Improvements In Clinical Care Research Articles

P124 Elucidating the role of risk variants in the BIM gene enhancer in T-Cell dysregulation and rheumatoid arthritis pathogenesis

Abstract Background/Aims The balance governing T-cell responses is pivotal for immune homeostasis. Disruptions to this balance may lead to aberrant behaviours, potentially resulting in autoimmunity. Rheumatoid Arthritis (RA), an autoimmune disorder primarily manifesting in the joints, is characterised by a defective immune response, resulting in chronic inflammation. Enhanced T-cell apoptosis resistance in this context can contribute to sustained activation and abnormal proliferation in a pro-inflammatory environment. Understanding these disease mechanisms could lead to improvements in clinical care. Genome-wide association studies (GWAS) have identified hundreds of single nucleotide polymorphisms (SNPs) associated with RA, preferentially enriched in non-coding, T-cell-specific putative enhancers. Enhancers are DNA elements that can regulate the transcription of specific genes, often from many kilobases away. Our previous work identified BCL2L11, or BIM, as the probable causal gene within the RA locus rs13396472, despite the GWAS variants' intronic positioning relative to ACOXL. The RA risk variant disrupts a distant enhancer regulating the BIM gene, pivotal for apoptosis. Given the role of apoptosis in immune tolerance, disruption of this pathway driven by RA risk variants could pave the way for autoimmune responses. Our aim was to investigate the effect of this enhancer on T-cell proliferation and function in an in vivo model. Methods We mapped the human RA-locus to the mouse genome and utilised CRISPR-Cas9 to delete this putative RA enhancer in mice. Two sgRNAs, combined with Cas9, were microinjected into C57BL6/J zygote pronuclei, followed by embryo transfer to pseudo-pregnant mice. PCR and Sanger sequencing confirmed enhancer deletion in pups, establishing an RA-enhancer deletion colony. To gauge cell proportion differences, murine splenocytes or thymocytes were stained with specific fluorochrome markers and analysed via a flow cytometer. For the antigen-induced arthritis (AIA) model, wildtype and RA-enhancer deletion mice were subjected to arthritis induction via intra-articular injection of methylated bovine serum albumin, following prior immunisation, and monitored for arthritis signs. Results We observed an increased CD4+CD8+ double positive (DP) T-cell population in aged mice homozygous and heterozygous for the RA-enhancer deletion, but not in younger and wild-type controls. Knockout mice exhibited visibly enlarged spleens in response to the immunisation step prior to AIA induction. Further work will establish the mechanisms underlying this and disease progression after arthritis induction. These observations underscore a potential impact this enhancer might have on immune responses and survival upon immune system alteration. Conclusion Our research indicates that perturbing mouse non-coding sequences syntenic to human GWAS loci can provide a physiological model to elucidate novel mechanisms underlying RA, potentially suggesting therapeutic targets. Future research will explore the mechanism by which the enhancer deletion leads to an increase in DP T-cells and the altered phenotype, and the implications of such a change for T- and B-cell biology and RA. Disclosure S. Rossi: None. E. Richards: None. J. Ding: None. C. Shi: None. M. Menon: None. J. Gibbs: None. R. Grencis: None. A. Adamson: None. G. Orozco: None.

Professional identity and GP trainers as educational leaders

ABSTRACT GP training in the UK has a long history of success, however that is measured. That success is in part due to the formality and credentialling that underlies preparation to take on that role of a GP teacher, which is somewhat under current threat due to workforce pressures. We identify three important factors associated with the GP trainer function [leadership, professional identity and clinical care improvement] that are not often analysed but are at some risk if preparation for the GP trainer role is reduced or devalued. Of particular note are the differing ways that GPs conceptualise their professional roles as teachers and clinicians, despite the transferable skills between them, the demonstrably improved patient care that occurs in practices that teach, and the necessary connections between educational theory and practice. We suggest that these areas define a research agenda ripe for exploration.

Electronic Patient-Reported Symptoms After Ambulatory Cancer Surgery

Complex cancer procedures are now performed in the ambulatory surgery setting. Remote symptom monitoring (RSM) with electronic patient-reported outcomes (ePROs) can identify patients at risk for acute hospital encounters. Defining normal recovery is needed to set patient expectations and optimize clinical team responses to manage evolving problems in real time. To describe the patterns of postoperative recovery among patients undergoing ambulatory cancer surgery with RSM using an ePRO platform-the Recovery Tracker. In this retrospective cohort study, patients who underwent 1 of 5 of the most common procedures (prostatectomy, nephrectomy, mastectomy, hysterectomy, or thyroidectomy) at the Josie Robertson Surgery Center at Memorial Sloan Kettering Cancer Center from September 2016 to June 2022. Patients completed the Recovery Tracker, a brief ePRO platform assessing symptoms for 10 days after surgery. Data were analyzed from September 2022 to May 2023. Symptom severity and interference were estimated by postoperative day and procedure. A total of 12 433 patients were assigned 110 936 surveys. Of these patients, 7874 (63%) were female, and the median (IQR) age at surgery was 57 (47-65) years. The survey response rate was 87% (10 814 patients responding to at least 1 of 10 daily surveys). Among patients who submitted at least 1 survey, the median (IQR) number of surveys submitted was 7 (4-8), and each assessment took a median (IQR) of 1.7 (1.2-2.5) minutes to complete. Symptom burden was modest in this population, with the highest severity on postoperative days 1 to 3. Pain was moderate initially and steadily improved. Fatigue was reported by 6120 patients (57%) but was rarely severe. Maximum pain and fatigue responses (very severe) were reported by 324 of 10 814 patients (3%) and 106 of 10 814 patients (1%), respectively. The maximum pain severity (severe or very severe) was highest after nephrectomy (92 of 332 [28%]), followed by mastectomy with reconstruction (817 of 3322 [25%]) and prostatectomy (744 of 3543 [21%]). Nausea (occasionally, frequently, or almost constantly) was common and experienced on multiple days by 1485 of 9300 patients (16%), but vomiting was less common (139 of 10 812 [1%]). Temperature higher than 38 °C was reported by 740 of 10 812 (7%). Severe or very severe shortness of breath was reported by 125 of 10 813 (1%). Defining detailed postoperative symptom burden through this analysis provides valuable data to inform further implementation and maintenance of RSM programs in surgical oncology patients. These data can enhance patient education, set expectations, and support research to allow iterative improvement of clinical care based on the patient-reported experience after discharge.

Prehospital Extended FAST Exams Improve Clinical Decision Making by Helicopter EMS Crews: A Retrospective Case Series

Point of Care Ultrasound (POCUS) has seen increasing use in the prehospital environment over the last decade, primarily with the extended focused assessment with sonography in trauma (eFAST) exam. Previous studies have shown prehospital eFAST exams are feasible in the helicopter transport environment but have yet to demonstrate effects on clinical care. This retrospective case series identified 655 patients with blunt thoraco-abdominal trauma or concern for pneumothorax due to penetrating injury transported by a single helicopter EMS (HEMS) program over a two-year period after introducing POCUS. Of those patients, 258 received prehospital ultrasound which was reported to change clinical care in seven cases (2.7%, 95%-CI [1.1–5.5]). This was primarily through preventing unnecessary needle thoracostomy and initiating blood transfusion for treatment of hemorrhagic shock in cases where the degree of shock was unclear due to inconsistent vital signs. This study highlights the improvements in clinical care that may result from the introduction of eFAST exams in the prehospital environment.

Use of point-of-care ultrasound in rural British Columbia: Scale, training, and barriers.

To determine the scale and scope of use of point-of-care ultrasound (POCUS) in rural British Columbia (BC). Online survey. Rural BC. Physicians practising in rural BC communities. Practitioner demographic and practice characteristics, locations and frequency of POCUS use, POCUS education and training, and practitioner attitudes about and barriers to POCUS use. Two hundred twenty-seven surveys were completed in fall 2021, corresponding to a response rate of 11.9% of all rural practitioners in BC. A total of 52.1% of respondents worked in communities with less than 10,000 people, while 24.9% had practices with relatively large proportions of Indigenous patients (more than 20% of the practice population). Respondents reported ease of access to local POCUS devices, with use highest in emergency departments (87.2%) followed by ambulatory care clinic (54.7%) and inpatient (50.3%) settings. Use of POCUS influenced clinical decision making in half the occasions in which it was employed, including a range of diagnostic and procedural applications. Barriers to use included lack of training, limited time to perform POCUS scans, and absence of image review or consultative support. Needed support for POCUS identified by respondents included real-time image acquisition advice and funding for both device acquisition and training. Recommendations for including POCUS training in undergraduate and residency education were strongly supported. Use of POCUS in BC is expanding in frequency, scope, and scale in practices serving rural areas and in rural communities with large Indigenous populations, with practitioners reporting important improvements in clinical care as a result. Future research could help improve systemic support for POCUS use, guide needed curriculum changes in medical school and postgraduate training, and be used to inform continuing professional development needs.

Vascular damage in systemic lupus erythematosus.

Vascular disease is a major cause of morbidity and mortality in patients with systemic autoimmune diseases, particularly systemic lupus erythematosus (SLE). Although comorbid cardiovascular risk factors are frequently present in patients with SLE, they do not explain the high burden of premature vascular disease. Profound innate and adaptive immune dysregulation seems to be the primary driver of accelerated vascular damage in SLE. In particular, evidence suggests that dysregulation of type 1 interferon (IFN-I) and aberrant neutrophils have key roles in the pathogenesis of vascular damage. IFN-I promotes endothelial dysfunction directly via effects on endothelial cells and indirectly via priming of immune cells that contribute to vascular damage. SLE neutrophils are vasculopathic in part because of their increased ability to form immunostimulatory neutrophil extracellular traps. Despite improvements in clinical care, cardiovascular disease remains the leading cause of mortality among patients with SLE, and treatments that improve vascular outcomes are urgently needed. Improved understanding of the mechanisms of vascular injury in inflammatory conditions such as SLE could also have implications for common cardiovascular diseases, such as atherosclerosis and hypertension, and may ultimately lead to personalized therapeutic approaches to the prevention and treatment of this potentially fatal complication.

Integrated Care and Social Protection for Senior Citizens In West Africa: A Scoping Review

Background: West Africa's population is aging at a rapid rate, and the prevalence of older adults with multiple chronic conditions is rising. However, there is little information available about healthcare policies for this age group in this region ten years after the Madrid International Plan of Action on Ageing (MIPAA). To manage the physical and psychosocial needs of senior citizens, a greater integration of healthcare services is required.
 Methods: A scoping review was conducted adhering to the Joana Briggs Institute’s systematic scoping review protocol guidelines. A simple search strategy was developed to collate relevant articles from PubMed, Google Scholar, and AJOL, as well as policy databases, between 2002 and 2022. Articles were included if published in English and related to primary care, social care, and multi-morbidity among older persons in West Africa.
 Results: The findings yielded three thematic issues. First, most West African countries have policies on healthy aging; however, only a few have coherent policies on access to healthcare for older people and the availability of social safety nets, highlighting the need for policymakers to provide coherence and avenues for integration. Secondly, while integration of non-communicable disease services focuses on individual-level services rather than multi-sectoral integration, there is also a poor focus on mental health and sexual and reproductive health integration. Finally the inherent capacity development needs and technical up-skilling requirements require a whole-system approach with contextual nuances.
 Conclusion: The literature is increasingly recognizing an aging population and the prevalence of multi-morbidity in West Africa. Countries in West Africa, in response to the MIPAA, have formulated policies with regards to older persons' healthcare needs; however, improvements in clinical care at the individual setting level may not be sufficient. A deliberate whole-system approach that fosters multi-sectoral collaboration for integrated healthcare might go a long way toward better outcomes for senior citizens and a step forward toward universal health coverage.

Blood Serum and Drainage Microbial and Mitochondrial Metabolites in Patients after Surgery for Pancreatic Cancer.

Pancreatic cancer (PC) has the highest mortality rate of all major cancers in the world despite improvements in clinical care and an understanding of the biology of pancreatic cancer. A study of 64 patients with verified pancreatic cancer who underwent surgery was included. Sampling was carried out at three points: before surgery and on days 1-3 after surgery and 5-7 days after surgery. Drainage fluid collection was taken from the drains installed intraoperatively one day after surgery. Tyrosine and phenylalanine metabolites and two mitochondrial metabolites, namely succinic and fumaric acids, were identified and quantified by GC-MS in the serum of healthy donors and patients. Differences in the metabolomic profile were found between the patients and healthy people. A statistically significant decrease in the level of p-hydroxyphenyllactic acid (p-HPhLA), the amount of sum 3 sepsis-associated metabolites (Σ 3AMM), as well as fumaric and succinic acids in patients was observed. It was also noted that p-hydroxyphenyllactic acid in the preoperative period may be considered as a predictor of complications and longer postoperative recovery.

The Value and Success of Live Plus Online Enduring CME/CE on Hematology/Oncology Specialists' Ability to Care for Patients with Hematologic Disorders

Background: As translational and clinical research across the continuum of classical and malignant hematology continues to accelerate at an unprecedented pace, hematologist/oncologists (hem/oncs) may find it challenging to stay up to date on new discoveries and constantly evolving standards of care. The ASH Annual Meeting offers an unparalleled opportunity to present live continuing medical education (CME/CE) activities to a broad cross-section of this clinician population. The reach of these programs is multiplied by converting recordings into accredited online CME activities available to interprofessional clinician audiences for on-demand learning. The objective of this study was to assess the impact of 9 live plus enduring symposia at ASH 2022 on hem/oncs' knowledge, competence, and confidence in providing comprehensive care for patients with hematologic disorders. Methods: The Medscape Education/Medscape Oncology educational portfolio at the 64 th ASH Annual Meeting consisted of nine 90-minute CME-accredited Friday Satellite Symposia presented live on December 9, 2022, and posted online within 3 weeks as CME-accredited enduring activities consisting of multimedia recordings with synchronized slides. Four of the enduring programs also offered nursing and/or pharmacy continuing education credit. Symposium topics included 2 programs on classical hematologic disorders, 3 on lymphoid malignancies, 3 on myeloid malignancies, and 1 addressing health equity across all hematologic malignancies developed in collaboration with the Leukemia & Lymphoma Society. Educational impact was measured with pre-/post-education assessments including multiple-choice knowledge/competence questions and 5-point Likert scale confidence questions. Data from all hem/onc learners who completed pre- and/or post-education assessments were aggregated across activities and stratified by learning themes. Relative changes in the percentage of correct responses and clinicians who were confident (value of 4 or 5) were used to measure improvement in knowledge, competence, and confidence. A McNemar test assessed significant levels of changes reported, with P values < .05 considered statistically significant. Data were collected through July 31, 2023. Results: The educational portfolio demonstrated a profound reach to 76,647 learners at the time of data cutoff (3361 live learners plus 73,286 enduring learners). Among them, 6821 were hem/onc learners, with other learners comprising additional physician specialties and interprofessional team members (eg, nurses, nurse practitioners, and pharmacists). In each learning theme, statistically significant improvements were observed in hem/oncs' knowledge, competence, and confidence after education (N = 161 to 640). Conclusions: Participation in live or recorded CME/CE-accredited activities presented at the ASH Annual Meeting resulted in statistically significant improvements in hem/onc learners' knowledge, competence, and confidence related to the comprehensive care of patients with a variety of hematologic disorders. These results have the ability to translate to real-world improvements in clinical care and to enhance patient outcomes and experiences. Despite these achievements, continued educational activities are needed to address residual gaps and further increase clinicians' ability in this dynamic clinical setting.

Acute Events Significantly Increase Risk for Long-Term End-Organ Sequelae in Sickle Cell Disease - a Retrospective Cohort Study Using Optum Electronic Health Records

Introduction: Sickle cell disease (SCD) is a hereditary red blood cell disorder characterized by hemolytic anemia and vaso-occlusive crisis (VOC), which are associated with acute organ insults and cumulative end-organ damage. However, real-world data (RWD) are lacking for a host of acute events and rates of long-term organ damage in people with SCD, including priapism and leg ulcers. The objective of this study was to use RWD from US patients to comprehensively assess the rates of acute and long-term SCD events, and to explore the association between acute events and the potential implications for long-term organ damage. Methods: This was a retrospective, non-interventional cohort study using Optum US-based Electronic Health Records data from January 1, 2007, to June 30, 2022. The index date followed a 183-day baseline period after initial diagnosis of SCD in the database. Patients with ≥1 inpatient or 2 outpatient SCD ICD-9-CM or ICD-10-CM codes ≥30 days apart were included. Follow-up for acute events and long-term organ damage started at the index date and continued until a patient was censored for lack of database activity, death, or the study period ended. The prevalences of acute events and long-term organ damage were estimated. Cox regression models were used to determine if acute events were associated with long-term organ damage. Acute events reported 1, 2, 3, and ≥4 times were captured and evaluated for their association with outcomes of long-term organ damage. Exposure was time-varying as patients contributed to the unexposed risk group prior to exposure (acute events) and then to subsequent risk groups after exposures accumulated. Hazard ratios (HR) for long-term organ damage between exposed acute event individuals and unexposed individuals with SCD were estimated. Results: A total of 19,214 patients with SCD were included in this study; median (range) age was 29 (0-88) years, 59% were women, and 81% were African American. The most common acute events were VOC episodes assessed through medical utilization (MU) in 39% of patients, acute chest syndrome (ACS) in 15%, and ischemic stroke and seizures, each in 8% of patients. The most common long-term events of organ damage were heart failure (HF) in 7% of patients, neurocognitive deficit in 6%, and pulmonary hypertension (PH) and chronic kidney disease in 5% of patients each (Table 1). After adjusting for age and sex, patients who at any time had an ischemic stroke had an increased risk of a recurrent event (HR=29.86, 95% CI 26.07-34.21), neurocognitive deficit (HR=8.67, 95% CI 7.22-10.40), and paralysis/hemiparesis (HR=21.19, 95% CI 17.25-26.04) compared with those with no pre-existing ischemic stroke event. Patients with ACS at any time had an increased risk of PH (HR=5.39, 95% CI 4.38-6.35), HF (HR=3.88, 95% CI 3.33-4.52), and oxygen dependency (HR=5.25, 95% CI 4.30-6.41) compared with those with no pre-existing ACS event. Patients who had leg ulcers at any time had an increased risk of amputation (HR=16.70, 95% CI 8.24-33.88) and osteomyelitis (HR=15.17, 95% CI 10.83-21.24) compared with those with no pre-existing leg ulcer event. In a similar manner, the risks were higher for long-term organ damage in corresponding organs among patients with an event of hemorrhagic stroke, avascular necrosis of the humerus or femur, gross hematuria, proteinuria, or priapism, than in patients with no pre-existing events. The risk of developing long-term organ damage following one or multiple acute events was assessed (Table 2). For all the HRs, both the upper and lower bounds of the 95% CI were greater than 1. Conclusions: Acute events remain common among patients with SCD, particularly for VOC episodes assessed via MU, ACS, ischemic stroke, and seizure. Compared with patients who never had acute events, those who had any acute events were at higher risk of long-term organ damage in the same organ. Despite improvements in clinical care, RWD in this study suggest patients with SCD who continue to experience a high rate of acute insults are at higher risk of long-term complications that can lead to organ damage. A limitation of this study is the results have not been corrected for hemoglobin (Hb), despite the known correlation between lower Hb levels and higher rates for some types of organ damage. With the development of new therapeutic interventions, it is critical to understand the impact of these new therapies on acute events and rates of long-term organ damage in patients with SCD.

Tackling Dementia Together via The Australian Dementia Network (ADNeT): A Summary of Initiatives, Progress and Plans.

In 2018, the Australian Dementia Network (ADNeT) was established to bring together Australia's leading dementia researchers, people with living experience and clinicians to transform research and clinical care in the field. To address dementia diagnosis, treatment, and care, ADNeT has established three core initiatives: the Clinical Quality Registry (CQR), Memory Clinics, and Screening for Trials. Collectively, the initiatives have developed an integrated clinical and research community, driving practice excellence in this field, leading to novel innovations in diagnostics, clinical care, professional development, quality and harmonization of healthcare, clinical trials, and translation of research into practice. Australia now has a national Registry for Mild Cognitive Impairment and dementia with 55 participating clinical sites, an extensive map of memory clinic services, national Memory and Cognition Clinic Guidelines and specialized screening for trials sites in five states. This paper provides an overview of ADNeT's achievements to date and future directions. With the increase in dementia cases expected over coming decades, and with recent advances in plasma biomarkers and amyloid lowering therapies, the nationally coordinated initiatives and partnerships ADNeT has established are critical for increased national prevention efforts, co-ordinated implementation of emerging treatments for Alzheimer's disease, innovation of early and accurate diagnosis, driving continuous improvements in clinical care and patient outcome and access to post-diagnostic support and clinical trials. For a heterogenous disorder such as dementia, which is now the second leading cause of death in Australia following cardiovascular disease, the case for adequate investment into research and development has grown even more compelling.

LAMA2-Related Muscular Dystrophy Across the Life Span: A Cross-sectional Study.

LAMA2-related muscular dystrophy (LAMA2-MD) is a rare neuromuscular disease characterized by proximal and axial muscle weakness, rigidity of the spine, scoliosis, and respiratory impairment. No curative treatment options exist, yet promising preclinical studies are ongoing. Currently, there is a paucity on natural history data, and appropriate clinical and functional outcome measures are needed. We aim for deep clinical phenotyping, establishment of a well-characterized baseline cohort for prospective follow-up and recruitment for future clinical trials, improvement of clinical care, and selection of outcome measures for reaching trial readiness. We performed a cross-sectional, single-center, observational study. This study included neurologic examination and functional measurements among others the Motor Function Measure 20/32 (MFM-20/32) as primary outcome measure, accelerometry, questionnaires, muscle ultrasound, respiratory function tests, electrocardiography and echocardiography, and dual-energy X-ray absorptiometry. Twenty-seven patients with genetically confirmed LAMA2-MD were included (21 ± 13 years; M = 9; ambulant = 7). Axial and proximal muscle weakness was most pronounced. The mean MFM-20/32 score was 42.0% ± 29.4%, with domain 1 (standing and transfers) being severely affected and domain 3 (distal muscle function) relatively spared. Physical activity as measured through accelerometry showed very strong correlations to MFM-20/32 (Pearson correlation, -0.928, p < 0.01). Muscle ultrasound showed symmetrically increased echogenicity, with the sternocleidomastoid muscle most affected. Respiratory function was impaired in 85% of patients without prominent diaphragm dysfunction and was independent of age. Ten patients (37%) needed (non)invasive ventilatory support. Cardiac assessment revealed QRS fragmentation in 62%, abnormal left ventricular global longitudinal strain in 25%, and decreased left ventricular ejection fraction in 14% of patients. Decreased bone quality leading to fragility fractures was seen in most of the patients. LAMA2-MD has a widely variable phenotype. Based on the results of this cross-sectional study and current standards of care for congenital muscular dystrophies, we advise routine cardiorespiratory follow-up and optimization of bone quality. We propose MFM-20/32, accelerometry, and muscle ultrasound for assessing disease severity and progression. For definitive clinical recommendations and outcome measures, natural history data are needed. This study was registered at clinicaltrials.gov (NCT04478981, 21 July 2020). The first patient was enrolled in September 2020.

Implementing shared decision making for early-stage breast cancer treatment using a coproduction learning collaborative: the SHAIR Collaborative protocol

BackgroundShared decision making (SDM) in breast cancer care improves outcomes, but it is not routinely implemented. Results from the What Matters Most trial demonstrated that early-stage breast cancer surgery conversation aids, when used by surgeons after brief training, improved SDM and patient-reported outcomes. Trial surgeons and patients both encouraged using the conversation aids in routine care. We will develop and evaluate an online learning collaborative, called the SHared decision making Adoption Implementation Resource (SHAIR) Collaborative, to promote early-stage breast cancer surgery SDM by implementing the conversation aids into routine preoperative care. Learning collaboratives are known to be effective for quality improvement in clinical care, but no breast cancer learning collaborative currently exists.Our specific aims are to (1) provide the SHAIR Collaborative resources to clinical sites to use with eligible patients, (2) examine the relationship between the use of the SHAIR Collaborative resources and patient reach, and (3) promote the emergence of a sustained learning collaborative in this clinical field, building on a partnership with the American Society of Breast Surgeons (ASBrS).MethodsWe will conduct a two-phased implementation project: phase 1 pilot at five sites and phase 2 scale up at up to an additional 32 clinical sites across North America. The SHAIR Collaborative online platform will offer free access to conversation aids, training videos, electronic health record and patient portal integration guidance, a feedback dashboard, webinars, support center, and forum. We will use RE-AIM for data collection and evaluation. Our primary outcome is patient reach. Secondary data will include (1) patient-reported data from an optional, anonymous online survey, (2) number of active sites and interviews with site champions, (3) Normalization MeAsure Development questionnaire data from phase 1 sites, adaptations data utilizing the Framework for Reporting Adaptations and Modifications-Extended/-Implementation Strategies, and tracking implementation facilitating factors, and (4) progress on sustainability strategy and plans with ASBrS.DiscussionThe SHAIR Collaborative will reach early-stage breast cancer patients across North America, evaluate patient-reported outcomes, engage up to 37 active sites, and potentially inform engagement factors affecting implementation success and may be sustained by ASBrS.

Information needs and health status in adolescents and young adults with differences of sex development or sex chromosome aneuploidies

When and how to provide condition-related information to adolescents and young adults (AYAs) with differences of sex development or sex chromosome aneuploidies (DSDs or SCAs) is largely based on anecdotal experience and lacks informed guidance. For AYAs with a DSD or SCA, having accurate information is critical for attaining optimal adjustment and well-being, participating in decision making related to treatment options, and transitioning successfully to adult health care, yet prior studies have focused exclusively on parental perspectives and not on the views of adolescents themselves. The objective of this study was to describe unmet information needs in AYAs with a DSD or SCA and examine associations with perceived global health. Participants were recruited from specialty clinics at Children's Hospital of Philadelphia (n=20) and Children's Hospital Colorado (n=60). AYAs ages 12-21 years with a DSD or SCA and a parent completed a survey assessing perceived information needs across 20 topics, importance of those topics, and global health using the PROMIS Pediatric Global Health questionnaire (PGH-7). AYAs had diagnoses of Klinefelter syndrome (41%), Turner syndrome (25%), and DSD (26%) and were 16.7 years (SD=2.56) and 44% female. Parent participants were primarily mothers (81%). AYAs perceived that 48.09% of their information needs were unmet (SD=25.18, range: 0-100). Parents perceived that 55.31% of AYAs' information needs were unmet (SD=27.46 range: 5-100). AYAs and parents across conditions reported unmet needs related to information about transition to adult health care, financial support for medical care, and how the condition might affect the AYA's health in the future. While AYA-reported PGH-7 scores were not associated with percentage of AYA unmet information needs, parent-reported PGH-7 scores were (r=-.46, p<.001), such that lower parent-reported global health was associated with higher percentage of AYA unmet information needs. On average, parents and AYAs perceived that half of AYAs' information needs were unmet, and a higher percentage of AYA unmet information needs was associated with lower perceived global health. The frequency of unmet needs in this sample of AYAs reflects an opportunity for improvement in clinical care. Future research is needed to understand how education to children and AYAs unfolds as they mature and to develop strategies to address the information needs of AYAs with a DSD or SCA, promote well-being, and facilitate AYA engagement in their own health care.

Dampak Implementasi Pembayaran Berbasis Kinerja (Pay-For-Performance) Pada Fasilitas Kesehatan Tingkat Pertama (FKTP) Terhadap Kualitas Layanan Kesehatan Di Berbagai Negara

The pay-for-performance (P4P) mechanism is a strategy in the health sector to increase the availability, quality and utilization of health services. In P4P, incentives are given after achieving a series of agreed outcomes by improving the performance of health workers in health facilities. This literature review was conducted with the aim of knowing the impact of implementing pay-for-performance at primary care (FKTP) on the quality of health services in various countries. The method is carried out by searching several databases, namely Pubmed, Embase, and Proquest with the main intervention being the implementation of pay-for-performance. The results of the review focused on the impact of implementing pay-for-performance at First Level Health Facilities on the quality of health services in various countries. From this study it can be concluded that pay-for-performance has been used in various countries with different numbers and areas (domains) of indicators adapted to the characteristics of primary care in a country. Some of the benefits of implementing pay-for-performance are that it can stimulate quality improvement in clinical care and improve patient experience of the role of general practitioners and the system of care. P4P can improve the process and outcome of cardiovascular treatment. Providing incentives can have an effect on improving the quality of performance in clinical practice. Providing P4P incentives can meet the quality measures of hypertension care recommended by the guidelines. In the United States, the provision of P4P incentives can increase physician compliance to provide hypertension drugs according to guidelines. Providing incentives can also have an impact on improving blood pressure control in hypertensive patients.

Pro-Con Debate: Interdisciplinary Perspectives on Industry-Sponsored Research.

Pro: Nearly all new devices and drugs come from industry that provides two-thirds of the funding for medical research, and a much higher fraction of clinical research. Realistically, without corporate-funded studies, perioperative research would stagnate with little innovation and few new products. Opinions are ubiquitous and normal, but do not constitute epidemiologic bias. Competent clinical research includes many protections against selection and measurement bias, and the publication process provides at least moderate protection against misinterpretation of results. Trial registries largely prevent selective data presentation. Sponsored trials are particularly protected against inappropriate corporate influence because they are usually codesigned with the US Food and Drug Administration, and analyses are based on formal predefined statistical plans, as well as being conducted with rigorous external monitoring. Novel products, which are essential for advances in clinical care, largely come from industry, and industry appropriately funds much of the required research. We should celebrate industry's contribution to improvements in clinical care. Con: While industry funding contributes to research and discovery, examples of industry-funded research demonstrate bias. In the setting of financial pressures and potential conflict of interest, bias can influence the type of study design, hypotheses being tested, rigor and transparency in data analysis, interpretation, as well as reporting of the results. Unlike public granting agencies, industry does not necessarily provide funding based on unbiased peer review following an open call for proposals. The focus on success can influence the choice of a comparator, which might not be ideal among the possible alternatives, the language used in the publication, and even the ability to publish. Unpublished negative trials can result in selected information being withheld from the scientific community and the public. Appropriate safeguards are needed to ensure that research addresses the most important and relevant questions, that results are available even when they do not support the use of a product produced by the funding company, that populations studied reflect the relevant patients, that the most rigorous approaches are applied, that studies have the appropriate power to address the question posed, and that conclusions are presented in an unbiased manner.

Pro-Con Debate: Interdisciplinary Perspectives on Industry-Sponsored Research

ProNearly all new devices and drugs come from industry that provides two-thirds of the funding for medical research, and a much higher fraction of clinical research. Realistically, without corporate-funded studies, perioperative research would stagnate with little innovation and few new products. Opinions are ubiquitous and normal but do not constitute epidemiologic bias. Competent clinical research includes many protections against selection and measurement bias, and the publication process provides at least moderate protection against misinterpretation of results. Trial registries largely prevent selective data presentation. Sponsored trials are particularly protected against inappropriate corporate influence because they are usually codesigned with the US Food and Drug Administration, and analyses are based on formal predefined statistical plans, as well as being conducted with rigorous external monitoring. Novel products, which are essential for advances in clinical care, largely come from industry, and industry appropriately funds much of the required research. We should celebrate industry’s contribution to improvements in clinical care. ConWhile industry funding contributes to research and discovery, examples of industry-funded research demonstrate bias. In the setting of financial pressures and potential conflict of interest, bias can influence the type of study design, hypotheses being tested, rigor and transparency in data analysis, interpretation, as well as reporting of the results. Unlike public granting agencies, industry does not necessarily provide funding based on unbiased peer review following an open call for proposals. The focus on success can influence the choice of a comparator, which might not be ideal among the possible alternatives, the language used in the publication, and even the ability to publish. Unpublished negative trials can result in selected information being withheld from the scientific community and the public. Appropriate safeguards are needed to ensure that research addresses the most important and relevant questions, that results are available even when they do not support the use of a product produced by the funding company, that populations studied reflect the relevant patients, that the most rigorous approaches are applied, that studies have the appropriate power to address the question posed, and that conclusions are presented in an unbiased manner.

Structural Sexism and Cancer Care: The Effects on the Patient and Oncologist.

Despite progress toward equity within our broad social context, the domains of gender as a social, cultural, and structural variable continue to exert influence on the delivery of oncology care. Although there have been vast advances in our understanding of the biological underpinnings of cancer and significant improvements in clinical care, disparities in cancer care for all women-including cisgender, transgender, and gender diverse women-persist. Similarly, despite inclusion within the oncology physician workforce, women and gender minorities, particularly those with additional identities under-represented in medicine, still face structural barriers to clinical and academic productivity and career success. In this article, we define and discuss how structural sexism influences both the equitable care of patients with cancer and the oncology workforce and explore the overlapping challenges in both realms. Solutions toward creating environments where patients with cancer of any gender receive optimal care and all physicians can thrive are put forward.

Survival, surveillance, and genetics in patients with Peutz-Jeghers syndrome: A nationwide study.

Peutz-Jeghers syndrome (PJS) is an autosomal dominant hereditary polyposis syndrome causing increased morbidity and mortality due to complications of polyposis and the development of cancer. STK11 is the only gene known to be associated with PJS, although in 10%-15% of patients fulfilling the diagnostic criteria no pathogenic variant (PV) is identified. The primary aim of this study was to identify the genetic etiology in all known PJS patients in Denmark and to estimate the risk of cancer, effect of surveillance and overall survival. We identified 56 patients (2-83 years old) with PJS. The detection rate of PVs was 96%, including three cases of mosaicism (6%). In two patients a variant was not detected. At the age of 40 years, the probabilities of cancer and death were 21% and 16%, respectively; at the age of 70 years these probabilities were 71% and 69%. Most cases of cancer (92%) were identified between the scheduled examinations in the surveillance program. These observations emphasize that PJS should be regarded as a general cancer predisposition syndrome, where improvement of clinical care is needed.

Development of a prosthetic fit and alignment assessment (ProFit) in persons with post-traumatic transtibial amputation.

There are no standards for reliably measuring the quality of prosthetic fit and alignment which is important for evaluation and improvement of clinical care for patients with transtibial amputation. The purpose of this study was to develop an instrument to quantitatively assess prosthetic fit and alignment in patients with transtibial amputation. Prospective cohort study. The fit and alignment assessment (ProFit) included 39 items for assessments of skin quality, stance and gait, and radiographic characteristics that could be feasibly captured in clinic using photographs, video, and radiographs. Data were collected on adults aged 18-60 years treated with transtibial amputation and followed up for 18 months at 1 of 27 US hospitals. One hundred thirteen assessments were conducted by 6 prosthetists using an online platform. Items demonstrating reliability and face validity were included in the ProFit score for subsequent validation testing. Validation measures included 18-month patient-reported function (Short Musculoskeletal Function Assessment ), tests of physical performance, patient-reported pain (Brief Pain Inventory ), satisfaction with prosthesis (Orthotics Prosthetics Users Survey), prosthesis use, and walking activity. The ProFit score included 10 of 39 items that demonstrated high inter-rater reliability and face validity. A higher ProFit score correlated with worse function on all domains of the Short Musculoskeletal Function Assessment except arm and hand and with worse performance on the 4-Square Step Test, Shuttle Run, and Illinois Agility Test. ProFit scores did not correlate with the Brief Pain Inventory, Orthotics Prosthetics Users Survey, prosthesis use, or walking activity. The ProFit score can be used by researchers and clinicians to measure the quality of socket fit and prosthetic alignment. Future prospective validation is necessary to verify the promising results observed in ProFit development and establish clinical utility.