Cho 2012.

Methods	A 12 week prospective, exploratory, open‐labeled cohort study to achieve symptomatic remission by OROS‐methylphenidate. The purpose of the study was to investigate a possible association between norepinephrine genes and cardiovascular side effects of OROS‐methylphenidate in Korean children with ADHD
Participants	Number of participants screened: not stated Number of participants included: 101 Number of participants followed up: 101 Number of withdrawals: 0 Diagnosis of ADHD: DSM‐IV‐TR (subtype: combined (67.6%), hyperactive‐impulsive (5.8%), inattentive (26.4%)) Age: 8.73 (SD 1.78) years, range 6‐12 IQ: 102.3 (SD 11.9) Sex: 81 males, 20 females Methylphenidate‐naïve: 100% Ethnicity: Asian Country: South Korea Comorbidity: anxiety disorders (8.8%), ODD (6.8%), transient tic disorder (6,8%), enuresis (5.9%) Comedication: not stated Inclusion criteria: ADHD according to DSM‐IV‐TR Aged 6‐12 years Severity of symptoms equal to or more than 'moderate degree' on the Clinical Global Impression‐Severity (CGI‐S) scale and severe enough to warrant medication treatment The absence of any history of exposure to psychostimulants such as methylphenidate Exclusion criteria: Other mental disorders than transient tic disorder, oppositional defiant disorder, mild anxiety disorder and enuresis A past or present history of brain damage or convulsive disorder Mental retardation, autism, language difficulties or developmental problems including learning disabilities
Interventions	Methylphenidate: osmotic release oral system Mean methylphenidate dosage: 0.98 (SD 0.52) mg/kg Administration schedule: not stated Duration of intervention: 12 weeks Titration: initial dosage was determined by child's body weight: if ≥ 30 kg, 27 mg was administered; if < 30 kg, 18 mg was administered. The dosages were increased every 2 weeks for 9 weeks until they were sufficient to achieve a therapeutic effect, on the basis of the investigators and parents' assessments of symptoms and side effects, and then these doses were maintained until the 12th week. Treatment compliance: not stated
Outcomes	Electrocardiographic (ECG) parameters, including QT interval. Resting heart rate, seated pulse, blood pressure. All measures collected at 12 weeks after treatment. These measurements were obtained 60‐120 minutes after a dose was given. The cardiovascular parameters for all participants were measured manually
Notes	Sample calculation: yes Ethics approval: approved by the institutional review board (IRB) for human subjects at the Seoul National University Hospital and at 5 other hospitals in South Korea. Parents/guardians provided written informed consent, and the children or adolescents provided verbal assent regarding participation in this study. Funding: BN Kim was supported by a Korea Research Foundation Grant funded by the Korean Government (MOEHRD) and by the Korean Janssen Pharmaceutical Company Vested interest/authors' affiliations: Janssen Korea Key conclusions of the study authors: the overall cardiovascular effects of OROS‐methylphenidate were modest. However, our findings show a positive association between norepinephrine‐related gene polymorphisms and cardiovascular response induced by methylphenidate in Korean children with ADHD. Consideration must be given to such children or adults with specific norepinephrine‐related genotypes, especially if they show significant changes in heart rate or diastolic blood pressure after OROS‐methylphenidate administration Comments from the study authors: monitoring only occurred at baseline and after 12 weeks of methylphenidate treatment. 9% of the study participants with ADHD had co‐morbid anxiety disorders which may have affected cardiovascular measures. As this study was exploratory we did not apply multiple comparison corrections for the 3 cardiovascular outcomes; future studies may strengthen and perhaps extend the current findings by applying such corrections in larger samples. According to the inclusion and exclusion criteria, no children enrolled in this study had clinical histories of hypertension, hypotension or cardiovascular disease. Therefore, no conclusions can be made about the use of methylphenidate in children with significant cardiovascular dysfunction or risk factors Supplemental information regarding outcome measures and protocol requested twice in January 2014 with no answer