Evaluating the costs of adverse drug events in hospitalized patients: a systematic review.

BACKGROUND: Adverse drug events (ADEs) are not only a safety and quality of care issue for patients, but also an economic issue with significant costs. Because they often occur during hospital stays, it is necessary to accurately quantify the costs of ADEs. This review aimed to investigate the methods to calculate these costs, and to characterize their nature. METHODS: A systematic literature review was conducted to identify methods used to assess the cost of ADEs on Medline, Web of Science and Google Scholar. Original articles published from 2017 to 2022 in English and French were included. Economic evaluations were included if they concerned inpatients. RESULTS: From 127 studies screened, 20 studies were analyzed. There was a high heterogeneity in nature of costs, methods used, values obtained, and time horizon chosen. A small number of studies considered non-medical (10%), indirect (20%) and opportunity costs (5%). Ten different methods for assessing the cost of ADEs have been reported and nine studies did not explain how they obtained their values. CONCLUSIONS: There is no consensus in the literature on how to assess the costs of ADEs, due to the heterogeneity of contexts and the choice of different economic perspectives. Our study adds a well-deserved overview of the existing literature that can be a solid lead for future studies and method implementation. TRIAL REGISTRATION: PROSPERO registration CRD42023413071.

Clinical impact of pharmaceutical consultations in patients treated for chronic obstructive pulmonary disease: Study protocol for a randomized controlled trial (BPCObs study).

Background: Chronic obstructive pulmonary disease (COPD) is an irreversible chronic respiratory disease which outcome depends on medication adherence. Pharmacists may increase this adherence by advising patients on inhaler devices proper use. This paper presents the protocol for a randomized controlled trial, which assesses impact of pharmaceutical consultations on COPD exacerbations, medical care, adherence to inhaler devices and quality of life. Methods: This trial will include 226 COPD patients treated with inhaler devices: 94 in a control group, 66 receiving a pharmaceutical consultation at hospital and 66 receiving up to 12 pharmaceutical consultations corresponding to dispensing at their community pharmacy. The aim of these interventions is to inform patients about COPD medication, train them in the use of inhaler devices and improve adherence. Patients included by hospital pharmacist will be randomly assigned to the control and hospital experimental groups. Community pharmacists (CP) will include patients in the experimental community group. CPs will follow-up all study patients for 12 months. Primary outcome is the mean number of COPD exacerbations. Secondary outcomes include number of medical consultations, emergency visits and hospitalizations, patients' adherence devices and quality of life. Discussion: This is the first French trial which assesses both hospital and community pharmaceutical interventions on COPD patients. Study limitations include recruitment and CP adherence to follow-up. Indeed, the success of this trial depends on the willingness of CPs to collect the data. This work is the first step towards building a network of CPs trained for clinical research. Trial registration: Clinicaltrials.gov, NCT03704545. Registered on October 12th, 2018. https://clinicaltrials.gov/ct2/show/NCT03704545?cond=COPD&cntry=FR&city=nimes&draw=2&rank=1.

Intervention of pharmacist included in multidisciplinary team to reduce adverse drug event: a qualitative systematic review.

BACKGROUND: Preventable harm in healthcare is a growing public health challenge. In addition to the economic costs of safety failures, adverse drug events (ADE) may lead to complication or even death. Multidisciplinary care team involving a pharmacist appears to be an adequate response to prevention of adverse drug event. This qualitative systematic review aims to identify and describe multidisciplinary planned team-based care involving at least one pharmacist to limit or prevent adverse drug events in the adult patients. METHODS: To determine the type of interprofessional collaboration to prevent adverse drug event in which a pharmacist was involved, we conducted a qualitative systematic review of the literature of randomized controlled trials. Two independent reviewers screened trials in three databases: Medline, Web of Science, ScienceDirect. Prospective studies of at least three different health professionals' interventions, one of whom was a pharmacist in the last five years were included. Two reviewers performed data extraction and quality appraisal independently. We used TIDieR checklist to appraise articles quality. RESULTS: In total 803 citations were retrieved, 34 were analysed and 16 full-text articles were reviewed. Only 3 studies published an implementation evaluation. More than half of the interventions (62%) targeted elderly patients including 6 whom lived in nursing homes. Studies outcomes were heterogeneous, and we did not perform a statistical analysis of the impact of these interventions. Most teams are composed of a physician/pharmacist/nurse trio (94%; 100%; 88%). Half of the teams were composed of the primary care physician. Other professionals were included such as physical therapists (25%), social worker (19%), occupational therapists (12%), and community health educator (6%). Multidisciplinary medication review was the most common intervention and was generally structured in four steps: data collection and baseline assessment, appraisal report by health professionals, a multidisciplinary medication review meeting and a patient follow-up. CONCLUSIONS: The most common multidisciplinary intervention to prevent ADE in the adult population is the multidisciplinary drug review meeting at least the physician/pharmacist/nurse trio. Interventions target mostly elderly people in nursing homes, although complex chronic patients could benefit from this type of assessment. TRIAL REGISTRATION: PROSPERO registration: CRD42022334685.

[The "Gradation instruction" of care: An opportunity to integrate clinical pharmacy activities in the cancer patient journey]. / Instruction de gradation des soins : une opportunité pour ancrer les activités de pharmacie clinique dans le parcours des patients atteints de cancer.

The ten-year cancer control strategy launched in 2021 highlights the structuring of supportive care as a strong axis to limit the side effects of treatments and simplify the patient's journeys. On the other hand, the "Gradation instruction" published in 2020, introduced new invoicing rules for outpatient hospital wards, which facilitates the coordinated interventions of several health professionals (medical, paramedical, or socio-educational) around patients. Among these professionals, the pharmacist has a particular role, inside the multidisciplinary oncology teams, since cancer oral therapies require therapeutic adherence and a continuum of care with retail pharmacists. Until now, these clinical pharmaceutical activities, which include carrying out medication reviews, developing personalized pharmaceutical plans and conducting pharmaceutical interviews with patients, have struggled to develop in a sustainable manner due to a lack of funding in hospitals. Finally, the "gradation instruction" represents a real opportunity to support clinical pharmacy actions, particularly in outpatient hospital wards. In order to save time for hospital teams wishing to initiate or consolidate these activities, we should consider points of vigilance and facilitating factors.

What Is the Medication Iatrogenic Risk in Elderly Outpatients for Chronic Pain?

PURPOSE: Medication iatrogeny is a major public health problem that increases as the population ages. Therapeutic escalation to control pain and associated disorders could increase polypharmacy and iatrogeny. This study aimed to characterize the medication iatrogenic risk of elderly outpatients with chronic pain. METHODS: This was a prospective cohort study recruiting patients 65 years or older with chronic pain. A medication iatrogenic assessment was performed based on the best possible medication history to record risk of adverse drug events (Trivalle score), STOPP (Screening Tool of Older Person's Prescriptions)/START (Screening Tool to Alert doctors to Right Treatment) criteria, and potentially inappropriate medications. RESULTS: We recruited 100 patients with an average age of 71 years. The median number of medications before pain consultation was 8 (interquartile range = [7;11]). Trivalle score showed that 43% of patients were at moderate or high medication iatrogenic risk. Before consultation, 79% and 75% of patients had at least 1 STOPP or START criterion on their orders, respectively. One-third of orders mentioned benzodiazepine prescribed for more than 4 weeks. At least 1 potentially inappropriate medication was prescribed for 54% of the patients, with a median of 1 per patient (interquartile range = [0;1]). A combination of several anticholinergics was prescribed in 23% of patients. CONCLUSION: Elderly patients with chronic pain are at risk of medication iatrogeny. Preventive measures as multidisciplinary medication review could reduce the iatrogenic risk in these outpatients.This study is registered at clinicaltrials.gov as NCT04006444 on July 3, 2019.

Impact of a pharmacist and geriatrician medication review on drug-related problems in older outpatients with cancer.

OBJECTIVES: Older patients with cancer have increased risk for comorbidity, polypharmacy (PP) and drug related problems (DRP). The aim of this study was to assess the effect of a clinical pharmacist and geriatrician medication review (MR) among older outpatients with cancer to optimize management of comorbidities during comprehensive geriatric assessment (CGA). MATERIAL AND METHODS: We conducted a single-center prospective study among older outpatients with cancer (≥75 years). A pharmacist consultation was added into CGA process. The clinical pharmacist detected and assessed PP and DRP such as potentially inappropriate medications (PIM) according to the Laroche French list and STOPP criteria, START criteria and adverse drug events (ADE) risk. After a multidisciplinary MR, the proposals for prescription modification were sent to general practitioners (GPs). RESULTS: Fifty-one consenting patients were recruited between May 2016 and March 2017, with a median age of 83 years. Prevalence of PP was 80.4%. 165 DRP were detected among 86% patients (median number of DRP = 3.0): 19.4% were misuse, 43.6% underuse, and 37.0% overuse. A significant decrease was observed in prevalence of PIM use (Laroche: 31.4% versus 5.9%, p = 0.002), START criteria (66.7% to 5.9%; P < 0.001) and ADE score (4.0 before MR versus 2.0 after, p = 0.023). A trend was observed for a lower number of medications (10.0 versus 8.0, p = 0.092) and on STOPP criteria prevalence (56.9% versus 31.4%, p = 0.12). CONCLUSION: A clinical pharmacist and a geriatrician MR is effective to detect and reduce DRP in older outpatients with cancer.

Effectiveness of a multicomponent pharmacist intervention at hospital discharge for drug-related problems: A cluster randomised cross-over trial.

AIMS: The aim of this study was to assess whether a pharmacist intervention associating medication reconciliation at discharge with a link to the community pharmacist reduces drug-related problems (DRP) in adult patients during the 7 days after hospital discharge in 22 university or general hospitals in France. METHODS: We conducted a cluster randomised cross-over superiority trial with hospital units as the cluster unit. The primary outcome was a composite of any kind of DRP (prescription/dispensation, patient error or gap due to no medication available) during the 7 days after discharge, assessed by phone with the patient and community pharmacist. Among secondary outcomes, we studied self-reported unplanned hospitalisations at day 35 after discharge and severe iatrogenic problems. RESULTS: A total of 1092 patients were enrolled in 48 units (538 in the experimental periods and 554 in the control periods). Three patients refused to have their data analysed and were excluded from the analyses. As compared with usual care, the pharmacist intervention led to a lower proportion of patients with at least one DRP (44.0% vs 50.6%; odds ratio [OR] 0.77, 95% confidence interval [CI] 0.61-0.98) and severe iatrogenic problems (5.2% vs 8.7%; OR 0.57, 95% CI 0.35-0.93) but no significant difference in unplanned hospitalisations at day 35 (5.8% vs 4.5%; OR 1.46, 95% CI 0.91-2.35). CONCLUSION: Medication reconciliation associated with communication between the hospital and community pharmacist may decrease patient exposure to DRP and severe iatrogenic problems but not unplanned hospitalisation. However, this intervention could be recommended in health policies to improve drug management.

Medication burden and inappropriate prescription risk among elderly with advanced chronic kidney disease.

BACKGROUND: Elderly patients with chronic kidney disease (CKD) frequently present comorbidities that put them at risk of polypharmacy and medication-related problems. This study aims to describe the overall medication profile of patients aged ≥75 years with advanced CKD from a multicenter French study and specifically the renally (RIMs) and potentially inappropriate-for-the-elderly medications (PIMs) that they take. METHODS: This is a cross-sectional analysis of medication profiles of individuals aged ≥75 years with eGFR < 20 ml/min/1.73 m2 followed by a nephrologist, who collected their active prescriptions at the study inclusion visit. Medication profiles were first analyzed according to route of administration, therapeutic classification. Second, patients were classified according to their risk of potential medication-related problems, based on whether the prescription was a RIM or a PIM. RIMs and PIMs have been defined according to renal appropriateness guidelines and to Beer's criteria in the elderly. RIMs were subclassified by 4 types of category: (a) contraindication; (b) dose modification is recommended based on creatinine clearance (CrCl); (c) dose modification based on CrCl is not recommended but a maximum daily dose is mentioned, (d) no specific recommendations based on CrCl: "use with caution", "avoid in severe impairment", "careful monitoring of dose is required" "reduce the dose". RESULTS: We collected 5196 individual medication prescriptions for 556 patients, for a median of 9 daily medications [7-11]. Antihypertensive agents, antithrombotics, and antianemics were the classes most frequently prescribed. Moreover, 77.0% of patients had at least 1 medication classified as a RIM. They accounted 31.3% of the drugs prescribed and 9.25% was contraindicated drugs. At least 1 PIM was taken by 57.6 and 45.5% of patients had at least one medication classified as RIM and PIM. The prescriptions most frequently requiring reassessment due to potential adverse effects were for proton pump inhibitors and allopurinol. The PIMs for which deprescription is especially important in this population are rilmenidine, long-term benzodiazepines, and anticholinergic drugs such as hydroxyzine. CONCLUSION: We showed potential drug-related problems in elderly patients with advanced CKD. Healthcare providers must reassess each medication prescribed for this population, particularly the specific medications identified here. TRIAL REGISTRATION: NCT02910908.

Impact of collaborative pharmaceutical care on in-patients' medication safety: study protocol for a stepped wedge cluster randomized trial (MEDREV study).

BACKGROUND: Clinical pharmaceutical care has long played an important role in the improvement of healthcare safety. Pharmaceutical care is a collaborative care approach, implicating all the actors of the medication circuit in order to prevent and correct drug-related problems that can lead to adverse drug events. The collaborative pharmaceutical care performed during patients' hospitalization requires two mutually reinforcing activities: medication reconciliation and medication review. Until now, the impact of the association of these two activities has not been clearly studied. METHODS: This is a multicentric stepped wedge randomized study involving six care units from six French University Hospitals (each unit corresponding to a cluster) over seven consecutive 14-day periods. Each hospital unit will start with a control period and switch to an experimental period after a randomized number of 14-day periods. Patients aged at least 65 years hospitalized in one of the participating care units and having given their consent to be called for a 30-day and 90-day follow-up can be enrolled. For each 14-day period, 15 patients will be recruited in each care unit to obtain a total of 630 patients enrolled in all centers. Patients with a hospital stay of more than 21 days will be excluded. During the control period, there will be no clinical pharmacist in the care unit, whereas during the experimental period a clinical pharmacist will perform medication reconciliation and review with the healthcare team. The primary outcome will assess the impact of collaborative pharmaceutical care on preventable medication error rate. The secondary outcomes will evaluate the clinical impact of the strategy, the acceptance rate of pharmaceutical interventions, the induced and avoided costs of the strategy (cost-consequence analysis), and the healthcare team's satisfaction. DISCUSSION: This study will assess the impact of collaborative pharmaceutical care associating medication reconciliation and review at patient admission to hospital in terms of preventable medication error rate and costs. This activity will prevent and correct medication errors arising earlier in the hospitalization. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02598115 . Registered on 4 November 2015.

Improving medication safety: Development and impact of a multivariate model-based strategy to target high-risk patients.

BACKGROUND: Preventive strategies to reduce clinically significant medication errors (MEs), such as medication review, are often limited by human resources. Identifying high-risk patients to allow for appropriate resource allocation is of the utmost importance. To this end, we developed a predictive model to identify high-risk patients and assessed its impact on clinical decision-making. METHODS: From March 1st to April 31st 2014, we conducted a prospective cohort study on adult inpatients of a 1,644-bed University Hospital Centre. After a clinical evaluation of identified MEs, we fitted and internally validated a multivariate logistic model predicting their occurrence. Through 5,000 simulated randomized controlled trials, we compared two clinical decision pathways for intervention: one supported by our model and one based on the criterion of age. RESULTS: Among 1,408 patients, 365 (25.9%) experienced at least one clinically significant ME. Eleven variables were identified using multivariable logistic regression and used to build a predictive model which demonstrated fair performance (c-statistic: 0.72). Major predictors were age and number of prescribed drugs. When compared with a decision to treat based on the criterion of age, our model enhanced the interception of potential adverse drug events by 17.5%, with a number needed to treat of 6 patients. CONCLUSION: We developed and tested a model predicting the occurrence of clinically significant MEs. Preliminary results suggest that its implementation into clinical practice could be used to focus interventions on high-risk patients. This must be confirmed on an independent set of patients and evaluated through a real clinical impact study.

Improving Patient's Primary Medication Adherence: The Value of Pharmaceutical Counseling.

Quality of transitions of care is one of the first concerns in patient safety. Redesigning the discharge process to incorporate clinical pharmacy activities could reduce the incidence of postdischarge adverse events by improving medication adherence. The present study investigated the value of pharmacist counseling sessions on primary medication adherence after hospital discharge.This study was conducted in a 1844-bed hospital in France. It was divided in an observational period and an interventional period of 3 months each. In both periods, ward-based clinical pharmacists performed medication reconciliation and inpatient follow-up. In interventional period, initial counseling and discharge counseling sessions were added to pharmaceutical care. The primary medication adherence was assessed by calling community pharmacists 7 days after patient discharge.We compared the measure of adherence between the patients from the observational period (n = 201) and the interventional period (n = 193). The rate of patients who were adherent increased from 51.0% to 66.7% between both periods (P < 0.01). When discharge counseling was performed (n = 78), this rate rose to 79.7% (P < 0.001). The multivariate regression performed on data from both periods showed that age of at least 78 years old, and 3 or less new medications on discharge order were predictive factors of adherence. New medications ordered at discharge represented 42.0% (n = 1018/2426) of all medications on discharge order. The rate of unfilled new medications decreased from 50.2% in the observational period to 32.5% in the interventional period (P < 10). However, patients included in the observational period were not significantly more often readmitted or visited the emergency department than the patients who experienced discharge counseling during the interventional period (45.3% vs. 46.2%; P = 0.89).This study highlights that discharge counseling sessions are essential to improve outpatients' primary medication adherence. We identified predictive factors of primary nonadherence in order to target the most eligible patients for discharge counseling sessions. Moreover, implementation of discharge counseling could be facilitated by using Health Information Technology to adapt human resources and select patients at risk of nonadherence.

Impact of admission medication reconciliation performed by clinical pharmacists on medication safety.

BACKGROUND: Many activities contribute to reduce drug-related problems. Among them, the medication reconciliation (MR) is used to compare the best possible medication history (BPMH) and the current admission medication order (AMO) to identify and solve unintended medication discrepancies (UMD). This study aims to assess the impact of the implementation of admission MR by clinical pharmacists on UMD. METHOD: This prospective study was carried out in two units of general medicine and infectious and tropical diseases in a 1844-bed French hospital. A retroactive MR performed in an observational period was compared to a proactive MR realized in an interventional period. We used a logistic regression to identify risk factors of UMD. RESULTS: During both periods, 394 patients were enrolled and 2,725 medications were analyzed in the BPMH. Proactive MR reduced the percentage of patients with at least one UMD compared with retroactive process (respectively 2.1% vs. 45.8%, p<0.001). Patients with at least one UMD during both periods were older compared to patients without UMD (79 vs. 72, p<0.005) and had more medications at admission (7 vs. 6, p<0.0001). UMD occur 38 times more often when there is no clinical pharmacist intervention. Among the 226 UMD detected in both periods, 42% would have required monitoring or intervention to preclude harm, and 10% had potential harm to the patient and 2% were life threatening. CONCLUSION: Proactive MR performed by clinical pharmacists is an acute process of detection and correction of UMD, but it requires a lot of human resources.