Cocaine induces DNA damage in distinct brain areas of female rats under different hormonal conditions.

We evaluated levels of neuronal DNA damage after acute or repeated cocaine treatment in different brain areas of female rats after ovariectomy or sham surgery. Rats in the control and acute groups were given saline i.p., whereas in the repeated group were given 15 mg/kg, i.p., cocaine for 8 days. After a 10 day washout period, the control group was given saline i.p., whereas rats in the acute and repeated groups were given a challenge dose of 15 mg/kg, i.p., cocaine. After behavioural assessment, rats were killed and the cerebellum, hippocampus, hypothalamus, prefrontal cortex and striatum were dissected for the Comet assay. Acute cocaine exposure induced DNA damage in all brain areas. This effect persisted after repeated administration, except in the hypothalamus, where repeated treatment did not cause increased DNA damage. Sexual hormones exhibited a neuroprotective effect, decreasing cocaine-induced DNA damage in cycling rats in all brain areas.

Impact of implementing a vancomycin protocol to reduce kidney toxicity: A comparative study.

Introduction: Vancomycin is a frequently used antibiotic for treating severe infections caused by multidrug-resistant, Gram-positive pathogens. To ensure its effectiveness and minimize the risk of nephrotoxicity, safe administration and dose monitoring are crucial. Understanding the impact of vancomycin serum levels on clinical outcomes is of paramount importance, necessitating improved knowledge on its use, dose monitoring, nephrotoxicity, and safe administration. Objective: This study aimed to evaluate the incidence of acute kidney injury (AKI) in patients receiving vancomycin before and after the implementation of an institutional protocol for vancomycin administration in a public tertiary hospital in southern Brazil. Materials and methods: A cross-sectional study design was employed, analyzing data from the electronic medical records of 422 patients who received vancomycin. The patient population was divided into two independent cohorts: those treated in 2016 (pre-protocol) and those treated in 2018 (post-protocol), following the implementation of the institutional vancomycin administration protocol. Results: The study included 211 patients in each year of assessment. Patients from both cohorts had a Charlson Comorbidity Index (CCI) score of 4. The post-protocol cohort consisted of older individuals, with a mean age of 62.8 years. In addition, patients in the post-protocol year had higher baseline creatinine levels, higher rates of intensive care unit (ICU) hospitalization, and increased use of vasopressors. In the pre-protocol year, patients received vancomycin therapy for a longer duration. When comparing the incidence of AKI between the two groups, an intervention study revealed rates of 38.4% in group 1 and 20.9% in group 2, indicating a significant reduction (p < 0.001) in the post-protocol group. A logistic regression model was developed to predict AKI, incorporating variables that demonstrated significance (p ≤ 0.250) in bivariate analysis and those recognized in the literature as important factors for AKI, such as the duration of therapy, vancomycin serum level, and ICU hospitalization. The logistic regression classification performance was assessed using a receiver operating characteristic (ROC) curve, yielding an area under the curve of 0.764, signifying acceptable discrimination of the regression model. Conclusion: Implementation of the institutional protocol for vancomycin administration resulted in a significant and cost-effective impact, ensuring appropriate therapeutic dosing, reducing adverse events (e.g., nephrotoxicity), and improving clinical outcomes for patients in the study population.

Antidepressant effect of taurine in diabetic rats.

Clinical and preclinical studies have shown that diabetic individuals present more depressive behaviors than non-diabetic individuals. Taurine, one of the most abundant free amino acids in the central nervous system, modulates a variety of biological functions and acts as an agonist at GABAA receptors. Our objective was to assess the antidepressant effect of taurine in diabetic rats. Additionally, we studied the effect of taurine on weight gain, water and food intake, and blood glucose levels in diabetic and non-diabetic rats. Male Wistar rats were divided into control (CTR) and streptozotocin-induced diabetic (STZ) groups and were administered daily 0, 25, 50 or 100 mg/kg of taurine (n = 10 per subgroup) intraperitoneally. After 28 days of treatment, the animals were exposed to the forced swimming test, and their behaviors were recorded. Weight gain, water and food intake, and blood glucose levels were measured weekly. Our results showed that STZ rats had a higher immobility duration than CTR rats, and taurine decreased this depressive-like behavior in STZ rats at doses of 25 and 100 mg/kg. Both of these doses of taurine also decreased water intake and improved weight gain in STZ rats. All doses of taurine decreased the water intake in CTR rats. Taurine, at a dose of 100 mg/kg, decreased food intake and blood glucose levels in STZ rats. Because taurine is a GABA agonist and both amino acids are lower in the plasma of diabetic and depressive individuals, we hypothesize that taurine may represent a new adjuvant drug for the treatment of depression in diabetic individuals.

Effect of progesterone on the expression of GABA(A) receptor subunits in the prefrontal cortex of rats: implications of sex differences and brain hemisphere.

Progesterone is a neuroactive hormone with non-genomic effects on GABA(A) receptors (GABA(A)R). Changes in the expression of GABA(A)R subunits are related to depressive-like behaviors in rats. Moreover, sex differences and depressive behaviors have been associated with prefrontal brain asymmetry in rodents and humans. Thus, our objective was to investigate the effect of progesterone on the GABA(A)R α1 and γ2 subunits mRNA expression in the right and left prefrontal cortex of diestrus female and male rats exposed to the forced swimming test (FST). Male and female rats (n = 8/group) were randomly selected to receive a daily dose of progesterone (0·4 mg·kg⁻¹) or vehicle, during two complete female estrous cycles (8-10 days). On the experiment day, male rats or diestrus female rats were euthanized 30 min after the FST. Our results showed that progesterone significantly increased the α1 subunit mRNA in both hemispheres of male and female rats. Moreover, there was an inverse correlation between depressive-like behaviors and GABA(A)R α1 subunit mRNA expression in the right hemisphere in female rats. Progesterone decreased the GABA(A)R γ2 mRNA expression only in the left hemisphere of male rats. Therefore, we conclude that the GABA(A) system displays an asymmetric distribution according to sex and that progesterone, at lower doses, presents an antidepressant effect after increasing the GABA(A) R α1 subunit expression in the right prefrontal cortex of female rats.

Social distancing and changes in drug use: Results from a cross-sectional study during the COVID-19 pandemic in Brazil.

Background: The outbreak of coronavirus disease 19 has led to measures of social distancing and quarantine worldwide. This stressful period may lead to psychological problems, including changes in substance use. In addition, sociodemographic factors are linked to changed levels of drug use and abuse observed during the COVID-19 pandemic, which are also associated with increased anxiety, depression, and other disorders. Thus, the aim of the study was to investigate (i) changes in drug use during the COVID-19 pandemic associated with social distancing, and (ii) to verify factors associated with those changes. Methods: A web-based cross-sectional observational survey was completed by a self-selected adult general population in Brazil (N = 2,435) during September/October 2020 (first wave) before and throughout the pandemic. Key outcomes: social distancing, self-reported drug use (ASSIST), and emotional states (DASS-21). Results: High social distancing was associated with fewer chances (prevalence ratio) of increased drug use for alcohol (0.71, CI95%: 0.64-0.80), tobacco (0.72; CI95%: 0.60-0.87), cannabis (0.65; CI95%: 0.55-0.78), and others. Low social distancing presented a higher DASS-21 score for anxiety (P = 0.017). Concerning covariates analysis by a general linear model, men (alcohol: 1. 71; cannabis: 3.86), younger age (alcohol: 0.97), less education (alcohol, tobacco, cannabis and cocaine/crack comparing several lower schooling categories vs. higher education), lower income (alcohol: 0.42; tobacco: 0.47; and cannabis: 0.36), and higher depression DASS-21 score (alcohol: 1.05; tobacco: 1.08; cannabis: 1.07; and cocaine/crack: 1.07) were associated with higher use prevalence of several drugs. Conclusions: Individuals reporting low social distancing increased the use of most drugs during the pandemic, while high social distancing significantly decreased drug use. Anxiety and depressive states and several sociodemographic factors (men; lower income; less education) were associated with higher drug use patterns.

Analysis of leukocytes in medication-overuse headache, chronic migraine, and episodic migraine.

OBJECTIVE: To evaluate the number of immune cells in the peripheral blood of medication-overuse headache (MOH), chronic migraine (CM), and migraine without aura (MWA) patients, as well as from controls. BACKGROUND: Migraine has been linked to immunologic disturbances, but the role of the immune system in chronic forms of headache that evolve from migraine has not been studied. Psychiatric co-morbidity has been related to both headache chronification and immunologic alterations. METHODS: This cross-sectional study comprised 68 subjects divided in 4 groups: MOH, CM, MWA, control. Subjects were gender-matched, had no physical co-morbidity, and were taking only acetaminophen. Clinical and psychological data were recorded in a standardized protocol. Samples of peripheral blood for hematological analysis were obtained in the morning during the ictal (MOH, CM, and MWA groups) and interictal periods (MWA group), as well from control group. RESULTS: A higher lymphocyte count was measured in MOH patients relative to the MWA patients (mean ± standard deviation: 2448.7/mm3 ± 775.8 vs. 1859.7/mm3 ± 564.7; P = .027). The numbers of blood lymphocytes for CM and control subjects were 2086.1/mm3 ± 540.5 and 1961.7/mm3 ± 385.6, respectively. Multiple linear regression analysis demonstrated that only MOH and MWA groups remained associated with lymphocyte count (B = 540.7; CI 95%: 55.2-1026.1; P = .03; R2 = 19.2%). Analysis for linearity of variables in the spectrum control/MWA/CM/MOH resulted positive for body mass index (from 23.5 ± 3.25 in controls to 26.5 ± 4.49 in MOH patients; P = .034), scores on Beck Depression Inventory (from 3.29 ± 3.05 to 14.65 ± 11.21; P < 0.001) and Hamilton Anxiety Scale (from 4.29 ± 3.93 to 23.24 ± 11.01; P < 0.001), hemoglobin (from 13.7 ± 0.79 to 14.6 ± 1.31; P = .022), and lymphocyte count (from 1961.7 ± 385.6 to 2448.7 ± 775.8; P = .01), but negative for CD8+ T lymphocytes (from 34.0 ± 8.82 to 30.0 ± 6.64; P = .046). CONCLUSIONS: A higher lymphocyte count in the MOH group relative to the MWA group may indicate a chronic inflammatory state. Several clinical and laboratorial characteristics have a range along a spectrum extending from healthy subjects to patients suffering from chronic forms of migraine.

Effects of insulin and clonazepam on DNA damage in diabetic rats submitted to the forced swimming test.

Diabetes mellitus (DM) is a chronic hyperglycemic state. DM may be associated with moderate cognitive deficits and neurophysiologic/structural changes in the brain (diabetic encephalopathy). Psychiatric manifestations seem to accompany this encephalopathy, since the prevalence of depression in diabetic patients is much higher than in the general population, and clonazepam is being used to treat this complication. The excessive production of oxygen free radicals that may occur in diabetes induces a variety of lesions in macromolecules, including DNA. In this work, we analyzed DNA damage in leukocytes from streptozotocin-induced diabetic rats submitted to the forced swimming test. The DNA damage index was significantly elevated (DI=61.00 ± 4.95) in the diabetic group compared to the control group (34.00 ± 1.26). Significant reductions of the damage index were observed in diabetic animals treated with insulin (45.00 ± 1.82), clonazepam (52.00 ± 1.22), or both agents (39.00 ± 5.83, not significantly different from control levels). Insulin plus clonazepam can protect against DNA damage in stressed diabetic rats.

Influence of depression and early adverse experiences on illicit drug dependence: a case-control study.

OBJECTIVE: The purpose of this study was to investigate the association between depression and illicit drug dependence among a Latin-American population. METHOD: illicit drug dependent patients (n = 137) and controls (n = 274) were interviewed using the Diagnostic Interview for Genetic Studies, in order to detect lifetime and current depressive disorder and illicit (cocaine, cannabis or inhalants) substance dependence. A regression analysis was used to estimate the odds ratio for drug dependence according to the diagnosis of depression. RESULTS: The lifetime diagnosis of depression (p = 0.001; OR = 4.9; 95% CI, 1.9-12.7) predicts illegal drugs dependence. Sociodemographic variables such as male gender (p < 0.001; OR = 36.8; 95% CI, 11.8-114) and occupational situation (p = 0.002; OR = 5.0; 95% CI, 1.8-13) as well as alcohol dependence (p = 0.01; OR = 3.4; 95% CI, 1.3-8.7) significantly influenced depression and drug dependence. Additional influent factors detected were having parents (p = 0.006; OR = 18.9; 95% CI, 2.3-158) or friends (p < 0.001; OR = 64.4; 95% CI, 6.5-636) who are illicit drugs dependents. CONCLUSION: although a causal relationship between dependence on illicit drugs and depression cannot be determined, comparison of the sequence of events point to the occurrence of depression later in life than dependence. It remains to be determined whether depression is a comorbidity of dependence, sharing etiological factors, or a consequence of drug abuse and/or abstinence.

Randomized clinical trial to change parental practices for drug use in a telehealth prevention program: a pilot study.

OBJECTIVES: Programs for parents have been found to have a direct positive impact on reducing the consumption of psychoactive substances by adolescents, as well as having an indirect impact on reducing risk factors and increasing protective factors. The present study aimed to verify if a telehealth prevention program based on a brief motivational intervention helps to reduce parental risk practices and increase parental protective practices for drug use in comparison with psychoeducation. METHODS: A pilot randomized controlled trial was performed at the National Service of Guidance and Information on Drug Use (Ligue 132), from September 2014 to December 2015, with the parents of adolescents (n=26). The outcome measures were parental style, risk, and protective parental practices. RESULTS: The brief motivational intervention was found to be more effective than psychoeducation in reducing the negligent behavior of parents. Furthermore, when comparing pre- and post-intervention data, the brief motivational intervention helped to change parental style and the large majority of parental practices: increasing positive monitoring, as well as decreasing physical abuse, relaxed discipline, inconsistent punishment, and negative monitoring. CONCLUSIONS: These results demonstrate that the telehealth intervention is effective in modifying the parental practices known to help in preventing drug use. Studies with more number of subjects are required so that the results can be substantiated and generalized.

Telephone counseling for young Brazilian cocaine and/or crack users. Who are these users?

OBJECTIVE: To describe the users' drug abuse characteristics, problematic behaviors associated with addiction, the motivation of teenagers and young adults to quit cocaine and/or crack abuse, and then compare these characteristics. METHODS: A cross-section study was conducted with 2390 cocaine/crack users (teenagers from 14 to 19 years of age, and young adults from 20 to 24 years of age); 1471 were young adults and 919 were teenagers who had called a phone counseling service between January 2006 and December 2013. Semi-structured interviews were performed via phone calls. The questionnaires included sociodemographic information; assessment of the characteristics of cocaine/crack abuse; assessment of the problematic behaviors; also, the Contemplation Ladder was used to evaluate the stages of readiness to cease substance abuse. RESULTS: Participants reported using cocaine (48.2%), crack and other smoking forms (36.7%) and combined consumption of both drugs (15%). Young adults were more prone to using crack or crack associated with cocaine (OR=1.9; CI 95%=1.05-1.57) and they were exposed to substance abuse for longer than two years (OR=3.45; CI 95%=2.84-4.18), when compared to teenagers. On the other hand, they showed higher readiness to quit. CONCLUSION: Data shows important differences in drug abuse characteristics, problematic behaviors and motivation to cease substance abuse between teenager and young adult cocaine and/or crack users. Behaviors displayed by young adults involve greater physical, mental and social health damages. These findings reinforce the importance of public policy to act on prevention and promoting health, to increase protection factors among teenagers and lower risks and losses during adult life.

CBI-20: Psychometric Properties for the Coping Behaviors Inventory for Alcohol Abuse in Brazil.

For any professional, it is of crucial importance to know not only how coping styles and strategies are present in an individual, but to know about its role to the treatment of alcohol abuse. Moreover, new approaches have emerged in this area in terms of relapse prevention and the counseling by phone can be an alternative. The aim of this study is to examine the factor structure of the Coping Behaviors Inventory (CBI) and to test its invariance across groups face-to-face and phone counseling in Brazil. For this purpose, two studies were carried out: study I, the factor structure was revisited in terms of exploratory factor analysis. Study II, face-to-face and phone counseling were examined through confirmatory factor analysis and multigroup analysis. The results confirmed the 4-factor solution with a revised model for the removal of 16 items. Thus presented, a reduced version with better indexes than the previous versions developed over the last 30 years that was ones reformulated from 60 items. The Internal consistency for study I presented α = 0.90 and homogeneity was between 0.17 and 0.5). In addition the KMO = 0.9 = 0.932, X ( df = 630 ) 2 = 6091.94, p < 0.0 < 0.001. In study II, cronbach's alpha = 0.91 and homogeneity 0.23-0.61 (telemedicine treatment) and α = 0.90 0.17 to 0.63 (face-to-face treatment). In the CFA, the examination of the current version has better fit than the that the traditional model. Moreover, the new version showed convergent validity with the IDHEA questionnaire. In the multigroup analysis no significant changes between groups to a metric level. Finally, the Brazilian version of inventory showed no differences between the phone counseling and face-to-face participants in a metric level after a multigroup analysis.

In vitro model to study cocaine and its contaminants.

Cocaine is one of the most popular illicit drug worldwide. Due its great addictive potential, which leads to euphoria and hyperactivity, it is considered a public health concern. At the central nervous system, the drug acts inhibiting catecholamine re-uptake. It is now known that in addition to the toxicity of the drug itself, the contaminants present in the street drug have raised concern about the harmful effects on health. Toxicological in vivo and in vitro studies have demonstrated the toxic effects of cocaine correlated with the generation of reactive oxygen species (ROS), which in turn lead to oxidative damage to the cells. Therefore the aim of this work was to propose an in vitro model that reunites the main parameters of toxicity of the cocaine already observed in the literature so far, and we tested this model using cocaine and seizure cocaine sample (SCS), kindly provided by Federal Police of Brazil. For that, we used a C6 glioblastoma cells and evaluated cell death, oxygen reactive species induction, oxidation of macromolecules as membrane lipids and DNA and loss of mitochondrial membrane potential after cocaine exposure. The results showed that cocaine can decrease cellular viability in a dose-dependent way in the C6 cell immortalized and astrocytes primary culture. Cocaine also induced cellular death by apoptosis. However, in the seizure cocaine sample (SCS), the predominant cell death was due to necrosis. Using dichlorofluorescein (DCF) assay, we confirmed ROS production after cocaine exposition. In agreement with these findings, occurred an increasing in MDA production, as well as increased superoxide dismutase (SOD) and catalase (CAT) activity. The induction of DNA damage was observed after cocaine. Our results demonstrate the occurrence of mitochondrial dysfunction by depolarization of mitochondrial membrane as a consequence of cocaine treatment. In summary, these results demonstrated that cocaine can induce reactive oxygen species formation, leading to oxidative stress. As a consequence of this unbalance, DNA damage, lipidic peroxidation and loss of mitochondrial membrane occurred, which could be an answer to cell death observed.

Oxidative stress parameters in diabetic rats submitted to forced swimming test: the clonazepam effect.

Diabetes-associated depression may occur due to changes in the quality of life imposed by treatment, or may be a consequence of the biochemical changes accompanying the disease. We evaluated the oxidative stress from diabetic animals submitted to an experimental model of depression and the effects of clonazepam. Male Wistar rats were induced to diabetes with streptozotocin and submitted to forced swimming test. Clonazepam was administered 24, 5 and 1 h before test. The animals were sacrificed by decapitation, and plasma and erythrocytes were separated, as well as hippocampus, cortex and striatum. Reactive species of thiobarbituric acid (TBARS) and total antioxidant reactivity (TAR) as well as antioxidant enzyme activities catalase (CAT) and superoxide dismutase (SOD) were evaluated. Results showed a significant increase of TBARS and a significant decrease of TAR in plasma from diabetic animals, which was altered by clonazepam. There were no effects of CAT and SOD activities in erythrocytes from tested animals. The results observed in hippocampus showed a significant increase of TBARS from diabetic rats, altered by clonazepam, and no one alteration was verified in TAR. The significant increase of TBARS and the significant decrease of TAR in cortex from diabetic rats were not altered by clonazepam administration. There were no alterations of TBARS and TAR in striatum from tested animals. Besides, clonazepam reverses the immobility in diabetic rats. Considering the action of clonazepam, it is suggested that it could be an alternative therapeutic for depression to diabetic patients, once it could give a protection against free radicals.

Correlation between drug treatment adherence and lithium treatment attitudes and knowledge by bipolar patients.

BACKGROUND: Non-adherence should always be investigated when there is a failure in bipolar treatments, since it is known that reported non-adherence rates in bipolar disorder treatment for long-term prophylactic pharmacotherapy range from 18% to 52%, with a median prevalence of 44.7%. Several factors are related to the poor adherence and reduction of medication efficiency, such as the different types of bipolar disorder, the presence of side effects, medication interactions, level of patient's knowledge about the disorder and their attitude towards treatment, complexity of medical regimens and the doctor-patient relationship. METHODS: Bipolar disorder outpatients under lithium treatment from the Hospital de Clínicas and Materno Infantil Presidente Vargas of Porto Alegre were recruited. All the patients had bipolar disorder and gave informed consent to participate in a clinical interview (106), answered the Lithium Attitudes Questionnaire (LAQ), Lithium Knowledge Test (LKT), Medication Adherence Rating Scale (MARS) and had plasma and red blood cells lithium measurements to assess their medication adherence and the factors that influenced it. RESULTS: 85.6% of bipolar disorder were adherent to lithium treatment showing plasma lithium between 0.6 and 1.2 mmol/L. There was an inverted correlation between the total LAQ score with plasma and red blood cells, a positive correlation between LKT and MARS with plasma and red blood cell lithium. CONCLUSION: These results confirmed that knowledge level is directly correlated to treatment adherence and patients' attitudes, lower adherence, general opposition to prophylaxis, fear of side effects, denial of therapeutic effectiveness and illness severity.

Laboratory diagnosis of toluene-based inhalants abuse.

UNLABELLED: Toluene is the main substance contained in products used as inhalants. The frequent abuse of toluene-based inhalants requires the definition of a simple laboratory parameter that allows acute exposure assessment. This study aimed at defining urinary hippuric acid (UHA) levels related to intentional exposure to toluene, and to correlate them to blood toluene concentration (BT). METHODS: BT and UHA levels were measured in 65 homeless adolescents of Porto Alegre, Brazil. RESULTS: Toluene was detected in 91.9% of the investigated population, who presented BT levels from 0.5 to 83.7 microg/mL. There was good correlation between UHA and BT concentrations (r = 0.78), and in homeless adolescents, UHA levels higher than 3.0 g/g creatinine indicate intentional exposure to toluene. CONCLUSIONS: The determination of UHA concentrations can be used as a screening method for the detection of intentional exposure to toluene, but its diagnosis must include BT toluene dosage, as well as circumstantial and clinical evidence.

Factors Associated With Attrition in Randomized Controlled Trials of Vocal Rehabilitation: Systematic Review and Meta-Analysis.

OBJECTIVES/HYPOTHESIS: This study aimed to determine the dropout rates and the reasons for dropout in randomized clinical trials of vocal rehabilitation. STUDY DESIGN: This study used systematic review and meta-analysis (CRD42013003807). METHODS: We included randomized controlled trials for voice disorders. In June 2015, we searched the following databases: MEDLINE, EMBASE, Cochrane, Clinical Trials, and AJSLP. The titles and abstracts or full texts of articles were independently analyzed by two reviewers. Study quality was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) scale. Our initial research base included more than 8491 articles. RESULTS: A total of 51 articles were obtained using our eligibility criteria. The low-quality studies evaluated had higher dropout rates (odds ratio: 3.3, 95% confidence interval: 1.04-12.9). Studies with healthy patients (45%) or vocal training versus no training (25%) also had higher dropout rates. Methodological issues seemed to have a greater influence on the dropout rates of the studies included in the co-occurrence matrix. CONCLUSIONS: Dropout rates of approximately 15% occur in randomized clinical trials of speech therapy when assessed by the Grading of Recommendations Assessment, Development and Evaluation. Studies with lower methodological quality had higher patient loss rates. Methodological and clinical reasons accounted for the highest dropout rates in the studies included in this meta-analysis.

Dropout Prevalence and Associated Factors in Randomized Clinical Trials of Adolescents Treated for Depression: Systematic Review and Meta-analysis.

PURPOSE: Depression currently affects 350 million people, and its prevalence among adolescents is 4% to 8%. Adolescents who abandon antidepressant treatment or drop out of clinical trials are less likely to recover or experience a remission of symptoms because they are not being followed up by a medical team. The objective of this study was to analyze the dropout rates of randomized clinical trials of depressed adolescents receiving treatment with antidepressant drugs and the factors associated with nonadherence by summarizing this information in a systematic review and meta-analysis. METHODS: Articles were retrieved from MEDLINE, EMBASE, Cochrane, Clinical Trial, PsycINFO, and Web of Science using the MeSH terms "depressive disorder," "randomized trials," and "adolescents." The evaluation of study quality was performed by using the Cochrane Handbook for Systematic Reviews of Interventions and the Jadad scale. FINDINGS: The final sample included 50 articles, of which 44 presented dropout rates. The overall dropout prevalence was 23% (95% CI, 20-27; P < 0.0001). Participants aged ≥16 years, those treated with serotonin norepinephrine reuptake inhibitors, and those receiving medication only exhibited the highest dropout prevalence, respectively (33% [95% CI, 27-39], 45% [95% CI, 31-64], and 15% [95% CI, 13-17]). The adverse effects most associated with dropout were attempted suicide followed by mania, skin rash, and headache. Problems relating to clinical trials and family arbitration were also related with dropout. IMPLICATIONS: Serotonin/norepinephrine reuptake inhibitor treatment, adolescent age >16 years, and receiving medication were the only factors demonstrating a higher association with dropout rates. Selective serotonin reuptake inhibitors were linked to the lowest prevalence, probably due to fewer perceived problems with related adverse effects and higher efficacy in adolescents. Cognitive-behavioral therapy combined with pharmacotherapy produced a lower nonadherence prevalence; this approach can be an alternative to avoid dropouts and relapse. Prospero identifier: CRD42014013475.

Ultrasonic rat vocalizations during the formalin test: a measure of the affective dimension of pain?

The emission of ultrasonic vocalization (USV) by rats submitted to the formalin test has not yet been demonstrated. We performed two experiments to establish the formalin concentration to induce USV and the relationship of USV emission with motor behaviors and the effects of morphine and naloxone on USV during the formalin test. Male Wistar rats were used. In Experiment 1, 3 different groups of rats were subcutaneously injected with 5%, 10%, or 12.5% formalin in 1 of the anterior paws. Experiment 2 was intended to verify the effect of morphine 1, 2.5, or 5 mg/kg on USV during the 12.5% formalin test, whereas other groups of rats received naloxone 2 mg/kg with each one of the morphine doses to verify the specificity of opioid action. USV and motor behaviors were simultaneously measured in 5-min windows for 40 min, and early (0-5 min), interphase (5-20 min), and late (20-40 min) phases of the test were characterized. Vocalization was detected mostly during the interphase of the formalin test, mainly after formalin 12.5%. Morphine suppressed USV in a naloxone-reversible manner. This is a demonstration of USV during the formalin test, allowing the inclusion of an additional nonreflex behavioral measure to help characterize more clinically relevant integrated behavioral patterns in this rat model of pain.

Validation of the Portuguese version of the Lithium Attitudes Questionnaire (LAQ) in bipolar patients treated with lithium: cross-over study.

BACKGROUND: Poor adherence to lithium is very common in bipolar patients and it is a frequent cause of recurrence during prophylactic treatment. Several reports suggest that attitudes of bipolar patients interfere with adherence to lithium. The Lithium Attitudes Questionnaire (LAQ) is a brief questionnaire developed as a means of identifying and grouping the problems patients commonly have with taking lithium regularly. The original version is validated in patients, but a validated version in Portuguese is not yet available. METHODS: One-hundred six patients with bipolar disorder (DSM-IV criteria) criteria under lithium treatment for at least one month were assessed using LAQ. LAQ is a brief questionnaire administered under interview conditions, which includes 19 items rating attitudes towards prophylactic lithium treatment. We analysed the internal consistency, concurrent validity, sensitivity and specificity of the Portuguese version of LAQ. RESULTS: The internal consistency, evaluated by Cronbach's alpha was 0.78. The mean total LAQ score was 4.1. Concurrent validity was confirmed by a negative correlation between plasma lithium concentration and total LAQ score (r = -0,198; p = 0.048). We analysed the scale's discriminative capacity revealing a sensitivity of 69% and a specificity of 71% in the identification of negative attitudes of bipolar patients. CONCLUSION: The psychometric assessment of the Portuguese version of LAQ showed good internal consistency, sensitivity and specificity. The results were similar to the original version in relation to attitudes of bipolar patients towards lithium therapy.

Adaptation and validation of the Portuguese version of the Lithium Knowledge Test (LKT) of bipolar patients treated with lithium: cross-over study.

OBJECTIVE: Adherence problems are a common feature among bipolar patients. A recent study showed that lithium knowledge was the main difference between adherent and non adherents bipolar patients. The Lithium Knowledge Test (LKT), a brief questionnaire, was developed as a means of identifying aspects of patients' practical and pharmacological knowledge which are important if therapy is to be safe and effective. The original English version is validated in psychiatric population, but a validated Portuguese one is not yet available. METHODS: One hundred six patients selected were diagnosed with bipolar disorder (I or II) according to DSM-IV criteria and had to be on lithium treatment for at least one month. The LKT was administered on only one occasion. We analysed the internal consistency, concurrent validity, sensitivity and specificity of the LKT for the detection of the knowledge about lithium treatment of bipolar patients. RESULTS: The internal consistency, evaluated by Cronbach's alpha was 0.596. The mean of total score LKT by bipolar patients was 9.0 (SD: 0.75) for men and 8.74 (SD: 0.44) for women. Concurrent validity based on plasma lithium concentration showed a significant correlation between the total LKT score and plasma lithium (r = 0.232; p = 0.020). The sensitivity was 84% and specificity was 81%. CONCLUSION: LKT is a rapid, reliable instrument which appears to be as effective as a lengthier standard interview with a lithium clinic doctor, and which has a high level of acceptability to lithium patients. We found that the psychometric assessment of the Portuguese version of LKT showed good internal consistency, sensitivity and specificity.