How do normal subjects learn a simple adaptative task: How and why do paranoid schizophrenic patients fail?

Summary The authors studied the behavior of normal subjects and paranoid schizophrenic patients in a simple problem-solving situation. The schizophrenics were divided into two sample groups, one of individuals under treatment and the other of individuals not under treatment.The learning process involved in this problem-solving situation is very similar to an instrumental conditioning, and can be understood by means of the following assumptions: (1) the subjects use decision functions in reacting to the stimuli, although they may be not fully aware of this; (2) learning is the result of successive transformations of these decisions in the course of time; (3) the changes have specific probabilities and are related to (a) those responses which are made to the latest stimuli, and (b) a differential probability for decision functions which were effective, or only interrupted painful reinforcement, or were completely ineffective.In schizophrenics further factors of importance were (1) an inertia factor and (2) the rigidly continued use of unsuccessful or only partially successful decision criteria.The authors used a systems theory based on Galois field theory and a calculus of operators specifying three groups of subjects. A computer program based on these hypotheses was tested in a simulation experiment.The statistical evaluation of the results showed a congruence between the theoretical approach and the experimental data.This work was carried out with financial support from the Institute de Alta Cultura, Lisbon, between 1970 and 1974     

Unsafe Drug Use and Arrhythmic Events in Brugada Patients with ICD: Results of a Long-Term Follow-Up

Purpose

Brugada syndrome is a hereditary disease linked with an increased risk of sudden death that may require an implantable cardioverter-defibrillator (ICD) in order to halt the arrhythmic events. The aim of this study was to identify possible triggers for appropriate ICD therapies in patients with Brugada syndrome, focusing on their past and current therapeutic profiles.

Methods

Thirty patients with high-risk Brugada syndrome, with ICD implanted at the Coimbra Hospital and University Center, were enrolled. Patients were questioned about their Brugada syndrome history, previous cardiac events, comorbidities, present and past medications, and physical activity. Patients were followed up during 5.8?±?5.3 years. The ICD was interrogated, and arrhythmic events and device therapies were recorded. The cohort who received appropriate ICD therapies was compared with the remaining patients to determine the potential link between clinical variables and potentially fatal arrhythmic events.

Results

More than half of the patients (53.3%) took at least one non-recommended drug, and 16.7% received appropriate ICD therapies, with a long-term rate of 4.0%/year. There was a tendency for more appropriate ICD therapies in patients who took unsafe drugs (85.7 versus 45.5%, p?=?0.062), and the mean time between unsafe drug intake and appropriate ICD therapies was 3.8?±?7.5 days.

Conclusions

This study revealed that the medical community is still unaware of the pharmacological restrictions imposed by Brugada syndrome. Patients who took non-recommended drugs seem to have a higher risk of ventricular arrhythmic events.

     

Platelet aggregation at discharge: A useful tool in acute coronary syndromes?

IntroductionInhibition of platelet aggregation appears two hours after the first dose of clopidogrel, becomes significant after the second dose, and progresses to a steady-state value of 55% by day seven. Low response to clopidogrel has been associated with increased risk of stent thrombosis and ischemic events, particularly in the context of stable heart disease treated by percutaneous coronary intervention.ObjectiveTo stratify medium-term prognosis of an acute coronary syndrome (ACS) population by platelet aggregation.MethodsWe performed a prospective longitudinal study of 70 patients admitted for an ACS between May and August 2009. Platelet function was assessed by ADP-induced platelet aggregation using a commercially available kit (Multiplate^® analyzer) at discharge. The primary endpoint was a combined outcome of mortality, non-fatal myocardial infarction, or unstable angina, with a median follow-up of 136.0 (79.0–188.0) days.ResultsThe median value of platelet aggregation was 16.0 U (11.0–22.5 U) with a maximum of 41.0 U and a minimum of 4.0 U (normal value according to the manufacturer: 53–122 U). After ROC curve analysis with respect to the combined endpoint (AUC 0.72), we concluded that a value of 18.5 U conferred a sensitivity of 75.0% and a specificity of 68% to that result. We therefore created two groups based on that level: group A – platelet aggregation <18.5 U, n = 44; and group B – platelet aggregation ≥18.5 U, n = 26. The groups were similar with respect to demographic data (age 60.5 [49.0–65.0] vs. 62.0 [49.0–65.0] years, p = 0.21), previous cardiovascular history, and admission diagnosis. There were no associations between left ventricular ejection fraction, GRACE risk score, or length of hospital stay and platelet aggregation. The groups were also similar with respect to antiplatelet, anticoagulant, proton pump inhibitor (63.6 vs. 46.2%, p = 0.15) and statin therapy. The variability in platelets and hemoglobin was also similar between groups. Combined event-free survival was higher in group A (96.0 vs. 76.7%, log-rank p < 0.01). Platelet aggregation higher than 18.5 U was an independent predictor of the combined event (HR 6.75, 95% CI 1.38–32.90, p = 0.02).ConclusionIn our ACS population platelet aggregation at discharge was a predictor of medium-term prognosis.     

Cross‐sectional survey of the disaster preparedness of nurses across the Asia–Pacific region

Healthcare workers who have received disaster preparedness education are more likely to report a greater understanding of disaster preparedness. However, research indicates that current nursing curricula do not adequately prepare nurses to respond to disasters. This is the first study to assess Asia–Pacific nurses' perceptions about their level of disaster knowledge, skills, and preparedness. A cross‐sectional survey was conducted with 757 hospital and community nurses in seven Asia–Pacific countries. Data were collected using the modified Disaster Preparedness Evaluation Tool. Participants were found to have overall low‐to‐moderate levels of disaster knowledge, skills and preparedness, wherein important gaps were identified. A majority of the variance in disaster preparedness scores was located at the level of the individual respondent, not linked to countries or institutions. Multilevel random effects modelling identified disaster experience and education as significant factors of positive perceptions of disaster knowledge, skills, and management. The first step toward disaster preparedness is to ensure frontline health workers are able to respond effectively to disaster events. The outcomes of this study have important policy and education implications.     

Pulmonary Tuberculosis Associated to Adalimumab: a Study of 3 Cases

Tumour necrosis factor-alpha antagonist drugs represent a significant advance in the treatment of inflammatory diseases, such as rheumatoid arthritis, spondyloarthropathies, and intestinal inflammatory disease. The increase in tuberculosis with infliximab is known, but there is less data available that specifically associates tuberculosis with adalimumab. We present the cases of 2 patients with rheumatoid arthritis and one patient with ankylopoietic spondylitis on treatment with adalimumab, who developed pulmonary and disseminated tuberculosis, despite following the screening and prophylaxis measures recommended in guidelines. We also review the association between treatment with tumour necrosis factor-alpha antagonists and tuberculosis.     

Primary chemotherapy with sequential docetaxel followed by docetaxel and epirubicin in large operable breast cancer

Primary chemotherapy is increasingly used in patients with large operable breast cancer. Docetaxel and epirubicin are the most active agents in breast cancer treatment. PURPOSE: To evaluate clinical response rate, breast conserving surgery and pathological response rate in patients with large operable breast cancer treated with docetaxel followed by docetaxel and epirubicin as primary chemotherapy. PATIENTS AND METHODS: Patients with operable breast cancer more than 3 cm in the longest diameter with T2N0, T2N1 and T3N0 disease were enrolled. Patients were treated with three cycles of docetaxel 100 mg/m2 followed by three cycles of docetaxel 75 mg/m2 and epirubicin 90 mg/m2 prior to surgery. RESULTS: Sixty-five patients were enrolled between 09/2002 and 12/2005. The median age was 48.9 years and 72.3% were premenopausal. Median tumour size was 4.26 cm, 10.8% were T3 tumours and 38.5% had clinical positive lymph nodes. Of the tumours 58.5% were grade 1/2, 33.9% ER positive and 21.5% c-erb negative. All six cycles were administered to 62 patients; six cycles were delayed and five had dose reductions. Complete clinical response occurred in 41.5% of patients and partial response in 49.2%. Breast conserving surgery was performed in 30% of patients however it was feasible in 57%. Complete pathological response occurred in both primary tumour and nodes in 28%, and in 34% just in the primary tumour. Nine percent of cases had neutropenia and 7.7% febrile neutropenia, and two cases had a hypersensitivity reaction to docetaxel. One associated treatment death occurred. CONCLUSION: Docetaxel followed by epirubicin and docetaxel as primary chemotherapy results in a high clinical and pathological response rate. The majority of adverse events were predictable and manageable.