Impact of movie and video game elements on tic manifestation in children.

BACKGROUND AND PURPOSE: Children in developed countries spend a significant portion of their waking hours engaging with audiovisual content and video games. The impact of media consumption on children's health and well-being has been widely studied, including its effects on tic disorders. Previous studies have shown that tic frequency can both increase and decrease during activities like gaming and television watching, resulting in mixed findings. METHODS: To better understand the impact of audiovisual media on tics, we conducted a fine-grained tic manifestation analysis. We focused on the effects of the impact of a movie scene with suspensful elements and a video game designed to heighten anticipation, thought to stimulate phasic and striatal dopamine release. We closely monitored tic frequency throuhghout these experiences based on moment-to-moment tic annotation. The study included 20 participants (19 males aged 7-16) diagnosed with tic disorders (Yale Global Tic Severity Scale≥8), and we tested the replicability of our findings with an independent group of 36 children (15 females, aged 7-15) with tic disorders. RESULTS: During film viewing, we observed significant synchronization in the temporal tic patterns of various individuals despite diversity in their tic profiles. Furthermore, employing a video game developed for our study, we found that tic frequency increases during anticipation of a pending reward. This finding was replicated in a second experiment with an independent cohort. CONCLUSIONS: Our results indicate that tic frequency is affected by media elements in the short-term, and call for further investigation of the long-term impacts of exposure to such tic triggers.

iCatcher+: Robust and Automated Annotation of Infants' and Young Children's Gaze Behavior From Videos Collected in Laboratory, Field, and Online Studies.

Technological advances in psychological research have enabled large-scale studies of human behavior and streamlined pipelines for automatic processing of data. However, studies of infants and children have not fully reaped these benefits because the behaviors of interest, such as gaze duration and direction, still have to be extracted from video through a laborious process of manual annotation, even when these data are collected online. Recent advances in computer vision raise the possibility of automated annotation of these video data. In this article, we built on a system for automatic gaze annotation in young children, iCatcher, by engineering improvements and then training and testing the system (referred to hereafter as iCatcher+) on three data sets with substantial video and participant variability (214 videos collected in U.S. lab and field sites, 143 videos collected in Senegal field sites, and 265 videos collected via webcams in homes; participant age range = 4 months-3.5 years). When trained on each of these data sets, iCatcher+ performed with near human-level accuracy on held-out videos on distinguishing "LEFT" versus "RIGHT" and "ON" versus "OFF" looking behavior across all data sets. This high performance was achieved at the level of individual frames, experimental trials, and study videos; held across participant demographics (e.g., age, race/ethnicity), participant behavior (e.g., movement, head position), and video characteristics (e.g., luminance); and generalized to a fourth, entirely held-out online data set. We close by discussing next steps required to fully automate the life cycle of online infant and child behavioral studies, representing a key step toward enabling robust and high-throughput developmental research.

Comparison of a Telehealth-Based Intensive Treatment Program with a Rewarding App vs. On-Site Care for Youth with Obesity: A Historical Cohort Study.

The recommended treatment for children with obesity includes numerous consultations by a multidisciplinary team, which is very cumbersome. Telehealth can assist in administering frequent care to children with obesity, yet the exact approaches and modes of delivery are still explored. During the COVID-19 pandemic, we developed an intensive telehealth-based treatment program that included a rewarding app for children with obesity. The aim of this study was to compare 6-month changes in body mass index (BMI) and body fat percent between participants in the program (n = 70) vs. children that underwent historic on-site care (n = 87). After 6 months, more participants in the telehealth group continued treatment compared to the on-site group (79% vs. 60%, p < 0.001). A significant reduction in the median BMI z-score (zBMI) was seen after 6 months in both groups (p < 0.01), with a similar proportion of zBMI reductions (71% in the telehealth group, 75% in the comparison group, p = 0.76). No statistically significant differences were found between the study groups in 6-month changes in BMI, zBMI, body fat percent or fat z-scores. We conclude that our telehealth program, which was executed during the COVID-19 pandemic, resulted in a high proportion of children with zBMI reduction that was comparable with the more personal on-site care.

Habituation Reflects Optimal Exploration Over Noisy Perceptual Samples.

From birth, humans constantly make decisions about what to look at and for how long. Yet, the mechanism behind such decision-making remains poorly understood. Here, we present the rational action, noisy choice for habituation (RANCH) model. RANCH is a rational learning model that takes noisy perceptual samples from stimuli and makes sampling decisions based on expected information gain (EIG). The model captures key patterns of looking time documented in developmental research: habituation and dishabituation. We evaluated the model with adult looking time collected from a paradigm analogous to the infant habituation paradigm. We compared RANCH with baseline models (no learning model, no perceptual noise model) and models with alternative linking hypotheses (Surprisal, KL divergence). We showed that (1) learning and perceptual noise are critical assumptions of the model, and (2) Surprisal and KL are good proxies for EIG under the current learning context.

Age Differences in Recovery Rate Following an Aerobic-Based Exercise Protocol Inducing Muscle Damage Among Amateur, Male Athletes.

Purpose: Compare recovery rates between active young (Y) and middle-aged (MA) males up to 48H post aerobically based, exercise-induced muscle damage (EIMD) protocol. A secondary aim was to explore the relationships between changes in indices associated with EIMD and recovery throughout this timeframe. Methods: Twenty-eight Y (n = 14, 26.1 ± 2.9y, 74.5 ± 9.3 kg) and MA (n = 14, 43.6 ± 4.1y, 77.3 ± 12.9 kg) physically active males, completed a 60-min downhill running (DHR) on a treadmill at -10% incline and at 65% of maximal heart rate (HR). Biochemical, biomechanical, psychological, force production and muscle integrity (using MRI diffusion tensor imaging) markers were measured at baseline, immediately-post, and up to 48H post DHR. Results: During the DHR, HR was lower (p < 0.05) in MA compared to Y, but running pace and distance covered were comparable between groups. No statistical or meaningful differences were observed between groups for any of the outcomes. Yet, Significant (p < 0.05) time-effects within each group were observed: markers of muscle damage, cadence and perception of pain increased, while TNF-a, isometric and dynamic force production and stride-length decreased. Creatine-kinase at 24H-post and 48H-post were correlated (p < 0.05, r range = -0.57 to 0.55) with pain perception, stride-length, and cadence at 24H-post and 48H-post. Significant (p < 0.05) correlations were observed between isometric force production at all time-points and IL-6 at 48H-post DHR (r range = -0.62 to (-0.74). Conclusion: Y and MA active male amateur athletes recover in a comparable manner following an EIMD downhill protocol. These results indicate that similar recovery strategies can be used by trainees from both age groups following an aerobic-based EIMD protocol.

Obesity screening in the pediatric emergency department - A missed opportunity?

Objectives: There is a low rate of body mass index measurements and obesity screening in primary pediatric care. Pediatric emergency department (PED) visits, with their large volumes and routine weight measurements, provide a unique opportunity to identify and address obesity. The study objectives were to examine the rate of addressing obesity in the PED and to identify its predicting factors. Methods: From electronic medical records of PED visits during 2010-2019, we extracted data on age, gender, weight, time, listed diagnoses, and discharge texts. The primary outcome was a listed diagnosis of "obesity" on discharge letters of children with obesity. Secondary outcomes were addressing weight in the discharge letter and written recommendations for obesity-related treatment. Mixed models were used to test for associations between each of the three outcomes and patient/visit characteristics. Results: There were 150,250 PED visits by 88,253 different children and adolescents. Obesity was found in 10,691 children (12.1%). Among these, listed "obesity" diagnosis was present in only 240 (1.5%) visits. Text addressing overweight/obesity was recorded in 721 (4.4%) visits, and weight-related recommendations were documented in 716 (4.4%) visits. "Obesity" was documented in females more often than in males, in older children, in children with higher weights, and in visits conducted during the mornings. Conclusions: The rate of obesity diagnosis in the PED was extremely low, hence the potential screening ability of the PED in this matter is highly under-utilized. PEDs could increase the recognition of obesity, thus assisting in the global efforts in tackling this disease.

Pediatric obesity and body weight following the COVID-19 pandemic.

BACKGROUND: The SARS-CoV-19 pandemic and its associated lockdowns affected children's lifestyle dramatically. The effect of such changes on children's weight and obesity status is unknown. The aim of this study was to compare body weight and obesity rates in children from before the pandemic to 6 months after the major periods of lockdowns in Israel. METHODS: We used data from medical records of pediatric emergency department visits, where weight is routinely measured, to compare weight and obesity prevalence in the fourth quartile of 2020 (n = 2468) as compared with the fourth quartiles of 2018-2019 (n = 5300). Weight was transformed to age- and sex-specific standard-deviation-scores (SDS) for analysis. RESULTS: Weight-SDS increased by a mean of 0.07 during the first 6 months of the pandemic, yet this was only significant in preschoolers. Obesity rates also increased in this age group only, by 37%, from 8.1% to 11.1% (p = 0.01). CONCLUSIONS: Weight-SDS and obesity prevalence increased during the SARS-CoV-19 pandemic, yet only in younger children. Additional studies from other populations are needed.

Epidemiology of childhood fractures in Israel during 2000-2019.

BACKGROUND: Differences have been reported in incidence rates of fractures in the pediatric population, between countries and over time. The aim of this study was to evaluate the incidence and characteristics of fractures over 20 years among Israeli children. METHODS: Incidence rates of fractures were derived from the electronic database of Meuhedet Health Services, a health maintenance organization providing healthcare services to 1.2 million people in Israel. Demographic and clinical data were extracted of all the fractures in individuals aged <18 years during 2000-2019. Fracture sites were determined according to ICD9 definitions. Fracture data were analyzed by age, sex, season and sector (general Jewish population, ultra-orthodox Jews and Arabs). RESULTS: During the study period 188,283 fractures occurred in 142,049 individuals. The most common were fractures of the upper limb (65%), followed by fractures of the lower limb [20%]. The overall fracture rate was 251 per 10,000 person- years (PY), and was higher for boys than girls (319 vs. 180 per 10,000 PY, p < 0.001). During 20 years, standardized fracture rates decreased significantly in the general Jewish population, among both boys (from 457 to 325 per 10,000 PY, p < 0.001) and girls (from 244 to 196 per 10,000 PY, p < 0.001); increased among ultra-orthodox Jewish boys (from 249 to 285 per 10,000 PY, p = 0.002) and girls (from 147 to 194 per 10,000 PY, p < 0.001); and did not change significantly among Arab boys and girls. The fracture rate peaked among girls aged 10-11 years and among boys aged 12-13 years. Seasonal variation showed a bimodal distribution with peaks during spring and autumn. CONCLUSIONS: The incidence of pediatric fractures is affected by age, gender, sector and season. Recognition of fracture characteristics may help identify specific populations and conditions for targeted prevention strategies.

Characteristics of Second-Line Investigations of Middle-Aged Athletes Who Failed Preparticipation Examinations.

OBJECTIVE: The role of exercise testing during preparticipation examinations (PPEs) of middle-aged athletes is uncertain. This study examined the characteristics of disqualifications after an initial PPE that includes an exercise test in competitive athletes older than 30 years. We investigated disqualification rates and reasons, second-line investigations performed, and final decisions regarding competitive sports participation. DESIGN: Chart review. SETTING: Sports medicine clinic. PARTICIPANTS: Athletes aged >30 years that performed an exercise test as part of their annual PPE at our sports medicine clinic (n = 866). INDEPENDENT VARIABLES: Age, sex, height, weight, sport type, cardiovascular risk factors, and abnormal PPE findings. MAIN OUTCOME MEASURES: Additional investigations performed, approval/disqualification regarding competitive sports participation. RESULTS: The initial disqualification rate of athletes was 9.8%. Three (3.6%) athletes were disqualified following questionnaire and physical examination, 19 (22.4%) because of resting electrocardiogram findings, and 65 (76.5%) following the exercise test. After additional work-up, only 5 athletes (0.4%) were ultimately found ineligible for competitive sports. From those, only 2 athletes (0.2%) were disqualified because of exercise test findings, which were episodes of supraventricular tachycardia and not ischemia-related. CONCLUSIONS: The addition of an exercise test to the PPE of middle-aged athletes is of limited value. If exercise testing of older athletes is performed, arrhythmias are probably of higher significance than ST-T changes.

A Cross-Cultural Examination of Parental Knowledge of Concussion in Three Countries.

The aim of the present study was to examine and compare knowledge regarding concussion among parents of youth soccer players, ages 5-17, from the United States, Israel, and Sicily. Results revealed parents from the United States were more knowledgeable than Israeli and Sicilian parents and were more likely to have a previous history of concussion in their children, themselves, and their social contacts. The success of concussion education, programming, and legislation in the US may account for the greater knowledge of US parents and is reason to advocate for similar resources for youth athletes internationally.

Associations Between Maternal Depression, Antidepressant Use During Pregnancy, and Adverse Pregnancy Outcomes: An Individual Participant Data Meta-analysis.

OBJECTIVE: To evaluate the associations of depressive symptoms and antidepressant use during pregnancy with the risks of preterm birth, low birth weight, small for gestational age (SGA), and low Apgar scores. DATA SOURCES: MEDLINE, EMBASE, ClinicalTrials.gov, and PsycINFO up to June 2016. METHODS OF STUDY SELECTION: Data were sought from studies examining associations of depression, depressive symptoms, or use of antidepressants during pregnancy with gestational age, birth weight, SGA, or Apgar scores. Authors shared the raw data of their studies for incorporation into this individual participant data meta-analysis. TABULATION, INTEGRATION, AND RESULTS: We performed one-stage random-effects meta-analyses to estimate odds ratios (ORs) with 95% CIs. The 215 eligible articles resulted in 402,375 women derived from 27 study databases. Increased risks were observed for preterm birth among women with a clinical diagnosis of depression during pregnancy irrespective of antidepressant use (OR 1.6, 95% CI 1.2-2.1) and among women with depression who did not use antidepressants (OR 2.2, 95% CI 1.7-3.0), as well as for low Apgar scores in the former (OR 1.5, 95% CI 1.3-1.7), but not the latter group. Selective serotonin reuptake inhibitor (SSRI) use was associated with preterm birth among women who used antidepressants with or without restriction to women with depressive symptoms or a diagnosis of depression (OR 1.6, 95% CI 1.0-2.5 and OR 1.9, 95% CI 1.2-2.8, respectively), as well as with low Apgar scores among women in the latter group (OR 1.7, 95% CI 1.1-2.8). CONCLUSION: Depressive symptoms or a clinical diagnosis of depression during pregnancy are associated with preterm birth and low Apgar scores, even without exposure to antidepressants. However, SSRIs may be independently associated with preterm birth and low Apgar scores. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42016035711.

Somatic engagement alters subsequent neurobehavioral correlates of affective mentalizing.

Socio-emotional encounters involve a resonance of others' affective states, known as affect sharing (AS); and attribution of mental states to others, known as theory-of-mind (ToM). Empathy necessitates the integration of both processes, yet their interaction during emotional episodes and subsequent generation of inferences on others' affective states has rarely been tested. To address this, we developed a novel experimental design, wherein we manipulated AS by presenting nonverbal emotionally negative movies twice-each time accompanied by one of two soundtracks that accentuated either somatic cues or externally generated sounds. Movies were followed by questions addressing affective-ToM (emotional inferences), cognitive-ToM (inferences on beliefs and knowledge), and non-ToM aspects. Results revealed a neural differentiation between AS, affective-ToM, and cognitive-ToM. AS movies activated regions that have been implicated in emotional (e.g., amygdala) and somatosensory processing, and synchronized brain activity between participants in the latter. Affective-ToM activated the middle insula, limbic regions, and both ventral and dorsal portions of the medial prefrontal cortex (ventral medial prefrontal cortex [VMPFC] and dorsal medial prefrontal cortex [DMPFC], respectively), whereas cognitive-ToM activated posteromedial and lateral-prefrontal and temporal cortices. Critically, AS movies specifically altered neural activation in AS and ToM-related regions during subsequent affective-ToM inferences, most notably in the DMPFC. Moreover, DMPFC-VMPFC connectivity correlated with affective-ToM accuracy, when such questions followed AS movies. Our results associate empathic processes with designated neural activations and shed light on how neuro-behavioral indices of affective ToM are shaped by preceding somatic engagement.

Asymptomatic Athlete With Short-Coupled Premature Ventricular Contractions.

We present an asymptomatic 26-year-old athlete, with no family history of sudden cardiac death and no structural heart disease, who displayed short-coupled premature ventricular contractions on exercise test and Holter monitoring. The rarity of the case as well as management dilemmas are discussed. (Level of Difficulty: Intermediate.).

When randomisation is not good enough: Matching groups in intervention studies.

Randomised assignment of individuals to treatment and controls groups is often considered the gold standard to draw valid conclusions about the efficacy of an intervention. In practice, randomisation can lead to accidental differences due to chance. Researchers have offered alternatives to reduce such differences, but these methods are not used frequently due to the requirement of advanced statistical methods. Here, we recommend a simple assignment procedure based on variance minimisation (VM), which assigns incoming participants automatically to the condition that minimises differences between groups in relevant measures. As an example of its application in the research context, we simulated an intervention study whereby a researcher used the VM procedure on a covariate to assign participants to a control and intervention group rather than controlling for the covariate at the analysis stage. Among other features of the simulated study, such as effect size and sample size, we manipulated the correlation between the matching covariate and the outcome variable and the presence of imbalance between groups in the covariate. Our results highlighted the advantages of VM over prevalent random assignment procedure in terms of reducing the Type I error rate and providing accurate estimates of the effect of the group on the outcome variable. The VM procedure is valuable in situations whereby the intervention to an individual begins before the recruitment of the entire sample size is completed. We provide an Excel spreadsheet, as well as scripts in R, MATLAB, and Python to ease and foster the implementation of the VM procedure.

Vitamin D supplementation to prevent acute respiratory infections: a systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials (RCTs) of vitamin D supplementation for the prevention of acute respiratory infections (ARIs) revealed a protective effect of this intervention. We aimed to examine the link between vitamin D supplementation and prevention of ARIs in an updated meta-analysis. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, the Cochrane Central Register of Controlled Trials, Web of Science, and the ClinicalTrials.gov registry for studies listed from database inception to May 1, 2020. Double-blind RCTs of vitamin D3, vitamin D2, or 25-hydroxyvitamin D (25[OH]D) supplementation for any duration, with a placebo or low-dose vitamin D control, were eligible if they had been approved by a research ethics committee, and if ARI incidence was collected prospectively and prespecified as an efficacy outcome. Studies reporting results of long-term follow-up of primary RCTs were excluded. Aggregated study-level data, stratified by baseline 25(OH)D concentration and age, were obtained from study authors. Using the proportion of participants in each trial who had one or more ARIs, we did a random-effects meta-analysis to obtain pooled odds ratios (ORs) and 95% CIs to estimate the effect of vitamin D supplementation on the risk of having one or more ARIs (primary outcome) compared with placebo. Subgroup analyses were done to estimate whether the effects of vitamin D supplementation on the risk of ARI varied according to baseline 25(OH)D concentration (<25 nmol/L vs 25·0-49·9 nmol/L vs 50·0-74·9 nmol/L vs >75·0 nmol/L), vitamin D dose (daily equivalent of <400 international units [IU] vs 400-1000 IU vs 1001-2000 IU vs >2000 IU), dosing frequency (daily vs weekly vs once per month to once every 3 months), trial duration (≤12 months vs >12 months), age at enrolment (<1·00 years vs 1·00-15·99 years vs 16·00-64·99 years vs ≥65·00 years), and presence versus absence of airway disease (ie, asthma only, COPD only, or unrestricted). Risk of bias was assessed with the Cochrane Collaboration Risk of Bias Tool. The study was registered with PROSPERO, CRD42020190633. FINDINGS: We identified 1528 articles, of which 46 RCTs (75 541 participants) were eligible. Data for the primary outcome were obtained for 48 488 (98·1%) of 49 419 participants (aged 0-95 years) in 43 studies. A significantly lower proportion of participants in the vitamin D supplementation group had one or more ARIs (14 332 [61·3%] of 23 364 participants) than in the placebo group (14 217 [62·3%] of 22 802 participants), with an OR of 0·92 (95% CI 0·86-0·99; 37 studies; I2=35·6%, pheterogeneity=0·018). No significant effect of vitamin D supplementation on the risk of having one or more ARIs was observed for any of the subgroups defined by baseline 25(OH)D concentration. However, protective effects of supplementation were observed in trials in which vitamin D was given in a daily dosing regimen (OR 0·78 [95% CI 0·65-0·94]; 19 studies; I2=53·5%, pheterogeneity=0·003), at daily dose equivalents of 400-1000 IU (0·70 [0·55-0·89]; ten studies; I2=31·2%, pheterogeneity=0·16), for a duration of 12 months or less (0·82 [0·72-0·93]; 29 studies; I2=38·1%, pheterogeneity=0·021), and to participants aged 1·00-15·99 years at enrolment (0·71 [0·57-0·90]; 15 studies; I2=46·0%, pheterogeneity=0·027). No significant interaction between allocation to the vitamin D supplementation group versus the placebo group and dose, dose frequency, study duration, or age was observed. In addition, no significant difference in the proportion of participants who had at least one serious adverse event in the vitamin supplementation group compared with the placebo group was observed (0·97 [0·86-1·07]; 36 studies; I2=0·0%, pheterogeneity=0·99). Risk of bias within individual studies was assessed as being low for all but three trials. INTERPRETATION: Despite evidence of significant heterogeneity across trials, vitamin D supplementation was safe and overall reduced the risk of ARI compared with placebo, although the risk reduction was small. Protection was associated with administration of daily doses of 400-1000 IU for up to 12 months, and age at enrolment of 1·00-15·99 years. The relevance of these findings to COVID-19 is not known and requires further investigation. FUNDING: None.

Primitive visual channels have a causal role in cognitive transfer.

Scientific investigations have long emphasized the cortex's role in cognitive transfer and arithmetic abilities. To date, however, this assumption has not been thoroughly empirically investigated. Here we demonstrated that primitive mechanisms-lower visual channels-have a causal role in cognitive transfer of complex skills such as symbolic arithmetic. We found that exposing only one monocular channel to a visuospatial training resulted in a larger transfer effect in the trained monocular channel compared to the untrained monocular channel. Such cognitive transfer was found for both novel figural-spatial problems (near transfer) and novel subtraction problems (far transfer). Importantly, the benefits of the trained eye were not observed in old problems and in other tasks that did not involve visuospatial abilities (the Stroop task, a multiplication task). These results challenge the exclusive role of the cortex in cognitive transfer and complex arithmetic. In addition, the results suggest a new mechanism for the emergence of cognitive skills, that could be shared across different species.

A Non-stop identity complex (NIC) supervises enterocyte identity and protects from premature aging.

A hallmark of aging is loss of differentiated cell identity. Aged Drosophila midgut differentiated enterocytes (ECs) lose their identity, impairing tissue homeostasis. To discover identity regulators, we performed an RNAi screen targeting ubiquitin-related genes in ECs. Seventeen genes were identified, including the deubiquitinase Non-stop (CG4166). Lineage tracing established that acute loss of Non-stop in young ECs phenocopies aged ECs at cellular and tissue levels. Proteomic analysis unveiled that Non-stop maintains identity as part of a Non-stop identity complex (NIC) containing E(y)2, Sgf11, Cp190, (Mod) mdg4, and Nup98. Non-stop ensured chromatin accessibility, maintaining the EC-gene signature, and protected NIC subunit stability. Upon aging, the levels of Non-stop and NIC subunits declined, distorting the unique organization of the EC nucleus. Maintaining youthful levels of Non-stop in wildtype aged ECs safeguards NIC subunits, nuclear organization, and suppressed aging phenotypes. Thus, Non-stop and NIC, supervise EC identity and protects from premature aging.

Vitamin D supplementation to prevent acute respiratory infections: systematic review and meta-analysis of aggregate data from randomised controlled trials.

BACKGROUND: A 2017 meta-analysis of data from 25 randomised controlled trials of vitamin D supplementation for the prevention of acute respiratory infections revealed a protective effect of the intervention. Since then, 20 new RCTs have been completed. METHODS: Systematic review and meta-analysis of data from randomised controlled trials (RCTs) of vitamin D for ARI prevention using a random effects model. Pre-specified sub-group analyses were done to determine whether effects of vitamin D on risk of ARI varied according to baseline 25-hydroxyvitamin D (25[OH]D) concentration or dosing regimen. We searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science and the ClinicalTrials.gov registry from inception to 1st May 2020. Double-blind RCTs of supplementation with vitamin D or calcidiol, of any duration, were eligible if they were approved by a Research Ethics Committee and if ARI incidence was collected prospectively and pre-specified as an efficacy outcome. Aggregate data, stratified by baseline 25(OH)D concentration, were obtained from study authors. The study was registered with PROSPERO (no. CRD42020190633). FINDINGS: We identified 45 eligible RCTs (total 73,384 participants). Data were obtained for 46,331 (98.0%) of 47,262 participants in 42 studies, aged 0 to 95 years. For the primary comparison of vitamin D supplementation vs. placebo, the intervention reduced risk of ARI overall (Odds Ratio [OR] 0.91, 95% CI 0.84 to 0.99; P for heterogeneity 0.01). No statistically significant effect of vitamin D was seen for any of the sub-groups defined by baseline 25(OH)D concentration. However, protective effects were seen for trials in which vitamin D was given using a daily dosing regimen (OR 0.75, 95% CI 0.61 to 0.93); at daily dose equivalents of 400-1000 IU (OR 0.70, 95% CI 0.55 to 0.89); and for a duration of ≤12 months (OR 0.82, 95% CI 0.72 to 0.93). No significant interaction was seen between allocation to vitamin D vs. placebo and dose frequency, dose size, or study duration. Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (OR 0.97, 95% CI 0.86 to 1.09). Risk of bias within individual studies was assessed as being low for all but three trials. A funnel plot showed left-sided asymmetry (P=0.008, Egger's test). INTERPRETATION: Vitamin D supplementation was safe and reduced risk of ARI, despite evidence of significant heterogeneity across trials. Protection was associated with administration of daily doses of 400-1000 IU vitamin D for up to 12 months. The relevance of these findings to COVID-19 is not known and requires investigation. FUNDING: None.