Assessing Outcomes for Cost-Utility Analysis in Children and Adolescents With Mental Health Problems: Are Multiattribute Utility Instruments Fit for Purpose?

OBJECTIVES: The objective of this study was to compare the concurrent and construct validity, as well as the sensitivity of 5 multiattribute utility instruments (MAUIs), including the Assessment of Quality of Life-6D (AQoL-6D), EQ-5D-Y, Health Utilities Index (HUI)-2 and HUI-3, and the Child Health Utility 9D, 1 generic pediatric quality of life instrument, with 3 routinely collected outcome measures in Australian mental health services (Strengths and Difficulties Questionnaire, Clinical Global Assessment Scale [CGAS] and the Health of the Nation Outcome Scale for Children and Adolescents) in children and adolescents diagnosed of internalizing (eg, anxiety/depression), externalizing (eg, attention deficit hyperactivity disorder/conduct disorders), and trauma/stress related mental disorders. METHODS: A cross-sectional survey of measures, including demographic and basic treatment information, in children/adolescents recruited via 5 child and youth mental health services in Queensland and Victoria, Australia. Measures were either proxy or self-report completed, the CGAS and the Health of the Nation Outcome Scale for Children and Adolescents were clinician completed. RESULTS: The sample included 426 participants and had a mean age of 13.7 years (range 7-18 years). Utilities (as calculated from MAUIs) were generally lower in older adolescents and those with internalizing disorders. All MAUIs and self-reported clinical measures significantly correlated with each other (absolute correlation range 0.40-0.90), with the AQoL-6D showing generally higher levels of correlations. Correlations between the MAUIs and clinician/proxy-reported measures were weak, regardless of diagnosis (absolute correlation range 0.09-0.47). Generally, EQ-5D-Y, HUI-2, and AQoL-6D were more sensitive than Child Health Utility 9D and HUI-3 when distinguishing between different severities according to clinician-assessed CGAS (effect size range 0.17-0.84). CONCLUSIONS: The study showed that the commonly used MAUIs had good concurrent and construct validity compared with routinely used self-complete measures but poor validity when compared with clinician/proxy-completed measures. These findings generally held across different diagnoses.

Prioritizing natural product compounds using 1D-TOCSY NMR spectroscopy.

Natural product (NP) secondary metabolites are designed evolutionarily to have biological effects in other organisms for defense and the mediation of ecological interactions. Their structural complexity and diversity complement biological systems, allowing them to display unique bioactivities. Although more than half of all pharmaceuticals stem from NPs, pharmaceutical companies have reduced NP-based drug discovery programs due to various time and cost-consuming pitfalls; the re-isolation of already known, bioactive compounds being one of the most common. Dereplication methods minimize cost and speed up the discovery of new, bioactive leads by quickly identifying known small molecules. Liquid chromatography coupled mass spectrometry (LC-MS) is the most widely utilized dereplication technique because of its sensitivity and the open-source availability of MS libraries. However, single-ionization techniques are not able to detect all metabolites in a biological sample. Even more concerning, bioactive isomers cannot be differentiated by their mass alone. In response to these issues, complementary dereplication tools are needed to assist MS. Total correlation spectroscopy (TOCSY) is an NMR experiment that illustrates the connection between all coupled protons in a spin system. Most molecules contain several spin systems, and together, these networks form a unique fingerprint that can be utilized to quickly differentiate and dereplicate known compounds, even those with identical masses. In addition, these fingerprints can be used to identify possible new compounds in a crude NP-extract that are structurally related to known small molecules. From a sample of the U.S. endemic lichen Niebla homalea, five non-cytotoxic, new triterpenoids and three known triterpenoids were isolated in our laboratory. As our goal is to discover both new and cytotoxic compounds, we developed a one-dimensional TOCSY-based dereplication method to quickly identify these non-bioactive triterpenoids. After prioritizing triterpenoid-free fractions that showed antiproliferative activity in various cancer cell lines, the new compound 11 was isolated from another Niebla species.

Psychometric assessment of a self-administered version of the Significant Other Survey.

While there are a number of general measures that assess interpersonal and psychological distress experienced by individuals who are in a close relationship with a substance abusing adult, until recently the field has lacked a psychometrically sound, self-administered multidimensional measure explicitly designed to measure the problems of non-substance-abusing adults who are concerned about a substance using loved one. This study examined the psychometric properties of a 54-item, self-administered (SA) version of the Significant Other Survey (SOS), a measure designed to address this gap. The SOS-SA assesses problems across seven problem domains (emotional, relationship, family, financial, physical violence, legal, health). Coefficient alpha estimates (N = 168) were good to excellent for five of the domains, the test-retest reliability (N = 83) across a 7-day time frame was fair to excellent for all seven domains. Similar reliability coefficients were identified regardless of whether the item queried about the problem frequency or perceived severity. There was preliminary support for the construct and discriminant validity of the SOS-SA. The SOS-SA appears to be a promising instrument given that it is brief, requires no specialized training to administer, and has good psychometric properties.