Antidepressants, suicidality and rebound effect: evidence of similitude?

Background: Samuel Hahnemann noticed that palliative treatments for the symptoms of chronic diseases, after an initial improvement, provoked symptoms similar but stronger symptoms to those initially suppressed. He regarded this as a consequence of the vital reaction of the organism: an automatic and instinctive capacity to return to the initial health condition altered by medicines. Using this homeostatic conception of the organism as a treatment rationale, Hahnemann proposed the therapy of similarity, administering to the patients medicines capable of causing, in healthy individuals, similar symptoms to the natural disease. Based on experimental observations, he proposed that the primary action of the drug was followed by the secondary and opposite action of the organism, inaugurating homeopathic pharmacology, and alerting to the harmful consequences of palliative medicines in susceptible individuals. Such liatrogenic events can be observed in contemporary medicine, after the withdrawal of modern enantiopathic medicines, according to the study of the rebound effect or paradoxical reaction of the organism. Method. This study reviews the recent studies which describe suicidallity after the suspension or discontinuation of second generation antidepressants according to the hypothesis of the paradoxical reaction of the organism. Conclusions: Rebound and withdrawal effects, including suicidality occur with antidepressant drugs. They are relatively rare but more intense than the primary action of the drug. The probability of such effects is influenced by patient factors including age and diagnosis, and drug factors including half-life. Homeopathy (2009) 98, 114-121.

Elevation of Uterine Basal Tone and Fetal Heart Rate Abnormalities After Labor Analgesia A Randomized Controlled Trial

OBJECTIVE: To estimate the effects of combined spinal-epidural and traditional epidural analgesia on uterine basal tone and its association with the occurrence of fetal heart rate (FHR) abnormalities. METHODS: Seventy-seven laboring patients who requested pain relief during labor were randomly assigned to combined spinal-epidural (n=41) or epidural analgesia (n=36). Uterine contractions and FHR were recorded 15 minutes before and after analgesia. Uterine tone was evaluated with intrauterine pressure catheter. Primary outcomes were the elevation of baseline uterine tone and occurrence of FHR prolonged decelerations or bradycardia after analgesia. The influence of other variables such as oxytocin use, hypotension, and speed of pain relief were estimated using a logistic regression model. RESULTS: The incidence of all outcomes was significantly greater in the combined spinal-epidural group compared with epidural: uterine hypertonus (17 compared with 6; P=.018), FHR abnormalities (13 compared with 2; P<.01), and both events simultaneously (11 compared with 1; P<.01). Logistic regression analysis showed the type of analgesia as the only independent predictor of uterine hypertonus (odds ratio 3.526, 95% confidence interval 1.21-10.36; P=.022). For the occurrence of FHR abnormalities, elevation of uterine tone was the independent predictor (odds ratio 18.624, 95% confidence interval 4.46-77.72; P<.001). Regression analysis also found a correlation between decrease on pain scores immediately after analgesia and the estimated probability of occurrence of hypertonus and FHR abnormalities. CONCLUSION: Combined spinal-epidural analgesia is associated with a significantly greater incidence of FHR abnormalities related to uterine hypertonus compared with epidural analgesia. The faster the pain relief after analgesia, the higher the probability of uterine hypertonus and FHR changes. CLINICAL TRIAL REGISTRATION: Umin Clinical Trials Registry, http://www.umin.ac.jp/ctr/index.htm, UMIN000001186

Cost-Effectiveness of Palliation of Unresectable Esophageal Cancer

Introduction Different modalities of palliation for obstructive symptoms in patients with unresectable esophageal cancer (EC) exist. However, these therapeutic alternatives have significant differences in costs and effectiveness. Methods A Markov model was designed to compare the cost-effectiveness (CE) of self-expandable stent (SES), brachytherapy and laser in the palliation of unresectable EC. Patients were assigned to one of the strategies, and the improvement in swallowing function was compared given the treatment efficacy, probability of survival, and risks of complications associated to each strategy. Probabilities and parameters for distribution were based on a 9-month time frame. Results Under the base-case scenario, laser has the lowest CE ratio, followed by brachytherapy at an incremental cost-effectiveness ratio (ICER) of $4,400.00, and SES is a dominated strategy. In the probabilistic analysis, laser is the strategy with the highest probability of cost-effectiveness for willingness to pay (WTP) values lower than $3,201 and brachytherapy for all WTP yielding a positive net health benefit (NHB) (threshold $4,440). The highest probability of cost-effectiveness for brachytherapy is 96%, and consequently, selection of suboptimal strategies can lead to opportunity losses for the US health system, ranging from US$ 4.32 to US$ 38.09 million dollars over the next 5-20 years. Conclusion Conditional to the WTP and current US Medicare costs, palliation of unresectable esophageal cancers with brachytherapy provides the largest amount of NHB and is the strategy with the highest probability of CE. However, some level of uncertainly remains, and wrong decisions will be made until further knowledge is acquired.

Microscopic origin of non-Gaussian distributions of financial returns

In this paper we study the possible microscopic origin of heavy-tailed probability density distributions for the price variation of financial instruments. We extend the standard log-normal process to include another random component in the so-called stochastic volatility models. We study these models under an assumption, akin to the Born-Oppenheimer approximation, in which the volatility has already relaxed to its equilibrium distribution and acts as a background to the evolution of the price process. In this approximation, we show that all models of stochastic volatility should exhibit a scaling relation in the time lag of zero-drift modified log-returns. We verify that the Dow-Jones Industrial Average index indeed follows this scaling. We then focus on two popular stochastic volatility models, the Heston and Hull-White models. In particular, we show that in the Hull-White model the resulting probability distribution of log-returns in this approximation corresponds to the Tsallis (t-Student) distribution. The Tsallis parameters are given in terms of the microscopic stochastic volatility model. Finally, we show that the log-returns for 30 years Dow Jones index data is well fitted by a Tsallis distribution, obtaining the relevant parameters. (c) 2007 Elsevier B.V. All rights reserved.

Sociodemographic Correlates of Transitions from Alcohol Use to Disorders and Remission in the Sao Paulo Megacity Mental Health Survey, Brazil

Aims: To evaluate sociodemographic correlates associated with transitions from alcohol use to disorders and remission in a Brazilian population. Methods: Data are from a probabilistic, multi-stage clustered sample of adult household residents in the Sao Paulo Metropolitan Area. Alcohol use, regular use (at least 12 drinks/year), DSM-IV abuse and dependence and remission from alcohol use disorders (AUDs) were assessed with the World Mental Health version of the Composite International Diagnostic Interview. Age of onset (AOO) distributions of the cumulative lifetime probability of each alcohol use stage were prepared with data obtained from 5037 subjects. Correlates of transitions were obtained from a subsample of 2942 respondents, whose time-dependent sociodemographic data were available. Results: Lifetime prevalences were 85.8% for alcohol use, 56.2% for regular use, 10.6% for abuse and 3.6% for dependence; 73.4 and 58.8% of respondents with lifetime abuse and dependence, respectively, had remitted. The number of sociodemographic correlates decreased from alcohol use to disorders. All transitions across alcohol use stages up to abuse were consistently associated with male gender, younger cohorts and lower education. Importantly, low education was a correlate for developing AUD and not remitting from dependence. Early AOO of first alcohol use was associated with the transition of regular use to abuse. Conclusion: The present study demonstrates that specific correlates differently contribute throughout alcohol use trajectory in a Brazilian population. It also reinforces the need of preventive programs focused on early initiation of alcohol use and high-risk individuals, in order to minimize the progression to dependence and improve remission from AUD.

Prognostic Impact of MYCN, DDX1, TrkA, and TrkC Gene Transcripts Expression in Neuroblastoma

Background. The aims of this study were to define the mRNA expression profiles of MYCN, DDX1, TrkA, and TrkC in biopsy tumor samples from 64 Brazilian patients with neuroblastomas of different risk stages and to correlate altered expression with prognostic values. Procedure. Patients were retrospectively classified into low- (n = 11), intermediate- (n = 18), and high-risk (n = 35) groups using standard criteria. The mRNA levels of the above genes were measured by quantitative real-time polymerase chain reaction. Univariate analyses were performed and survival curves were plotted by the Kaplan-Meier method. Results. Of the 64 patients, 53% were female and 62.5% were older than 18 months. The 5-year overall survival (OS) for the entire cohort was 40.3%, with inferior median OS in patients identified in the intermediate- and high-risk groups. A significant difference in OS with respect to TrkA mRNA expression was found for the high-risk group vs. either the low- or intermediate-risk groups (P < 0.01, log rank test). Within the intermediate-risk group, neuroblastoma patients with positive TrkA mRNA expression had better clinical outcomes than patients with no TrkA transcript expression (P = 0.004). Another difference in OS was only found between the intermediate- and high-risk groups (P < 0.027, log rank test). No significant correlation of mRNA expression and survival outcome could be detected for the MYCN, DDX1. Conclusions. Positive expression of TrkA mRNA may be a clinically useful addition to the current risk classification system, allowing the identification of NB tumors with favorable prognosis. Pediatr Blood Cancer 2011; 56: 749-756. (c) 2010 Wiley-Liss, Inc.

Sao Paulo Lung Transplantation Waiting List: Patient Characteristics and Predictors of Death

Introduction. Nowadays, lung transplantation (LTx) allocation in Brazil is based mainly oil waiting time. There is a need to evaluate the equity of the current lung allocation system. Objectives. We sought to (1) determine the characteristics of registered patients on the waiting list and (2) identify predictors of death on the list. Materials and Methods. We analyzed the medical records as well as clinical and laboratory data of 164 patients registered on the waiting list from 2001 to June 2008. Predictors of mortality were obtained using Cox proportional hazards analysis. Results. Patients who were registered on the waiting list showed a mean age of 36.1 +/- 15.0 vs. 42.2 +/- 15.7 years, considering those who did versus did not, die on the list, respectively (P = .054). Emphysema was the most prevalent underlying disease among the patients who did not die on the list (28.8%); its prevalence was low among the patients who died on the list (6.5%; P = .009). The following variables correlated with the probability of death on the waiting list: emphysema or bronchiectasis diagnosis (hazard ratio [HR] = 0.15; P = .002); activated partial thromboplastin time > 30 seconds (HR = 3.28; P = .002); serum albumin > 3.5 g/dL (HR = 0.41; P = .033); and hemoglobin saturation > 85% (HR = 0.44; P = .031). Conclusions. Some variables seemed to predict death on the LTx waiting list; these characteristics should be used to improve the LTx allocation criteria in Brazil.

Supporting content-based image retrieval and computer-aided diagnosis systems with association rule-based techniques

In this work, we take advantage of association rule mining to support two types of medical systems: the Content-based Image Retrieval (CBIR) systems and the Computer-Aided Diagnosis (CAD) systems. For content-based retrieval, association rules are employed to reduce the dimensionality of the feature vectors that represent the images and to improve the precision of the similarity queries. We refer to the association rule-based method to improve CBIR systems proposed here as Feature selection through Association Rules (FAR). To improve CAD systems, we propose the Image Diagnosis Enhancement through Association rules (IDEA) method. Association rules are employed to suggest a second opinion to the radiologist or a preliminary diagnosis of a new image. A second opinion automatically obtained can either accelerate the process of diagnosing or to strengthen a hypothesis, increasing the probability of a prescribed treatment be successful. Two new algorithms are proposed to support the IDEA method: to pre-process low-level features and to propose a preliminary diagnosis based on association rules. We performed several experiments to validate the proposed methods. The results indicate that association rules can be successfully applied to improve CBIR and CAD systems, empowering the arsenal of techniques to support medical image analysis in medical systems. (C) 2009 Elsevier B.V. All rights reserved.

Hepatitis B viral markers in banked human milk before and after Holder pasteurization

Background: Blood screening for hepatitis B virus (HBV) is not universally performed for donor selection in human milk banks. Objectives: To evaluate the frequency of detection of HBV surface antigen (HBsAg) and HBV-DNA in colostrum of HBV-infected nursing mothers before and after Holder pasteurization. Study design: Forty-two concentrated breast milk samples were obtained within two postnatal weeks from 24 HBsAg-positive women (4 HBeAg-positive and 20 HBeAg-negative, anti-HBe-positive) were tested for the presence of HBsAg and HBV-DNA before and after Holder pasteurization (30 min at 62.5 degrees C). Results: Before pasteurization, HBsAg and HBV-DNA were found in 14/24 (58%), and 20/24 (75%) first milk samples, respectively, obtained by 4 days after delivery. At least one marker was detected in 20/24 (83%) milk samples. Both markers were identified in milk of HBeAg-positive mothers, and most mothers with anti-HBe in blood had at least one HBV marker. Once detected, viral markers were frequently found in milk samples subsequently obtained from the same woman. Holder pasteurization did not affect the probability of detecting HBsAg (8/18, 44%), HBV-DNA (12/18, 67%). or at least one of them (15118, 83%). Conclusions: Although the biological implications of these findings remain to be determined, considering that HBV is highly contagious and most recipients of banked human milk are preterm infants, these findings should be taken into account when donors are enlisted for human milk banks without serological screening. (C) 2009 Elsevier B.V. All rights reserved.

Small-World Effect in Epidemics Using Cellular Automata

The spread of an infectious disease in a population involves interactions leading to an epidemic outbreak through a network of contacts. Extending on Watts and Strogatz (1998) who showed that short-distance connections create a small-world effect, a model combining short-and long-distance probabilistic and regularly updated contacts helps considering spatial heterogeneity. The method is based on cellular automata. The presence of long-distance connections accelerates the small-world effect, as if the world shrank in proportion of their total number.

A general hazard model for lifetime data in the presence of cure rate

Historically, the cure rate model has been used for modeling time-to-event data within which a significant proportion of patients are assumed to be cured of illnesses, including breast cancer, non-Hodgkin lymphoma, leukemia, prostate cancer, melanoma, and head and neck cancer. Perhaps the most popular type of cure rate model is the mixture model introduced by Berkson and Gage [1]. In this model, it is assumed that a certain proportion of the patients are cured, in the sense that they do not present the event of interest during a long period of time and can found to be immune to the cause of failure under study. In this paper, we propose a general hazard model which accommodates comprehensive families of cure rate models as particular cases, including the model proposed by Berkson and Gage. The maximum-likelihood-estimation procedure is discussed. A simulation study analyzes the coverage probabilities of the asymptotic confidence intervals for the parameters. A real data set on children exposed to HIV by vertical transmission illustrates the methodology.

Adiponectin: serum levels, promoter polymorphism, and associations with birth size and cardiometabolic outcome in young adults born large for gestational age

Objective: To assess whether the -11391G > A polymorphism in the regulatory region of the adiponectin gene (ADIPOQ) is associated with birth size, postnatal growth, adiponectinemia, and cardiometabolic risk in adult life. Design: Case-control study nested within a prospective cohort of 2063 community subjects born in 1978/1979 and followed since birth to date. Methods: ADIPOQ -11391G > A genotype-phenotype associations were evaluated in 116 subjects born large for gestational age (LGA) and 392 gender-matched controls at birth (birth size), at 8-10 years (catch-down growth), and at 23-25 years of age (cardiometabolic profile). Results: The -11391A variant allele frequency was higher in LGA subjects (P=0.04). AA genotype was associated with augmented probability of being born LGA (odds ratio=4.14; 95% confidence interval: 1.16-16.7; P=0.03). This polymorphism was associated neither with body composition nor with postnatal growth pattern. At the age of 23-25 years, the -11391A variant allele was associated with higher serum adiponectin levels (GG: 10.7 +/- 6.2 versus GA: 12.2 +/- 6.5 versus AA: 14.2 +/- 6.8 mu g/ml; P < 0.01). Subjects born LGA presented higher body mass index (BMI; P=0.01), abdominal circumference (P=0.04), blood pressure (P=0.04), and homeostasis assessment model for insulin resistance (P=0.01) than adequate for gestational age. Symmetry at birth did not influence these variables. The occurrence of catch-down of weight was associated with lower BMI and abdominal circumference (P < 0.001) at 23-25 years. Conclusions: The -11391A ADIPOQ gene variant was associated with increased chance of being born LGA and with higher adiponectin levels in early adult life.

Dietary patterns and nutritional adequacy in a Mediterranean country

Dietary patterns have been related to health outcomes and morbi-mortality. Mediterranean diet indexes are correlated With adequate nutrient intake. The objective of the present study was to analyse the adequacy of nutrient intake of a posteriori defined Mediterranean (MDP) and Western (WDP) diet patterns in the Seguimiento Universidad de Navarra (SUN) cohort. A sample of 17 197 subjects participated in the study. Participants completed I 136-item validated semi-quantitative FFQ. Principal component analysis was used to define dietary patterns. Individuals were classified according to quintiles of adherence based on dietary pattern scores. Non-dietary variables, such as smoking and physical activity habits, were also taken into account. The probability approach was used to assess nutrient intake adequacy of certain vitamins (vitamins B(12), B(6), B(3), B(2), B(1), A, C, D and E) and minerals (Na, Zn, iodine, Se, folic acid, P, Mg, K, Fe and Ca). Logistic regression analysis was used to assess the adequacy of nutrient intake according to adherence to dietary patterns. WDP and MDP were defined. A higher quintile of adherence to an MDP was associated to I lower prevalence of inadequacy for the intake of Zn, iodine, vitamin E, Mg, Fe, vitamin B I, vitamin A, Se, vitamin C and folic acid. The adjusted OR for not reaching at least six (or at leas( ten) nutrient recommendations were 0.09 (95% Cl: 0.07, 0.11) (and 0.02 (95% Cl: 0.00, 0.16)) for the upper quintile of MDP and 4.4 (95% Cl: 3.6, 5.5) and 2.5 (95 % Cl: 1.1, 5.4) for the WDP. The MDP was associated to a better profile of nutrient intake.

Nasal allergies in the Latin American population: Results from the Allergies in Latin America survey

Allergies in Latin America is the first cross-national survey that describes the symptoms, impact, and treatment of nasal allergies (NAs) in individuals >= 4 years old in Latin America (LA). In total, 22,012 households across the Latin American countries of Argentina, Brazil, Chile, Colombia, Ecuador, Mexico, Peru, and Venezuela were screened for children, adolescents, and adults with a diagnosis of NA and either symptoms or treatment in the past 12 months. A total of 1088 adults and 457 children and adolescents were included and the sample was probability based to ensure valid statistical inference to the population. Approximately 7% of the LA population was diagnosed with NAs with two of three respondents stating that their allergies were seasonal or intermittent in nature. A general practice physician or otolaryngologist diagnosed the majority of individuals surveyed. Nasal congestion was the most common and bothersome symptom of NAs. Sufferers indicated that their symptoms affected productivity and sleep and had a negative impact on quality of life. Two-thirds of patients reported taking some type of medication for their NAs, with a roughly equal percentage of patients reporting taking over-the-counter versus prescription medications. Changing medications was most commonly done in those reporting inadequate efficacy. The most common reasons cited for dissatisfaction with current medications were related to inadequate effectiveness, effectiveness wearing off with chronic use, failure to provide 24-hour relief, and bothersome side effects (e.g., unpleasant taste and retrograde drainage into the esophagus). Findings from this cross-national survey on NAs have confirmed a high prevalence of physician-diagnosed NAs and a considerable negative impact on daily quality of life and work productivity as well as substantial disease management challenges in LA. Through identification of disease impact on the LA population and further defining treatment gaps, clinicians in LA may better understand and treat NAs, thus leading to improvements in overall patient satisfaction and quality of life. (Allergy Asthma Proc 31:S9-S27, 2010; doi: 10.2500/aap.2010.31.3347)

Development and characterization of 15 microsatellite loci for Cariniana estrellensis and transferability to Cariniana legalis, two endangered tropical tree species

From a genomic library enriched for GA/CA repeats, 15 highly polymorphic microsatellite markers were developed for Cariniana estrellensis, a tropical forest tree. The microsatellite loci were screened in 49 mature trees found between Pardo river and Mogi-Gua double dagger u river basins, in the state of So Paulo, Brazil. A total of 140 alleles were detected with an average of 9.33 alleles per locus. The expected heterozygosity ranged from 0.37 to 0.88. These loci showed a high probability of paternity exclusion. Additionally, 12 loci were effectively transferred to Cariniana legalis. High levels of polymorphism make the present SSR markers useful for population genetic studies.