Publications by authors named "Brian D Nicholson"

57 Publications

Rapid community point-of-care testing for COVID-19 (RAPTOR-C19): protocol for a platform diagnostic study.

Diagn Progn Res 2021 Feb 8;5(1). Epub 2021 Feb 8.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Radcliffe Observatory Quarter, Woodstock Road, Oxford, OX2 6GG, UK.

Background: The aim of RApid community Point-of-care Testing fOR COVID-19 (RAPTOR-C19) is to assess the diagnostic accuracy of multiple current and emerging point-of-care tests (POCTs) for active and past SARS-CoV2 infection in the community setting. RAPTOR-C19 will provide the community testbed to the COVID-19 National DiagnOstic Research and Evaluation Platform (CONDOR).

Methods: RAPTOR-C19 incorporates a series of prospective observational parallel diagnostic accuracy studies of SARS-CoV2 POCTs against laboratory and composite reference standards in patients with suspected current or past SARS-CoV2 infection attending community settings. Adults and children with suspected current SARS-CoV2 infection who are having an oropharyngeal/nasopharyngeal (OP/NP) swab for laboratory SARS-CoV2 reverse transcriptase Digital/Real-Time Polymerase Chain Reaction (d/rRT-PCR) as part of clinical care or community-based testing will be invited to participate. Adults (≥ 16 years) with suspected past symptomatic infection will also be recruited. Asymptomatic individuals will not be eligible. At the baseline visit, all participants will be asked to submit samples for at least one candidate point-of-care test (POCT) being evaluated (index test/s) as well as an OP/NP swab for laboratory SARS-CoV2 RT-PCR performed by Public Health England (PHE) (reference standard for current infection). Adults will also be asked for a blood sample for laboratory SARS-CoV-2 antibody testing by PHE (reference standard for past infection), where feasible adults will be invited to attend a second visit at 28 days for repeat antibody testing. Additional study data (e.g. demographics, symptoms, observations, household contacts) will be captured electronically. Sensitivity, specificity, positive, and negative predictive values for each POCT will be calculated with exact 95% confidence intervals when compared to the reference standard. POCTs will also be compared to composite reference standards constructed using paired antibody test results, patient reported outcomes, linked electronic health records for outcomes related to COVID-19 such as hospitalisation or death, and other test results.

Discussion: High-performing POCTs for community use could be transformational. Real-time results could lead to personal and public health impacts such as reducing onward household transmission of SARS-CoV2 infection, improving surveillance of health and social care staff, contributing to accurate prevalence estimates, and understanding of SARS-CoV2 transmission dynamics in the population. In contrast, poorly performing POCTs could have negative effects, so it is necessary to undertake community-based diagnostic accuracy evaluations before rolling these out.

Trial Registration: ISRCTN, ISRCTN14226970.
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http://dx.doi.org/10.1186/s41512-021-00093-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7868893PMC
February 2021

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

Lancet Gastroenterol Hepatol 2021 03 15;6(3):199-208. Epub 2021 Jan 15.

Clinical Trial Service Unit and Epidemiological Studies Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Medical Research Council Population Health Research Unit, Nuffield Department of Population Health, University of Oxford, Oxford, UK; Big Data Institute, University of Oxford, Oxford, UK.

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.
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http://dx.doi.org/10.1016/S2468-1253(21)00005-4DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7808901PMC
March 2021

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

Hypertension 2021 03 16;77(3):846-855. Epub 2020 Dec 16.

From the Nuffield Department of Primary Care Health Sciences, University of Oxford, United Kingdom (J.P.S., B.D.N., J.L., D.M., J.S., C.K., J.O., N.R.J., W.H., L.A., O.V.H., S.L.-F., C.R.B., H.L., J.W., F.F., M.D.F., M.P.J., S.d.L., F.D.R.H.).

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.
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http://dx.doi.org/10.1161/HYPERTENSIONAHA.120.16472DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7884248PMC
March 2021

At what times during infection is SARS-CoV-2 detectable and no longer detectable using RT-PCR-based tests? A systematic review of individual participant data.

BMC Med 2020 11 4;18(1):346. Epub 2020 Nov 4.

Centre for Medical Imaging, University College London, 2nd Floor, Charles Bell House, 43-45 Foley Street, London, W1W 7TS, UK.

Background: Tests for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) viral ribonucleic acid (RNA) using reverse transcription polymerase chain reaction (RT-PCR) are pivotal to detecting current coronavirus disease (COVID-19) and duration of detectable virus indicating potential for infectivity.

Methods: We conducted an individual participant data (IPD) systematic review of longitudinal studies of RT-PCR test results in symptomatic SARS-CoV-2. We searched PubMed, LitCOVID, medRxiv, and COVID-19 Living Evidence databases. We assessed risk of bias using a QUADAS-2 adaptation. Outcomes were the percentage of positive test results by time and the duration of detectable virus, by anatomical sampling sites.

Results: Of 5078 studies screened, we included 32 studies with 1023 SARS-CoV-2 infected participants and 1619 test results, from - 6 to 66 days post-symptom onset and hospitalisation. The highest percentage virus detection was from nasopharyngeal sampling between 0 and 4 days post-symptom onset at 89% (95% confidence interval (CI) 83 to 93) dropping to 54% (95% CI 47 to 61) after 10 to 14 days. On average, duration of detectable virus was longer with lower respiratory tract (LRT) sampling than upper respiratory tract (URT). Duration of faecal and respiratory tract virus detection varied greatly within individual participants. In some participants, virus was still detectable at 46 days post-symptom onset.

Conclusions: RT-PCR misses detection of people with SARS-CoV-2 infection; early sampling minimises false negative diagnoses. Beyond 10 days post-symptom onset, lower RT or faecal testing may be preferred sampling sites. The included studies are open to substantial risk of bias, so the positivity rates are probably overestimated.
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http://dx.doi.org/10.1186/s12916-020-01810-8DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7609379PMC
November 2020

Letter: extending FIT from DG30 to NG12 patients. Letter: faecal immunochemical testing for adults with symptoms of colorectal cancer - ready for prime time? Authors' reply: a unified approach to safety netting negative FITs is required.

Aliment Pharmacol Ther 2020 10;52(8):1420-1421

Clinical Biochemistry, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

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http://dx.doi.org/10.1111/apt.16082DOI Listing
October 2020

Excess mortality in the first COVID pandemic peak: cross-sectional analyses of the impact of age, sex, ethnicity, household size, and long-term conditions in people of known SARS-CoV-2 status in England.

Br J Gen Pract 2020 12 26;70(701):e890-e898. Epub 2020 Nov 26.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford.

Background: The SARS-CoV-2 pandemic has passed its first peak in Europe.

Aim: To describe the mortality in England and its association with SARS-CoV-2 status and other demographic and risk factors.

Design And Setting: Cross-sectional analyses of people with known SARS-CoV-2 status in the Oxford RCGP Research and Surveillance Centre (RSC) sentinel network.

Method: Pseudonymised, coded clinical data were uploaded from volunteer general practice members of this nationally representative network ( = 4 413 734). All-cause mortality was compared with national rates for 2019, using a relative survival model, reporting relative hazard ratios (RHR), and 95% confidence intervals (CI). A multivariable adjusted odds ratios (OR) analysis was conducted for those with known SARS-CoV-2 status ( = 56 628, 1.3%) including multiple imputation and inverse probability analysis, and a complete cases sensitivity analysis.

Results: Mortality peaked in week 16. People living in households of ≥9 had a fivefold increase in relative mortality (RHR = 5.1, 95% CI = 4.87 to 5.31, <0.0001). The ORs of mortality were 8.9 (95% CI = 6.7 to 11.8, <0.0001) and 9.7 (95% CI = 7.1 to 13.2, <0.0001) for virologically and clinically diagnosed cases respectively, using people with negative tests as reference. The adjusted mortality for the virologically confirmed group was 18.1% (95% CI = 17.6 to 18.7). Male sex, population density, black ethnicity (compared to white), and people with long-term conditions, including learning disability (OR = 1.96, 95% CI = 1.22 to 3.18, = 0.0056) had higher odds of mortality.

Conclusion: The first SARS-CoV-2 peak in England has been associated with excess mortality. Planning for subsequent peaks needs to better manage risk in males, those of black ethnicity, older people, people with learning disabilities, and people who live in multi-occupancy dwellings.
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http://dx.doi.org/10.3399/bjgp20X713393DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575407PMC
December 2020

CASNET2: evaluation of an electronic safety netting cancer toolkit for the primary care electronic health record: protocol for a pragmatic stepped-wedge RCT.

BMJ Open 2020 08 24;10(8):e038562. Epub 2020 Aug 24.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK.

Introduction: Safety-netting in primary care is the best practice in cancer diagnosis, ensuring that patients are followed up until symptoms are explained or have resolved. Currently, clinicians use haphazard manual solutions. The ubiquitous use of electronic health records provides an opportunity to standardise safety-netting practices.A new electronic safety-netting toolkit has been introduced to provide systematic ways to track and follow up patients. We will evaluate the effectiveness of this toolkit, which is embedded in a major primary care clinical system in England:Egerton Medical Information System(EMIS)-Web.

Methods And Analysis: We will conduct a stepped-wedge cluster RCT in 60 general practices within the RCGP Research and Surveillance Centre (RSC) network. Groups of 10 practices will be randomised into the active phase at 2-monthly intervals over 12 months. All practices will be activated for at least 2 months. The primary outcome is the primary care interval measured as days between the first recorded symptom of cancer (within the year prior to diagnosis) and the subsequent referral to secondary care. Other outcomes include referrals rates and rates of direct access cancer investigation.Analysis of the clustered stepped-wedge design will model associations using a fixed effect for intervention condition of the cluster at each time step, a fixed effect for time and other covariates, and then include a random effect for practice and for patient to account for correlation between observations from the same centre and from the same participant.

Ethics And Dissemination: Ethical approval has been obtained from the North West-Greater Manchester West National Health Service Research Ethics Committee (REC Reference 19/NW/0692). Results will be disseminated in peer-reviewed journals and conferences, and sent to participating practices. They will be published on the University of Oxford Nuffield Department of Primary Care and RCGP RSC websites.

Trial Registration Number: ISRCTN15913081; Pre-results.
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http://dx.doi.org/10.1136/bmjopen-2020-038562DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449309PMC
August 2020

Understanding the role of GPs' gut feelings in diagnosing cancer in primary care: a systematic review and meta-analysis of existing evidence.

Br J Gen Pract 2020 09 27;70(698):e612-e621. Epub 2020 Aug 27.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford.

Background: Growing evidence for the role of GPs' gut feelings in cancer diagnosis raises questions about their origin and role in clinical practice.

Aim: To explore the origins of GPs' gut feelings for cancer, their use, and their diagnostic utility.

Design And Setting: Systematic review and meta-analysis of international research on GPs' gut feelings in primary care.

Method: Six databases were searched from inception to July 2019, and internet searches were conducted. A segregated method was used to analyse, then combine, quantitative and qualitative findings.

Results: Twelve articles and four online resources were included that described varied conceptualisations of gut feelings. Gut feelings were often initially associated with patients being unwell, rather than with a suspicion of cancer, and were commonly experienced in response to symptoms and non-verbal cues. The pooled odds of a cancer diagnosis were four times higher when gut feelings were recorded (OR 4.24, 95% confidence interval = 2.26 to 7.94); they became more predictive of cancer as clinical experience and familiarity with the patient increased. Despite being included in some clinical guidelines, GPs had varying experiences of acting on gut feelings as some specialists questioned their diagnostic value. Consequently, some GPs ignored or omitted gut feelings from referral letters, or chose investigations that did not require specialist approval.

Conclusion: GPs' gut feelings for cancer were conceptualised as a rapid summing up of multiple verbal and non-verbal patient cues in the context of the GPs' clinical knowledge and experience. Triggers of gut feelings not included in referral guidance deserve further investigation as predictors of cancer. Non-verbal cues that trigger gut feelings appear to be reliant on continuity of care and clinical experience; they tend to remain poorly recorded and are, therefore, inaccessible to researchers.
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http://dx.doi.org/10.3399/bjgp20X712301DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7449376PMC
September 2020

Prioritising primary care patients with unexpected weight loss for cancer investigation: diagnostic accuracy study.

BMJ 2020 08 13;370:m2651. Epub 2020 Aug 13.

Medical School, University of Exeter, Exeter, UK.

Objective: To quantify the predictive value of unexpected weight loss (WL) for cancer according to patient's age, sex, smoking status, and concurrent clinical features (symptoms, signs, and abnormal blood test results).

Design: Diagnostic accuracy study.

Setting: Clinical Practice Research Datalink electronic health records data linked to the National Cancer Registration and Analysis Service in primary care, England.

Participants: 63 973 adults (≥18 years) with a code for unexpected WL from 1 January 2000 to 31 December 2012.

Main Outcome Measures: Cancer diagnosis in the six months after the earliest weight loss code (index date). Codes for additional clinical features were identified in the three months before to one month after the index date. Diagnostic accuracy measures included positive and negative likelihood ratios, positive predictive values, and diagnostic odds ratios.

Results: Of 63 973 adults with unexpected WL, 37 215 (58.2%) were women, 33 167 (51.8%) were aged 60 years or older, and 16 793 (26.3%) were ever smokers. 908 (1.4%) had a diagnosis of cancer within six months of the index date, of whom 882 (97.1%) were aged 50 years or older. The positive predictive value for cancer was above the 3% threshold recommended by the National Institute for Health and Care Excellence for urgent investigation in male ever smokers aged 50 years or older, but not in women at any age. 10 additional clinical features were associated with cancer in men with unexpected WL, and 11 in women. Positive likelihood ratios in men ranged from 1.86 (95% confidence interval 1.32 to 2.62) for non-cardiac chest pain to 6.10 (3.44 to 10.79) for abdominal mass, and in women from 1.62 (1.15 to 2.29) for back pain to 20.9 (10.7 to 40.9) for jaundice. Abnormal blood test results associated with cancer included low albumin levels (4.67, 4.14 to 5.27) and raised values for platelets (4.57, 3.88 to 5.38), calcium (4.28, 3.05 to 6.02), total white cell count (3.76, 3.30 to 4.28), and C reactive protein (3.59, 3.31 to 3.89). However, no normal blood test result in isolation ruled out cancer. Clinical features co-occurring with unexpected WL were associated with multiple cancer sites.

Conclusion: The risk of cancer in adults with unexpected WL presenting to primary care is 2% or less and does not merit investigation under current UK guidelines. However, in male ever smokers aged 50 years or older and in patients with concurrent clinical features, the risk of cancer warrants referral for invasive investigation. Clinical features typically associated with specific cancer sites are markers of several cancer types when they occur with unexpected WL.
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http://dx.doi.org/10.1136/bmj.m2651DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7424394PMC
August 2020

Faecal immunochemical testing for adults with symptoms of colorectal cancer attending English primary care: a retrospective cohort study of 14 487 consecutive test requests.

Aliment Pharmacol Ther 2020 09 17;52(6):1031-1041. Epub 2020 Jul 17.

Department of Clinical Biochemistry, John Radcliffe Hospital, Oxford University Hospitals Trust, Oxford, UK.

Background: Faecal immunochemical testing (FIT) is recommended by the National Institute for Health and Care Excellence (NICE) to triage symptomatic primary care patients for further investigation of colorectal cancer.

Aim: To ascertain the diagnostic performance of FIT in symptomatic adult primary care patients.

Methods: Faecal samples from routine primary care practice in Oxfordshire, UK were analysed using the HM-JACKarc FIT method between March 2017 and March 2020. Clinical details were recorded. Patients were followed for up to 36 months in linked hospital records for evidence of benign and serious (colorectal cancer, high-risk adenomas and bowel inflammation) colorectal disease. The diagnostic accuracy of FIT is reported by gender, age group and FIT threshold.

Results: In 9896 adult patients with at least 6-month follow-up, a FIT result ≥10 µg Hb/g faeces had a sensitivity for colorectal cancer of 90.5% (95% CI 84.9%-96.1%), specificity 91.3% (90.8%-91.9%), positive predictive value (PPV) 10.1% (8.15%-12.0%) and negative predictive value (NPV) 99.9% (99.8%-100.0%). The PPV and specificity for serious colorectal disease were higher and the sensitivity and NPV lower than for colorectal cancer alone. The area under the curve for all adults did not change substantially by gender or by increasing the minimum age of testing. Using ≥10 µg Hb/g faeces, 10% of adults would be investigated to detect 91% of cancers, a number needed to scope of ten to detect one cancer. Using ≥7, ≥50 and ≥150 µg Hb/g faeces, 11%, 4% and 3% of adults would be investigated, and 91%, 74% and 54% cancers detected, respectively.

Conclusion: A FIT threshold of ≥10 µg Hb/g faeces would be appropriate to triage adult patients presenting to primary care with symptoms of serious colorectal disease. FIT may be used to reprioritise patients referred with colorectal cancer symptoms whose investigations have been delayed by the COVID-19 pandemic.
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http://dx.doi.org/10.1111/apt.15969DOI Listing
September 2020

The association between unexpected weight loss and cancer diagnosis in primary care: a matched cohort analysis of 65,000 presentations.

Br J Cancer 2020 Jun 15;122(12):1848-1856. Epub 2020 Apr 15.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, OX2 6GG, UK.

Background: We aimed to understand the time period of cancer diagnosis and the cancer types detected in primary care patients with unexpected weight loss (UWL) to inform cancer guidelines.

Methods: This retrospective matched cohort study used cancer registry linked electronic health records from the UK's Clinical Practice Research Datalink from between 2000 and 2014. Univariable and multivariable time-to-event analyses examined the association between UWL, and all cancers combined, cancer site and stage.

Results: In all, 63,973 patients had UWL recorded, of whom 1375 (2.2%) were diagnosed with cancer within 2 years (days-to-diagnosis: mean 181; median 80). Men with UWL (HR 3.28 (2.88-3.73)) and women (1.87 (1.68-2.08)) were more likely than comparators to be diagnosed with cancer within 3 months. The association was greatest in men aged ≥50 years and women ≥70 years. The commonest cancers were pancreas, cancer of unknown primary, gastro-oesophageal, lymphoma, hepatobiliary, lung, bowel and renal-tract. The majority were late-stage, but there was some evidence of association with stage II and stage III cancers. In the 3-24 months after presenting with UWL, cancer diagnosis was less likely than in comparators.

Conclusion: UWL recorded in primary care is associated with a broad range of cancer sites of early and late-stage.
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http://dx.doi.org/10.1038/s41416-020-0829-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7283307PMC
June 2020

Death audits and reviews for reducing maternal, perinatal and child mortality.

Cochrane Database Syst Rev 2020 03 25;3:CD012982. Epub 2020 Mar 25.

University of Oxford, Nuffield Department of Primary Care Health Sciences, Oxford, UK.

Background: The United Nations' Sustainable Development Goals (SDGs) include reducing the global maternal mortality rate to less than 70 per 100,000 live births and ending preventable deaths of newborns and children under five years of age, in every country, by 2030. Maternal and perinatal death audit and review is widely recommended as an intervention to reduce maternal and perinatal mortality, and to improve quality of care, and could be key to attaining the SDGs. However, there is uncertainty over the most cost-effective way of auditing and reviewing deaths: community-based audit (verbal and social autopsy), facility-based audits (significant event analysis (SEA)) or a combination of both (confidential enquiry).

Objectives: To assess the impact and cost-effectiveness of different types of death audits and reviews in reducing maternal, perinatal and child mortality.

Search Methods: We searched the following from inception to 16 January 2019: CENTRAL, Ovid MEDLINE, Embase OvidSP, and five other databases. We identified ongoing studies using ClinicalTrials.gov and the World Health Organization (WHO) International Clinical Trials Registry Platform, and searched reference lists of included articles.

Selection Criteria: Cluster-randomised trials, cluster non-randomised trials, controlled before-and-after studies and interrupted time series studies of any form of death audit or review that involved reviewing individual cases of maternal, perinatal or child deaths, identifying avoidable factors, and making recommendations. To be included in the review, a study needed to report at least one of the following outcomes: perinatal mortality rate; stillbirth rate; neonatal mortality rate; mortality rate in children under five years of age or maternal mortality rate.

Data Collection And Analysis: We used standard Cochrane Effective Practice and Organisation of Care (EPOC) group methodological procedures. Two review authors independently extracted data, assessed risk of bias and assessed the certainty of the evidence using GRADE. We planned to perform a meta-analysis using a random-effects model but included studies were not homogeneous enough to make pooling their results meaningful.

Main Results: We included two cluster-randomised trials. Both introduced death review and audit as part of a multicomponent intervention, and compared this to current care. The QUARITE study (QUAlity of care, RIsk management, and TEchnology) concerned maternal death reviews in hospitals in West Africa, which had very high maternal and perinatal mortality rates. In contrast, the OPERA trial studied perinatal morbidity/mortality conferences (MMCs) in maternity units in France, which already had very low perinatal mortality rates at baseline. The OPERA intervention in France started with an outreach visit to brief obstetricians, midwives and anaesthetists on the national guidelines on morbidity/mortality case management, and was followed by a series of perinatal MMCs. Half of the intervention units were randomised to receive additional support from a clinical psychologist during these meetings. The OPERA intervention may make little or no difference to overall perinatal mortality (low certainty evidence), however we are uncertain about the effect of the intervention on perinatal mortality related to suboptimal care (very low certainty evidence).The intervention probably reduces perinatal morbidity related to suboptimal care (unadjusted odds ratio (OR) 0.62, 95% confidence interval (CI) 0.40 to 0.95; 165,353 births; moderate-certainty evidence). The effect of the intervention on stillbirth rate, neonatal mortality, mortality rate in children under five years of age, maternal mortality or adverse effects was not reported. The QUARITE intervention in West Africa focused on training leaders of hospital obstetric teams using the ALARM (Advances in Labour And Risk Management) course, which included one day of training about conducting maternal death reviews. The leaders returned to their hospitals, established a multidisciplinary committee and started auditing maternal deaths, with the support of external facilitators. The intervention probably reduces inpatient maternal deaths (adjusted OR 0.85, 95% CI 0.73 to 0.98; 191,167 deliveries; moderate certainty evidence) and probably also reduces inpatient neonatal mortality within 24 hours following birth (adjusted OR 0.74, 95% CI 0.61 to 0.90; moderate certainty evidence). However, QUARITE probably makes little or no difference to the inpatient stillbirth rate (moderate certainty evidence) and may make little or no difference to the inpatient neonatal mortality rate after 24 hours, although the 95% confidence interval includes both benefit and harm (low certainty evidence). The QUARITE intervention probably increases the percent of women receiving high quality of care (OR 1.87, 95% CI 1.35 - 2.57, moderate-certainty evidence). The effect of the intervention on perinatal mortality, mortality rate in children under five years of age, or adverse effects was not reported. We did not find any studies that evaluated child death audit and review or community-based death reviews or costs.

Authors' Conclusions: A complex intervention including maternal death audit and review, as well as development of local leadership and training, probably reduces inpatient maternal mortality in low-income country district hospitals, and probably slightly improves quality of care. Perinatal death audit and review, as part of a complex intervention with training, probably improves quality of care, as measured by perinatal morbidity related to suboptimal care, in a high-income setting where mortality was already very low. The WHO recommends that maternal and perinatal death reviews should be conducted in all hospitals globally. However, conducting death reviews in isolation may not be sufficient to achieve the reductions in mortality observed in the QUARITE trial. This review suggests that maternal death audit and review may need to be implemented as part of an intervention package which also includes elements such as training of a leading doctor and midwife in each hospital, annual recertification, and quarterly outreach visits by external facilitators to provide supervision and mentorship. The same may also apply to perinatal and child death reviews. More operational research is needed on the most cost-effective ways of implementing maternal, perinatal and paediatric death reviews in low- and middle-income countries.
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http://dx.doi.org/10.1002/14651858.CD012982.pub2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7093891PMC
March 2020

Democracy and implementation of non-communicable disease policies - Authors' reply.

Lancet Glob Health 2020 04;8(4):e484

Nuffield Department of Primary Care Health Science, University of Oxford, Oxford, OX2 6CG, UK.

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http://dx.doi.org/10.1016/S2214-109X(20)30033-4DOI Listing
April 2020

Public preferences for using quantitative faecal immunochemical test versus colonoscopy as diagnostic test for colorectal cancer: evidence from an online survey.

BJGP Open 2020 1;4(1). Epub 2020 May 1.

Programme Manager, UCLH Cancer Collaborative, University College London Hospitals, London, UK.

Background: There has been interest in using the non-invasive, home-based quantitative faecal immunochemical test (FIT) to rule out colorectal cancer (CRC) in high-risk symptomatic patients.

Aim: To elicit public preferences for FIT versus colonoscopy (CC) and its delivery in primary care.

Design & Setting: A cross-sectional online survey in England.

Method: A total of 1057 adults (without CRC symptoms and diagnosis) aged 40-59 years were invited from an English online survey panel. Responders were asked to imagine they had been experiencing CRC symptoms that would qualify them for a diagnostic test. Participants were presented with choices between CC and FIT in ascending order of number of CRCs missed by FIT (from 1-10%). It was measured at what number of missed CRCs responders preferred CC over FIT.

Results: While 150 participants did not want either of the tests when both missed 1% CRCs, the majority ( = 741, 70.0%) preferred FIT to CC at that level of accuracy. However, this preference reduced to 427 (40.4%) when FIT missed one additional cancer. Women were more likely to tolerate missing CRC when using FIT. Having lower numeracy and perceiving a higher level of risk meant participants were less likely to tolerate a false negative test. Most of those who chose FIT preferred to return it by mail (62.2%), to be informed about normal test results by letter (42.1%), and about abnormal test results face to face (32.5%).

Conclusion: While the majority of participants preferred FIT over CC when both tests had the same sensitivity, tolerance for missed CRCs was low.
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http://dx.doi.org/10.3399/bjgpopen20X101007DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7330201PMC
May 2020

Negotiating the risks of computed tomography in primary care.

Br J Gen Pract 2020 Feb 30;70(691):86-87. Epub 2020 Jan 30.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford.

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http://dx.doi.org/10.3399/bjgp20X708029DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018410PMC
February 2020

Bridging the gap between care: is speed dating the answer?

Br J Gen Pract 2020 02 30;70(691):73. Epub 2020 Jan 30.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford

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http://dx.doi.org/10.3399/bjgp20X707513DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7018422PMC
February 2020

Implementation of non-communicable disease policies: a geopolitical analysis of 151 countries.

Lancet Glob Health 2020 01 5;8(1):e50-e58. Epub 2019 Dec 5.

Centre of Health Policy, Institute of Global Health Innovation, Imperial College London, London, UK.

Background: Most countries have endorsed WHO non-communicable disease (NCD) best buy policies, but we know very little about global implementation patterns and about the geopolitical factors affecting implementation. We aimed to assess global implementation based on analysis of multiple geopolitical datasets.

Methods: We used the 2015 and 2017 WHO NCD progress monitor reports to calculate aggregate implementation scores for 151 countries, based on their implementation of 18 WHO-recommended NCD policies. We ranked all countries and used descriptive statistics to analyse global trends. We used linear regression to assess the associations between policy implementation and World Bank geographic region, risk of premature NCD mortality, percentage of all deaths caused by NCDs, World Bank income group, human capital index, democracy index, and tax burden.

Findings: In 2017, the mean NCD policy implementation score was 49·3% (SD 18·4%). Costa Rica and Iran had the joint-highest implementation scores (86·1% of all WHO-recommended policies). Scores were lowest in Haiti and South Sudan (5·5%). Between 2015 and 2017, aggregate implementation scores rose in 109 countries and regressed in 32 countries. Mean implementation rose for all of the 18 policies except for those targeting alcohol and physical activity. The most commonly implemented policies were clinical guidelines, graphic warnings on tobacco packaging, and NCD risk factor surveys. Our multiple linear regression model explained 61·1% of the variance in 2017 aggregate scores (p<0·0001), but we found evidence of a high degree of collinearity between the explanatory variables.

Interpretation: Implementation of WHO-recommended NCD policies is increasing over time. On average, countries implemented just under half of the NCD policies recommended by WHO in 2017. Nutrition-related policies saw gains, while those related to alcohol and physical activity were the most likely to have been dropped. Aggregate implementation scores tended to be highest in high-income countries that invest in health care and education.

Funding: National Institute for Health Research, Imperial College London, University of Oxford.
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http://dx.doi.org/10.1016/S2214-109X(19)30446-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7024987PMC
January 2020

Quality improvements of safety-netting guidelines for cancer in UK primary care: insights from a qualitative interview study of GPs.

Br J Gen Pract 2019 Dec 28;69(689):e819-e826. Epub 2019 Nov 28.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford.

Background: Safety netting is a diagnostic strategy that involves monitoring patients with symptoms possibly indicative of serious illness, such as cancer, until they are resolved. Optimising safety-netting practice in primary care has been proposed to improve quality of care and clinical outcomes. Introducing guidelines is a potential means to achieve this.

Aim: To seek the insight of frontline GPs regarding proposed safety-netting guidelines for suspected cancer in UK primary care.

Design And Setting: A qualitative interview study with 25 GPs practising in Oxfordshire, UK.

Method: Transcripts from semi-structured interviews were analysed thematically by a multidisciplinary research team using a mind-mapping approach.

Results: GPs were supportive of initiatives to optimise safety netting. Guidelines on establishing who has responsibility for follow-up, keeping patient details up to date, and ensuring test result review is conducted by someone with knowledge of cancer guidelines were already being followed. Sharing diagnostic uncertainty and ensuring an up-to-date understanding of guidelines were only partially implemented. Neither informing patients of all (including negative) test results nor ensuring recurrent unexplained symptoms are always flagged and referred were considered feasible. The lack of detail, for example, the expected duration of symptoms, caused some concern. Overall, doubts were expressed about the feasibility of the guidelines given the time, recruitment, and resource challenges faced in UK primary care.

Conclusion: GPs expressed general support for safety netting, yet were unconvinced that key elements of the guidelines were feasible, especially in the context of pressures on general practice staffing and time.
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http://dx.doi.org/10.3399/bjgp19X706565DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6833915PMC
December 2019

Experience of adopting faecal immunochemical testing to meet the NICE colorectal cancer referral criteria for low-risk symptomatic primary care patients in Oxfordshire, UK.

Frontline Gastroenterol 2019 Oct 9;10(4):347-355. Epub 2018 Oct 9.

Department of Clinical Biochemistry, John Radcliffe Hospital, Oxford University Hospitals Trust, Oxford, UK.

Objective: To compare the diagnostic performance of guaiac faecal occult blood (gFOB) testing with faecal immunochemical test (FIT) in a low-risk symptomatic primary care population to provide objective data on which to base local referral guidelines.

Design: Stool samples from routine primary care practice sent for faecal occult blood testing were analysed by a standard gFOB method and the HM-JACKarc FIT between January and March 2016. Symptoms described on the test request were recorded. Patients were followed up over 21 months for evidence of serious gastrointestinal pathology including colorectal adenocarcinoma.

Results: In 238 patients, the sensitivity and specificity for colorectal adenocarcinoma detection using gFOB were 85.7% and 65.8%, respectively, compared with 85.7% and 89.2% for FIT. The positive predictive value (PPV) for gFOB was 7.1% and negative predictive value (NPV) was 99.3%. Comparatively, the PPV for FIT was 19.4% and NPV 99.5%. The improved performance of FIT over gFOB was due to a lower false positive rate (10.8 vs 34.2, p≤0.01) with no increase in the false negatives rate. For any significant colorectal disease, the PPV for FIT increased to 35.5% with a reduction in NPV to 95.7%.

Conclusion: In this low-risk symptomatic patient group, the proportion of samples considered positive by FIT was considerably lower than gFOB with the same rate of colorectal adenocarcinoma detection. One in three of those with positive FIT had a significant colorectal disease. This supports National Institute of Health and Care Excellence recommendation that FIT can be reliably used as a triage test in primary care without overburdening endoscopy resources.
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http://dx.doi.org/10.1136/flgastro-2018-101052DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6788275PMC
October 2019

When should unexpected weight loss warrant further investigation to exclude cancer?

BMJ 2019 Sep 23;366:l5271. Epub 2019 Sep 23.

Nuffield Department of Primary Care Health Sciences, University of Oxford OX2 6GG, UK.

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http://dx.doi.org/10.1136/bmj.l5271DOI Listing
September 2019

How do GPs and patients share the responsibility for cancer safety netting follow-up actions? A qualitative interview study of GPs and patients in Oxfordshire, UK.

BMJ Open 2019 09 12;9(9):e029316. Epub 2019 Sep 12.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford, UK

Objective: To explore patients' and General Practitioners' (GPs) accounts of how responsibility for follow-up was perceived and shared in their experiences of cancer safety netting occurring within the past 6 months.

Design: In-depth interviews were recorded and transcribed verbatim. Data were analysed through an abductive process, exploring anticipated and emergent themes. Conceptualisations of 'responsibility' were explored by drawing on a to continuum drawing from the shared decision-making literature.

Settings And Participants: A purposive sample of 25 qualified GPs and 23 adult patients in Oxfordshire, UK.

Results: The transactional sharing approach involves responsibility being passed from GP to patient. Patients expected and were willing to accept responsibility in this way as long as they received clear guidance from their GP and had capacity. In interdependent sharing, GPs principally aimed to reach consensus and share responsibility with the patient by explaining their rationale, uncertainty or by stressing the potential seriousness of the situation. Patients sharing this responsibility could be put at risk if no follow-up or timeframe was suggested, they had inadequate information, were falsely reassured or their concerns were not addressed at re-consultation.

Conclusion: GPs and patients exchange and share responsibility using a combination of transactional and interdependent styles, tailoring information based on patient characteristics and each party's level of concern. Clear action plans (written where necessary) at the end of every consultation would help patients decide when to re-consult. Further research should investigate how responsibility is shared within and outside the consultation, within primary care teams and with specialist services.
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http://dx.doi.org/10.1136/bmjopen-2019-029316DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6747661PMC
September 2019

General practitioners' awareness of the recommendations for faecal immunochemical tests (FITs) for suspected lower gastrointestinal cancers: a national survey.

BMJ Open 2019 04 11;9(4):e025737. Epub 2019 Apr 11.

Research Department of Behavioural Science and Health, UCL, London, UK.

Objectives: In July 2017, UK National Institute for Health and Care Excellence (NICE) published a diagnostic guidance (DG30) recommending the use of faecal immunochemical tests (FITs) for symptomatic patients who do not meet the urgent referral pathway for suspected colorectal cancer (CRC). We assessed general practitioners' (GP) awareness of DG30 in primary care 6 months after its publication.

Design And Setting: Cross-sectional online survey of GPs hosted by an English panel of Primary health care professionals.

Participants: In December 2017, 1024 GPs registered on an online panel (M3) based in England took part in an online survey.

Outcomes And Variables: We investigated a number of factors including previous experience of using FIT and guaiac faecal occult blood tests (FOBTs), the number of urgent referrals for CRC that GPs have made in the last year and their sociodemographic and professional characteristics that could be associated with their self-reported awareness of the FIT diagnostic guidance.

Results: Of the 1024 GPs who completed the survey, 432 (42.2%) were aware of the current recommendation but only 102 (10%) had used it to guide their referrals. Awareness was lowest in North West England compared with London (30.5% vs 44.9%; adjusted OR: 0.55, 95% CI 0.33 to 0.92). Awareness of the FIT guidance was positively associated with test usage after the NICE update (adjusted OR: 13.00, 95% CI 6.87 to 24.61) and having specialist training (adjusted OR: 1.48, 95% CI 1.05 to 2.08). The number of urgent referrals, the previous use of FOBt, GPs' age and gender, work experience and practice size (both in terms of the number of GPs or patients at the practice) were not associated with awareness.

Conclusions: Less than half of GPs in this survey recognised the current guidance on the use of FIT. Self-reported awareness was not systematically related to demographic of professional characteristics.
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http://dx.doi.org/10.1136/bmjopen-2018-025737DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6500239PMC
April 2019

Patient consultation rate and clinical and NHS outcomes: a cross-sectional analysis of English primary care data from 2.7 million patients in 238 practices.

BMC Health Serv Res 2019 Apr 6;19(1):219. Epub 2019 Apr 6.

Centre for Academic Primary Care, Bristol Medical School, University of Bristol, Bristol, UK.

Background: Primary care workload is high and increasing in the United Kingdom. We sought to examine the association between rates of primary care consultation and outcomes in England.

Methods: Cross sectional observational study of routine electronic health care records in 283 practices from the Clinical Practice Research Datalink from April 2013 to March 2014. Outcomes included mortality rate, hospital admission rate, Quality and Outcomes Framework (QOF) performance and patient satisfaction. Relationships between consultation rates (with a general practitioner (GP) or nurse) and outcomes were investigated using negative binomial and ordinal logistic regression models.

Results: Rates of GP and nurse consultation (per patient person-year) were not associated with mortality or hospital admission rates: mortality incidence rate ratio (IRR) per unit change in GP/ nurse consultation rate = 1.01, 95% CI [0.98 to 1.04]/ 0.97, 95% CI [0.93 to 1.02]; hospital admission IRR per unit change in GP/ nurse consultation rate = 1.02, 95% CI [0.99 to 1.04]/ 0.98, 95% CI [0.94 to 1.032]. Higher rates of nurse but not GP consultation were associated with higher QOF achievement: OR = 1.91, 95% CI [1.39 to 2.62] per unit change in nurse consultation rate vs. OR = 1.04, 95% CI [0.87 to 1.24] per unit change in GP consultation rate. The association between the rates of GP/ nurse consultations and patient satisfaction was mixed.

Conclusion: There are few associations between primary care consultation rates and outcomes. Previously identified demographic and staffing factors, rather than practice workload, appear to have the strongest relationships with mortality, admissions, performance and satisfaction. Studies with more detailed patient-level data would be required to explore these findings further.
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http://dx.doi.org/10.1186/s12913-019-4036-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6451312PMC
April 2019

Faecal immunochemical (rule-in) testing in general practice.

Br J Gen Pract 2019 04;69(681):178

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford.

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http://dx.doi.org/10.3399/bjgp19X702173DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6428482PMC
April 2019

The internal validation of weight and weight change coding using weight measurement data within the UK primary care Electronic Health Record.

Clin Epidemiol 2019 25;11:145-155. Epub 2019 Jan 25.

Nuffield Department of Primary Care Health Sciences, University of Oxford, Oxford OX26GG, UK,

Purpose: To use recorded weight values to internally validate weight status and weight change coding in the primary care Electronic Health Record (EHR).

Patients And Methods: We included adult patients with weight-related Read codes recorded in the UK's Clinical Practice Research Datalink EHR between 2000 and 2017. Weight status codes were compared to weight values recorded on the same day and positive predictive values (PPVs) were calculated for commonly used codes. Weight change codes were validated using three methods: the percentage (%) difference in kilograms at the time of the code and 1) the previous weight measurement, 2) the weight predicted using linear regression, and 3) the historic mean weight. Weight change codes were validated if estimates were consistent across two out of three methods.

Results: A total of 8,108,481 weight codes were recorded in 1,000,002 patients' EHR. Twice as many were recorded in females (n=5,208,593, 64%). The mean body mass index for "overweight" codes ranged from 31.9 kg/m to 46.9 kg/m and from 17.4 kg/m to 19.2 kg/m for "underweight" codes. PPVs for the most commonly used weight status codes ranged from 81.3% (80%-82.5%) to 99.3% (99.2%-99.4%). Across the estimation methods, and using only validated weight change codes, mean weight loss ranged from - 5.2% (SD 5.8%) to -7.9% (SD 7.3%) and mean weight gain from 4.2 % (SD 5.5%) to 7.9 % (SD 8.2%). The previous and predicted weight methods were most consistent.

Conclusion: We have developed an internationally applicable methodology to internally validate weight-related EHR coding by using available weight measurement data. We demonstrate the UK Read codes that can be confidently used to classify weight status and weight change in the absence of weight values. We provide the first evidence from primary care that a Read code for unexpected weight loss represents a mean loss of ≥ 5 % in a 6-month period, which was broadly consistent across age groups and gender.
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http://dx.doi.org/10.2147/CLEP.S189989DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6354686PMC
January 2019

The diagnostic performance of current tumour markers in surveillance for recurrent testicular cancer: A diagnostic test accuracy systematic review.

Cancer Epidemiol 2019 04 15;59:15-21. Epub 2019 Jan 15.

Nuffield Department of Primary Care Health Sciences, University of Oxford, UK. Electronic address:

In this diagnostic test accuracy systematic review we summarise the evidence on the diagnostic accuracy of blood α-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH) in surveillance for testicular cancer recurrence in adults. We searched four electronic databases for studies that reported the diagnostic accuracy of HCG, AFP, and/or LDH in sufficient detail for sensitivity and specificity to be calculated by extracting a 2 × 2 table comparing biomarker positivity with testicular cancer recurrence. Screening, data extraction and QUADAS-2 quality assessment were completed by two independent reviewers. From 2406 studies, nine met our inclusion criteria. Eight reported data at the per-patient level. Sample sizes were small (range 5 to 449 patients) and clinical heterogeneity precluded meta-analysis. In most studies the specificity for recurrence with AFP and HCG was high (90-100%) but sensitivity was often relatively low, suggesting that many recurrences would not be detected by tumour markers alone. The diagnostic performance of LDH appears poorer. Studies were methodologically weak, with probable selection, incorporation and partial verification bias, and many studies were excluded for not reporting on recurrence-free patients. Limitations including small sample sizes, high heterogeneity, and inconsistent and incomplete reporting mean these results must be interpreted with caution. Despite inclusion of biomarkers in international surveillance guidance, there remains a lack of high quality evidence about their accuracy, optimal thresholds, and the most effective surveillance strategy in relation to contemporary investigative modalities. Higher quality research using data from modern-day follow-up cohorts is necessary to identify opportunities to reduce unnecessary testing.
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http://dx.doi.org/10.1016/j.canep.2019.01.001DOI Listing
April 2019

National cancer control plans.

Lancet Oncol 2018 12;19(12):e665

Medical School, University of Exeter, Exeter, UK.

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http://dx.doi.org/10.1016/S1470-2045(18)30830-1DOI Listing
December 2018

The elusive diagnosis of cancer: testing times.

Br J Gen Pract 2018 11;68(676):510-511

Department of Family Medicine, University of Washington, US.

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http://dx.doi.org/10.3399/bjgp18X699461DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193796PMC
November 2018

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

Br J Gen Pract 2018 Nov 8;68(676):e757-e764. Epub 2018 Oct 8.

Research Department of Behavioural Science and Health.

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 ( = 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.
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http://dx.doi.org/10.3399/bjgp18X699413DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6193787PMC
November 2018

The mapping of cancer incidence and mortality trends in the UK from 1980-2013 reveals a potential for overdiagnosis.

Sci Rep 2018 10 2;8(1):14663. Epub 2018 Oct 2.

University of Oxford, Nuffield Department of Primary Care Health Sciences, Oxford, OX2 6GG, United Kingdom.

The incidence of cancer in the United Kingdom has increased significantly over the last four decades. The aim of this study was to examine trends in UK cancer incidence and mortality by cancer site and assess the potential for overdiagnosis. Using Cancer Research UK incidence and mortality data for the period (1971-2014) we estimated percentage change in incidence and mortality rates and the incidence-mortality ratio (IMR) for cancers in which incidence had increased >50%. Incidence and mortality trend plots were used to assess the potential for overdiagnosis. Incidence rates increased from 67% (uterine) to 375% (melanoma). Change in mortality rates ranged from -69% (cervical) to +239% (liver). The greatest divergences occurred in uterine (IMR = 132), prostate (IMR = 9.6), oral (IMR = 9.8) and thyroid cancer (IMR = 5.3). Only in liver cancer did mortality track incidence (IMR = 1.1). For four cancer sites; uterine, prostate, oral and thyroid, incidence and mortality trends are suggestive of overdiagnosis. Trends in melanoma and kidney cancer suggest potential overdiagnosis and an underlying increase in true risk, whereas for cervical and breast cancer, trends may also reflect improvements in treatments or earlier diagnosis. A more detailed analysis is required to fully understand these patterns.
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http://dx.doi.org/10.1038/s41598-018-32844-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6168593PMC
October 2018