Combining simple blood tests to identify primary care patients with unexpected weight loss for cancer investigation: Clinical risk score development, internal validation, and net benefit analysis.

BACKGROUND: Unexpected weight loss (UWL) is a presenting feature of cancer in primary care. Existing research proposes simple combinations of clinical features (risk factors, symptoms, signs, and blood test data) that, when present, warrant cancer investigation. More complex combinations may modify cancer risk to sufficiently rule-out the need for investigation. We aimed to identify which clinical features can be used together to stratify patients with UWL based on their risk of cancer. METHODS AND FINDINGS: We used data from 63,973 adults (age: mean 59 years, standard deviation 21 years; 42% male) to predict cancer in patients with UWL recorded in a large representative United Kingdom primary care electronic health record between January 1, 2000 and December 31, 2012. We derived 3 clinical prediction models using logistic regression and backwards stepwise covariate selection: Sm, symptoms-only model; STm, symptoms and tests model; Tm, tests-only model. Fifty imputations replaced missing data. Estimates of discrimination and calibration were derived using 10-fold internal cross-validation. Simple clinical risk scores are presented for models with the greatest clinical utility in decision curve analysis. The STm and Tm showed improved discrimination (area under the curve ≥ 0.91), calibration, and greater clinical utility than the Sm. The Tm was simplest including age-group, sex, albumin, alkaline phosphatase, liver enzymes, C-reactive protein, haemoglobin, platelets, and total white cell count. A Tm score of 5 balanced ruling-in (sensitivity 84.0%, positive likelihood ratio 5.36) and ruling-out (specificity 84.3%, negative likelihood ratio 0.19) further cancer investigation. A Tm score of 1 prioritised ruling-out (sensitivity 97.5%). At this threshold, 35 people presenting with UWL in primary care would be referred for investigation for each person with cancer referred, and 1,730 people would be spared referral for each person with cancer not referred. Study limitations include using a retrospective routinely collected dataset, a reliance on coding to identify UWL, and missing data for some predictors. CONCLUSIONS: Our findings suggest that combinations of simple blood test abnormalities could be used to identify patients with UWL who warrant referral for investigation, while people with combinations of normal results could be exempted from referral.

Impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England: a population-based study.

BACKGROUND: There are concerns that the COVID-19 pandemic has had a negative effect on cancer care but there is little direct evidence to quantify any effect. This study aims to investigate the impact of the COVID-19 pandemic on the detection and management of colorectal cancer in England. METHODS: Data were extracted from four population-based datasets spanning NHS England (the National Cancer Cancer Waiting Time Monitoring, Monthly Diagnostic, Secondary Uses Service Admitted Patient Care and the National Radiotherapy datasets) for all referrals, colonoscopies, surgical procedures, and courses of rectal radiotherapy from Jan 1, 2019, to Oct 31, 2020, related to colorectal cancer in England. Differences in patterns of care were investigated between 2019 and 2020. Percentage reductions in monthly numbers and proportions were calculated. FINDINGS: As compared to the monthly average in 2019, in April, 2020, there was a 63% (95% CI 53-71) reduction (from 36 274 to 13 440) in the monthly number of 2-week referrals for suspected cancer and a 92% (95% CI 89-95) reduction in the number of colonoscopies (from 46 441 to 3484). Numbers had just recovered by October, 2020. This resulted in a 22% (95% CI 8-34) relative reduction in the number of cases referred for treatment (from a monthly average of 2781 in 2019 to 2158 referrals in April, 2020). By October, 2020, the monthly rate had returned to 2019 levels but did not exceed it, suggesting that, from April to October, 2020, over 3500 fewer people had been diagnosed and treated for colorectal cancer in England than would have been expected. There was also a 31% (95% CI 19-42) relative reduction in the numbers receiving surgery in April, 2020, and a lower proportion of laparoscopic and a greater proportion of stoma-forming procedures, relative to the monthly average in 2019. By October, 2020, laparoscopic surgery and stoma rates were similar to 2019 levels. For rectal cancer, there was a 44% (95% CI 17-76) relative increase in the use of neoadjuvant radiotherapy in April, 2020, relative to the monthly average in 2019, due to greater use of short-course regimens. Although in June, 2020, there was a drop in the use of short-course regimens, rates remained above 2019 levels until October, 2020. INTERPRETATION: The COVID-19 pandemic has led to a sustained reduction in the number of people referred, diagnosed, and treated for colorectal cancer. By October, 2020, achievement of care pathway targets had returned to 2019 levels, albeit with smaller volumes of patients and with modifications to usual practice. As pressure grows in the NHS due to the second wave of COVID-19, urgent action is needed to address the growing burden of undetected and untreated colorectal cancer in England. FUNDING: Cancer Research UK, the Medical Research Council, Public Health England, Health Data Research UK, NHS Digital, and the National Institute for Health Research Oxford Biomedical Research Centre.

Association Between Blood Pressure Control and Coronavirus Disease 2019 Outcomes in 45 418 Symptomatic Patients With Hypertension: An Observational Cohort Study.

Hypertension has been identified as a risk factor for coronavirus disease 2019 (COVID-19) and associated adverse outcomes. This study examined the association between preinfection blood pressure (BP) control and COVID-19 outcomes using data from 460 general practices in England. Eligible patients were adults with hypertension who were tested or diagnosed with COVID-19. BP control was defined by the most recent BP reading within 24 months of the index date (January 1, 2020). BP was defined as controlled (<130/80 mm Hg), raised (130/80-139/89 mm Hg), stage 1 uncontrolled (140/90-159/99 mm Hg), or stage 2 uncontrolled (≥160/100 mm Hg). The primary outcome was death within 28 days of COVID-19 diagnosis. Secondary outcomes were COVID-19 diagnosis and COVID-19-related hospital admission. Multivariable logistic regression was used to examine the association between BP control and outcomes. Of the 45 418 patients (mean age, 67 years; 44.7% male) included, 11 950 (26.3%) had controlled BP. These patients were older, had more comorbidities, and had been diagnosed with hypertension for longer. A total of 4277 patients (9.4%) were diagnosed with COVID-19 and 877 died within 28 days. Individuals with stage 1 uncontrolled BP had lower odds of COVID-19 death (odds ratio, 0.76 [95% CI, 0.62-0.92]) compared with patients with well-controlled BP. There was no association between BP control and COVID-19 diagnosis or hospitalization. These findings suggest BP control may be associated with worse COVID-19 outcomes, possibly due to these patients having more advanced atherosclerosis and target organ damage. Such patients may need to consider adhering to stricter social distancing, to limit the impact of COVID-19 as future waves of the pandemic occur.

Attitudes towards faecal immunochemical testing in patients at increased risk of colorectal cancer: an online survey of GPs in England.

BACKGROUND: There is increasing interest in using a quantitative faecal immunochemical test (FIT) to rule out colorectal cancer (CRC) in patients with high-risk symptoms in primary care. AIM: This study aimed to investigate GPs' attitudes and willingness to use a FIT over an urgent 2-week wait (2WW) referral. DESIGN AND SETTING: A cross-sectional online survey involving 1024 GPs working across England. METHOD: Logistic regression models were used to explore the likelihood of GPs using a FIT instead of a 2WW referral, and reported using odds ratios (ORs) and 95% confidence intervals (95% CIs). RESULTS: Just over one-third of GPs (n = 365) preferred to use a FIT as a rule-out test over a 2WW referral. GPs were more willing if they were: aged 36-45 years (OR 1.59 [95% CI = 1.04 to 2.44]); 46-55 years (OR 1.99 [95% CI = 1.14 to 3.47]); thought a FIT was highly accurate (OR 1.63 [95% CI = 1.16 to 2.29]); thought patients would benefit compared with having a colonoscopy (OR 2.02 [95% CI = 1.46 to 2.79]); and were highly confident about discussing the benefits of a FIT (OR 2.14 [95% CI = 1.46 to 3.16]). GPs were less willing if they had had >10 urgent referrals in the past year (OR 0.62 [95% CI = 0.40 to 0.94]) and thought that longer consultations would be needed (OR 0.61 [95% CI = 0.44 to 0.83]). CONCLUSION: The study findings suggest that the acceptability of using a FIT as a rule-out test in primary care is currently low, with less than half of GPs who perceived the test to be accurate preferring it over colonoscopy. Any potential guideline changes recommending a FIT in patients with high-risk symptoms, instead of urgent referral to rule out CRC, are likely to require intensive supporting educational outreach to increase GP confidence in the accuracy and application of a FIT in this context.

The Suspected CANcer (SCAN) pathway: protocol for evaluating a new standard of care for patients with non-specific symptoms of cancer.

INTRODUCTION: Cancer survival in England lags behind most European countries, due partly to lower rates of early stage diagnosis. We report the protocol for the evaluation of a multidisciplinary diagnostic centre-based pathway for the investigation of 'low-risk but not no-risk' cancer symptoms called the Suspected CANcer (SCAN) pathway. SCAN is a new standard of care being implemented in Oxfordshire; one of a number of pathways implemented during the second wave of the Accelerate, Coordinate, Evaluate (ACE) programme, an initiative which aims to improve England's cancer survival rates through establishing effective routes to early diagnosis. METHODS AND ANALYSIS: To evaluate SCAN, we are collating a prospective database of patients referred onto the pathway by their general practitioner (GP). Patients aged over 40 years, with non-specific symptoms such as weight loss or fatigue, who do not meet urgent cancer referral criteria or for whom symptom causation remains unclear after investigation via other existing pathways, can be referred to SCAN. SCAN provides rapid CT scanning, laboratory testing and clinic review within 2 weeks. We will follow all patients in the primary and secondary care record for at least 2 years. The data will be used to understand the diagnostic yield of the SCAN pathway in the short term (28 days) and the long term (2 years). Routinely collected primary and secondary care data from patients not referred to SCAN but with similar symptoms will also be used to evaluate SCAN. We will map the routes to diagnosis for patients referred to SCAN to assess cost-effectiveness. Acceptability will be evaluated using patient and GP surveys. ETHICS AND DISSEMINATION: The Oxford Joint Research Office Study Classification Group has judged this to be a service evaluation and so outside of research governance. The results of this project will be disseminated by peer-reviewed publication and presentation at conferences.

What carcinoembryonic antigen level should trigger further investigation during colorectal cancer follow-up? A systematic review and secondary analysis of a randomised controlled trial.

BACKGROUND: Following primary surgical and adjuvant treatment for colorectal cancer, many patients are routinely followed up with blood carcinoembryonic antigen (CEA) testing. OBJECTIVE: To determine how the CEA test result should be interpreted to inform the decision to undertake further investigation to detect treatable recurrences. DESIGN: Two studies were conducted: (1) a Cochrane review of existing studies describing the diagnostic accuracy of blood CEA testing for detecting colorectal recurrence; and (2) a secondary analysis of data from the two arms of the FACS (Follow-up After Colorectal Surgery) trial in which CEA testing was carried out. SETTING AND PARTICIPANTS: The secondary analysis was based on data from 582 patients recruited into the FACS trial between 2003 and 2009 from 39 NHS hospitals in England with access to high-volume services offering surgical treatment of metastatic recurrence and followed up for 5 years. CEA testing was undertaken in general practice. RESULTS: In the systematic review we identified 52 studies for meta-analysis, including in aggregate 9717 participants (median study sample size 139, interquartile range 72-247). Pooled sensitivity at the most commonly recommended threshold in national guidelines of 5 µg/l was 71% [95% confidence interval (CI) 64% to 76%] and specificity was 88% (95% CI 84% to 92%). In the secondary analysis of FACS data, the diagnostic accuracy of a single CEA test was less than was suggested by the review [area under the receiver operating characteristic curve (AUC) 0.74, 95% CI 0.68 to 0.80]. At the commonly recommended threshold of 5 µg/l, sensitivity was estimated as 50.0% (95% CI 40.1% to 59.9%) and lead time as about 3 months. About four in 10 patients without a recurrence will have at least one false alarm and six out of 10 tests will be false alarms (some patients will have multiple false alarms, particularly smokers). Making decisions to further investigate based on the trend in serial CEA measurements is better (AUC for positive trend 0.85, 95% CI 0.78 to 0.91), but to maintain approximately 70% sensitivity with 90% specificity it is necessary to increase the frequency of testing in year 1 and to apply a reducing threshold for investigation as measurements accrue. LIMITATIONS: The reference standards were imperfect and the main analysis was subject to work-up bias and had limited statistical precision and no external validation. CONCLUSIONS: The results suggest that (1) CEA testing should not be used alone as a triage test; (2) in year 1, testing frequency should be increased (to monthly for 3 months and then every 2 months); (3) the threshold for investigating a single test result should be raised to 10 µg/l; (4) after the second CEA test, decisions to investigate further should be made on the basis of the trend in CEA levels; (5) the optimal threshold for investigating the CEA trend falls over time; and (6) continuing smokers should not be monitored with CEA testing. Further research is needed to explore the operational feasibility of monitoring the trend in CEA levels and to externally validate the proposed thresholds for further investigation. STUDY REGISTRATION: This study is registered as PROSPERO CRD42015019327 and Current Controlled Trials ISRCTN93652154. FUNDING: The main FACS trial and this substudy were funded by the National Institute for Health Research Health Technology Assessment programme.

Variation in Direct Access to Tests to Investigate Cancer: A Survey of English General Practitioners.

BACKGROUND: The 2015 NICE guidelines for suspected cancer recommend that English General Practitioners have direct access to diagnostic tests to investigate symptoms of cancer that do not meet the criteria for urgent referral. We aimed to identify the proportion of GPs in England with direct access to these tests. METHODS: We recruited 533 English GPs through a national clinical research network to complete an online survey about direct access to laboratory, radiology, and endoscopy tests in the three months leading up to the release of the 2015 NICE guidance. If they had direct access to a diagnostic test, GPs were asked about the time necessary to arrange a test and receive a report. Results are reported by NHS sub-region and, adjusting for sampling, for England as a whole. RESULTS: Almost all GPs reported direct access to x-ray and laboratory investigations except faecal occult blood testing (54%, 95% CI 49-59%) and urine protein electrophoresis (89%, 95% CI 84-92%). Fewer GPs had direct access to CT scans (54%, 95% CI 49-59%) or endoscopy (colonoscopy 32%, 95% CI 28-37%; gastroscopy 72%, 95% CI 67-77%). There was significant variation in direct access between NHS regions for the majority of imaging tests-for example, from 20 to 85% to MRI. Apart from x-ray, very few GPs (1-22%) could access radiology and endoscopy within the timescales recommended by NICE. The modal request to test time was 2-4 weeks for routine radiology and 4-6 weeks for routine endoscopy with results taking another 1-2 weeks. CONCLUSION: At the time that the 2015 NICE guideline was released, local investment was required to not only provide direct access but also reduce the interval between request and test and speed up reporting. Further research using our data as a benchmark is now required to identify whether local improvements in direct access have been achieved in response to the NICE targets. If alternative approaches to test access are to be proposed they must be piloted comprehensively and underpinned by robust effectiveness data.

The social reality of migrant men with tuberculosis in Kathmandu: implications for DOT in practice.

OBJECTIVE: To establish which of the many possible linkages between tuberculosis (TB), direct observation of treatment (DOTS), and the social reality of migrant workers in Kathmandu are the most relevant to the health outcomes and economic and social well-being of these populations, and which are amenable to possible interventions and high-yield policy changes. METHODS: Fourteen semi-structured in-depth interviews were conducted through an interpreter with male migrant TB patients aged 18-50 years recruited from three DOTS clinics in the Kathmandu valley in May 2005. The interviews were coded using constant comparison and analysed using a grounded theory method. RESULTS: The economic burden of TB treatment is far greater than the financial reserve of migrants. Consequently remittances sent to families are reduced and migrants remain in debt long after treatment completion, tied to the treatment location paying off high interest loans. Forced to attend clinics far away from their home, and isolated by the stigma associated with TB, migrants are vulnerable without social support networks. Migrants find that daily clinic visits are incompatible with working schedules and important cultural festivals, which forces them into defaulting. CONCLUSION: The needs of migrant workers with TB living in Kathmandu are not being adequately met. Current service provision needs to be reviewed to build in greater flexibility and support for migrant men.