Purpose: Preclinical studies have demonstrated that antagonism of β₂-adrenergic signaling inhibits several pathways necessary for breast tumor progression and metastasis. A series of population-based observational studies were conducted to examine associations between beta blocker use and breast tumor characteristics at diagnosis or breast cancer–specific mortality. Patients and Methods: Linked national cancer registry and prescription dispensing data were used to identify women with a diagnosis of stage I to IV invasive breast cancer between January 1, 2001, and December 31, 2006. Women taking propranolol (β₁/β₂ antagonist; n = 70) or atenolol (β₁ antagonist; n = 525), in the year before breast cancer diagnosis were matched (1:2) to women not taking a beta blocker (n = 4,738). Associations between use of propranolol or atenolol and risk of local tumor invasion at diagnosis (T4 tumor), nodal or metastatic involvement at diagnosis (N2/N3/M1 tumor), and time to breast cancer–specific mortality were assessed. Results: Propranolol users were significantly less likely to present with a T4 (odds ratio [OR], 0.24, 95% CI, 0.07 to 0.85) or N2/N3/M1 (OR, 0.20; 95% CI, 0.04 to 0.88) tumor compared with matched nonusers. The cumulative probability of breast cancer–specific mortality was significantly lower for propranolol users compared with matched nonusers (hazard ratio, 0.19; 95% CI, 0.06 to 0.60). There was no difference in T4 or N2/N3/M1 tumor incidence or breast cancer–specific mortality between atenolol users and matched nonusers. Conclusion: The results provide evidence in humans to support preclinical observations suggesting that inhibiting the β₂-adrenergic signaling pathway can reduce breast cancer progression and mortality.

Objectives To estimate the association between the duration and level of exposure to different classes of anticholinergic drugs and subsequent incident dementia. Design Case-control study. Setting General practices in the UK contributing to the Clinical Practice Research Datalink. Participants 40 770 patients aged 65-99 with a diagnosis of dementia between April 2006 and July 2015, and 283 933 controls without dementia. Interventions Daily defined doses of anticholinergic drugs coded using the Anticholinergic Cognitive Burden (ACB) scale, in total and grouped by subclass, prescribed 4-20 years before a diagnosis of dementia. Main outcome measures Odds ratios for incident dementia, adjusted for a range of demographic and health related covariates. Results 14 453 (35%) cases and 86 403 (30%) controls were prescribed at least one anticholinergic drug with an ACB score of 3 (definite anticholinergic activity) during the exposure period. The adjusted odds ratio for any anticholinergic drug with an ACB score of 3 was 1.11 (95% confidence interval 1.08 to 1.14). Dementia was associated with an increasing average ACB score. When considered by drug class, gastrointestinal drugs with an ACB score of 3 were not distinctively linked to dementia. The risk of dementia increased with greater exposure for antidepressant, urological, and antiparkinson drugs with an ACB score of 3. This result was also observed for exposure 15-20 years before a diagnosis. Conclusions A robust association between some classes of anticholinergic drugs and future dementia incidence was observed. This could be caused by a class specific effect, or by drugs being used for very early symptoms of dementia. Future research should examine anticholinergic drug classes as opposed to anticholinergic effects intrinsically or summing scales for anticholinergic exposure. Trial registration Registered to the European Union electronic Register of Post-Authorisation Studies EUPAS8705.

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Potentially inappropriate prescribing (PIP) refers to medications that should generally be avoided in older populations and doses or frequencies of administrations that should not be exceeded. Studies of PIP have been primarily based on US indicators of appropriateness such as the Beers criteria due to the lack of European specific indicators.• PIP has not been assessed in full national samples.• The total cost of PIP drugs and the cost in relation to overall national pharmaceutical expenditure have not been described. WHAT THIS STUDY ADDS • One third of the Irish population aged ≥70 years were prescribed at least one potentially inappropriate medication in 2007 based on European criteria.• There was a signficant association between polypharmacy and the risk of PIP. Polypharmacy was evaluated as the number of different repeat drug classes (≥ three prescription claims) per claimant.• The most prevalent PIP drugs were: proton pump inhibitors at maximum therapeutic dosage for >8 weeks (40 mg daily omeprazole, pantoprazole and esomeprazole, 30 mg daily lansoprazole and 20 mg daily rabeprazole); non‐steroidal anti‐inflammatories for >3 months; long‐acting benzodiazepines for >1 month and drug duplication within the same therapeutic class.• The total expenditure on potentially inappropriate drugs was €45 631 319 in 2007 which is 9% of the overall expenditure on pharmaceuticals in those aged ≥70 years in Ireland.AIMS Optimization of drug prescribing in older populations is a priority due to the significant clinical and economic costs of drug‐related illness. This study aimed to: (i) estimate the prevalence of potentially inappropriate prescribing (PIP) in a national Irish older population using European specific explicit prescribing criteria; (ii) investigate the association between PIP, number of drug classes, gender and age and; (iii) establish the total cost of PIP.METHODS This was a retrospective national population study (n= 338 801) using the Health Service Executive Primary Care Reimbursement Service (HSE‐PCRS) pharmacy claims database. The HSE‐PCRS uses the WHO Anatomical Therapeutic Chemical (ATC) classification system and details of every drug dispensed and claimants' demographic data are available. Thirty PIP indicators (STOPP) were applied to prescription claims for those ≥70 years in Ireland in 2007. STOPP is a physiological system based screening tool of older persons' potentially inappropriate prescriptions assessing drug–drug and drug–disease interactions, dose and duration.RESULTS In our study population PIP prevalence was 36% (121 454 claimants). The main contributors to this were: 56 560 (17%) prescribed proton pump inhibitors at maximum therapeutic dose for >8 weeks, 29 691 (9%) prescribed non‐steroidal anti‐inflammatories for >3 months, 17 676 (5%) prescribed long‐acting benzodiazepines for >1 month and 16 201 (5%) prescribed duplicate drugs. The main determinant of PIP was polypharmacy. The likelihood of PIP increased with a significant linear and quadratic trend (P < 0.0001) with the number of drug classes.The maximum net ingredient cost of PIP was estimated to be €38 664 640. Total PIP expenditure was estimated to be €45 631 319, 9% of the overall expenditure on pharmaceuticals in those ≥70 years in 2007.CONCLUSIONS The findings identify a high prevalence of PIP in Ireland with significant cost consequences.

Increasing attention is being paid to interventions for cognitive impairment (CI) post-stroke, including for CI that does not meet dementia criteria. The aim of this paper was to conduct a systematic review and meta-analysis of the prevalence of cognitive impairment no dementia (CIND) within one year post-stroke. Pubmed, EMBASE and PsychInfo were searched for papers published in English in 1995–2017. Included studies were population or hospital-based cohort studies for first-ever/recurrent stroke, assessing CIND using standardised criteria at 1–12 months post-stroke. Abstracts were screened, followed by full text review of potentially relevant articles. Data were extracted using a standard form, and study quality was appraised using the Crowe Critical Appraisal Tool. A pooled prevalence of CIND with 95% confidence intervals (CI) was estimated using random-effects meta-analysis. Heterogeneity was measured using the I² statistic. A total of 7000 abstracts were screened, followed by 1028 full text articles. Twenty-three articles were included in the systematic review, and 21 in the meta-analysis. The pooled CIND prevalence was 38% [95% CI = 32–43%] (I²=92.5%, p < 0.01). Study quality emerged as one source of heterogeneity. The five studies with the highest quality scores had no heterogeneity (I²=0%, p = 0.99), with a similar pooled prevalence (39%, 95%CI = 35–42%). Other sources of heterogeneity were stroke type, inclusion of pre-stroke CI, and age at assessment time. Discussion and conclusion: Meta-analysis of available studies indicates that in the first year post-stroke, 4 in 10 patients display a level of cognitive impairment that does not meet the criteria for dementia.

Aims: The aim of this systematic review and meta‐analysis was to synthesise the evidence relating to medication non‐adherence and its association with health outcomes in people aged ≥50 years.Methods: Seven databases were searched up to February 2019 for observational studies that measured medication (non‐)adherence as a predictor of the following health outcomes in adults aged ≥50 years: healthcare utilisation (hospitalisation, emergency department visits, outpatient visits and general practitioner visits), mortality, adverse clinical events and quality of life. Screening and quality assessment using validated criteria were completed by 2 reviewers independently. Random effects models were used to generate pooled estimates of association using adjusted study results. The full methodological approach was published on PROSPERO (ID: CRD42017077264).Results: Sixty‐six studies were identified for qualitative synthesis, with 11 of these studies eligible for meta‐analyses. A meta‐analysis including 3 studies measuring medication non‐adherence in adults aged ≥55 years showed a significant association with all‐cause hospitalisation (adjusted odds ratio 1.17, 95% confidence interval [CI] 1.12, 1.21). A meta‐analysis including 2 studies showed that medication non‐adherence was not significantly associated with an emergency department visit (adjusted odds ratio 1.05, 95% CI 0.90, 1.22). Good adherence was associated with a 21% reduction in long‐term mortality risk in comparison to medication non‐adherence (adjusted hazard ratio 0.79, 95% CI 0.63, 0.98).Conclusion: Medication non‐adherence may be significantly associated with all‐cause hospitalisation and mortality in older people. Medication adherence should be monitored and addressed in this cohort to minimise hospitalisation, improve clinical outcomes and reduce healthcare costs.

BACKGROUND.: Five years of treatment provides the optimum duration of tamoxifen therapy for the prevention of breast cancer recurrence and mortality. Durations of adjuvant tamoxifen therapy less than 5 years are associated with poorer outcomes for breast cancer patients. The purpose of the study was to assess rates of tamoxifen nonpersistence (early discontinuation) in women aged 35 years or older using prescription refill data from a national prescribing database.METHODS.: A cohort of 2816 women commencing tamoxifen as initial hormonal therapy was identified between January 2001 and January 2004. The cumulative tamoxifen persistence rate was calculated for these women and the relation between nonpersistence and clinical and demographic variables assessed.RESULTS.: Within 1 year of commencing treatment the cumulative tamoxifen nonpersistence rate was 22.1%. This is twice the rate of treatment discontinuation observed in other studies by this time. By the end of follow‐up at 3.5 years, the cumulative nonpersistence rate had increased to 35.2%. Determinants of nonpersistence identified included age and a history of antidepressant use.CONCLUSIONS.: The rate of nonpersistence with tamoxifen therapy is higher than previously reported. This study demonstrates that persistence with tamoxifen cannot be assumed and raises concerns about persistence with other oral hormonal therapies for breast cancer and oral antineoplastics in general. Oncologists need to identify those at risk of nonpersistence and develop strategies to combat this barrier to treatment success. Cancer 2007. © 2007 American Cancer Society.