Dupilumab is effective in type 2-high asthma patients receiving high-dose inhaled corticosteroids at baseline

Background

Dupilumab blocks the shared receptor component for interleukin (IL)-4/IL-13, key drivers of type 2 inflammation. In phase 2b (NCT01854047) and phase 3 LIBERTY ASTHMA QUEST (NCT02414854), add-on dupilumab 200/300 mg every 2 weeks (q2w) reduced severe exacerbations, improved prebronchodilator (pre-BD) forced expiratory volume in 1 second (FEV₁) and quality of life measures, and it was generally well tolerated in patients with uncontrolled, persistent (phase 2b), or moderate-to-severe (phase 3) asthma.

Methods

In patients on high-dose inhaled corticosteroids (ICS) with type 2-high asthma (subgroups including baseline blood eosinophils ≥150/300 cells/µL and/or fractional exhaled nitric oxide [FeNO] ≥25 ppb), annualized severe exacerbation rates over the treatment period, changes from baseline in pre-BD FEV₁ and asthma control (5-item asthma control questionnaire [ACQ-5]) were analyzed.

Results

In high-dose ICS type 2-high subgroups, dupilumab 200/300 mg q2w vs placebo in the phase 2b (24 weeks) and phase 3 (52 weeks) studies significantly reduced severe exacerbations by 55%-69%/57%-60% (all P<.05) and 53%-69%/48%-66% (all P < .001), respectively, except in patients with ≥ 300 eosinophils/µL in phase 2b study (24%/50% (P = .52/0.15). Across subgroups, pre-BD FEV₁ improved by 0.18-0.22 L/0.19-0.24 L (all P < .05) and 0.23-0.36 L/0.15-0.25 L (all P < .01) and ACQ-5 scores were reduced by 0.46-0.55/0.47-0.85 (all P < .05) and 0.38-0.50/0.24-0.30 (all P < .05), respectively, except dupilumab 200 mg q2w in phase 2b in patients with FeNO ≥ 25 ppb (0.41; P = .09). Dupilumab was also effective in patients taking medium-dose ICS.

Conclusion

Dupilumab significantly reduced severe exacerbations and improved lung function and asthma control in patients with type 2-high asthma on high-dose ICS at baseline.

     

Wasting during pregnancy increases the risk of mother-to-child HIV-1 transmission

OBJECTIVES: To examine whether wasting during pregnancy, as measured by weight loss and low weight gain, is associated with increased mother-to-child transmission (MTCT) of HIV-1. METHODS: This was a cohort study in Dar es Salaam, Tanzania, among 957 HIV-1-infected pregnant women. Weight was measured at the first prenatal visit and every month thereafter until delivery. Weight loss was defined as a weekly rate of weight gain 0 and /=167 g/wk, weight loss during pregnancy was related to higher risk of intrauterine MTCT (adjusted relative risk [RR] = 2.32, 95% CI = 1.23-4.36, P = 0.009), HIV positive at birth or fetal death (RR = 2.13, 95% CI = 1.40-3.24, P = 0.0004), and HIV positive at birth or early neonatal death (RR = 1.96, 95% CI = 1.26-3.07, P = 0.003). The rate of weight gain during the 3rd trimester was inversely related to the risk of intrapartum/early breast-feeding transmission (adjusted P value, test for trend = 0.05). CONCLUSIONS: Weight loss during pregnancy increases the risk of early MTCT. Identifying causes of wasting during pregnancy may provide clues for new strategies to prevent MTCT.     

Selective impairment of paired associate learning after administration of a centrally-acting adrenergic agonist (clonidine)

Eight normal volunteers had IV infusions of 200 g clonidine (a centrally-acting adrenergic agonist which reduces noradrenaline release), and saline in a double-blind cross-over design. Clonidine reduced subjective estimates of arousal but did not affect performance on the Digit Symbol Substitution Test. Clonidine impaired pairedassociate learning, but it did not affect performance on a number of measures of short and long term memory. The findings suggest either 1) that there is a specific (adrenergic) mechanism involved in the acquisition of novel associations, but not in other types of learning, or 2) that paired associate learning is more vulnerable than other learning tasks to disruption of adrenergic transmission.     

The two-syndrome concept: origins and current status

The two-syndrome concept postulates two "dimensions of pathology" underlying schizophrenia--a reversible (and potentially neuroleptic-responsive) component and a sometimes progressive and relatively irreversible component associated with the deficit state and poor long-term outcome. Negative symptoms (narrowly defined) appear to be more closely associated with the latter component (the type II syndrome), as also are cognitive impairments, abnormal involuntary movements, and behavioral deterioration. This syndrome is assumed to be more closely related than the type I syndrome of positive symptoms to the structural brain changes inferred from pneumoencephalograms, computed tomography scans, and recent post-mortem studies. However, since both syndromes often occur in the same patient--sometimes at the same point in time--they presumably have the same etiology.     

Describing the Use of a Mindfulness-Based App for Sleep and Mental Well-Being,Across Age,in Children

Child & Youth Care Forum - In the United States, 68% of children do not get the recommended nine hours of sleep, which can lead to many negative health outcomes (e.g., mental health)....     

The Effects of Sleep Quality and Resilience on Perceived Stress,Dietary Behaviors,and Alcohol Misuse: A Mediation-Moderation Analysis of Higher Education Students from Asia,Europe, and North America during the COVID-19 Pandemic

Background: The coronavirus disease 2019 (COVID-19) pandemic has increased the already high levels of stress that higher education students experience. Stress influences health behaviors, including those related to dietary behaviors, alcohol, and sleep; yet the effects of stress can be mitigated by resilience. To date, past research studying the connections between dietary behaviors, alcohol misuse, sleep, and resilience commonly investigated singular relationships between two of the constructs. The aim of the current study was to explore the relationships between these constructs in a more holistic manner using mediation and moderation analyses. Methods: Higher education students from China, Ireland, Malaysia, South Korea, Taiwan, the Netherlands, and the United States were enrolled in a cross-sectional study from April to May 2020, which was during the beginning of the COVID-19 pandemic for most participants. An online survey, using validated tools, was distributed to assess perceived stress, dietary behaviors, alcohol misuse, sleep quality and duration, and resilience. Results: 2254 students completed the study. Results indicated that sleep quality mediated the relationship between perceived stress and dietary behaviors as well as the relationship between perceived stress and alcohol misuse. Further, increased resilience reduced the strength of the relationship between perceived stress and dietary behaviors but not alcohol misuse. Conclusion: Based on these results, higher education students are likely to benefit from sleep education and resilience training, especially during stressful events.     

Effects of Advertising: A Qualitative Analysis of Young Adults’ Engagement with Social Media About Food

Young adults are constantly exposed to energy-dense, nutrient-poor food and beverages, particularly through advertising. Exposure can influence poor food choices and negatively impact health. This study aimed to understand young adults’ attitudes and experiences associated with food-related advertisements, particularly on social media. This qualitative analysis involved n = 166 Australian 18 to 24-year-olds who were involved in a four-week online conversation on different areas relating to health, social media, and eating. Inductive thematic analysis was utilised on two forums on the recall and perceptions of food-related advertisements. Young adults commonly mentioned aspects of the marketing mix (promotion, product, price, and place) in food advertisements. Participants were more readily able to recall energy-dense, nutrient-poor food advertisements compared to healthy food-related advertisements. Digital advertisements were often discussed alongside the use of ad-blockers and algorithms which tailored their social media viewing to what they like. Participants felt constant exposure to unhealthy food advertisements hindered their ability to realise healthy eating behaviours and created feelings of guilt. This current analysis highlights the need to provide an advertising environment that appropriately motivates healthy eating and a food environment that allows healthy food to be the affordable and convenient option.     

Ecological Systems Affecting Urban Childbearing Puerto Rican Women in the City of Philadelphia

Maternal and Child Health Journal - The purpose of this study was to explore socio-ecological influences affecting the daily lives of urban, pregnant Puerto Rican women and factors negatively...     

Veridical causal inference using propensity score methods for comparative effectiveness research with medical claims

Health Services and Outcomes Research Methodology - Medical insurance claims are becoming increasingly common data sources to answer a variety of questions in biomedical research. Although...