Longitudinal associations between psychosomatic and emotional status and selected food portion sizes in European children and adolescents: IDEFICS/I.Family study.

This study aims to investigate the influence of psychosomatic and emotional status on food portion sizes (PSs) consumption from high energy-dense food groups in European children and adolescents. We hypothesized that psychosomatic and emotional status would have a significant association with the PS selection of energy-dense food. The study included 7355 children aged between 2 and 9.9 years at baseline (T0) (48.8% females); 3869 after 2 years (T1) (48.2% females), and 2971 (51.8% females) after 6 years of follow-up (T3). Psychosomatic and emotional status were measured using emotional well-being during the last week score (KINDL) and Strengths and Difficulties Questionnaire. PS was calculated from daily food intake recorded in 24-hour dietary recalls. The associations between emotional status indicators and PS from selected energy-dense food groups were assessed by multilevel linear regression models. In the cross-sectional analysis, we observed that higher KINDL scores were linked to lower PS consumption from sweet bakery products and savory snacks in both genders. Moreover, we found that adolescent females with high emotional and peer problem scores tended to consume larger PS of carbohydrate-rich and sugar-fatty food items (P < .017). Longitudinally, higher peer problem scores were associated with increased PS from bread and rolls, margarine and lipids, and dairy products in all genders and age groups (P< .017). In adolescents, psychosomatic and emotional status could be a trigger for consuming large PS from carbohydrate-rich and sugar-fatty energy-dense foods. Thus, nutritional interventions should consider emotional status to decrease unhealthy dietary habits in children and adolescents.

Factors affecting continuous participation in follow-up evaluations during a lifestyle intervention programme for type 2 diabetes prevention: The Feel4Diabetes-study.

AIMS: Community- and school-based lifestyle interventions are an efficient method of preventing type 2 diabetes in vulnerable populations. Many participants, however, fail to complete the necessary follow-ups. We investigated factors affecting the continuous participation in follow-up evaluations during the Feel4Diabetes-study, a multilevel intervention programme implemented across Europe. METHODS: Socioeconomic, sociodemographic and clinical factors were assessed for 2702 participants within six participating countries: Bulgaria and Hungary (low-to-middle-income countries, LMIC), Belgium and Finland (high-income countries, HIC) and Greece and Spain (high-income countries under austerity measures, HICAM). RESULTS: Statistically significant differences were detected with respect to sex, control group, education level, employment status, BMI and blood pressure measurements (systolic and diastolic blood pressure). Post hoc analysis revealed significant differences within socioeconomic regions. Higher levels of education were associated with significantly lower attrition in HIC (p < 0.05) and HICAM (p < 0.001), higher employment status was associated with lower attrition in HICAM (p < 0.001) and being female was associated with lower attrition in LMIC (p < 0.001). Surprisingly, the intervention group exhibited higher-than-expected attrition in HIC (p < 0.001) and HICAM (p = 0.003), and lower attrition in LMIC (p = 0.007). When tested together in the same multivariable predictive model, all sociodemographic and socioeconomic variables along with higher BMI retained their statistical significance, while systolic and diastolic blood pressure failed to remain significant. CONCLUSIONS: Key socioeconomic and sociodemographic factors along with BMI play a significant role in determining continuous participation in follow-up evaluations during school- and community-based intervention programmes.

Post-diagnosis adiposity, physical activity, sedentary behaviour, dietary factors, supplement use and colorectal cancer prognosis: Global Cancer Update Programme (CUP Global) summary of evidence grading.

Based on the World Cancer Research Fund Global Cancer Update Programme, we performed systematic reviews and meta-analyses to investigate the association of post-diagnosis adiposity, physical activity, sedentary behaviour, and dietary factors with colorectal cancer prognosis. We searched PubMed and Embase until 28th February, 2022. An independent expert committee and expert panel graded the quality of evidence. A total of 167 unique publications were reviewed, and all but five were observational studies. The quality of the evidence was graded conservatively due to the high risk of several biases. There was evidence of non-linearity in the associations between body mass index and colorectal cancer prognosis. The associations appeared reverse J-shaped, and the quality of this evidence was graded as limited (likelihood of causality: limited-no conclusion). The evidence on recreational physical activity and lower risk of all-cause mortality (relative risk [RR] highest vs. lowest: 0.69, 95% confidence interval [CI]: 0.62-0.77) and recurrence/disease-free survival (RR: 0.80, 95% CI: 0.70-0.92) was graded as limited-suggestive. There was limited-suggestive evidence for the associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), intake of whole grains and coffee with lower risk of all-cause mortality, and between unhealthy dietary patterns and intake of sugary drinks with higher risk of all-cause mortality. The evidence for other exposures on colorectal cancer outcomes was sparse and graded as limited-no conclusion. Analyses were conducted excluding cancer patients with metastases without substantial changes in the findings. Well-designed intervention and cohort studies are needed to support the development of lifestyle recommendations for colorectal cancer patients.

Post-diagnosis dietary factors, supplement use and colorectal cancer prognosis: A Global Cancer Update Programme (CUP Global) systematic literature review and meta-analysis.

The role of diet in colorectal cancer prognosis is not well understood and specific lifestyle recommendations are lacking. We searched for randomised controlled trials (RCTs) and longitudinal observational studies on post-diagnosis dietary factors, supplement use and colorectal cancer survival outcomes in PubMed and Embase from inception until 28th February 2022. Random-effects dose-response meta-analyses were conducted when at least three studies had sufficient information. The evidence was interpreted and graded by the CUP Global independent Expert Committee on Cancer Survivorship and Expert Panel. Five RCTs and 35 observational studies were included (30,242 cases, over 8700 all-cause and 2100 colorectal cancer deaths, 3700 progression, recurrence, or disease-free events). Meta-analyses, including 3-10 observational studies each, were conducted for: whole grains, nuts/peanuts, red and processed meat, dairy products, sugary drinks, artificially sweetened beverages, coffee, alcohol, dietary glycaemic load/index, insulin load/index, marine omega-3 polyunsaturated fatty acids, supplemental calcium, circulating 25-hydroxyvitamin D (25[OH]D) and all-cause mortality; for alcohol, supplemental calcium, circulating 25(OH)D and colorectal cancer-specific mortality; and for circulating 25(OH)D and recurrence/disease-free survival. The overall evidence was graded as 'limited'. The inverse associations between healthy dietary and/or lifestyle patterns (including diets that comprised plant-based foods), whole grains, total, caffeinated, or decaffeinated coffee and all-cause mortality and the positive associations between unhealthy dietary patterns, sugary drinks and all-cause mortality provided 'limited-suggestive' evidence. All other exposure-outcome associations provided 'limited-no conclusion' evidence. Additional, well-conducted cohort studies and carefully designed RCTs are needed to develop specific lifestyle recommendations for colorectal cancer survivors.

Benralizumab in severe eosinophilic asthma by previous biologic use and key clinical subgroups: real-world XALOC-1 programme.

BACKGROUND: Pivotal Phase 3 trials and real-world studies have demonstrated benralizumab's overall efficacy and safety in severe eosinophilic asthma (SEA). Additional large-cohort data are needed to confirm its real-world effectiveness in SEA according to previous biologic use and key baseline characteristics important for treatment selection. METHODS: XALOC-1 is a large, multinational, retrospective, observational, real-world study programme of benralizumab in adults with SEA. This 48-week integrated analysis assessed annualised exacerbation rate (AER), maintenance oral corticosteroid (mOCS) use, asthma symptom control and lung function during a 12-month baseline period and up to 48 weeks after benralizumab initiation. Subgroup analyses were based on previous biologic use and key baseline clinical characteristics (mOCS use, blood eosinophil count, exacerbation history, age at asthma diagnosis, fractional exhaled nitric oxide level and presence of atopy and chronic rhinosinusitis with nasal polyps). RESULTS: Of 1002 patients analysed, 380 were biologic-experienced. At Week 48, 71.3% were exacerbation-free (versus 17.2% at baseline); relative reduction in AER was 82.7% overall and 72.9% in biologic-experienced patients; rates were maintained across all key clinical characteristic subgroups. Of patients using mOCS at baseline (n=274), 47.4% (130/274) eliminated their use by Week 48; the mean reduction from baseline in daily dose was 51.2% and, notably, 34.9% in biologic-experienced patients (n=115). Clinically significant improvements in asthma symptom control and lung function were observed. CONCLUSION: In this large, real-world programme, SEA patients treated with benralizumab had substantial improvements in clinical outcomes irrespective of previous biologic use and key clinical characteristics important to therapeutic decision-making in clinical practice.

Use of CompEx in eosinophilic patients with severe, uncontrolled asthma on benralizumab.

Background: CompEx Asthma, a composite end-point for asthma exacerbations, captures clinically relevant, diary-based acute worsening events (AWEs) (defined as deterioration in daily peak expiratory flow concurrent with deterioration in asthma symptoms and/or rescue therapy use) and severe exacerbations (SevEx) (defined by American Thoracic Society/European Respiratory Society guidelines). We hypothesised that CompEx and SevEx would show similar benralizumab treatment effects and correlations to blood eosinophil counts in patients with severe asthma. Methods: This post hoc analysis of pooled 12-month data from two phase 3 studies included patients aged ≥16 years with severe, uncontrolled asthma who were randomised to benralizumab 30 mg or placebo. Annualised event rates were analysed using a negative binomial model. The impact of blood eosinophil count on treatment effect was assessed. Results: Among patients with a blood eosinophil count ≥300 cells·µL-1 (n=913), benralizumab reduced the annualised event rate versus placebo for CompEx (1.57 versus 2.57; risk ratio 0.61, 95% CI 0.53-0.70, p<0.001), SevEx (0.94 versus 1.55; risk ratio 0.60, 95% CI 0.52-0.70, p<0.001) and AWE (0.92 versus 1.57; risk ratio 0.59, 95% CI 0.48-0.72, p<0.001), with greater treatment effects observed for higher blood eosinophil counts. In patients with blood eosinophil count ≥300 cells·µL-1, benralizumab was associated with shorter median event duration (CompEx: 10.5 days versus 17.0 days; SevEx: 10.0 days versus 15.0 days; AWE: 5.0 days versus 6.0 days). Conclusions: Benralizumab reduced the risk of CompEx events with treatment effects similar to those for SevEx and AWEs across a range of blood eosinophil counts. Use of CompEx supports the evaluation of benralizumab and other novel drugs in clinical studies.

The Pharmacokinetics, Safety and Tolerability of Aclidinium Bromide 400 µg Administered by Inhalation as Single and Multiple (Twice Daily) Doses in Healthy Chinese Participants.

Purpose: To date, aclidinium pharmacokinetic (PK) studies have focused on Caucasian populations, and no data are available for Chinese populations. We aimed to characterize the PK and safety profile of aclidinium and its metabolites (LAS34823 and LAS34850) following single and multiple (twice-daily; BID) dosing in healthy Chinese participants, and to compare PK data between Chinese and Caucasian populations. Materials and methods: In this Phase I, open-label study (NCT03276052), healthy participants from a single site in China received aclidinium bromide 400 µg via a dry powder inhaler. The Day 1 single dose was followed by a washout period of 96 hours. On Days 5 through 8, participants received BID doses. Results: Twenty healthy Chinese participants, aged 18-45 years, were enrolled. Aclidinium absorption was rapid (median time to maximum concentration [tmax] 0.08 hours post-dose following single/multiple doses). LAS34823 had a similar median tmax of 0.08 hours, whereas LAS34850 tmax occurred later (median 2.50-3.00 hours). Aclidinium, LAS34823, and LAS34850 concentrations declined in a bi-phasic manner; geometric mean half-life was 13.5 hours (single dosing) and 21.4 hours (multiple dosing), while steady state was generally achieved after 5 days' continuous dosing. Area under the concentration-time curve during a dosage interval (AUCτ) metabolite to parent ratios for LAS34823 were 2.6 (Day 1) and 2.9 (Day 9), while LAS34850 had ratios of 136.0 and 94.8, respectively. Aclidinium accumulation occurred after 5 days of BID dosing (LS mean accumulation ratio for AUCτ Day 9/Day 1: 214.1% [90% CI, 176.5, 259.6]); LAS34823 accumulation was similar, while LAS34850 accumulation was lower. Between-participant exposure variability was moderate to high for aclidinium and LAS34823, and low for LAS34850. Conclusion: Single and multiple doses of aclidinium were well tolerated in healthy Chinese participants. The safety profile of and exposure to aclidinium was consistent with previous studies conducted in Caucasian populations.

Efficacy and safety of aclidinium/formoterol versus monotherapies and aclidinium versus placebo in Chinese and other Asian patients with moderate-to-severe COPD: The AVANT Phase 3 study.

AVANT was a Phase 3, 24-week, randomized, parallel-group, double-blind, double-dummy, placebo-controlled study to assess the efficacy and safety of aclidinium/formoterol 400 µg/12 µg combination vs monotherapies and aclidinium vs placebo (1:1:1:1) in Asian patients (∼70% of whom were Chinese) with moderate-to-severe stable chronic obstructive pulmonary disease. Endpoints were analyzed hierarchically to incorporate type I error control. At Week 24, aclidinium/formoterol demonstrated improvements from baseline in 1-h morning post-dose forced expiratory volume in 1 s (FEV1) vs aclidinium (least squares [LS] mean 92 mL; 95% confidence interval [CI] 60, 124 mL; p < 0.001), and in trough FEV1 vs formoterol (LS mean 85 mL; 95% CI 53, 117 mL; p < 0.001). Furthermore, aclidinium provided improvements in trough FEV1 vs placebo (LS mean 134 mL; 95% CI 103, 166 mL; p < 0.001). There was an improvement in transition dyspnea index focal score at Week 24 for aclidinium/formoterol vs placebo (LS mean 0.8; 95% CI 0.2, 1.3; p = 0.005) but not for aclidinium vs placebo (LS mean 0.4; 95% CI -0.1, 1.0; p = 0.132). Improvements in St George's Respiratory Questionnaire total scores occurred for aclidinium/formoterol vs placebo (LS mean -4.0; 95% CI -6.7, -1.4; p = 0.003) and aclidinium vs placebo (LS mean -2.9; 95% CI -5.5, -0.3; p = 0.031). Aclidinium/formoterol and aclidinium were well tolerated and safety findings were consistent with known profiles; rates of treatment-emergent adverse events (AEs) (aclidinium/formoterol: 54.8%; aclidinium: 47.4%; placebo: 53.9%), serious AEs (7.2, 7.9, and 7.8%, respectively), and AEs leading to discontinuation of study medication (2.3, 1.5, and 2.2%, respectively) were similar between groups.

Gender detransition: A critical review of the literature.

Gender detransition is the act of stopping or reversing the social, medical, and/or administrative changes achieved during a gender transition process. It is an emerging phenomenon of significant clinical and social interest.

Impact of Initiating Biologics in Patients With Severe Asthma on Long-Term Oral Corticosteroids or Frequent Rescue Steroids (GLITTER): Data From the International Severe Asthma Registry.

BACKGROUND: Effectiveness of biologics has neither been established in patients with high oral corticosteroid exposure (HOCS) nor been compared with effectiveness of continuing with HOCS alone. OBJECTIVE: To examine the effectiveness of initiating biologics in a large, real-world cohort of adult patients with severe asthma and HOCS. METHODS: This was a propensity score-matched, prospective cohort study using data from the International Severe Asthma Registry. Between January 2015 and February 2021, patients with severe asthma and HOCS (long-term OCSs for ≥1 year or ≥4 courses of rescue OCSs within a 12-month period) were identified. Biologic initiators were identified and, using propensity scores, matched 1:1 with noninitiators. The impact of biologic initiation on asthma outcomes was assessed using generalized linear models. RESULTS: We identified 996 matched pairs of patients. Both groups improved over the 12-month follow-up period, but improvement was greater for biologic initiators. Biologic initiation was associated with a 72.9% reduction in the average number of exacerbations per year versus noninitiators (0.64 vs 2.06; rate ratio, 0.27 [95% CI, 0.10-0.71]). Biologic initiators were 2.2 times more likely than noninitiators to take a daily long-term OCS dose of less than 5 mg (risk probability, 49.6% vs 22.5%; P = .002) and had a lower risk of asthma-related emergency department visits (relative risk, 0.35 [95% CI, 0.21-0.58]; rate ratio, 0.26 [0.14-0.48]) and hospitalizations (relative risk, 0.31 [95% CI, 0.18-0.52]; rate ratio, 0.25 [0.13-0.48]). CONCLUSIONS: In a real-world setting, including patients with severe asthma and HOCS from 19 countries, and within an environment of clinical improvement, initiation of biologics was associated with further improvements across multiple asthma outcomes, including exacerbation rate, OCS exposure, and health care resource utilization.

Differences in Anthropometric Parameters of Children in Six European Countries.

BACKGROUND: The databases of children's anthropometric parameters are often outdated, rarely representative and are not always available at an international level. OBJECTIVES: To present children's anthropometric parameters in six European countries that contributed to the Feel4Diabetes project and find country-specific differences. DESIGN/SETTING: The Feel4Diabetes study was performed between 2016 and 2018, targeting children in Belgium, Bulgaria, Finland, Greece, Hungary and Spain. The current study presents data from the baseline and the yearly follow-up anthropometric measurements. SUBJECTS: In total, 20,832 measurements of children (48.7% boys) between 6 and 10 years of age were conducted. MAIN OUTCOME MEASURE: weight, height, BMI. RESULTS: Belgian boys had the lowest body weight and height, while Greek boys had the highest body weight, and Finnish had the highest body height. The highest proportion of overweight (percentile above 85%) and obese boys (percentile above 95%) was in Greece, followed by Hungarian, Spanish, Bulgarian and Finnish boys. In contrast, Belgian boys had the lowest ratio in both categories. Among girls, Greece had the highest; Belgium had the lowest body weight; Finland was the highest in all age categories. The ratio in the overweight range was the highest in Greece, followed by Spanish, Bulgarian and Hungarian girls, who were second in the obese category. Finnish girls had lower and Belgian girls had the lowest ratio in both BMI categories. All the detailed data are presented in tables, and the trends are figures. CONCLUSIONS: Our study presents fresh and comparable anthropometric data of children between 6 and 10 years of age in six European countries, supporting the need for appropriate obesity prevention.

Association of Mediterranean diet with survival after breast cancer diagnosis in women from nine European countries: results from the EPIC cohort study.

BACKGROUND: The Mediterranean diet has been associated with lower risk of breast cancer (BC) but evidence from prospective studies on the role of Mediterranean diet on BC survival remains sparse and conflicting. We aimed to investigate whether adherence to Mediterranean diet prior to diagnosis is associated with overall and BC-specific mortality. METHODS: A total of 13,270 incident breast cancer cases were identified from an initial sample of 318,686 women in 9 countries from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Adherence to Mediterranean diet was estimated through the adapted relative Mediterranean diet (arMED), a 16-point score that includes 8 key components of the Mediterranean diet and excludes alcohol. The degree of adherence to arMED was classified as low (score 0-5), medium (score 6-8), and high (score 9-16). Multivariable Cox proportional hazards models were used to analyze the association between the arMED score and overall mortality, and Fine-Gray competing risks models were applied for BC-specific mortality. RESULTS: After a mean follow-up of 8.6 years from diagnosis, 2340 women died, including 1475 from breast cancer. Among all BC survivors, low compared to medium adherence to arMED score was associated with a 13% higher risk of all-cause mortality (HR 1.13, 95%CI 1.01-1.26). High compared to medium adherence to arMED showed a non-statistically significant association (HR 0.94; 95% CI 0.84-1.05). With no statistically significant departures from linearity, on a continuous scale, a 3-unit increase in the arMED score was associated with an 8% reduced risk of overall mortality (HR3-unit 0.92, 95% CI: 0.87-0.97). This result sustained when restricted to postmenopausal women and was stronger among metastatic BC cases (HR3-unit 0.81, 95% CI: 0.72-0.91). CONCLUSIONS: Consuming a Mediterranean diet before BC diagnosis may improve long-term prognosis, particularly after menopause and in cases of metastatic breast cancer. Well-designed dietary interventions are needed to confirm these findings and define specific dietary recommendations.

Destransición de género: Una revisión crítica de la literatura / Gender detransition: a critical review of the literature

Introducción. La destransición de género es el acto de detenero revertir los cambios sociales, médicos y/o administrativos conseguidos durante un proceso de transición de género. Se trata de un fenómeno emergente de gran interés a nivel clínico y social. Método. Se condujo una búsqueda sistemática en siete bases de datos entre 2010 y 2022, se rastrearon manualmente las referencias de los artículos y se consultaron libros especializados. Se realizó un análisis cuantitativo y de contenido. Resultados. Se incluyeron 138 registros, 37% correspondientes a estudios empíricos y 38,4% publicados en 2021. Se identifican al menos ocho términos para hacer referencia a la destransición, con diferencias en sus definiciones. La prevalencia difiere en función del criterio utilizado, siendo menor para la destransición/arrepentimiento (0-13,1%) que para la descontinuación de la asistencia/tratamiento médico (1,9%-29,8%),y menor para la destransición/arrepentimiento tras cirugía (0-2,4%) que para la destransición/arrepentimiento tras tratamiento hormonal (0-9,8%). Se describen más de 50 factores psicológicos, médicos y socioculturales que influyen en la decisión de destransicionar, así como 16 factores predictores/asociados a la destransición. No se encuentran guías de abordaje sanitario ni legislativo. Los debates actuales se centran en los interrogantes sobre la naturaleza de la disforia de género y el desarrollo de la identidad, el papel de los profesionales con respecto al acceso a los tratamientos médicos y el impacto de las destransiciones sobre la futura accesibilidad a dichos tratamientos. Conclusiones. La destransición de género es una realidad compleja, heterogénea, poco estudiada y escasamente comprendida. Se requiere un abordaje y estudio sistemático que permita comprender su prevalencia real, implicaciones y manejo a nivel sanitario. (AU)

Introduction. Gender detransition is the act of stoppingor reversing the social, medical, and/or administrative changesachieved during a gender transition process. It is an emergingphenomenon of significant clinical and social interest.Methods. We systematically searched seven databasesbetween 2010 and 2022, manually traced article references,and consulted specialized books. Quantitative and contentanalyses were carried out.Results. We included 138 registers, 37% of which were empirical studies and 38.4% of which were published in 2021. Atleast eight terms related to detransition were identified, withdifferences in their definitions. Prevalence estimates differ according to the criteria used, being lower for detransition/regret (0-13.1%) than for discontinuation of care/medical treatment (1.9%-29.8%), and for detransition/regret after surgery(0-2.4%) than for detransition/regret after hormonal treatment (0-9.8%). More than 50 psychological, medical, and sociocultural factors influencing the decision to detransition and16 predictors/associated factors are described. No health orlegal guidelines are found. Current debates focus on the nature of gender dysphoria and identity development, the role ofprofessionals in accessing medical treatments, and the impactof detransition on future access to these treatments.Conclusions. Gender detransition is a complex, heterogeneous, under-researched, and poorly understood reality. Asystematic study and approach to the topic is needed to understand its prevalence, implications, and management from a healthcare perspective. (AU)

Comparative effectiveness of anti-IL5 and anti-IgE biologic classes in patients with severe asthma eligible for both.

BACKGROUND: Patients with severe asthma may present with characteristics representing overlapping phenotypes, making them eligible for more than one class of biologic. Our aim was to describe the profile of adult patients with severe asthma eligible for both anti-IgE and anti-IL5/5R and to compare the effectiveness of both classes of treatment in real life. METHODS: This was a prospective cohort study that included adult patients with severe asthma from 22 countries enrolled into the International Severe Asthma registry (ISAR) who were eligible for both anti-IgE and anti-IL5/5R. The effectiveness of anti-IgE and anti-IL5/5R was compared in a 1:1 matched cohort. Exacerbation rate was the primary effectiveness endpoint. Secondary endpoints included long-term-oral corticosteroid (LTOCS) use, asthma-related emergency room (ER) attendance, and hospital admissions. RESULTS: In the matched analysis (n = 350/group), the mean annualized exacerbation rate decreased by 47.1% in the anti-IL5/5R group and 38.7% in the anti-IgE group. Patients treated with anti-IL5/5R were less likely to experience a future exacerbation (adjusted IRR 0.76; 95% CI 0.64, 0.89; p < 0.001) and experienced a greater reduction in mean LTOCS dose than those treated with anti-IgE (37.44% vs. 20.55% reduction; p = 0.023). There was some evidence to suggest that patients treated with anti-IL5/5R experienced fewer asthma-related hospitalizations (IRR 0.64; 95% CI 0.38, 1.08), but not ER visits (IRR 0.94, 95% CI 0.61, 1.43). CONCLUSIONS: In real life, both anti-IgE and anti-IL5/5R improve asthma outcomes in patients eligible for both biologic classes; however, anti-IL5/5R was superior in terms of reducing asthma exacerbations and LTOCS use.

Severe Asthma Standard-of-Care Background Medication Reduction With Benralizumab: ANDHI in Practice Substudy.

BACKGROUND: The phase IIIb, randomized, parallel-group, placebo-controlled ANDHI double-blind (DB) study extended understanding of the efficacy of benralizumab for patients with severe eosinophilic asthma. Patients from ANDHI DB could join the 56-week ANDHI in Practice (IP) single-arm, open-label extension substudy. OBJECTIVE: Assess potential for standard-of-care background medication reductions while maintaining asthma control with benralizumab. METHODS: Following ANDHI DB completion, eligible adults were enrolled in ANDHI IP. After an 8-week run-in with benralizumab, there were 5 visits to potentially reduce background asthma medications for patients achieving and maintaining protocol-defined asthma control with benralizumab. Main outcome measures for non-oral corticosteroid (OCS)-dependent patients were the proportions with at least 1 background medication reduction (ie, lower inhaled corticosteroid dose, background medication discontinuation) and the number of adapted Global Initiative for Asthma (GINA) step reductions at end of treatment (EOT). Main outcomes for OCS-dependent patients were reductions in daily OCS dosage and proportion achieving OCS dosage of 5 mg or lower at EOT. RESULTS: For non-OCS-dependent patients, 53.3% (n = 208 of 390) achieved at least 1 background medication reduction, increasing to 72.6% (n = 130 of 179) for patients who maintained protocol-defined asthma control at EOT. A total of 41.9% (n = 163 of 389) achieved at least 1 adapted GINA step reduction, increasing to 61.8% (n = 110 of 178) for patients with protocol-defined EOT asthma control. At ANDHI IP baseline, OCS dosages were 5 mg or lower for 40.4% (n = 40 of 99) of OCS-dependent patients. Of OCS-dependent patients, 50.5% (n = 50 of 99) eliminated OCS and 74.7% (n = 74 of 99) achieved dosages of 5 mg or lower at EOT. CONCLUSIONS: These findings demonstrate benralizumab's ability to improve asthma control, thereby allowing background medication reduction.

Efficacy and safety of lebrikizumab in moderate-to-severe atopic dermatitis: 52-week results of two randomized double-blinded placebo-controlled phase III trials.

BACKGROUND: Lebrikizumab is a novel, high-affinity monoclonal antibody that selectively binds to interleukin (IL)-13. OBJECTIVES: To evaluate the efficacy and safety of lebrikizumab monotherapy in adolescent and adult patients with moderate-to-severe atopic dermatitis (AD) over 52 weeks of treatment in ADvocate1 (NCT04146363) and ADvocate2 (NCT04178967). METHODS: Patients who responded to lebrikizumab 250 mg every 2 weeks (Q2W) at the end of the 16-week induction period were re-randomized 2 : 2 : 1 to receive lebrikizumab Q2W, lebrikizumab 250 mg every 4 weeks (Q4W) or placebo Q2W (lebrikizumab withdrawal) for 36 additional weeks. Response at week 16 was defined as achieving a 75% reduction in Eczema Area Severity Index (EASI 75) or an Investigator's Global Assessment (IGA) of 0 or 1, with a ≥ 2-point improvement and no rescue medication use. Multiple imputation was used to handle missing data. Intermittent use of topical therapy was permitted during the maintenance period. RESULTS: After 52 weeks, an IGA of 0 or 1 with a ≥ 2 point improvement was maintained by 71.2% of patients treated with lebrikizumab Q2W, 76.9% of patients treated with lebrikizumab Q4W and 47.9% of patients in the lebrikizumab withdrawal arm. EASI 75 was maintained by 78.4% of patients treated with lebrikizumab Q2W, 81.7% of patients treated with lebrikizumab Q4W and 66.4% of patients in the lebrikizumab withdrawal arm at week 52. Across treatment arms, proportions of patients using any rescue therapy were 14.0% (ADvocate1) and 16.4% (ADvocate2). During the combined induction and maintenance periods of ADvocate1 and ADvocate2, 63.0% of lebrikizumab-treated patients reported any treatment emergent adverse event, with most events (93.1%) being mild or moderate in severity. CONCLUSIONS: After a 16-week induction period with lebrikizumab Q2W, lebrikizumab Q2W and Q4W maintained similar improvement of the signs and symptoms of moderate-to-severe AD, with a safety profile consistent with previously published data.

Dietary patterns related to biological mechanisms and survival after breast cancer diagnosis: results from a cohort study.

BACKGROUND: Inflammatory, insulin and oestrogenic pathways have been linked to breast cancer (BC). We aimed to examine the relationship between pre-diagnostic dietary patterns related to these mechanisms and BC survival. METHODS: The diabetes risk reduction diet (DRRD), inflammatory score of diet (ISD) and oestrogen-related dietary pattern (ERDP) were calculated using dietary data from the European Prospective Investigation into Cancer and Nutrition (EPIC) study. Cox proportional hazards models were used to assess associations between dietary patterns and overall mortality and competing risk models for associations with BC-specific mortality. RESULTS: We included 13,270 BC cases with a mean follow-up after diagnosis of 8.6 years, representing 2340 total deaths, including 1475 BC deaths. Higher adherence to the DRRD score was associated with lower overall mortality (HR1-SD 0.92; 95%CI 0.87-0.96). Greater adherence to pro-inflammatory diets was borderline associated with 6% higher mortality HR1-SD 1.06; 95%CI 1.00-1.12. No significant association with the oestrogen-related dietary pattern was observed. None of the dietary patterns were associated with BC-specific mortality. CONCLUSIONS: Greater adherence to an anti-diabetic and anti-inflammatory diet prior to diagnosis is associated with lower overall mortality among BC survivors. Long-term adherence to these dietary patterns could be a means to improve the prognosis of BC survivors.

Cross-sectional and longitudinal associations between family meals frequency and children's overweight/obesity in families at high risk of type 2 diabetes: The Feel4Diabetes-study.

BACKGROUND: The frequency of family meals has been suggested as a protective factor against obesity among children. OBJECTIVE: This study aimed to investigate the cross-sectional and longitudinal associations between family meals frequency and children's overweight/obesity in families at high risk of type 2 diabetes (T2D) across six European countries. METHODS: 989 parent-child dyads (52% girls and 72% mothers) were included. Participants completed validated measures to assess the frequency of family meals and anthropometrics. Multivariable regression models were applied to examine the longitudinal associations between family meals frequency and overweight/obesity in children. Logistic regression was performed to predict the odds of having overweight/obesity depending on changes in family meals frequency over a two-year follow-up period. Analyses were stratified for children's sex. RESULTS: High frequency of family breakfasts and/or dinners was inversely associated with children's BMI in boys and girls at T2. Results showed decreased odds of overweight/obesity at follow-up among both boys (OR = 0.65; 95% CI 0.41, 0.96) and girls (OR = 0.53; 95% CI 0.31, 0.87) who consumed minimum of three times family breakfasts and/or family dinners a week at baseline. An increase in family breakfasts and/or dinners frequency was associated with lower odds of overweight/obesity in both boys and girls at follow-up. CONCLUSION: A high frequency of family breakfasts and/or dinners but not lunch during childhood is associated with lower odds of overweight/obesity development in children from families at high risk of T2D. The promotion of family meals could help in preventing the development of overweight/obesity among children.

Association of diet quality with glycemia, insulinemia, and insulin resistance in families at high risk for type 2 diabetes mellitus in Europe: Feel4 Diabetes Study.

OBJECTIVE: The aim of the present study was to investigate the association of diet quality with fasting glycemia, insulinemia, and insulin resistance in a cross-sectional sample of adults from families at high risk for type 2 diabetes mellitus (T2DM) from six European countries, taking into account their socioeconomic status (SES). METHODS: Baseline data from non-diabetic adults from the Feel4 Diabetes study were used and diet was assessed by the Healthy Diet Score (HDS). Insulin resistance (IR) was determined by homeostasis model assessment of IR (HOMA-IR). Sociodemographic and lifestyle characteristics were assessed through standardized questionnaires. Multiple linear regressions were adjusted for many confounders, in the total sample and by SES category. RESULTS: In 1980 adults, the third tertile of diet quality was inversely associated with insulin levels (-1.48; 95% confidence interval [CI], -2.34 to 0.62), and HOMA-IR (-0.33; 95% CI, -0.57 to 0.09), yet with no statistically significant results for glucose levels. In the SES subgroup analysis, in the high SES group, both second and third diet score tertiles were inversely associated with insulin levels (-1.81; 95% CI, -2.66 to 0.95) and HOMA-IR values (-0.45; 95% CI -0.69 to 0.21), independent of age, sex, smoking and body mass index. No such associations were observed for glucose levels in the high SES group and for all indices in the low SES group. CONCLUSION: In adults from families at high risk for T2DM, higher diet quality was negatively associated with fasting insulin levels and IR, only in the high SES group and not in the low SES group. Future larger studies may be able to explore further this association, as well as the potential factors that mitigate its strength in the low SES groups.