Marie C. Bradley

Interventions to improve the appropriate use of polypharmacy in older people: a Cochrane systematic review

Objective To summarise the findings of an updated Cochrane review of interventions aimed at improving the appropriate use of polypharmacy in older people. Design Cochrane systematic review. Multiple electronic databases were searched including MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials (from inception to November 2013). Hand searching of references was also performed. Randomised controlled trials (RCTs), controlled clinical trials, controlled before-and-after studies and interrupted time series analyses reporting on interventions targeting appropriate polypharmacy in older people in any healthcare setting were included if they used a validated measure of prescribing appropriateness. Evidence quality was assessed using the Cochrane risk of bias tool and GRADE (Grades of Recommendation, Assessment, Development and Evaluation). Setting All healthcare settings. Participants Older people (≥65 years) with ≥1 long-term condition who were receiving polypharmacy (≥4 regular medicines). Primary and secondary outcome measures Primary outcomes were the change in prevalence of appropriate polypharmacy and hospital admissions. Medication-related problems (eg, adverse drug reactions), medication adherence and quality of life were included as secondary outcomes. Results 12 studies were included: 8 RCTs, 2 cluster RCTs and 2 controlled before-and-after studies. 1 study involved computerised decision support and 11 comprised pharmaceutical care approaches across various settings. Appropriateness was measured using validated tools, including the Medication Appropriateness Index, Beers’ criteria and Screening Tool of Older Persons Prescriptions (STOPP)/ Screening Tool to Alert doctors to Right Treatment (START). The interventions demonstrated a reduction in inappropriate prescribing. Evidence of effect on hospital admissions and medication-related problems was conflicting. No differences in health-related quality of life were reported. Conclusions The included interventions demonstrated improvements in appropriate polypharmacy based on reductions in inappropriate prescribing. However, it remains unclear if interventions resulted in clinically significant improvements (eg, in terms of hospital admissions). Future intervention studies would benefit from available guidance on intervention development, evaluation and reporting to facilitate replication in clinical practice.

Potentially inappropriate prescribing among older people in the United Kingdom

BackgroundPotentially inappropriate prescribing (PIP) in older people is associated with increases in morbidity, hospitalisation and mortality. The objective of this study was to estimate the prevalence of and factors associated with PIP, among those aged ≥70 years, in the United Kingdom, using a comprehensive set of prescribing indicators and comparing these to estimates obtained from a truncated set of the same indicators.MethodsA retrospective cross-sectional study was carried out in the UK Clinical Practice Research Datalink (CPRD), in 2007. Participants included those aged ≥ 70 years, in CPRD. Fifty-two PIP indicators from the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria were applied to data on prescribed drugs and clinical diagnoses. Overall prevalence of PIP and prevalence according to individual STOPP criteria were estimated. The relationship between PIP and polypharmacy (≥4 medications), comorbidity, age, and gender was examined. A truncated, subset of 28 STOPP criteria that were used in two previous studies, were further applied to the data to facilitate comparison.ResultsUsing 52 indicators, the overall prevalence of PIP in the study population (n = 1,019,491) was 29%. The most common examples of PIP were therapeutic duplication (11.9%), followed by use of aspirin with no indication (11.3%) and inappropriate use of proton pump inhibitors (PPIs) (3.7%). PIP was strongly associated with polypharmacy (Odds Ratio 18.2, 95% Confidence Intervals, 18.0-18.4, P < 0.05). PIP was more common in those aged 70–74 years vs. 85 years or more and in males. Application of the smaller subset of the STOPP criteria resulted in a lower PIP prevalence at 14.9% (95% CIs 14.8-14.9%) (n = 151,598). The most common PIP issues identified with this subset were use of PPIs at maximum dose for > 8 weeks, NSAIDs for > 3 months, and use of long-term neuroleptics.ConclusionsPIP was prevalent in the UK and increased with polypharmacy. Application of the comprehensive set of STOPP criteria allowed more accurate estimation of PIP compared to the subset of criteria used in previous studies. These findings may provide a focus for targeted interventions to reduce PIP.

Electronic prescribing and other forms of technology to reduce inappropriate medication use and polypharmacy in older people: a review of current evidence.

This review provided an overview of the current evidence in relation to the use of e-prescribing and other forms of technology, such as CDSS, to reduce inappropriate prescribing in older people. The evidence indicates that various types of e-prescribing and CDSS interventions have the potential to reduce inappropriate prescribing and polypharmacy in older people, but the magnitude of their effect varies according to study design and setting. There was significant heterogeneity in the studies reported in terms of study designs, intervention design, patient settings, and outcome measures with patient outcomes seldom reported. Widespread diffusion of these interventions has not occurred in any of the health care settings examined. Overall, health care providers report being satisfied with e-prescribing systems and see the systems as having a positive impact on the safety of their prescribing practices, yet the problem of overriding or ignoring alerts persists. The problem of large numbers of inaccurate and insignificant alerts and this issue, along with the other barriers that have been identified, warrant further investigation.

Non steroidal anti inflammatory drugs and pancreatic cancer risk a nested case control study

Background:Non-steroidal anti-inflammatory drug (NSAID) use has been linked with pancreatic cancer risk; however, findings from epidemiological studies are inconsistent.Methods:A nested case–control study was conducted within the UK General Practice Research Database. Cases (n=1141) had a diagnosis of primary cancer of the exocrine pancreas between January 1995 and June 2006. Controls (n=7954) were matched with each case on general practice site, sex and year of birth. Conditional logistic regression analyses were used to generate odds ratios (OR) and 95% confidence intervals (CI) associated with NSAID use compared with non-use.Results:Any use of NSAID in the 5 years before the index date or since entry into the database (excluding the year before diagnosis) was not associated with risk of pancreatic cancer; OR 0.96 (95% CI, 0.84–1.10) and 1.03 (95% CI 0.89–1.19), respectively. Exposure to NSAIDs for > 773 days, in the 5 years pre-diagnosis, was associated with a reduced risk of pancreatic cancer OR 0.78 (95%CI 0.62–0.97). There was evidence of reduced pancreatic cancer risk with long-term use (5 years or more) of lower doses of NSAIDs OR 0.70 (95% CI 0.49–0.99).Conclusion:Long-term exposure to NSAIDs may be associated with a reduction in risk of pancreatic cancer.

Effectiveness of a Multifaceted Intervention for Potentially Inappropriate Prescribing in Older Patients in Primary Care: A Cluster-Randomized Controlled Trial (OPTI-SCRIPT Study)

PURPOSE Potentially inappropriate prescribing (PIP) is common in older people and can result in increased morbidity, adverse drug events, and hospitalizations. The OPTI-SCRIPT study (Optimizing Prescribing for Older People in Primary Care, a cluster-randomized controlled trial) tested the effectiveness of a multifaceted intervention for reducing PIP in primary care. METHODS We conducted a cluster-randomized controlled trial among 21 general practitioner practices and 196 patients with PIP. Intervention participants received a complex, multifaceted intervention incorporating academic detailing; review of medicines with web-based pharmaceutical treatment algorithms that provide recommended alternative-treatment options; and tailored patient information leaflets. Control practices delivered usual care and received simple, patient-level PIP feedback. Primary outcomes were the proportion of patients with PIP and the mean number of potentially inappropriate prescriptions. We performed intention-to-treat analysis using random-effects regression. RESULTS All 21 practices and 190 patients were followed. At intervention completion, patients in the intervention group had significantly lower odds of having PIP than patients in the control group (adjusted odds ratio = 0.32; 95% CI, 0.15–0.70; P = .02). The mean number of PIP drugs in the intervention group was 0.70, compared with 1.18 in the control group (P = .02). The intervention group was almost one-third less likely than the control group to have PIP drugs at intervention completion, but this difference was not significant (incidence rate ratio = 0.71; 95% CI, 0.50–1.02; P = .49). The intervention was effective in reducing proton pump inhibitor prescribing (adjusted odds ratio = 0.30; 95% CI, 0.14–0.68; P = .04). CONCLUSIONS The OPTI-SCRIPT intervention incorporating academic detailing with a pharmacist, and a review of medicines with web-based pharmaceutical treatment algorithms, was effective in reducing PIP, particularly in modifying prescribing of proton pump inhibitors, the most commonly occurring PIP drugs nationally.

Addressing potentially inappropriate prescribing in older patients: development and pilot study of an intervention in primary care (the OPTI-SCRIPT study)

BackgroundPotentially inappropriate prescribing (PIP) in older people is common in primary care and can result in increased morbidity, adverse drug events, hospitalizations and mortality. The prevalence of PIP in Ireland is estimated at 36% with an associated expenditure of over €45 million in 2007. The aim of this paper is to describe the application of the Medical Research Council (MRC) framework to the development of an intervention to decrease PIP in Irish primary care.MethodsThe MRC framework for the design and evaluation of complex interventions guided the development of the study intervention. In the development stage, literature was reviewed and combined with information obtained from experts in the field using a consensus based methodology and patient cases to define the main components of the intervention. In the pilot stage, five GPs tested the proposed intervention. Qualitative interviews were conducted with the GPs to inform the development and implementation of the intervention for the main randomised controlled trial.ResultsThe literature review identified PIP criteria for inclusion in the study and two initial intervention components - academic detailing and medicines review supported by therapeutic treatment algorithms. Through patient case studies and a focus group with a group of 8 GPs, these components were refined and a third component of the intervention identified - patient information leaflets. The intervention was tested in a pilot study. In total, eight medicine reviews were conducted across five GP practices. These reviews addressed ten instances of PIP, nine of which were addressed in the form of either a dose reduction or a discontinuation of a targeted medication. Qualitative interviews highlighted that GPs were receptive to the intervention but patient preference and time needed both to prepare for and conduct the medicines review, emerged as potential barriers. Findings from the pilot study allowed further refinement to produce the finalised intervention of academic detailing with a pharmacist, medicines review with web-based therapeutic treatment algorithms and tailored patient information leaflets.ConclusionsThe MRC framework was used in the development of the OPTI-SCRIPT intervention to decrease the level of PIP in primary care in Ireland. Its application ensured that the intervention was developed using the best available evidence, was acceptable to GPs and feasible to deliver in the clinical setting. The effectiveness of this intervention is currently being tested in a pragmatic cluster randomised controlled trial.Trial registrationCurrent controlled trials ISRCTN41694007

Proton pump inhibitors and histamine-2-receptor antagonists and pancreatic cancer risk: a nested case–control study

Background:The relationship between use of proton pump inhibitors (PPIs) and histamine-2-receptor antagonists (H2RAs) and pancreatic cancer risk has yet to be examined. Data from a range of studies suggest biologically plausible mechanisms, whereby these drugs (or the conditions for which they are prescribed) may affect pancreatic cancer risk. The objective of this study was to investigate the relationship between use of PPIs/H2RAs and pancreatic cancer risk.Methods:A nested case–control study was conducted within the UK general practice research database (GPRD). Cases had a diagnosis of exocrine pancreatic cancer and controls were matched to cases on general practice site, sex and year of birth. Exposure to PPIs and to H2RAs since entry into GPRD until 2 years before the diagnosis date (corresponding date in controls) and in the 5 years before the diagnosis date were separately assessed. Conditional logistic regression analyses were used to generate odds ratios (ORs) and 95% confidence intervals (CIs) associated with PPI or H2RA use compared with nonuse.Results:Ever use of PPIs since entry into the GPRD (excluding the 2 years prior to diagnosis) was not associated with risk of pancreatic cancer; OR (95% CI) 1.02 (0.85–1.22). Neither the dose nor the duration of PPI or H2RA use was associated with pancreatic cancer risk. No consistent patterns of association were seen when cumulative exposure (dose and duration) to these drugs was examined separately or together.Conclusion:PPI/H2RA use, in a UK population, was not associated with pancreatic cancer risk.

Risk of diabetes complications among those with diabetes receiving androgen deprivation therapy for localized prostate cancer

PurposeAndrogen deprivation therapy (ADT), used increasingly in the treatment of localized prostate cancer, is associated with substantial long-term adverse consequences, including incident diabetes. While previous studies have suggested that ADT negatively influences glycemic control in existing diabetes, its association with diabetes complications has not been investigated. In this study, we examined the association between ADT use and diabetes complications in prostate cancer patients.MethodsA retrospective cohort study was conducted among men with newly diagnosed localized prostate cancer between 1995 and 2008, enrolled in three integrated health care systems. Men had radical prostatectomy or radiotherapy (curative intent therapy), existing type II diabetes mellitus (T2DM), and were followed through December 2010 (n = 5,336). Cox proportional hazards models were used to examine associations between ADT use and diabetes complications (any complication), and individual complications (diabetic neuropathy, diabetic retinopathy, diabetic amputation or diabetic cataract) after prostate cancer diagnosis.ResultsADT use was associated with an increased risk of any diabetes complication after prostate cancer diagnosis (adjusted hazard ratio, AHR, 1.12, 95% CI 1.03–1.23) as well as an increased risk of each individual complication compared to non-use.ConclusionADT use in men with T2DM, who received curative intent therapy for prostate cancer, was associated with an increased risk of diabetes complications. These findings support those of previous studies, which showed that ADT worsened diabetes control. Additional, larger studies are required to confirm these findings and to potentially inform the development of a risk-benefit assessment for men with existing T2DM, before initiating ADT.

Abstract 878: Pre-diagnostic aspirin use, lymph node involvement and mortality in women with stage I-III breast cancer: A study in the Prostate Lung Colorectal and Ovarian cancer screening trial

Background Inhibition of the cyclooxygenase (COX) / prostaglandin pathway has been shown to suppress the development of lymphatic metastases in animal models of breast cancer. A recent population based study reported that women with pre-diagnostic aspirin use (COX1/COX2 inhibitor) were significantly less likely to present with a lymph node metastasis at diagnosis than non-users. Pre-diagnostic aspirin use was also associated with lower 5-year breast cancer-specific mortality among women with lymph node-negative tumors. This study aims to confirm these results in a US population. Objective To examine the association between pre-diagnostic aspirin use, lymph node metastasis at breast cancer diagnosis, and breast cancer mortality, among women in the Prostate Lung Colorectal and Ovarian (PLCO) screening trial. Methods Women with stage I-III breast cancer were identified in PLCO. Pre-diagnostic aspirin use was ascertained from a self-reported questionnaire completed at trial entry. Adjusted risk ratios (RR) were calculated for associations between pre-diagnostic aspirin use and lymph node-positive status at diagnosis. Adjusted hazard ratios (HR) were estimated for associations between pre-diagnostic aspirin use at baseline and mortality, stratified by lymph node status. Ever vs never use of aspirin was examined and analyses incorporating updated measures of aspirin exposure are ongoing. Results There were 2925 women with stage I-III breast cancer, 716 of whom had lymph node metastases at diagnosis. Median time between assessment of pre-diagnostic aspirin exposure and diagnosis was 70 months. Aspirin users (n = 1274) were more likely than non-users (n = 1651) to have a greater number of comorbidities (p = 0.005) and were also more likely to be current or former smokers (p = 0.008). No association was observed between pre-diagnostic aspirin use and lymph node involvement at diagnosis RR 1.06 (95% CI 0.93-1.19). Pre-diagnostic aspirin use was not associated with lower breast cancer specific mortality HR 0.86 (0.60-1.23). However, in analyses stratified by lymph node status at diagnosis aspirin use was associated with lower breast cancer-specific mortality among women with lymph node-negative tumors (HR = 0.48, 95%CIs 0.27- 0.88), but not lymph node-positive tumors (HR 1.30 95%CIs 0.81- 2.09). Tests for effect-modification were statistically significant (P-interaction = 0.0001). Conclusion These data suggest that in women using aspirin prior to a breast cancer diagnosis, negative nodal status predicts a subsequent survival benefit from aspirin use.They partly reflect the findings in the previous study and may contribute to the understanding of aspirin9s potential mechanism of action in breast cancer progression. However further etiologic research to understand this association is warranted. Citation Format: Marie C. Bradley, Amanda Black, Andrew N. Freedman, Robert N. Hoover, Kala Visvanathan Visvanathan, Thomas I. Barron. Pre-diagnostic aspirin use, lymph node involvement and mortality in women with stage I-III breast cancer: A study in the Prostate Lung Colorectal and Ovarian cancer screening trial. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 878. doi:10.1158/1538-7445.AM2015-878