The importance of dimensional approaches is widely recognized, but an empirical base for clinical application is lacking. This is particularly true for irritability, a dimensional phenotype that cuts ...across many areas of psychopathology and manifests early in life. We examine longitudinal, dimensional patterns of irritability and their clinical import in early childhood.
Irritability was assessed longitudinally over an average of 16 months in a clinically enriched, diverse community sample of preschoolers (N = 497; mean = 4.2 years; SD = 0.8). Using the Temper Loss scale of the Multidimensional Assessment Profile of Disruptive Behavior (MAP-DB) as a developmentally sensitive indicator of early childhood irritability, we examined its convergent/divergent, clinical, and incremental predictive validity, and modeled its linear and nonlinear associations with clinical risk.
The Temper Loss scale demonstrated convergent and divergent validity to child and maternal factors. In multivariate analyses, Temper Loss predicted mood (separation anxiety disorder SAD, generalized anxiety disorder GAD, and depression/dysthymia), disruptive (oppositional defiant disorder ODD, attention-deficit/hyperactivity disorder ADHD, and conduct disorder CD) symptoms. Preschoolers with even mildly elevated Temper Loss scale scores showed substantially increased risk of symptoms and disorders. For ODD, GAD, SAD, and depression, increases in Temper Loss scale scores at the higher end of the dimension had a greater impact on symptoms relative to increases at the lower end. Temper Loss scale scores also showed incremental validity over DSM-IV disorders in predicting subsequent impairment. Finally, accounting for the substantial heterogeneity in longitudinal patterns of Temper Loss significantly improved prediction of mood and disruptive symptoms.
Dimensional, longitudinal characterization of irritability informs clinical prediction. A vital next step will be empirically generating parameters for the incorporation of dimensional information into clinical decision-making with reasonable certainty.
Telehealth is an emerging approach that uses technology to provide healthcare remotely. Recent publications have outlined the importance of supporting the transition to self‐management of adolescents ...with allergic conditions. However, no synthesis of the evidence base on the use and impact of telehealth interventions for this purpose has been conducted to date. This review achieves these aims, in addition to exploring the language use surrounding these interventions, and their implementation. Four databases were searched systematically. References were independently screened by two reviewers. Methodological quality was assessed using the Mixed Methods Appraisal Tool. A narrative synthesis was undertaken. Eighteen articles were included, reporting on 15 telehealth interventions. A total of 86% targeted adolescents with asthma. Mobile applications were the most common telehealth modality used, followed by video‐conferencing, web‐based, virtual reality and artificial intelligence. Five intervention content categories were identified; educational, monitoring, behavioural, psychosocial and healthcare navigational. Peer and/or healthcare professional interaction, gamification and tailoring may increase engagement. The studies showed positive effects of the interventions or no difference from active controls, in self‐management outcomes such as knowledge, health outcomes such as quality‐of‐life, and economic outcomes such as healthcare utilization. The most common implementation outcomes reported were acceptability, appropriateness, feasibility and fidelity.
Antibody responses are an important part of immunity after Coronavirus Disease 2019 (COVID-19) vaccination. However, antibody trajectories and the associated duration of protection after a second ...vaccine dose remain unclear. In this study, we investigated anti-spike IgG antibody responses and correlates of protection after second doses of ChAdOx1 or BNT162b2 vaccines for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the United Kingdom general population. In 222,493 individuals, we found significant boosting of anti-spike IgG by the second doses of both vaccines in all ages and using different dosing intervals, including the 3-week interval for BNT162b2. After second vaccination, BNT162b2 generated higher peak levels than ChAdOX1. Older individuals and males had lower peak levels with BNT162b2 but not ChAdOx1, whereas declines were similar across ages and sexes with ChAdOX1 or BNT162b2. Prior infection significantly increased antibody peak level and half-life with both vaccines. Anti-spike IgG levels were associated with protection from infection after vaccination and, to an even greater degree, after prior infection. At least 67% protection against infection was estimated to last for 2-3 months after two ChAdOx1 doses, for 5-8 months after two BNT162b2 doses in those without prior infection and for 1-2 years for those unvaccinated after natural infection. A third booster dose might be needed, prioritized to ChAdOx1 recipients and those more clinically vulnerable.
Recent work has added to the understanding of the burden of Campylobacter jejuni, C. coli, and non-jejuni/coli Campylobacter strains in children living in the developing world.
New diagnostic ...modalities and carefully designed field studies are demonstrating that the burden of Campylobacter diarrhea in children in the developing world has been greatly underestimated. Furthermore, there is emerging recognition of an association between Campylobacter infection and malnutrition. Important progress has been made toward a Campylobacter jejuni vaccine. Finally, evidence of antibiotic resistance continues to be an important issue that is accentuated by the realization that the burden of disease is greater than previously recognized.
Additional research is needed to refine our understanding of the epidemiology of Campylobacter infections in developing countries, in particular to improve estimates of the burden of Campylobacter diarrhea in endemic settings, to determine the impact of recurrent Campylobacter infections on child development, and to describe the prevalence and clinical significance of non-jejuni/coli Campylobacter infections. Progressive antibiotic resistance of isolates argues for augmented and expanded control measures of antibiotics in livestock. Continued work in vaccine development is warranted as is the extension of data available on the serotypes related to burden in different areas of the world and the relationship of serotypes to disease severity.
Background. During late summer/fall 2014, pediatric cases of acute flaccid myelitis (AFM) occurred in the United States, coincident with a national outbreak of enterovirus D68 (EV-D68)-associated ...severe respiratory illness. Methods. Clinicians and health departments reported standardized clinical, epidemiologic, and radiologic information on AFM cases to the Centers for Disease Control and Prevention (CDC), and submitted biological samples for testing. Cases were ≤21 years old, with acute onset of limb weakness 1 August-31 December 2014 and spinal magnetic resonance imaging (MRI) showing lesions predominantly restricted to gray matter. Results. From August through December 2014, 120 AFM cases were reported from 34 states. Median age was 7.1 years (interquartile range, 4.8–12.1 years); 59% were male. Most experienced respiratory (81%) or febrile (64%) illness before limb weakness onset. MRI abnormalities were predominantly in the cervical spinal cord (103/118). All but 1 case was hospitalized; none died. Cerebrospinal fluid (CSF) pleocytosis (>5 white blood cells/μL) was common (81%). At CDC, 1 CSF specimen was positive for EV-D68 and Epstein-Barr virus by real-time polymerase chain reaction, although the specimen had >3000 red blood cells/μL. The most common virus detected in upper respiratory tract specimens was EV-D68 (from 20%, and 47% with specimen collected ≤7 days from respiratory illness/fever onset). Continued surveillance in 2015 identified 16 AFM cases reported from 13 states. Conclusions. Epidemiologic data suggest this AFM cluster was likely associated with the large outbreak of EV-D68-associated respiratory illness, although direct laboratory evidence linking AFM with EV-D68 remains inconclusive. Continued surveillance will help define the incidence, epidemiology, and etiology of AFM.
Sacubitril/valsartan is an angiotensin receptor–neprilysin inhibitor indicated for the treatment of patients with chronic heart failure (HF) with reduced ejection fraction; however, its mechanism of ...benefit remains unclear. Biomarkers that are linked to ventricular remodeling, myocardial injury, and fibrosis may provide mechanistic insight and important clinical guidance regarding sacubitril/valsartan use.
This 52-week, multicenter, open-label, single-arm study is designed to (1) correlate biomarker changes with cardiac remodeling parameters, cardiovascular outcomes, and patient-reported outcome data and (2) determine short- and long-term changes in concentrations of biomarkers related to potential mechanisms of action and effects of sacubitril/valsartan therapy. Approximately 830 patients with HF with reduced ejection fraction will be initiated and titrated on sacubitril/valsartan according to United States prescribing information. Primary efficacy end points include the changes in N-terminal pro–B-type natriuretic peptide concentrations and cardiac remodeling from baseline to 1 year. Secondary end points include changes in concentrations of N-terminal pro–B-type natriuretic peptide and remodeling to 6 months, and changes in patient-reported outcomes using the Kansas City Cardiomyopathy Questionnaire-23 from baseline to 1 year. In addition, several other relevant biomarkers will be measured. Biomarker changes relative to the number of cardiovascular events in 12 months will also be assessed as exploratory end points.
Results from the Prospective Study of Biomarkers, Symptom Improvement, and Ventricular Remodeling During Sacubitril/Valsartan Therapy for Heart Failure (PROVE-HF) will help establish a mechanistic understanding of angiotensin receptor–neprilysin inhibitor therapeutic benefits and provide clinicians with clarity on how to interpret information on biomarkers during treatment (PROVE-HF ClinicalTrials.gov identifier: NCT02887183).
X = vital status/events (CV death, HF hospitalization, worsening HF), physical examination, blood sampling, urine sampling, HF symptom assessment, KCCQ-23.
*Standard HF therapy is continued throughout the study. †At day 45, KCCQ-23 was not administered.
At selected sites, samples will be collected in protease inhibitor tubes at each timepoint (n = 180). Display omitted
In many countries, areas delineated for conservation purposes can only achieve their objectives if effective law enforcement occurs within them. However, there is no method currently available to ...allocate law enforcement effort in a way that protects species and habitats in a cost‐effective manner. Law enforcement is expensive and effort is usually concentrated near the locations of patrol stations where rangers are based. This hampers effective conservation, particularly in large protected areas, or regions with limited enforcement capacity. Using the spatial planning tool Marxan, we demonstrate a method for prioritizing law enforcement in a globally important conservation landscape (the Greater Virunga Landscape, GVL, in central Africa) using data on the spatial distribution of illegal activities and conservation features within the landscape. Our analysis of current patrol data shows that law enforcement activity is inadequate with only 22% of the landscape being effectively patrolled and most of this activity occurring within 3 km of a patrol post. We show that the current patrol effort does not deter illegal activities beyond this distance. We discover that when we account for the costs of effective patrolling and set targets for covering key species populations and habitats, we can reduce the costs of meeting all conservation targets in the landscape by 63%, to $2·2–3·0 million USD, relative to the cost of patrolling the entire landscape. This cost is well within the current expenditure of approximately $5·9 million USD for the GVL but would better target effort from both patrol posts and mobile patrol units in the landscape. Synthesis and applications. Our results demonstrate a method that can be used to plan enforcement patrolling, resulting in more cost‐efficient prevention of illegal activities in a way that is targeted at halting declines in species of conservation concern.
The target of inference in microbiome analyses is usually relative abundance (RA) because RA in a sample (e.g., stool) can be considered as an approximation of RA in an entire ecosystem (e.g., gut). ...However, inference on RA suffers from the fact that RA are calculated by dividing absolute abundances (AAs) over the common denominator (CD), the summation of all AA (i.e., library size). Because of that, perturbation in one taxon will result in a change in the CD and thus cause false changes in RA of all other taxa, and those false changes could lead to false positive/negative findings. We propose a novel analysis approach (IFAA) to make robust inference on AA of an ecosystem that can circumvent the issues induced by the CD problem and compositional structure of RA. IFAA can also address the issues of overdispersion and handle zero-inflated data structures. IFAA identifies microbial taxa associated with the covariates in Phase 1 and estimates the association parameters by employing an independent reference taxon in Phase 2. Two real data applications are presented and extensive simulations show that IFAA outperforms other established existing approaches by a big margin in the presence of unbalanced library size.
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