Summary Background About 50% of patients (age ≥60 years) who have acute myeloid leukaemia and are otherwise medically healthy (ie, able to undergo intensive chemotherapy) achieve a complete remission ...(CR) after intensive chemotherapy, but with a substantially increased risk of early death (ED) compared with younger patients. We verified the association of standard clinical and laboratory variables with CR and ED and developed a web-based application for risk assessment of intensive chemotherapy in these patients. Methods Multivariate regression analysis was used to develop risk scores with or without knowledge of the cytogenetic and molecular risk profiles for a cohort of 1406 patients (aged ≥60 years) with acute myeloid leukaemia, but otherwise medically healthy, who were treated with two courses of intensive induction chemotherapy (tioguanine, standard-dose cytarabine, and daunorubicin followed by high-dose cytarabine and mitoxantrone; or with high-dose cytarabine and mitoxantrone in the first and second induction courses) in the German Acute Myeloid Leukaemia Cooperative Group 1999 study. Risk prediction was validated in an independent cohort of 801 patients (aged >60 years) with acute myeloid leukaemia who were given two courses of cytarabine and daunorubicin in the Acute Myeloid Leukaemia 1996 study. Findings Body temperature, age, de-novo leukaemia versus leukaemia secondary to cytotoxic treatment or an antecedent haematological disease, haemoglobin, platelet count, fibrinogen, and serum concentration of lactate dehydrogenase were significantly associated with CR or ED. The probability of CR with knowledge of cytogenetic and molecular risk (score 1) was from 12% to 91%, and without knowledge (score 2) from 21% to 80%. The predicted risk of ED was from 6% to 69% for score 1 and from 7% to 63% for score 2. The predictive power of the risk scores was confirmed in the independent patient cohort (CR score 1, from 10% to 91%; CR score 2, from 16% to 80%; ED score 1, from 6% to 69%; and ED score 2, from 7% to 61%). Interpretation The scores for acute myeloid leukaemia can be used to predict the probability of CR and the risk of ED in older patients with acute myeloid leukaemia, but otherwise medically healthy, for whom intensive induction chemotherapy is planned. This information can help physicians with difficult decisions for treatment of these patients. Funding Deutsche Krebshilfe and Deutsche Forschungsgemeinschaft.
Background Attention-deficit/hyperactivity disorder (ADHD) symptoms are dimensionally distributed in the population. This study aimed to assess the role of the catechol-O-methyltransferase ( COMT ) ...and of the dopamine transporter ( DAT1 ) genes on ADHD symptoms in the general population. Methods We investigated 4101 individuals from the 1993 Pelotas Birth Cohort Study using the parent version of the Strengths and Difficulties Questionnaire (SDQ) at ages 11 and 15 years. The SDQ hyperactivity/inattention scores were the main outcomes. Limitations Linear regression analyses demonstrated that the increasing number of COMT158 Val and DAT1 10R alleles significantly predicted increasing SDQ hyperactivity/inattention scores in boys at both 11 and 15 years of age (β coefficient = 0.049, t = 2.189, p = 0.029, R2 = 0.012, and β coefficient = 0.064, t = 2.832, p = 0.005, R2 = 0.008, respectively). The presence of both COMT158 Val and DAT1 10R alleles was also associated with full categorical ADHD diagnosis at 18 years of age in boys (χ2 = 4.561, p = 0.033, odds ratio 2.473, 95% confidence interval 1.048–5.838) from this cohort. We did not observe these associations in girls. Results Our analyses of SDQ hyperactivity/inattention scores were not corrected for SDQ scores of conduct problems because these variables were highly correlated. Conclusion This study demonstrates a role for COMT and DAT1 genes on hyperactivity/inattention symptoms and provides further support for ADHD as the extreme of traits that vary in the population. It also confirms previous evidence for sexual dimorphism on COMT and DAT1 gene expression.
Mental health problems affect 10–20% of children and adolescents worldwide. Despite their relevance as a leading cause of health-related disability in this age group and their longlasting effects ...throughout life, the mental health needs of children and adolescents are neglected, especially in low-income and middle-income countries. In this report we review the evidence and the gaps in the published work in terms of prevalence, risk and protective factors, and interventions to prevent and treat childhood and adolescent mental health problems. We also discuss barriers to, and approaches for, the implementation of such strategies in low-resource settings. Action is imperative to reduce the burden of mental health problems in future generations and to allow for the full development of vulnerable children and adolescents worldwide.
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