Background Food protein–induced enterocolitis syndrome (FPIES) is a non–IgE-mediated gastrointestinal allergic disorder. Large population-based FPIES studies are lacking. Objective We sought to ...determine the incidence and clinical characteristics of FPIES in Australian infants. Methods An Australia-wide survey (2012-2014) was undertaken through the Australian Paediatric Surveillance Unit, with monthly notification of new cases of acute FPIES in infants aged less than 24 months by 1400 participating pediatricians. Results Two hundred thirty infants with FPIES were identified. The incidence of FPIES in Australian infants (<24 months) was 15.4/100,000/y. Median age of first episode, diagnosis, and notification were 5, 7, and 10 months, respectively. There was no sex predilection. Seven percent of infants had siblings with a history of FPIES, and 5% reacted during exclusive breast-feeding. Sixty-eight had a single food trigger (20% had 2 and 12% had ≥3 food triggers). The most common FPIES triggers were rice (45%), cow's milk (33%), and egg (12%). Fifty-one percent of infants reacted on their first known exposure. Infants with FPIES to multiple versus single food groups were younger at the initial episode (4.6 vs 5.8 months mean, P = .001) and more frequently had FPIES to fruits, vegetables, or both (66% vs 21%, P < .0001). Infants exclusively breast-fed for more than 4 months had a trend toward lower rates of FPIES to multiple food groups (23% vs 36%, P = .06). Sixty-four percent of infants with FPIES to multiple foods, which included cow's milk, had coassociated FPIES to solid foods. Forty-two percent of infants with FPIES to fish reacted to other food groups. Conclusions FPIES is not rare, with an estimated incidence of 15.4/100,000/y. Rice is the most common food trigger in Australia. Factors associated with FPIES to multiple foods included early-onset disease and FPIES to fruits, vegetables, or both.
Even early in the COVID-19 pandemic, adherence to physical distancing measures was variable, exposing some communities to elevated risk. While cognitive factors from the Health Belief Model (HBM) and ...resilience correlate with compliance with physical distancing, external conditions may preclude full compliance with physical distancing guidelines. Our objective was to identify HBM and resilience constructs that could be used to improve adherence to physical distancing even when full compliance is not possible. We examined adherence as expressed through 7-day non-work, non-household contact rates in two cohorts: 1) adults in households with children from Minnesota and Iowa; and 2) adults ≥50 years-old from Minnesota, one-third of whom had Parkinson's disease. We identified multiple cognitive factors associated with physical distancing adherence, specifically perceived severity, benefits, self-efficacy, and barriers. However, the magnitude, and occasionally the direction, of these associations was population-dependent. In Cohort 1, perceived self-efficacy for remaining 6-feet from others was associated with a 29% lower contact rate (RR 0.71; 95% CI 0.65, 0.77). This finding was consistent across all race/ethnicity and income groups we examined. The barriers to adherence of having a child in childcare and having financial concerns had the largest effects among individuals from marginalized racial and ethnic groups and high-income households. In Cohort 2, self-efficacy to quarantine/isolate was associated with a 23% decrease in contacts (RR 0.77; 95% CI 0.66, 0.89), but upon stratification by education level, the association was only present for those with at least a Bachelor's degree. Education also modified the effect of the barrier to adherence leaving home for work, increasing contacts among those with a Bachelor's degree and reducing contacts among those without. Our findings suggest that public health messaging tailored to the identified cognitive factors has the potential to improve physical distancing adherence, but population-specific needs must be considered to maximize effectiveness.
Highlights • Seven TLR7/8 agonists were synthesized and analyzed for their adjuvanting capacity. • Agonists stimulated cytokine production and matured both mDCs and pDCs. • The oxoadenine compounds ...were more potent than the imidazoquinolines. • An oxoadenine compound augmented the adaptive immune response to antigen in pigs.
A diagnosis of congenital heart disease increases perioperative risk for children having surgical procedures. Some will require anaesthesia at a specialist cardiac centre, while for others it is safe ...and appropriate to have their procedure in a local district general hospital. Children with complex congenital heart disease and poor physiological status carry the highest risk of cardiac arrest and mortality. Clinical features of cardiomyopathy, cyanosis, pulmonary hypertension, arrhythmia and cardiac failure are most likely to require specialist input and tertiary referral, whereas those with a preoperative stay of less than 10 days undergoing elective, minor surgery, who are older than 2 years of age and physiologically well may be safely anaesthetized in a district general hospital. In order to maximize safety, the anaesthetist must carry out a thorough preoperative assessment, have an understanding of the patient's individual physiology and be prepared for the potential effects of general anaesthesia. Systemic vascular resistance is reduced by most induction agents and volatile anaesthetics; pulmonary vascular resistance is affected by changes in ventilation and gas exchange. The anaesthetist should also be alert to particular potential complications, such as arrhythmias, hypoxia, bleeding and cardiac arrest.
Purpose of Review
Telehealth-delivered medication-assisted treatment for opioid use disorder (tele-MOUD) has received increased attention, with the intersection of the opioid epidemic and COVID-19 ...pandemic, but research on recent developments is scattered. We critically review recent literature on tele-MOUD and synthesize studies reporting primary data under four themes: clinical effectiveness, non-clinical effectiveness, perceptions, and regulatory considerations.
Recent Findings
Despite increasing publications, most failed to include long-term comprehensive assessments. Findings indicate favorable outcomes such as improvements in retention and abstinence rates, positive experiences, and improved feasibility with the relaxation of regulatory measures. With increased adoption, clinician and patient perceptions appeared largely positive. Negative findings, albeit minor, were primarily associated with workflow adaptation difficulties and limited access of underserved populations to technology and internet connection.
Summary
Additional financial, logistical, outreach, and training support for clinicians, patients, and support staff is recommended, in addition to permanent evidence-based regulatory reforms, to scale and optimize tele-MOUD services. Comprehensive recommendations to overcome limitations are expanded therein.
Previous research has demonstrated that sleep disturbances show little improvement with evidence‐based psychotherapy for posttraumatic stress disorder (PTSD); however, sleep improvements are ...associated with PTSD treatment outcomes. The goal of the current study was to evaluate changes in self‐reported insomnia symptoms and the association between insomnia symptoms and treatment outcome during a 3‐week intensive treatment program (ITP) for veterans with PTSD that integrated cognitive processing therapy (CPT), mindfulness, yoga, and other ancillary services. As part of standard clinical procedures, veterans (N = 165) completed self‐report assessments of insomnia symptoms at pre‐ and posttreatment as well as self‐report assessments of PTSD and depression symptoms approximately every other day during treatment. Most veterans reported at least moderate difficulties with insomnia at both pretreatment (83.0%–95.1%) and posttreatment (69.1–71.3%). Statistically significant reductions in self‐reported insomnia severity occurred from pretreatment to posttreatment; however, the effect size was small, d = 0.33. Longitudinal mixed‐effects models showed a significant interactive effect of Changes in Insomnia × Time in predicting PTSD and depression symptoms, indicating that patients with more improvements in insomnia had more positive treatment outcomes. These findings suggest that many veterans continued to struggle with sleep disruption after a 3‐week ITP, and successful efforts to improve sleep could lead to better PTSD treatment outcomes. Further research is needed to establish how adjunctive sleep interventions can be used to maximize both sleep and PTSD outcomes.
Few studies have examined characteristics distinguishing Veteran and civilian suicide decedents. An understanding of unique risk factors for Veteran suicide is critical to develop effective ...preventive interventions. This is particularly imperative for female Veterans, who have near double the suicide mortality rate of same-aged female civilians. The objectives of this study were to examine whether Veteran and civilian suicide decedents differed on risk factors and suicide-event characteristics, and to determine whether predictors changed based on sex.
Data from 116,515 suicides collected by the National Violent Death Reporting System in 27 states between 2003 and 2015 were analyzed in 2018 in sex-stratified analyses. Logistic regression models examined population differences in risk factors and suicide-event characteristics.
Relative to male civilians, male Veterans were more likely to have a contributing physical health problem (AOR=1.10, 95% CI=1.06, 1.14) and to use a firearm for their suicide (AOR=1.41, 95% CI=1.36, 1.47); they were less likely to have substance use problems (AOR=0.70, 95% CI=0.66, 0.75), depressed mood (AOR=0.93, 95% CI=0.90, 0.97), or financial problems (AOR=0.91, 95% CI=0.86, 0.97). Female Veterans were more likely to use a firearm for their suicide (AOR=1.39, 95% CI=1.19, 1.63) relative to female civilians.
Firearm use as a suicide method was a key distinguishing feature of Veteran suicide. Means restriction and firearm safety are pertinent to preventing Veteran suicide. Given low utilization of mental health care and frequent presence of physical health problems in this population, safe storage messages may have a greater preventive impact if delivered in primary care or other nonpsychiatric settings.
TIGIT is an immune checkpoint receptor expressed on activated and memory T cells, immunosuppressive T regulatory cells, and natural killer (NK) cells. TIGIT has emerged as an attractive target for ...antitumor therapies, due to its proposed immunosuppressive effects on lymphocyte function and T cell activation. We generated an anti-TIGIT monoclonal antibody (mAb) that binds with high affinity to human, non-human primate, and murine TIGIT and through multiple experimental methodologies demonstrated that checkpoint blockade alone is insufficient for antitumor activity. Generating anti-TIGIT mAbs with various Fc backbones we show that muting the Fc-Fcγ receptor (FcγR) interaction failed to drive antitumor activity, while mAbs with Fc functional backbones demonstrate substantial antitumor activity, mediated through activation of antigen-presenting cells (APCs), T cell priming, and NK-mediated depletion of suppressive Tregs and exhausted T cells. Further, nonfucosylation of the Fc backbone resulted in enhanced immune responses and antitumor activity relative to the intact IgG1 backbone. The improved activity correlated with the biased FcγR interaction profile of the nonfucosylated anti-TIGIT mAb, which supports that FcγRIIIa binding with decreased FcγRIIb binding favorably activates APCs and enhances tumor-specific CD8
T cell responses. The anti-TIGIT mAbs with intact FcγR interacting backbones also demonstrated synergistic enhancement of other standard antitumor treatments, including anti-PD-1 treatment and a model monomethyl auristatin E antibody-drug conjugate. These findings highlight the importance of the anti-TIGIT mAb's Fc backbone to its antitumor activity and the extent to which this activity can be enhanced through nonfucosylation of the backbone.
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