Ketamine for mood disorders, anxiety, and suicidality in children and adolescents: a systematic review.

Mood disorders, anxiety, and suicidality in youth are increasing and rapid-acting treatments are urgently needed. One potential is ketamine or its enantiomer esketamine, which was FDA approved in 2019 to treat major depressive disorder with suicidality in adults. This systematic review evaluated the evidence for the clinical use of ketamine to treat mood disorders, anxiety, and suicidality in youth. The PRISMA guidelines were used, and a protocol registered prospectively ( https://osf.io/9ucsg/ ). The literature search included Pubmed/MEDLINE, Ovid/MEDLINE, Scopus, CINAHL, PsychInfo, and Google Scholar. Trial registries and preprint servers were searched, and authors contacted for clarification. Studies reported on the clinical use of ketamine to treat anxiety, depression, bipolar disorder, or suicidality in youth ≤19 years old and assessed symptoms before and after ketamine use. Study screening and data extraction were conducted independently by 2-4 authors. Safety, tolerability, and efficacy data were collected. The Cochrane Risk of Bias guidelines assessed the quality of the evidence. Twenty-two published reports based on 16 studies were identified: 7 case studies, 6 observational studies, 3 randomized trials, and 6 secondary data analyses. Studies reported immediate improvements in depression, anxiety, and suicidality. Improvements were maintained for weeks-months following treatment. Ketamine was well-tolerated with the most common side effects being dizziness, nausea, and mild dissociation. Transient hemodynamic changes were reported, all of which resolved quickly and did not require medical intervention. Initial evidence suggests ketamine is safe and may be effective for mood disorders, anxiety, and suicidality in youth. Further randomized trials are warranted.

Impact of social media "challenges" on poison center case volume for intentional ingestions among school-aged children: an observational study.

INTRODUCTION: Mental health problems among youth have escalated over the past decade, with increased rates of self-harm, including suicide attempts by ingestion. Social media use has been linked to youth mental health, including "challenges" urging youth to ingest substances for recreational and other purposes. We hypothesized that social media challenges for particular substances would temporally correspond with increased ingestions of these substances. METHODS: We identified peak Google Trends search times for social media ingestion challenges involving diphenhydramine, laundry pods, nutmeg, and cinnamon, and used data from America's Poison Centers National Poison Data System to plot reported ingestions 3 months before and after peak searches in school-aged children. RESULTS: There were 2,169 individuals in the analysis. Diphenhydramine was the most frequently reported ingestion for misuse/abuse and suicidal purposes (n = 266 and 1,609, respectively). For all ingestions together, 45 percent (n = 979) had a moderate health effect, and 6.35 percent (n = 137) had a major health effect. Time of peak searches corresponded with increased ingestions for each substance. DISCUSSION: We found a temporal relationship between peak Google Trends searches for ingestion challenges and ingestions of that substance reported to United States poison centers. Compared to misuse/abuse ingestions, most suicidal ingestions peaked 1-2 months later, suggesting a public health opportunity for intervention. LIMITATIONS: This retrospective observational study does not establish causal effect. All data are a result of self-reporting of the exposures, which may lead to a reporting bias. Google Trends is not the only search engine and likely underestimates the true incidence of social media posts. CONCLUSIONS: Additional research is needed on the relationship between social media and youth mental health, particularly around "challenges" that place youths' health at risk. There may be opportunities for intervention to decrease medical and mental health sequelae of these challenges.

The Effects of Yoga Breathing Before Motor Speech Practice in Acquired Apraxia of Speech: An n-of-1 Trial.

A previous study discovered that two speakers with moderate apraxia of speech increased their sequential motion rates after unilateral forced-nostril breathing (UFNB) practiced as an adjunct to speech-language therapy in an AB repeated-measures design. The current study sought to: (1) delineate possible UFNB plus practice effects from practice effects alone in motor speech skills; (2) examine the relationships between UFNB integrity, participant-reported stress levels, and motor speech performance; and (3) sample a participant-led UFNB training schedule to contribute to the literature's growing understanding of UFNB dosage. A single-subject (n-of-1 trial), ABAB reversal design was used across four motor speech behaviors. A 60-year-old female with chronic, severe apraxia of speech participated. The researchers developed a breathing app to assess UFNB practice integrity and administer the Simple Aphasia Stress Scale after each UFNB session. The participant improved from overall severe to moderate apraxia of speech on the Apraxia Battery for Adults. Visual inspection of graphs confirmed robust motor speech practice effects for all variables. Articulatory-kinematic variables demonstrated sensitivity to the UFNB-plus-practice condition and correlated to stress scale scores but not UFNB integrity scores. The participant achieved 20-minute UFNB sessions 4 times per week. Removal of UFNB during A2 (UFNB withdrawal) and after a 10-day break during B2 (UFNB full dosage) revealed UFNB practice effects on stress scale scores. UFNB with motor speech practice may benefit articulatory-kinematic skills compared to motor speech practice alone. Regular, cumulative UFNB practice appeared to lower self-perceived stress levels. These findings, along with prior work, provide a foundation to further explore yoga breathing and its use with speakers who have apraxia of speech.

Listening to What Matters Most: Consumer Endorsed Patient Reported Outcome Measures (PROMs) for Use in Multiple Myeloma Clinical Trials: A Descriptive Exploratory Study.

BACKGROUND: Patients with multiple myeloma (MM) experience some of the highest levels of symptom burden of all hematological malignancies. Therefore, assessment of quality of life (QoL) is critical for the delivery of patient-centered cancer care. Patient reported outcome measures (PROMs) are commonly used to measure QoL in people with MM. However, it is unknown whether measures used, are appropriate and informative to address issues that matter most to patients. AIM: This exploratory study was designed to establish consumer endorsed PROMs to measure QoL in people with MM. METHOD: This was a descriptive, exploratory study. Participants were invited to provide feedback on the acceptability, appropriateness, and practicability of ten commonly used PROMs via telephone-based, semi-structured interviews and surveys. Data were analyzed using a manifest content analysis approach and descriptive statistics. RESULTS: 26 individuals participated in the study. Participants emphasized the importance of selecting a suite of PROMs that captures the diversity of quality-of-life experiences and priorities reported over the course of treatment, while minimizing the burden of completing PROMs. Based on these criteria, a suite of three PROMs - the MyPOS, the Brief Fatigue Inventory, and COST-FACIT were endorsed by study participants. CONCLUSION: To our knowledge, this is the first study of its kind to establish a suite of consumer-endorsed PROMs for use in clinical trials in patients with MM. Ensuring that the patient voice is at the center of advances in cancer treatment is a hallmark of quality cancer care.

The impact of a novel policy for pediatric mental health patients in the emergency department.

OBJECTIVES: Pediatric mental health presentations continue to increase across the US. These patients often board for significant periods of time and may require more resources than other acute non-mental health patients. This has important implications for the overall function of the emergency department (ED) as well as care of all ED patients. METHODS: This study evaluated a policy developed to allow for inpatient hospital admission when 30% of the ED was occupied by boarding patients at a tertiary care children's hospital. RESULTS: We found an increase in the number of patients for whom this policy applied, and increased days/month this policy was executed over time. There was an increase in the average ED LOS and left without being seen rate during this time which we hypothesize would have been higher without this policy. CONCLUSIONS: A hospital policy allowing mental health patients to be admitted to the inpatient hospital once stabilized has the potential to improve ED flow and functionality.

A Volunteer Crossover Feasibility Study to Compare Standard Oxygen Cannula Used at High-Flow to Proprietary High-Flow Humidified Nasal Oxygen Systems.

BACKGROUND AND AIM: Supplemental oxygen is routinely administered to patients prior to and during induction of general anesthesia and sedation. This increases the fraction of oxygen in the lungs, increases oxygen delivery, and increases the time to oxygen desaturation. Proprietary Transnasal Humidified Rapid-Insufflation Ventilatory Exchange (THRIVE) systems, which deliver warmed and humidified oxygen, have been extensively researched in the perioperative and critical care setting and have been shown to significantly prolong time to desaturation and as a means of ventilatory support. The use of traditional nasal oxygen cannula used at maximum flow rates is currently used in short bursts as it is poorly tolerated. There is however a dearth of data examining the use of this technique. We hypothesized that traditional nasal oxygen cannulae used at maximum flow rates can deliver oxygen as effectively as THRIVE in this setting. METHODS: We designed a crossover volunteer feasibility study. The participants were 10 healthy anesthetists. We compared the two methods of oxygen delivery by measuring transcutaneous oxygen measurement and pharyngeal oxygen concentration. Comfort and noise levels were recorded. The aforementioned parameters were compared between the two groups. RESULTS: We observed that a standard oxygen cannula used at high flows delivers comparable oxygen delivery and tissue oxygenation performance to proprietary THRIVE systems. However, they are less comfortable and make more noise. DISCUSSION: To the authors' knowledge this study is the first to study the oxygen delivery of traditional nasal oxygen cannula used at maximum flow rates and make comparisons to the well-studied THRIVE technique. While similar transcutaneous partial pressure of oxygen and pharyngeal gas concentrations were observed with both techniques, the standard cannulae were deemed to be a lot less comfortable than THRIVE and made a lot more noise which likely limit the utility of this technique outside of short bursts. CONCLUSION: In this study, a standard nasal oxygen cannula used at high flows achieved similar oxygen delivery to THRIVE at the expense of poor comfort and increased noise.

Trends in intentional abuse and misuse ingestions in school-aged children and adolescents reported to US poison centers from 2000-2020.

CONTEXT: Childhood and adolescent misuse and abuse exposures remain a serious public health challenge in the United States. This study aimed to describe recent trends and patterns of intentional substance misuse and abuse exposures among school-aged children and adolescents in the United States. METHODS: This study was a retrospective cohort study of intentional misuse and abuse exposures in children 6 through 18 years reported to the National Poison Data System (NPDS) from January 1, 2000, through December 31, 2020. Demographic trends, reported clinical effects, treatments, management sites, and health outcomes were assessed overall and within four age categories: 6-9, 10-12, 13-15, and 16-18. RESULTS: Between 2000 and 2020, there were 338,727 cases regarding intentional misuse and abuse exposures for children ages 6 through 18 years old. Overall, misuse/abuse ingestions fluctuated over time, with a peak in 2011. The majority of intentional misuse/abuse ingestions occurred in males (58.3%), and more than 80% of all reported exposure cases occurred in youth aged 13 to 18. 32.6% of ingestions resulted in worse than minor clinical outcomes. Older age groups had a greater number of severe medical outcomes compared to younger age groups. Major or life-threatening exposures (including those resulting in death) were more common in males. Overall, deaths were rare (n = 450), 0.1%). Male sex, older age, abuse ingestions, exposure site of a public area or other residence, and multiple ingested substances were other factors associated with increased mortality. Marijuana exposure rates had the highest average monthly increase overall, with the most dramatic rise occurring from 2017 to 2020. Edible marijuana preparations accounted for the highest increase in call rates compared with all other forms of marijuana. DISCUSSION AND CONCLUSION: With over 330,000 poison center cases reported during the 20-year study period, intentional substance misuse and abuse exposures substantially impact the pediatric population. The substances most commonly misused/abused are more widely available substances such as over-the-counter medications, household products and pharmaceuticals commonly prescribed to youth. Differences in age and sex were evident, with males and adolescents more likely to abuse and misuse substances. Our study describes an upward trend in marijuana misuse/abuse exposures among youth, especially those involving edible products. These findings highlight an ongoing concern about the impact of rapidly evolving cannabis legalization on this vulnerable population.

A Survey of Resources and Nursing Workforce for Clinical Research Delivery in Paediatric Intensive Care Within the UK / Ireland.

Introduction: Clinical research within Paediatric Intensive Care (PICU) is necessary to reduce morbidity and mortality associated within this resource-intensive environment. With UK PICUs encouraged to be research-active there was a drive to understand how centres support research delivery. Aim: To identify the research workforce available within UK/Ireland PICUs to support clinical research delivery. Method: An electronic survey, endorsed by the Paediatric Critical Care Society (PCCS), was designed and reported in accordance with CHERRIES guidelines. The survey was distributed by email to all UK/Ireland Nurse Managers and Medical/ Nursing Research leads, aiming for one response per site during the period of April-June 2021. Only one response per site was included in analysis. Results: 44 responses were received, representing 24/30 UK/Ireland sites (80% response rate). Responses from n = 21/30 units are included (three excluded for insufficient data). 90% (n = 19/21) units were research active, although only 52% (n = 11) had permanent research roles funded within their staffing establishment. The majority of units (n = 18, 86%) had less than two WTE research nurses. Resources were felt to be sufficient for current research delivery by 43% of units (n = 9), but this confidence diminished to 19% (n = 4) when considering their ability to support future research. The top barriers to research conduct were insufficiently funded/unfunded studies (52%; n = 11), clinical staff too busy to support research activity (52%; n = 11) and short-term/fixed-term contracts for research staff (38%; n = 8). Conclusion: Despite the perceived importance of research and 90% of responding UK/Ireland PICUs being research active, the majority have limited resources to support research delivery. This has implications for their ability to participate in future multi-centre trials and opportunities to support the development of future medical/nursing clinical academics. Further work is required to identify optimum models of clinical research delivery.

Trends Over 2 Decades in Adolescent Suicidal and Recreational Ingestions of Over-the-Counter Coricidin Preparations.

OBJECTIVE: The aim of this study was to assess national trends in recreational and suicidal ingestions of over-the-counter cough preparations that contain Coricidin. METHODS: Using the American Association of Poison Control Center's National Poison Data System, we obtained data from 2004 to 2017 on patients aged 13 to 19 years with an ingestion of "Coricidin." We examined trends over time overall and ingestion intent (recreational vs suicidal) using linear regression. We compared patient characteristics, substances ingested, clinical effects and therapies, and outcomes by suicidal versus misuse or recreational intention. RESULTS: An initial search with the inclusion criteria found 19,213 calls that matched study inclusion criteria. On average, there was a yearly linear increase of 180.0 (95% confidence interval [CI], 136.6-223.3; P < 0.01) ingestions per year. Within suicide ingestions, there was an average yearly increase of 97.9 (95% CI, 66.9-128.9; P < 0.01) ingestions, and within misuse/recreational ingestions, there was an average yearly increase of 82.1 (95% CI, 60.3-103.9; P < 0.01) ingestions. The most common clinical effect was tachycardia, which occurred in 42.4% of ingestions. Altered mental status, mydriasis, and ataxia were all more common in misuse/recreational ingestions. Suicidal ingestions resulted in more hospital admissions and need for medical treatment. Recreational-use coded calls peaked in 2013, whereas calls coded for suicide attempts have continued to rise dramatically, with a 50% increase in the 14-year study period. CONCLUSION: Combination Coricidin products are a major source of morbidity in adolescents. Targeted preventive measures in primary care offices or larger-scale policy/legislative efforts may be helpful to address this.

Precision rehabilitation for aphasia by patient age, sex, aphasia severity, and time since stroke? A prespecified, systematic review-based, individual participant data, network, subgroup meta-analysis.

BACKGROUND: Stroke rehabilitation interventions are routinely personalized to address individuals' needs, goals, and challenges based on evidence from aggregated randomized controlled trials (RCT) data and meta-syntheses. Individual participant data (IPD) meta-analyses may better inform the development of precision rehabilitation approaches, quantifying treatment responses while adjusting for confounders and reducing ecological bias. AIM: We explored associations between speech and language therapy (SLT) interventions frequency (days/week), intensity (h/week), and dosage (total SLT-hours) and language outcomes for different age, sex, aphasia severity, and chronicity subgroups by undertaking prespecified subgroup network meta-analyses of the RELEASE database. METHODS: MEDLINE, EMBASE, and trial registrations were systematically searched (inception-Sept2015) for RCTs, including ⩾ 10 IPD on stroke-related aphasia. We extracted demographic, stroke, aphasia, SLT, and risk of bias data. Overall-language ability, auditory comprehension, and functional communication outcomes were standardized. A one-stage, random effects, network meta-analysis approach filtered IPD into a single optimal model, examining SLT regimen and language recovery from baseline to first post-intervention follow-up, adjusting for covariates identified a-priori. Data were dichotomized by age (⩽/> 65 years), aphasia severity (mild-moderate/ moderate-severe based on language outcomes' median value), chronicity (⩽/> 3 months), and sex subgroups. We reported estimates of means and 95% confidence intervals. Where relative variance was high (> 50%), results were reported for completeness. RESULTS: 959 IPD (25 RCTs) were analyzed. For working-age participants, greatest language gains from baseline occurred alongside moderate to high-intensity SLT (functional communication 3-to-4 h/week; overall-language and comprehension > 9 h/week); older participants' greatest gains occurred alongside low-intensity SLT (⩽ 2 h/week) except for auditory comprehension (> 9 h/week). For both age-groups, SLT-frequency and dosage associated with best language gains were similar. Participants ⩽ 3 months post-onset demonstrated greatest overall-language gains for SLT at low intensity/moderate dosage (⩽ 2 SLT-h/week; 20-to-50 h); for those > 3 months, post-stroke greatest gains were associated with moderate-intensity/high-dosage SLT (3-4 SLT-h/week; ⩾ 50 hours). For moderate-severe participants, 4 SLT-days/week conferred the greatest language gains across outcomes, with auditory comprehension gains only observed for ⩾ 4 SLT-days/week; mild-moderate participants' greatest functional communication gains were associated with similar frequency (⩾ 4 SLT-days/week) and greatest overall-language gains with higher frequency SLT (⩾ 6 days/weekly). Males' greatest gains were associated with SLT of moderate (functional communication; 3-to-4 h/weekly) or high intensity (overall-language and auditory comprehension; (> 9 h/weekly) compared to females for whom the greatest gains were associated with lower-intensity SLT (< 2 SLT-h/weekly). Consistencies across subgroups were also evident; greatest overall-language gains were associated with 20-to-50 SLT-h in total; auditory comprehension gains were generally observed when SLT > 9 h over ⩾ 4 days/week. CONCLUSIONS: We observed a treatment response in most subgroups' overall-language, auditory comprehension, and functional communication language gains. For some, the maximum treatment response varied in association with different SLT-frequency, intensity, and dosage. Where differences were observed, working-aged, chronic, mild-moderate, and male subgroups experienced their greatest language gains alongside high-frequency/intensity SLT. In contrast, older, moderate-severely impaired, and female subgroups within 3 months of aphasia onset made their greatest gains for lower-intensity SLT. The acceptability, clinical, and cost effectiveness of precision aphasia rehabilitation approaches based on age, sex, aphasia severity, and chronicity should be evaluated in future clinical RCTs.

Mental Health Diagnoses and Seasonal Trends at a Pediatric Emergency Department and Hospital, 2015-2019.

BACKGROUND: Increasingly, youth with mental health disorders and suicidality are presenting to emergency departments (EDs) and requiring hospitalization. For youth with suicidality, studies reveal seasonal variations in frequency of presentations but do not identify associated diagnoses or whether other primary mental health complaints also reveal seasonal variations. METHODS: Data were collected between January 2015 and December 2019 by a child and adolescent psychiatry consultation-liaison service in a pediatric ED and hospital. Descriptive analysis and multiple linear regression were performed to assess volume over time, seasonal trends, and associated diagnoses. RESULTS: A total of 2367 patients were included, with an average age of 13.9 years and female predominance (62.3%). During the study period, annual ED consultations increased 87.5% and hospital consultations increased 27.5%. Consultations revealed seasonal trends, with highest volumes during January, April, May, October, and November (P < .001; adjusted R 2 = 0.59). The most frequent diagnostic categories were depressive disorders and trauma- or stressor-related disorders. Thirty-six percent of patients presented after a suicide attempt, with the highest rates in spring (P = .03; adjusted R 2 = 0.19). Boarding rates revealed significant seasonality, with higher instances in February, March, April, May, and October (P = .009; adjusted R 2 = 0.32). CONCLUSIONS: Mental health presentations to a pediatric ED and hospital reveal seasonal trends, with the highest volumes in fall and spring and the most common diagnoses being depressive and trauma-related disorders. Suicide attempts are highest in late spring. Knowledge of these trends should inform hospitals, mental health services, and school systems regarding staffing, safety, surveillance, and prevention.

Access to Outpatient Pediatric Mental Health Care After Emergency Department Discharge.

OBJECTIVES: Pediatric mental health presentations to emergency departments (EDs) have shown dramatic increases nationally. This study aimed to identify the ability of patients discharged with mental health from the ED to establish outpatient care. METHODS: This was a cross-sectional study of all mental health patients aged 7 to 19 years who were seen by a child psychiatry consult team in a tertiary care pediatric ED from September 2016 to January 2017. Patients were contacted by phone at least 6 months after discharge. Data obtained included time to follow-up, reasons for delayed follow-up, type of provider seen, and frequency of outpatient visits. RESULTS: Two hundred twenty-eight charts were reviewed and 51 were successfully interviewed. The median age was 14 years and 61% were female. Most patients (61%) reported seeing a psychiatrist or therapist, whereas 19% reported a primary care provider and 19% reporting "other." The majority were able to establish care within 1 month (73%), whereas 9% reported never obtaining outpatient follow-up. Most patients (58%) were able to be seen more than once per month. The most common reason for delayed follow-up was provider availability. CONCLUSIONS: This study found that a large number of patients were able to be seen within 1 month of discharge for mental health care. However, almost 10% of patients never established outpatient care, which is concerning and is an area needing further research.

The Crisis and Transition Services (CATS) Model: A Program to Divert Youths in Mental Health Crisis From the Emergency Department.

The Crisis and Transition Services (CATS) program is a novel approach to safely transitioning youths from the emergency department to outpatient care. The program provides intensive community-based support during the high-risk period after discharge from the emergency department. Preliminary results indicate that the CATS program is reaching youths in a short time frame, engaging families in comprehensive safety planning, connecting youths with ongoing outpatient services, and improving family confidence in navigating mental health crises.

High glucose levels increase influenza-associated damage to the pulmonary epithelial-endothelial barrier.

Diabetes mellitus is a known susceptibility factor for severe influenza virus infections. However, the mechanisms that underlie this susceptibility remain incompletely understood. Here, the effects of high glucose levels on influenza severity were investigated using an in vitro model of the pulmonary epithelial-endothelial barrier as well as an in vivo murine model of type II diabetes. In vitro we show that high glucose conditions prior to IAV infection increased virus-induced barrier damage. This was associated with an increased pro-inflammatory response in endothelial cells and the subsequent damage of the epithelial junctional complex. These results were subsequently validated in vivo. This study provides the first evidence that hyperglycaemia may increase influenza severity by damaging the pulmonary epithelial-endothelial barrier and increasing pulmonary oedema. These data suggest that maintaining long-term glucose control in individuals with diabetes is paramount in reducing the morbidity and mortality associated with influenza virus infections.

The Role of Parental Knowledge and Attitudes about ADHD and Perceptions of Treatment Response in the Treatment Utilization of Families of Children with ADHD.

The present study examined the impact of parental knowledge and attitudes about attention-deficit/hyperactivity disorder (ADHD), and parental perceptions of treatment response on the utilization of behavioral and pharmacological ADHD treatments, using data from a longitudinal treatment study designed to assess physical growth in children with ADHD. It also explored if these relations were moderated by race/ethnicity. Participants include 230 (74% Hispanic) families of treatment naïve children with ADHD (M age = 7.56, SD = 1.94; 73% male). Families were randomly assigned to receive behavior therapy (BT) or stimulant medication (MED; which also included low dose BT). After 6 months, families whose children still showed at least moderate impairment had access to either treatment for a total of 30 months. Utilization was measured using the number of BT sessions attended and total mg of MED taken over the study period. Families who reported more willingness to use medication for their child's ADHD at baseline were more likely to use MED and less likely to use BT, regardless of race/ethnicity. Parental knowledge about ADHD was only important in predicting BT utilization for White non-Hispanic families. Greater reduction in ADHD symptoms and impairment significantly predicted more MED utilization for Hispanic families. Results highlight the need to explore multiple parent (e.g., medication willingness) and child (e.g., symptom severity) factors when considering treatment utilization. Results also highlight ethnic differences in which factors affect treatment utilization.

A High-Fat Diet Increases Influenza A Virus-Associated Cardiovascular Damage.

BACKGROUND: Influenza A virus (IAV) causes a wide range of extrarespiratory complications. However, the role of host factors in these complications of influenza virus infection remains to be defined. METHODS: Here, we sought to use transcriptional profiling, virology, histology, and echocardiograms to investigate the role of a high-fat diet in IAV-associated cardiac damage. RESULTS: Transcriptional profiling showed that, compared to their low-fat counterparts (LF mice), mice fed a high-fat diet (HF mice) had impairments in inflammatory signaling in the lung and heart after IAV infection. This was associated with increased viral titers in the heart, increased left ventricular mass, and thickening of the left ventricular wall in IAV-infected HF mice compared to both IAV-infected LF mice and uninfected HF mice. Retrospective analysis of clinical data revealed that cardiac complications were more common in patients with excess weight, an association which was significant in 2 out of 4 studies. CONCLUSIONS: Together, these data provide the first evidence that a high-fat diet may be a risk factor for the development of IAV-associated cardiovascular damage and emphasizes the need for further clinical research in this area.