Impact of investigations in general practice on timeliness of referral for patients subsequently diagnosed with cancer: Analysis of national primary care audit data

This is the final published version. Available from Springer Nature via the DOI in this record.Background:For patients with symptoms of possible cancer who do not fulfil the criteria for urgent referral, initial investigation in primary care has been advocated in the United Kingdom and supported by additional resources. The consequence of this strategy for the timeliness of diagnosis is unknown.Methods:We analysed data from the English National Audit of Cancer Diagnosis in Primary Care on patients with lung (1494), colorectal (2111), stomach (246), oesophagus (513), pancreas (327), and ovarian (345) cancer relating to the ordering of investigations by the General Practitioner and their nature. Presenting symptoms were categorised according to National Institute for Health and Care Excellence (NICE) guidance on referral for suspected cancer. We used linear regression to estimate the mean difference in primary-care interval by cancer, after adjustment for age, gender, and the symptomatic presentation category.Results:Primary-care investigations were undertaken in 3198/5036 (64%) of cases. The median primary-care interval was 16 days (IQR 5-45) for patients undergoing investigation and 0 days (IQR 0-10) for those not investigated. Among patients whose symptoms mandated urgent referral to secondary care according to NICE guidelines, between 37% (oesophagus) and 75% (pancreas) were first investigated in primary care. In multivariable linear regression analyses stratified by cancer site, adjustment for age, sex, and NICE referral category explained little of the observed prolongation associated with investigation.Interpretation:For six specified cancers, investigation in primary care was associated with later referral for specialist assessment. This effect was independent of the nature of symptoms. Some patients for whom urgent referral is mandated by NICE guidance are nevertheless investigated before referral. Reducing the intervals between test order, test performance, and reporting can help reduce the prolongation of primary-care intervals associated with investigation use. Alternative models of assessment should be considered.National Institute for Health Research (NIHR

Training peers to treat Ebola centre workers with anxiety and depression in Sierra Leone

Background: Following the 2014 Ebola virus disease (EVD) outbreak in West Africa, the UK Department for International Development funded South London and Maudsley National Health Service (NHS) to develop a psychological intervention that ex-Ebola Treatment Centre (ETC) staff could be trained to deliver to their peers to improve mental health in Sierra Leone. / Aim: The two key aims were to assess the feasibility of training a national team to deliver a cognitive behavioural therapy (CBT)–based group intervention, and to evaluate the effectiveness of the overall intervention within this population. / Methods: UK clinicians travelled to Sierra Leone to train a small team of ex-ETC staff in a three-phased CBT-based intervention. Standardised clinical measures, as well as bespoke measures, were applied with participants through the intervention to assess changes in mental health symptomology, and the effectiveness of the intervention. / Results: The results found improvements across all factors of mental health in the bespoke measure from phase 1 to phase 3. Additionally, the majority of standardised clinical measures showed improvements between phase 2 and the start of phase 3, and pre- and post-phase 3. / Conclusion: Overall, the findings suggest that it is possible to train staff from ETCs to deliver effective CBT interventions to peers. The implications of these results are discussed, including suggestions for future research and clinical intervention implementation within this population. The limitations of this research are also addressed

The relative length of the patient and the primary care interval in patients with 28 common and rarer cancers

This is the final version. Available from the publisher via the DOI in this record.BACKGROUND: Appreciating variation in the length of pre- or post-presentation diagnostic intervals can help prioritise early diagnosis interventions with either a community or a primary care focus.METHODS: We analysed data from the first English National Audit of Cancer Diagnosis in Primary Care on 10 953 patients with any of 28 cancers. We calculated summary statistics for the length of the patient and the primary care interval and their ratio, by cancer site.RESULTS: Interval lengths varied greatly by cancer. Laryngeal and oropharyngeal cancers had the longest median patient intervals, whereas renal and bladder cancer had the shortest (34.5 and 30 compared with 3 and 2 days, respectively). Multiple myeloma and gallbladder cancer had the longest median primary care intervals, and melanoma and breast cancer had the shortest (20.5 and 20 compared with 0 and 0 days, respectively). Mean patient intervals were longer than primary care intervals for most (18 of 28) cancers, and notably so (two- to five-fold greater) for 10 cancers (breast, melanoma, testicular, vulval, cervical, endometrial, oropharyngeal, laryngeal, ovarian and thyroid).CONCLUSIONS: The findings support the continuing development and evaluation of public health interventions aimed at shortening patient intervals, particularly for cancers with long patient interval and/or high patient interval over primary care interval ratio.National Institute for Health Research (NIHR)Cancer Research UKPublic Health WalesBetsi Cadwaladr University Health Boar

Variation in promptness of presentation among 10,297 patients subsequently diagnosed with one of 18 cancers: Evidence from a National Audit of Cancer Diagnosis in Primary Care

This is the final published version. Available from Wiley via the DOI in this record.Cancer awareness public campaigns aim to shorten the interval between symptom onset and presentation to a doctor (the 'patient interval'). Appreciating variation in promptness of presentation can help to better target awareness campaigns. We explored variation in patient intervals recorded in consultations with general practitioners among 10,297 English patients subsequently diagnosed with one of 18 cancers (bladder, brain, breast, colorectal, endometrial, leukaemia, lung, lymphoma, melanoma, multiple myeloma, oesophageal, oro-pharyngeal, ovarian, pancreatic, prostate, renal, stomach, and unknown primary) using data from of the National Audit of Cancer Diagnosis in Primary Care (2009-2010). Proportions of patients with 'prompt'/'non-prompt' presentation (0-14 or 15+ days from symptom onset, respectively) were described and respective odds ratios were calculated by multivariable logistic regression. The overall median recorded patient interval was 10 days (IQR 0-38). Of all patients, 56% presented promptly. Prompt presentation was more frequent among older or housebound patients (p < 0.001). Prompt presentation was most frequent for bladder and renal cancer (74% and 70%, respectively); and least frequent for oro-pharyngeal and oesophageal cancer (34% and 39%, respectively, p <.001). Using lung cancer as reference, the adjusted odds ratios of non-prompt presentation were 2.26 (95% confidence interval 1.57-3.25) and 0.42 (0.34-0.52) for oro-pharyngeal and bladder cancer, respectively. Sensitivity analyses produced similar findings. Routinely recorded patient interval data reveal considerable variation in the promptness of presentation. These findings can help to prioritise public awareness initiatives and research focusing on symptoms of cancers associated with greater risk of non-prompt presentation, such as oro-pharyngeal and oesophageal cancer. What's new? A critical aspect of cancer diagnosis is how promptly patients consult a doctor after they first notice initial symptoms. Here, the authors examine differences in this so-called patient interval in English patients subsequently diagnosed with one of 18 cancers. On average, patients with bladder and renal cancer as well as older and housebound patients consulted a doctor relatively promptly while patients with oro-pharyngeal and oesophageal cancer took the longest until first presenting to a general practitioner. The authors point out that cancer awareness campaigns should encompass symptoms of oro-pharyngeal and oesophageal cancer aiming to shorten the patient interval for these cancers. © 2014 The Authors. Published by Wiley Periodicals, Inc. on behalf of UICC.National Institute for Health Research (NIHR)NHS Public Health Training Schem

A qualitative exploration of the effect of visual field loss on daily life in home-dwelling stroke survivors

Objective: To explore the effect of visual field loss on the daily life of community-dwelling stroke survivors. Design: A qualitative interview study. Participants: Adult stroke survivors with visual field loss of at least six months’ duration. Methods: Semi-structured interviews were conducted with a non-purposive sample of 12 stroke survivors in their own homes. These were recorded, transcribed verbatim and analyzed with the framework method, using an inductive approach. Results: Two key analytical themes emerged. ‘Perception, experience and knowledge’ describes participant’s conflicted experience of having knowledge of their impaired vision but lacking perception of that visual field loss and operating under the assumption that they were viewing an intact visual scene when engaged in activities. Inability to recognize and deal with visual difficulties, and experiencing the consequences, contributed to their fear and loss of self-confidence. ‘Avoidance and adaptation’ were two typologies of participant response to visual field loss. Initially, all participants consciously avoided activities. Some later adapted to vision loss using self-directed head and eye scanning techniques. Conclusions: Visual field loss has a marked impact on stroke survivors. Stroke survivors lack perception of their visual loss in everyday life, resulting in fear and loss of confidence. Activity avoidance is a common response, but in some, it is replaced by self-initiated adaptive techniques

Elliptic logarithms, diophantine approximation and the Birch and Swinnerton-Dyer conjecture

Most, if not all, unconditional results towards the abc-conjecture rely ultimately on classical Baker's method. In this article, we turn our attention to its elliptic analogue. Using the elliptic Baker's method, we have recently obtained a new upper bound for the height of the S-integral points on an elliptic curve. This bound depends on some parameters related to the Mordell-Weil group of the curve. We deduce here a bound relying on the conjecture of Birch and Swinnerton-Dyer, involving classical, more manageable quantities. We then study which abc-type inequality over number fields could be derived from this elliptic approach.Comment: 20 pages. Some changes, the most important being on Conjecture 3.2, three references added ([Mas75], [MB90] and [Yu94]) and one reference updated [BS12]. Accepted in Bull. Brazil. Mat. So

Improved healing response in delayed unions of the tibia with low-intensity pulsed ultrasound: results of a randomized sham-controlled trial

<p>Abstract</p> <p>Background</p> <p>We compared the healing response of tibial delayed unions between subjects treated with low-intensity pulsed ultrasound (LIPUS) (n = 51) and subjects treated with a sham device (n = 50). Fracture age was ≥ 4 months in all cases. Study personnel and participants were blinded to random treatment assignment throughout the study.</p> <p>Methods</p> <p>This multi-center randomized sham-controlled trial was undertaken at six hospitals in Germany. Adult patients who had sustained a tibial shaft fracture that subsequently showed inadequate progress toward healing (i.e., delayed union) were enrolled and randomized to receive either LIPUS (Exogen 2000/2000+, Smith & Nephew GmbH, Schenefeld, Germany) or an identical nonoperative sham device. The daily treatment duration was 20 minutes, for a period of 16 weeks. Subjects randomly assigned to active treatment had the ultrasound pressure wave signal set at the following parameters: 1.5 MHz frequency, 1 kHz repetition rate, 200 μs pulse duration, 30 mW/cm²spatial intensity. Progress toward healing was estimated from changes in bone mineral density (BMD) and gap area as determined from computed tomography scans. Intention-to-treat analysis was conducted using a multiple imputation methodology.</p> <p>Results</p> <p>Based on log-transformed data, mean improvement in BMD was 1.34 (90% confidence interval (CI) 1.14 to 1.57) times greater for LIPUS-treated subjects compared to sham (p = 0.002). A mean reduction in bone gap area also favored LIPUS treatment (p = 0.014).</p> <p>Conclusions</p> <p>These findings demonstrate significantly greater progress toward bone healing after LIPUS treatment compared to no LIPUS treatment in subjects with established delayed unions of the tibia.</p

HPV infection and immunochemical detection of cell-cycle markers in verrucous carcinoma of the penis

Penile verrucous carcinoma is a rare disease and little is known of its aetiology or pathogenesis. In this study we examined cell-cycle proteins expression and correlation with human papillomavirus infection in a series of 15 pure penile verrucous carcinomas from a single centre. Of 148 penile tumours, 15 (10%) were diagnosed as pure verrucous carcinomas. The expression of the cell-cycle-associated proteins p53, p21, RB, p16INK4A and Ki67 were examined by immunohistochemistry. Human papillomavirus infection was determined by polymerase chain reaction to identify a wide range of virus types. The expression of p16INK4A and Ki67 was significantly lower in verrucous carcinoma than in usual type squamous cell carcinoma, whereas the expression of p53, p21 and RB was not significantly different. p53 showed basal expression in contrast to usual type squamous cell carcinoma. Human papillomavirus infection was present in only 3 out of 13 verrucous carcinomas. Unique low-risk, high-risk and mixed viral infections were observed in each of the three cases. In conclusion, lower levels of p16INK4A and Ki67 expressions differentiate penile verrucous carcinoma from usual type squamous cell carcinoma. The low Ki67 index reflects the slow-growing nature of verrucous tumours. The low level of p16INK4A expression and human papillomavirus detection suggests that penile verrucous carcinoma pathogenesis is unrelated to human papillomavirus infection and the oncogenes and tumour suppressor genes classically altered by virus infection.Peer reviewedFinal Accepted Versio

Predicting developmental dysplasia of the hip in at-risk newborns.

BACKGROUND: The development of developmental dysplasia of the hip can be attributed to several risk factors and often in combination with each other. When predicting the likelihood of developing this condition, clinicians tend to over and underestimate its likelihood of occurring. Therefore, the study aim is to determine among at-risk newborns how to best predict developmental dysplasia of the hip (DDH) within 8 weeks post-partum. METHODS: Prospective cohort study in secondary care. Patient population included newborns at-risk for DDH - we assessed 13,276 consecutive newborns for the presence of DDH risk factors. Only newborns with at least one of the predefined risk factors and those showing an abnormal examination of the hip were enrolled (n = 2191). For the development of a risk prediction model we considered 9 candidate predictors and other variables readily available at childbirth. The main outcome measure was ultrasonography at a median age of 8 weeks using consensus diagnostic criteria; outcome assessors were blinded. RESULTS: The risk model includes four predictors: female sex (OR = 5.6; 95% CI: 2.9-10.9; P  4000 g (OR = 1.6; 95% CI: 0.6-4.2; P = 0.34), and abnormal examination of hip (OR = 58.8; 95% CI: 31.9, 108.5; P <  0.001). This model demonstrated excellent discrimination (C statistic = 0.9) and calibration of observed and predicted risk (P = 0.35). A model without the variable 'hip examination' demonstrated similar performance. CONCLUSION: The risk model quantifies absolute risk of DDH within 8 weeks postpartum in at-risk newborns. Based on clinical variables readily available at the point of childbirth, the model will enhance parental counselling and could serve as the basis for real time decisions prior to discharge from maternity wards