Trends in Utilization of Electronic Consultations Associated With Patient Payer and Language Among US Academic Medical Centers During the COVID-19 Pandemic.

Importance: Electronic consultations (eConsultations) are increasingly used to obtain specialist guidance, avoiding unnecessary face-to-face patient visits for certain clinical questions. During the COVID-19 pandemic, when in-person care was limited, eConsultations may have helped clinicians obtain specialist input to guide patient care. Objective: To understand how the use of eConsultations changed during the COVID-19 pandemic and whether trends in eConsultation utilization differed based on patient's payer and primary language. Design, Setting, and Participants: This retrospective cohort study was conducted at 6 academic medical centers in the United States, all participating in the Association of American Colleges Coordinating Optimal Referral Experiences program. Participants included adult patients who had an outpatient visit, referral, or eConsultation during the study period. Data were analyzed from June 4, 2019, to July 28, 2020. Main Outcomes and Measures: The primary outcome was the eConsultation proportion of specialty contact, defined as the number of completed eConsultations divided by the sum of the number of completed eConsultations and specialty referrals, expressed as a percentage. eConsultation percentages of specialty contact were further stratified by payer type and language. Payers included commercial, Medicare, Medicaid, self-pay or uninsured, and other. Primary language included English and non-English languages. Results: A total of 14 545 completed eConsultations and 189 776 referrals were included. More eConsultations were completed for English-speaking patients (11 363 eConsultations [95.0%]) than non-English-speaking patients (597 eConsultations [5.0%]). Patients with commercial insurance represented the highest number of completed eConsultations (8848 eConsultations [60.8%]) followed by Medicare (3891 eConsultations [26.8%]), Medicaid (930 eConsultations [6.4%]), other insurance (745 eConsultations [5.1%]), and self-pay or no insurance (131 eConsultations [0.9%]). At the start of the pandemic, across all academic medical centers, the percentage of specialty contact conducted via eConsultation significantly increased by 6.21% (95% CI, 4.97%-7.44%; P < .001). When stratified by payer and language, the percentage of specialty contact conducted via eConsultation significantly increased at the beginning of the pandemic for both English-speaking patients (change, 6.09% (95% CI, 4.82% to 7.37%; P < .001) and non-English-speaking patients (change, 8.48% [95% CI, 5.79% to 11.16%]; P < .001) and for all payers, except self-pay and uninsured patients (change, -0.21% [95% CI, [-1.35% to 0.92%]; P = .70). Conclusions and Relevance: This retrospective cohort study found that eConsultations provided an accessible mechanism for clinicians to receive specialist input when in-person care was limited.

A Comparison of Patient-Reported Outcomes Related to Telephone Follow-Up Visits and Conventional Office Visits in Medical Specialty Practices.

Background/Introduction: Scheduled telephone follow-up visits (TFVs) are one strategy for improving access to specialty care practices, primarily because TFVs can be completed in less time with lower overhead costs than conventional office-based follow-up visits (OFVs). Beginning January 2015, scheduled TFVs were introduced in three specialty care practices at University of California San Francisco (UCSF) as a substitute for scheduled OFVs. As there is limited data on the relative advantage to patients from such a program, we conducted a survey to evaluate patient-reported outcomes associated with both TFVs and OFVs. Materials and Methods: All patients who completed a follow-up visit in Endocrinology, Hepatology, or Multiple Sclerosis clinics between March and May 2016 were surveyed. Primary outcomes included out-of-pocket costs associated with follow-up visits, visit duration, and satisfaction. Responses were analyzed using univariate and bivariate statistics, and both t-tests and chi-square tests were employed to determine significance. Results: A total of 2,741 patients were surveyed, of which 16% (n = 432) responded. Median self-reported costs associated with OFVs, including travel was $50 (interquartile range [IQR]: 20,100), and median visit duration was 240 (IQR: 150; 420) minutes. Of all TFV respondents, only one reported a cost of $15, and 99% of TFV respondents reported being satisfied with their TFV experience. Discussion/Conclusion: At UCSF, TFVs offer an efficient alternative to office-based visits in a manner that is both acceptable and affordable to patients. This study fills an important gap in understanding the patient's perception of telephone follow-up care, and represents a critical first step in mobilizing health plans to pay for TFVs.

Design and development of referrals automation, a SMART on FHIR solution to improve patient access to specialty care.

BACKGROUND: Referring patients to specialty care is an inefficient and error-prone process. Gaps in the referral process lead to delays in patients' access to care, negative patient experience, worse health outcomes, and increased operational costs. While implementation of standards-based electronic referral options can alleviate some of these inefficiencies, many referrals to tertiary and quaternary care centers continue to be sent via fax. OBJECTIVE: We describe the design process and architecture for a software application that has been developed and deployed to optimize the referrals intake process by automating the processing and digitization of incoming specialty referral faxes, extracting key data elements and integrating them into the electronic health record (EHR), and organizing referrals. METHODS: A human-centered design approach was used to identify and describe the inefficiencies in the external referral process at our large, urban tertiary care center. Referrals Automation, an application to convert referral faxes to digital referrals in the EHR, was conceptualized based on key stakeholder interviews and time and motion studies. This application was designed using Substitutable Medical Applications and Reusable Technologies (SMART) and Fast Healthcare Interoperability Resource (FHIR) platforms to allow for adaptability into other healthcare organizations. RESULTS: Referrals Automation software was developed as a healthcare information technology solution to streamline the fax to referral process. The application was implemented into several specialty clinics. Metrics were built-in to the applications to evaluate and guide the further iteration of these features. CONCLUSIONS: Referrals Automation will enhance the referrals process by further streamlining and organizing the patient referral process.

Rapid Utilization of Telehealth in a Comprehensive Cancer Center as a Response to COVID-19: Cross-Sectional Analysis.

BACKGROUND: The emergence of the coronavirus disease (COVID-19) pandemic in March 2020 created unprecedented challenges in the provision of scheduled ambulatory cancer care. As a result, there has been a renewed focus on video-based telehealth consultations as a means to continue ambulatory care. OBJECTIVE: The aim of this study is to analyze the change in video visit volume at the University of California, San Francisco (UCSF) Comprehensive Cancer Center in response to COVID-19 and compare patient demographics and appointment data from January 1, 2020, and in the 11 weeks after the transition to video visits. METHODS: Patient demographics and appointment data (dates, visit types, and departments) were extracted from the electronic health record reporting database. Video visits were performed using a HIPAA (Health Insurance Portability and Accountability Act)-compliant video conferencing platform with a pre-existing workflow. RESULTS: In 17 departments and divisions at the UCSF Cancer Center, 2284 video visits were performed in the 11 weeks before COVID-19 changes were implemented (mean 208, SD 75 per week) and 12,946 video visits were performed in the 11-week post-COVID-19 period (mean 1177, SD 120 per week). The proportion of video visits increased from 7%-18% to 54%-72%, between the pre- and post-COVID-19 periods without any disparity based on race/ethnicity, primary language, or payor. CONCLUSIONS: In a remarkably brief period of time, we rapidly scaled the utilization of telehealth in response to COVID-19 and maintained access to complex oncologic care at a time of social distancing.

Rapid design and implementation of an integrated patient self-triage and self-scheduling tool for COVID-19.

OBJECTIVE: To rapidly deploy a digital patient-facing self-triage and self-scheduling tool in a large academic health system to address the COVID-19 pandemic. MATERIALS AND METHODS: We created a patient portal-based COVID-19 self-triage and self-scheduling tool and made it available to all primary care patients at the University of California, San Francisco Health, a large academic health system. Asymptomatic patients were asked about exposure history and were then provided relevant information. Symptomatic patients were triaged into 1 of 4 categories-emergent, urgent, nonurgent, or self-care-and then connected with the appropriate level of care via direct scheduling or telephone hotline. RESULTS: This self-triage and self-scheduling tool was designed and implemented in under 2 weeks. During the first 16 days of use, it was completed 1129 times by 950 unique patients. Of completed sessions, 315 (28%) were by asymptomatic patients, and 814 (72%) were by symptomatic patients. Symptomatic patient triage dispositions were as follows: 193 emergent (24%), 193 urgent (24%), 99 nonurgent (12%), 329 self-care (40%). Sensitivity for detecting emergency-level care was 87.5% (95% CI 61.7-98.5%). DISCUSSION: This self-triage and self-scheduling tool has been widely used by patients and is being rapidly expanded to other populations and health systems. The tool has recommended emergency-level care with high sensitivity, and decreased triage time for patients with less severe illness. The data suggests it also prevents unnecessary triage messages, phone calls, and in-person visits. CONCLUSION: Patient self-triage tools integrated into electronic health record systems have the potential to greatly improve triage efficiency and prevent unnecessary visits during the COVID-19 pandemic.

Comparing Patients' Experiences with Electronic and Traditional Consultation: Results from a Multisite Survey.

BACKGROUND: There have been no large-scale studies to date of patients' experiences with electronic consultation (eConsult) between primary and specialty care. OBJECTIVE: Compare experiences with eConsult and referral for in-person specialist consultation. DESIGN: Online survey 2-6 weeks following eConsult or referral at 9 US academic medical centers. PARTICIPANTS: Adult patients with no more than one eConsult or referral order from a primary care provider (PCP) in the prior month. Over 9 months, 29,291 email invitations were sent (88% referral; 12% eConsult). MAIN MEASURES: Trust in and satisfaction with PCP; consult type awareness; agreement with decision to seek specialist input; timeliness of care; mode of PCP-patient eConsult communication; satisfaction with specialist's recommendations; future preference for eConsult or referral. KEY RESULTS: A 27.6% response rate yielded 8087 respondents (88.4% referral; 11.6% eConsult). Many did not know that their PCP had placed a referral (32.8% unaware) or eConsult (52.9%), and eConsult awareness was significantly higher among patients reporting better health (OR 1.62, 95% CI 1.18-2.23). Most (81.4% eConsult; 82.0% referral) were satisfied with the specialist's recommendations. Those who had a good primary care experience were more likely to be satisfied (eConsult: OR 10.63, 95% CI 2.95-38.32; referral: OR 2.87, 95% CI 1.86-4.44). For a similar problem in the future, 78% of eConsult and 32% percent of referral patients preferred eConsult. CONCLUSIONS: This multisite study demonstrates that many patients find virtual consultation to be an acceptable strategy for the management of their medical condition and that trust and confidence in one's PCP are crucial ingredients for a satisfying eConsult experience. The lack of awareness of eConsult among many patients who were beneficiaries of the service warrants an increased effort to include patients in eConsult decision-making and communication. Further research is needed to assess eConsult acceptability and satisfaction in more diverse patient populations.

Transitioning Patients From Specialty Care to Primary Care: What We Know and What We Can Do.

Growing demand for specialty care has resulted in longer wait times for appointments, particularly at US academic referral centers. A proportion of specialty visits are for routine follow-up care of stable problems, and there is evidence that primary care providers are willing and able to take responsibility for a significant proportion of these patients. However, little is known about how to transition care back to a referring primary care clinician in a manner that is acceptable to everyone involved. In this article, we describe social, legal, and financial barriers to effective care transition and propose communication strategies to overcome them.

Psychiatric Consultation at Your Fingertips: Descriptive Analysis of Electronic Consultation From Primary Care to Psychiatry.

BACKGROUND: Mental health problems are commonly encountered in primary care, with primary care providers (PCPs) experiencing challenges referring patients to specialty mental health care. Electronic consultation (eConsult) is one model that has been shown to improve timely access to subspecialty care in a number of medical subspecialties. eConsults generally involve a PCP-initiated referral for specialty consultation for a clinical question that is outside their expertise but may not require an in-person evaluation. OBJECTIVE: Our aim was to describe the implementation of eConsults for psychiatry in a large academic health system. METHODS: We performed a content analysis of the first 50 eConsults to psychiatry after program implementation. For each question and response, we coded consults as pertaining to diagnosis and/or management as well as categories of medication choice, drug side effects or interactions, and queries about referrals and navigating the health care system. We also performed a chart review to evaluate the timeliness of psychiatrist responses and PCP implementation of recommendations. RESULTS: Depression was the most common consult template selected by PCPs (20/50, 40%), followed by the generic template (12/50, 24%) and anxiety (8/50, 16%). Most questions (49/50, 98%) pertained primarily to management, particularly for medications. Psychiatrists commented on both diagnosis (28/50, 56%) and management (50/50, 100%), responded in an average of 1.4 days, and recommended in-person consultation for 26% (13/50) of patients. PCPs implemented psychiatrist recommendations 76% (38/50) of the time. CONCLUSIONS: For the majority of patients, psychiatrists provided strategies for ongoing management in primary care without an in-person evaluation, and PCPs implemented most psychiatrist recommendations. eConsults show promise as one means of supporting PCPs to deliver mental health care to patients with common psychiatric disorders.

Analysis of an electronic consultation program at an academic medical centre: Primary care provider questions, specialist responses, and primary care provider actions.

Introduction Electronic consultations (eConsults) increase access to specialty care, but little is known about the types of questions primary care providers (PCPs) ask through eConsults, and how they respond to specialist recommendations. Methods This is a retrospective descriptive analysis of the first 200 eConsults completed in the UCSF eConsult program. Participating PCPs were from eight adult primary care sites at the University of California, San Francisco (UCSF), USA. Medicine subspecialties participating were Cardiology, Endocrinology, Gastroenterology/hepatology, Hematology, Infectious diseases, Nephrology, Pulmonary medicine, Rheumatology, and Sleep medicine. We categorized eConsult questions into "diagnosis," "treatment," and/or "monitoring." We performed medical record reviews to determine the percentage of specialist recommendations PCPs implemented, and the proportion of patients with a specialist visit in the same specialty as the eConsult, emergency department visit, or hospital admission during the subsequent six months. Results PCP questions related to diagnosis in 71% of cases, treatment in 46%, and monitoring in 21%. Specialist responses related to diagnosis in 76% of cases, treatment in 64%, and monitoring in 40%. PCPs ordered 79% of all recommended laboratory tests, 86% of recommended imaging tests and procedures, 65% of recommended new medications, and 73% of recommended medication changes. In the six months after the eConsult, 14% of patients had a specialist visit within the UCSF system in the same specialty as the eConsult. Discussion eConsults provide guidance to PCPs across the spectrum of patient care. PCPs implement specialists' recommendations in the large majority of cases, and few patients subsequently require in-person specialty care related to the reason for the eConsult.

Referring wisely: orthopedic referral guidelines at an academic institution.

OBJECTIVES: To develop local orthopedic guidelines for use in referral decision support and electronic consultation programs at University of California, San Francisco Health. STUDY DESIGN: Modified Delphi method. METHODS: We performed a 2-phase modified Delphi study to identify consensus between primary care and orthopedic clinicians for common musculoskeletal problems. RESULTS: Clinicians agreed that confirming patient interest in an orthopedic procedure should be completed prior to referral in 81% of clinical scenarios, as well as conservative management in 80%, physical therapy in 60%, and x-ray prior to referral in 42% of scenarios. Clinicians agreed an MRI should not be performed prior to referral in most (58%) clinical scenarios. CONCLUSIONS: In the absence of national guidelines, a process for local guideline generation is needed in order to provide nuanced and detailed decision support at the point of referral. The Delphi method proved an effective process to achieve this end.

Teaching residents screening, brief intervention, and referral to treatment (SBIRT) skills for alcohol use: Using chart-stimulated recall to assess curricular impact.

BACKGROUND: Screening, brief intervention, and referral to treatment (SBIRT) improves identification and intervention for patients at risk for developing an alcohol use disorder (AUD). Residency curriculum is designed to teach SBIRT skills, but resources are needed to promote skill implementation. The electronic health record (EHR) can facilitate implementation through integration of decision-support tools. The authors developed electronic tools to facilitate documentation of alcohol assessment and brief intervention and to reinforce skills from an SBIRT curriculum. This prospective cohort study assessed primary care internal medicine residents' use of SBIRT skills and EHR tools in practice using chart-stimulated recall (CSR). METHODS: Postgraduate year 2 and 3 residents received a 5-hour SBIRT curriculum with skills practice and instruction on SBIRT electronic tools. Participants were then given a list of their patients seen in a 1-year period who were drinking at/above the recommended limit. Trainees selected 3 patients to review with a faculty member in a CSR. Faculty used a 24-item chart checklist to assess application of SBIRT skills and electronic tool use and met with residents to complete a CSR interview. CSR interview notes were analyzed qualitatively to understand application of SBIRT skills and EHR tool use. RESULTS: Eighteen of 20 residents participated in the CSR, and 5 faculty reviewed 46 patient charts. Residents documented alcohol use (84.2% of charts) and assessment of quantity/frequency of use (71.0%) but were less likely to document assessment for an AUD (34%), an appropriate plan (50.0%), or follow-up (55%). Few residents used EHR tools. Residents reported barriers in addressing alcohol use, including lack of knowledge, patient barriers, and time constraints. CONCLUSIONS: More intensive training in SBIRT with opportunities for practice and feedback may be necessary for residents to consistently apply SBIRT skills in practice. EHR tools need to be better integrated into the clinic workflow in order to be useful.

Optimizing the pre-referral workup for gastroenterology and hepatology specialty care: consensus using the Delphi method.

RATIONALE, AIMS AND OBJECTIVES: Specialty care referrals have doubled in the last decade. Optimization of the pre-referral workup by a primary care doctor can lead to a more efficient first specialty visit with the patient. Guidance regarding pre-referral laboratory testing is a first step towards improving the specialty referral process. Our aim was to establish consensus regarding appropriate pre-referral workup for common gastrointestinal and liver conditions. METHODS: The Delphi method was used to establish local consensus for recommending certain laboratory tests prior to specialty referral for 13 clinical conditions. Seven conditions from The University of Michigan outpatient referral guidelines were used as a baseline. An expert panel of three PCPs and nine gastroenterologists from three academic hospitals participated in three iterative rounds of electronic surveys. Each panellist ranked each test using a 5-point Likert scale (strongly disagree to strongly agree). Local panellists could recommend additional tests for the initial diagnoses, and also recommended additional diagnoses needing guidelines: iron deficiency anaemia, abdominal pain, irritable bowel syndrome, fatty liver disease, liver mass and cirrhosis. Consensus was defined as ≥70% of experts scoring ≥4 (agree or strongly agree). RESULTS: Applying Delphi methodology to extrapolate externally developed referral guidelines for local implementation resulted in considerable modifications. For some conditions, many tests from the external group were eliminated by the local group (abdominal bloating; iron deficiency anaemia; irritable bowel syndrome). In contrast, for chronic diarrhoea, abnormal liver enzymes and viral hepatitis, all/most original tests were retained with additional tests added. For liver mass, fatty liver disease and cirrhosis, there was high concordance among the panel with few tests added or eliminated. CONCLUSIONS: Consideration of externally developed referral guidelines using a consensus-building process leads to significant local tailoring and adaption. Our next steps include implementation and dissemination of these guidelines and evaluating their impact on care efficiency in clinical practice.

Using Rapid Ethnography to Support the Design and Implementation of Health Information Technologies.

Ethnography is the defining practice - and art - of anthropology. Among health information technology (IT) developers, however, ethnography remains a little used and undervalued mode of inquiry and representation. In this chapter we demonstrate that ethnography can make important contributions to the design and implementation of more user-oriented health IT devices and systems. In particular, we propose 'rapid ethnography' as a pragmatic strategy that draws on classic ethnographic methods, but emphasizes shorter periods of fieldwork and quick turnaround of findings to inform (re)design, programming and implementation efforts. Rapid ethnography is theoretically and empirically situated in science and technology studies' explorations of a) the entanglement of social and technical dimensions of technology use; b) how getting tools to 'work' requires aligning interests across a wide range of human and non-human actors; and c) the ways in which humans and technology transform each other as they interact. We provide two detailed case studies to illustrate the evolution and uses of rapid ethnography at a U.S. academic medical center. By providing deeper insights into the experiences of users, and the contexts and communities in which new tools are introduced, rapid ethnography can serve as a valuable component of Techno-Anthropology and health IT innovation.

Transforming the endocrine consult: asynchronous provider consultations.

OBJECTIVE: To analyze the impact of virtual consultations on the spectrum and volume of endocrine consults, access to endocrine care, and downstream healthcare utilization. METHODS: A program (eConsults) designed to enable and reimburse asynchronous consultations between primary care physicians (PCPs) and specialists at the University of California, San Francisco, was launched in 2012. All eConsults (n = 158) submitted to endocrinology over the first year were analyzed for clinical focus and use of structured referral templates. PCP compliance with specialist recommendations was measured and stratified by provider type. Impact on endocrine referral volume was calculated using simple linear regression. Changes in wait times to endocrine care were analyzed comparing administrative data from the year of and the year prior to the introduction of eConsults. Downstream endocrine office visits, emergency department visits, and hospitalizations were captured by chart abstraction for all standard endocrine eConsults (n = 113). RESULTS: The proportion of endocrine referrals sent as eConsults (15 to 22%) was significantly higher than the combined average for all other participating specialties (7.4%) (P<.001). Overall, 76.0% of endocrinologist recommendations were fully implemented. There was no induced demand in total volume of referrals to endocrinology, and introduction of eConsults significantly improved access to endocrine care (odds ratio, 3.6; 95% confidence interval, 2.7 to 4.9). Rates of downstream healthcare utilization within 6 months of a completed eConsult were low. CONCLUSION: Use of virtual consultations in a fee-for-service, academic medical center setting significantly improved access to endocrine care and the quality of referrals. Increasing recognition and reimbursement of nontraditional consultation models will be essential to scaling and disseminating these programs.

Native California soils are selective reservoirs for multidrug-resistant bacteria.

Soil bacteria can exhibit extensive antibiotic resistomes and act as reservoirs of important antibiotic resistance traits. However, the geographic sources and evolutionary drivers of resistance traits are poorly understood in these natural settings. We investigated the prevalence, spatial structure and evolutionary drivers of multidrug resistance in natural populations of Bradyrhizobium, a cosmopolitan bacterial lineage that thrives in soil and aquatic systems as well as in plant and human hosts. We genotyped > 400 isolates from plant roots and soils across California and assayed 98 of them for resistance traits against 17 clinically relevant antibiotics. We investigated the geographic and phylogenetic structure of resistance traits, and analysed correlations of resistance with strain abundance, host infection capacity and in vitro fitness. We found: (i) multidrug resistance at all sites, (ii) subsets of resistance traits that are spatially structured and (iii) significant associations between resistance traits and increased strain abundance or host infection capacity. Our results highlight multiple selective factors that can result in the spread of resistance traits in native Bradyrhizobium populations.

When to repatriate? Clinicians' perspectives on the transfer of patient management from specialty to primary care.

BACKGROUND: Subspecialty ambulatory care visits have doubled in the past 10 years and nearly half of all visits are for follow-up care. Could some of this care be provided by primary care providers (PCPs)? OBJECTIVE: To determine how often PCPs and specialists agree that a mutual patient's condition could be managed exclusively by the PCP, and to understand PCPs' perspectives on factors that influence decisions about 'repatriation,' or the transfer of patient management to primary care. DESIGN: A mixed method approach including paired surveys of PCPs and specialists about the necessity for ongoing specialty care of mutual patients, and interviews with PCPs about care coordination practices and reasons for differing opinions with specialists. PARTICIPANTS: One hundred and eighty-nine PCPs and 59 physicians representing five medicine subspecialties completed paired surveys for 343 patients. Semi-structured interviews were conducted with 16 PCPs. MEASUREMENTS: For each patient, PCPs and specialists were asked, "Could this diagnosis be managed exclusively by the PCP?" RESULTS: Specialists and PCPs agreed that transfer to primary care was appropriate for 16% of patients, whereas 36% had specialists and PCPs who agreed that ongoing specialty care was appropriate. Specialists were half as likely as PCPs to identify patients as appropriate for transfer to primary care. PCPs identified several factors that influence the likelihood that patients will be transferred to primary care, including perceived patient preferences, limited access to physician appointments, excessive workload, inter-clinician communication norms, and differences in clinical judgment. We group these factors into two domains: 'push-back' and 'pull-back' to primary care. CONCLUSIONS: At a large academic medical center, approximately one in six patients receiving ongoing specialty care could potentially be managed exclusively by a PCP. PCPs identified several non-clinical factors to explain continuation of specialty care when patient transfer to PCP is clinically appropriate.

Diffusivity of solutes measured in glass capillaries using Taylor's analysis of dispersion and a commercial CE instrument.

We present a strategy for the rapid, efficient, and accurate measurement of the coefficient of diffusion (D) of solutes using a commercial capillary electrophoresis (CE) instrument. This approach utilizes the classic analysis of Taylor of the dispersion of solutes pumped hydrostatically through glass capillaries. To obtain accurate values of D, we modified Taylor's analysis of dispersion to account for the finite time required to reach steady-state flow in the capillary when using a CE instrument. Neglecting this effect results in measured diffusivities of phenylalanine, a model solute, that are in error by as much as 60% when compared with published values. We provide an analysis of this effect and a simple strategy for avoiding these errors. Using this approach, we analyze profiles of concentration fronts and measured values of D for phenylalanine to within 5% of published values. We also analyze profiles of pulses of solute. To determine values of D accurately, measurements of dispersion first need to be made as a function of injection volume to correct for the finite width of the injection plug, before they are corrected for unsteady-state flow. This approach also yields values of D for phenylalanine to within 5% of published values. In contrast to other techniques used for the determination of D, this approach requires no fluorescent labeling and is applicable to solutes of any molecular weight.

Measurement of enzyme kinetics using microscale steady-state kinetic analysis.

This paper describes a new technique--microscale steady-state kinetic analysis (microSKA)--that enables the rapid and parallel analysis of enzyme kinetics. Rather than physically defining a microscopic reactor through microfabrication, we show how the relative rates of reaction and transport in a macroscopic flow chamber, where the enzyme is immobilized on one wall of the chamber, results in the confinement of an enzyme-catalyzed reaction to a microscopic reactor volume adjacent to this wall. This volume has linear dimensions that are orders of magnitude smaller than the physical dimensions of the system (i.e., micrometer vs millimeter). Conversion within this volume is monitored at steady state as a function of position, rather than time. In this way, limitations due to reactor dead time and mixing are avoided. We use microSKA to determine kinetic parameters for the alkaline phosphatase-catalyzed de-phosphorylation of nonfluorescent methylumbelliferyl phosphate (MUP) to fluorescent 7-hydroxy-4-methylcoumarin (HMC) at two different values of pH. Kinetic parameters measured with microSKA are in good agreement with values obtained using conventional methods, if one takes into account effects of immobilization on enzyme activity. This technique provides a rapid and simple method for determining enzyme kinetics using small amounts of sample material and may be useful for applications in proteomics, drug discovery, biocatalyst development, and clinical diagnostics.