Selection of men for investigation of possible testicular cancer in primary care: a large case-control study using electronic patient records

This is the author accepted manuscript. The final version is available from the Royal College of General Practitioners via the DOI in this record.BACKGROUND: Testicular cancer incidence has risen over the last two decades and is expected to continue to rise. There are no primary care studies on the clinical features of testicular cancer, with recent National Institute for Health and Care Excellence (NICE) guidance based solely upon clinical consensus. AIM: To identify clinical features of testicular cancer and to quantify their risk in primary care patients, with the aim of improving the selection of patients for investigation. DESIGN AND SETTING: A matched case-control study in males aged ≥17 years, using Clinical Practice Research Datalink records. METHOD: Putative clinical features of testicular cancer were identified and analysed using conditional logistic regression. Positive predictive values (PPVs) were calculated for those aged <50 years. RESULTS: In all, 1398 cases were available, diagnosed between 2000 and 2012, with 4956 age-, sex-, and practice-matched controls. Nine features were independently associated with testicular cancer, the top three being testicular swelling (odds ratio [OR] 280, 95% confidence interval [CI] = 110 to 690), testicular lump (OR 270, 95% CI = 100 to 740), and scrotal swelling (OR 170, 95% CI = 35 to 800). The highest PPV for 17-49-year-olds was testicular lump, at 2.5% (95% CI = 1.1 to 5.6). Combining testicular lump with testicular swelling or testicular pain produced PPVs of 17% and 10%, respectively. CONCLUSION: Testicular enlargement carries a risk of cancer of 2.5% - close to the current 3% threshold in UK referral guidance. Contrary to traditional teaching, painful testicular enlargement may signify cancer. Some initial hydrocele diagnoses appear to be wrong, with missed cancers, suggesting an ultrasound may be useful when a hydrocele diagnosis is uncertain. These results support the existing NICE guidelines, and help to characterise when an ultrasound should be considered in symptomatic men.Funding was provided by the Policy Research Unit in Cancer Awareness, Screening and Early Diagnosis. The views expressed in this paper are those of the authors and not necessarily those of the NHS, the Department of Health, or the Policy Research Unit, which receives funding for a research programme from the Department of Health Policy Research Programme. It is a collaboration between researchers from seven institutions (Queen Mary University of London, University College London [UCL], King’s College London, London School of Hygiene and Tropical Medicine, Hull York Medical School, Durham University, and University of Exeter Medical School)

How useful is thrombocytosis in predicting an underlying cancer in primary care? Systematic review protocol

Early diagnosis of cancer is imperative to reduce the cancer burden in the UK and improve cancer survival. Identifying early markers of cancer can help general practitioners to direct patients at the greatest risk of cancer to appropriate investigative services. A raised platelet count, or thrombocytosis, has been linked to malignancy and identified as a marker of poor prognosis in secondary care, but there is little evidence around the importance of this marker in a primary care setting, within a diagnostic context. This review aims to identify and explore the body of evidence concerning the association between thrombocytosis and cancer in primary care. This protocol was produced using guidance from the PRISMA-P statement

Symptoms of adult chronic and acute leukaemia before diagnosis: large primary care case-control studies using electronic records

This is the author accepted manuscript. The final version is available from Royal College of General Practitioners via the DOI in this record.BACKGROUND: Leukaemia is the eleventh commonest UK cancer. The four main subtypes have different clinical profiles, particularly between chronic and acute types. AIM: To identify the symptom profiles of chronic and acute leukaemia in adults in primary care. DESIGN AND SETTING: Matched case-control studies using Clinical Practice Research Datalink records. METHOD: Putative symptoms of leukaemia were identified in the year before diagnosis. Conditional logistic regression was used for analysis, and positive predictive values (PPVs) were calculated to estimate risk. RESULTS: Of cases diagnosed between 2000 and 2009, 4655 were aged ≥40 years (2877 chronic leukaemia (CL), 937 acute leukaemia (AL), 841 unreported subtype). Ten symptoms were independently associated with CL, the three strongest being: lymphadenopathy (odds ratio [OR] 22, 95% confidence interval [CI] = 13 to 36), weight loss (OR 3.0, 95% CI = 2.1 to 4.2), and bruising (OR 2.3, 95% CI = 1.6 to 3.2). Thirteen symptoms were independently associated with AL, the three strongest being: nosebleeds and/or bleeding gums (OR 5.7, 95% CI = 3.1 to 10), fever (OR 5.3, 95% CI = 2.7 to 10), and fatigue (OR 4.4, 95% CI = 3.3 to 6.0). No individual symptom or combination of symptoms had a PPV >1%. CONCLUSION: The symptom profiles of CL and AL have both overlapping and distinct features. This presents a dichotomy for GPs: diagnosis, by performing a full blood count, is easy; however, the symptoms of leukaemia are non-specific and of relatively low risk. This explains why many leukaemia diagnoses are unexpected findings.This article presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0608– 10045). Fiona M Walter is part-funded by an NIHR Clinician Scientist award. Richard D Neal is part-funded by Public Health Wales and Betsi Cadwaladr University Health Board. Willie Hamilton is supported by the NIHR Collaboration for Leadership in Applied Health Research and Care South West Peninsula at the Royal Devon and Exeter NHS Foundation Trust. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR, or the Department of Health

Quantifying the risk of multiple myeloma from symptoms reported in primary care patients: a large case-control study using electronic records

This is the author accepted manuscript. The final version is available from Royal College of General Practitioners via the DOI in this record.BACKGROUND: Patients with myeloma experience the longest diagnostic delays compared with patients with other cancers in the UK; 37% are diagnosed through emergency presentations. AIM: To identify and quantify the risk of myeloma from specific clinical features reported by primary care patients. DESIGN AND SETTING: Matched case-control study using General Practice Research Database primary care electronic records. METHOD: Putative clinical features of myeloma were identified and analysed using conditional logistic regression. Positive predictive values (PPVs) were calculated for the consulting population. RESULTS: A total of 2703 patients aged ≥40 years, diagnosed with myeloma between 2000 and 2009, and 12 157 age, sex, and general practice-matched controls were identified. Sixteen features were independently associated with myeloma: hypercalcaemia, odds ratio 11.4 (95% confidence interval [CI] = 7.1 to 18), cytopenia 5.4 (95% CI = 4.6 to 6.4), raised inflammatory markers 4.9 (95% CI = 4.2 to 5.8), fracture 3.1 (95% CI = 2.3 to 4.2), raised mean corpuscular volume 3.1 (95% CI = 2.4 to 4.1), weight loss 3.0 (95% CI = 2.0 to 4.5), nosebleeds 3.0 (95% CI = 1.9 to 4.7), rib pain 2.5 (95% CI = 1.5 to 4.4), back pain 2.2 (95% CI = 2.0 to 2.4), other bone pain 2.1 (95% CI = 1.4 to 3.1), raised creatinine 1.8 (95% CI = 1.5 to 2.2), chest pain 1.6 (95% CI = 1.4 to 1.8), joint pain 1.6 (95% CI = 1.2 to 2.2), nausea 1.5 (95% CI = 1.1 to 2.1), chest infection 1.4 (95% CI = 1.2 to 1.6), and shortness of breath 1.3 (95% CI = 1.1 to 1.5). Individual symptom PPVs were generally 10% for some symptoms when combined with leucopenia or hypercalcaemia. CONCLUSION: Individual symptoms of myeloma in primary care are generally low risk, probably explaining diagnostic delays. Once simple primary care blood tests are taken, risk estimates change. Hypercalcaemia and leucopenia are particularly important abnormalities, and coupled with symptoms, strongly suggest myeloma.This article presents independent research funded by the National Institute for Health Research (NIHR) under its Programme Grants for Applied Research Programme (Grant Reference Number RP-PG-0608- 10045). The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Fiona M Walter is part-funded by a NIHR Clinician Scientist award. Richard D Neal is part funded by Public Health Wales and Betsi Cadwaladr University Health Board

Species-diagnostic microsatellite loci for the fig wasp genus Pegoscapus

To obtain tools for the estimation of inbreeding and assignment of offspring to matrilines, we developed 13 microsatellite loci from the fig wasps that pollinate Ficus obtusifolia. Based on morphological studies, it was thought that a single species (Pegoscapus hoffmeyer) pollinated this fig. However, our data revealed the presence of two coexisting cryptic species. Several diagnostic microsatellite markers may be used to distinguish these two cryptic species. The new microsatellites can be used across a wide range of fig-pollinating wasp species for both evolutionary and population genetic studies

Recognizing sinonasal cancer in primary care: a matched case-control study using electronic records.

This is the final version. Available from Oxford University Press via the DOI in this record. BACKGROUND: Cancers of the nasopharynx, nasal cavity, and accessory sinuses ("sinonasal") are rare in England, with around 750 patients diagnosed annually. There are no specific National Institute for Health and Care Excellence (NICE) referral guidelines for these cancers and no primary care research published. OBJECTIVE: To identify and quantify clinical features of sinonasal cancer in UK primary care patients. METHODS: This matched case-control study used UK Clinical Practice Research Datalink (CPRD) data. Patients were aged ≥40 years with a diagnosis of sinonasal cancer between January 1, 2000 and December 31, 2009 and had consulted their GP in the year before diagnosis. Clinical features of sinonasal cancer were analysed using conditional logistic regression. Positive predictive values (PPVs) for single and combined features were calculated. RESULTS: In total, 155 cases and 697 controls were studied. Nine symptoms and one abnormal investigation were significantly associated with the cancer: nasal mass; odds ratio, 95 (95% confidence interval 7.0, 1315, P = 0.001); head and neck lumps, 68 (12, 387, P < 0.001); epistaxis, 17 (3.9, 70, P < 0.001); rhinorrhoea, 14 (4.6, 44, P < 0.001); visual disturbance, 12 (2.2, 67, P = 0.004); sinusitis, 7.3 (2.2, 25, P = 0.001); sore throat, 6.0 (2.0, 18, P = 0.001); otalgia, 5.4 (1.6, 18, P = 0.007); headache, 3.6 (1.4, 9.5, P = 0.01); raised white cell count, 8.5 (2.8, 27, P < 0.001). Combined PPVs for epistaxis/rhinorrhoea, epistaxis/sinusitis, and rhinorrhoea/sinusitis were 0.62%. CONCLUSION: This is the first primary care study identifying epistaxis, sinusitis, and rhinorrhoea as part of the clinical prodrome of sinonasal cancer. Although no PPVs meet the 3% NICE referral threshold, these results may help clinicians identify who warrants safety-netting and possible specialist referral, potentially reducing the number of advanced-stage diagnoses of sinonasal cancer.National Institute for Health Researc

Socio-Economic Instability and the Scaling of Energy Use with Population Size

The size of the human population is relevant to the development of a sustainable world, yet the forces setting growth or declines in the human population are poorly understood. Generally, population growth rates depend on whether new individuals compete for the same energy (leading to Malthusian or density-dependent growth) or help to generate new energy (leading to exponential and super-exponential growth). It has been hypothesized that exponential and super-exponential growth in humans has resulted from carrying capacity, which is in part determined by energy availability, keeping pace with or exceeding the rate of population growth. We evaluated the relationship between energy use and population size for countries with long records of both and the world as a whole to assess whether energy yields are consistent with the idea of an increasing carrying capacity. We find that on average energy use has indeed kept pace with population size over long time periods. We also show, however, that the energy-population scaling exponent plummets during, and its temporal variability increases preceding, periods of social, political, technological, and environmental change. We suggest that efforts to increase the reliability of future energy yields may be essential for stabilizing both population growth and the global socio-economic system

Mapping the UK renal psychosocial workforce : the first comprehensive workforce survey

Background: Emerging evidence of psychosocial problems in CKD patients has led to an acceptance that a focus on the emotional wellbeing of the patient should be included in the provision of comprehensive CKD care. It is unclear if an increased attention for psychosocial needs in guidelines and policy documents has led to a rise in psychosocial staffing levels or change in composition of staff since the last workforce mapping in 2002. This paper offers a critical analysis and in-depth discussion of findings and their implications, in addition to providing an international perspective and exposing gaps in current knowledge. Methods: Data on psychosocial staffing levels was taken from a survey based on the Scottish Renal Association’s (SRA) staffing survey that was sent to all units in England, Wales and Northern-Ireland in 2016. In addition, data from a psychosocial staffing survey designed by and distributed via psychosocial professional groups was used. This data was then completed with Freedom of Information (FOI) requests and collated to describe the current renal psychosocial workforce in all 84 UK renal units. This was compared to results from the last renal workforce mapping in 2002. Results: The results from this mapping show great variability in models of service provision, significant exceeding of benchmarks for staffing levels, and a change in staffing patterns over the past 15 years. Adult psychology services have increased in number, but provision remains low due to increased patient numbers, whereas adult social work and paediatric services have decreased. Conclusion: A lack in the provision of renal psychosocial services has been identified, together with the absence of a general service provision model. These findings provide a valuable benchmark for units, a context from which to review and monitor provision alongside patient need. Along with recommendations, this paper forms a foundation for future research and workforce planning. Research into best practice models of service provision and the psychosocial needs of CKD patients lies at the heart of the answers to many identified questions

Does the GP method of recording possible cancer symptoms reflect the probability that cancer is present?

Special Issue: Abstracts of the Cancer and Primary Care Research International (Ca-PRI) Network 8th Annual Meeting, 20-22 May 2015, DenmarkPoster presentation abstractThis is the author accepted manuscript. The final version is available from Wiley via the DOI in this record

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

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