Cattram Nguyen

Stability of language performance at 4 and 5 years: measurement and participant variability

BACKGROUND Language impairment (LI) in the preschool years is known to vary over time. Stability in the diagnosis of LI may be influenced by children’s individual variability, the measurement error of commonly used assessment instruments and the cut-points used to define impairment. AIMS To investigate the agreement between two different age-based versions of a language assessment instrument and the stability of the classification of LI using the two measures over a 12-month period. METHODS & PROCEDURES A total of 945 participants completed the Clinical Evaluation of Language Fundamentals(CELF—Preschool 2 or 4th Edn) at 4 and 5 years of age. Agreement and stability were analysed using Bland–Altman plots, correlation and odds ratios. Sensitivity and specificity were calculated for two thresholds of the CELF-P2 using the diagnostic category on the child’s subsequent CELF-4. OUTCOMES & RESULTS For all CELF scores, mean differences for the cohort between 4 and 5 years were within 1.5 scale score units. In contrast, at the individual level variability was found across the range of scores and was of a greater magnitude than previously reported. Stability in LI classification was low, with 36% of 5-year-olds with LI (defined as a standard score below –1.25) classified as typical at 4 years, even though odds ratios calculated from classifications at the two time points suggested that 4-year-olds with LI had 23 times greater odds than their typical peers to receive a diagnosis of LI at 5 years. The CELF-P2 did not demonstrate adequate levels of diagnostic accuracy for LI at 5 years: sensitivity of 64% and specificity of 92.9%. CONCLUSIONS Substantial variability across the entire range of possible CELF scores was observed in this community cohort between the ages of 4 and 5 years. The stability of LI classification was lower than that reported in previous research conducted primarily on smaller clinical cohorts. The current study’s results suggest that the variability observed in developmental language pathways is the result of a combination of limitations in measurement instruments, individual children’s abilities and the arbitrary nature of the boundaries defining LI.

Bidirectional associations between child sleep problems and internalizing and externalizing difficulties from preschool to early adolescence

Importance Although multiple cross-sectional and longitudinal studies have established that sleep problems and behavioral difficulties are associated in children, the directionality of this association and whether sleep problems are differentially associated with different types of childhood behavioral difficulties are unclear. Understanding these associations will inform the focus and timing of interventions. Objective To determine whether longitudinal and reciprocal associations exist between child sleep problems and externalizing, internalizing, or both behavioral difficulties. Design, Setting, and Participants Prospective cohort study using nationally representative data from the first 5 waves (2004, 2006, 2008, 2010, and 2012) of the kindergarten cohort (4983 children aged 4-5 years in 2004) collected for the Longitudinal Study of Australian Children. Associations were evaluated using cross-lagged structural equation model analyses performed from May 25, 2016, to September 20, 2017. Main Outcomes and Measures Child sleep problems and internalizing and externalizing behavioral difficulties. Sleep problems were defined using parent-reported child sleep problem severity and specific difficulties (ie, difficulty getting to sleep at night, not happy sleeping alone, waking during the night, and restless sleep) on 4 or more nights of the week. Child behavioral difficulties were defined using the parent-reported Strengths and Difficulties Questionnaire for externalizing difficulties (conduct problems and hyperactivity/inattention subscales) and internalizing difficulties (emotional problems subscale). Results The 4983 children enrolled in 2004 had a mean (SD) age of 4.7 (0.2) years and comprised a similar percentage of boys (2536 [50.9%]) and girls. In 2012, 3956 children (79.4%) aged 12 to 13 years were retained. Significant bidirectional associations were detected between sleep problems and externalizing difficulties during the elementary school transition period, with greater sleep problems associated with later externalizing behavior and vice versa (cross-lagged path coefficient, 0.04 [95% CI, 0.01-0.08] to 0.09 [95% CI, 0.06-0.13]). Although sleep was a significant driver of later internalizing difficulties (coefficient, 0.10 [95% CI, 0.07-0.14] to 0.16 [95% CI, 0.12-0.19]), the reverse association was not significant. In the final model that included all 3 constructs, the associations were attenuated but remained significant over time. Conclusions and Relevance These results suggest that future studies should investigate whether implementing sleep problem intervention decreases the occurrence of both externalizing and internalizing difficulties. Interventions targeting externalizing, but not internalizing, difficulties may benefit childhood sleep.

Diagnosing problems with imputation models using the Kolmogorov-Smirnov test: a simulation study

BackgroundMultiple imputation (MI) is becoming increasingly popular as a strategy for handling missing data, but there is a scarcity of tools for checking the adequacy of imputation models. The Kolmogorov-Smirnov (KS) test has been identified as a potential diagnostic method for assessing whether the distribution of imputed data deviates substantially from that of the observed data. The aim of this study was to evaluate the performance of the KS test as an imputation diagnostic.MethodsUsing simulation, we examined whether the KS test could reliably identify departures from assumptions made in the imputation model. To do this we examined how the p-values from the KS test behaved when skewed and heavy-tailed data were imputed using a normal imputation model. We varied the amount of missing data, the missing data models and the amount of skewness, and evaluated the performance of KS test in diagnosing issues with the imputation models under these different scenarios.ResultsThe KS test was able to flag differences between the observations and imputed values; however, these differences did not always correspond to problems with MI inference for the regression parameter of interest. When there was a strong missing at random dependency, the KS p-values were very small, regardless of whether or not the MI estimates were biased; so that the KS test was not able to discriminate between imputed variables that required further investigation, and those that did not. The p-values were also sensitive to sample size and the proportion of missing data, adding to the challenge of interpreting the results from the KS test.ConclusionsGiven our study results, it is difficult to establish guidelines or recommendations for using the KS test as a diagnostic tool for MI. The investigation of other imputation diagnostics and their incorporation into statistical software are important areas for future research.

Model checking in multiple imputation: an overview and case study

AbstractBackgroundMultiple imputation has become very popular as a general-purpose method for handling missing data. The validity of multiple-imputation-based analyses relies on the use of an appropriate model to impute the missing values. Despite the widespread use of multiple imputation, there are few guidelines available for checking imputation models. AnalysisIn this paper, we provide an overview of currently available methods for checking imputation models. These include graphical checks and numerical summaries, as well as simulation-based methods such as posterior predictive checking. These model checking techniques are illustrated using an analysis affected by missing data from the Longitudinal Study of Australian Children.ConclusionsAs multiple imputation becomes further established as a standard approach for handling missing data, it will become increasingly important that researchers employ appropriate model checking approaches to ensure that reliable results are obtained when using this method.

Sustained antibody responses 6 years following 1, 2, or 3 doses of quadrivalent Human Papillomavirus (HPV) vaccine in adolescent Fijian girls, and subsequent responses to a single dose of bivalent HPV vaccine: a prospective cohort study

Background The duration of antibody response following reduced human papillomavirus (HPV) vaccine doses has not been determined. We compared the antibody responses in girls previously vaccinated with zero, 1, 2, or 3 doses of quadrivalent HPV vaccine (4vHPV; Gardasil, Merck) 6 years previously. Methods A prospective cohort study was undertaken in 200 Fijian girls 15-19 years of age. Approximately equal numbers of girls from 2 main ethnic groups (Fijians of Indian descent [FID] and Indigenous Fijians [iTaukei]) in Fiji were recruited for each dosage groups. Blood was drawn before and 28 days following a single dose of bivalent HPV vaccine (2vHPV; Cervarix, GlaxoSmithKline). We measured neutralizing antibodies (NAb) against HPV-6, -11, -16, and -18 using the pseudovirion-based neutralization assay. Results After 6 years (before a dose of 2vHPV was given), the geometric mean NAb titers for all 4 HPV types were not statistically different between 2-dose (2D) and 3-dose (3D) recipients: HPV-6 (3D: 2216 [95% confidence interval {CI},1695-2896]; 2D: 1476 [95% CI, 1019-2137]; P = .07), HPV-11 (3D: 4431 [95% CI, 3396-5783]; 2D: 2951 [95% CI, 1984-4390]; P = .09), HPV-16 (3D: 3373 [95% CI, 2511-4530]; 2D: 3275 [95% CI, 2452-4373]; P = .89); HPV-18 (3D: 628 [95% CI: 445-888]; 2D: 606 [95% CI, 462-862]; P = .89), and were higher in FID than iTaukei girls. Although 1-dose recipients had significantly lower NAb titers than 2-/3-dose recipients, their NAb titers were 5- to 30-fold higher than unvaccinated girls. Post-2vHPV NAb titers against HPV-16 and -18 were not statistically different between girls who received 1, 2, or 3 doses of 4vHPV previously. Conclusions Two doses of 4vHPV provide similar NAb titers as 3 doses for 6 years, although the clinical significance is unknown. A single dose of 4vHPV elicits antibodies that persisted for at least 6 years, and induced immune memory, suggesting possible protection against HPV vaccine types after a single dose of 4vHPV.

Determining the pneumococcal conjugate vaccine coverage required for indirect protection against vaccine-type pneumococcal carriage in low and middle-income countries: a protocol for a prospective observational study

Introduction Pneumococcal conjugate vaccines (PCVs) prevent disease through both direct protection of vaccinated individuals and indirect protection of unvaccinated individuals by reducing nasopharyngeal (NP) carriage and transmission of vaccine-type (VT) pneumococci. While the indirect effects of PCV vaccination are well described, the PCV coverage required to achieve the indirect effects is unknown. We will investigate the relationship between PCV coverage and VT carriage among undervaccinated children using hospital-based NP pneumococcal carriage surveillance at three sites in Asia and the Pacific. Methods and analysis We are recruiting cases, defined as children aged 2–59 months admitted to participating hospitals with acute respiratory infection in Lao People’s Democratic Republic, Mongolia and Papua New Guinea. Thirteen-valent PCV status is obtained from written records. NP swabs are collected according to standard methods, screened using lytA qPCR and serotyped by microarray. Village-level vaccination coverage, for the resident communities of the recruited cases, is determined using administrative data or community survey. Our analysis will investigate the relationship between VT carriage among undervaccinated cases (indirect effects) and vaccine coverage using generalised estimating equations. Ethics and dissemination Ethical approval has been obtained from the relevant ethics committees at participating sites. The results are intended for publication in open-access peer-reviewed journals and will demonstrate methods suitable for low- and middle-income countries to monitor vaccine impact and inform vaccine policy makers about the PCV coverage required to achieve indirect protection.

High agreement between the new Mongolian electronic immunization register and written immunization records: a health centre based audit

Introduction Monitoring of vaccination coverage is vital for the prevention and control of vaccine-preventable diseases. Electronic immunization registers have been increasingly adopted to assist with the monitoring of vaccine coverage; however, there is limited literature about the use of electronic registers in low- and middle-income countries such as Mongolia. We aimed to determine the accuracy and completeness of the newly introduced electronic immunization register for calculating vaccination coverage and determining vaccine effectiveness within two districts in Mongolia in comparison to written health provider records. Methods We conducted a cross-sectional record review among children 2–23 months of age vaccinated at immunization clinics within the two districts. We linked data from written records with the electronic immunization register using the national identification number to determine the completeness and accuracy of the electronic register. Results Both completeness (90.9%; 95% CI: 88.4–93.4) and accuracy (93.3%; 95% CI: 84.1–97.4) of the electronic immunization register were high when compared to written records. The increase in completeness over time indicated a delay in data entry. Conclusion Through this audit, we have demonstrated concordance between a newly introduced electronic register and health provider records in a middle-income country setting. Based on this experience, we recommend that electronic registers be accompanied by routine quality assurance procedures for the monitoring of vaccination programmes in such settings.

Validation of administrative data to estimate vaccine impact: Audit of the Fiji hospital admissions electronic database, 2007–2011 & 2014–2015

OBJECTIVES Post-licensure studies to evaluate vaccine impact are an important component of introducing new vaccines. Such studies often rely on routinely collected data but the limitations to these data must be understood. To validate administrative data for use in 10-valent pneumococcal conjugate and rotavirus vaccine impact evaluations we have audited the two electronic database capturing hospital admissions in Fiji for completeness and consistency. METHODS Hospital admission data for one week per year between 2007-2011 and 2014-2015 was collected from ward registers for selected hospitals. Ward registers were defined as the reference standard and compared to data captured in electronic databases. Data quality was assessed for completeness of admissions data (percentage of admissions in the electronic database, expressed as sensitivity), consistency of complete reporting (determined by identifying variables associated to complete reporting), and completeness of coding (percentage of admissions in the electronic database with an assigned ICD-10-AM code). RESULTS Over all hospitals and years, the sensitivity for completeness of admission data was 83% (95% CI: 81.3, 84.6). Consistency of complete reporting varied and was highest at tertiary hospitals using the electronic database (sensitivity: 89.1%, 95% CI: 87.4, 90.7). The overall completeness of coding at tertiary hospitals was 90.8% (95% CI: 90.5, 91.1) with annual and hospital variation. CONCLUSION The administrative data in the electronic databases in Fiji are of reasonable quality for the vaccine impact evaluation. This quantification of the missing data can be used to adjust the vaccine impact estimates.

What Influences Parental Engagement in Early Intervention? Parent, Program and Community Predictors of Enrolment, Retention and Involvement

Poor participant engagement undermines individual and public health benefits of early intervention programs. This study assessed the extent to which three types of engagement (participant enrolment, retention and involvement) were influenced by individual, program and contextual factors. Data were from a cluster randomised controlled trial (N = 1447) of a community-based parenting program, delivered at two levels of intensity (group sessions with and without individualised home coaching) conducted in Victoria, Australia. Individual (parent and family) factors and program factors were assessed by parent report and administrative records, and contextual factors by area-level population statistics. Data were analysed using multilevel logistic or linear regression models. Individual and contextual factors predicted enrolment, while family and program factors were more influential on program retention and parents’ active involvement. Provision of individualised support was important to all forms of engagement, particularly for families experiencing the greatest barriers to participation. These findings indicate that different strategies are required to effectively support families in the processes of enrolling, continuing to attend and actively participating in early intervention programs.

Cellular Immune Responses 6 Years Following 1, 2, or 3 Doses of Quadrivalent HPV Vaccine in Fijian Girls and Subsequent Responses to a Dose of Bivalent HPV Vaccine

Abstract Background This study examined the cellular immunity of 0, 1, 2, and 3 doses of Gardasil vaccine (4vHPV) in girls after 6 years and their responses to a subsequent dose of Cervarix vaccine (2vHPV). Methods A subset of girls (n = 59) who previously received 0, 1, 2, or 3 doses of 4vHPV 6 years earlier were randomly selected from a cohort study of Fijian girls (age 15–19 years). Blood was collected before and 28 days after a dose of 2vHPV. The HPV16- and HPV18-specific cellular immune response was determined by IFNγ-ELISPOT and by measurement of cytokines in peripheral blood mononuclear cell supernatants. Results Six years after 4vHPV vaccination, HPV18-specific responses were significantly lower in the 1- (1D) or 2-dose (2D) recipients compared with 3-dose recipients (2D: IFNγ-ELISPOT: P = .008; cytokines, IFNγ: P = .002; IL-2: P = .022; TNFα: P = .016; IL-10: P = .018; 1D: IL-2: P = .031; IL-10: P = .014). These differences were no longer significant post-2vHPV. No significant differences in HPV16 responses (except IL-2, P < .05) were observed between the 2- or 1-dose recipients and 3-dose recipients. Conclusions These data suggest that cellular immunity following reduced-dose schedules was detectable after 6 years, although the responses were variable between HPV types and dosage groups. The clinical significance of this is unknown. Further studies on the impact of reduced dose schedules are needed, particularly in high–disease burden settings.