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)

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

Targeted encouragement of GP consultations for possible cancer symptoms: a randomised controlled trial

BACKGROUND: For some common cancers, survival is lower in the UK than in comparable high-income countries. AIM: To assess the effectiveness of a targeted postal intervention (to promote awareness of cancer symptoms and earlier help seeking) on patient consultation rates. DESIGN AND SETTING: A two-arm randomised controlled trial was carried out on patients aged 50-84 years registered at 23 general practices in rural and urban areas of Greater London, Greater Manchester, and the North East of England. METHOD: Patients who had not had a consultation at their general practice in the previous 12 months and had at least two other risk factors for late presentation with cancer were randomised to intervention and control arms. The intervention consisted of a posted letter and leaflet. Primary outcome was the number of consultations at the practice with patients randomised to each arm in the 6 months subsequent to posting the intervention. All patients with outcome data were included in the intention-to-treat analyses. RESULTS: In total, 1513 patients were individually randomised to the intervention (n = 783) and control (n = 730) arms between Nov 2016 - May 2017; outcome data were available for 749 and 705 patients, respectively, with a statistically significantly higher rate of consultation in the intervention arm compared with the control arm: 436 versus 335 consultations (relative risk 1.40, 95% confidence interval = 1.11 to 1.77, P = 0.004). There was, however, no difference in the numbers of patients consulting. CONCLUSION: Targeted interventions of this nature can change behaviour; there is a need to develop interventions that can be more effective at engaging patients with primary care. This study demonstrates that targeted interventions promoting both awareness of possible cancer symptoms and earlier health seeking, can change behaviour. There is a need to develop and test interventions that can be more effective at engaging the most at-risk patients

Improving NLO-parton shower matched simulations with higher order matrix elements

In recent times the algorithms for the simulation of hadronic collisions have been subject to two substantial improvements: the inclusion, within parton showering, of exact higher order tree level matrix elements (MEPS) and, separately, next-to-leading order corrections (NLOPS). In this work we examine the key criteria to be met in merging the two approaches in such a way that the accuracy of both is preserved, in the framework of the POWHEG approach to NLOPS. We then ask to what extent these requirements may be fulfilled using existing simulations, without modifications. The result of this study is a pragmatic proposal for merging MEPS and NLOPS events to yield much improved MENLOPS event samples. We apply this method to W boson and top quark pair production. In both cases results for distributions within the remit of the NLO calculations exhibit no discernible changes with respect to the pure NLOPS prediction; conversely, those sensitive to the distribution of multiple hard jets assume, exactly, the form of the corresponding MEPS results.Comment: 38 pages, 17 figures. v2: added citations and brief discussion of related works, MENLOPS prescription localized in a subsection. v3: cited 4 more MEPS works in introduction

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

Coherent Parton Showers with Local Recoils

We outline a new formalism for dipole-type parton showers which maintain exact energy-momentum conservation at each step of the evolution. Particular emphasis is put on the coherence properties, the level at which recoil effects do enter and the role of transverse momentum generation from initial state radiation. The formulated algorithm is shown to correctly incorporate coherence for soft gluon radiation. Furthermore, it is well suited for easing matching to next-to-leading order calculations.Comment: 24 pages, 3 figure

Pituitary models

pre-printPituitary tumor animal models provide researchers a microenvironment that simulates the clinical situation; however, in comparison with astrocytoma and meningioma tumor research where intracranial xenograft transplantations are increasingly being used to test various therapeutic modalities, in vivo therapeutic research on pituitary animal models focuses on direct drug therapy to the tumor because of the lack of established intracranial pituitary tumor models. The rat subcutaneous prolactin-secreting pituitary model allows investigators to noninvasively measure tumor size and the effect of direct tumor-guided therapy in a serial manner and is considered biologically relevant because it has proven to be histologically, immunocytochemically, and ultrastructurally consistent with human pituitary tumors

A Suborbital Payload for Soft X-ray Spectroscopy of Extended Sources

We present a suborbital rocket payload capable of performing soft X-ray spectroscopy on extended sources. The payload can reach resolutions of ~100(lambda/dlambda) over sources as large as 3.25 degrees in diameter in the 17-107 angstrom bandpass. This permits analysis of the overall energy balance of nearby supernova remnants and the detailed nature of the diffuse soft X-ray background. The main components of the instrument are: wire grid collimators, off-plane grating arrays and gaseous electron multiplier detectors. This payload is adaptable to longer duration orbital rockets given its comparatively simple pointing and telemetry requirements and an abundance of potential science targets.Comment: Accepted to Experimental Astronomy, 12 pages plus 1 table and 17 figure

Targeted encouragement of GP consultations for possible cancer symptoms: a randomised controlled trial

This is the final version. Available on open access from the Royal College of General Practitioners via the DOI in this recordBackground For some common cancers, survival is lower in the UK than in comparable high-income countries. Aim To assess the effectiveness of a targeted postal intervention (to promote awareness of cancer symptoms and earlier help seeking) on patient consultation rates. Design and setting A two-arm randomised controlled trial was carried out on patients aged 50-84 years registered at 23 general practices in rural and urban areas of Greater London, Greater Manchester, and the North East of England. Method Patients who had not had a consultation at their general practice in the previous 12 months and had at least two other risk factors for late presentation with cancer were randomised to intervention and control arms. The intervention consisted of a posted letter and leaflet. Primary outcome was the number of consultations at the practice with patients randomised to each arm in the 6 months subsequent to posting the intervention. All patients with outcome data were included in the intention-to-treat analyses. Results In total, 1513 patients were individually randomised to the intervention (n = 783) and control (n = 730) arms between Nov 2016 — May 2017; outcome data were available for 749 and 705 patients, respectively, with a statistically significantly higher rate of consultation in the intervention arm compared with the control arm: 436 versus 335 consultations (relative risk 1.40, 95% confidence interval = 1.11 to 1.77, P = 0.004). There was, however, no difference in the numbers of patients consulting. Conclusion Targeted interventions of this nature can change behaviour; there is a need to develop interventions that can be more effective at engaging patients with primary care. This study demonstrates that targeted interventions promoting both awareness of possible cancer symptoms and earlier health seeking, can change behaviour. There is a need to develop and test interventions that can be more effective at engaging the most at-risk patients.National Institute for Health Research (NIHR

Misinformation increases symptom reporting: a test – retest study

OBJECTIVES: We examined whether misleading information (i.e. misinformation) may promote symptom reporting in non-clinical participants. DESIGN: A test-retest study in which we collected baseline data about participants' psychological symptoms and then misinformed them that they had rated two target symptoms relatively highly. During an interview, we determined whether participants would notice this misinformation and at direct and one-week follow-up, we evaluated whether the misinformation would exacerbate retest measures of the same symptoms. SETTING: A psychological laboratory. PARTICIPANTS: A total of 78 undergraduate students. MAIN OUTCOME MEASURES: Participants' scores on a widely used self-report measure of psychological symptoms. RESULTS: We found that most participants (63%) were blind to the discrepancies between their original symptom ratings and the upgraded scores they were misinformed with. Furthermore, at the one-week follow-up retest, blind participants revised their symptom ratings in the direction of the misinformation (i.e. they increased their ratings of these symptoms). CONCLUSION: Introspective monitoring of common psychological symptoms is poor and this creates an opportunity for misinformation and symptom escalation. Our finding bears relevance to theories about the iatrogenic amplification of medically unexplained symptoms