Metabolic syndrome in adolescence: can it be predicted from natal and parental profile? The Prediction of Metabolic Syndrome in Adolescence (PREMA) study.

BACKGROUND: There are well-established predisposing factors for the development of metabolic syndrome (MetS) in childhood or adolescence, but no specific risk profile has been identified as yet. The Prediction of Metabolic Syndrome in Adolescence (PREMA) study was conducted (1) to construct a classification score that could detect children at high risk for MetS in adolescence and (2) to test its predictive accuracy. METHODS AND RESULTS: In the derivation cohort (1270 children), data from natal and parental profile and from initial laboratory assessment at 6 to 8 years of age were used to detect independent predictors of MetS at 13 to 15 years of age according to the International Diabetes Federation definition. In the validation cohort (1091 adolescents), the discriminatory capacity of the derived prediction score was tested on an independent adolescent population. MetS was diagnosed in 105 adolescents in the derivation phase (8%), whereas birth weight <10th percentile (odds ratio, 6.02; 95% confidence interval, 2.53-10.12, P<0.001), birth head circumference <10th percentile (odds ratio, 4.15; 95% confidence interval, 2.04-7.14, P<0.001), and parental overweight or obesity (in at least 1 parent; odds ratio, 3.22; 95% confidence interval, 1.30-5.29, P<0.01) were independently associated with diagnosis of MetS in adolescence. Among adolescents in the validation cohort (86 [8%] with MetS), the presence of all these 3 predictors predicted MetS with a sensitivity of 91% and a specificity of 98%. CONCLUSIONS: The coexistence of low birth weight, small head circumference, and parental history of overweight or obesity may be useful for detection of children at risk of developing MetS in adolescence.

Fever of unknown origin: discrimination between infectious and non-infectious causes.

OBJECTIVE: The present study aimed to develop and evaluate a simple diagnostic model that could aid physicians to discriminate between infectious and non-infectious causes of fever of unknown origin (FUO). DESIGN/SETTING/SUBJECTS: Patients with classical FUO were studied in two distinct, prospective, observational phases. In the derivation phase that lasted from 1992 to 2000, 33 variables regarding demographic characteristics, history, symptoms, signs, and laboratory profile were recorded and considered in a logistic regression analysis using the diagnosis of infection as a dependent variable. In the validation phase, the discriminatory capacity of a score based on the derived predictors of infection was calculated for FUO patients assessed from 2001 to 2007. RESULTS: Data from 112 individuals (mean age 56.5+/-11.2 years) were analyzed in the derivation cohort. The final diagnoses included infections, malignancies, non-infectious inflammatory diseases, and miscellaneous conditions in 30.4%, 10.7%, 33% and 5.4% of subjects, whereas 20.5% of cases remained undiagnosed. C-reactive protein>60 mg/L (odds ratio 6.0 [95% confidence intervals 2.5, 9.8]), eosinophils<40/mm(3) (4.1 [2.0, 7.3]) and ferritin<500 microg/L (2.5 [1.3, 5.2]) were independently associated with diagnosis of infection. Among the 100 patients of the validation cohort, the presence of > or =2 of the above factors predicted infection with sensitivity, specificity, and positive and negative predictive values of 91.4%, 92.3%, 86.5%, and 95.2%, respectively. CONCLUSIONS: The combination of C-reactive protein, ferritin and eosinophil count may be useful in discriminating infectious from non-infectious causes in patients hospitalised for classical FUO.

Smoking cessation increases serum adiponectin levels in an apparently healthy Greek population.

BACKGROUND: Smoking has been associated with low serum levels of adiponectin, an adipocytokine with insulin-sensitizing, anti-inflammatory and anti-atherogenic properties. The objective of this study was to assess the early effect on adiponectin levels of smoking cessation supported by bupropion. METHODS: Apparently healthy smokers of both sexes with no additional cardiovascular risk factors were administered 150mg sustained-release bupropion twice daily for 9 weeks. Quitters constituted the active group and non-quitters the control group. Sandwich enzyme-linked immunosorbent assays were employed for the measurement of serum adiponectin and cotinine, the latter used for validation of self-reported abstinence. RESULTS: Among the 106 participants (mean age 44.5+/-11.3 years, 57 females, Brinkman index 512.2+/-98.4, basal adiponectin 7.2+/-1.5mg/L), 45 (42.5%) had quitted smoking at week 9. Quitters' post-cessation adiponectin levels were significantly increased (mean difference with baseline 1.9+/-0.8mg/L, 95% CI 1.2, 2.3; p<0.001), while non-quitters' adiponectin remained unaltered. A multiple regression model including female gender (standardized beta coefficient=0.480, p=0.002), age (0.355, p=0.003), body mass index (BMI) (-0.308, p=0.005), waist circumference (-0.276, p=0.008), smoking status (-0.255, p=0.010), and cotinine levels (-0.233, p=0.021) explained about two thirds of the variation in adiponectin levels (adjusted R(2)=0.656). CONCLUSIONS: Serum adiponectin levels appear to increase considerably within 2 months after smoking cessation. This finding may provide further insight into the mechanisms related to the detrimental effects of smoking and the benefits of quitting.

Arterial stiffness: determinants and relationship to the metabolic syndrome.

This study aimed to investigate independent determinants of arterial stiffness and evaluate the association of arterial stiffness with the presence of metabolic syndrome (MS). Demographic characteristics, hemodynamic parameters, and cardiovascular (CV) risk factors were assessed in Greek food industry employees with no history of diabetes or CV disease in order to isolate multiple correlates of arterial stiffness as assessed by pulse wave velocity (PWV). Subsequently, logistic regression analysis was performed using as end point the presence of MS, defined according to the National Cholesterol Education Program. Data from 424 participants (mean age 45.3 -/+ 15.5 years, 298 [70.3%] males, average PWV 8.5 -/+ 3.6 m/s) were analyzed. PWV was higher in men (8.8 -/+ 3.1 m/s) compared to women (7.7 -/+ 2.9 m/s, p < 0.01). Age, systolic blood pressure, and heart rate were isolated as multivariate determinants of PWV (adjusted R2 0.511 [p < 0.0001] in men and 0.538 [p < 0.0001] in women). The overall prevalence of the MS was 14.6%, being similar in both genders. Four variables were shown to be independent predictors of the presence of MS: waist circumference >102 cm (men)/88 cm (women) (OR 8.6, [95% CI 2.8, 20.6], p < 0.001), insulin resistance (homeostasis model assessment >4) (6.3, [2.1, 17.6], p < 0.001), total cholesterol >240 mg/dL (5.5, [1.7, 12.4], p < 0.01), PWV >9 m/s (4.1, [1.5, 9.9], p < 0.01). High PWV, which was found to be mostly determined by advanced age, elevated systolic BP, and accelerated heart rate, appeared to exhibit a strong independent association with the presence of MS together with adiposity and insulin resistance. This index should be considered as a useful marker for CV risk stratification.

Prognostic significance of plasma resistin levels in patients with atherothrombotic ischemic stroke.

BACKGROUND: Resistin (RSN) is an adipocytokine involved in insulin resistance, obesity and atherosclerosis. This study aimed to investigate the association between plasma RSN and outcome after ischemic stroke. METHODS: RSN measured within 24 h after the event was related to functional outcome and 5-year survival in 211 subjects with first-ever atherothrombotic ischemic stroke. Prognosis was assessed by the Kaplan Meier and the Cox techniques. RESULTS: The probabilities of death were 80.4%, 46.2% and 15.7% (p<0.001) for patients stratified according to tertiles of RSN (>30 ng/mL, 20-30 ng/mL and<20 ng/mL, respectively). The proportion of dependency (modified Rankin Scale score>or=3) was greater in 5-year survivors with RSN in the upper tertile (6/11 [54.5%]) compared to the middle (20/56 [35.7%]) and the lowest tertile (8/43 [18.6%]; p<0.01). C-reactive protein levels (hazard ratio [HR] 3.96 [95% CI 2.06, 8.91]; p<0.001), coronary heart disease (2.69 [1.62, 6.23]; p<0.001), RSN levels (2.12 [1.31, 5.08] p<0.001), National Institute of Health Stroke Scale score (2.02 [1.23, 4.49]; p<0.01) and age (1.84 [1.19, 3.93]; p<0.01) were independent predictors of death. CONCLUSIONS: High plasma RSN appears to be associated with increased risk of 5-year mortality or disability after atherothrombotic ischemic stroke, independently of other adverse predictors.

Factors contributing to inappropriate ordering of tests in an academic medical department and the effect of an educational feedback strategy.

AIMS: To identify factors contributing to laboratory overutilisation in an academic medical department, and to assess the effect of an educational feedback strategy on inappropriate test-ordering behaviour. METHODS: The records of 426 patients admitted during a 6-month period were reviewed. The usefulness of 25 investigations (haematology, basic biochemistry and arterial blood gases) was assessed according to implicit criteria. Trainees' acquaintance with investigation costs was assessed via a multiple-choice questionnaire. The medical staff was informed about their test-ordering behaviour, cost awareness and the factors associated with overuse of diagnostic tests. The test-ordering behaviour of the same doctors was reassessed on 214 patients managed during 6 months after the intervention. RESULTS: Overall, 24 482 laboratory tests were ordered before the intervention (mean 2.96 tests/patient/day). Among those, 67.9% were not considered to have contributed towards management of patients (mean avoidable 2.01 tests/patient/day). Patient age >/=65 years, hospitalisation beyond 7 days and increased case difficulty (death or inability to establish a diagnosis) were factors independently associated with overuse of laboratory tests. Senior trainees ordered more laboratory examinations, but the percentage of avoidable tests requested by junior trainees was higher. A moderate and disparate level of trainees' awareness about the cost of common laboratory examinations was disclosed. The avoidable tests/patient/day were significantly decreased after the intervention (mean 1.58, p = 0.002), but containment of unnecessary ordering of tests gradually waned during the semester after the intervention. CONCLUSION: Repeated audit, continuous education and alertness of doctors, on the basis of assessment of factors contributing to laboratory overutilisation, result in restraining the redundant ordering of tests in the hospital setting.

Thymoma with immunodeficiency (Good's syndrome): review of the literature apropos three cases.

Good's syndrome is the association of thymoma with immunodeficiency, characterized by hypogammaglobulinaemia, depleted B-cells, diminished T-cells and inversion of the CD4/CD8 ratio. The initial clinical presentation is either with a mass lesion-thymoma that is usually benign, or with recurrent infections due to immunodeficiency. Thymectomy usually favourably affects associated conditions, such as pure red cell aplasia, but does not improve hypogammaglobulinaemia, thus the patient remains dependent on intravenous immune globulin and prone to infections. Infections usually affect the respiratory and/or the gastrointestinal tract. Common respiratory, opportunistic, and eventually life-threatening infections may occur. Moreover, patients with Good's syndrome may present other haematological conditions. We report 3 cases with long follow-up, sharing some common manifestations of the syndrome, but also showing unique features. The principal features of this rare syndrome are further discussed.

Plasma adiponectin levels and five-year survival after first-ever ischemic stroke.

BACKGROUND AND PURPOSE: This study aimed to investigate the association between plasma adiponectin levels and 5-year survival after first-ever ischemic stroke. METHODS: Plasma adiponectin measured within 24 hours after first-ever ischemic stroke was related to 5-year outcome. The Kaplan-Meier technique was applied in survival analysis, and the Cox proportional hazards model was used to evaluate the relationship between risk factors and prognosis. RESULTS: The probabilities of death were 92.8%, 52.5%, and 10.5% (P<0.001) for patients stratified according to tertiles of adiponectin (<4 microg/mL, 4 to 7 microg/mL, and >7 microg/mL, respectively). The relative risk of death was 8.1 (95% CI, 3.1, 24.5; P<0.001) for individuals with adiponectin levels in the lowest tertile compared with the upper tertile. Adiponectin <4 microg/mL (hazard ratio [HR], 5.2; 95% CI, 2.1, 18.4; P<0.001), score >15 in the National Institutes of Health Stroke Scale (HR, 3.6; 95% CI, 1.7, 15.9; P<0.001), and coronary heart disease (HR, 2.9; 95% CI, 1.5, 12.3; P<0.001) were independently associated with mortality. CONCLUSIONS: Low plasma adiponectin is related to an increased risk of 5-year mortality after first-ever ischemic stroke, independently of other adverse predictors.

Reproducibility of home and ambulatory blood pressure in children and adolescents.

OBJECTIVE: To evaluate the reproducibility of blood pressure measured at home (HBP) in comparison with ambulatory (ABP) and clinic blood pressure (CBP) in children and adolescents. PARTICIPANTS AND METHODS: Individuals aged 8-17 years who had been referred for elevated CBP were included. CBP was measured at two visits, HBP on 5 days and ABP for 24 h. A second session including all the above measurements was performed after 8 weeks. The reproducibility of CBP (second visit of each session), HBP (average of days 2-5 of each session) and ABP (average 24-h, awake and asleep) was quantified using test-retest correlations coefficients (r) and the standard deviation of differences (SDD) between repeated measurements. RESULTS: Sixteen individuals were included [mean age 13.3+/-2.9 (SD)] years, range 8-17, nine boys]. According to Task Force CBP criteria, eight were classified as hypertensives, three as high normal and five as normotensives. The reproducibility of HBP (systolic/diastolic r, 0.74/0.82, SDD 7.0/4.3) was superior to that of CBP (r, 0.63/0.80, SDD 10.4/6.3). However, ABP appeared to provide the most reproducible values (r, 0.87/0.84, SDD 5.5/4.3 for 24-h ABP; r, 0.85/0.76, SDD 5.9/5.0 for awake; r, 0.76/0.79, SDD 7.0/5.0 for asleep ABP). Aspects of the diurnal ABP variation were poorly reproducible (r, 0.62/0.14, SDD 6.8/5.5 for awake-asleep ABP difference; r, 0.55/0.26, SDD 0.07/0.11 for awake : asleep ratio). CONCLUSION: These data suggest that in children and adolescents home blood pressure measurements are more reproducible than clinic measurements. However, 24-h ambulatory monitoring appears to provide the most reproducible blood pressure values.

Intraindividual blood pressure responses to angiotensin-converting enzyme inhibition and angiotensin receptor blockade.

This study aims to test the hypothesis that in some hypertensive subjects the blood pressure (BP) response to angiotensin-converting enzyme inhibition differs from that to angiotensin receptor blockade (ARB); a responder to angiotensin-converting enzyme inhibition may not respond to ARB or the opposite. A randomized, open-label, crossover, comparative trial of lisinopril 20 mg compared with telmisartan 80 mg (5 weeks per treatment period) was conducted in 32 untreated hypertensives using 24-hour ambulatory BP monitoring. Subjects were classified as "responders" and "nonresponders" using an arbitrary threshold of ambulatory BP response (> or =10 mm Hg systolic or > or =5 diastolic) or the median response achieved by each drug. No difference was detected between the drugs in their effect on ambulatory BP (mean difference 1.2+/-7.1/0.7+/-5.1 mm Hg, systolic/diastolic). Significant correlations were found between the antihypertensive responses to the two drugs (r=0.77, p<0.001). Using the arbitrary response criterion, there was a difference between the drugs in the responses in 28%/13% of subjects (9/4 patients) for systolic/diastolic BP (19%/25% using the median response criterion). These data suggest that in some hypertensive patients the BP response to angiotensin-converting enzyme inhibition may fail to predict the response to ARB. It appears that there are differences in the antihypertensive action of angiotensin-converting enzyme inhibitors and ARBs that may be clinically important.

Out-of-office blood pressure in children and adolescents: disparate findings by using home or ambulatory monitoring.

BACKGROUND: The validity of home blood pressure (HBP) measurements in children has not been evaluated, although in clinical practice such measurements are being used. This study compares HBP, with clinic (CBP) and daytime ambulatory blood pressure (ABP) in children and adolescents. METHODS: Fifty-five children and adolescents aged 6 to 18 years were evaluated with CBP (three visits), HBP (6 days), and daytime ABP. Mean age was 12.3 +/- 2.9 (SD) years, 33 boys. According to the Task Force CBP criteria, 26 were hypertensives, 6 had high-normal BP (hypertensive group), and 23 were normotensives (normotensive group). RESULTS: In the hypertensive group, CBP was 130.8 +/- 7.6/72.5 +/- 8.1 mm Hg (systolic/diastolic), HBP 118.9 +/- 6.3/73.7 +/- 6.7, and ABP 130.8 +/- 8.1/75.5 +/- 8.3. In the normotensive group, CBP was 112.8 +/- 8/63.1 +/- 6.3, HBP 106.7 +/- 8.4/67.2 +/- 5.2, and ABP 123.9 +/- 7.2/72 +/- 4.3. Strong correlations (P < .001) were observed between CBP-HBP (r = 0.73/0.57, systolic/diastolic), CBP-ABP (r = 0.59/0.49), and HBP-ABP (r = 0.72/0.66). In normotensive subjects, ABP was higher than both CBP and HBP for systolic and diastolic BP (P < .001). Furthermore, systolic HBP was lower than CBP (P < .01), whereas the opposite was true for diastolic BP (P < .05). In hypertensive subjects systolic HBP was lower than both CBP and ABP (P < .001), whereas CBP did not differ from ABP. For diastolic BP no differences were found among measurement methods. CONCLUSIONS: These data suggest that, in contrast to adults in whom HBP is close to the levels of daytime ABP, in children and adolescents HBP appears to be significantly lower than daytime ABP. Until more data become available, caution is needed in the interpretation of HBP in children and adolescents.

White coat effect in treated versus untreated hypertensive individuals: a case-control study using ambulatory and home blood pressure monitoring.

BACKGROUND: Some studies have shown a significant white coat effect (WCE) (i.e., difference between clinic blood pressure [CBP] and awake ambulatory blood pressure [ABP]) to be present not only in untreated but also in treated hypertensive individuals. This study aims to assess 1) the prevalence and the magnitude of the WCE in treated versus untreated hypertensive persons, and 2) the usefulness of home blood pressure (HBP) versus ABP in the detection of this phenomenon. METHODS: A case-control study was conducted in 138 treated hypertensive patients and same number of sex- and age-matched untreated hypertensive subjects who had measurements of CBP (at least three visits), HBP, and ABP. Subjects with a WCE of >20/10 mm Hg (systolic/diastolic) were classified as clinic reactors. RESULTS: There was a trend for a larger WCE assessed by ABP monitoring in the untreated group (mean difference in systolic WCE, 1.8 +/- 22.2 mm Hg, 95% CI -2.0 to 5.5; diastolic 1.8 +/- 11.9 mm Hg, 95% CI -0.2 to 3.8) and for more untreated clinic reactors (27% untreated v 20% treated, odds ratio 1.5, 95% CI 0.9 to 2.7). The sensitivity, specificity, and positive and negative predictive values of HBP to detect clinic reactors correctly were 56%/62% (treated/untreated), 87%/84%, 52%/59%, and 89%/86%, respectively, with moderate agreement between HBP and ABP (kappa 0.42/0.46). CONCLUSIONS: In treated hypertensive patients, WCE seems to be reduced compared with that in untreated hypertensive persons but is not eliminated. In both untreated and treated hypertensive individuals HBP monitoring appears to be useful in the detection of the WCE, but it may not be appropriate as an alternative to the ABP method.

Blood pressure- and pulse pressure-lowering effects, trough:peak ratio and smoothness index of telmisartan compared with lisinopril.

OBJECTIVE: To compare lisinopril with telmisartan, in regard to: 1) their effect on blood pressure (BP) and pulse pressure (PP), and 2) the duration and the homogeneity of their antihypertensive effect. PATIENTS AND METHODS: A randomized, open-label, crossover, comparative study of telmisartan 80 mg versus lisinopril 20 mg was conducted in 32 untreated hypertensive patients using clinic and 24-hour ambulatory BP measurements. Trough: peak ratio (TPR) and smoothness index (SI) were calculated for each drug. RESULTS: Using both measurement techniques no difference was detected between the 2 drugs in their effects either on BP (mean difference in 24-hour systolic BP 1.2 +/- 7.1 mm Hg, 95% confidence intervals -1.4, 3.8, and diastolic 0.7 +/- 5.1, -1.2, 2.5) or on PP (0.5 +/- 3.5, -0.7, 1.8). There was no difference between the TPR and the SI values of telmisartan (TPR 0.85/0.61 for systolic/diastolic BP and SI 1.46/1.2) and lisinopril (TPR 0.74/0.64 and SI 1.3/1.17). CONCLUSIONS: These data suggest that telmisartan is as effective as lisinopril in reducing BP and PP. Both drugs seem to provide smooth and sustained effects throughout the full 24-hour period.

Acute pyelonephritis in adults: prediction of mortality and failure of treatment.

BACKGROUND: To formulate a classification tool for early recognition of patients admitted with acute pyelonephritis (AP) who are at high risk for failure of treatment or for death. METHODS: A retrospective chart review of 225 patients (102 men) admitted with AP. We considered 13 potential risk factors in a multivariate analysis. RESULTS: Recent hospitalization, previous use of antibiotics, and immunosuppression were found to be independent correlates of the prevalence of resistant pathogens in both sexes. Additional predictors included nephrolithiasis in women and a history of recurrent AP in men. Prolonged hospitalization should be expected for a man with diabetes and long-term catheterization who is older than 65 years or for a woman of any age with the same characteristics, when the initial treatment was changed according to the results of urine culture. For mortality prediction, we derived an integer-based scoring system with 6 points for shock, 4 for bedridden status, 4 for age greater than 65 years, and 3 for previous antibiotic treatment for men and 6 points for shock, 4 for bedridden status, 4 for age greater than 65 years, and 3 for immunosuppression for women. Among patients with at least 11 points, the risk for in-hospital death was 100% for men and 91% for women. CONCLUSIONS: Simple variables available at presentation can be used for risk stratification of patients with AP. The additional identification of certain risk factors by means of a carefully obtained history could contribute to early recognition of patients infected by resistant bacteria and optimize the selection of antimicrobial agents.

Comparison of the smoothness index, the trough : peak ratio and the morning : evening ratio in assessing the features of the antihypertensive drug effect.

OBJECTIVE: To provide a direct comparison of the trough : peak ratio (TPR), the morning : evening home blood pressure ratio (MER) and the smoothness index (SI) in assessing the features of the antihypertensive drug effect. PATIENTS AND METHODS: A total of 27 untreated hypertensives were randomized to receive lisinopril 20 mg o.d. or losartan 50 mg o.d. for 5 weeks and were subsequently crossed-over to the alternative treatment for a second 5-week period. Twenty-four hour ambulatory and 5-day home blood pressure were monitored before randomization and at the end of each treatment period. TPR, MER and SI were calculated for each drug for the total study population and for responders only. RESULTS: When all patients were considered, lisinopril provided higher values of TPR [0.63/0.66 for systolic/diastolic blood pressure (SBP/DBP)], MER (1.02/0.77) and SI (1.01/0.87) than losartan (0.35/0.51, 0.60/0.60 and 0.64/0.53, respectively). Analysis of responders only, again showed a clear advantage of lisinopril over losartan in TPR (0.77/0.67 versus 0.44/0.47, respectively) and MER (0.86/0.87 versus 0.48/0.61), whereas there was no difference in SI (1.25/1.13 for lisinopril versus 1.11/1.12 for losartan). CONCLUSIONS: These data suggest that the assessment of the duration of the antihypertensive drug effect provided by the MER is consistent to that by the TPR and that two drugs with different levels of TPR and MER may have the same level of SI. It appears that the SI is not simply a more reliable index of the features of the antihypertensive drug effect, but offers a different type of information complementary to that provided by the TPR and the MER, in regard to the homogeneity and the magnitude but not the duration of the antihypertensive effect.

Differentiation between patients with acute upper gastrointestinal bleeding who need early urgent upper gastrointestinal endoscopy and those who do not. A prospective study.

OBJECTIVE: To differentiate, among patients presented at the emergency department with acute upper gastrointestinal bleeding, those who need early urgent upper gastrointestinal endoscopy from those who do not. METHODS: Seventeen variables for each patient presenting with upper gastrointestinal bleeding were prospectively recorded and considered in a multivariate analysis. We used the presence of active bleeding during early urgent upper gastrointestinal endoscopy within 12 h from admission as the end point. The derived score was validated with data from the next consecutive patients presenting with upper gastrointestinal bleeding. RESULTS: Among 190 consecutive patients (mean age 63.7 +/- 16 years; 64.7% men), active bleeding was observed in 51 patients (26.8%). Four variables were identified as independent predictors (P < 0.05) of active bleeding in early urgent upper gastrointestinal endoscopy and were used for the derivation of the following integer-based scoring system: number of points = 6 (fresh blood in nasogastric tube) + 4 (haemodynamic instability) + 4 (haemoglobin < 8 g/dl) + 3 (white blood cell count > 12 000/microl). The validation study consisted of 110 patients (71 men; mean age 66.1 +/- 14 years; 28 patients [25.5%] with active bleeding). In this study, a cut off of < 7 points indicated absence of active bleeding and >/= 11 points indicated presence of active bleeding; this gave a sensitivity of 96%, specificity of 98%, positive predictive value of 96% and negative predictive value of 98%. CONCLUSIONS: Simple clinical and laboratory variables available at presentation can be used to differentiate patients with upper gastrointestinal bleeding who do not need an early urgent upper gastrointestinal endoscopy from those who do.

A mortality prediction model in diabetic ketoacidosis.

AIM: To assess the value of clinical and laboratory parameters in predicting mortality in patients presenting with diabetic ketoacidosis (DKA). METHODS: The records of all DKA admissions within 10 years were reviewed. Eighteen variables were evaluated at initial presentation and 20 variables at 4, 12 and 24 h from admission. A scoring system derived from these variables was compared to the APACHE III scoring system. RESULTS: Among 154 patients (52 males, mean age 58 +/- 12 years), 20 (13%) died in hospital. Multivariate analysis yielded six variables as significant independent predictors (P < 0.05) of mortality: severe coexisting diseases (SCD) and pH < 7.0, at presentation; units of regular insulin required in the first 12 h > 50 and serum glucose > 16.7 mmo/l, after 12 h; depressed mental state and fever, after 24 h. An integer-based scoring system was derived, as follows: number of points = 6 (SCD at presentation) + 4 (pH < 7.0 at presentation) + 4 (regular insulin required > 50 IU after 12 h) + 4 (serum glucose > 16.7 mmo/l after 12 h) + 4 (depressed mental state after 24 h) + 3 (fever after 24 h). Patients with 0-14 points had 0.86% risk of death, whereas for those with 19-25 points the risk was 93.3%. Median APACHE III scores differed significantly (P < 0.001) among groups of patients stratified according to the above scoring system. CONCLUSIONS: Risk stratification of patients with diabetic ketoacidosis is possible from simple clinical and laboratory variables available during the first day of hospitalization.

Clinic, home and ambulatory pulse pressure: comparison and reproducibility.

OBJECTIVE: Recent evidence suggests that pulse pressure (PP) is an independent predictor of cardiovascular risk. The objective of this study was to compare mean values and reproducibility of PP obtained in the clinic (CPP), at home (HPP) and with ambulatory monitoring (APP) and to evaluate potential implications for trials aiming to assess drug effects on PP. METHODS: A total of 393 hypertensive subjects [mean age 51.5 +/- 11.5 (SD) years, 59% men, 35% treated] measured CPP (two visits), HPP (6 days) and APP (24 h). The reproducibility of PP was assessed using the SD of differences (SDD) between measurements in 133 untreated subjects who had repeated CPP (five visits), HPP (6 days) and APP measurements (two occasions). RESULTS: There was no difference between mean CPP (51.0 +/- 13.3 mmHg) and HPP (50.2 +/- 11.0) whereas APP (48.8 +/- 8.4) was lower than both CPP [mean difference 2.3 +/- 10.3 mmHg; 95% confidence interval (CI), 1.2, 3.3; P < 0.01] and HPP (1.5 +/- 7.8; 95% CI, 0.7, 2.3; P < 0.01). The SDD between repeated measurements was about 10 mmHg for CPP (one visit), 5.2 mmHg for HPP (2 days) and 4 mmHg for APP (24-h). For a parallel comparative trial aiming to detect a difference of 3 mmHg PP in the effect of two drugs, 415 subjects would be required when using CPP, compared to 127 using HPP and 63 using APP. CONCLUSIONS: These data suggest that although differences among mean values of CPP, HPP and APP are small, differences in their reproducibility are important and should be taken into account in the design of trials assessing drug effects on PP.

Effect of estrogen receptor modulator tamoxifen on blood pressure, plasma renin activity, and renal sodium excretion.

BACKGROUND: Adjuvant treatment with the estrogen receptor modulator tamoxifen is a well established long-term therapy in breast cancer. This study investigated the effect of tamoxifen on blood pressure (BP) and on factors by which it might be influenced. METHODS: Normotensive postmenopausal women on > 12 months adjuvant tamoxifen therapy were randomized to withdraw or continue tamoxifen for 6 weeks and then to crossover to the alternative regimen for a second 6-week period. Measurements of clinic and ambulatory BP, plasma renin activity (PRA), and fractional sodium excretion (FE(Na)) were performed at baseline and at the end of each study period. RESULTS: Twenty-three women completed the study (mean age 60.6 +/- 8.3 years). There was no effect of tamoxifen on clinic BP (mean difference between withdrawal and continuation for systolic BP, 0.4 +/- 8.4 mm Hg, 95% confidence interval [CI] -4.0 to 3.2, and diastolic 0.6 +/- 4.7, 95%CI -1.4 to 2.7) or 24-hour ambulatory BP (systolic 0.7 +/- 7.4 mmHg, 95%CI -2.6 to 3.9; diastolic BP, 1.9 +/- 5.5, 95% CI -0.5 to 4.2). Furthermore, no effect of tamoxifen on PRA (mean difference between withdrawal and continuation 0.03 +/- 0.5 ng/mL/h, 95% CI -0.3 to 0.2) or FENa (0.05 +/- 0.5, 95% CI -0.2 to 0.2) was detected. CONCLUSIONS: Tamoxifen seems to have no effect on BP, PRA, or FE(Na) in normotensive postmenopausal women.

Parallel morning and evening surge in stroke onset, blood pressure, and physical activity.

BACKGROUND AND PURPOSE: A circadian variation with a morning peak on waking and arising is known to occur in both blood pressure (BP) and cardiovascular event onset. A second peak in BP has been described to occur after an afternoon sleep (siesta). This study was designed to investigate the hypothesis that the 2-peak diurnal variation of BP is dependent on physical activity and occurs in parallel with the diurnal variation of stroke onset. METHODS: The diurnal variation of stroke onset was compared with the diurnal variation of BP, pulse rate (PR), and physical activity in 3 independent groups of Greek hypertensives 51 to 80 years of age (633 stroke patients, 379 subjects with 24-hour ambulatory BP monitoring, and 50 subjects with 24-hour physical activity monitoring through wrist devices). RESULTS: The diurnal variation of stroke onset, BP, and PR all showed 1 morning and 1 evening peak with a decline in the afternoon and at night that occurred in parallel with the diurnal variation in physical activity (P<0.001 for differences among morning, afternoon, evening, and nighttime intervals in BP, PR, activity, and stroke). The afternoon decline in BP, PR, and activity was significant only in subjects with a siesta. CONCLUSIONS: The 2-peak diurnal variation in stroke onset occurred in parallel with the variation in BP, PR, and physical activity. These data support the hypothesis that an abrupt change in physical activity is not only a major determinant of the 2-peak diurnal variation of BP but also an important triggering factor for a cerebrovascular event.