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Up to 80 million people worldwide take oral anticoagulant medications — primarily warfarin — to treat thromboembolic disorders such as atrial fibrillation (AF), pulmonary embolism, and deep-vein thrombosis (the latter two are known as venous thromboembolism, or VTE). Because warfarin can dangerously interact with other drugs and foods, causing highly variable anticoagulation that could lead to both thromboembolism and bleeding, conventional warfarin management can be difficult. Patients taking warfarin are typically monitored by prothrombin time-international normalized ratio (PT-INR), a test that gauges how long it takes blood to clot.
In addition, many clinical guidelines now prefer newer direct oral anticoagulants (DOACs), which do not require regular blood monitoring, over warfarin for AF and VTE patients. According to large clinical trials, DOACs like dabigatran, apixaban, and rivaroxaban are safer than warfarin in nonvalvular AF and VTE, although warfarin remains safer and more effective for high-risk patients such as those with mechanical heart valves, rheumatic heart disease, and antiphospholipid antibody syndrome. Moreover, due to its low cost, warfarin is often still the global treatment of choice for AF and VTE.
A cross-disciplinary team at Landspitali National University Hospital of Iceland has developed a new warfarin monitoring test that optimizes affordability, safety, and effectiveness, outperforming PT-INR–monitored warfarin and in some cases even the more expensive DOACs.
Warfarin, which is known as a vitamin K agonist (VKA) anticoagulant, inhibits the formation of four vitamin K-dependent coagulation factors (F): II, VII, IX, and X. Conventional PT-INR monitors FII, FVII, and FX and is highly influenced by FVII, which has the shortest half-life of the four factors. The antithrombotic effect of VKAs is mainly generated by safely reducing FII and FX.
The new test, called the Fiix-test (Fiix-PT), is sensitive only to reductions in FII and FX and is intended to stabilize anticoagulation variability, according to Pall Onundarson, MD, professor emeritus of hematology and laboratory medicine at the Landspitali National University Hospital of Iceland.
“There is much less anticoagulation variability with the Fiix test,” he explained. “Fewer tests are needed and there is reduced need for dose adjustments.” According to Onundarson, there is a 40% to 56% lower chance of thromboembolism without an increase in major bleeding compared to traditional PT-INR–monitored warfarin treatment.
The benefit was initially shown in a blinded, randomized controlled trial published in the journal The Lancet Haematology in 2015, and a pre-post study published in Blood in 2021 confirmed this finding. Another study, published in May 2025 in Blood VTH, also suggests the Fiix test can improve warfarin management. Further, it provides evidence that Fiix-warfarin could be more effective than DOAC drugs for patients with AF.
With a 34% decrease in annual monitoring tests and a 33% increase in the median interval between dose changes (from 60 days to 90 days), resource utilization is significantly reduced, Onundarson said. He estimates that these findings could translate to a savings of $395 million annually worldwide.
“In addition, with Fiix monitoring of warfarin, markedly fewer patients suffer strokes, systemic embolic events, heart attacks, and other life-threatening complications,” which results in fewer hospitalizations, less disability, and even reduced deaths, he explained.
“The savings from the reduced number of monitoring tests are considerable,” Onundarson said. “However, savings from reduced hospitalizations for acute and chronic care would be considerably more if the test would become generally applied in patients needing warfarin.”
If the improved clinical outcomes with Fiix monitoring lead some patients to be switched from DOACs to warfarin, even more cost savings can be achieved, resulting in about $2,000 per AF patient per year, according to his group’s calculations.
The Fiix initiative, which was recognized with honors of distinction by UNIVANTS, is highly scalable, but will require the strong involvement of a test manufacturer and possibly a patient advocacy initiative, Onundarson said.
Syphilis remains a significant global public health concern, with millions of new cases reported annually. In China, between 2014 and 2019, the rate of syphilis rose from 30.93 cases per 100,000 to 38.37 per 100,000, a 4.41% annual growth rate. The proportions of latent and tertiary syphilis also increased, underscoring the urgent need for accurate and early diagnosis to mitigate transmission and improve patient outcomes.
Traditional stepwise syphilis testing involves an initial screening with a nontreponemal test such as rapid plasma reagin (RPR) followed by a confirmatory treponemal test like treponema pallidum particle agglutination (TPPA). However, this “one test at a time” method often leads to missed diagnoses, misdiagnoses, and patient loss to follow-up, resulting in delayed treatment, according to Jing Peng, deputy chief technologist of laboratory medicine at Tongji Hospital in Wuhan, China. Such inefficiencies increase the risk for transmission and progression, placing additional burden on the healthcare system.
In 2009, Tongji Hospital launched a new protocol, the “Innovative Reflex Simultaneous Testing Strategy,” to replace stepwise testing. It includes:
Compared with traditional syphilis testing, the new initiative streamlines the testing process and reduces diagnostic turnaround time, according to Peng. The approach enables clinicians to manage syphilis patients comprehensively and accurately, facilitating early diagnosis and treatment. In addition, it minimizes the risk of missed diagnoses and misdiagnoses, thereby alleviating patient anxiety and financial burdens.
As a result of the new testing protocol, among patients with isolated CLIA-reactive results, 14.9% were diagnosed with syphilis during follow-up. The initiative also resulted in a 67% reduction in the number of visits required for diagnosis, resulting in an average cost savings of 113.7 renminbi (RMB) per patient. This equates to about $16. The savings are attributable to reduced transportation fees and minimized work loss from multiple appointments. The strategy also prevented progression to late-stage syphilis, which brings additional treatment costs ranging from RMB 2,100–4,300 ($293–$599) per person.
“Early diagnosis avoids more expensive late-stage treatment, which can range from RMB 7,700–9,800 [$1,073–$1,366] per visit,” Peng said.
The strategy is highly scalable, Peng said, noting that it demonstrates high adaptability, allowing for straightforward implementation in comparable institutions and clinical centers. The assays involved — CLIA, TPPA, and RPR — are readily accessible, and the accompanying algorithms are user-friendly and easy to execute. Two hospitals in Hubein Province have successfully implemented the initiative, and 24 more medical institutions across four provinces have been influenced by academic exchange and demonstration efforts, Peng said.
The initiative, which was recognized with honors of distinction by UNIVANTS, also resulted in an overall increase in testing at the hospital. Between 2008 and 2024, excluding the pandemic years (2020-2022), total testing volume surged from 41,374 to 283,804.
“The consistent upward trend suggests that the strategy has had a definite impact on syphilis testing rates,” Peng said. “The specific reasons can be attributed to a combination of factors, including improved access, enhanced clinical protocols, public health initiatives as well as our care initiative.”
Hepatocellular carcinoma (HCC) is the sixth most common cancer worldwide. Liver transplantation currently offers the best prognosis for HCC patients, with a 5-year survival rate exceeding 70% globally using the University of California San Francisco (UCSF) criteria — standard guidelines for determining who qualifies for transplantation.
The problem is that many patients are excluded as transplant candidates due to locally advanced tumors. For these patients, the focus is usually on palliative care. The 3-year survival rate for them without transplantation is 20%–30%.
In 2020, a team from the transplant center at Chang Gung Memorial Hospital in Kaohsiung, Taiwan, developed a new approach to identify more transplant-eligible patients. In addition to using UCSF criteria, the center integrated alpha-fetoprotein (AFP) levels and positron emission tomography (PET) results to create a predictive model for post-transplant recurrence.
Before transplant, the team applied transarterial radioembolization (TARE, Yttrium-90) or proton therapy — two forms of radiation — to patients with locally advanced HCC to reduce the size or extent of their liver tumors (downstage them). After transplant, they used lenvatinib for adjuvant treatment in high-risk recipients.
Among 43 patients treated with these therapies, 24 were successfully downstaged and subsequently received liver transplants. Compared to historical data, these 24 patients demonstrated a decreased recurrence rate (8.3% at 3 years versus 35.2% prior to the initiative) and improved overall survival (85.9% at 3 years versus 69.3%).
“For patients with locally advanced HCC, who were previously considered incurable and ineligible for liver transplantation, we have successfully performed transplants on seven such patients, with only one patient experiencing disease recurrence at median follow-up of 20 months,” said Chih-Che Lin, vice superintendent at the hospital. “Our strategy has given previously ineligible patients a chance for a cure, leading to enhanced survival rates and elevating the reputation of our medical team.”
Since the hospital implemented the initiative, its use of AFP and PET for screening high-risk liver cancer patients has increased, as has the annual utilization of proton therapy and Y90 treatments. Patients treated with proton therapy increased from 56 patients in 2019 to 141 in 2023. Those treated with Y90 rose from 10 in 2019 to 20 in 2024.
According to Lin, the project — which was recognized with honors of distinction by UNIVANTS — has the potential to be adopted as a national policy, significantly enhancing longevity and reducing mortality rates. Although liver transplant costs $114,404 per patient, the initiative can reduce the amount of money spent on palliative treatments. There are also positive cost effects for the economy overall, Lin noted.
“We have provided previously incurable patients with an opportunity for liver transplantation, achieving an estimated 5-year survival rate of over 80%,” he said. “Considering Taiwan’s per capita GDP of $32,687, each patient has the potential to generate more than $100,000 in economic value for the country.”
The initiative is unique, as Chang Gung Memorial is the only hospital in the world that uses this method to identify high-risk patients and successfully reduce their risk by attempting treatment with protons or TARE. Implementation in other facilities would require moderate effort.
Numerous factors influence how quickly patients who enter emergency departments (EDs) can be safely discharged or admitted to the hospital, including registration, triage, the availability of rooms or providers, test completion, and a review of results to determine next steps. In general, the longer patients stay in the hospital, the more likely they are to have a poor outcome — which is concerning because many EDs struggle with long lengths of stay (LOS).
In February 2023, Banner Health and Laboratory Sciences in Sun City, Arizona, implemented an initiative to reduce LOS in their ED. A multidisciplinary team collaborated to evaluate current practices, analyze performance data, and identify opportunities for improvement. The team consisted of ED clinicians, quality improvement specialists, laboratory and radiology professionals, and hospital administrators and leaders, according to Teri Dahn, Banner’s director of quality improvement. The project focused on two large community hospitals, Banner Boswell Medical Center and Banner Del E. Webb Medical Center.
The hospitals implemented a direct-bedding model featuring a coordinated “swarm team” approach. In other words, rather than waiting to get a traditional triage assessment, each patient would receive immediate access to a phlebotomist, nurse, and provider. In cases where direct bedding was not possible, lab leaders helped create phlebotomy-specific areas within triage, allowing teams to get lab services to patients immediately. This approach enables simultaneous clinical assessment and specimen collection, eliminating sequential delays and accelerating the diagnostic process from the moment of patient arrival, Dahn explained.
“By implementing our ED throughput performance improvement project, we enhanced lab turnaround times through strategic measures,” said Hites Patel, MD, medical director of emergency services. “Drawing labs directly in the lobby phlebotomy stations and prioritizing the swift placement of orders enabled timely blood draws and expedited specimen transfers to the lab. This seamless workflow significantly reduced delays, ensuring more efficient patient care and improving overall operational efficiency.”
As a result of the initiative, patient LOS in the ED decreased by 20.2% over 17 months. Many factors contributed to this. For example, imaging turnaround time decreased 17.5%, from 160 minutes to 132 minutes. The time from patients’ registration to when they were seen by a provider also declined 70.4%, from 27 minutes to 8 minutes, and wait time from when providers completed disposition until patient discharge decreased by 47%, from 41.5 minutes to 22 minutes.
During the 17 months, the number of patients who left the ED without being treated also declined by 65%, from 26 to 9. What’s more, there was an 82% increase in point-of-care testing (POCT), from 59 to 323 per month.
While the concept of direct bedding is not new, it had not been applied before at Banner’s two large community hospitals, Dahn noted.
“It takes collaboration between departments to direct bed patients consistently,” she said. “Also, the addition of dedicated phlebotomy areas for use when direct bedding was not possible due to bed availability was unique to our facilities.”
The initiative required moderate effort: Some infrastructure changes were required, including the addition of POCT instruments. Dahn noted the approach of integrating mixed methodologies is highly scalable and is already used for most interdepartmental projects.
Helicobacter pylori (H. pylori) is an infectious organism that causes dyspepsia, peptic ulcer disease, and gastric cancer. Almost half of the world’s population is estimated to be infected, although many people don’t have symptoms. In 2017, the World Health Organization listed H. pylori as one of 10 antibiotic-resistant pathogens of concern.
To tackle this infection, a multidisciplinary team at University Hospitals Health System in Cleveland in 2019 developed an innovative and cost-effective molecular susceptibility assay to detect resistance-related mutations in H. pylori. The test was incorporated into routine anatomic pathology clinical workflows in 2020, and test reports were generated with personalized treatment recommendations based on genetic markers of resistance.
The team developed a pharmacist-led intervention to ensure molecular-guided treatment was utilized, according to Navid Sadri, MD, PhD, chief of the division of genomic and molecular pathology at the health system. The pharmacist directly messaged endoscopists with molecular results that had treatment recommendations. This intervention reduced the use of ineffective regimens and lowered the rate of no treatment. Once providers were fully educated on how to prescribe treatment in line with the recommended regimens based on test reports, this intervention was no longer needed, Sadri explained.
The initiative significantly improved patient outcomes, with a more-than-17% increase in successful eradication compared to previous empirical treatments. It also resulted in a 4.4-fold increase in success with recommended regimens versus unrecommended treatments.
By avoiding ineffective regimens like clarithromycin triple therapy in high-resistance settings, patients experience fewer treatment failures and complications, Sadri said. The initiative also expands treatment options for those without antimicrobial resistance markers, offering more tolerable and convenient alternatives to standard empiric regimens.
Overall, the intervention — which was recognized with honors of achievement by UNIVANTS — reduced the proportion of treatments that were expected to be ineffective from 15% to 10% and decreased the rate of no treatment from 12% to 5%.
Using tailored therapy based on resistance markers also prevents use of unnecessary antimicrobial agents, according to Leila Hojat, MD, director of antimicrobial stewardship in the health system.
“Even short courses of therapy using the agents included in the available regimens can be associated with adverse effects, alter the microbiome, and increase the risk of acquired resistance both in the patient and the community,” she said. “Thus, using molecular susceptibility testing to identify the most optimal treatment regimen first and avoid subsequent courses has a major impact.”
In fact, the initiative reduced clarithromycin resistance by 30% over 4 years by minimizing unnecessary macrolide use.
The approach minimizes the need for costly repeat procedures and extended care resulting from failed therapies, Sadri said. By incorporating cost-effective generic medications into treatment protocols, it also reduces costs for payors and insurance plans, while lessening the burden of managing chronic complications of H. pylori, such as peptic ulcer disease and gastric cancer, for patients and providers.
“While the long-term costs of these conditions may not be immediately evident to payors, addressing them is a significant public health priority with practical solutions available to improve healthcare quality and safety today,” he said.
The initiative has also improved clinician confidence in choice of eradication therapy, according to Linda Cummings, MD, senior attending physician in gastroenterology.
“This initiative has markedly increased our ability to eradicate H. pylori with the first course of treatment, reducing the need for multiple rounds of treatment and the frustrations associated with salvage therapy,” she said.
This approach could easily be adopted by other institutions, Sadri said. The testing method was developed using existing next-generation sequencing (NGS) equipment to detect key antibiotic-resistance mutations. It can be adapted by institutions without NGS by using PCR technology or utilizing a reference laboratory for testing.
Chronic kidney disease (CKD) affects more than 1 in 7 adults in the United States — an estimated 35.5 million people. For Americans with diabetes or high blood pressure, the two most common causes of kidney disease, the risk is even greater. About 1 in 3 people who have diabetes, and 1 in 5 with high blood pressure, also have CKD.
The National Kidney Foundation (NKF) and Sanford Health (Sioux Falls, South Dakota) in 2023 partnered to improve the quality of CKD care among patients with diabetes. An initial data analysis revealed low levels of urine albumin-to-creatinine ratio (uACR) testing, gaps in CKD diagnosis in primary care settings, and limited prescribing of disease-modifying interventions that could slow CKD progression and reduce associated cardiovascular risk, according to Elizabeth Montgomery, national vice president, clinical practice innovation and population health, at NKF.
Albuminuria, which is diagnosed with uACR testing, is often an early indication of kidney disease and may occur before kidney function begins to decline, explained Montgomery, adding that uACR findings are one of the strongest predictors of cardiovascular events and mortality in people with diabetes.
Using NKF recommendations, Sanford developed a system-wide intervention to improve CKD testing and diagnosis and increase the use of sodium-glucose co-transporter-2 inhibitors (SGLT2i). Sanford Health nephrologists helped create the algorithm outlining the care pathway and provided education about CKD.
The intervention included implementing the NKF-recommended Kidney Profile into the lab and updating relevant electronic health record (EHR) SmartSets to ensure easy access to CKD testing and relevant guideline-directed medical information. It also involved adding CKD testing to the EHR health-maintenance menu, along with embedding other tools and resources.
From the time the program began in 2023 until October 2024, the percentage of people with diabetes receiving guideline-concordant CKD testing, which includes both uACR and estimated glomerular filtration rate (eGFR) tests, rose from 38% of the diabetes population tested to 70%. In addition, the rates of CKD diagnosis among the same patient population with abnormal eGFR and/or uACR values increased from 20% to 73%.
While the rate of SGLT2i utilization among people with diabetes alone remained low, the rate of SGLT2i prescriptions among those with CKD increased from less than 2% to 9.7%. Treatment with SGLT2i is associated with a significant reduction in CKD progression and the rising cardiovascular risk associated with it.
As of October 2024, several thousand new CKD diagnoses were rendered for people with diabetes and laboratory evidence of CKD in their EHR, raising the rate of recognition of CKD from 20% at the program’s inception to 73%, said Montgomery.
“Several studies have demonstrated that documentation of CKD in the EHR favorably impacts CKD-related quality of care,” she noted. “Guideline-recommended testing for all adults with diabetes will ensure those individuals with proteinuria will be detected early in the course of the disease, offering the opportunity for treatment to reduce albuminuria and its impacts, including cardiovascular disease.”
Laboratory intelligence was the foundation of the CKD initiative, said Montgomery. “It identified significant gaps in uACR testing in the institution as well as illuminating that a large population of people with diabetes and laboratory evidence of CKD did not have an accurate diagnosis and appropriate staging of CKD in their health record,” she said. “A dramatic increase in uACR testing, coupled with greater awareness of the clinical significance of albuminuria, increased rates of CKD diagnosis.”
The initiative, which was recognized with honors of achievement by UNIVANTS, is simple to employ and highly scalable for other institutions, said Montgomery. NFK is currently working with more than 20 other institutions to implement this model. The organization provides guidance on the required data analysis, suggests updates to the lab and EHR systems, and develops tools and resources to support implementation.
“Previously, we had many undiagnosed patients with CKD,” she explained. “Identification earlier on in the disease progression helps us to be able to provide the care we need to delay that progression and reduce the associated risk of adverse cardiovascular events. We are very proud of our increase in diagnoses.”
Each of these initiatives highlights how clinical laboratories are actively involved in multidisciplinary efforts to diagnose and treat health conditions earlier and more effectively, thus potentially reducing mortality.
To learn more about the UNIVANTS of Healthcare Excellence award program, please visit UnivantsHCE.com.
Read the full September-October issue of CLN here.
The Fiix project: Reducing anticoagulation variability and adverse patient outcomes through safe and cost-effective factor II and X (Fiix) monitoring in place of conventional PT-INR warfarin monitoring
Landspitali National University Hospital of Iceland
Reykjavik, Iceland
Pall T. Onundarson
Brynja R. Gudmundsdottir
David O. Arnar
Einar S. Bjornsson
Charles W. Francis
Implementation of a comprehensive syphilis screening strategy for cost-effective and timely syphilis management
Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology
Hubei, China
Liming Cheng
Jing Peng
Yong Zhang
Sainan Shu
Huijun Li
Reduced hepatocellular carcinoma recurrence with enhanced 3-year survival for patients post liver transplant
Kaohsiung Chang Gung Memorial Hospital
Kaohsiung, Taiwan
Chih-Che Lin
Jen-Yu Cheng
Hsin-You Ou
Chien-Chin Hsu
Wan-Ting Huang
Improved patient experiences and decreased patient length of stay in the emergency department through a multidisciplinary approach
Banner Health and Laboratory Sciences of Arizona
Sun City, Arizona
Teri Dahn
Brian Thomas
Chris Zufall
Hites Patel
Gordon Weimer
Personalizing H. pylori antibiotic therapy for enhanced safety and H. pylori eradication
University Hospitals Cleveland
Cleveland, Ohio
Navid Sadri
Linda C. Cummings
Leila S. Hojat
Rachel A. Wells
Enhancing wellness through guideline concordant follow-up and treatment for patients with diabetes and chronic kidney disease
National Kidney Foundation, New York, New York
Sanford Health, Sioux Falls, South Dakota
Christina Lankhorst
Andrew Burgard
Clark Casarella
Rochelle Odenbrett
Elizabeth Montgomery