Using Expert Elicitation to Adjust Published Intervention Effects to Reflect the Local Context.

Background. Local health services make limited use of economic evaluation to inform decisions to fund new health service interventions. One barrier is the relevance of published intervention effects to the local setting, given these effects can strongly reflect the original evaluation context. Expert elicitation methods provide a structured approach to explicitly and transparently adjust published effect estimates, which can then be used in local-level economic evaluations to increase their local relevance. Expert elicitation was used to adjust published effect estimates for 2 interventions targeting the prevention of inpatient hypoglycemia. Methods. Elicitation was undertaken with 6 clinical experts. They were systematically presented with information regarding potential differences in patient characteristics and quality of care between the published study and local contexts, and regarding the design and application of the published study. The experts then assessed the intervention effects and provided estimates of the most realistic, most pessimistic, and most optimistic intervention effect sizes in the local context. Results. The experts estimated both interventions would be less effective in the local setting compared with the published effect estimates. For one intervention, the experts expected the lower complexity of admitted patients in the local setting would reduce the intervention's effectiveness. For the other intervention, the reduced effect was largely driven by differences in the scope of implementation (hospital-wide in the local setting compared with targeted implementation in the evaluation). Conclusions. The pragmatic elicitation methods reported in this article provide a feasible and acceptable approach to assess and adjust published intervention effects to better reflect expected effects in the local context. Further development and application of these methods is proposed to facilitate the use of local-level economic evaluation. Highlights: Local health services make limited use of economic evaluation to inform their decisions on the funding of new health service interventions. One barrier to use is the relevance of published intervention evaluations to the local setting.Expert elicitation methods provide a structured way to consider differences between the evaluation and local settings and to explicitly and transparently adjust published effect estimates for use in local economic evaluations.The pragmatic elicitation methods reported in this article offer a feasible and acceptable approach to adjusting published intervention effects to better reflect the effects expected in the local context. This increases the relevance of economic evaluations for local decision makers.

A framework for local-level economic evaluation to inform implementation decisions: health service interventions to prevent hospital-acquired hypoglycemia.

OBJECTIVES: Published evidence on health service interventions should inform decision-making in local health services, but primary effectiveness studies and cost-effectiveness analyses are unlikely to reflect contexts other than those in which the evaluations were undertaken. A ten-step framework was developed and applied to use published evidence as the basis for local-level economic evaluations that estimate the expected costs and effects of new service intervention options in specific local contexts. METHODS: Working with a multidisciplinary group of local clinicians, the framework was applied to evaluate intervention options for preventing hospital-acquired hypoglycemia. The framework included: clinical audit and analyses of local health systems data to understand the local context and estimate baseline event rates; pragmatic literature review to identify evidence on relevant intervention options; expert elicitation to adjust published intervention effect estimates to reflect the local context; and modeling to synthesize and calibrate data derived from the disparate data sources. RESULTS: From forty-seven studies identified in the literature review, the working group selected three interventions for evaluation. The local-level economic evaluation generated estimates of intervention costs and a range of cost, capacity and patient outcome-related consequences, which informed working group recommendations to implement two of the interventions. CONCLUSIONS: The applied framework for modeled local-level economic evaluation was valued by local stakeholders, in particular the structured, formal approach to identifying and interpreting published evidence alongside local data. Key methodological issues included the handling of alternative reported outcomes and the elicitation of the expected intervention effects in the local context.

Is there a multinational consensus of tobramycin prescribing and monitoring for cystic fibrosis? Survey of current therapeutic drug monitoring practices in USA/Canada, UK/Ireland, and Australia/New Zealand.

OBJECTIVES: Sophisticated scientific methods have facilitated dose individualisation with substantial advancements in therapeutic drug monitoring (TDM) practice. It is unclear whether these methods have translated to the clinical setting. This study aimed to determine current TDM practice for tobramycin monitoring in cystic fibrosis (CF) centres in the USA and Canada, UK and Ireland, and Australia and New Zealand due to a high prevalence of CF. METHODS: A web-based survey was developed and circulated via CF specialist groups within the targeted geographical regions. Themes included centre demographics, tobramycin usage, dosing and infusion practices, TDM practices, and blood sampling methods. RESULTS: In total 77 responses were received from 75 different CF centres over the 3-month evaluation period (October 2019-January 2020). Respondents were from the USA and Canada (60%), Australia and New Zealand (25%), and the UK and Ireland (15%). Tobramycin was used in 97% of sites, with an international variation in practice across all survey aspects including dosing and infusion practice. TDM-based dose adjustment in the UK and Ireland was most commonly based only on trough sample collection for avoidance of toxicity, where use of computer programs for targeting both efficacy and toxicity endpoints were most common in Australia and New Zealand. The underlying pharmacokinetic basis of that program was not known by 33% of sites who utilised a computer program for tobramycin dose individualisation. CONCLUSION: There remains substantial heterogeneity in tobramycin management worldwide. Despite two decades of research into TDM of tobramycin, there has been a slow uptake of new technologies and evolution of practice. An improved understanding of TDM processes is required for translation of evidence-based research into clinical practice. International guidelines require updating due to the advances in research to support confidence in the changes in clinical practice.

Safety and Clinical Outcomes of Hospital in the Home.

OBJECTIVES: The aim of the study was to evaluate clinical outcomes and adverse events (AEs) experienced by patients treated within the Hospital in the Home (HITH) service of a major metropolitan hospital in South Australia. METHODS: A retrospective case note audit of 100 HITH episodes among adults who received continuous intravenous antimicrobial therapy via an elastomeric or electronic infusion device was undertaken. Age- and sex-adjusted binomial logistic regression analyses were undertaken to identify factors associated with major and minor AEs. RESULTS: Of the 100 patients included, 71 were male and the mean (SD) patient age was 62.8 (17.19) years. Elastomeric infusion devices were used for 98 patients. The mean (SD) HITH treatment duration was 20.1 (11.9) days. Overall, 130 AEs were documented for 72 patients (72%), of whom 12 patients experienced a major AE and 68 patients experienced a minor AE. There were 45 occasions among 23 patients where an infusion administered through an elastomeric device did not run to completion. Fifteen patients were readmitted to hospital. Minor AEs were more likely among people with more vascular line days (adjusted odds ratio [aOR] = 1.05; 95% confidence interval (CI) = 1.01-1.10 per day increase) and females (aOR = 4.43; 95% CI = 1.14-17.17). An increased number of vascular line days was associated with an increased likelihood of an incomplete infusion (aOR = 1.05; 95% CI = 1.01-1.09). Hospital readmission was more likely with increasing age (aOR = 1.06; 95% CI = 1.01-1.11 per year increase). CONCLUSIONS: Adverse events need to be monitored carefully when HITH treatment is provided for extended periods.

The impact of a pilot continuing professional development module on hospital pharmacists' preparedness to provide contemporary advice on the clinical use of vancomycin.

BACKGROUND: Revised international clinical guidelines for the antibiotic vancomycin have changed the advice pharmacists need to provide to medical and nursing colleagues. OBJECTIVES: (1) To determine the self-reported confidence of hospital pharmacists to provide contemporary advice on vancomycin and (2) to evaluate hospital pharmacists' knowledge to provide contemporary advice on vancomycin following a pilot continuing professional development (CPD) module. METHODS: The study was a prospective two-phase design in an Australian teaching hospital. Phase one: a survey of pharmacist self-reported confidence to eight questions on providing contemporary advice on vancomycin. Responses were recorded using a Likert scales. Phase two: The provision of a pilot online CPD module on vancomycin containing knowledge-based assessment based on a clinical vignette. Likert scales recorded self-reported confidence were reported as median and interquartile range (IQR). Knowledge assessment was reported using descriptive statistics. The main outcome measure were the self-reported confidence, and knowledge of pharmacists regarding provision of contemporary advice on clinical vancomycin use. RESULTS: Response rates for surveys; confidence n = 35 (72.9 %) and knowledge n = 31 (58.5 %). Phase one: confidence was highest regarding vancomycin dosing and monitoring with 71.4-81.6 % of respondents agreeing or strongly agreeing that they were confident in these domains. Respondents agreeing or strongly agreeing were least confident regarding intravenous administration and infusion related reactions, 57.1 and 45.7 % respectively. Respondents who provided advice on vancomycin >10 times in the prior 12 months reported significantly higher confidence in; therapeutic range 1 (IQR 1-2) versus 2 (IQR 1-3) p = 0.02; amending dosage based on therapeutic drug monitoring results 2 (IQR 1-3) versus 3 (IQR 2-3) p = <0.001, and providing general advice to prescribers on vancomycin 2 (IQR 1-3) versus 2 (IQR 2-4) p = <0.009. Knowledge questions were answered correctly post CPD by >75 % of pharmacists. CONCLUSION: Pharmacists' self-reported confidence to managing vancomycin was variable but generally high. Knowledge scores were consistently high after pharmacists completed a pilot CPD module on vancomycin. These data provides impetus for a randomised controlled study across multiple sites to determine the extent to which pharmacist knowledge on vancomycin can be attributed to completion of an online CPD.

Accuracy of information on medication use and adverse drug reactions recorded in pregnancy hand-held records.

BACKGROUND: Pregnancy hand-held records (PHR) are a personally controlled health record utilised in the promotion of continuity of care across pregnancy by providing a single resource for the recording of pregnancy-related health information. AIMS: To determine the accuracy of the PHR in relation to information on medications and adverse drug reactions (ADRs) and to examine the frequency and nature of any identified discrepancies. MATERIALS AND METHODS: A 12-week prospective clinical audit of 300 women admitted to either the antenatal or postnatal ward at a tertiary-level maternity hospital. A detailed medication history was completed for each woman by a pharmacist, with women interviewed about medication use prior to and during their pregnancy as well as any ADRs. The medication history and PHR were compared to identify discrepancies. RESULTS: Medication discrepancies were extremely common, with 254 (84.7%; 95% CI 80.6-88.8%) women having at least one or more medication-related discrepancy involving 686 (55%; 95% CI 52.2-57.8%) prescription and nonprescription medications. Most common reasons for prescription medication discrepancies included the medication details being incomplete (44%), missing (29%) or incorrect (17%). ADRs and allergy discrepancies were also common, identified among 59 (20%; 95% CI 15.5-24.5%) women. CONCLUSIONS: The PHR is of low accuracy in relation to the recording of medications and ADRs. This warrants further research to examine the impact of these discrepancies on patient care and outcomes. The identification of strategies for improving the recording of information on medications and ADRs in the PHR is also required.

INITIAT-E.D.: Impact of timing of INITIation of Antibiotic Therapy on mortality of patients presenting to an Emergency Department with sepsis.

OBJECTIVES: To analyse the association between time from triage to administration of initial antibiotics and mortality in all patients presenting with sepsis to a tertiary hospital ED. METHODS: A retrospective review of patients presenting to the ED with sepsis from January to December 2012 was conducted at Flinders Medical Centre, South Australia. Outcome measures were: time elapsed from triage to administration of initial antibiotic therapy and in-hospital mortality. RESULTS: A total of 220 patients presented with sepsis, comprising 102 cases of uncomplicated sepsis and 118 severe sepsis. The median time to antibiotic administration was 3.5 h (interquartile range [IQR] 1.7-6.6) and in-hospital mortality was 28.6% (95% CI 22.6-34.6%). There was no association observed between delays to antibiotics and mortality in the total patient population. When stratified by presenting severity, patients with severe sepsis demonstrated a trend towards increased mortality when delays to antibiotics exceeded 6 h from triage (HR = 2.25, 95% CI 0.91-5.59, P = 0.08) in comparison with <1 h. Significant delays to antibiotic administration occurred when initial agents were charted as a 'regular medicine' (9.4 h, IQR 5.1-16.6) in comparison with a 'once only order' (3.4 h, IQR 1.7-6.7), P < 0.001. CONCLUSIONS: Early administration of antibiotics specifically in patients with severe sepsis might be beneficial. Further studies within the ED are warranted to establish the effect of delayed antibiotics in a generalised sepsis cohort.

Nicotine as an antiepileptic agent in ADNFLE: an N-of-one study.

PURPOSE: To test nicotine patch treatment for a patient with a defined mutation for autosomal dominant nocturnal frontal lobe epilepsy (ADNFLE) whose seizures were refractory to standard antiepileptic therapy. METHODS: Open and double-blind trials of nicotine patches in an "n-of-one" study. The double-blind trial comprised periods during which either placebo or nicotine patches were each used for three periods of 2 weeks, randomized in a double-blind manner. RESULTS: In an open study, nicotine patches reduced seizures from 1.65 +/- 2.36 to 0.01 +/- 0.0 seizures per day (p < 0.0001). In a double-blinded placebo-controlled phase, the average frequency of seizures on nicotine versus placebo was 0 +/- 0 versus 0.56 +/- 1.14 seizures per day (p < 0.0001). CONCLUSIONS: Nicotine patches may be of benefit to some individuals with ADNFLE.

Assessment of an age-adjusted warfarin initiation protocol.

OBJECTIVE: To examine the time taken to reach a stable international normalized ratio (INR), as well as the incidence of overanticoagulation of an age-adjusted warfarin initiation protocol. METHODS: Inpatients and outpatients commencing warfarin therapy at 2 teaching hospitals were dosed according to the age-adjusted protocol. Data were collected prospectively. MAIN OUTCOME MEASURES: Time to reach a stable INR of 2-3 and the number of patients experiencing an INR > or =4 during the first week of warfarin therapy. RESULTS: Seventy-three patients were assessed; at the completion of the 4-day titration protocol, 63% had achieved a stable INR. After an additional 2 days of empiric dosage adjustment by the attending physician, 86% of the subjects demonstrated a stable INR. Five patients (7%) experienced an INR > or =4. These patients had a nonsignificant trend toward a lower plasma albumin level compared with other patients (p = 0.057, Student's t-test). The INR-driven dose adjustments on days 3 and 4 of this protocol coped with other variables that have been shown to affect maintenance warfarin dosing. These included weight, gender, pharmacologic factors affecting clearance, and the presence of certain predesignated risk factors. CONCLUSIONS: The age-adjusted dosing protocol rapidly achieved a stable INR with minimal overanticoagulation. Patients with low serum albumin levels (<3.0 g/dL) may be sensitive to the effects of warfarin during the loading phase.