Archive for month: August, 2020

Despite significant inherent advantages of liquid chromatography-tandem mass spectrometry (LC-MS/MS) over immunoassay techniques in clinical laboratory applications, its adoption into routine practice has been slower than might have been expected. The barriers to more widespread uptake are a function of issues in the laboratory workflow. This article analyses those issues and discusses how they can be overcome by improved automation and integration with the laboratory information management system, drawing on examples from the North West London Pathology (NWLP) clinical laboratories at Imperial College Healthcare NHS Trust.

by Dr Emma L. Williams

Introduction
Liquid chromatography-tandem mass spectrometry (LC-MS/MS) has seen over two decades of use in specialist clinical laboratories in the UK, offering a number of significant advantages over immunoassay techniques. These advantages include increased specificity, sensitivity and accuracy, as well as the detection of multiple analytes within a single assay. There is no need for an antibody for analyte detection and the method is not susceptible to the antibody-based interferences that plague immunoassays [1]. LC-MS/MS is suitable for multiple sample matrices and avoids the need for radioactive tracers. LC-MS/MS assays also have a wider dynamic measurement range and have improved between-method bias when compared to immunoassays.

LC-MS/MS initially played a role in specialist clinical laboratories in areas such as newborn screening, inborn errors of metabolism, toxicology and in immunosuppressant and therapeutic drug monitoring. More recently LC-MS/MS has established a role in diagnostic endocrinology, with the first appearance of LC/MS-MS for the measurement of vitamin D in the international vitamin D external quality assurance scheme (DEQAS) in 2005. There are now over 150 labs registered in this scheme using LC/MS-MS for the measurement of vitamin D. However, automated immunoassay still dominates and represents 69% of participants registered in the DEQAS scheme. Why has there not been more widespread adoption?

A number of issues have inhibited wider adoption and routine use of LC/MS-MS in the clinical laboratory. First among these is the use of labour-intensive manual workflows, which result in lower throughput, decreased productivity and longer turnaround time. Furthermore, a high level of technical expertise is needed, not only for method development, but also for troubleshooting assay and equipment failures. In addition to the high initial capital costs of purchasing the equipment, ongoing personnel costs are higher because of the need for more technically competent staff. With a clear understanding of where the bottlenecks in the process arise, these barriers can be overcome.

Figure 1 depicts the six main steps of a typical LC/MS-MS workflow, from sample receipt and extraction, separation in the LC, MS/MS analysis, data review and reporting of the results [2]. Of these steps it is the pre- and post-analytical stages that are the most time consuming and therefore if there is a focus on streamlining these, maximum benefit can be achieved. A number of steps can be taken to streamline the workflow, and these come under three broad headings of reduced manual processes, increased throughput and improved integration. Dependence on manual processes can be reduced by the automation of liquid handling and extraction, use of barcode reading for worklist generation and implementation of automated data analysis. Throughput can be increased with strategic column and sample management and by analyte multiplexing. Integration can be improved by bi-directional interfacing of the LC/MS-MS system to the laboratory information management system (LIMS) allowing automatic worklist upload and results download. These three strategic areas will be discussed in more detail below.

Reduced manual processes
Unlike the case with immunoassay, samples for LC-MS/MS usually require extraction prior to analysis. Historically this extraction step utilized liquid–liquid extraction or protein precipitation, these being carried out after the addition of internal standard to the calibrators, quality controls and patient samples. All of these steps involved manual pipetting and were very slow and time consuming. Use of an automated liquid-handling platform for the pipetting of samples and addition of internal standard allows some of the steps of liquid–liquid extraction and protein-precipitation methods to be automated. These liquid-handling platforms are available from a number of suppliers including Hamilton and Tecan.

With the advent of 96-well plate technology it became possible to carry out fully automated off-line solid phase extraction (SPE) using platforms such as the Freedom Evo (Tecan) and the Biomek NX (Beckman Coulter). More recently, supported liquid extraction (SLE), which allows solvent extraction to occur on a diatomaceous earth inert support, has also become available in a 96-well plate format. The Extrahera system (Biotage) enables automation of SLE by carrying out all of the pipetting and extraction steps required. In the NWLP laboratory, this system is used for the extraction of patient samples for vitamin D measurement by LC-MS/MS. A sample throughput of up to 50,000 samples per annum is achieved with capacity remaining for additional extractions for use in other LC-MS/MS applications. The system is robust and reliable with good pipetting precision and uses disposable pipette tips, thus avoiding sample carry over. Figure 2 depicts the Tecan Freedom Evo 200 and Biotage Extrahera liquid handlers in use in the NWLP laboratory.

In some manufacturers’ LC-MS/MS systems, on-line sample preparation and extraction is enabled by use of turbo flow or 2D chromatography. On-line protein precipitation and SPE is also now available using the Clinical Laboratory Automated sample preparation Module (CLAM)-2000 (Shimadzu Corporation) [3] and the Rapidfire 365 MS system (Agilent) [4] respectively. These latter examples most closely resemble the immunoassay workflow, whereby samples are introduced into the analytical system without any sample preparation or pre-treatment.

Increased throughput
Increased throughput can be achieved through the use of column and sample managers, allowing multiple assay batches to be queued up for overnight analysis of different LC-MS/MS assays. LC multiplexing enables multiple columns to be coupled to one tandem mass spectrometry system, maximizing the MS detection capability. In this approach, the use of quaternary solvent pumps in the LC enables column switching between different columns using different mobile phases. Finally there is analyte multiplexing, which can use manufacturers’ kits or in-house laboratory developed tests (LDTs). This approach enables multiple analytes to be detected in a single chromatographic separation by the use of multiple reaction monitoring for MS/MS detection. Perkin Elmer and Chromsystems both provide kits enabling the simultaneous measurement of multiple steroid hormones within a single assay panel. In the NWLP laboratory an in-house LDT steroid panel for the simultaneous measurement of androstenedione, 17-hydroxyprogesterone and testosterone has been implemented. This multiplexed assay has replaced the previous stand-alone assays for these analytes, thus increasing throughput and offering faster turnaround time. The assay utilizes off-line SPE using Waters Oasis PRiME HLB 96-well plates and the Tecan Freedom Evo 200 automated liquid handler [5].

Improved integration
Improved integration can be achieved by the use of bi-directional interfacing between the LIMS and the LC-MS/MS instrument software. Nowadays, manufacturers of LC-MS/MS systems offer customer support to allow their systems to be interfaced to the LIMS. One example is the MassLynx LIMS interface (Waters), which enables both worklist download and results upload. The MassLynx LIMS interface is accessed via the LC-MS/MS system software allowing sample worklists, created by barcode scanning of the patient samples, to be imported directly. Following peak integration and analyte quantitation the results are directly transmitted from the LC-MS/MS to the LIMS via an HL7 interface. This avoids the need for manual transcription thus saving a great deal of staff time and eliminating transcription errors.

The ultimate aim of LC-MS/MS integration is to achieve complete integration of LC-MS/MS instruments into the automated workflow of high-throughput routine clinical laboratories. With the recent launch of the Cascadion LC-MS/MS analyser (Thermo Fisher Scientific) this ultimate aim has now been achieved [6]. This analyser offers a complete LC-MS/MS solution including primary blood tube sampling, on-board sample extraction, LIMS connectivity and a random access workflow enabling the provision of a 24/7 service. Traceable manufacturer’s kits are offered for the measurement of a panel of immunosuppressant drugs, testosterone and vitamin D with further assay kits in the development pipeline. The Cascadion analyser is shown in Figure 3.

Summary
LC/MS-MS automation and integration is now a reality, allowing faster sample processing and improved turnaround time, as well as offering increased staff productivity, improved quality and reduced error rate. Staff time is liberated for further service development, allowing the more rapid introduction of validated in-house LDTs into the assay repertoire. Finally there is the possibility of complete analyser integration allowing routine, high-throughput analysis, as is already the standard approach for the common immunoassay platforms. This exciting development will support the more widespread adoption of LC-MS/MS in the routine clinical laboratory by offering complete automation and integration, overcoming the barriers discussed in this article and enabling the inherent advantages of LC/MS-MS in clinical laboratory practice to be more fully realized.

References
1. Jones AM, Honour JW. Unusual results from immunoassays and the role of the clinical endocrinologist. Clin Endocrinol Oxf 2006; 64: 234–244.
2. Zhang YV, Rockwood A. Impact of automation on mass spectrometry. Clin Chim Acta 2015; 450: 298–303.
3. Shimadzu. CLAM-2000. Fully automated sample preparation module for LCMS. (https://www.shimadzu.com/an/lcms/clam/index.html).
4. Jannetto PJ, Langman LJ. High-throughput online solid-phase extraction tandem mass spectrometry: Is it right for your clinical laboratory? Clin Biochem 2016; 49: 1032–1034.
5. Williams EL. LC-MS/MS measurement of serum steroids in the clinical laboratory. Clinical Laboratory International 2017; Sept: 18–20.
6. ThermoFisher Scientific. Cascadion SM Clinical Analyzer (www.thermofisher.com/cascadion).

The author
Emma L. Williams PhD, FRCPath
North West London Pathology, Imperial College Healthcare NHS Trust, London, UK

E-mail: emma.walker15@nhs.net

The growth in the use of modern, implantable cardiovascular devices has been accompanied by efforts to have them monitored by professionals at a distance. The principal driver for this has been convenience. However, over recent years, remote monitoring (RM) of cardiovascular devices is emerging not only as an alternative to the clinic, but in some cases as a source for enhancements to quality of care. Several professional societies have issued authoritative guidelines recommending RM for all eligible patients.

Device complexity and data transfer
Formally known as cardiovascular implantable electronic devices (CIEDs), equipment such as pacemakers, cardioverter defibrillators, loop recorders and hemodynamic monitors are technologically complex and equipped with an array of microelectronics, high computational capability and onboard firmware.
In turn, this allows for assessment, storage and remote transfer of a range of data via a transmitter placed in proximity to the patient. Examples of such data include device function, diagnostics and fault codes, to therapy delivery and intra-cardiac hemodynamics, as well as reports on patient clinical status and alerts on cardiovascular events.

Developments in remote monitoring technology
On their part, remote monitoring techniques too have undergone their own evolution  – from the original telephonic check-up of pacemaker battery levels and wand-based systems with patient-driven downloads, to current generation products which transmit data through stationary or mobile transmitters by either analogue/digital wired or wireless communication. Once transmitted, medical staff can check the information via a secure Website. Both the type and volume of transmitted data is similar to that obtained from direct interrogation.
Technically, it is important to differentiate between ‘remote interrogation’ and ‘remote monitoring’. The former involves periodic device interrogation performed manually at home by the patient or automatically at predefined points by the monitoring system. RM involves continuous device monitoring, one of whose key features is to trigger transmissions in case of alerts.

Convenience and workflow bottlenecks
Remote monitoring eliminates the need for routine, periodic visits to a clinic after CIED implantation. Most international guidelines specify that patients fitted with CIEDs should be followed up routinely, with the frequency depending on the device type and model – for instance, at Months 1 and 3  for implantable cardioverter defibrillators (ICDs). Key checks include those on battery, lead impedance, sensing amplitude, pacing threshold and arrhythmic events.
One of the most perceptible advantages of RM is of course convenience. Before it became available, patients with CIEDs had to visit clinics for periodic checks. This was a problem for several categories of patients – above all, those living in rural areas and those needing to be escorted by families due to frailty. These factors assume additional significance since the number of CIED patients has not only been increasing due to maturing technology and expanded indications, but also because an ageing society means that more people are in need of the devices. As a result, it is becoming ever-tougher to make appointments for CIED checks, and many patients who do not have RM can spend several hours waiting at a hospital for their turn.
Remote monitoring eliminates such bottlenecks and choke points. Analysis of RM data before a patient visit can shorten the time required for direct interrogation and intervention, especially should a need arise to determine the cause and management of a problem. If such a problem is only detected during a clinic visit, a patient would have to wait for the results to be verified, while the problem is detected, analysed and resolved.
According to some estimates, time required by physician to review RM data is approximately 10 minutes compared to a half-hour to complete CIED follow-up visits in a clinic.
Apart from routine transmission, special real-time protocols exist in RM for alerts, such as data anomalies, inappropriate therapy or other abnormalities. In such cases, the transmitter is usually linked to a central secure server to back up or distribute the results to a larger number of experts for further analysis and opinion.

RM data essentials
Typical data reported by RM include arrhythmic events (real-time intra-cardiac electrocardiogram, to determine if the event is supra-ventricular or ventricular), premature ventricular contractions (based on PVC frequency recording), atrial fibrillation (especially promising for patients with no prior history of AF, to allow rapid anticoagulant drug administration and prevent stroke), non-sustained VT (although this is mainly considered for ICD or CRT-D patients, rather than those with pacemakers) and VT/VF (to enable a therapy decision and whether it can be managed at home).

The Finnish ICD study
Meanwhile, rigorous observational and randomized studies have demonstrated a variety of clinical benefits, along with a high degree of patient satisfaction as well as cost effectiveness.
One of the first major studies on remote monitoring of ICDs was carried out in 2005-2006 at the Oulu University Hospital, Finland. The system consisted of a portable patient monitor, a secure database and website, at which clinicians could view and analyse data.
The study’s goal was to provide comprehensive information on the safety, ease of use, satisfaction and data acceptance by both clinicians and patients, and the cost-effectiveness of remote monitoring in a location characterized by long travel distances to the clinic.
The outcomes were satisfactory.
There were, first of all, no device-related adverse events.
80% of the remote-monitoring sessions were performed by the patients without any assistance. Indeed, ease of use and satisfaction by both patients and clinicians made an especially strong case. Most patients found the instructions ‘clear’ or ‘very clear’, with monitor set up ‘easy’ or ‘very easy’. What was equally significant was the lack of any major difference in patient feedback from the first test, at 3 and 6 months, and even during unscheduled visits.
On their side, clinicians too drew similar conclusions on ease of use and satisfaction, with the majority finding data comparable to traditional device interrogation. Just two of 137 physicians felt an in-office visit would have provided more detailed information on device function, as it was not possible to measure the pacing threshold remotely.

Early detection of clinical events
Since then, other studies have reconfirmed the immense promise of RM.
In 2010 ‘Circulation’ published results of a trial on automated remote monitoring of implantable cardioverter-defibrillator called TRUST (Lumos-T Safely Reduces Routine Office Device Follow-up).
This study, on 1,339 patients, confirmed that the burden of visiting a clinic was greatly reduced by using RM, and that it saved valuable time and resources. The study found that in-hospital evaluation numbers dropped by 45% without affecting morbidity.
The TRUST trial also established that RM facilitated early detection of clinical events, in some cases dramatically. For example, the median period from onset to physician evaluation of combined first atrial fibrillation (AF), ventricular tachycardia (VT), and ventricular fibrillation (VF) events with RM was 1 day. By comparison, conventional care reported a median period of 35.5 days. System-related problems (such as lead out-of-range impedance) occurred over four times less frequently with the RM group, although the incidence in either setting was far too low to make meaningful comparisons.

Wireless RM and cardiac hospitalization stays
The utility of wireless remote monitoring with automatic clinician alerts was the subject of another trial called CONNECT (Clinical Evaluation of Remote Notification to Reduce Time to Clinical Decision).  This multicentre, prospective, randomized study of almost 2,000 patients with high-energy CIEDs lasted for 15 months. Its results were published in ‘The Journal of the American College of Cardiology’ in 2011, and reported a decrease in mean length of stay per cardiovascular hospitalization visit from 4 days in an in-office setting to 3.3 days with RM. The CONNECT study also found a dramatic reduction in the median time to a clinical decision in response to events, from 22 days at a clinic to 4.6 days using RM.

Other benefits of RM
RM has also established some other dramatic benefits. In 2013, ‘The European Heart Journal’ reported on ECOST, a randomized study on remote follow-up of ICDs. ECOST found that patients with RM had a 52% reduction in inappropriate shocks, fewer hospital admissions after such events and 76% fewer capacitor charges, leading to longer battery life.
In December 2014, a report in ‘The Journal of Arrhythmia’ noted that in prophylactic ICD recipients, the recommended 3-month in-office follow-up interval could be extended to 12 months with automatic daily RM, and that this reduced the ICD follow-up burden over a 27-month period after implantation. The 12-month interval resulted in more than halving the total number of in-clinic ICD follow-ups. In addition, no significant difference was found between the two groups (3-month in-clinic follow-up versus 12-month RM) in mortality, hospitalization rate, or hospitalization length over the observation period.

Mortality reduction with RM
Indeed, some experts propose that RM may reduce mortality in patients with CIEDs.
One study called ALTITUDE assessed long-term outcomes after ICD and cardiac resynchronization therapy (CRT) implantation and the impact of RM on almost 70,000 ICD and CRT-plus-defibrillator (CRT-D) patients. It found that one- and 5-year survival rates were 50% higher in comparison to about 115,000 patients who received CIED follow-up in office visits.

The future: patients generally satisfied with RM
As technology continues to evolve, both new possibilities and questions are emerging.  In the years to come, remote monitoring holds forth considerable promise for future research, given that massive amounts of data have already been collected from patients. 
In spite of some typical first-mover tech concerns, RM has proven to be easy to use and well accepted, even by the elderly people and patients with low education levels. There are some patients, however, who do not accept RM. This is mainly due to suspicions about technology and the risk of losing human contact with nurses and physicians. In such cases, patient education is critical.
The other challenge involves keeping track of a flood of data and alerts from a fast-growing pool of patients. As described previously, RM detects cardiovascular events much earlier than conventional follow-up. As a result, it is becoming essential to assess whether this translates into clinical benefits for patients, or whether earlier detection of events due to RM excessively increases clinic visits; the latter might well reduce clinical benefits.
On their part, patients continue to be satisfied with RM in terms of ease of use. One Italian study at San Filippo Neri Hospital in Rome has reported a more favourable change in quality of life over a 16-month period in RM patients, compared to those lacking access to RM. Benefits which have been specifically highlighted include the patients’ peace of mind, psychological well-being, and safety.

Two studies on information technology and patient safety were released in the US in April 2018.
The first, by ECRI Institute and its Partnership for Health IT Patient Safety stakeholder collaborative, takes a searching look at the hidden risks of healthcare IT (information technology) systems.
The second report, by Pew Charitable Trusts, focuses on electronic health records (EHRs), and is based on its long-standing view that in spite of more than 30 billion dollars (£25 billion) of federal health IT investment over the past decade, the transition from paper to electronic records has yet to reach its potential to enhance healthcare coordination and improve patient safety.
Both studies call for a much greater degree of proactivity to anticipate problems before they run out of control. Interestingly, there also seem to be several parallels in their respective analyses of the challenges.

A broad-based look at patient safety
One of the first priorities for healthcare organizations is to tie health IT into existing patient safety initiatives. The challenges that exist whenever older systems are updated or replaced, or integrated with successor technologies, can ideally become learning opportunities. However, this requires the organization to have a collaborative management culture that makes initiatives such as IT safety and other best practices part of their daily workflow.
Both the ECRI and Pew are emphatic about the need for collaboration. ECRI lays down specific recommendations on obtaining feedback from stakeholders (patients, payers, cybersecurity experts, regulators, providers and others). The Pew report also maintains that collaboratively gathering inputs from across the healthcare stakeholder spectrum is critical to improve patient care and reduce provider burden in the context of EHR use.

Tip of the iceberg
The ECRI Safe Practice Recommendations begin with an ominous warning – that the known universe of IT-related safety problems are likely to be just the tip of the proverbial iceberg. The net risk from such issues is that a variety of bugs are lurking beneath the surface, and, in the ECRI’s view, pose permanent dangers to patients. Such risks, in turn, are compounded by the sharp growth in recent years of ransomware and other cybersecurity threats which seek to exploit loopholes in codes. For ECRI, this is a key reason why both providers and vendors need to make health IT safety an integral part of their overall patient safety program.

The ‘over’-customization quandary
In general, the roots of healthcare IT problems stretch back to the 1980s and 1990s when demands for customization led to ad-hoc rewriting of legacy programs, so as to avoid loss of functionalities. So-called patches, as part of platform updates, also sought to retain some of these functionalities, many of which had been proven – or otherwise become indispensable – over the years.  During this process, poor documentation of code changes was commonplace. In addition, since legacy systems faced many problems communicating with one another across their proverbial silos, layers of integrative middleware were added in sequence until they became cluttered and unmanageable.
Many such concerns are reflected by Pew. Over customization, auto-refresh mix-ups and unclear default settings with EHRs, as well as alert fatigue, can all result in patient harm.
An earlier Pew report in December 2017 had explained that safety problems could be caused by the very design of an EHR system (e.g. complex interfaces and guidance terminology) or by its customization during implementation and adaptation. Like the middleware in an IT system, Pew explains that an EHR “interface that is cluttered may cause confusion or an inability to locate key information, whereas an overly bare display may force the clinician to search for information in multiple places.”
Indeed, some of the reasons for risky over-customization of EHRs directly reflect those made during program rewrites to legacy IT systems in the 1980s and 1990s.
As the Pew study observes, healthcare facilities often work with vendors to customize certain aspects of their EHR system which fit their workflow, for example by displaying data which is critical for specific clinicians at a particular facility. However, it warns, such customizations “may not have undergone rigorous testing and could lead to unintended safety consequences.”

Specific risks with EHRs
The Pew report highlights a range of specific risks. One of the most commonplace may consist of mix-ups in auto-refresh of patient lists when EHRs revert to the default view. In such cases, providers can inadvertently make medical decisions based on another patient, rather than the one being treated, if they do not realize the system has just refreshed a particular list.
Default EHR settings are also seen as a specific danger for medication dosages. Healthcare providers may think they are ordering a fixed dose of a particular drug, while what they enter instead “is multiplied by the patient’s weight, potentially contributing to overdoses,” Pew notes.
Yet another problem consists of incomplete laboratory results, which can result in erroneous medical decisions since a provider lacks complete information on a particular patient. In effect, physicians may fail to realize that not all lab results are displayed on a screen, or that results may have been delayed – among other reasons, because samples might still be undergoing testing.

In its recommendation to integrate health IT safety into a broader safety program, the ECRI report also pointed explicitly to the rise in duplicate medication errors after a new EHR implementation. Contributing factors include the design of the EHR as well as the occurrence of task-related changes (such as multiple persons entering orders for the same patient at the same time).
Other EHR-related problems mentioned as cases by ECRI included data entry of a pediatric patient’s weight in pounds rather than kilograms – followed by erroneous medication dose, incorrect alert responses due to the simultaneous opening of multiple patient charts, the inability to account for problems such as a pending swallow evaluation before a dietary order, or an allergy to eggs which contraindicate propofol.
Some of the most frequent EHR problems concerned mix-ups of patients, in one instance due to two having the same name !

New safety approaches: collaboration and workflow integration
Beyond EHRs, as the hitherto-unknown problems in the health IT iceberg become more apparent with time, users are advised by the ECRI to collaborate in order to integrate and embed new safety practices into their daily workflow. Suggestions include the provision of inc entives for actively working together on safety-related efforts, and to learn and share analysis of near-misses and other hazards, as well as workaround strategies.

Pew too had stressed the importance of collaboration for improved EHR use, in its December 2017 report.  One way towards this is to bring stakeholders together to share data on patient safety incidents and do this in a “nonpunitive environment.” After this, stakeholders can be encouraged to “develop solutions for common and significant usability issues.”
Pew also suggests that safety tests on functionality and usability are conducted by entities throughout the entire EHR life-cycle – from development and after implementation. Such a process should bring together developers, IT professionals, clinicians, nurses and pharmacists – in essence, every one using the EHR system.
Pew cautions that one specific area for attention is alert fatigue (due to too many unnecessary or false alerts). This can result in genuine life-saving warnings being missed. One concrete means to avoid such conundrums is by designing EHR systems to specifically verify and red flag certain potential problems (e.g. dangerous drug interactions with different medications).

The need for encouraging a collaborative culture to enhance healthcare IT safety has also been identified in Europe. In 2015, a team led by Solvejg Kristensen at Denmark’s Aalborg University studied the association of quality management systems with teamwork and safety from seven European countries. Although they found different approaches to quality management systems and to perceptions of teamwork and safety climate, they noted the importance of organizations investing in leadership, time, capital and technical expertise to attain continuous quality improvement and enhance patient safety.
Indeed, at whichever facet of the healthcare technology spectrum one looks at, proactive, meaningfully structured collaboration may be the only way to achieve a unified vision of safe health IT and a wider culture of safety in the health enterprise.
As healthcare IT becomes increasingly pervasive, such concerns are bound to demand increasing attention.
The National Patient Safety Foundation and IHI
Many of these issues – in terms of both challenge and response – were the subject of a set of eight recommendations made in 2015 in a report from the National Patient Safety Foundation (NPSF) in the US to ensure “that technology is safe and optimized to improve patient safety”. The recommendations are as follows:

1. Ensure that leaders establish and sustain a safety culture
2. Create centralized and coordinated oversight of patient safety
3. Create a common set of safety metrics that reflect meaningful outcomes
4. Increase funding for research in patient safety and implementation science
5. Address safety across the entire care continuum
6. Support the healthcare workforce
7. Partner with patients and families for the safest care
8. Ensure that technology is safe and optimized to improve patient safety

European initiatives
In 2016, the NPSF added that it was also important  to make health IT-related patient safety an organizational priority by securing management commitment, and to develop an environment which was “conducive to  detecting, fixing and learning from system vulnerabilities.”
The NPSF was merged with the Institute for Healthcare Improvement (IHI) last year, and some of its initiatives are likely to be transferred to Europe via the IHI Health Improvement Alliance Europe (HIAE), which aims to improve work processes and create new delivery models relevant to European health systems. The HIAE has already established connections with professional societies in several countries, including Britain, Denmark and Belgium.
One good example of HIAE efforts is the The Platform for Continuous Improvement of Quality of Care and Patient Safety (PAQS), a Belgium-based initiative which aims to consolidate relationships between various stakeholders in healthcare in order to work together, in a consistent and cohesive manner.
Other facets of IHI which are expected to make a mark in Europe include the so-called Open School Online Courses. Several of these are directly concerned with IT-focused elements of patient safety and the need to build a culture of safety in a health organization.