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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. [ABSTRACT FROM AUTHOR]

Background older people living in care-homes are particularly vulnerable to adverse effects of psychotropic and anticholinergic drugs. Methods anonymised dispensed prescription data from all 4,478 residents aged ≥ 60 years in 147 care-homes in two Scottish health boards were analysed. Psychotropic medicines examined were antipsychotics, antidepressants, hypnotic/anxiolytics, opioids and gabapentinoids. Anticholinergic burden was measured using the modified anticholinergic risk scale (mARS). Variation between care-homes and associations with individual and care-home characteristics were examined using multilevel logistic regression. Results 63.5% of residents were prescribed at least one psychotropic drug, and 27.0% two or more, most commonly antidepressants (41.6%), opioids (20.3%), hypnotic/anxiolytics (16.9%) and antipsychotics (16.7%). 48.1% were prescribed an anticholinergic drug, and 12.1% had high anticholinergic burden (mARS ≥ 3). Variation between care-homes was high for antipsychotics (intra-cluster correlation coefficient [ICC] 8.2%) and hypnotics/anxiolytics (ICC = 7.3%), and moderate for antidepressants (ICC = 4.7%) and anticholinergics (ICC = 2.8%). Prescribing of all drugs was lower in the oldest old. People with dementia were more likely to be prescribed antipsychotics (adjusted OR = 1.45, 95%CI 1.23–1.71) but less likely to be prescribed anticholinergics (aOR = 0.61, 95%CI 0.51–0.74). Prescribing of antipsychotics was higher in Tayside (aOR = 1.52, 95%CI 1.20–1.92), whereas prescribing of antidepressants (particularly tricyclic-related) was lower (aOR = 0.66, 95%CI 0.56–0.79). There was no association with care-home regulator quality scores. Conclusion care-home residents have high psychotropic and anticholinergic burden, with considerable variation between care-homes that is not related to existing measures of quality of care. Research to better understand variation between care-homes and the interaction with local prescribing cultures is needed. [ABSTRACT FROM AUTHOR]

Background: Preclinical evidence suggests that statins could delay cancer progression. Previous epidemiological findings have been inconsistent and some have been limited by small sample sizes, as well as certain time-related biases. This study aimed to investigate whether breast cancer patients who were exposed to statins had reduced breast cancer-specific mortality.Methods: We conducted a retrospective cohort study of 15,140 newly diagnosed invasive breast cancer patients diagnosed from 2009 to 2012 within the Scottish Cancer Registry. Dispensed medication usage was obtained from linkages to the Scottish Prescribing Information System and breast cancer-specific deaths were identified from National Records of Scotland Death Records. Using time-dependent Cox regression models, hazard ratios (HR) and 95 % confidence intervals (CI) were calculated for the association between post-diagnostic exposure to statins (including simvastatin) and breast cancer-specific mortality. Adjustments were made for a range of potential confounders including age at diagnosis, year of diagnosis, cancer stage, grade, cancer treatments received, comorbidities, socioeconomic status and use of aspirin.Results: A total of 1,190 breast cancer-specific deaths occurred up to January 2015. Overall, after adjustment for potential confounders, there was no evidence of an association between statin use and breast cancer-specific death (adjusted HR 0.93, 95 % CI 0.77, 1.12). No significant associations were observed in dose-response analyses or in analysis of all-cause mortality. For simvastatin use specifically, a weak non-significant reduction in breast cancer-specific mortality was observed compared to non-users (adjusted HR 0.89, 95 % CI 0.73, 1.08). Statin use before diagnosis was weakly associated with a reduction in breast cancer-specific mortality (adjusted HR 0.85, 95 % CI 0.74, 0.98).Conclusion: Overall, we found little evidence of a protective association between post-diagnostic statin use and cancer-specific mortality in a large nation-wide cohort of breast cancer patients. These findings will help inform the decision whether to conduct randomised controlled trials of statins as an adjuvant treatment in breast cancer. [ABSTRACT FROM AUTHOR]

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., (© 2024. The Author(s).)

Objective: To estimate the effectiveness, cost effectiveness (to be reported elsewhere), and safety of pharmacy independent prescribers in care homes., Design: Cluster randomised controlled trial, with clusters based on triads of a pharmacist independent prescriber, a general practice, and one to three associated care homes., Setting: Care homes across England, Scotland, and Northern Ireland, their associated general practices, and pharmacy independent prescribers, formed into triads., Participants: 49 triads and 882 residents were randomised. Participants were care home residents, aged ≥65 years, taking at least one prescribed drug, recruited to 20 residents/triad., Intervention: Each pharmacy independent prescriber provided pharmaceutical care to approximately 20 residents across one to three care homes, with weekly visits over six months. Pharmacy independent prescribers developed a pharmaceutical care plan for each resident, did medicines reviews/reconciliation, trained staff, and supported with medicines related procedures, deprescribing, and authorisation of prescriptions. Participants in the control group received usual care., Main Outcomes Measures: The primary outcome was fall rate/person at six months analysed by intention to treat, adjusted for prognostic variables. Secondary outcomes included quality of life (EQ-5D by proxy), Barthel score, Drug Burden Index, hospital admissions, and mortality. Assuming a 21% reduction in falls, 880 residents were needed, allowing for 20% attrition., Results: The average age of participants at study entry was 85 years; 70% were female. 697 falls (1.55 per resident) were recorded in the intervention group and 538 falls (1.26 per resident) in the control group at six months. The fall rate risk ratio for the intervention group compared with the control group was not significant (0.91, 95% confidence interval 0.66 to 1.26) after adjustment for all model covariates. Secondary outcomes were not significantly different between groups, with exception of the Drug Burden Index, which significantly favoured the intervention. A third (185/566; 32.7%) of pharmacy independent prescriber interventions involved medicines associated with falls. No adverse events or safety concerns were identified., Conclusions: Change in the primary outcome of falls was not significant. Limiting follow-up to six months combined with a small proportion of interventions predicted to affect falls may explain this. A significant reduction in the Drug Burden Index was realised and would be predicted to yield future clinical benefits for patients. This large trial of an intensive weekly pharmacist intervention with care home residents was also found to be safe and well received., Trial Registration: ISRCTN 17847169., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at https://www.icmje.org/disclosure-of-interest/ and declare: support from the NIHR for the submitted work; DW has received speaker fees from Desitin Pharma and speaker fees and unrestricted education grants from Rosemont Pharmaceuticals; CB has received personal fees as editor in chief of the International Journal of Pharmacy Practice, during the conduct of the study; CH was a commissioned member of the NIHR HS&DR Panel (2015-19); GB was a member of a CTU funded by NIHR (to 2021); LS was a member of the NIHR EME Funding Committee (2010-14); AA was a commissioned member of the NIHR HS&DR Board (2014-16); AZ was a member of the NIHR HTA MPOH Pharmaceuticals Panel (2011-18); no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY. No commercial re-use. See rights and permissions. Published by BMJ.)

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., (Copyright © 2021 by The American College of Gastroenterology.)

Purpose: Preclinical studies show statins inhibit pathways involved in gastric cancer progression, with observational studies demonstrating reduced gastric cancer risk in statin users. However, few studies have investigated statin use and survival in gastric cancer. We investigated statin use and survival in two large population-based gastric cancer cohorts., Methods: Patients diagnosed with gastric cancer from 1998 to 2012 were identified from English and Scottish cancer registries. Statin prescriptions were identified from linkages to the UK Clinical Practice Research Datalink in England and the Prescribing Information System in Scotland, and deaths identified from national mortality records. Time-dependent Cox regression models were used to calculate hazard ratios (HR) and 95% confidence intervals (CIs) for cancer-specific mortality by statin use in multivariate analysis. Meta-analysis techniques pooled results across the cohorts., Results: The combined cohorts contained 3833 patients with gastric cancer and 2392 cancer-specific deaths. Statin use after diagnosis was associated with reduced cancer-specific mortality (adjusted HR 0.83; 95% CI, 0.74-0.92). HRs for less than 1 year and over 1 year of statin use were similar (adjusted HR 0.83; 95% CI, 0.73-0.94 and adjusted HR 0.83; 95% CI, 0.64-1.01, respectively). Statin use prior to diagnosis was also associated with reduced cancer-specific mortality (adjusted HR 0.91; 95% CI, 0.84-0.98)., Conclusions: In two independent UK cohorts, there was some evidence that statin use was associated with reduced cancer-specific mortality. However, these associations were weak in magnitude and did not follow a clear dose response, and we cannot rule out confounding by stage., (© 2018 John Wiley & Sons, Ltd.)