External validity of an automated delirium prediction model (DEMO) and comparison to the manual VMS-questions: a retrospective cohort study.

BACKGROUND: It is estimated that one-third of delirium cases in hospitals could be prevented with appropriate interventions. In Dutch hospitals a manual instrument (VMS-questions) is used to identify patients at-risk for delirium. Delirium Model (DEMO) is an automated model which could support delirium prevention more efficiently. However, it has not been validated beyond the hospital it was developed in. AIM: To externally validate the DEMO and compare its performance to the VMS-questions. METHOD: A retrospective cohort study between July and December 2018 was conducted. Delirium cases were identified through a chart review, and the VMS-questions were extracted from the electronic health records. The DEMO was validated in patients ≥ 60 years, and a comparison with the VMS-questions was made in patients ≥ 70 years. RESULTS: In total 1,345 admissions were included. The DEMO predicted 59 out of 75 delirium cases (sensitivity 0.79, 95% CI = 0.68-0.87; specificity 0.75, 95% CI = 0.72-0.77). Compared to the VMS-questions, the DEMO showed a lower specificity (0.64 vs. 0.72; p < 0.001) and a comparable sensitivity (0.83 vs. 0.80; p = 0.56). The VMS-questions were missing in 20% of admissions, in which the DEMO correctly predicted 10 of 12 delirium cases. CONCLUSION: The DEMO showed acceptable performance for delirium prediction. Overall the DEMO predicted more delirium cases because the VMS-questions were missing in 20% of admissions. This study shows that automated instruments such as DEMO could play a key role in the efficient and timely deployment of measures to prevent delirium.

Psychiatric risk factors for chronic high-dose opioid prescribing: register-based cohort study.

BACKGROUND: Chronic high-dose (CHD) prescription opioid use is a major public health concern. Although CHD opioid use has been associated with psychiatric disorders, the causality could go both ways. Some studies have already linked psychiatric disorders to an increased risk of transitioning to chronic opioid use, and longitudinal data identifying psychiatric disorders as predictors of CHD opioid use could shed further light on this issue. AIMS: To prospectively examine the relationship between the presence of a psychiatric disorder and subsequent development of CHD opioid use in primary care patients newly receiving opioids. METHOD: Data were included from 137 778 primary care patients in The Netherlands. Cox regression modelling was used to examine the association between psychiatric disorders prior to a new opioid prescription and subsequent CHD opioid use (≥90 days; ≥50 mg/day oral morphine equivalents) in the subsequent 2 years. RESULTS: Of all patients receiving a new opioid prescription, 2.0% developed CHD opioid use. A psychiatric disorder before the start of an opioid prescription increased the risk of CHD opioid use (adjusted hazard ratio HR = 1.74; 95% CI 1.62-1.88), specifically psychotic disorders, substance use disorders, neurocognitive disorders and multiple co-occurring psychiatric episodes. Similarly, pharmacotherapy for psychosis, substance use disorders and mood and/or anxiety disorders increased the risk of CHD opioid use. Psychiatric polypharmacy conferred the greatest risk of developing CHD opioid use. CONCLUSIONS: Psychiatric disorders increase the risk of developing CHD opioid use in patients newly receiving prescription opioids. To reduce the public health burden of CHD opioid use, careful monitoring and optimal treatment of psychiatric conditions are advised when opioid therapy is initiated.

Monitoring Opioids in Europe: The Need for Shared Definitions and Measuring Drivers of Opioid Use and Related Harms.

The past 20 years, the USA is facing a serious opioid crisis initiated by an increase in prescription opioid use. Europe has also seen an increase in prescription opioid use, but the extent of related harm is still largely unknown. Given the impact of the US opioid epidemic, it is important to closely monitor signs of emerging opioid-related problems to guarantee early warnings and timely actions. Shared and meaningful definitions for opioid use and related harms, and relevant information about specific drivers for opioid use and related problems are needed for an adequate policy response. In this commentary, we discuss these definitions, the need to know more about the specific drivers for increased opioid use, its related harm, and proposals for strategies to move forward. Policy recommendations include making a distinction between licit and illicit opioids when monitoring and reporting on opioid-related harm, and using oral morphine equivalents to quantify prescription opioid use in a clinically relevant and comparable manner. A major topic of further research is exploring unique and universal drivers of prescription opioid (mis)use across Europe, in particular the role of opioid diversion.

Is Europe facing an opioid crisis like the United States? An analysis of opioid use and related adverse effects in 19 European countries between 2010 and 2018.

BACKGROUND: Given the ongoing opioid crisis in the United States (US), we investigated the opioid situation in Europe. The aims of the study are to provide an overview of trends in prescription opioid (PO) use and opioid-related adversities between 2010 and 2018 for different opioids in 19 European countries and to present a comparison with similar data from the US. METHODS: A multisource database study with national data from 19 European countries evaluating trends between 2010 and 2018 in (a) PO consumption, (b) high-risk (HR) opioid users, (c) opioid-related hospital admissions, (d) opioid-related overdose deaths, (e) opioid use disorder treatment entries, and (f) patients in opioid substitution therapy (OST). Within and between-country comparisons and comparisons with data from the US were made. RESULTS: There was considerable variation between European countries. Most countries showed increased PO consumption with the largest increase and the highest consumption in the United Kingdom (UK) compared to the rest of Europe and the US in 2018 (UK: 58,088 defined daily doses for statistical purposes/1000 population/day). In 2018, Scotland had the highest rates (per 100,000 population) of HR opioid users (16·2), opioid-related hospital admissions (118), opioid-related deaths (22·7), opioid use disorder treatment admissions (190), and OST patients (555) of all included European countries. These rates were similar or even higher than those in the US in 2018. Other countries with high rates of opioid-related adversities were Northern Ireland (synthetic and "other" opioids), Ireland (heroin and methadone), and England (all opioids). All other countries had no or little increase in opioid-related adversities. CONCLUSIONS: Apart from the British Isles and especially Scotland, there is no indication of an opioid crisis comparable to that in the US in the 19 European countries that were part of this study. More research is needed to identify drivers and develop interventions to stop the emerging opioid crisis in the UK and Ireland.

The effects of substitution of hospital ward care from medical doctors to physician assistants on non-adherence to guidelines on medication prescribing.

AIM: This study determined the effect of substitution of inpatient care from medical doctors (MDs) to physician assistants (PAs) on non-adherence to guidelines on medication prescribing. METHODS: A multicenter matched-controlled study was performed comparing wards on which PAs provide medical care in collaboration with MDs (PA/MD model), with wards on which only MDs provide medical care (MD model). A set of 17 quality indicators to measure non-adherence to guidelines on medication prescribing by PAs and MDs was composed by 14 experts in a modified Delphi procedure. The indicators covered different pharmacotherapeutic subjects, such as gastric protection in case of use of NSAID or prevention of obstipation in case of use of opioids. These indicators were expressed in proportions by dividing the number of patients in which the prescriber did not adhere to a guideline, by all patients that were applicable. Multivariable regression analysis was performed in order to adjust for potential confounders. RESULTS: 1021 patients from 17 hospital wards in the 'PA/MD model' group and 1286 patients from 17 hospital wards in the 'MD model' group were included. Two of the 17 quality indicators showed significantly less non-adherence to guidelines for the PA/MD model; the indicators concerning prescribing gastric protection in case of use of NSAID in combination with corticosteroids (OR 0.42, 95% CI 0.19-0.90) and in case of use of NSAID in patients older than 70 years (OR 0.47, 95% 0.23-0.95). For none of the other quality indicators for prescribing of medication a difference between the MD model and the PA/MD model was found. CONCLUSION: This study suggests that the non-adherence to guidelines on medication prescribing on wards with the PA/MD model does not differ from wards with traditional house staffing by MDs only. Further research is needed to determine quality, efficiency and safety of prescribing behavior of PAs.

Prediction of clinically relevant adverse drug events in surgical patients.

BACKGROUND: Risk stratification of hospital patients for adverse drug events would enable targeting patients who may benefit from interventions aimed at reducing drug-related morbidity. It would support clinicians and hospital pharmacists in selecting patients to deliver a more efficient health care service. This study aimed to develop a prediction model that helps to identify patients on the day of hospital admission who are at increased risk of developing a clinically relevant, preventable adverse drug event during their stay on a surgical ward. METHODS: Data of the pre-intervention measurement period of the P-REVIEW study were used. This study was designed to assess the impact of a multifaceted educational intervention on clinically relevant, preventable adverse drug events in surgical patients. Thirty-nine variables were evaluated in a univariate and multivariate logistic regression analysis, respectively. Model performance was expressed in the Area Under the Receiver Operating Characteristics. Bootstrapping was used for model validation. RESULTS: 6780 admissions of patients at surgical wards were included during the pre-intervention period of the PREVIEW trial. 102 patients experienced a clinically relevant, adverse drug event during their hospital stay. The prediction model comprised five variables: age, number of biochemical tests ordered, heparin/LMWH in therapeutic dose, use of opioids, and use of cardiovascular drugs. The AUROC was 0.86 (95% CI 0.83-0.88). The model had a sensitivity of 80.4% and a specificity of 73.4%. The positive and negative predictive values were 4.5% and 99.6%, respectively. Bootstrapping generated parameters in the same boundaries. CONCLUSIONS: The combined use of a limited set of easily ascertainable patient characteristics can help physicians and pharmacists to identify, at the time of admission, surgical patients who are at increased risk of developing ADEs during their hospital stay. This may serve as a basis for taking extra precautions to ensure medication safety in those patients.

Bisecting Microfluidic Channels with Metallic Nanowires Fabricated by Nanoskiving.

This paper describes the fabrication of millimeter-long gold nanowires that bisect the center of microfluidic channels. We fabricated the nanowires by nanoskiving and then suspended them over a trench in a glass structure. The channel was sealed by bonding it to a complementary poly(dimethylsiloxane) structure. The resulting structures place the nanowires in the region of highest flow, as opposed to the walls, where it approaches zero, and expose their entire surface area to fluid. We demonstrate active functionality, by constructing a hot-wire anemometer to measure flow through determining the change in resistance of the nanowire as a function of heat dissipation at low voltage (<5 V). Further, passive functionality is demonstrated by visualizing individual, fluorescently labeled DNA molecules attached to the wires. We measure rates of flow and show that, compared to surface-bound DNA strands, elongation saturates at lower rates of flow and background fluorescence from nonspecific binding is reduced.