A comparison of tumour and host prognostic factors in screen-detected versus non screen-detected colorectal cancer: a contemporaneous study

Aim: In addition to TNM stage, there are adverse tumour and host factors, such as venous invasion and the presence of an elevated systemic inflammatory response (SIR) that influence the outcome in colorectal cancer. The present study aimed to examine how these factors varied in screen detected (SD) and non-screen detected tumours (NSD). Method: Prospectively maintained databases of the prevalence round of a biennial population FOBt screening programme and a regional cancer audit database were analysed. Interval cancers (INT) were defined as cancers identified within two years of a negative screening test. Results: Of the 395 097 invited, 204 535 (52%) responded, 6159 (3%) tested positive, and 421 (9%) had cancer detected. From this cohort, a further 708 (63%) NSD patients were identified (468 (65%) non-responders, 182 (25%) INT cancers and 58 (10%) did not attend or did not have cancer diagnosed at colonoscopy). Comparing SD and NSD patients, SD patients were more likely to be male, and have a tumour with a lower Dukes stage (both p<0.05). On stage-by-stage analysis, SD patients had less evidence of an elevated SIR (p<0.05). Both the presence of venous invasion (p=0.761) and an elevated SIR (p=0.059) were similar between those with INT cancers and in those that arose in non-responders. Conclusion: Independent of TNM stage, SD tumours have more favourable host prognostic factors than NSD tumours. There is no evidence that INT cancers are biologically more aggressive than those that develop in the rest of the population and hence are likely to be due to limitations of screening in its current format

Impact of an informed choice invitation on uptake of screening for diabetes in primary care (DICISION): randomised trial

Objective To compare the effect of an invitation promoting informed choice for screening with a standard invitation on attendance and motivation to engage in preventive action

Developing a complex intervention to improve prescribing safety in primary care:mixed methods feasibility and optimisation pilot study

Objectives (A) To measure the extent to which different candidate outcome measures identified high-risk prescribing that is potentially changeable by the data-driven quality improvement in primary care (DQIP) intervention.(B) To explore the value of reviewing identified high-risk prescribing to clinicians.(C) To optimise the components of the DQIP intervention.  Design Mixed method study.  Setting General practices in two Scottish Health boards.  Participants 4 purposively sampled general practices of varying size and socioeconomic deprivation.  Outcome measures Prescribing measures targeting (1) high-risk use of the non-steroidal anti-inflammatory drugs (NSAIDs) and antiplatelets; (2) ‘Asthma control’ and (3) ‘Antithrombotics in atrial fibrillation (AF)’.  Intervention The prescribing measures were used to identify patients for review by general practices. The ability of the measures to identify potentially changeable high-risk prescribing was measured as the proportion of patients reviewed where practices identified a need for action. Field notes were recorded from meetings between researchers and staff and key staff participated in semistructured interviews exploring their experience of the piloted intervention processes.  Results Practices identified a need for action in 68%, 25% and 18% of patients reviewed for prescribing measures (1), (2) and (3), respectively. General practitioners valued being prompted to review patients, and perceived that (1) ‘NSAID and antiplatelet’ and (2) ‘antithrombotics in AF’ were the most important to act on. Barriers to initial and ongoing engagement and to sustaining improvements in prescribing were identified.  Conclusions ‘NSAIDs and antiplatelets’ measures were selected as the most suitable outcome measures for the DQIP trial, based on evidence of this prescribing being more easily changeable. In response to the barriers identified, the intervention was designed to include a financial incentive, additional ongoing feedback on progress and reprompting review of patients, whose high-risk prescribing was restarted after a decision to stop.  Trial registration number Clinicaltrials.govNCT01425502

Evaluating Active U: an Internet-mediated physical activity program.

Background: Engaging in regular physical activity can be challenging, particularly during the winter months. To promote physical activity at the University of Michigan during the winter months, an eight-week Internet-mediated program (Active U) was developed providing participants with an online physical activity log, goal setting, motivational emails, and optional team participation and competition. Methods: This study is a program evaluation of Active U. Approximately 47,000 faculty, staff, and graduate students were invited to participate in the online Active U intervention in the winter of 2007. Participants were assigned a physical activity goal and were asked to record each physical activity episode into the activity log for eight weeks. Statistics for program reach, effectiveness, adoption, and implementation were calculated using the Re-Aim framework. Multilevel regression analyses were used to assess the decline in rates of data entry and goal attainment during the program, to assess the likelihood of joining a team by demographic characteristics, to test the association between various predictors and the number of weeks an individual met his or her goal, and to analyze server load. Results: Overall, 7,483 individuals registered with the Active U website (≈16% of eligible), and 79% participated in the program by logging valid data at least once. Staff members, older participants, and those with a BMI < 25 were more likely to meet their weekly physical activity goals, and average rate of meeting goals was higher among participants who joined a competitive team compared to those who participated individually (IRR = 1.28, P < .001). Conclusion: Internet-mediated physical activity interventions that focus on physical activity logging and goal setting while incorporating team competition may help a significant percentage of the target population maintain their physical activity during the winter months

Effect on smoking quit rate of telling patients their lung age: the Step2quit randomised controlled trial

Objective To evaluate the impact of telling patients their estimated spirometric lung age as an incentive to quit smoking.Design Randomised controlled trial.Setting Five general practices in Hertfordshire, England.Participants 561 current smokers aged over 35.Intervention All participants were offered spirometric assessment of lung function. Participants in intervention group received their results in terms of "lung age" (the age of the average healthy individual who would perform similar to them on spirometry). Those in the control group received a raw figure for forced expiratory volume at one second (FEV1). Both groups were advised to quit and offered referral to local NHS smoking cessation services.Main outcome measures The primary outcome measure was verified cessation of smoking by salivary cotinine testing 12 months after recruitment. Secondary outcomes were reported changes in daily consumption of cigarettes and identification of new diagnoses of chronic obstructive lung disease.Results Follow-up was 89%. Independently verified quit rates at 12 months in the intervention and control groups, respectively, were 13.6% and 6.4% (difference 7.2%, P=0.005, 95% confidence interval 2.2% to 12.1%; number needed to treat 14). People with worse spirometric lung age were no more likely to have quit than those with normal lung age in either group. Cost per successful quitter was estimated at 280 pound ((euro) 365, $556). A new diagnosis of obstructive lung disease was made in 17% in the intervention group and 14% in the control group; a total of 16% (89/561) of participants.Conclusion Telling smokers their lung age significantly improves the likelihood of them quitting smoking, but the mechanism by which this intervention achieves its effect is unclear.Trial registration National Research Register N0096173751

Collaborative research between academia and industry using a large clinical trial database: a case study in Alzheimer's disease

<p>Abstract</p> <p>Background</p> <p>Large clinical trials databases, developed over the course of a comprehensive clinical trial programme, represent an invaluable resource for clinical researchers. Data mining projects sponsored by industry that use these databases, however, are often not viewed favourably in the academic medical community because of concerns that commercial, rather than scientific, goals are the primary purpose of such endeavours. Thus, there are few examples of sustained collaboration between leading academic clinical researchers and industry professionals in a large-scale data mining project. We present here a successful example of this type of collaboration in the field of dementia.</p> <p>Methods</p> <p>The Donepezil Data Repository comprised 18 randomised, controlled trials conducted between 1991 and 2005. The project team at Pfizer determined that the data mining process should be guided by a diverse group of leading Alzheimer's disease clinical researchers called the "Expert Working Group." After development of a list of potential faculty members, invitations were extended and a group of seven members was assembled. The Working Group met regularly with Eisai/Pfizer clinicians and statisticians to discuss the data, identify issues that were currently of interest in the academic and clinical communities that might lend themselves to investigation using these data, and note gaps in understanding or knowledge of Alzheimer's disease that these data could address. Leadership was provided by the Pfizer Clinical Development team leader; Working Group members rotated responsibility for being lead and co-lead for each investigation and resultant publication.</p> <p>Results</p> <p>Six manuscripts, each published in a leading subspecialty journal, resulted from the group's work. Another project resulted in poster presentations at international congresses and two were cancelled due to resource constraints.</p> <p>Conclusions</p> <p>The experience represents a particular approach to optimising the value of data mining of large clinical trial databases for the combined purpose of furthering clinical research and improving patient care. Fruitful collaboration between industry and academia was fostered while the donepezil data repository was used to advance clinical and scientific knowledge. The Expert Working Group approach warrants consideration as a blueprint for conducting similar research ventures in the future.</p

Acceptance and Perception of Artificial Intelligence Usability in Eye Care (APPRAISE) for Ophthalmologists: A Multinational Perspective

Background: Many artificial intelligence (AI) studies have focused on development of AI models, novel techniques, and reporting guidelines. However, little is understood about clinicians' perspectives of AI applications in medical fields including ophthalmology, particularly in light of recent regulatory guidelines. The aim for this study was to evaluate the perspectives of ophthalmologists regarding AI in 4 major eye conditions: diabetic retinopathy (DR), glaucoma, age-related macular degeneration (AMD) and cataract. Methods: This was a multi-national survey of ophthalmologists between March 1st, 2020 to February 29th, 2021 disseminated via the major global ophthalmology societies. The survey was designed based on microsystem, mesosystem and macrosystem questions, and the software as a medical device (SaMD) regulatory framework chaired by the Food and Drug Administration (FDA). Factors associated with AI adoption for ophthalmology analyzed with multivariable logistic regression random forest machine learning. Results: One thousand one hundred seventy-six ophthalmologists from 70 countries participated with a response rate ranging from 78.8 to 85.8% per question. Ophthalmologists were more willing to use AI as clinical assistive tools (88.1%, n = 890/1,010) especially those with over 20 years' experience (OR 3.70, 95% CI: 1.10–12.5, p = 0.035), as compared to clinical decision support tools (78.8%, n = 796/1,010) or diagnostic tools (64.5%, n = 651). A majority of Ophthalmologists felt that AI is most relevant to DR (78.2%), followed by glaucoma (70.7%), AMD (66.8%), and cataract (51.4%) detection. Many participants were confident their roles will not be replaced (68.2%, n = 632/927), and felt COVID-19 catalyzed willingness to adopt AI (80.9%, n = 750/927). Common barriers to implementation include medical liability from errors (72.5%, n = 672/927) whereas enablers include improving access (94.5%, n = 876/927). Machine learning modeling predicted acceptance from participant demographics with moderate to high accuracy, and area under the receiver operating curves of 0.63–0.83. Conclusion: Ophthalmologists are receptive to adopting AI as assistive tools for DR, glaucoma, and AMD. Furthermore, ML is a useful method that can be applied to evaluate predictive factors on clinical qualitative questionnaires. This study outlines actionable insights for future research and facilitation interventions to drive adoption and operationalization of AI tools for Ophthalmology

Awareness and knowledge of intra-abdominal hypertension and abdominal compartment syndrome: results of an international survey

Background: Surveys have demonstrated a lack of physician awareness of intra-abdominal hypertension and abdominal compartment syndrome (IAH/ACS) and wide variations in the management of these conditions, with many intensive care units (ICUs) reporting that they do not measure intra-abdominal pressure (IAP). We sought to determine the association between publication of the 2006/2007 World Society of the Abdominal Compartment Syndrome (WSACS) Consensus Definitions and Guidelines and IAH/ACS clinical awareness and management. Methods: The WSACS Executive Committee created an interactive online survey with 53 questions, accessible from November 2006 until December 2008. The survey was endorsed by the WSACS, the European Society of Intensive Care Medicine (ESICM) and the Society of Critical Care Medicine (SCCM). A link to the survey was emailed to all members of the supporting societies. Participants of the 3rd World Congress on Abdominal Compartment Syndrome meeting (March 2007, Antwerp, Belgium) were also asked to complete the questionnaire. No reminders were sent. Based on 13 knowledge questions, an overall score was calculated (expressed as percentage). Results: A total of 2,244 of the approximately 10,000 clinicians who were sent the survey responded (response rate: 22.4%). Most of the 2,244 respondents (79.2%) completing the survey were physicians or physicians in training and the majority were residing in North America (53.0%). The majority of responders (85%) were familiar with IAP/IAH/ACS, but only 28% were aware of the WSACS consensus definitions for IAH/ACS. Three quarters of respondents considered the cut-off for IAH to be at least 15 mm Hg, and nearly two thirds believed the cut-off for ACS was higher than the currently suggested consensus definition (20 mm Hg). In 67.8% of respondents, organ dysfunction was only considered a problem with IAP of 20 mm Hg or higher. IAP was measured most frequently via the bladder (91.9%), but the majority reported that they instilled volumes well above the current guidelines. Surgical decompression was frequently used to treat IAH/ACS, whereas medical management was only attempted by about half of the respondents. Decisions to decompress the abdomen were predominantly based on the severity of IAP elevation and presence of organ dysfunction (74.4%). Overall knowledge scores were low (43 +/- 15%); respondents who were aware of the WSACS had a better score compared to those who were not (49.6% vs 38.6%, P < 0.001). Conclusions: This survey showed that although most responding clinicians claim to be familiar with IAH and ACS, knowledge of published consensus definitions, measurement techniques, and clinical management is inadequate

Enhanced invitation methods and uptake of health checks in primary care. Rapid randomised controlled trial using electronic health records

Background: A national programme of health checks to identify risk of cardiovascular disease is being rolled out but is encountering difficulties of low uptake. Objective: To evaluate the effectiveness of an enhanced invitation method using the Question-Behaviour Effect (QBE), with or without the offer of a financial incentive to return the QBE questionnaire, at increasing the uptake of health checks. Secondary objectives were to evaluate reasons for low uptake of invitations and to compare case-mix for invited and opportunistic health checks. Trial design: Three-arm randomised trial. Participants: All participants invited for health checks from 18 general practices. Randomisation: Individual participants were randomised. Interventions: i) standard health check invitation only, ii) QBE questionnaire followed by standard invitation; iii) QBE questionnaire with offer of a financial incentive to return the questionnaire, followed by standard invitation. Outcomes: The primary outcome was completion of health check within six months of randomisation. A P value of 0.0167 was used for significance. Case-mix was evaluated for invited and opportunistic health checks. Blinding: Participants were not aware that several types of invitation were in use. The research team were blind to trial arm allocation at outcome data extraction. Results: There were 12,459 participants allocated and health check uptake was evaluated for 12,052 participants for whom outcome data were collected. Health check uptake was: standard invitation, 590 / 4,095 (14.4%); QBE questionnaire, 630 / 3,988 (15.8%); QBE questionnaire and financial incentive, 629 / 3,969 (15.9%). The increase in uptake associated with QBE questionnaire was 1.43% (95% confidence interval -0.12 to 2.97%, P=0.070) and for the QBE questionnaire and offer of financial incentive was 1.52% (-0.03 to 3.07%, P=0.054). The difference in uptake associated with the offer of an incentive to return the QBE questionnaire was -0.01% (-1.59 to 1.58%, P=0.995). During the study, 58% of health check cardiovascular risk assessments did not follow a trial invitation. People who received ‘opportunistic’ health checks had greater odds of ≥10% cardiovascular disease (CVD) risk; adjusted odds ratio 1.70, 95% confidence interval 1.45 to 1.99, P<0.001) compared with invited health checks. Conclusion: Uptake of health checks following an invitation letter is low and is not increased through an enhanced invitation method using the QBE, with or without an incentive. A high proportion of all health checks are performed opportunistically. Participants receiving opportunistic checks are at higher risk of CVD than those responding to standard invitations. Trial registration: Current Controlled Trials ISRCTN42856343

Lung cancer screening participation: attitudinal, socioeconomic and smoking-related factors

Socioeconomic and smoking-related biases in participation threaten the equity and effectiveness of any future UK lung cancer screening programme. This thesis used a mixed methods approach to investigate psychosocial and cognitive factors that might contribute to these biases, with the aim of identifying possible targets for intervention in screening communication strategies. This informed the design of screening invitation materials aimed at engaging low socioeconomic position (SEP) smokers with a screening offer, which were tested using a randomised controlled pilot trial. The findings of these studies suggest that the introduction of a lung cancer screening programme would be acceptable to older English adults. However, while there was high willingness to be screened (>91%), this was not matched by high uptake of screening in the pilot trial (55%). Chapters 4 to 7 showed that negative beliefs about outcomes and early detection for lung cancer were prevalent among participants recruited from low SEP communities, and associated with current smoking status. Compared with their non-smoking counterparts, smokers more commonly expressed fatalistic beliefs about risk, survival and treatment for lung cancer (including early stage disease), worried about lung cancer and the outcome of screening, and perceived smoking and lung cancer to be stigmatised. Intervention screening invitation materials were designed to improve uptake by minimising these factors but an early interim analysis of the pilot trial testing these materials showed no effect on uptake of lung cancer screening appointments (n=241; final target N=2000). Lower SEP smokers’ more negative expectations of risk, stigma, treatment and outcomes for lung cancer, particularly for older high risk adults, appear to undermine the salience and perceived personal benefit of lung cancer screening. Further work needs to be done to explore whether interventions can effectively modify these perceptions to improve engagement with screening among the very group most likely to benefit