Cancer incidence following a high-normal platelet count: cohort study using electronic healthcare records from English primary care

This is the final version. Available on open access from the Royal College of General Practitioners via the DOI in this recordBackground A raised platelet count (thrombocytosis) measuring >400 × 109/l is associated with high cancer incidence. It is uncertain whether platelet counts at the upper end of the normal range (high-normal: 326–400 × 109/l) are also associated with cancer. Aim To investigate cancer incidence following a normal platelet count in primary care. Design and setting A prospective cohort study was undertaken using data from the Clinical Practice Research Datalink and National Cancer Registration and Analysis Service, dating from 1 May 2005 to 30 April 2014. Method One-year cancer incidence was estimated for 295 312 patients with normal platelet counts (150–400 × 109/l). Patients with platelet counts >325 × 109/l were oversampled to maximise precision of estimates of cancer incidence. All patients were aged ≥40 years with no prior cancer diagnoses. The effects of age, sex, and smoking were explored. Non-melanoma skin cancers were omitted from exclusions and incidence. Results One-year cancer incidence increased greatly with age, male sex, and higher platelet count. Males aged ≥60 years with a high-normal count had an incidence of 4.2% (95% confidence interval [CI] = 4.0 to 4.4). The highest incidence of 6.7% (95% CI = 5.3 to 8.4) was found in males aged ≥80 years, who had platelets in the range of 376–400 × 109/l; this was 3.1 percentage points higher than the incidence for patients in the same age group with lower-normal counts of 150–325 × 109/l. Risks for all female subgroups were <3%. Patients with high-normal platelet counts were most at risk of lung and colorectal cancers and, in general, had advanced-stage cancer at diagnosis. Conclusion Platelet counts at the high-normal range in males aged ≥60 years may be indicative of an underlying malignancy, and referral for further investigation should be considered.National Institute for Health Research (NIHR

Clinical implications of increased testing in primary care

This is the final version. Available from BMJ Publishing Group via the DOI in this recor

Examining methodology to identify patterns of consulting in primary care for different groups of patients before a diagnosis of cancer: An exemplar applied to oesophagogastric cancer

This is the final version. Available on open access from Elsevier via the DOI in this recordBackground Current methods for estimating the timeliness of cancer diagnosis are not robust because dates of key defining milestones, for example first presentation, are uncertain. This is exacerbated when patients have other conditions (multimorbidity), particularly those that share symptoms with cancer. Methods independent of this uncertainty are needed for accurate estimates of the timeliness of cancer diagnosis, and to understand how multimorbidity impacts the diagnostic process. Methods Participants were diagnosed with oesophagogastric cancer between 2010 and 2019. Controls were matched on year of birth, sex, general practice and multimorbidity burden calculated using the Cambridge Multimorbidity Score. Primary care data (Clinical Practice Research Datalink) was used to explore population-level consultation rates for up to two years before diagnosis across different multimorbidity burdens. Five approaches were compared on the timing of the consultation frequency increase, the inflection point for different multimorbidity burdens, different aggregated time-periods and sample sizes. Results We included 15,410 participants, of which 13,328 (86.5 %) had a measurable multimorbidity burden. Our new maximum likelihood estimation method found evidence that the inflection point in consultation frequency varied with multimorbidity burden, from 154 days (95 %CI 131.8–176.2) before diagnosis for patients with no multimorbidity, to 126 days (108.5–143.5) for patients with the greatest multimorbidity burden. Inflection points identified using alternative methods were closer to diagnosis for up to three burden groups. Sample size reduction and changing the aggregation period resulted in inflection points closer to diagnosis, with the smallest change for the maximum likelihood method. Discussion Existing methods to identify changes in consultation rates can introduce substantial bias which depends on sample size and aggregation period. The direct maximum likelihood method was less prone to this bias than other methods and offers a robust, population-level alternative for estimating the timeliness of cancer diagnosis.National Institute for Health Research (NIHR)Cancer Research U

Identifying Factors Leading to Harm in English General Practices

This is the author accepted manuscript. The final version is available from Lippincott, Williams & Wilkins via the DOI in this record.Objective The aim of the study was to identify the main factors leading to harm in primary care based on the experiences reported by patients. Methods We conducted a mixed-methods, cross-sectional study in 45 primary care centers in England. A random sample of 6736 patients was invited to complete the Patient-Reported Experiences and Outcomes of Safety in Primary Care questionnaire. We fitted structural equation modeling on the quantitative data (n = 1244 respondents) to identify contributory factors and primary incidents leading to harm. We conducted content analyses of responses to seven open-ended questions (n = 386) to obtain deeper insight into patient perceptions of the causes of harm experienced. Results from quantitative and qualitative analyses were triangulated. Results Patients reported harm related to physical health (13%), pain (11%), and mental health (19%) and harm that increased limitations in social activities (14%). Physical harm was associated with incidents affecting diagnosis (β = 0.43; delayed and wrong), and treatment (0.12; delayed, wrong treatment, or dose), which were in turn associated with incidents with patient-provider communication, coordination between providers, appointments, and laboratory tests. Pain was associated with laboratory tests (0.21; caused when collecting blood or tissue samples) and with problems booking an appointment when needed (0.13; delaying treatment for pain). Harm to mental health was associated with incidents related to the following: diagnosis (0.28), patient-provider communication (0.18), appointments (0.17), coordination between different providers (0.14), and laboratory tests (0.12). Harm increasing limitations in social activities was associated with incidents related to diagnosis (0.42) and diagnostic and monitoring procedures (0.20). Conclusions Our findings suggest the need for patient-centered strategies to reduce harm in primary care focusing on the improvement of the quality of diagnosis and patient-provider communication

Quantifying the impact of pre-existing conditions on the stage of oesophagogastric cancer at diagnosis: a primary care cohort study using electronic medical records

This is the final version. Available on open access from Oxford University Press via the DOI in this recordData availability: The anonymized patient data from this study are not available due to legal privacy restrictions enforced by the CPRD. Code lists and symptom libraries are available from the authors by request.Background Pre-existing conditions interfere with cancer diagnosis by offering diagnostic alternatives, competing for clinical attention or through patient surveillance. Objective To investigate associations between oesophagogastric cancer stage and pre-existing conditions. Methods Retrospective cohort study using Clinical Practice Research Datalink (CPRD) data, with English cancer registry linkage. Participants aged ≥40 years had consulted primary care in the year before their incident diagnosis of oesophagogastric cancer in 01/01/2010–31/12/2015. CPRD records pre-diagnosis were searched for codes denoting clinical features of oesophagogastric cancer and for pre-existing conditions, including those providing plausible diagnostic alternatives for those features. Logistic regression analysed associations between stage and multimorbidity (≥2 conditions; reference category: no multimorbidity) and having ‘diagnostic alternative(s)’, controlling for age, sex, deprivation and cancer site. Results Of 2444 participants provided, 695 (28%) were excluded for missing stage, leaving 1749 for analysis (1265/1749, 72.3% had advanced-stage disease). Multimorbidity was associated with stage [odds ratio 0.63, 95% confidence interval (CI) 0.47–0.85, P = 0.002], with moderate evidence of an interaction term with sex (1.76, 1.08–2.86, P = 0.024). There was no association between alternative explanations and stage (odds ratio 1.18, 95% CI 0.87–1.60, P = 0.278). Conclusions In men, multimorbidity is associated with a reduced chance of advanced-stage oesophagogastric cancer, to levels seen collectively for women.USF Health Morsani College of Medicine, Research, Innovation & Scholarly EndeavorsNational Institute for Health Research (NIHR)Cancer Research U

Chest x-ray sensitivity and lung cancer outcomes: A retrospective observational study

Background Chest X-ray (CXR) is the first-line investigation for lung cancer in many healthcare systems. An understanding of the consequences of false-negative CXRs on time to diagnosis, stage, and survival is limited. Aim To determine the sensitivity of CXR for lung cancer and to compare stage at diagnosis, time to diagnosis, and survival between those with CXR that detected, or did not detect, lung cancer. Design and setting Retrospective observational study using routinely collected healthcare data. Method All patients diagnosed with lung cancer in Leeds Teaching Hospitals NHS Trust during 2008–2015 who had a GP-requested CXR in the year before diagnosis were categorised based on the result of the earliest CXR performed in that period. The sensitivity of CXR was calculated and analyses were performed with respect to time to diagnosis, survival, and stage at diagnosis. Results CXR was negative for 17.7% of patients (n = 376/2129). Median time from initial CXR to diagnosis was 43 days for those with a positive CXR and 204 days for those with a negative CXR. Of those with a positive CXR, 29.8% (95% confidence interval [CI] = 27.9% to 31.8%) were diagnosed at stage I or II, compared with 33.5% (95% CI = 28.8% to 38.6%) with a negative CXR. Conclusion GPs should consider lung cancer in patients with persistent symptoms even when CXR is negative. Despite longer duration to diagnosis for those with false-negative CXRs, there was no evidence of an adverse impact on stage at diagnosis or survival; however, this comparison is likely to be affected by confounding variables

Comorbid conditions delay diagnosis of colorectal cancer: a cohort study using electronic primary care records

This is the author accepted manuscript. The final version is available from Cancer Research UK via the DOI in this record.BACKGROUND: Pre-existing non-cancer conditions may complicate and delay colorectal cancer diagnosis. METHOD: Incident cases (aged ⩾40 years, 2007-2009) with colorectal cancer were identified in the Clinical Practice Research Datalink, UK. Diagnostic interval was defined as time from first symptomatic presentation of colorectal cancer to diagnosis. Comorbid conditions were classified as 'competing demands' (unrelated to colorectal cancer) or 'alternative explanations' (sharing symptoms with colorectal cancer). The association between diagnostic interval (log-transformed) and age, gender, consultation rate and number of comorbid conditions was investigated using linear regressions, reported using geometric means. RESULTS: Out of the 4512 patients included, 72.9% had ⩾1 competing demand and 31.3% had ⩾1 alternative explanation. In the regression model, the numbers of both types of comorbid conditions were independently associated with longer diagnostic interval: a single competing demand delayed diagnosis by 10 days, and four or more by 32 days; and a single alternative explanation by 9 days. For individual conditions, the longest delay was observed for inflammatory bowel disease (26 days; 95% CI 14-39). CONCLUSIONS: The burden and nature of comorbidity is associated with delayed diagnosis in colorectal cancer, particularly in patients aged ⩾80 years. Effective clinical strategies are needed for shortening diagnostic interval in patients with comorbidity.British Journal of Cancer advance online publication: 11 May 2017 doi:10.1038/bjc.2017.127 www.bjcancer.com.There was no direct funding for this work. JMV was supported by a National Institute of Health Research (NIHR) Clinician Scientist Award for the study of the management of patients with multimorbidity in primary care

Impact of multi-morbidity on quality of healthcare and its implications for health policy, research and clinical practice. A scoping review

This is the author accepted manuscript. The final version is available from Taylor & Francis via the DOI in this recordThe simultaneous presence of multiple conditions in one patient (multi-morbidity) is a key challenge facing healthcare systems globally. It potentially threatens the coordination, continuity and safety of care. In this paper, we report the results of a scoping review examining the impact of multi-morbidity on the quality of healthcare. We used its results as a basis for a discussion of the challenges that research in this area is currently facing. In addition, we discuss its implications for health policy and clinical practice. The review identified 37 studies focussing on multi-morbidity but using conceptually different approaches. Studies focusing on 'comorbidity' (i.e. the 'index disease' approach) suggested that quality may be enhanced in the presence of synergistic conditions, and impaired by antagonistic or neutral conditions. Studies on 'multi-morbidity' (i.e. multiplicity of problems) and 'morbidity burden' (i.e. the total severity of conditions) suggested that increasing number of conditions and severity may be associated with better quality of healthcare when measured by process or intermediate outcome indicators, but with worse quality when patient-centred measures are used. However, issues related to the conceptualization and measurement of multi-morbidity (inconsistent across studies) and of healthcare quality (restricted to evaluations for each separate condition without incorporating considerations about multi-morbidity itself and its implications for management) compromised the generalizability of these observations. Until these issues are addressed and robust evidence becomes available, clinicians should apply minimally invasive and patient-centred medicine when delivering care for clinically complex patients. Health systems should focus on enhancing primary care centred coordination and continuity of care

Predicting Incident Multimorbidity.

This is the author accepted manuscript. The final version is available from Annals of Family Medicine via the DOI in this record.PURPOSE: Multimorbidity is associated with adverse outcomes, yet research on the determinants of its incidence is lacking. We investigated which sociodemographic, health, and individual lifestyle (eg, physical activity, smoking behavior, body mass index) characteristics predict new cases of multimorbidity. METHODS: We used data from 4,564 participants aged 50 years and older in the English Longitudinal Study of Aging that included a 10-year follow-up period. Discrete time-to-event (complementary log-log) models were constructed for exploring the associations of baseline characteristics with outcomes between 2002-2003 and 2012-2013 separately for participants with no initial conditions (n = 1,377) developing multimorbidity, any increase in conditions within 10 years regardless of initial conditions, and the impact of individual conditions on incident multimorbidity. RESULTS: The risks of developing multimorbidity were positively associated with age, and they were greater for the least wealthy, for participants who were obese, and for those who reported the lowest levels of physical activity or an external locus of control (believing that life events are outside of one's control) for all groups regardless of baseline conditions (all linear trends <.05). No significant associations were observed for sex, educational attainment, or social detachment. For participants with any increase in conditions (n = 4,564), a history of smoking was the only additional predictor. For participants with a single baseline condition (n = 1,534), chronic obstructive pulmonary disease (COPD), asthma, and arrhythmia showed the strongest associations with subsequent multimorbidity. CONCLUSIONS: Our findings support the development and implementation of a strategy targeting the prevention of multimorbidity for susceptible groups. This approach should incorporate behavior change addressing lifestyle factors and target health-related locus of control.There was no direct funding for this study. Dr Mounce was supported by the National Health Service, Cambridgeshire, and through an National Institute for Health Research Clinical Scientist Award granted to Dr Valderas

Ethnic inequalities in routes to diagnosis of cancer: a population-based UK cohort study

This is the final version. Available from Springer Nature via the DOI in this record. Background: UK Asian and Black ethnic groups have poorer outcomes for some cancers and are less likely to report a positive care experience than their White counterparts. This study investigated ethnic differences in the route to diagnosis (RTD) to identify areas in patients' cancer journeys where inequalities lie, and targeted intervention might have optimum impact. Methods: We analysed data of 243,825 patients with 10 cancers (2006-2016) from the RTD project linked to primary care data. Crude and adjusted proportions of patients diagnosed via six routes (emergency, elective GP referral, two-week wait (2WW), screen-detected, hospital, and Other routes) were calculated by ethnicity. Adjusted odds ratios (including two-way interactions between cancer and age, sex, IMD, and ethnicity) determined cancer-specific differences in RTD by ethnicity. Results: Across the 10 cancers studied, most patients were diagnosed via 2WW (36.4%), elective GP referral (23.2%), emergency (18.2%), hospital routes (10.3%), and screening (8.61%). Patients of Other ethnic group had the highest proportion of diagnosis via the emergency route, followed by White patients. Asian and Black group were more likely to be GP-referred, with the Black and Mixed groups also more likely to follow the 2WW route. However, there were notable cancer-specific differences in the RTD by ethnicity. Conclusion: Our findings suggest that, where inequalities exist, the adverse cancer outcomes among Asian and Black patients are unlikely to be arising solely from a poorer diagnostic process.Cancer Research UKCancer Research UKNational Institute for Health ResearchNational Institute for Health Researc