Liquid antimicrobials: a national analysis of critical shortages.

Medicine shortages, especially those involving antibiotics, pose a global public health dilemma that can lead to adverse health outcomes. The aim of this study was to assess the supply situation of various antimicrobials in liquid dosage forms, which represent the mainstay of therapy for paediatric infections. The availability was examined over a period of 27 weeks in Austria. During the time period investigated, 34 products (81.0%) were not available for over 50% of the time; eight of those (19.0%) experienced complete unavailability. Only four products (9.5%) demonstrated continuous availability. Regarding penicillin antibiotics, amoxicillin was not available for 77.8% of the time (21 weeks) and amoxicillin/clavulanic acid for 59.3% (16 weeks). Regular monitoring of availability status can help mitigate this issue; however, cross-national strategies are urgently needed to guarantee a constant supply in the future.

The Impact of Clinical Pharmacy Services in a Tertiary Care Center Specialized in Pediatric Hemato-Oncology.

Clinical pharmacy services (CPS) have shown beneficial effects on several outcome measures in hospital patients, including the reduction of drug-related problems (DRP) and of therapy costs. Less is known about the impact of CPS in pediatric haemato-oncology, even though this patient population is highly susceptible to DRP. CPS were implemented in a tertiary care children's hospital specialized in hemato-oncology and hematopoietic stem cell transplantation. The main outcome measures were type and number of DRP, type and number of pharmaceutical interventions (PI), their acceptance rate, and their clinical significance and economic benefit. During 6 months and 32 ward rounds, 275 DRP were identified and addressed by PI. The acceptance of PI was high (73.4%), and up to 80% of PI were rated as very significant or significant by independent external raters. The estimated therapy cost reductions were substantial, approaching at least EUR 54,600 for avoided follow-up costs. Conclusion: CPS improve medication safety in pediatric hemato-oncology and may reduce therapy costs.

Eculizumab use in a tertiary care nephrology center: data from the Vienna TMA cohort.

BACKGROUND: Practice patterns of eculizumab use are not well described. We examined indications for, and outcomes of, eculizumab therapy in a tertiary care nephrology center. METHODS: We used the "Vienna TMA cohort" and the hospital pharmacy database at the Medical University of Vienna to identify patients that received eculizumab treatment between 2012 and 2019. We describe clinical characteristics, details of eculizumab use, and outcomes of patients with complement gene-variant mediated TMA (cTMA), secondary TMA (sTMA) and C3 glomerulopathy (C3G). RESULTS: As of December 2019, 23 patients received complement blockade at the Division of Nephrology and Dialysis: 15 patients were diagnosed with cTMA, 6 patients with sTMA and 2 patients with C3G. Causes of sTMA were bone marrow transplantation (n = 2), malignant hypertension, malignant tumor, systemic lupus erythematosus, antiphospholipid syndrome and lung transplantation (each n = 1). Across all indications, patients had a median age of 31 and were predominantly female (78%) and the median duration of treatment was 227 days. Hematological recovery was seen in most patients, while renal response was best in patients with cTMA. Adverse events were recorded in 26%. CONCLUSIONS: In summary, eculizumab is the treatment of choice for cTMA patients that do not respond to plasma therapy. In patients with sTMA and C3G, the response rates to therapy are much lower and therefore, the decision to start therapy needs to be considered carefully.

Tackling the challenges of nanomedicines: are we ready?

PURPOSE: This review provides an overview of the proceedings of the symposium "Tackling the Challenges of Nanomedicines: Are We Ready?" organized by the International Pharmaceutical Federation (FIP) Hospital Pharmacy Section and Non-Biological Complex Drugs (NBCDs) Working Group at the 2019 FIP World Congress of Pharmacy and Pharmaceutical Sciences. Debate centered on reasons underlying the current complex regulatory landscape for nanomedicines and their follow-on products (referred to as nanosimilars) and the pivotal role of hospital pharmacists in selecting, handling, and guiding usage of nanomedicines and nanosimilars. SUMMARY: The evaluation and use of nanomedicines are recognized among scientific, pharmaceutical, and regulatory bodies as complex. Interchangeability and substitutability of nanomedicines and nanosimilars are confounded by a lack of pharmaceutical and pharmacological equivalence, reflecting the inherent complex nature of these drug products and manufacturing processes. Consequences include implications for clinical safety and efficacy and, ultimately, comparability. Local regulatory approvals of some nanomedicines have occurred, but there is no standard to ensure streamlined evaluation and use of consistent measures of therapeutic equivalence of reference products and their nanosimilars. Hospital pharmacists are expected to be experts in the selection, handling, and substitution of nanomedicines and familiarize themselves with the limitations of current methods of assessing pharmaceutical and clinical equivalence of nanosimilars in order to ensure informed formulary decision-making and eventual patient benefit. CONCLUSION: Supportive guidance for pharmacists focusing on the substitutability and/or interchangeability of nanomedicines and their nanosimilars is needed. Current FIP guidance for pharmacists on therapeutic interchange and substitution should be extended to include nanomedicines and nanosimilars.

Risks in Antibiotic Substitution Following Medicine Shortage: A Health-Care Failure Mode and Effect Analysis of Six European Hospitals.

Introduction: Medicine shortages result in great risk for the continuity of patient care especially for antimicrobial treatment, potentially enhancing resistance rates and having a higher economic impact. This study aims to identify, describe, assess, and assign risk priority levels to potential failures following substitution of antimicrobial treatment due to shortages among European hospitals. Furthermore, the study investigated the impact of corrective actions on risk reduction so as to provide guidance and improve future patient care. Methods: Health-care failure mode and effect analysis (HFMEA) was applied to hospitals in Austria (H-AT), Belgium (H-BE), Croatia (H-CR), Greece (H-GR), Spain (H-SP), and Serbia (H-SR). Multidisciplinary teams identified processes, failure modes, causes, and corrective actions related to antibiotic substitution following medicine shortages. Characteristics of study hospitals as well as severity, probability, and hazard scores (HSs) of failure modes/causes were analyzed using Microsoft Office Excel 2010 and IBM SPSS Statistics® via descriptive and inferential statistics. Results: Through HFMEA, 74 failure modes were identified, with 53 of these scoring 8 or above on the basis of assigned severity and probability for a failure. Severity of failure modes differed before and after corrective actions in H-CR, H-GR, and H-SR (p < 0.005). Their probability differed in all study hospitals (p < 0.005) when compared before and after corrective actions aimed to be implemented. The highest number of failure-mode causes was detected in H-CR (46) and the lowest in H-SP (16). Corrective actions can address failure modes and lower HSs; therein, all teams proposed the following: structuring communication among stakeholders, introducing electronic prescribing, strengthening pharmacists' involvement, and increasing effectiveness of the ward stock assessment. These proposed actions led to HS reductions up to 83%. Conclusion: There is a lack of structure in addressing risks associated with antibiotic substitution following shortages. Furthermore, lack of communication, data scarcity on availability of antibiotics, non-supportive information technology (IT) systems, and lack of internal substitution protocols hinder quick assessment of alternatives addressing patient needs. Nevertheless, the study shows that health-care professionals manage to secure optimal antimicrobial treatment for patients using available IT and human resources.

Pharmacy Practice and Education in Austria.

The PHARMINE (“Pharmacy Education in Europe”) project studied pharmacy practice and education in the European Union (EU) member states. The work was carried out using an electronic survey sent to chosen pharmacy representatives. The surveys of the individual member states are now being published as reference documents for students and staff interested in research on pharmacy education in the EU and in mobility. This paper presents the results of the PHARMINE survey on pharmacy practice and education in Austria. In the light of this, we examine the harmonisation of practice and education in Austria with EU norms.

Dalteparin or vitamin K antagonists to prevent recurrent venous thromboembolism in cancer patients: a patient-level economic analysis for France and Austria.

BACKGROUND: International guidelines recommend extended duration secondary prophylaxis in cancer patients who develop primary venous thromboembolism (VTE). Agent selection is guided in part by one large randomized trial (i.e., CLOT; Lee et al., N Engl J Med 349:146-53, 2003) which demonstrated that dalteparin reduced the relative risk of recurrence by 52% compared with oral vitamin K antagonists (VKA; HR = 0.48, 95% CI, 0.30 to 0.77). In a subgroup analysis from that same trial, patients with renal impairment also derived benefit with dalteparin (VTE rates = 3% vs. 17%; p = 0.011). To measure the economic value of secondary VTE prophylaxis with dalteparin, a patient-level pharmacoeconomic analysis was conducted from the Austrian and French healthcare system perspectives. METHODS: Chapter 1 Healthcare resource use collected during the CLOT trial was extracted and converted into direct cost estimates. Incremental cost differences between the dalteparin and VKA groups were then combined with health state utilities to measure the cost per quality-adjusted life year (QALY) gained. RESULTS: The dalteparin group had significantly higher costs than the VKA group in both countries (Austria: dalteparin = €2687 vs. VKA = €2012; France: dalteparin = €2053 vs. VKA = €1352: p < 0.001). However, when the incremental costs were combined with the utility gain, dalteparin had a cost of €6600 and €4900 per QALY gained in Austria and France, respectively. The analyses in patients with renal impairment suggested an even better economic profile, with the cost per QALY gained being less than €4000 in both countries. CONCLUSIONS: Secondary prophylaxis with dalteparin is a cost-effective alternative to VKA for the prevention of recurrent VTE in patients with cancer.

Vildagliptin and pioglitazone in patients with impaired glucose tolerance after kidney transplantation: a randomized, placebo-controlled clinical trial.

BACKGROUND: New-onset diabetes after transplantation (NODAT) is a serious complication after kidney transplantation affecting graft and patient survival. Currently, no guidelines exist for the management of renal transplant patients with impaired glucose tolerance (IGT), a risk factor for the development of NODAT and an independent predictor of death. METHODS: In a population of 48 stable renal transplant recipients at least 6 months from time of transplantation with newly diagnosed IGT, we tested the dipeptidylpeptidase-4 inhibitor vildagliptin, the thiazolidinedione pioglitazone, or placebo for 3 months in addition to lifestyle counseling. Outcome measures were difference in change in oral glucose tolerance test between the groups and between baseline and end of study as well as change in HbA1c, serum lipids, and renal and hepatic function. RESULTS: In both treatment groups, 2-hr plasma glucose at 3 months was significantly reduced compared with baseline (vildagliptin: -20±24 mg/dL; P=0.002 and pioglitazone: -23±29 mg/dL; P=0.004), and pioglitazone also significantly improved fasting plasma glucose (-11±14 mg/dL; P=0.003), although the primary outcome (difference in change in 2-hr plasma glucose among the three groups) did not reach statistical significance. Furthermore, HbA1c was decreased in both treatment arms (vildagliptin: -0.1%±0.3%; P=0.046 and pioglitazone: -0.2%±0.3%; P=0.029). In the placebo group, no significant changes in these parameters were observed. Only mild adverse events occurred and at a similar rate in all three groups. CONCLUSIONS: These data demonstrate that both vildagliptin and pioglitazone are of potential benefit in patients with IGT after renal transplantation in addition to lifestyle modification.

The clinical pharmacist's contributions within the multidisciplinary patient care team of an intern nephrology ward.

OBJECTIVE: To describe and evaluate newly implemented clinical pharmacy services and ward round participation on a specialized nephrology ward in a large tertiary care hospital. METHOD: All issues addressed by the clinical pharmacist were systematically collected, and the contributions were classified by type. Where applicable, physicians' acceptance rates were recorded. The drugs most commonly affected by the clinical pharmacist's contributions are described. RESULTS: A total of 158 clinical pharmacist's contributions were recorded. Approximately 90% (n = 104) of applicable suggestions (117 out of 158; 74%) were accepted by the treating physicians. Most issues were discussed with physicians (85%); the remaining issues were discussed with nurses and medical students. Antimicrobials, drugs affecting the alimentary system and metabolism, and cardiovascular drugs were among the most commonly affected drugs. Issues concerning dosage and drug-therapy selection were common. The clinical pharmacist was also involved in developing dosing guidelines and performing literature searches. CONCLUSION: The observed effects of a newly implemented clinical pharmacy service on an internal nephrology ward are encouraging; acceptance rates of suggestions and the multidisciplinary appreciation of clinical pharmacy services are high.

Clinical pharmacy activities in chronic kidney disease and end-stage renal disease patients: a systematic literature review.

BACKGROUND: Chronic kidney disease (CKD) and end-stage renal disease (ESRD) represent worldwide health problems with an epidemic extent. Therefore, attention must be given to the optimisation of patient care, as gaps in the care of CKD and ESRD patients are well documented. As part of a multidisciplinary patient care strategy, clinical pharmacy services have led to improvements in patient care. The purpose of this study was to summarise the available evidence regarding the role and impact of clinical pharmacy services for these patient populations. METHODS: A literature search was conducted using the Medline, Embase and International Pharmaceutical Abstracts databases to identify relevant studies on the impact of clinical pharmacists on CKD and ESRD patients, regarding disease-oriented and patient-oriented outcomes, and clinical pharmacist interventions on drug-related problems. RESULTS: Among a total of 21 studies, only four (19%) were controlled trials. The majority of studies were descriptive (67%) and before-after studies (14%). Interventions comprised general clinical pharmacy services with a focus on detecting, resolving and preventing drug-related problems, clinical pharmacy services with a focus on disease management, or clinical pharmacy services with a focus on patient education in order to increase medication knowledge. Anaemia was the most common comorbidity managed by clinical pharmacists, and their involvement led to significant improvement in investigated disease-oriented outcomes, for example, haemoglobin levels. Only four of the studies (including three controlled trials) presented data on patient-oriented outcomes, for example, quality of life and length of hospitalisation. Studies investigating the number and type of clinical pharmacist interventions and physician acceptance rates reported a mean acceptance rate of 79%. The most common reported drug-related problems were incorrect dosing, the need for additional pharmacotherapy, and medical record discrepancies. CONCLUSIONS: Few high-quality trials addressing the benefit and impact of clinical pharmacy services in CKD and ESRD patients have been published. However, all available studies reported some positive impact resulting from clinical pharmacist involvement, including various investigated outcome measures that could be improved. Additional randomised controlled trials investigating patient-oriented outcomes are needed to further determine the role of clinical pharmacists and the benefits of clinical pharmacy services to CKD and ESRD patients.

A randomized, placebo-controlled, double-blind, prospective trial to evaluate the effect of vildagliptin in new-onset diabetes mellitus after kidney transplantation.

BACKGROUND: New-onset diabetes mellitus after transplantation (NODAT), a frequent and serious complication after transplantation, is associated with decreased graft and patient survival. Currently, it is diagnosed and treated primarily according to existing guidelines for type II diabetes. To date, only a few trials have studied antidiabetic drugs in patients with NODAT. Vildagliptin is a novel dipeptidyl peptidase-4 (DPP-4) inhibitor that improves pancreatic islet function by enhancing both α- and ß-cell responsiveness to increased blood glucose. Experimental data show potential protective effects of DPP-4 inhibitors on islet function after exogenous stress stimuli including immunosuppressants. Therefore, the therapy of NODAT with this class of compounds seems attractive. At present, vildagliptin is used to treat type II diabetes as monotherapy or in combination with other antidiabetic drugs, since that it efficiently decreases glycated hemoglobin (HbA1c) values. Additionally, vildagliptin has been shown to be safe in patients with moderately impaired kidney function. This study will evaluate the safety and efficacy of vildagliptin monotherapy in renal transplant recipients with recently diagnosed NODAT. METHODS/DESIGN: This study is a randomized, placebo-controlled, double-blind, prospective phase II trial. Using the results of routinely performed oral glucose tolerance tests (OGTT) in stable renal transplant patients at our center, we will recruit patients without a history of diabetes and a 2 h glucose value surpassing 200 mg/dl (11.1 mmol/l). They are randomized to receive either 50 mg vildagliptin or placebo once daily. A total of 32 patients with newly diagnosed NODAT will be included. The primary endpoint is the difference in the 2 h glucose value between baseline and the repeated OGTT performed 3 months after treatment start, compared between the vildagliptin- and the placebo-group. Secondary endpoints include changes in HbA1c and fasting plasma glucose (FPG). The safety of vildagliptin in renal transplant patients will be assessed by the number of symptomatic hypoglycemic episodes (glucose <72 mg/dl or 4 mmol/l), the number of adverse events, and possible medication-associated side-effects. DISCUSSION: NODAT is a severe complication after kidney transplantation. Few trials have assessed the safety and efficacy of antidiabetic drugs for these patients. The purpose of this study is to assess the safety and efficacy of vildagliptin in renal transplant patients with NODAT. TRIAL REGISTRATION: ClinicalTrials.gov NCT00980356.

Sex-specific differences in metabolic control, cardiovascular risk, and interventions in patients with type 2 diabetes mellitus.

BACKGROUND: Sex-specific differences appear particularly relevant in the management of type 2 diabetes mellitus (T2DM), with women experiencing greater increases in cardiovascular morbidity and mortality than do men. OBJECTIVE: The aim of this article was to investigate the influence of biological sex on clinical care and microvascular and macrovascular complications in patients with T2DM in a Central European university diabetes clinic. METHODS: In a cross-sectional study, sex-specific disparities in metabolic control, cardiovascular risk factors, and diabetic complications, as well as concomitant medication use and adherence to treatment recommendations, were evaluated in 350 consecutive patients who were comparable for age, diabetes duration, and body mass index. Study inclusion criteria included age ≤75 years, T2DM, a documented history of presence or absence of coronary heart disease (CHD), and informed consent. Patients were followed in the diabetes outpatient clinic between November 2007 and March 2008. RESULTS: Two hundred and one patients with T2DM met inclusion criteria (93 [46.3%] women, 108 [53.7%] men). Women with T2DM had higher mean (SE) systolic blood pressure (155.4 [22.5] vs 141.0 [19.8] mm Hg for men; P < 0.001) and total cholesterol (TC) (5.28 [1.34] vs 4.86 [1.29] mmol/L for men; P < 0.05), but a lower TC:HDL-C ratio (4.1 [1.19] vs 4.5 [1.2] for men; P < 0.05). Slightly more men (32.4%) than women (26.9%) reached the therapeutic goal of <7.0% for glycosylated hemoglobin. Women with shorter diabetes duration (<10 years) received oral antihyperglycemic therapy less frequently (P < 0.05). Women with longer disease duration had hypertension more frequently than did their male counterparts (100% vs 86.0%, respectively; P < 0.01). Despite a similar rate of CHD, men were twice as likely as women to have had coronary interventions (percutaneous transluminal coronary angioplasty/coronary artery bypass graft, 25.0% vs 12.9%, respectively; P < 0.05). Women with CHD also had a higher rate of cerebral ischemia than did men (27.6% vs 5.4%, respectively; P < 0.05) and received aspirin less frequently for secondary prevention (P < 0.001). Men had greater overall adherence to diabetes and cardiovascular risk guidelines than did women (66.4% vs 58.9%, respectively; P < 0.01). CONCLUSIONS: In this study of diabetes clinic outpatients, women with T2DM had a worse cardiovascular risk profile and achieved therapeutic goals less frequently than did men. Treatment strategies should be improved in both sexes, but women with diabetes may be in need of more aggressive treatment, especially when cardiovascular disease is present.

Evaluation of risk factor management of patients treated on an internal nephrology ward: a pilot study.

BACKGROUND: The objectives of this pilot study were to evaluate treatment quality for the risk factors of hypertension, diabetes and hyperlipidemia as well as the overall treatment quality for patients on an internal nephrology ward. This evaluation included the collection of data concerning the quality of therapeutic drug monitoring, drug use and potential drug-drug interactions. Establishing such baseline information highlights areas that have a need for further therapeutic intervention and creates a foundation for improving patient care, a subject that could be addressed in future clinical pharmacy research projects. METHODS: Medical charts of patients treated on a single internal nephrology ward were retrospectively evaluated using a predefined data collection form. Assessment of further need for therapeutic intervention was performed. RESULTS: For 76.5% (n = 78) of the total study population (n = 102), there was either a possibility (39.2%, n = 40) or a need (37.3%, n = 38) for further intervention based on the overall assessment. For the risk factors of hypertension, diabetes and hyperlipidemia, the proportions of patients that require further intervention were 78.8% (n = 71), 90.6% (n = 58) and 87.9% (n = 58), respectively. Patients with diabetes or hyperlipidemia were less likely to have optimal risk factor control. The number of drugs prescribed and the number of potential drug-drug interactions were significantly higher after in-hospital treatment. CONCLUSION: Risk factor treatment needs optimisation. Risk factor management, systematic medication reviews, and screening for and management of potential drug-drug interactions deserve great attention. Clinical pharmacy services could help in the achievement of treatment goals.