Evaluation of Sexual Dimorphism in the Efficacy and Safety of Simvastatin/Atorvastatin Therapy in a Southern Brazilian Cohort

Background: Dyslipidemia is the primary risk factor for cardiovascular disease, and statins have been effective in controlling lipid levels. Sex differences in the pharmacokinetics and pharmacodynamics of statins contribute to interindividual variations in drug efficacy and toxicity. Objective: To evaluate the presence of sexual dimorphism in the efficacy and safety of simvastatin/atorvastatin treatment. Methods: Lipid levels of 495 patients (331 women and 164 men) were measured at baseline and after 6 ± 3 months of simvastatin/atorvastatin treatment to assess the efficacy and safety profiles of both drugs. Results: Women had higher baseline levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C) compared with men (p < 0.0001). After treatment, women exhibited a greater decrease in plasma TC and LDL-C levels compared with men. After adjustment for covariates, baseline levels of TC and LDL-C influenced more than 30% of the efficacy of lipid-lowering therapy (p < 0.001), regardless of sex. Myalgia [with or without changes in creatine phosphokinase (CPK) levels] occurred more frequently in women (25.9%; p = 0.002), whereas an increase in CPK and/or abnormal liver function was more frequent in in men (17.9%; p = 0.017). Conclusions: Our results show that baseline TC and LDL-C levels are the main predictors of simvastatin/atorvastatin therapy efficacy, regardless of sex. In addition, they suggest the presence of sexual dimorphism in the safety of simvastatin/atorvastatin. The effect of sex differences on receptors, transporter proteins, and gene expression pathways needs to be better evaluated and characterized to confirm these observations.

The social adjustment of patients with schizophrenia: implications to the mental health policy in Brazil

A sample (n=124) of schizophrenic patients from a defined catchment area of the city os S.Paulo, Brazil, who had been consecutively admitted to hospital, was assessed for psychopathological status and social adjustment levels. Sociodemographic, socio-economic and occupational characteristics were recorded: almost 30% of the subjects had no occupation and received no social benefit, more than two-thirds had a monthly per capita income of US$ 100.00 or less. Sixty-five percent presented with Schneiderian firstrank symptoms. Nearly half the sample showed poor or very poor social adjustment in the month prior to admission. The most affected areas of social functioning were participation in the household activities, work and social withdrawal. The current mental health policy of promoting extra-mural care as an alternative to the previous hospital-based model will then mean the investment in a network of new community-based services, that give effective treatment and support to patients and their families. The need of further research into the current picture of mental disorders in the country is stressed.

Family expectation, social adjustment and gender differences in a sample of schizophrenic patients

A case series to study factors related to family expectation regarding schizophrenic patients was conducted in an out-patient setting in the city of S. Paulo, Brazil. Patients diagnosed as presenting schizophrenia by the ICD 9th Edition and having had the disease for more than four years were included in the study. Family Expectation was measured by the difference between the Katz Adjustment Scale (R2 and R3) scores based on the relative's expectation and the socially expected activities of the patient (Discrepancy Score), and social adjustment was given by the DSM-III-R Global Assessment Scale (GAS) . Outcome assessments were made independently, and 44 patients comprised the sample (25 males and 19 females). The Discrepancy mean score was twice as high for males as for females (p < 0.02), and there was an inverse relationship between the discrepancy score and social adjustment (r =-0.46, p < 0.001). Moreover, sex and social adjustment exerted independent effects on the discrepancy score when age, age at onset and number of psychiatric admissions were controlled by means of a multiple regression technique. There was an interaction between sex and social adjustment, the inverse relationship between social adjustment and discrepancy score being more pronounced for males. These findings are discussed in the light of the potential association between the family environment, gender and social adjustment of schizophrenic patients, and the need for further research, i.e. ethnographic accounts of interactions between patient and relatives sharing households particularly in less developed countries.

BASS 4: a software system for ergonomic design and evaluation of working hours

OBJECTIVE: To extend an existing computer programme for the evaluation and design of shift schedules (BASS 3) by integrating workload as well as economic aspects. METHODS: The redesigned prototype BASS 4 includes a new module with a suitable and easily applicable screening method (EBA) for the assessment of the intensity of physical, emotional and cognitive workload components and their temporal patterns. Specified criterion functions based on these ratings allow for an adjustment of shift and rest duration according to the intensity of physical and mental workload. Furthermore, with regard to interactive effects both workload and temporal conditions, e.g. time of day, are taken into account. In a second new module, important economic aspects and criteria have been implemented. Different ergonomic solutions for scheduling problems can now also be evaluated with regard to their economic costs. RESULTS: The new version of the computer programme (BASS 4) can now simultaneously take into account numerous ergonomic, legal, agreed and economic criteria for the design and evaluation of working hours. CONCLUSIONS: BASS 4 can now be used as an instrument for the design and the evaluation of working hours with regard to legal, ergonomic and economic aspects at the shop floor as well as in administrative (e.g. health and safety inspection) and research problems.

Linking better shiftwork arrangements with safety and health management systems

OBJECTIVE: Various support measures useful for promoting joint change approaches to the improvement of both shiftworking arrangements and safety and health management systems were reviewed. A particular focus was placed on enterprise-level risk reduction measures linking working hours and management systems. METHODS: Voluntary industry-based guidelines on night and shift work for department stores and the chemical, automobile and electrical equipment industries were examined. Survey results that had led to the compilation of practicable measures to be included in these guidelines were also examined. The common support measures were then compared with ergonomic checkpoints for plant maintenance work involving irregular nightshifts. On the basis of this analysis, a new night and shift work checklist was designed. RESULTS: Both the guidelines and the plant maintenance work checkpoints were found to commonly cover multiple issues including work schedules and various job-related risks. This close link between shiftwork arrangements and risk management was important as shiftworkers in these industries considered teamwork and welfare services to be essential for managing risks associated with night and shift work. Four areas found suitable for participatory improvement by managers and workers were work schedules, ergonomic work tasks, work environment and training. The checklist designed to facilitate participatory change processes covered all these areas. CONCLUSIONS: The checklist developed to describe feasible workplace actions was suitable for integration with comprehensive safety and health management systems and offered valuable opportunities for improving working time arrangements and job content together.

Neonatal mortality: description and effect of hospital of birth after risk adjustment

OBJECTIVE: To assess the effect of hospital of birth on neonatal mortality. METHODS: A birth cohort study was carried out in Pelotas, Southern Brazil, in 2004. All hospital births were assessed by daily visits to all maternity hospitals and 4558 deliveries were included in the study. Mothers were interviewed regarding potential risk factors. Deaths were monitored through regular visits to hospitals, cemeteries and register offices. Two independent pediatricians established the underlying cause of death based on information obtained from medical records and home visits to parents. Logistic regression was used to estimate the effect of hospital of birth, controlling for confounders related to maternal and newborn characteristics, according to a conceptual model. RESULTS: Neonatal mortality rate was 12.7‰ and it was highly influenced by birthweight, gestational age, and socioeconomic variables. Immaturity was responsible for 65% of neonatal deaths, followed by congenital anomalies, infections and intrapartum asphyxia. Adjusting for maternal characteristics, a three-fold increase in neonatal mortality was seen between similar complexity hospitals. The effect of hospital remained, though lower, after controlling for newborn characteristics. CONCLUSIONS: Neonatal mortality was high, mainly related to immaturity, and varied significantly across maternity hospitals. Further investigations comparing delivery care practices across hospitals are needed to better understand NMR variation and to develop strategies for neonatal mortality reduction.

Comorbidity adjustment index for the international classification of diseases, 10

OBJECTIVE: To develop a Charlson-like comorbidity index based on clinical conditions and weights of the original Charlson comorbidity index. METHODS: Clinical conditions and weights were adapted from the International Classification of Diseases, 10th revision and applied to a single hospital admission diagnosis. The study included 3,733 patients over 18 years of age who were admitted to a public general hospital in the city of Rio de Janeiro, southeast Brazil, between Jan 2001 and Jan 2003. The index distribution was analyzed by gender, type of admission, blood transfusion, intensive care unit admission, age and length of hospital stay. Two logistic regression models were developed to predict in-hospital mortality including: a) the aforementioned variables and the risk-adjustment index (full model); and b) the risk-adjustment index and patient's age (reduced model). RESULTS: Of all patients analyzed, 22.3% had risk scores >1, and their mortality rate was 4.5% (66.0% of them had scores >1). Except for gender and type of admission, all variables were retained in the logistic regression. The models including the developed risk index had an area under the receiver operating characteristic curve of 0.86 (full model), and 0.76 (reduced model). Each unit increase in the risk score was associated with nearly 50% increase in the odds of in-hospital death. CONCLUSIONS: The risk index developed was able to effectively discriminate the odds of in-hospital death which can be useful when limited information is available from hospital databases.

Association between social capital and self-perception of health in Brazilian adults

OBJECTIVE To investigate the association between social capital and social capital and self-perception of health based on examining the influence of health-related behaviors as possible mediators of this relationship.METHODS A cross-sectional study was used with 1,081 subjects, which is representative of the population of individuals aged 40 years or more in a medium-sized city in Southern Brazil. The subjects who perceived their health as fine, bad or very bad were considered to have a negative self-perception of their health. The social capital indicators were: number of friends, people from whom they could borrow money from when needed; the extent of trust in community members; whether or not members of the community helped each other; community safety; and extent of participation in community activities. The behaviors were: physical activity during leisure time, fruits and vegetable consumption, tobacco use and alcohol abuse. The odds ratios (OR) and confidence intervals (CI) 95% were calculated by binary logistic regression. The significance of mediation was verified using the Sobel test.RESULTS Following adjustment for demographic and clinical variables, subjects with fewer friends (OR = 1.39, 95%CI 1.08;1.80), those who perceived less frequently help from people in the neighborhood (OR = 1.30, 95%CI 1.01;1.68), who saw the violent neighborhood (OR = 1.33, 95%CI 1.01;1.74) and who had not participated in any community activity (OR = 1.39, 95%CI 1.07;1.80) had more negative self-perception of their health. Physical activity during leisure time was a significant mediator in the relationship between all social capital indicators (except for the borrowed money variable) and self-perceived health. Fruit and vegetable consumption was a significant mediator of the relationship between the extent of participation in community activities and self-perceived health. Tobacco use and alcohol abuse did not seem to have a mediating role in any relationship.CONCLUSIONS Lifestyle seems to only partially explain the relationship between social capital and self-perceived health. Among the investigated behaviors, physical activity during leisure time is what seems to have the most important role as a mediator of this relationship.

Safety and efficacy of fenproporex for obesity treatment: a systematic review

ABSTRACT OBJECTIVE To evaluate clinical evidence on the safety and efficacy of fenproporex for treating obesity. METHODS MEDLINE, LILACS and Cochrane Controlled Trials Register were searched as well as references cited by articles and relevant documents. Two authors independently assessed the studies for inclusion and regarding risk of bias, collected data, and accuracy. Eligible studies were all those placebo-controlled that provided data on the efficacy and safety of Fenproporex to treat obesity. RESULTS Only four controlled studies met the inclusion criteria. One randomized, placebo-controlled trial on Fenproporex was found on electronic databases. Three placebo-controlled studies (in non-indexed journals) were identified by hand-searching. Patients with cardiovascular and other comorbidities were excluded in all studies. Trials lasted from 40 to 364 days and doses ranged from 20 to 33.6 mg/d. All controlled studies found that weight loss among Fenproporex-treated patients was greater than that produced by the placebo, but drug effect was modest. Fenproporex produced additional weight reductions of 4.7 kg (one year), 3.8 kg (six months) and 1.55 kg (two months) in average, in relation to diet and exercise only (three trials). Insomnia, irritability, and anxiety were the most frequently reported side effects in the four studies. CONCLUSIONS There is a paucity of randomized, placebo-controlled trials on Fenproporex and those identified here present major methodological flaws. These studies suggest that Fenproporex is modestly effective in promoting weight loss. Nonetheless, they failed to provide evidence that it reduces obesity-associated morbidity and mortality. Data from these studies are insufficient to determine the risk-benefit profile of Fenproporex. Abuse potential and amphetamine-like adverse effects are causes for concern.

Safety and immunogenicity of hepatitis B vaccine ButaNG in adults

Recombinant yeast-derived hepatitis B vaccine manufactured by Instituto Butantan was administered in two groups of adult volunteers (I, II) following two different schedules of immunization. In the first trial (10 mg doses and 0, 1, 3 months vaccination schedule) 106 individuals completed the full immunization program. The results of seroconversion by age group varied from 70 to 100% and the GMT from 46.5 to 124.9 mIU mL-1. In the second trial with 68 individuals (for dosage comparison and 0, 1, 6 months vaccination schedule) indicated that the vaccine formulated in 20 mg was more effective than in 10 mg. The adverse reactions observed in the vaccinees were less frequent than the ones previously found since the introduction of similar vaccines.

Safety and skin delayed-type hypersensitivity response in vervet monkeys immunized with Leishmania donovani sonicate antigen delivered with adjuvants

In this study, we report on the safety and skin delayed-type hypersensitivity (DTH), responses of the Leishmania donovani whole cell sonicate antigen delivered in conjunction with alum-BCG (AlBCG), Montanide ISA 720 (MISA) or Monophosphoryl lipid A (MPLA) in groups of vervet monkeys. Following three intradermal injections of the inoculums on days 0, 28 and 42, safety and DTH responses were assessed. Preliminary tumor necrosis factor alpha (TNF-α) and interferon gamma (IFN-γ) levels were also measured and these were compared with DTH. Only those animals immunized with alum-BCG reacted adversely to the inoculum by producing ulcerative erythematous skin indurations. Non-parametric analysis of variance followed by a post-test showed significantly higher DTH responses in the MISA+Ag group compared with other immunized groups (p < 0.001). The MPLA+Ag group indicated significantly lower DTH responses to the sonicate antigen compared with the AlBCG+Ag group. There was a significant correlation between the DTH and cytokine responses (p < 0.0001). Based on this study we conclude that Leishmania donovani sonicate antigen containing MISA 720 is safe and is associated with a strong DTH reaction following immunization.

Safety evaluation of SPF66 malaria vaccine in Brazil

The frequency and description of side effects secondaiy to the subcutaneous application of SPf66 malaria vaccine and placebo are reported for each dose of application in the participants of the vaccine efficacy trial in Brazil. Side effects evaluated two hours after each application were detected in 8.0%, 30.2% and 8.8%, for the Is', and 3"' dose, respectively, in the SPf66group, and in 7.0%, 8.5% and 2.9% in the placebo group. Local reactions such as mild inflammation, nodule and pain or erythema frequently accompanied by pruritus were the most common reactions detected in both groups (3-8%, 29.1% and 8.5% in the SPf66 group and 4.0%, 7.6% and 2.5% in the placebo group). Among vaccinees, local side effects after the 2nd dose were more frequent in females. Systemic side effects were expressed mainly through general symptoms referred by the participants and were most frequent after the 1st dose in both groups (4.3% in the SPf66 group and 3-0% in the placebo group). Muscle aches and fever were refewred by few participants. No severe adverse reactions were detected for either dose of application or group.

Feasibility study of the immunogenicity and safety of a novel DTPw/Hib (PRP-T) Brazilian combination compared to a licensed vaccine in healthy children at 2, 4, and 6 months of age

Vaccination of infants with conjugated Haemophilus influenzae type b (Hib) vaccines has been proven to reduce Hib meningitis by 95% and pneumoniae by 20%. The routine use of Hib vaccine is facilitated by the introduction of combination vaccines into the EPI (Expanded Plan of Immunization). The objective of this study was to compare the immunogenicity and reactogenicity of an extemporaneously mixed DTPw/Hib (diphtheria-tetanus-whole cell pertussis) combination, using the technology of two Brazilian manufacturers, against a licensed DTPw/Hib European combination in 108 infants vaccinated at 2, 4 and 6 months according to the local national schedule. The Brazilian combination was highly immunogenic with Hib seroprotection rates (anti-PRP > 0.15 mg /ml of 98% after 2 doses and 100% after 3). Also for tetanus and pertussis the new Brazilian combination was as immunogenic as the European counterpart, except the diphtheria seroprotection rates and titers were lower. There was also no clinically relevant difference in reactogenicity. If these feasibility results are confirmed, the Brazilian DTPw/Hib combination should help to boost the uptake of Hib vaccination in Brazil.