Correction: External validation of risk prediction models for incident colorectal cancer using UK Biobank.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

External validation of risk prediction models for incident colorectal cancer using UK Biobank.

BACKGROUND: This study aimed to compare and externally validate risk scores developed to predict incident colorectal cancer (CRC) that include variables routinely available or easily obtainable via self-completed questionnaire. METHODS: External validation of fourteen risk models from a previous systematic review in 373 112 men and women within the UK Biobank cohort with 5-year follow-up, no prior history of CRC and data for incidence of CRC through linkage to national cancer registries. RESULTS: There were 1719 (0.46%) cases of incident CRC. The performance of the risk models varied substantially. In men, the QCancer10 model and models by Tao, Driver and Ma all had an area under the receiver operating characteristic curve (AUC) between 0.67 and 0.70. Discrimination was lower in women: the QCancer10, Wells, Tao, Guesmi and Ma models were the best performing with AUCs between 0.63 and 0.66. Assessment of calibration was possible for six models in men and women. All would require country-specific recalibration if estimates of absolute risks were to be given to individuals. CONCLUSIONS: Several risk models based on easily obtainable data have relatively good discrimination in a UK population. Modelling studies are now required to estimate the potential health benefits and cost-effectiveness of implementing stratified risk-based CRC screening.

Pre-referral general practitioner consultations and subsequent experience of cancer care: evidence from the English Cancer Patient Experience Survey.

Prolonged diagnostic intervals may negatively affect the patient experience of subsequent cancer care, but evidence about this assertion is sparse. We analysed data from 73 462 respondents to two English Cancer Patient Experience Surveys to examine whether patients with three or more (3+) pre-referral consultations were more likely to report negative experiences of subsequent care compared with patients with one or two consultations in respect of 12 a priori selected survey questions. For each of 12 experience items, logistic regression models were used, adjusting for prior consultation category, cancer site, socio-demographic case-mix and response tendency (to capture potential variation in critical response tendencies between individuals). There was strong evidence (P < 0.01 for all) that patients with 3+ pre-referral consultations reported worse care experience for 10/12 questions, with adjusted odds ratios compared with patients with 1-2 consultations ranging from 1.10 (95% confidence intervals 1.03-1.17) to 1.68 (1.60-1.77), or between +1.8% and +10.6% greater percentage reporting a negative experience. Associations were stronger for processes involving primary as opposed to hospital care; and for evaluation than report items. Considering 1, 2, 3-4 and '5+' pre-referral consultations separately a 'dose-response' relationship was apparent. We conclude that there is a negative association between multiple pre-diagnostic consultations with a general practitioner and the experience of subsequent cancer care.

The relative length of the patient and the primary care interval in patients with 28 common and rarer cancers.

BACKGROUND: Appreciating variation in the length of pre- or post-presentation diagnostic intervals can help prioritise early diagnosis interventions with either a community or a primary care focus. METHODS: We analysed data from the first English National Audit of Cancer Diagnosis in Primary Care on 10 953 patients with any of 28 cancers. We calculated summary statistics for the length of the patient and the primary care interval and their ratio, by cancer site. RESULTS: Interval lengths varied greatly by cancer. Laryngeal and oropharyngeal cancers had the longest median patient intervals, whereas renal and bladder cancer had the shortest (34.5 and 30 compared with 3 and 2 days, respectively). Multiple myeloma and gallbladder cancer had the longest median primary care intervals, and melanoma and breast cancer had the shortest (20.5 and 20 compared with 0 and 0 days, respectively). Mean patient intervals were longer than primary care intervals for most (18 of 28) cancers, and notably so (two- to five-fold greater) for 10 cancers (breast, melanoma, testicular, vulval, cervical, endometrial, oropharyngeal, laryngeal, ovarian and thyroid). CONCLUSIONS: The findings support the continuing development and evaluation of public health interventions aimed at shortening patient intervals, particularly for cancers with long patient interval and/or high patient interval over primary care interval ratio.

Impact of investigations in general practice on timeliness of referral for patients subsequently diagnosed with cancer: analysis of national primary care audit data.

BACKGROUND: For patients with symptoms of possible cancer who do not fulfil the criteria for urgent referral, initial investigation in primary care has been advocated in the United Kingdom and supported by additional resources. The consequence of this strategy for the timeliness of diagnosis is unknown. METHODS: We analysed data from the English National Audit of Cancer Diagnosis in Primary Care on patients with lung (1494), colorectal (2111), stomach (246), oesophagus (513), pancreas (327), and ovarian (345) cancer relating to the ordering of investigations by the General Practitioner and their nature. Presenting symptoms were categorised according to National Institute for Health and Care Excellence (NICE) guidance on referral for suspected cancer. We used linear regression to estimate the mean difference in primary-care interval by cancer, after adjustment for age, gender, and the symptomatic presentation category. RESULTS: Primary-care investigations were undertaken in 3198/5036 (64%) of cases. The median primary-care interval was 16 days (IQR 5-45) for patients undergoing investigation and 0 days (IQR 0-10) for those not investigated. Among patients whose symptoms mandated urgent referral to secondary care according to NICE guidelines, between 37% (oesophagus) and 75% (pancreas) were first investigated in primary care. In multivariable linear regression analyses stratified by cancer site, adjustment for age, sex, and NICE referral category explained little of the observed prolongation associated with investigation. INTERPRETATION: For six specified cancers, investigation in primary care was associated with later referral for specialist assessment. This effect was independent of the nature of symptoms. Some patients for whom urgent referral is mandated by NICE guidance are nevertheless investigated before referral. Reducing the intervals between test order, test performance, and reporting can help reduce the prolongation of primary-care intervals associated with investigation use. Alternative models of assessment should be considered.

Inequalities in reported cancer patient experience by socio-demographic characteristic and cancer site: evidence from respondents to the English Cancer Patient Experience Survey.

Patient experience is a critical dimension of cancer care quality. Understanding variation in experience among patients with different cancers and characteristics is an important first step for designing targeted improvement interventions. We analysed data from the 2011/2012 English Cancer Patient Experience Survey (n = 69,086) using logistic regression to explore inequalities in care experience across 64 survey questions. We additionally calculated a summary measure of variation in patient experience by cancer, and explored inequalities between patients with cancers treated by the same specialist teams. We found that younger and very old, ethnic minority patients and women consistently reported worse experiences across questions. Patients with small intestine/rarer lower gastrointestinal, multiple myeloma and hepatobiliary cancers were most likely to report negative experiences whereas patients with breast, melanoma and testicular cancer were least likely (top-to-bottom odds ratio = 1.91, P < 0.0001). There were also inequalities in experience among patients with cancers treated by the same specialty for five of nine services (P < 0.0001). Specifically, patients with ovarian, multiple myeloma, anal, hepatobiliary and renal cancer reported notably worse experiences than patients with other gynaecological, haematological, gastrointestinal and urological malignancies respectively. Initiatives to improve cancer patient experience across oncology services may be suitably targeted on patients at higher risk of poorer experience.

Prevalence of polypharmacy in a Scottish primary care population.

PURPOSE: Polypharmacy-the use of multiple medications by a single patient-is an important issue associated with various adverse clinical outcomes and rising costs. It is also a topic rarely addressed by clinical guidelines. We used routine Scottish health records to address the lack of data on the prevalence of polypharmacy in the broader, adult primary care population, particularly in relation to long-term conditions. METHODS: We conducted a cross-sectional analysis of adult electronic primary healthcare records and used linear regression models to examine the association between the number of medicines prescribed regularly and both multimorbidity and specific clinical conditions, adjusting for age, gender and socioeconomic deprivation. RESULTS: Overall, 16.9 % of the adults assessed were receiving four to nine medications, and 4.6 % were receiving ten or more medications, increasing with age (28.6 and 7.4 %, respectively, in those aged 60-69 years; 51.8 and 18.6 %, respectively, in those aged ≥ 80 years), but relatively unaffected by gender or deprivation. Of those patients with two clinical conditions, 20.8 % were receiving four to nine medications, and 1.1 % were receiving ten or more medications; in those patients with six or more comorbidities, these values were 47.7 and 41.7 %, respectively. The number of medications varied considerably between clinical conditions, with cardiovascular conditions associated with the greatest number of additional medications. The accumulation of additional medicines was less with concordant conditions. CONCLUSIONS: Polypharmacy is common in UK primary care. The main factor associated with this is multimorbidity, although considerable variation exists between different conditions. The impact of clinical conditions on the number of medicines is generally less in the presence of co-existing concordant conditions.

Accuracy of routinely recorded ethnic group information compared with self-reported ethnicity: evidence from the English Cancer Patient Experience survey.

OBJECTIVE: To describe the accuracy of ethnicity coding in contemporary National Health Service (NHS) hospital records compared with the 'gold standard' of self-reported ethnicity. DESIGN: Secondary analysis of data from a cross-sectional survey (2011). SETTING: All NHS hospitals in England providing cancer treatment. PARTICIPANTS: 58 721 patients with cancer for whom ethnicity information (Office for National Statistics 2001 16-group classification) was available from self-reports (considered to represent the 'gold standard') and their hospital record. METHODS: We calculated the sensitivity and positive predictive value (PPV) of hospital record ethnicity. Further, we used a logistic regression model to explore independent predictors of discordance between recorded and self-reported ethnicity. RESULTS: Overall, 4.9% (4.7-5.1%) of people had their self-reported ethnic group incorrectly recorded in their hospital records. Recorded White British ethnicity had high sensitivity (97.8% (97.7-98.0%)) and PPV (98.1% (98.0-98.2%)) for self-reported White British ethnicity. Recorded ethnicity information for the 15 other ethnic groups was substantially less accurate with 41.2% (39.7-42.7%) incorrect. Recorded 'Mixed' ethnicity had low sensitivity (12-31%) and PPVs (12-42%). Recorded 'Indian', 'Chinese', 'Black-Caribbean' and 'Black African' ethnic groups had intermediate levels of sensitivity (65-80%) and PPV (80-89%, respectively). In multivariable analysis, belonging to an ethnic minority group was the only independent predictor of discordant ethnicity information. There was strong evidence that the degree of discordance of ethnicity information varied substantially between different hospitals (p<0.0001). DISCUSSION: Current levels of accuracy of ethnicity information in NHS hospital records support valid profiling of White/non-White ethnic differences. However, profiling of ethnic differences in process or outcome measures for specific minority groups may contain a substantial and variable degree of misclassification error. These considerations should be taken into account when interpreting ethnic variation audits based on routine data and inform initiatives aimed at improving the accuracy of ethnicity information in hospital records.

Heritability and gene-environment interactions for melanocytic nevus density examined in a U.K. adolescent twin study.

Risk factors for melanoma include environmental (particularly ultraviolet exposure) and genetic factors. In rare families, susceptibility to melanoma is determined by high penetrance mutations in the genes CDKN2A or CDK4, with more common, less penetrant genes also postulated. A further, potent risk factor for melanoma is the presence of large numbers of melanocytic nevi so that genes controlling nevus phenotype could be such melanoma susceptibility genes. A large Australian study involving twins aged 12 y of predominantly U.K. ancestry showed strong evidence for genetic influence on nevus number and density. We carried out essentially the same study in the U.K. to gain insight into gene-environment interactions for nevi. One hundred and three monozygous (MZ) and 118 dizygous (DZ) twin pairs aged 10-18 y were examined in Yorkshire and Surrey, U.K. Nevus counts were, on average, higher in boys (mean = 98.6) than girls (83.8) (p = 0.009) and higher in Australia (110.4) than in the U.K. (79.2, adjusted to age 12 y, p < 0.0001), and nevus densities were higher on sun-exposed sites (92 per m2) than sun-protected sites (58 per m2) (p < 0.0001). Correlations in sex and age adjusted nevus density were higher in MZ pairs (0.94, 95%CI 0.92-0.96) than in DZ pairs (0.61, 95%CI 0.49-0.72), were notably similar to those of the Australian study (MZ = 0.94, DZ = 0.60), and were consistent with high heritability (65% in the U.K., 68% in Australia). We conclude that emergence of nevi in adolescents is under strong genetic control, whereas environmental exposures affect the mean number of nevi.

Using single nucleotide polymorphisms to investigate association between a candidate gene and disease.

A range of study designs, using unrelated or family controls, were used to investigate the pattern of association with disease of single nucleotide polymorphisms (SNPs) within candidate gene 1 (simulated data). Strong evidence of disease association at the functional locus was detected using all study designs, and in the "general" but not the "isolated" population the functional polymorphism displayed considerably higher association than surrounding SNPs. There was much variation in the strength of association of SNPs with disease, up to 70% of which was explained by SNP allele frequency and distance from the functional polymorphism. Some common polymorphisms very close to the functional locus however showed no association with disease. Analysis of short haplotypes of SNPs reduced but did not totally remove this feature.