Financial impact of medication reviews by clinical pharmacists to reduce in-hospital adverse drug events: a return-on-investment analysis.

BACKGROUND: Adverse drug events contribute to rising health care costs. Clinical pharmacists can reduce their risks by identifying and solving drug-related problems (DRPs) through medication review. AIM: To develop an economic model to determine whether medication reviews performed by clinical pharmacists could lead to a reduction in health care costs associated with the prevention of potential adverse drug events. METHOD: Two pharmacists performed medication reviews during ward rounds in an internal medicine setting over one year. Avoided costs were estimated by monetizing five categories of DRPs (improper drug selection, drug interactions, untreated indications, inadequate dosages, and drug use without an indication). An expert panel assessed potential adverse drug events and their probabilities of occurrence for 20 randomly selected DRPs in each category. The costs of adverse drug events were extracted from internal hospital financial data. A partial economic study from a hospital perspective then estimated the annual costs avoided by resolving DRPs identified by 3 part-time clinical pharmacists (0.9 full-time equivalent) from 2019 to 2020. The return on investment (ROI) of medication review was calculated. RESULTS: The estimated annual avoided costs associated with the potential adverse drug events induced by 676 DRPs detected was € 304,170. The cost of a 0.9 full-time equivalent clinical pharmacist was € 112,408. Extrapolated to 1 full-time equivalent, the annual net savings was € 213,069 or an ROI of 1-1.71. Sensitivity analyses showed that the economic model was robust. CONCLUSION: This economic model revealed the positive financial impact and favorable return on investment of a medication review intervention performed by clinical pharmacists. These findings should encourage the future deployment of a pharmacist-led adverse drug events prevention program.

Electronic monitoring of potential adverse drug events related to lopinavir/ritonavir and hydroxychloroquine during the first wave of COVID-19.

During Switzerland's first wave of COVID-19, clinical pharmacy activities during medical rounds in Geneva University Hospitals were replaced by targeted remote interventions. We describe using the electronic PharmaCheck system to screen high-risk situations of adverse drug events (ADEs), particularly targeting prescriptions of lopinavir/ritonavir (LPVr) and hydroxychloroquine (HCQ) in the presence of contraindications or prescriptions outside institutional guidelines. Of 416 patients receiving LPVr and/or HCQ, 182 alerts were triggered for 164 (39.4%) patients. The main associated risk factors of ADEs were drug-drug interactions, QTc interval prolongation, electrolyte disorder and inadequate LPVr dosage. Therapeutic optimisation recommended by a pharmacist or proposals for additional monitoring were accepted in 80% (n=36) of cases. Combined with pharmacist contextualisation to the clinical context, PharmaCheck made it possible to successfully adapt clinical pharmacist activities by switching from a global to a targeted analysis mode in an emergency context.

Development and retrospective evaluation of a clinical decision support system for the efficient detection of drug-related problems by clinical pharmacists.

BACKGROUND: Clinical decision support systems (CDSS) can help identify drug-related problems (DRPs). However, the alert specificity remains variable. Defining more relevant alerts for detecting DRPs would improve CDSS. AIM: Develop electronic queries that assist pharmacists in conducting medication reviews and an assessment of the performance of this model to detect DRPs. METHOD: Electronic queries were set up in CDSS using "triggers" from electronic health records: drug prescriptions, laboratory values, medical problems, vital signs, demographics. They were based on a previous study where 315 patients admitted in internal medicine benefited from a multidisciplinary medication review (gold-standard) to highlight potential DRPs. Electronic queries were retrospectively tested to assess performance in detecting DRPs revealed with gold-standard. For each electronic query, sensitivity, specificity, positive and negative predictive value were computed. RESULTS: Of 909 DRPs, 700 (77.8%) were used to create 366 electronic queries. Electronic queries correctly detected 77.1% of DRPs, median sensitivity and specificity reached 100.0% (IQRs, 100.0%-100.0%) and 99.7% (IQRs, 97.0%-100.0%); median positive predictive value and negative predictive value reached 50.0% (IQRs, 12.5%-100.0%) and 100.0% (IQRs, 100.0%-100.0%). Performances varied according to "triggers" (p < 0.001, best performance in terms of predictive positive value when exclusively involving drug prescriptions). CONCLUSION: Electronic queries based on electronic heath records had high sensitivity and negative predictive value and acceptable specificity and positive predictive value and may contribute to facilitate medication review. Implementing some of these electronic queries (the most effective and clinically relevant) in current practice will allow a better assessment of their impact on the efficiency of the clinical pharmacist.

Patients' perceptions of conflicting information on chronic medications: a prospective survey in Switzerland.

OBJECTIVE: The number of patients with chronic diseases and subsequent visits to various healthcare professionals has been rising over the past decades, exposing patients to potential risks of receiving conflicting medication information. This study aims to investigate the prevalence of conflicting information on medications perceived by chronic patients in Switzerland and to understand its impact on patients' medication self-management and navigation in the healthcare system. PARTICIPANTS: This cross-sectional study included adult patients taking at least one prescribed medication for at least 6 months, who had visited at least two physicians in the past 3 months. MAIN OUTCOME MEASURES: Data on patients' perceptions of conflicting information were collected in person through a 17-item questionnaire available on paper and electronically with four domains: (1) whether the patient had perceived any conflicting information, (2) categories of conflicting information, (3) impact and (4) sources involved in the conflicting information. RESULTS: Of the 405 included patients, 47% perceived conflicting information related to one or more medication topics including indication, schedule, dosage, risk, severity or duration of side effects. Patients who perceived conflicting information were prescribed more drugs than those perceiving no conflicting information (p<0.01). Consequently, 65% of the participants modified their navigation of the healthcare system and 34% reported medication non-adherence. General practitioners (82%), specialist physicians (74%) and pharmacists (49%) were the healthcare professionals most often involved in conflicting information. Experience with the medication, its package insert and significant others were more frequently involved in conflicting information than internet or social media. CONCLUSION: Nearly half the patients in our study perceived conflicting information in the outpatient healthcare system, which can decrease medication effectiveness and pose safety issues. This issue is widely overlooked and unaddressed. Consistency of information among healthcare providers in partnership with patients should be reinforced through guidelines and new models of interprofessional care.

Development and assessment of PharmaCheck: an electronic screening tool for the prevention of twenty major adverse drug events.

BACKGROUND: Adverse drug events (ADEs) can be prevented by deploying clinical decision support systems (CDSS) that directly assist physicians, via computerized order entry systems, and clinical pharmacists performing medication reviews as part of medical rounds. However, physicians using CDSS are known to be exposed to the alert-fatigue phenomenon. Our study aimed to assess the performance of PharmaCheck-a CDSS to help clinical pharmacists detect high-risk situations with the potential to lead to ADEs-and its impact on clinical pharmacists' activities. METHODS: Twenty clinical rules, divided into four risk classes, were set for the daily screening of high-risk situations in the electronic health records of patients admitted to our General Internal Medicine Department. Alerts to clinical pharmacists encouraged them to telephone prescribers and suggest any necessary treatment adjustments. PharmaCheck's performance was assessed using the intervention's positive predictive value (PPV), which characterizes the proportion of interventions for each alert triggered. PharmaCheck's impact was assessed by considering clinical pharmacists as a filter for ruling out futile alerts and by comparing the final clinical PPV with a pharmacist (the proportion of interventions that led to a change in the medical regimen) to the final clinical PPV without a pharmacist. RESULTS: Over 132 days, 447 alerts were triggered for 383 patients, leading to 90 interventions (overall intervention PPV = 20.1%). By risk class, intervention PPVs made up 26.9% (n = 65/242) of abnormal laboratory value alerts, 3.1% (4/127) of alerts for contraindicated medications or medications to be used with caution, 28.2% (20/71) of drug-drug interaction alerts, and 14.3% (1/7) of inadequate mode of administration alerts. Clinical PPVs reached 71.0% (64/90) when pharmacists filtered alerts and 14% (64/242) if they were not doing it. CONCLUSION: PharmaCheck enabled clinical pharmacists to improve their traditional processes and broaden their coverage by focusing on 20 high-risk situations. Alert management by pharmacists seemed to be a more effective way of preventing risky situations and alert-fatigue than a model addressing alerts to physicians exclusively. Some fine-tuning could enhance PharmaCheck's performance by considering the information quality of triggers, the variability of clinical settings, and the fact that some prescription processes are already highly secured.

PIM-Check: development of an international prescription-screening checklist designed by a Delphi method for internal medicine patients.

OBJECTIVES: Potentially inappropriate medication (PIM) occurs frequently and is a well-known risk factor for adverse drug events, but its incidence is underestimated in internal medicine. The objective of this study was to develop an electronic prescription-screening checklist to assist residents and young healthcare professionals in PIM detection. DESIGN: Five-step study involving selection of medical domains, literature review and 17 semistructured interviews, a two-round Delphi survey, a forward/back-translation process and an electronic tool development. SETTING: 22 University and general hospitals from Canada, Belgium, France and Switzerland. PARTICIPANTS: 40 physicians and 25 clinical pharmacists were involved in the study.Agreement with the checklist statements and their usefulness for healthcare professional training were evaluated using two 6-point Likert scales (ranging from 0 to 5). PRIMARY AND SECONDARY OUTCOME MEASURES: Agreement and usefulness ratings were defined as: >65% of the experts giving the statement a rating of 4 or 5, during the first Delphi-round and >75% during the second. RESULTS: 166 statements were generated during the first two steps. Mean agreement and usefulness ratings were 4.32/5 (95% CI 4.28 to 4.36) and 4.11/5 (4.07 to 4.15), respectively, during the first Delphi-round and 4.53/5 (4.51 to 4.56) and 4.36/5 (4.33 to 4.39) during the second (p<0.001). The final checklist includes 160 statements in 17 medical domains and 56 pathologies. An algorithm of approximately 31 000 lines was developed including comorbidities and medications variables to create the electronic tool. CONCLUSION: PIM-Check is the first electronic prescription-screening checklist designed to detect PIM in internal medicine. It is intended to help young healthcare professionals in their clinical practice to detect PIM, to reduce medication errors and to improve patient safety.

Muropeptide signature of inhibitors of protein synthesis correlates with ß-lactam synergism against methicillin-resistant Staphylococcus aureus.

Quinupristin/dalfopristin (Q/D) and ß-lactams interact positively against methicillin-resistant Staphylococcus aureus (MRSA). The effect extends to other inhibitors of protein synthesis, but not to inhibitors of polynucleotide synthesis or assembly, or to Q/D plus non-ß-lactam cell wall inhibitors. Moreover, electron microscopy studies have correlated this effect with a thickened cell wall. In this study, we sought to determine whether inhibitors of protein synthesis might produce a specific peptidoglycan muropeptide signature that would correlate with their positive ß-lactam interaction. The muropeptides of six S. aureus isolates (three methicillin-susceptible and three MRSA) were analysed using high-performance liquid chromatography and mass spectrometry. Exposure to 0.25× the minimum inhibitory concentration of inhibitors of protein synthesis consistently produced three main alterations irrespective of methicillin resistance: (i) an increase in peak 12 (a cyclic dimer of glycine-containing disaccharide-tetrapeptide); (ii) an increase in poorly resolved late-eluting materials; and (iii) a decrease in peak 1 (a disaccharide-pentapeptide). Eventually, the rate of autolysis was also decreased, supporting the structural alteration of the peptidoglycan. Other drug classes did not produce these anomalies. An increase in peak 12 was also observed in staphylococci treated with fosfomycin, which decreases expression of the native penicillin-binding protein (PBP) 2 and 4. Parallel blockage of normal PBPs with ß-lactams abolished the anomalies, indicating that they resulted from altered function of native PBPs. This underlines the potential of inhibiting both protein synthesis and transpeptidation simultaneously and suggests that such a drug combination strategy might be efficaciously exploited.

[Potentially inappropriate medications in geriatrics: Which tools to detect them?] / Prescriptions médicamenteuses potentiellement inappropriées en gériatrie : quels outils utiliser pour les détecter ?

BACKGROUND: Potentially inappropriate prescriptions include over-prescription, which refers to prescription of more drugs than clinically needed, mis-prescription which refers to incorrect prescription of a drug that is needed (as per drug, dose, drug interactions, duration of therapy, duplication, follow-up, etc.) and under-prescription which stands for failure to prescribe drugs that are needed. They are associated with adverse drug events, increased use of health-care services, morbimortality and health-care costs, and poorer quality of life. Due to polymorbidity and polypharmacy, potentially inappropriate prescription is common among the elderly. In the last 2 decades, explicit indicators to detect inappropriate prescriptions were developed in geriatrics. OBJECTIVE: The aim of this review is to summarize, compare and critically review existing explicit criteria. DOCUMENTARY SOURCES AND STUDY SELECTION: We conducted a systematic literature search in PubMed, Embase, Cochrane Library and Google Scholar, from January 1991 to November 2015. The following keywords were used: "("inappropriate prescribing" [MeSH Terms] OR "medication errors" [MeSH Terms] AND "potentially inappropriate medications" [MeSH Terms] AND "elderly" [MeSH All field] AND "explicit criteria" [MeSH Terms])". Articles describing the development of new list of explicit indicators dedicated to geriatrics, in English and in French, were included in this review. Their characteristics, organization, content, and assessments of their validity and of the optimal tool for geriatrics are presented. RESULTS: Fourteen lists of explicit indicators were included in the review. An organization based on physiological systems and pathologies, as observed in ACOVE, 5th version of Beers criteria and STOPP/START enables quick application in general practice. A low overlap among criteria was observed between tools. This may be due to a lack of completeness for some tools. Mimica, ACOVE, PIEA, and STOPP/START are the most exhaustive ones, only the last three addressing the under-prescription issue. Finally, the ability to detect and reduce inappropriate prescriptions has only been evaluated for few tools; STOPP/START is the only one, which has demonstrated its ability to reduce them in a prospective study.

Drug-related problems identification in general internal medicine: The impact and role of the clinical pharmacist and pharmacologist.

BACKGROUND: Patients admitted to general internal medicine wards might receive a large number of drugs and be at risk for drug-related problems (DRPs) associated with increased morbidity and mortality. This study aimed to detect suboptimal drug use in internal medicine by a pharmacotherapy evaluation, to suggest treatment optimizations and to assess the acceptance and satisfaction of the prescribers. METHODS: This was a 6-month prospective study conducted in two internal medicine wards. Physician rounds were attended by a pharmacist and a pharmacologist. An assessment grid was used to detect the DRPs in electronic prescriptions 24h in advance. One of the following interventions was selected, depending on the relevance and complexity of the DRPs: no intervention, verbal advice of treatment optimization, or written consultation. The acceptance rate and satisfaction of prescribers were measured. RESULTS: In total, 145 patients were included, and 383 DRPs were identified (mean: 2.6 DRPs per patient). The most frequent DRPs were drug interactions (21%), untreated indications (18%), overdosages (16%) and drugs used without a valid indication (10%). The drugs or drug classes most frequently involved were tramadol, antidepressants, acenocoumarol, calcium-vitamin D, statins, aspirin, proton pump inhibitors and paracetamol. The following interventions were selected: no intervention (51%), verbal advice of treatment optimization (42%), and written consultation (7%). The acceptance rate of prescribers was 84% and their satisfaction was high. CONCLUSION: Pharmacotherapy expertise during medical rounds was useful and well accepted by prescribers. Because of the modest allocation of pharmacists and pharmacologists in Swiss hospitals, complementary strategies would be required.

Impact of clinical decision support guidelines on therapeutic drug monitoring of gentamicin in newborns.

BACKGROUND: Our institution's gentamicin dosing and therapeutic drug monitoring (TDM) practices for newborns were suspected to be very heterogeneous. Once-daily dosing (ODD) or extended-interval dosing (EID) and trough concentration measurement were recommended. Clinical decision support guidelines were developed and implemented as clinical decision support in the computerized prescriber order entry system. Impact on dosing, TDM practices, and blood sampling were evaluated. METHODS: A 1-year retrospective historically controlled study before (April 2008-March 2009) and after the implementation of guidelines (January 2010-December 2010) for newborns (<30 days of life) receiving gentamicin. Blood concentrations (% of peak concentrations sampled, % of patients with zero or one concentration sampled, % of trough concentrations ≤1 mg/L) and dose regimen (ODD/EID) were compared between groups. Factors potentially associated with gentamicin concentration were analyzed (multivariate analysis). RESULTS: One hundred thirty-two (postguidelines) versus 102 (preguidelines) patients were included (median gestational age: 34.3 versus 35.8 weeks, P > 0.05). After implementation of the guidelines, an ODD/EID regimen was almost exclusively used (97.7% versus 61.6%, P < 0.001), the percentage of peak concentrations (0.9% versus 17.2%, P < 0.001) and the number of blood samples per patient (87.1% having 0 or 1 concentration measured versus 48.0, P < 0.001) sharply reduced. A significantly higher percentage of trough concentrations were ≤1 mg/L (68.5% versus 33.0%, P < 0.001). The probability of a trough concentration ≤1 mg/L increased with an ODD/EID regimen (odds ratio, 7.23; 95% confidence interval: 3.48-15.0, P < 0.001) and in the postguidelines group (odds ratio, 2.02; 95% confidence interval: 1.01-4.02, P = 0.045). CONCLUSIONS: Guideline implementation generated a sharp reduction in blood sampling. Clinical benefits of better gentamicin dosing and TDM practices were evident. Cost-effectiveness and clinical benefit of reduced blood sampling should be evaluated.

Evaluation of tools to prevent drug incompatibilities in paediatric and neonatal intensive care units.

OBJECTIVE: Intravenous drug administration in neonatal (NICU) and paediatric intensive care units (PICU) is critical because of poor venous access, polymedication, fluid restriction and low infusion rate. Risk is further increased by inadequate information on the physicochemical compatibility of drugs. Eight decision-supporting tools were hence evaluated to improve the detection of drug incompatibilities in paediatric wards. SETTING: NICU and PICU, University hospital. METHOD: Eight tools (Thériaque 2007, Stabilis 3, Perfysi 2 databases; KIK 3.0 software; Neofax 2007 handbook; King 2008 Guide, CHUV 9.0, pH 2007 cross-tables) were assessed by two pharmacists using 40 drug pairs (20 incompatible; 20 compatible) frequently prescribed in PICUs and NICUs. Trissel's 14th Ed. handbook served as the gold standard. Four criteria were evaluated (each with a maximum of 250 points): accuracy (sensitivity, specificity, positive and negative predictive values), completeness (number of drug pairs documented), comprehensiveness (presence of 16 different items), and applicability (by combining the time needed by 7 pharmacists to classify 5 drug pairs, plus an evaluation of their design, usefulness, reliability and ergonomics, using visual analogy scales). The percentage of non-compliant answers (NCA) was calculated for both the performing pharmacists and the tools. MAIN OUTCOME MEASURE: Global score of drug incompatibilities (accuracy + completeness + comprehensiveness + applicability). RESULTS: Thériaque obtained the best global score (840/1000 points), followed by pH (807), CHUV (803), Perfysi (776), Neofax (678), King Guide (642), Stabilis (584) and KIK (523), respectively. The highest scores were reached by Thériaque for accuracy (234/250); Thériaque and pH for completeness (200/250); Thériaque and Perfysi for comprehensiveness (218/250); and pH for applicability (298/250). The range of pharmacists' NCAs was between 9% (4/45 NCAs) and 33% (15/45), whereas that for drug pairs was between 10% (6/63) and 30% (19/63). The range of NCAs for tools was between 6% (2/35, pH) and 49% (18/35, Perfysi). CONCLUSIONS: Thériaque proved outstanding as a drug-incompatibility tool. However, all resources showed some shortcomings. The large ranges of pharmacists' NCAs shows that such an assessment is subject to different interpretations. Standard operating procedures for drug-incompatibility assessment should be implemented in drug-information centres. Tools with low NCA percentage, such as the pH or CHUV tables, may be useful for nurses in ICUs.

Practical evaluation of the drug-related problem management process in Swiss community pharmacies.

OBJECTIVE: To develop and evaluate a coding system integrated into pharmaceutical software to routinely report and assess the process of community pharmacists' interventions related to medical prescriptions. SETTING: A convenient sample of 20 Swiss community pharmacies. METHOD: Pharmacists documented their interventions concerning all drug-related problems (DRPs) related to medical prescriptions during four consecutive weeks in 2005. The coding system assesses each step of the DRP management process; that is, the type of problem, possible negative outcomes, pharmaceutical decisions, and individuals involved. In order to be comprehensive, the management process of technical problems related to prescriptions and clinical DRPs was analysed separately. MAIN OUTCOME MEASURE: DRP intervention rate and characterization of each step of the process. RESULTS: Of 38,663 prescriptions, 287 clinical DRPs required interventions. This corresponds to a mean intervention rate of 0.77% per pharmacy (SD = 0.61%). There was a large variability among pharmacies (0-2.6%). Most of the clinical DRPs were associated with dosage problems (n = 91) and drug-drug interactions (n = 45). The most frequent potential negative outcomes reported were quantitative inefficacy (n = 101) and quantitative safety (n = 94). Two-thirds of clinical DRPs required a prescription modification (n = 186), the most frequent being a change in dosage or drug regimen. In 110 interventions (38%), physicians were immediately contacted to take part in the decision. In 122 interventions (43%), pharmacists managed the interventions alone. However, in 55 interventions (19%), pharmacists managed the DRPs with the patient. From these 287 clinical interventions, 134 different codes were reported. Seven hundred and thirty-six technical problems related to prescriptions required intervention, which corresponded to a mean intervention rate of 1.90% per pharmacy. The main type of problem was a discrepancy with the medication record (n = 208). There were 494 instances that required a prescription modification. Pharmacists resolved 45% of all technical problems by themselves. CONCLUSION: The developed coding system could describe the management process for DRPs. The observed intervention rate and the frequency of steps involved were comparable to those previously observed for pharmacists' interventions. Data regarding the entire process used to manage drug-related problems can be useful in improving medication safety, education, and collaborative care.

Detection of live and antibiotic-killed bacteria by quantitative real-time PCR of specific fragments of rRNA.

Assessing bacterial viability by molecular markers might help accelerate the measurement of antibiotic-induced killing. This study investigated whether rRNA could be suitable for this purpose. Cultures of penicillin-susceptible and penicillin-tolerant (Tol1 mutant) Streptococcus gordonii were exposed to mechanistically different penicillin and levofloxacin. Bacterial survival was assessed by viable counts and compared to quantitative real-time PCR amplification of either the 16S rRNA genes or the 16S rRNA, following reverse transcription. Penicillin-susceptible S. gordonii lost > or =4 log(10) CFU/ml of viability over 48 h of penicillin treatment. In comparison, the Tol1 mutant lost < or =1 log(10) CFU/ml. Amplification of a 427-bp fragment of 16S rRNA genes yielded amplicons that increased proportionally to viable counts during bacterial growth but did not decrease during drug-induced killing. In contrast, the same 427-bp fragment amplified from 16S rRNA paralleled both bacterial growth and drug-induced killing. It also differentiated between penicillin-induced killing of the parent and the Tol1 mutant (> or =4 log(10) CFU/ml and < or =1 log(10) CFU/ml, respectively) and detected killing by mechanistically unrelated levofloxacin. Since large fragments of polynucleotides might be degraded faster than smaller fragments, the experiments were repeated by amplifying a 119-bp region internal to the original 427-bp fragment. The amount of 119-bp amplicons increased proportionally to viability during growth but remained stable during drug treatment. Thus, 16S rRNA was a marker of antibiotic-induced killing, but the size of the amplified fragment was critical for differentiation between live and dead bacteria.

Beta-lactams against methicillin-resistant Staphylococcus aureus.

Methicillin-resistant Staphylococcus aureus (MRSA) have developed resistance to virtually all non-experimental antibiotics. They are intrinsically resistant to beta-lactams by virtue of newly acquired low-affinity penicillin-binding protein 2A (PBP2A). Because PBP2A can build the wall when other PBPs are blocked by beta-lactams, designing beta-lactams capable of blocking this additional target should help solve the issue. Older molecules including penicillin G, amoxicillin and ampicillin had relatively good PBP2A affinities, and successfully treated experimental endocarditis caused by MRSA, provided that the bacterial penicillinase could be inhibited. Newer anti-PBP2A beta-lactams with over 10-fold greater PBP2A affinities and low minimal inhibitory concentrations were developed, primarily in the cephem and carbapenem classes. They are also very resistant to penicillinase. Most have demonstrated anti-MRSA activity in animal models of infection, and two--the carbapenem CS-023 and the cephalosporin ceftopibrole medocaril--have proceeded to Phase II and Phase III clinical evaluation. Thus, clinically useful anti-MRSA beta-lactams are imminent.