There is growing public concern about neurodegenerative changes (e.g., Chronic Traumatic Encephalopathy) that may occur chronically following clinically apparent and clinically silent (i.e., sub-concussive blows) pediatric mild traumatic brain injury (pmTBI). However, there are currently no biomarkers that clinicians can use to objectively diagnose patients or predict those who may struggle to recover. Non-invasive neuroimaging, electrophysiological and neuromodulation biomarkers have promise for providing evidence of the so-called "invisible wounds" of pmTBI. Our systematic review, however, belies that notion, identifying a relative paucity of high-quality, clinically impactful, diagnostic or prognostic biomarker studies in the sub-acute injury phase (36 studies on unique samples in 28 years), with the majority focusing on adolescent pmTBI. Ultimately, well-powered longitudinal studies with appropriate control groups, as well as standardized and clearly-defined inclusion criteria (time post-injury, injury severity and past history) are needed to truly understand the complex pathophysiology that is hypothesized (i.e., still needs to be determined) to exist during the acute and sub-acute stages of pmTBI and may underlie post-concussive symptoms.

Background Interventions aimed at modifying behavior for promoting health and disease management are traditionally resource intensive and difficult to scale. Mobile health apps are being used for these purposes; however, their effects on health outcomes have been mixed. Objective This study aims to summarize the evidence of rigorously evaluated health-related apps on health outcomes and explore the effects of features present in studies that reported a statistically significant difference in health outcomes. Methods A literature search was conducted in 7 databases (MEDLINE, Scopus, PsycINFO, CINAHL, Global Index Medicus, Cochrane Central Register of Controlled Trials, and Cochrane Database of Systematic Reviews). A total of 5 reviewers independently screened and extracted the study characteristics. We used a random-effects model to calculate the pooled effect size estimates for meta-analysis. Sensitivity analysis was conducted based on follow-up time, stand-alone app interventions, level of personalization, and pilot studies. Logistic regression was used to examine the structure of app features. Results From the database searches, 8230 records were initially identified. Of these, 172 met the inclusion criteria. Studies were predominantly conducted in high-income countries (164/172, 94.3%). The majority had follow-up periods of 6 months or less (143/172, 83.1%). Over half of the interventions were delivered by a stand-alone app (106/172, 61.6%). Static/one-size-fits-all (97/172, 56.4%) was the most common level of personalization. Intervention frequency was daily or more frequent for the majority of the studies (123/172, 71.5%). A total of 156 studies involving 21,422 participants reported continuous health outcome data. The use of an app to modify behavior (either as a stand-alone or as part of a larger intervention) confers a slight/weak advantage over standard care in health interventions (standardized mean difference=0.38 [95% CI 0.31-0.45]; I2=80%), although heterogeneity was high. Conclusions The evidence in the literature demonstrates a steady increase in the rigorous evaluation of apps aimed at modifying behavior to promote health and manage disease. Although the literature is growing, the evidence that apps can improve health outcomes is weak. This finding may reflect the need for improved methodological and evaluative approaches to the development and assessment of health care improvement apps. Trial Registration PROSPERO International Prospective Register of Systematic Reviews CRD42018106868; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=106868

Key PointsQuestionWhat are the characteristics of citations of the retracted 1998 article by Wakefield et al that purported to show an association between the measles-mumps-rubella vaccine and autism?FindingsIn this cross-sectional bibliographic analysis of 1153 works citing the article by Wakefield et al, citation characteristics were mostly negative, but since the notice of retraction was issued in 2010, many of the citing works published afterward did not indicate that the article was retracted.MeaningThe findings suggest that improvements are needed from publishers, bibliographic databases, and citation management software to ensure that retracted articles are accurately documented.

Author Contributions: Ms Suelzer had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

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