Use of 5-alpha reductase inhibitors and risk of gastrointestinal cancers in men with benign prostatic hyperplasia: A population-based cohort study.

Pre-clinical evidence suggests that 5-alpha reductase inhibitors (5ARi's), prescribed in the treatment of benign prostatic hyperplasia, reduce colorectal and gastro-oesophageal cancer incidence via action on the male hormonal pathway. However, few studies to date have investigated this association at the population level. Our study aimed to investigate the risk of colorectal and gastro-oesophageal cancers with the use of 5ARi's. We conducted a retrospective cohort study of new users of 5ARi's and alpha-blockers among patients with benign prostatic hyperplasia in the UK Clinical Practice Research Datalink. Patients were followed until a first ever diagnosis of colorectal or gastro-oesophageal cancer, death from any cause or end of registration with the general practice or 31st of December 2017. Cox proportional hazards models with inverse probability of treatment weights were used to calculate weighted hazard ratios (HR) and 95% confidence intervals (CIs) of incident colorectal cancer or gastro-oesophageal cancer associated with the use of 5ARi's compared to alpha-blockers. During a mean follow-up of 6.6 years, we found no association between the use of 5ARi's and colorectal (HR: 1.13, 95% CI 0.91-1.41) or gastro-oesophageal (HR 1.14, 95% CI 0.76-1.63) cancer risk compared to alpha-blockers. Sensitivity analysis showed largely consistent results when varying lag periods, using multiple imputations, and accounting for competing risk of death. Our study found no association between the use of 5ARi's and risk of colorectal or gastro-oesophageal cancer in men with benign prostatic hyperplasia.

Hormone replacement therapy and cancer mortality in women with 17 site-specific cancers: a cohort study using linked medical records.

BACKGROUND: There is limited evidence on the safety of Hormone Replacement Therapy (HRT) in women with cancer. Therefore, we systematically examined HRT use and cancer-specific mortality in women with 17 site-specific cancers. METHODS: Women newly diagnosed with 17 site-specific cancers from 1998 to 2019, were identified from general practitioner (GP) records, hospital diagnoses or cancer registries in Scotland, Wales and England. Breast cancer patients were excluded because HRT is contraindicated in breast cancer patients. The primary outcome was time to cancer-specific mortality. Time-dependent Cox regression models were used to calculate adjusted hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer-specific mortality by systemic HRT use. RESULTS: The combined cancer cohorts contained 182,589 women across 17 cancer sites. Overall 7% of patients used systemic HRT after their cancer diagnosis. There was no evidence that HRT users, compared with non-users, had higher cancer-specific mortality at any cancer site. In particular, no increase was observed in common cancers including lung (adjusted HR = 0.98 95% CI 0.90, 1.07), colorectal (adjusted HR = 0.79 95% CI 0.70, 0.90), and melanoma (adjusted HR = 0.77 95% CI 0.58, 1.02). CONCLUSIONS: We observed no evidence of increased cancer-specific mortality in women with a range of cancers (excluding breast) receiving HRT.

Exposure to weak opioids and risk of gastrointestinal tract cancers: A series of nested case-control studies.

AIMS: There is evidence gastrointestinal (GI) motility may play a role in the development of GI cancers. Weak opioids (codeine and dihydrocodeine) decrease GI motility, but their effect on GI cancer risk has not been assessed. We aim to assess the association between weak opioids and cancers of the GI tract. METHODS: A series of nested case-control studies was conducted using Scottish general practice records from the Primary Care Clinical Informatics Unit Research database. Oesophageal (n = 2432), gastric (n = 1443) and colorectal cancer (n = 8750) cases, diagnosed between 1999 and 2011, were identified and matched with up to five controls. Weak opioid use was identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression, adjusting for relevant comorbidities and medication use. RESULTS: There was no association between weak opioids and colorectal cancer (adjusted OR = 0.96, CI 0.90, 1.02, P = 0.15). There was an increased risk of oesophageal (adjusted OR = 1.16, CI 1.04, 1.29, P = 0.01) and gastric cancer (adjusted OR = 1.26, CI 1.10, 1.45, P = 0.001). The associations for oesophageal cancer, but not gastric cancer, were attenuated when weak opioid users were compared with users of another analgesic (adjusted OR = 1.03 CI 0.86, 1.22, P = 0.76 and adjusted OR = 1.29 CI 1.02, 1.64, P = 0.04 respectively). CONCLUSIONS: In this large population-based study, there was no consistent evidence of an association between weak opioids and oesophageal or colorectal cancer risk, but a small increased risk of gastric cancer. Further investigation is required to determine whether this association is causal or reflects residual confounding or confounding by indication.

Validated frailty measures using electronic primary care records: a review of diagnostic test accuracy.

INTRODUCTION: Identification of people who have or are at risk of frailty enables targeted interventions, and the use of tools that screen for frailty using electronic records (which we term as validated electronic frailty measures (VEFMs)) within primary care is incentivised by NHS England. We carried out a systematic review to establish the sensitivity and specificity of available primary care VEFMs when compared to a reference standard in-person assessment. METHODS: Medline, Pubmed, CENTRAL, CINHAL and Embase searches identified studies comparing a primary care VEFM with in-person assessment. Studies were quality assessed using Quality Assessment of Diagnostic Accuracy Studies revised tool. Sensitivity and specificity values were extracted or were calculated and pooled using StatsDirect. RESULTS: There were 2,245 titles screened, with 10 studies included. These described three different index tests: electronic frailty index (eFI), claims-based frailty index (cFI) and polypharmacy. Frailty Phenotype was the reference standard in each study. One study of 60 patients examined the eFI, reporting a sensitivity of 0.84 (95% CI = 0.55, 0.98) and a specificity of 0.78 (0.64, 0.89). Two studies of 7,679 patients examined cFI, with a pooled sensitivity of 0.48 (95% CI = 0.23, 0.74) and a specificity of 0.80 (0.53, 0.98). Seven studies of 34,328 patients examined a polypharmacy as a screening tool (defined as more than or equal to five medications) with a pooled sensitivity of 0.61 (95% CI = 0.50, 0.72) and a specificity of 0.66 (0.58, 0.73). CONCLUSIONS: eFI is the best-performing VEFM; however, based on our analysis of an average UK GP practice, it would return a high number of false-positive results. In conclusion, existing electronic frailty tools may not be appropriate for primary care-based population screening.

Barriers and facilitators of adherence to the use of ASICA, a digital app designed to support people previously treated for melanoma: concise report of a qualitative study.

We developed the Achieving Self-directed Integrated Cancer Aftercare (ASICA) in melanoma app to support monthly total-skin self-examinations (TSSE) by people previously treated for melanoma. A randomized 12-month trial demonstrated ASICA supported optimal monthly TSSE adherence in a third of participants (ClinicalTrials.gov NCT03328247). However, a further third of participants adhered well initially but subsequently dropped off, and a final third did not adhere at all. This follow-up qualitative study investigated trial participants' perceptions of barriers and facilitators to TSSE adherence using the app. Three former trial participants participated in a single focus group and 11 participated in new semistructured telephone interviews. These were analysed thematically alongside secondary analysis of 13 qualitative interviews conducted during the trial. All transcripts were recorded, transcribed and analysed thematically. Five themes encompassing barriers and facilitators to ASICA adherence emerged. These were: technology, role of others, tailoring, disease journey and competing priorities. These data will inform further development of ASICA to increase user adherence.

Oral antibiotic use and early-onset colorectal cancer: findings from a case-control study using a national clinical database.

BACKGROUND: Antibiotic-induced gut dysbiosis has been associated with colorectal cancer (CRC) in older adults. This study will investigate whether an association exists between antibiotic usage and early-onset colorectal cancer (CRC), and also evaluate this in later-onset CRC for comparison. METHODS: A case-control study was conducted using primary care data from 1999-2011. Analysis were conducted separately in early-onset CRC cases (diagnosed < 50 years) and later-onset cases (diagnosed ≥ 50 years). Conditional logistic regression was used to calculate odds ratios and 95% confidence intervals (CI) for the associations between antibiotic exposure and CRC by tumour location, adjusting for comorbidities. RESULTS: Seven thousands nine hundred and three CRC cases (445 aged <50 years) and 30,418 controls were identified. Antibiotic consumption was associated with colon cancer in both age-groups, particularly in the early-onset CRC cohort (<50 years: adjusted Odds Ratio (ORadj) 1.49 (95% CI 1.07, 2.07), p = 0·018; ≥50 years (ORadj (95% CI) 1.09 (1.01, 1.18), p = 0·029). Antibiotics were not associated with rectal cancer (<50 years: ORadj (95% CI) 1.17 (0.75, 1.84), p = 0.493; ≥50 years: ORadj (95% CI) 1.07 (0.96, 1.19), p = 0.238). CONCLUSION: Our findings suggest antibiotics may have a role in colon tumour formation across all age-groups.

How does social context influence appraisal and help-seeking for potential cancer symptoms in adults aged 50 and over? A qualitative interview study.

OBJECTIVE: To investigate how social context and social network activation influence appraisal and help-seeking for symptoms potentially indicative of cancer. METHODS: Semi-structured telephone interview study. Community dwelling adults who had experienced at least one symptom potentially indicative of cancer within the last month were sampled from a national symptom survey. RESULTS: Thirty-four interviews were conducted. Participants looked to peers and wider society to judge whether symptoms might be normal for their age. Involvement of others in symptom appraisal promoted an active management strategy, such as contacting a healthcare professional or trying a medication. There were practical, emotional, attitudinal, normative and moral barriers to involving others. Cancer narratives from significant others, public health campaigns and the media influenced symptom appraisal. Participants held mental representations of types of people who get cancer, for example, smokers and unfit people. This had two consequences. First, participants did not identify themselves as a candidate for cancer; impeding help-seeking. Second, social judgements about lifestyle introduced stigma. CONCLUSION: Involving friends/family in symptom appraisal facilitates help-seeking but barriers exist to involving others. Campaigns to promote earlier cancer diagnosis should incorporate age-appropriate narratives, address misconceptions about 'types' of people who get cancer and tackle stigma about lifestyle factors.

Exposure to Ranitidine and Risk of Bladder Cancer: A Nested Case-Control Study.

INTRODUCTION: Ranitidine has been shown to contain the carcinogen N-nitrosodimethylamine and increase urinary N-nitrosodimethylamine in humans. We investigated whether ranitidine use is associated with increased bladder cancer risk. METHODS: A nested case-control study was conducted within the Primary Care Clinical Informatics Unit Research database which contains general practice records from Scotland. Bladder cancer cases, diagnosed between 1999 and 2011, were identified and matched with up to 5 controls (based on age, sex, general practice, and date of registration). Ranitidine, other histamine-2 receptor agonists, and proton pump inhibitors were identified from prescribing records. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression after adjusting for comorbidities and smoking. RESULTS: There were 3,260 cases and 14,037 controls. There was evidence of an increased risk of bladder cancer in ranitidine users, compared with nonusers (fully adjusted OR = 1.22; 95% CI 1.06-1.40), which was more marked with use for over 3 years of ranitidine (fully adjusted OR = 1.43; 95% CI 1.05-1.94). By contrast, there was little evidence of any association between proton pump inhibitor use and bladder cancer risk based on any use (fully adjusted OR = 0.98; 95% CI 0.88-1.11) or over 3 years of use (fully adjusted OR = 0.98; 95% CI 0.80-1.20). DISCUSSION: In this large population-based study, the use of ranitidine particularly long-term use was associated with an increased risk of bladder cancer. Further studies are necessary to attempt to replicate this finding in other settings.

The effect of COVID-19 public health restrictions on the health of people with musculoskeletal conditions and symptoms: the CONTAIN study.

OBJECTIVE: To quantify the change in quality of life, disease-specific indicators, health and lifestyle before and during the COVID-19 pandemic among people with musculoskeletal diagnoses and symptoms. METHODS: We undertook an additional follow-up of two existing UK registers involving people with axial spondyloarthritis (axSpA) or psoriatic arthritis (PsA) and participants in a trial in the UK who had regional pain and were identified at high risk of developing chronic widespread pain. Participants completed the study questionnaire between July and December 2020, throughout which time there were public health restrictions in place. RESULTS: The number of people taking part in the study was 1054 (596 axSpA, 162 PsA, 296 regional pain). In comparison with their previous (pre-pandemic) assessment, there was an age-adjusted significant, small decrease in quality of life measured by EQ-5D [-0.020 (95% CI -0.030, -0.009)] overall and across all population groups examined. This was primarily related to poorer mental health and pain. There was a small increase in fibromyalgia symptoms, but a small decrease in sleep problems. There was a small deterioration in axSpA disease activity, and disease-specific quality of life and anxiety in PsA participants. Predictors of poor quality of life were similar pre- and during the pandemic. The effect of lockdown on activity differed according to age, gender and deprivation. CONCLUSION: Important lessons include focusing on addressing anxiety and providing enhanced support for self-management in the absence of normal health care being available, and awareness that all population groups are likely to be affected.

Hormone replacement therapy in women with cancer and risk of cancer-specific mortality and cardiovascular disease: a protocol for a cohort study from Scotland and Wales.

BACKGROUND: Hormone replacement therapy (HRT) is widely used and has proven benefits for women with menopausal symptoms. An increasing number of women with cancer experience menopausal symptoms but the safety of HRT use in women with cancer is unclear. There are particular concerns that HRT could accelerate cancer progression in women with cancer, and also that HRT could increase the risk of cardiovascular disease in such women. Therefore, our primary aim is to determine whether HRT use alters the risk of cancer-specific mortality in women with a range of common cancers. Our secondary objectives are to investigate whether HRT alters the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. METHODS: The study will utilise independent population-based data from Wales using the SAIL databank and Scotland based upon the national Prescribing Information System. The study will include women newly diagnosed with common cancers from 2000 to 2016, identified from cancer registries. Women with breast cancers will be excluded. HRT will be ascertained using electronic prescribing in Wales or dispensing records in Scotland. The primary outcome will be time to cancer-specific mortality from national mortality records. Time-dependent cox regression models will be used to calculate hazard ratios (HR) and 95% confidence intervals (95% CIs) for cancer specific death in HRT users compared with non-users after cancer diagnosis after adjusting for relevant confounders, stratified by cancer site. Analysis will be repeated investigating the impact of HRT use immediately before cancer diagnosis. Secondary analyses will be conducted on the risk of second cancers, cardiovascular disease, venous thromboembolism and all-cause mortality. Analyses will be conducted within each cohort and pooled across cohorts. DISCUSSION: Our study will provide evidence to inform guidance given to women diagnosed with cancer on the safety of HRT use and/or guide modifications to clinical practice.

Achieving integrated self-directed Cancer aftercare (ASICA) for melanoma: how a digital intervention to support total skin self-examination was used by people treated for cutaneous melanoma.

BACKGROUND: Melanoma incidence has quadrupled since 1970 and melanoma is now the second most common cancer in individuals under 50. Targeted immunotherapies for melanoma now potentially enable long-term remission even in advanced melanoma, but these melanoma survivors require ongoing surveillance, with implications for NHS resources and significant social and psychological consequences for patients. Total skin self-examination (TSSE) can detect recurrence earlier and improve clinical outcomes but is underperformed in the UK. To support survivors, the Achieving Self-directed Integrated Cancer Aftercare (ASICA) intervention was developed to prompt and improve TSSE performance, with subsequent reporting of concerns and submission of skin photos to a Dermatology Nurse Practitioner (DNP). ASICA was delivered as a randomized pilot trial. METHODS: This paper reports on process evaluation. Data on participants' demographics and the concerns they reported during the trial were tabulated and displayed using Microsoft Excel and SPSS. We explored which participants used ASICA, and how frequently, to report any skin concerns. We also determined how the interactions had worked in terms of quality of skin photographs submitted, clinical assessments made by the DNP, and the assessments and decisions made for each concern. Finally, we explored significant events occurring during the trial. Data on participants' demographics and the concerns they reported during the trial were tabulated and displayed using SPSS. A semi-structured interview was undertaken with the DNP to gain perspective on the range of concerns presented and how they were resolved. RESULTS: Of 121 recruited melanoma patients receiving ASICA for 12 months, 69 participants submitted a total of 123 reports detailing 189 separate skin-related concerns and including 188 skin photographs. Where participants fully complied with follow-up by the DNP, concerns were usually resolved remotely, but 19 (10.1%) were seen at a secondary care clinic and 14 (7.4%) referred to their GP. 49 (25.9%) of concerns were not completely resolved due to partial non-compliance with DNP follow-up. CONCLUSION: Melanoma patients randomized to the ASICA intervention were able to report skin-related concerns that could be resolved remotely through interaction with a DNP. Feasibility issues highlighted by ASICA will support further development and optimization of this digital tool. TRIAL REGISTRATION: Clinical Trials.gov , NCT03328247 . Registered on 1 November 2017.

Can-Pain-a digital intervention to optimise cancer pain control in the community: development and feasibility testing.

PURPOSE: To develop a novel digital intervention to optimise cancer pain control in the community. This paper describes intervention development, content/rationale and initial feasibility testing. METHODS: Determinants of suboptimal cancer pain management were characterised through two systematic reviews; patient, caregiver and healthcare professional (HCP) interviews (n = 39); and two HCP focus groups (n = 12). Intervention mapping was used to translate results into theory-based content, creating the app "Can-Pain". Patients with/without a linked caregiver, their general practitioners and community palliative care nurses were recruited to feasibility test Can-Pain over 4 weeks. RESULTS: Patients on strong opioids described challenges balancing pain levels with opioid intake, side effects and activities and communicating about pain management problems with HCPs. Can-Pain addresses these challenges through educational resources, contemporaneous short-acting opioid tracking and weekly patient-reported outcome monitoring. Novel aspects of Can-Pain include the use of contemporaneous breakthrough analgesic reports as a surrogate measure of pain control and measuring the level at which pain becomes bothersome to the individual. Patients were unwell due to advanced cancer, making recruitment to feasibility testing difficult. Two patients and one caregiver used Can-Pain for 4 weeks, sharing weekly reports with four HCPs. Can-Pain highlighted unrecognised problems, promoted shared understanding about symptoms between patients and HCPs and supported shared decision-making. CONCLUSIONS: Preliminary testing suggests that Can-Pain is feasible and could promote patient-centred pain management. We will conduct further small-scale evaluations to inform a future randomised, stepped-wedge trial. TRIAL REGISTRATION: Qualitative research: ClinicalTrials.gov , reference NCT02341846 Feasibility study: NIHR CPMS database ID 34172.

Statin use and risk of liver cancer: Evidence from two population-based studies.

Epidemiological studies of statin use and liver cancer risk have produced conflicting results. We examined the association between statin use and risk of primary liver cancer in two large independent study populations taking account of important covariates and main indications of statins such as high cholesterol and chronic liver disease. We performed a nested case-control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database. Five controls were matched to cases with primary liver cancer and we used conditional logistic regression to calculate odds ratios (ORs) and 95% confidence intervals (CIs) for associations with statin use. We also conducted a prospective cohort study within the UK Biobank using self-reported statin use and cancer-registry recorded primary liver cancer outcomes. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs. In the PCCIU case-control analysis, 434 liver cancer cases were matched to 2,103 controls. In the UK Biobank cohort, 182 out of 475,768 participants developed incident liver cancer. Statin use was associated with 39% lower risk of liver cancer in the PCCIU (adjusted OR 0.61, 95% CI 0.43-0.87). When we examined specific subtypes of liver cancer in the UK Biobank, statin use was associated with lower risk of hepatocellular carcinoma (HCC; adjusted HR, 0.48; 95% CI, 0.24-0.94) but not intrahepatic bile duct carcinoma (IBDC; adjusted HR, 1.09; 95% CI, 0.45-2.64). In conclusion, we found a consistent inverse relationship between statin use and risk of primary liver cancer which was only seen for HCC but not IBDC.

Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies.

BACKGROUND: Studies have shown increased gastric cancer risk in users of proton pump inhibitors (PPI) and histamine-2 receptor antagonists, questioning the safety of gastric acid suppression. Therefore, we conducted a case-control study within the Scottish Primary Care Clinical Informatics Unit (PCCIU) database and a cohort study in the UK Biobank. METHODS: In PCCIU, five controls were matched to cases diagnosed in 1999-2011, and medications were determined from GP records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression. In the UK Biobank, medications were self-reported at cohort entry 2006-2010, and gastric cancer ascertained from cancer registries until 2014. Hazard ratios (HR) were calculated using Cox regression. RESULTS: PCCIU contained 1119 cases and 5394 controls. UK Biobank contained 250 cases in 471,779 participants. PPI users had a higher gastric cancer risk in PCCIU and UK Biobank when applying a 1-year lag (adjusted OR = 1.49, 95% CI 1.24, 1.80; adjusted HR = 1.28, 95% CI 0.86, 1.90, respectively), but these associations were attenuated when using a 2-year lag (adjusted OR = 1.13, 95% CI 0.91, 1.40; adjusted HR = 1.15, 95% CI 0.73, 1.82, respectively). CONCLUSIONS: Overall, we observed little consistent evidence of an increased risk of gastric cancer with PPI use.

The role of 5α-reductase inhibitors in gastro-oesophageal cancer risk: A nested case-control study.

PURPOSE: The strong male predominance of gastro-oesophageal cancer suggests that sex hormones play an important role. 5α-Reductase (5AR) inhibitors have antiandrogen effects and have been shown to decrease cancer cell proliferation and metastasis. We conducted the first epidemiologic investigation into the association between 5AR inhibitor use and gastro-oesophageal cancer risk. METHODS: We conducted a nested case-control study within the Scottish Primary Care Clinical Information Unit Research database. Male cases diagnosed with oesophageal or gastric cancer between 1999 and 2011 were matched to up to five male controls based on birth year, diagnosis year, and general practice. We used electronic prescribing records to ascertain medication use. We used conditional logistic regression to calculate odds ratios (ORs) for the association between 5AR inhibitor use and cancer risk, after adjusting for comorbidities and aspirin, statin, or proton pump inhibitor use. RESULTS: The study included 2003 gastro-oesophageal cancer cases and 9650 controls. There was some evidence of reduced gastro-oesophageal cancer risk among 5AR inhibitor users (adjusted OR = 0.75; 95% CI, 0.56-1.02), particularly for finasteride (adjusted OR = 0.68; 95% CI, 0.50-0.94). These decreases were more marked among those who received at least 3 years of 5AR inhibitors (adjusted OR = 0.54; 95% CI, 0.27-1.05; P value = .071) or finasteride (adjusted OR = 0.49; 95% CI, 0.24-0.99; P value = .046). CONCLUSIONS: We found evidence of reduced gastro-oesophageal cancer risk among users of 5AR inhibitors, particularly finasteride. However, larger epidemiological studies are required before randomised controlled trials are considered.

Validation of self-reported help-seeking, and measurement of the patient interval, for cancer symptoms: an observational study to inform methodological challenges in symptomatic presentation research.

BACKGROUND: To improve earlier presentation with potential symptoms of cancer, accurate data are needed on how people respond to these symptoms. It is currently unclear how self-reported medical help-seeking for symptoms associated with cancer by people from the community correspond to what is recorded in their general practice records, or how well the patient interval (time from symptom onset to first presentation to a health-professional) can be estimated from patient records. METHOD: Data from two studies that reviewed general practice electronic records of residents in Scotland, (i) the 'Useful Study': respondents to a general population survey who reported experiencing symptoms potentially associated with one of four common cancers (breast, colorectal, lung and upper gastro-intestinal) and (ii) the 'Detect Cancer Early' programme: cancer patients with one of the same four cancers. Survey respondents' self-reported help-seeking (yes/no) was corroborated; Cohen's Kappa assessed level of agreement. Combined data on the patient interval were evaluated using descriptive analysis. RESULTS: 'Useful Study' respondents' self-report of help-seeking showed exact correspondence with general practice electronic records in 72% of cases (n = 136, kappa 0.453, moderate agreement). Between both studies, 1269 patient records from 35 general practices were reviewed. The patient interval could not be determined in 44% (n = 809) of symptoms presented by these individuals. CONCLUSIONS: Patient self-report of help-seeking for symptoms potentially associated with cancer offer a reasonably accurate method to research responses to these symptoms. Incomplete patient interval data suggest routine general practice records are unreliable for measuring this important part of the patient's symptom journey.

Cancer diagnosis in Scottish primary care: Results from the National Cancer Diagnosis Audit.

OBJECTIVE: To characterize cancer diagnosis in Scottish primary care and draw comparisons with cancer diagnostic activity in England. METHOD: A national audit of cancer diagnosis was conducted in Scottish and English general practices. Participating GPs collected diagnostic pathway data on patients diagnosed in 2014 from medical records. Data were supplemented by linkage to national cancer registries. Analysis explored and compared patient characteristics, diagnostic intervals, and routes to diagnosis. RESULTS: 7.7% of all Scottish general practices in 2017 provided data on 2,014 cancer diagnoses. 71.5% of cases presented to GPs and 37.4% were referred using the "Urgent-Suspected Cancer" route. The median primary care interval was 5 days (IQR 0-23 days) and median diagnostic interval was 30 days (IQR 13-68). Both varied by cancer-site. Diagnostic intervals were longer in the most remote patients and those with more comorbidities. Scottish and English samples corresponded closely in key characteristics. CONCLUSIONS: Most people diagnosed with cancer in Scotland present to a GP first. Most are referred and diagnosed quickly, with variations by cancer-site. Intervals were longest for the most remote patients. GPs in Scotland and England appear to perform equally but, in view of growing differences between health systems, future comparative audits may be informative.

The Chest Australia Trial: a randomised controlled trial of an intervention to increase consultation rates in smokers at risk of lung cancer.

BACKGROUND: International research has focused on screening and mass media campaigns to promote earlier patient presentation and detect lung cancer earlier. This trial tested the effect of a behavioural intervention in people at increased risk of lung cancer on help-seeking for respiratory symptoms. METHODS: Parallel, individually randomised controlled trial. Eligible participants were long-term smokers with at least 20 pack-years, aged 55 and above. The CHEST intervention entailed a consultation to discuss and implement a self-help manual, followed by self-monitoring reminders to encourage help-seeking for respiratory symptoms. The control group received a brief discussion about lung health. Both groups had baseline spirometry. Telephone randomisation was conducted, 1:1, stratified Medical Research Council (MRC) dyspnoea score and general practice. Participants could not be blinded; data extraction and statistical analyses were performed blinded to group assignment. The primary outcome was respiratory consultation rates. RESULTS: We randomised 551 participants (274 intervention, 277 control) from whom the primary outcome was determined for 542 (269 intervention, 273 control). There was a 40% relative increase in respiratory consultations in the intervention group: (adjusted rates (95% CI) intervention 0.57 (0.47 to 0.70), control 0.41 (0.32 to 0.52), relative rate 1.40 (1.08 to 1.82); p=0.0123). There were no significant differences in time to first respiratory consultation, total consultation rates or measures of psychological harm. The incremental cost-effectiveness ratio was $A1289 per additional respiratory consultation. CONCLUSIONS: A behavioural intervention can significantly increase consulting for respiratory symptoms in patients at increased risk of lung cancer. This intervention could have an important role in primary care as part of a broader approach to improve respiratory health in patients at higher risk. TRIAL REGISTRATION NUMBER: Australian New Zealand Clinical Trial Registry (1261300039 3752). This was registered pre-results.

The use, quality and effectiveness of pelvic examination in primary care for the detection of gynaecological cancer: a systematic review.

BACKGROUND: Urgent suspected cancer referral guidelines recommend that women with gynaecological cancer symptoms should have a pelvic examination (PE) prior to referral. We do not know to what extent GPs comply, their competency at PE, or if PE shortens the diagnostic interval. OBJECTIVES: We conducted a systematic review of the use, quality and effectiveness of PE in primary care for women with suspected gynaecological cancer. METHOD: PRISMA guidelines were followed. Three databases were searched using four terms: PE, primary care, competency and gynaecological cancer. Citation lists of all identified papers were screened independently for eligibility by two reviewers. Data extraction was performed in duplicate and independently. Paper quality was assessed using the relevant Critical Appraisal Skills Programme checklist. Emergent themes and contrasting issues were explored in a narrative ecological synthesis. MAIN FINDINGS: Twenty papers met the inclusion criteria. 52% or less of women with suspicious symptoms had a PE. No papers directly explored GPs' competence at performing PE. Pre-referral PE was associated with reduced diagnostic delay and earlier stage diagnosis. Ecological synthesis demonstrated a complex interplay between patient and practitioner factors and the environment in which examination is performed. Presenting symptoms are commonly misattributed by patients and practitioners resulting in misdiagnosis and lack of PE. CONCLUSION: We do not know if pre-referral PE leads to better outcomes for patients. PE is often not performed for women with gynaecological cancer symptoms, and evidence that it may result in earlier stage of diagnosis is weak. More research is needed.

Medications that relax the lower oesophageal sphincter and risk of oesophageal cancer: An analysis of two independent population-based databases.

Excessive lower oesophageal sphincter relaxation increases gastro-oesophageal acid reflux, an oesophageal adenocarcinoma risk factor. Medications that relax this sphincter (benzodiazepines, calcium channel blockers, nitrates, ß2 agonists and xanthines) could promote cancer. These medications were investigated in two independent datasets. In the Scottish Primary Care Clinical Informatics Unit (PCCIU) database, a nested case-control study of oesophageal cancer was performed using GP prescription records. Conditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CIs) for medication use and oesophageal cancer. In UK Biobank, a cohort study was conducted using self-reported medication use. Cox regression was used to calculate hazard ratios (HRs) and 95% CIs for medication use and oesophageal cancer, and by tumour subtype. Overall, 1,979 oesophageal cancer patients were matched to 9,543 controls in PCCIU, and 355 of 475,768 participants developed oesophageal cancer in UK Biobank. None of the medications investigated were significantly associated with oesophageal cancer risk apart from ß2 agonists, which were associated with increased oesophageal cancer risk in PCCIU (adjusted OR 1.38, 95% CI 1.12, 1.70) but not in UK Biobank (adjusted HR 1.21, 95% CI 0.70, 2.08). Medications that relax the lower oesophageal sphincter were not associated with oesophageal cancer, apart from ß2 agonists. This increased cancer risk in ß2 agonist users merits further investigation.