ABSTRACT
AIMS: Therapeutic drug monitoring (TDM) aims to optimize drug therapy. As demand on health resources increases, and the technology underpinning TDM becomes more sophisticated, the economic benefits of TDM in hospitals is unclear. The aim of this systematic review was to summarize the economic evidence that could be used to support investment in TDM in hospital settings. In so doing, we sought to provide guidance for future economic evaluations. METHODS: Medline, Embase, CENTRAL, Econlit and NHS Economic Evaluation databases were searched (inception to December 2022) for economic evaluations of hospital-based TDM. Two authors reviewed the studies and extracted data. Overall quality of economic analysis reporting was assessed using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS) checklist. RESULTS: Ten prospective studies (including six randomized studies) and nine retrospective studies were eligible. Overall study reporting was poor, publications meeting a median (range) of 61% (46-82%) of CHEERS checklist criteria. An antimicrobial TDM intervention for adult patients was the focus of most studies (n = 18). Variable clinical outcomes were reported, and length of stay was the primary economic outcome for most studies (n = 13). The majority of studies determined that TDM was economically and clinically favourable (n = 14), four studies reporting a cost-reduction in patient sub-populations. CONCLUSIONS: Significant improvements in both economic and clinical outcomes may be realized with TDM interventions, particularly when targeted to complex patient populations. Attainment of therapeutic target could serve as a feasible surrogate measure of benefit for hospital-based TDM interventions. However, systematic reporting of economic outcomes is needed to inform investment decisions.
Subject(s)
Cost-Benefit Analysis , Drug Monitoring , Humans , Drug Monitoring/economics , Drug Monitoring/methods , Length of Stay/economics , Length of Stay/statistics & numerical data , HospitalsABSTRACT
BACKGROUND: The applicability of currently available tacrolimus population pharmacokinetic models in guiding dosing for lung transplant recipients is unclear. In this study, the predictive performance of relevant tacrolimus population pharmacokinetic models was evaluated for adult lung transplant recipients. METHODS: Data from 43 lung transplant recipients (1021 tacrolimus concentrations) administered an immediate-release oral formulation of tacrolimus were used to evaluate the predictive performance of 17 published population pharmacokinetic models for tacrolimus. Data were collected from immediately after transplantation up to 90 days after transplantation. Model performance was evaluated using (1) prediction-based assessments (bias and imprecision) of individual predicted tacrolimus concentrations at the fourth dosing based on 1 to 3 previous dosings and (2) simulation-based assessment (prediction-corrected visual predictive check; pcVPC). Both assessments were stratified based on concomitant azole antifungal use. Model performance was clinically acceptable if the bias was within ±20%, imprecision was ≤20%, and the 95% confidence interval of bias crossed zero. RESULTS: In the presence of concomitant antifungal therapy, no model showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33), and pcVPC plots displayed poor model fit to the data set. However, this fit slightly improved in the absence of azole antifungal use, where 4 models showed acceptable performance in predicting tacrolimus concentrations at the fourth dosing (n = 33). CONCLUSIONS: Although none of the evaluated models were appropriate in guiding tacrolimus dosing in lung transplant recipients receiving concomitant azole antifungal therapy, 4 of these models displayed potential applicability in guiding dosing in recipients not receiving concomitant azole antifungal therapy. However, further model refinement is required before the widespread implementation of such models in clinical practice.
Subject(s)
Immunosuppressive Agents , Lung Transplantation , Models, Biological , Tacrolimus , Humans , Tacrolimus/pharmacokinetics , Tacrolimus/therapeutic use , Immunosuppressive Agents/pharmacokinetics , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/administration & dosage , Middle Aged , Female , Male , Adult , Antifungal Agents/pharmacokinetics , Antifungal Agents/therapeutic use , Transplant Recipients , AgedABSTRACT
Vancomycin's widespread use as the mainstay antibiotic against methicillin-resistant Staphylococcus aureus infections is complicated by its narrow therapeutic index. Therapeutic drug monitoring using area under the concentration-time curve (AUC)-guided dosing is recommended to optimize therapy and prevent vancomycin-associated nephrotoxicity (VAN). In 2018, a consultative therapeutic drug monitoring Advisory Service (the Service) was piloted at an Australian hospital to enable AUC-guided vancomycin dosing. This study sought to compare the incidence of VAN pre- and post-Service implementation. A 4-year retrospective observational study of intravenous vancomycin therapy (greater than 48 hours) in adults (aged 18 years or older), spanning 3 years before and 1-year after implementation of the Service was undertaken. Nephrotoxicity was defined as an increase in serum creatinine concentrations of 26.5 µmol/L or greater or 50% or more from baseline, on 2 or more consecutive days. Univariate analysis was performed to compare patients before and after implementation, and with and without VAN. Independent factors associated with VAN were identified using a multivariate model. In total, 971 courses of vancomycin therapy, administered to 781 patients, were included: 764 courses (603 patients) before implementation and 207 courses (163 patients) after implementation. The incidence of VAN decreased by 5% after Service implementation (15% before implementation vs 10% after implementation; P = .075). Independent factors associated with VAN were sepsis, heart failure, solid-organ transplant, concomitant piperacillin-tazobactam, and average vancomycin AUC during therapy. In conclusion, there was a nonsignificant trend toward a reduced incidence of VAN after the Service. Larger prospective studies are needed to confirm the efficacy of the Service.
Subject(s)
Acute Kidney Injury , Methicillin-Resistant Staphylococcus aureus , Adult , Humans , Vancomycin , Drug Monitoring , Acute Kidney Injury/chemically induced , Australia/epidemiology , Anti-Bacterial Agents/adverse effects , Retrospective StudiesABSTRACT
BACKGROUND: People with substance use disorder are at high risk of harms from COVID-19 infection. Vaccine hesitancy is common in this population and compounds pre-existing barriers to accessing health care. A drug and alcohol service in Sydney, Australia introduced strategies to enhance COVID-19 vaccination in people receiving opioid agonist treatment (OAT). We report vaccination outcomes and staff experiences of this. METHODS: This mixed methods study (i) retrospectively evaluated vaccine uptake in people accessing OAT and (ii) explored perceptions of staff who delivered vaccination interventions through surveys and semi-structured interviews. RESULTS: Of the 984 patients receiving OAT on 9 December 2021, 90.9% had received the first COVID-19 vaccination and 86.7% the second. Australia wide vaccination rates on that date were 93.1% and 88.7% for first and second doses, respectively. Staff commented that having a deep knowledge, understanding and connection with the patient group drove implementation and success of vaccination interventions. This was further supported by staff engagement with the vaccination interventions, and communication and sharing information, both between staff and with patients. CONCLUSION: High rates of COVID-19 vaccination can be achieved in a vulnerable population. Engaged staff providing information and facilitating access to healthcare underpin this success.
Subject(s)
COVID-19 , Substance-Related Disorders , Humans , COVID-19/prevention & control , COVID-19 Vaccines/administration & dosage , Retrospective Studies , VaccinationABSTRACT
OBJECTIVES: Identification of inappropriate medications in people living with severe dementia is a complex task which has the potential to reduce avoidable adverse events and increase quality of life. This scoping review (i) identifies published tools intended to aid deprescribing in people living with severe dementia and (ii) describes evaluations of their usefulness in clinical practice. METHODS: A scoping review was undertaken, with Medline, Medline in Process, EMBASE, Cochrane Library, CINAHL, Scopus and Web of Science databases, from inception to April 2023, identifying tools for deprescribing in severe dementia. A tool was considered as any resource for deprescribing, including clinical study, scientific publication, health guideline, website, algorithm, model or framework. Two reviewers assessed the eligibility of articles through abstract and full text review. Data extracted from included studies were summarized through narrative synthesis. RESULTS: Twelve studies were identified from 18,633 articles screened. Tools were categorized into three groups: deprescribing interventions (n = 2), consensus-based deprescribing criteria (n = 5), and medication-specific recommendations (n = 5). Six studies developed tools using expert opinion and ten tools were tested in people living with severe dementia. Only one of the four studies that evaluated patient outcomes (cognitive change and adverse events) identified clear clinical benefit from medication withdrawal. CONCLUSIONS: Clinical application of current deprescribing tools is limited due to the lack of evidence-based research on the clinical effects of individual medication deprescribing in people with severe dementia. Further research on patient outcomes, including cognitive change and adverse events, will help clarify the role of these tools in clinical care.
Subject(s)
Dementia , Deprescriptions , Humans , Quality of Life , Dementia/drug therapyABSTRACT
AIMS: This study investigated the safe use of metformin in patients with (1) type 2 diabetes mellitus (T2DM) and heart failure on metformin, and (2) heart failure without T2DM and metformin naïve. METHODS: Two prospective studies on heart failure patients were undertaken. The first was a cross-sectional study with two patient cohorts, one with T2DM on metformin (n = 44) and one without T2DM metformin naive (n = 47). The second was a 12-week interventional study of patients without T2DM (n = 27) where metformin (500 mg immediate release, twice daily) was prescribed. Plasma metformin and lactate concentrations were monitored. Individual pharmacokinetics were compared between cohorts. Univariable and multivariable analysis analysed the effects of variables on plasma lactate concentrations. RESULTS: Plasma metformin and lactate concentrations mostly (99.9%) remained below safety thresholds (5 mg/L and 5 mmol/L, respectively). Metformin concentration had no significant relationship with lactic acidosis safety markers. In the interventional study, New York Heart Association (NYHA) II (P < .03) and III (P < .001) grading was associated with higher plasma lactate concentrations, whereas male sex was associated with 47% higher plasma lactate concentrations (P < .05). The pharmacokinetics of heart failure patients with and without T2DM were similar. CONCLUSIONS: We observed no unsafe plasma lactate concentrations in patients with heart failure treated with metformin. Metformin exposure did not influence plasma lactate concentrations, but NYHA class and sex did. The pharmacokinetics of metformin in heart failure patients are similar irrespective of T2DM. These findings may support the safe use of metformin in heart failure patients with and without T2DM.
Subject(s)
Diabetes Mellitus, Type 2 , Heart Failure , Metformin , Humans , Male , Metformin/adverse effects , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/drug therapy , Cross-Sectional Studies , Hypoglycemic Agents/adverse effects , Longitudinal Studies , Prospective Studies , Lactic Acid , Heart Failure/complications , Heart Failure/drug therapy , Heart Failure/chemically inducedABSTRACT
Dose-prediction software is recommended to enable area under the curve over 24 h (AUC24 )-guided dosing of the antibiotic vancomycin. However, uncertainty remains about how best to implement software in the clinic. We describe the activity, over 18 months, of a consultative therapeutic drug monitoring Advisory Service (the Service) for vancomycin that used dose-prediction software alongside clinical expertise, identifying factors that influence attainment of therapeutic targets. Of the 408 vancomycin dose reports provided for 182 courses of therapy, most (57%) recommended a dose change. The majority (82.8%, 193/233) of recommended dose adjustments were accepted by treating teams. A dose report was not published for 125 courses of therapy, with reasons including patient in intensive care unit or service error. An estimated 26.6 h of staff time was allocated to Service activities each month. Publication of a dose report facilitated attainment of therapeutic targets (P = .002). Software integration could improve Service outcomes, avoiding errors and reducing staff workload.
Subject(s)
Consultants , Vancomycin , Humans , Drug Monitoring , Anti-Bacterial Agents , Intensive Care UnitsABSTRACT
AIM: Existing tacrolimus population pharmacokinetic models are unsuitable for guiding tacrolimus dosing in heart transplant recipients. This study aimed to develop and evaluate a population pharmacokinetic model for tacrolimus in heart transplant recipients that considers the tacrolimus-azole antifungal interaction. METHODS: Data from heart transplant recipients (n = 87) administered the oral immediate-release formulation of tacrolimus (Prograf®) were collected. Routine drug monitoring data, principally trough concentrations, were used for model building (n = 1099). A published tacrolimus model was used to inform the estimation of Ka , V2 /F, Q/F and V3 /F. The effect of concomitant azole antifungal use on tacrolimus CL/F was quantified. Fat-free mass was implemented as a covariate on CL/F, V2 /F, V3 /F and Q/F on an allometry scale. Subsequently, stepwise covariate modelling was performed. Significant covariates influencing tacrolimus CL/F were included in the final model. Robustness of the final model was confirmed using prediction-corrected visual predictive check (pcVPC). The final model was externally evaluated for prediction of tacrolimus concentrations of the fourth dosing occasion (n = 87) from one to three prior dosing occasions. RESULTS: Concomitant azole antifungal therapy reduced tacrolimus CL/F by 80%. Haematocrit (∆OFV = -44, P < .001) was included in the final model. The pcVPC of the final model displayed good model adequacy. One recent drug concentration is sufficient for the model to guide tacrolimus dosing. CONCLUSION: A population pharmacokinetic model that adequately describes tacrolimus pharmacokinetics in heart transplant recipients, considering the tacrolimus-azole antifungal interaction was developed. Prospective evaluation is required to assess its clinical utility to improve patient outcomes.
Subject(s)
Heart Transplantation , Tacrolimus , Humans , Tacrolimus/pharmacokinetics , Immunosuppressive Agents/pharmacokinetics , Antifungal Agents , Azoles , Models, Biological , Transplant Recipients , Cytochrome P-450 CYP3AABSTRACT
Pharmacological therapy is the mainstay of treatment for cancer patients. Despite wide interpatient variability in systemic drug concentrations for numerous antineoplastics, dosing based on body size remains the predominant approach. Therapeutic drug monitoring (TDM) is used for few antineoplastics in specific scenarios. We conducted a rapid bibliometric evaluation of TDM in oncology to capture a snapshot of research in this area over time and explore topics that reflect development in the field. Reports with the composite, indexed term 'therapeutic drug monitoring' in the title and abstract were extracted from MEDLINE (inception to August 2021). Reports related to applications in cancer were selected for inclusion and were tagged by study design, antineoplastic drugs and concepts related to TDM. We present a timeline from 1980 to the present indicating the year of first report of antineoplastic agents and key terms. The reports in our sample primarily reflected development and validation of analytical methods with few relating to clinical outcomes to support implementation. Our work emphasises evidence gaps that may contribute to poor uptake of TDM in oncology.
ABSTRACT
OBJECTIVE: To understand and synthesize factors influencing user acceptance of digital interventions used for antimicrobial prescribing and monitoring in hospitals. MATERIALS AND METHODS: A meta-synthesis was conducted to identify qualitative studies that explored user acceptance of digital interventions for antimicrobial prescribing and/or monitoring in hospitals. Databases were searched and qualitative data were extracted and systematically classified using the unified theory of acceptance and use of technology (UTAUT) model. RESULTS: Fifteen qualitative studies met the inclusion criteria. Eleven papers used interviews and four used focus groups. Most digital interventions evaluated in studies were decision support for prescribing (n = 13). Majority of perceptions were classified in the UTAUT performance expectancy domain in perceived usefulness and relative advantage constructs. Key facilitators in this domain included systems being trusted and credible sources of information, improving performance of tasks and increasing efficiency. Reported barriers were that interventions were not considered useful for all settings or patient conditions. Facilitating conditions was the second largest domain, which highlights the importance of users having infrastructure to support system use. Digital interventions were viewed positively if they were compatible with values, needs, and experiences of users. CONCLUSIONS: User perceptions that drive users to accept and utilize digital interventions for antimicrobial prescribing and monitoring were predominantly related to performance expectations and facilitating conditions. To ensure digital interventions for antimicrobial prescribing are accepted and used, we recommend organizations ensure systems are evaluated and benefits are conveyed to users, that utility meets expectations, and that appropriate infrastructure is in place to support use.
Subject(s)
Anti-Infective Agents , Anti-Bacterial Agents/therapeutic use , Anti-Infective Agents/therapeutic use , Efficiency , Hospitals , Humans , Qualitative ResearchABSTRACT
BACKGROUND AND AIM: Identification of the most appropriate population pharmacokinetic model-based Bayesian estimation is required prior to its implementation in routine clinical practice to inform tacrolimus dosing decisions. This study aimed to determine the predictive performances of relevant population pharmacokinetic models of tacrolimus developed from various solid organ transplant recipient populations in adult heart transplant recipients, stratified based on concomitant azole antifungal use. Concomitant azole antifungal therapy alters tacrolimus pharmacokinetics substantially, necessitating dose adjustments. METHODS: Population pharmacokinetic models of tacrolimus were selected (n = 17) for evaluation from a recent systematic review. The models were transcribed and implemented in NONMEM version 7.4.3. Data from 85 heart transplant recipients (2387 tacrolimus concentrations) administered the oral immediate-release formulation of tacrolimus (Prograf) were obtained up to 391 days post-transplant. The performance of each model was evaluated using: (i) prediction-based assessment (bias and imprecision) of the individual predicted tacrolimus concentration of the fourth dosing occasion (MAXEVAL = 0, FOCE-I) from 1-3 prior dosing occasions; and (ii) simulation-based assessment (prediction-corrected visual predictive check). Both assessments were stratified based on concomitant azole antifungal use. RESULTS: Regardless of the number of prior dosing occasions (1-3) and concomitant azole antifungal use, all models demonstrated unacceptable individual predicted tacrolimus concentration of the fourth dosing occasion (n = 152). The prediction-corrected visual predictive check graphics indicated that these models inadequately predicted observed tacrolimus concentrations. CONCLUSION: All models evaluated were unable to adequately describe tacrolimus pharmacokinetics in adult heart transplant recipients included in this study. Further work is required to describe tacrolimus pharmacokinetics for our heart transplant recipient cohort.
Subject(s)
Heart Transplantation , Tacrolimus , Adult , Antifungal Agents , Azoles , Bayes Theorem , Humans , Immunosuppressive Agents/pharmacokinetics , Models, Biological , Tacrolimus/pharmacokinetics , Transplant RecipientsABSTRACT
BACKGROUND: Therapeutic drug monitoring is recommended to guide tacrolimus dosing because of its narrow therapeutic window and considerable pharmacokinetic variability. This study assessed tacrolimus dosing and monitoring practices in heart transplant recipients and evaluated the predictive performance of a Bayesian forecasting software using a renal transplant-derived tacrolimus model to predict tacrolimus concentrations. METHODS: A retrospective audit of heart transplant recipients (n = 87) treated with tacrolimus was performed. Relevant data were collected from the time of transplant to discharge. The concordance of tacrolimus dosing and monitoring according to hospital guidelines was assessed. The observed and software-predicted tacrolimus concentrations (n = 931) were compared for the first 3 weeks of oral immediate-release tacrolimus (Prograf) therapy, and the predictive performance (bias and imprecision) of the software was evaluated. RESULTS: The majority (96%) of initial oral tacrolimus doses were guideline concordant. Most initial intravenous doses (93%) were lower than the guideline recommendations. Overall, 36% of initial tacrolimus doses were administered to transplant recipients with an estimated glomerular filtration rate of <60 mL/min/1.73 m despite recommendations to delay the commencement of therapy. Of the tacrolimus concentrations collected during oral therapy (n = 1498), 25% were trough concentrations obtained at steady-state. The software displayed acceptable predictions of tacrolimus concentration from day 12 (bias: -6%; 95%confidence interval, -11.8 to 2.5; imprecision: 16%; 95% confidence interval, 8.7-24.3) of therapy. CONCLUSIONS: Tacrolimus dosing and monitoring were discordant with the guidelines. The Bayesian forecasting software was suitable for guiding tacrolimus dosing after 11 days of therapy in heart transplant recipients. Understanding the factors contributing to the variability in tacrolimus pharmacokinetics immediately after transplant may help improve software predictions.
Subject(s)
Heart Transplantation , Tacrolimus , Adult , Bayes Theorem , Humans , Immunosuppressive Agents/pharmacokinetics , Retrospective Studies , Software , Tacrolimus/pharmacokinetics , Transplant RecipientsABSTRACT
AIMS: Accurate documentation of medication administration time is imperative for many therapeutic decisions, including dosing of intravenous antimicrobials. The objectives were to determine (1) the discrepancy between actual and documented administration times for antimicrobial infusions and (2) whether day of the week, time of day, nurse-to-patient ratio and drug impacted accuracy of documented administration times. METHODS: Patient and dosing data were collected (June-August 2019) for 55 in-patients receiving antimicrobial infusions. "Documented" and "actual" administration times (n = 660) extracted from electronic medication management systems and smart infusion pumps, respectively, were compared. Influence of the day (weekday/weekend), time of day (day/evening/night), nurse-to-patient ratio (high 1:1/low 1:5) and drug were examined. Monte Carlo simulation was used to predict the impact on dose adjustments for vancomycin using the observed administration time discrepancies compared to the actual administration time. RESULTS: The median discrepancy between actual and documented administration times was 16 min (range, 2-293 min), with discrepancies greater than 60 minutes in 7.7% of administrations. Overall, discrepancies (median [range]) were similar on weekends (17 [2-293] min) and weekdays (16 [2-188] min), and for high (16 [2-157] min) and low nurse-to-patient ratio wards (16 [2-293] min). Discrepancies were smallest for night administrations (P < .05), and antimicrobials with shorter half-lives (P < .0001). The observed discrepancies in vancomycin administration time resulted in a different dose recommendation in 58% of cases (30% higher, 28% lower). CONCLUSIONS: Overall, there were discrepancies between actual and documented antimicrobial infusion administration times. For vancomycin, these discrepancies in administration time were predicted to result in inappropriate dose recommendations.
Subject(s)
Infusion Pumps , Pharmaceutical Preparations , Anti-Bacterial Agents , Documentation , Humans , Infusions, Intravenous , VancomycinABSTRACT
AIMS: Despite the availability of international consensus guidelines, vancomycin dosing and therapeutic drug monitoring (TDM) remain suboptimal. This study aimed to assess concordance of vancomycin dosing and TDM with institutional guidelines and to identify factors taken into consideration by clinicians when prescribing vancomycin. METHODS: A retrospective audit of 163 patients receiving vancomycin therapy (≥48 hours) was undertaken. Data collected included patient characteristics, dosing history and plasma vancomycin and creatinine concentrations. Concordance of dosing and TDM with institutional guidelines was evaluated. Semi-structured interviews, including simulated prescribing scenarios, were undertaken with prescribers (n = 17) and transcripts analysed. RESULTS: Plasma vancomycin concentrations (n = 1043) were collected during 179 courses of therapy. Only 24% of courses commenced with a loading dose with 72% lower than recommended. The initial maintenance dose was concordant in 42% of courses with 34% lower than recommended. Only 14% of TDM samples were trough vancomycin concentrations. Dose was not adjusted for 60% (21/35) of subtherapeutic and 43% (18/42) of supratherapeutic trough vancomycin concentrations, respectively. Interview participants reported that patient characteristics (including renal function), vancomycin concentrations, guidelines and expert advice influenced vancomycin prescribing decisions. Despite referring to guidelines when completing simulated prescribing scenarios, only 37% of prescribing decisions aligned with guideline recommendations. CONCLUSION: Poor compliance with institutional vancomycin guidelines was observed, despite prescriber awareness of available guidelines. Multifaceted strategies to support prescriber decision-making are required to improve vancomycin dosing and monitoring.
Subject(s)
Anti-Bacterial Agents , Vancomycin , Anti-Bacterial Agents/therapeutic use , Drug Monitoring , Humans , Retrospective StudiesABSTRACT
AIMS: Dose-prediction software can optimise vancomycin therapy, improving therapeutic drug monitoring processes and reducing drug toxicity. Success of software in hospitals may be dependent on prescriber uptake of software recommendations. This study aimed to identify the perceived psychosocial and environmental barriers and facilitators to prescriber acceptance of dose-prediction software. METHODS: Semi-structured interviews, incorporating prescribing scenarios, were undertaken with 17 prescribers. Participants were asked to prescribe the next maintenance dose of vancomycin for a scenario(s) and then asked if they would accept a recommendation provided by a dose-prediction software. Interviews further explored opinions of dose-prediction software. Interview transcripts were analysed using an inductive approach to identify themes and the Theoretical Domains Framework was used to synthesise barriers and facilitators to software acceptance. RESULTS: When presented with software recommendations, half of the participants were comfortable with accepting the recommendation. Key barriers to acceptance of software recommendations aligned with 2 Theoretical Domains Framework domains: Knowledge (uncertainty of software capability) and Beliefs about Consequences (perceived impact of software on clinical outcomes and workload). Key facilitators aligned with 2 domains: Beliefs about Consequences (improved efficiency) and Social Influences (influence of peers). A novel domain, Trust, was identified as influential. CONCLUSION: Prescribers reported barriers to acceptance of dose-prediction software aligned with limited understanding of, and scepticism about, software capabilities, as well as concerns about clinical outcomes. Identification of key barriers and facilitators to acceptance provides essential information to design of implementation strategies to support the introduction of this intervention into the workplace.
Subject(s)
Drug-Related Side Effects and Adverse Reactions , Trust , Humans , Software , WorkloadABSTRACT
Gout is the most common form of inflammatory arthritis in men, yet both patients and the public often do not recognise gout as a form of arthritis. Instead, due to historical misconceptions, gout is typically seen as a lifestyle disease caused by poor diet. In reality, there are a number of risk factors that contribute to gout, including genetic factors. Views of gout as precipitated by lifestyle alone can lead to stigma, and maladaptive beliefs that it should be treated primarily through dietary changes. This is thought to contribute to poor uptake of, and adherence to, effective pharmaceutical treatments. Gout has some of the poorest medication adherence rates of any chronic disease, contributing to suboptimal health outcomes for patients. Recent research suggests that when gout is referred to as 'urate crystal arthritis' (a rarely used name for gout), the perception of the disease by members of the public was more accurate. It was viewed as being less under personal control (i.e. less appropriately managed by behaviours such as dietary intake), and more appropriately managed by long-term medical treatment. This finding raises the possibility that patients themselves might also benefit from gout being explicitly labelled as arthritis. Indeed, parallels can be drawn between this case and other diseases that have recently had their names changed to improve outcomes, namely primary biliary cirrhosis and schizophrenia. A movement away from the term gout may benefit those living with the disease by changing illness perceptions and increasing uptake of, and adherence to, guideline-recommended treatment(s).
Subject(s)
Gout , Chronic Disease , Gout/drug therapy , Gout Suppressants/therapeutic use , Humans , Male , Medication Adherence , Uric Acid/therapeutic useABSTRACT
AIMS: Bayesian forecasting software can assist in guiding therapeutic drug monitoring (TDM)-based dose adjustments for amikacin to achieve therapeutic targets. This study aimed to evaluate amikacin prescribing and TDM practices, and to determine the suitability of the amikacin model incorporated into the DoseMeRx® software as a replacement for the previously available software (Abbottbase®). METHODS: Patient demographics, pathology, amikacin dosing history, amikacin concentrations and Abbottbase® predicted TDM targets (area under the curve up to 24 hours, maximum concentration and trough concentration) were collected for adults receiving intravenous amikacin (2012-2017). Concordance with the Australian Therapeutic Guidelines was assessed. Observed and predicted amikacin concentrations were compared to determine the predictive performance (bias and precision) of DoseMeRx®. Amikacin TDM targets were predicted by DoseMeRx® and compared to those predicted by Abbottbase®. RESULTS: Overall, guideline compliance for 63 courses of amikacin in 47 patients was suboptimal. Doses were often lower than recommended. For therapy >48 h, TDM sample collection timing was commonly discordant with recommendations, therapeutic target attainment low and 34% of dose adjustments inappropriate. DoseMeRx® under-predicted amikacin concentrations by 0.9 mg/L (95% confidence interval [CI] -1.4 to -0.5) compared with observed concentrations. However, maximum concentration values (n = 19) were unbiased (-1.7 mg/L 95%CI -5.8 to 0.8) and precise (8.6% 95%CI 5.4-18.1). Predicted trough concentration values (n = 7) were, at most, 1 mg/L higher than observed. Amikacin area under the curve values estimated using Abbottbase® (181 mg h/L 95%CI 161-202) and DoseMeRx® (176 mg h/L 95%CI 152-199) were similar (P = .59). CONCLUSION: Amikacin dosing and TDM practice was suboptimal compared with guidelines. The model implemented by DoseMeRx® is satisfactory to guide amikacin dosing.
Subject(s)
Amikacin , Anti-Bacterial Agents , Adult , Australia , Bayes Theorem , Drug Monitoring , Humans , SoftwareABSTRACT
Many important drugs exhibit substantial variability in pharmacokinetics and pharmacodynamics leading to a loss of the desired clinical outcomes or significant adverse effects. Forecasting drug exposures using pharmacometric models can improve individual target attainment when compared with conventional therapeutic drug monitoring (TDM). However, selecting the "correct" model for this model-informed precision dosing (MIPD) is challenging. We derived and evaluated a model selection algorithm (MSA) and a model averaging algorithm (MAA), which automates model selection and finds the best model or combination of models for each patient using vancomycin as a case study, and implemented both algorithms in the MIPD software "TDMx." The predictive performance (based on accuracy and precision) of the two algorithms was assessed in (i) a simulation study of six distinct populations and (ii) a clinical dataset of 180 patients undergoing TDM during vancomycin treatment and compared with the performance obtained using a single model. Throughout the six virtual populations the MSA and MAA (imprecision: 9.9-24.2%, inaccuracy: less than ± 8.2%) displayed more accurate predictions than the single models (imprecision: 8.9-51.1%; inaccuracy: up to 28.9%). In the clinical dataset, the predictive performance of the single models applying at least one plasma concentration varied substantially (imprecision: 28-62%, inaccuracy: -16 to 25%), whereas the MSA or MAA utilizing these models simultaneously resulted in unbiased and precise predictions (imprecision: 29% and 30%, inaccuracy: -5% and 0%, respectively). MSA and MAA approaches implemented in TDMx might thereby lower the burden of fit-for-purpose validation of individual models and streamline MIPD.