Prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among university students / Prevalência e fatores associados ao uso de metilfenidato para neuroaprimoramento farmacológico entre estudantes universitários

ABSTRACT Objective To estimate the prevalence of and factors associated with the use of methylphenidate for cognitive enhancement among undergraduate students. Methods Simple random sample of students of the Universidade Federal de Minas Gerais (n=438), invited to answer an online questionnaire about the use of methylphenidate. Data collection occurred from September 2014 to January 2015. The sample was described by means of proportions, means and standard deviations. A multivariate analysis was performed using the Classification and Regression Tree algorithm to classify the cases of use of methylphenidate for cognitive enhancement in groups, based on the exposure variables. Results Out of 378 students included, 5.8% (n=22) reported using methylphenidate for cognitive enhancement; in that, 41% (9/22) in the 4 weeks prior to the survey. The housing situation was the variable most often associated with the use of methylphenidate for cognitive enhancement. Eleven students reported using methylphenidate for cognitive enhancement and other purposes 4 weeks prior to the survey, 27% of whom had no medical prescription to purchase it. Conclusion The use of methylphenidate for cognitive enhancement is frequent among Brazilian undergraduate students and should be considered a serious public health problem, especially due to risks of harm and adverse effects associated with its use.

RESUMO Objetivo Estimar a prevalência e os fatores associados ao uso de metilfenidato para neuroaprimoramento entre estudantes universitários. Métodos Amostra aleatória simples de discentes da Universidade Federal de Minas Gerais (n=438), convidados a responder um questionário online sobre o consumo de metilfenidato. A coleta ocorreu de setembro de 2014 a janeiro de 2015. A amostra foi descrita em termos de proporções, médias e desvio padrão. A análise multivariada foi realizada utilizando o algoritmo Classification and Regression Tree para classificação dos casos de uso do metilfenidato para neuroaprimoramento em grupos, com base nas variáveis de exposição. Resultados Dos 378 alunos incluídos, 5,8% (n=22) declararam ter feito uso de metilfenidato para neuroaprimoramento, sendo 41% (9/22) nas 4 semanas anteriores à pesquisa. A situação da moradia foi a variável mais associada ao uso de metilfenidato para neuroaprimoramento. Relataram o uso do metilfenidato para neuroaprimoramento e outros fins nas 4 semanas anteriores à pesquisa 11 estudantes, sendo que 27% não apresentaram prescrição médica para adquiri-lo. Conclusão O uso de metilfenidato para neuroaprimoramento ocorre no meio acadêmico brasileiro e deve ser considerado sério problema de saúde pública, principalmente diante dos riscos de danos e efeitos adversos associados ao seu uso.

Comparison of Nine Instruments to Calculate Anticholinergic Load in a Large Cohort of Older Outpatients: Association with Cognitive and Functional Decline, Falls, and Use of Laxatives.

OBJECTIVE: A patient's risk for anticholinergic adverse effects is frequently estimated by instruments evaluating the drugs included in his medication profile. It remains unknown, however, which characteristics should be included in such an assessment instrument aiming to reliably predict adverse anticholinergic outcomes. DESIGN: Cross-sectional study. SETTING: ESTHER cohort (Germany). PARTICIPANTS: Home-dwelling participants (N = 2,761) aged between 60 and 87 years. MEASUREMENTS: The association between anticholinergic load calculated with nine different instruments and four anticholinergic adverse outcomes was investigated in univariate and multivariate analyses. Therefore, linear models complemented with Kendall's tau rank correlation coefficients (ԏ) were applied for continuous outcomes and generalized linear models were used to derive odds ratios (ORs) with 95% confidence intervals (CIs) for binary endpoints. RESULTS: Based on the respective identification criteria for anticholinergic drugs, the nine instruments identified between 245 (9%) and 866 (31%) anticholinergic drug users (mean age ± SD: 73 ± 6 years; Mini-Mental State Examination [MMSE] score: 28.3 ± 2.07; Barthel Index: 97.1 ± 7.5; 291 reporting falls; 29 taking laxatives [surrogate for constipation]). In the multivariate analysis, only two instruments indicated a significant association between anticholinergic load and all four outcomes. The instrument considering the prescribed dose showed the strongest association with MMSE scores (ԏ = -0.10), falls (OR: 2.30; 95% CI: 1.50-3.52), and the use of laxatives (OR: 3.11; 95% CI: 1.04-9.36). CONCLUSIONS: Instruments most reliably predicted anticholinergicadverse events if they were either based on the drugs' serum anticholinergic activity and the suggestions of clinician experts or considered the actual prescribed dose.

Phytochemical analysis of hydroethanolic extract of Turnera diffusa Willd and evaluation of its effects on astrocyte cell death / Análise fitoquímica do extrato hidroetanólico de Turnera diffusa Willd e avaliação de seus efeitos na morte de astrócitos

ABSTRACT Objective To evaluate the phytochemical composition of hydroethanolic extracts from powdered aerial parts of Turnera diffusa Willd (Turneraceae; T. diffusa), as well as its toxicity in astrocytes. Methods Chemical analyses of hydroethanolic extract from powdered aerial parts ofT. diffusa were carried out using HPLC-DAD-ESI-MS/MS.In vitro assays using astrocytes culture were performed to evaluate cell death. Results Flavone-C, O-diglycosides, such as, luteolin-8-C-[6-deoxy-2-O-rhamnosyl]-xylo-hexos-3-uloside, apigenin-8-C-[6-deoxy-2-O-rhamnosyl]-xylo-hexos-3-uloside and apigenin-7-O-6”-p-coumaroylglucoside were the main compounds found in this hydroethanolic extract. Concentration time-effect demonstrated the toxicity of this extract at a concentration of 1,000µg/mL in astrocyte culture, after 6 and 24 hours of incubation. Conclusion In phytochemical analyses, important antioxidants (mainly flavonoids) were observed. T. diffusa extracts presented cytotoxic effect in high concentrations, leading to increased cell death in astrocyte culture.

RESUMO Objetivo Avaliar a composição fitoquímica do extrato hidroetanólico das partes aéreas de Turnera diffusa Willd (Turneraceae; T. diffusa) e sua toxicidade em astrócitos. Métodos Análises químicas do extrato hidroetanólico de partes aéreas de T. diffusa foram feitas por HPLC-DAD-ESI-MS/MS. Os ensaiosin vitro utilizaram culturas de astrócitos para avaliar morte celular. Resultados Flavonas-C, O-diglicosídeos, como, luteolina-8-C-[6-deoxi-2-O-raminosil]-xilo-hexos-3-ulosideo, apigenina-8-C-[6-deoxi-2-O-raminosil]-xilo-hexos-3-ulosideo e apigenina-7-O-6”-p-cumaroilglucosídeo foram os principais constituintes encontrados neste extrato hidroetanólico. Uma curva tempo-concentração demonstrou toxicidade desse extrato na concentração de 1.000µg/mL, na cultura de astrócitos após 6 e 24 horas de incubação. Conclusão Nas análises fitoquímicas, importantes antioxidantes, sobretudo flavonoides, foram observados. Extratos de T. diffusa apresentaram efeitos citotóxicos em altas concentrações, ocasionando aumento de morte celular em cultura de astrócitos.

Cognitive impairment following consumption of alcohol with and without energy drinks.

BACKGROUND: The aim of this study was to assess the relative effects of alcohol mixed with energy drink (AmED) versus alcohol alone on cognitive performance across the ascending and descending breath alcohol concentration (BrAC) limb using doses similar to real-world intake. METHODS: Using a single-blind, placebo-controlled, crossover design, 19 participants completed 4 sessions where they received: (i) placebo, (ii) alcohol, (iii) AmED 500 ml energy drink (ED), and (iii) AmED 750 ml ED. Performance on measures of psychomotor function (Compensatory Tracking Task [CTT]), information processing (Digit Symbol Substitution Task [DSST]; Inspection Time Task [ITT]), and response inhibition (Brief Stop-Signal Task [Brief SST]) was assessed at ~0.05% ascending BrAC, ~0.08% peak BrAC, and ~0.05% descending BrAC. RESULTS: The ITT and Brief SST showed no differential effect of AmED versus alcohol (gs < 0.30 and gs < 0.36, respectively). Moderate magnitude improvements in alcohol-induced impairment of CTT and DSST performance were observed after AmED versus alcohol on the descending BrAC limb (gs > 0.45 and gs > 0.37, respectively). A moderate magnitude decrease in DSST errors was also observed after AmED relative to alcohol at 0.050% ascending target BrAC (gs > 0.43). CONCLUSIONS: Changes in cognitive function after AmED administration were dependent on the degree of intoxication, BrAC curve limb, and ED volume. Co-administration of ED doses which matched (500 ml) and exceeded (500 ml) maximum daily intake guidelines with alcohol decreased impairment of psychomotor function and global information processing after alcohol consumption. These results cannot be necessarily interpreted to suggest that people are less impaired after AmED, as behavior is the result of coordination of multiple cognitive functions, and reduced impairment on one aspect of cognition may not translate into global improvements.

Detecting impairment: sensitive cognitive measures of dose-related acute alcohol intoxication.

The cognitive impairment that results from acute alcohol intoxication is associated with considerable safety risks. Other psychoactive substances, such as medications, pose a similar risk to road and workplace safety. However, there is currently no legal limit for operating vehicles or working while experiencing drug-related impairment. The current study sought to identify a brief cognitive task sensitive to a meaningful degree of impairment from acute alcohol intoxication to potentially stand as a reference from which to quantify impairment from other similar substances. A placebo-controlled single-blind crossover design was employed to determine the relative sensitivity of four commonly-administered cognitive tasks (Compensatory Tracking Task, Digit Symbol Substitution Test, Brief Stop Signal Task and Inspection Time Task) to alcohol-related impairment in male social drinkers at ~0.05% ascending breath alcohol concentration (BrAC), ~0.08% peak BrAC and 0.05% descending BrAC. The Inspection Time Task was identified as the most sensitive task, detecting a medium to large magnitude increase in impairment (g ≈ 0.60) at 0.05% ascending and descending BrAC, and a large magnitude effect size (g = 0.80) at 0.08% peak BrAC. The remaining tasks failed to demonstrate sensitivity to dose-dependent and limb-dependent changes in alcohol-induced impairment. The Inspection Time Task was deemed the most sensitive task for screening alcohol-related impairment based on the present results. Confirmation of equivalence with other drug-related impairment and sensitivity to alcohol-induced impairment in real-world settings should be established in future research.