SFlt-1/PlGF ratio as a prognostic marker of adverse outcomes in women with early-onset preeclampsia

Soluble fms-like tyrosine kinase 1 (sFlt-1) is an anti-angiogenic factor released in higher amounts by preeclamptic placentas and it has been implicated in the endothelial dysfunction observed in the disease. In this study we evaluated if circulating sFlt-1/PlGF ratio is useful to predict adverse outcomes in women with early-onset preeclampsia. This is a cohort study of 88 preeclamptic women with singleton pregnancies at ≤35 weeks of gestation. According to definitions used, adverse outcomes occurred in 46.5% (N = 43) of the patients. The median sFlt1/PlGF ratio (25th-75th centile) for all patients evaluated was of 42.26 (13.1-226.1). The median sFlt-1/PlGF ratio among women who had any adverse outcome (N = 43) versus no adverse outcomes (N = 45) was of 227.6 (80.3-346.1) versus 14.4 (3.35-30.0), (P < 0.0001). According to our analyses a sFlt-1/PlGF ratio cut-point of ≥85 gave a sensitivity of 74.0% and specificity of 97.0%. The positive predictive value and the negative predictive value were 96.0% and 80.0%, respectively. The median sFlt-1/PlGF ratio (25th-75th centile) for patients who delivered within <7 days was 260.0 (127.7-404.7) as compared to 14.4 (3.35-34.97) for those patients who delivered within two weeks or more (P < 0.0001). Our results suggest that sFlt-1/PlGF ratio is a promising marker for adverse outcomes in women with early-onset preeclampsia. © 2013 International Society for the Study of Hypertension in Pregnancy. Published by Elsevier B.V. All rights reserved.

Possible adverse drug events leading to hospital admission in a Brazilian teaching hospital

OBJECTIVES: Drug safety problems can lead to hospital admission. In Brazil, the prevalence of hospitalization due to adverse drug events is unknown. This study aims to estimate the prevalence of hospitalization due to adverse drug events and to identify the drugs, the adverse drug events, and the risk factors associated with hospital admissions. METHOD: A cross-sectional study was performed in the internal medicine ward of a teaching hospital in São Paulo State, Brazil, from August to December 2008. All patients aged ≥18 years with a length of stay ≥24 hours were interviewed about the drugs used prior to hospital admission and their symptoms/complaints/causes of hospitalization. RESULTS: In total, 248 patients were considered eligible. The prevalence of hospitalization due to potential adverse drug events in the ward was 46.4%. Overprescribed drugs and those indicated for prophylactic treatments were frequently associated with possible adverse drug events. Frequently reported symptoms were breathlessness (15.2%), fatigue (12.3%), and chest pain (9.0%). Polypharmacy was a risk factor for the occurrence of possible adverse drug events. CONCLUSION: Possible adverse drug events led to hospitalization in a high-complexity hospital, mainly in polymedicated patients. The clinical outcomes of adverse drug events are nonspecific, which delays treatment, hinders causality analysis, and contributes to the underreporting of cases.

The reasons of the nursing staff to notify adverse events

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Comparison of anesthetic efficacy and adverse effects associated with peribulbar injection of ropivacaine performed with and without ultrasound guidance in dogs

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Causes for the underreporting of adverse drug events by health professionals: a systematic review

Objective: Identifying the main causes for underreporting of Adverse Drug Reaction (ADR) by health professionals. Method: A systematic review carried out in the following databases: LILACS, PAHO, SciELO, EMBASE and PubMed in the period between 1992 and 2012. Descriptors were used in the search for articles, and the identified causes of underreporting were analyzed according to the classification of Inman. Results: In total, were identified 149 articles, among which 29 were selected. Most studies were carried out in hospitals (24/29) for physicians (22/29), and pharmacists (10/29). The main causes related to underreporting were ignorance (24/29), insecurity (24/29) and indifference (23/29). Conclusion: The data show the eighth sin in underreporting, which is the lack of training in pharmacovigilance. Therefore, continuing education can increase adherence of professionals to the service and improve knowledge and communication of risks due to drug use.

Impact of educational interventions on adverse drug events reporting

Spontaneous adverse drug events (ADE) reporting is the main source of data for assessing the risk/benefit of drugs available in the pharmaceutical market. However, its major limitation is underreporting, which hinders and delays the signal detection by Pharmacovigilance (PhV). To identify the techniques of educational intervention (EI) for promotion of PhV by health professionals and to assess their impact. A systematic review was performed in the PUBMED, PAHO, LILACS and EMBASE databases, from November/2011 to January/2012, updated in March/2013. The strategy search included the use of health descriptors and a manual search in the references cited by selected papers. 101 articles were identified, of which 16 met the inclusion criteria. Most of these studies (10) were conducted in European hospitals and physicians were the health professionals subjected to most EI (12), these studies lasted from one month to two years. EI with multifaceted techniques raised the absolute number, the rate of reporting related to adverse drug reactions (ADR), technical defects of health technologies, and also promoted an improvement in the quality of reports, since there was increased reporting of ADR classified as serious, unexpected, related to new drugs and with high degree of causality. Multifaceted educational interventions for multidisciplinary health teams working at all healthcare levels, with sufficient duration to reach all professionals who act in the institution, including issues related to medication errors and therapeutic ineffectiveness, must be validated, with the aim of standardizing the Good Practice of PhV and improve drug safety indicators.

Causes for the underreporting of adverse drug events by health professionals: a systematic review

Objective: Identifying the main causes for underreporting of Adverse Drug Reaction (ADR) by health professionals. Method: A systematic review carried out in the following databases: LILACS, PAHO, SciELO, EMBASE and PubMed in the period between 1992 and 2012. Descriptors were used in the search for articles, and the identified causes of underreporting were analyzed according to the classification of Inman. Results: In total, were identified 149 articles, among which 29 were selected. Most studies were carried out in hospitals (24/29) for physicians (22/29), and pharmacists (10/29). The main causes related to underreporting were ignorance (24/29), insecurity (24/29) and indifference (23/29). Conclusion: The data show the eighth sin in underreporting, which is the lack of training in pharmacovigilance. Therefore, continuing education can increase adherence of professionals to the service and improve knowledge and communication of risks due to drug use.

Minimal residual disease in cerebrospinal fluid at diagnosis: a more intensive treatment protocol was able to eliminate the adverse prognosis in children with acute lymphoblastic leukemia

We analyzed cerebrospinal fluid (CSF) samples from 65 consecutive children with acute lymphoblastic leukemia (ALL) treated according to two different treatment protocols (GBTLI-ALL-93 and -99) with no puncture accident for minimal residual disease (MRD) in the central nervous system (CNS). Minimal residual disease was detected by polymerase chain reaction (PCR) with homo/heteroduplex analysis using consensus primers to IgH and TCR genes. MRD in the CSF at diagnosis was detected by PCR in 46.8% of children with no puncture accident or morphological involvement. In patients treated with GBTLI-ALL-93 a significantly lower 5-year event-free survival (EFS) was demonstrated for those with CSF involvement, in univariate (p = 0.01) and multivariate (p = 0.04) analysis. This observation was not true for patients treated with the more intensive protocol GBTLI-ALL-99 (p = 0.81). These findings suggest that MRD detection in the CSF is a common event in children with ALL. Treatment intensification provided by the GBTLI-ALL-99 apparently overcomes the detrimental effect of CNS minimal residual disease at diagnosis.

Late Adverse Effects of the Coadministration of Valproate and Lamotrigine

Individuals treated with combined valproate-lamotrigine rarely present late adverse effects (unrelated to introduction and titration). We describe four patients in whom such effects occurred after continuous, long-term use of valproate-lamotrigine (at 9 months to 2 years after final antiepileptic drug adjustment). The patients presented heterogeneous disturbances, including ataxia, vertigo, and headache, and rare movement disorders, such as tics and abnormal eye movements. Although these effects are heterogeneous in their occurrence and timing, they can alert physicians to the possibility of late neurologic disturbances, and must be considered in order to avoid unnecessary ancillary tests. Treatment discontinuation is unnecessary, given that a small decrease in dose led to remission of these adverse effects. (c) 2012 Elsevier Inc. All rights reserved.

Incidence of adverse events associated with percutaneous muscular biopsy among healthy and diseased subjects

The development of the percutaneous muscle biopsy technique is recognized as one of the most important scientific contributions in advancing our understanding of skeletal muscle physiology. However, a concern that this procedure may be associated with adverse events still exists. We reported the incidence of adverse outcomes associated with percutaneous muscle biopsy in healthy and diseased subjects. Medical records of 274 volunteers (496 muscle biopsies) were reviewed. This included 168 healthy subjects (330 muscle biopsies) as well as 106 chronically ill patients (166 muscle biopsies). This latter group encompassed patients with type II diabetes (n=28), osteoarthritis (n=39), inclusion body myositis (n=4), polymyositis (n=4), and chronic heart failure (n=31). The most common occurrences were pain (1.27%), erythema (1.27%), and ecchymosis (1.27%). Panic episode, bleeding, and edema were also reported (0.21%, 0.42%, and 0.84%, respectively), while infection, hematoma, inflammation, denervation, numbness, atrophy, and abnormal scarring were not verified. The percent of incidents did not differ between healthy and ill individuals. In conclusion, the incidence of complications associated with percutaneous muscle biopsy is scarce and of minor clinical relevance. Additionally, the rate of adverse events is comparable between healthy and chronically ill subjects.

Adverse Drug Events Leading Children to Hospital Emergency Care

To determine the incidence of adverse drug events (ADE) that resulted in the need for children's emergency care, a total of 23,286 pediatric emergency case notes were analyzed. They were selected on the basis of the ICD code indicating a possible ADE. ADEs were found in 13 case notes (0.06%), predominantly among girls and mainly in the 1 to 5 year age group. About half of the observed events occurred as a result of accidental ingestion, 27.3% were suicide attempts, and 27.3% arose due to the discontinuation of treatment. Antiepileptic drugs were those most often involved. Three (23%) were serious. The results suggest that children have easy access to medications and are involved in the majority of accidental occurrences. Using drugs involves risks, and drawing attention to such risks while prescribing and dispensing them fosters the sharing of responsibility and the empowerment of the users, measures necessary to health promotion.

Impact of the Level of Disclosure of Financial Information on the Pricing of Shares in the Context of Adverse Selection: an experimental research

Managers know more about the performance of the organization than investors, which makes the disclosure of information a possible strategy for competitive differentiation, minimizing adverse selection. This paper's main goal is to analyze whether or not an entity's level of diclosure may affect the risk perception of individuals and the process of evaluating their shares. The survey was carried out in an experimental study with 456 subjects. In a stock market simulation, we investigated the pricing of the stocks of two companies with different levels of information disclosure at four separate stages. The results showed that, when other variables are constant, the level of disclosure of an entity can affect the expectations of individuals and the process of evaluating their shares. A higher level of disclosure by an entity affected the value of its share and the other company's.

Incidence and Predictors of Adverse Drug Reactions Caused by Drug-Drug Interactions in Elderly Outpatients: A Prospective Cohort Study

Purpose. The primary objective of this study was to investigate the incidence of drug-drug interactions (DDIs) related to adverse drug reactions (ADRs) in elderly outpatients who attended public primary healthcare units in a southeastern region of Brazil. The secondary objective was to investigate the possible predictors of DDI-related ADRs. Methods. A prospective cohort study was conducted between November 1, 2010, and November 31, 2011, in the primary public healthcare system in the Ourinhos micro-region in Brazil. Patients who were at least 60 years old, with at least one potential DDI, were eligible for inclusion in the study. Eligible patients were assessed by clinical pharmacists for DDI-related ADRs for 4 months. The causality of DDI-related ADRs was assessed independently by four clinicians using three decisional algorithms. The incidence of DDI-related ADRs during the study period was calculated. Logistic regression analysis was used to study DDI-related ADR predictors. Results. A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6.5%. A multivariate analysis indicated that the adjusted odds ratios (ORs) rose from 0.91 (95% confidence interval [CI] = 0.75-1.12, p = 0.06) in patients aged 65-69 years to 4.40 (95% CI = 3.00-6.12, p < 0.01) in patients aged 80 years or older. Patients who presented two to three diagnosed diseases presented lower adjusted ORs (OR = 0.93 [95% CI = 0.68-1.18, p = 0.08]) than patients who presented six or more diseases (OR = 1.12 [95% CI = 1.02-2.01, p < 0.01]). Elderly patients who took five or more drugs had a significantly higher risk of DDI-related ADRs (OR = 2.72 [95% CI = 1.92-3.12, p < 0.01]) than patients who took three to four drugs (OR = 0.93 [95% CI = 0.74-1.11, p = 0.06]). No significant difference was found with regard to sex (OR = 1.08 [95% CI 0.48-2.02, p = 0.44]). Conclusion. The incidence of DDI-related ADRs in elderly outpatients was significant, and most of the events presented important clinical consequences. Because clinicians still have difficulty managing this problem, highlighting the factors that increase the risk of DDI-related ADRs is essential. Polypharmacy was found to be a significant predictor of DDI-related ADRs in our sample.

Adverse drug reactions caused by drug-drug interactions in elderly outpatients: a prospective cohort study

Although the prevalence of drug-drug interactions (DDIs) in elderly outpatients is high, many potential DDIs do not have any actual clinical effect, and data on the occurrence of DDI-related adverse drug reactions (ADRs) in elderly outpatients are scarce. This study aimed to determine the incidence and characteristics of DDI-related ADRs among elderly outpatients as well as the factors associated with these reactions. A prospective cohort study was conducted between 1 November 2010 and 31 November 2011 in the primary public health system of the Ourinhos micro-region, Brazil. Patients aged a parts per thousand yen60 years with at least one potential DDI were eligible for inclusion. Causality, severity, and preventability of the DDI-related ADRs were assessed independently by four clinicians using validated methods; data were analysed using descriptive analysis and multiple logistic regression. A total of 433 patients completed the study. The incidence of DDI-related ADRs was 6 % (n = 30). Warfarin was the most commonly involved drug (37 % cases), followed by acetylsalicylic acid (17 %), digoxin (17 %), and spironolactone (17 %). Gastrointestinal bleeding occurred in 37 % of the DDI-related ADR cases, followed by hyperkalemia (17 %) and myopathy (13 %). The multiple logistic regression showed that age a parts per thousand yen80 years [odds ratio (OR) 4.4; 95 % confidence interval (CI) 3.0-6.1, p < 0.01], a Charlson comorbidity index a parts per thousand yen4 (OR 1.3; 95 % CI 1.1-1.8, p < 0.01), consumption of five or more drugs (OR 2.7; 95 % CI 1.9-3.1, p < 0.01), and the use of warfarin (OR 1.7; 95 % CI1.1-1.9, p < 0.01) were associated with the occurrence of DDI-related ADRs. With regard to severity, approximately 37 % of the DDI-related ADRs detected in our cohort necessitated hospital admission. All DDI-related ADRs could have been avoided (87 % were ameliorable and 13 % were preventable). The incidence of ADRs not related to DDIs was 10 % (n = 44). The incidence of DDI-related ADRs in elderly outpatients is high; most events presented important clinical consequences and were preventable or ameliorable.