medical costs. There was a very small adjusted difference in QoL of 0.006 in favour of the control group (95% CI: -0.04 to +0.02). CONCLUSION: Our study revealed that exercise therapy is probably cost saving, without the risk of noteworthy negative health effects. TRIAL REGISTRATION NUMBER: NTR1462.

Effectiveness of exercise therapy added to general practitioner care in patients with hip osteoarthritis: a pragmatic randomized controlled trial.

OBJECTIVE: To assess the effectiveness of exercise therapy added to general practitioner (GP) care compared with GP care alone, in patients with hip osteoarthritis (OA) during 12 months follow-up. METHODS: We performed a multi-center parallel pragmatic randomized controlled trial in 120 general practices in the Netherlands. 203 patients, aged ≥45 years, with a new episode of hip complaints, complying with the ACR criteria for hip OA were randomized to the intervention group (n = 101; GP care with additional exercise therapy) or the control group (n = 102; GP care only). GP care was given by patient's own GP. The intervention group received, in addition, a maximum of 12 exercise therapy sessions in the first 3 months and hereafter three booster sessions. Blinding was not possible. Primary outcomes were hip pain and hip-related function measured with the HOOS questionnaire (score 0-100). RESULTS: The overall estimates on hip pain and function during the 12-month follow-up showed no between-group difference (intention-to-treat). At 3-months follow-up there was a statistically significant between-group difference for HOOS pain -3.7 (95% CI: -7.3; -0.2), effect size -0.23 and HOOS function -5.3 (95% CI: -8.9; -1.6), effect size -0.31. No adverse events were reported. CONCLUSIONS: No differences were found during 12-months follow-up on pain and function. At 3-months follow-up, pain and function scores differed in favor of patients allocated to the additional exercise therapy compared with GP care alone. TRIAL REGISTRATION: The Netherlands Trial Registry NTR1462.

A Method for Delineation of Bone Surfaces in Photoacoustic Computed Tomography of the Finger.

Photoacoustic (PA) imaging of interphalangeal peripheral joints is of interest in the context of using the synovial membrane as a surrogate marker of rheumatoid arthritis. Previous work has shown that ultrasound (US) produced by absorption of light at the epidermis reflects on the bone surfaces within the finger. When the reflected signals are backprojected in the region of interest, artifacts are produced, confounding interpretation of the images. In this work, we present an approach where the PA signals known to originate from the epidermis are treated as virtual US transmitters, and a separate reconstruction is performed as in US reflection imaging. This allows us to identify the bone surfaces. Furthermore, the identification of the joint space is important as this provides a landmark to localize a region-of-interest in seeking the inflamed synovial membrane. The ability to delineate bone surfaces allows us to identify not only the artifacts but also the interphalangeal joint space without recourse to new US hardware or a new measurement. We test the approach on phantoms and on a healthy human finger.

Quantitative detection of gold nanoparticles on individual, unstained cancer cells by scanning electron microscopy.

Gold nanoparticles are rapidly emerging for use in biomedical applications. Characterization of the interaction and delivery of nanoparticles to cells through microscopy is important. Scanning electron microscopes have the intrinsic resolution to visualize gold nanoparticles on cells. A novel sample preparation protocol was developed to enable imaging of cells and gold nanoparticles with a conventional below lens scanning electron microscopes. The negative influence of 'charging' on the quality of scanning electron microscopes' images could be limited by deposition of biological cells on a conductive (gold) surface. The novel protocol enabled high-resolution scanning electron microscopes' imaging of small clusters and individual gold nanoparticles on uncoated cell surfaces. Gold nanoparticles could be counted on cancer cells with automated routines.

Comparison of impedance cardiography and dye dilution method for measuring cardiac output.

OBJECTIVE: To assess the degree of agreement between impedance cardiography, using the NCCOM3-R7 device, and the gold standard--the dye dilution method--both under basal conditions and after stimulation of cardiac output. PATIENTS: 35 paired measurements in five healthy male volunteers. INTERVENTIONS: To obtain higher levels of cardiac output, cardiac performance was stimulated with a dopamine infusion. RESULTS: In 35 paired measurements, the mean of all the impedance values was higher than that of the dye dilution values, at 10.2 v 7.4 l/min (p < 0.0001). The mean discrepancy between the two methods was 3.3 l/min, and the mean bias -2.9 l/min, with limits of agreement of -9.0 and 3.2 l/min. A change in cardiac output could not adequately be predicted by the NCCOM3-R7. In 20 of 25 measurements obtained during continuous intravenous dopamine infusions there was a rise in dye dilution cardiac output (range 0.2 to 5.9 l/min). Neither the magnitude nor the direction of the change in dye dilution values corresponded with the change measured by impedance cardiography. The mean discrepancy here between the two methods was 1.8 l/min, and the mean bias -0.8 l/min, with limits of agreement of -4.9 and 3.3 l/min. CONCLUSIONS: In healthy volunteers, impedance cardiography with NCCOM3-R7 is inadequate for assessing cardiac output when compared with the dye dilution method.

[Preferential posture in infants; serious demands on health care]. / Voorkeurshouding bij zuigelingen; groot beroep op de gezondheidszorg.

OBJECTIVE: To determine the prevalence of preferential posture in infants up to the age of six months; to determine the percentage of referrals for diagnostics and (or) treatment; to gather information about risk factors. SETTING: Infant Health Care (IHC) centres in the Netherlands. DESIGN: Descriptive controlled investigation. METHOD: During September 1995 a total of 7609 infants were examined by 167 IHC doctors for the presence of preferential posture. Data on the physical examination and on the occurrence of risk factors were registered for every child with preferential posture (n = 623) and for a next child of the same age and the same sex without preferential posture. Six months later 468 children with preferential posture were re-examined. RESULTS: The prevalence of preferential posture was 8.2% and was highest in children below 16 weeks of age. The ratio boy:girl was 3:2. Firstborns, premature children and children in breech position at the time of delivery, had a higher risk for preferential posture. The position of the child after the first week of life and the way of feeding proved to be significant risk factors. After six months 32% of the children with preferential posture had been referred for additional diagnostics and, if necessary, treatment. CONCLUSION: Preferential posture is frequently observed and leads to referral, additional diagnostics and (or) treatment in 2.5% of all children up to 6 months of age.

Natriuretic effect of nitrendipine is preceded by transient systemic and renal hemodynamic effects.

This study investigated whether the acute natriuretic effect of nitrendipine is related to its initial renal hemodynamic effects. We investigated 16 patients (10 men and 6 women, mean age 52 +/- 2 years) with essential hypertension, whose treatment, if any, was stopped 3 weeks before the study. They were admitted to a metabolic ward for 9 days and kept on a constant sodium diet of 55 mmol/day. During two 24-hour experiments, subjects randomly received a single oral dose of placebo/nitrendipine 10 mg (group 1, n = 8) or placebo/nitrendipine 20 mg (group 2, n = 8), according to a double-blind crossover study design. Patients fasted during the experiments, but their sodium intake was ensured by a constant intravenous saline infusion of 2.3 mmol/hr. Mean arterial pressure (MAP) and heart rate were determined for 5 hours following the administration of nitrendipine or placebo. Effective renal plasma flow (ERPF), glomerular filtration rate, active plasma renin concentration, angiotensin II, aldosterone, atrial natriuretic peptide, and catecholamines were determined every hour for 5 hours. Hourly urine collections were used to assess sodium, potassium, and creatinine excretions. Relative to placebo, only in group 2 (nitrendipine 20 mg) was a fall in MAP and a rise in ERPF observed 2 hours after the start of the experiment. The effects, however, lasted only for 1 hour. No such changes were seen in group 1. In neither group did nitrendipine affect hormonal concentrations. Sodium excretion was enhanced after the 20-mg dose of nitrendipine only (p < 0.05). Nitrendipine 20 mg induced a significant increase in sodium excretion, which may be dissociated from its acute hemodynamic effects.

Baseline and postcaptopril renal blood flow measurements in hypertensives suspected of renal artery stenosis.

UNLABELLED: Renal blood flow (RBF) measurements using first-pass radionuclide angiography with DTPA, a glomerularly filtered agent, failed to show significant differences between normal and stenotic kidneys. Since MAG3 is an ideal agent for the study of RBF, this agent might be an attractive alternative tracer to detect differences in RBF. METHODS: An angiographically controlled prospective study was performed in 48 hypertensive patients, in whom a diagnosis of renovascular hypertension was suspected on clinical grounds. The study was done to determine whether RBF measurements using first-pass radionuclide angiography with 99mTc-MAG3 could be helpful in the diagnostic work-up of the patients. Additionally, the study was done before and after ACE-inhibition. RESULTS: On renal angiography, 29 patients showed to have normal renal arteries (50 patients had normal kidneys and 8 patients had small kidneys). Nineteen patients had renal artery stenosis (13 uni- and 6 bilateral disease). In the patients with normal kidneys, the mean value of RBF measurements ranged from 10.5% to 10.9% of cardiac output. Only small stenotic and small kidneys with normal renal arteries showed a significant reduced baseline RBF as compared with normal kidneys (both p < 0.05); this difference disappeared after ACE-inhibition only for the small kidneys with normal renal arteries. In patients with stenosed kidneys, RBF tended to be reduced both at baseline and after captopril, but the differences with normal kidneys were not statistically significant. After ACE-inhibition RBF increased in the majority of kidneys, but postcaptopril RBF data did not differ significantly from those at baseline. CONCLUSION: RBF measurements using first-pass radionuclide angiography with 99mTc-MAG3, either before or after ACE-inhibition, cannot reliably discriminate between patients with essential hypertension and patients with renal artery stenosis.

Heterogeneous patterns of sodium excretion during sodium restriction in essential hypertensive patients.

OBJECTIVE: To study the sodium excretory pattern by which sodium balance is reached. METHODS: Ninety untreated essential hypertensives with a median age of 47 (range: 18-70 years) were admitted to a metabolic ward for 7 days and put on a sodium diet of 55 mmol/day. During these 7 days urinary excretions of sodium, potassium and creatinine were determined daily along with mean arterial pressure (MAP) and weight. RESULTS: Changes in urinary sodium excretion were not uniform, but according to the pattern of attaining sodium balance, subjects could be divided into four groups. Group 1 (n = 31) gradually reached sodium balance, whereas group 2 (n = 10) showed an abrupt fall in sodium excretion on the third day and an extremely fluctuating sodium excretion thereafter. Group 3 (n = 32) reached sodium balance on day four, but displayed a rise in sodium excretion during the following days and group 4 (n = 17) attained sodium balance only very slowly or not at all. Compared to the other groups, group 4 lost more sodium and at the same time displayed a greater fall in blood pressure. CONCLUSIONS: Our data suggest that there may be at least four different patterns by which sodium balance can be reached following a reduction in sodium intake. The determinants of these responses remain, however, elusive.

Sodium sensitivity of blood pressure in hypertensives is not related to sodium, but rather to renin.

OBJECTIVE: To investigate whether a certain degree of sodium-sensitivity of blood pressure (BP) in essential hypertensives during sodium restriction is related to cumulative sodium loss. METHODS: One-hundred and seventeen untreated essential hypertensives were admitted to a metabolic ward for 7 days and put on a sodium restricted diet of 55 mmol/day. During these 7 days urinary excretions of sodium, potassium and creatinine were determined daily along with mean arterial pressure (MAP) and weight. Active plasma renin concentration (APRC), aldosterone (ALDO), renal plasma flow (RPF) and plasma volume (PV) were assessed after 7 days under steady state condition. The population was divided into tertiles based on the final changes in BP after 7 days. RESULTS: Textile 1 displayed a median fall in MAP of -13 (-42 to -9) mm Hg, whereas in tertile 2 and 3 a fall of -6 (-9 to -4) mm Hg and a rise of +1 (-3 to +11) mm Hg respectively, was encountered. Baseline characteristics were comparable between the tertiles. When tertile 1 was compared to tertile 3 no significant differences between these tertiles were found with respect to cumulative sodium and potassium balances and weight loss. Furthermore, APRC levels were significantly higher in tertile 3 as compared to tertile 1 (22 and 27 mU/l, respectively). Renal vascular resistance (RVR) tended to be higher in tertile 3, although this was not statistically significant. Aldo, RPF and PV were comparable between the tertiles. CONCLUSIONS: In contrast with tertile 1, MAP in tertile 3 is maintained at its original level, despite comparable sodium losses. In tertile 3, however, levels of renin are higher compared to the group that is more sodium-sensitive. Therefore, our data suggest that the degree of sodium-sensitivity of BP in essential hypertensive subjects is not determined by sodium status, but rather by renin.

Peripheral haemodynamics and renal function in relation to the menstrual cycle.

1. The objective of this study was to investigate whether the luteal phase of the menstrual cycle differs from the follicular phase by the development of a state of general vascular relaxation. 2. Once in the follicular and once in the luteal phase of the menstrual cycle, we measured by non-invasive techniques: arterial blood pressure (by finger blood pressure measurements), vascular tone (by pulse-wave velocity and plethysmography), blood flow to skin (by laser-Doppler), blood flow to forearm (by plethysmography) and blood flow to kidneys (by para-aminohippurate clearance), and the glomerular filtration rate (by inulin clearance). The data points obtained in the luteal phase were compared with those in the follicular phase by non-parametric tests. 3. Arterial blood pressure, vascular tone and the blood flows to the forearm and kidneys were comparable in the two phases of the menstrual cycle. In contrast, the blood flow to the skin was consistently lower, and the glomerular filtration rate higher in the luteal phase of the menstrual cycle. 4. The results of the present study do not support our hypothesis of a general vascular relaxation in the luteal phase of the menstrual cycle. The lower skin flow in the luteal phase may be an adaptation needed to ensure the higher core temperature of 0.3-0.5 degree C in the luteal phase. The higher glomerular filtration rate was in most case paralleled by a higher renal blood flow in the luteal phase. This suggests that the higher glomerular filtration rate is secondary to a selective vasorelaxation of the afferent renal arterioles.

Renal extraction of atrial natriuretic peptide in hypertensive patients with or without renal artery stenosis.

The renin-angiotensin-aldosterone system plays a major role in renovascular hypertension, but the relationship between renin release and the renal fractional extraction of atrial natriuretic peptide (ANP) in this condition is not well defined. We measured ANP levels in the renal veins and aortas of 49 untreated hypertensive patients studied under standardized conditions immediately before renal angiography. Twenty-one patients had renal artery stenosis, 13 of which were unilateral and 8 bilateral. Five of the 13 patients with unilateral renal artery stenosis had an elevated renin ratio (> or = 1.5). Patients with renal artery stenosis were older (P < .01) and had higher systolic pressures (P < .05) than patients with essential hypertension. Arterial levels of ANP were significantly higher in patients with unilateral or bilateral renal artery stenosis than in patients with essential hypertension (P < .05). Patients with hypertension and left ventricular hypertrophy had significantly higher arterial ANP levels than those with no hypertrophy (40 versus 26 pmol/L, P < .05), but in patients with renal artery stenosis, arterial ANP levels were similar in those with or without hypertrophy. Renal venous ANP levels were significantly higher in stenotic than in normal kidneys. Moreover, in unilateral renal artery stenosis, stenotic kidneys of patients with an elevated renin ratio (stenotic kidney/contralateral kidney > or = 1.5) had a significantly higher renal venous ANP level than stenotic kidneys of patients with normal renin ratio (30 versus 17 pmol/L, P < .05). However, the median fractional extraction of ANP was similar, around 0.50 (range, 0 to 0,83), in normal kidneys of hypertensive patients and in stenotic and contralateral kidneys of patients with renal artery stenosis. A significant inverse correlation between arterial ANP and renal venous active plasma renin concentration was found for normal kidneys (r= -.62, P < .01) of hypertensive patients without hypertrophy. However, for stenotic kidneys, no such relationship was apparent. A significant correlation between arterial ANP and the arteriovenous difference of ANP (r = +.92, P < .001) was found. This relationship was similar for normal and stenotic kidneys. In conclusion, an inverse relationship between arterial ANP and renal venous active plasma renin concentration exists in normal kidneys of essential hypertensive patients without left ventricular hypertrophy. Furthermore, data of ANP extraction through normal and stenotic kidneys suggest that saturation of ANP extraction does not occur. Increased levels of ANP in renal artery stenosis are likely caused by enhanced cardiac secretion of this peptide.

Repeated automatic versus ambulatory blood pressure measurement: the effects of age and sex in a normal ageing population.

OBJECTIVES: To study blood pressure adaptation in relation to age and sex. In a subsample, laboratory blood pressure measurements were compared with ambulatory daytime blood pressure measurements to determine the degree of agreement between the two methods. The night-time blood pressure reduction was analysed as a function of blood pressure status, age and sex. DESIGN: A cross-sectional study in 469 healthy volunteers, aged 23-82 years, stratified for age, sex and educational level. METHODS: Laboratory blood pressure was measured automatically (Dinamap 8100) five times during a 20 min recording session. Cardiovascular events in the medical history were identified in order to treat the cardiovascular event-free group separately in subsequent analyses. Within 3 weeks after laboratory blood pressure measurement, ambulatory blood pressure was measured for 24 h in 135 volunteers from the main study. RESULTS: Both diastolic and systolic blood pressure varied markedly in a single measurement session as a function of age, independent of mean pressure level. After 15 min no further blood pressure decrease was observed. On the basis of the average of the final two blood pressure measurements, 18.8% of the subjects were in the hypertensive range (WHO/ISH guidelines). Ambulatory blood pressure measurements were in accord with earlier findings and correlated 0.74 and 0.73 with laboratory diastolic and systolic blood pressure, respectively, but weighted kappa values indicated only moderate agreement (0.42 and 0.51). Women showed a more profound reduction in cnight-time blood pressure than did men. CONCLUSIONS: There is a substantial change in blood pressure during a single measurement session which is greater in older age groups. The moderate agreement between the two methods of blood pressure measurement supports the notion that blood pressure measured in a single session has limited generalizability to average daytime levels in a population sample.

'Captopril test', with blood pressure and peripheral renin as response variables in hypertensive patients with suspected renal artery stenosis.

In forty six hypertensive patients in whom a high level of clinical suspicion for renovascular hypertension was present on the basis of clinical clues, a captopril test was performed with either 25 mg of captopril or placebo on 2 separate days to determine prospectively the value of the captopril test. Blood pressure (BP) and peripheral renin were used as response variables. All patients had discontinued their anti-hypertensive medication and were not salt depleted. In all patients selective renal angiography was performed irrespective of the results of the captopril test. Twenty patients proved to have uni- or bilateral renal artery stenosis (RAS) giving a prevalence of 43%. After the placebo and after captopril there were no significant changes (absolute or proportional) in BP values between patients with essential hypertension or RAS, either for all measurements or if only the fall in BP was taken into account. The receiver operator characteristic curves of both baseline and post-captopril peripheral renin levels indicate that the captopril test does not discriminate appropriately between patients with essential hypertension and RAS. Therefore, we would not advise the use of the captopril test as a screening test for RAS in hypertensive patients in whom a high level of clinical suspicion for RAS is already present.

Renal arterial and venous endothelin in hypertensive patients with or without renal artery stenosis.

Immunoreactive endothelin (ir-ET) levels were measured in the renal veins and aorta of 43 untreated hypertensive patients immediately before renal angiography. None of the patients used antihypertensive medication. Twenty-seven patients had renal artery stenosis, 17 of which were unilateral and 10 bilateral. Seven of the 17 patients with unilateral renal artery stenosis had an elevated renin ratio. Of the 16 patients with essential hypertension 6 had a unilateral small kidney with a normal blood supply. Although there was a trend towards higher levels of ir-ET in patients with renal artery stenosis, no significant differences in endothelin levels (venous or arterial) were found between different groups of patients or groups of kidneys. More than 75% of kidneys extracted endothelin, there being no significant differences between groups of kidneys. In conclusion, our data demonstrate that endothelin levels and renal endothelin extraction are comparable in essential hypertension and in hypertension associated with renal artery stenosis. Whereas renal uptake or endothelin is the rule, some kidneys, however, release this peptide irrespective of the presence or absence of renal artery stenosis.

Doxazosin versus nitrendipine: a double-blind comparative study in patients adhering to a sodium-restricted diet.

The aim of this double-blind parallel-group study was to compare the effects of doxazosin, a selective alpha 1-adrenoceptor antagonist with a long plasma half-life, with nitrendipine, a long-acting calcium-entry blocking drug. Following a 4-week placebo period, 26 patients with mild-to-moderate essential hypertension were randomly allocated to treatment with either doxazosin (n = 12) or nitrendipine (n = 14). Over a period of 10 weeks, doses were titrated to obtain a standing diastolic pressure below 90 mmHg. Thereafter, optimal doses were continued for another 4 weeks. Both drugs were administered once daily; median doses were 4 mg/day for doxazosin and 10 mg/day for nitrendipine. During the titration period three patients in the doxazosin group and one in the nitrendipine group dropped out from the study; one patient on doxazosin was considered a nonresponder. Twenty-one patients completed the study. The percentage of patients showing an adequate hypotensive effect (standing diastolic pressure below 90 mmHg) at the end of the study was similar in the two groups (42% vs. 50% in the intention-to-treat analysis and 56% vs. 54% in the per-protocol analysis). Casual, basal, and standing blood pressure and heart rate did not differ between groups throughout the study; serum lipids and blood glucose remained unchanged. We conclude that doxazosin and nitrendipine given as monotherapy are equally effective in mild to moderate hypertension.

24-hour ambulatory blood pressure monitoring and spirapril in mild to severe essential hypertension: a randomized dose comparison.

This was a multicentre randomized, double-blind, parallel-group study to compare the antihypertensive efficacy of spirapril at 3 mg with 12 mg once daily, as determined by 24-hour ambulatory blood pressure monitoring (ABPM), in patients with mild to severe essential hypertension. Following a 4-week placebo run-in phase, 52 male and female outpatients, aged 23-67 years with mild to severe essential hypertension [diastolic blood pressure (DBP) > or = 100 mmHg and < 120 mmHg] were randomized to receive spirapril at either 3 mg or 12 mg once daily for 8 weeks. At the end of active treatment and using the standard mercury sphygmomanometer, the number of responders (sitting DBP < 90 mmHg, but decrease > or = 10 mmHg) was the same in both groups (32% and 37%). There were mean decrease in both systolic blood pressure (SBP) and DBP at trough with both 3 mg and 12 mg doses: -9/-7 mmHg and -12/-7 mmHg, respectively. The rate of normalization (trough DBP < or = 90 mmHg) was 12% and 30% with the 3 mg and 12 mg doses, respectively. Of the 44 patients whose daytime ABPM could be compared, one of 20 patients taking 3 mg of spirapril, and 9 of 24 taking 12 mg of spirapril achieved a DBP < or = 90 mmHg for all time intervals while awake. The differences in blood pressure-lowering were significant with both SBP and DBP during the day and at the end of the dosing interval (p < 0.001 and p < 0.01, respectively). The changes from baseline at 24 hours postdose for SBP/DBP were -3/-6 mmHg with 3 mg and -14/-12 mmHg with 12 mg of spirapril.(ABSTRACT TRUNCATED AT 250 WORDS)