Reduction of Cross-Reactive Carbohydrate Determinants in Plant Foodstuff: Elucidation of Clinical Relevance and Implications for Allergy Diagnosis

Background: A longstanding debate in allergy is whether or not specific immunoglobulin-E antibodies (sIgE), recognizing cross-reactive carbohydrate determinants (CCD), are able to elicit clinical symptoms. In pollen and food allergy, $20% of patients display in-vitro CCD reactivity based on presence of a1,3-fucose and/or b1,2-xylose residues on N-glycans of plant (xylose/fucose) and insect (fucose) glycoproteins. Because the allergenicity of tomato glycoallergen Lyc e 2 was ascribed to N-glycan chains alone, this study aimed at evaluating clinical relevance of CCD-reduced foodstuff in patients with carbohydrate-specific IgE (CCD-sIgE). Methodology/Principal Findings: Tomato and/or potato plants with stable reduction of Lyc e 2 (tomato) or CCD formation in general were obtained via RNA interference, and gene-silencing was confirmed by immunoblot analyses. Two different CCD-positive patient groups were compared: one with tomato and/or potato food allergy and another with hymenopteravenom allergy (the latter to distinguish between CCD- and peptide-specific reactions in the food-allergic group). Nonallergic and CCD-negative food-allergic patients served as controls for immunoblot, basophil activation, and ImmunoCAP analyses. Basophil activation tests (BAT) revealed that Lyc e 2 is no key player among other tomato (glyco)allergens. CCDpositive patients showed decreased (re)activity with CCD-reduced foodstuff, most obvious in the hymenoptera venomallergic but less in the food-allergic group, suggesting that in-vivo reactivity is primarily based on peptide- and not CCDsIgE. Peptide epitopes remained unaffected in CCD-reduced plants, because CCD-negative patient sera showed reactivity similar to wild-type. In-house-made ImmunoCAPs, applied to investigate feasibility in routine diagnosis, confirmed BAT results at the sIgE level. Conclusions/Significance: CCD-positive hymenoptera venom-allergic patients (control group) showed basophil activation despite no allergic symptoms towards tomato and potato. Therefore, this proof-of-principle study demonstrates feasibility of CCD-reduced foodstuff to minimize ‘false-positive results’ in routine serum tests. Despite confirming low clinical relevance of CCD antibodies, we identified one patient with ambiguous in-vitro results, indicating need for further component-resolved diagnosis

Anxiety Assessment and Treatment in Typically Developing Children

Anxiety disorders are highly prevalent in youth and have been associated with difficulties in adolescence and adulthood. The field has responded with empirical investigations of assessment methods and therapeutic interventions. This chapter highlights some considerations in the assessment and treatment of childhood anxiety disorders as well as the strengths and limitations of commonly used intervention assessment tools. The need for easily accessible, consumer-friendly, and effective interventions for childhood anxiety disorders is paramount, and much of the intervention research has focused on the use of cognitive-behavioral therapy for the treatment of childhood anxiety disorders. While cognitive behavioral treatments vary in terms of emphases, therapy formats, and populations targeted, most cognitive-behavioral therapies share common elements including psychoeducation, exposure, cognitive restructuring, parent training, relaxation, modeling, and self-monitoring. These techniques have been packaged together to treat a variety of anxiety diagnoses, and empirical support for treatment of each disorder is reviewed within the chapter. Future research considerations are discussed

Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression: a systematic review and component network meta-analysis using individual participant data

Background: Internet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom. Methods: We did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683. Findings: We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD −1·83 [95% credible interval (CrI) −2·90 to −0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. Interpretation: The individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package. Funding: Japan Society for the Promotion of Science

Dismantling, optimising, and personalising internet cognitive behavioural therapy for depression: a systematic review and component network meta-analysis using individual participant data

Background: Internet cognitive behavioural therapy (iCBT) is a viable delivery format of CBT for depression. However, iCBT programmes include training in a wide array of cognitive and behavioural skills via different delivery methods, and it remains unclear which of these components are more efficacious and for whom. Methods: We did a systematic review and individual participant data component network meta-analysis (cNMA) of iCBT trials for depression. We searched PubMed, PsycINFO, Embase, and the Cochrane Library for randomised controlled trials (RCTs) published from database inception to Jan 1, 2019, that compared any form of iCBT against another or a control condition in the acute treatment of adults (aged ≥18 years) with depression. Studies with inpatients or patients with bipolar depression were excluded. We sought individual participant data from the original authors. When these data were unavailable, we used aggregate data. Two independent researchers identified the included components. The primary outcome was depression severity, expressed as incremental mean difference (iMD) in the Patient Health Questionnaire-9 (PHQ-9) scores when a component is added to a treatment. We developed a web app that estimates relative efficacies between any two combinations of components, given baseline patient characteristics. This study is registered in PROSPERO, CRD42018104683. Findings: We identified 76 RCTs, including 48 trials contributing individual participant data (11 704 participants) and 28 trials with aggregate data (6474 participants). The participants' weighted mean age was 42·0 years and 12 406 (71%) of 17 521 reported were women. There was suggestive evidence that behavioural activation might be beneficial (iMD −1·83 [95% credible interval (CrI) −2·90 to −0·80]) and that relaxation might be harmful (1·20 [95% CrI 0·17 to 2·27]). Baseline severity emerged as the strongest prognostic factor for endpoint depression. Combining human and automated encouragement reduced dropouts from treatment (incremental odds ratio, 0·32 [95% CrI 0·13 to 0·93]). The risk of bias was low for the randomisation process, missing outcome data, or selection of reported results in most of the included studies, uncertain for deviation from intended interventions, and high for measurement of outcomes. There was moderate to high heterogeneity among the studies and their components. Interpretation: The individual patient data cNMA revealed potentially helpful, less helpful, or harmful components and delivery formats for iCBT packages. iCBT packages aiming to be effective and efficient might choose to include beneficial components and exclude ones that are potentially detrimental. Our web app can facilitate shared decision making by therapist and patient in choosing their preferred iCBT package. Funding: Japan Society for the Promotion of Science