Exploring primary care level provider interpretation and management of potential breast and cervical cancer signs and symptoms in South Africa.

OBJECTIVES: Women with potential breast and cervical cancer symptoms in South Africa (SA) usually self-present to primary health care (PHC) clinics. The aim of this study was to explore PHC provider interpretation and management of potential breast and cervical cancer signs and symptoms. METHODS: In-depth interviews with PHC providers incorporating vignettes were conducted between April and May 2019 in two sites in SA. Four vignettes (two breast and two cervical) were developed by the research team to capture aspects of provider symptom interpretation, reasoning, actions and challenges. The content of the vignettes was informed by a preceding community-based survey and qualitative interviews with symptomatic women. Interviews were audio recorded, transcribed verbatim and analysed using a thematic analysis approach. RESULTS: Twenty-four PHC providers were interviewed (12 urban, 12 rural; median age: 43 years). Four main themes relating to clinical assessment and reasoning; referral and feedback challenges; awareness of breast and cervical cancer policy guidelines and training and education needs emerged. Vignette-prompted questions relating to presenting symptoms, and possible accompanying symptoms and signs, demonstrated comprehensive proposed history taking and clinical assessment by PHC providers. Cancer was considered as a potential diagnosis by the majority of PHC providers. PHC providers also considered the possibility of infectious causes for both breast and cervical vignettes indicating they would ask questions around human immunodeficiency virus status, use of anti-retroviral therapy, and, for those with cervical symptoms, would need to rule out a sexually transmitted infection. Sexual assault was considered in assessing the cervical symptom scenarios. Providers raised issues around cumbersome booking systems and lack of feedback from referral centres. The need for provider and patient education and training to improve timely diagnosis of breast and cervical cancer was raised. Most providers were not aware of current breast or cervical cancer policy guidelines. CONCLUSION: Clinical assessment at PHC level is complex and influenced by local health issues. Providing context-relevant training and support for PHC providers, and improving referral and feedback systems, could assist timely diagnosis of women with symptomatic breast and cervical cancer.

Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Lower Gastrointestinal Cancers: A Systematic Review and Meta-Analysis.

INTRODUCTION: Lower gastrointestinal (GI) cancers are a major cause of cancer deaths worldwide. Prognosis improves with earlier diagnosis, and non-invasive biomarkers have the potential to aid with early detection. Substantial investment has been made into the development of biomarkers; however, studies are often carried out in specialist settings and few have been evaluated for low-prevalence populations. METHODS: We aimed to identify novel biomarkers for the detection of lower GI cancers that have the potential to be evaluated for use in primary care. MEDLINE, Embase, Emcare and Web of Science were systematically searched for studies published in English from January 2000 to October 2019. Reference lists of included studies were also assessed. Studies had to report on measures of diagnostic performance for biomarkers (single or in panels) used to detect colorectal or anal cancers. We included all designs and excluded studies with fewer than 50 cases/controls. Data were extracted from published studies on types of biomarkers, populations and outcomes. Narrative synthesis was used, and measures of specificity and sensitivity were meta-analysed where possible. RESULTS: We identified 142 studies reporting on biomarkers for lower GI cancers, for 24,844 cases and 45,374 controls. A total of 378 unique biomarkers were identified. Heterogeneity of study design, population type and sample source precluded meta-analysis for all markers except methylated septin 9 (mSEPT9) and pyruvate kinase type tumour M2 (TuM2-PK). The estimated sensitivity and specificity of mSEPT9 was 80.6% (95% CI 76.6-84.0%) and 88.0% (95% CI 79.1-93.4%) respectively; TuM2-PK had an estimated sensitivity of 81.6% (95% CI 75.2-86.6%) and specificity of 80.1% (95% CI 76.7-83.0%). CONCLUSION: Two novel biomarkers (mSEPT9 and TuM2-PK) were identified from the literature with potential for use in lower-prevalence populations. Further research is needed to validate these biomarkers in primary care for screening and assessment of symptomatic patients.

Artificial Intelligence Techniques That May Be Applied to Primary Care Data to Facilitate Earlier Diagnosis of Cancer: Systematic Review.

BACKGROUND: More than 17 million people worldwide, including 360,000 people in the United Kingdom, were diagnosed with cancer in 2018. Cancer prognosis and disease burden are highly dependent on the disease stage at diagnosis. Most people diagnosed with cancer first present in primary care settings, where improved assessment of the (often vague) presenting symptoms of cancer could lead to earlier detection and improved outcomes for patients. There is accumulating evidence that artificial intelligence (AI) can assist clinicians in making better clinical decisions in some areas of health care. OBJECTIVE: This study aimed to systematically review AI techniques that may facilitate earlier diagnosis of cancer and could be applied to primary care electronic health record (EHR) data. The quality of the evidence, the phase of development the AI techniques have reached, the gaps that exist in the evidence, and the potential for use in primary care were evaluated. METHODS: We searched MEDLINE, Embase, SCOPUS, and Web of Science databases from January 01, 2000, to June 11, 2019, and included all studies providing evidence for the accuracy or effectiveness of applying AI techniques for the early detection of cancer, which may be applicable to primary care EHRs. We included all study designs in all settings and languages. These searches were extended through a scoping review of AI-based commercial technologies. The main outcomes assessed were measures of diagnostic accuracy for cancer. RESULTS: We identified 10,456 studies; 16 studies met the inclusion criteria, representing the data of 3,862,910 patients. A total of 13 studies described the initial development and testing of AI algorithms, and 3 studies described the validation of an AI algorithm in independent data sets. One study was based on prospectively collected data; only 3 studies were based on primary care data. We found no data on implementation barriers or cost-effectiveness. Risk of bias assessment highlighted a wide range of study quality. The additional scoping review of commercial AI technologies identified 21 technologies, only 1 meeting our inclusion criteria. Meta-analysis was not undertaken because of the heterogeneity of AI modalities, data set characteristics, and outcome measures. CONCLUSIONS: AI techniques have been applied to EHR-type data to facilitate early diagnosis of cancer, but their use in primary care settings is still at an early stage of maturity. Further evidence is needed on their performance using primary care data, implementation barriers, and cost-effectiveness before widespread adoption into routine primary care clinical practice can be recommended.

Identifying Novel Biomarkers Ready for Evaluation in Low-Prevalence Populations for the Early Detection of Upper Gastrointestinal Cancers: A Systematic Review.

INTRODUCTION: Detecting upper gastrointestinal (GI) cancers in primary care is challenging, as cancer symptoms are common, often non-specific, and most patients presenting with these symptoms will not have cancer. Substantial investment has been made to develop biomarkers for cancer detection, but few have reached routine clinical practice. We aimed to identify novel biomarkers for upper GI cancers which have been sufficiently validated to be ready for evaluation in low-prevalence populations. METHODS: We systematically searched MEDLINE, Embase, Emcare, and Web of Science for studies published in English from January 2000 to October 2019 (PROSPERO registration CRD42020165005). Reference lists of included studies were assessed. Studies had to report on second measures of diagnostic performance (beyond discovery phase) for biomarkers (single or in panels) used to detect pancreatic, oesophageal, gastric, and biliary tract cancers. We included all designs and excluded studies with less than 50 cases/controls. Data were extracted on types of biomarkers, populations and outcomes. Heterogeneity prevented pooling of outcomes. RESULTS: We identified 149 eligible studies, involving 22,264 cancer cases and 49,474 controls. A total of 431 biomarkers were identified (183 microRNAs and other RNAs, 79 autoantibodies and other immunological markers, 119 other proteins, 36 metabolic markers, 6 circulating tumour DNA and 8 other). Over half (n = 231) were reported in pancreatic cancer studies. Only 35 biomarkers had been investigated in at least two studies, with reported outcomes for that individual marker for the same tumour type. Apolipoproteins (apoAII-AT and apoAII-ATQ), and pepsinogens (PGI and PGII) were the most promising biomarkers for pancreatic and gastric cancer, respectively. CONCLUSION: Most novel biomarkers for the early detection of upper GI cancers are still at an early stage of matureness. Further evidence is needed on biomarker performance in low-prevalence populations, in addition to implementation and health economic studies, before extensive adoption into clinical practice can be recommended.

Missed opportunities for diagnosing brain tumours in primary care: a qualitative study of patient experiences.

BACKGROUND: Brain tumours are uncommon, and have extremely poor outcomes. Patients and GPs may find it difficult to recognise early symptoms because they are often non-specific and more likely due to other conditions. AIM: To explore patients' experiences of symptom appraisal, help seeking, and routes to diagnosis. DESIGN AND SETTING: Qualitative study set in the East and North West of England. METHOD: In-depth interviews with adult patients recently diagnosed with a primary brain tumour and their family members were analysed thematically, using the Model of Pathways to Treatment as a conceptual framework. RESULTS: Interviews were carried out with 39 patients. Few participants (n = 7; 18%) presented as an emergency without having had a previous GP consultation; most had had one (n = 15; 38%), two (n = 9; 23%), or more (n = 8; 21%) GP consultations. Participants experienced multiple subtle 'changes' rather than 'symptoms', often noticed by others rather than the patient, which frequently led to loss of interest or less ability to engage with daily living activities. The most common changes were in cognition (speaking, writing, comprehension, memory, concentration, and multitasking), sleep, and other 'head feelings' such as dizziness. Not all patients experienced a seizure, and few seizures were experienced 'out of the blue'. Quality of communication in GP consultations played a key role in patients' subsequent symptom appraisal and the timing of their decision to re-consult. CONCLUSION: Multiple subtle changes and frequent GP visits often precede brain tumour diagnosis, giving possible diagnostic opportunities for GPs. Refined community symptom awareness and GP guidance could enable more direct pathways to diagnosis, and potentially improve patient experiences and outcomes.

'It was nothing that you would think was anything': Qualitative analysis of appraisal and help seeking preceding brain cancer diagnosis.

BACKGROUND: The patient's interpretation of the events and decisions leading up to consultation with a healthcare professional for symptoms of brain cancer is under researched. The aim of this study was to document responses to noticing the changes preceding a diagnosis of brain cancer and living with them, focusing on appraisal of changes and the decision to seek (and re-seek) help, with attention to the psychological processes underpinning the appraisal and help-seeking intervals. METHOD: In this qualitative study set in Eastern and NW England, in-depth interviews with adult patients recently diagnosed with primary brain cancer and their family members were analysed thematically, using the Model of Pathways to Treatment as a conceptual framework. RESULTS: 39 adult patients were interviewed. Regarding the appraisal interval, cognitive heuristics were found to underpin explanations of changes/symptoms. The subtlety and normality of changes often suggested nothing serious was wrong. Common explanations included stress or being busy at work, or age and these did not seem to warrant a visit to a doctor. Explanations and the decision to seek help were made within the social context, with friends, family and work colleagues contributing to appraisal and help-seeking decisions. Regarding the help-seeking interval, barriers to seeking help reflected components of Social Cognitive Theory, and included having other priorities, outcome expectations (e.g. 'feeling silly', not sure much can be done about it, not wanting to waste doctors' time) and accessibility of a preferred healthcare professional. CONCLUSION: Application of psychological theory facilitated understanding of the influences on cognition and behaviour. The study highlights implications for theory, awareness campaigns and potential opportunities promoting more timely help-seeking.