Explicit criteria as clinical tools to minimize inappropriate medication use and its consequences

Polypharmacy and prescribing of potentially inappropriate medications (PIMs) are the key elements of inappropriate medication use (IMU) in older multimorbid people. IMU is associated with a range of negative healthcare consequences including adverse drug events and unplanned hospitalizations. Furthermore, prescribing guidelines are commonly derived from randomized controlled clinical trials which have specifically excluded older adults with multimorbidity. Consequently, indiscriminate application of single disease pharmacotherapy guidelines to older multimorbid patients can lead to increased risk of drug?drug interactions, drug?disease interactions and poor drug adherence. Both polypharmacy and PIMs are highly prevalent in older people and strategies to improve the quality and safety of prescribing, largely through avoidance of IMU, are needed. In the last 30?years, numerous explicit PIM criteria-based tools have been developed to assist physicians with medication management in clinically complex multimorbid older people. Very few of these PIM criteria sets have been tested as an intervention compared with standard pharmaceutical care in well-designed clinical trials. In this review, we describe the most widely used sets of explicit PIM criteria to address inappropriate polypharmacy with particular focus on STOPP/START criteria and FORTA criteria which have been associated with positive patient-related outcomes when used as interventions in recent randomized controlled trials

Methods to reduce prescribing errors in elderly patients with multimorbidity

The global population of multimorbid older people is growing steadily. Multimorbidity is the principal cause of complex polypharmacy, which in turn is the prime risk factor for inappropriate prescribing and adverse drug reactions and events. Those who prescribe for older frailer multimorbid people are particularly prone to committing prescribing errors of various kinds. The causes of prescribing errors in this patient population are multifaceted and complex, including prescribers’ lack of knowledge of aging physiology, geriatric medicine, and geriatric pharmacotherapy, overprescribing that frequently leads to major polypharmacy, inappropriate prescribing, and inappropriate drug omission. This review examines the various ways of minimizing prescribing errors in multimorbid older people. The role of education in physician prescribers and clinical pharmacists, the use of implicit and explicit prescribing criteria designed to improve medication appropriateness in older people, and the application of information and communication-technology systems to minimize errors are discussed in detail. Although evidence to support any single intervention to prevent prescribing errors in multimorbid elderly people is inconclusive or lacking, published data support focused prescriber education in geriatric pharmacotherapy, routine application of STOPP/START (screening tool of older people’s prescriptions/screening tool to alert to right treatment) criteria for potentially inappropriate prescribing, electronic prescribing, and close liaison between clinical pharmacists and physicians in relation to structured medication review and reconciliation. Carrying out a structured medication review aimed at optimizing pharmacotherapy in this vulnerable patient population presents a major challenge. Another challenge is to design, build, validate, and test by clinical trials suitably versatile and efficient software engines that can reliably and swiftly perform complex medication reviews in older multimorbid people. The European Union-funded SENATOR and OPERAM clinical trials commencing in 2016 will examine the impact of customized software engines in reducing medication-related morbidity, avoidable excess cost, and rehospitalization in older multimorbid people

Potentially inappropriate medications defined by STOPP criteria and the risk of adverse drug events in older hospitalized patients

Background: Previous studies have not demonstrated a consistent association between potentially inappropriate medicines (PIMs) in older patients as defined by Beers criteria and avoidable adverse drug events (ADEs). This study aimed to assess whether PIMs defined by new STOPP (Screening Tool of Older Persons' potentially inappropriate Prescriptions) criteria are significantly associated with ADEs in older people with acute illness. Methods: We prospectively studied 600 consecutive patients 65 years or older who were admitted with acute illness to a university teaching hospital over a 4-month interval. Potentially inappropriate medicines were defined by both Beers and STOPP criteria. Adverse drug events were defined by World Health Organization- Uppsala Monitoring Centre criteria and verified by a local expert consensus panel, which also assessed whether ADEs were causal or contributory to current hospitalization. Hallas criteria defined ADE avoidability. We compared the proportions of patients taking Beers criteria PIMs and STOPP criteria PIMs with avoidable ADEs that were causal or contributory to admission. Results: A total of 329 ADEs were detected in 158 of 600 patients (26.3%); 219 of 329 ADEs (66.6%) were considered causal or contributory to admission. Of the 219 ADEs, 151(68.9%) considered causal or contributory to admission were avoidable or potentially avoidable. After adjusting for age, sex, comorbidity, dementia, baseline activities of daily living function, and number of medications, the likelihood of a serious avoidable ADE increased significantly when STOPP PIMs were prescribed (odds ratio, 1.847; 95% confidence interval [CI], 1.506-2.264;P<.001);prescription of Beers criteria PIMs did not significantly increase ADE risk (odds ratio, 1.276; 95% CI, 0.945-1.722; P=.11). Conclusion: STOPP criteria PIMs, unlike Beers criteria PIMs, are significantly associated with avoidable ADEs in older people that cause or contribute to urgent hospitalization

STOPP/START criteria for potentially inappropriate prescribing in older people: version 2

Purpose: screening tool of older people’s prescriptions (STOPP) and screening tool to alert to right treatment (START) criteria were first published in 2008. Due to an expanding therapeutics evidence base, updating of the criteria was required. Methods: we reviewed the 2008 STOPP/START criteria to add new evidence-based criteria and remove any obsolete criteria. A thorough literature review was performed to reassess the evidence base of the 2008 criteria and the proposed new criteria. Nineteen experts from 13 European countries reviewed a new draft of STOPP & START criteria including proposed new criteria. These experts were also asked to propose additional criteria they considered important to include in the revised STOPP & START criteria and to highlight any criteria from the 2008 list they considered less important or lacking an evidence base. The revised list of criteria was then validated using the Delphi consensus methodology. Results: the expert panel agreed a final list of 114 criteria after two Delphi validation rounds, i.e. 80 STOPP criteria and 34 START criteria. This represents an overall 31% increase in STOPP/START criteria compared with version 1. Several new STOPP categories were created in version 2, namely antiplatelet/anticoagulant drugs, drugs affecting, or affected by, renal function and drugs that increase anticholinergic burden; new START categories include urogenital system drugs, analgesics and vaccines. Conclusion: STOPP/START version 2 criteria have been expanded and updated for the purpose of minimizing inappropriate prescribing in older people. These criteria are based on an up-to-date literature review and consensus validation among a European panel of experts

An in vivo root hair assay for determining rates of apoptotic-like programmed cell death in plants

In Arabidopsis thaliana we demonstrate that dying root hairs provide an easy and rapid in vivo model for the morphological identification of apoptotic-like programmed cell death (AL-PCD) in plants. The model described here is transferable between species, can be used to investigate rates of AL-PCD in response to various treatments and to identify modulation of AL-PCD rates in mutant/transgenic plant lines facilitating rapid screening of mutant populations in order to identify genes involved in AL-PCD regulation

Detection and prevention of adverse drug reactions in multi-morbid older patients

Adverse drug reactions (ADRs) are a recognised unintentional form of iatrogenic harm, which commonly occur in older adults who have high levels of multi-morbidity and associated polypharmacy. Previous studies estimate that at least one in 10 hospitalised older patients will experience an ADR. While recent research indicates that this could be as high as 39% in hospitalised multi-morbid, older adults, up to two-thirds of these ADRs can be considered preventable and therefore potentially avoidable. In addition to increasing patient morbidity and contributing to avoidable mortality, there is an associated cost implication with ADR occurrence. This commentary summarises current mainstream research in terms of ADR detection, prediction and prevention in multi-morbid older patients. At present, the biggest barrier to understanding and comparing ADRs in the literature is the large heterogeneity that exists in the population and study methods. Furthermore, there is the lack of standardised universally accepted methodology for ADR prediction, detection, causality assessment and subsequent prevention in older people. Standard available methods of ADR prediction applied to a heterogeneous multi-morbid population are generally unsatisfactory. Without an instrument that consistently and reliably predicts ADR risk in a reproducible manner, ADR prevention in multi-morbid older patients is challenging. Further attention should be focused on the culprit drugs that commonly lead to major ADRs in older multi-morbid hospitalised patients with polypharmacy. Risk associated with particular drug classes may possibly predict ADR occurrence better than patient characteristics alone. Current research is examining this drug class focus for ADR prevention in multi-morbid older people

In-hospital adverse drug reactions in hospitalised older adults - a systematic review

Introduction: Studies indicate 1 in 4 older people experience hospital-related adverse drug reactions [ADRs]. This systematic-review aims to evaluate in-hospital ADRs in hospitalised older-adults in terms of incidence, prevalence, most commonly involved drug classes, severity, and consequences. Methods: Using PRISMA methodology [PROSPERO CRD42018079095], we searched PubMed, Embase, Ebsco-CINAHL, Cochrane Library, library hosted sources, Google scholar, and ‘grey’ literature, using terms; aged, ADRs, hospitalized, multi-morbid, polypharmacy and hospital-acquired. References of editorials and systematic reviews were hand searched. Studies of all languages and dates until 15/01/2018 were included. All studies reporting ADRs outcomes, ≥65 years, hospitalised at time of ADR occurrence were included. Two researchers screened all papers for inclusion, risk of bias and data extraction. Results: Initial search yielded 1721 abstracts, 200 underwent full text screening. 60 were potentially suitable for inclusion; 48 papers reported combined ages, 12 papers reported directly on ADRs in our age cohort [2 papers reported the same data]. 11 studies [4424 patients] were analysed; 24% [1064] experienced ADRs. 7 reported severity (n = 707); 31% [220] being severe. 5 reported on post-ADR outcomes i.e. length of stay [n = 3], death [n = 1] and functional decline [n = 1]. Frequency of culprit drug-groups were described in 6 [672 ADRs]; 43% [291] cardiovascular system, 17% [114] central nervous system, 16% [112] clotting pathways, 13% [90] anti-microbials. Conclusions: One in four over 65 years experience an ADR during hospitalisation, one third being severe, and almost half cardiovascular system drugs. Clinical outcomes associated with ADRs are generally poorly described in the literature.Poster presentatio

Deprescribing in multi-morbid older people with polypharmacy: agreement between STOPPFrail explicit criteria and gold standard deprescribing using 100 standardized clinical cases

Purpose: Older people with advanced frailty are among the highest consumers of medications. When life expectancy is limited, some of these medications are likely to be inappropriate. The aim of this study was to compare STOPPFrail, a concise, easy-to-use, deprescribing tool based on explicit criteria, with gold standard, systematic geriatrician-led deprescribing. Methods: One hundred standardized clinical cases involving 1024 medications were prepared. Clinical cases were based on anonymized hospitalized patients aged ≥ 65 years, with advanced frailty (Clinical Frailty Scale ≥ 6), receiving ≥ 5 regular medications, who were selected from a recent observational study. Level of agreement between deprescribing methods was measured by Cohen’s kappa coefficient. Sensitivity and positive predictive value of STOPPFrail-guided deprescribing relative to gold standard deprescribing was also measured. Results: Overall, 524 medications (51.2%) of medications prescribed to this frail, elderly cohort were potentially inappropriate by gold standard criteria. STOPPFrail-guided deprescribing led to the identification of 70.2% of the potentially inappropriate medications. Cohen’s kappa was 0.60 (95% confidence interval 0.55–0.65; p < 0.001) indicating moderate agreement between STOPPFrail-guided and gold standard deprescribing. The positive predictive value of STOPPFrail was 89.3% indicating that the great majority of deprescribing decisions aligned with gold standard care. Conclusions: STOPPFrail removes an important barrier to deprescribing by explicitly highlighting circumstances where commonly used medications can be safely deprescribed in older people with advanced frailty. Our results suggest that in multi-morbid older patients with advanced frailty, the use of STOPPFrail criteria to address inappropriate polypharmacy may be reasonable alternative to specialist medication review

Evolution dynamics of a dense frozen Rydberg gas to plasma

Dense samples of cold Rydberg atoms have previously been observed to spontaneously evolve to a plasma, despite the fact that each atom may be bound by as much as 100 cm−1. Initially, ionization is caused by blackbody photoionization and Rydberg-Rydberg collisions. After the first electrons leave the interaction re- gion, the net positive charge traps subsequent electrons. As a result, rapid ionization starts to occur after 1 μs caused by electron-Rydberg collisions. The resulting cold plasma expands slowly and persists for tens of microseconds. While the initial report on this process identified the key issues described above, it failed to resolve one key aspect of the evolution process. Specifically, redistribution of population to Rydberg states other than the one initially populated was not observed, a necessary mechanism to maintain the energy balance in the system. Here we report new and expanded observations showing such redistribution and confirming theoretical predictions concerning the evolution to a plasma. These measurements also indicate that, for high n states of purely cold Rydberg samples, the initial ionization process which leads to electron trapping is one involving the interactions between Rydberg atoms

Evolution dynamics of a dense frozen Rydberg gas to plasma

Dense samples of cold Rydberg atoms have previously been observed to spontaneously evolve to a plasma, despite the fact that each atom may be bound by as much as 100 cm−1. Initially, ionization is caused by blackbody photoionization and Rydberg-Rydberg collisions. After the first electrons leave the interaction re- gion, the net positive charge traps subsequent electrons. As a result, rapid ionization starts to occur after 1 μs caused by electron-Rydberg collisions. The resulting cold plasma expands slowly and persists for tens of microseconds. While the initial report on this process identified the key issues described above, it failed to resolve one key aspect of the evolution process. Specifically, redistribution of population to Rydberg states other than the one initially populated was not observed, a necessary mechanism to maintain the energy balance in the system. Here we report new and expanded observations showing such redistribution and confirming theoretical predictions concerning the evolution to a plasma. These measurements also indicate that, for high n states of purely cold Rydberg samples, the initial ionization process which leads to electron trapping is one involving the interactions between Rydberg atoms