Oral prednisolone and warfarin and risk of oesophageal cancer: A case-control study.

BACKGROUND: A recent epidemiological study systematically screened 250 prescription medications for associations with oesophageal cancer risk, using Scottish data, and identified an increased risk with use of prednisolone and warfarin. We investigated whether oral prednisolone or warfarin use was associated with increased oesophageal cancer risk. METHODS: A case-control study was conducted within the Clinical Practice Research Datalink. In the primary analysis oesophageal cancer cases were identified from linked cancer registry records. Up to 5 cancer-free controls were matched to each case (based upon sex, birth year, GP practice and year of GP registration). Prednisolone and warfarin medications were identified from prescribing records. Odds ratios (OR) and 95% confidence intervals (CI) were calculated using conditional logistic regression after adjusting for covariates including demographics, comorbidities and medication use. RESULTS: There were 4552 oesophageal cancer cases and 22,601 matched control participants. Overall, there was no evidence of an increased risk of oesophageal cancer with oral prednisolone use (unadjusted OR=1.16 95% CI 1.06, 1.27 and adjusted OR=0.99 95% CI 0.89, 1.11) or warfarin use (unadjusted OR=1.12 95% CI 0.99, 1.28 and adjusted OR=1.08 95% CI 0.92, 1.27). CONCLUSIONS: In this large population-based study, oral prednisolone and warfarin were not associated with oesophageal cancer risk.

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.

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.

Prescriber Variation in Relation to Prescribing Trends within the Preferred Drugs Initiative in Ireland (2012-2015): An Interrupted Time-Series Study Using Latent Curve Models.

OBJECTIVES: To examine the impact of the Preferred Drugs Initiative (PDI), an Irish health policy aimed at reducing prescribing variation. DESIGN: Interrupted time series spanning 2012 to 2015. SETTING: Health Service Executive pharmacy claims data for General Medical Services (GMS) patients, approximately 40% of the Irish population. PARTICIPANTS: Prescribers issuing preferred drug group items to GMS adults before and after PDI guidelines. PRIMARY OUTCOME: The percentage coverage of PDI medications within each drug class per calendar quarter per prescriber. METHODS: Latent curve models with structured residuals (LCM-SRs) were used to model coverage of the preferred drugs over time. The number of GMS adults receiving medication and the percentage who were 65 years and older at the start of the study were included as covariates. RESULTS: In the quarter following PDI guidelines, coverage of the preferred drugs increased most in absolute terms for proton pump inhibitors (PPIs) (1.50% [SE 0.15], P < 0.001) and selective and norepinephrine reuptake inhibitors (SNRIs) (1.17% [SE 0.26], P < 0.001). Variation between prescribers remained relatively unchanged and increased for urology medications. Prescribers who increased coverage of the preferred PPI also increased coverage of the preferred statin immediately following guidelines (correlation 0.47 [SE 0.13], P < 0.001). Where guidelines were disseminated simultaneously, coverage of one preferred drug did not significantly predict coverage of the other preferred drug in the next calendar quarter. Prescribing of preferred drugs was not moderated by prescriber-level factors. CONCLUSIONS: Modest changes in prescribing of the preferred drugs have been observed over the course of the PDI. However, the guidelines have had little impact in reducing variation between prescribers. Further strategies may be necessary to reduce variation in clinical practice and enhance patient care.

Quantifying patient preferences for symptomatic breast clinic referral: a decision analysis study.

OBJECTIVES: Decision analysis study that incorporates patient preferences and probability estimates to investigate the impact of women's preferences for referral or an alternative strategy of watchful waiting if faced with symptoms that could be due to breast cancer. SETTING: Community-based study. PARTICIPANTS: Asymptomatic women aged 30-60 years. INTERVENTIONS: Participants were presented with 11 health scenarios that represent the possible consequences of symptomatic breast problems. Participants were asked the risk of death that they were willing to take in order to avoid the health scenario using the standard gamble utility method. This process was repeated for all 11 health scenarios. Formal decision analysis for the preferred individual decision was then estimated for each participant. PRIMARY OUTCOME MEASURE: The preferred diagnostic strategy was either watchful waiting or referral to a breast clinic. Sensitivity analysis was used to examine how each varied according to changes in the probabilities of the health scenarios. RESULTS: A total of 35 participants completed the interviews, with a median age 41 years (IQR 35-47 years). The majority of the study sample was employed (n=32, 91.4%), with a third-level (university) education (n=32, 91.4%) and with knowledge of someone with breast cancer (n=30, 85.7%). When individual preferences were accounted for, 25 (71.4%) patients preferred watchful waiting to referral for triple assessment as their preferred initial diagnostic strategy. Sensitivity analysis shows that referral for triple assessment becomes the dominant strategy at the upper probability estimate (18%) of breast cancer in the community. CONCLUSIONS: Watchful waiting is an acceptable strategy for most women who present to their general practitioner (GP) with breast symptoms. These findings suggest that current referral guidelines should take more explicit account of women's preferences in relation to their GPs initial management strategy.