William J. Ferguson

Vulnerability of point-of-care test reagents and instruments to environmental stresses: implications for health professionals and developers

Abstract Strategic integration of point-of-care (POC) diagnostic tools during crisis response can accelerate triage and improve management of victims. Timely differential diagnosis is essential wherever care is provided to rule out or rule in disease, expedite life-saving treatment, and improve utilization of limited resources. POC testing needs to be accurate in any environment in which it is used. Devices are exposed to potentially adverse storage and operating conditions, such as high/low temperature and humidity during emergencies and field rescues. Therefore, characterizing environmental conditions allows technology developers, operators, and responders to understand the broad operational requirements of test reagents, instruments, and equipment in order to improve the quality and delivery of care in complex emergencies, disasters, and austere environmental settings. This review aims to describe the effects of environmental stress on POC testing performance and its impact on decision-making, to describe how to study the effects, and to summarize ways to mitigate the effects of environmental stresses through good laboratory practice, development of robust reagents, and novel thermal packaging solutions.

Molecular detection and point-of-care testing in Ebola virus disease and other threats: a new global public health framework to stop outbreaks

Ultrahigh sensitivity and specificity assays that detect Ebola virus disease or other highly contagious and deadly diseases quickly and successfully upstream in Spatial Care Paths™ can stop outbreaks from escalating into devastating epidemics ravaging communities locally and countries globally. Even had the WHO and CDC responded more quickly and not misjudged the dissemination of Ebola in West Africa and other world regions, mobile rapid diagnostics were, and still are, not readily available for immediate and definitive diagnosis, a stunning strategic flaw that needs correcting worldwide. This article strategizes point-of-care testing for diagnosis, triage, monitoring, recovery and stopping outbreaks in the USA and other countries; reviews Ebola molecular diagnostics, summarizes USA FDA emergency use authorizations and documents why they should not be stop-gaps; and reduces community risk from internal and external infectious disease threats by enabling public health at points of need.

Effects of dynamic temperature and humidity stresses on point-of-care glucose testing for disaster care.

OBJECTIVE To characterize the performance of glucose meter test strips using simulated dynamic temperature and humidity disaster conditions. METHODS Glucose oxidase- and glucose dehydrogenase-based test strips were dynamically stressed for up to 680 hours using an environmental chamber to simulate conditions during Hurricane Katrina. Paired measurements vs control were obtained using 3 aqueous reagent levels for GMS1 and 2 for GMS2. RESULTS Stress affected the performance of GMS1 at level 1 (P < .01); and GMS2 at both levels (P < .001), lowering GMS1 results but elevating GMS2 results. Glucose median-paired differences were elevated at both levels on GMS2 after 72 hours. Median-paired differences (stress minus control) were as much as -10 mg/dL (range, -65 to 33) at level 3 with GMS1, with errors as large as 21.9%. Glucose median-paired differences were as high as 5 mg/dL (range, -1 to 10) for level 1 on GMS2, with absolute errors up to 24.4%. CONCLUSIONS The duration of dynamic stress affected the performance of both GMS1 and GMS2 glucose test strips. Therefore, proper monitoring, handling, and storage of point-of-care (POC) reagents are needed to ensure their integrity and quality of actionable results, thereby minimizing treatment errors in emergency and disaster settings.

Innovations in point-of-care testing for enhanced United States disaster caches.

OBJECTIVE To describe, innovate, recommend, and foster the implementation of point-of-care (POC) testing in disaster caches to enhance crisis standards of care and to improve triage, diagnosis, monitoring, treatment, and management of victims and volunteers in complex emergencies and disasters. DESIGN AND SETTINGS The authors compared POC testing in United States disaster caches to commercially available POC testing to enhance the caches and to reflect current state-of-the-art diagnostic capabilities. The authors also provided recommendations based on literature review and knowledge from newly developed POC technologies from the UC Davis Point-of-Care Technologies Center. RESULTS Presently, US POC testing caches comprise chemistry/electrolytes, pregnancy, hemoglobin, cardiac biomarkers, hematology, fecal occult blood, drugs of abuse, liver function, blood gases, and limited infectious diseases. Deficiencies with existing POC tests for cardiac biomarkers, hematology, and infectious diseases should be eliminated. POC resources can be customized for pandemics, complex emergencies, or disasters based on geographic location and potential infectious diseases. Additionally, a new thermally stabilized container can help alleviate environmental stresses that reduce test quality. CONCLUSIONS Innovations in POC technologies can improve response preparedness with enhanced diagnostic capabilities. Several innovations, such as the i-STAT® Wireless, OraQuick ADVANCE® HIV-1/2, VereTrop™ Lab-on-a-Chip, and new compact hematology analyzers will improve test clusters that facilitate evidence-based decision making and crisis standards of care during US national disaster responses. Additionally, strategic resources and operator training should be globally harmonized to improve the efficiency of international responses.

Using a geographic information system to enhance patient access to point-of-care diagnostics in a limited-resource setting

BackgroundRapid and accurate diagnosis drives evidence-based care in health. Point-of-care testing (POCT) aids diagnosis by bringing advanced technologies closer to patients. Health small-world networks are constrained by natural connectivity in the interactions between geography of resources and social forces. Using a geographic information system (GIS) we can understand how populations utilize their health networks, visualize their inefficiencies, and compare alternatives.MethodsThis project focuses on cardiac care resource in rural Isaan, Thailand. A health care access analysis was created using ArcGIS Network Analyst 10.1 from data representing aggregated population, roads, health resource facilities, and diagnostic technologies. The analysis quantified cardiac health care access and identified ways to improve it using both widespread and resource-limited strategies.ResultsResults indicated that having diagnostic technologies closer to populations streamlines critical care paths. GIS allowed us to compare the effectiveness of the implementation strategies and put into perspective the benefits of adopting rapid POCT within health networks.ConclusionsGeospatial analyses derive high impact by improving alternative diagnostic placement strategies in limited-resource settings and by revealing deficiencies in health care access pathways. Additionally, the GIS provides a platform for comparing relative costs, assessing benefits, and improving outcomes. This approach can be implemented effectively by health ministries seeking to enhance cardiac care despite limited resources.

The Ebola Spatial Care Path™: Accelerating point-of-care diagnosis, decision making, and community resilience in outbreaks

OBJECTIVES To present a vision where point-of-care testing (POCT) accelerates an Ebola Spatial Care Path™ (SCP) and future molecular diagnostics enable facilitated-access self-testing (FAST POC); to design an alternate care facility (ACF) for the SCP; to innovate an Ebola diagnostic center (DC); and to propel rapid POCT to the frontline to create resilience that stops future outbreaks. DESIGN PubMed, literature, and web searches. Centers for Disease Control and Prevention (CDC), Food and Drug Administration (FDA), Medicine Without Frontiers, and World Health Organization (WHO) document analyses. Investigations in China, the Philippines, Thailand, and the United States. Review of SE Asia, US, and West Africa isolation-treatment centers. Innovation of a SCP, ACF, and DC suitable for American and other communities. OUTCOMES The authors designed an ACF and DC to integrate SCP principles for urgent Ebola care. FDA emergency use authorizations for Ebola molecular diagnostics were discovered, but no portable, handheld, or self-contained molecular POC instruments are yet available, although feasible. The WHO initiated design criteria and an acceptance protocol for testing. Financial investment in POCT will downsize Ebola outbreaks. CONCLUSIONS POCT is facilitating global health. Now, global health problems are elevating POCT to new levels of importance for accelerating diagnosis and evidence-based decision making during disease outbreaks. Authorities concur that rapid diagnosis has potential to stop disease spread. With embedded POCT, strategic SCPs planned by communities fulfill CDC recommendations. POC devices should consolidate multiplex test clusters supporting patients with Ebola in isolation. The ultimate future solution is FAST POC. New technologies offer minimally significant risks. Diagnostic centers in ACFs and transportable formats also will optimize Ebola SCPs.

Short-term thermal-humidity shock affects point-of-care glucose testing: Implications for health professionals and patients

Objective: The objective was to assess the effects of short-term (≤1 hour) static high temperature and humidity stresses on the performance of point-of-care (POC) glucose test strips and meters. Background: Glucose meters are used by medical responders and patients in a variety of settings including hospitals, clinics, homes, and the field. Reagent test strips and instruments are potentially exposed to austere environmental conditions. Methods: Glucose test strips and meters were exposed to a mean relative humidity of 83.0% (SD = 8.0%) and temperature of 42°C (107.6°F, SD = 3.2) in a Tenney BTRC environmental chamber. Stressed and unstressed glucose reagent strips and meters were tested with spiked blood samples (n = 40 measurements per time point for each of 4 trials) after 15, 30, 45, and 60 minutes of exposure. Wilcoxon’s signed rank test was applied to compare measurements test strip and meter measurements to isolate and characterize the magnitude of meter versus test strip effects individually. Results: Stressed POC meters and test strips produced elevated glucose results, with stressed meter bias as high as 20 mg/dL (17.7% error), and stressed test strip bias as high as 13 mg/dL (12.2% error). The aggregate stress effect on meter and test strips yielded a positive bias as high as 33 mg/dL (30.1% error) after 15 minutes of exposure. Conclusions: Short-term exposure (15 minutes) to high temperature and humidity can significantly affect the performance of POC glucose test strips and meters, with measurement biases that potentially affect clinical decision making and patient safety.

Effects of environmental conditions on point-of-care cardiac biomarker test performance during a simulated rescue: implications for emergency and disaster response.

OBJECTIVE To characterize the effects of environmental stress on point-of-care (POC) cardiac biomarker testing during a simulated rescue. DESIGN Multiplex test cassettes for cardiac troponin I (cTnI), brain natriuretic peptide (BNP), CK-MB, myoglobin, and D-dimer were exposed to environmental stresses simulating a 24-hour rescue from Hawaii to the Marshall Islands and back. We used Tenney environmental chambers (T2RC and BTRC) to simulate flight conditions (20°C, 10 percent relative humidity) and ground conditions (22.3-33.9°C, 73-77 percent). We obtained paired measurements using stressed versus control (room temperature) cassettes at seven time points (T1-7 with T1,2,6,7 during flight and T3-5 on ground). We analyzed paired differences (stressed minus control) with Wilcoxon signed rank test. We assessed the impact on decision-making at clinical thresholds. RESULTS cTnI results from stressed test cassettes (n = 10) at T4 (p < 0.05), T5 (p < 0.01), and T7 (p < 0.05) differed significantly from control, when testing samples with median cTnI concentration of 90 ng/L. During the ground rescue, 36.7 percent (11/30) of cTnI measurements from stressed cassettes generated significantly lowered results. At T5, 20 percent (2/10) of cTnI results were highly discrepant-stressed cassettes reported normal results, when control results were >100 ng/L. With sample median concentration of 108 pg/mL, BNP results from stressed test cassettes differed significantly from controls (p < 0.05). CONCLUSION Despite modest, short-term temperature elevation, environmental stresses led to erroneous results. False negative cTnI and BNP results potentially could miss acute myocardial infarction and congestive heart failure, confounded treatment, and increased mortality and morbidity. Therefore, rescuers should protect POC reagents from temperature extremes.

Dynamic temperature and humidity environmental profiles: Impact for future emergency and disaster preparedness and response

INTRODUCTION During disasters and complex emergencies, environmental conditions can adversely affect the performance of point-of-care (POC) testing. Knowledge of these conditions can help device developers and operators understand the significance of temperature and humidity limits necessary for use of POC devices. First responders will benefit from improved performance for on-site decision making. OBJECTIVE To create dynamic temperature and humidity profiles that can be used to assess the environmental robustness of POC devices, reagents, and other resources (eg, drugs), and thereby, to improve preparedness. METHODS Surface temperature and humidity data from the National Climatic Data Center (Asheville, North Carolina USA) was obtained, median hourly temperature and humidity were calculated, and then mathematically stretched profiles were created to include extreme highs and lows. Profiles were created for: (1) Banda Aceh, Indonesia at the time of the 2004 Tsunami; (2) New Orleans, Louisiana USA just before and after Hurricane Katrina made landfall in 2005; (3) Springfield, Massachusetts USA for an ambulance call during the month of January 2009; (4) Port-au-Prince, Haiti following the 2010 earthquake; (5) Sendai, Japan for the March 2011 earthquake and tsunami with comparison to the colder month of January 2011; (6) New York, New York USA after Hurricane Sandy made landfall in 2012; and (7) a 24-hour rescue from Hawaii USA to the Marshall Islands. Profiles were validated by randomly selecting 10 days and determining if (1) temperature and humidity points fell inside and (2) daily variations were encompassed. Mean kinetic temperatures (MKT) were also assessed for each profile. RESULTS Profiles accurately modeled conditions during emergency and disaster events and enclosed 100% of maximum and minimum temperature and humidity points. Daily variations also were represented well with 88.6% (62/70) of temperature readings and 71.1% (54/70) of relative humidity readings falling within diurnal patterns. Days not represented well primarily had continuously high humidity. Mean kinetic temperature was useful for severity ranking. CONCLUSIONS Simulating temperature and humidity conditions clearly reveals operational challenges encountered during disasters and emergencies. Understanding of environmental stresses and MKT leads to insights regarding operational robustness necessary for safe and accurate use of POC devices and reagents. Rescue personnel should understand these principles before performing POC testing in adverse environments.

Effects of humidity on foil and vial packaging to preserve glucose and lactate test strips for disaster readiness.

OBJECTIVE Efficient emergency and disaster response is challenged by environmental conditions exceeding test reagent storage and operating specifications. We assessed the effectiveness of vial and foil packaging in preserving point-of-care (POC) glucose and lactate test strip performance in humid conditions. METHODS Glucose and lactate test strips in both packaging were exposed to mean relative humidity of 97.0 ± 1.1% in an environmental chamber for up to 168 hours. At defined time points, stressed strips were removed and tested in pairs with unstressed strips using whole blood samples spiked to glucose concentrations of 60, 100, and 250 mg/dL (n = 20 paired measurements per level). A Wilcoxon signed rank test was used to compare stressed and unstressed test strip measurements. RESULTS Stressed glucose and lactate test strip measurements differed significantly from unstressed strips, and were inconsistent between experimental trials. Median glucose paired difference was as high as 12.5 mg/dL at the high glucose test concentration. Median lactate bias was -0.2 mmol/L. Stressed strips from vial (3) and foil (7) packaging failed to produce results. CONCLUSIONS Both packaging designs appeared to protect glucose and lactate test strips for at least 1 week of high humidity stress. Documented strip failures revealed the need for improved manufacturing process.