Short-term effects of the strengthening families Program (SFP 10-14) in Brazil: a cluster randomized controlled trial.

INTRODUCTION: This study reports the evaluation of the short-term effects of the Strengthening Families Program (SFP 10-14), adapted as Famílias Fortes (Strong Families) in Brazil, on preventing adolescent drug use and improving parenting behaviors. METHODS: A two-arm, parallel cluster randomized controlled trial was conducted in 60 Social Assistance Reference Centers (SARC) from 12 Brazilian municipalities. In each city, the SARC were randomly assigned to the intervention or control group. A total of 805 families participated in the study, each contributing data from one parent or legal guardian and one adolescent totaling 1,610 participants. Data collection occurred before intervention implementation and 6 months after baseline collection. Data were analyzed using multilevel mixed-effects modeling with repeated measures in two different paradigms: Intention to Treat (ITT) and Per protocol (PP). The study was registered in the Brazilian Ministry of Health Register of Clinical Trials (REBEC), under protocol no. RBR-5hz9g6z. RESULTS: Considering the ITT paradigm, the program reduced the chance of parents and legal guardians being classified as negligent by 60% (95%CI 0.21; 0.78), increased the use of nonviolent discipline by caregivers (Coef 0.33, 95%CI 0.01; 0.64) and decreased the chance of adults exposing adolescents to their drunken episodes by 80% (95%CI 0.06; 0.54). No program effects were observed on outcomes related to adolescent drug use. Similar results were found for the PP paradigm. CONCLUSION: The positive effects on family outcomes suggest preventive potential of the program among the Brazilian population. Long-term evaluations are necessary to verify if the program can also achieve the drug use reduction goals not observed in the short term.

Substance use and adolescent mental health during the COVID-19 pandemic in Brazil: a longitudinal approach.

OBJECTIVE: To describe the changes in alcohol and drug use by Brazilian adolescents during the COVID-19 pandemic (April-August 2021), and to analyze the relationship between alcohol use changes and psychiatric symptomatology. METHODS: A secondary analysis with a longitudinal approach was performed with data from a cluster-randomized controlled trial, conducted in 73 public middle schools in three Brazilian cities, to evaluate the effectiveness of a drug use prevention program. The sample included 535 students (61% girls; Mage = 15.2 years). Data were collected pre-intervention (February-March 2019), after 9 months (November-December 2019), and after 26 months (April-August 2021), when the students were in their first year of high school. The authors analyzed drug use prevalence (alcohol, binge drinking, tobacco, inhalants, marijuana, cocaine, and crack) in a lifetime, past year, and past month periods, and the association between alcohol use change subsamples with psychiatric symptoms. Logistic regressions were adjusted by sex, age, socioeconomic status, city, and group (control and intervention). RESULTS: The present findings suggest that the COVID-19 pandemic led to a decrease in past-year substance use and in past-month substance use frequency, despite the gradually increased (but decelerating) prevalence of lifetime use. However, some adolescents initiated, maintained, or increased the frequency of their alcohol use. Mainly, they were more likely to present behavioral problems, as well as symptoms of inattentive hyperactivity, and peer and emotional problems. CONCLUSIONS: Despite the extensive decline in substance use during the pandemic period, these results suggest an association between previous mental health conditions and behavioral risk factors, leading to increased alcohol consumption and behavioral disorders manifestations.

Economic Evaluation of Novel Models of Care for Patients With Acute Medical Problems.

Importance: During COVID-19, Singapore simultaneously experienced a dengue outbreak, and acute hospitals were under pressure to lower bed occupancy rates. This led to new models of care to treat patients with acute, low-severity medical conditions either at home, in a hospital-at-home (HaH) model, or in a clinic-style setting sited at the emergency department in an ambulatory care team (ACT) model, but a reliable cost analysis for these models is lacking. Objective: To compare personnel costs of HaH and ACT with inpatient care. Design, Setting, and Participants: In this economic evaluation study, time-driven activity-based costing was used to compare the personnel cost of inpatient care with treating dengue via HaH and treating chest pain via ACT. Participants were patients with nonsevere dengue and chest pain unrelated to a coronary event admitted via the emergency department to the internal medicine service of a tertiary hospital in Singapore. Exposures: HaH for dengue and ACT for chest pain. Main Outcomes and Measures: A process map was created for the patient journey for a typical patient with each condition. The amount of time personnel spent on delivering care was estimated and the cost per minute determined based on their wages in 2022. The total cost of care was calculated by multiplying the time spent by the per-minute cost of the personnel resource and summing all costs. Results: Compared with inpatient care, HaH used 50% less nursing time (418 minutes, 95% uncertainty interval [UI], 370 to 465 minutes) but 80% more medical time (303 minutes, 95% UI, 270 to 338 minutes) per case of dengue. If implemented nationally, HaH would save an estimated 56 828 SGD per year (95% UI, -169 497 to 281 412 SGD [US $41 856; 95% UI, -$124 839 to $207 268]). The probability that HaH is cost saving was 69.2%. Compared with inpatient care, ACT used 15% less nursing time (296 minutes, 95% UI, 257 to 335 minutes) and 50% less medical time (57 minutes, 95% UI, 46 to 69 minutes) per case of chest pain. If implemented nationally, ACT would save an estimated 1 561 185 SGD per year (95% UI, 1 040 666 to 2 086 518 SGD [US $1 149 862; 95% UI, $766 483 to $1 536 786]). The probability that ACT is cost saving was 100%. Conclusions and Relevance: This economic evaluation found that the HaH and ACT models decreased the overall personnel cost of care. Reorganizing hospital resources may help hospitals reap the benefits of reduced hospital-acquired infections, improved patient recovery, and reduced hospital bed occupancy rates.

Use of integrative and complementary health practices by Brazilian population: results from the 2019 National Health Survey.

BACKGROUND: In 2006, Brazil implemented the National Policy on Integrative and Complementary Practices of the SUS. and in 2015, the Brazilian Ministry of Health issued a reinforcement to this policy to increase access to integrative and complementary health practices (ICHP). In this study, we described the prevalence of ICHP in Brazilian adults according to their sociodemographic characteristics, self-perceived health, and chronic diseases. METHODS: This is a nationally representative cross-sectional survey including 64,194 participants from the 2019 Brazilian National Health Survey. Types of ICHP were categorized according to their purposes: health promotion (Tai chi/Lian gong/Qi gong, yoga, meditation, and integrative community therapy) or therapeutic practices (acupuncture, auricular acupressure, herbal treatment and phytotherapy, and homeopathy). Participants were classified as non-practitioners and practitioners, who in turn were grouped according to use of ICHP in the last 12 months: only used health promotion practices (HPP); only used therapeutic practices (TP); used both (HPTP). Multinomial logistic regressions were performed to estimate the associations of ICHP with sociodemographic characteristics, self-perceived health status, and chronic diseases. RESULTS: Brazilian adults showed an ICHP use prevalence of 6.13% [95%CI = 5.75-6.54]. Compared to non-practitioners, women and middle-aged adults were more likely to use any ICHP. Afro-Brazilians were less likely to use both HPP and HPTP, whereas Indigenous people were more likely to use both HPP and TP. We found a positive gradient of association among participants with higher income and educational attainment and access to any ICHP. People from rural areas and those with negative self-perceived health were more likely to use TP. Participants with arthritis/rheumatism, chronic back problems, and depression were more likely to use any ICHP. CONCLUSIONS: We found that 6% of Brazilian adults reported using ICHP in the previous 12 months. Women, middle-aged individuals, chronic patients, people with depression, and wealthier Brazilians are more likely to use any type of ICHP. Of note, rather than suggesting to expand the offer of these practices in the Brazilian public health system, this study diagnosed Brazilians' behavior of seeking for complementary healthcare.

The Indirect Effect of #Tamojunto2.0 Program on Bullying Through Reduction of Alcohol Use Initiation.

PURPOSE: The Brazilian version of the prevention program Unplugged, #Tamojunto, has had a positive effect on bullying prevention. However, the curriculum has recently been revised, owing to its negative effects on alcohol outcomes. This study evaluated the effect of the new version, #Tamojunto2.0, on bullying. For adolescents exposed to the school-based program #Tamojunto2.0, we investigated (1) whether the prevalence of bullying victimization and perpetration was reduced, (2) whether this reduction was moderated by gender, and (3) whether the program's effect on bullying was mediated by adolescents' alcohol use. METHODS: A cluster randomized controlled trial was conducted using 5,208 eighth-grade students from 73 Brazilian public schools. Baseline data were collected before program implementation, and follow-up data were collected nine months later. We used a multilevel mixed-effects model to examine the effect of #Tamojunto2.0 on bullying, and a moderation model to test the moderating effect of gender on program outcomes. A mediation analysis was performed to determine lifetime alcohol use as a mediator of the intervention effect on bullying. RESULTS: We found that the positive effect of #Tamojunto2.0 on bullying victimization (ß = -0.019, 95% confidence interval = -0.035; -0.002) and perpetration (ß = -0.027, 95% confidence interval = -0.051; -0.004) was mediated by a decrease in alcohol use, but not moderated by gender. DISCUSSION: #Tamojunto2.0 program can be indirectly effective in the prevention of bullying by decreasing adolescents' alcohol use. Moreover, alcohol and drug use prevention programs might also affect bullying outcomes through mediation, and we suggest that future studies consider this.

Strategically managing learning during perceptual decision making.

Making optimal decisions in the face of noise requires balancing short-term speed and accuracy. But a theory of optimality should account for the fact that short-term speed can influence long-term accuracy through learning. Here, we demonstrate that long-term learning is an important dynamical dimension of the speed-accuracy trade-off. We study learning trajectories in rats and formally characterize these dynamics in a theory expressed as both a recurrent neural network and an analytical extension of the drift-diffusion model that learns over time. The model reveals that choosing suboptimal response times to learn faster sacrifices immediate reward, but can lead to greater total reward. We empirically verify predictions of the theory, including a relationship between stimulus exposure and learning speed, and a modulation of reaction time by future learning prospects. We find that rats' strategies approximately maximize total reward over the full learning epoch, suggesting cognitive control over the learning process.

Factors associated with attending "open bar" parties amongst early adolescents.

BACKGROUND: "Open bar" parties are events where a flat fee is paid for unlimited alcohol consumption. At these events, alcohol intoxication is frequent amongst attendees. This study explored the prevalence of "open bar" attendance amongst Brazilian youth and the factors associated with this practice. METHODS: Data was collected at the baseline of randomized controlled trial amongst 5,213 8th grade students in three Brazilian cities. Weighted logistic regression was performed. RESULTS: Mean age was of 13.23 years (SE 0.01) and 17.1% of the students have reported attending "open bar" events in the past year. Attendees were wealthier, had higher odds to engage in binge drinking, to use marijuana, to be exposed to alcohol advertising, and to report more alcohol problems and clinical psychiatric symptoms when compared with non-attendees. CONCLUSIONS: The ban on selling alcohol to minors has not been properly enforced. Legislation to restrict alcohol promotions and advertising in Brazil needs to be implemented and effectively monitored.

Binge drinking in Brazilian adolescents: results of a national household survey.

This study aimed to estimate the prevalence of binge drinking and other alcohol consumption patterns and analyze the sociodemographic characteristics associated with binge drinking among Brazilian adolescents aged 15 to 17 years. A cross-sectional household survey including 2,315 adolescents from the 2019 Brazilian National Health Survey who answered a questionnaire on alcohol consumption (weekly frequency, average amount consumed in a drinking day, and binge drinking). A descriptive analysis of alcohol consumption by sociodemographic characteristics and a multivariable logistic regression model were performed. The prevalence of binge drinking (past 30 days) was 8.1% (95%CI: 6.2-10.3). Adolescents who did not attend school (OR = 2.8; 95%CI: 1.6-5.0) had greater odds of binge drinking than adolescents attending school. Higher socioeconomic status (measured via wealth score) was also associated with higher odds of binge drinking compared with lower socioeconomic status (e.g., 5th quintile vs. 1st quintile: OR = 2.9; 95%CI: 1.1-7.7). Girls had lower odds of binge drinking (OR = 0.5; 95%CI: 0.2-0.8) than boys. The prevalence of binge drinking among adolescents, especially boys, who did not attend school and had higher socioeconomic status was high. Monitoring alcohol consumption patterns in adolescents may provide important information on policies or actions to prevent binge drinking.

Does #Tamojunto alter the dynamic between drug use and school violence among youth? Secondary analysis from a large cluster-randomized trial.

The present study investigated how intervention might alter the relationship between perpetrating violence and later drug use. A cluster-randomized controlled trial design involving 72 schools (38 intervention, 34 control) and 6390 students attending grades 7 and 8 was employed in Brazil. Drug use and violence were assessed at three points. A random-intercept cross-lagged panel model examined the reciprocal association between drug use and school violence domains across the three data collection waves. For both groups, we found that the cross-lagged effect of perpetration on further drug use in adolescents was stronger than the reverse, but the interrelationship was not statistically significant between #Tamojunto and control schools. The carry-over effects of drug use and violence were also not significantly different between groups. There is a lack of evidence showing that #Tamojunto can modify the dynamics between drug use and school violence across the 21-month period. The direction of the causal effect (i.e., the more perpetration behavior, the more subsequent drug use behavior) is present, but weak in both groups. The trial registration protocol at the national Brazilian Register of Clinical Trials (REBEC) is #RBR-4mnv5g.

Maternal depression trajectories in childhood, subsequent maltreatment, and adolescent emotion regulation and self-esteem: the 2004 Pelotas birth cohort.

This study aimed to examine the impact of maternal depressive symptoms trajectories on 15-year-old adolescents' self-esteem and emotion regulation and test the mediating role of child maltreatment in this association. The 2004 Pelotas Birth Cohort is an ongoing cohort study originally comprised of 4231 live births in a southern Brazilian city. We examined a subsample of 1949 adolescents at age 15 years. Maternal depressive symptoms were assessed using the Edinburgh Postnatal Depression Scale. Trajectories of maternal depression from 3 months until the 11-year follow-up were calculated using a group-based modeling approach. Child maltreatment at age 11 years was measured using the parent-report version of the Parent-Child Conflict Tactics Scale. Adolescent outcomes at age 15 years were assessed by the self-report version of the Rosenberg Self-esteem Scale and the Emotion Regulation Index for Children and Adolescents. Path model analysis was conducted using a structural equation modeling framework in Mplus software. All maternal depression trajectories were negatively associated with offspring self-esteem and emotion regulation compared to the reference group (low depression trajectory). There was a significant indirect effect of maternal depression trajectories on emotion regulation mediated via child maltreatment. No evidence of moderation by sex was found for any pathway. The effects of maternal depression on adolescents' emotion regulation are partly mediated by child maltreatment at age 11.

Screen-and-treat approach in managing cervical cancer precursor lesions: An observational study with 524 women.

OBJECTIVE: To detect factors related to overtreatment with the "Screen-and-treat" approach (S&T) in women with suspicious cervical precancerous lesions. STUDY DESIGN: A retrospective observational study of 524 women with high-grade squamous intraepithelial lesions (HSIL) or more severe (HSIL+) in cytology, treated by the Large Loop Excision of the Transformation Zone (LLETZ): 161 without a previous biopsy (S&T group) and 363 with a previous biopsy (biopsy group) from January 2017 to July 2020. The main outcome was a diagnosis of LLETZ: negative (negative or low-grade squamous intraepithlelial lesion LSIL) or HSIL+. A negative diagnosis was interpreted as "overtreatment." Results were analyzed as a function of the S&T approach (whether previous biopsy or not). Variables were obtained from medical records, and were compared with Chi-square or Fisher's exact test (p, p-value), to estimate the chances of a logistic regression analysis (Odds Ratio, OR, or admitting a Confidence Interval (CI) of 95 %). RESULTS: No differences were observed in groups regarding menopausal status, smoking, hormonal contraceptive use, colposcopy findings, LLETZ diagnosis, and recurrence. Comparing biopsy vs S&T groups, the frequency of women over 40 years was 28.4 % vs 39.7 % (p = 0.011), and transformation zone type 3 was 12.2 vs 26.8 % (p < 0.001), respectively. In women managed by S&T, when compared to a LLETZ diagnosis, an HSIL+ result was more frequent in women presenting with TZ 1 (93.1 % TZ1 vs 78.5 % TZ2 vs 73.8 % TZ3, p = 0.008) and in women with abnormal colposcopy (92.9 % abnormal vs 38.1 % negative, p < 0.001). Multiple regression analysis found that women with negative colposcopic findings presented a higher risk for negative LLETZ diagnosis (LSIL/Negative final histology) (18.6; 6.18-56.02). CONCLUSIONS: No difference was observed in the LLETZ diagnosis in women who did or did not use the S&T approach: it was adequate for women referred by cytological HSIL along with high-grade colposcopic findings.

Changes in alcohol beliefs mediate the effects of a school-based prevention program on alcohol use among Brazilian adolescents.

OBJECTIVE: To investigate the mechanisms of the #Tamojunto2.0 program that mediated the prevention of lifetime alcohol and drug use, including drug knowledge, behavioral beliefs, attitudes, decision-making skills, and refusal skills. METHODS: A cluster-randomized controlled trial was conducted in 73 public middle schools in three Brazilian cities. The sample included 5208 students (49.4 % girls; Mage = 13.2 years). The intervention group attended twelve #Tamojunto2.0 lessons conducted by their previously trained teachers. The control group did not receive any intervention. Data were collected pre-intervention and at the 9-months follow-up. We performed multiple mediation models (for the whole sample, users, and non-users) with a post-estimation adjustment to standard errors to account for nesting. We analyzed all available mediators simultaneously according to each drug: alcohol, binge drinking, tobacco, marijuana, and inhalant lifetime use. To handle missing data, we used the "full-information maximum-likelihood" paradigm. RESULTS: Outcomes in the whole sample and among non-users showed that #Tamojunto2.0 indirectly prevented lifetime alcohol use and binge drinking by increasing negative and non-positive alcohol beliefs. Only the direct effect on decreasing lifetime alcohol consumption was statistically significant. However, an indirect increase in binge drinking was observed through knowledge about alcohol, but the direct effect was not statistically significant. No effects were reported for marijuana, tobacco, or inhalants. Among users, no statistically significant effects were found for alcohol or drug use. CONCLUSIONS: The results suggest that the #Tamojunto2.0 program was only effective in delaying alcohol consumption via increasing negative and non-positive alcohol beliefs. It seems that mediating mechanisms vary depending on contextual characteristics, differences in socializing among adolescents, features of the educational systems, psychosocial conditions, or, fidelity issues of program implementation.

Effectiveness of D.A.R.E/Keepin' it REAL bullying prevention program among Brazilian students.

INTRODUCTION: Given the growing scientific evidence on the detrimental effects of bullying, several prevention programs have been implemented internationally to prevent this behavior among students. Brazil's Educational Program for Drug and Violence Resistance (PROERD) is an adaptation of US' DARE/Keepin' it REAL program, being the most widespread school-based prevention program in the country. However, it has been offered without any effectiveness evaluation. As such, this study evaluates the effectiveness of PROERD in reducing bullying perpetration and victimization among students. METHODS: Two cluster randomized controlled trials were carried out with 4030 students (1727 5th graders and 2303 7th graders) in 30 public schools in São Paulo, Brazil. The intervention group attended 10 PROERD classes taught by trained police officers whereas the control group underwent no intervention. Data were collected by self-administered questionnaires using smartphones at two moments (baseline preintervention and 9-month follow-up). Multilevel analysis included two paradigms, complete cases (CC) and intention-to-treat (ITT), using Full Information Maximum Likelihood (FIML) and Multiple Imputation (MI). RESULTS AND CONCLUSION: Results show no statistical difference between groups, indicating lack of evidence on PROERD's effectiveness in preventing bullying behaviors. The insufficient number of classes on bullying prevention and the lack of cultural adaptation may explain these unexpected results. New in-depth evaluation studies concerning the program's components and process are needed.

Early Detrusor Application of Botulinum Toxin A Results in Reduced Bladder Hypertrophy and Fibrosis after Spinal Cord Injury in a Rodent Model.

Following spinal cord injury (SCI), pathological reflexes develop that result in altered bladder function and sphincter dis-coordination, with accompanying changes in the detrusor. Bladder chemodenervation is known to ablate the pathological reflexes, but the resultant effects on the bladder tissue are poorly defined. In a rodent model of contusion SCI, we examined the effect of early bladder chemodenervation with botulinum toxin A (BoNT-A) on bladder histopathology and collagen deposition. Adult female Long Evans rats were given a severe contusion SCI at spinal level T9. The SCI rats immediately underwent open laparotomy and received detrusor injections of either BoNT-A (10 U/animal) or saline. At eight weeks post injury, the bladders were collected, weighed, and examined histologically. BoNT-A injected bladders of SCI rats (SCI + BoNT-A) weighed significantly less than saline injected bladders of SCI rats (SCI + saline) (241 ± 25 mg vs. 183 ± 42 mg; p < 0.05). Histological analyses showed that SCI resulted in significantly thicker bladder walls due to detrusor hypertrophy and fibrosis compared to bladders from uninjured animals (339 ± 89.0 µm vs. 193 ± 47.9 µm; p < 0.0001). SCI + BoNT-A animals had significantly thinner bladder walls compared to SCI + saline animals (202 ± 55.4 µm vs. 339 ± 89.0 µm; p < 0.0001). SCI + BoNT-A animals had collagen organization in the bladder walls similar to that of uninjured animals. Detrusor chemodenervation soon after SCI appears to preserve bladder tissue integrity by reducing the development of detrusor fibrosis and hypertrophy associated with SCI.

Implementation fidelity of a Brazilian drug use prevention program and its effect among adolescents: a mixed-methods study.

BACKGROUND: Based on the US DARE-kiR, a version of the Keepin' it REAL program, the Drug and Violence Resistance Educational Program (PROERD) is the most widely implemented Brazilian prevention program. It originates from the translation of the DARE-kiR, a version of the Keepin' it REAL program. Previous results suggest its inefficiency in preventing drug use among Brazilian adolescents. Since kiR fidelity can impact program outcomes, this mixed-methods study evaluates the PROERD implementation fidelity and its effects on preventing drug use among adolescents. METHODS: Data from two cluster randomized controlled trials (cRCTs) with 4,030 students from 30 public schools in São Paulo (1,727 fifth graders and 2,303 seventh graders), assessed at two-time points, were analyzed quantitatively. After implementing each lesson during the cRCT, 19 PROERD instructors answered fidelity forms. The effect of PROERD fidelity on alcohol, cigarettes, marijuana, inhalant, and cocaine use (the last two only among seventh graders) in the six months prior to follow-up assessment was analyzed by logistic regressions for fifth grade and mixed effect models for seventh graders. For qualitative analysis, semi-structured interviews were conducted with PROERD instructors and investigated by thematic analysis. RESULTS: Quantitative analysis showed that PROERD implementation fidelity had no impact on drug use among fifth and seventh graders. Conversely, the qualitative analysis revealed important aspects that may influence implementation fidelity and consequently program effectiveness, such as adaptations made by instructors, school infrastructure, among others, besides program application. CONCLUSION: PROERD requires cultural adaptation to improve its implementation in Brazilian public schools.

Revisão sistemática sobre o efeito do programa escolar de prevenção ao uso de drogas Keepin' it REAL: traduzido e implementado no Brasil pelo PROERD / A systematic review of the effect of the school-based drug prevention program Keepin' it REAL: translated and implemented in Brazil by PROERD

Resumo O Programa Educacional de Resistência às Drogas (PROERD) é o programa escolar de prevenção mais disseminado no Brasil, seu atual currículo é baseado no programa norte-americano Keepin'it REAL (kiR). Não há na literatura evidência de efetividade do PROERD na prevenção ao uso de drogas, sendo necessários estudos complementares que auxiliem a compreensão desses achados. O objetivo do presente estudo é realizar uma síntese das evidências do efeito do currículo que deu origem ao PROERD: o kiR. Através de revisão sistemática encontrou-se 17 estudos que reportaram resultados de efeito de diferentes versões do kiR no uso de drogas e/ou violência. Com exceção do estudo brasileiro, não foram encontrados estudos que avaliassem o efeito no uso de drogas da versão aplicada por policiais (DARE-kiR), a mesma implementada pelo PROERD. Foram encontradas evidências favoráveis do kiR na prevenção ao uso de drogas para o currículo do 7º ano, que contrariam os resultados de efeito nulo do PROERD. Não foram encontradas evidências internacionais do efeito do kiR no currículo do 5º ano, assim como o estudo do PROERD. Sugere-se que revisões no currículo do 7º ano do PROERD para que ele possa refletir os resultados internacionais e que o currículo do 5º ano posso ser repensado considerando as evidências negativas internacionais.

Abstract The Drug Resistance Educational Program (PROERD) is Brazil's most widespread school-based prevention program; its current curriculum is based on the North American Keepin' it REAL (kiR) program. There is no evidence of the effectiveness of PROERD in preventing drug use, pointing to the need for further studies to understand these findings. The aim of the study was to synthesis the evidence of the effect of the kiR curriculum (PROERD) through a systematic review. We found 17 studies that reported the effects of different versions of kiR on drug use and/or violence. Except for the Brazilian study, no studies were found that assessed the effect on drug use of the version applied by police officers (DARE-kiR), the same one implemented by PROERD. Favorable evidence of kiR in drug use prevention was found for the 7th-grade curriculum, which contradicts the PROERD's null-effect results. No international evidence of the effect of kiR was found in the 5th-grade curriculum, in the same line as the PROERD's study. It is suggested that PROERD's 7th-grade curriculum should be revised to reflect international results and that the 5th-grade curriculum should be reconsidered in light of the negative international evidence.

Mast cell-T cell axis alters development of colitis-dependent and colitis-independent colorectal tumours: potential for therapeutically targeting via mast cell inhibition.

BACKGROUND: Colorectal cancer (CRC) has a high mortality rate and can develop in either colitis-dependent (colitis-associated (CA)-CRC) or colitis-independent (sporadic (s)CRC) manner. There has been a significant debate about whether mast cells (MCs) promote or inhibit the development of CRC. Herein we investigated MC activity throughout the multistepped development of CRC in both human patients and animal models. METHODS: We analyzed human patient matched samples of healthy colon vs CRC tissue alongside conducting a The Cancer Genome Atlas-based immunogenomic analysis and multiple experiments employing genetically engineered mouse (GEM) models. RESULTS: Analyzing human CRC samples revealed that MCs can be active or inactive in this disease. An activated MC population decreased the number of tumor-residing CD8 T cells. In mice, MC deficiency decreased the development of CA-CRC lesions, while it increased the density of tumor-based CD8 infiltration. Furthermore, co-culture experiments revealed that tumor-primed MCs promote apoptosis in CRC cells. In MC-deficient mice, we found that MCs inhibited the development of sCRC lesions. Further exploration of this with several GEM models confirmed that different immune responses alter and are altered by MC activity, which directly alters colon tumorigenesis. Since rescuing MC activity with bone marrow transplantation in MC-deficient mice or pharmacologically inhibiting MC effects impacts the development of sCRC lesions, we explored its therapeutic potential against CRC. MC activity promoted CRC cell engraftment by inhibiting CD8+ cell infiltration in tumors, pharmacologically blocking it inhibits the ability of allograft tumors to develop. This therapeutic strategy potentiated the cytotoxic activity of fluorouracil chemotherapy. CONCLUSION: Therefore, we suggest that MCs have a dual role throughout CRC development and are potential druggable targets against this disease.

A systematic review of the effect of the school-based drug prevention program Keepin' it REAL: translated and implemented in Brazil by PROERD. / Revisão sistemática sobre o efeito do programa escolar de prevenção ao uso de drogas Keepin' it REAL: traduzido e implementado no Brasil pelo PROERD.

The Drug Resistance Educational Program (PROERD) is Brazil's most widespread school-based prevention program; its current curriculum is based on the North American Keepin' it REAL (kiR) program. There is no evidence of the effectiveness of PROERD in preventing drug use, pointing to the need for further studies to understand these findings. The aim of the study was to synthesis the evidence of the effect of the kiR curriculum (PROERD) through a systematic review. We found 17 studies that reported the effects of different versions of kiR on drug use and/or violence. Except for the Brazilian study, no studies were found that assessed the effect on drug use of the version applied by police officers (DARE-kiR), the same one implemented by PROERD. Favorable evidence of kiR in drug use prevention was found for the 7th-grade curriculum, which contradicts the PROERD's null-effect results. No international evidence of the effect of kiR was found in the 5th-grade curriculum, in the same line as the PROERD's study. It is suggested that PROERD's 7th-grade curriculum should be revised to reflect international results and that the 5th-grade curriculum should be reconsidered in light of the negative international evidence.

O Programa Educacional de Resistência às Drogas (PROERD) é o programa escolar de prevenção mais disseminado no Brasil, seu atual currículo é baseado no programa norte-americano Keepin'it REAL (kiR). Não há na literatura evidência de efetividade do PROERD na prevenção ao uso de drogas, sendo necessários estudos complementares que auxiliem a compreensão desses achados. O objetivo do presente estudo é realizar uma síntese das evidências do efeito do currículo que deu origem ao PROERD: o kiR. Através de revisão sistemática encontrou-se 17 estudos que reportaram resultados de efeito de diferentes versões do kiR no uso de drogas e/ou violência. Com exceção do estudo brasileiro, não foram encontrados estudos que avaliassem o efeito no uso de drogas da versão aplicada por policiais (DARE-kiR), a mesma implementada pelo PROERD. Foram encontradas evidências favoráveis do kiR na prevenção ao uso de drogas para o currículo do 7º ano, que contrariam os resultados de efeito nulo do PROERD. Não foram encontradas evidências internacionais do efeito do kiR no currículo do 5º ano, assim como o estudo do PROERD. Sugere-se que revisões no currículo do 7º ano do PROERD para que ele possa refletir os resultados internacionais e que o currículo do 5º ano posso ser repensado considerando as evidências negativas internacionais.

Dose-sparing effect of two adjuvant formulations with a pandemic influenza A/H7N9 vaccine: A randomized, double-blind, placebo-controlled, phase 1 clinical trial.

The emergence of potentially pandemic viruses has resulted in preparedness efforts to develop candidate vaccines and adjuvant formulations. We evaluated the dose-sparing effect and safety of two distinct squalene-based oil-in-water adjuvant emulsion formulations (IB160 and SE) with influenza A/H7N9 antigen. This phase I, randomized, double-blind, placebo-controlled, dose-finding trial (NCT03330899), enrolled 432 healthy volunteers aged 18 to 59. Participants were randomly allocated to 8 groups: 1A) IB160 + 15µg H7N9, 1B) IB160 + 7.5µg H7N9, 1C) IB160 + 3.75µg H7N9, 2A) SE + 15µg H7N9, 2B) SE + 7.5µg H7N9, 2C) SE + 3.75µg H7N9, 3) unadjuvanted vaccine 15µg H7N9 and 4) placebo. Immunogenicity was evaluated through haemagglutination inhibition (HI) and microneutralization (MN) tests. Safety was evaluated by monitoring local and systemic, solicited and unsolicited adverse events (AE) and reactions (AR) 7 and 28 days after each study injection, respectively, whereas serious adverse events (SAE) were monitored up to 194 days post-second dose. A greater increase in antibody geometric mean titers (GMT) was observed in groups receiving adjuvanted vaccines. Vaccinees receiving IB160-adjuvanted formulations showed the greatest response in group 1B, which induced an HI GMT increase of 4.7 times, HI titers ≥40 in 45.2% of participants (MN titers ≥40 in 80.8%). Vaccinees receiving SE-adjuvanted vaccines showed the greatest response in group 2A, with an HI GMT increase of 2.5 times, HI titers ≥40 in 22.9% of participants (MN titers ≥40 in 65.7%). Frequencies of AE and AR were similar among groups. Pain at the administration site and headache were the most frequent local and systemic solicited ARs. The vaccine candidates were safe and the adjuvanted formulations have a potential dose-sparing effect on immunogenicity against influenza A/H7N9. The magnitude of this effect could be further explored.