Establishing a consensus on research priorities in orthopaedic trauma within South Africa.

BACKGROUND: Musculoskeletal (MSK) injuries are one of the leading causes of disability worldwide. Despite improvements in trauma-related morbidity and mortality in high-income countries over recent years, outcomes following MSK injuries in low- and middle-income countries, such as South Africa (SA), have not. Despite governmental recognition that this is required, funding and research into this significant health burden are limited within SA. This study aims to identify research priorities within MSK trauma care using a consensus-based approach amongst MSK healthcare practitioners within SA. METHOD: Members from the Orthopaedic Research Collaboration in Africa (ORCA), based in SA, collaborated using a two round modified Delphi technique to form a consensus on research priorities within orthopaedic trauma care. Members involved in the process were orthopaedic healthcare practitioners within SA. RESULTS: Participants from the ORCA network, working within SA, scored research priorities across two Delphi rounds from low to high priority. We have published the overall top 10 research priorities for this Delphi process. Questions were focused on two broad groups-clinical effectiveness in trauma care and general trauma public health care. Both groups were represented by the top two priorities, with the highest ranked question regarding the overall impact of trauma in SA and the second regarding the clinical treatment of open fractures. CONCLUSION: This study has defined research priorities within orthopaedic trauma in South Africa. Our vision is that by establishing consensus on these research priorities, policy and research funding will be directed into these areas. This should ultimately improve musculoskeletal trauma care across South Africa and its significant health and socioeconomic impacts.

Capitalizing on Central Registries for Expanded Cancer Surveillance and Research.

BACKGROUND: State central cancer registries are an essential component of cancer surveillance and research that can be enriched through linkages to other databases. This study identified and described state central registry linkages to external data sources and assessed the potential for a more comprehensive data infrastructure with registries at its core. METHODS: We identified peer-reviewed papers describing linkages to state central cancer registries in all 50 states, Washington, DC, and Puerto Rico, published between 2010 and 2020. To complement the literature review, we surveyed registrars to learn about unpublished linkages. Linkages were grouped by medical claims (public and private insurers), medical records, other registries (eg, human immunodeficiency virus/acquired immunodeficiency syndrome registries, birth certificates, screening programs), and data from specific cohorts (eg, firefighters, teachers). RESULTS: We identified 464 data linkages with state central cancer registries. Linkages to cohorts and other registries were most common. Registries in predominately rural states reported the fewest linkages. Most linkages are not ongoing, maintained, or available to researchers. A third of linkages reported by registrars did not result in published papers. CONCLUSIONS: Central cancer registries, often in collaboration with researchers, have enriched their data through linkages. These linkages demonstrate registries' ability to contribute to a data infrastructure, but a coordinated and maintained approach is needed to leverage these data for research. Sparsely populated states reported the fewest linkages, suggesting possible gaps in our knowledge about cancer in these states. Many more linkages exist than have been reported in the literature, highlighting potential opportunities to further use the data for research purposes.

Developing a national trauma research action plan: Results from the Burn Research Gap Delphi Survey.

BACKGROUND: The 2016 National Academies of Science, Engineering and Medicine call for a national integrated, military-civilian trauma action plan to achieve zero preventable deaths and disability after injury included a proposal to establish a National Trauma Research Action Plan to "strengthen trauma research and ensure that the resources available for this research are commensurate with the importance of injury and the potential for improvement in patient outcomes." The Department of Defense funded the Coalition for National Trauma Research to generate a comprehensive research agenda spanning the continuum of trauma/burn care from prehospital to rehabilitation. The Burn/Reconstructive Surgery group represents one focus area for this research agenda development. METHODS: Experts in burn and reconstructive surgery research identified gaps in knowledge, generated research questions and prioritized questions using a consensus driven Delphi survey approach. Participants were identified using established Delphi recruitment guidelines to ensure heterogeneity and generalizability with military and civilian representatives. Literature reviews informed the panel. Panelists were encouraged to use a PICO format to generate research questions: Patient/Population; Intervention; Compare/Control; Outcome. Participants ranked the priority of each question on a nine-point Likert scale, which was categorized to represent low, medium, and high priority items. Consensus was defined based on ≥60% panelist agreement. RESULTS: Subject matter experts generated 949 research questions in 29 Burn & 26 Reconstruction topics. Five hundred ninety-seven questions reached consensus. Of these, 338 (57%) were high-priority, 180 (30%), medium-priority, and 78 (13%) low-priority questions. CONCLUSION: Many high-priority questions translate to complex wound management and outcomes. Panel recognition that significant gaps in knowledge exist in understanding functional outcomes after injury underscores the importance of long-term recovery metrics even when studying acute injury or interventions such as resuscitation or inhalation injury. Funding agencies and burn/reconstructive surgery researchers should consider these gaps when they prioritize future research. LEVEL OF EVIDENCE: Expert consensus, Level IV.

Moving Forward in the Next Decade: Radiation Oncology Sciences for Patient-Centered Cancer Care.

In a time of rapid advances in science and technology, the opportunities for radiation oncology are undergoing transformational change. The linkage between and understanding of the physical dose and induced biological perturbations are opening entirely new areas of application. The ability to define anatomic extent of disease and the elucidation of the biology of metastases has brought a key role for radiation oncology for treating metastatic disease. That radiation can stimulate and suppress subpopulations of the immune response makes radiation a key participant in cancer immunotherapy. Targeted radiopharmaceutical therapy delivers radiation systemically with radionuclides and carrier molecules selected for their physical, chemical, and biochemical properties. Radiation oncology usage of "big data" and machine learning and artificial intelligence adds the opportunity to markedly change the workflow for clinical practice while physically targeting and adapting radiation fields in real time. Future precision targeting requires multidimensional understanding of the imaging, underlying biology, and anatomical relationship among tissues for radiation as spatial and temporal "focused biology." Other means of energy delivery are available as are agents that can be activated by radiation with increasing ability to target treatments. With broad applicability of radiation in cancer treatment, radiation therapy is a necessity for effective cancer care, opening a career path for global health serving the medically underserved in geographically isolated populations as a substantial societal contribution addressing health disparities. Understanding risk and mitigation of radiation injury make it an important discipline for and beyond cancer care including energy policy, space exploration, national security, and global partnerships.

[Adapting to the SARS-CoV2 pandemic: Experience of the Curie Institute]. / S'adapter face à la pandémie SARS-CoV2 : l'expérience de l'Institut Curie.

The Curie Institute exclusively cares for cancer patients, who were considered particularly "vulnerable" from the start of the SARS-CoV 2 pandemic. This pandemic, which took the medical world by surprise, suddenly required the Institute's hospital to undergo rapid and multimodal restructuring, while having an impact on everyone to varying degrees. We will examine here how this hospital has coped, with the concern for a new benefit-risk balance, in times of greater medical uncertainty and scarcity of certain resources, for these "vulnerable" patients but also for their relatives and staff. We will highlight by theme the positive aspects and difficulties encountered, and then what could be useful for other hospitals as the pandemic is ongoing.

Lay Stakeholders in Science and Research Initiative: A Science Advisory From the American Heart Association.

The American Heart Association (AHA) is the largest not-for-profit funder of cardiovascular and cerebrovascular disease research in the United States. It has supported research of independent scientists for 7 decades with the goal of finding novel discoveries that will reduce death and disability from these diseases and ultimately improve overall health. In 2014, the AHA approved a pilot initiative to include lay stakeholders (patients, caregivers, and passionate advocates) in its research and science operations. The initiative was based on the premise that lay stakeholders would add a unique and necessary perspective that would improve decisions concerning research funding, research direction, and scientific guidelines. The AHA developed a framework for the initiative that defined lay stakeholder, created a volunteer recruitment and training program, established policies for incorporating lay stakeholders into science operations, and set metrics for evaluating the initiative over time. It has instituted creative ways to engage lay volunteers and to foster lay and scientist cooperation. Program assessments have been consistently positive and have identified needed future improvements. The benefits of lay/scientist collaboration have far exceeded the AHA's expectations. The AHA will continue to strengthen lay volunteer engagement throughout its science and research operations; to focus on developing a larger, diverse group of qualified lay stakeholders; to educate scientists on how to communicate research effectively to the public and donors; and to retain the respect of donors for the rigors of its research funding, scientific statements, and clinical guidelines.

Expanding Implementation Research to Prevent Chronic Diseases in Community Settings.

Chronic disease prevention continues to be inadequate, overall and in achieving health equity, in spite of the many evidence-based practices and policies (EBPPs) available to address risk behaviors such as unhealthful eating, lack of physical activity, and tobacco use. Although clinical settings are needed for EBPPs that involve medical procedures such as immunization or early detection, dissemination of EBPPs can be effective in a variety of settings such as schools and childcare centers, worksites, social service organizations, and religious organizations. More implementation research is needed to meet challenges of effective application of EBPPs in such community settings, in which primary missions, capacity, cultures, and values do not focus on health services delivery. To address health equity, consideration of social and economic contexts of people reached in these settings is essential. This review presents lessons learned from past studies to guide future implementation research and practice across diverse settings and geographies.

The Impact of Hospital/University Affiliation on Research Productivity Among US-Based Authors in the Fields of Trauma, Surgical Critical Care, Acute Care, and Emergency General Surgery.

BACKGROUND: Research productivity is critical to academic surgery and essential for advancing surgical knowledge and evidence-based practice. We aim to determine if surgeon affiliation with top US universities/hospitals (TOPS) is associated with increased research productivity measured by numbers of peer-reviewed publications in PubMed (PMIDs). METHODS: A bibliometric analysis was performed for PMIDs. Affiliated authors who published in trauma surgery (TS), surgical critical care (SCC), acute care surgery (ACS), and emergency general surgery (EGS) were evaluated for publications between 2015 and 2019, and lifetime productivity. Our analysis included 3443 authors from 443 different institutions. Our main outcome was PMIDs of first author (FA) and senior author (SA) in each field (2015-2019) and total lifetime publications. RESULTS: Significant differences exist between PMIDs from TOPS vs non-TOPS in FA-TS (1.34 vs 1.23, P = .001), SA-TS (1.71 vs 1.46, P < .001), total SA-PMIDs (44.10 vs 26.61, P < .001), and SA-lifetime PMIDs (90.55 vs 59.03, P < .001). There were no significant differences in PMIDs for FA or SA-SCC, FA or SA-ACS, FA or SA-EGS, FA-total PMIDs 2015-2019, or FA-lifetime PMIDs (P > .05 for all). CONCLUSION: There were significantly higher TS PMIDs among FAs and SAs affiliated with top US institutions in 2015-2019, along with higher total PMIDs (2015-2019) and lifetime PMIDs. These findings are of significance to future graduate medical applicants and academic surgeons who need to make decisions about training and future career opportunities.

Top 10 priorities for future infertility research: an international consensus development study.

STUDY QUESTION: Can the priorities for future research in infertility be identified? SUMMARY ANSWER: The top 10 research priorities for the four areas of male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care for people with fertility problems were identified. WHAT IS KNOWN ALREADY: Many fundamental questions regarding the prevention, management, and consequences of infertility remain unanswered. This is a barrier to improving the care received by those people with fertility problems. STUDY DESIGN, SIZE, DURATION: Potential research questions were collated from an initial international survey, a systematic review of clinical practice guidelines, and Cochrane systematic reviews. A rationalized list of confirmed research uncertainties was prioritized in an interim international survey. Prioritized research uncertainties were discussed during a consensus development meeting. Using a formal consensus development method, the modified nominal group technique, diverse stakeholders identified the top 10 research priorities for each of the categories male infertility, female and unexplained infertility, medically assisted reproduction, and ethics, access, and organization of care. PARTICIPANTS/MATERIALS, SETTING, METHODS: Healthcare professionals, people with fertility problems, and others (healthcare funders, healthcare providers, healthcare regulators, research funding bodies and researchers) were brought together in an open and transparent process using formal consensus methods advocated by the James Lind Alliance. MAIN RESULTS AND THE ROLE OF CHANCE: The initial survey was completed by 388 participants from 40 countries, and 423 potential research questions were submitted. Fourteen clinical practice guidelines and 162 Cochrane systematic reviews identified a further 236 potential research questions. A rationalized list of 231 confirmed research uncertainties were entered into an interim prioritization survey completed by 317 respondents from 43 countries. The top 10 research priorities for each of the four categories male infertility, female and unexplained infertility (including age-related infertility, ovarian cysts, uterine cavity abnormalities, and tubal factor infertility), medically assisted reproduction (including ovarian stimulation, IUI, and IVF), and ethics, access, and organization of care, were identified during a consensus development meeting involving 41 participants from 11 countries. These research priorities were diverse and seek answers to questions regarding prevention, treatment, and the longer-term impact of infertility. They highlight the importance of pursuing research which has often been overlooked, including addressing the emotional and psychological impact of infertility, improving access to fertility treatment, particularly in lower resource settings, and securing appropriate regulation. Addressing these priorities will require diverse research methodologies, including laboratory-based science, qualitative and quantitative research, and population science. LIMITATIONS, REASONS FOR CAUTION: We used consensus development methods, which have inherent limitations, including the representativeness of the participant sample, methodological decisions informed by professional judgement, and arbitrary consensus definitions. WIDER IMPLICATIONS OF THE FINDINGS: We anticipate that identified research priorities, developed to specifically highlight the most pressing clinical needs as perceived by healthcare professionals, people with fertility problems, and others, will help research funding organizations and researchers to develop their future research agenda. STUDY FUNDING/ COMPETING INTEREST(S): The study was funded by the Auckland Medical Research Foundation, Catalyst Fund, Royal Society of New Zealand, and Maurice and Phyllis Paykel Trust. Geoffrey Adamson reports research sponsorship from Abbott, personal fees from Abbott and LabCorp, a financial interest in Advanced Reproductive Care, committee membership of the FIGO Committee on Reproductive Medicine, International Committee for Monitoring Assisted Reproductive Technologies, International Federation of Fertility Societies, and World Endometriosis Research Foundation, and research sponsorship of the International Committee for Monitoring Assisted Reproductive Technologies from Abbott and Ferring. Siladitya Bhattacharya reports being the Editor-in-Chief of Human Reproduction Open and editor for the Cochrane Gynaecology and Fertility Group. Hans Evers reports being the Editor Emeritus of Human Reproduction. Andrew Horne reports research sponsorship from the Chief Scientist's Office, Ferring, Medical Research Council, National Institute for Health Research, and Wellbeing of Women and consultancy fees from Abbvie, Ferring, Nordic Pharma, and Roche Diagnostics. M. Louise Hull reports grants from Merck, grants from Myovant, grants from Bayer, outside the submitted work and ownership in Embrace Fertility, a private fertility company. Neil Johnson reports research sponsorship from Abb-Vie and Myovant Sciences and consultancy fees from Guerbet, Myovant Sciences, Roche Diagnostics, and Vifor Pharma. José Knijnenburg reports research sponsorship from Ferring and Theramex. Richard Legro reports consultancy fees from Abbvie, Bayer, Ferring, Fractyl, Insud Pharma and Kindex and research sponsorship from Guerbet and Hass Avocado Board. Ben Mol reports consultancy fees from Guerbet, iGenomix, Merck, Merck KGaA and ObsEva. Ernest Ng reports research sponsorship from Merck. Craig Niederberger reports being the Co Editor-in-Chief of Fertility and Sterility and Section Editor of the Journal of Urology, research sponsorship from Ferring, and retains a financial interest in NexHand. Jane Stewart reports being employed by a National Health Service fertility clinic, consultancy fees from Merck for educational events, sponsorship to attend a fertility conference from Ferring, and being a clinical subeditor of Human Fertility. Annika Strandell reports consultancy fees from Guerbet. Jack Wilkinson reports being a statistical editor for the Cochrane Gynaecology and Fertility Group. Andy Vail reports that he is a Statistical Editor of the Cochrane Gynaecology & Fertility Review Group and of the journal Reproduction. His employing institution has received payment from HFEA for his advice on review of research evidence to inform their 'traffic light' system for infertility treatment 'add-ons'. Lan Vuong reports consultancy and conference fees from Ferring, Merck and Merck Sharp and Dohme. The remaining authors declare no competing interests in relation to the present work. All authors have completed the disclosure form. TRIAL REGISTRATION NUMBER: Not applicable.

Adherence to the 2018 World Cancer Research Fund/American Institute for Cancer Research Recommendations and Breast Cancer in the SUN Project.

A proportion of breast cancer cases are attributable to combined modifiable risk factors. The World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) has recently updated the recommendations for cancer prevention and a standard scoring system has been published. The aim of this study was to evaluate the association between compliance with the 2018 WCRF/AICR cancer prevention recommendations (Third Expert Report) and the risk of breast cancer in the SUN ("Seguimiento Universidad de Navarra") prospective cohort. Spanish female university graduates, initially free of breast cancer, were included (n = 10,930). An 8-item score to measure compliance to the recommendations was built: body fat, physical activity, consumption of wholegrains/vegetables/fruit/beans, "fast foods", red/processed meat consumption, sugar-sweetened drinks consumption, alcohol intake, and breastfeeding. A stratified analysis was conducted according to menopausal status. A non-significant inverse association was observed for overall breast cancer. The inverse association became statistically significant for post-menopausal breast cancer after multivariable adjustment (hazard ratio for > 5 vs. ≤ 3 points = 0.27; 95% CI: 0.08-0.93). The results suggested that the possible inverse association with breast cancer was attributable to the combined effects of the different nutritional and lifestyle components.

Smouldering ashes: burning questions after the outbreak of electronic cigarette or vaping-associated lung injury (EVALI).

In the summer of 2019, the Center for Disease Control and Prevention (CDC) declared an emergency of electronic cigarettes and/or vaping (vaping)-associated lung injury (EVALI) in the USA. The outbreak abated by January 2020, which the CDC attributed to heightened public awareness, 'user actions to reduce risk' and potentially the removal of vitamin E acetate (VEA) from vaping products (VEA is an oily chemical cutting agent, strongly associated with the disease). Even though the EVALI outbreak appears to be over, numerous epidemiological and medical questions are left still open. First, why were there practically no cases outside the USA, which represents nearly a quarter of the global vaping market? Comparative studies to map the differences in device/fluids/user habits between countries might be needed urgently. Second, what is the pathomechanism that sickens vapers irrespective of VEA exposure? VEA was only confirmed in about half of the cases and the presumed toxicity is yet to be determined. Aetiology/epidemiology focused research is needed to investigate/interpret the broader context to explain the outbreak. Third, could any socioeconomic/environmental factors have influenced the course of the outbreak? Finally, what should we expect in the years to come? Was EVALI a serious but reversible emergency medicine condition or is vaping as detrimental to long-term health as smoking? Besides the complex legislative, regulatory, ethical aspects of EVALI, biomedical research is also difficult: in-vitro experiments have limited inferential value to real real-life vaping due to its complexity; user habits are self-reported and under-researched; there is an active black market pouring unknown quality counterfeit products and, in the USA, federal restrictions limit cannabis research. Vaping is a toxicological, multidimensional conundrum; therefore, stringent quality control, transparent legal/ethical boundaries, meticulous international research and user education are paramount to prevent potential future outbreaks and determine the parameters safe vaping (if these exist).

Porcine cancer models: potential tools to enhance cancer drug trials.

INTRODUCTION: The amount of time and money invested into cancer drug research, development, and clinical trials has continually increased over the past few decades. Despite record high cancer drug approval rates, cancer remains a leading cause of death. This suggests the need for more effective tools to help bring novel therapies to clinical practice in a timely manner. AREAS COVERED: In this review, current issues associated with clinical trials are discussed, specifically focusing on poor accrual rates and time for trial completion. In addition, details regarding preclinical studies required before advancing to clinical trials are discussed, including advantages and limitations of current preclinical animal cancer models and their relevance to human cancer trials. Finally, new translational porcine cancer models (Oncopig Cancer Model (OCM)) are presented as potential co-clinical trial models. EXPERT OPINION: In order to address issues impacting the poor success rate of oncology clinical trials, we propose the incorporation of the transformative OCM 'co-clinical trial' pathway into the cancer drug approval process. Due to the Oncopig's high homology to humans and similar tumor phenotypes, their utilization can provide improved preclinical prediction of both drug safety and efficacy prior to investing significant time and money in human clinical trials.

'Go for it, dream big, work hard and persist': A message to the next generation of CF leaders in recognition of International Women's Day 2020.

The focus for International Women's Day 2020 is gender equity:'We can actively choose to challenge stereotypes, fight bias, broaden perceptions, improve situations and celebrate women's achievements. Collectively, each one of us can help create a gender equal world.' We have come together as an international group of women holding senior positions within CF to raise awareness. There is growing recognition of gender imbalance within our sector in senior leadership, grant and publication success. Several institutions, such as National Institutes of Health, have missions to tackle this. The issues raised by our panellists were wide-ranging: decisions around starting a family, impact on career progression; experiences of bias in appointments or promotions; selfbelief. We hope that raising these issues will encourage future leaders in CF to step up, to build teams based on fairness, equity and diversity, and to catalyse steps towards this goal in their institutions and society more widely.

Spondyloarthritis Research Consortium of Canada sacroiliac joint inflammation and structural scores: change score reliability and recalibration utility in children.

BACKGROUND: The SPARCC sacroiliac joint inflammation (SIS) and structural (SSS) scores are reliable measures to quantify abnormalities in the pediatric sacroiliac joint. We aimed to evaluate the utility of online calibration modules for the SIS and SSS and the reliability of their component change scores. METHODS: Change score reliability of 6 raters was assessed by overall and pairwise intraclass correlation coefficients (ICCs) before and after the use of real-time iterative calibration (RETIC) modules for both the SIS and SSS comprised of 20 adult cases. Acceptable ICC for change scores was > 0.7 for SIS and > 0.5 for all SSS components. Sensitivity to change was assessed by the standardized response mean (SRM). RESULTS: In scoring exercise 1, the SIS had acceptable reliability with a change score ICC of 0.80 and sclerosis was the only SSS lesion that met the acceptability threshold with a change score ICC of 0.52. After RETIC calibration, the SIS overall (ICC = 0.83) and mean pairwise (ICC = 0.83) change scores remained reliable with a large SRM (0.90). All SSS components except sclerosis met the overall and mean pairwise change score ICC acceptability thresholds-backfill: overall = 0.54, mean pairwise = 0.50; fat metaplasia: overall = 0.65, mean pairwise = 0.57; erosion: overall = 0.60, mean pairwise = 0.58; and ankylosis: overall = 0.96, mean pairwise = 0.96. The SSS RETIC module augmented the number of SSS components surpassing the acceptability threshold from 1 to 4. Sensitivity to change, as measured by the SRM, was large for erosion (0.96), moderate for backfill (0.55) and sclerosis (0.70), and small for fat metaplasia (0.36) and ankylosis (0.28). CONCLUSION: RETIC modules improved the overall reliability of SPARCC SIS and SSS change scores for previously calibrated raters. SIS recalibration was not as helpful to the most experienced raters who achieved high levels of agreement before recalibration. The SPARCC SIS and all SSS components except sclerosis are reliable measures to quantify change over time in children. A pediatric-specific RETIC tool should be developed to enhance the calibration of readers.