The impact of pharmacists' interventions within the Closed Loop Medication Management process on medication safety: An analysis in a German university hospital.

Background: Single elements of the Closed Loop Medication Management process (CLMM), including electronic prescribing, involvement of clinical pharmacists (CPs), patient individual logistics and digital administration/documentation, have shown to improve medication safety and patient health outcomes. The impact of the complete CLMM on patient safety, as reflected in pharmacists' interventions (PIs), is largely unknown. Aim: To evaluate the extent and characterization of routine PIs performed by hospital-wide CPs at a university hospital with an implemented CLMM. Methods: This single-center study included all interventions documented by CPs on five self-chosen working days within 1 month using the validated online-database DokuPIK (Documentation of Pharmacists' Interventions in the Hospital). Based on different workflows, two groups of CPs were compared. One group operated as a part of the CLMM, the "Closed Loop Clinical Pharmacists" (CL-CPs), while the other group worked less dependent of the CLMM, the "Process Detached Clinical Pharmacists" (PD-CPs). The professional experience and the number of medication reviews were entered in an online survey. Combined pseudonymized datasets were analyzed descriptively after anonymization. Results: A total of 1,329 PIs were documented by nine CPs. Overall CPs intervened in every fifth medication review. The acceptance rate of PIs was 91.9%. The most common reasons were the categories "drugs" (e.g., indication, choice of formulation/drug and documentation/transcription) with 42.7%, followed by "dose" with 29.6%. One-quarter of PIs referred to the therapeutic subgroup "J01 antibacterials for systemic use." Of the 1,329 underlying PIs, 1,295 were classified as medication errors (MEs) and their vast majority (81.5%) was rated as "error, no harm" (NCC MERP categories B-D). Among PIs performed by CL-CPs (n = 1,125), the highest proportion of errors was categorized as B (56.5%), while in the group of PIs from PD-CPs (n = 170) errors categorized as C (68.2%) dominated (p < 0.001). Conclusion: Our study shows that a structured CLMM enables CPs to perform a high number of medication reviews while detecting and solving MEs at an early stage before they can cause harm to the patient. Based on key quality indicators for medication safety, the complete CLMM provides a suitable framework for the efficient medication management of inpatients.

Evaluating the use of prescription sequence symmetry analysis as a pharmacovigilance tool: A scoping review.

BACKGROUND: The (prescription) sequence symmetry analysis (PSSA) design has been used to identify potential prescribing cascade signals by assessing the prescribing sequence of an index drug relative to a marker drug presumed to treat an adverse drug event provoked by the index drug. OBJECTIVES: This review aimed to explore the use of the PSSA design as a pharmacovigilance tool with a particular focus on the breadth of identified signals and advances in PSSA methodology. METHODS: We searched Embase, PubMed/Medline, Google Scholar, Web of Science and grey literature to identify studies that used the PSSA methodology. Two reviewers independently extracted relevant data for each included article. Study characteristics including signals identified, exposure time window, stratified analyses, and use of controls were extracted. RESULTS: We identified 53 studies which reported original results obtained using PSSA methodology or quantified the validity of components of the PSSA design. Of those, nine studies provided validation metrics showing reasonable sensitivity and high specificity of PSSA to identify prescribing cascade signals. We identified 340 unique index drug - marker drug signals published in the PSSA literature, representing 281 unique index - marker pharmacological class dyads (i.e., unique fourth-level Anatomical Therapeutic Chemical [ATC] classification dyads). Commonly observed signals were identified for index drugs acting upon the nervous system (34%), cardiovascular system (21%), and blood and blood-forming organs (15%), and many marker drugs were related to the nervous system (25%), alimentary tract and metabolism (23%), cardiovascular system (17%), and genitourinary system and sex hormones (14%). Negative controls and positive controls were utilized in 21% and 13% of studies, respectively. CONCLUSIONS: The PSSA methodology has been used in 53 studies worldwide to detect and evaluate over 300 unique prescribing cascades signals. Researchers should consider sensitivity analyses incorporating negative and/or positive controls and additional time windows to evaluate time-varying biases when designing PSSA studies.

Effects of hydrocodone rescheduling on opioid use outcomes: A systematic review.

OBJECTIVE: To evaluate opioid prescribing, dispensing, and use in relation to hydrocodone-containing product (HCP) rescheduling. METHODS: Seven biomedical databases and grey literature sources were searched with keywords and database-specific controlled vocabulary relevant to HCP rescheduling for items published between January 2014 and July 2019. We included English-language quasi-experimental studies that assessed changes in HCP and other opioid prescribing, dispensing, utilization, and opioid-related health outcomes before and after HCP rescheduling. A data extraction sheet was created for this review. Two authors evaluated risk of bias for each included study. Two of 4 authors each independently extracted patient demographics and opioid-related outcomes from the included studies. Conflicts were resolved by a third author. RESULTS: All studies identified (n = 44) were quasi-experimental in design with 10 using an interrupted time series approach. A total of 24 studies reported a decrease in HCP prescribing by 3.1%-66.0%. Six studies reported a decrease in HCP days' supply or doses by 14.0%-80.8%. There was increased prescribing of oxycodone-containing products by 4.5%-13.9% in 5 studies, tramadol by 2.7%-53.0% in 9 studies, codeine-containing products by 0.8%-1352.9% in 8 studies). Five studies reported a decrease in morphine equivalents by at least 10%, whereas 2 studies reported an increase in morphine equivalents. Differences in populations, sample sizes, and approaches did not allow for a meta-analysis. Details regarding approach and findings were limited in published conference abstracts (n = 16). CONCLUSIONS: Hydrocodone rescheduling was associated with reductions in prescribing and use of HCPs but was also associated with increased prescribing and use of other opioids, both schedule II and nonschedule II.

Chronic Opioid Therapy: A Scoping Literature Review on Evolving Clinical and Scientific Definitions.

The management of chronic noncancer pain (CNCP) with chronic opioid therapy (COT) is controversial. There is a lack of consensus on how COT is defined resulting in unclear clinical guidance. This scoping review identifies and evaluates evolving COT definitions throughout the published clinical and scientific literature. Databases searched included PubMed, Embase, and Web of Science. A total of 227 studies were identified from 8,866 studies published between January 2000 and July 2019. COT definitions were classified by pain population of application and specific dosage/duration definition parameters, with results reported according to PRISMA-ScR. Approximately half of studies defined COT as "days' supply duration >90 days" and 9.3% defined as ">120 days' supply," with other days' supply cut-off points (>30, >60, or >70) each appearing in <5% of total studies. COT was defined by number of prescriptions in 63 studies, with 16.3% and 11.0% using number of initiations or refills, respectively. Few studies explicitly distinguished acute treatment and COT. Episode duration/dosage criteria was used in 90 studies, with 7.5% by Morphine Milligram Equivalents + days' supply and 32.2% by other "episode" combination definitions. COT definitions were applied in musculoskeletal CNCP (60.8%) most often, and typically in adults aged 18 to 64 (69.6%). The usage of ">90 days' supply" COT definitions increased from 3.2 publications/year before 2016 to 20.7 publications/year after 2016. An increasing proportion of studies define COT as ">90 days' supply." The most recent literature trends toward shorter duration criteria, suggesting that contemporary COT definitions are increasingly conservative. PERSPECTIVE: This study summarized the most common, current definition criteria for chronic opioid therapy (COT) and recommends adoption of consistent definition criteria to be utilized in practice and research. The most recent literature trends toward shorter duration criteria overall, suggesting that COT definition criteria are increasingly stringent.

Characterization of a multianalyte GC-MS/MS procedure for detecting and quantifying polycyclic aromatic hydrocarbons (PAHs) and PAH derivatives from air particulate matter for an improved risk assessment.

A correct description of the concentration and distribution of particle bound polycyclic aromatic hydrocarbons is important for risk assessment of atmospheric particulate matter. A new targeted GC-MS/MS method was developed for analyzing 64 PAHs including compounds with a molecular weight >300, as well as nitro-, methyl-, oxy- and hydroxyl derivatives in a single analysis. The instrumental LOD ranged between 0.03 and 0.7 pg/µL for PAHs, 0.2-7.9 pg/µL for hydroxyl and oxy PAHs, 0.1-7.4 pg/µL for nitro PAHs and 0.06-0.3 pg/µL for methyl-PAHs. As an example for the relevance of this method samples of PM10 were collected at six sampling sites in Medellin, Colombia, extracted and the concentration of 64 compounds was determined. The 16 PAHs from the EPA priority list contributed only from 54% to 69% to the sum of all analyzed compounds, PAH with high molecular weight accounted for 8.8%-18.9%. Benzo(a)pyrene equivalents (BaPeq) were calculated for the estimation of the life time cancer (LCR). The LCR according to the samples ranged from 2.75 × 10-5 to 1.4 × 10-4 by a calculation with toxic equivalent factors (TEF) and 5.7 × 10-5 to 3.8 × 10-4 with potency equivalent factor (PEF). By using the new relative potency factors (RPF) recommended by US Environmental Protection Agency (U.S.EPA) the LCR ranged from 1.3 × 10-4 to 7.2 × 10-4. Hence, it was around six times higher than the well-known TEF. The novel method enables the reliable quantification of a more comprehensive set of PAHs bound on PM and thus will facilitate and improve the risk assessment of them.