The negative binomial-beta Weibull regression model to predict the cure of prostate cancer

In this article, for the first time, we propose the negative binomial-beta Weibull (BW) regression model for studying the recurrence of prostate cancer and to predict the cure fraction for patients with clinically localized prostate cancer treated by open radical prostatectomy. The cure model considers that a fraction of the survivors are cured of the disease. The survival function for the population of patients can be modeled by a cure parametric model using the BW distribution. We derive an explicit expansion for the moments of the recurrence time distribution for the uncured individuals. The proposed distribution can be used to model survival data when the hazard rate function is increasing, decreasing, unimodal and bathtub shaped. Another advantage is that the proposed model includes as special sub-models some of the well-known cure rate models discussed in the literature. We derive the appropriate matrices for assessing local influence on the parameter estimates under different perturbation schemes. We analyze a real data set for localized prostate cancer patients after open radical prostatectomy.

Bivariate gamma-geometric law and its induced Levy process

In this article we introduce a three-parameter extension of the bivariate exponential-geometric (BEG) law (Kozubowski and Panorska, 2005) [4]. We refer to this new distribution as the bivariate gamma-geometric (BGG) law. A bivariate random vector (X, N) follows the BGG law if N has geometric distribution and X may be represented (in law) as a sum of N independent and identically distributed gamma variables, where these variables are independent of N. Statistical properties such as moment generation and characteristic functions, moments and a variance-covariance matrix are provided. The marginal and conditional laws are also studied. We show that BBG distribution is infinitely divisible, just as the BEG model is. Further, we provide alternative representations for the BGG distribution and show that it enjoys a geometric stability property. Maximum likelihood estimation and inference are discussed and a reparametrization is proposed in order to obtain orthogonality of the parameters. We present an application to a real data set where our model provides a better fit than the BEG model. Our bivariate distribution induces a bivariate Levy process with correlated gamma and negative binomial processes, which extends the bivariate Levy motion proposed by Kozubowski et al. (2008) [6]. The marginals of our Levy motion are a mixture of gamma and negative binomial processes and we named it BMixGNB motion. Basic properties such as stochastic self-similarity and the covariance matrix of the process are presented. The bivariate distribution at fixed time of our BMixGNB process is also studied and some results are derived, including a discussion about maximum likelihood estimation and inference. (C) 2012 Elsevier Inc. All rights reserved.

Homicide and public security indicator trends in the city of Sao Paulo between 1996 and 2008: a time-series ecological study

The scope of this paper was to analyze the association between homicides and public security indicators in Sao Paulo between 1996 and 2008, after monitoring the unemployment rate and the proportion of youths in the population. A time-series ecological study for 1996 and 2008 was conducted with Sao Paulo as the unit of analysis. Dependent variable: number of deaths by homicide per year. Main independent variables: arrest-incarceration rate, access to firearms, police activity. Data analysis was conducted using Stata. IC 10.0 software. Simple and multivariate negative binomial regression models were created. Deaths by homicide and arrest-incarceration, as well as police activity were significantly associated in simple regression analysis. Access to firearms was not significantly associated to the reduction in the number of deaths by homicide (p>0,05). After adjustment, the associations with both the public security indicators were not significant. In Sao Paulo the role of public security indicators are less important as explanatory factors for a reduction in homicide rates, after adjustment for unemployment rate and a reduction in the proportion of youths. The results reinforce the importance of socioeconomic and demographic factors for a change in the public security scenario in Sao Paulo.

The impact of climate on Leptospirosis in Sao Paulo, Brazil

In this work, we correlate the daily number of human leptospirosis cases with several climatic factors. We used a negative binomial model that considers hospital daily admissions due to leptospirosis as the dependent variable, and the climatic variables of daily precipitation pattern, and maximum and minimum temperature as independent variables. We calculated the monthly leptospirosis admission probabilities from the precipitation and maximum temperature variables. The month of February showed the highest probability, although values were also high during the spring months. The month of February also showed the highest number of hospital admissions. Another interesting result is that, for every 20 mm precipitation, there was an average increase of 31.5% in hospital admissions. Additionally, the relative risk of leptospirosis varied from 1.1 to 2.0 when the precipitation varied from 20 to 140 mm.

Ecological implications on the aggregation of Amblyomma fuscum (Acari: Ixodidae) on Thrichomys laurentius (Rodentia: Echimyidae), in northeastern Brazil

We investigated the Amblyomma fuscum load on a pullulating wild rodent population and the environmental and biological factors influencing the tick load on the hosts. One hundred and three individuals of Thrichomys laurentius were caught in an Atlantic forest fragment in northeastern Brazil, as part of a longitudinal survey on ticks infesting non-volant small mammals. Ticks (n = 342) were found on 45 individuals and the overall mean intensity of infestation was 7.6 ticks per infested rodent. Ticks were highly aggregated in the host population and the negative binomial distribution model provides a statistically satisfactory fit. The aggregated distribution was influenced by sex and age of the host. The microhabitat preference by T. laurentius probably increases contact opportunities between hosts and aggregated infesting stages of the ticks and represents important clues about the habitat suitability for A. fuscum.

A Poisson mixed model with nonnormal random effect distribution

In this paper, we propose a random intercept Poisson model in which the random effect is assumed to follow a generalized log-gamma (GLG) distribution. This random effect accommodates (or captures) the overdispersion in the counts and induces within-cluster correlation. We derive the first two moments for the marginal distribution as well as the intraclass correlation. Even though numerical integration methods are, in general, required for deriving the marginal models, we obtain the multivariate negative binomial model from a particular parameter setting of the hierarchical model. An iterative process is derived for obtaining the maximum likelihood estimates for the parameters in the multivariate negative binomial model. Residual analysis is proposed and two applications with real data are given for illustration. (C) 2011 Elsevier B.V. All rights reserved.

Effectiveness of a multifactorial falls prevention program in community-dwelling older people when compared to usual care: study protocol for a randomised controlled trial (Prevquedas Brazil)

Background Falling in older age is a major public health concern due to its costly and disabling consequences. However very few randomised controlled trials (RCTs) have been conducted in developing countries, in which population ageing is expected to be particularly substantial in coming years. This article describes the design of an RCT to evaluate the effectiveness of a multifactorial falls prevention program in reducing the rate of falls in community-dwelling older people. Methods/design Multicentre parallel-group RCT involving 612 community-dwelling men and women aged 60 years and over, who have fallen at least once in the previous year. Participants will be recruited in multiple settings in Sao Paulo, Brazil and will be randomly allocated to a control group or an intervention group. The usual care control group will undergo a fall risk factor assessment and be referred to their clinicians with the risk assessment report so that individual modifiable risk factors can be managed without any specific guidance. The intervention group will receive a 12-week Multifactorial Falls Prevention Program consisting of: an individualised medical management of modifiable risk factors, a group-based, supervised balance training exercise program plus an unsupervised home-based exercise program, an educational/behavioral intervention. Both groups will receive a leaflet containing general information about fall prevention strategies. Primary outcome measures will be the rate of falls and the proportion of fallers recorded by monthly falls diaries and telephone calls over a 12 month period. Secondary outcomes measures will include risk of falling, fall-related self-efficacy score, measures of balance, mobility and strength, fall-related health services use and independence with daily tasks. Data will be analysed using the intention-to-treat principle.The incidence of falls in the intervention and control groups will be calculated and compared using negative binomial regression analysis. Discussion This study is the first trial to be conducted in Brazil to evaluate the effectiveness of an intervention to prevent falls. If proven to reduce falls this study has the potential to benefit older adults and assist health care practitioners and policy makers to implement and promote effective falls prevention interventions. Trial registration ClinicalTrials.gov (NCT01698580)

Gram-negative osteomyelitis: clinical and microbiological profile

Introduction: Despite the growing interest in the study of Gram-negative bacilli (GNB) infections, very little information on osteomyelitis caused by GNB is available in the medical literature. Objectives and methods: To assess clinical and microbiological features of 101 cases of osteomyelitis caused by GNB alone, between January 2007 and January 2009, in a reference center for the treatment of high complexity traumas in the city of Sao Paulo. Results: Most patients were men (63%), with median age of 42 years, affected by chronic osteomyelitis (43%) or acute osteomyelitis associated to open fractures (32%), the majority on the lower limbs (71%). The patients were treated with antibiotics as inpatients for 40 days (median) and for 99 days (median) in outpatient settings. After 6 months follow-up, the clinical remission rate was around 60%, relapse 19%, amputation 7%, and death 5%. Nine percent of cases were lost to follow-up. A total of 121 GNB was isolated from 101 clinical samples. The most frequently isolated pathogens were Enterobacter sp. (25%), Acinetobacter baumannii (21%) e Pseudomonas aeruginosa (20%). Susceptibility to carbapenems was about 100% for Enterobacter sp., 75% for Pseudomonas aeruginosa and 60% for Acinetobacter baumannii. Conclusion: Osteomyelitis caused by GNB remains a serious therapeutic challenge, especially when associated to nonfermenting bacteria. We emphasize the need to consider these agents in diagnosed cases of osteomyelitis, so that an ideal antimicrobial treatment can be administered since the very beginning of the therapy. (C) 2012 Elsevier Editora Ltda. All rights reserved.

Sorafenib in Combination With Capecitabine: An Oral Regimen for Patients With HER2-Negative Locally Advanced or Metastatic Breast Cancer

Purpose Sorafenib is a multikinase inhibitor with antiangiogenic/antiproliferative activity. A randomized, double-blind, placebo-controlled phase IIB trial assessed sorafenib with capecitabine for locally advanced or metastatic human epidermal growth factor receptor 2 (HER2) -negative breast cancer. Patients and Methods Patients were randomly assigned to first-or second-line capecitabine 1,000 mg/m(2) orally twice a day for days 1 to 14 of every 21-day cycle with sorafenib 400 mg orally twice a day or placebo. The primary end point was progression-free survival (PFS). Results In total, 229 patients were enrolled. The addition of sorafenib to capecitabine resulted in a significant improvement in PFS versus placebo (median, 6.4 v 4.1 months; hazard ratio [HR], 0.58; 95% CI, 0.41 to 0.81; P = .001) with sorafenib favored across subgroups, including first-line (HR, 0.50; 95% CI, 0.30 to 0.82) and second-line (HR, 0.65; 95% CI, 0.41 to 1.04) treatment. There was no significant improvement for overall survival (median, 22.2 v 20.9 months; HR, 0.86; 95% CI, 0.61 to 1.23; P = .42) and overall response (38% v 31%; P = .25). Toxicities (sorafenib v placebo) of any grade included rash (22% v 8%), diarrhea (58% v 30%), mucosal inflammation (33% v 21%), neutropenia (13% v 4%), hypertension (18% v 12%), and hand-foot skin reaction/hand-foot syndrome (HFSR/HFS; 90% v 66%); grade 3 to 4 toxicities were comparable between treatment arms except HFSR/HFS (44% v 14%). Reasons for discontinuation in the sorafenib and placebo arms included disease progression (63% v 82%, respectively), adverse events (20% v 9%, respectively), and death (0% v 1%, respectively). Conclusion Addition of sorafenib to capecitabine improved PFS in patients with HER2-negative advanced breast cancer. The dose of sorafenib used in this trial resulted in unacceptable toxicity for many patients. A phase III confirmatory trial has been initiated with a reduced sorafenib dose.

Minocycline benefits negative symptoms in early schizophrenia: a randomised double-blind placebo-controlled clinical trial in patients on standard treatment

The onset and early course of schizophrenia is associated with subtle loss of grey matter which may be responsible for the evolution and persistence of symptoms such as apathy, emotional blunting, and social withdrawal. Such 'negative' symptoms are unaffected by current antipsychotic therapies. There is evidence that the antibiotic minocycline has neuroprotective properties. We investigated whether the addition of minocycline to treatment as usual (TAU) for 1 year in early psychosis would reduce negative symptoms compared with placebo. In total, 144 participants within 5 years of first onset in Brazil and Pakistan were randomised to receive TAU plus placebo or minocycline. The primary outcome measures were the negative and positive syndrome ratings using the Positive and Negative Syndrome Scale. Some 94 patients completed the trial. The mean improvement in negative symptoms for the minocycline group was 9.2 and in the placebo group 4.7, an adjusted difference of 3.53 (s.e. 1.01) 95% CI: 1.55, 5.51; p < 0.001 in the intention-to-treat population. The effect was present in both countries. The addition of minocycline to TAU early in the course of schizophrenia predominantly improves negative symptoms. Whether this is mediated by neuroprotective, anti-inflammatory or others actions is under investigation.

Transthoracic cardiac ultrasonic stimulation induces a negative chronotropic effect

The objective of this study is to investigate cardiac bioeffects resulting from ultrasonic stimulation using a specific set of acoustical parameters. Ten Sprague-Dawley rats were anesthetized and exposed to 1-MHz ultrasound pulses of 3-MPa peak rarefactional pressure and approximately 1% duty factor. The pulse repetition frequency started slightly above the heart rate and was decreased by 1 Hz every 10 s, for a total exposure duration of 30 s. The control group was composed of five rats. Two-way analysis of variance for repeated measures and Bonferroni post hoc tests were used to compare heart rate and ejection fraction, which was used as an index of myocardial contractility. It was demonstrated for the first time that transthoracic ultrasound has the potential to decrease the heart rate by similar to 20%. The negative chronotropic effect lasted for at least 15 min after ultrasound exposure and there was no apparent gross damage to the cardiac tissue.

Negative and positive predictive values of nerve monitoring in thyroidectomy

Background Recurrent nerve injury is 1 of the most important complications of thyroidectomy. During the last decade, nerve monitoring has gained increasing acceptance in several centers as a method to predict and to document nerve function at the end of the operation. We evaluated the efficacy of a nerve monitoring system in a series of patients who underwent thyroidectomy and critically analyzed the negative predictive value (NPV) and positive predictive value (PPV) of the method. Methods. NIM System efficacy was prospectively analyzed in 447 patients who underwent thyroidectomy between 2001 and 2008 (366 female/81 male; 420 white/47 nonwhite; 11 to 82 years of age; median, 43 years old). There were 421 total thyroidectomies and 26 partial thyroidectomies, leading to 868 nerves at risk. The gold standard to evaluate inferior laryngeal nerve function was early postoperative videolaryngoscopy, which was repeated after 4 to 6 months in all patients with abnormal endoscopic findings. Results. At the early evaluation, 858 nerves (98.8%) presented normal videolaryngoscopic features after surgery. Ten paretic/paralyzed nerves (1.2%) were detected (2 unexpected unilateral paresis, 2 unexpected bilateral paresis, 1 unexpected unilateral paralysis, 1 unexpected bilateral paralyses, and 1 expected unilateral paralysis). At the late videolaryngoscopy, only 2 permanent nerve paralyses were noted (0.2%), with an ultimate result of 99.8% functioning nerves. Nerve monitoring showed absent or markedly reduced electrical activity at the end of the operations in 25/868 nerves (2.9%), including all 10 endoscopically compromised nerves, with 15 false-positive results. There were no false-negative results. Therefore, the PPV was 40.0%, and the NPV was 100%. Conclusions. In the present series, nerve monitoring had a very high PPV but a low NPV for the detection of recurrent nerve injury. (C) 2011 Wiley Periodicals, Inc. Head Neck 34: 175-179, 2012

THE NEGATIVE EFFECTS OF ALCOHOL HANGOVER ON HIGH-ANXIETY PHENOTYPE RATS ARE INFLUENCED BY THE GLUTAMATE RECEPTORS OF THE DORSAL MIDBRAIN

Alcoholism is a chronic disorder characterized by the appearance of a withdrawal syndrome following the abrupt cessation of alcohol intake that includes symptoms of physical and emotional disturbances, anxiety being the most prevalent symptom. In humans, it was shown that anxiety may increase the probability of relapse. In laboratory animals, however, the use of anxiety to predict alcohol preference has remained difficult. Excitatory amino acids as glutamate have been implicated in alcohol hangover and may be responsible for the seizures and anxiety observed during withdrawal. The dorsal periaqueductal gray (DPAG) is a midbrain region critical for the modulation/expression of anxiety- and fear-related behaviors and the propagation of seizures induced by alcohol withdrawal, the glutamate neurotransmission being one of the most affected. The present study was designed to evaluate whether low- (LA) and high-anxiety rats (HA), tested during the alcohol hangover phase, in which anxiety is the most prevalent symptom, are more sensitive to the reinforcing effects of alcohol when tested in a voluntary alcohol drinking procedure. Additionally, we were interested in investigating the main effects of reducing the excitatory tonus of the dorsal midbrain, after the blockade of the ionotropic glutamate receptors into the DPAG, on the voluntary alcohol intake of HA and LA motivated rats that were made previously experienced with the free operant response of alcohol drinking. For this purpose, we used local infusions of the N-metil D-Aspartato (NMDA) and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA)-kainate receptors antagonist DL-2-Amino-7-phosphonoheptanoic acid - DL-AP7 (10 nmol/0.2 mu l) and L-glutamic acid diethyl ester - GDEE (160 nmol/0.2 mu l) respectively. Alcohol intoxication was produced by 10 daily bolus intraperitonial (IP) injections of alcohol (2.0 g/kg). Peak-blood alcohol levels were determined by gas-chromatography analysis in order to assess blood-alcohol content. Unconditioned and conditioned anxiety-like behavior was assessed by the use of the fear-potentiated startle procedure (FPS). Data collected showed that anxiety and alcohol drinking in HA animals are positively correlated in animals that were made previously familiarized with the anxiolytic effects of alcohol. In addition, anxiety-like behavior induced during alcohol hangover seems to be an effect of changes in glutamatergic neurotransmission into DPAG possibly involving AMPA/kainate and NMDA receptors, among others. (C) 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

Bronchoscopy for the diagnosis of pulmonary tuberculosis in patients with negative sputum smear microscopy results

Objective: To evaluate the diagnostic accuracy of bronchoscopy in patients with clinical or radiological suspicion of tuberculosis who were unable to produce sputum or with negative sputum smear microscopy results. Methods: A prospective cross-sectional study involving 286 patients under clinical or radiological suspicion of having pulmonary tuberculosis and submitted to bronchoscopy-BAL and transbronchial biopsy (TBB). The BAL specimens were submitted to direct testing and culture for AFB and fungi, whereas the TBB specimens were submitted to histopathological examination. Results: Of the 286 patients studied, 225 (79%) were diagnosed on the basis of bronchoscopic findings, as follows: pulmonary tuberculosis, in 127 (44%); nonspecific chronic inflammation, in 51 (18%); pneumocystis, fungal infections, or nocardiosis, in 20 (7%); bronchiolitis obliterans organizing pneumonia, alveolites, or pneumoconiosis, in 14 (5%); lung or metastatic neoplasms, in 7 (2%); and nontuberculous mycobacterium infections, in 6 (2%). For the diagnosis of tuberculosis, BAL showed a sensitivity and a specificity of 60% and 100%, respectively. Adding the TBB findings significantly increased this sensitivity (to 84%), as did adding the post-bronchoscopy sputum smear microscopy results (total sensitivity, 94%). Minor post-procedure complications occurred in 5.6% of the cases. Conclusions: Bronchoscopy is a reliable method for the diagnosis of pulmonary tuberculosis, with low complication rates. The combination of TBB and BAL increases the sensitivity of the method and facilitates the differential diagnosis with other diseases.

Approach to the Patient with Persistent Hyperprolactinemia and Negative Sellar Imaging

Hyperprolactinemia is a common cause of menstrual disturbances affecting young women. There is a diversity of causes, from physiological, such as pregnancy, to pharmacological and pathological, such as hypothyroidism. Renal and hepatic failure, intercostal nerve stimulation by trauma or surgery, prolactinomas, other tumors in the hypothalamus-pituitary region, as well as macroprolactinemia can also be considered. Identifying the correct cause is important to establish the correct treatment. Should all these causes be ruled out and pituitary imaging revealed as negative, idiopathic hyperprolactinemia is therefore diagnosed. In symptomatic patients, treatment with dopaminergic agonists is indicated. As for the asymptomatic hyperprolactinemic individuals, macroprolactinemia should be screened, and once it is detected, there is no need for pituitary imaging study or for dopaminergic agonist use. (J Clin Endocrinol Metab 97: 2211-2216, 2012)