Machine learning-based approach for automated classification of cell and extracellular matrix using nanomechanical properties.

Fibrosis characterized by excess accumulation of extracellular matrix (ECM) due to complex cell-ECM interactions plays a pivotal role in pathogenesis. Herein, we employ the pancreatic ductal adenocarcinoma (PDAC) model to investigate dynamic alterations in nanomechanical attributes arising from the cell-ECM interactions to study the fibrosis paradigm. Several segregated studies performed on cellular and ECM components fail to recapitulate their complex collaboration. We utilized collagen and fibronectin, the two most abundant PDAC ECM components, and studied their nanomechanical attributes. We demonstrate alteration in morphology and nanomechanical attributes of collagen with varying thicknesses of collagen gel. Furthermore, by mixing collagen and fibronectin in various stoichiometry, their nanomechanical attributes were observed to vary. To demonstrate the dynamicity and complexity of cell-ECM, we utilized Panc-1 and AsPC-1 cells with or without collagen. We observed that Panc-1 and AsPC-1 cells interact differently with collagen and vice versa, evident from their alteration in nanomechanical properties. Further, using nanomechanics data, we demonstrate that ML-based techniques were able to classify between ECM as well as cell, and cell subtypes in the presence/absence of collagen with higher accuracy. This work demonstrates a promising avenue to explore other ECM components facilitating deeper insights into tumor microenvironment and fibrosis paradigm.

Exploration of pain assessment and management processes in oncology outpatient services with healthcare professionals: a qualitative study.

OBJECTIVES: This study explored cancer pain management practices and clinical care pathways used by healthcare professionals (HCPs) to understand the barriers and facilitators for standardised pain management in oncology outpatient services (OS). DESIGN: Data were collected using semistructured interviews that were audio-recorded and transcribed. The data were analysed using thematic analysis. SETTING: Three NHS trusts with oncology OS in Northern England. PARTICIPANTS: Twenty HCPs with varied roles (eg, oncologist and nurse) and experiences (eg, registrar and consultant) from different cancer site clinics (eg, breast and lung). Data were analysed using thematic analysis. RESULTS: HCPs discussed cancer pain management practices during consultation and supporting continuity of care beyond consultation. Key findings included : (1) HCPs' level of clinical experience influenced pain assessments; (2) remote consulting impeded experienced HCPs to do detailed pain assessments; (3) diffusion of HCP responsibility to manage cancer pain; (4) nurses facilitated pain management support with patients and (5) continuity of care for pain management was constrained by the integration of multidisciplinary teams. CONCLUSIONS: These data demonstrate HCP cancer pain management practices varied and were unstructured. Recommendations are made for a standardised cancer pain management intervention: (1) detailed evaluation of pain with a tailored self-management strategy; (2) implementation of a structured pain assessment that supports remote consultations, (3) pain assessment tool that can support both experienced and less experienced clinicians. These findings will inform the development of a cancer pain management tool to integrate within routine oncology OS.

Increased Breast and Colorectal Cancer Risk in Type 2 Diabetes: Awareness Among Adults With and Without Diabetes and Information Provision on Diabetes Websites.

BACKGROUND: People with type 2 diabetes mellitus (T2DM) have a higher risk of developing breast and bowel cancers but are less likely to participate in cancer screening. PURPOSE: Two interlinked studies examined public awareness of the fact that T2DM increases breast and bowel cancer risk, and provision of this information on diabetes websites. METHODS: Study-1: phase-1 surveyed awareness of T2DM-increased cancer risk in a nationally-representative British sample aged 50-74 (N = 1,458) and compared respondents with and without T2DM (n = 125 vs. n = 1,305); phase-2 surveyed an additional exclusively T2DM sample (N = 319). Study-2: High-ranking diabetes websites (N = 25) were reviewed to determine the rate of inclusion of cancer risk and cancer screening information in evident sections about diabetes-related health conditions. RESULTS: A low proportion of respondents were aware that T2DM increases risk of breast (13.7%) and bowel (27.6%) cancers, compared to much higher awareness of other diabetes-related conditions such as sight loss (82.2%) and foot problems (81.8%). Respondents with T2DM were significantly more likely than those without T2DM to be aware of all the surveyed diabetes-related health conditions (e.g., sight loss, OR: 3.14, 95%CI: 1.61-6.15; foot problems, OR: 2.58, 95%CI: 1.38-4.81), except breast (OR: 0.82, 95%CI: 0.46-1.45) and bowel (OR: 0.95, 95%CI: 0.63-1.45) cancer, for which awareness was equally low among people with and without T2DM. Few diabetes websites with a section on diabetes-related health conditions included cancer in this section (n = 4/19), and fewer still included cancer screening among any noted cancer-protective behaviors (n = 2/4). CONCLUSIONS: There is low public awareness that T2DM increases the risk of developing breast and bowel cancers, even among people with T2DM, which may be partly due to limited information provision regarding T2DM-increased cancer risk from diabetes care providers and organizations.

People with type 2 diabetes (T2D) have a higher risk of developing breast and bowel cancers. Despite this, they are less likely to participate in cancer screening, which can improve survival from cancer. We addressed two questions. Are people aware that T2D increases the risk of breast and bowel cancer? Are people being told about this by diabetes care providers and organizations? We surveyed a large representative sample of the British public (aged 50­74). We also reviewed key information about diabetes-related health problems provided on 25 top-ranking diabetes websites. There were three main findings. (1) Relatively few people knew that T2D increases the risk of breast and bowel cancer. In contrast, many people knew that T2D increases the risk of other conditions like sight loss, foot problems, and heart disease. (2) Awareness of higher cancer risk was equally low among people with T2D and those without. In contrast, knowledge of other diabetes-related conditions (e.g., sight loss, foot problems) was higher among people with T2D than those without. (3) Few websites included cancer in their key information about diabetes-related health problems. In contrast, nearly all the diabetes websites listed the more well-known risks of sight loss, foot problems, and heart disease.

Using Fracture Patterns and Planned Operative Modality to Identify Fractured Neck of Femur Patients at High Risk of Blood Transfusion.

Background Fractured neck of femurs is common, serious injuries usually requiring operative management. Red blood cell transfusions are often required to treat perioperative anaemia, but these are not without adverse effects. Aims and objectives The aim of this study is to identify subgroups of fractured neck of femur patients more likely to require red blood cell transfusions. We try to identify targeted strategies to reduce blood transfusion-associated adverse effects and thus improve outcomes. Design and methods A retrospective cohort study of 324 patients. Patients were divided into cohorts based on radiological fracture patterns and operations performed. Data were collected from patient records, picture archiving and communication systems, the local transfusion laboratory, and the national hip fracture database. The primary outcome was blood transfusion rates in different fracture patterns in fractured necks of femur patients. The secondary outcome was blood transfusion rates in different operation types for fractured neck of femur patients. Chi-squared tests for independence were performed. Results 14.9%, 34.7% and 33.3% of patients with intracapsular, intertrochanteric and subtrochanteric fractures, respectively, received blood transfusions. There was a significant relationship between fracture pattern and blood transfusion (X 2 (2, N = 324) = 17.1687, p = 0.000187). 47% of patients receiving long intramedullary nails, 45% of short intramedullary nails, 27% of open reduction internal fixations, 18% of hemiarthroplasties and 9% of total hip arthroplasties resulted in blood transfusions. There was a significant relationship between operative modality and blood transfusion (X 2 (4, N = 302) = 22.0184, p = 0.000199). Conclusion In patients who have sustained a fractured neck of the femur, the fracture pattern and operative modality are both independently associated with the rates of red blood cell transfusion. In these identified groups, we propose that increased vigilance and awareness regarding transfusion avoiding strategies are utilised with the goal of improving patient outcomes.

Staff experiences of implementing Dementia Care Mapping to improve the quality of dementia care in care homes: a qualitative process evaluation.

BACKGROUND: Dementia Care Mapping™ (DCM) is a widely used, staff-led, psychosocial intervention to support the implementation of person-centred care. Efficacy evaluations in care homes have produced mixed outcomes, with implementation problems identified. Understanding the experiences of staff trained to lead DCM implementation is crucial to understanding implementation challenges, yet this has rarely been formally explored. This study aimed to examine the experiences of care home staff trained to lead DCM implementation, within a large cluster randomised controlled trial. METHODS: Process evaluation including, semi-structured interviews with 27 trained mappers from 16 intervention allocated care homes. Data were analysed using template variant of thematic analysis. RESULTS: Three main themes were identified 1) Preparedness to lead - While mappers overwhelmingly enjoyed DCM training, many did not have the personal attributes required to lead practice change and felt DCM training did not adequately equip them to implement it in practice. For many their expectations of the mapper role at recruitment contrasted with the reality once they began to attempt implementation; 2) Transferring knowledge into practice - Due to the complex nature of DCM, developing mastery required regular practice of DCM skills, which was difficult to achieve within available time and resources. Gaining engagement of and transferring learning to the wider staff team was challenging, with benefits of DCM largely limited to the mappers themselves, rather than realised at a care home level; and 3) Sustaining DCM - This required a perception of DCM as beneficial, allocation of adequate resources and support for the process which was often not able to be provided, for the mapper role to fit with the staff member's usual duties and for DCM to fit with the home's ethos and future plans for care. CONCLUSIONS: Many care homes may not have staff with the requisite skills to lead practice change using DCM, or the requisite staffing, resources or leadership support required for sustainable implementation. Adaptations to the DCM tool, process and training may be required to reduce its complexity and burden and increase chances of implementation success. Alternatively, models of implementation not reliant on care home staff may be required.

Effectiveness of Dementia Care Mapping™ to reduce agitation in care home residents with dementia: an open-cohort cluster randomised controlled trial.

OBJECTIVES: Agitation is common and problematic in care home residents with dementia. This study investigated the (cost)effectiveness of Dementia Care Mapping™ (DCM) for reducing agitation in this population. METHOD: Pragmatic, cluster randomised controlled trial with cost-effectiveness analysis in 50 care homes, follow-up at 6 and 16 months and stratified randomisation to intervention (n = 31) and control (n = 19). Residents with dementia were recruited at baseline (n = 726) and 16 months (n = 261). Clusters were not blinded to allocation. Three DCM cycles were scheduled, delivered by two trained staff per home. Cycle one was supported by an external DCM expert. Agitation (Cohen-Mansfield Agitation Inventory (CMAI)) at 16 months was the primary outcome. RESULTS: DCM was not superior to control on any outcomes (cross-sectional sample n = 675: 287 control, 388 intervention). The adjusted mean CMAI score difference was -2.11 points (95% CI -4.66 to 0.44, p = 0.104, adjusted ICC control = 0, intervention 0.001). Sensitivity analyses supported the primary analysis. Incremental cost per unit improvement in CMAI and QALYs (intervention vs control) on closed-cohort baseline recruited sample (n = 726, 418 intervention, 308 control) was £289 and £60,627 respectively. Loss to follow-up at 16 months in the original cohort was 312/726 (43·0%) mainly (87·2%) due to deaths. Intervention dose was low with only a quarter of homes completing more than one DCM cycle. CONCLUSION: No benefits of DCM were evidenced. Low intervention dose indicates standard care homes may be insufficiently resourced to implement DCM. Alternative models of implementation, or other approaches to reducing agitation should be considered.

Serum D-dimer should not be used in the diagnosis of venous thromboembolism within 28 days of total knee replacement surgery.

BACKGROUND: Serum D-dimer is frequently used to rule out a diagnosis of venous thromboembolism (VTE), a recognised complication following total knee replacement (TKR). TKR is known to cause a rise in D-dimer levels, reducing its specificity. Previous studies have demonstrated that D-dimer remains elevated within 10 days of TKR and therefore should be avoided. The aim of this study was to determine whether serum D-dimer tests are clinically appropriate in identifying VTE when performed within 28 days of TKR. METHODS: Case notes for patients who had a serum D-dimer test performed for clinically suspected VTE at ≥ 28 days following TKR were retrospectively reviewed for a 6-year period. Demographics, D-dimer result, time after surgery and further radiological investigations were recorded. RESULTS: Fifty patients underwent D-dimer tests at ≥ 28 days following surgery (median 60 days, range 29-266); 48 of these patients had a positive result. Of these, five had confirmed VTE on radiological investigations. Serum D-dimer was raised in 96% of the patients. Only 10.42% of these patients had confirmed VTE. No patients with negative D-dimers had confirmed VTE. CONCLUSIONS: These findings suggest that serum D-dimer remains raised for at least 28 days and possibly considerably longer following TKR. Serum D-dimer should not be used in patients with clinically suspected VTE within this period because of its unacceptably low specificity of 4.44% and positive predictive value of 10.42%, which can lead to a delay in necessary further radiological investigations, waste of resources and unnecessary exposure to harm.

Dementia Care Mapping™ to reduce agitation in care home residents with dementia: the EPIC cluster RCT.

BACKGROUND: The quality of care for people with dementia in care homes is of concern. Interventions that can improve care outcomes are required. OBJECTIVE: To investigate the clinical effectiveness and cost-effectiveness of Dementia Care Mapping™ (DCM) for reducing agitation and improving care outcomes for people living with dementia in care homes, versus usual care. DESIGN: A pragmatic, cluster randomised controlled trial with an open-cohort design, follow-up at 6 and 16 months, integrated cost-effectiveness analysis and process evaluation. Clusters were not blinded to allocation. The primary end point was completed by staff proxy and independent assessors. SETTING: Stratified randomisation of 50 care homes to the intervention and control groups on a 3 : 2 ratio by type, size, staff exposure to dementia training and recruiting hub. PARTICIPANTS: Fifty care homes were randomised (intervention, n = 31; control, n = 19), with 726 residents recruited at baseline and a further 261 recruited after 16 months. Care homes were eligible if they recruited a minimum of 10 residents, were not subject to improvement notices, had not used DCM in the previous 18 months and were not participating in conflicting research. Residents were eligible if they lived there permanently, had a formal diagnosis of dementia or a score of 4+ on the Functional Assessment Staging Test of Alzheimer's Disease, were proficient in English and were not terminally ill or permanently cared for in bed. All homes were audited on the delivery of dementia and person-centred care awareness training. Those not reaching a minimum standard were provided training ahead of randomisation. Eighteen homes took part in the process evaluation. INTERVENTION: Two staff members from each intervention home were trained to use DCM and were asked to carry out three DCM cycles; the first was supported by an external expert. MAIN OUTCOME MEASURES: The primary outcome was agitation (Cohen-Mansfield Agitation Inventory), measured at 16 months. Secondary outcomes included resident behaviours and quality of life. RESULTS: There were 675 residents in the final analysis (intervention, n = 388; control, n = 287). There was no evidence of a difference in agitation levels between the treatment arms. The adjusted mean difference in Cohen-Mansfield Agitation Inventory score was -2.11 points, being lower in the intervention group than in the control (95% confidence interval -4.66 to 0.44; p = 0.104; adjusted intracluster correlation coefficient: control = 0, intervention = 0.001). The sensitivity analyses results supported the primary analysis. No differences were detected in any of the secondary outcomes. The health economic analyses indicated that DCM was not cost-effective. Intervention adherence was problematic; only 26% of homes completed more than their first DCM cycle. Impacts, barriers to and facilitators of DCM implementation were identified. LIMITATIONS: The primary completion of resident outcomes was by staff proxy, owing to self-report difficulties for residents with advanced dementia. Clusters were not blinded to allocation, although supportive analyses suggested that any reporting bias was not clinically important. CONCLUSIONS: There was no benefit of DCM over control for any outcomes. The implementation of DCM by care home staff was suboptimal compared with the protocol in the majority of homes. FUTURE WORK: Alternative models of DCM implementation should be considered that do not rely solely on leadership by care home staff. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82288852. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 16. See the NIHR Journals Library website for further project information.

Agitation is common in care home residents and may result from care that does not meet individual needs. Dementia Care Mapping™ (DCM) is a tool used within care homes to improve the delivery of person-centred care, which may help reduce agitation. This randomised controlled trial aimed to understand whether or not DCM is better than usual care at reducing resident agitation, behaviours that staff may find difficult to support and the use of antipsychotic medicines, as well as at improving residents' quality of life and staff communication. It also assessed its value for money. We recruited 726 residents with dementia from 50 care homes. After initial data collection, care homes were randomly assigned to DCM (31/50) or told to continue with usual care (19/50) and data were collected again after 6 and 16 months. A further 261 residents were recruited after 16 months. We also interviewed staff, relatives and residents about the use of DCM after the final data collection had taken place. Two staff members in each DCM home were trained to use DCM and were helped by an expert to use it for the first time. They were asked to use it again a further two times without support. Results showed that DCM was no better than usual care in relation to any of the outcomes. It was also not shown to be value for money. Only one-quarter of care homes used DCM more than once. The care staff who were interviewed said that the benefits of using DCM included reduced resident boredom and increased staff confidence. There were also many challenges, including the time needed to complete DCM, a lack of managerial support and problems with staffing levels. Putting DCM into practice in care homes was difficult, even with expert support, and most care homes did not complete three DCM cycles. Future research should explore models of implementing DCM that do not rely on care home staff to lead them.

Are more experienced clinicians better able to tolerate uncertainty and manage risks? A vignette study of doctors in three NHS emergency departments in England.

BACKGROUND: Risk aversion among junior doctors that manifests as greater intervention (ordering of tests, diagnostic procedures and so on) has been proposed as one of the possible causes for increased pressure in emergency departments (EDs). Here we tested the prediction that doctors with more experience would be more tolerant of uncertainty and therefore less risk-averse in decision making. METHODS: In this cross-sectional, vignette-based study, doctors working in three EDs were asked to complete a questionnaire measuring experience (length of service in EDs), reactions to uncertainty (Gerrity et al, 1995) and risk aversion (responses about the appropriateness of patient management decisions). RESULTS: Data from 90 doctors were analysed. Doctors had worked in the ED for between 5 weeks and 21 years. We found a large association between experience and risk aversion so that more experienced clinicians made less risk-averse decisions (r=0.47, p<0.001). We also found a large association between experience and reactions to uncertainty (r=-0.50, p<0.001), with more experienced doctors being much more at ease with uncertainty. Mediation analyses indicated that tolerance of uncertainty partially mediated the relationship between experience and lower risk aversion, explaining about a quarter of the effect. CONCLUSION: While we might be tempted to conclude from this research that experience and the ability to tolerate uncertainty lead to positive outcomes for patients (less risk-averse management strategies and higher levels of safety netting), what we are unable to conclude from this design is that these less risk-averse strategies improve patient safety.

Barriers and facilitators to implementing dementia care mapping in care homes: results from the DCM™ EPIC trial process evaluation.

BACKGROUND: Psychosocial person-centred interventions are considered best practice for addressing complex behaviours and care needs such as agitation and anxiety, and for improving the quality of life of people with dementia in care homes. Dementia Care Mapping (DCM™) is an established practice development tool and process aimed to help care home staff deliver more person-centred care. To date, few studies have evaluated the efficacy of DCM™ and have found mixed results. These results are suggested to be the outcome of intervention implementation, which may be impacted by a range of factors. This study reports the barriers and facilitators to DCM™ implementation in care homes found during the process evaluation conducted as part of a randomized controlled trial. METHODS: Eighteen of the 31 DCM™ intervention care homes were recruited to participate in the embedded process evaluation. Semi-structured interviews were conducted with 83 participants, comprising care home managers, trained DCM™ users (mappers), expert external mappers, staff members, relatives, and residents. RESULTS: Barriers and facilitators to DCM™ implementation were found at the mapper level (e.g. motivation and confidence), the DCM™ intervention level (e.g. understanding of DCM™) and the care home level (e.g. staffing issues, manager support). Further barriers caused by the burden of trial participation were also identified (e.g. additional paperwork). CONCLUSIONS: Implementing DCM™ is complex and a greater consideration of potential barriers and facilitators in planning future studies and in practice could help improve implementation. TRIAL REGISTRATION: Current Controlled Trials ISRCTN82288852 , registered 16/01/2014.

Information, Advocacy and Signposting as a Low-Level Support for Adults with High-Functioning Autism Spectrum Disorder: An Example from the UK.

'Low-level' support is championed to support adults with high functioning autism spectrum disorder (HFASD) to achieve good quality health and social care, yet research in the area is sparse. Drawing on semi-structured interview data, this paper considers the efficacy of an intervention to provide low-level support to adults with HFASD with little or no funded support. The intervention led to a number of perceived positive outcomes for adults with HFASD, their families, and service providers in the city, including increased access to education, volunteering, support and information, socialising, improved health and wellbeing, and managing day-to-day. Although many of life's difficulties still persisted, the intervention helped service users overcome barriers to availing further support, possibly leading to beneficial outcomes down the line.