Prospective assessment of the frequency of and risk factors for bleeding events in patients treated with cefazolin.

PURPOSE: Major bleedings have been described with cefazolin. The objective was to determine the frequency of bleeding events in cefazolin-treated patients and to identify risk factors for these complications. METHODS: Monocenter prospective observational study of all consecutive cefazolin-treated patients. Patients benefited from a daily clinical assessment of bleedings and a twice-a-week blood sampling including hemostasis. Bleedings were classified according to the International Society on Thrombosis and Hemostasis classification: major, clinically relevant non-major bleedings (CRNMB) and minor bleedings. RESULTS: From September 2019 to July 2020, 120 patients were included, with a mean age of 59.4 (± 20.7) years; 70% of them (84/120) were men. At least 1 CRNMB or major bleeding were observed in 10% of the patients (12/120). Compared to patients with no or minor bleeding, patients with CRNMB or major bleeding were, upon start of cefazolin, more frequently hospitalized in an intensive care unit (7/12, 58.3%, vs. 12/108, 11.1%, P < 0.001, respectively) and receiving vitamin K antagonists (4/12, 33.3%, vs. 8/108, 7.4%, P = 0.019, respectively). After multivariate analysis, patients receiving vitamin K antagonists the day prior bleeding and/or treated for endocarditis were factors associated with an increased risk of CRNMB or major bleeding (odd ratio 1.36, confidence interval 95%, 1.06-1.76, P = 0.020 and 1.30, 1.06-1.61, P = 0.015, respectively). CONCLUSIONS: Bleeding events associated with cefazolin treatment are frequent. Close clinical monitoring should be performed for patients treated for endocarditis and/or receiving vitamin K antagonists. Hemostasis work-up could be restricted to these patients.

Hospital-based health technology assessment of innovative medical devices: insights from a nationwide survey in France.

OBJECTIVES: To better understand the process of hospital acquisition of innovative medical devices (MDs) and the hospital-based health technology assessment (HB-HTA) pathways in France, an in-depth study based on a quantitative approach is needed. The aim of the present study was to assess through a national survey how HB-HTA is currently implemented in French hospitals and to identify its level of formalization. METHODS: A quantitative online survey was conducted among hospitals performing HB-HTA in France, with a focus on the acquisition of innovative MDs for individual use. The survey, conducted between March and June 2022, was developed by a scientific board composed of members of the French-speaking Society for HB-HTA. RESULTS: Sixty-seven out of 131 surveyed hospitals with HB-HTA activities responded, including 29 university hospitals, 24 nonprofit private hospitals, and 14 local hospitals. Sixty-one respondents (91 percent) reported the existence of a process dedicated to evaluating innovative MDs; of these, 16 declared that their hospitals had a formalized unit with HB-HTA activity. These units were more frequently found in larger hospitals with more than 500 inpatient beds (n = 16, p = 0.0160) and in university hospitals (n = 12, p = 0.0158). No hospital reported any collaboration with HAS, the French national HTA agency. CONCLUSION: A diverse range of HB-HTA organizations with different structural levels exist in France for MD procurement linked to the category of hospitals. The study highlights the need for recognition of HB-HTA activity at the regulatory level in France and for direct collaboration between HTA activities performed at local and national levels.

Psychometric Properties of a Machine Learning-Based Patient-Reported Outcome Measure on Medication Adherence: Single-Center, Cross-Sectional, Observational Study.

BACKGROUND: Medication adherence plays a critical role in controlling the evolution of chronic disease, as low medication adherence may lead to worse health outcomes, higher mortality, and morbidity. Assessment of their patients' medication adherence by clinicians is essential for avoiding inappropriate therapeutic intensification, associated health care expenditures, and the inappropriate inclusion of patients in time- and resource-consuming educational interventions. In both research and clinical practices the most extensively used measures of medication adherence are patient-reported outcome measures (PROMs), because of their ability to capture subjective dimensions of nonadherence. Machine learning (ML), a subfield of artificial intelligence, uses computer algorithms that automatically improve through experience. In this context, ML tools could efficiently model the complexity of and interactions between multiple patient behaviors that lead to medication adherence. OBJECTIVE: This study aimed to create and validate a PROM on medication adherence interpreted using an ML approach. METHODS: This cross-sectional, single-center, observational study was carried out a French teaching hospital between 2021 and 2022. Eligible patients must have had at least 1 long-term treatment, medication adherence evaluation other than a questionnaire, the ability to read or understand French, an age older than 18 years, and provided their nonopposition. Included adults responded to an initial version of the PROM composed of 11 items, each item being presented using a 4-point Likert scale. The initial set of items was obtained using a Delphi consensus process. Patients were classified as poorly, moderately, or highly adherent based on the results of a medication adherence assessment standard used in the daily practice of each outpatient unit. An ML-derived decision tree was built by combining the medication adherence status and PROM responses. Sensitivity, specificity, positive and negative predictive values (NPVs), and global accuracy of the final 5-item PROM were evaluated. RESULTS: We created an initial 11-item PROM with a 4-point Likert scale using the Delphi process. After item reduction, a decision tree derived from 218 patients including data obtained from the final 5-item PROM allowed patient classification into poorly, moderately, or highly adherent based on item responses. The psychometric properties were 78% (95% CI 40%-96%) sensitivity, 71% (95% CI 53%-85%) specificity, 41% (95% CI 19%-67%) positive predictive values, 93% (95% CI 74%-99%) NPV, and 70% (95% CI 55%-83%) accuracy. CONCLUSIONS: We developed a medication adherence tool based on ML with an excellent NPV. This could allow prioritization processes to avoid referring highly adherent patients to time- and resource-consuming interventions. The decision tree can be easily implemented in computerized prescriber order-entry systems and digital tools in smartphones. External validation of this tool in a study including a larger number of patients with diseases associated with low medication adherence is required to confirm its use in analyzing and assessing the complexity of medication adherence.

Pharmaceutical consultation to detect drug interactions in patients treated with oral chemotherapies: A descriptive cross-sectional study.

OBJECTIVE: The development of oral chemotherapy (OC) has led to the recent establishment of multidisciplinary programmes involving pharmacists. We evaluated the utility of our local programme for detecting potential interactions with OCs, particularly drug-drug interactions (DDIs) and herbal-drug interactions (HDIs). METHODS: We performed a single-centre retrospective descriptive study of patients on OC attending a pharmaceutical consultation (PC) during a seven-month period. These consultations included the use of various complementary tools/databases to search for interactions. RESULTS: We analysed 308 treatments taken by 42 consecutive patients. Fifty-four potential interactions with OCs were detected in 26% (n = 79) of the treatments taken by patients: 46 DDIs (32 minor, 12 major, 2 contraindicated) and eight HDIs. Five interventions associated with interactions were suggested by pharmacists during the consultations (4 were taken into account by oncologists). The total mean time spent on each PC for an individual patient was 80 minutes (36 minutes of preparation, 44 minutes with the patient). CONCLUSION: This pilot study highlights the importance of studying interactions in such patients, and of the expertise of pharmacists for detecting interactions, which were found in more than one in four treatment lines. The further development of such activities, which already take up considerable amounts of time, is therefore warranted.

Effectiveness of a 'do not interrupt' vest intervention to reduce medication errors during medication administration: a multicenter cluster randomized controlled trial.

BACKGROUND: The use of a 'do not interrupt' vest during medication administration rounds is recommended but there have been no controlled randomized studies to evaluate its impact on reducing administration errors. We aimed to evaluate the impact of wearing such a vest on reducing such errors. The secondary objectives were to evaluate the types and potential clinical impact of errors, the association between errors and several risk factors (such as interruptions), and nurses' experiences. METHODS: This was a multicenter, cluster, controlled, randomized study (March-July 2017) in 29 adult units (4 hospitals). Data were collected by direct observation by trained observers. All nurses from selected units were informed. A 'Do not interrupt' vest was implemented in all units of the experimental group. A poster was placed at the entrance of these units to inform patients and relatives. The main outcome was the administration error rate (number of Opportunities for Error (OE), calculated as one or more errors divided by the Total Opportunities for Error (TOE) and multiplied by 100). RESULTS: We enrolled 178 nurses and 1346 patients during 383 medication rounds in 14 units in the experimental group and 15 units in the control group. During the intervention period, the administration error rates were 7.09% (188 OE with at least one error/2653 TOE) for the experimental group and 6.23% (210 OE with at least one error/3373 TOE) for the control group (p = 0.192). Identified risk factors (patient age, nurses' experience, nurses' workload, unit exposition, and interruption) were not associated with the error rate. The main error type observed for both groups was wrong dosage-form. Most errors had no clinical impact for the patient and the interruption rates were 15.04% for the experimental group and 20.75% for the control group. CONCLUSIONS: The intervention vest had no impact on medication administration error or interruption rates. Further studies need to be performed taking into consideration the limitations of our study and other risk factors associated with other interventions, such as nurse's training and/or a barcode system. TRIAL REGISTRATION: The PERMIS study protocol (V2-1, 11/04/2017) was approved by institutional review boards and ethics committees (CPP Ile de France number 2016-A00211-50, CNIL 21/03/2017, CCTIRS 11/04/2016). It is registered at ClinicalTrials.gov (registration number: NCT03062852 , date of first registration: 23/02/2017).

Conditional prescriptions of oral antihypertensive drugs for the management of hypertension urgencies in the inpatient setting: An observational study.

WHAT IS KNOWN AND OBJECTIVES: The management of hypertension urgencies during hospitalization may generally not necessitate urgent care. However, physicians frequently prescribe 'as needed' antihypertensive drugs for which administration is triggered by blood pressure thresholds. The lack of rationale for this hospital practice led us to study oral conditional antihypertensive (OCA) prescriptions. We aimed to estimate the prevalence of OCA prescriptions and to establish their characteristics. METHODS: In our institution, prescriptions are computerized. The study was retrospectively performed using a hospital clinical data warehouse over a 5-year period. RESULTS AND DISCUSSION: The prevalence of OCA prescriptions was 6.9% among subjects treated with an antihypertensive drug. The median duration of these prescriptions was 4 days, until the day of the patient discharge in 78.8% stays. The calcium channel inhibitors were the main (79.9%) pharmacological class prescribed, with mostly prescriptions of nicardipine. OCA prescriptions were associated with another antihypertensive medication in 58.8% of the prescriptions; for 19.3%, it was a medication belonging to the same pharmacological class than the OCA drug prescribed. Regarding the computerized drafting, 39.6% of the conditional prescriptions were considered uninterpretable. At least one administration by nurses concerned 65.1% of the OCA prescriptions. The mean SBP and DBP before the initiation of an OCA drug was 142.9 ± 28.2 and 75.8 ± 24.5 mm Hg, respectively, relative to 143.0 ± 24.9 and 77.6 ± 19.9 mm Hg after the initiation (P = .8 for SBP and P = .06 for DBP). WHAT IS NEW AND CONCLUSION: The originality of this study lies in the use of a clinical data warehouse to evaluate OCA prescriptions in hospital. These prescriptions are current, often uninterpretable and mostly ordered until patient discharge. Such drug orders could be associated with an increased risk of iatrogenic events and/or administration errors. This underlies the need for developing decision support tools and computerized protocols to manage hypertension urgencies.

Pharmaceutical interventions to improve safety of chemotherapy-treated cancer patients: A cross-sectional study.

PURPOSE: Cancer chemotherapy is a high-risk process. To improve patient safety, a systematic pharmaceutical analysis of chemotherapy prescriptions is performed in our institution. The aim of this study was to assess the impact of pharmaceutical interventions (PIs) on the safety of patient chemotherapy prescriptions. METHODS: This prospective cross-sectional study was conducted in an 800-bed university hospital with oncology departments. All chemotherapy prescriptions were included and PIs were collected prospectively during one month. The clinical impact of PIs was scored by an expert panel of oncologists and pharmacists, using the Hatoum scale. Univariate and multivariate analysis were conducted to identify factors associated with a higher frequency of PIs. RESULTS: Of 1346 prescriptions included, 129 required a PI (9.6% (95% CI: 8.1-11.4)). Most PIs were scored as having at least a significant impact for patient safety (69.8% (95% CI: 60.4-76.9)). The frequency of PIs was significantly associated with tumour site (p = 0.04) and weekday of prescription (p = 0.005). Multivariate analysis identified factors independently associated with PI performance, including pancreas and biliary tract cancers (odds ratio = 2.8 (95% CI: 1.4-5.3)), ovary cancers (odds ratio = 2.4 (95% CI: 1.2-4.8)) and head and neck cancers (odds ratio = 2.4 (95% CI: 1.1-5.1)) and the day 1 of the protocol with a cytotoxic agent (odds ratio = 3.7 (95% CI: 1.1-11.1)). CONCLUSIONS: Oncology pharmacists have a critical role in the safety of chemotherapy prescriptions. The coordination between healthcare professionals and access to patient data seem essential to improve the PIs' relevance and their clinical impact on patient safety.

Impact of drug storage systems: a quasi-experimental study with and without an automated-drug dispensing cabinet.

OBJECTIVE: To compare the costs and benefits of an automated-drug dispensing cabinet (ADC) versus traditional floor stock storage (TFSS). DESIGN: A quasi-experimental multicenter study conducted during 2015. SETTING: A teaching hospital (814 beds) equipped with 43 ADCs and a not-for-profit teaching hospital (643 beds) equipped with 38 TFSS systems, in Paris, France. PARTICIPANTS: All the wards of the two hospitals were included in the study. INTERVENTION(S): ADC versus TFSS. MAIN OUTCOME MEASURE(S): A composite outcome composed of cost and benefits. RESULTS: The total cost with payback period was substantially higher for the ADCs (574 006€ for 41 ADCs) than TFSS (190 305€ for 30 TFSS systems). The mean number of costly drugs and units were significantly higher for ADCs (P < 0.001). There was no significant difference in the mean number of overall drugs and units. There were significantly fewer urgent global deliveries with ADCs than TFSS units. Nurses' satisfaction with ADCs was high and the prevalence of medication process errors related to ADCs was low. No event due to storage errors was reported for ADCs and nine events were reported for TFSS units. On the contrary, informatic-related events increased with the use of ADCs, as expected. CONCLUSIONS: Overall, ADCs are well-established in wards and are particularly appreciated by nurses. A significant difference in the initial investment cost was confirmed, but it must be adjusted over time. This difference is offset in the long-term by gains in preparation time and fewer medication process errors, securing the medication process.

A centralized automated-dispensing system in a French teaching hospital: return on investment and quality improvement.

OBJECTIVES: To evaluate the return on investment (ROI) and quality improvement after implementation of a centralized automated-dispensing system after 8 years of use. DESIGN: Prospective evaluation of ROI; before and after study to evaluate dispensing errors; user satisfaction questionnaire after 8 years of use. SETTING: The study was conducted at a French teaching hospital in the pharmacy department, which is equipped with decentralized automated medication cabinets in the wards. PARTICIPANTS: Pharmacy staff (technicians and residents). INTERVENTION(S): Implementation of a centralized automated-dispensing robot. MAIN OUTCOME MEASURE(S): The true ROI was prospectively and annually compared to estimated returns calculated after implementation and upgrade of the robot; dispensing errors determined by observation of global deliveries and the satisfaction of users based on a validated questionnaire were evaluated. RESULTS: Following the upgrade, we found little difference for the ROI (+1.86%). The payback period increased by almost 3 years. There was a significant reduction of dispensing errors, from 2.9% to 1.7% (P < 0.001). User satisfaction of the robot by the pharmacy staff was reported (score of 5.52 ± 1.20 out of 7). CONCLUSIONS: These systems are worthwhile investments and largely contribute to improving the quality and safety of the medication process.

Providing physicians with feedback on medication adherence for people with chronic diseases taking long-term medication.

BACKGROUND: Poor medication adherence decreases treatment efficacy and worsens clinical outcomes, but average rates of adherence to long-term pharmacological treatments for chronic illnesses are only about 50%. Interventions for improving medication adherence largely focus on patients rather than on physicians; however, the strategies shown to be effective are complex and difficult to implement in clinical practice. There is a need for new care models addressing the problem of medication adherence, integrating this problem into the patient care process. Physicians tend to overestimate how well patients take their medication as prescribed. This can lead to missed opportunities to change medications, solve adverse effects, or propose the use of reminders in order to improve patients' adherence. Thus, providing physicians with feedback on medication adherence has the potential to prompt changes that improve their patients' adherence to prescribed medications. OBJECTIVES: To assess the effects of providing physicians with feedback about their patients' medication adherence for improving adherence. We also assessed the effects of the intervention on patient outcomes, health resource use, and processes of care. SEARCH METHODS: We conducted a systematic search of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, and Embase, all from database inception to December 2016 and without any language restriction. We also searched ISI Web of Science, two trials registers, and grey literature. SELECTION CRITERIA: We included randomised trials, controlled before-after studies, and interrupted time series studies that compared the effects of providing feedback to physicians about their patients' adherence to prescribed long-term medications for chronic diseases versus usual care. We included published or unpublished studies in any language. Participants included any physician and any patient prescribed with long-term medication for chronic disease. We included interventions providing the prescribing physician with information about patient adherence to medication. Only studies in which feedback to the physician was the sole intervention or the essential component of a multifaceted intervention were eligible. In the comparison groups, the physicians should not have had access to information about their patients' adherence to medication. We considered the following outcomes: medication adherence, patient outcomes, health resource use, processes of care, and adverse events. DATA COLLECTION AND ANALYSIS: Two independent review authors extracted and analysed all data using standard methodological procedures expected by Cochrane and the Effective Practice and Organisation of Care group. Due to heterogeneity in study methodology, comparison groups, intervention settings, and measurements of outcomes, we did not carry out meta-analysis. We describe the impact of interventions on outcomes in tabular form and make a qualitative assessment of the effects of studies. MAIN RESULTS: We included nine studies (23,255 patient participants): eight randomised trials and one interrupted time series analysis. The studies took place in primary care and other outpatient settings in the USA and Canada. Seven interventions involved the systematic provision of feedback to physicians concerning all their patients' adherence to medication, and two interventions involved issuing an alert for non-adherent patients only. Seven studies used pharmacy refill data to assess medication adherence, and two used an electronic device or self-reporting. The definition of adherence differed across studies, making comparisons difficult. Eight studies were at high risk of bias, and one study was at unclear risk of bias. The most frequent source of bias was lack of protection against contamination.Providing physicians with feedback may lead to little or no difference in medication adherence (seven studies, 22,924 patients), patient outcomes (two studies, 1292 patients), or health resource use (two studies, 4181 patients). Providing physicians with feedback on medication adherence may improve processes of care (e.g. more medication changes, dialogue with patient, management of uncontrolled hypertension) compared to usual care (four studies, 2780 patients). None of the studies reported an adverse event due to the intervention. The certainty of evidence was low for all outcomes, mainly due to high risk of bias, high heterogeneity across studies, and indirectness of evidence. AUTHORS' CONCLUSIONS: Across nine studies, we observed little or no evidence that provision of feedback to physicians regarding their patients adherence to prescribed medication improved medication adherence, patient outcomes, or health resource use. Feedback about medication adherence may improve processes of care, but due to the small number of studies assessing this outcome and high risk of bias, we cannot draw firm conclusions on the effect of feedback on this outcome. Future research should use a clear, standardised definition of medication adherence and cluster-randomisation to avoid the risk of contamination.

[Improving health care practices and organization: methodology for intervention studies]. / Améliorer les pratiques et l'organisation des soins?: méthodologie des études d'interventions.

Interventions designed to improve professional practices and healthcare organization are regularly implemented in all health systems. Their effectiveness on quality of care should be properly evaluated prior to their widespread implementation. Intervention studies can be conducted for this purpose according to a rigorous methodology in order to provide results with a good level of evidence. This article describes the main phases of an intervention study, including definition of the intervention, choice of study design, outcomes assessment, and writing of the report. It also addresses methodological issues of intervention studies designed to improve quality of care, such as cluster-randomization or the use of quasi-experimental designs. One of the specific features of these studies is that professionals are the targets, while patients are the beneficiaries of the intervention. A good knowledge of the specific features of studies designed to improve quality of care is essential to conduct research, or to evaluate the quality of the evidence from published studies.

[Improving practice and organisation of care: methodology for systematic reviews]. / Améliorer les pratiques et l'organisation des soins?: méthodologie des revues systématiques.

The number of intervention studies designed to improve quality of care is increasing exponentially, making it difficult to access all available information on a given subject. Systematic reviews are tools that provide health professionals with comprehensive and objective information. This article describes the main phases of a systematic review: formulating the research question, search and selection of studies, data extraction and analysis, assessment of the methodological quality of studies, and synthesis of the results. Interventions designed to improve professional practices and organisation of care have specific characteristics that determine the methodology of systematic reviews. For example, the often substantial heterogeneity between populations, organisations, and intervention settings among studies must be taken into account, which makes meta-analysis more difficult. Knowledge on specific features of systematic reviews designed to improve quality of care is essential to ensure a good review of the literature, or to evaluate the level of evidence of published systematic reviews.

Genicular artery embolization for knee osteoarthritis: Results of the LipioJoint-1 trial.

PURPOSE: The purpose of this study was to evaluate the safety and efficacy of transient genicular artery embolization (GAE) using an ethiodized oil-based emulsion for the treatment of knee osteoarthritis (KOA). MATERIALS AND METHODS: This prospective, single-arm, open-label, multicenter, first-in-human cohort trial was registered on ClinicalTrials.gov (NCT04733092). The main inclusion criterion was diagnosis of KOA according to a visual analogue scale (VAS) pain score ≥ 40 mm (score range: 0-100 mm), despite conservative treatment for at least three months. Treatment efficacy was assessed using changes in VAS pain score, Mean Western Ontario & McMaster Universities osteoarthritis (WOMAC) function score (normalized to 100; score ranging from 0 to100) and outcome measures in rheumatoid arthritis clinical trials (OMERACT)-Osteoarthritis Research Society (OARSI) set of responder criteria. RESULTS: Twenty-two consecutive participants (13 women; mean age, 66 ± 9 [standard deviation (SD)]) were included and underwent GAE. Emulsion consisted in a mixture of ioversol and ethiodized oil (ratio 1:3, respectively) prepared extemporaneously. The rate of serious adverse events attributed to GAE within one month was 5% (1/22), corresponding to reversible worsening of renal function. Immediate technical success rate was 100%. Mean VAS pain score dropped from 74.4 ± 16.5 (SD) mm at baseline to 37.2 ± 26.7 (SD) mm at three months (P < 0.001). Mean WOMAC function score (normalized to 100: score ranging from 0 to 100) decreased from 57.3 ± 17.1 (SD) at baseline to 33.5 ± 25.9 (SD) at three months (P < 0.001). At three months, 16 out of 22 participants (73%) were considered responders according to the OMERACT-OARSI set of responder criteria, including high improvement in either pain or WOMAC function, or improvement in both pain and WOMAC function. CONCLUSION: GAE using an ethiodized oil-based emulsion is safe and improves pain and function in participants with KOA for at least three months.

First-in-man use of a cardiovascular cell-derived secretome in heart failure. Case report.

BACKGROUND: There is increased evidence that the effects of stem cells can mostly be duplicated by administration of their secretome which might streamline the translation towards the clinics. METHODS: The 12-patient SECRET-HF phase 1 trial has thus been designed to determine the feasibility and safety of repeated intravenous injections of the extracellular vesicle (EV)-enriched secretome of cardiovascular progenitor cells differentiated from pluripotent stem cells in severely symptomatic patients with drug-refractory left ventricular (LV) dysfunction secondary to non-ischemic dilated cardiomyopathy. Here we report the case of the first treated patient (baseline NYHA class III; LV Ejection Fraction:25%) in whom a dose of 20 × 109 particles/kg was intravenously infused three times three weeks apart. FINDINGS: In addition to demonstrating the feasibility of producing a cardiac cell secretome compliant with Good Manufacturing Practice standards, this case documents the excellent tolerance of its repeated delivery, without any adverse events during or after infusions. Six months after the procedure, the patient is in NYHA Class II with improved echo parameters, a reduced daily need for diuretics (from 240 mg to 160 mg), no firing from the previously implanted automatic internal defibrillator and no alloimmunization against the drug product, thereby supporting its lack of immunogenicity. INTERPRETATION: The rationale underlying the intravenous route is that the infused EV-enriched secretome may act by rewiring endogenous immune cells, both circulating and in peripheral organs, to take on a reparative phenotype. These EV-modified immune cells could then traffic to the heart to effect tissue repair, including mitigation of inflammation which is a hallmark of cardiac failure. FUNDING: This trial is funded by the French Ministry of Health (Programme Hospitalier de Recherche CliniqueAOM19330) and the "France 2030" National Strategy Program (ANR-20-F2II-0003). It is sponsored by Assistance Publique-Hôpitaux de Paris.

Evaluation of drug administration errors in a teaching hospital.

BACKGROUND: Medication errors can occur at any of the three steps of the medication use process: prescribing, dispensing and administration. We aimed to determine the incidence, type and clinical importance of drug administration errors and to identify risk factors. METHODS: Prospective study based on disguised observation technique in four wards in a teaching hospital in Paris, France (800 beds). A pharmacist accompanied nurses and witnessed the preparation and administration of drugs to all patients during the three drug rounds on each of six days per ward. Main outcomes were number, type and clinical importance of errors and associated risk factors. Drug administration error rate was calculated with and without wrong time errors. Relationship between the occurrence of errors and potential risk factors were investigated using logistic regression models with random effects. RESULTS: Twenty-eight nurses caring for 108 patients were observed. Among 1501 opportunities for error, 415 administrations (430 errors) with one or more errors were detected (27.6%). There were 312 wrong time errors, ten simultaneously with another type of error, resulting in an error rate without wrong time error of 7.5% (113/1501). The most frequently administered drugs were the cardiovascular drugs (425/1501, 28.3%). The highest risks of error in a drug administration were for dermatological drugs. No potentially life-threatening errors were witnessed and 6% of errors were classified as having a serious or significant impact on patients (mainly omission). In multivariate analysis, the occurrence of errors was associated with drug administration route, drug classification (ATC) and the number of patient under the nurse's care. CONCLUSION: Medication administration errors are frequent. The identification of its determinants helps to undertake designed interventions.

Identifying homogeneous healthcare use profiles and treatment sequences by combining sequence pattern mining with care trajectory clustering in kidney cancer patients on oral anticancer drugs: A case study.

OBJECTIVE: We evaluated the ability of a coupled pattern-mining and clustering method to identify homogeneous groups of subjects in terms of healthcare resource use, prognosis and treatment sequences, in renal cancer patients beginning oral anticancer treatment. METHODS: Data were retrieved from the permanent sample of the French medico-administrative database. We applied the CP-SPAM algorithm for pattern mining to healthcare use sequences, followed by hierarchical clustering on principal components (HCPC). RESULTS AND CONCLUSION: We identified 127 individuals with renal cancer with a first reimbursement of an oral anticancer drug between 2010 and 2017. Clustering identified three groups of subjects, and discrimination between these groups was good. These clusters differed significantly in terms of mortality at six and 12 months, and medical follow-up profile (predominantly outpatient or inpatient care, biological monitoring, reimbursement of supportive care drugs). This case study highlights the potential utility of applying sequence-mining algorithms to a large range of healthcare reimbursement data, to identify groups of subjects homogeneous in terms of their care pathways and medical behaviors.

Association Between Exposure to Effervescent Paracetamol and Hospitalization for Acute Heart Failure: A Case-Crossover Study.

We investigated whether effervescent paracetamol, as an important source of nondietary sodium and fluid load, is associated with a transient increase in the risk of hospitalization for acute heart failure (AHF). We conducted a unidirectional case-crossover study using data from the 1 in 97th representative sample from the French health care database. Subjects aged ≥18 years, hospitalized for AHF during the 2014-2016 period, were included. Exposure to effervescent paracetamol was compared between a risk period (ie, 15 days immediately before admission for AHF) and 3 earlier 15-day control periods, to test a possible trigger effect of effervescent paracetamol intake on AHF. Adjusted odds ratios (aORs) were estimated with a conditional logistic regression. We identified 4301 patients hospitalized for AHF. We found that 5.7% of AHF subjects were exposed to effervescent paracetamol during the risk period, as compared with 4.1% during the control periods (aOR, 1.56 [95% confidence interval [CI], 1.27-1.90]; P < .001). This association was also found in the subgroup of subjects with hypertension (aOR, 1.45 [95%CI, 1.13-1.87]; P = .004, n = 2648) and in the subgroup of subjects aged ≥83 years (aOR, 1.70 [95%CI: 1.28-2.24], P < .001, n = 2238). A similar analysis, considering exposure to noneffervescent paracetamol, did not support the existence of an indication bias likely to explain the association observed for effervescent paracetamol. This study suggests an association between effervescent paracetamol and admission for AHF and should be confirmed with other complementary study designs.

Prophylactic levosimendan in patients with low ejection fraction undergoing coronary artery bypass grafting: A pooled analysis of two multicentre randomised controlled trials.

OBJECTIVES: To assess the effect of preoperative levosimendan on mortality at day 90 in patients with left ventricular ejection fraction (LVEF) ≤ 40%, and to investigate a possible differential effect between patients undergoing isolated coronary artery bypass grafting (CABG) versus CABG combined with valve replacement surgery. DESIGN: Pooled analysis of two multicentre randomised controlled trials (RCT) investigating prophylactic levosimendan versus placebo prior to CABG surgery on mortality at day 90 in patients with LVEF ≤ 40%. A meta-analysis of all RCT investigating the same issue was also conducted. RESULTS: A cohort of 1084 patients (809 isolated CABG, and 275 combined surgery) resulted from the merging of LEVO-CTS and LICORN databases. Seventy-two patients were dead at day 90. The mortality at day 90 was not different between levosimendan and placebo (Hazard Ratio (HR): 0.73, 95% CI: 0.41-1.28, p = 0.27). However, there was a significant interaction between the type of surgery and the study drug (p = 0.004). We observed a decrease in mortality at day 90 in the isolated CABG subgroup (HR: 0.39, 95% CI: 0.19-0.82, p = 0.013), but not in the combined surgery subgroup (HR: 1.73, 95% CI: 0.77-3.92, p = 0.19). The meta-analysis of 6 RCT involving 1441 patients confirmed the differential effect on mortality at day 30 between the 2 subgroups. CONCLUSIONS: Preoperative levosimendan did not reduce mortality in a mixed surgical population with LV dysfunction. However, the subgroup of patients undergoing isolated CABG had a reduction in mortality at day 90, whereas there was no significant effect in combined surgery patients. This finding requires confirmation with a specific prospective trial.