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The usefulness of symptoms alone or combined for general practitioners in considering the diagnosis of a brain tumour: a case-control study using the clinical practice research database (CPRD) (2000-2014)
  1. Mio Ozawa1,
  2. Paul M Brennan2,
  3. Karolis Zienius2,
  4. Kathreena M Kurian1,
  5. William Hollingworth1,
  6. David Weller3,
  7. Robin Grant4,
  8. Willie Hamilton5,
  9. Yoav Ben-Shlomo1
  1. 1Population Health Sciences, University of Bristol, Bristol, UK
  2. 2Department of Clinical Neurosciences, Western General Hospital, Edinburgh, UK
  3. 3General Practice, University of Edinburgh, Edinburgh, UK
  4. 4Centre for Clinical Brain Sciences, University of Edinburgh, Edinburgh, UK
  5. 5Primary Care Diagnostics, University of Exeter Medical School, Exeter, UK
  1. Correspondence to Professor Yoav Ben-Shlomo; Y.Ben-Shlomo{at}


Objectives To evaluate the utility of different symptoms, alone or combined, presented to primary care for an adult brain tumour diagnosis.

Design and setting Matched case-control study, using the data from Clinical Practice Research Datalink (2000–2014) from primary care consultations in the UK.

Method All presentations within 6 months of the index diagnosis date (cases) or equivalent (controls) were coded into 32 symptom groups. Sensitivity, specificity, positive predictive values (PPVs) and positive likelihood ratios were calculated for symptoms and combinations of symptoms with headache and cognitive features. Diagnostic odds ratios were calculated using conditional logistic regression, adjusted for age group, sex and Charlson comorbidity. Stratified analyses were performed for age group, sex and whether the tumour was of primary or secondary origin.

Results We included 8,184 cases and 28,110 controls. Seizure had the highest PPV of 1.6% (95% CI 1.4% to 1.7%) followed by weakness 1.5% (1.3 to 1.7) and confusion 1.4% (1.3 to 1.5). Combining headache with other symptoms increased the PPV. For example, headache plus combined cognitive symptoms PPV 7.2% (6.0 to 8.6); plus weakness 4.4% (3.2 to 6.2), compared with headache alone PPV 0.1%. The diagnostic ORs were generally larger for patients <70 years; this was most marked for confusion, seizure and visual symptoms.

Conclusion We found seizure, weakness and confusion had relatively higher predictive values than many other symptoms. Headache on its own was a weak predictor but this was enhanced when combined with other symptoms especially in younger patients. Clinicians need to actively search for other neurological symptoms such as cognitive problems.

  • neurological oncology
  • primary care
  • brain tumour
  • symptoms
  • diagnosis
  • clinical practice research datalink

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  • Contributors Paul M Brennan (PB), Kathreena M Kurian (KK), William Hollingworth (WHo), David Weller (DW), Robin Grant (RG), Willie Hamilton (WHa) and Yoav Ben-Shlomo (YBS) got funding for the work. Mio Ozawa (MO), Karolis Zienius (KZ), PB, KK, WHo, DW, RG, WHa and YBS designed the analysis plan. KZ, WH and YBS helped devise the symptom domains of the study. MO and YBS undertook the data analysis. MO, KZ, PB, KK, WHo, DW, RG, WHa and YBS were involved with the data interpretation. MO and YBS co-wrote the first draft of the paper which was then modified after comments and suggestions from KZ, PB, KK, WHo, DW, RG and WHa.

  • Funding This project has been funded by a grant from the Brain Tumour Charity (GN-000295) as part of a programme of work on understanding the diagnostic pathway for brain tumours in adults and its potential impact on clinical care and outcomes. The funders had no role in the design, analysis, interpretation and reporting of the results.

  • Competing interests None declared.

  • Patient consent for publication Not required.

  • Ethics approval This study was approved by the CPRD’s Independent Scientific Advisory Committee (ISAC), protocol number: 16_222R.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Data availability statement Data may be obtained from a third party and are not publicly available.

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