The Kiddie Schedule for Affective Disorders and Schizophrenia Present and Lifetime Version (K-SADS-PL) for DSM-5: A validation for neurodevelopmental disorders in Japanese outpatients.

OBJECTIVE: The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) is a widely used semi-structured diagnostic interview in child and adolescent psychiatry. However, given the extensive use of the K-SADS-PL in clinical practice and research and its adaptation for use in many languages and cultures, validation studies of the instrument are scarce. This study was designed to examine the inter-rater reliability, criterion validity and construct validity of the updated instrument, the K-SADS-PL for DSM-5, in Japanese outpatients totaling 95 children and adolescents. METHOD: We translated and adapted the updated instrument into Japanese using a standard forward-backward translation procedure. Two of nine experienced clinicians independently made diagnoses using the interview for each patient in a conjoint session. Discrepancies in diagnosis between two clinicians were resolved by consensus, and the consensus diagnosis was compared with a "best-estimate" diagnosis made by five experienced clinicians using all available data sources for patients who were blinded to the diagnosis using the K-SADS-PL for DSM-5. The "best-estimate" diagnosis of ASD was also based on the Diagnostic Interview for Social and Communication Disorders. RESULTS: The inter-rater reliability was very good, as shown by κ ≥ 0.8 for all disorders examined: autism spectrum disorder (ASD), attention-deficit hyperactivity disorder, tic disorders, selective mutism, enuresis and encopresis. The criterion validity was good, as shown by κ ≥ 0.6 for all disorders examined, except for ASD (κ = 0.59). This study also revealed good construct validity of the instrument by confirming the expected associations with each scale from the Social Responsiveness Scale-2nd edition and the Strengths and Difficulties Questionnaire. CONCLUSION: These results suggest that the K-SADS-PL for DSM-5 generates valid diagnoses in child and adolescent psychiatry.

Psychometrics of rating scales for externalizing disorders in Japanese outpatients: The ADHD-Rating Scale-5 and the Disruptive Behavior Disorders Rating Scale.

OBJECTIVES: This study validated the Japanese version of the Attention-Deficit/Hyperactivity Disorder-Rating Scale-5 (ADHD-RS-5) and the Disruptive Behavior Disorders Rating Scale. We extended the ADHD-RS-5 by adding the oppositional defiant disorder and conduct disorder subscales to compare the two rating scales psychometrically. METHODS: We examined the internal consistency, test-retest reliability, construct validity and criterion validity of the two rating scales in 135 Japanese outpatients aged 6-18 years. RESULTS: The internal consistency and test-retest reliability were good for all the subscales of the two rating scales except for the conduct disorder subscale of the ADHD-RS-5 extended. Good construct validity was revealed by expected correlational patterns between subscales from the two rating scales and the Children Behavior Checklist. The criterion validity was good for all the subscales of the two rating scales rated by parents, while teacher-ratings revealed substantially lower predictive ability for all the subscales. Agreement between parent- and teacher-ratings of the two rating scales was generally moderate and using predictive ratings alone of both ratings showed the best predictive ability among the integration methods examined. CONCLUSION: The two rating scales have sound psychometric properties and will aid in screening and severity assessment of externalizing disorders in Japanese clinical settings.

Population pharmacokinetics and limited sampling strategy for therapeutic drug monitoring of mycophenolate mofetil in Japanese patients with lupus nephritis.

BACKGROUND: Mycophenolate mofetil (MMF), a prodrug of the immunosuppressive agent mycophenolic acid (MPA), is difficult to administer because of the pharmacokinetic complexity of MPA. Although dosage adjustment according to the 12-h area under the concentration-time curve (AUC0-12) is thought to be desirable, multiple blood samplings for AUC calculation may pose a clinical challenge. A limited sampling strategy (LSS) would provide a solution; however, little is known about MPA pharmacokinetics in lupus nephritis patients, especially in those with Asian backgrounds, or few, if any, LSSs are reported for them. METHODS: Thirty-four adult Japanese patients receiving MMF for lupus nephritis were examined retrospectively. MPA pharmacokinetics were investigated, and a PPK model was developed using Phoenix® NLME™ software. Single and double blood sampling strategies from Bayesian estimation using the PPK model and from multiple linear regression were compared. Tolerability was also evaluated. RESULTS: In the pharmacokinetic analysis, renal function and serum albumin had significant effects on dose-normalized AUC0-12; and serum albumin, concomitant proton pump inhibitor (PPI) and iron/magnesium oxide did on dose-normalized maximum concentration. As a PPK model, a two-compartment model was developed with a transit absorption model and first-order elimination, in which creatinine clearance and serum albumin were covariates for MPA clearance. The double sampling strategy at 1 and 4 h by multiple linear regression showed the best agreement with the observed AUC0-12 (r2 = 0.885). Of the single sampling strategies, the one at 6 h by Bayesian estimation performed best (r2 = 0.769). The tolerability evaluation showed that correlations were suggested for gastrointestinal involvement. CONCLUSIONS: The present study developed the first PPK model of MPA for Japanese lupus nephritis patients. As for LSSs, a double sampling strategy at 1 and 4 h by multiple linear regression would work best; when only a single blood sampling is allowed, a strategy at 6 h by Bayesian estimation using the PPK model developed in this study would be best. The LSSs good enough for clinical use may facilitate safer, more effective, and individualized therapy.

Psychometrics of the kiddie schedule for affective disorders and schizophrenia present and lifetime version for DSM-5 in Japanese outpatients.

OBJECTIVE: The Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime version (K-SADS-PL) is a widely used semi-structured diagnostic interview in child and adolescent psychiatry. However, the psychometric properties of its updated version, the K-SADS-PL for DSM-5, have scarcely been examined, especially for criterion validity. This study was designed to examine the inter-rater reliability, criterion validity and construct validity of the K-SADS-PL for DSM-5 in 137 Japanese outpatients. METHODS: Two of 12 experienced clinicians independently performed the K-SADS interview for each patient in a conjoint session, and the resulting consensus diagnosis was compared with a "best-estimate" diagnosis made by two of eight experienced clinicians using all available information for the patient. RESULTS: The inter-rater reliability was excellent, as shown by κ > 0.75 for all disorders, with the exception of current separation anxiety disorder. The criterion validity was fair to good, as shown by κ > 0.40 for all disorders, with the exception of current and lifetime agoraphobia. The construct validity was also good, as shown by theoretically expected associations between the K-SADS-PL diagnoses and subscales of the child behavior checklist. CONCLUSION: The K-SADS-PL for DSM-5, now available in Japanese, generates valid diagnoses in child and adolescent psychiatry.

Practical applications of brief screening questionnaires for autism spectrum disorder in a psychiatry outpatient setting.

OBJECTIVES: This study was designed to examine the diagnostic performance of the social and communication disorders checklist (SCDC) and strength and difficulties questionnaire (SDQ) to detect autism spectrum conditions (ASC), along with the social responsiveness scale-second edition (SRS-2) as reference, in a psychiatry outpatient setting. METHODS: We translated the SCDC into Japanese since its Japanese version was unavailable. We examined its test-retest reliability as well as the internal consistency reliability and diagnostic performance of the three questionnaires among 41 Japanese psychiatric outpatients, using the best-estimate diagnosis of ASC based on the diagnostic interview for social and communication disorders, as a gold standard. RESULTS: The test-retest reliability was high for the SCDC. Although the internal consistency reliability was high for the SCDC and SRS-2, that was low for the prosocial and peer problem subscales of the SDQ. The performance of the SCDC, SDQ, and SRS-2 to detect ASC was moderate: the area under the ROC curve of 0.78, 0.78, and 0.84, respectively. CONCLUSIONS: Although questionnaires to detect ASC, including the three examined, generally have only moderate performance in this setting, these can be successfully applied to high-risk populations such as psychiatry outpatients, when multi-level rather than dichotomous likelihood ratios are used.