Development, validation, and evaluation of prediction models to identify individuals at high risk of lung cancer for screening in the English primary care population using the QResearch database: research protocol and statistical analysis plan

Background and research aim: Lung cancer is a research priority in the UK. Early diagnosis of lung cancer can improve patients' survival outcomes. The DART-QResearch project is part of a larger academic-industrial collaborative initiative, using big data and artificial intelligence to improve patient outcomes with thoracic diseases. There are two general research aims in the DART-QResearch project: (1) to understand the natural history of lung cancer, (2) to develop, validate, and evaluate risk prediction models to select patients at high risk for lung cancer screening. Methods: This population-based cohort study uses the QResearch database (version 45) and includes patients aged between 25 and 84 years old and without a diagnosis of lung cancer at cohort entry (study period: 1 January 2005 to 31 December 2020). The team conducted a literature review (with additional clinical input) to inform the inclusion of variables for data extraction from the QResearch database. The following statistical techniques will be used for different research objectives, including descriptive statistics, multi-level modelling, multiple imputation for missing data, fractional polynomials to explore non-linear relationships between continuous variables and the outcome, and Cox regression for the prediction model. We will update our QCancer (lung, 10-year risk) algorithm, and compare it with the other two mainstream models (LLP and PLCOM2012) for lung cancer screening using the same dataset. We will evaluate the discrimination, calibration, and clinical usefulness of the prediction models, and recommend the best one for lung cancer screening for the English primary care population. Discussion: The DART-QResearch project focuses on both symptomatic presentation and asymptomatic patients in the lung cancer care pathway. A better understanding of the patterns, trajectories, and phenotypes of symptomatic presentation may help GPs consider lung cancer earlier. Screening asymptomatic patients at high risk is another route to achieve earlier diagnosis of lung cancer. The strengths of this study include using large-scale representative population-based clinical data, robust methodology, and a transparent research process. This project has great potential to contribute to the national cancer strategic plan and yields substantial public and societal benefits through earlier diagnosis of lung cancer.

Care of Transgender Patients: A General Practice Quality Improvement Approach

Primary care must ensure high quality lifelong care is offered to trans and gender minority patients who are known to have poor health and adverse healthcare experiences. This quality improvement project aimed to interrogate and audit the data of trans and gender minority patients in one primary care population in England. A new data collection instrument was created examining pathways of care, assessments and interventions undertaken, monitoring, and complications. General practitioners identified a sample from the patient population and then performed an audit to examine against an established standard of care. No appropriate primary care audit standard was found. There was inconsistency between multiple UK gender identity clinics’ (GIC) individual recommended schedules of care and between specialty guidelines. Using an international, secondary care, evidence-informed guideline, it appeared that up to two-thirds of patients did not receive all recommended monitoring standards, largely due to inconsistencies between GIC and international guidance. It is imperative that an evidence-based primary care guideline is devised alongside measurable standards. Given the findings of long waits, high rates of medical complexity, and some undesired treatment outcomes (including a fifth of patients stopping hormones of whom more than half cited regret or detransition experiences), this small but population-based quality improvement approach should be replicated and expanded upon at scale.

Diabetes, Obesity, and Osteoporosis in an Ethnically Diverse Population of Women Receiving Osteoporosis Screening

Osteoporosis screening by bone density (BMD) testing is recommended for women aged 65-75 years. However, patients with diabetes, a risk factor for fracture, often have higher body mass index (BMI) which contributes to higher BMD. These factors may vary by race/ethnicity. The relationship of diabetes (≥2 diagnoses and treatment), obesity (BMI ≥30), and BMD-defined osteoporosis (femoral neck BMD T-score ≤ -2.5) was examined in a diverse primary care population of 44,313 non-Hispanic White, 6,103 Black, 7,777 Hispanic, and 12,634 Asian women aged 65-75 years who underwent BMD screening. Those with recent fracture, osteoporosis treatment, bone disorders, and metastatic cancer were excluded. Modified log-Poisson regression was used to examine the association of diabetes and BMD-osteoporosis. Among 70,827 women, 18% had diabetes. The prevalence of diabetes was 2-fold higher in Black, Hispanic and Asian women compared to White women. Overall, women with diabetes (versus no diabetes) were more likely to be obese and, except for Hispanic women, less likely to have BMD-osteoporosis. In unadjusted analyses, diabetes was associated with lower risk of BMD-defined osteoporosis in White, Black, and Asian women, but not Hispanic women. However, the association was attenuated or no longer evident after adjusting for BMI, suggesting that the lower burden of BMD-osteoporosis in women with diabetes is mediated in part by higher BMI. These findings support consideration of diabetes when assessing fracture risk in women undergoing osteoporosis screening. However, more studies in non-White populations with a high burden of diabetes are important since these relationships appear to differ by race/ethnicity.

Causation Research on Diabetic Foot Complications—What I Learned From Roger Pecoraro: The 2021 Roger E. Pecoraro Award Lecture

Roger Pecoraro made important contribution to diabetic foot research and is primarily responsible for instilling in me an interest in these complications. Our collaboration in the final years of his life led to the development of the Seattle Diabetic Foot Study. At the time it began, the Seattle Diabetic Foot Study was perhaps unique in being a prospective study of diabetic foot ulcer conducted in a non-specialty primary care population of patients with diabetes and without foot ulcer. Important findings from this research include the demonstration that neurovascular measurements, diabetes characteristics, past history of ulcer or amputation, body weight, and poor vision all significantly and independently predict foot ulcer risk. A prediction model from this research that included only readily available clinical information showed excellent ability to discriminate between patients who did and did not develop ulcer during follow-up (area under ROC curve=0.81 at one year). Identification of limb-specific amputation risk factors showed considerable overlap with those risk factors identified for foot ulcer, but suggested arterial perfusion as playing a more important role. Risk of foot ulcer in relation to peak plantar pressure estimated at the site of the pressure measurement showed a significant association over the metatarsal heads, but not other foot locations, suggesting that the association between pressure and this outcome may differ by foot location. The Seattle Diabetic Foot Study has helped to expand our knowledge base on risk factors and potential causes of foot complications. Translating this information into preventive interventions remains a continuing challenge.

Causation Research on Diabetic Foot Complications—What I Learned From Roger Pecoraro: The 2021 Roger E. Pecoraro Award Lecture

Roger Pecoraro made important contribution to diabetic foot research and is primarily responsible for instilling in me an interest in these complications. Our collaboration in the final years of his life led to the development of the Seattle Diabetic Foot Study. At the time it began, the Seattle Diabetic Foot Study was perhaps unique in being a prospective study of diabetic foot ulcer conducted in a non-specialty primary care population of patients with diabetes and without foot ulcer. Important findings from this research include the demonstration that neurovascular measurements, diabetes characteristics, past history of ulcer or amputation, body weight, and poor vision all significantly and independently predict foot ulcer risk. A prediction model from this research that included only readily available clinical information showed excellent ability to discriminate between patients who did and did not develop ulcer during follow-up (area under ROC curve=0.81 at one year). Identification of limb-specific amputation risk factors showed considerable overlap with those risk factors identified for foot ulcer, but suggested arterial perfusion as playing a more important role. Risk of foot ulcer in relation to peak plantar pressure estimated at the site of the pressure measurement showed a significant association over the metatarsal heads, but not other foot locations, suggesting that the association between pressure and this outcome may differ by foot location. The Seattle Diabetic Foot Study has helped to expand our knowledge base on risk factors and potential causes of foot complications. Translating this information into preventive interventions remains a continuing challenge.

Suicidality and Its Relation with Physical and Mental Conditions: Results from a Cross-Sectional Study of the Nationwide Primary Care Population Sample in Latvia

Background and Objectives: Physical and mental conditions are important risk factors for suicidality. However, there is no clear understanding of these relationships and the effect of co-occurrence on suicidality. We aimed to investigate the associations between current suicidality and mental disorders, physical conditions, and health-related factors in the nationwide primary care population in Latvia. Materials and Methods: A cross-sectional study was performed within the framework of the National Research Program BIOMEDICINE 2014–2017 at 24 primary care settings across Latvia in 2015. Adult patients were evaluated over one week at each facility. Socio-demographic variables, physical condition, and health-related factors were assessed on-site by trained psychiatrists. Mental disorders and suicidality were determined using the Mini International Neuropsychiatric Interview, and assessments were conducted over the telephone within two weeks after the visit to the general practitioner. Results: Of the 1485 cases, 18.6% reported suicidality. Only current depression, any anxiety disorder, any alcohol use disorder, and physical-mental multimorbidity were significantly associated with suicidality in the multivariate logistic regression analysis. Gastrointestinal diseases were associated with current depression alone (odds ratio (OR) 10.36; 95% confidence interval (CI) 2.34–45.76) and comorbid depression with any anxiety disorder (OR 7.55; 95% CI 2.15–26.49) among persons with current suicidality. Conclusions: Screening for depression, anxiety, and alcohol use disorders regularly among patients with physical illness may be important to help recognise suicidality in primary care that could improve the quality of life of patients and prevent suicides.