The I-frame vs. S-frame: how neoliberalism has led behavioral sciences astray

In their recently published paper, Chater and Loewenstein critically elaborate on the differences between interventions that focus on individual behavior (‘i-frame’), as opposed to the systems in which health behavior occurs (‘s-frame’). They point out that behavioral scientists frequently rely on individual-level interventions, rather than systemic change to improve population health. As individual-level interventions have fallen short of the author’s expectations to fix health problems, the authors argue that behavioral scientists should focus more on system-level change. They warn behavioral scientists that by framing disease as an individual problem they hinder real change. We agree with the arguments made by the authors; nevertheless, we propose that bringing underlying causes for the i-frame focus to light would advance their argument. In our commentary, we discuss that neoliberalism might be a reason for the focus on individual interventions in behavioral health sciences

Antiplatelet agents for the treatment of adults with COVID-19

Background Severe coronavirus disease 2019 (COVID‐19) can cause thrombotic events that lead to severe complications or death. Antiplatelet agents, such as acetylsalicylic acid, have been shown to effectively reduce thrombotic events in other diseases: they could influence the course of COVID‐19 in general. Objectives To assess the efficacy and safety of antiplatelets given with standard care compared to no treatment or standard care (with/without placebo) for adults with COVID‐19. Search methods We searched the Cochrane COVID‐19 Study Register (which comprises MEDLINE (PubMed), Embase, ClinicalTrials.gov, WHO ICTRP, medRxiv, CENTRAL), Web of Science, WHO COVID‐19 Global literature on coronavirus disease and the Epistemonikos COVID‐19 L*OVE Platform to identify completed and ongoing studies without language restrictions to December 2022. Selection criteria We followed standard Cochrane methodology. We included randomised controlled trials (RCTs) evaluating antiplatelet agents for the treatment of COVID‐19 in adults with COVID‐19, irrespective of disease severity, gender or ethnicity. Data collection and analysis We followed standard Cochrane methodology. To assess bias in included studies, we used the Cochrane risk of bias tool (RoB 2) for RCTs. We rated the certainty of evidence using the GRADE approach for the outcomes. Main results Antiplatelets plus standard care versus standard care (with/without placebo) Adults with a confirmed diagnosis of moderate to severe COVID‐19 We included four studies (17,541 participants) that recruited hospitalised people with a confirmed diagnosis of moderate to severe COVID‐19. A total of 8964 participants were analysed in the antiplatelet arm (either with cyclooxygenase inhibitors or P2Y12 inhibitors) and 8577 participants in the control arm. Most people were older than 50 years and had comorbidities such as hypertension, lung disease or diabetes. The studies were conducted in high‐ to lower middle‐income countries prior to wide‐scale vaccination programmes. Antiplatelets compared to standard care: – probably result in little to no difference in 28‐day mortality (risk ratio (RR) 0.95, 95% confidence interval (CI) 0.85 to 1.05; 3 studies, 17,249 participants; moderate‐certainty evidence). In absolute terms, this means that for every 177 deaths per 1000 people not receiving antiplatelets, there were 168 deaths per 1000 people who did receive the intervention (95% CI 151 to 186 per 1000 people); – probably result in little to no difference in worsening (new need for invasive mechanical ventilation or death up to day 28) (RR 0.95, 95% CI 0.90 to 1.01; 2 studies, 15,266 participants; moderate‐certainty evidence); – probably result in little to no difference in improvement (participants discharged alive up to day 28) (RR 1.00, 95% CI 0.96 to 1.04; 2 studies, 15,454 participants; moderate‐certainty evidence); – probably result in a slight reduction of thrombotic events at longest follow‐up (RR 0.90, 95% CI 0.80 to 1.02; 4 studies, 17,518 participants; moderate‐certainty evidence); – may result in a slight increase in serious adverse events at longest follow‐up (Peto odds ratio (OR) 1.57, 95% CI 0.48 to 5.14; 1 study, 1815 participants; low‐certainty evidence), but non‐serious adverse events during study treatment were not reported; – probably increase the occurrence of major bleeding events at longest follow‐up (Peto OR 1.68, 95% CI 1.29 to 2.19; 4 studies, 17,527 participants; moderate‐certainty evidence). Adults with a confirmed diagnosis of asymptomatic SARS‐CoV‐2 infection or mild COVID‐19 We included two RCTs allocating participants, of whom 4209 had confirmed mild COVID‐19 and were not hospitalised. A total of 2109 participants were analysed in the antiplatelet arm (treated with acetylsalicylic acid) and 2100 participants in the control arm. No study included people with asymptomatic SARS‐CoV‐2 infection. Antiplatelets compared to standard care: – may result in little to no difference in all‐cause mortality at day 45 (Peto OR 1.00, 95% CI 0.45 to 2.22; 2 studies, 4209 participants; low‐certainty evidence); – may slightly decrease the incidence of new thrombotic events up to day 45 (Peto OR 0.37, 95% CI 0.09 to 1.46; 2 studies, 4209 participants; low‐certainty evidence); – may make little or no difference to the incidence of serious adverse events up to day 45 (Peto OR 1.00, 95% CI 0.60 to 1.64; 1 study, 3881 participants; low‐certainty evidence), but non‐serious adverse events were not reported. The evidence is very uncertain about the effect of antiplatelets on the following outcomes (compared to standard care plus placebo): – admission to hospital or death up to day 45 (Peto OR 0.79, 95% CI 0.57 to 1.10; 2 studies, 4209 participants; very low‐certainty evidence); – major bleeding events up to longest follow‐up (no event occurred in 328 participants; very low‐certainty evidence). Quality of life and adverse events during study treatment were not reported. Authors' conclusions In people with confirmed or suspected COVID‐19 and moderate to severe disease, we found moderate‐certainty evidence that antiplatelets probably result in little to no difference in 28‐day mortality, clinical worsening or improvement, but probably result in a slight reduction in thrombotic events. They probably increase the occurrence of major bleeding events. Low‐certainty evidence suggests that antiplatelets may result in a slight increase in serious adverse events. In people with confirmed COVID‐19 and mild symptoms, we found low‐certainty evidence that antiplatelets may result in little to no difference in 45‐day mortality and serious adverse events, and may slightly reduce thrombotic events. The effects on the combined outcome admission to hospital or death up to day 45 and major bleeding events are very uncertain. Quality of life was not reported. Included studies were conducted in high‐ to lower middle‐income settings using antiplatelets prior to vaccination roll‐outs. We identified a lack of evidence concerning quality of life assessments, adverse events and people with asymptomatic infection. The 14 ongoing and three completed, unpublished RCTs that we identified in trial registries address similar settings and research questions as in the current body of evidence. We expect to incorporate the findings of these studies in future versions of this review

Socio-economic inequalities in body mass index among preschool children: do sports programs in early childhood education and care centers make a difference?

Background Overweight in childhood is considered to be one of the most serious public health challenges. Many studies have investigated individual-level determinants of children's body mass index (BMI), yet studies exploring determinants at the meso-level are sparse. The aim of our study was to examine how a sports focus at early childhood education and care (ECEC) centers moderates the effect of parental socio-economic position (SEP) on children's BMI. Methods We used data from the German National Educational Panel Study and included 1,891 children (955 boys and 936 girls) from 224 ECEC centers in our analysis. Linear multilevel regressions were used to estimate the main effects of family SEP and the ECEC center sports focus, as well as their interaction, on children's BMI. All analyses were stratified by sex and adjusted for age, migration background, number of siblings, and employment status of parents. Results Our analysis confirmed the wellknown health inequalities in childhood overweight with a social gradient toward a higher BMI for children from lower SEP families. An interactive effect between family SEP and ECEC center sports focus was found. Boys with low family SEP not attending a sports-focused ECEC center had the highest BMI among all boys. In contrast, boys with low family SEP attending a sports-focused ECEC center had the lowest BMI. For girls, no association regarding ECEC center focus or interactive effects emerged. Girls with a high SEP had the lowest BMI, independent of the ECEC center focus. Conclusion We provided evidence for the gender-specific relevance of sports-focused ECEC centers for the prevention of overweight. Especially boys from low SEP families benefited from a sports focus, whereas for girls the family's SEP was more relevant. As a consequence, gender differences in determinants for BMI at different levels and their interaction should be considered in further research and preventive measures. Our research indicates that ECEC centers may decrease health inequalities by providing opportunities for physical activity. </sec

Young people’s experiences of COVID-19 messaging at the start of the UK lockdown:Lessons for positive engagement and information sharing

BACKGROUND: To reduce COVID-19 infection rates during the initial stages of the pandemic, the UK Government mandated a strict period of restriction on freedom of movement or 'lockdown'. For young people, closure of schools and higher education institutions and social distancing rules may have been particularly challenging, coming at a critical time in their lives for social and emotional development. This study explored young people's experiences of the UK Government's initial response to the pandemic and related government messaging.METHODS: This qualitative study combines data from research groups at the University of Southampton, University of Edinburgh and University College London. Thirty-six online focus group discussions (FGDs) were conducted with 150 young people (Southampton: n = 69; FGD = 7; Edinburgh: n = 41; FGD = 5; UCL: n = 40; FGD = 24). Thematic analysis was conducted to explore how young people viewed the government's response and messaging and to develop recommendations for how to best involve young people in addressing similar crises in the future. RESULTS: The abrupt onset of lockdown left young people shocked, confused and feeling ignored by government and media messaging. Despite this, they were motivated to adhere to government advice by the hope that life might soon return to normal. They felt a responsibility to help with the pandemic response, and wanted to be productive with their time, but saw few opportunities to volunteer.CONCLUSIONS: Young people want to be listened to and feel they have a part to play in responding to a national crisis such as the COVID-19 epidemic. To reduce the likelihood of disenfranchising the next generation, Government and the media should focus on developing messaging that reflects young people's values and concerns and to provide opportunities for young people to become involved in responses to future crises

Socio-economic inequalities in body mass index among preschool children: do sports programs in early childhood education and care centers make a difference?

BackgroundOverweight in childhood is considered to be one of the most serious public health challenges. Many studies have investigated individual-level determinants of children's body mass index (BMI), yet studies exploring determinants at the meso-level are sparse. The aim of our study was to examine how a sports focus at early childhood education and care (ECEC) centers moderates the effect of parental socio-economic position (SEP) on children's BMI.MethodsWe used data from the German National Educational Panel Study and included 1,891 children (955 boys and 936 girls) from 224 ECEC centers in our analysis. Linear multilevel regressions were used to estimate the main effects of family SEP and the ECEC center sports focus, as well as their interaction, on children's BMI. All analyses were stratified by sex and adjusted for age, migration background, number of siblings, and employment status of parents.ResultsOur analysis confirmed the wellknown health inequalities in childhood overweight with a social gradient toward a higher BMI for children from lower SEP families. An interactive effect between family SEP and ECEC center sports focus was found. Boys with low family SEP not attending a sports-focused ECEC center had the highest BMI among all boys. In contrast, boys with low family SEP attending a sports-focused ECEC center had the lowest BMI. For girls, no association regarding ECEC center focus or interactive effects emerged. Girls with a high SEP had the lowest BMI, independent of the ECEC center focus.ConclusionWe provided evidence for the gender-specific relevance of sports-focused ECEC centers for the prevention of overweight. Especially boys from low SEP families benefited from a sports focus, whereas for girls the family's SEP was more relevant. As a consequence, gender differences in determinants for BMI at different levels and their interaction should be considered in further research and preventive measures. Our research indicates that ECEC centers may decrease health inequalities by providing opportunities for physical activity

Breast cancer risks associated with missense variants in breast cancer susceptibility genes

BACKGROUND: Protein truncating variants in ATM, BRCA1, BRCA2, CHEK2, and PALB2 are associated with increased breast cancer risk, but risks associated with missense variants in these genes are uncertain. METHODS: We analyzed data on 59,639 breast cancer cases and 53,165 controls from studies participating in the Breast Cancer Association Consortium BRIDGES project. We sampled training (80%) and validation (20%) sets to analyze rare missense variants in ATM (1146 training variants), BRCA1 (644), BRCA2 (1425), CHEK2 (325), and PALB2 (472). We evaluated breast cancer risks according to five in silico prediction-of-deleteriousness algorithms, functional protein domain, and frequency, using logistic regression models and also mixture models in which a subset of variants was assumed to be risk-associated. RESULTS: The most predictive in silico algorithms were Helix (BRCA1, BRCA2 and CHEK2) and CADD (ATM). Increased risks appeared restricted to functional protein domains for ATM (FAT and PIK domains) and BRCA1 (RING and BRCT domains). For ATM, BRCA1, and BRCA2, data were compatible with small subsets (approximately 7%, 2%, and 0.6%, respectively) of rare missense variants giving similar risk to those of protein truncating variants in the same gene. For CHEK2, data were more consistent with a large fraction (approximately 60%) of rare missense variants giving a lower risk (OR 1.75, 95% CI (1.47-2.08)) than CHEK2 protein truncating variants. There was little evidence for an association with risk for missense variants in PALB2. The best fitting models were well calibrated in the validation set. CONCLUSIONS: These results will inform risk prediction models and the selection of candidate variants for functional assays and could contribute to the clinical reporting of gene panel testing for breast cancer susceptibility

Incorporating progesterone receptor expression into the PREDICT breast prognostic model

Background: Predict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2).Method: The prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance.Results: Having a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0. 902 for patients with ER-positive tumours (p = 2.3 x 10(-6)) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted.Conclusion: The inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predic-tions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration. (C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

Incorporating progesterone receptor expression into the PREDICT breast prognostic model

Background: Predict Breast (www.predict.nhs.uk) is an online prognostication and treatment benefit tool for early invasive breast cancer. The aim of this study was to incorporate the prognostic effect of progesterone receptor (PR) status into a new version of PREDICT and to compare its performance to the current version (2.2).Method: The prognostic effect of PR status was based on the analysis of data from 45,088 European patients with breast cancer from 49 studies in the Breast Cancer Association Consortium. Cox proportional hazard models were used to estimate the hazard ratio for PR status. Data from a New Zealand study of 11,365 patients with early invasive breast cancer were used for external validation. Model calibration and discrimination were used to test the model performance.Results: Having a PR-positive tumour was associated with a 23% and 28% lower risk of dying from breast cancer for women with oestrogen receptor (ER)-negative and ER-positive breast cancer, respectively. The area under the ROC curve increased with the addition of PR status from 0.807 to 0.809 for patients with ER-negative tumours (p = 0.023) and from 0.898 to 0. 902 for patients with ER-positive tumours (p = 2.3 x 10(-6)) in the New Zealand cohort. Model calibration was modest with 940 observed deaths compared to 1151 predicted.Conclusion: The inclusion of the prognostic effect of PR status to PREDICT Breast has led to an improvement of model performance and more accurate absolute treatment benefit predic-tions for individual patients. Further studies should determine whether the baseline hazard function requires recalibration. (C) 2022 The Author(s). Published by Elsevier Ltd. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).Peer reviewe

The BRCA2 c.68-7T > A variant is not pathogenic: A model for clinical calibration of spliceogenicity.

Although the spliceogenic nature of the BRCA2 c.68-7T>A variant has been demonstrated, its association with cancer risk remains ontroversial. In this study, we accurately quantified by real-time PCR and digital PCR the BRCA2 isoforms retaining or missing exon 3. In addition, the combined odds ratio for causality of the variant was estimated using genetic and clinical data, and its associated cancer risk was estimated by case-control analysis in 83,636 individuals. Co-occurrence in trans with pathogenic BRCA2 variants was assessed in 5,382 families. Exon 3 exclusion rate was 4.5-fold higher in variant carriers (13%) than controls (3%), indicating an exclusion rate for the c.68-7T>A allele of approximately 20%. The posterior probability of pathogenicity was 7.44 x 10-115. There was neither evidence for increased risk of breast cancer (OR 1.03; 95% CI 0.86-1.24), nor for a deleterious effect of the variant when co-occurring with pathogenic variants. Our data provide for the first time robust evidence of the non-pathogenicity of the BRCA2 c.68-7T>A. Genetic and quantitative transcript analyses together inform the threshold for the ratio between functional and altered BRCA2 isoforms compatible with normal cell function. These findings might be exploited to assess the relevance for cancer risk of other BRCA2 spliceogenic variants