Predição de Pré-Eclâmpsia no Primeiro Trimestre em Gravidezes de Baixo Risco: Determinação do Cut-Off numa Amostra da População Portuguesa

Objective:We aimed to identify the cut-off for risk of pre-eclampsia (PE) in Portuguese population by applying the first trimester prediction model from Fetal Medicine Foundation (FMF) in a prospective enrolled cohort of low risk pregnant women. Population and methods: A prospective cohort of low risk singleton pregnancies underwent routine first-trimester scree - ning from 2011 through 2013. Maternal characteristics, blood pressure, uterine artery Doppler, levels of pregnancy-associated plasma protein-A (PAPP-A) and free b-human chorionic gonadotropin were evaluated. The prediction of PE in first trimester was calculated through software Astraia, the outcome obtained from medical records and the cutoff value was subse quently calculated. Results:Of the 273 enrolled patients, 7 (2.6%) developed PE. In first trimester women who developed PE presented higher uterine arteries resistance, represented by higher values of lowest and mean uterine pulsatility index, p <0.005. There was no statistical significance among the remaining maternal characteristics, body mass index, blood pressure and PAPP-A. Using the FMF first trimester PE algorithm, an ideal cut-off of 0.045 (1/22) would correctly detect 71% women who developed PE for a 12% false positive rate and a likelihood ratio of 12.98 (area under the curve: 0.69; confidence interval 95%: 0.39-0.99). By applying the reported cutoff to our cohort, we would obtain 71.4% true positives, 88.3% true negatives, 11.4% false positives and 28.6% false negatives. Conclusion: By applying a first trimester PE prediction model to low risk pregnancies derived from a Portuguese population, a significant proportion of patients would have been predicted as high risk. New larger studies are required to confirm the present findings.

Cortisol, family coping and burden in informal caregivers of addicts

This study focuses on the prospective mediation role of family coping between burden and cortisol levels in informal caregivers of addicts as well as on the feasible use of two different ways to analyse the salivary cortisol levels. Participants were 120 Portuguese informal caregivers of addicts. The cortisol samples were collected at awakening, 45 minutes later and after a 30 minute presentation of images taken from the International Affective Picture System. Family coping and caregiver burden were measured using the Portuguese versions of the Caregiver Reaction Assessment, and the Family Crisis Oriented Personal Evaluation Scale. Cortisol samples were collected in salivettes and the results were computed in order to determine the Area Under the Curve scores (AUCg, AUCi). Results found family coping to be negatively correlated with burden and AUCg levels (i.e. overall intensity) and positively correlated with either AUCg and AUCi (i.e. change over time). The mediation model revealed that family coping was a partial mediator in the relationship between the burden and AUCg levels. Therefore, Family Coping appears to be an essential variable in understanding the stress response and should be considered in further studies and interventions. In addition, the use of two different formulas for calculating cortisol levels provided important new information concerning the relationship between cortisol, burden and family coping. It seems that burden has a more profound effect on the overall intensity of the neuroendocrine response to caregiver stress and not so much on the sensitivity of the system.

Incidence and Predictors of Cardiovascular Complications and Death after Vascular Surgery

AbstractBackground:Patients undergoing arterial vascular surgery are considered at increased risk for post-operative complications.Objective:To assess the incidence and predictors of complications and death, as well as the performance of two models of risk stratification, in vascular surgery.Methods:This study determined the incidence of cardiovascular complications and deaths within 30 days from surgery in adults. Univariate comparison and logistic regression assessed the risk factors associated with the outcomes, and the receiver operating characteristic (ROC) curve assessed the discriminatory capacity of the revised cardiac risk index (RCRI) and vascular study group of New England cardiac risk index (VSG-CRI).Results:141 patients (mean age, 66 years; 65% men) underwent the following surgeries: carotid (15); lower limbs (65); abdominal aorta (56); and others (5). Cardiovascular complications and death occurred within 30 days in 28 (19.9%) and 20 (14.2%) patients, respectively. The risk predictors were: age, obesity, stroke, poor functional capacity, altered scintigraphy, surgery of the aorta, and troponin change. The scores RCRI and VSG-CRI had area under the curve of 0.635 and 0.639 for early cardiovascular complications, and 0.562 and 0.610 for death in 30 days.Conclusion:In this small and selected group of patients undergoing arterial vascular surgery, the incidence of adverse events was elevated. The risk assessment indices RCRI and VSG-CRI did not perform well for complications within 30 days.

Very Long-Term Prognostic Role of Admission BNP in Non-ST Segment Elevation Acute Coronary Syndrome

Abstract Background: BNP has been extensively evaluated to determine short- and intermediate-term prognosis in patients with acute coronary syndrome, but its role in long-term mortality is not known. Objective: To determine the very long-term prognostic role of B-type natriuretic peptide (BNP) for all-cause mortality in patients with non-ST segment elevation acute coronary syndrome (NSTEACS). Methods: A cohort of 224 consecutive patients with NSTEACS, prospectively seen in the Emergency Department, had BNP measured on arrival to establish prognosis, and underwent a median 9.34-year follow-up for all-cause mortality. Results: Unstable angina was diagnosed in 52.2%, and non-ST segment elevation myocardial infarction, in 47.8%. Median admission BNP was 81.9 pg/mL (IQ range = 22.2; 225) and mortality rate was correlated with increasing BNP quartiles: 14.3; 16.1; 48.2; and 73.2% (p < 0.0001). ROC curve disclosed 100 pg/mL as the best BNP cut-off value for mortality prediction (area under the curve = 0.789, 95% CI= 0.723-0.854), being a strong predictor of late mortality: BNP < 100 = 17.3% vs. BNP ≥ 100 = 65.0%, RR = 3.76 (95% CI = 2.49-5.63, p < 0.001). On logistic regression analysis, age >72 years (OR = 3.79, 95% CI = 1.62-8.86, p = 0.002), BNP ≥ 100 pg/mL (OR = 6.24, 95% CI = 2.95-13.23, p < 0.001) and estimated glomerular filtration rate (OR = 0.98, 95% CI = 0.97-0.99, p = 0.049) were independent late-mortality predictors. Conclusions: BNP measured at hospital admission in patients with NSTEACS is a strong, independent predictor of very long-term all-cause mortality. This study allows raising the hypothesis that BNP should be measured in all patients with NSTEACS at the index event for long-term risk stratification.

Long-term citalopram administration reduces responsiveness of HPA axis in patients with major depression: relationship with S-citalopram concentrations in plasma and cerebrospinal fluid (CSF) and clinical response.

RATIONALE: A dysregulation of the hypothalamic-pituitary-adrenal (HPA) axis is a well-documented neurobiological finding in major depression. Moreover, clinically effective therapy with antidepressant drugs may normalize the HPA axis activity. OBJECTIVE: The aim of this study was to test whether citalopram (R/S-CIT) affects the function of the HPA axis in patients with major depression (DSM IV). METHODS: Twenty depressed patients (11 women and 9 men) were challenged with a combined dexamethasone (DEX) suppression and corticotropin-releasing hormone (CRH) stimulation test (DEX/CRH test) following a placebo week and after 2, 4, and 16 weeks of 40 mg/day R/S-CIT treatment. RESULTS: The results show a time-dependent reduction of adrenocorticotrophic hormone (ACTH) and cortisol response during the DEX/CRH test both in treatment responders and nonresponders within 16 weeks. There was a significant relationship between post-DEX baseline cortisol levels (measured before administration of CRH) and severity of depression at pretreatment baseline. Multiple linear regression analyses were performed to identify the impact of psychopathology and hormonal stress responsiveness and R/S-CIT concentrations in plasma and cerebrospinal fluid (CSF). The magnitude of decrease in cortisol responsivity from pretreatment baseline to week 4 on drug [delta-area under the curve (AUC) cortisol] was a significant predictor (p<0.0001) of the degree of symptom improvement following 16 weeks on drug (i.e., decrease in HAM-D21 total score). The model demonstrated that the interaction of CSF S-CIT concentrations and clinical improvement was the most powerful predictor of AUC cortisol responsiveness. CONCLUSION: The present study shows that decreased AUC cortisol was highly associated with S-CIT concentrations in plasma and CSF. Therefore, our data suggest that the CSF or plasma S-CIT concentrations rather than the R/S-CIT dose should be considered as an indicator of the selective serotonergic reuptake inhibitors (SSRIs) effect on HPA axis responsiveness as measured by AUC cortisol response.

Quantifying uncertainty: physicians' estimates of infection in critically ill neonates and children.

To determine the diagnostic accuracy of physicians' prior probability estimates of serious infection in critically ill neonates and children, we conducted a prospective cohort study in 2 intensive care units. Using available clinical, laboratory, and radiographic information, 27 physicians provided 2567 probability estimates for 347 patients (follow-up rate, 92%). The median probability estimate of infection increased from 0% (i.e., no antibiotic treatment or diagnostic work-up for sepsis), to 2% on the day preceding initiation of antibiotic therapy, to 20% at initiation of antibiotic treatment (P&lt;.001). At initiation of treatment, predictions discriminated well between episodes subsequently classified as proven infection and episodes ultimately judged unlikely to be infection (area under the curve, 0.88). Physicians also showed a good ability to predict blood culture-positive sepsis (area under the curve, 0.77). Treatment and testing thresholds were derived from the provided predictions and treatment rates. Physicians' prognoses regarding the presence of serious infection were remarkably precise. Studies investigating the value of new tests for diagnosis of sepsis should establish that they add incremental value to physicians' judgment.

Tibial or hip BMD predict clinical fracture risk equally well: results from a prospective study in 700 elderly Swiss women.

SUMMARY: In a randomly selected cohort of Swiss community-dwelling elderly women prospectively followed up for 2.8 +/- 0.6 years, clinical fractures were assessed twice yearly. Bone mineral density (BMD) measured at tibial diaphysis (T-DIA) and tibial epiphysis (T-EPI) using dual-energy X-ray absorptiometry (DXA) was shown to be a valid alternative to lumbar spine or hip BMD in predicting fractures. INTRODUCTION: A study was carried out to determine whether BMD measurement at the distal tibia sites of T-EPI and T-DIA is predictive of clinical fracture risk. METHODS: In a predefined representative cohort of Swiss community-dwelling elderly women aged 70-80 years included in the prospective, multi-centre Swiss Evaluation of the Methods of Measurement of Osteoporotic Fracture risk (SEMOF) study, fracture risk profile was assessed and BMD measured at the lumbar spine (LS), hip (HIP) and tibia (T-DIA and T-EPI) using DXA. Thereafter, clinical fractures were reported in a bi-yearly questionnaire. RESULTS: During 1,786 women-years of follow-up, 68 clinical fragility fractures occurred in 61 women. Older age and previous fracture were identified as risk factors for the present fractures. A decrease of 1 standard deviation in BMD values yielded a 1.5-fold (HIP) to 1.8-fold (T-EPI) significant increase in clinical fragility fracture hazard ratio (adjusted for age and previous fracture). All measured sites had comparable performance for fracture prediction (area under the curve range from 0.63 [LS] to 0.68 [T-EPI]). CONCLUSION: Fracture risk prediction with BMD measurements at T-DIA and T-EPI is a valid alternative to BMD measurements at LS or HIP for patients in whom these sites cannot be accessed for clinical, technical or practical reasons.

Could Hyperglycaemia and Troponin I predict outcome in intensive care after congenital heart surgery in children?

Objective: To establish if hyperglycaemia and cardiac Troponin I (cTnI) after congenital heart surgery on cardiopulmonary bypass in children could predict outcome in intensive care unit. Methods: retrospective cohort study including 274 children (mean age 4.6 years; range 0 - 17 years-old). CTnI and glucose values were retrieved from our database. Integrated values (area under the curve (AUC)) were calculated for evaluation of sustained hyperglycaemia and then normalised per hour (48h-Gluc/h). Maximal cTnI, fi rst glucose value (Gluc1) and 48h-Gluc/h were then correlated with duration of mechanical ventilation, ICU stay and mortality using cut-off values. Results: The mean duration of mechanical ventilation was 5.1 ± 7.2 days and ICU stay was 11.0 ± 13.3 days, 11 patients (3.9%) died. Hyperglycaemia (>6.1 mmol/l) was present in 68% of children at admission and was sustained in 85% for 48 hours. The mean value of Gluc1 (7.3 ± 2.7 vs. 11.8 ± 6.4 mmol/l, p < 0.0001), 48h-Gluc/h (7.4 ± 1.4 vs. 9.9 ± 4.6 mmol/l/h, p < 0.0001) and cTnI max (16.7 ± 21.8 vs. 59.2 ± 41.4 mcg/l, p < 0.0001) were signifi cantly lower in survivors vs. non survivors. Cut-off values and odds ratio are summarised in Table 1. Analyses for duration of mechanical ventilation and for length of stay in ICU are depicted in Table 2. Conclusions: Hyperglycaemia is frequent after cardiopulmonary bypass and sustained in the fi rst 48 hours. Admission glycaemia and cTnI max are associated with a high risk of mortality, prolonged duration of mechanical ventilation and prolonged length of stay in ICU.

Noninvasive detection of macrophage-rich atherosclerotic plaque in hyperlipidemic rabbits using "positive contrast" magnetic resonance imaging.

OBJECTIVES: This study was designed to identify macrophage-rich atherosclerotic plaque noninvasively by imaging the tissue uptake of long-circulating superparamagnetic nanoparticles with a positive contrast off-resonance imaging sequence (inversion recovery with ON-resonant water suppression [IRON]). BACKGROUND: The sudden rupture of macrophage-rich atherosclerotic plaques can trigger the formation of an occlusive thrombus in coronary vessels, resulting in acute myocardial infarction. Therefore, a noninvasive technique that can identify macrophage-rich plaques and thereby assist with risk stratification of patients with atherosclerosis would be of great potential clinical utility. METHODS: Experiments were conducted on a clinical 3-T magnetic resonance imaging (MRI) scanner in 7 heritable hyperlipidemic and 4 control rabbits. Monocrystalline iron-oxide nanoparticles (MION)-47 were administrated intravenously (2 doses of 250 mumol Fe/kg), and animals underwent serial IRON-MRI before injection of the nanoparticles and serially after 1, 3, and 6 days. RESULTS: After administration of MION-47, a striking signal enhancement was found in areas of plaque only in hyperlipidemic rabbits. The magnitude of enhancement on magnetic resonance images had a high correlation with the number of macrophages determined by histology (p < 0.001) and allowed for the detection of macrophage-rich plaque with high accuracy (area under the curve: 0.92, SE: 0.04, 95% confidence interval: 0.84 to 0.96, p < 0.001). No significant signal enhancement was measured in remote areas without plaque by histology and in control rabbits without atherosclerosis. CONCLUSIONS: Using IRON-MRI in conjunction with superparamagnetic nanoparticles is a promising approach for the noninvasive evaluation of macrophage-rich, vulnerable plaques.

Pharmacokinetic interaction between methotrexate and chloral hydrate.

We report the case of a drug interaction between methotrexate (MTX) and chloral hydrate (CH) observed in a child treated for acute leukemia. Significantly slower MTX clearance and increased MTX exposure occurred on the first three courses of a high-dose chemotherapy when co-administered with CH despite normal renal function, adequate hydration, and alkalinization. Mean MTX area under the curve associated with CH administration was 1,134 µmol hours/L, compared to 608 µmol hours/L after discontinuation of CH. This interaction possibly resulted from a competition between anionic CH metabolites and MTX for renal tubular excretion.

Should Hyperglycemia in Critically Ill Children Be Treated?

Introduction: In adults, strict control of hyperglycemia reduces mortality and morbidity. There is controversy in medical patients and neurological patients who can suffer of neuroglucopenia. Objectives: To determine prevalence and prognostic significance of hyperglycemia among critically ill non-diabetic children. To evaluate which patients will best benefit of insulin treatment. Methods: Retrospective study using blood glucose levels (GLUC: 9015 values, 923 patients) in our PICU from 01.2003 to 12.2005. 11 Patients with DKA were excluded. Overall PICU mortality was 3.7%. Hyperglycemia was defined at 6.1 mmol/L and different cutoff values (6.1, 8.3 and 11.1 mmol/l) were analyzed for glycemia at admission (GLUC). Sustained hyperglycemia was evaluated with the area under the curve normalized per hour (48h-AUC/h) for the first 48 h. The prevalence of hypo (_3mmol/L), hyperglycemia and PICU death were analyzed. Results: Trough the use of different cutoff values (_6.1, _8.3 and _11.1 mmol/l), prevalence of hyperglycemia at admission was 31.8 %, 16.8% and 10.3%; associated mortality was 2.8%, 4.0% and 15.2% respectively, significantly correlated to cutoff values (r_0.95, p_0.05). Prevalence of hypoglycemia at admission was low (0.9% with no death). 48h-AUC(mmol/L/h) was computed in 747 children (30 deaths). Prevalence of hyperglycemic 48h-AUC values was 47.5%, 17.3% and 4.0% with a respective mortality of 3.4%, 6.3% and 20.7% (r_0.97, p_0.03). For those with high GLUC and high 48h-AUC (_ 11.1 mmol/L) mortality was high (31.5%), but it decrease dramatically to 5.5% when 48h-AUC decrease spontaneously to values _8.3 mmol/L/h. Finally, when patients with severe neurological lesions (GCS_3, n_22) where excluded, increased mortality was observed only for GLUC (n_ 86) and 48h-AUC (n_26) higher than 11.1 mmol/L. Conclusions: Hyperglycemia at admission and even more sustained hyperglycemia (AUC) are highly correlated to mortality in PICU. But children who will have benefit of insulin therapy represent only 3% of our population, much lower than for adults.

Clinical outcome after trimipramine in patients with delusional depression - a pilot study

The treatment of delusional depression is a major challenge in psychopharmacology. Hypothalamic-pituitary-adrenocortical (HPA) overdrive may contribute, via increased dopaminergic activity, to the pathophysiology of the disorder. Trimipramine appears to be an interesting potential candidate, since it is an atypical antidepressant that is known to inhibit HPA activity. In a four-week open trial we investigated its effects in 15 inpatients with delusional depression. The dosage was increased within 7 days up to 300 - 400 mg/d and was then maintained for three weeks. Psychometric assessments and safety monitoring were conducted weekly. Assessment of the HPA activity was achieved by a combined dexamethasone suppression/corticotropin-releasing hormone stimulation (Dex/CRH) test before and after four weeks of treatment. Therapeutic response was defined as a decrease in the HAMD-score of at least 50 %. Eight out of 13 completers were rated as responders. Therapeutic response was associated with L, D-trimipramine concentrations higher than 160 ng/ml. Intent-to-treat analysis showed significant improvement in psychometric variables. Despite the high dosage, the substance was generally well tolerated, with the exception of one patient who suffered from a hypotensive reaction. Mean +/- SD concentration of L-trimipramine and D-trimipramine were 138 +/- 61 ng/ml and 119 +/- 50 ng/ml at a final dose of 346 +/- 50 mg/d. The ACTH and cortisol area under the curve in the Dex/CRH tests decreased significantly, reflecting a decrease of activity in the HPA system. We suggest that the clinical use of high-dose trimipramine in delusional depression seems to be a promising treatment strategy.

Comparison of 2 frailty indexes for prediction of falls, disability, fractures, and death in older women.

BACKGROUND: Frailty, as defined by the index derived from the Cardiovascular Health Study (CHS index), predicts risk of adverse outcomes in older adults. Use of this index, however, is impractical in clinical practice. METHODS: We conducted a prospective cohort study in 6701 women 69 years or older to compare the predictive validity of a simple frailty index with the components of weight loss, inability to rise from a chair 5 times without using arms, and reduced energy level (Study of Osteoporotic Fractures [SOF index]) with that of the CHS index with the components of unintentional weight loss, poor grip strength, reduced energy level, slow walking speed, and low level of physical activity. Women were classified as robust, of intermediate status, or frail using each index. Falls were reported every 4 months for 1 year. Disability (> or =1 new impairment in performing instrumental activities of daily living) was ascertained at 4(1/2) years, and fractures and deaths were ascertained during 9 years of follow-up. Area under the curve (AUC) statistics from receiver operating characteristic curve analysis and -2 log likelihood statistics were compared for models containing the CHS index vs the SOF index. RESULTS: Increasing evidence of frailty as defined by either the CHS index or the SOF index was similarly associated with an increased risk of adverse outcomes. Frail women had a higher age-adjusted risk of recurrent falls (odds ratio, 2.4), disability (odds ratio, 2.2-2.8), nonspine fracture (hazard ratio, 1.4-1.5), hip fracture (hazard ratio, 1.7-1.8), and death (hazard ratio, 2.4-2.7) (P < .001 for all models). The AUC comparisons revealed no differences between models with the CHS index vs the SOF index in discriminating falls (AUC = 0.61 for both models; P = .66), disability (AUC = 0.64; P = .23), nonspine fracture (AUC = 0.55; P = .80), hip fracture (AUC = 0.63; P = .64), or death (AUC = 0.72; P = .10). Results were similar when -2 log likelihood statistics were compared. CONCLUSION: The simple SOF index predicts risk of falls, disability, fracture, and death as well as the more complex CHS index and may provide a useful definition of frailty to identify older women at risk of adverse health outcomes in clinical practice.

Dynamic arterial elastance to predict arterial pressure response to volume loading in preload-dependent patients

INTRODUCTION Hemodynamic resuscitation should be aimed at achieving not only adequate cardiac output but also sufficient mean arterial pressure (MAP) to guarantee adequate tissue perfusion pressure. Since the arterial pressure response to volume expansion (VE) depends on arterial tone, knowing whether a patient is preload-dependent provides only a partial solution to the problem. The objective of this study was to assess the ability of a functional evaluation of arterial tone by dynamic arterial elastance (Ea(dyn)), defined as the pulse pressure variation (PPV) to stroke volume variation (SVV) ratio, to predict the hemodynamic response in MAP to fluid administration in hypotensive, preload-dependent patients with acute circulatory failure. METHODS We performed a prospective clinical study in an adult medical/surgical intensive care unit in a tertiary care teaching hospital, including 25 patients with controlled mechanical ventilation who were monitored with the Vigileo(®) monitor, for whom the decision to give fluids was made because of the presence of acute circulatory failure, including arterial hypotension (MAP ≤65 mmHg or systolic arterial pressure <90 mmHg) and preserved preload responsiveness condition, defined as a SVV value ≥10%. RESULTS Before fluid infusion, Ea(dyn) was significantly different between MAP responders (MAP increase ≥15% after VE) and MAP nonresponders. VE-induced increases in MAP were strongly correlated with baseline Ea(dyn) (r(2) = 0.83; P < 0.0001). The only predictor of MAP increase was Ea(dyn) (area under the curve, 0.986 ± 0.02; 95% confidence interval (CI), 0.84-1). A baseline Ea(dyn) value >0.89 predicted a MAP increase after fluid administration with a sensitivity of 93.75% (95% CI, 69.8%-99.8%) and a specificity of 100% (95% CI, 66.4%-100%). CONCLUSIONS Functional assessment of arterial tone by Ea(dyn), measured as the PVV to SVV ratio, predicted arterial pressure response after volume loading in hypotensive, preload-dependent patients under controlled mechanical ventilation.

Minor compounds of olive oil have postprandial anti-inflammatory effects

High postprandial levels of TAG may further induce endothelial dysfunction and inflammation in subjects with high fasting levels of TAG, an effect that seems to be related to oxidative stress. The present study investigated whether minor compounds of olive oil with antioxidant activity decrease postprandial levels of soluble isoforms of intercellular adhesion molecule 1 (sICAM-1) and vascular cell adhesion molecule 1 (sVCAM-1), as surrogate markers of vascular inflammation, after a high-fat meal. A randomized crossover and blind trial on fourteen healthy and fourteen hypertriacylglycerolaemic subjects was performed. The study involved a 1-week adaptation lead-in period on a National Cholesterol Education Program Step I diet supplemented with extra-virgin olive oil (EVOO) containing 1125 mg polyphenols/kg and 350 mg tocopherols/kg, or refined olive oil (ROO) with no polyphenols or tocopherols. After a 12 h fast, the participants ate a high-fat meal enriched in EVOO or ROO (50 g/m2 body surface area), which on average provided 3700 kJ energy with a macronutrient profile of 72% fat, 22% carbohydrate and 6% protein. Blood samples drawn hourly over the following 8 h demonstrated a similar postprandial TAG response for both EVOO and ROO meals. However, in both healthy and hypertriacylglycerolaemic subjects the net incremental area under the curve for sICAM-1 and sVCAM-1 were significantly lower after the EVOO meal. In conclusion,the consumption of EVOO with a high content of minor antioxidant compounds may have postprandial anti-inflammatory protective effects.