Reshaping the Tumor Microenvironment of KRASG12D Pancreatic Ductal Adenocarcinoma with combined SOS1 and MEK Inhibition for Improved Immunotherapy Response.

KRAS inhibitors have demonstrated exciting pre-clinical and clinical responses, although resistance occurs rapidly. Here, we investigate the effects of KRAS-targeting therapies on the tumor microenvironment using a library of KRASG12D, p53 mutant, murine PDAC-derived cell lines (KPCY) to leverage immune-oncology combination strategies for long-term tumor efficacy. Our findings show that SOS1 and MEK inhibitors (SOS1i+MEKi) suppressed tumor growth in syngeneic models and increased intra-tumoral CD8+ T cells without durable responses. scRNA-sequencing revealed an increase in inflammatory cancer associated fibroblasts (iCAFs), M2 macrophages, and a decreased dendritic cell quality that ultimately resulted in a highly immunosuppressive microenvironment driven by IL6+ iCAFs. Agonist CD40 treatment was effective to revert macrophage polarization and overcome the lack of mature antigen presenting DCs after SOS1i+MEKi therapy. Treatment increased the overall survival of KPCY tumor-bearing mice. The addition of checkpoint blockade to SOS1i+MEKi combination resulted in tumor free mice with established immune memory. Our data suggests that KRAS inhibition affects myeloid cell maturation and highlights the need for combining KRAS cancer-targeted therapy with myeloid activation to enhance and prolong anti-tumor effects.

Evaluating thromboprophylaxis in the sickle cell disease population: Navigating the evidence gap.

Sickle cell disease (SCD) arises from beta-globin gene mutations, with global estimates indicating around 500 000 affected neonates in 2021. In the United States, it is considered rare, impacting fewer than 200 000 individuals. The key pathogenic flaw lies in mutant haemoglobin S, prone to polymerization under low oxygen conditions, causing erythrocytes to adopt a sickled shape. This leads to complications like vascular occlusion, haemolytic anaemia, inflammation and organ damage. Beyond erythrocyte abnormalities however, there is a body of literature highlighting the hypercoagulable state that is likely a contributor to many of the complications we see in SCD. The persistent activation of the coagulation cascade results in thromboembolic events, notably venous thromboembolism (VTE) which is independently associated with increased mortality in both adults and children with SCD. While the increased risk of VTE in the SCD population seems well established, there is a lack of guidelines for thromboprophylaxis in this population. This Wider Perspective will describe the hypercoagulable state and increased thrombosis risk in the SCD population, as well as advocate for the development of evidence-based guidelines to aid in the prevention of VTE in SCD.

Health care utilization and the associated costs attributable to cardiovascular disease in Ireland: a cross-sectional study.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of mortality and disability globally. We examined healthcare service utilization and costs attributable to CVD in Ireland in the period before the introduction of a major healthcare reform in 2016. METHODS: Secondary analysis of data from 8 113 participants of the first wave of The Irish Longitudinal Study on Ageing. CVD was defined as having a self-reported doctor's diagnosis of myocardial infarction, angina, heart failure, stroke, atrial fibrillation or transient ischaemic attack. Participants self-reported the utilization of healthcare services in the year preceding the interview. Negative binomial regression with average marginal effects (AME) was used to estimate the incremental number of general practitioner (GP) and outpatient department (OPD) visits, accident and emergency department attendances and hospitalisations in population with CVD relative to population without CVD. We calculated the corresponding costs at individual and population levels, by gender and age groups. RESULTS: The prevalence of CVD was 18.2% (95% CI: 17.3, 19.0) Participants with CVD reported higher utilization of all healthcare services. In adjusted models, having CVD was associated with incremental 1.19 (95% CI: 0.99, 1.39) GP and 0.79 (95% CI: 0.65, 0.93) OPD visits. There were twice as many incremental hospitalisations in males with CVD compared to females with CVD (AME (95% CI): 0.20 (0.16, 0.23) vs 0.10 (0.07, 0.14)). The incremental cost of healthcare service use in population with CVD was an estimated €352.2 million (95% CI: €272.8, €431.7), 93% of which was due to use of secondary care services. CONCLUSION: We identified substantially increased use of healthcare services attributable to CVD in Ireland. Continued efforts aimed at CVD primary prevention and management are required.

A high-throughput small volume matrix based calibration using isotope dilution liquid chromatography tandem mass spectrometry analysis for 42 per and polyfluoroalkyl substances in groundwater.

A novel method for the determination of per- and polyfluoroalkyl substances (PFAS) in groundwater is presented using a subsample, matrix-matched calibrators, 96-well plate solid phase extraction (SPE), and ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS). Accuracy, precision, measurement of uncertainty (MOU), method detection limit (MDL), method quantitation limit (MQL), analytical measurement range, interferences/ion suppression, and analyte stability were determined as part of the in-house method validation. The method quantitates 42 PFAS compounds from nine different compound classes. Accuracy for the reference material (RM) and matrix spike (MS) ranged from 52.3 to 117.8 %, and precision for the MS and matrix spike duplicate (MSD) had a coefficient of variation (CV) from 2.0 % to 23.3 %. MDLs spanned from 0.07 to 1.97 ng L-1, with MQLs ranging from 0.20 to 5.90 ng L-1. Suppression studies determined that iron and manganese have effects on analytes that do not have paired isotopically labeled standards. The results from the in-house validation indicated that this Michigan Department of Health and Human Services laboratory developed test meets the necessary accuracy, precision, MDL, MQL and reporting limits requirement established by the laboratory's quality system essentials (QSEs) and select criteria from the Department of Defense (DoD) Quality Systems Manual for Environmental Laboratories and American Industrial Hygiene Association Laboratory Accreditation Program, LLC (AIHA LAP, LLC) accrediting International Standard Organization (ISO/IEC 17025:2017) check list.

The views of parents and carers on managing acute otitis media in urban Aboriginal and Torres Strait Islander children: a qualitative study.

OBJECTIVES: To explore the views of parents and carers regarding the management of acute otitis media in urban Aboriginal and Torres Strait Islander children who are at low risk of complications living in urban communities. STUDY DESIGN: Qualitative study; semi-structured interviews and short telephone survey. SETTING, PARTICIPANTS: Interviews: purposive sample of parents and carers of urban Aboriginal and Torres Strait Islander children (18 months - 16 years old) screened in Aboriginal medical services in Queensland, New South Wales, and Canberra for the WATCH study, a randomised controlled trial that compared immediate antibiotic therapy with watchful waiting for Aboriginal and Torres Strait Islander children with acute otitis media. SURVEY: parents and carers recruited for the WATCH trial who had completed week two WATCH surveys. RESULTS: We interviewed twenty-two parents and carers, including ten who had declined participation in or whose children were ineligible for the WATCH trial. Some interviewees preferred antibiotics for managing acute otitis media, others preferred watchful waiting, expressing concerns about side effects and reduced efficacy with overuse of antibiotics. Factors that influenced this preference included the severity, duration, and recurrence of infection, and knowledge about management gained during the trial and from personal and often multigenerational experience of ear disease. Participants highlighted the importance of shared decision making by parents and carers and their doctors. Parents and carers of 165 of 262 WATCH participants completed telephone surveys (63%); 81 were undecided about whether antibiotics should always be used for treating acute otitis media. Open-ended responses indicated that antibiotic use should be determined by clinical need, support for general practitioners' decisions, and the view that some general practitioners prescribed antibiotics too often. CONCLUSIONS: Parents and carers are key partners in managing acute otitis media in urban Aboriginal and Torres Strait Islander children. Our findings support shared decision making informed by the experience of parents and carers, which could also lead to reduced antibiotic use for managing acute otitis media.

Exploring Elinor Ostrom's principles for collaborative group working within a user-led project: lessons from a collaboration between researchers and a user-led organisation.

BACKGROUND: Some research has been undertaken into the mechanisms that shape successful participatory approaches in the context of efforts to improve health and social care. However, greater attention needs to be directed to how partnerships between researchers and user-led organisations (ULOs) might best be formed, practiced, managed, and assessed. We explored whether political economist Elinor Ostrom's Nobel prize winning analysis of common pool resource management-specifically eight principles to enhance collaborative group working as derived from her empirical research-could be usefully applied within a user-led project aiming to co-design new services to support more inclusive involvement of Disabled people in decision-making processes in policy and practice. METHODS: Participant observation and participatory methods over a 16-month period comprising observational notes of online user-led meetings (26 h), online study team meetings (20 h), online Joint Interpretive Forum meetings (8 h), and semi-structured one-to-one interviews with project participants (44 h) at two time points (months 6 and 10). RESULTS: Initially it proved difficult to establish working practices informed by Ostrom's principles for collaborative group working within the user-led project. Several attempts were made to put a structure in place that met the needs of both the research study and the aims of the user-led project, but this was not straightforward. An important shift saw a move away from directly applying the principles to the working practices of the group and instead applying them to specific tasks the group were undertaking. This was a helpful realisation which enabled the principles to become-for most but not all participants-a useful facilitation device in the latter stages of the project. Eventually we applied the principles in a way that was useful and enabled collaboration between researchers and a ULO (albeit in unexpected ways). CONCLUSIONS: Our joint reflections emphasise the importance of being reflexive and responsive when seeking to apply theories of collaboration (the principles) within user-led work. At an early stage, it is important to agree shared definitions and understanding of what 'user-led' means in practice. It is crucial to actively adapt and translate the principles in ways that make them more accessible and applicable within groups where prior knowledge of their origins is both unlikely and unnecessary.

Academic researchers and members of Shaping Our Lives­a national network and user-led organisation of Disabled people and service users­came together to explore whether Elinor Ostrom's Nobel Prize winning work on collaborative group working could usefully inform efforts to co-design new services to promote the inclusive involvement of Disabled people in decision-making processes. We wanted to see if Ostrom's 'principles for collaborative group working' were relevant to and could perhaps facilitate a co-design process led by a user led organisation. At first, we struggled to decide how Ostrom's principles might inform the user-led project. We tried different ways to achieve this and eventually found an approach that most but not all of us found helpful. An important change we made was to stop focusing on how the members of the user-led group were collaborating together and instead to apply the principles to specific aspects of the co-design project that were complex and could be responded to in multiple ways. By the end of the 16-month study we had found a way of using the principles to better enable collaboration between academic researchers and a user-led organisation (although not in the way we had initially anticipated). We learned how Ostrom's principles could be used to facilitate discussion of aspects of project work that are complex and the pros and cons of different plans of action. This project has demonstrated that collaboration between researchers and user-led organisations can be challenging but also has great potential for shared learning.

Outcomes and Safety of Suprapubic vs Urethral Catheterization Following Pelvic Fascia‒Sparing Robotic Prostatectomy.

INTRODUCTION: Urethral catheter (UC) discomfort remains a burden following robotic-assisted radical prostatectomy (RARP). Suprapubic catheters (SPCs) may reduce patient discomfort and increase satisfaction. Pelvic fascia‒sparing (PFS) RARP reduces the technical challenges of intraoperative SPC placement. We examined postoperative outcomes of SPC vs UC placement following PFS-RARP. METHODS: We conducted a retrospective review of a prospective institutional review board‒approved database of PFS-RARP patients from June 2020 to December 2022 receiving SPC (n = 108) or UC (n = 104) postoperatively. Demographics and clinical and perioperative outcomes were captured. Postoperative patient-reported quality of life was measured using EPIC-CP (Expanded Prostate Cancer Index Composite for Clinical Practice). Patients with intraoperative complications or intraoperative leaks or undergoing salvage prostatectomy were excluded. Univariate and multivariate regression analyses were performed to compare outcomes. RESULTS: No significant differences in demographics or oncologic outcomes existed. There were no differences in complications, including urethral stricture or anastomotic leak. Men receiving SPC vs UC had earlier return to continence (7 vs 16 days, P < .001) and higher continence rates at catheter removal (67.6% vs 43.3%, P = .0003). On adjusted analyses, SPC was an independent predictor of continence at catheter removal (OR 2.21, P = .023). There were no differences between groups in preoperative or postoperative EPIC-CP scores, including no differences in postoperative quality of life (P = .46). CONCLUSIONS: SPC after PFS-RARP is a safe and feasible alternative to UC. SPC is associated with an earlier return to continence and higher continence rates at catheter removal. Use of SPC may increase overall patient satisfaction following PFS-RARP.

Comparing super-utilizers and lower-utilizers among commercial- and Medicare-insured adults with sickle cell disease.

ABSTRACT: Sickle cell disease (SCD) is a rare but costly condition in the United States. Super-utilizers have been defined as a subset of the population with high health care encounters or expenditures. Although super-utilizers have been described in other disease states, little is known about super-utilizers among adults with SCD. This study aimed to characterize the differences in expenditures, overall health care encounters, and pain episode encounters between super-utilizers (top 10% expenditures) and lower-utilizers with SCD (high, top 10%-24.9%; moderate, 25%-49.9%; and low, bottom 50% expenditures). A retrospective longitudinal cohort of adults with SCD were identified using validated algorithms in MarketScan and Medicare claim databases from 2016 to 2020. Encounters and expenditures were analyzed from inpatient, outpatient, and emergency department settings. Differences in encounters and expenditures between lower-utilizers and super-utilizers were compared using logistic regression. Among super-utilizers, differences in encounters and expenditures were compared according to incidences of pain episode encounters. The study population included 5666 patients with commercial insurance and 8600 with Medicare. Adjusted total annual health care expenditure was 43.46 times higher for super-utilizers than for low-utilizers among commercial-insured and 13.37 times higher in Medicare-insured patients. Among super-utilizers, there were patients with few pain episode encounters who had higher outpatient expenditures than patients with a high number of pain episode encounters. Our findings demonstrate the contribution of expensive outpatient care among SCD super-utilizers, in which analyses of high expenditure have largely focused on short-term care. Future studies are needed to better understand super-utilizers in the SCD population to inform the effective use of preventive interventions and/or curative therapies.

Apixaban versus no anticoagulation for the prevention of venous thromboembolism in children with newly diagnosed acute lymphoblastic leukaemia or lymphoma (PREVAPIX-ALL): a phase 3, open-label, randomised, controlled trial.

BACKGROUND: Paediatric patients with acute lymphoblastic leukaemia or lymphoma are at increased risk of venous thromboembolism resulting in increased mortality and morbidity. We hypothesised that apixaban, a direct oral anticoagulant, would safely reduce venous thromboembolism in this patient population. METHODS: PREVAPIX-ALL was a phase 3, open-label, randomised, controlled trial conducted in 74 paediatric hospitals in 9 countries. Participants aged 1 year or older to younger than 18 years with newly diagnosed acute lymphoblastic leukaemia (pre-B cell or T cell) or lymphoblastic lymphoma (B cell or T cell immunophenotype) and a central venous line in place throughout induction were randomly assigned 1:1 to standard of care (SOC, ie, no systemic anticoagulation) or weight-adjusted twice-daily apixaban during induction. Randomisation was performed centrally and stratified by age (those <10 years or those ≥10 years). Participants weighing 35 kg or less were administered 2·5 mg twice daily of apixaban as a 2·5 mg tablet, 0·5 mg tablets, or 0·4 mg/mL oral solution, while those weighing more than 35 kg were administered weight-adjusted prophylactic doses using 0·5 mg tablets or the 0·4 mg/mL oral solution twice daily. Primary outcomes were assessed by a blinded central adjudication committee. The primary efficacy outcome for the intention to treat population was the composite of symptomatic or clinically unsuspected venous thromboembolism, the primary safety outcome was major bleeding, and secondary safety outcomes included clinically relevant non-major (CRNM) bleeding. Patients were screened for venous thromboembolism by ultrasound and echocardiogram at the end of induction. The trial was registered with ClinicalTrials.gov (NCT02369653) and is now complete. FINDINGS: Between Oct 22, 2015, and June 4, 2021, 512 participants were randomly assigned and included in analyses (222 [43%] female and 290 [57%] male; 388 [76%] White, 52 [10%] Asian, 24 [5%] Black or African American, and 48 [9%] other races; and 122 [24%] Hispanic or Latino ethnicity). During a median follow-up period of 27 days (IQR 26-28), 31 (12%) of 256 patients on apixaban had a composite venous thromboembolism compared with 45 (18%) of 256 participants receiving SOC (relative risk [RR] 0·69, 95% CI 0·45-1·05; p=0·080). Two major bleeding events occurred in each group (RR 1·0, 95% CI 0·14-7·01; p=1·0). A higher incidence of CRNM bleeding, primarily grade 1 or 2 epistaxis, occurred in the apixaban group (11 [4%] of 256 participants) compared with the SOC group (3 [1%] of 256; RR 3·67, 95% CI 1·04-12·97, p=0·030). The most frequent grade 3-5 adverse events in both groups were thrombocytopenia (n=28 for the apixaban group and n=20 for the SOC group) or platelet count decreased (n=49 and n=45), anaemia (n=77 and n=74), febrile neutropenia (n=27 and n=20), and neutropenia (n=16 and n=17) or neutrophil count decreased (n=22 and n=25). Five deaths occurred, which were due to infection (n=3 in the SOC group), cardiac arrest (n=1 in apixaban group), and haemorrhagic cerebral sinus vein thrombosis (n=1 in the SOC group). There was one apixaban-related death (coagulopathy and haemorrhage after cardiac arrest of unknown cause). INTERPRETATION: PREVAPIX-ALL is, to our knowledge, the first trial assessing primary thromboprophylaxis using a direct oral anticoagulant in paediatric patients with acute lymphoblastic leukaemia or lymphoma. No statistically significant treatment benefit was identified in participants receiving apixaban. Major and CRNM bleeding were infrequent overall, but a higher incidence of CRNM bleeding (primarily epistaxis in younger children) occurred in participants receiving apixaban. For patients deemed to be at particularly high risk of thrombosis, PREVAPIX-ALL provides encouraging safety data for the use of apixaban in clinical settings in which the potential benefits are thought to outweigh the risk of bleeding. FUNDING: Bristol Myers Squibb-Pfizer Alliance.

Mobile Application Measurement of Menstrual Cycle Characteristics and Their Association with Dysmenorrhea and Activity Limitation in Early Adolescents.

OBJECTIVE: Real-time tracking of menstrual bleeding is a barrier to research due to limitations with traditional data collection tools. This prospective cohort study utilized a mobile application (TDot app) in young adolescents aged 10-14 years to assess the relationship between heavy menstrual bleeding (HMB), dysmenorrhea, and activity limitation. METHODS: Menstrual cycles were captured over six months in real-time using the Pictorial Blood loss Assessment Chart (PBAC). A median PBAC score of >100 was used to identify participants with HMB. Participants also completed a modified WaLIDD (Working ability, Location, Intensity, Days of pain, Dysmenorrhea) scale. Impact of menses on daily activities was collected for each cycle. RESULTS: A total of 160 participants enrolled and 100 (63%) participants with ≥3 cycles recorded in the mobile app were analyzed. HMB was noted in 41% of participants. Median modified WaLIDD score was significantly higher in participants with HMB than those without HMB (p=0.01). No significant differences were found in activity limitations between participants with and without HMB (p=0.34). Median modified WaLIDD score for participants with activity limitation was significantly higher than those without activity limitation (p=0.01). CONCLUSION: Utilizing mobile app technology, we were able to gather real-time menstrual outcome data from young adolescents on heaviness of flow, dysmenorrhea and activity limitations. While we did not find that patients with HMB were more likely to have activity limitations, we did find that those with limitations had modestly higher dysmenorrhea scores. Future studies should focus on identifying additional variables that impact activity limitation during menstruation.

Mapping Interpersonal Emotion Regulation in Everyday Life.

The growing literature on interpersonal emotion regulation has largely focused on the strategies people use to regulate. As such, researchers have little understanding of how often people regulate in the first place, what emotion regulation goals they have when they regulate, and how much effort they invest in regulation. To better characterize features of the regulation process, we conducted two studies using daily diary (N = 171) and experience sampling methods (N = 239), exploring interpersonal emotion regulation in the context of everyday social interactions. We found people regulated others' emotions nearly twice a day, regulated their own emotions through others around once a day, and regulated both their own and others' emotions in the same interaction roughly every other day. Furthermore, not only did people regulate others' emotions more often than regulating their own emotions through others, but they also put in more effort to do so. The goals of regulation were primarily to make themselves or others feel better, most often through increasing positive emotions, rather than decreasing negative emotions. Together, these findings provide a foundational picture of the interpersonal emotion regulation landscape, and lay the groundwork for future exploration into this emerging subfield of affective science. Supplementary Information: The online version contains supplementary material available at 10.1007/s42761-023-00223-z.

Venous thromboembolism prophylaxis practices for patients with sickle cell disease prior to and during the COVID-19 pandemic.

Patients with sickle cell disease (SCD) are predisposed to a hypercoagulable state due to alterations in the coagulation system. Despite concern for the development of venous thromboembolism (VTE) in this population, there are no standardized guidelines for routine thromboprophylaxis. The objective of this study was to assess thromboprophylaxis practices of adult and pediatric treaters of SCD before and during the coronavirus disease of 2019 (COVID-19) pandemic. A cross-sectional electronic survey was distributed to pediatric and adult hematology oncology practitioners through seven SCD-specific interest groups between May 29, 2020, and July 13, 2020. Of 93 total responses, 14% ( N  = 13) reported they only treat patients more than 21 years old; 38.7% ( N  = 36) only treat patients 0-21 years old and 47.3% ( N  = 44) reported they treat both. Our study showed that before the COVID-19 pandemic, 96% of adult practitioners would recommend pharmacologic thromboprophylaxis, mechanical thromboprophylaxis or both for hospitalized adults with thromboprophylaxis, but only 76% of pediatric treaters would recommend any thromboprophylaxis in hospitalized children ( P  < 0.0001), with 24% of pediatric treaters choosing no thromboprophylaxis at all. During the COVID-19 pandemic, pharmacologic thromboprophylaxis specifically was recommended for adults by 94% of treaters and for pediatric patients by 76% of treaters. These findings suggest that despite the lack of evidence-based thromboprophylaxis guidelines in adults and children with thromboprophylaxis, subspecialty treaters routinely provide pharmacologic thromboprophylaxis in their adult patients and will modify their practice in pediatric patients who are considered at a high risk for VTE.

Clinicians' perspectives on barriers and facilitators to sperm banking in adolescent males with cancer: a mixed-methods study.

PURPOSE: To examine processes, barriers, and facilitators to sperm banking counseling and decision-making for adolescent males newly diagnosed with cancer from the perspective of clinicians who completed Oncofertility communication training. We also identify opportunities for improvement to inform future interventions and implementation. METHODS: A survey (N=104) and subsequent focus groups (N=15) were conducted with non-physician clinicians practicing in pediatric oncology who completed Oncofertility communication training. RESULTS: Most survey participants were confident in communicating about the impact of cancer on fertility (n=87, 83.7%) and fertility preservation options (n=80, 76.9%). Most participants reported never/rarely using a sperm banking decision tool (n=70, 67.3%), although 98.1% (n=102) said a decision tool with a family-centered approach would be beneficial. Primary themes in the subsequent focus groups included variable processes/workflows (inconsistent approaches to consult initiation; involvement of adolescents, caregivers, and various clinician types; assessment of puberty/sexual experience), structural and psychosocial barriers (cost and logistics, developmental, cultural, clinical acuity/prognosis), and facilitators (educational materials, alternative options for banking). Opportunities and strategies for improvement (including fertility preservation in existing research protocols; additional staffing/resources; oncologist education and buy-in; and development of decision tools) were informed by challenges identified in the other themes. CONCLUSION: Barriers to adolescent sperm banking remain, even among clinicians who have completed Oncofertility training. Although training is one factor necessary to facilitate banking, structural and psychosocial barriers persist. Given the complexities of offering sperm banking to pediatric populations, continued efforts are needed to mitigate structural barriers and develop strategies to facilitate decision-making before childhood cancer treatment.

Pregnancy-related thromboembolism in women with sickle cell disease: An analysis of National Medicaid Data.

Pregnancy and sickle cell disease (SCD) both individually carry a risk of thromboembolism (TE). Pregnancy in people with SCD may further enhance the prothrombotic effect of the underlying disease. The objectives of this study were to determine the rate and risk factors for arterial and venous thrombosis in pregnant people with SCD. Administrative claims data from the United States Centers for Medicare and Medicaid Service Analytic eXtract from 2006 to 2018 were used. The study population included people with SCD from the start of their first identified pregnancy until 1 year postpartum and a control cohort of pregnant people without SCD of similar age and race. Outcomes of interest were identified with ICD-9 or 10 codes. Logistic regression analyses were used to analyze risk factors. We identified infant deliveries in 6388 unique people with SCD and 17 110 controls. A total of 720 venous thromboembolism (11.3%) and 335 arterial TE (5.2%) were observed in people with SCD compared to 202 (1.2%) and 95 (0.6%) in controls. People with SCD had an 8-11 times higher odds of TE compared to controls (p < .001). Within the SCD cohort, age, hemoglobin SS (HbSS) genotype, hypertension, and history of thrombosis were identified as independent risk factors for pregnancy-related TE. Pregnancy-specific factors (pre-eclampsia, eclampsia, multigestational pregnancy) were not associated with TE. In conclusion, the risk of pregnancy-related TE is considerably higher in people with SCD compared with controls without SCD. Hence, people with SCD, particularly those with multiple risk factors may be candidates for thromboprophylaxis during pregnancy and the postpartum period.

Comparison of thromboembolism outcomes in patients with sickle cell disease prescribed hormonal contraception.

Patients with sickle cell disease (SCD) are at a risk of thromboembolism (TE), and use of hormonal contraception can further increase that risk. This study aims to assess patterns of hormonal contraceptive use and compare risk of contraception-related TE between combined hormonal contraceptives (CHCs) and progestin-only contraceptives (POCs). Patients with SCD aged between 12 and 44 years with a new prescription of a hormonal contraceptive in the Centers for Medicare and Medicaid Services Medicaid Analytic eXtract database (2006-2018) were followed up to 1 year. We identified 7173 new users: 44.6% initiated CHC and 55.4% initiated POC. Combined oral contraceptive pills (OCPs; 36.5%) and progestin-only depot medroxyprogesterone acetate (33.9%) were the most frequently prescribed agents. A total of 1.8% of contraception users had a new diagnosis of TE within 1 year of the first identified contraception prescription. There were no significant differences in TE event rates between CHC and POC users (17.2 and 24.7 events per 1000 person-years, respectively). In patients prescribed OCP, there were no differences in TE event rates based on estrogen dose or progestin generation. Transdermal patch had a 2.4-fold increased risk of TE as compared with that of OCP. Although limited by the retrospective study design and use of administrative claims data, this study found no significant differences in TE rates between new users of CHC and POC in patients with SCD. Careful evaluation of underlying TE risk factors should be considered for each patient with SCD before initiation of hormonal contraception.

Addressing child and adolescent obesity management in Ireland: identifying facilitators and barriers in clinical practice.

Background: Ireland's Model of Care for the Management of Overweight and Obesity outlines a plan for treating adolescent and child obesity (CO). However, engagement with key stakeholders is required to support its implementation and improve health services. Aim: This study aims to map the perceived barriers and facilitators related to CO management across healthcare settings, professional disciplines, and regions in the Republic of Ireland (ROI). Materials and methods: An online cross-sectional survey of registered healthcare professionals (HPs), designed to adhere to the Consolidated Framework for Implementation Research (CFIR), was co-developed by a project team consisting of researchers, healthcare professionals, and patient advocates. The survey was pilot tested with project stakeholders and distributed online to professional groups and via a social media campaign, between September 2021 and May 2022, using "SurveyMonkey." Data were summarised using descriptive statistics and thematic analyses. Themes were mapped to the CFIR framework to identify the type of implementation gaps that exist for treating obesity within the current health and social care system. Results: A total of 184 HPs completed the survey including nurses (18%), physicians (14%), health and social care professionals (60%), and other HPs (8%). The majority were female (91%), among which 54% reported conducting growth monitoring with a third (32.6%) giving a diagnosis of paediatric/adolescent obesity as part of their clinical practice. Nearly half (49%) of the HPs reported having the resources needed for clinical assessment. However, 31.5% of the HPs reported having enough "time," and almost 10% of the HPs reported having no/limited access to suitable anthropometric measurement tools. Most HPs did not conduct obesity-related clinical assessments beyond growth assessment, and 61% reported having no paediatric obesity training. CFIR mapping identified several facilitators and barriers including time for clinical encounters, suitable materials and equipment, adequate training, perceived professional competency and self-efficacy, human equality and child-centredness, relative priorities, local attitudes, referral protocols, and long waiting times. Conclusions: The findings provide actionable information to guide the implementation of the Model of Care for the Management of Overweight and Obesity in Ireland. Survey findings will now inform a qualitative study to explore implementation barriers and facilitators and prioritise actions to improve child and adolescent obesity management.

Venous thromboembolism prophylaxis in sickle cell disease: a multicenter cohort study of adolescent inpatients.

Patients with sickle cell disease (SCD) are predisposed to a hypercoagulable state. Despite the increased risk of venous thromboembolism in the SCD population, there is limited evidence available to guide thromboprophylaxis (TP) practices in these patients. This study aimed to assess the use of pharmacologic and nonpharmacologic TP in adolescent patients with SCD using the Pediatric Health Information System (PHIS). We hypothesized that TP was increasingly used in hospitalized adolescent patients with SCD. The study included patients with SCD aged 13 to 21 years, admitted to a PHIS hospital between 1 January, 2010, and 30 June, 2021. A total of 7202 unique patients consisting of 34 094 unique admissions were included for analyses. Pharmacologic or mechanical TP was used in 2600 (7.6%) admissions, with 3.6% of admissions (n = 1225) receiving pharmacologic prophylaxis and 4.3% (n = 1474) receiving mechanical prophylaxis. Pharmacologic TP increased in use from 1.3% of admissions in 2010 to 14.4% in the first half of 2021. Enoxaparin was the most commonly prescribed anticoagulant, used in 87% of admissions in which pharmacologic TP was used. The use of prophylactic direct oral anticoagulants was first documented in 2018 and increased to 25% of admissions with pharmacologic TP by 2021. This study demonstrates a steady increase in TP use in adolescent patients with SCD admitted to the hospital. Prospective cohort studies are needed to determine VTE risk factors in adolescents and children with SCD and the efficacy and safety of prophylactic regimens.

Everyday emotional functioning in COVID-19 lockdowns.

Throughout the COVID-19 pandemic, policy makers have tried to balance the effectiveness of lockdowns (i.e., stay-at-home orders) with their potential mental health costs. Yet, several years into the pandemic, policy makers lack solid evidence about the toll of lockdowns on daily emotional functioning. Using data from two intensive longitudinal studies conducted in Australia in 2021, we compared the intensity, persistence, and regulation of emotions on days in and out of lockdown. Participants (N = 441, observations = 14,511) completed a 7-day study either entirely in lockdown, entirely out of lockdown, or both in and out of lockdown. We assessed emotions in general (Dataset 1) and in the context of social interactions (Dataset 2). Lockdowns took an emotional toll, but this toll was relatively mild: In lockdown, people experienced slightly more negative and less positive emotion; returned to a mildly negative emotional state more quickly; and used low-effort emotion-regulation strategies (i.e., distraction). There are three interpretations for our findings, which are not mutually exclusive. First, people may be relatively resilient to the emotional challenges posed by repeated lockdowns. Second, lockdowns may not compound the emotional challenges of the pandemic. Third, because we found effects even in a mostly childless and well-educated sample, lockdowns may take a greater emotional toll in samples with less pandemic privilege. Indeed, the high level of pandemic privilege of our sample limits the generalizability of our findings (e.g., to people with caregiving roles). (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Can foodborne illness estimates from different countries be legitimately compared?: case study of rates in the UK compared with Australia, Canada and USA.

OBJECTIVE: Mathematical models have gained traction when estimating cases of foodborne illness. Model structures vary due to differences in data availability. This begs the question as to whether differences in foodborne illness rates internationally are real or due to differences in modelling approaches.Difficulties in comparing illness rates have come into focus with COVID-19 infection rates being contrasted between countries. Furthermore, with post-EU Exit trade talks ongoing, being able to understand and compare foodborne illness rates internationally is a vital part of risk assessments related to trade in food commodities. DESIGN: We compared foodborne illness estimates for the United Kingdom (UK) with those from Australia, Canada and the USA. We then undertook sensitivity analysis, by recreating the mathematical models used in each country, to understand the impact of some of the key differences in approach and to enable more like-for-like comparisons. RESULTS: Published estimates of overall foodborne illness rates in the UK were lower than the other countries. However, when UK estimates were adjusted to a more like-for-like approach to the other countries, differences were smaller and often had overlapping credible intervals. When comparing rates by specific pathogens, there were fewer differences between countries. The few large differences found, such as virus rates in Canada, could at least partly be traced to methodological differences. CONCLUSION: Foodborne illness estimation models are country specific, making international comparisons problematic. Some of the disparities in estimated rates between countries can be shown to be attributed to differences in methodology rather than real differences in risk.