Assessing the impact of rurality on oesophagogastric cancer survival in the North-East of Scotland- a prospective population cohort study.

INTRODUCTION: Despite advances in oncology therapies and surgical techniques, survival from oesophagogastric cancer remains low. Poorer cancer outcomes and survival for rural dwellers is documented worldwide and has been an area of focus in Scotland since 2007 when changes to suspected cancer national referral guidelines and governmental mandates on delivering remote and rural healthcare occurred. Whether these changes in clinical practice has impacted upon upper gastrointestinal cancer remains unclear. METHODS: A prospective, single-centre observation study was performed. Data from the regional oesophagogastric cancer MDT between 2013 and 2019 were included. The Scottish Index of Multiple Deprivation 2020 tool provided a rurality code (1 or 2) based on patient postcode at time of referral. Survival outcomes for urban and rural patients were compared across demographic factors, disease factors and stage at presentation. RESULTS: A total of 1038 patients were included in this study. There was no significant difference between rural and urban groups in terms of sex of patient, age at diagnosis, cancer location, or tumour stage. Furthermore, no difference was identified between those commenced on a radical therapy with other treatment plans. Despite this, rurality predicted for an improved outcome on survival analysis (p = 0.012) and this was independent of other factors on multivariable analysis (HR = 0.78, 95%CI 0.66-0.98; p = 0.032). DISCUSSION: The difference in survival demonstrated here between urban and rural groups is not easily explained but may represent improvements to rural access to healthcare delivered as a result of Scottish Government reports.

A systematic assessment of the association between frequently prescribed medicines and the risk of common cancers: a series of nested case-control studies.

BACKGROUND: Studies systematically screening medications have successfully identified prescription medicines associated with cancer risk. However, adjustment for confounding factors in these studies has been limited. We therefore investigated the association between frequently prescribed medicines and the risk of common cancers adjusting for a range of confounders. METHODS: A series of nested case-control studies were undertaken using the Primary Care Clinical Informatics Unit Research (PCCIUR) database containing general practice (GP) records from Scotland. Cancer cases at 22 cancer sites, diagnosed between 1999 and 2011, were identified from GP records and matched with up to five controls (based on age, gender, GP practice and date of registration). Odds ratios (OR) and 95% confidence intervals (CI) comparing any versus no prescriptions for each of the most commonly prescribed medicines, identified from prescription records, were calculated using conditional logistic regression, adjusting for comorbidities. Additional analyses adjusted for smoking use. An association was considered a signal based upon the magnitude of its adjusted OR, p-value and evidence of an exposure-response relationship. Supplementary analyses were undertaken comparing 6 or more prescriptions versus less than 6 for each medicine. RESULTS: Overall, 62,109 cases and 276,580 controls were included in the analyses and a total of 5622 medication-cancer associations were studied across the 22 cancer sites. After adjusting for comorbidities 2060 medicine-cancer associations for any prescription had adjusted ORs greater than 1.25 (or less than 0.8), 214 had a corresponding p-value less than or equal to 0.01 and 118 had evidence of an exposure-dose relationship hence meeting the criteria for a signal. Seventy-seven signals were identified after additionally adjusting for smoking. Based upon an exposure of 6 or more prescriptions, there were 118 signals after adjusting for comorbidities and 82 after additionally adjusting for smoking. CONCLUSIONS: In this study a number of novel associations between medicine and cancer were identified which require further clinical and epidemiological investigation. The majority of medicines were not associated with an altered cancer risk and many identified signals reflected known associations between medicine and cancer.

Analysing the impact of living in a rural setting on the presentation and outcome of colorectal cancer. A prospective single centre observational study.

INTRODUCTION: Approximately 17% of the Scottish population lives in a remote or rural location. Current research is contradictory as to whether living a rural location leads to poorer outcomes or affects survival from colorectal cancer (CRC). We aimed to assess if living in a rural location influences outcome of CRC patients in 21st century UK medicine. METHODS: A prospective single-centre observational study was conducted. All patients who underwent resection for colorectal cancer 2005-2016 in NHS Grampian were included. Patients were split into two groups for comparison (urban post-code vs rural) using the Scottish government two-tier classification system. Tumour location, one-year survival, lymph node involvement and extra-mural vascular invasion was recorded and compared between the groups. RESULTS: Of 2463 patients, 843 (34.2%) lived in a rural area. Rural patients were more likely to be detected through screening (17.4% versus 14.6%, p = 0.04). There were no differences in pathology between rural and urban groups if detected through screening. However, rural patients detected through symptomatic pathways were more likely to be node positive p = 0.015. On multivariable analysis, rurality did not independently predict for node positive presentation. Furthermore, there were no differences in cumulative survival between the two groups. CONCLUSION: Although there were some differences in pathological characteristics between rural and urban patients, place of residence did not independently predict for outcome in this cohort. Rurality had previously been shown to impact on outcome up to 20 years ago. Improvements in infrastructure and rural healthcare may have influenced this change.

A systematic review of the use, quality and effects of pelvic examination in primary care for the detection of gynaecological cancer.

AIM: This three part systematic review gathered all the current evidence on the use, quality and effects of pelvic examination (abdominal palpation, bimanual vaginal examination ± visualisation of the cervix) in primary care in diagnosing gynaecological cancer. Research questions • Do primary care practitioners perform pelvic examination during the assessment of symptoms, which are potentially indicative of gynaecological cancer? (RQ1) • What is the quality of pelvic examination performed in primary care, in terms of technical competence and interpretation of findings? (RQ2) • Is pelvic examination associated with the referral of patients with gynaecological cancer, and if so, in what way? (RQ3) Methods: PRISMA guidelines were followed. MEDLINE, EMBASE and Cochrane databases were searched using a combination of four terms, their MeSH terms and synonyms: pelvic examination; primary care; competency and gynaecological cancer. Inclusion and exclusion criteria were defined. Citation lists of all identified papers were searched. Two authors (PW and PM or CMB or CB) independently screened titles, abstracts and the full texts of publications. Data extraction was performed by PW and duplicated in all papers by a second reviewer (PM, CMB or CB). Paper quality was assessed using CASP methodology. RESULTS: Nine hundred fifty four references were identified: 21 met the inclusion criteria: 5 RQ1; 6 RQ2; 10 RQ3. Examination rates prior to referral were generally low: one paper identified pre-referral PE in 52% of the patients; remaining papers demonstrated examination in less than half of the patients with suspicious symptoms. No papers explored GPs' competence at performing PE directly; but one paper identified 39% of 'clinically suspicious' cervices referred for colposcopy as having no abnormality. Pre-referral PE was associated with reduced diagnostic delay and early stage diagnosis. CONCLUSIONS: Pre-referral pelvic examination in symptomatic women appears to be under-performed, despite urgent suspected cancer referral guideline recommendation to do so (Healthcare Improvement Scotland 2014 ; National Institute for Health and Care Excellence 2015 ). While no evidence was found to confirm GPs' competence for performing PE, there was an association with shorter diagnostic delay and better outcomes in those women where it was performed.

Evidence of advanced stage colorectal cancer with longer diagnostic intervals: a pooled analysis of seven primary care cohorts comprising 11 720 patients in five countries.

BACKGROUND: The benefits from expedited diagnosis of symptomatic cancer are uncertain. We aimed to analyse the relationship between stage of colorectal cancer (CRC) and the primary and specialist care components of the diagnostic interval. METHODS: We identified seven independent data sets from population-based studies in Scotland, England, Canada, Denmark and Spain during 1997-2010 with a total of 11 720 newly diagnosed CRC patients, who had initially presented with symptoms to a primary care physician. Data were extracted from patient records, registries, audits and questionnaires, respectively. Data sets were required to hold information on dates in the diagnostic interval (defined as the time from the first presentation of symptoms in primary care until the date of diagnosis), symptoms at first presentation in primary care, route of referral, gender, age and histologically confirmed stage. We carried out reanalysis of all individual data sets and, using the same method, analysed a pooled individual patient data set. RESULTS: The association between intervals and stage was similar in the individual and combined data set. There was a statistically significant convex (∩-shaped) association between primary care interval and diagnosis of advanced (i.e., distant or regional) rather than localised CRC (P=0.004), with odds beginning to increase from the first day on and peaking at 90 days. For specialist care, we saw an opposite and statistically significant concave (∪-shaped) association, with a trough at 60 days, between the interval and diagnosis of advanced CRC (P<0.001). CONCLUSIONS: This study provides evidence that longer diagnostic intervals are associated with more advanced CRC. Furthermore, the study cannot define a specific 'safe' waiting time as the length of the primary care interval appears to have negative impact from day one.

Identifying people at higher risk of melanoma across the U.K.: a primary-care-based electronic survey.

BACKGROUND: Melanoma incidence is rising rapidly worldwide among white populations. Defining higher-risk populations using risk prediction models may help targeted screening and early detection approaches. OBJECTIVES: To assess the feasibility of identifying people at higher risk of melanoma using the Williams self-assessed clinical risk estimation model in U.K. primary care. METHODS: We recruited participants from the waiting rooms of 22 general practices covering a total population of > 240 000 in three U.K. regions: Eastern England, North East Scotland and North Wales. Participants completed an electronic questionnaire using tablet computers. The main outcome was the mean melanoma risk score using the Williams melanoma risk model. RESULTS: Of 9004 people approached, 7742 (86%) completed the electronic questionnaire. The mean melanoma risk score for the 7566 eligible participants was 17·15 ± 8·51, with small regional differences [lower in England compared with Scotland (P = 0·001) and Wales (P < 0·001), mainly due to greater freckling and childhood sunburn among Scottish and Welsh participants]. After weighting to the age and sex distribution, different potential cut-offs would allow between 4% and 20% of the population to be identified as higher risk, and those groups would contain 30% and 60%, respectively of those likely to develop melanoma. CONCLUSIONS: Collecting data on the melanoma risk profile of the general population in U.K. primary care is both feasible and acceptable for patients in a general practice setting, and provides opportunities for new methods of real-time risk assessment and risk stratified cancer interventions.

General practice performance in referral for suspected cancer: influence of number of cases and case-mix on publicly reported data.

BACKGROUND: Publicly available data show variation in GPs' use of urgent suspected cancer (USC) referral pathways. We investigated whether this could be due to small numbers of cancer cases and random case-mix, rather than due to true variation in performance. METHODS: We analysed individual GP practice USC referral detection rates (proportion of the practice's cancer cases that are detected via USC) and conversion rates (proportion of the practice's USC referrals that prove to be cancer) in routinely collected data from GP practices in all of England (over 4 years) and northeast Scotland (over 7 years). We explored the effect of pooling data. We then modelled the effects of adding random case-mix to practice variation. RESULTS: Correlations between practice detection rate and conversion rate became less positive when data were aggregated over several years. Adding random case-mix to between-practice variation indicated that the median proportion of poorly performing practices correctly identified after 25 cancer cases were examined was 20% (IQR 17 to 24) and after 100 cases was 44% (IQR 40 to 47). CONCLUSIONS: Much apparent variation in GPs' use of suspected cancer referral pathways can be attributed to random case-mix. The methods currently used to assess the quality of GP-suspected cancer referral performance, and to compare individual practices, are misleading. These should no longer be used, and more appropriate and robust methods should be developed.

Smartphone applications for melanoma detection by community, patient and generalist clinician users: a review.

Smartphone health applications ('apps') are widely available but experts remain cautious about their utility and safety. We reviewed currently available apps for the detection of melanoma (July 2014), aimed at general community, patient and generalist clinician users. A proforma was used to extract and assess each app that met the inclusion criteria, and we undertook content analysis to evaluate their content and the evidence applied in their development. Thirty-nine apps were identified with the majority available only for Apple users. Over half (n = 22) provided information or education about melanoma, ultraviolet radiation exposure prevention advice, and skin self-examination strategies, mainly using the ABCDE (A, Asymmetry; B, Border; C, Colour; D, Diameter; E, Evolving) method. Half (n = 19) helped users take and store images of their skin lesions either for review by a dermatologist or for self-monitoring to identify change, an important predictor of melanoma; a similar number (n = 18) used reminders to help users monitor their skin lesions. A few (n = 9) offered expert review of images. Four apps provided a risk assessment to patients about the probability that a lesion was malignant or benign, and one app calculated users' future risk of melanoma. None of the apps appeared to have been validated for diagnostic accuracy or utility using established research methods. Smartphone apps for detecting melanoma by nonspecialist users have a range of functions including information, education, classification, risk assessment and monitoring change. Despite their potential usefulness, and while clinicians may choose to use apps that provide information to educate their patients, apps for melanoma detection require further validation of their utility and safety.

Time from first presentation in primary care to treatment of symptomatic colorectal cancer: effect on disease stage and survival.

BACKGROUND: British 5-year survival from colorectal cancer (CRC) is below the European average, but the reasons are unclear. This study explored if longer provider delays (time from presentation to treatment) were associated with more advanced stage disease at diagnosis and poorer survival. METHODS: Data on 958 people with CRC were linked with the Scottish Cancer Registry, the Scottish Death Registry and the acute hospital discharge (SMR01) dataset. Time from first presentation in primary care to first treatment, disease stage at diagnosis and survival time from date of first presentation in primary care were determined. Logistic regression and Cox survival analyses, both with a restricted cubic spline, were used to model stage and survival, respectively, following sequential adjustment of patient and tumour factors. RESULTS: On univariate analysis, those with <4 weeks from first presentation in primary care to treatment had more advanced disease at diagnosis and the poorest prognosis. Treatment delays between 4 and 34 weeks were associated with earlier stage (with the lowest odds ratio occurring at 20 weeks) and better survival (with the lowest hazard ratio occurring at 16 weeks). Provider delays beyond 34 weeks were associated with more advanced disease at diagnosis, but not increased mortality. Following adjustment for patient, tumour factors, emergency admissions and symptoms and signs, no significant relationship between provider delay and stage at diagnosis or survival from CRC was found. CONCLUSIONS: Although allowing for a nonlinear relationship and important confounders, moderately long provider delays did not impact adversely on cancer outcomes. Delays are undesirable because they cause anxiety; this may be fuelled by government targets and health campaigns stressing the importance of very prompt cancer diagnosis. Our findings should reassure patients. They suggest that a health service's primary emphasis should be on quality and outcomes rather than on time to treatment.

Can we use technology to encourage self-monitoring by people treated for melanoma? A qualitative exploration of the perceptions of potential recipients.

PURPOSE: People with melanoma traditionally attend cancer centre-based follow-up. Most recurrences and new primary melanomas are, however, detected by patients between hospital visits. Despite this, total skin self-examination (TSSE) practices are suboptimal. Digital technologies could be used to support TSSE. The attitudes of potential users are unknown; this study aims to explore the attitudes of people with melanoma towards using digital technologies and the effect of personal characteristics on their attitudes. METHODS: Twenty-one hospital joint melanoma clinic patients aged 37-83 were purposively recruited. Semi-structured interviews were conducted to explore patients' views on the use of digital technology during follow-up and identify barriers or facilitators. Interviews were transcribed verbatim and subject to framework analysis. RESULTS: Participants had a wide range of IT skills. All used a mobile phone, most had heard of telemedicine and several had used Skype. Participants felt that with thought, tailoring and training, technology could enable self-monitoring as part of melanoma follow-up. Technological benefits included having a co-ordinating nurse specialist, contactable electronically, and having a personalised skin map and tailored information about melanoma. Participants cautioned that technological developments must take account of personal needs and characteristics. Few had security concerns. CONCLUSIONS: People are not currently equipped to undertake self-monitoring as part of their melanoma follow-up, but many would be keen to employ technology to support this. A range of technologies could be utilised with potential benefits. Technologies should be carefully designed and individually tailored, considering age, familiarity with technology, place of residence and time since diagnosis.

Incidence and drug treatment of emotional distress after cancer diagnosis: a matched primary care case-control study.

BACKGROUND: Emotional distress is common in cancer patients. This study aimed to describe, in the year after a cancer diagnosis: the incidence of anxiety, depression and excessive alcohol use; the pattern of these diagnoses and treatment over time; and the nature and duration of the prescribed treatment. METHODS: A matched case-control study was conducted using routinely collected primary care data from 173 Scottish general practices. A presumptive diagnosis of emotional distress (anxiety, depression and/or excessive alcohol use) was based on prescription data or diagnostic code. Prescriptions for psychotropic drugs were described in terms of drug class, volume and treatment duration. RESULTS: In total, 7298 cancer cases and 14 596 matched-controls were identified. Overall, 1135 (15.6%) cases and 201 (1.4%) controls met criteria for emotional distress (odds ratio 13.7, 95% confidence interval 11.6-16.1). Psychotropic drugs were prescribed in the 6 months following initial cancer diagnosis for 1066 (14.6%) cases and 161 (1.1%) controls. The volume and duration of anxiolytic and antipsychotic prescribing was significantly different between cases and controls. CONCLUSION: This study quantified the higher incidence of new emotional distress in cancer patients in the first year post diagnosis. Clinicians should be aware of the possibility of emotional distress at any time in the year after cancer diagnosis.

The effect of medications associated with drug-induced pancreatitis on pancreatic cancer risk: A nested case-control study of routine Scottish data.

BACKGROUND: Inflammation plays a role in pancreatic cancer. Many medications cause pancreatic inflammation, with some leading to a diagnosis of drug-induced pancreatitis (DIP), but few studies have examined these medications and pancreatic cancer risk. We therefore investigated the associations between pancreatic cancer risk and commonly-prescribed medicines for which there is strongest evidence of DIP. METHODS: A nested case-control study was undertaken using the Primary Care Clinical Informatics Unit Research database containing general practice (GP) records from Scotland. Pancreatic cancer cases, diagnosed between 1999 and 2011, were identified and matched with up to five controls (based on age, gender, GP practice and date of registration). Medicines in the highest category of evidence for DIP, based on a recent systematic review, and used by more than 2 % of controls were identified. Odds ratios (OR) and 95 % confidence intervals (CI) for associations with pancreatic cancer were calculated using conditional logistic regression after adjusting for comorbidities. RESULTS: There were 1,069 cases and 4,729 controls. Thirteen medicines in the highest category of evidence for DIP were investigated. There was little evidence of an association between any of these medications and pancreatic cancer risk apart from metronidazole (adjusted OR 1.69, 95 % CI 1.18, 2.41) and ranitidine (adjusted OR 1.37, 95 %CI 1.10, 1.70). However, no definitive exposure-response relationships between these medicines and cancer risk were observed. CONCLUSIONS: There is little evidence that commonly-prescribed medicines associated with inflammation of the pancreas are also associated with pancreatic cancer. These findings should provide reassurance to patients and prescribing clinicians.

Patient satisfaction with GP-led melanoma follow-up: a randomised controlled trial.

BACKGROUND: There are no universally accepted guidelines for the follow-up of individuals with cutaneous melanoma. Furthermore, to date, there have been no randomised controlled trials of different models of melanoma follow-up care. This randomised controlled trial was conducted to evaluate the effects of GP-led melanoma follow-up on patient satisfaction, follow-up guideline compliance, anxiety and depression, as well as health status. METHODS: A randomised controlled trial of GP-led follow-up of cutaneous melanoma was conducted over a period of 1 year with assessment by self-completed questionnaires and review of general practice-held medical records at baseline and 12 months later. It took place in 35 general practices in North-east Scotland. Subjects were 142 individuals (51.4% women 48.6% men; mean (s.d.) age 59.2 (15.2) years previously treated for cutaneous melanoma and free of recurrent disease. The intervention consisted of protocol-driven melanoma reviews in primary care, conducted by trained GPs and supported by centralised recall, rapid access pathway to secondary care and a patient information booklet. The main outcome measure was patient satisfaction measured by questionnaire. Secondary outcomes were adherence to guidelines, health status measured by Short Form-36 and the Hospital Anxiety and Depression Scale. RESULTS: There were significant improvements in 5 out of 15 aspects of patient satisfaction during the study year in those receiving GP-led melanoma follow-up (all P

Achieving Self-Directed Integrated Cancer Aftercare (ASICA) in melanoma: protocol for a randomised patient-focused pilot trial of delivering the ASICA intervention as a means to earlier detection of recurrent and second primary melanoma.

BACKGROUND: Melanoma is common; 15,906 people in the UK were diagnosed with melanoma in 2015 and incidence has increased fivefold in 30 years. Melanoma affects old and young people, with poor prognosis once metastatic. UK guidelines recommend people treated for cutaneous melanoma receive extended outpatient, hospital follow up to detect recurrence or new primaries. Such follow up of the growing population of melanoma survivors is burdensome for both individuals and health services. Follow up is important since approximately 20% of patients with early-stage melanoma experience a recurrence and 4-8% develop a new primary; the risk of either is highest in the first 5 years. Achieving Self-directed Integrated Cancer Aftercare (ASICA) is a digital intervention to increase total-skin-self-examination (TSSE) by people treated for melanoma, with usual follow up. METHODS: We aim to recruit 240 adults with a previous first-stage 0-2C primary cutaneous melanoma, from secondary care in North-East Scotland and the East of England. Participants will be randomised to receive the ASICA intervention (a tablet-based digital intervention to prompt and support TSSE) or control group (treatment as usual). Patient-reported and clinical data will be collected at baseline, including the modified Melanoma Worry Scale (MWS), the Hospital Anxiety and Depression Scale (HADs), the EuroQoL 5-dimension 5-level questionnaire (EQ-5D-5 L), and questions about TSSE practice, intentions, self-efficacy and planning. Participants will be followed up by postal questionnaire at 3, 6 and 12 months following randomization, along with a 12-month review of clinical data. The primary timepoint for outcome analyses will be12 months after randomisation. DISCUSSION: If the ASICA intervention improves the practice of TSSE in those affected by melanoma, this may lead to improved psychological well-being and earlier detection of recurrent and new primary melanoma. This could impact both patients and National Health Service (NHS) resources. This study will determine if a full-scale randomised controlled trial can be undertaken in the UK NHS to provide the high-quality evidence needed to determine the effectiveness of the intervention. ASICA is a pilot study evaluating the effectiveness of the practice of digitally supported TSSE in those affected by melanoma. TRIAL REGISTRATION: Clinical Trials.gov, NCT03328247 . Registered on 1 November 2017.

Excising basal cell carcinomas: comparing the performance of general practitioners, hospital skin specialists and other hospital specialists.

BACKGROUND: General practitioners (GPs) are not encouraged to excise basal cell carcinomas (BCCs). Despite this, as many of 10% of BCCs may be excised by GPs. GPs may be able to have a greater role in the diagnosis and management of BCC, but much needs to be learnt before this can be advocated. OBJECTIVE: To compare the practice of GPs, skin specialists (dermatologists and plastic surgeons) and other hospital specialists in excising BCCs. METHODS: A retrospective analysis of all BCCs excised in the Grampian region between 1 January and 31 December 2005 was carried out In total, 1087 reports were rated for source, quality of clinical information provided and extent of excision. RESULTS: GPs perform significantly less well than skin specialists when diagnosing and excising BCCs, but appear equal in diagnostic skill and better at excision than other hospital specialists. Non-specialized GPs appear to perform as well as GPs with special interest (GPwSI) in adequately excising BCCs. In 18.7% of all cases, the information supplied to the pathologist with the biopsy sample was inadequate to draw a conclusion. CONCLUSIONS: GPs compare unfavourably with skin specialists in diagnosing and excising BCCs. The performance of nonspecialized GPs does not appear to differ markedly from that of GPwSI. There is considerable room to optimize current GP performance, particularly with lesions of the head and neck, and it may be that novel approaches to GP training are required to achieve this. Structured request forms may improve the quality of clinical information provided when skin biopsies are submitted for pathological examination.

Proton pump inhibitor and histamine-2 receptor antagonist use and risk of liver cancer in two population-based studies.

BACKGROUND: Proton pump inhibitors (PPIs) and histamine-2 receptor antagonists (H2RAs) are commonly used. PPIs have been shown to promote liver cancer in rats; however, only one study has examined the association in humans. AIMS: To investigate PPIs and H2RAs and risk of primary liver cancer in two large independent study populations. METHODS: We conducted a nested case-control study within the Primary Care Clinical Informatics Unit (PCCIU) database in which up to five controls were matched to cases with primary liver cancer, recorded by General Practitioners. Odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations with prescribed PPIs and H2RAs were calculated using conditional logistic regression. We also conducted a prospective cohort study within the UK Biobank using self-reported medication use and cancer-registry recorded primary liver cancer. Hazard ratios (HRs) and 95% CIs were calculated using Cox regression. RESULTS: In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2103 controls. In the UK Biobank cohort, 182 of 475 768 participants developed liver cancer. In both, ever use of PPIs was associated with increased liver cancer risk (adjusted OR 1.80, 95% CI 1.34, 2.41 and adjusted HR 1.99, 95% CI 1.34, 2.94 respectively). There was little evidence of association with H2RA use (adjusted OR 1.21, 95% CI 0.84, 1.76 and adjusted HR 1.70, 95% CI 0.82, 3.53 respectively). CONCLUSIONS: We found some evidence that PPI use was associated with liver cancer. Whether this association is causal or reflects residual confounding or reverse causation requires additional research.

Effect of longer health service provider delays on stage at diagnosis and mortality in symptomatic breast cancer.

PURPOSE: This study explored whether longer provider delays (between first presentation and treatment) were associated with later stage and poorer survival in women with symptomatic breast cancer. METHODS: Data from 850 women with symptomatic breast cancer were linked with the Scottish Cancer Registry; Death Registry; and hospital discharge dataset. Logistic regression and Cox survival analyses with restricted cubic splines explored relationships between provider delays, stage and survival, with sequential adjustment for patient and tumour factors. RESULTS: Although confidence intervals were wide in both adjusted analyses, those with the shortest provider delays had more advanced breast cancer at diagnosis. Beyond approximately 20 weeks, the trend suggests longer delays are associated with more advanced stage, but is not statistically significant. Those with symptomatic breast cancer and the shortest presentation to treatment time (within 4 weeks) had the poorest survival. Longer time to treatment was not significantly associated with worsening mortality. CONCLUSIONS: Poor prognosis patients with breast cancer are being triaged for rapid treatment with limited effect on outcome. Prolonged time to treatment does not appear to be strongly associated with poorer outcomes for patients with breast cancer, but the power of this study to assess the effect of very long delays (>25 weeks) was limited. Efforts to reduce waiting times are important from a quality of life perspective, but tumour biology may often be a more important determinant of stage at diagnosis and survival outcome.

Secondary prevention clinics for coronary heart disease: a 10-year follow-up of a randomised controlled trial in primary care.

OBJECTIVES: To evaluate the effects of nurse-led secondary prevention clinics for coronary heart disease (CHD) in primary care on total mortality and coronary event rates after 10 years. DESIGN: Follow-up of a randomised controlled trial by review of national datasets. SETTING: Stratified random sample of 19 general practices in northeast Scotland. PARTICIPANTS: Original study cohort of 1343 patients, aged <80 years, with a working diagnosis of CHD, but without dementia or terminal illness and not housebound. INTERVENTION: Nurse-led secondary prevention clinics promoted medical and lifestyle aspects of secondary prevention and offered regular follow-up for 1 year, MAIN OUTCOME MEASURES: Total mortality and coronary events (non-fatal myocardial infarctions (MIs) and coronary deaths). RESULTS: Mean (SD) follow-up was at 10.2 (0.19) years. No significant differences in total mortality or coronary events were found at 10 years. 254 patients in the intervention group and 277 patients in the control group had died: cumulative death rates were 38% and 41%, respectively (p = 0.177). 196 coronary events occurred in the intervention group and 195 in the control group: cumulative event rates were 29.1% and 29.1%, respectively (p = 0.994). When Kaplan-Meier survival analysis, adjusted for age, sex and general practice, was used, proportional hazard ratios were 0.88 (0.74 to 1.04) for total mortality and 0.96 (0.79 to 1.18) for coronary death or non-fatal MI. No significant differences in the distribution of cause of death classifications was found at either 4 or 10 years. CONCLUSIONS: After 10 years, differences between groups were no longer significant. Total mortality survival curves for the intervention and control groups had not converged, but the coronary event survival curves had. Possibly, therefore, the earlier that secondary prevention is optimised, the less likely a subsequent coronary event is to prove fatal.