Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 7.379
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33535410

RESUMO

Alopecia areata (AA) is an autoimmune disease that causes sudden hair loss. Although few studies have reported the association between AA and attention-deficit/hyperactivity disorder (ADHD), the impact of methylphenidate (MPH) on AA has not been examined. This study examined whether AA risk is higher in children with ADHD than in those without ADHD as well as the impact of MPH use on AA risk in children with ADHD. From the Taiwan Maternal and Child Health Database, we enrolled all 1,750,456 newborns from 2004 to 2017 in Taiwan. Of them, 90,016 children received a diagnosis of ADHD whereas the remaining 1,660,440 did not. To compare AA risk in ADHD and the impact of MPH treatment on it, multiple Cox regression with adjustments for covariates (i.e., age, sex, and psychiatric comorbidities) was performed. The results indicated that 88 (0.098%) children with ADHD and 1191 (0.072%) children without ADHD had AA. Nevertheless, after adjustment for the covariates, AA risk was higher in children with ADHD than in those without ADHD (adjusted hazard ratio [aHR]: 1.30, 95% confidence interval [CI]: 1.04-1.64). Our data indicated a considerable reduction in AA risk (aHR: 0.64) among children with ADHD who received MPH than among those who did not receive MPH; however, this difference was nonsignificant, indicated by a wide 95% CI (0.32-1.25). In conclusion, ADHD and AA may share some underlying mechanisms.


Assuntos
Alopecia em Áreas , Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Metilfenidato , Alopecia em Áreas/tratamento farmacológico , Alopecia em Áreas/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estimulantes do Sistema Nervoso Central/efeitos adversos , Criança , Estudos de Coortes , Humanos , Recém-Nascido , Metilfenidato/efeitos adversos , Taiwan/epidemiologia
2.
Epidemiol Psychiatr Sci ; 30: e14, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33583471

RESUMO

AIMS: Although the relationship between attention-deficit/hyperactivity disorder (ADHD) and transport accidents has been shown, there is limited information on the relationship between medication and dose-response effects and transport accident risk. This study aims to determine whether young people with ADHD, including adolescents, are more prone to transport accidents than those without, and the extent to which methylphenidate (MPH) prescription in these patients reduces the risk. METHODS: We identified 114 486 patients diagnosed with ADHD from Taiwan's National Health Insurance Research Database from 1997 to 2013. Using a Cox regression model, we compared the risk of transport accidents between ADHD and non-ADHD groups and estimated the effect of MPH on accidents. Furthermore, we applied a self-control case-series analysis to compare the risk of accidents during the medication periods with the same patients' non-medication periods. RESULTS: Male ADHD patients had a higher risk of transport accidents than non-ADHD individuals (adjusted hazard ratio [aHR] = 1.24, [95% confidence interval (CI) 1.10-1.39]), especially for those comorbid with epilepsy, oppositional defiant disorder/conduct disorder (ODD/CD), and intellectual disabilities (ID). Female ADHD patients showed no relationship, except for comorbid with autism spectrum disorder (ASD) or ID. We found a reduced risk of transport accidents in patients with ADHD with MPH medication than those without MPH, with a plausible dose-response relationship (aHR of 0.23 to 0.07). A similar pattern was found in self-controlled case-series analysis. CONCLUSIONS: Male patients with ADHD, especially those comorbid with epilepsy, ODD/CD, or ID, were at high risk of transport accidents. Female patients, when comorbid with ASD or ID, also exhibited a higher risk of accidents. MPH treatment lowered the accident risk with a dose-response relationship.


Assuntos
Acidentes de Trânsito/estatística & dados numéricos , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/efeitos adversos , Metilfenidato/efeitos adversos , Vigilância da População/métodos , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/epidemiologia , Estudos de Casos e Controles , Estimulantes do Sistema Nervoso Central/uso terapêutico , Estudos de Coortes , Comorbidade , Transtorno da Conduta/epidemiologia , Feminino , Humanos , Deficiência Intelectual/epidemiologia , Masculino , Metilfenidato/uso terapêutico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Fatores Sexuais
3.
Cochrane Database Syst Rev ; 1: CD013011, 2021 01 18.
Artigo em Inglês | MEDLINE | ID: mdl-33460048

RESUMO

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is characterized by symptoms of inattention or impulsivity or both, and hyperactivity, which affect children, adolescents, and adults. In some countries, methylphenidate is the first option to treat adults with moderate or severe ADHD. However, evidence on the efficacy and adverse events of immediate-release (IR) methylphenidate in the treatment of ADHD in adults is limited and controversial. OBJECTIVES: To evaluate the efficacy and harms (adverse events) of IR methylphenidate for treating ADHD in adults. SEARCH METHODS: In January 2020, we searched CENTRAL, MEDLINE, Embase, eight additional databases and three trial registers. We also searched internal reports on the European Medicines Agency and the US Food and Drug Administration websites. We checked citations of included trials to identify additional trials not captured by the electronic searches. SELECTION CRITERIA: Randomized controlled trials (RCTs) comparing IR methylphenidate, at any dose, with placebo or other pharmacological interventions (including extended-release formulations of methylphenidate) for ADHD in adults. Primary outcomes comprised changes in the symptoms of ADHD (efficacy) and harms. Secondary outcomes included changes in the clinical impression of severity and improvement, level of functioning, depression, anxiety and quality of life. Outcomes could have been rated by investigators or participants. DATA COLLECTION AND ANALYSIS: Two review authors extracted data independently on the characteristics of the trials, participants, interventions; outcomes and financial conflict of interests. We resolved disagreements by discussion or consulting a third review author. We obtained additional, unpublished information from the authors of one included trial that had reported efficacy data in a graph. We calculated mean differences (MDs) or standardized MDs (SMDs) with 95% confidence intervals (CIs) for continuous data reported on the same or different scales, respectively. We summarized dichotomous variables as risk ratios (RRs) with 95% CI. MAIN RESULTS: We included 10 trials published between 2001 and 2016 involving 497 adults with ADHD. Three trials were conducted in Europe and one in Argentina; the remaining trials did not report their location. The RCTs compared IR methylphenidate with placebo, an osmotic-release oral system (OROS) of methylphenidate (an extended-release formulation), an extended-release formulation of bupropion, lithium, and Pycnogenol® (maritime pine bark extract). Participants comprised outpatients, inpatients in addiction treatment, and adults willing to attend an intensive outpatient program for cocaine dependence. The duration of the follow-up ranged from 6 to 18 weeks. IR methylphenidate versus placebo We found very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce symptoms of ADHD when measured with investigator-rated scales (MD -20.70, 95% CI -23.97 to -17.43; 1 trial, 146 participants; end scores; Adult ADHD Investigator Symptom Report Scale (AISRS), scored from 0 to 54), but the evidence is uncertain. The effect of IR methylphenidate on ADHD symptoms when measured with participant-rated scales was moderate, but the certainty of the evidence is very low (SMD -0.59, 95% CI -1.25 to 0.06; I2 = 69%; 2 trials, 138 participants; end scores). There is very low-certainty evidence that, compared with placebo, IR methylphenidate may reduce the clinical impression of the severity of ADHD symptoms (MD -0.57, 95% CI -0.85 to -0.28; 2 trials, 139 participants; I2 = 0%; change and end scores; Clinical Global Impression (CGI)-Severity scale (scored from 1 (very much improved) to 7 (very much worse))). There is low-certainty evidence that, compared with placebo, IR methylphenidate may slightly impact the clinical impression of an improvement in symptoms of ADHD (MD -0.94, 95% CI -1.37 to -0.51; 1 trial, 49 participants; end scores; CGI-Improvement scale (scored from 1 (very much improved) to 7 (very much worse))). There is no clear evidence of an effect on anxiety (MD -0.20, 95% CI -4.84 to 4.44; 1 trial, 19 participants; change scores; Hamilton Anxiety Scale (HAM-A; scored from 0 to 56); very low-certainty evidence) or depression (MD 2.80, 95% CI -0.09 to 5.69; 1 trial, 19 participants; change scores; Hamilton Depression Scale (HAM-D; scored from 0 to 52); very low-certainty evidence) in analyses comparing IR methylphenidate with placebo. IR methylphenidate versus lithium Compared with lithium, it is uncertain whether IR methylphenidate increases or decreases symptoms of ADHD (MD 0.60, 95% CI -3.11 to 4.31; 1 trial, 46 participants; end scores; Conners' Adult ADHD Rating Scale (scored from 0 to 198); very low-certainty evidence); anxiety (MD -0.80, 95% CI -4.49 to 2.89; 1 trial, 46 participants; end scores; HAM-A; very low-certainty evidence); or depression (MD -1.20, 95% CI -3.81 to 1.41, 1 trial, 46 participants; end scores; HAM-D scale; very low-certainty evidence). None of the included trials assessed participant-rated changes in symptoms of ADHD, or clinical impression of severity or improvement in participants treated with IR methylphenidate compared with lithium. Adverse events were poorly assessed and reported. We rated all trials at high risk of bias due to selective outcome reporting of harms and masking of outcome assessors (failure to blind outcome assessor to measure adverse events). Overall, four trials with 203 participants who received IR methylphenidate and 141 participants who received placebo described the occurrence of harms. The use of IR methylphenidate in these trials increased the risk of gastrointestinal complications (RR 1.96, 95% CI 1.13 to 2.95) and loss of appetite (RR 1.77, 95% CI 1.06 to 2.96). Cardiovascular adverse events were reported inconsistently, preventing a comprehensive analysis. One trial comparing IR methylphenidate to lithium reported five and nine adverse events, respectively. We considered four trials to have notable concerns of vested interests influencing the evidence, and authors from two trials omitted information related to the sources of funding and conflicts of interest. AUTHORS' CONCLUSIONS: We found no certain evidence that IR methylphenidate compared with placebo or lithium can reduce symptoms of ADHD in adults (low- and very low-certainty evidence). Adults treated with IR methylphenidate are at increased risk of gastrointestinal and metabolic-related harms compared with placebo. Clinicians should consider whether it is appropriate to prescribe IR methylphenidate, given its limited efficacy and increased risk of harms. Future RCTs should explore the long-term efficacy and risks of IR methylphenidate, and the influence of conflicts of interest on reported effects.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/administração & dosagem , Metilfenidato/administração & dosagem , Adulto , Antidepressivos de Segunda Geração/administração & dosagem , Ansiedade/tratamento farmacológico , Viés , Bupropiona/administração & dosagem , Estimulantes do Sistema Nervoso Central/efeitos adversos , Depressão/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Feminino , Flavonoides/administração & dosagem , Humanos , Compostos de Lítio/administração & dosagem , Masculino , Metilfenidato/efeitos adversos , Pessoa de Meia-Idade , Placebos/administração & dosagem , Extratos Vegetais/administração & dosagem , Ensaios Clínicos Controlados Aleatórios como Assunto/estatística & dados numéricos , Adulto Jovem
4.
Clin Drug Investig ; 41(2): 149-159, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33368026

RESUMO

BACKGROUND AND OBJECTIVES: Viloxazine extended-release (viloxazine ER, SPN-812) is a novel non-stimulant with activity at serotonin receptors and the norepinephrine transporter, which is under investigation as a potential treatment for attention-deficit/hyperactivity disorder. Given the potential for viloxazine ER to be coadministered with other pharmacotherapies, this trial investigated the pharmacokinetics and safety of combination viloxazine ER + methylphenidate versus viloxazine ER or methylphenidate alone. METHODS: In this single-center, crossover, open-label trial, healthy adult participants received oral administration of 700 mg viloxazine ER alone, 36 mg methylphenidate alone, and combination viloxazine ER (700 mg) + methylphenidate (36 mg), with blood samples collected over 4 days post-administration. The active drug in viloxazine ER (viloxazine) and methylphenidate was measured using chromatographic tandem mass spectrometry. Safety assessments included adverse events (AEs), vital signs, echocardiograms, and clinical laboratory evaluations. RESULTS: Of 36 healthy adults who were enrolled, 34 completed the trial. The geometric least squares mean ratios are reported as [combination/single drug (90% confidence intervals)]. For viloxazine ER, maximum measured plasma concentration (Cmax) = 100.98% (96.21-105.99), area under the concentration-time curve from time zero to the last measurable time (AUCt) = 98.62% (96.21-101.08), and area under the concentration-time curve from time zero to infinity (AUC∞) = 98.96% (96.55-101.44). For methylphenidate, Cmax = 103.55% (97.42-110.07), AUCt = 106.67% (101.01-112.64), and AUC∞ = 106.61% (100.99-112.54). All reported AEs were mild in severity. CONCLUSIONS: Coadministration of viloxazine ER and methylphenidate did not impact the pharmacokinetics of viloxazine or methylphenidate relative to administration of either drug alone. The combination appeared to be safe and well tolerated.


Assuntos
Estimulantes do Sistema Nervoso Central/administração & dosagem , Metilfenidato/administração & dosagem , Viloxazina/administração & dosagem , Administração Oral , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estudos Cross-Over , Preparações de Ação Retardada , Feminino , Humanos , Masculino , Metilfenidato/farmacocinética , Pessoa de Meia-Idade , Proteínas da Membrana Plasmática de Transporte de Norepinefrina/metabolismo , Viloxazina/farmacocinética , Adulto Jovem
5.
Rev. neurol. (Ed. impr.) ; 71(12): 438-446, 16 dic., 2020. graf, tab
Artigo em Espanhol | IBECS | ID: ibc-199337

RESUMO

INTRODUCCIÓN: El trastorno por déficit de atención/hiperactividad (TDAH) es uno de los trastornos mentales más comunes en la infancia. Los síntomas nucleares del TDAH se tratan con estimulantes como el metilfenidato; aun así, existe mucha controversia respecto a sus efectos secundarios. OBJETIVOS: Analizar los patrones de actividad en niños con TDAH durante un período de 24 horas durante siete días, antes y después de tomar tratamiento farmacológico estimulante (metilfenidato), y observar si existen diferencias entre las diferentes presentaciones del trastorno (subtipo inatento y combinado). PACIENTES Y MÉTODOS: Un total de 30 niños y adolescentes (recién diagnosticados de TDAH según los criterios diagnósticos del DSM-IV) fueron evaluados a través de un actígrafo, un instrumento que permite monitorizar los movimientos corporales analizando los patrones de movimiento y las diferencias entre sueño y vigilia. RESULTADOS: Existen diferencias significativas antes y después de realizar el tratamiento, con niveles de actividad más altos en los pacientes con TDAH antes de empezar el tratamiento y un decrecimiento de esta actividad tras el tratamiento farmacológico. También existen diferencias entre los subtipos inatento y combinado, y el último grupo muestra un nivel de actividad mayor. CONCLUSIONES: El nivel de activación que presentan los sujetos con TDAH es mayor antes de tomar tratamiento, e influye en los patrones circadianos, el sueño y la calidad de vida. El tratamiento farmacológico ayuda a disminuir el nivel de activación


INTRODUCTION: Attention deficit hyperactivity disorder (ADHD) is one of the most common mental disorders in childhood. The nuclear symptoms of ADHD are treated with stimulant medication such as methylphenidate; however, there's a lot of controversy regarding its side effects. AIMS. To analyse the activity patterns in children with ADHD during a period of 24 hours for seven days, before and after taking pharmacological treatment with stimulants (methylphenidate) and observe the differences between the different presentations of ADHD (inattentive and combined subtype). PATIENTS AND METHODS: A total of 30 children and adolescents (newly diagnosed with ADHD according to DSM-IV). Analyses were carried out through actigraphy, an instrument that allows us to monitor body movements by analysing movement patterns and differences between sleep and wakefulness. RESULTS: There were significant differences before and after treatment showing higher activity levels in patients with ADHD before treatment, and a decrease in this situation after taking pharmacological treatment. There are also differences between inattentive and combined subtype, showing the last group, higher activity levels. CONCLUSIONS: The level of activation presented by ADHD subjects is higher before taking stimulant treatment, influencing circadian patterns, sleep and quality of life. Pharmacological treatments help to decrease the level of activation


Assuntos
Humanos , Masculino , Feminino , Criança , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Ritmo Circadiano/efeitos dos fármacos , Resultado do Tratamento , Polissonografia/métodos , Sono/fisiologia , Transtornos do Sono-Vigília/fisiopatologia , Vigília/fisiologia , Transtorno do Deficit de Atenção com Hiperatividade/psicologia , Fatores de Tempo , Actigrafia/métodos
6.
Cad Saude Publica ; 36(12): e00056420, 2020.
Artigo em Português | MEDLINE | ID: mdl-33331541

RESUMO

Attention deficit and hyperactivity disorder (ADHD) is considered one of the most frequent behavioral and neurodevelopmental problems in school-age children and adolescents, both in Portugal and worldwide. The diagnostic categorization of ADHD and the prescription of psychostimulants as its first-line treatment have been the object not only of scientific research and clinical validation, but also of controversy and social critique, especially in light of the concept of medicalization. Despite its high profile and salience in such diverse fields as education, pharmaceuticals, mental health, and public policy, a significant gap remains in the characterization of social-historical, ethical, and institutional dimensions of ADHD outside English-speaking countries. Combining historical and ethnographic research with document and media analysis, the article addresses that challenge by tracing the social trajectory of ADHD in Portugal, from the emergence of "hyperactivity" in the 1970s and 1980s to the current public and political debates on psychostimulant treatments and prescribing trends. From this interdisciplinary perspective and based on the Portuguese case study, the aim of this article is to contextualize the definition, validation, and expansion of ADHD as part of a dynamic and socially situated process in which global diagnostic and pharmaceutical systems intersect with institutional and socioeconomic contingencies, as well as local specificities and needs. More broadly, the article discusses how the case study of ADHD contributes to the development of interdisciplinary research that helps rethinking the social scope of mental health across local and global health contexts.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Saúde Global , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/diagnóstico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Brasil , Criança , Humanos , Saúde Mental , Portugal
7.
Nihon Yakurigaku Zasshi ; 155(6): 413-425, 2020.
Artigo em Japonês | MEDLINE | ID: mdl-33132261

RESUMO

Lisdexamfetamine dimesylate (hereinafter referred to as "lisdexamfetamine"; brand name, Vyvanse®), was developed for the treatment of attention-deficit/hyperactivity disorder (ADHD). This drug, which is classified as a central nervous system (CNS) stimulant for once-daily oral administration, received marketing approval in March 2019 and was launched in December 2019 in Japan. Lisdexamfetamine is a prodrug that is hydrolyzed to its active form d-amphetamine in the blood following oral administration. Pharmacologically, d-amphetamine competitively inhibits the dopamine transporter (DAT) and the noradrenaline transporter (NAT) to increase dopamine (DA) and noradrenaline (NA) concentrations in the synaptic cleft. In addition to inhibiting the reuptake of DA and NA, d-amphetamine has also an effect in promoting the release of these neurotransmitters by being taken up into neuronal cells and then acting on the vesicular monoamine transporter. The mechanisms of action by which d-amphetamine exerts a therapeutic effect on ADHD may be based on the above-described effects. Clinical studies conducted in Japan and overseas have demonstrated the efficacy of lisdexamfetamine over placebo in the treatment of pediatric ADHD patients. The most of the adverse events with a higher incidence than in the placebo were mild, and long-term administration of the drug was not associated with an increase in the incidence of adverse events or the rate of treatment discontinuation. Lisdexamfetamine, which is designated as raw material for stimulants and therefore requires strict distribution control in Japan, is expected to be effective in the treatment of ADHD patients with inadequate responses to existing therapeutic agents.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Cápsulas , Criança , Dextroanfetamina/farmacologia , Humanos , Japão , Dimesilato de Lisdexanfetamina
8.
Lakartidningen ; 1172020 10 26.
Artigo em Sueco | MEDLINE | ID: mdl-33107581

RESUMO

Amphetamine is an illicit central nervous system stimulant that is also used for the treatment of attention-decific/hyperacticity disorder (ADHD). Amphetamine exits as two enantiomers, dex(tro)amphetamine (D-amphetamine; also called S-amphetamine) and levoamphetamine (L-amphetamine; or R-amphetamine), of which mainly the former is used as medication for ADHD, whereas illicit street amphetamine is a racemic mixture. To monitor patient compliance with treatment and detect (side) intake of racemic amphetamine, chiral analysis in samples of urine, oral fluid, or blood is used and has traditionally involved reporting of the L/D ratio. Today in Sweden, however, only ADHD medications based on D-amphetamine (lisdexamphetamine lysate and dexamphetamine sulfate) are approved, so no L-amphetamine should be found in the samples provided treatment compliance. It is therefore advisable to instead report the total amphetamine concentration and the relative amount of L-amphetamine. A proposed L-amphetamine cutoff for compliance with ADHD medication is less than 1%, or as low as possible in samples with low amphetamine concentration, as there may be traces of L-amphetamine in the approved pharmaceutical products. Since (supervised) urine sampling is sometimes considered sensitive to ADHD patients without any underlying drug problem, using oral fluid testing is a less invasive alternative and would facilitate sampling for both patients and healthcare professionals. However, an analytical disadvantage is that the amphetamine concentration is generally lower in oral fluid than in urine.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Anfetamina , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Seguimentos , Humanos , Suécia
9.
Rev Prat ; 70(5): 509-513, 2020 May.
Artigo em Francês | MEDLINE | ID: mdl-33058636

RESUMO

What prescription for psychostimulants in children? The Attention Deficit and Hyperactivity Disorder (ADHD) is a frequent disorder in children and adolescents. The diagnosis is clinical with the input of several informants (child, family, teachers…). ADHD is a risk factor for academic difficulties, school dropout, social isolation, injury, oppositional behaviour. In school-age children and adolescents having moderate to high or persistent impairment despite psycho-educational support and environmental modification, the first-line treatment is methylphenidate. Group or individual cognitive behavioural therapy for parents and/or children and adolescents is recommended for co-occurring disorders and persistent impairment. In France, the initiation of methylphenidate requires an annual hospital prescription by a paediatrician or psychiatrist, and a regular medical supervision (weight, heart rate, blood pressure…). At least once a year, the indication of methyphenidate needs to be re-evaluated and confirmed at the hospital. In case of lack of efficiency and/or poor tolerance, therapeutic alternatives including non-psychostimulants should be considered.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Adolescente , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Terapia Cognitivo-Comportamental , França/epidemiologia , Humanos , Pais
11.
J Clin Psychiatry ; 81(5)2020 09 08.
Artigo em Inglês | MEDLINE | ID: mdl-32926603

RESUMO

BACKGROUND: Attention-deficit/hyperactivity disorder (ADHD) is present in 25%-50% of parents of children with ADHD, compromising parenting and child behavioral treatment. Efforts to treat multiplex ADHD families have not compared behavioral parenting interventions to parent psychopharmacology without confounds of other treatments. This report describes a pilot early intervention study directly comparing parent lisdexamfetamine dimesylate (LDX) to behavioral parent training (BPT) in families in which the mother had currently untreated ADHD and the young child displayed ADHD symptoms. METHODS: Mothers with ADHD (N = 35) of 4- to 8-year-old stimulant-naive children (N = 35) were randomly assigned to an 8-week trial of LDX (starting at 20 mg/d and titrated to a maximum of 70 mg/d) or BPT. Outcomes included multi-method, multi-informant measures of (1) maternal ADHD symptoms (Conners' Adult ADHD Rating Scales) and impairment (Clinical Global Impressions-Severity of Illness scale [CGI-S] and CGI-Improvement scale [CGI-I]), (2) parenting (Alabama Parenting Questionnaire [APQ] and Dyadic Parent-Child Interaction Coding System, Fourth Edition), and (3) child ADHD symptoms (Conners Parent Rating Scale Revised-Short Form and Conners Early Childhood Scale) and impairment (CGI-S, CGI-I, and Child Impairment Rating Scale). RESULTS: At 8 weeks, both treatments improved mothers' self-reported emotion regulation and mothers' functioning on the CGI, but only LDX improved mothers' self-reported core ADHD symptoms. LDX was associated with improvement in parents' perception of their own ADHD symptoms (Conners Inattention [P < .0001] and ADHD Index scores [P < .0001]) and their child's ADHD symptoms (P = .009). Fifty-six percent of the mothers treated with LDX (n = 10) were "much" or "very much" improved with regard to their adult ADHD based on the CGI-I scores versus 6% of mothers receiving BPT (n = 1; P = .003). BPT improved parenting on self-reported positive parenting (P = .007), inconsistent discipline (P > .0001), and corporal punishment (P = .001), while LDX improved reported inconsistent discipline (P = .001) and corporal punishment (P = .04) on the APQ, consistent with prior research. In contrast to parental LDX, which did not improve observed parenting, BPT was associated with increased positive parenting during child-directed play (P = .0002) and clean-up (P = .04) and less negative parenting (P = .04) during child-directed play. Six percent of children (n = 1) whose mothers were randomized to LDX (n = 18) were "much" or "very much" improved on the CGI-I compared to 35% (n = 16) of those treated with BPT (P = .04). CONCLUSIONS: LDX and BPT each had unique effects on maternal ADHD symptoms and parenting, but modest effects on at-risk children. In general, LDX was more effective at treating mothers' core ADHD symptoms, but both LDX and BPT improved mothers' emotion regulation, and BPT resulted in more consistent effects on parenting measures via both maternal report and direct observation. As most children remained significantly impaired after 8 weeks of unimodal treatment, combination treatment and/or longer treatment duration may be necessary to improve functioning of multiplex ADHD families. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01816074​.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/terapia , Terapia Comportamental/métodos , Estimulantes do Sistema Nervoso Central/uso terapêutico , Dimesilato de Lisdexanfetamina/uso terapêutico , Mães/psicologia , Poder Familiar , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Criança , Pré-Escolar , Feminino , Humanos , Poder Familiar/psicologia , Escalas de Graduação Psiquiátrica , Resultado do Tratamento
12.
N Z Med J ; 133(1522): 84-95, 2020 09 25.
Artigo em Inglês | MEDLINE | ID: mdl-32994619

RESUMO

AIMS: Global trends show an increase in medication dispensing for attention-deficit/hyperactivity disorder (ADHD) in young people over time. The current study aimed to examine whether similar trends were observed in New Zealand youth over the period of 2007/08 to 2016/17. METHODS: We estimated the prevalence in ADHD medication dispensing using national pharmaceutical data for each fiscal year from 2007/08 to 2016/17 in approximately 2.4 million New Zealand youth aged 1-24 years. We also examined whether trends varied by sociodemographic factors. RESULTS: The total dispensing prevalence almost doubled from 516 per 100,000 to 996 per 100,000 over the study period. Males had a consistently higher dispensing prevalence relative to females. Young people aged 7-17 years had the highest dispensing prevalence. The most deprived quintile had a slightly lower dispensing prevalence relative to other quintiles. Ethnic differences in dispensing prevalence were apparent, with deprivation differences also existing within most ethnic groups. CONCLUSIONS: Overall, our study showed an increase in ADHD medication use by young people in New Zealand, similar to international findings. Further research is needed into why disparities in dispensing prevalence occur across ethnic and socioeconomic groups.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Prescrições de Medicamentos/estatística & dados numéricos , Adolescente , Adulto , Criança , Pré-Escolar , Grupos de Populações Continentais/estatística & dados numéricos , Estudos Transversais , Grupos Étnicos/estatística & dados numéricos , Feminino , Disparidades em Assistência à Saúde/estatística & dados numéricos , Humanos , Lactente , Masculino , Nova Zelândia/epidemiologia , Prevalência , Adulto Jovem
13.
Cochrane Database Syst Rev ; 9: CD008294, 2020 09 29.
Artigo em Inglês | MEDLINE | ID: mdl-32990945

RESUMO

BACKGROUND: Pine bark (Pinus spp.) extract is rich in bioflavonoids, predominantly proanthocyanidins, which are antioxidants. Commercially-available extract supplements are marketed for preventing or treating various chronic conditions associated with oxidative stress. This is an update of a previously published review. OBJECTIVES: To assess the efficacy and safety of pine bark extract supplements for treating chronic disorders. SEARCH METHODS: We searched three databases and three trial registries; latest search: 30 September 2019. We contacted the manufacturers of pine bark extracts to identify additional studies and hand-searched bibliographies of included studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) evaluating pine bark extract supplements in adults or children with any chronic disorder. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial eligibility, extracted data and assessed risk of bias. Where possible, we pooled data in meta-analyses. We used GRADE to evaluate the certainty of evidence. Primary outcomes were participant- and investigator-reported clinical outcomes directly related to each disorder and all-cause mortality. We also assessed adverse events and biomarkers of oxidative stress. MAIN RESULTS: This review included 27 RCTs (22 parallel and five cross-over designs; 1641 participants) evaluating pine bark extract supplements across 10 chronic disorders: asthma (two studies; 86 participants); attention deficit hyperactivity disorder (ADHD) (one study; 61 participants), cardiovascular disease (CVD) and risk factors (seven studies; 338 participants), chronic venous insufficiency (CVI) (two studies; 60 participants), diabetes mellitus (DM) (six studies; 339 participants), erectile dysfunction (three studies; 277 participants), female sexual dysfunction (one study; 83 participants), osteoarthritis (three studies; 293 participants), osteopenia (one study; 44 participants) and traumatic brain injury (one study; 60 participants). Two studies exclusively recruited children; the remainder recruited adults. Trials lasted between four weeks and six months. Placebo was the control in 24 studies. Overall risk of bias was low for four, high for one and unclear for 22 studies. In adults with asthma, we do not know whether pine bark extract increases change in forced expiratory volume in one second (FEV1) % predicted/forced vital capacity (FVC) (mean difference (MD) 7.70, 95% confidence interval (CI) 3.19 to 12.21; one study; 44 participants; very low-certainty evidence), increases change in FEV1 % predicted (MD 7.00, 95% CI 0.10 to 13.90; one study; 44 participants; very low-certainty evidence), improves asthma symptoms (risk ratio (RR) 1.85, 95% CI 1.32 to 2.58; one study; 60 participants; very low-certainty evidence) or increases the number of people able to stop using albuterol inhalers (RR 6.00, 95% CI 1.97 to 18.25; one study; 60 participants; very low-certainty evidence). In children with ADHD, we do not know whether pine bark extract decreases inattention and hyperactivity assessed by parent- and teacher-rating scales (narrative synthesis; one study; 57 participants; very low-certainty evidence) or increases the change in visual-motoric coordination and concentration (MD 3.37, 95% CI 2.41 to 4.33; one study; 57 participants; very low-certainty evidence). In participants with CVD, we do not know whether pine bark extract decreases diastolic blood pressure (MD -3.00 mm Hg, 95% CI -4.51 to -1.49; one study; 61 participants; very low-certainty evidence); increases HDL cholesterol (MD 0.05 mmol/L, 95% CI -0.01 to 0.11; one study; 61 participants; very low-certainty evidence) or decreases LDL cholesterol (MD -0.03 mmol/L, 95% CI -0.05 to 0.00; one study; 61 participants; very low-certainty evidence). In participants with CVI, we do not know whether pine bark extract decreases pain scores (MD -0.59, 95% CI -1.02 to -0.16; one study; 40 participants; very low-certainty evidence), increases the disappearance of pain (RR 25.0, 95% CI 1.58 to 395.48; one study; 40 participants; very low-certainty evidence) or increases physician-judged treatment efficacy (RR 4.75, 95% CI 1.97 to 11.48; 1 study; 40 participants; very low-certainty evidence). In type 2 DM, we do not know whether pine bark extract leads to a greater reduction in fasting blood glucose (MD 1.0 mmol/L, 95% CI 0.91 to 1.09; one study; 48 participants;very low-certainty evidence) or decreases HbA1c (MD -0.90 %, 95% CI -1.78 to -0.02; 1 study; 48 participants; very low-certainty evidence). In a mixed group of participants with type 1 and type 2 DM we do not know whether pine bark extract decreases HbA1c (MD -0.20 %, 95% CI -1.83 to 1.43; one study; 67 participants; very low-certainty evidence). In men with erectile dysfunction, we do not know whether pine bark extract supplements increase International Index of Erectile Function-5 scores (not pooled; two studies; 147 participants; very low-certainty evidence). In women with sexual dysfunction, we do not know whether pine bark extract increases satisfaction as measured by the Female Sexual Function Index (MD 5.10, 95% CI 3.49 to 6.71; one study; 75 participants; very low-certainty evidence) or leads to a greater reduction of pain scores (MD 4.30, 95% CI 2.69 to 5.91; one study; 75 participants; very low-certainty evidence). In adults with osteoarthritis of the knee, we do not know whether pine bark extract decreases composite Western Ontario and McMaster Universities Osteoarthritis Index scores (MD -730.00, 95% CI -1011.95 to -448.05; one study; 37 participants; very low-certainty evidence) or the use of non-steroidal anti-inflammatory medication (MD -18.30, 95% CI -25.14 to -11.46; one study; 35 participants; very low-certainty evidence). We do not know whether pine bark extract increases bone alkaline phosphatase in post-menopausal women with osteopenia (MD 1.16 ug/L, 95% CI -2.37 to 4.69; one study; 40 participants; very low-certainty evidence). In individuals with traumatic brain injury, we do not know whether pine bark extract decreases cognitive failure scores (MD -2.24, 95% CI -11.17 to 6.69; one study; 56 participants; very low-certainty evidence) or post-concussion symptoms (MD -0.76, 95% CI -5.39 to 3.87; one study; 56 participants; very low-certainty evidence). For most comparisons, studies did not report outcomes of hospital admissions or serious adverse events. AUTHORS' CONCLUSIONS: Small sample sizes, limited numbers of RCTs per condition, variation in outcome measures, and poor reporting of the included RCTs mean no definitive conclusions regarding the efficacy or safety of pine bark extract supplements are possible.


Assuntos
Antioxidantes/uso terapêutico , Doença Crônica/tratamento farmacológico , Flavonoides/uso terapêutico , Casca de Planta/química , Extratos Vegetais/uso terapêutico , Adolescente , Adulto , Asma/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Viés , Doenças Ósseas Metabólicas/tratamento farmacológico , Lesões Encefálicas Traumáticas/tratamento farmacológico , Doenças Cardiovasculares/tratamento farmacológico , Criança , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Disfunção Erétil/tratamento farmacológico , Feminino , Humanos , Hipertensão/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Osteoartrite/tratamento farmacológico , Pinus , Ensaios Clínicos Controlados Aleatórios como Assunto , Disfunções Sexuais Psicogênicas/tratamento farmacológico , Insuficiência Venosa/tratamento farmacológico
14.
Artigo em Inglês | MEDLINE | ID: mdl-32942345

RESUMO

Background: There is a paucity of studies on treatment of childhood-onset bipolar disorder and its associated comorbidities, which leads to a wide diversity of opinion on choice and sequencing of treatment options. Methods: From December 2018 to January 2019, a graphic depiction of medications and weekly ratings of symptoms of mania, depression, anxiety, attention-deficit/hyperactivity disorder (ADHD), and oppositional behavior that parents had rated on their 9-year-old child over a period of several years was sent to experts in child and adult bipolar disorder. These responding medical doctors (MDs, 8 child and 18 adult psychiatrists) rated a comprehensive list of medications that they would choose (and with what priority) to treat the child's now improved mood (mania and depression) but continued mild to moderate symptoms of anxiety, ADHD, and oppositional behavior. Results: In the whole group, the drugs most highly endorsed were lamotrigine: 69%, lithium: 62%, lurasidone: 62%, quetiapine: 54%, aripiprazole: 46%, and valproate: 42%. Among the antidepressants, 38% endorsed a selective serotonin reuptake inhibitor, 12% a serotonin-norepinephrine reuptake inhibitor, and 27% bupropion. Of the child MDs, 75% suggested increasing the 1-mg dose of risperidone, while few adult MDs suggested this. Conversely, 56% of the adult MDs suggested using valproate, while only 1 child MD did so. There was little consensus on how to manage ADHD symptoms unresponsive to methylphenidate 36 mg/d. How these treatment options were sequenced also varied widely. Conclusions: There was wide variation in suggestions on to how to treat persistent symptoms of anxiety, ADHD, and oppositional behavior in a child whose mania and depression had been brought under good control. We surmise that this great diversity in recommendations among experts in child and adult bipolar disorder stems at least partially from inadequate literature on treatment and that a new emphasis on funding and conducting studies on efficacy and effectiveness is needed.


Assuntos
Transtornos de Ansiedade/tratamento farmacológico , Transtornos de Deficit da Atenção e do Comportamento Disruptivo/tratamento farmacológico , Transtorno Bipolar/tratamento farmacológico , Psicotrópicos/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno Bipolar/terapia , Criança , Consenso , Feminino , Humanos , Prevenção Primária , Indução de Remissão
15.
Pediatrics ; 146(4)2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32958613

RESUMO

OBJECTIVES: The youngest children in a classroom are at increased risk of being medicated for attention-deficit/hyperactivity disorder (ADHD). We examined the association between children's birth month and ADHD medication rates in Finland. METHODS: Using a population-based study, we analyzed ADHD medication use among children born in 2005 to 2007. Cases (n = 7054) were identified from the first purchase of medication for ADHD. Cox proportional hazard models and hazard ratios (HRs) were examined by birth month and sex. Finnish children start first grade in the year of their seventh birthday. The cutoff date is December 31. RESULTS: Risk of ADHD medication use increased throughout the year by birth month (ie, January through April to May through August to September through December). Among boys born in September to December, the association remained stable across cohorts (HR: 1.3; 95% confidence interval [CI]: 1.1-1.5). Among girls born in September to December, the HR in the 2005 cohort was 1.4 (95% CI: 1.1-1.8), whereas in the 2007 cohort it was 1.7 (95% CI: 1.3-2.2). In a restricted follow-up, which ended at the end of the year of the children's eighth birthday, the HRs for boys and girls born in September to December 2007 were 1.5 (95% CI: 1.3-1.7) and 2.0 (95% CI: 1.5-2.8), respectively. CONCLUSIONS: Relative immaturity increases the likelihood of ADHD medication use in Finland. The association was more pronounced during the first school years. Increased awareness of this association is needed among clinicians and teachers.


Assuntos
Fatores Etários , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Criança , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Modelos de Riscos Proporcionais , Fatores Sexuais , Fatores de Tempo
16.
PLoS One ; 15(9): e0239257, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32946507

RESUMO

OBJECTIVE: This comprehensive review examined sex differences in prescription rates and efficacy or effectiveness of pharmacotherapy treatment in girls and women with attention deficit hyperactivity disorder (ADHD), while identifying gaps in the scientific knowledge on this topic. METHOD: A rigorous electronic database search was carried out in order to identify all published studies on female-specific effects of stimulants and non-stimulants in the treatment of ADHD. In total, 2672 studies were screened of which 21 studies (seven on prescription rates, 14 on effects of pharmacotherapy) met the inclusion criteria and were included for analysis. RESULTS: In all seven studies on ADHD prescription rates, girls received significantly less prescriptions than boys, a difference however no longer seen in adults with the exception of one study. Each of the 14 studies on effectiveness / efficacy found at least one sex-difference in the effects of ADHD pharmacotherapy. CONCLUSION: Several sex-differences are demonstrated in the prescription, usage and efficacy /effectiveness of both stimulant and non-stimulant ADHD pharmacotherapy. A single daily use of MPH may possibly not be optimal for girls with ADHD and ATX may be a promising medication for girls and women with ADHD. The robustness of this result requires further investigation.


Assuntos
Cloridrato de Atomoxetina/uso terapêutico , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Caracteres Sexuais , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Transtorno do Deficit de Atenção com Hiperatividade/patologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Criança , Pré-Escolar , Bases de Dados Factuais , Prescrições de Medicamentos/normas , Feminino , Humanos , Masculino , Homens , Metilfenidato/uso terapêutico , Adulto Jovem
18.
Medicine (Baltimore) ; 99(27): e20931, 2020 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-32629693

RESUMO

Various psychotropic drugs may affect the hematological and biochemical profiles of plasma and its metabolism. Carbamazepine, the most well-known psychotropic drug, can cause substantial hyponatremia. Methylphenidate, a piperidine derivative structurally related to amphetamines, acts as a central nervous system stimulant. The current study evaluated whether methylphenidate affects hematological and biochemical parameters of patients diagnosed with attention deficit hyperactivity disorder.Patients undergoing treatment for attention deficit hyperactivity disorder at our Adolescent Psychiatric Clinic were enrolled in the study. Blood samples for complete blood count and common biochemical analyses were collected before patients started methylphenidate and after 3 months of continuous treatment.Participants included 64 patients comprised the study cohort. There were 48 (75%) males and 16 (25%) females, with a median age of 16 years (range 11-31). The total median potassium level decreased by 0.6 mg/dL (P < .0001), while glucose rose by 15 mg/dL (P < .0001), sodium decreased in 0.7meq/L, (P = .006). The white blood count rose by 1350 cells/µL (P < .033) due to neutrophilia, lymphocytosis and eosinophilia. Hemoglobin rose slightly by 0.1 (P = .041). Changes in calcium, phosphorus, protein, albumin, and liver enzyme levels were not significant.The results indicate that methylphenidate may cause hypokalemia and elevated glucose, leukocyte, neutrophil, lymphocyte and eosinophil counts.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Estimulantes do Sistema Nervoso Central/uso terapêutico , Metilfenidato/uso terapêutico , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/sangue , Estimulantes do Sistema Nervoso Central/farmacologia , Criança , Estudos de Coortes , Feminino , Humanos , Hipoglicemia/induzido quimicamente , Leucócitos/efeitos dos fármacos , Masculino , Metilfenidato/farmacologia , Neutrófilos/efeitos dos fármacos , Adulto Jovem
19.
J Clin Psychiatry ; 81(4)2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32726522

RESUMO

Attention-deficit/hyperactivity disorder (ADHD) is usually treated with stimulant drugs such as methylphenidate (MPH). ADHD is associated with an increased risk of seizures and, in this context, concerns have been expressed that stimulant drugs, including MPH, may increase the seizure risk. However, 4 large observational studies have found that ADHD drugs in general and stimulant drugs in particular are not associated with increased seizure risk and may, in fact, be associated with a reduced risk of seizures; these studies were largely conducted in children and adolescents, including those with epilepsy, with or without other brain comorbidities. The findings were obtained in both between-subjects and within-subjects analyses; the latter controlled for time-invariant inadequately measured, unmeasured, and unknown confounds. These reassuring results support the results of many small, short-duration trials that found that MPH was not associated with increased seizure risk. One other observational study however found that MPH was indeed associated with an increased risk of seizures, but only during the first 30 days after drug initiation; there was no increase in risk in earlier or later time windows. There are many reasons why this single finding should be viewed with reservation; in any case, even if the finding is valid, the absolute risk of seizures with MPH appears to be very low. It is therefore reasonable to conclude that MPH may be safely used in children and adolescents, even those with a current or past history of epilepsy; however, prudence dictates that attention be paid to potential seizure triggers during the first month of treatment. This risk needs to be specifically reexamined in future research.


Assuntos
Estimulantes do Sistema Nervoso Central/efeitos adversos , Metilfenidato/efeitos adversos , Convulsões/induzido quimicamente , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Humanos
20.
Nord J Psychiatry ; 74(7): 479-488, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32664781

RESUMO

BACKGROUND: A growing number of adults are receiving pharmacological treatment for ADHD but a sizable proportion also discontinues or have gaps in treatment. The primary aims of this study were to identify how many patients treated for ADHD in adulthood, have at least one event of discontinuation in treatment and to identify possible associated variables. METHODS: Within the Danish population aged 18-60 years on the 1st of January 2013, we identified the number of individuals who had been prescribed ADHD-medication at least once during the 1st of January 2002-31st of December 2013 using Danish register data. Among those who filed more than one prescription, treatment discontinuation was defined as having more than 211 days between two prescriptions. In crude and adjusted logistic regression analysis, we explored potential associations to discontinuation for variables such as gender and age at treatment initiation. RESULTS: In a population, if N = 3,165,844 individuals, n = 42,892 had received at least one prescription for ADHD medication. Among those with more than one prescription (N = 38,289), 29.4% had discontinued their treatment at least once, according to our definition of treatment discontinuation. ADHD treatment discontinuation was associated with being male, unemployment, lower educational attainment, receiving incapacity benefits and younger age at treatment initiation (p < 0.001). CONCLUSIONS: A large proportion of individuals treated for ADHD had at least one discontinuation of treatment according to our definition. Although the present study does not allow for investigating the direction of these effects, nor whether some patients later resumed treatment, having at least one discontinuation was associated with a range of variables relating to e.g. age and gender, and provides an emerging profile for clinicians of patients more likely to discontinue.


Assuntos
Transtorno do Deficit de Atenção com Hiperatividade , Estimulantes do Sistema Nervoso Central , Adolescente , Adulto , Transtorno do Deficit de Atenção com Hiperatividade/tratamento farmacológico , Transtorno do Deficit de Atenção com Hiperatividade/epidemiologia , Estimulantes do Sistema Nervoso Central/uso terapêutico , Estudos Transversais , Dinamarca/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...