Antituberculosis drug-induced hepatotoxicity: a comparison between patients with and without human immunodeficiency virus seropositivity

INTRODUCTION: The prevalence and risk factors for rifampin, isoniazid and pyrazinamide hepatotoxicity were evaluated in HIV-infected subjects and controls. METHODS: Patients with tuberculosis (30 HIV positive and 132 HIV negative), aged between 18 and 80 years-old, admitted to hospital in Brazil, from 2005 to 2007, were selected for this investigation. Three definitions of hepatotoxicity were used: I) a 3-fold increase in the lower limit of normal for alanine-aminotransferase (ALT); II) a 3-fold increase in the upper limit of normal (ULN) for ALT, and III) a 3-fold increase in the ULN for ALT plus a 2-fold increase in the ULN of total bilirubin. RESULTS: In groups with and without HIV infection the frequency of hepatotoxicity I was 77% and 46%, respectively (p < 0.01). Using hepatotoxicity II and III definitions no difference was observed in the occurrence of antituberculosis drug-induced hepatitis. Of the 17 patients with hepatotoxicity by definition III, 3 presented no side effects and treatment was well tolerated. In 8 (36.4%) out of 22, symptoms emerged and treatment was suspended. Alcohol abuse was related to hepatotoxicity only for definition I. CONCLUSIONS: Depending on the definition of drug-induced hepatitis, HIV infection may or may not be associated with hepatotoxicity. The impact that minor alterations in the definition had on the results was impressive. No death was related to drug-induced hepatotoxicity. The emergence of new symptoms after initiating antituberculosis therapy could not be attributed to hepatotoxicity in over one third of the cases.

Relating the spatial component and users interests to improve applications based on questions, petitions and participatory processes

Nowadays, participatory processes attending the need for real democracy and transparency in governments and collectives are more needed than ever. Immediate participation through channels like social networks enable people to give their opinion and become pro-active citizens, seeking applications to interact with each other. The application described in this dissertation is a hybrid channel of communication of questions, petitions and participatory processes based on Public Participation Geographic Information System (PPGIS), Participation Geographic Information System (PGIS) and ���soft��� (subjective data) Geographic Information System (SoftGIS) methodologies. To achieve a new approach to an application, its entire design is focused on the spatial component related with user interests. The spatial component is treated as main feature of the system to develop all others depending on it, enabling new features never seen before in social actions (questions, petitions and participatory processes). Results prove that it is possible to develop a working application mainly using open source software, with the possibility of spatial and subject filtering, visualizing and free download of actions within application. The resulting application empowers society by releasing soft data and defines a new breaking approach, unseen so far.

Drug resistance of Mycobacterium tuberculosis strains in southern Brazil

INTRODUCTION: The aim of this work was to evaluate the prevalence of Mycobacterium tuberculosis (MT) strains with mutations that could result in resistance to the main drugs used in treatment in a region with one of the highest numbers of tuberculosis (TB) cases in southern Brazil. METHODS: Deoxyribonucleic acid (DNA) from 120 sputum samples from different patients suspicious of pulmonary tuberculosis who attended the Municipal Public Laboratory for Mycobacterium sp. diagnosis was directly amplified and analyzed by PCR-SSCP. The DNA was amplified in known hotspot mutation regions of the genes rpoB, ahpC, embB, katG, inhA, and pncA. RESULTS: The percentage of samples positive by culture was 9.2% (11/120); 5% (6/120) were positive by bacilloscopy and MT-PCR, and DNA fragments of the aforementioned resistance genes could be amplified from seven (7) of the eleven (11) samples with positive results, either by culture or PCR/bacilloscopy. All presented a SSCP pattern similar to a native, nonresistant genotype, with the ATCC strain 25177 as control, except for one sample (0.01%), which presented a SSCP profile demonstrating mutation at the embB gene. CONCLUSIONS: These results are consistent with the empirical observations by physicians treating TB patients in our region of a low occurrence of cases that are refractory to conventional treatment schemes, in contrast to other parts of the country. Continued surveillance, especially molecular, is essential to detect and monitor the outbreak of MT-resistant strains.

The patent expiry as a major inflection point in a branded Rx drug's life and strategies to counter generic competition - exemplified at Pfizer's blockbuster drug Lipitor in the USA

A large number of expensive, but highly profitable branded prescription drugs will go off-patent in the USA between 2011 and 2015. Their revenues are crucial to fund the immense costs associated with the development of an innovative drug. The rising cost pressure on pharmaceutical stakeholders has increased the demand for more affordable medications, as provided by the branded drug's generic counterpart. Yet, research based incumbents are moving beyond the traditional late lifecycle strategies and deploy more aggressive tactics in order to protect their brands, as seen with Pfizer's Lipitor!. It is doubtful, whether these efforts will help the blockbuster business model to resist current market conditions.

Assessing the community needs of mental health residential care service users in Republic of Moldova

RESUMO: Background: Problemas de sa��de mental s��o um grande problema cl��nico e social na Rep��blica da Mold��via, representando uma quota significante de defici��ncia, sendo classificada no top cinco das dez linhas na hierarquia das condi����es. A taxa de incid��ncia tem sido crescente na Rep��blica da Mold��via, atingindo cerca de 15.000 por ano (14,655 em 2011), ou seja, 411,4 por 100 mil habitantes, e uma taxa de preval��ncia de 97.525 pessoas em 2011, ou seja, 2,737.9 por 100 mil habitantes. Sistema de atendimento psiqui��trico fornece servi��os de sa��de mental escassos a n��vel da comunidade, visando principalmente terapia hospitalar, centralizada, atrav��s de uma rede de tr��s hospitais psiqui��tricos, com 1.860 camas e 4 sanat��rios psico- neurol��gicos com 1890 camas, assim alimentando-se a estigmatiza����o do paciente. Objetivos: O objetivo deste estudo foi a avalia����o das necessidades individuais dos benefici��rios e do seu n��vel de autonomia dentro de cuidados residenciais, para o planeamento de reformas de sa��de mental e desinstitucionaliza����o na Rep��blica da Mold��via. Este estudo foi encomendado pelo Minist��rio do Trabalho, Prote����o Social e da Fam��lia e pelo Minist��rio da Sa��de, com o apoio da Organiza����o Mundial da Sa��de, para determinar o cumprimento eficaz do artigo 19 da Conven����o da ONU. O estudo tem os seguintes objetivos: Avaliar o n��vel de autonomia dos residentes nos hospitais psiqui��tricos e sanat��rios psico-neurol��gico, usando uma amostra representativa de 10 por ce nto do n��mero total de pacientes/residentes e compara����o cruzada; Para avaliar quatro sanat��rios psico-neurol��gicos para adultos e tr��s hospitais psiqui��tricos; Para desenvolver recomenda����es para o planeamento da desinstitucionaliza����o das pessoas com problemas de sa��de mental e coloca����o na comunidade com base nos resultados do estudo. Metodologia e resultados: O estudo fez uso de duas ferramentas globais: question��rio para a avalia����o individual dos residentes do estabelecimento de sa��de mental, e question��rio de avalia����o institucional. Todos os entrevistados foram divididos em quatro categorias conforme com o grau de depend��ncia e prepara����o de viver de forma independente na comunidade. Apenas 1,2% dos entrevistados de PNHB eram totalmente dependentes de terceiros ou servi��os especializados, tornando-se a categoria 4, que necessitam de cuidados e apoio cont��nuo. No PH esta categoria de pessoas �� ausente. Conclus��es: A condi����o dos entrevistados foi pior em PNBH que em PH. No entanto, ainda, aqueles que est��o prontos para ser desinstitucionalizados correspondem com a maior parte dos entrevistados. Todos os hospitais tinham o consentimento do utente para admiss��o e tratamento, enquanto n��o houve consentimento qualquer em PNBH. �� bastante ��bvio que tanto os hospitais como tamb��m a sistema de assist��ncia residencial n��o atingem a sua finalidade, o que significa que a maioria dos utentes pode ser desinstitucionalizados, sem qualquer terapia de suporte.------------------ABSTRACT: Background: Mental health problems are a major clinical and social issue in the Republic of Moldova,accounting for a significant share of disability and ranking in top five of the ten lines in the hierarchy of conditions. The incidence rate has been growing in the Republic of Moldova to reach approximately 15 thousand a year (14,655 in 2011), i.e. 411.4 per 100 thousand population, and a prevalence rate of 97,525 thousand people in 2011, i.e. 2,737.9 per 100 thousand population. Psychiatric care system provides for scanty mental health services at community level, aiming mainly at centralized hospital-based therapy through a network of three psychiatric hospitals tallying up 1,860 beds and 4 psycho-neurological boarding houses with 1,890 beds, thus fuelling up patient stigmatization. Objectives: The purpose of this study was to assess the individual needs of beneficiaries and their level of autonomy within residential care for the planning of mental health system reforms and deinstitutionalization in the Republic of Moldova. This study was commissioned by the Ministry of Labour, Social Protection and Family and by the Ministry of Health, with the World Health Organization support, to provide for effective enforcement of article 19 of the UN CRPD. The study pursued the following goals: To evaluate the level of autonomy of the psychiatric hospital and psycho-neurological boarding house residents by using a representative sample of 10 per cent of the total number of patients / residents and cross-comparison; To evaluate four psycho-neurological boarding houses for adults and three psychiatric hospitals; To develop recommendations for planning the deinstitutionalization of people with mental health problems and community placement based on the study findings.Methodology and results: The study made use of two global tools: questionnaire for individual assessment of mental health facility residents, and institutional assessment questionnaire. All interviewees were divided into four categories by one���s degree of dependence and readiness to live independently in the community. Only 1.2% of respondents from PNHB were fully dependent on a third party or specialized services, making up category 4, requiring continuous care and support. In PH this category of people is absent.Conclusions: The condition of respondents was worse in PNBH than in PH. However, yet, those ready to be deinstitutionalized accounted for most of respondents there. All hospitals had the resident���s consent to admission and treatment, whereas there was no consent in PNBH whatsoever. It is quite obvious that both the hospitals and residential care system do not achieve their intended purpose, meaning that the majority of residents may be deinstitutionalized without any support therapy.

Adverse reactions following mass drug administration with diethylcarbamazine in lymphatic filariasis endemic areas in the Northeast of Brazil

INTRODUCTION: The Global Programme to Eliminate Lymphatic Filariasis was launched with the goal of eliminating this disease via the annual mass drug administration (MDA) of a single dose of antifilarial drugs. Adverse drug reactions following MDA are a major factor of poor treatment adherence in several countries. This study assessed the occurrence of adverse drug reactions (ADRs) following the first round of mass treatment in two communities treated with different dosages of diethylcarbamazine (DEC) in the City of Recife, Brazil. METHODS: Population-based cross-sectional surveys were conducted in a random sample of the population living in both communities (Areas I and II). The dose of DEC recommended by the WHO (6mg/kg) was calculated based on the individual's weight-for-age. In Area II, weight differences between the genders were also considered when determining dosage. Data were obtained through interviews conducted in the first 12 to 48h and on the 5th day after MDA during household visits. RESULTS: A total of 487 and 365 individuals were interviewed in Areas I and II, respectively. The prevalence of ADRs in Area I (23.6; 95%CI: 19.1-29.5) was higher than in Area II (16.2; 95%CI:11.9-21.5)(p=0.0078). The prevalence of ADRs among females was higher than in males in Area I (p=0.0021). In Area II, no significant difference between the genders was observed (p=0.1840). Age was not associated with ADRs in either area. CONCLUSIONS: Adjusting MDA dosage schedules according to weight-for-age and sex may be may contribute to reduce the occurrence of adverse drug reactions in the population.

How do Facebook users interact and what are the underlying reasons that trigger these interactions

This research was conducted to understand how Facebook users interact and the underlying reasons for doing so with a focus on one-to-mass communication interactions. Different methods and sources were used to generate accurate and valid insights. It was discovered that liking, groups, commenting, events and sharing are essential interactions, whereby liking, commenting and sharing were investigated in more detail. This investigations proves that emotions do trigger these three interactions; The most influencing emotions are Surprise/Wonder, Deep Respect/ Impressiveness and Fun/Joy. Moreover a variety of specific factors that trigger each of the interactions are revealed.

Environmental isolation, biochemical identification, and antifungal drug susceptibility of Cryptococcus species

Introduction The incidence of opportunistic fungal infections has increased in recent years and is considered an important public health problem. Among systemic and opportunistic mycoses, cryptococcosis is distinguished by its clinical importance due to the increased risk of infection in individuals infected by human immunodeficiency virus. Methods To determine the occurrence of pathogenic Cryptococcus in pigeon excrement in the City of Araraquara, samples were collected from nine environments, including state and municipal schools, abandoned buildings, parks, and a hospital. The isolates were identified using classical tests, and susceptibility testing for the antifungal drugs (fluconazole, itraconazole, voriconazole, and amphotericin B) independently was also performed. After collection, the excrement samples were plated on Niger agar and incubated at room temperature. Results A total of 87 bird dropping samples were collected, and 66.6% were positive for the genus Cryptococcus. The following species were identified: Cryptococcus neoformans (17.2%), Cryptococcus gattii (5.2%), Cryptococcus ater (3.5%), Cryptococcus laurentti (1.7%), and Cryptococcus luteolus (1.7%). A total of 70.7% of the isolates were not identified to the species level and are referred to as Cryptococcus spp. throughout the manuscript. Conclusions Although none of the isolates demonstrated resistance to antifungal drugs, the identification of infested areas, the proper control of birds, and the disinfection of these environments are essential for the epidemiological control of cryptococcosis.

How to engage low category users through social media- The case of the make-up sector in Portugal

Purpose: This work project should be inevitably deemed as a practical approach to a marketing problem; ���How to engage low category users through the social media ��� the case of the make-up sector in Portugal���. Design/methodology/approach: Online structured questionnaires and in-depth interviews were used. The questionnaire was answered by 110 women aged from 15 to 45 years old and the interviews were conducted with 14 women of the same age. The interviews provided key insights for the questionnaire formulation. Findings: Women are poorly informed on make-up properties and characteristics, feeling a genuine concern in regard to this subject. Lack of time, occasional usage and skin damage are the main barriers for make-up usage by low category users. Overcoming these aspects pass by demystifying the association of make-up with skin damage and emphasise the functional and emotional benefits of make-up. Further, brands need to create contents more consumer-oriented and ask directly to fans/followers suggestions and other insights. Resort to Portuguese ���common��� women for greater empathy in campaigns, promote online meetings between followers and make-up professionals on social media; and finally take advantage of the hybrid condition of Facebook, which incorporates multiple forms of content presentation, including videos, the most appealing format of make-up presentation for women. Research limitations/implications: Further studies addressing this topic, by using larger samples and study of specific make-up brands and campaign programs, over social media to reach a solid growth potential of make-up market evidences in Portugal. Originality/ value: Make-up brands are emphasising their interest in linking social media and marketing their promotional mix around social marketing.

Novel antibiotic-loaded orthopaedic bone cements: insights on drug release profiles and biocompatibility

Acrylic bone cement (BC) is widely used as an anchor of artificial joints. Bacterial infection due to biofilm formation and inflammation are common and difficult to treat problems associated with commercial available BC formulations. Research on novel BC compositions is urgently needed. The main objective of this thesis was to develop a new biocompatible antibiotic-loaded BC with improved release profile. To achieve that aim several additives were incorporated, as an antibiotic (levofloxacin) to combat bacterial growth, an anti-inflammatory drug (diclofenac) to decrease the inflammatory process and two well-known and broadly used biopolymers, alginate and chitosan in order to increase matrix porosity, and in this way to intensify the amount of released drug. Novel BC formulations were tested in order to find the most suitable one that had potential to proceed to clinical application. Numerous tests were conducted as: a) evaluation of drug release profiles in different biomimetic media, b) mechanical and surface studies, c) microbiological activity testing against Staphylococcus aureus and d) in vitro biocompatibility assays (fibroblasts and osteoblasts). In general, the addition of biopolymers increased drug release, didn���t compromised BC mechanical properties and increased BC hydrophilicity. Microbiological testing revealed that Lev[BC]Chi was the only matrix that reduced significantly biofilm formation. On the contrary, alginate and diclofenac loading into BC seemed to increase biofilm growth. Biocompatibility studies showed some decrease in cell viability, in particularly on osteoblasts, mainly due to the high amounts of released drugs. In conclusion, the present work has shown that the matrix with more potential to proceed in further investigations was Lev[BC]Chi. Other conditions (namely additives and drugs concentrations) should be evaluated with the other tested BC matrices before being discharged.

Ecstasy intoxication: the toxicological basis for treatment

Youngsters are increasingly using 3,4 methylenedioxymethamphetamine, known as ecstasy, because it is wrongly believed that it does not induce harm. However, there are many reports of adverse effects, including acute intoxication, abuse potential, and possible neurotoxic effects. Therefore, health care providers need to promptly recognize the symptoms of systemic intoxication in order to initiate early treatment. The drug is used by the oral route for long hours during crowded dance parties. Acutely, ecstasy increases the release of serotonin and decreases its reuptake, leading to hypertension, hyperthermia, trismus, and vomiting. There is debate on whether recreational doses of ecstasy cause permanent damage to human serotonergic neurons. Ecstasy users showed a high risk of developing psychopathological disturbances. The prolonged use of ecstasy might induce dependence, characterized by tolerance and hangover. Acute ecstasy intoxication needs emergency-type treatment to avoid the dose-dependent increase in adverse reactions and in severity of complications. There are no specific antidotes to be used during acute intoxication. Supportive measures and medical treatment for each one of the complications should be implemented, keeping in mind that symptoms originate mainly from the central nervous system and the cardiovascular system.

Titanium pigment in tissues of drug addicts: report of 5 necropsied cases

The aim of this report is to describe the anatomic-pathologic findings from necropsies of 5 drug addicts with titanium pigment in several organs after chronic intravenous injection of crushed propoxyphene hydrochloride tablets. Samples from liver, spleen, lungs, lymph nodes, and bone marrow were obtained, and after being grossly studied, they were submitted to evaluation using common light and polarized microscopy. In all 5 cases, a pigment with characteristics of titanium dioxide was found within tissue samples of the organs studied. Our findings suggest that research concerning titanium pigment within body tissues should be enhanced, considering the potential contribution of this morphologic data to forensic pathology.