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

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.

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.

Short-Term Thermal-Humidity Shock Affects Point-of-Care Glucose Testing: Implications for Health Professionals and Patients.

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. 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. 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. 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. 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.

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.

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.

Optimizing Global Resiliency in Public Health, Emergency Response, and Disaster Medicine.

Resiliency through use of point-of-care (POC) testing in small-world networks will change the future landscape by bringing evidence-based decision-making to sites of need globally. This issue of Point of Care addresses fundamental principles and essential building blocks that mitigate crises and enhance standards of care. Several papers on needs assessment support the case for onsite testing in different medical situations. Then, the focus shifts to how to protect POC devices and reagents from extremes of temperature and humidity that are encountered virtually anywhere POC testing is used outside hospitals. Indeed, the effects of environmental stresses can no longer be ignored. We have observed the advent of the "hybrid laboratory" where POC whole-blood analysis is performed using transportable instruments in non-laboratory settings and the rapid expansion of portable and handheld testing now found ubiquitously worldwide. Emerging new POC technologies will propel personalized medicine by targeting treatment. Trendy as these advances are, in low-resource settings POC instruments often represent the default armamentarium of the small community hospital. Hence, education and competency become essential prerequisites for creating, maintaining, harmonizing, and standardizing accuracy and quality as new cost-effective technologies become available. Excellent performance brings value, which is one of the keys to this next phase in the history of point of care. By increasing the value of decision-making at the site of care, we can assure resiliency, for the individual patient who might be in need of self-monitoring, for rational responses to crises, and for nations made up of more resilient individual communities.

Strategic Point-of-Care Requirements of Hospitals and Public Health for Preparedness in Regions At Risk.

OBJECTIVES: To study health resources and point-of-care (POC) testing requirements for urgent, emergency, and disaster care in Phang Nga Province, Thailand; to determine instrument design specifications through a direct needs assessment survey; to describe POC test menus useful in the small-world network; and to assess strategies for preparedness following the 2004 Tsunami. METHODS: We surveyed medical professionals in community hospitals, a regional hospital, and the Naval Base Hospital; and officials at the offices of Provincial Public Health and Disaster Prevention and Mitigation. Questions covered: a) demographics and test requirements, b) POC needs, c) device design specifications, and d) pathogen detection options. Respondents scored choices. Scores determined priorities. RESULTS: Respondents selected complete blood count, electrolytes/chemistry, blood type, oxygen saturation (by pulse oximeter), hematocrit, and microbiology as top priorities, and preferred direct blood sampling with cassettes. Cardiac biomarkers were important in alternate care facilities. Staphylococcus aureus, SARS, Streptococcus pneumoniae, and hepatitis B were top infectious disease problems. Temperature, vibration, humidity, and impact shock were four important environmental conditions during extreme conditions. CONCLUSIONS: Point-of-care testing can be used on a daily basis for competency and efficiency. Familiarity improves preparedness. Instrument designs must anticipate user preferences and environment stresses. The results show how a region at risk can adapt its small-world network. Point-of-care testing has become an important risk-reducing modality for crises and works equally well in low-resource settings to speed the delivery of routine and urgent care.

Assessing Point-of-Care Device Specifications and Needs for Pathogen Detection in Emergencies and Disasters.

BACKGROUND: We assessed point-of-care device specifications and needs for pathogen detection in urgent care, emergencies, and disasters. METHODS: We surveyed American Association for Clinical Chemistry members and compared responses to those of disaster experts. Online SurveyMonkey questions covered performance characteristics, device design, pathogen targets, and other specifications. RESULTS: For disasters, respondents preferred direct sample collection with a disposable test cassette that stores biohazardous material (P<0.001). They identified methicillin-resistant Staphylococcus aureus, Salmonella typhi, Vibrio cholerae, Escherichia coli, Staphylococcus aureus, and Streptococcus pneumoniae as high priority pathogens. First responders were deemed the professional group who should perform POC testing in disasters (P<0.001). CONCLUSIONS: Needs assessment now is requisite for competitive funding, so the results in this report will be useful to investigators preparing grant applications. Point-of-care devices used in disasters should address the needs of first responders, who give high priority to contamination-free whole-blood sampling, superior performance pathogen detection, and HIV-1/2 blood donor screening. There was surprising concordance of preferences among different professional groups, which presages formulation of global consensus guidelines to assist high impact preparedness.

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.

POINT-OF-CARE HEMATOLOGY AND COAGULATION TESTING IN PRIMARY, RURAL EMERGENCY, AND DISASTER CARE SCENARIOS.

The purpose of this article is to review current principles and criteria for obtaining Clinical Laboratory Improvement Amendments of 1988 (CLIA '88) waiver, identify existing point-of-care (POC) coagulation and hematology technologies, and analyze regulatory challenges regarding CLIA-waiver for those and future devices. CLIA '88 documentation requires tests performed by laboratories with a Certificate of Waiver to be so simple that the likelihood of erroneous results by the user is negligible, or poses no unreasonable risk of harm to the patient if performed incorrectly as determined by the Secretary of Health and Human Services. "Simple" means that the test uses unprocessed samples, has a direct read-out of test results, does not have specifications for user training, and includes instructions for confirmatory testing when advisable. Currently the CLIA-waived hematology and coagulation POC devices only test for hemoglobin (Hb), hematocrit (Hct), and prothrombin time/international normalized ratio (PT/INR). The problem with these devices is the lack of multiplexing. POC coagulation and hematology devices face challenges for obtaining a waiver. These challenges include the lack of clinical needs assessment, miniturized assays that correct for interfering substances, and assays simple enough to be combined in a multiplex platform. Several scenarios demonstrate how POC coagulation or hematology devices can improve crisis care. Industry should perform needs assessment on clinicians and emergency responders to determine which analytes to incorporate on multiplex POC coagulation and hematology devices, and produce devices that address confounding factors.

Enhancing crisis standards of care using innovative point-of-care testing.

OBJECTIVE: To identify strategies with tactics that enable point-of-care (POC) testing (medical testing at or near the site of care) to effectively improve outcomes in emergencies, disasters, and public health crises, especially where community infrastructure is compromised. DESIGN: Logic model-critical path-feedback identified needs for improving practices. Reverse stress analysis showed POC should be integrated, responders should be properly trained, and devices should be staged in small-world networks (SWNs). First responder POC resources were summarized, test clusters were strategized, assay environmental vulnerabilities were assessed, and tactics useful for SWNs, alternate care facilities, shelters, point-of-distribution centers, and community hospitals were designed. PARTICIPANTS AND ENVIRONMENT: Emergency-disaster needs assessment survey respondents and Center experience. OUTCOMES: Important tactics are as follows: a) develop training/education courses and '"just-in-time" on-line web resources to ensure the competency of POC coordinators and high-quality testing performance; b) protect equipment from environmental extremes by sealing reagents, by controlling temperature and humidity to which they are exposed, and by establishing near-patient testing in defined environments that operate within current Food and Drug Administration licensing claims (illustrated with human immunodeficiency virus-1/2 tests); c) position testing in defined sites within SWNs and other environments; d) harden POC devices and reagents to withstand wider ranges of environmental extremes in field applications; e) promote new POC technologies for pathogen detection and other assays, per needs assessment results; and f) select tests according to mission objectives and value propositions. CONCLUSIONS: Careful implementation of POC testing will facilitate evidence-based triage, diagnosis, treatment, and monitoring of victims and patients, while advancing standards of care in emergencies and disasters, as well as public health crises.