Different tools for estimating cardiovascular risk in Brazilian postmenopausal women

Objective: To compare estimation of cardiovascular risk using the Framinghan Risk Score (FRS) and the presence of the metabolic syndrome (MetS) in postmenopausal women to prevent primary cardiovascular disease (CVD). Methods: This cross-sectional study included 497 Brazilian women (aged 45 years and amenorrhea >12months). Cardiovascular risk was calculated using the FRS that includes age, total cholesterol, HDL, systolic blood pressure and smoking status. Women showing three or more of the following criteria were diagnosed with MetS: waist circumference (WC) >88cm, blood pressure 130/85mmHg, triglycerides 150mg/dl, HDL<50mg/dl and glucose 100mg/dl. For statistical analysis, the Chi-square, Fisher's exact, and logistic regression (odds ratio-OR) were used. Results: The mean age was 55.3±7.0 years and time since menopause 7.2±5.9 years. Based on FRS, 72.4% of women were classified as low-risk, 16.5% moderate risk and 11.1% a high-risk. MetS was identified in 40% of the women, and 46.2% were considered of moderate risk for CVD, while 84.9% of those without MetS were classified as low-risk (p<0.001). The risk for CVD increased significantly with age at menopause (OR1.10; 95% CI, 1.04-1.17), time since menopause (OR1.13; 95% CI, 1.08-1.18), elevated triglycerides (OR1.03; 95% CI, 1.0-1.10) and presence of MetS (OR1.72; 95% CI 1.48-1.84). Conclusions: By using only FRS to estimate cardiovascular risk, a substantial number of postmenopausal women showing evidence of MetS were not identified, even though women with MetS are at higher risk of CVD. © 2013 Informa UK Ltd.

Electroretinographic findings associated with panretinal photocoagulation (PRP) versus PRP plus intravitreal ranibizumab treatment for high-risk proliferative diabetic retinopathy

To evaluate changes in electroretinographic (ERG) findings after panretinal photocoagulation (PRP) compared to PRP plus intravitreal injection of ranibizumab (IVR) in eyes with high-risk proliferative diabetic retinopathy (PDR). Patients with high-risk PDR and no prior laser treatment were assigned randomly to receive PRP (PRP group; n = 9) or PRP plus IVR (PRPplus group; n = 11). PRP was administered in two sessions (weeks 0 and 2), and IVR was administered at the end of the first laser session (week 0) in the PRPplus group. Standardized ophthalmic evaluations including (ETDRS) best-corrected visual acuity (BCVA), and fluorescein angiography to measure area of fluorescein leakage (FLA), were performed at baseline and at weeks 16 (+/- 2), 32 (+/- 2) and 48 (+/- 2). ERG was measured according to ISCEV standards at baseline and at week 48 (+/- 2). At 48 weeks, 2,400-3,000 laser spots had been placed in eyes in the PRP group, while only 1,400-1,800 spots had been placed in the PRPplus group. Compared to baseline, there was a statistically significant (P < 0.05) FLA reduction observed at all study visits in both groups, with the reduction observed in the PRPplus group significantly larger than that in the PRP group at week 48. ROD b-wave amplitude was significantly reduced to 46 +/- A 5 % (P < 0.05) of baseline in the PRP group and 64 +/- A 6 % (P < 0.05) in the PRPplus group. This reduction was significantly larger in the PRP group than in the PRPplus group (P = 0.024; t Test). Similar results were observed for the dark-adapted Combined Response (CR) b-wave amplitude, with a reduction at 48 weeks compared to baseline of 45 +/- A 4 % in the PRP group and 62 +/- A 5 % in the PRPplus group; the reduction in CR b-wave amplitude was significantly larger in the PRP group than in the PRPplus group (P = 0.0094). CR a-wave, oscillatory potentials, cone single flash, and 30 Hz flicker responses showed statistically significant within-group reductions, but no differences in between-group analyses. These results suggest that treating high-risk PDR with PRP plus IVR is effective for PDR control, and permits the use of less extensive PRP which, in turn, induces less retinal functional loss, in particular for rod-driven post-receptoral responses, than treatment with PRP alone.

Longitudinal outcomes of high-risk human papillomavirus (HPV) infections as competing-risks events following cervical HPV test at baseline visit in the *NIS-LAMS** cohort

Background: The complex natural history of human papillomavirus (HPV) infections following a single HPV test can be modeled as competing-risks events (i.e., no-, transient- or persistent infection) in a longitudinal setting. The covariates associated with these compet ng events have not been previously assessed using competing-risks regression models. Objectives: To gain further insights in the outcomes of cervical HPV infections, we used univariate- and multivariate competing-risks regression models to assess the covariaies associated with these competing events. Study Design and Methods: Covariates associated with three competing outcomes (no-, transient- or persistent HR-HPV infection) were analysed in a sub-cohort of 1,865 women prospectively followed-up in the NIS (n = 3,187) and LAMS Study (n = 12,114). Results: In multivariate competing-risks models (with two other outcomes as competing events), permanently HR-HPV negative outcome was significantly predicted only by the clearance of ASCUS+Pap during FU, while three independent covariates predicted transient HR-HPV infections: i) number of recent (< 12 months) sexual partners (risk increased), ii) previous Pap screening history (protective), and history of previous CIN (increased risk). The two most powerful predictors of persistent HR-HPV infections were persistent ASCUS+Pap (risk increased), and previous Pap screening history (protective). In pair-wise comparisons, number of recent sexual partners and previous CIN history increase the probability of transient HR-HPV infection against the HR-HPV negative competing event, while previous Pap screening history is protective. Persistent ASCUS+Pap during FU and no previous Pap screening history are significantly associated with the persistent HR-HPV outcome (compared both with i) always negative, and ii) transient events), whereas multiparity is protective. Conclusions: Different covariates are associated with the three main outcomes of cervical HPV infections. The most significant covariates of each competing events are probably distinct enough to enable constructing of a risk-profile for each main outcome.

Low Apgar scores at 5 minutes in a low risk population: maternal and obstetrical factors and postnatal outcome

Objective: To evaluate the association between Apgar scores of less than seven at five minutes (AS(5min) < 7) and antenatal factors and postnatal outcomes. Methods: A retrospective cohort and case-control study of 27,252 consecutive term newborns in a low risk obstetrical population between January 2003 and December 2010. Maternal and infant databases were reviewed from all cases with AS(5min) < 7 (n = 121; 0.4%) and 363 cases with AS(5min) >= 7 at 5 minutes who were randomly selected by a computer program. The main outcomes were neonatal death, newborn respiratory distress, need for orotracheal intubation and neonatal intensive care unit (NICU), and hypoxic-ischemic-encephalopathy. Results: After multiple regression analysis, repeated late decelerations on cardiotocography (OR: 2.4; 95% CI: 1.4-4.1) and prolonged second stage of labor (OR: 3.3; 95% CI: 1.3-8.3) were associated with AS(5min) < 7, as well as neonatal respiratory distress (OR: 3.0; 95% CI: 1.3-6.9), orotracheal intubation (OR: 2.5; 95% CI: 1.2-4.8), need for NICU (OR: 9.5; 95% CI: 6.7-16.8), and hypoxic-ischemic-encephalopathy (OR: 14.1; 95% CI: 3.6-54.7). No other antenatal factors were associated with AS(5min) < 7 (p > 0.05). Conclusion: Repeated late decelerations and prolonged second stage of labor in the low-risk population are predictors of AS(5min) < 7, a situation associated with increased risk of neonatal respiratory distress, need for mechanical ventilatory support and NICU, and hypoxic-ischemic-encephalopathy.

Maternal obesity in high-risk pregnancies and postpartum infectious complications

Objective: To analyze the association between maternal obesity and postnatal infectious complications in high-risk pregnancies. Methods: Prospective study from August 2009 through August 2010 with the following inclusion criteria: women up to the 5th postpartum day; age L 18 years; high-risk pregnancy; singleton pregnancy with live fetus at labor onset; delivery at the institution; maternal weight measured on day of delivery. The nutritional status in late pregnancy was assessed by the body mass index (BMI), with the application of the Atalah et al. curve. Patients were graded as underweight, adequate weight, overweight, or obese. Postpartum complications investigated during the hospital stay and 30 days post-discharge were: surgical wound infection and/or secretion, urinary infection, postpartum infection, fever, hospitalization, antibiotic use, and composite morbidity (at least one of the complications mentioned). Results: 374 puerperal women were included, graded according to the final BMI as: underweight (n = 54, 14.4%); adequate weight (n = 126, 33.7%); overweight (n = 105, 28.1%); and obese (n = 89, 23.8%). Maternal obesity was shown to have a significant association with the following postpartum complications: surgical wound infection (16.7%, p = 0.042), urinary infection (9.0%, p = 0.004), antibiotic use (12.3%, p < 0.001), and composite morbidity (25.6%, p = 0.016). By applying the logistic regression model, obesity in late pregnancy was found to be an independent variable regardless of the composite morbidity predicted (OR: 2.09; 95% CI: 1.15-3.80, p = 0.015). Conclusion: Maternal obesity during late pregnancy in high-risk patients is independently associated with postpartum infectious complications, which demonstrates the need for a closer follow-up of maternal weight gain in these pregnancies.

Long-Term Prospective Study of the Influence of Estrone Levels on Events in Postmenopausal Women with or at High Risk for Coronary Artery Disease

Background. The link between endogenous estrogen, coronary artery disease (CAD), and death in postmenopausal women is uncertain. We analyzed the association between death and blood levels of estrone in postmenopausal women with known coronary artery disease (CAD) or with a high-risk factor score for CAD. Methods. 251 postmenopausal women age 50-90 years not on estrogen therapy. Fasting blood for estrone and heart disease risk factors were collected at baseline. Women were grouped according to their estrone levels (<15 and >= 15 pg/mL). Fatal events were recorded after 5.8 perpendicular to 1.4 years of followup. Results. The Kaplan-Meier survival curve showed a significant trend (P = 0.039) of greater all-cause mortality in women with low estrone levels (< 15 pg/mL). Cox multivariate regression analysis model adjusted for body mass index, diabetes, dyslipidemia, family history, and estrone showed estrone (OR = 0.45; P = 0.038) as the only independent variable for all-cause mortality. Multivariate regression model adjusted for age, body mass index, hypertension, diabetes, dyslipidemia, family history, and estrone showed that only age (OR = 1.06; P = 0.017) was an independent predictor of all-cause mortality. Conclusions. Postmenopausal women with known CAD or with a high-risk factor score for CAD and low estrone levels (< 15 pg/mL) had increased all-cause mortality.

Covariates of high-risk human papillomavirus (HPV) infections are distinct for incident CIN1, CIN2 and CIN3 as disclosed by competing-risks regression models

Background: In addition to the oncogenic human papillomavirus (HPV), several cofactors are needed in cervical carcinogenesis, but whether the HPV covariates associated with incident i) CIN1 are different from those of incident ii) CIN2 and iii) CIN3 needs further assessment. Objectives: To gain further insights into the true biological differences between CIN1, CIN2 and CIN3, we assessed HPV covariates associated with incident CIN1, CIN2, and CIN3. Study Design and Methods: HPV covariates associated with progression to CIN1, CIN2 and CIN3 were analysed in the combined cohort of the NIS (n = 3,187) and LAMS study (n = 12,114), using competing-risks regression models (in panel data) for baseline HR-HPV-positive women (n = 1,105), who represent a sub-cohort of all 1,865 women prospectively followed-up in these two studies. Results: Altogether, 90 (4.8%), 39 (2.1%) and 14 (1.4%) cases progressed to CIN1, CIN2, and CIN3, respectively. Among these baseline HR-HPV-positive women, the risk profiles of incident GIN I, CIN2 and CIN3 were unique in that completely different HPV covariates were associated with progression to CIN1, CIN2 and CIN3, irrespective which categories (non-progression, CIN1, CIN2, CIN3 or all) were used as competing-risks events in univariate and multivariate models. Conclusions: These data confirm our previous analysis based on multinomial regression models implicating that distinct covariates of HR-HPV are associated with progression to CIN1, CIN2 and CIN3. This emphasises true biological differences between the three grades of GIN, which revisits the concept of combining CIN2 with CIN3 or with CIN1 in histological classification or used as a common end-point, e.g., in HPV vaccine trials.

Expression of Mitochondrial Non-coding RNAs (ncRNAs) Is Modulated by High Risk Human Papillomavirus (HPV) Oncogenes

The study of RNA and DNA oncogenic viruses has proved invaluable in the discovery of key cellular pathways that are rendered dysfunctional during cancer progression. An example is high risk human papillomavirus (HPV), the etiological agent of cervical cancer. The role of HPV oncogenes in cellular immortalization and transformation has been extensively investigated. We reported the differential expression of a family of human mitochondrial non-coding RNAs (ncRNAs) between normal and cancer cells. Normal cells express a sense mitochondrial ncRNA (SncmtRNA) that seems to be required for cell proliferation and two antisense transcripts (ASncmtRNAs). In contrast, the ASncmtRNAs are down-regulated in cancer cells. To shed some light on the mechanisms that trigger down-regulation of the ASncmtRNAs, we studied human keratinocytes (HFK) immortalized with HPV. Here we show that immortalization of HFK with HPV-16 or 18 causes down-regulation of the ASncmtRNAs and induces the expression of a new sense transcript named SncmtRNA-2. Transduction of HFK with both E6 and E7 is sufficient to induce expression of SncmtRNA-2. Moreover, E2 oncogene is involved in down-regulation of the ASncmtRNAs. Knockdown of E2 in immortalized cells reestablishes in a reversible manner the expression of the ASncmtRNAs, suggesting that endogenous cellular factors(s) could play functions analogous to E2 during non-HPV-induced oncogenesis.

Goal-directed fluid management based on pulse pressure variation monitoring during high-risk surgery: a pilot randomized controlled trial

Abstract Introduction Several studies have shown that maximizing stroke volume (or increasing it until a plateau is reached) by volume loading during high-risk surgery may improve post-operative outcome. This goal could be achieved simply by minimizing the variation in arterial pulse pressure (ΔPP) induced by mechanical ventilation. We tested this hypothesis in a prospective, randomized, single-centre study. The primary endpoint was the length of postoperative stay in hospital. Methods Thirty-three patients undergoing high-risk surgery were randomized either to a control group (group C, n = 16) or to an intervention group (group I, n = 17). In group I, ΔPP was continuously monitored during surgery by a multiparameter bedside monitor and minimized to 10% or less by volume loading. Results Both groups were comparable in terms of demographic data, American Society of Anesthesiology score, type, and duration of surgery. During surgery, group I received more fluid than group C (4,618 ± 1,557 versus 1,694 ± 705 ml (mean ± SD), P < 0.0001), and ΔPP decreased from 22 ± 75 to 9 ± 1% (P < 0.05) in group I. The median duration of postoperative stay in hospital (7 versus 17 days, P < 0.01) was lower in group I than in group C. The number of postoperative complications per patient (1.4 ± 2.1 versus 3.9 ± 2.8, P < 0.05), as well as the median duration of mechanical ventilation (1 versus 5 days, P < 0.05) and stay in the intensive care unit (3 versus 9 days, P < 0.01) was also lower in group I. Conclusion Monitoring and minimizing ΔPP by volume loading during high-risk surgery improves postoperative outcome and decreases the length of stay in hospital. Trial registration NCT00479011

Prodromal Questionnaire: translation, adaptation to Portuguese and preliminary results in ultra-high risk individuals and first episode psychosis

OBJECTIVE: The Prodromal Questionnaire (PQ) is a 92-item self-report screening tool for individuals at ultra-high risk (UHR) to develop psychosis. This study aims to present the translation to Portuguese and preliminary results in UHR and first episode (FE) psychosis in a Portuguese sample. METHODS: The PQ was translated from English to Portuguese by two bilingual researchers from the research program on early psychosis of the Instituto de Psiquiatria HCFMUSP, São Paulo, Brazil (ASAS - "Evaluation and Follow up of Adolescents and Young Adults in São Paulo") and back translated by two other researchers. The study participants (n = 11-) were evaluated through the Portuguese version of the Prodromal Questionnaire (PQ) and SIPS. RESULTS: The individuals at UHR (n = 7) presented a lower score than first episode patients (n = 4). The UHR mean scores and standard deviation on Portuguese version of the PQ were: 13.0 ± 10.0 points on positive symptoms subscale, and FE patients: 33.0 ± 10.0. CONCLUSION: The UHR and FE patients' of this study presented PQ scores similar to the ones found in the literature; what suggests that it is possible to use the PQ in Brazilian help-seeking individuals as a screening tool.

Successful treatment of childhood high-risk hepatoblastoma with dose-intensive multiagent chemotherapy and surgery: final results of the SIOPEL-3HR study

The primary objective was to determine the efficacy of a newly designed preoperative chemotherapy regimen in an attempt to improve the cure rate of children with high-risk hepatoblastoma.

Urethral toxicity vs. cancer control-Lessons to be learned from high-dose rate brachytherapy combined with intensity-modulated radiation therapy in intermediate- and high-risk prostate cancer

To describe biochemical relapse-free survival (BRFS) and late toxicity after combined high-dose rate brachytherapy (HDR-B) and intensity-modulated radiation therapy (IMRT) in intermediate- and high-risk prostate cancer patients.

Disability in people clinically at high risk of psychosis

Decline in social functioning occurs in individuals who later develop psychosis.

Prediction of psychosis in adolescents and young adults at high risk: results from the prospective European prediction of psychosis study

Indicated prevention is currently regarded as the most promising strategy to attenuate, delay, or even avert psychosis. Existing criteria need improvement in terms of specificity and individual risk assessment to allow for better targeted and earlier interventions.

Combinations of prognostic tools for identification of high-risk normotensive patients with acute symptomatic pulmonary embolism

In haemodynamically stable patients with acute symptomatic pulmonary embolism (PE), studies have not evaluated the usefulness of combining the measurement of cardiac troponin, transthoracic echocardiogram (TTE), and lower extremity complete compression ultrasound (CCUS) testing for predicting the risk of PE-related death.