Early use of alcohol associated with sociodemographic, nutritional and lifestyle factors: survival analysis with Brazilian students.

BACKGROUND: To evaluate the early age of onset (AOO) of alcohol consumption and its association with sociodemographic, nutritional and lifestyle characteristics. METHODS: A national cross-sectional multi-centered study assessed 12-17-year old adolescents from 1247 public and private schools in 124 Brazilian municipalities with more than 100 000 habitants. Our variable of interest was the AOO of alcohol consumption. Covariates comprised sociodemographic status, lifestyle habits and nutritional parameters. We used adapted survival models to investigate the association between covariates and the AOO of alcohol consumption. RESULTS: From a sample of 67 672 adolescents, 50% were females. The mean AOO of alcohol consumption was 12.9 years. Male adolescents had a lower mean age of alcohol experimentation when compared to females in Northeast and South regions. The difference between private and public school for AOO was observed only for the Northeast Region (12.6 versus 13.1, respectively). Adolescents who reported smoking or mental health problems or from the Southern Region presented earlier alcohol use. Physical activity and overweight were positively associated with earlier use of alcohol. CONCLUSIONS: There is no homogeneity in the AOO of alcohol consumption among adolescents, which should be considered when formulating public policies and government campaigns directed toward reducing alcohol consumption.

Violence and child mental health in Brazil: The Itaboraí Youth Study methods and findings.

OBJECTIVES: To demonstrate a study design that could be useful in low-resource and violent urban settings and to estimate the prevalence of child violence exposure (at home, community, and school) and child mental health problems in a low-income medium-size city. METHODS: The Itaboraí Youth Study is a Norway-Brazil collaborative longitudinal study conducted in Itaboraí city (n = 1409, 6-15 year olds). A 3-stage probabilistic sampling plan (random selection of census units, eligible households, and target child) generated sampling weights that were used to obtain estimates of population prevalence rates. RESULTS: Study strengths include previous pilot study and focus groups (testing procedures and comprehension of questionnaire items), longitudinal design (2 assessment periods with a mean interval of 12.9 months), high response rate (>80%), use of standardized instruments, different informants (mother and adolescent), face-to-face interviews to avoid errors due to the high frequency of low-educated respondents, and information gathered on a variety of potential predictors and protective factors. Children and adolescents presented relevant levels of violence exposure and clinical mental health problems. CONCLUSIONS: Prevalence estimates are probably valid to other Brazilian low-income medium-size cities due to similarities in terms of precarious living conditions. Described study methods could be useful in other poor and violent world regions.

Comorbid depressive symptoms in treatment-seeking PTSD outpatients affect multiple domains of quality of life.

PURPOSE: No study has examined the impact of the comorbid Axis I conditions on the quality of life (QoL) of patients with a primary diagnosis of PTSD. Our goal was to investigate the influence of comorbid disorders on the QoL of treatment-seeking outpatients with PTSD. METHODS: The diagnoses of PTSD and of the comorbid disorders were established using the SCID-I. The 54 volunteers also completed the Posttraumatic Stress Disorder Checklist - Civilian Version, the BDI, the BAI, the Trauma History Questionnaire, and a socio-demographic questionnaire. Quality of life was assessed by means of the WHOQOL-BREF, a 26-item self-administered scale that measures four domains of QoL: psychological, physical, social, and environmental. Multiple linear regression models were fitted to investigate the relationship between the severity of post-traumatic, mood, and anxiety symptoms; the presence of specific current comorbid disorders and of psychotic symptoms, the number of current comorbid conditions, and a history of child abuse for each of the four domains of QoL, after adjusting for the effect of socio-demographic characteristics. RESULTS: The severity of PTSD symptoms impacted negatively on the psychological and physical domains. The severity of depressive symptoms correlated negatively with QoL in all domains, independently of sex, age, occupation, and marital status. The psychotic symptoms impacted negatively on the environmental domain. A history of child abuse was negatively associated with the psychological and the social domains. CONCLUSIONS: The severity of comorbid depressive symptoms is one of the most important factors in the determination of the QoL in patients with PTSD.

Physical restraints versus seclusion room for management of people with acute aggression or agitation due to psychotic illness (TREC-SAVE): a randomized trial.

BACKGROUND: After de-escalation techniques have failed, restraints, seclusion and/or rapid tranquillization may be used for people whose aggression is due to psychosis. Most coercive acts of health care have not been evaluated in trials. METHOD: People admitted to the emergency room of Instituto Philippe Pinel, Rio de Janeiro, Brazil, whose aggression/agitation was thought due to psychosis and for whom staff were unsure if best to restrict using physical restraints or a seclusion room, were randomly allocated to one or the other and followed up to 14 days. The primary outcomes were 'no need to change intervention early - within 1 h' and 'not restricted by 4 h'. RESULTS: A total of 105 people were randomized. Two-thirds of the people secluded were able to be fully managed in this way. Even taking into account the move out of seclusion into restraints, this study provides evidence that embarking on the less restrictive care pathway (seclusion) does not increase overall time in restriction of some sort [not restricted by 4 h: relative risk 1.09, 95% confidence interval 0.75-1.58; mean time to release: restraints 337.6 (s.d.=298.2) min, seclusion room 316.3 (s.d.=264.5) min, p=0.48]. Participants tended to be more satisfied with their care in the seclusion group (17.0% v. 11.1%) but this did not reach conventional levels of statistical significance (p=0.42). CONCLUSIONS: This study should be replicated, but suggests that opting for the least restrictive option in circumstances where there is clinical doubt does not harm or prolong coercion.

Effect of aerobic training on EEG alpha asymmetry and depressive symptoms in the elderly: a 1-year follow-up study

The effect of physical exercise on the treatment of depressive elderly adults has not been investigated thus far in terms of changes in cortical hemispheric activity. The objective of the present study was to identify changes in depressive symptoms, quality of life, and cortical asymmetry produced by aerobic activity. Elderly subjects with a diagnosis of major depressive disorder (DSM-IV) were included. Twenty patients (70 percent females, 71 ± 3 years) were divided into an exercise group (pharmacological treatment plus aerobic training) and a control group (undergoing pharmacological treatment) in a quasi-experimental design. Pharmacological treatment was maintained stable throughout the study (antidepressants and anxiolytics). Subjects were evaluated by depression scales (Beck Depression Inventory, Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale) and the Short Form Health Survey-36, and electroencephalographic measurements (frontal and parietal alpha asymmetry) before and after 1 year of treatment. After 1 year, the control group showed a decrease in cortical activity on the right hemisphere (increase of alpha power), which was not observed in the exercise group. The exercise group showed a significant decrease of depressive symptoms, which was not observed in the control group. This result was also accompanied by improved treatment response and remission rate after 1 year of aerobic exercise associated with treatment. This study provides support for the effect of aerobic training on alpha activity and on depressive symptoms in elderly patients. Exercise facilitates the treatment of depressive elderly adults, leading to clinical and physical improvement and protecting against a decrease in cortical activity.

Effect of aerobic training on EEG alpha asymmetry and depressive symptoms in the elderly: a 1-year follow-up study.

The effect of physical exercise on the treatment of depressive elderly adults has not been investigated thus far in terms of changes in cortical hemispheric activity. The objective of the present study was to identify changes in depressive symptoms, quality of life, and cortical asymmetry produced by aerobic activity. Elderly subjects with a diagnosis of major depressive disorder (DSM-IV) were included. Twenty patients (70% females, 71 +/- 3 years) were divided into an exercise group (pharmacological treatment plus aerobic training) and a control group (undergoing pharmacological treatment) in a quasi-experimental design. Pharmacological treatment was maintained stable throughout the study (antidepressants and anxiolytics). Subjects were evaluated by depression scales (Beck Depression Inventory, Hamilton Depression Rating Scale, Montgomery-Asberg Depression Rating Scale) and the Short Form Health Survey-36, and electroencephalographic measurements (frontal and parietal alpha asymmetry) before and after 1 year of treatment. After 1 year, the control group showed a decrease in cortical activity on the right hemisphere (increase of alpha power), which was not observed in the exercise group. The exercise group showed a significant decrease of depressive symptoms, which was not observed in the control group. This result was also accompanied by improved treatment response and remission rate after 1 year of aerobic exercise associated with treatment. This study provides support for the effect of aerobic training on alpha activity and on depressive symptoms in elderly patients. Exercise facilitates the treatment of depressive elderly adults, leading to clinical and physical improvement and protecting against a decrease in cortical activity.

Rapid tranquillisation in psychiatric emergency settings in Brazil: pragmatic randomised controlled trial of intramuscular haloperidol versus intramuscular haloperidol plus promethazine.

OBJECTIVE: To determine whether haloperidol alone results in swifter and safer tranquillisation and sedation than haloperidol plus promethazine. DESIGN: Pragmatic randomised open trial (January-July 2004). SETTING: Psychiatric emergency room, Rio de Janeiro, Brazil. PARTICIPANTS: 316 patients who needed urgent intramuscular sedation because of agitation, dangerous behaviour, or both. INTERVENTIONS: Open treatment with intramuscular haloperidol 5-10 mg or intramuscular haloperidol 5-10 mg plus intramuscular promethazine up to 50 mg; doses were at the discretion of the prescribing clinician. MAIN OUTCOME MEASURES: The primary outcome was proportion tranquil or asleep by 20 minutes. Secondary outcomes were asleep by 20 minutes; tranquil or asleep by 40, 60, and 120 minutes; physically restrained or given additional drugs within 2 hours; severe adverse events; another episode of agitation or aggression; additional visit from the doctor during the subsequent 24 hours; overall antipsychotic load in the first 24 hours; and still in hospital after 2 weeks. RESULTS: Primary outcome data were available for 311 (98.4%) people, 77% of whom were thought to have a psychotic illness. Patients allocated haloperidol plus promethazine were more likely to be tranquil or asleep by 20 minutes than those who received intramuscular haloperidol alone (relative risk 1.30, 95% confidence interval 1.10 to 1.55; number needed to treat 6, 95% confidence interval 4 to 16; P=0.002). No differences were found after 20 minutes. However, 10 cases of acute dystonia occurred, all in the haloperidol alone group. CONCLUSIONS: Haloperidol plus promethazine is a better option than haloperidol alone in terms of speed of onset of action and safety. Enough data are now available to change guidelines that continue to recommend treatments that leave people exposed to longer periods of aggression than necessary and patients vulnerable to distressing and unsafe adverse effects. TRIAL REGISTRATION: Current Controlled Trials ISRCTN83261243 [controlled-trials.com].

Construction and biological properties of yellow fever 17D/dengue type 1 recombinant virus.

Dengue virus, a mosquito-borne flavivirus, is one of the most formidable public health threats in tropical and subtropical regions. As yet, there is no licensed vaccine to protect against the disease. A chimeric yellow fever (YF) 17D/dengue (DEN) type 1 virus was constructed by replacing the pre-membrane and envelope genes of YF 17D virus with those from DEN 1 VeMir95 virus, a Venezuelan isolate. The chimeric YF 17D/DEN 1 VeMir95 virus was regenerated from full-length infectious clones stably propagated in Escherichia coli by transfection of Vero cells with in vitro transcribed RNA. The chimeric virus proliferated efficiently in Vero cells ( approximately 6.6 log(10) plaque-forming units/ml). The chimeric virus was not neurovirulent to 3-week-old Swiss Webster mice inoculated by the intracerebral route, in contrast to the YF 17DD vaccine strain that was lethal for 90% of the mice. The YF 17D/DEN 1 virus at Passage 6 was more attenuated for rhesus monkeys than the YF 17DD commercial vaccine after intracerebral inoculation according to the standard neurovirulence test. This virus is a potential candidate to be included in a tetravalent DEN vaccine formulation. The availability of the cloned cDNA allows further structure/function studies on the viral envelope.

Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys

A chimeric yellow fever (YF)-dengue serotype 2 (dengue 2) virus was constructed by replacing the premembrane and envelope genes of the YF 17D virus with those from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high titers in Vero cells and, after passage 2, was used for immunogenicity and attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response associated with the protection of 6 of 7 monkeys against viremia by wild-type dengue 2 virus. Neutralizing antibody titers to dengue 2 were significantly lower in YF-immune animals than in YF-naive monkeys and protection against challenge with wild-type dengue 2 virus was observed in only 2 of 11 YF-immune monkeys. An anamnestic response to dengue 2, indicated by a sharp increase of neutralizing antibody titers, was observed in the majority of the monkeys after challenge with wild-type virus. Virus attenuation was demonstrated using the standard monkey neurovirulence test. The 17D-D2 chimera caused significantly fewer histological lesions than the YF 17DD virus. The attenuated phenotype could also be inferred from the limited viremias compared to the YF 17DD vaccine. Overall, these results provide further support for the use of chimeric viruses for the development of a new live tetravalent dengue vaccine.

Attenuation and immunogenicity of recombinant yellow fever 17D-dengue type 2 virus for rhesus monkeys.

A chimeric yellow fever (YF)-dengue serotype 2 (dengue 2) virus was constructed by replacing the premembrane and envelope genes of the YF 17D virus with those from dengue 2 virus strains of Southeast Asian genotype. The virus grew to high titers in Vero cells and, after passage 2, was used for immunogenicity and attenuation studies in rhesus monkeys. Subcutaneous immunization of naive rhesus monkeys with the 17D-D2 chimeric virus induced a neutralizing antibody response associated with the protection of 6 of 7 monkeys against viremia by wild-type dengue 2 virus. Neutralizing antibody titers to dengue 2 were significantly lower in YF-immune animals than in YF-naive monkeys and protection against challenge with wild-type dengue 2 virus was observed in only 2 of 11 YF-immune monkeys. An anamnestic response to dengue 2, indicated by a sharp increase of neutralizing antibody titers, was observed in the majority of the monkeys after challenge with wild-type virus. Virus attenuation was demonstrated using the standard monkey neurovirulence test. The 17D-D2 chimera caused significantly fewer histological lesions than the YF 17DD virus. The attenuated phenotype could also be inferred from the limited viremias compared to the YF 17DD vaccine. Overall, these results provide further support for the use of chimeric viruses for the development of a new live tetravalent dengue vaccine.

Zuclopenthixol acetate for acute schizophrenia and similar serious mental illnesses.

BACKGROUND: Medication used for acute aggression in psychiatry must have rapid onset of effect, low frequency of administration and low levels of adverse effects. Zuclopenthixol acetate is said to have these properties. OBJECTIVES: To estimate the clinical effects of zuclopenthixol acetate for the management of acute aggression or violence thought to be due to serious mental illnesses, in comparison to other drugs used to treat similar conditions. SEARCH STRATEGY: We supplemented past searches of Current Controlled Trials (10/2000), the Cochrane Library (1997) and MEDLINE (1966-1997) and appeals for unpublished data with an update search of the Cochrane Schizophrenia Group's Register of trials (September 2003). SELECTION CRITERIA: All randomised clinical trials involving people thought to have serious mental illnesses comparing zuclopenthixol acetate with other drugs. DATA COLLECTION AND ANALYSIS: Data were extracted independently by two reviewers and cross-checked. We calculated fixed effects relative risks (RR) and 95% confidence intervals (CI) for dichotomous data. Where possible, the number needed to treat/harm statistic (NNT/H) was calculated. We analyzed by intention-to-treat. Mean differences were used for continuous variables. MAIN RESULTS: We found no data for the primary outcome, tranquilisation. Compared with haloperidol, zuclopenthixol acetate was no more sedating at two hours (n=40, 1 RCT, RR 0.60 CI 0.27 to 1.34). People given zuclopenthixol acetate were not at reduced risk of being given supplementary antipsychotics (n=134, 3 RCTs, RR 1.49 CI 0.97 to 2.30) although additional use of benzodiazepines was less (n=50, 1 RCT, RR 0.03 CI 0.00 to 0.47, NNT 2 CI 2 to 4). People given zuclopenthixol acetate had fewer injections over seven days compared with those allocated to haloperidol IM (n=70, 1 RCT, RR 0.39 CI 0.18 to 0.84, NNT 4 CI 3 to 14). We found no data on more episodes of aggression or harm to self or others. One trial (n=148) reported no significant difference in adverse effects for people receiving zuclopenthixol acetate compared with those allocated haloperidol at one, three and six days (RR 0.74 CI 0.43 to 1.27). Compared with haloperidol or clotiapine, people allocated zuclopenthixol did not seem to be at more risk of a range of movement disorders (<20%). Three studies found no difference in the proportion of people getting blurred vision/ dry mouth (n=192, 2 RCTs, RR at 24 hours 0.90 CI 0.48 to 1.70). Similarly dizziness was equally infrequent for those allocated zuclopenthixol acetate compared with haloperidol (n=192, 2 RCTs, RR at 24 hours 1.15 CI 0.46 to 2.88). There was no difference between treatments for leaving the study before completion (n=522, RR 0.85 CI 0.31 to 2.31). REVIEWERS' CONCLUSIONS: Recommendations on the use of zuclopenthixol acetate for the management of psychiatric emergencies in preference to 'standard' treatment have to be viewed with caution. Most trials present important methodological flaws and findings are poorly reported. This review did not find any suggestion that zuclopenthixol acetate is more or less effective in controlling aggressive acute psychosis, or in preventing adverse effects than intramuscular haloperidol, and neither seemed to have a rapid onset of action. Well-conducted pragmatic randomised controlled trials are needed.