Research priorities for the management of major trauma: an international priority setting partnership with the James Lind Alliance.

OBJECTIVE: The objective of this study is to determine research priorities for the management of major trauma, representing the shared priorities of patients, their families, carers and healthcare professionals. DESIGN/SETTING: An international research priority-setting partnership. PARTICIPANTS: People who have experienced major trauma, their carers and relatives, and healthcare professionals involved in treating patients after major trauma. The scope included chest, abdominal and pelvic injuries as well as major bleeding, multiple injuries and those that threaten life or limb. METHODS: A multiphase priority-setting exercise was conducted in partnership with the James Lind Alliance over 24 months (November 2021-October 2023). An international survey asked respondents to submit their research uncertainties which were then combined into several indicative questions. The existing evidence was searched to ensure that the questions had not already been sufficiently answered. A second international survey asked respondents to prioritise the research questions. A final shortlist of 19 questions was taken to a stakeholder workshop, where consensus was reached on the top 10 priorities. RESULTS: A total of 1572 uncertainties, submitted by 417 respondents (including 132 patients and carers), were received during the initial survey. These were refined into 53 unique indicative questions, of which all 53 were judged to be true uncertainties after reviewing the existing evidence. 373 people (including 115 patients and carers) responded to the interim prioritisation survey and 19 questions were taken to a final consensus workshop between patients, carers and healthcare professionals. At the final workshop, a consensus was reached for the ranking of the top 10 questions. CONCLUSIONS: The top 10 research priorities for major trauma include patient-centred questions regarding pain relief and prehospital management, multidisciplinary working, novel technologies, rehabilitation and holistic support. These shared priorities will now be used to guide funders and teams wishing to research major trauma around the globe.

Future research priorities for soft-tissue knee injuries.

Aims: To identify unanswered questions about the prevention, diagnosis, treatment, and rehabilitation and delivery of care of first-time soft-tissue knee injuries (ligament injuries, patella dislocations, meniscal injuries, and articular cartilage) in children (aged 12 years and older) and adults. Methods: The James Lind Alliance (JLA) methodology for Priority Setting Partnerships was followed. An initial survey invited patients and healthcare professionals from the UK to submit any uncertainties regarding soft-tissue knee injury prevention, diagnosis, treatment, and rehabilitation and delivery of care. Over 1,000 questions were received. From these, 74 questions (identifying common concerns) were formulated and checked against the best available evidence. An interim survey was then conducted and 27 questions were taken forward to the final workshop, held in January 2023, where they were discussed, ranked, and scored in multiple rounds of prioritization. This was conducted by healthcare professionals, patients, and carers. Results: The top ten included questions regarding prevention, diagnosis, treatment, and rehabilitation. The number one question was, 'How urgently do soft-tissue knee injuries need to be treated for the best outcome?'. This reflects the concerns of patients, carers, and the wider multidisciplinary team. Conclusion: This validated process has generated ten important priorities for future soft-tissue knee injury research. These have been submitted to the National Institute for Health and Care Research. All 27 questions in the final workshop have been published on the JLA website.

Research priorities for children's cancer: a James Lind Alliance Priority Setting Partnership in the UK.

OBJECTIVES: To engage children who have experienced cancer, childhood cancer survivors, their families and professionals to systematically identify and prioritise research questions about childhood cancer to inform the future research agenda. DESIGN: James Lind Alliance Priority Setting Partnership. SETTING: UK health service and community. METHODS: A steering group oversaw the initiative. Potential research questions were collected in an online survey, then checked to ensure they were unanswered. Shortlisting via a second online survey identified the highest priority questions. A parallel process with children was undertaken. A final consensus workshop was held to determine the Top 10 priorities. PARTICIPANTS: Children and survivors of childhood cancer, diagnosed before age 16, their families, friends and professionals who work with this population. RESULTS: Four hundred and eighty-eight people submitted 1299 potential questions. These were refined into 108 unique questions; 4 were already answered and 3 were under active study, therefore, removed. Three hundred and twenty-seven respondents completed the shortlisting survey. Seventy-one children submitted questions in the children's surveys, eight children attended a workshop to prioritise these questions. The Top 5 questions from children were taken to the final workshop where 23 questions in total were discussed by 25 participants (young adults, carers and professionals). The top priority was 'can we find effective and kinder (less burdensome, more tolerable, with fewer short and long-term effects) treatments for children with cancer, including relapsed cancer?' CONCLUSIONS: We have identified research priorities for children's cancer from the perspectives of children, survivors, their families and the professionals who care for them. Questions reflect the breadth of the cancer experience, including diagnosis, relapse, hospital experience, support during/after treatment and the long-term impact of cancer. These should inform funding of future research as they are the questions that matter most to the people who could benefit from research.

Greener Operations: a James Lind Alliance Priority Setting Partnership to define research priorities in environmentally sustainable perioperative practice through a structured consensus approach.

OBJECTIVES: To agree on the 'top 10' research priorities for environmentally sustainable perioperative practice. DESIGN: Surveys and literature review; final consensus workshop using a nominal group technique. SETTING: UK-based setting. PARTICIPANTS: Healthcare professionals, patients, carers and the public. OUTCOME MEASURES: Initial survey-suggested research questions; interim survey-shortlist of 'indicative' questions (the 20 most frequently nominated by patients, carers and the public, and healthcare professionals); final workshop-ranked research priorities. RESULTS: Initial survey-1926 suggestions by 296 respondents, refined into 60 indicative questions. Interim survey-325 respondents. Final workshop-21 participants agreed the 'top 10': (1) How can more sustainable reusable equipment safely be used during and around the time of an operation? (2) How can healthcare organisations more sustainably procure (obtain) medicines, equipment and items used during and around the time of an operation? (3) How can healthcare professionals who deliver care during and around the time of an operation be encouraged to adopt sustainable actions in practice? (4) Can more efficient use of operating theatres and associated practices reduce the environmental impact of operations? (5) How can the amount of waste generated during and around the time of an operation be minimised? (6) How do we measure and compare the short-term and long-term environmental impacts of surgical and non-surgical treatments for the same condition? (7) What is the environmental impact of different anaesthetic techniques (eg, different types of general, regional and local anaesthesia) used for the same operation? (8) How should the environmental impact of an operation be weighed against its clinical outcomes and financial costs? (9) How can environmental sustainability be incorporated into the organisational management of operating theatres? (10) What are the most sustainable forms of effective infection prevention and control used around the time of an operation (eg, personal protective equipment, drapes, clean air ventilation)? CONCLUSIONS: A broad range of 'end-users' have identified research priorities for sustainable perioperative care.

Elbow conditions: research priorities setting in partnership with the James Lind Alliance.

OBJECTIVE: To undertake a UK-based James Lind Alliance (JLA) Priority Setting Partnership for elbow conditions and be representative of the views of patients, carers and healthcare professionals (HCPs). SETTING: This was a national collaborative study organised through the British Elbow and Shoulder Society. PARTICIPANTS: Adult patients, carers and HCPs who have managed or experienced elbow conditions, their carers and HCPs in the UK involved in managing of elbow conditions. METHODS: The rigorous JLA priority setting methodology was followed. Electronic and paper scoping surveys were distributed to identify potential research priority questions (RPQs). Initial responses were reviewed and a literature search was performed to cross-check categorised questions. Those questions already sufficiently answered were excluded and the remaining questions were ranked in a second survey according to priority for future elbow conditions research. Using the JLA methodology, responses from HCP and patients were combined to create a list of the top 18 questions. These were further reviewed in a dedicated multistakeholder workshop where the top 10 RPQs were agreed by consensus. RESULTS: The process was completed over 24 months. The initial survey resulted in 467 questions from 165 respondents (73% HCPs and 27% patients/carers). These questions were reviewed and combined into 46 summary topics comprising: tendinopathy, distal biceps pathology, arthritis, stiffness, trauma, arthroplasty and cubital tunnel syndrome. The second (interim prioritisation) survey had 250 respondents (72% HCP and 28% patients/carers). The top 18 ranked questions from this survey were taken to the final workshop where a consensus was reached on the top 10 RPQs. CONCLUSIONS: The top 10 RPQs highlight areas of importance that currently lack sufficient evidence to guide diagnosis, treatment and rehabilitation of elbow conditions. This collaborative process will guide researchers and funders regarding the topics that should receive most future attention and benefit patients and HCPs.

Identifying the top research priorities in medically not yet explained symptoms (MNYES): a James Lind Alliance priority setting partnership.

OBJECTIVES: This study establishes research priorities for medically not yet explained symptoms (MNYES), also known as persistent physical symptoms or medically unexplained symptoms, from the perspective of patients, caregivers and clinicians, in a priority setting partnership (PSP) following the James Lind Alliance (JLA) approach. Research into such symptoms in general has been poorly funded over the years and so far has been primarily researcher-led with minimal input from patients, caregivers and clinicians; and sometimes has been controversial. DESIGN: JLA PSP method. The PSP termed these symptoms MNYES. METHODS: The study was conducted according to the JLA's detailed methodology for conducting priority setting exercises. It involved five key stages: defining the appropriate term for the conditions under study by the PSP Steering Group; gathering questions on MNYES from patients, caregivers and clinicians in a publicly accessible survey; checking these research questions against existing evidence; interim prioritisation in a second survey; and a final multi-stakeholder consensus meeting to determine the top 10 unanswered research questions using the modified nominal group methodology. RESULTS: Over 700 responses from UK patients, caregivers and clinicians were identified in the two surveys and charities contributed from a broad range of medical specialties and primary care. The final top 10 unanswered research questions cover, among others: treatment strategies, personalisation of treatment, collaborative care pathways, training for clinicians and outcomes that matter to patients. INTERPRETATION: The top 10 unanswered research questions are expected to generate much needed, relevant and impactful research into MNYES.

JAGGED-NOTCH3 signaling in vascular remodeling in pulmonary arterial hypertension.

Within the pulmonary arterial tree, the NOTCH3 pathway is crucial in controlling vascular smooth muscle cell proliferation and maintaining smooth muscle cells in an undifferentiated state. Pulmonary arterial hypertension (PAH) is a fatal disease without cure, characterized by elevated pulmonary vascular resistance due to vascular smooth muscle cell proliferation in precapillary arteries, perivascular inflammation, and asymmetric neointimal hyperplasia. Here, we show that human PAH is characterized by overexpression of the NOTCH ligand JAGGED-1 (JAG-1) in small pulmonary artery smooth muscle cells and that JAG-1 selectively controls NOTCH3 signaling and cellular proliferation in an autocrine fashion. In contrast, the NOTCH ligand DELTA-LIKE 4 is minimally expressed in small pulmonary artery smooth muscle cells from individuals with PAH, inhibits NOTCH3 cleavage and signaling, and retards vascular smooth muscle cell proliferation. A new monoclonal antibody for the treatment of PAH, which blocks JAG-1 cis- and trans-induced cleavage of the NOTCH3 receptor in the pulmonary vasculature, was developed. Inhibition of JAG-1-induced NOTCH3 signaling in the lung reverses clinical and pathologic pulmonary hypertension in two rodent models of disease, without toxic side effects associated with nonspecific NOTCH inhibitors. Our data suggest opposing roles of NOTCH ligands in the pulmonary vasculature in pulmonary hypertension. We propose that selectively targeting JAG-1 activation of NOTCH3 may be an effective, safe strategy to treat PAH.

Research priorities for the management of complex fractures: a UK priority setting partnership with the James Lind Alliance.

OBJECTIVE: To determine research priorities for the management of complex fractures, which represent the shared priorities of patients, their families, carers and healthcare professionals. DESIGN/SETTING: A national (UK) research priority setting partnership. PARTICIPANTS: People who have experienced a complex fracture, their carers and relatives, and relevant healthcare professionals and clinical academics involved in treating patients with complex fractures. The scope includes open fractures, fractures to joints broken into multiple pieces, multiple concomitant fractures and fractures involving the pelvis and acetabulum. METHODS: A multiphase priority setting exercise was conducted in partnership with the James Lind Alliance over 21 months (October 2019 to June 2021). A national survey asked respondents to submit their research uncertainties which were then combined into several indicative questions. The existing evidence was searched to ensure that the questions had not already been sufficiently answered. A second national survey asked respondents to prioritise the research questions. A final shortlist of 18 questions was taken to a stakeholder workshop, where a consensus was reached on the top 10 priorities. RESULTS: A total of 532 uncertainties, submitted by 158 respondents (including 33 patients/carers) were received during the initial survey. These were refined into 58 unique indicative questions, of which all 58 were judged to be true uncertainties after review of the existing evidence. 136 people (including 56 patients/carers) responded to the interim prioritisation survey and 18 questions were taken to a final consensus workshop between patients, carers and healthcare professionals. At the final workshop, a consensus was reached for the ranking of the top 10 questions. CONCLUSIONS: The top 10 research priorities for complex fracture include questions regarding rehabilitation, complications, psychological support and return to life-roles. These shared priorities will now be used to guide funders and teams wishing to research complex fractures over the coming decade.

Andexanet Alfa Use for Small Bowel Obstruction Patient With History of Sugiura Procedure.

This case report is about a 51-year-old active duty male with JAK2 mutation and medical history significant for prehepatic portal hypertension from portal vein thrombus on lifelong anticoagulation with rivaroxaban, an oral factor Xa inhibitor, presenting with closed-loop small bowel obstruction requiring emergent laparotomy. We present this surgical case as it required emergent reversal of the oral factor Xa inhibitor with andexanet alfa.

Needle localization of small pulmonary nodules: Lessons learned.

BACKGROUND: Lung nodules that are small and deep within lung parenchyma, and have semisolid characteristics are often challenging to localize with video-assisted thoracoscopic surgery (VATS). We describe our cumulative experience using needle localization of small nodules before surgical resection. We report procedural tips, operative results, and lessons learned over time. METHODS: A retrospective review of all needle localization cases between July 1, 2006, and December 30, 2016, at a single institution was performed. A total of 253 patients who underwent needle localization of lung nodules ranging from 0.6 to 1.2 cm before operation were enrolled. Nodules were localized by placing two 20-gauge Hawkins III coaxial needles from different trajectories with tips adjacent to the nodule, injection of 0.3 to 0.6 mL of methylene blue, and deployment of 2 hookwires, under computed tomography guidance. Patients then underwent VATS wedge resection for diagnosis, followed by anatomic resection for lung carcinoma. Procedural and perioperative outcomes were assessed. RESULTS: Needle localization was successful in 245 patients (96.8%). Failures included both wires falling out of lung parenchyma before operation (5 patients), wire migration (2 patients), and bleeding resulting in hematoma requiring transfusion (1 patient). The most common complication of needle localization was asymptomatic pneumothorax (11/253 total patients; 4.3%) and was higher in patients with bullous emphysema (9/35 patients; 25.7%). Of the 8 individuals who had unsuccessful needle localization, 7 had successful wedge resection in the area of methylene blue injection that included the nodule; 1 required segmentectomy for diagnosis. Completion lobectomy (154 VATS, 2 minithoracotomies) or VATS segmentectomy (18 patients) was performed in 174 individuals with a diagnosis of non-small cell carcinoma or carcinoid. The average length of hospital stay was 1.4 days for wedge resection, 1.9 days for VATS segmentectomy, 3.1 days for VATS lobectomy, and 4.9 days for minithoracotomy. Perioperative survival was 100%. CONCLUSIONS: Needle localization with hookwire deployment and methylene blue injection is a safe and feasible strategy to localize small, deep lung nodules for wedge resection and diagnosis. Multidisciplinary coordination between the thoracic surgeon and the interventional radiologist is key to the success of this procedure.

Noninvasive positive pressure ventilation in the immediate post-bariatric surgery care of patients with obstructive sleep apnea: a systematic review.

BACKGROUND: Obstructive sleep apnea is common in morbidly obese patients, and noninvasive positive pressure ventilation (NIPPV) is the standard treatment. Postoperatively, NIPPV is highly effective in preventing hypoxia and apneic episodes; however, the concern of gastric distention leading to increased risk of an anastomotic dehiscence limits universal acceptance. OBJECTIVE: To perform a systematic review of the literature to determine if the use of NIPPV during immediate post-bariatric surgery care is safe. METHODS: Between January 1, 2000 and January 1, 2015 a comprehensive literature search for English-language articles was performed. Search terms were related to NIPPV use and bariatric surgery. Three reviewers independently reviewed the full-text version of the articles for relevance. Due to lack of randomized controlled trials and common incidence of zero for leak rate, a meta-analysis was not conducted. RESULTS: A total of 824 studies were identified for screening using our search criteria, and 811 were rejected based on exclusion criteria. Thirteen studies with 5465 patients were identified for abstract review. All articles were either favorable or equivocal on the use of NIPPV in this patient population. Comparative studies did not identify an increased rate of anastomotic dehiscence in the patients who did receive NIPPV. The use of NIPPV was associated with a decreased risk of respiratory complications but not of reintubation or unplanned intensive care unit admission. CONCLUSION: This systematic review of the available literature does not provide evidence of a signal that there is an increased anastomotic dehiscence risk when NIPPV is administered during immediate post-bariatric surgery care.

Research activity and the association with mortality.

INTRODUCTION: The aims of this study were to describe the key features of acute NHS Trusts with different levels of research activity and to investigate associations between research activity and clinical outcomes. METHODS: National Institute for Health Research (NIHR) Comprehensive Clinical Research Network (CCRN) funding and number of patients recruited to NIHR Clinical Research Network (CRN) portfolio studies for each NHS Trusts were used as markers of research activity. Patient-level data for adult non-elective admissions were extracted from the English Hospital Episode Statistics (2005-10). Risk-adjusted mortality associations between Trust structures, research activity and, clinical outcomes were investigated. RESULTS: Low mortality Trusts received greater levels of funding and recruited more patients adjusted for size of Trust (n = 35, 2,349 £/bed [95% CI 1,855-2,843], 5.9 patients/bed [2.7-9.0]) than Trusts with expected (n = 63, 1,110 £/bed, [864-1,357] p<0.0001, 2.6 patients/bed [1.7-3.5] p<0.0169) or, high (n = 42, 930 £/bed [683-1,177] p = 0.0001, 1.8 patients/bed [1.4-2.1] p<0.0005) mortality rates. The most research active Trusts were those with more doctors, nurses, critical care beds, operating theatres and, made greater use of radiology. Multifactorial analysis demonstrated better survival in the top funding and patient recruitment tertiles (lowest vs. highest (odds ratio & 95% CI: funding 1.050 [1.033-1.068] p<0.0001, recruitment 1.069 [1.052-1.086] p<0.0001), middle vs. highest (funding 1.040 [1.024-1.055] p<0.0001, recruitment 1.085 [1.070-1.100] p<0.0001). CONCLUSIONS: Research active Trusts appear to have key differences in composition than less research active Trusts. Research active Trusts had lower risk-adjusted mortality for acute admissions, which persisted after adjustment for staffing and other structural factors.

Getting involved in clinical trials research in the UK: how can Clinical Research Networks help?

The Clinical Research Networks of the National Institute of Health Research have transformed clinical research in the UK, leading to a doubling in the number of patients involved in clinical research studies over the past 3 years. This has been achieved by streamlining the trials approvals process, by providing local infrastructure such as research nurse support for clinical trials recruitment and through recognition of the time and funding necessary for clinicians to contribute to clinical research. Here, we describe the structure and roles of the Comprehensive Clinical Research Networks in gastrointestinal disease and hepatology, particularly in England. We will explain how the networks have already accelerated clinical research in gastrointestinal and liver disease, as well as provide a simple guide about how individual clinicians can contribute to ongoing studies via the networks.