A multicenter record review of in-hospital adverse drug events requiring a higher level of care.

OBJECTIVE: Adverse drug events (ADEs) are a worldwide concern, particularly when leading to a higher level of care. This study defines a higher level of care as an unplanned (re)admission to an intensive care unit or an intervention by a Medical Emergency Team. The objectives are to describe the incidence and preventability of ADEs leading to a higher level of care, to assess the types of drug involved, and to identify the risk factors. METHODS: A three-stage retrospective review was performed in six Belgian hospitals. Patient records were assessed by a trained clinical team consisting of a nurse, a physician, and a clinical pharmacist. Descriptive statistics, univariate, and multiple logistic regressions were used. RESULTS: In this study, 830 patients were detected for whom a higher level of care had been needed. In 160 (19.3%) cases, an ADE had occurred; 134 (83.8%) of these were categorized as preventable adverse drug events (pADEs). The overall incidence rate of patients transferred to a higher level of care because of a pADE was 33.9 (95% CI: 28.5-39.3) per 100,000 patient days at risk. Antibiotics and antithrombotic agents accounted both for one-fifth of all pADEs. Multivariate analysis indicated American Society of Anaesthesiologists physical status score as a risk factor for pADEs. CONCLUSIONS: The high number of pADE with patient harm shows that there is a need for structural improvement of pharmacotherapeutic care. Detection of these pADEs can be the basis for the implementation of these improvements.

One fourth of unplanned transfers to a higher level of care are associated with a highly preventable adverse event: a patient record review in six Belgian hospitals.

OBJECTIVE: The objectives of this study are to determine the prevalence and preventability of adverse events requiring an unplanned higher level of care, defined as an unplanned transfer to the ICU or an in-hospital medical emergency team intervention, and to assess the type and the level of harm of each adverse event. DESIGN: A three-stage retrospective review process of screening, record review, and consensus judgment was performed. SETTING: Six Belgian acute hospitals. PATIENTS: During a 6-month period, all patients with an unplanned need for a higher level of care were selected. INTERVENTIONS: The records 6-month period, the records of all patients with an unplanned need for a higher level of care were assessed by a trained clinical team consisting of a research nurse, a physician, and a clinical pharmacist. MEASUREMENTS AND MAIN RESULTS: Adverse events were found in 465 of the 830 reviewed patient records (56%). Of these, 215 (46%) were highly preventable. The overall incidence rate of patients being transferred to a higher level of care involving an adverse event was 117.6 (95% CI, 106.9-128.3) per 100,000 patient days at risk, of which 54.4 (95% CI, 47.15-61.65) per 100,000 patient days at risk involving a highly preventable adverse event. This means that 25.9% of all unplanned transfers to a higher level of care were associated with a highly preventable adverse event. The adverse events were mainly associated with drug therapy (25.6%), surgery (23.7%), diagnosis (12.4%), and system issues (12.4%). The level of harm varied from temporary harm (55.7%) to long-term or permanent impairment (19.1%) and death (25.2%). Although the direct causality is often hard to prove, it is reasonable to consider these adverse events as a contributing factor. CONCLUSION: Adverse events were found in 56% of the reviewed records, of which almost half were considered highly preventable. This means that one fourth of all unplanned transfers to a higher level of care were associated with a highly preventable adverse event.

Detectability and acceptability of continuous pulse signals for the MemoPatch(®) device, an electronic skin patch intended to deliver tactile medication reminder signals.

BACKGROUND: Unintended forgetfulness is the most common cause of medication nonadherence. MemoPatch(®) is an electronic skin patch intended to deliver discreet tactile medication reminder stimuli. This study aimed 1) to evaluate, within an experimental setup, the detectability and acceptability of fifteen continuous bipolar pulse signals; 2) to identify variables, if any, associated with differential perception of the candidate reminder signals; and 3) to collect safety data as reported by subjects or observed by staff. METHODS: This was a laboratory experiment involving 147 healthy adult volunteers (55.1% female, 98.0% Caucasian, with age 41.8±16.0 years, body mass index [BMI] 24.7±4.4, upper body adiposity 28.5%±8.3% body fat, and skin impedance 367.6±140.8 Ω) and using an experimental version of the MemoPatch(®). Following four training signals administered in fixed order, subjects were exposed to a set of fifteen randomly sequenced signals varying in rise and fall time, width, and current, to be rated in terms of detectability ("too weak", "appropriate", or "too strong") and acceptability. RESULTS: Ratings of "appropriate" were virtually independent of such variables as sex, BMI, upper body adiposity, and skin impedance at the patch location. Five signals were rated as "appropriate" by ≥67% of subjects and acceptable by ≥95% of subjects, virtually independently of the indicators of interest, and were retained as candidate signals for use in next stages of development and commercialization. Nine adverse events, none serious, were observed in six subjects. CONCLUSION: This study yielded five effective and safe candidate signals for potential use in the MemoPatch(®) device, all equally considered to be of appropriate detectability and high acceptability, in an experimental context. The signals were independent from, and therefore highly robust relative to, sex, BMI, upper body adiposity, and skin impedance at the patch site, lending additional generalizability to the signals and hence their potential relevance to broad commercial application.

Detectability and appraisal thresholds of split pulse signals for the MemoPatch™ device, an electronic skin patch intended to deliver tactile medication reminder signals (study TS-104).

Patient non-adherence to prescribed medication regimens is a significant problem and affects clinical treatment outcomes. The MemoPatch™ medical device, currently in development, is an electronic skin patch intended to deliver tactile medication reminder signals. Fifty volunteers completed a laboratory experiment that evaluated the detectability and appraisal thresholds of five split signals; specifically, the current thresholds (in mA) at which a signal was detected (threshold T1), was considered sufficiently detectable to serve as a reminder signal (threshold T2), and became too strong as a reminder signal (threshold T3). Signals were selected under consideration of three data points: T1Max and T2Max (defined as, resp., the maximum current observed at T1 and T2) and T3Pct90 (the T3 current at the 90(th) percentile). A signal was considered to be useable in future versions of the MemoPatch™ device if it met the constraint that (T3Pct90-T2Max) should not be negative. One signal met the constraint requirement as its T3Pct90-T2Max=0.96mA.

Design of a medical record review study on the incidence and preventability of adverse events requiring a higher level of care in Belgian hospitals.

BACKGROUND: Adverse events are unintended patient injuries that arise from healthcare management resulting in disability, prolonged hospital stay or death. Adverse events that require intensive care admission imply a considerable financial burden to the healthcare system. The epidemiology of adverse events in Belgian hospitals has never been assessed systematically. FINDINGS: A multistage retrospective review study of patients requiring a transfer to a higher level of care will be conducted in six hospitals in the province of Limburg. Patient records are reviewed starting from January 2012 by a clinical team consisting of a research nurse, a physician and a clinical pharmacist. Besides the incidence and the level of causation and preventability, also the type of adverse events and their consequences (patient harm, mortality and length of stay) will be assessed. Moreover, the adequacy of the patient records and quality/usefulness of the method of medical record review will be evaluated. DISCUSSION: This paper describes the rationale for a retrospective review study of adverse events that necessitate a higher level of care. More specifically, we are particularly interested in increasing our understanding in the preventability and root causes of these events in order to implement improvement strategies. Attention is paid to the strengths and limitations of the study design.

Meropenem -valproic acid interaction in patients with cefepime-associated status epilepticus.

PURPOSE: Two case reports of rapid decreases in valproic acid levels after initiation of meropenem in patients who developed new-onset seizure activity during treatment with cefepime are presented. SUMMARY: A 60-year-old Caucasian woman with myelodysplasia was transferred to the medical intensive care unit (MICU) on day 11 of her hospitalization. Cefepime was given as empiric therapy for febrile neutropenia. Pulmonary invasive aspergillosis was diagnosed. On day 16 of hospitalization, epileptic activity was confirmed. Valproic acid was initiated. Cefepime was discontinued and meropenem was initiated for treatment of cefepime-resistant pneumonia. Serum valproic acid levels decreased to subtherapeutic levels within 24 hours. Meropenem was discontinued and ceftazidime was started on day 22; serum valproic acid levels gradually increased but never reached therapeutic levels again. The patient died of intractable invasive aspergillosis on day 33. A 54-year-old Caucasian man with myelodysplasia was admitted to the MICU for nonconvulsive status epilepticus. Ten days before admission, cefepime had been started empirically for the treatment of neutropenic fever. One day before MICU admission, valproic acid was initiated as treatment for status epilepticus. The next day, serum valproic acid levels were therapeutic; cefepime was switched to meropenem. Serum valproic acid levels decreased within 24 hours and phenytoin was added. On day 4, the patient's serum valproic acid levels decreased further and meropenem was discontinued. Although the valproic acid dosage was increased, valproic acid levels did not return to the therapeutic range. The patient died on day 11. CONCLUSION: Following cefepime therapy, a clinically important interaction between meropenem and valproic acid occurred in two critically ill patients with new-onset status epilepticus.