Agreement between pharmacists and physicians on the assessment of appropriateness of antimicrobial prescribing.

INTRODUCTION: Audits for monitoring the quality of antimicrobial prescribing are a main tool in antimicrobial stewardship programs; however, interobserver reliability has not been conclusively assessed. Our objective was to measure the level of agreement between pharmacists and physicians on the appropriateness of antimicrobials prescribing in hospitals. METHODS: A national multicenter, cross-sectional study was conducted of patients who were receiving antimicrobials one day of April 2021. Hospital participation was voluntary, and the study population was randomly selected. Pharmacists and physicians performed a simultaneous, independent assessment of the quality of antimicrobial prescriptions. The observers used an assessment method by which all indicators of the quality of antimicrobial use were considered. Finally, an algorithm was used to rate overall antimicrobial prescribing as appropriate, suboptimal, inappropriate, or not assessable. Gwet's AC1 coefficient was used to assess interobserver agreement. RESULTS: In total, 101 hospitals participated, and 411 hospital antimicrobial prescriptions were reviewed. The strength of agreement was moderate regarding the overall quality of prescribing (AC1=0.51; 95%CI=[0.44-0.58]). A very good level of agreement (AC1>0.80) was observed between pharmacists and physicians in all indicators of the quality, except for duration of treatment, rated as good (AC1=0.79; 95%CI=[0.75-0.83]), and registration on the medical record, rated as fair (AC1=0.34; 95%CI=[0.26-0.43]). The agreement was greater in critical care, onco-hematology, and pediatric units than in medical and surgery units. CONCLUSIONS: In this point prevalence study, a moderate level of agreement was observed between pharmacists and physicians in the evaluation of the appropriateness of antimicrobials prescribing in hospitals.

Remdesivir and SARS-CoV-2 monoclonal antibodies to prevent COVID-19 progression in hematological patients: an observational study.

BACKGROUND: Patients with hematological malignancies (HM) are at high risk of COVID-19 progression. Hence, early treatments to prevent progression are needed. The aim of our work was to evaluate the effectiveness and safety of remdesivir (RDV) and SARS-CoV-2 monoclonal antibodies (mAb) in patients with HM and mild-to-moderate disease in real clinical practice. METHODS: We conducted a prospective study in a tertiary hospital in 55 HM patients with mild-to-moderate SARS-CoV-2 disease diagnosed between August 2021 and July 2022 and who received RDV or mAb to prevent COVID-19 progression (related death or hospitalization). The primary endpoint was COVID-19 progression on day 28. Other outcomes were COVID-19 progression beyond day 28 and viral load evolution. RESULTS: RDV was administered to 44 (80.0%) patients and mAb to 11 (20.0%) patients. Death occurred in 1 (1.8%) patient and hospitalization in 9 (16.4%) patients by day 28, respectively; 3 patients (5.5%) required intensive care and 8 (14.5%), oxygen support. Of note, 5 additional patients [15, (27.3%) in total] died or required hospitalization after day 28. Two hazard Cox regression models yielded the absence of anti-SARS-CoV-2 antibodies, age over 65 years, and ECOG-performance status ≥ 2 as the main risk factors for COVID-19-related death or hospitalization. CONCLUSION: Our results from clinical practice suggest that RDV and SARS-CoV-2 mAb therapies elicit worse outcomes in hematological patients than those reported for high-risk population in clinical trials.

[Translated article] 2022 update of the indicators for quality of care and pharmaceutical care for people living with human immunodeficiency virus.

OBJECTIVE: To update and define indicators for improving the quality of care and Pharmaceutical Care for people living with HIV infection in Spain. METHOD: The present project, which updates the previous version of the 2013 document, was developed in four work phases carried out between January and June 2022. In phase 1, the organization phase, a working group was created, made up of seven hospital pharmacy specialists with extensive experience in pharmaceutical care and from different SFHs in Spain. In addition, another 34 specialists participated in the evaluation of the indicators through two rounds of online evaluation to generate consensus. For phase 2, initially, a review of the identified reference literature was carried out with the aim of establishing a basis from which to define a proposal for quality criteria and indicators. Then, a preliminary proposal of criteria was made and revisions were established for their adjustment in several telematic work meetings. In phase 3, consensus was established based on the Delphi-Rand/UCLA consensus methodology. In addition, all the indicators classified as appropriate and necessary were grouped according to two levels of monitoring recommendation, so as to guide the hospital pharmacy services in the priority of their measurement: key and advanced. Finally, in phase 4, the final project document was prepared, along with the corresponding descriptive sheets for each indicator in order to facilitate the measurement and evaluation of the indicators by the hospital pharmacy services. RESULTS: Following the consensus methodology used, a list of items made up of 79 appropriate and necessary indicators was drawn up to establish a follow-up and monitoring of the quality and activity of Pharmaceutical Care for people living with HIV. Of these, 60 were established as key and 19 advanced. CONCLUSIONS: The indicators defined and updated, since the previous version of 2013, are intended to be a tool for professionals to guide decision-making and facilitate the measurement and assessment of the most relevant aspects of the quality and pharmaceutical care of people living with HIV.

2022 update of the indicators for quality of care and pharmaceutical care for people living with human immunodeficiency virus. / Actualización 2022 de los indicadores para la calidad asistencial y la atención farmacéutica a las personas que viven con el virus de la inmunodeficiencia humana.

OBJECTIVE: To update and define indicators for improving the quality of care and pharmaceutical care for people living with HIV infection in Spain. METHOD: The present project, which updates the previous version of the 2013 document, was developed in four work phases carried out between January and June 2022. In phase 1, the organization phase, a working group was created, made up of seven hospital pharmacy specialists with extensive experience in pharmaceutical care and from different SFHs in Spain. In addition, another 34 specialists participated in the evaluation of the indicators through two rounds of online evaluation to generate consensus. For phase 2, initially, a review of the identified reference literature was carried out with the aim of establishing a basis from which to define a proposal for quality criteria and indicators. Then, a preliminary proposal of criteria was made and revisions were established for their adjustment in several telematic work meetings. In phase 3, consensus was established based on the Delphi-Rand/UCLA consensus methodology. In addition, all the indicators classified as appropriate and necessary were grouped according to two levels of monitoring recommendation, so as to guide the hospital pharmacy services in the priority of their measurement: key and advanced. Finally, in phase 4, the final project document was prepared, along with the corresponding descriptive sheets for each indicator in order to facilitate the measurement and evaluation of the indicators by the hospital pharmacy services. RESULTS: Following the consensus methodology used, a list of items made up of 79 appropriate and necessary indicators was drawn up to establish a follow-up and monitoring of the quality and activity of pharmaceutical care for people living with HIV. Of these, 60 were established as key and 19 advanced. CONCLUSIONS: The indicators defined and updated, since the previous version of 2013, are intended to be a tool for professionals to guide decision-making and facilitate the measurement and assessment of the most relevant aspects of the quality and pharmaceutical care of people living with HIV.

Simplification and Multidimensional Adaptation of the Stratification Tool for Pharmaceutical Care in People Living With HIV.

BACKGROUND: People living with human immunodeficiency virus (HIV) require specific pharmaceutical care (PC). Although the 2017 Capacity-Motivation-Opportunity (CMO) PC model allows a multidisciplinary approach that focuses on patient needs, it is too complex and presents room for improvement. OBJECTIVE: The aim of this study is to simplify and adapt the previous 2017 PC tool through a multidimensional approach to improve HIV patient care, to prove the validity of the model in real-life patients. METHODS: The new PC tool was generated by keeping some of the variables of the 2017 document and conducting a literature search. Content validity was determined by a 2-round Delphi methodology with an expert panel of 42 pharmacists. Consensus for the first and second rounds was defined as ≥70% agreement. The tool generated was validated in 407 real-life patients. RESULTS: Thirty-seven experts completed the first round of the Delphi survey and 36 the second. No consensus was reached for 3 variables, any of the frequency options and 4 interventions, while the experts agreed not to include 1 intervention in round 1. Consensus to include them was found for all but 1 variable and 1 intervention in round 2. The final tool obtained to select and stratify HIV-positive patients was composed of 9 dimensions divided into 17 variables. The new tool was validated with real-life patients and 3 priority levels were defined. CONCLUSIONS AND RELEVANCE: We created a new pyramid of score thresholds to classify patients into priority levels. The new tool simplifies the 2017 model and improves its utility to help HIV-positive patients, owing to its multidimensional approach.

Utility of 1,3 ß-d-Glucan Assay for Guidance in Antifungal Stewardship Programs for Oncologic Patients and Solid Organ Transplant Recipients.

The implementation of 1,3 ß-d-glucan (BDG) has been proposed as a diagnostic tool in antifungal stewardship programs (ASPs). We aimed to analyze the influence of serum BDG in an ASP for oncologic patients and solid organ transplant (SOT) recipients. We conducted a pre-post study. In the initial period (PRE), the ASP was based on bedside advice, and this was complemented with BDG in the post-period (POST). Performance parameters of the BDG assay were determined. Antifungal (AF) use adequacy was evaluated using a point score. Clinical outcomes and AF costs were also compared before and after the intervention. Overall, 85 patients were included in the PRE-period and 112 in the POST-period. Probable or proven fungal infections were similar in both groups (54.1% vs. 57.1%; p = 0.67). The determination of BDG contributed to improved management in 75 of 112 patients (66.9%). The AF adequacy score improved in the POST-period (mean 7.75 vs. 9.29; p < 0.001). Median days of empiric AF treatment was reduced in the POST-period (9 vs. 5 days, p = 0.04). All-cause mortality (44.7% vs. 34.8%; p = 0.16) was similar in both periods. The cost of AF treatments was reduced in the POST-period with a difference of 779.6 €/patient. Our data suggest that the use of BDG was a cost-effective strategy that contributed to safely improving the results of an ASP for SOT and oncologic patients.

Error Detection and Cost Savings With an Image-Based Workflow Management System Connected to a Computerized Prescription Order Entry Program for Antineoplastic Compounding.

OBJECTIVE: The aim of the study was to analyze both the prevalence of errors with the implementation of an image-based workflow management system during the antineoplastic compounding process, and the estimated costs associated with the negative clinical outcome if the errors had not been intercepted. METHODS: Three months after the implementation of Phocus Rx system at a hospital pharmacy department, the identification, classification (type, preparation stage, and cause), and potential severity degree (from negligible to catastrophic) of the errors intercepted were determined. The probability of an error causing an adverse event if it had reached the patient (from nil [0] to high [0.6]) and its consequences was estimated by a team of clinical pharmacists and physicians. Cost-effectiveness analysis from the hospital's perspective was performed. RESULTS: Overall, 9872 antineoplastic medications were prepared using Phocus Rx. The total compounding error rate was 0.8% (n = 78, 56 [69.2%] were related to incorrect dose, 20 [28.2%] to incorrect drug preparation or conditioning technique, and 2 [2.6%] were wrong drugs). Approximately 70% of the detected errors were classified as undetectable via the previous verification practice, with 11.55% judged to be potentially severe (n = 9) and 51.3% moderate (n = 29). Likelihood of occurrence of an adverse event was medium (0.4) to high (0.6) for 37.2% of the errors. Estimated cost ratio and return on investment were €4.21 and 321%, respectively. CONCLUSIONS: The implementation of Phocus Rx prevented antineoplastic preparation errors that would have reached the patient otherwise. In addition, acquisition of this technology was estimated to be cost-effective.

Evaluation of the use, effectiveness and safety of tyrosine kinase inhibitors in chronic myelogenous leukaemia in a general university hospital.

OBJECTIVES: To evaluate the use, effectiveness and safety of tyrosine kinase inhibitors (TKIs) for chronic myelogenous leukaemia (CML) in clinical practice. METHODS: A retrospective longitudinal study of patients with CML who received TKIs for at least 6 months was performed. Endpoints to evaluate effectiveness were haematological, cytogenetic and molecular responses. Safety was assessed according to the occurrence of adverse events. RESULTS: Sixty-two patients were included. All received imatinib as the initial TKI; 8% switched to nilotinib due to lack of major molecular response (MMR) to imatinib and 3% switched to dasatinib because of progression to blast crisis or lack of MMR. At the end of the study all patients had achieved at least a complete cytogenetic response. With regard to safety, in 11 patients the dose of imatinib was decreased and four patients switched to a second-generation TKI due to imatinib toxicity. CONCLUSIONS: Considering the good responses of most patients and its better known safety profile, imatinib should remain a good option for first-line treatment of CML.

Improving surgical antibiotic prophylaxis adherence and reducing hospital readmissions: a bundle of interventions including health information technologies.

OBJECTIVES: Infection following orthopaedic surgery is a feared complication and an indicator of the quality of the hospital. Surgical antibiotic prophylaxis (SAP) guidelines are not always properly followed. Our aim was to describe and evaluate the impact of a multidisciplinary intervention on antibiotic prophylaxis adherence to hospital guidelines and 30-day postoperative outcomes. METHODS: The study was carried out from January to May 2016 and consisted of creating a multidisciplinary team, updating institutional guidelines and embedding the recommendations in the computerised physician order entry system which is linked to dose and renal function alerts, educational activities and pharmaceutical bedside care of patients in the orthopaedic department. A prospective pre-post study was carried out in accordance with the Declaration of Helsinki. The following information was recorded: patient and surgery characteristics, adherence to SAP guidelines, surgical site infections, length of hospital stay and rate of readmission 30 days after discharge. Statistical analyses were performed using SPSS 18.0. RESULTS: Eighty three orthopaedic patients of mean±SD age 68.2±17.0 years (44.6% male, 40 in the pre-intervention group and 43 in the intervention group) were included. Cefazolin was the recommended and most commonly administered antibiotic agent. In the intervention group, an improvement in global adherence to guidelines was achieved (76.7% vs 89.9%; p=0.039): antibiotic duration (75.0% vs 97.7%), correct dosage post-surgery (55.0% vs 76.7%), timing of administration (57.5% vs 72.1%), antibiotic pre-surgery prescription (92.5% vs 97.7%). Three surgical site infections were detected in the pre-intervention group and none in the intervention group (p>0.05). Length of hospital stay was reduced by 1 day and readmission decreased by 15% (p=0.038). CONCLUSIONS: SAP is used in daily practice in most orthopaedic patients. The implementation of a multidisciplinary programme based on health technology improved the adherence to guidelines and appeared to reduce the readmission rate.

Risks and medication errors analysis to evaluate the impact of a chemotherapy compounding workflow management system on cancer patients' safety.

A failure modes, effects and criticality analysis was supported by an observational medication error rate study to analyze the impact of Phocus Rx®, a new image-based workflow software system, on chemotherapy compounding error rates. Residual risks that should be a target for additional action were identified and prioritized and pharmacy staff satisfaction with the new system was evaluated. In total, 16 potential failure modes were recognized in the pre-implementation phase and 21 after Phocus Rx® implementation. The total reduction of the criticality index was 67 percent, with a reduction of 46 percent in material preparation, 76 percent in drug production and 48 percent in quality control subprocesses. The relative risk reduction of compounding error rate was 63 percent after the implementation of Phocus Rx®, from 0.045 to 0.017 percent. The high-priority recommendations defined were identification of the product with batch and expiration date from scanned bidimensional barcodes on drug vials and process improvements in image-based quality control. Overall satisfaction index was 8.30 (SD 1.06) for technicians and 8.56 (SD 1.42) for pharmacists (p = 0.655). The introduction of a new workflow management software system was an effective approach to increasing safety in the compounding procedures in the pharmacy department, according to the failure modes, effects and criticality analysis method.

A retrospective cohort of invasive fusariosis in the era of antimould prophylaxis.

Mould-active prophylaxis is affecting the epidemiology of invasive mycoses in the form of a shift toward less common entities such as fusariosis. We analyze the characteristics of invasive fusariosis and its association to antifungal prophylaxis in a retrospective cohort (2004-2017) from a tertiary hospital in Madrid, Spain. Epidemiological, clinical, microbiological, and antifungal consumption data were retrieved. Isolates were identified to molecular level, and antifungal susceptibility was tested. Eight cases of invasive fusariosis were diagnosed. Three periods were identified according to incidence: <2008 (three cases), 2008-2013 (zero cases), >2014 (five cases). All except one case involved breakthrough fusariosis. During the earliest period, the episodes occurred while the patient was taking itraconazole (two) or fluconazole (one); more recently, while on micafungin (three) or posaconazole (one). Early cases involved acute leukemia at induction/consolidation, recent cases relapsed/refractory disease (P = .029). Main risk factor for fusariosis (62.5%) was prolonged neutropenia (median 44 days). Galactomannan and beta-D-glucan were positive in 37.5% and 100% of cases, respectively. All isolates except F. proliferatum presented high minimal inhibitory concentrations (MICs) against the azoles and lower MIC to amphotericin B. Most patients received combined therapy. Mortality at 42 days was 62.5%. Resolution of neutropenia was associated with survival (P = .048). Invasive fusariosis occurs as breakthrough infection in patients with hematologic malignancy, prolonged neutropenia, and positive fungal biomarkers. Recent cases were diagnosed in a period of predominant micafungin use in patients who had more advanced disease and protracted neutropenia and for whom mortality was extremely high. Resolution of neutropenia was a favorable prognostic factor.

Switching to a rilpivirine/emtricitabine/tenofovir single-tablet regimen in RNA-suppressed patients infected with human immunodeficiency virus 1: Effectiveness, safety and costs at 96 weeks.

OBJECTIVES: This study evaluates the effectiveness, safety and costs of switching to a rilpivirine/emtricitabine/tenofovir disoproxil fumarate (RPV/FTC/TDF) regimen in treatment-experienced HIV-1-infected patients with sustained virological suppression. METHODS: Observational, prospective study. Study population included all treatment-experienced patients with sustained virological suppression who switched to RPV/FTC/TDF during 2013 in a tertiary hospital. Patients were followed until they completed 96 weeks of treatment. The effectiveness end-point was defined as the proportion of patients who maintained virological suppression at week 96 by intention-to-treat analysis (discontinuation=failure). The safety of RPV/FTC/TDF (incidence of adverse events leading to discontinuation and laboratory abnormalities) and adherence to this regimen were evaluated, and the cost of switching was analysed. RESULTS: One-hundred forty-six patients were included. At week 96, 71.9% of patients remained virologically suppressed; 6.8% experienced virological failure. During follow-up, 25.3% of patients discontinued RPV/FTC/TDF (14.4% because of adverse events, mainly renal impairment). Throughout the 96 weeks, there were significant decreases in total cholesterol (TC) (14.0 mg/dL, P<.001), TC/HDL cholesterol ratio (0.4 mg/dL, P=.019) and triglycerides (42.0 mg/dL, P<.001). A slight decrease in glomerular filtration rate was observed (4.3 mL/min/1.73 m2 , P<.001). Switching to RPV/FTC/TDF improved adherence in the subgroup of patients whose previous treatment was based on a twice-daily schedule, although differences did not reach statistical significance. Switching to RPV/FTC/TDF reduced the annual per-patient antiretroviral cost by €1744 (P<.001). CONCLUSIONS: In virologically suppressed patients, the switch to a RPV/FTC/TDF regimen was associated with a mild but maintained improvement in lipid parameters and a significant reduction in costs. However, the relatively high rates of virological failure and treatment discontinuation because of adverse events make this combination a less favourable choice over other regimens currently available.

Adding value through pharmacy validation: a safety and cost perspective.

RATIONALE, AIMS AND OBJECTIVES: Prescribing errors (PE) are frequent, cause significant harm to patients and prove costly. Few studies demonstrate the impact of pharmacist interventions. The objectives of this study were to characterize the severity and cost of the potential outcome of PE that pharmacists can prevent and to develop an economic analysis. METHOD: We performed a non-randomized, prospective, observational study of all prescriptions made to adult patients admitted to a 1300-bed tertiary teaching hospital in Madrid (Spain) by means of a computerized physician order entry tool combined with a clinical decision support system. We analysed PE intercepted through the pharmacist validation process between January and June 2013. An independent team determined the severity of the potential adverse drug event (ADE) and the probability of causing an ADE (PAE). We estimated the cost avoidance and performed an economic analysis. A kappa statistic was used to verify inter-observer agreement. RESULTS: 484 PE were intercepted: 36.2% of PE were classified as being of minor severity, 59.1% as moderate and 4.7% as serious. The most common type of moderate-serious PE found was excessive dose (30%, 94/309), followed by insufficient dose (20%, 62/309), and omission (19%, 58/309). The most frequent families of drugs involved in moderate-serious PE were antineoplastic agents (22.3%, 69/309) and antimicrobials (17.2%, 53/309). The PAE was higher than 40% in 49% of PE. We estimated a cost avoidance of €291,422 and a return on investment of €1.7 for each €1 spent on a pharmacist's salary. The overall inter-rater agreement for the participants was moderate for severity (κ = 0.57; P <0.005) and strong for the PAE (κ = 0.77; P <0.005). CONCLUSIONS: Pharmacists add important value in preventing PE, and their interventions are financially beneficial for the institution.

Prevalence of Hypothyroidism and Its Association with Diabetes Mellitus in Patients of an Ambulatory Clinic.

Hypothyroidism is the most common thyroid disorder in the adult population. Studies have found a higher prevalence of overt hypothyroidism in type 2 diabetic population than in the general population, but the relationship between subclinical hypothyroidism and diabetes mellitus 2 is still controversial. The aim of this study is to estimate the prevalence rate of hypothyroidism in the adult population receiving services in an ambulatory clinic and to determine if there is an association between hypothyroidism and diabetes mellitus. From the database of all adult patients who attended the outpatient clinic at Family Medicine Center Policlínica Bella Vista in Mayagüez, P.R. during 2014, a random sample of 200 subjects was obtained and the medical records were reviewed. The prevalence rate of diabetes mellitus in this group was 22% and the prevalence rate of hypothyroidism was 17%. The prevalence rate of hypothyroidism in diabetic patients was 10/44 (22.7%). The prevalence rate of hypothyroidism in non-diabetic patients was 24/156 (15.4%). The prevalence ratio was 1.48 (95% CI: 0.77, 2.85; X2 = 1.31, p = 0.25). The results of this cross-sectional study showed a non-statistically significant tendency for a higher prevalence of hypothyroidism in diabetic patients, which suggest that screening for hypothyroidism among patients with diabetes should be considered. More studies with more patients are necessary to investigate the association between thyroid dysfunction and diabetic patients.

Evaluation of antifungal use in a tertiary care institution: antifungal stewardship urgently needed.

OBJECTIVES: To assess the quality of antifungal use, to propose a point score for this evaluation and to estimate the potential economic savings of an antifungal stewardship programme. METHODS: From December 2010 to January 2011, we identified 100 adult inpatients receiving systemic antifungals. Antifungal use was evaluated by means of a predefined score that considered indication, drug selection, dosage, adjustments after microbiology results, switching to an oral agent and length of treatment. Total antifungal prescriptions [in defined daily doses (DDDs) and days of therapy (DOTs)] and potential cost savings were calculated. RESULTS: Overall, 43% of prescriptions came from medical departments, 25% from haematology/oncology and 17% from intensive care units. The main reasons for starting antifungals were empirical (42%), pre-emptive (20%) and targeted treatment (20%). Antifungals were unnecessary in 16% of cases. Inadequacies in other aspects of antifungal prescription were: drug selection, 31%; dosing, 16%; no switch from intravenous to oral administration, 20%; no adjustment after microbiological results, 35%; and length of therapy, 27%. The number of antifungal DDDs per 1000 patient-days was 65.1. The total number of DOTs was 1556, which added a direct cost of €219 364. Only 51.3% of DOTs were considered optimal. The potential estimated savings would be €50 536. CONCLUSIONS: Major efforts should be made to improve the selection and duration of antifungal therapy. Our study demonstrated the potential cost savings that could be achieved by optimizing antifungal therapy. A stewardship programme should include an instrument to objectively evaluate the adequacy of antifungal use.