On the alert: future priorities for alerts in clinical decision support for computerized physician order entry identified from a European workshop

Background: Clinical decision support (CDS) for electronic prescribing systems (computerized physician order entry) should help prescribers in the safe and rational use of medicines. However, the best ways to alert users to unsafe or irrational prescribing are uncertain. Specifically, CDS systems may generate too many alerts, producing unwelcome distractions for prescribers, or too few alerts running the risk of overlooking possible harms. Obtaining the right balance of alerting to adequately improve patient safety should be a priority. Methods: A workshop funded through the European Regional Development Fund was convened by the University Hospitals Birmingham NHS Foundation Trust to assess current knowledge on alerts in CDS and to reach a consensus on a future research agenda on this topic. Leading European researchers in CDS and alerts in electronic prescribing systems were invited to the workshop. Results: We identified important knowledge gaps and suggest research priorities including (1) the need to determine the optimal sensitivity and specificity of alerts; (2) whether adaptation to the environment or characteristics of the user may improve alerts; and (3) whether modifying the timing and number of alerts will lead to improvements. We have also discussed the challenges and benefits of using naturalistic or experimental studies in the evaluation of alerts and suggested appropriate outcome measures. Conclusions: We have identified critical problems in CDS, which should help to guide priorities in research to evaluate alerts. It is hoped that this will spark the next generation of novel research from which practical steps can be taken to implement changes to CDS systems that will ultimately reduce alert fatigue and improve the design of future systems

Evaluation of quality of life in adults with neurofibromatosis 1 (NF1) using the Impact of NF1 on Quality Of Life (INF1-QOL) questionnaire

Background Neurofibromatosis 1 (NF1) is an inherited, multi-system, tumour suppressor disorder with variable complications that cause psychological distress and social isolation. The study aim was to develop and validate a disease-specific questionnaire to measure quality of life (QOL) in NF1 that is suitable both as an assessment tool in clinical practice and in clinical trials of novel therapy. Methods The Impact of NF1 on Quality of Life (INF1-QOL) questionnaire was developed by a literature search for common terms, focus group (n=6), semi-structured interviews (n=21), initial drafts (n =50) and final 14 item questionnaire (n=50). Bivariate correlations between items, exploratory factor analysis, correlations with severity and EuroQol were employed. Results INF1-QOL showed good internal reliability (Cronbach’s alpha 0.87), mean total INF1-QOL score was 8.64 (SD 6.3), median 7.00, range 0-30 (possible range 0-42); no significant correlations with age or gender. The mean total EuroQol score was 7.38 (SD 2.87), median 6.5, mean global EuroQol score was 76.34 (SD 16.56), median 80. Total INF1-QOL score correlated with total EuroQol r=0.82, p<0.0001. The highest impact on QOL was moderate or severe problems with anxiety and depression (32%) and negative effects of NF1 on role and outlook on life (42%). The mean inter-relater reliability for grading of clinical severity scores was 0.71 (range 0.65-0.79), and intra-class correlation was 0.92. The mean clinical severity score was 1.95 (SD 0.65) correlating r=0.34 with total INF1-QOL score p<0.05 and correlated 0.37 with total EuroQol score p<0.01. The clinical severity score was mild in 17 (34%), moderate in 16 (32%) and 17 (34%) individuals had severe disease. Conclusions INF1-QOL is a validated, reliable disease specific questionnaire that is easy and quick to complete. Role and outlook on life and anxiety and depression have the highest impact on QOL indicating the variability, severity and unpredictability of NF1. INFI-QOL correlates moderately with clinical severity. The moderate relationship between INF1-QOL and physician rated severity emphasizes the difference between clinical and patient perception. INFI-QOL will be useful in individual patient assessment and as an outcome measure for clinical trials

How to assess pharmacogenomic tests for implementation in the NHS in England

AIMS: Pharmacogenomic testing has the potential to target medicines more effectively towards those who will benefit and avoid use in individuals at risk of harm. Health economies are actively considering how pharmacogenomic tests can be integrated into health care systems to improve use of medicines. However, one of the barriers to effective implementation is evaluation of the evidence including clinical usefulness, cost-effectiveness, and operational requirements. We sought to develop a framework that could aid the implementation of pharmacogenomic testing. We take the view from the National Health Service (NHS) in England. METHODS: We used a literature review using EMBASE and Medline databases to identify prospective studies of pharmacogenomic testing, focusing on clinical outcomes and implementation of pharmacogenomics. Using this search, we identified key themes relating to the implementation of pharmacogenomic tests. We used a clinical advisory group with expertise in pharmacology, pharmacogenomics, formulary evaluation, and policy implementation to review data from our literature review and the interpretation of these data. With the clinical advisory group, we prioritized themes and developed a framework to evaluate proposals to implement pharmacogenomics tests. RESULTS: Themes that emerged from review of the literature and subsequent discussion were distilled into a 10-point checklist that is proposed as a tool to aid evidence-based implementation of pharmacogenomic testing into routine clinical care within the NHS. CONCLUSION: Our 10-point checklist outlines a standardized approach that could be used to evaluate proposals to implement pharmacogenomic tests. We propose a national approach, taking the view of the NHS in England. Using this approach could centralize commissioning of appropriate pharmacogenomic tests, reduce inequity and duplication using regional approaches, and provide a robust and evidence-based framework for adoption. Such an approach could also be applied to other health systems

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

Aims: Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition. Methods: Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken. Results: One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m−2. Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide. Conclusions: Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required

A systematic review and meta-analysis of thiazide-induced hyponatraemia: time to reconsider electrolyte monitoring regimens after thiazide initiation?

Aims: Hyponatraemia is one of the major adverse effects of thiazide and thiazide-like diuretics and the leading cause of drug-induced hyponatraemia requiring hospital admission. We sought to review and analyze all published cases of this important condition. Methods: Ovid Medline, Embase, Web of Science and PubMed electronic databases were searched to identify all relevant articles published before October 2013. A proportions meta-analysis was undertaken. Results: One hundred and two articles were identified of which 49 were single patient case reports. Meta-analysis showed that mean age was 75 (95% CI 73, 77) years, 79% were women (95% CI 74, 82) and mean body mass index was 25 (95% CI 20, 30) kg m−2. Presentation with thiazide-induced hyponatraemia occurred a mean of 19 (95% CI 8, 30) days after starting treatment, with mean trough serum sodium concentration of 116 (95% CI 113, 120) mm and serum potassium of 3.3 (95% CI 3.0, 3.5) mm. Mean urinary sodium concentration was 64 mm (95% CI 47, 81). The most frequently reported drugs were hydrochlorothiazide, indapamide and bendroflumethiazide. Conclusions: Patients with thiazide-induced hyponatraemia were characterized by advanced age, female gender, inappropriate saliuresis and mild hypokalaemia. Low BMI was not found to be a significant risk factor, despite previous suggestions. The time from thiazide initiation to presentation with hyponatraemia suggests that the recommended practice of performing a single investigation of serum biochemistry 7–14 days after thiazide initiation may be insufficient or suboptimal. Further larger and more systematic studies of thiazide-induced hyponatraemia are required