Pathways to MPN presentation and time-to-diagnosis: results from a cross-sectional study.

BACKGROUND: Early cancer recognition is key to improving patient outcomes. Diagnosis is often delayed in myeloproliferative neoplasm (MPN) patients, putting them at risk of thromboembolic events and other complications pre-diagnosis. A clear understanding of the barriers to presentation and diagnosis is required. AIMS: To explore barriers and factors influencing delayed presentation and diagnosis of MPNs. DESIGN & SETTING: A cross-sectional study of MPN patients within the United Kingdom and the Republic of Ireland. METHOD: An online cross-sectional survey of MPN patients. Symptoms and factors influencing patient and General Practitioner (GP) delay were examined. Adjusted odds ratios (aOR) were calculated to explore the relationship between these factors and patient/GP delay. RESULTS: Most (80.2%) of the 620 patients completing the survey reported symptomatic presentation. The most common symptoms associated with patient delay were pruritus (aOR 1.89, 95% CI 1.19-3.01), headaches (aOR 1.86, 95% CI 1.13-2.82) and concentration difficulties (aOR 1.75, 95% CI 1.12-2.76). Attributing symptoms to ageing (aOR 1.92, 95% CI 1.19-3.11) and not wanting to burden the GP (aOR 2.17, 95% CI 1.35-3.50) were significantly associated with patient delay. Those reporting >3 blood cancer warning signs were more likely to experience GP delay than those experiencing fewer (aOR 3.26, 95% CI 1.75-6.29), and lack of relational continuity of GP care was significantly associated with GP delay (aOR 3.41, 95% CI 1.65-7.28). CONCLUSION: Debunking misconceptions around ageing, encouraging timely communication with GPs and improving relational continuity of GP care could assist in reducing diagnostic delays, prevent potentially fatal disease complications and ultimately improve MPN patient outcomes.

Reproductive Pattern of Parous Women and the Risk of Cancer in Later Life.

We assessed the risk of any and site-specific cancers in a case-control study of parous women living in northeast Scotland in relation to: total number of pregnancies, cumulative time pregnant, age at first delivery and interpregnancy interval. We analysed 6430 women with cancer and 6430 age-matched controls. After adjustment for confounders, women with increasing number of pregnancies had similar odds of cancer diagnosis as women with only one pregnancy. The adjusted odds of cancer diagnosis were no higher in women with cumulative pregnancy time 50-150 weeks compared to those pregnant ≤ 50 weeks. Compared with women who had their first delivery at or before 20 years of age, the adjusted odds ratio (AOR) among those aged 21-25 years was 0.81, 95% CI 0.74, 0.88; 26-30 years AOR 0.77, 95% CI 0.69, 0.86; >30 years AOR 0.63, 95% CI 0.55, 0.73. After adjustment, the odds of having any cancer were higher in women who had an inter-pregnancy interval >3 years compared to those with no subsequent pregnancy (AOR 1.17, 95% CI 1.05, 1.30). Older age at first pregnancy was associated with increased risk of breast and gastrointestinal cancer, and reduced risk of invasive cervical, carcinoma in situ of the cervix and respiratory cancer.

Exploring the influence of rural residence on uptake of organized cancer screening - A systematic review of international literature.

Lower screening uptake could impact cancer survival in rural areas. This systematic review sought studies comparing rural/urban uptake of colorectal, cervical and breast cancer screening in high income countries. Relevant studies (n = 50) were identified systematically by searching Medline, EMBASE and CINAHL. Narrative synthesis found that screening uptake for all three cancers was generally lower in rural areas. In meta-analysis, colorectal cancer screening uptake (OR 0.66, 95 % CI = 0.50-0.87, I2 = 85 %) was significantly lower for rural dwellers than their urban counterparts. The meta-analysis found no relationship between uptake of breast cancer screening and rural versus urban residency (OR 0.93, 95 % CI = 0.80-1.09, I2 = 86 %). However, it is important to note the limitation of the significant statistical heterogeneity found which demonstrates the lack of consistency between the few studies eligible for inclusion in the meta-analyses. Cancer screening uptake is apparently lower for rural dwellers which may contribute to poorer survival. National screening programmes should consider geography in planning.

Is place or person more important in determining higher rural cancer mortality? A data-linkage study to compare individual versus area-based measures of deprivation.

Data from Northeast Scotland for 11,803 cancer patients (diagnosed 2007-13) were linked to UK Censuses to explore relationships between hospital travel-time, timely-treatment and one-year-mortality, adjusting for both area and individual-level socioeconomic status (SES). Adjusting for area-based SES, those living >60 minutes from hospital received timely-treatment more often than those living <15 minutes. Substituting individual-level SES changed little. Adjusting for area-based SES those living >60 minutes from hospital died within one year more often than those living <15 minutes. Again, substituting individual-level SES changed little. In Northeast Scotland distance to services, rather than individual SES, likely explains poorer rural cancer survival. BACKGROUND AND OBJECTIVE: The Northeast and Aberdeen Scottish Cancer and Residence (NASCAR) study found rural-dwellers are treated quicker but more likely to die within a year of a cancer diagnosis. A potential confounder of the relationship between geography and cancer mortality is socioeconomic status (SES). We linked the original NASCAR cohort to the UK Censuses of 2001 and 2011, at an individual level, to explore the relationship between travel time to key healthcare facilities, timely cancer treatment and one-year mortality adjusting for both area and individual-level markers of socioeconomic status. METHODS: A data linkage study of 11803 patients examined the association between travel times, timely treatment and one-year mortality with adjustment for area, and for individual-level, markers of socioeconomic status. RESULTS: Following adjustment for area-based SES measures those living more than 60 minutes from the cancer treatment centre were significantly more likely to be treated within 62 days of GP referral than those living within 15 minutes (Odds Ratio [OR]) 1.41; 95% (Confidence Interval [CI]) 1.23, 1.60]. Replacing area-based with individual-level SES measures from UK Censuses made little impact on the results [OR 1.39; 95% CI 1.22, 1.57].Following adjustment for area-based SES measures of socioeconomic status those living more than 60 minutes from the cancer treatment centre were significantly more likely to die within one year than those living closer by [OR 1.22; 95% CI 1.08, 1.38]. Again, replacing area-based with individual-level SES measures from UK Censuses made little impact on the result [OR 1.20; CI 1.06, 1.35]. CONCLUSIONS: Distribution of individual measures of socioeconomic status did not differ significantly between rural and urban cancer patients. The relationship between distance to service, timely treatment and one-year survival were the same adjusting for both area-based and individual SES. Overall, it seems that distance to services, rather than personal characteristics, influences poorer rural cancer survival.

Contemporary hormonal contraception and cervical cancer in women of reproductive age.

To determine cervical cancer risk associated with contemporary hormonal contraceptives, we conducted a cohort study of women aged 15 to 49 living in Denmark from 1995 to 2014, using routinely collected information about redeemed prescriptions, incident cancer and potential confounders. Poisson regression calculated adjusted cervical cancer risks among different contraceptive user groups by duration of use, time since last use, hormonal content and cancer histology. During >20 million person-years, 3643 incident cervical cancers occurred. Ever users of any hormonal contraceptives compared to never users had a relative risk (RR) of 1.19 (95% confidence interval [CI] 1.10-1.29). Increased risks were seen in current or recent users of any hormonal: RR 1.30 (95% CI 1.20-1.42) and combined: RR 1.40 (95% CI 1.28-1.53), but not progestin-only contraception: RR 0.91 (95% CI 0.78-1.07). Current or recent users of any hormonal contraception had an increased risk of both adenocarcinoma (RR 1.29, 95% CI 1.05-1.60) and squamous cancer (RR 1.31, 95% CI 1.19-1.44). The risk pattern among any hormonal and combined contraceptive users generally increased with longer duration of use and declined after stopping, possibly taking longer to disappear among prolonged users. Combined products containing different progestins had similar risks. Approximately one extra cervical cancer occurred for every 14 700 women using combined contraceptives for 1 year. Most women in our study were not vaccinated against human papillomavirus (HPV) infections. Our findings reinforce the urgent need for global interventions such as systematic screening, treatment of cervical intraepithelial neoplasia and HPV vaccination programmes to prevent cervical cancer, especially among users of combined contraceptives.

Contemporary hormonal contraception and risk of endometrial cancer in women younger than age 50: A retrospective cohort study of Danish women.

OBJECTIVE: To examine the association between contemporary hormonal contraceptives and endometrial cancer risk in women younger than age 50. STUDY DESIGN: Cohort study of women living in Denmark aged 15-49 years through 1995-2014. National registries provided information about hormonal contraception use, incident endometrial cancer and confounders. Ever, current or recent, and former users of any hormonal contraception were compared with non-users, using Poisson regression to calculate incidence rate ratios (RR) with 95% confidence intervals. Duration, time since last use, tumor-specific and product-specific analyses, and population prevented fraction, were calculated. RESULTS: During 21.1 million person-years, 549 incident endometrial cancers occurred, with ever users of any hormonal contraception having a reduced premenopausal endometrial cancer risk compared with non-users; RR 0.60 (95% Confidence Interval 0.49 to 0.73). A lower risk of endometrial cancer was seen in all current or recent users of any hormonal contraception; 0.65 (0.52 to 0.83) and combined contraceptives; 0.57 (0.43 to 0.75), but not progestin-only contraceptives; levonorgestrel intrauterine system, LNG-IUS; 0.97 (0.66 to 1.42); other progestin-only contraceptives; 0.61 (0.27 to 1.37). Increased RRs were found for current use of any hormonal, combined contraceptives or LNG-IUS of ≤one year, probably because of protopathic bias. Longer durations of use were associated with significant reductions that became stronger with longer use. Former users of any hormonal contraception continued to benefit from a reduced risk of endometrial cancer >10 years after stopping. There was little evidence of differences in risk reduction by the type of progestin in combined oral contraceptives. Current or recent use of any hormonal contraception was associated with an approximate halving of risk of the most common tumor type I carcinoma, and an increased risk of the rarer sarcoma. Overall the estimated absolute reduced risk of endometrial cancer in ever users of hormonal contraceptives was 1.4 per 100,000 person-years, or approximately one less endometrial cancer for every 71,400 women of reproductive age who used hormonal contraception for one year. Use of hormonal contraception was estimated to prevent 25% of endometrial cancers in this population. CONCLUSIONS: Currently available combined hormonal contraceptives are still associated with enduring protection against endometrial cancer, particularly for type I carcinomas. IMPLICATIONS: We report substantive evidence of the association between different types of contemporary hormonal contraception and endometrial cancer risk in a national cohort of young Danish women. Currently available combined hormonal contraceptives are still associated with enduring protection against endometrial cancer, particularly for type I carcinomas.

Clinical features in primary care electronic records before diagnosis of ankylosing spondylitis: a nested case-control study.

BACKGROUND: Ankylosing spondylitis (AS) often has a long period from first symptom presentation to diagnosis. We examined the occurrence of symptoms, prescriptions and diagnostic tests in primary care electronic records over time prior to a diagnosis of AS. METHODS: Nested case-control study using anonymised primary care electronic health records from Scotland. Cases were 74 adults with a first diagnosis of AS between 2000 and 2010. Controls were matched for age, sex and GP practice: (a) 296 randomly selected adults (b) 169 adults whose records contained codes indicating spinal conditions or symptoms. We extracted clinical features (symptoms, AS-related disorders, prescriptions and diagnostic tests). Conditional logistic regression was used to examine the association between clinical features (both individually and in combinations) and diagnosis of AS. We examined the associations between clinical features and diagnosis over time prior to diagnosis. RESULTS: Several new composite pointers were predictive of AS: including distinct episodes of axial pain separated by more than 6 months (OR 12.7, 95% CI 4.7 to 34.6); the occurrence of axial pain with and tendon symptoms within the same year (OR 21.7, 95% CI 2.6 to 181.5); and the co-occurrence (within 30 days) of axial pain and a prescription for nonsteroidal anti-inflammatory drug (OR 10.4, 95%CI 4.9 to 22.1). Coded episodes of axial pain increased steadily over the 3 years before diagnosis. In contrast, large joint symptoms and enthesopathy showed little or no time trend prior to diagnosis. CONCLUSIONS: We identified novel composite pointers to a diagnosis of AS in GP records. These may represent valuable targets for diagnostic support systems.

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.

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.

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.

Correction: Hormonal contraceptive use and risk of pancreatic cancer-A cohort study among premenopausal women.

[This corrects the article DOI: 10.1371/journal.pone.0206358.].

Hormonal contraceptive use and risk of pancreatic cancer-A cohort study among premenopausal women.

IMPORTANCE: The association between the use of hormonal contraceptive and pancreatic cancer among premenopausal women has until now been unclear. This is the first study to investigate the risk of pancreatic cancer in pre-menopausal women. OBJECTIVE: To determine whether hormonal contraception increases the risk of developing pancreatic cancer in pre-menopausal women. DESIGN: A nationwide prospective cohort study followed all women in Denmark in the age range of 15-49 years without previous cancer or venous thrombosis from 1995 to 2014. The Danish National Prescription Registry provided individually updated exposure information on use of hormonal contraception. The Danish Cancer Registry provided cancer diagnoses, and the Danish National Patient Register containing clinical diagnoses and surgical codes at discharge from public and private hospitals. SETTING: Population-based cohort study. PARTICIPANTS: All women living in Denmark aged 15-49 years at January 1st, 1995, and those subsequently reaching age 15 years up to December 31st, 2014 were eligible for the study. RESULTS: Among 1.9 million women who were followed on average for 11.4 years, 235 pancreatic cancers occurred. Compared to never users, ever users of any type of hormonal contraception had a relative risk (RR) of pancreatic cancer of 0.90 (95% confidence interval (CI) 0.68-1.19). No overall association between duration of hormonal contraceptive use and pancreatic cancer risk was found. Neither was long-term use of hormonal contraception associated with pancreas cancer, RR 0.83 (95% CI 0.47-1.50). The risk did not vary between users of combined and progestogen-only products. All models were adjusted for age, completed or ongoing education, polycystic ovary syndrome, endometriosis and among parous women; parity, age at first birth, smoking and body mass index. CONCLUSIONS AND RELEVANCE: Compared to never users the risk of pancreatic cancer is not significantly higher among current and recent users of contemporary hormonal contraception and does not vary between users of combined and progestogen-only products. In conclusion, our study suggests no risk of pancreatic cancer with use of any type of hormonal contraception.

Association between contemporary hormonal contraception and ovarian cancer in women of reproductive age in Denmark: prospective, nationwide cohort study.

OBJECTIVES: To investigate the association between contemporary combined hormonal contraceptives (including progestogen types in combined preparations and all progestogen-only products) and overall and specific types of ovarian cancer. DESIGN: Prospective, nationwide cohort study. SETTING: Denmark, 1995-2014. PARTICIPANTS: All women aged 15-49 years during 1995-2014 were eligible. Women were excluded if they immigrated after 1995, had cancer (except non-melanoma skin cancer), had venous thrombosis, or were treated for infertility before entry (final study population included 1 879 227 women). Women were categorised as never users (no record of being dispensed hormonal contraception), current or recent users (≤1 year after stopping use), or former users (>1 year after stopping use) of different hormonal contraceptives. MAIN OUTCOME MEASURES: Poisson regression was used to calculate relative risk of ovarian cancer among users of any contemporary combined hormonal contraceptives and by progestogen type in combined preparations and all progestogen-only products, including non-oral preparations. Separate analyses examined women followed up to their first contraception type switch and those with full contraceptive histories. Duration, time since last use, and tumour histology were examined and the population prevented fraction were calculated. RESULTS: During 21.4 million person years, 1249 incident ovarian cancers occurred. Among ever users of hormonal contraception, 478 ovarian cancers were recorded over 13 344 531 person years. Never users had 771 ovarian cancers during 8 150 250 person years. Compared with never users, reduced risks of ovarian cancer occurred with current or recent use and former use of any hormonal contraception (relative risk 0.58 (95% confidence interval 0.49 to 0.68) and 0.77 (0.66 to 0.91), respectively). Relative risks among current or recent users decreased with increasing duration (from 0.82 (0.59 to 1.12) with ≤1 year use to 0.26 (0.16 to 0.43) with >10 years' use; P<0.001 for trend). Similar results were achieved among women followed up to their first switch in contraceptive type. Little evidence of major differences in risk estimates by tumour type or progestogen content of combined oral contraceptives was seen. Use of progestogen-only products were not associated with ovarian cancer risk. Among ever users of hormonal contraception, the reduction in the age standardised absolute rate of ovarian cancer was 3.2 per 100 000 person years. Based on the relative risk for the never use versus ever use categories of hormonal contraception (0.66), the population prevented fraction was estimated to be 21%-that is, use of hormonal contraception prevented 21% of ovarian cancers in the study population. CONCLUSIONS: Use of contemporary combined hormonal contraceptives is associated with a reduction in ovarian cancer risk in women of reproductive age-an effect related to duration of use, which diminishes after stopping use. These data suggest no protective effect from progestogen-only products.

Impact of rurality on processes and outcomes in melanoma care: results from a whole-Scotland melanoma cohort in primary and secondary care.

BACKGROUND: Those living in rural areas have poorer cancer outcomes, but current evidence on how rurality impacts melanoma care and survival is contradictory. AIM: To investigate the impact of rurality on setting of melanoma excision and mortality in a whole-nation cohort. DESIGN AND SETTING: Analysis of linked routine healthcare data comprising every individual in Scotland diagnosed with melanoma, January 2005-December 2013, in primary and secondary care. METHOD: Multivariate binary logistic regression was used to explore the relationship between rurality and setting of melanoma excision; Cox proportional hazards regression between rurality and mortality was used, with adjustments for key confounders. RESULTS: In total 9519 patients were included (54.3% [n = 5167] female, mean age 60.2 years [SD 17.5]). Of melanomas where setting of excision was known, 90.3% (n = 8598) were in secondary care and 8.1% (n = 771) in primary care. Odds of primary care excision increased with increasing rurality/remoteness. Compared with those in urban areas, those in the most remote rural locations had almost twice the odds of melanoma excision in primary care (adjusted odds ratio [aOR] 1.92; 95% confidence interval [CI] = 1.33 to 2.77). No significant association was found between urban or rural residency and all-cause mortality. Melanoma-specific mortality was significantly lower in individuals residing in accessible small towns than in large urban areas (adjusted hazards ratio [HR] 0.53; 95% CI = 0.33 to 0.87) with no trend towards poorer survival with increasing rurality. CONCLUSION: Patients in Scottish rural locations were more likely to have a melanoma excised in primary care. However, those in rural areas did not have significantly increased mortality from melanoma. Together these findings suggest that current UK melanoma management guidelines could be revised to be more realistic by recognising the role of primary care in the prompt diagnosis and treatment of those in rural locations.

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.

Contemporary Hormonal Contraception and the Risk of Breast Cancer.

BACKGROUND: Little is known about whether contemporary hormonal contraception is associated with an increased risk of breast cancer. METHODS: We assessed associations between the use of hormonal contraception and the risk of invasive breast cancer in a nationwide prospective cohort study involving all women in Denmark between 15 and 49 years of age who had not had cancer or venous thromboembolism and who had not received treatment for infertility. Nationwide registries provided individually updated information about the use of hormonal contraception, breast-cancer diagnoses, and potential confounders. RESULTS: Among 1.8 million women who were followed on average for 10.9 years (a total of 19.6 million person-years), 11,517 cases of breast cancer occurred. As compared with women who had never used hormonal contraception, the relative risk of breast cancer among all current and recent users of hormonal contraception was 1.20 (95% confidence interval [CI], 1.14 to 1.26). This risk increased from 1.09 (95% CI, 0.96 to 1.23) with less than 1 year of use to 1.38 (95% CI, 1.26 to 1.51) with more than 10 years of use (P=0.002). After discontinuation of hormonal contraception, the risk of breast cancer was still higher among the women who had used hormonal contraceptives for 5 years or more than among women who had not used hormonal contraceptives. Risk estimates associated with current or recent use of various oral combination (estrogen-progestin) contraceptives varied between 1.0 and 1.6. Women who currently or recently used the progestin-only intrauterine system also had a higher risk of breast cancer than women who had never used hormonal contraceptives (relative risk, 1.21; 95% CI, 1.11 to 1.33). The overall absolute increase in breast cancers diagnosed among current and recent users of any hormonal contraceptive was 13 (95% CI, 10 to 16) per 100,000 person-years, or approximately 1 extra breast cancer for every 7690 women using hormonal contraception for 1 year. CONCLUSIONS: The risk of breast cancer was higher among women who currently or recently used contemporary hormonal contraceptives than among women who had never used hormonal contraceptives, and this risk increased with longer durations of use; however, absolute increases in risk were small. (Funded by the Novo Nordisk Foundation.).

Is initial excision of cutaneous melanoma by General Practitioners (GPs) dangerous? Comparing patient outcomes following excision of melanoma by GPs or in hospital using national datasets and meta-analysis.

BACKGROUND: Melanomas are initially excised in primary care, and rates vary internationally. Until now, there has been no strong evidence one way or the other that excising melanomas in primary care is safe or unsafe. European guidelines make no recommendations, and the United Kingdom (UK) melanoma guidelines require all suspicious skin lesions to be initially treated in secondary care based on an expert consensus, which lacks supporting evidence, that primary care excision represents substandard care. Despite this, studies have found that up to 20% of melanomas in the UK are excised by general practitioners (GPs). Patients receiving primary care melanoma excision may fear that their care is substandard and their long-term survival threatened, neither of which may be justified. METHODS: Scottish cancer registry data from 9367 people diagnosed with melanoma in Scotland between 2005 and 2013 were linked to pathology records, hospital data and death records. A Cox proportional hazards regression analysis, adjusting for key confounders, explored the association between morbidity and mortality and setting of primary melanoma excision (primary versus secondary care). A pooled estimate of the relative hazard of death of having a melanoma excised in primary versus secondary care including 7116 patients from a similar Irish study was also performed. RESULTS: The adjusted hazard ratio (95% CI) of death from melanoma for those having primary care excision was 0.82 (0.61-1.10). Those receiving primary care excision had a median (IQR) of 8 (3-14) out-patient attendances compared to 10 (4-17) for the secondary care group with an adjusted relative risk (RR) (95% CI) of 0.98 (0.96-1.01). Both groups had a median of 1 (0-2) hospital admissions with an adjusted rate ratio of 1.05 (0.98-1.13). In the meta-analysis, with primary care as the reference, the pooled adjusted hazard ratio (HR, 95% CI) was 1.26 (1.07-1.50) indicating a significantly higher all-cause mortality among those with excision in secondary care. CONCLUSIONS: The results of the Scottish and pooled analyses suggest that those receiving an initial excision for melanoma in primary care do not have poorer survival or increased morbidity compared to those being initially treated in secondary care. A randomised controlled trial to inform a greater role for GPs in the initial excision of melanoma is justified in the light of these results.

Pointers to earlier diagnosis of endometriosis: a nested case-control study using primary care electronic health records.

BACKGROUND: Endometriosis is a condition with relatively non-specific symptoms, and in some cases a long time elapses from first-symptom presentation to diagnosis. AIM: To develop and test new composite pointers to a diagnosis of endometriosis in primary care electronic records. DESIGN AND SETTING: This is a nested case-control study of 366 cases using the Practice Team Information database of anonymised primary care electronic health records from Scotland. Data were analysed from 366 cases of endometriosis between 1994 and 2010, and two sets of age and GP practice matched controls: (a) 1453 randomly selected females and (b) 610 females whose records contained codes indicating consultation for gynaecological symptoms. METHOD: Composite pointers comprised patterns of symptoms, prescribing, or investigations, in combination or over time. Conditional logistic regression was used to examine the presence of both new and established pointers during the 3 years before diagnosis of endometriosis and to identify time of appearance. RESULTS: A number of composite pointers that were strongly predictive of endometriosis were observed. These included pain and menstrual symptoms occurring within the same year (odds ratio [OR] 6.5, 95% confidence interval [CI] = 3.9 to 10.6), and lower gastrointestinal symptoms occurring within 90 days of gynaecological pain (OR 6.1, 95% CI = 3.6 to 10.6). Although the association of infertility with endometriosis was only detectable in the year before diagnosis, several pain-related features were associated with endometriosis several years earlier. CONCLUSION: Useful composite pointers to a diagnosis of endometriosis in GP records were identified. Some of these were present several years before the diagnosis and may be valuable targets for diagnostic support systems.