Beliefs, experiences and concerns of using artificial intelligence in healthcare: A qualitative synthesis.

Objective: Artificial intelligence (AI) is a developing field in the context of healthcare. As this technology continues to be implemented in patient care, there is a growing need to understand the thoughts and experiences of stakeholders in this area to ensure that future AI development and implementation is successful. The aim of this study was to conduct a literature search of qualitative studies exploring the opinions of stakeholders such as clinicians, patients, and technology experts in order to establish the most common themes and ideas that have been presented in this research. Methods: A literature search was conducted of existing qualitative research on stakeholder beliefs about the use of AI use in healthcare. Twenty-one papers were selected and analysed resulting in the development of four key themes relating to patient care, patient-doctor relationships, lack of education and resources, and the need for regulations. Results: Overall, patients and healthcare workers are open to the use of AI in care and appear positive about potential benefits. However, concerns were raised relating to the lack of empathy in interactions of AI tools, and potential risks that may arise from the data collection needed for AI use and development. Stakeholders in the healthcare, technology, and business sectors all stressed that there was a lack of appropriate education, funding, and guidelines surrounding AI, and these concerns needed to be addressed to ensure future implementation is safe and suitable for patient care. Conclusion: Ultimately, the results found in this study highlighted that there was a need for communication between stakeholder in order for these concerns to be addressed, mitigate potential risks, and maximise benefits for patients and clinicians alike. The results also identified a need for further qualitative research in this area to further understand stakeholder experiences as AI use continues to develop.

Experiences of using artificial intelligence in healthcare: a qualitative study of UK clinician and key stakeholder perspectives.

OBJECTIVES: Artificial intelligence (AI) is a rapidly developing field in healthcare, with tools being developed across various specialties to support healthcare professionals and reduce workloads. It is important to understand the experiences of professionals working in healthcare to ensure that future AI tools are acceptable and effectively implemented. The aim of this study was to gain an in-depth understanding of the experiences and perceptions of UK healthcare workers and other key stakeholders about the use of AI in the National Health Service (NHS). DESIGN: A qualitative study using semistructured interviews conducted remotely via MS Teams. Thematic analysis was carried out. SETTING: NHS and UK higher education institutes. PARTICIPANTS: Thirteen participants were recruited, including clinical and non-clinical participants working for the NHS and researchers working to develop AI tools for healthcare settings. RESULTS: Four core themes were identified: positive perceptions of AI; potential barriers to using AI in healthcare; concerns regarding AI use and steps needed to ensure the acceptability of future AI tools. Overall, we found that those working in healthcare were generally open to the use of AI and expected it to have many benefits for patients and facilitate access to care. However, concerns were raised regarding the security of patient data, the potential for misdiagnosis and that AI could increase the burden on already strained healthcare staff. CONCLUSION: This study found that healthcare staff are willing to engage with AI research and incorporate AI tools into care pathways. Going forward, the NHS and AI developers will need to collaborate closely to ensure that future tools are suitable for their intended use and do not negatively impact workloads or patient trust. Future AI studies should continue to incorporate the views of key stakeholders to improve tool acceptability. TRIAL REGISTRATION NUMBER: NCT05028179; ISRCTN15113915; IRAS ref: 293515.

Acceptance and Commitment Therapy for people living with motor neuron disease: an uncontrolled feasibility study.

BACKGROUND: Motor neuron disease (MND) is a fatal, progressive neurodegenerative disease that causes progressive weakening and wasting of limb, bulbar, thoracic and abdominal muscles. Clear evidence-based guidance on how psychological distress should be managed in people living with MND (plwMND) is lacking. Acceptance and Commitment Therapy (ACT) is a form of psychological therapy that may be particularly suitable for this population. However, to the authors' knowledge, no study to date has evaluated ACT for plwMND. Consequently, the primary aim of this uncontrolled feasibility study was to examine the feasibility and acceptability of ACT for improving the psychological health of plwMND. METHODS: PlwMND aged ≥ 18 years were recruited from 10 UK MND Care Centres/Clinics. Participants received up to 8 one-to-one ACT sessions, developed specifically for plwMND, plus usual care. Co-primary feasibility and acceptability outcomes were uptake (≥ 80% of the target sample [N = 28] recruited) and initial engagement with the intervention (≥ 70% completing ≥ 2 sessions). Secondary outcomes included measures of quality of life, anxiety, depression, disease-related functioning, health status and psychological flexibility in plwMND and quality of life and burden in caregivers. Outcomes were assessed at baseline and 6 months. RESULTS: Both a priori indicators of success were met: 29 plwMND (104%) were recruited and 76% (22/29) attended ≥ 2 sessions. Attrition at 6-months was higher than anticipated (8/29, 28%), but only two dropouts were due to lack of acceptability of the intervention. Acceptability was further supported by good satisfaction with therapy and session attendance. Data were possibly suggestive of small improvements in anxiety and psychological quality of life from baseline to 6 months in plwMND, despite a small but expected deterioration in disease-related functioning and health status. CONCLUSIONS: There was good evidence of acceptability and feasibility. Limitations included the lack of a control group and small sample size, which complicate interpretation of findings. A fully powered RCT to evaluate the clinical and cost-effectiveness of ACT for plwMND is underway. TRIAL REGISTRATION: The study was pre-registered with the ISRCTN Registry (ISRCTN12655391).

Treatment of axial spondyloarthritis with biologic and targeted synthetic DMARDs: British Society for Rheumatology guideline scope.

Pharmacological management has advanced considerably since the 2015 British Society for Rheumatology axial spondyloarthritis (axSpA) guideline to incorporate new classes of biologic DMARDs (bDMARDs, including biosimilars), targeted synthetic DMARDs (tsDMARDs) and treatment strategies such as drug tapering. The aim of this guideline is to provide an evidence-based update on pharmacological management of adults with axSpA (including AS and non-radiographic axSpA) using b/tsDMARDs. This guideline is aimed at health-care professionals in the UK who care directly for people with axSpA, including rheumatologists, rheumatology specialist nurses, allied health professionals, rheumatology specialty trainees and pharmacists; people living with axSpA; and other stakeholders, such as patient organizations and charities.

PROTEUS Study: A Prospective Randomized Controlled Trial Evaluating the Use of Artificial Intelligence in Stress Echocardiography.

BACKGROUND: Stress echocardiography (SE) is one of the most commonly used diagnostic imaging tests for coronary artery disease (CAD) but requires clinicians to visually assess scans to identify patients who may benefit from invasive investigation and treatment. EchoGo Pro provides an automated interpretation of SE based on artificial intelligence (AI) image analysis. In reader studies, use of EchoGo Pro when making clinical decisions improves diagnostic accuracy and confidence. Prospective evaluation in real world practice is now important to understand the impact of EchoGo Pro on the patient pathway and outcome. METHODS: PROTEUS is a randomized, multicenter, 2-armed, noninferiority study aiming to recruit 2,500 participants from National Health Service (NHS) hospitals in the UK referred to SE clinics for investigation of suspected CAD. All participants will undergo a stress echocardiogram protocol as per local hospital policy. Participants will be randomized 1:1 to a control group, representing current practice, or an intervention group, in which clinicians will receive an AI image analysis report (EchoGo Pro, Ultromics Ltd, Oxford, UK) to use during image interpretation, indicating the likelihood of severe CAD. The primary outcome will be appropriateness of clinician decision to refer for coronary angiography. Secondary outcomes will assess other health impacts including appropriate use of other clinical management approaches, impact on variability in decision making, patient and clinician qualitative experience and a health economic analysis. DISCUSSION: This will be the first study to assess the impact of introducing an AI medical diagnostic aid into the standard care pathway of patients with suspected CAD being investigated with SE. TRIAL REGISTRATION: Clinicaltrials.gov registration number NCT05028179, registered on 31 August 2021; ISRCTN: ISRCTN15113915; IRAS ref: 293515; REC ref: 21/NW/0199.

Ca2+ release or Ca2+ entry, that is the question: what governs Ca2+ oscillations in pancreatic ß cells?

The standard model for Ca2+ oscillations in insulin-secreting pancreatic ß cells centers on Ca2+ entry through voltage-activated Ca2+ channels. These work in combination with ATP-dependent K+ channels, which are the bridge between the metabolic state of the cells and plasma membrane potential. This partnership underlies the ability of the ß cells to secrete insulin appropriately on a minute-to-minute time scale to control whole body plasma glucose. Though this model, developed over more than 40 years through many cycles of experimentation and mathematical modeling, has been very successful, it has been challenged by a hypothesis that calcium-induced calcium release from the endoplasmic reticulum through ryanodine or inositol trisphosphate (IP3) receptors is instead the key driver of islet oscillations. We show here that the alternative model is in fact incompatible with a large body of established experimental data and that the new observations offered in support of it can be better explained by the standard model.

Obstinate leg ulceration secondary to prolidase deficiency, treated with 5% topical proline.

Prolidase deficiency is a rare cause of chronic ulceration with less than 100 reported cases in the literature. This article highlights to clinicians the features of this uncommon genodermatosis, the challenge of diagnosis, and treatment options.

The Wnt Pathway Inhibitor RXC004 Blocks Tumor Growth and Reverses Immune Evasion in Wnt Ligand-dependent Cancer Models.

Wnt signaling is implicated in the etiology of gastrointestinal tract cancers. Targeting Wnt signaling is challenging due to on-target toxicity concerns and lack of druggable pathway components. We describe the discovery and characterization of RXC004, a potent and selective inhibitor of the membrane-bound o-acyl transferase Porcupine, essential for Wnt ligand secretion. Absorption, distribution, metabolism, and excretion and safety pharmacology studies were conducted with RXC004 in vitro, and pharmacokinetic exposure assessed in vivo. RXC004 effects on proliferation and tumor metabolism were explored in genetically defined colorectal and pancreatic cancer models in vitro and in vivo. RXC004 effects on immune evasion were assessed in B16F10 immune "cold" and CT26 immune "hot" murine syngeneic models, and in human cell cocultures. RXC004 showed a promising pharmacokinetic profile, inhibited Wnt ligand palmitoylation, secretion, and pathway activation, and demonstrated potent antiproliferative effects in Wnt ligand-dependent (RNF43-mutant or RSPO3-fusion) colorectal and pancreatic cell lines. Reduced tumor growth and increased cancer cell differentiation were observed in SNU-1411 (RSPO3-fusion), AsPC1 and HPAF-II (both RNF43-mutant) xenograft models, with a therapeutic window versus Wnt homeostatic functions. Additional effects of RXC004 on tumor cell metabolism were confirmed in vitro and in vivo by glucose uptake and 18fluorodeoxyglucose-PET, respectively. RXC004 stimulated host tumor immunity; reducing resident myeloid-derived suppressor cells within B16F10 tumors and synergizing with anti-programmed cell death protein-1 (PD-1) to increase CD8+/regulatory T cell ratios within CT26 tumors. Moreover, RXC004 reversed the immunosuppressive effects of HPAF-II cells cocultured with human peripheral blood mononuclear cells, confirming the multiple anticancer mechanisms of this compound, which has progressed into phase II clinical trials. Significance: Wnt pathway dysregulation drives many gastrointestinal cancers; however, there are no approved therapies that target the pathway. RXC004 has demonstrated the potential to block both tumor growth and tumor immune evasion in a genetically defined, clinically actionable subpopulation of Wnt ligand-dependent gastrointestinal cancers. The clinical utility of RXC004, and other Porcupine inhibitors, in such Wnt ligand-dependent cancers is currently being assessed in patient trials.

Investigating cognitive factors and diagnostic error in a presentation of complicated multisystem disease.

OBJECTIVES: To use a case review approach for investigating the types of cognitive error identifiable following a complicated patient admission with a multisystem disorder in an acute care setting where diagnosis was difficult and delayed. METHODS: A case notes review was undertaken to explore the cognitive factors associated with diagnostic error in the case of an 18-year-old male presenting acutely unwell with myalgia, anorexia and vomiting. Each clinical interaction was analysed and identified cognitive factors were categorised using a framework developed by Graber et al. RESULTS: Cognitive factors resulting in diagnostic errors most frequently occurred within the first five days of hospital admission. The most common were premature closure; failure to order or follow up an appropriate test; over-reliance on someone else's findings or opinion; over-estimating or underestimating usefulness or salience of a finding, and; ineffective, incomplete or faulty history and physical examination. Cognitive factors were particularly frequent around transitions of care and patient transfers from one clinical area to another. The presence of senior staff did not necessarily mitigate against diagnostic error from cognitive factors demonstrated by junior staff or diagnostic errors made out-of-hours. CONCLUSIONS: Cognitive factors are a significant cause of diagnostic error within the first five days after admission, especially around transitions of care between different clinical settings and providers. Medical education interventions need to ensure clinical reasoning training supports individuals and teams to develop effective strategies for mitigating cognitive factors when faced with uncertainty over complex patients presenting with non-specific symptoms in order to reduce diagnostic error.

Cutaneous manifestations of COVID-19 in children (and adults): A virus that does not discriminate.

Coronavirus disease 2019 (COVID-19) is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), a beta coronavirus with a characteristic S-glycoprotein spike on the cell surface. Initial reports did not include cutaneous manifestations as a feature of COVID-19; however, there is a growing repertoire of reports demonstrating an array of dermatologic manifestations on the skin in children and adults. Dermatologic afflictions have been summarized into different categories several times, with the most recent analysis identifying six clinical patterns: urticaria, maculopapular-morbilliform eruption, papulovesicular exanthem, chilblain-like acral pattern, livedo reticularis-livedo racemosa pattern, and purpuric vasculitic pattern. In children, the dermatologic features appear to occur before or concomitantly with other COVID-19 manifestations. Dermatologists play a key role in diagnosing patients with COVID-19 who may present for the first time unwittingly exhibiting early signs of COVID-19. We have reviewed the current evidence on the dermatologic impact of COVID-19 in both the adult and pediatric populations.

Treating to target in psoriatic arthritis: assessing real-world outcomes and optimising therapeutic strategy for adults with psoriatic arthritis-study protocol for the MONITOR-PsA study, a trials within cohorts study design.

BACKGROUND: The Tight Control of psoriatic arthritis (TICOPA) trial confirmed improved clinical outcomes with a treat to target (T2T) strategy in psoriatic arthritis (PsA). This consisted of 4-weekly review and escalation of 'step up' therapy (single disease modifying therapy (DMARD), combination DMARDs and then biologics) based on remission criteria. Based on this, a T2T approach is supported by European PsA treatment recommendations. However, it is not commonly implemented in routine care primarily due to feasibility and cost concerns. In the TICOPA trial, the same treatment regime was used for all participants regardless of their disease profile. Despite the recognition of PsA as a highly heterogeneous condition, no studies have tailored which drugs are used depending on disease severity. The cohort will establish real world outcomes for the T2T approach in PsA and also form the basis of a trials within cohorts (TWiCs) design to test alternative therapeutic approaches within embedded clinical trials providing an evidence base for treatment strategy in PsA. METHODS: The Multicentre Observational Initiative in Treat to target Outcomes in Psoriatic Arthritis (MONITOR-PsA) cohort will apply a T2T approach within routine care. It will recruit newly diagnosed adult patients with PsA starting systemic therapies. The cohort is observational allowing routine therapeutic care within NHS clinics but a T2T approach will be supported when monitoring treatment within the cohort. Eligible participants will be adults (≥18 years) with active PsA with ≥ 1 tender or swollen joints or enthesis who have not previously had treatment with DMARDs for articular disease. DISCUSSION: This study is the first TWiC designed to support a fully powered randomised drug trial. The results from the observational cohort will be compared with those observed in the TICOPA trial investigating the clinical effectiveness and health care costs of the pragmatic T2T approach. Nested trials will provide definitive RCT evidence establishing the optimal management of PsA within the T2T approach. The TWiCs design allows robust generalizability to routine healthcare, avoids disappointment bias, aids recruitment and in future will allow assessment of longer-term outcomes. TRIAL REGISTRATION: ClinicalTrials.gov NCT03531073 . Retrospectively registered on 21 May 2018.

Increased staple loading pressures and reduced staple heights in laparoscopic sleeve gastrectomy reduce intraoperative bleeding.

BACKGROUND: In laparoscopic sleeve gastrectomy, tissue thickness and closed staple height of the staple cartridge determine the pressure applied to the tissue. Prior studies have suggested 8 g/mm2 to be ideal to minimize leaks or bleeding. METHODS: We evaluated the relationship between staple loading pressure applied to gastric tissue and bleeding rate prospectively with a novel tissue measuring device and video-recorded operative findings for 116 patients undergoing laparoscopic sleeve gastrectomy performed by 2 surgeons at a single institution. Stapling protocol 1 was used for 64 cases, defined as standard practice, typically using green-blue-blue-blue Ethicon staple cartridges. Stapling protocol 2 was defined as blue-blue-white-white or gold-blue-white-white. RESULTS: Tissue thickness measurements from 39 cases and staple load selection showed that surgeons preferred a median staple loading pressure of 15 g/mm2. Tissue thickness measurements at 15 g/mm2 had a mean of 1.86 mm at the antrum, 1.71 mm at the body, and 1.15 mm at the fundus, all significantly thinner than tissue thickness at 8 g/mm2. For each 10 g/mm2 increase in minimum pressure and maximum pressure value within each cartridge zone, there was a reduction in bleeding rate by 59.8% and 38.7%, respectively. Compared with stapling protocol 1, stapling protocol 2 had a lower intraoperative bleeding rate (90.2% vs 70.7%; P < .0001), usage of preventive hemostatic techniques (100% vs 10%; P < .0001), and hemostatic treatments (66% vs 46%; P = .04). In the 30-day postoperative period, there was 1 bleed in stapling protocol 1; there were no leaks. CONCLUSION: Our data suggest using shorter closed staple heights to exert higher staple loading pressures decreases intraoperative bleeding rates in laparoscopic sleeve gastrectomy.

Lack of association between clinical and ultrasound measures of disease activity in rheumatoid arthritis remission.

OBJECTIVES: The objective of this study was to assess the prevalence of ultrasound (US) abnormalities and association with clinical parameters in rheumatoid arthritis (RA) clinical remission. METHODS: Patients with established RA in clinical remission (DAS28-CRP < 2.4) taking conventional synthetic disease-modifying anti-rheumatic drugs were recruited as part of the Biomarkers of Remission in Rheumatoid Arthritis (BioRRA) Study. In addition, patients from the Newcastle Early Arthritis Clinic (NEAC) with early active RA (DAS28-CRP > 2.4) or seronegative non-inflammatory arthralgia (NIA) were studied as positive and negative controls, respectively. The association between individual dependent variables (synovial power Doppler and greyscale, tenosynovial greyscale, and erosions) and clinical parameters was assessed by multivariate ordinal logistic regression, with adjustment for multiple testing. RESULTS: A total of 294 patients were included: 66 RA in remission, 146 active RA, and 82 NIA. Within the active RA group, significant associations were observed between swollen joint count and higher total synovial greyscale score (OR 1.17 95% CI 1.08-1.26, p < 0.001) and higher total synovial power Doppler score (OR 1.20, 95% CI 1.12-1.30, p < 0.001). No significant associations were observed for the NIA group. In the RA remission group, US abnormalities were frequently observed and comparable for both DAS28-CRP and 2011 ACR/EULAR Boolean remission, with no significant association with clinical parameters identified. CONCLUSION: We observed widespread subclinical US findings in RA patients in clinical remission, even when remission is defined using the stringent ACR/EULAR Boolean criteria. In contrast to active disease, synovial power Doppler failed to show significant association with any of the clinical parameters in RA remission. Our results suggest that clinical and US examinations are non-overlapping in evaluating RA remission, challenging the proposition of US-driven management strategies in this setting.

Cell function profiling to assess clone stability.

In cell line development the identification of stable Chinese hamster ovary cells for production is a critical but onerous task. The stability trial focus upon high-level attributes can mask profound underlying cellular changes, leading to unstable clones mistakenly being chosen for production. The challenge is to assay underlying cell pathways and subsystems without pushing up cell line development costs. ChemStress® cell function profiling is a simple, multiwell plate-based assay that uses a panel of active chemicals to mimic known bioprocess stresses and challenge key pathways. After 3 days of static culture on the plate, functional responses are assayed, for example, titer and growth. Here this approach is used to monitor 131 clones as they change over real stability trials. A novel stability metric is defined over the data to identify stable clones that remain unperturbed across many components of cell function. This allows stability trials to look beneath the titer to identify clones that are internally more stable.