Perinatal Cannabis Use and Cannabis Use during Breastfeeding: the Role of Health Care Workers.

OBJECTIVE: This study aimed to estimate the proportion of perinatal women reporting a health care worker (HCW) discussed cannabis use during pregnancy or breastfeeding with them and to evaluate the association between HCWs' discussions and perinatal cannabis use and cannabis use while breastfeeding. STUDY DESIGN: Data from Health eMoms (a longitudinal, state-representative survey of Colorado mothers, collected from 2018 to 2020 [n = 3,193]) were utilized in logistic regressions assessing the relationship between HCW discussions about cannabis and perinatal cannabis use and cannabis use while breastfeeding at two time points postpartum, adjusting for sociodemographic factors. RESULTS: A total of 5.8% of the sample reported cannabis use either during their most recent pregnancy or while breastfeeding at 3 to 6 months' postpartum. A total of 67.8% of the sample reported an HCW-discussed cannabis at prenatal visits. Women reporting perinatal use were more likely to report HCW discussing cannabis compared with nonusers (82.2 vs. 65.3%, p < 0.01). There was not a significant association between HCW discussions and cannabis use while breastfeeding at either time point postpartum. Compared with nonusers, women using perinatally were more likely to report cannabis Web sites (28.9 vs. 6.5%), cannabis stores (15.7 vs. 3.8%), or word-of-mouth (28.4 vs. 17.1%) as trusted sources of cannabis-related information. CONCLUSION: HCW discussions about cannabis use during pregnancy or breastfeeding are not universally reported. This study highlights the need for further encouragement of universal HCW discussions of cannabis use during pregnancy and breastfeeding, strengthening of messaging around cannabis use during these periods, and improved delivery of reliable cannabis-related health information to this population. KEY POINTS: · HCW discussions of perinatal cannabis use are not universally reported by women.. · Women reporting perinatal use were more likely to report HCW discussions of cannabis.. · Women reporting perinatal cannabis use were more likely to trust word-of-mouth or cannabis stores or Web sites..

Clinical utility of vinblastine therapeutic drug monitoring for the treatment of infantile myofibroma patients: A case series.

Infantile myofibroma is a rare, benign tumour of infancy typically managed surgically. In a minority of cases, more aggressive disease is seen and chemotherapy with vinblastine and methotrexate may be used, although evidence for this is limited. Chemotherapy dosing in infants is challenging, and vinblastine disposition in infants is unknown. We describe the use of vinblastine therapeutic drug monitoring in four cases of infantile myofibroma. Marked inter- and intrapatient variability was observed, highlighting the poorly understood pharmacokinetics of vinblastine in children, the challenges inherent in treating neonates, and the role of adaptive dosing in optimising drug exposure in challenging situations.

The Association Between Maternal Mortality, Adverse Childhood Experiences, and Social Determinant of Health: Where is the Evidence?

INTRODUCTION: Social determinants of health and adverse childhood experiences have been implicated as driving causes of maternal mortality but the empirical evidence to substantiate those relationships is lacking. We aimed to understand the prevalence and intersection of social determinants of health and adverse childhood experiences among maternal deaths in Colorado based on a review of records obtained for our state's maternal mortality review committee. METHODS: A 5-member interdisciplinary team adapted the Protocol for Responding to and Assessing Patients' Assets, Risk, and Experiences and the Adverse Childhood Experiences tools to create a data collection tool. The team reviewed records collected for the purpose of maternal mortality review for pregnancy-associated deaths that occurred in Colorado between 2014 and 2016 (N = 94). RESULTS: The review identified an overwhelming lack of information regarding social determinants of health or adverse childhood experiences in the records used to review maternal deaths. The most common finding of the social determinants of health was a lack of conclusive evidence in the record (35.1-94.7%). Similarly, the reviewers were unable to make a determination from the available records for 92.1% of adverse childhood experience indicators. DISCUSSION: The lack of social and contextual information in the records points to challenges of relying on medical records for identification of non-medical causes of maternal mortality. Maternal mortality review committees would be well served to invest in alternative data sources, such as community dashboards and informant interviews, to inform a more comprehensive understanding of causes of maternal mortality.

The impact of pretrial publicity on mock juror and jury verdicts: A meta-analysis.

OBJECTIVE: We updated and extended a meta-analysis on pretrial publicity (PTP) conducted by Steblay et al. (1999) by reexamining the effect of negative (antidefendant) PTP on individual (juror) and deliberating group (jury) verdicts and the effect of positive (pro-defendant) PTP on individual verdicts. HYPOTHESES: We hypothesized that exposure to negative PTP would increase guilty verdicts from both jurors and juries, whereas exposure to positive PTP would decrease guilty verdicts. We predicted that the relationship between negative PTP and juror verdicts would vary according to methodological and theoretical variables. For methodological variables, we hypothesized that published studies, community-member participants, and crime-related comparison conditions would have a stronger PTP effect. For theoretical variables related to the story model, source monitoring bias, and predecisional distortion, we predicted that the effect of PTP would be stronger with more serious crimes, longer time delays, greater amounts of PTP, and more-severe PTP. METHOD: We analyzed 77 unique effect sizes extracted from 27 published and 18 unpublished reports based on 11,240 individual participants. RESULTS: Negative PTP increased juror guilty verdicts (r = .16) and jury verdicts (r = .35), whereas positive PTP decreased guilty verdicts (r = -.21). Moderator analyses revealed that negative PTP's effect on juror verdicts was stronger for published studies, student participants, and unrelated crime or no additional information control groups. Additionally, the biasing effect of negative PTP was stronger for nonviolent crimes, trial delays of less than 1 week, PTP presented in one article with multiple facts, and moderate-severity PTP. CONCLUSIONS: PTP has a modest biasing effect when it favors or disfavors the defendant. Nonetheless, the impact of negative PTP on individuals varies according to studies' methodological variables and variables theoretically related to the mechanism underlying PTP's biasing effect. (PsycInfo Database Record (c) 2022 APA, all rights reserved).

Factors that influence women's engagement with breastfeeding support: A qualitative evidence synthesis.

Breastfeeding is an integral part of early childhood interventions as it can prevent serious childhood and maternal illnesses. For breastfeeding support programmes to be effective, a better understanding of contextual factors that influence women's engagement and satisfaction with these programmes is needed. The aim of this synthesis is to suggest strategies to increase the level of satisfaction with support programmes and to better match the expectations and needs of women. We systematically searched for studies that used qualitative methods for data collection and analysis and that focused on women's experiences and perceptions regarding breastfeeding support programmes. We applied a maximum variation purposive sampling strategy and used thematic analysis. We assessed the methodological quality of the studies using a modified version of the CASP tool and assessed our confidence in the findings using the GRADE-CERQual approach. We included 51 studies of which we sampled 22 for in-depth analysis. Our sampled studies described the experiences of women with formal breastfeeding support by health care professionals in a hospital setting and informal support as for instance from community support groups. Our findings illustrate that the current models of breastfeeding support are dependent on a variety of contextual factors encouraging and supporting women to initiate and continue breastfeeding. They further highlight the relevance of providing different forms of support based on socio-cultural norms and personal backgrounds of women, especially if the support is one-on-one. Feeding decisions of women are situated within a woman's personal situation and may require diverse forms of support.

Prospective Study Testing a Simplified Paclitaxel Premedication Regimen in Patients with Early Breast Cancer.

BACKGROUND: In early trials, hypersensitivity reactions (HSRs) to paclitaxel were common, thus prompting the administration of antihistamines and corticosteroids before every paclitaxel dose. We tested the safety of omitting corticosteroids after cycle 2 during the paclitaxel portion of the dose-dense (DD) doxorubicin-cyclophosphamide (AC)-paclitaxel regimen. PATIENTS, MATERIALS, AND METHODS: In this prospective, single-arm study, patients who completed four cycles of DD-AC for stage I-III breast cancer received paclitaxel 175 mg/m2 every 2 weeks for four cycles. Patients received a standard premedication protocol containing dexamethasone, diphenhydramine, and a histamine H2 blocker prior to the first two paclitaxel cycles. Dexamethasone was omitted in cycles three and four if there were no HSRs in previous cycles. We estimated the rate of grade 3-4 HSRs. RESULTS: Among 127 patients enrolled, 125 received more than one dose of protocol therapy and are included in the analysis. Fourteen (11.2%; 90% confidence interval, 6.9%-20.0%) patients had any-grade HSRs, for a total of 22 (4.5%; 3.1%-6.4%) HSRs over 486 paclitaxel cycles. Any-grade HSRs occurred in 1.6% (0.3%-5.0%), 6.5% (3.3%-11.3%), 7.4% (3.9%-12.5%), and 2.6% (0.7%-6.6%) of patients after paclitaxel cycles 1, 2, 3, and 4, respectively. Dexamethasone use was decreased by 92.8% in cycles 3 and 4. Only one patient experienced grade 3 HSR in cycles 3 or 4, for a rate of grade 3/4 HSR 0.4% (0.02%-2.0%) (1/237 paclitaxel infusions). That patient had grade 2 HSR during cycle 2, and the subsequent grade 3 event occurred despite usual dexamethasone premedication. A sensitivity analysis restricted to patients not known to have received dexamethasone in cycles 3 and 4 found that any-grade HSRs occurred in 2.7% (3/111; 0.7%-6.8%) and 0.9% (1/109; 0.05%-4.3%) of patients in cycle 3 and 4, respectively. CONCLUSION: Corticosteroid premedication can be safely omitted in cycles 3 and 4 of dose-dense paclitaxel if HSRs are not observed during cycles 1 and 2. IMPLICATIONS FOR PRACTICE: Because of the potential for hypersensitivity reactions (HSRs) to paclitaxel, corticosteroids are routinely prescribed prior to each dose, on an indefinite basis. This prospective study, including 125 patients treated with 486 paclitaxel cycles, demonstrates that corticosteroids can be safely omitted in future cycles if HSRs did not occur during cycles 1 and 2 of paclitaxel and that this strategy reduces the use of corticosteroids in cycles 3 and 4 by 92.8% relative to current standard of care.

Influences on the Implementation of Mobile Learning for Medical and Nursing Education: Qualitative Systematic Review by the Digital Health Education Collaboration.

BACKGROUND: In the past 5 decades, digital education has increasingly been used in health professional education. Mobile learning (mLearning), an emerging form of educational technology using mobile devices, has been used to supplement learning outcomes through enabling conversations, sharing information and knowledge with other learners, and aiding support from peers and instructors regardless of geographic distance. OBJECTIVE: This review aimed to synthesize findings from qualitative or mixed-methods studies to provide insight into factors facilitating or hindering implementation of mLearning strategies for medical and nursing education. METHODS: A systematic search was conducted across a range of databases. Studies with the following criteria were selected: examined mLearning in medical and nursing education, employed a mixed-methods or qualitative approach, and published in English after 1994. Findings were synthesized using a framework approach. RESULTS: A total of 1946 citations were screened, resulting in 47 studies being selected for inclusion. Most studies evaluated pilot mLearning interventions. The synthesis identified views on valued aspects of mobile devices in terms of efficiency and personalization but concerns over vigilance and poor device functionality; emphasis on the social aspects of technology, especially in a clinical setting; the value of interaction learning for clinical practice; mLearning as a process, including learning how to use a device; and the importance of institutional infrastructure and policies. CONCLUSIONS: The portability of mobile devices can enable interactions between learners and educational material, fellow learners, and educators in the health professions. However, devices need to be incorporated institutionally, and learners and educators need additional support to fully comprehend device or app functions. The strategic support of mLearning is likely to require procedural guidance for practice settings and device training and maintenance services on campus.

Lifestyle weight management programmes for children: A systematic review using Qualitative Comparative Analysis to identify critical pathways to effectiveness.

This study aimed to identify critical features of successful lifestyle weight management interventions for overweight children (0-11years). Eleven qualitative UK-based studies examining children's, parents' and providers' perspectives and experiences of programmes were synthesised to identify components felt to be critical. Studies for this views synthesis were identified from existing reviews and an update of one review's search, which was run in December 2015. The identified components were then explored in a synthesis of intervention evaluations (five 'most effective' and 15 'least effective') conducted in western Europe, North America, Australia or New Zealand. The intervention evaluations were identified from existing reviews and an update of one review's search, which was run in March 2016. This evaluation synthesis was carried out using Qualitative Comparative Analysis. Three important mechanisms were present in all the most effective interventions but absent in all the least effective: 1/ showing families how to change: a) providing child physical activity sessions, b) delivering practical behaviour change strategy sessions, c) providing calorie intake advice; 2/ ensuring all the family are on board: a) delivering discussion/education sessions for both children and parents, b) delivering child-friendly sessions, c) aiming to change behaviours across the whole family; 3/ enabling social support for both parents and children by delivering both child group sessions and parent group sessions. To conclude, programmes should ensure the whole family is on board the programme, that parents and children can receive social support and are not just told what to change, but shown how.

The importance of service-users' perspectives: A systematic review of qualitative evidence reveals overlooked critical features of weight management programmes.

BACKGROUND: Extensive research effort shows that weight management programmes (WMPs) targeting both diet and exercise are broadly effective. However, the critical features of WMPs remain unclear. OBJECTIVE: To develop a deeper understanding of WMPs critical features, we undertook a systematic review of qualitative evidence. We sought to understand from a service-user perspective how programmes are experienced, and may be effective, on the ground. SEARCH STRATEGY: We identified qualitative studies from existing reviews and updated the searches of one review. INCLUSION CRITERIA: We included UK studies capturing the views of adult WMP users. DATA EXTRACTION AND SYNTHESIS: Thematic analysis was used inductively to code and synthesize the evidence. MAIN RESULTS: Service users were emphatic that supportive relationships, with service providers or WMP peers, are the most critical aspect of WMPs. Supportive relationships were described as providing an extrinsic motivator or "hook" which helped to overcome barriers such as scepticism about dietary advice or a lack confidence to engage in physical activity. DISCUSSION AND CONCLUSIONS: The evidence revealed that service-users' understandings of the critical features of WMPs differ from the focus of health promotion guidance or descriptions of evaluated programmes which largely emphasize educational or goal setting aspects of WMPs. Existing programme guidance may not therefore fully address the needs of service users. The study illustrates that the perspectives of service users can reveal unanticipated intervention mechanisms or underemphasized critical features and underscores the value of a holistic understanding about "what happens" in complex psychosocial interventions such as WMPs.

Weight management programmes: Re-analysis of a systematic review to identify pathways to effectiveness.

BACKGROUND: Previous systematic reviews of weight management programmes (WMPs) have not been able to account for heterogeneity of effectiveness within programmes using top-down behavioural change taxonomies. This could be due to overlapping causal pathways to effectiveness (or lack of effectiveness) in these complex interventions. Qualitative comparative analysis (QCA) can help identify these overlapping pathways. METHODS: Using trials of adult WMPs with dietary and physical activity components identified from a previous systematic review, we selected the 10 most and 10 least effective interventions by amount of weight loss at 12 months compared to minimal treatment. Using intervention components suggested by synthesis of studies of programme user views, we labelled interventions as to the presence of these components and, using qualitative comparative analysis, developed pathways of component combinations that created the conditions sufficient for interventions to be most effective and least effective. RESULTS: Informed by the synthesis of views studies, we constructed 3 truth tables relating to quality of the user-provider relationship; perceived high need for guidance from providers; and quality of the relationship between peers in weight management programmes. We found effective interventions were characterized by opportunities to develop supportive relationships with providers or peers, directive provider-led goal setting and components perceived to foster self-regulation. CONCLUSIONS: Although QCA is an inductive method, this innovative approach has enabled the identification of potentially critical aspects of WMPs, such as the nature of relationships within them, which were previously not considered to be as important as more concrete content such as dietary focus.

Appetite for change: a multidisciplinary team approach to behavioral modification for weight management in a community health group setting.

PURPOSE: Obesity is a growing issue in Australia with limited evidence for brief community based intervention. This preliminary study aimed to investigate the long term effects of a 4-week group based multidisciplinary behavior management program for weight loss in the community health setting. METHOD: A quasi-experimental study design was employed recruiting patients referred to two Community Health Centers. Participants completed a 4-week Appetite for change program, comprising four 2-h group sessions co-facilitated by a multidisciplinary team. The mindfulness self efficacy scale (MSES), quality of life scale (QoL), and self-reported knowledge and stages of change were measured pre-treatment, immediately post-treatment and, 6 and 12 months post-treatment. Weight and waist circumference were additionally measured at baseline, 6 and 12 months post-treatment. RESULTS: Eighty participants (mean age 63 ± 12.1 years) comprising 73 % women consented to participate. Statistically significant improvements (p ≤ 0.01) from pre-treatment were found at both 6 and 12 months, with a clinically significant mean percentage weight loss of approximately 4 %, and a mean improvement of 8.5 point on QoL at 12 months follow-up. Self-reported improvements in stages of change and knowledge were also maintained at 12 months. CONCLUSION: Clinically and statistically significant long term improvements in all outcomes were found following a multidisciplinary brief intervention program for overweight/obese adults in the community health setting. The promising results following the Appetite for Change program warrant further controlled investigation.

Understanding the role of the volunteer in specialist palliative care: a systematic review and thematic synthesis of qualitative studies.

BACKGROUND: Volunteers make a major contribution to palliative patient care, and qualitative studies have been undertaken to explore their involvement. With the aim of making connections between existing studies to derive enhanced meanings, we undertook a systematic review of these qualitative studies including synthesising the findings. We sought to uncover how the role of volunteers with direct contact with patients in specialist palliative care is understood by volunteers, patients, their families, and staff. METHODS: We searched for relevant literature that explored the role of the volunteer including electronic citation databases and reference lists of included studies, and also undertook handsearches of selected journals to find studies which met inclusion criteria. We quality appraised included studies, and synthesised study findings using a novel synthesis method, thematic synthesis. RESULTS: We found 12 relevant studies undertaken in both inpatient and home-care settings, with volunteers, volunteer coordinators, patients and families. Studies explored the role of general volunteers as opposed to those offering any professional skills. Three theme clusters were found: the distinctness of the volunteer role, the characteristics of the role, and the volunteer experience of the role. The first answers the question, is there a separate volunteer role? We found that to some extent the role was distinctive. The volunteer may act as a mediator between the patient and the staff. However, we also found some contradictions. Volunteers may take on temporary surrogate family-type relationship roles. They may also take on some of the characteristics of a paid professional. The second cluster helps to describe the essence of the role. Here, we found that the dominant feature was that the role is social in nature. The third helps to explain aspects of the role from the point of view of volunteers themselves. It highlighted that the role is seen by volunteers as flexible, informal and sometimes peripheral. These characteristics some volunteers find stressful. CONCLUSIONS: This paper demonstrates how qualitative research can be sythnesised systematically, extending methodological techniques to help answer difficult research questions. It provides information that may help managers and service planners to support volunteers appropriately.

The role of self-interest in unethical pro-organizational behavior: A nomological network meta-analysis.

To date, the unethical pro-organizational behavior (UPB) literature has been guided by a prosocial perspective, which argues that people engage in UPB primarily to benefit the employers with whom they identify and have a positive social exchange. According to this perspective, employees who are characteristically self-interested are less likely to engage in UPB. However, recent evidence suggests self-interest may play a larger role in motivating UPB than originally theorized. To clarify this controversy, we offer two different, but not necessarily mutually exclusive, perspectives of UPB-one in which UPB is driven primarily by prosocial motives and one in which it is driven primarily by self-interest. We tested which of these accounts of UPB was more strongly supported by comparing UPB's relationships with two nomological networks: one containing relatively prosocially motivated constructs and the other containing relatively self-interest-motivated constructs. Two of the eight hypotheses from the prosocial perspective were supported, while seven of the eight hypotheses from the self-interest perspective were supported. Additionally, the average absolute value of UPB's correlations with prosocial perspective constructs was .09, while the comparable average correlation with self-interest perspective constructs was .33. Thus, the results favored the self-interest perspective. We discuss how these findings change our theoretical understanding of UPB by acknowledging both its prosocial and self-interest motivations, and we accordingly propose a revised definition for UPB that allows for both of these motivations. We also examined more broadly the relationship between UPB and other constructs to provide a comprehensive meta-analytic overview of this literature. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

American Midwifery Certification Board Certification Demographic and Employment Data, 2016 to 2020: The Certified Nurse-Midwife and Certified Midwife Workforce.

INTRODUCTION: Expansion and diversification of the midwifery workforce is a federal strategy to address the maternal health crisis in the United States. Understanding characteristics of the current midwifery workforce is essential to creating approaches to its development. Certified nurse-midwives and certified midwives (CNMs/CMs) certified by the American Midwifery Certification Board (AMCB) constitute the largest portion of the US midwifery workforce. This article aims to describe the current midwifery workforce based on data collected from all AMCB-certified midwives at the time of certification. METHODS: Midwife initial certificants and recertificants were administered an electronic survey about personal and practice characteristics at the time of certification by AMCB between 2016 and 2020 for administrative purposes. Given the standard 5-year certification cycle, every midwife certified during this period completed the survey once. The AMCB Research Committee conducted a secondary data analysis of deidentified data to describe the CNM/CM workforce. RESULTS: In 2020 there were 12,997 CNMs/CMs in the United States. The workforce was largely White and female with an average age of 49. There has been a slow increase (15% to 21%) of initial certificants identifying as midwives of color. The proportion of CMs to all AMCB-certified midwives remained less than 2%. Physician-owned practices were the most common employer. Approximately 60% of midwives attend births, and hospitals were the most common birth setting. Over 10% of those certified to practice reported not working within the discipline of midwifery. DISCUSSION: Targeted recruitment and retention of midwives must take into consideration not just expansion but dispersion, scope of practice, and diversification. The proportion of midwives attending births was lower than reported in previous years. Expansion of the CM credential and accessible educational pathways are 2 potential solutions to workforce growth. Developing strategies to retain those who are trained but not practicing presents an opportunity for workforce maintenance.

The selection of search sources influences the findings of a systematic review of people's views: a case study in public health.

BACKGROUND: For systematic reviews providing evidence for policy decisions in specific geographical regions, there is a need to minimise regional bias when seeking out relevant research studies. Studies on people's views tend to be dispersed across a range of bibliographic databases and other search sources. It is recognised that a comprehensive literature search can provide unique evidence not found from a focused search; however, the geographical focus of databases as a potential source of bias on the findings of a research review is less clear. This case study describes search source selection for research about people's views and how supplementary searches designed to redress geographical bias influenced the findings of a systematic review. Our research questions are: a) what was the impact of search methods employed to redress potential database selection bias on the overall findings of the review? and b) how did each search source contribute to the identification of all the research studies included in the review? METHODS: The contribution of 25 search sources in locating 28 studies included within a systematic review on UK children's views of body size, shape and weight was analysed retrospectively. The impact of utilising seven search sources chosen to identify UK-based literature on the review's findings was assessed. RESULTS: Over a sixth (5 out of 28) of the studies were located only through supplementary searches of three sources. These five studies were of a disproportionally high quality compared with the other studies in the review. The retrieval of these studies added direction, detail and strength to the overall findings of the review. All studies in the review were located within 21 search sources. Precision for 21 sources ranged from 0.21% to 1.64%. CONCLUSIONS: For reducing geographical bias and increasing the coverage and context-specificity of systematic reviews of people's perspectives and experiences, searching that is sensitive and aimed at reducing geographical bias in database sources is recommended.

Comparing midwife-led and doctor-led maternity care: a systematic review of reviews.

AIMS: A report of a systematic review of reviews which examines the impact of having midwives-led maternity care for low-risk women, rather than physicians. BACKGROUND: A rising birth rate, increasing complexity of births, and economic constraints pose difficulties for maternity services in the UK. Evidence about the most effective, cost-effective, and efficient ways to give maternity services is needed. DATA SOURCES: Searches were carried out in August-September 2009 of ten electronic databases, 16 key nursing and research websites, and reference lists of 56 relevant reviews. We also contacted 38 experts for information. No date restrictions were employed. REVIEW METHODS: A narrative review of systematic reviews or 'meta review' was conducted using transparent and systematic procedures to limit bias at all stages. Systematic reviews that compared midwife-led care during pregnancy and birth with physician-led care were eligible for inclusion. RESULTS: Three meta-analytic reviews were included. Midwife-led care for low-risk women was found to be better for a range of maternal outcomes, reduced the number of procedures in labour, and increased satisfaction with care. For some maternal, foetal, and neonatal outcomes reviews found no evidence that care led by midwives is different to that led by physicians. No adverse outcomes associated with midwife-led care were identified. CONCLUSIONS: For low-risk women, health and other benefits can result from having their maternity care led by midwives rather than physicians. Moreover, there appear to be no negative impacts on mothers and infants receiving midwife-led care.

Clinical Efficacy and Whole-Exome Sequencing of Liquid Biopsies in a Phase IB/II Study of Bazedoxifene and Palbociclib in Advanced Hormone Receptor-Positive Breast Cancer.

PURPOSE: Sensitivity to endocrine therapy (ET) is critical for the clinical benefit from the combination of palbociclib plus ET in hormone receptor-positive/HER2-negative (HR+/HER2-) advanced breast cancer. Bazedoxifene is a third-generation selective estrogen receptor (ER) modulator and selective ER degrader with activity in preclinical models of endocrine-resistant breast cancer, including models harboring ESR1 mutations. Clinical trials in healthy women showed that bazedoxifene is well tolerated. PATIENTS AND METHODS: We conducted a phase Ib/II study of bazedoxifene plus palbociclib in patients with HR+/HER2- advanced breast cancer who progressed on prior ET (N = 36; NCT02448771). RESULTS: The study met its primary endpoint, with a clinical benefit rate of 33.3%, and the safety profile was consistent with what has previously been seen with palbociclib monotherapy. The median progression-free survival (PFS) was 3.6 months [95% confidence interval (CI), 2.0-7.2]. An activating PIK3CA mutation at baseline was associated with a shorter PFS (HR = 4.4; 95% CI, 1.5-13; P = 0.0026), but activating ESR1 mutations did not impact the PFS. Longitudinal plasma circulating tumor DNA whole-exome sequencing (WES; N = 68 plasma samples) provided an overview of the tumor heterogeneity and the subclonal genetic evolution, and identified actionable mutations acquired during treatment. CONCLUSIONS: The combination of palbociclib and bazedoxifene has clinical efficacy and an acceptable safety profile in a heavily pretreated patient population with advanced HR+/HER2- breast cancer. These results merit continued investigation of bazedoxifene in breast cancer.

The views of young children in the UK about obesity, body size, shape and weight: a systematic review.

BACKGROUND: There are high levels of concern about childhood obesity, with obese children being at higher risk of poorer health both in the short and longer terms. Children's attitudes to, and beliefs about, their bodies have also raised concern. Children themselves have a stake in this debate; their perspectives on this issue can inform the ways in which interventions aim to work.This systematic review of qualitative and quantitative research aimed to explore the views of UK children about the meanings of obesity and body size, shape or weight and their own experiences of these issues. METHODS: We conducted sensitive searches of electronic databases and specialist websites, and contacted experts. We included studies published from the start of 1997 which reported the perspectives of UK children aged 4-11 about obesity or body size, shape or weight, and which described key aspects of their methods. Included studies were coded and quality-assessed by two reviewers independently.Findings were synthesised in two analyses: i) an interpretive synthesis of findings from open-ended questions; and ii) an aggregative synthesis of findings from closed questions. We juxtaposed the findings from the two syntheses. The effect of excluding the lowest quality studies was explored. We also consulted young people to explore the credibility of a subset of findings. RESULTS: We included 28 studies. Instead of a focus on health, children emphasised the social impact of body size, describing experiences and awareness of abuse and isolation for children with a greater weight. Body size was seen as under the individual's control and children attributed negative characteristics to overweight people. Children actively assessed their own size; many wished their bodies were different and some were anxious about their shape.Reviewers judged that children's engagement and participation in discussion had only rarely been supported in the included studies, and few study findings had depth or breadth. CONCLUSIONS: Initiatives need to consider the social aspects of obesity, in particular unhelpful beliefs, attitudes and discriminatory behaviours around body size. Researchers and policy-makers should involve children actively and seek their views on appropriate forms of support around this issue.

A Phase 1 Dose-Escalation Trial of Radiation Therapy and Concurrent Cisplatin for Stage II and III Triple-Negative Breast Cancer.

PURPOSE: Patients with triple-negative breast cancer (TNBC) experience higher local-regional recurrence rates than those with luminal or HER2-positive tumors. This prospective, phase 1B trial was designed to assess the safety and to establish the maximum tolerated dose (MTD) of cisplatin with radiation therapy for women with early-stage TNBC. METHODS AND MATERIALS: Eligible patients had stage II or III TNBC. Cisplatin was initiated at 10 mg/m2 intravenously once weekly during radiation and then escalated in a 3 + 3 design by 10 mg/m2 at each dose level until 40 mg/m2, or the MTD, was reached. Patients undergoing breast-conserving therapy (BCT) or mastectomy were accrued in separate parallel cohorts during dose escalation, followed by a 10-patient expansion at the MTD. RESULTS: During 2013 to 2018, 55 patients were accrued. Four patients developed dose-limiting toxicity. In the BCT cohort, 1 patient receiving 40 mg/m2 developed tinnitus resulting in a cisplatin delay; therefore, this was the BCT cohort MTD. In the mastectomy cohort, 1 patient receiving 20 mg/m2 developed a grade 3 urinary infection, and 2 additional patients had dose-limiting toxicities at 40 mg/m2 (grade 3 neutropenia and grade 2 tinnitus), both resulting in cisplatin delay. Thus, 30 mg/m2 was the mastectomy cohort MTD. Median follow-up was 48.5 months. Three-year disease-free survival was 74.7% for the BCT cohort and 64.4% for the mastectomy cohort. CONCLUSIONS: Adjuvant radiation therapy with concurrent cisplatin is feasible with a recommended phase 2 dose of 30 mg/m2 and 40 mg/m2 intravenously weekly in mastectomy and BCT cohorts, respectively.

School closure in response to epidemic outbreaks: Systems-based logic model of downstream impacts.

Background: School closures have been a recommended non-pharmaceutical intervention in pandemic response owing to the potential to reduce transmission of infection between children, school staff and those that they contact. However, given the many roles that schools play in society, closure for any extended period is likely to have additional impacts. Literature reviews of research exploring school closure to date have focused upon epidemiological effects; there is an unmet need for research that considers the multiplicity of potential impacts of school closures. Methods: We used systematic searching, coding and synthesis techniques to develop a systems-based logic model. We included literature related to school closure planned in response to epidemics large and small, spanning the 1918-19 'flu pandemic through to the emerging literature on the 2019 novel coronavirus. We used over 170 research studies and a number of policy documents to inform our model. Results: The model organises the concepts used by authors into seven higher level domains: children's health and wellbeing, children's education, impacts on teachers and other school staff, the school organisation, considerations for parents and families, public health considerations, and broader economic impacts. The model also collates ideas about potential moderating factors and ethical considerations. While dependent upon the nature of epidemics experienced to date, we aim for the model to provide a starting point for theorising about school closures in general, and as part of a wider system that is influenced by contextual and population factors. Conclusions: The model highlights that the impacts of school closures are much broader than those related solely to health, and demonstrates that there is a need for further concerted work in this area. The publication of this logic model should help to frame future research in this area and aid decision-makers when considering future school closure policy and possible mitigation strategies.