Drugs Aging DOI 10.1007/s40266-016-0352-7

REVIEW ARTICLE

Optimization of Geriatric Pharmacotherapy: Role of Multifaceted Cooperation in the Hospital Setting Mirko Petrovic1 • Annemie Somers2 • Graziano Onder3

 Springer International Publishing Switzerland 2016

Abstract Because older patients are more vulnerable to adverse drug-related events, there is a need to ensure appropriate pharmacotherapy in these patients. This narrative review describes approaches to improve pharmacotherapy in older people in the hospital setting. Screening to identify older patients at risk of drug-related problems and adverse drug reactions (ADRs) is the first critical step within a multistep approach to geriatric pharmacotherapy. Two methods that have been developed are the GerontoNet ADR risk score and the Brighton Adverse Drug Reactions Risk (BADRI) model, which take into account a number of factors, the most important of which is the number of medicines. In order to reduce potentially inappropriate prescribing in older patients, different types of interventions exist, such as pharmacist-led medication reviews, educational interventions, computerized decision support systems, and comprehensive geriatric assessment. The effects of these interventions have been studied, sometimes in a multifaceted approach, by combining different techniques. None of the existing interventions shows a clear beneficial effect on patients’ health outcomes if applied in isolation; however, when these interventions are combined within the context of a multidisciplinary team, positive effects on patients’ health outcomes can be expected.

& Mirko Petrovic [email protected] 1

Department of Geriatrics, Ghent University Hospital, De Pintelaan 185, Ghent, Belgium

2

Department of Pharmacy, Ghent University Hospital, Ghent, Belgium

3

Centro Medicina dell’Invecchiamento, Department of Geriatrics, Policlinico A. Gemeli, Catholic University of the Sacred Heart, Rome, Italy

Appropriate geriatric pharmacotherapy, global assessment of patients’ clinical and functional parameters, and integration of skills from different healthcare professionals are needed to address medical complexity of older adults.

Key Points Increasing the awareness of healthcare professionals with regard to geriatric pharmacotherapy should be encouraged by individualized, interactive, multidisciplinary, and multifaceted programs. The available approaches to optimize prescribing in older patients should be harmonized and integrated in a single standardized intervention.

1 Introduction The clinical impact of drug-related problems (DRPs) in older people is illustrated by the high incidence of drugrelated hospital admissions. Although older patients are often hospitalized in acute geriatric wards under professional care, including evidence-based pharmacotherapy, the risk of DRPs during hospitalization is still present [1– 3]. Prolongation of drug therapy initiated prior to hospital admission, in combination with the acute treatment prescribed during admission, often makes the drug scheme complex. This is not only due to numerous drugs but also the need for careful evaluation of drugs that should be continued, changed, and temporarily or definitely stopped, and drugs that should be started with follow-up of therapeutic effects and side effects.

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Older people are more prone to the occurrence of adverse drug reactions (ADRs). These can lead to hospital admission or can occur during hospitalization because of worsening condition, multiple diseases, or drug–drug interactions DDIs). The reported percentages of ADRs in hospitalized patients vary between 2.4 and 10.9 % [4, 5]. Moreover, older patients usually take a higher number of drugs in comparison to younger patients, which is a wellknown risk factor for developing ADRs. At the same time, one commonly known characteristic of voluntary ADR reporting systems is the underreporting of ADRs [6, 7]. Therefore, when studying their incidence, efforts should be made to combine spontaneous ADR reporting by different caregivers (physicians and nurses), with information taken directly from the patient—for example, by interview during ward rounds. Hospitalization might be seen as an opportunity to optimize older person’s medicines. In hospital, the expertise and resources to review patient’s medicines may be more readily available than in the community, and there is often a change in the patient’s diagnosis, function, and prognosis. In the literature, a wide range of drug-related hospital admissions are reported, with percentages varying between 4 and 30 %. The majority of these problems concern ADRs, with avoidability ranging between 50 and 97 % [8– 10]. In the prospective, multicenter HARM study (Hospital Admissions Related to Medications), 13,000 unplanned hospital admissions were screened and 5.6 % identified as drug-related. The results show that the mean age of drugrelated admissions was significantly higher compared with the mean age of all unplanned admissions [11]. Various factors can explain the high incidence of DRPs in older people [12–18]. Older people often suffer from different diseases simultaneously and, consequently, are treated with many drugs, which place them at a higher risk of adverse reactions and DDIs. In addition, changes in pharmacokinetic and pharmacodynamic properties make older people more prone to the occurrence of DRPs. Moreover, older patients are often treated by multiple healthcare professionals, in particular different prescribing physicians. Therefore, it can be difficult to provide an overview of the different medications prescribed in terms of indications, duration of therapy, monitoring of adverse reactions, and follow-up of the effectiveness of the drugs for the different medical problems. In addition, decreased capability to handle drugs (e.g. taking tablets out of blisters, or inhalation techniques) can lead to decreased compliance and potentially inappropriate drug therapy. Older people are usually prescribed the same drugs as younger adults, but these drugs can work differently in older persons and are also more frequently combined [19–21]. Despite these risks, little data have been generated about

the efficacy and safety of medicines in older people. Older people, particularly multimorbid and/or frail patients who consume multiple medicines, are underrepresented in clinical trials [22]. In order to define preventive strategies for DRPs in older people, we must look at the factors explaining the high frequency of DRPs. The event of an older patient’s hospital admission could therefore be the ideal moment to take a close look at the drug regimen in order to avoid misuse, overuse, and underuse. Moreover, moments of transition between care settings (e.g. unplanned hospital admission or discharge from hospital to the community) can lead to unintended discrepancies in the drug list and to DRPs after discharge. This narrative review describes approaches to improve pharmacotherapy in older people in the hospital setting.

2 Identification of Older Patients at Risk for Developing Adverse Drug Reactions (ADRs) The first step within a multistep approach to geriatric pharmacotherapy concerns identification of older patients at risk for developing an ADR, as not all clinicians, pharmacists, nurses, or patients are able to recognize ADRs. The difficulty in differentiating drug-induced symptoms from non-drugrelated symptoms to afford a medical diagnosis often results in the addition of yet another drug to treat symptoms, which increases the risk of DDIs and ADRs—a phenomenon known as ‘the prescribing cascade’ [23]. Therefore, in an attempt to improve ADR recognition in older adults, its diagnosis should routinely be part of the broader diagnostic approach. In older patients taking drugs, the differential diagnosis should always include the possibility of ADRs. One potential strategy to find a way to reduce ADR occurrences is to identify those patients who are at risk of an ADR and to target additional resources toward this group. An example of this approach might be that when a patient is identified as being at risk, the physician, nurse, and/or pharmacist pay extra attention to all the medications that the patient receives. 2.1 GerontoNet ADR Risk Score Based on these considerations, an efficient and simple method of identifying patients who are at increased risk of an ADR in a population of older inpatients has been developed and validated in 2010: the GerontoNet ADR risk score [24], presented in Table 1. Score range is 0–10 points; a cutoff point between 3 and 4 provides a good balance between sensitivity (68 %) and specificity (65 %) and may be used to identify patients at high risk for ADRs.

Role of Multifaced Cooperation in Geriatric Pharmacotherapy Table 1 The GerontoNet ADR risk score Points Four or more comorbid conditions

1

Congestive heart failure

1

Liver diseasea

1

No of drugs \5

0

5–7

1

C8

4

Previous ADR

2

Renal failureb

1

ADR adverse drug reaction a

Defined as liver function tests [2 9 upper limit of normal

b

Defined as creatinine clearance \40 ml/min

was attributed to each variable. The sensitivity value for the BADRI model during development was 80 %, exceeding that of GerontoNet at 68 %, and demonstrating that BADRI performs better at detecting patients who go on to have an ADR. However, its specificity value (or true negative) of 55 %, was lower than GerontoNet’s, at 65 %. Index was found to be greatest when the cutoff score was 1. A direct comparison of the BADRI score with the GerontoNet risk score shows that both perform similarly on levels of discrimination (0.71 GerontoNet vs. 0.74 BADRI). Both risk scores have so far only been validated in hospitalized patients. 2.3 Drug Burden Index

The GerontoNet ADR risk score also allows stratification of patients according to the likelihood of developing an ADR, and is hoped to significantly improve prescribing practice and reduce the occurrence of ADRs amongst older patients. Moreover, the GerontoNet ADR risk score represents a pragmatic approach to identifying patients at increased risk of an ADR. All the variables included in calculation of the risk score address conditions or problems usually evaluated during a standard geriatric assessment, and no specific test or complex biological parameter is required. However, a recent observational study showed that the GerontoNet ADR risk score missed almost 40 % of those at risk of an ADR, underlining the need for identification of new risk factors to be added to the score [25]. Despite these concerns, the GerontoNet ADR risk score represents the first tool available to date to identify patients at risk of ADRs, which may be the target of interventions aimed at reducing their risk of ADRs. 2.2 Brighton Adverse Drug Reactions Risk (BADRI) Model Recently, another simple model to apply ADR risk score in a population of the oldest old has been developed and validated: Brighton Adverse Drug Reactions Risk (BADRI) model [26], presented in Table 2. An equal weighting of 1

Table 2 Brighton Adverse Drug Reactions Risk (BADRI) score Points Hyperlipidemia

1

No. of drugs C8

1

Length of stay C12 days

1

Use of antidiabetic agents

1

High White Blood Cell count on admission

1

The cumulative effect of multiple drugs with anticholinergic properties that block muscarinic receptors in the cholinergic nervous system is known as the ‘anticholinergic burden’. Several scales have so far been developed to assess ‘anticholinergic burden’, the most recent of which is the Drug Burden Index (DBI). Hilmer et al. showed that increasing DBI had a positive correlation with deterioration in functions of grip strength and gait. Therefore, the DBI might be used to help clinicians identify ADRs that present as cognitive or physical functional impairment, to quantify the effects of anticholinergic and sedative drugs, and the effects of interventions to reduce the DBI [27].

3 Reducing Potentially Inappropriate Prescribing (PIP) in Older Patients Different types of interventions have been used in order to reduce potentially inappropriate prescribing (PIP) in older patients (i.e. prescribing of medications that introduce a significant risk of an adverse drug event (ADE) when there exists evidence for an equally or more effective, but lower risk, alternative therapy for treating the same medical condition) [28]. These can be roughly categorized into pharmacist-led medication reviews, educational interventions, tools for the detection of PIP in older people, computerized decision support systems, and geriatric medicine services interventions. 3.1 Pharmacist-Led Medication Reviews Over the last few decades, the pharmacy profession has transitioned from a traditional drug-oriented perspective towards a patient-centered approach, which can be traced back to the concept of pharmaceutical care [29]. Pharmaceutical care is delivered by clinical pharmacists with the aim of improving outcomes and safety of drug therapy. The pharmaceutical care process consists of the following

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cyclic steps for an individual patient: patient’s medication history obtained by pharmacists, medication review, design of a pharmaceutical care plan, and follow-up of this plan [30]. While a standardized approach is necessary for the adequate detection and evaluation of DRPs, drug therapy should be reviewed in-depth by having full access to medical records, laboratory values, and nursing notes. Thus, the cycle starts with the patient’s medication history obtained by pharmacists to identify all the medications that the patient is taking and was taking in the past (including information on previous ADRs and DRPs), followed by the medication review, which becomes an individualized assessment during which the medication scheme is analyzed in a structured manner in order to identify DRPs. Consequently, the drug scheme is screened for any misuse, underuse, or overuse of drugs. Possible solutions to any DRPs are then discussed with the treating physician and, if possible, with the patient him/herself. Finally, a medication management plan is created to address any issues, and the pharmacist discusses with the patient how the medications are best taken. Targeted medication reconciliation can reduce discrepancies and is defined as ‘the process of identifying the most accurate list of a patient’s current medicines, including the name, dosage, frequency and route, and comparing them to the current list in use, recognizing discrepancies, and documenting any changes, thus resulting in a complete list of medications, accurately communicated [31]. A recent review suggests that when pharmacists play a proactive role in performing medication reviews, pharmacotherapy for older people can be improved, but the evidence for the impact of pharmacists’ medication reviews on health outcomes, quality of life, or cost effectiveness of care is mixed and not conclusive [32]. However, a recent randomized clinical trial (RCT) involving 851 adults hospitalized with acute coronary syndromes or acute heart failure did not significantly alter the per-patient number of clinically important medication errors [incidence rate ratio 0.92, 95 % confidence interval (CI) 0.77–1.10] or ADEs (incidence rate ratio 1.09, 95 % CI 0.86–1.39) [33]. The RCT utilized an approach based on pharmacist-assisted medication reconciliation, inpatient pharmacist counselling, low-literacy adherence aids, and individualized telephone follow-up after discharge. Why this trial failed is puzzling. Although clinical pharmacists perform the pharmaceutical care process to manage the patient’s drug therapy in everyday clinical practice, it is the physician who takes ultimate responsibility for the care of the patient. Better results have been reported when pharmacists are skilled in clinical issues (clinical pharmacy) and work in the context of a multidisciplinary team, in close collaboration with physicians, nurses, and other caregivers.

Possibly the level of integration regarding caregivers within this RCT was insufficient. In contrast, another RCT performed among in-hospital patients aged 70 years or older demonstrated that pharmaceutical care provided by an experienced clinical pharmacist who had direct contacts with the treating geriatric team resulted in a more appropriate use of medicines during the hospital stay and after discharge [34]. In addition, a recent meta-analysis showed that team-based care, including pharmacists, resulted in a 47 % reduction of ADEs [35]. These findings illustrate that safe drug use goes hand in hand with global assessment of patients’ clinical and functional parameters. Indeed, a potential limitation of research assessing the role of pharmacists in preventing ADRs is that many studies may have provided pharmacists with too little education and training updates on geriatric pharmacotherapy given the complexity of optimizing pharmacotherapy in frail older individuals suffering from multiple conditions and receiving multiple medications. In addition, sample sizes of available RCTs assessing the effect of an approach based on pharmacists working in a multidisciplinary team on ADRs were small, indicating the need for large-scale, multicenter trials [36–39]. 3.2 Educational Interventions Educational interventions, including teaching, interactive workshops, provision of decision algorithms, and face-toface interactions have mixed effects on the appropriateness of prescribing [40]. Passive dissemination of guidelines does not seem to be effective. Nonetheless, academic detailing (i.e. university-based educational outreach that involves face-to-face education of prescribers by trained healthcare professionals, typically pharmacists and physicians) in addition to audit and feedback, and peer benchmarking has been shown to improve the drug treatment [41, 42]. Increasing the awareness of healthcare professionals with regard to prescribing medication in older patients should be encouraged by individualized, interactive, multidisciplinary, and multifaceted programs. 3.3 Tools for Detection of PIP and Potentially Inappropriate Medications (PIMs) in Older People Several methods and instruments have been developed for the purpose of medication appropriateness assessment, and are categorized as explicit (criteria-based) or implicit (judgment-based) tools (Table 3). Explicit tools are based on lists of potentially inappropriate medications (PIMs), drugs to avoid or always to avoid in older patients, or indicators for appropriate prescribing for several drugs or diseases. Explicit criteria used

Role of Multifaced Cooperation in Geriatric Pharmacotherapy Table 3 Frequently used tools for optimization of pharmacotherapy in older people

Explicit tools (drugs to avoid, drugs to avoid in certain diseases/syndromes, drugs to be used with caution) Beers (1991, updates 1997, 2003, 2012) [54, 55] McLeod (1997) [43] ACOVE: Assessing Care of Vulnerable Elders (2001) [44] IPET: Improved Prescribing in the Elderly Tool (2002) [45] Zhan criteria (2001) [46] Rancourt criteria (2004) [47] Laroche criteria (2007): French Consensus Panel List [48] Australian Prescribing Indicator Tool (2008) [49, 50] Thailand criteria (2008) [51] STOPP: Screening Tool of Older Person’s Potentially inappropriate prescriptions (2008, update 2015) [56, 57] NORGEP: Norwegian General Practice Criteria (2009) [52] PRISCUS list (2010) [53] Implicit tools MAI: Medication Appropriateness Index (1992) [60] Indication, effectiveness, drug-disease interactions, dose, correct directions, correct directions practical for the patient, drug–drug interactions, duplication of therapy, duration, costs STRIP: Systematic Tool to Reduce Inappropriate Prescribing [61] Structured history-taking of medication use, structured pharmaceutical analysis, pharmaceutical care plan (pharmacist–physician), patient consultation, follow-up and monitoring

with prescription data alone or with clinical data are commonly used to detect PIP. Various explicit tools are available [43–53], although only the Beers criteria [54, 55] and STOPP (Screening Tool of Older Persons’ Prescriptions) [56, 57] criteria have been evaluated for predictive validity. In 1991, Beers and colleagues developed a set of criteria with the intent of providing a tool for assessing the quality of prescribing in older persons [54]. In their latest version updated by the American Geriatrics Society in 2012, Beers criteria identify a list of 53 PIMs or drug classes divided into three categories: PIMs to avoid independent of comorbidities, PIMs to avoid in older adults with certain diseases and syndromes, and medications to be used with caution [55]. Several studies also reported a link between the use of drugs listed by Beers and adverse outcomes. Limitation of the Beers criteria include the fact that they were developed for application to older adults living in the US, and thus accounting for differences in drug policy and pharmaceutical marketing in other countries could be problematic. The STOPP tool for screening PIMs, as well as a tool for the detection of potential prescribing omissions of indicated, potentially beneficial drugs called START (Screening Tool to Alert doctors to Right—appropriate, indicated—Treatment) were developed in 2008 and updated in 2015 [56, 57]. These criteria, which have been endorsed by the European Union Geriatric Medicine Society (EUGMS), are organized according to physiological systems and include both PIP and

omission of potentially beneficial pharmacotherapy. Recent data showed that the use of STOPP/START criteria to assess older inpatients’ medications leads to significant and lasting improvements in the appropriateness of prescribing at discharge and for up to 6 months after discharge, suggesting that this tool represents a simple method of optimizing prescribing appropriateness in older inpatients [58]. In addition, in a study performed among 600 inpatients aged 65 year or older, a total of 329 ADEs were detected in 158 patients (26.3 %); 219 of 329 ADEs (66.6 %) caused or contributed to admission, and 151 of these 219 ADEs (68.9 %) 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 was prescribed (odds ratio 1.847, 95 % CI 1.506–2.264; p \ 0.001) [59]. Using an implicit tool means that clinical information of the individual patient is taken into account to judge appropriateness. The Medication Appropriateness Index (MAI) represents a comprehensive and validated implicit tool [60]. It is a judgment-based process measure of prescribing appropriateness that assesses ten elements of prescribing: indication, effectiveness, dose, correct directions, practical directions, DDIs, drug–disease interactions, duplication, duration, and cost. These elements are assessed based on clinical judgment rather than objective measures, and the ratings generate a weighted score that serves as a summary measure of prescribing appropriateness. Limitations of the

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index are related to the fact that it is time-consuming and does not assess underprescribing. The Systematic Tool to Reduce Inappropriate Prescribing (STRIP) is another implicit tool based on the Polypharmacy Optimization Method (POM) and has proven effective when used by general practitioners [61, 62]. The STRIP consists of a clinical medication review and involves the patient, pharmacist, and physician. The following five steps are implemented in a medication review: [1] structured history taking of medication use; [2] structured pharmaceutical analysis [(a) undertreatment ? START criteria; (b) ineffective treatment; (c) unnecessary treatment ? STOPP criteria; (d) potential adverse effects ? STOPP criteria; (e) contraindications and interactions ? STOPP criteria; (f) dosage or problems in use]; [3] pharmaceutical care plan (pharmacist and physician); [4] patient consultation; and [5] follow-up and monitoring. The second step of the STRIP is the structured pharmaceutical analysis, in which indication, treatment goals, undertreatment, unnecessary treatment, side effects, interactions, contraindications, and dosage are weighed to create an appropriate list of medications [63]. The checklists of START and STOPP criteria are applied in the STRIP. 3.4 Computerized Decision Support Systems Computerized decision support systems are based on interactive softwares designed to assist physicians to correct prescription, with the aim of reducing prescribing errors, improving prescribing appropriateness, and ultimately leading to a reduction of iatrogenic illness. These software programs provide support at the time of prescription by implementing different algorithms and tools to identify PIP, drug interactions, risk of iatrogenic illness, appropriate drug dosage, and contraindicated treatments. Computer-based prescribing systems have shown the potential to change mainly healthcare provider behavior. There are also targeted studies that show success in certain drugs or disease classes [64–66]. The main limitation of computer-based prescribing systems relates to their non-standardized nature: all employ different types of tools or algorithms depending on the setting or population considered. In addition, because they are mainly focused on pharmacological issues, they often do not assess the relationship of older patients to comorbidity,,nor recognize geriatric syndromes and impairments in multiple systems (for instance, cognitive and functional impairments). Future applications of computer-based prescribing systems should integrate the clinical and prescribing information, for example context dosing support, guidance for medication-related laboratory testing and drug–disease contraindications.

3.5 Geriatric Medicine Services Interventions Multidisciplinary geriatric teams allow management of the geriatric patient complexity at several levels, including pharmacotherapy. A key point in preventing ADRs relates to the fact that medical complexity of geriatric patients should always be considered before prescribing a pharmacological treatment in order to minimize the risk of drug-related illness. Integrated medicine management (IMM) is delivered at admission, inpatient stay and discharge, is seamless to the patient, and is based on an unobstructed information flow between hospital physicians, nurses, clinical pharmacists, general practitioners, and community pharmacists. Its use has shown a benefit in terms of reduced length of stay when incorporated into routine practice, increased time to readmission and reduction in the number of readmissions to hospital within a 1-year period [67]. The traditional approach to patients’ diseases and needs does not sufficiently provide information on these problematic areas. Therefore, a comprehensive geriatric assessment (CGA) may be necessary to optimize the quality of prescribing. An extensive literature has documented that the use of CGA within a multidisciplinary team of geriatricians, nurses, social workers, and other professionals assessing and managing the healthcare problems identified by the CGA—developing individualized care plans—has resulted in more detailed evaluation, improved care planning, and overall better quality of care [68]. CGA additionally allows a complete and global assessment and management of the healthcare problems, including evaluation of drugs with the goal of recognizing and preventing potential DRPs, and improving the quality of prescribing. CGA is oriented towards evaluation of drug treatment as part of a more global assessment of characteristics of older adults. CGA can evaluate the appropriateness of medication use in complicated cases of older patients, aligning treatments with clinical guideline recommendations, functional (i.e. risk of falls) and cognitive (i.e. dementia, risk of delirium) impairment, geriatric syndromes, and limited life expectancy. Moreover, a full and global evaluation of these problems and needs obtained by CGA may be helpful in simplifying drug prescription and prioritizing pharmacological and healthcare needs, resulting in an improvement in quality of prescribing and in a reduction in the risk of drug-related illness [69, 70]. Several studies so far have assessed the effect of CGA and management on drug prescribing and drug-related illness, showing a substantial improvement in the quality of prescription [71, 72]. In this context, the CRIME (CRIteria to assess appropriate Medication use among Elderly complex patients) project produced 19 explicit recommendations on the

Role of Multifaced Cooperation in Geriatric Pharmacotherapy Table 4 Advantages and limitations of approaches to lower inappropriate drug prescribing Approach

Advantages

Limitations

Pharmacist-driven medication reviews

• Pharmacist has more in-depth knowledge about drug adverse effects than the treating physician

• Mixed/insufficient evidence for effect on health outcomes, health-related quality of life, and costeffectiveness of care

• Can educate other healthcare professionals

• Working outside of the multidisciplinary team often fails

• Ongoing individualized, interactive, multidisciplinary, and multifaceted programs can be helpful

• Need to define what is required to assess adequacy for a given level of intervention

Educational intervention

• Simple dissemination of guidelines unlikely to be effective Instruments to detect inappropriate prescribing in older people

• Implicit: comprehensive and systematic approach; includes operational definitions, clear instructions, and examples; good as an educational tool

• Implicit: knowledge-dependent, time-consuming, and does not assess underprescribing

• Explicit: relatively easy to remember and to detect; provide support to identify inappropriate prescribing in older people

• Explicit: time-consuming unless process is automated, and the patient’s perspective is often not taken into consideration

Computerized decision support systems

• Have the potential to alert the prescribing physician to drug-prescribing issues

• Existing systems are not geriatric-specific; limited evidence for improvement in patient outcomes; high volume of alerts: risk of unimportant warnings

Geriatric medical services interventions

• Integrated care and detailed geriatric assessment can reduce the length of hospital stay and the number of readmissions

• Pharmacotherapy must be part of the initial geriatric assessment for the approach to work well

pharmacological treatment of five common chronic conditions: diabetes, hypertension, congestive heart failure, atrial fibrillation, and coronary heart disease. Its intent is to guide pharmacologic prescription in older patients by considering the complex aspects of aging (including limited life expectancy, functional and cognitive impairment, and geriatric syndromes) that may limit benefits of drug treatment or lead to negative effects [73]. A large study assessing the effect of CGA associated with a multidisciplinary team approach, compared with usual care, also showed a 35 % reduction in the risk of a serious ADR and a substantial reduction in unnecessary and potentially inappropriate drug use, and also in the number of conditions with omitted drugs significantly associated with the intervention [74].

4 Conclusions None of the discussed approaches in this review shows a clear beneficial effect on patients’ health outcomes if applied in isolation (Table 4). However, when these interventions are combined (for example, studies assessing the efficacy of medication review performed by experienced pharmacists within the context of a multidisciplinary team), positive effects on patients’ health outcomes can be expected. This finding indicates that appropriate pharmacotherapy must be united with global assessment of patients’ clinical and functional parameters, and that

• Heterogeneity in terms of structural components and care processes

integration of skills from different healthcare professionals are needed to address medical complexity of older adults. The challenge for future research is to integrate valuable information obtained by combinations of methods in a multifaceted, complete, and global approach targeting all potential factors involved in the onset of ADRs. With regard to the role of policy, key performance indicators and/or standards in prompting and sustaining practice change in hospital, the following aspects might be considered for implementation. There is a need for focused attention regarding drug-related hospital admissions of older patients. Clinical pharmacists should perform medication review for older patients with polypharmacy, and in particular with drugs for the central nervous system. A structured approach for assessment of medication appropriateness should be used. Drug-related problems (i.e. ADRs, inappropriate doses, DDIs, etc.) should carefully be reported in the patient’s file. Clinical pharmacists should play an active role in the detection of drug-related problems and should make recommendations to other caregivers to optimize drug therapy for older people. In order to move knowledge forward, the available approaches to optimize geriatric pharmacotherapy should be harmonized and integrated in a single standardized intervention. Moreover, a software application has to be developed to support and standardize the integrated approach, and, finally, the effectiveness of the integrated intervention should be testes in an RCT.

M. Petrovic et al. Acknowledgments This article is based on a presentation given at the 42nd ESCP Symposium on the Implementation of Clinical Pharmacy Practice: Research, Education and Management, held in Prague, Czech Republic, 16–18 October 2013. Compliance with Ethical Standards Funding No sources of funding were received for the preparation of this review. Conflicts of interest Mirko Petrovic, Annemie Somers, and Graziano Onder declare no conflicts of interest in regard to this review.

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