Intensive behavioural interventions based on applied behaviour analysis for young children with autism: An international collaborative individual participant data meta-analysis

This individual participant data meta-analysis is the most intensive possible evaluation of the effectiveness of early intensive applied behaviour analysis–based interventions for pre-school autistic children compared with treatment as usual/eclectic interventions. Data from 491 participants (originally collected in 10 studies) were included. Children receiving early intensive applied behaviour analysis–based interventions improved more on the Vineland adaptive behaviour scale (MD = 7.00; 95% confidence interval = 1.95–12.06) and cognitive ability (intelligence quotient) (MD = 14.13; 95% confidence interval = 9.16–19.10) relative to comparators at 2 years; though effects varied considerably across studies. Evidence for other outcomes was inconclusive due to insufficient evidence and there were few data on longer-term effects. All studies were at risk of bias across several domains, often due to the lack of randomisation or blinding of outcome assessors. Given the emerging evidence of modest, albeit short term, effects of a range of pre-school autism interventions and the limitations of the quality of evaluation studies to date, future research should investigate which supports and interventions are most effective for children and families prioritising outcomes measures that are meaningful for the autism community and longer-term follow-up. Further systematic reviews of the existing evidence are unlikely to add to the findings presented here. Lay abstract Early intensive applied behaviour analysis–based interventions are designed to support young autistic children’s learning and development. Unfortunately, the available evidence about the effectiveness of these interventions remains unclear. Several reviews have focused on the published findings rather than contacting the authors to collect and analyse data about the individual participants in the original studies. Also, most of the studies were carried out by groups involved in delivering the interventions leading to the potential bias in interpreting the results. Our research team (supported by an international advisory group) carried out an independent individual patient data review by collecting the original participant data from the authors of the studies, to examine the effectiveness of these interventions. The results suggested that early intensive applied behaviour analysis–based interventions might lead to some changes in children’s cognitive ability (intelligence quotient) and everyday life skills after 2 years, compared with standard treatments. However, all the studies had problems with the way they were designed. Also, few of the studies looked at outcomes that have been described as most important to autistic people or followed children beyond 2 years. We think that further systematic reviews of the existing evidence are unlikely to add to the findings of our review. Furthermore, we recommend that future research should investigate which types of supports and interventions are most effective for children and families, prioritising outcomes measures that are meaningful for the autism community and include, wherever possible, longer-term follow-up.

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Subclinical thyroid dysfunction and depressive symptoms: protocol for a systematic review and individual participant data meta-analysis of prospective cohort studies

BMJ Open ◽

10.1136/bmjopen-2019-029716 ◽

2019 ◽

Vol 9 (7) ◽

pp. e029716

Author(s):

Lea Wildisen ◽

Elisavet Moutzouri ◽

Shanthi Beglinger ◽

Lamprini Syrogiannouli ◽

Anne R Cappola ◽

...

Keyword(s):

Systematic Review ◽

Depressive Symptoms ◽

Cohort Studies ◽

Prospective Cohort ◽

Thyroid Dysfunction ◽

Meta Analysis ◽

Individual Participant Data ◽

Prospective Cohort Studies ◽

Individual Participant

IntroductionProspective cohort studies on the association between subclinical thyroid dysfunction and depressive symptoms have yielded conflicting findings, possibly because of differences in age, sex, thyroid-stimulating hormone cut-off levels or degree of baseline depressive symptoms. Analysis of individual participant data (IPD) may help clarify this association.Methods and analysisWe will conduct a systematic review and IPD meta-analysis of prospective studies on the association between subclinical thyroid dysfunction and depressive symptoms. We will identify studies through a systematic search of the literature in the Ovid Medline, Ovid Embase, Cochrane Central Register of Controlled Trials (CENTRAL) and Cumulative Index to Nursing and Allied Health Literature (CINAHL) databases from inception to April 2019 and from the Thyroid Studies Collaboration. We will ask corresponding authors of studies that meet our inclusion criteria to collaborate by providing IPD. Our primary outcome will be depressive symptoms at the first available individual follow-up, measured on a validated scale. We will convert all the scores to the Beck Depression Inventory scale. For each cohort, we will estimate the mean difference of depressive symptoms between participants with subclinical hypothyroidism or hyperthyroidism and control adjusted for depressive symptoms at baseline. Furthermore, we will adjust our multivariable linear regression analyses for age, sex, education and income. We will pool the effect estimates of all studies in a random-effects meta-analysis. Heterogeneity will be assessed by I2. Our secondary outcomes will be depressive symptoms at a specific follow-up time, at the last available individual follow-up and incidence of depression at the first, last and at a specific follow-up time. For the binary outcome of incident depression, we will use a logistic regression model.Ethics and disseminationFormal ethical approval is not required as primary data will not be collected. Our findings will have considerable implications for patient care. We will seek to publish this systematic review and IPD meta-analysis in a high-impact clinical journal.PROSPERO registration numberCRD42018091627.

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Exercise-based cardiac rehabilitation for chronic heart failure: the EXTRAMATCH II individual participant data meta-analysis

Health Technology Assessment ◽

10.3310/hta23250 ◽

2019 ◽

Vol 23 (25) ◽

pp. 1-98 ◽

Cited By ~ 3

Author(s):

Rod S Taylor ◽

Sarah Walker ◽

Oriana Ciani ◽

Fiona Warren ◽

Neil A Smart ◽

...

Keyword(s):

Heart Failure ◽

Chronic Heart Failure ◽

Exercise Capacity ◽

Meta Analysis ◽

Patient Characteristics ◽

Individual Participant Data ◽

Significant Difference ◽

Individual Participant ◽

The Impact

Background Current national and international guidelines on the management of heart failure (HF) recommend exercise-based cardiac rehabilitation (ExCR), but do not differentiate this recommendation according to patient subgroups. Objectives (1) To obtain definitive estimates of the impact of ExCR interventions compared with no exercise intervention (control) on mortality, hospitalisation, exercise capacity and health-related quality of life (HRQoL) in HF patients; (2) to determine the differential (subgroup) effects of ExCR in HF patients according to their age, sex, left ventricular ejection fraction, HF aetiology, New York Heart Association class and baseline exercise capacity; and (3) to assess whether or not the change in exercise capacity mediates for the impact of the ExCR on final outcomes (mortality, hospitalisation and HRQoL), and determine if this is an acceptable surrogate end point. Design This was an individual participant data (IPD) meta-analysis. Setting An international literature review. Participants HF patients in randomised controlled trials (RCTs) of ExCR. Interventions ExCR for at least 3 weeks compared with a no-exercise control, with 6 months’ follow-up. Main outcome measures All-cause and HF-specific mortality, all-cause and HF-specific hospitalisation, exercise capacity and HRQoL. Data sources IPD from eligible RCTs. Review methods RCTs from the Exercise Training Meta-Analysis of Trials for Chronic Heart Failure (ExTraMATCH/ExTraMATCH II) IPD meta-analysis and a 2014 Cochrane systematic review of ExCR (Taylor RS, Sagar VA, Davies EJ, Briscoe S, Coats AJ, Dalal H, et al. Exercise-based rehabilitation for heart failure. Cochrane Database Syst Rev 2014;4:CD003331). Results Out of the 23 eligible RCTs (4398 patients), 19 RCTs (3990 patients) contributed data to this IPD meta-analysis. There was a wide variation in exercise programme prescriptions across included studies. Compared with control, there was no statistically significant difference in pooled time-to-event estimates in favour of ExCR, although confidence intervals (CIs) were wide: all-cause mortality had a hazard ratio (HR) of 0.83 (95% CI 0.67 to 1.04); HF-related mortality had a HR of 0.84 (95% CI 0.49 to 1.46); all-cause hospitalisation had a HR of 0.90 (95% CI 0.76 to 1.06); and HF-related hospitalisation had a HR of 0.98 (95% CI 0.72 to 1.35). There was a statistically significant difference in favour of ExCR for exercise capacity and HRQoL. Compared with the control, improvements were seen in the 6-minute walk test (6MWT) (mean 21.0 m, 95% CI 1.57 to 40.4 m) and Minnesota Living with Heart Failure Questionnaire score (mean –5.94, 95% CI –1.0 to –10.9; lower scores indicate improved HRQoL) at 12 months’ follow-up. No strong evidence for differential intervention effects across patient characteristics was found for any outcomes. Moderate to good levels of correlation (R 2 trial > 50% and p > 0.50) between peak oxygen uptake (VO2peak) or the 6MWT with mortality and HRQoL were seen. The estimated surrogate threshold effect was an increase of 1.6 to 4.6 ml/kg/minute for VO2peak. Limitations There was a lack of consistency in how included RCTs defined and collected the outcomes: it was not possible to obtain IPD from all includable trials for all outcomes and patient-level data on exercise adherence was not sought. Conclusions In comparison with the no-exercise control, participation in ExCR improved the exercise and HRQoL in HF patients, but appeared to have no effect on their mortality or hospitalisation. No strong evidence was found of differential intervention effects of ExCR across patient characteristics. VO2peak and 6MWT may be suitable surrogate end points for the treatment effect of ExCR on mortality and HRQoL in HF. Future studies should aim to achieve a consensus on the definition of outcomes and promote reporting of a core set of HF data. The research team also seeks to extend current policies to encourage study authors to allow access to RCT data for the purpose of meta-analysis. Study registration This study is registered as PROSPERO CRD42014007170. Funding The National Institute for Health Research Health Technology Assessment programme.

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Physical Activity, Mental Health, and Well-Being in Very Pre-Term and Term Born Adolescents: An Individual Participant Data Meta-Analysis of Two Accelerometry Studies

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph18041735 ◽

2021 ◽

Vol 18 (4) ◽

pp. 1735

Author(s):

Asteria Brylka ◽

Dieter Wolke ◽

Sebastian Ludyga ◽

Ayten Bilgin ◽

Juliane Spiegler ◽

...

Keyword(s):

Mental Health ◽

Physical Activity ◽

Meta Analysis ◽

Well Being ◽

Emotional And Behavioral Problems ◽

Future Research ◽

Individual Participant Data ◽

Very Preterm ◽

Individual Participant ◽

Health And Well Being

This study examined whether physical activity is associated with better mental health and well-being among very preterm (≤32 weeks) and term born (≥37 weeks) adolescents alike or whether the associations are stronger in either of the groups. Physical activity was measured with accelerometry in children born very preterm and at term in two cohorts, the Basel Study of Preterm Children (BSPC; 40 adolescents born ≤32 weeks of gestation and 59 term born controls aged 12.3 years) and the Millennium Cohort Study (MCS; 45 adolescents born ≤32 weeks of gestation and 3137 term born controls aged 14.2 years on average). In both cohorts, emotional and behavioral problems were mother-reported using the Strengths and Difficulties Questionnaire. Subjective well-being was self-reported using the Kidscreen-52 Questionnaire in the BSPC and single items in the MCS. Hierarchical regressions with ‘preterm status × physical activity’-interaction effects were subjected to individual participant data (IPD) meta-analysis. IPD meta-analysis showed that higher levels of physical activity were associated with lower levels of peer problems, and higher levels of psychological well-being, better self-perception/body image, and school related well-being. Overall, the effect-sizes were small and the associations did not differ significantly between very preterm and term born adolescents. Future research may examine the mechanisms behind effects of physical activity on mental health and wellbeing in adolescence as well as which type of physical activity might be most beneficial for term and preterm born children.

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The efficacy of antidepressant medication and interpersonal psychotherapy for adult acute-phase depression: study protocol of a systematic review and meta-analysis of individual participant data

BJPsych Open ◽

10.1192/bjo.2021.4 ◽

2021 ◽

Vol 7 (2) ◽

Author(s):

Ellen Driessen ◽

Zachary D. Cohen ◽

Myrna M. Weissman ◽

John C. Markowitz ◽

Erica S. Weitz ◽

...

Keyword(s):

Systematic Review ◽

Outcome Measures ◽

Acute Phase ◽

Meta Analysis ◽

Antidepressant Medication ◽

Depression Treatment ◽

Individual Participant Data ◽

Individual Participant ◽

Meta Analyses

Background Antidepressant medication and interpersonal psychotherapy (IPT) are both recommended interventions in depression treatment guidelines based on literature reviews and meta-analyses. However, ‘conventional’ meta-analyses comparing their efficacy are limited by their reliance on reported study-level information and a narrow focus on depression outcome measures assessed at treatment completion. Individual participant data (IPD) meta-analysis, considered the gold standard in evidence synthesis, can improve the quality of the analyses when compared with conventional meta-analysis. Aims We describe the protocol for a systematic review and IPD meta-analysis comparing the efficacy of antidepressants and IPT for adult acute-phase depression across a range of outcome measures, including depressive symptom severity as well as functioning and well-being, at both post-treatment and follow-up (PROSPERO: CRD42020219891). Method We will conduct a systematic literature search in PubMed, PsycINFO, Embase and the Cochrane Library to identify randomised clinical trials comparing antidepressants and IPT in the acute-phase treatment of adults with depression. We will invite the authors of these studies to share the participant-level data of their trials. One-stage IPD meta-analyses will be conducted using mixed-effects models to assess treatment effects at post-treatment and follow-up for all outcome measures that are assessed in at least two studies. Conclusions This will be the first IPD meta-analysis examining antidepressants versus IPT efficacy. This study has the potential to enhance our knowledge of depression treatment by comparing the short- and long-term effects of two widely used interventions across a range of outcome measures using state-of-the-art statistical techniques.

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The effects of dietary and lifestyle interventions among pregnant women with overweight or obesity on early childhood outcomes: an individual participant data meta-analysis from randomised trials

BMC Medicine ◽

10.1186/s12916-021-01995-6 ◽

2021 ◽

Vol 19 (1) ◽

Author(s):

Jennie Louise ◽

Amanda J. Poprzeczny ◽

Andrea R. Deussen ◽

Christina Vinter ◽

Mette Tanvig ◽

...

Keyword(s):

Early Childhood ◽

Childhood Obesity ◽

Pregnant Women ◽

Lifestyle Intervention ◽

Literature Search ◽

Meta Analysis ◽

Systematic Literature Search ◽

Individual Participant Data ◽

Individual Participant

Abstract Background The impact of maternal obesity extends beyond birth, being independently associated with an increased risk of child obesity. Current evidence demonstrates that women provided with a dietary intervention during pregnancy improve their dietary quality and have a modest reduction in gestational weight gain. However, the effect of this on longer-term childhood obesity-related outcomes is unknown. Methods We conducted an individual participant data meta-analysis from RCTs in which women with a singleton, live gestation between 10+0 and 20+0 weeks and body mass index (BMI) ≥ 25 kg/m2 in early pregnancy were randomised to a diet and/or lifestyle intervention or continued standard antenatal care and in which longer-term maternal and child follow-up at 3–5 years of age had been undertaken. The primary childhood outcome was BMI z-score above the 90th percentile. Secondary childhood outcomes included skinfold thickness measurements and body circumferences, fat-free mass, dietary and physical activity patterns, blood pressure, and neurodevelopment. Results Seven primary trials where follow-up of participants occurred were identified by a systematic literature search within the International Weight Management in Pregnancy (i-WIP) Collaborative Group collaboration, with six providing individual participant data. No additional studies were identified after a systematic literature search. A total of 2529 children and 2383 women contributed data. Approximately 30% of all child participants had a BMI z-score above the 90th percentile, with no significant difference between the intervention and control groups (aRR 0.97; 95% CI 0.87, 1.08; p=0.610). There were no statistically significant differences identified for any of the secondary outcome measures. Conclusions In overweight and obese pregnant women, we found no evidence that maternal dietary and/or lifestyle intervention during pregnancy modifies the risk of early childhood obesity. Future research may need to target the pre-conception period in women and early childhood interventions. Trial registration PROSPERO, CRD42016047165

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Abstract P209: Heterogeneity of Absolute/Relative Measures of Cardiovascular Mortality Among Cohorts in an Individual Participant Data Meta-Analysis: An EPOCH-JAPAN Study

Circulation ◽

10.1161/circ.137.suppl_1.p209 ◽

2018 ◽

Vol 137 (suppl_1) ◽

Author(s):

Yoshitaka Murakami ◽

Tomonori Okamura ◽

Katsuyuki Miura ◽

Hirotsugu Ueshima ◽

Keyword(s):

Risk Factors ◽

Blood Pressure ◽

Cohort Studies ◽

Meta Analysis ◽

Mortality Rates ◽

Individual Participant Data ◽

Individual Participant ◽

Rate Ratios ◽

Meta Analyses

Introduction: Individual participant data (IPD) meta-analyses involve participant-level data from multiple cohort studies. However, these cohorts have different periods (years) of follow-up, target regions, and distributions of risk factors (including patient age). It remains unclear if these variations affect the heterogeneity of absolute/relative measures of mortality in cardiovascular disease (CVD), stroke, and coronary heart disease (CHD) among cohorts. Hypothesis: There is diverse heterogeneity in absolute measures of mortality, but negligible heterogeneity in relative measures among cohorts in IPD meta-analyses. Methods: The Evidence for Cardiovascular Prevention from Observational Cohorts in Japan (EPOCH-JAPAN) study is an IPD meta-analysis of cardiovascular epidemiology. This project comprises 14 cohort studies with 105,945 Japanese subjects (total CVD deaths: 5,314). First, we examined the correlation between the follow-up periods of the baseline surveys and multivariate-adjusted mortality rates (CVD, stroke, and CHD) among the cohorts. Next, we estimated the cohort-specific mortality rates that adjusted for the stated follow-up periods, regions, age, and other risk factors using Poisson regression. Finally, we explored the heterogeneity of multivariate-adjusted mortality rates, mortality rate ratios, and rate ratios of 10-mmHg increases in systolic blood pressure using Higgins’s I 2 , which measures heterogeneity in meta-analyses. Results: High correlations were observed between the stated follow-up periods of the cohorts and their mortality rates (CVD [men, -0.70; women, -0.79], stroke [men, -0.65; women, -0.73], CHD [men, -0.24; women, -0.89]). In the multivariate-adjusted mortality rates, we observed clear heterogeneity in mortality rates among the cohorts (CVD [I 2 : men, 98.6%; women, 99.3%], stroke [I 2 : men, 98.5%; women, 98.3%], and CHD [I 2 : men, 98.2%; women 92.4%]). In the rate ratio comparison of 10-mmHg increases in systolic blood pressure, no heterogeneity was detected among the cohorts (CVD [I 2 : men, 0.0%; women, 17.9%]). Our results indicated that the ratio measure, which shows the magnitude of each risk factor, was stable even in the heterogeneity of absolute measures. Conclusions: A clear heterogeneity in mortality was observed in absolute measures, but not in relative measures, among cohorts after adjusting for the periods of follow-up, regions, and other risk factors.

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012 Mechanical thrombectomy in pediatric stroke: systematic review, individual patient-data meta-analysis, and case series

Journal of Neurology Neurosurgery & Psychiatry ◽

10.1136/jnnp-2019-anzan.12 ◽

2019 ◽

Vol 90 (e7) ◽

pp. A5.1-A5

Author(s):

Kartik Bhatia ◽

Hans Kortman ◽

Chris Blair ◽

Geoffrey Parker ◽

David Brunacci ◽

...

Keyword(s):

Systematic Review ◽

Scale Score ◽

Mechanical Thrombectomy ◽

Meta Analysis ◽

Secondary Outcome ◽

Individual Participant Data ◽

Neurological Outcomes ◽

Paediatric Patients ◽

Individual Participant

IntroductionIn adults, there is strong evidence demonstrating the superiority of mechanical thrombectomy (MT) plus intravenous thrombolysis over thrombolysis alone for the treatment of acute ischemic stroke due to large vessel occlusion (LVO). The role of MT in the paediatric stroke population is less clear. Here we present an updated systematic review addressing the use of MT in paediatric patients, including three cases from our centre in Sydney, Australia. We have also completed an individual participant data (IPD) meta-analysis of clinical and angiographic outcomes based on these results.MethodOur systematic review and IPD meta-analysis was performed according to PRISMA-IPD (Preferred Reporting Items for Systematic Reviews and Meta-Analyses: Individual Participant Data) guidelines. Primary outcomes measures were change in NIHSS (National Institute of Health Stroke Scale) score following MT, and mRS (modified Rankin Scale) score at final reported follow-up. The secondary outcome measure was final angiographic result using the mTICI (modified Treatment in Cerebral Ischemia) scale.ResultsMT resulted in good long-term neurological outcomes (mRS 0–2) in 60/67 cases (89.6%;follow-up timing µ=4.1 months: 95%CI 2.9–5.3), good short-term neurological outcomes (reduction in NIHSS by 8 or more points or post-MT NIHSS of 0–1) in 37/52 cases (71.2%), and successful recanalization (mTICI 2b/3) in 57/67 cases (85.1%).ConclusionsIn paediatric patients, MT is an effective treatment for ischaemic stroke due to LVO. In the absence of a dedicated prospective registry and with randomized control trails unfeasible, this report represents the best available evidence for the use of MT in the paediatric setting.

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