Association of prior treatment with nitrogen-containing bisphosphonates on outcomes of COVID-19 positive patients.

COVID-19 infection has resulted in significant morbidity and mortality globally, especially among older adults. Repurposed drugs have demonstrated activity in respiratory illnesses, including nitrogen-containing bisphosphonates. In this retrospective longitudinal study at 4 academic medical centers, we show no benefit of nitrogen-containing bisphosphonates regarding ICU admission, ventilator use, and mortality among older adults with COVID-19 infection. We specifically evaluated the intravenous bisphosphonate zoledronic acid and found no difference compared to oral bisphosphonates. BACKGROUND: Widely used in osteoporosis treatment, nitrogen-containing bisphosphonates (N-BP) have been associated with reduced mortality and morbidity among older adults. Based on prior studies, we hypothesized that prior treatment with N-BP might reduce intensive care unit (ICU) admission, ventilator use, and death among older adults diagnosed with COVID-19. METHODS: This retrospective analysis of the PCORnet Common Data Model across 4 academic medical centers through 1 September 2021 identified individuals age >50 years with a diagnosis of COVID-19. The composite outcome included ICU admission, ventilator use, or death within 15, 30, and 180 days of COVID-19 diagnosis. Use of N-BP was defined as a prescription within 3 years prior. ICU admission and ventilator use were determined using administrative codes. Death included both in-hospital and out-of-hospital events. Patients treated with N-BP were matched 1:1 by propensity score to patients without prior N-BP use. Secondary analysis compared outcomes among those prescribed zoledronic acid (ZOL) to those prescribed oral N-BPs. RESULTS: Of 76,223 COVID-19 patients identified, 1,853 were previously prescribed N-BP, among whom 559 were prescribed ZOL. After propensity score matching, there were no significant differences in the composite outcome at 15 days (HR 1.22, 95% CI: 0.89-1.67), 30 days (HR 1.24, 95% CI: 0.93-1.66), or 180 days (HR 1.17, 95% CI: 0.93-1.48), comparing those prescribed and not prescribed N-BP. Compared to those prescribed oral N-BP, there were no significant differences in outcomes among those prescribed ZOL. CONCLUSION: Among older COVID-19 patients, prior exposure to N-BP including ZOL was not associated with a reduction in ICU admission, ventilator use, or death.

Automatically Identifying Financial Stress Information from Clinical Notes for Patients with Prostate Cancer.

Background: Financial stress, one of the social determinants, is common among cancer patients because of high out-ofpocket costs for treatment, as well as indirect costs. The National Academy of Medicine (NAM) has advised providers to recognize and discuss cost concerns with patients in order to enhance shared decision-making for treatment and exploration of financial assistant programs. However, financial stress is rarely assessed in clinical practice or research, thus, under-coded and under-documented in clinical practice. Natural language processing (NLP) offers great potential that can automatically extract and process data on financial stress from clinical free text existing in the patient electronic health record (EHR). Methods: We developed and evaluated an NLP approach to identify financial stress from clinical narratives for patients with prostate cancer. Of 4,195 eligible prostate cancer patients, we randomly sampled 3,138 patients (75%) as a training dataset (150,990 documents) to develop a financial stress lexicon and NLP algorithms iteratively. The remaining 1,057 patients (25%) were used as a test dataset (55,516 documents) to evaluate the NLP algorithm performance. The common terms representing financial stress were "financial concerns," "unable to afford," "insurance issue," "unemployed," and "financial assistance." Negations were used to exclude false mentions of financial stress. Results: Applying both pre- and post-negation, the NLP algorithm identified 209 patients (6.0%) from the training sample and 66 patients (6.2%) with 161 notes from the test sample as having documented financial stress. Two independent domain experts manually reviewed all 161 notes with NLP identified positives and randomly selected 161 notes with NLP-identified negatives, the NLP algorithm yielded 0.86 for precision, 1 for recall, and 0.9.2 for F-score. Conclusions: Financial stress information is not commonly documented in the EHR, neither in structured format nor in clinical narratives. However, natural language processing can accurately extract financial stress information from clinical notes when such narrative information is available.

EHR Big Data Deep Phenotyping. Contribution of the IMIA Genomic Medicine Working Group.

OBJECTIVES: Given the quickening speed of discovery of variant disease drivers from combined patient genotype and phenotype data, the objective is to provide methodology using big data technology to support the definition of deep phenotypes in medical records. METHODS: As the vast stores of genomic information increase with next generation sequencing, the importance of deep phenotyping increases. The growth of genomic data and adoption of Electronic Health Records (EHR) in medicine provides a unique opportunity to integrate phenotype and genotype data into medical records. The method by which collections of clinical findings and other health related data are leveraged to form meaningful phenotypes is an active area of research. Longitudinal data stored in EHRs provide a wealth of information that can be used to construct phenotypes of patients. We focus on a practical problem around data integration for deep phenotype identification within EHR data. The use of big data approaches are described that enable scalable markup of EHR events that can be used for semantic and temporal similarity analysis to support the identification of phenotype and genotype relationships. CONCLUSIONS: Stead and colleagues' 2005 concept of using light standards to increase the productivity of software systems by riding on the wave of hardware/processing power is described as a harbinger for designing future healthcare systems. The big data solution, using flexible markup, provides a route to improved utilization of processing power for organizing patient records in genotype and phenotype research.

Design and evaluation of a wireless electronic health records system for field care in mass casualty settings.

BACKGROUND: There is growing interest in the use of technology to enhance the tracking and quality of clinical information available for patients in disaster settings. This paper describes the design and evaluation of the Wireless Internet Information System for Medical Response in Disasters (WIISARD). MATERIALS AND METHODS: WIISARD combined advanced networking technology with electronic triage tags that reported victims' position and recorded medical information, with wireless pulse-oximeters that monitored patient vital signs, and a wireless electronic medical record (EMR) for disaster care. The EMR system included WiFi handheld devices with barcode scanners (used by front-line responders) and computer tablets with role-tailored software (used by managers of the triage, treatment, transport and medical communications teams). An additional software system provided situational awareness for the incident commander. The WIISARD system was evaluated in a large-scale simulation exercise designed for training first responders. A randomized trial was overlaid on this exercise with 100 simulated victims, 50 in a control pathway (paper-based), and 50 in completely electronic WIISARD pathway. All patients in the electronic pathway were cared for within the WIISARD system without paper-based workarounds. RESULTS: WIISARD reduced the rate of the missing and/or duplicated patient identifiers (0% vs 47%, p<0.001). The total time of the field was nearly identical (38:20 vs 38:23, IQR 26:53-1:05:32 vs 18:55-57:22). CONCLUSION: Overall, the results of WIISARD show that wireless EMR systems for care of the victims of disasters would be complex to develop but potentially feasible to build and deploy, and likely to improve the quality of information available for the delivery of care during disasters.

A Public Health Grid (PHGrid): Architecture and value proposition for 21st century public health.

PURPOSE: This manuscript describes the value of and proposal for a high-level architectural framework for a Public Health Grid (PHGrid), which the authors feel has the capability to afford the public health community a robust technology infrastructure for secure and timely data, information, and knowledge exchange, not only within the public health domain, but between public health and the overall health care system. METHODS: The CDC facilitated multiple Proof-of-Concept (PoC) projects, leveraging an open-source-based software development methodology, to test four hypotheses with regard to this high-level framework. The outcomes of the four PoCs in combination with the use of the Federal Enterprise Architecture Framework (FEAF) and the newly emerging Federal Segment Architecture Methodology (FSAM) was used to develop and refine a high-level architectural framework for a Public Health Grid infrastructure. RESULTS: The authors were successful in documenting a robust high-level architectural framework for a PHGrid. The documentation generated provided a level of granularity needed to validate the proposal, and included examples of both information standards and services to be implemented. Both the results of the PoCs as well as feedback from selected public health partners were used to develop the granular documentation. CONCLUSIONS: A robust high-level cohesive architectural framework for a Public Health Grid (PHGrid) has been successfully articulated, with its feasibility demonstrated via multiple PoCs. In order to successfully implement this framework for a Public Health Grid, the authors recommend moving forward with a three-pronged approach focusing on interoperability and standards, streamlining the PHGrid infrastructure, and developing robust and high-impact public health services.

Internet-based monitoring of patients with rheumatoid arthritis.

Patient-derived measures have been increasingly recognized as a valuable means for monitoirng patients with rheumatoid arthritis. One advantage of this data is that it can be collected remotely. This would allow more frequent and more rapid assessments, which could optimize therapeutic intervention and patient outcome.

IMPACT4: a framework for rapid, modular construction of web-based patient decision support systems and preference measurement tools.

To support the rapid creation of software systems that provide patients with decision support and measure patients' preferences, we have develop a framework called iMPACT4. The framework, which combines XML and Flash, has rich client-side state navigation control capabilities, reusable components, cross-platform compatibility, and facilitated access for persons with disabilities. It has many of the advanced navigation capabilities of complex server controlled web software while retaining an architecture that allows automated generation of web sites similar to our previous software system iMPACT3.

iMPACT3: Internet-based development and administration of utility elicitation protocols.

iMPACT3 (Internet Multimedia Preference Assessment Instrument Construction Tool, version 3) is a software development environment that helps researchers build Internet-capable multimedia utility elicitation software programs. The program is a free, openly accessible Web site (http.// preferences.ucsd.edu/impact3/asp). To develop a utility elicitation software program using iMPACT3, a researcher selects modular protocol components from a library and custom tailors the components to the details of his or her research protocol. iMPACT3 builds a Web site implementing the protocol and downloads it to the researcher's computer. In a study of 75 HIV-infected patients, an iMPACT3-generated protocol showed substantial evidence of construct validity and good internal consistency (logic error rates of 4% to 10% and procedural invariance error rates of 10% to 28%, depending on the elicitation method) but only fair 3- to 6-week test-retest reliability (intraclass correlation coefficient= 0.42 to 0.55). Further work may be needed on specific utility assessment procedures, but this study's results confirm iMPACT3's feasibility in facilitating the collection of health state utility data.

Can utility-weighted health-related quality-of-life estimates capture health effects of quality improvement for depression?

BACKGROUND: Utility methods that are responsive to changes in desirable outcomes are needed for cost-effectiveness (CE) analyses and to help in decisions about resource allocation. OBJECTIVES: Evaluated is the responsiveness of different methods that assign utility weights to subsets of SF-36 items to average improvements in health resulting from quality improvement (QI) interventions for depression. DESIGN: A group level, randomized, control trial in 46 primary care clinics in six managed care organizations. Clinics were randomized to one of two QI interventions or usual care. SUBJECTS: One thousand one hundred thirty-six patients with current depressive symptoms and either 12-month, lifetime, or no depressive disorder identified through screening 27,332 consecutive patients. MEASURES: Utility weighted SF-12 or SF-36 measures, probable depression, and physical and mental health-related quality of life scores. RESULTS: Several utility-weighted measures showed increases in utility values for patients in one of the interventions, relative to usual care, that paralleled the improved health effects for depression and emotional well being. However, QALY gains were small. Directly elicited utility values showed a paradoxical result of lower utility during the first year of the study for intervention patients relative to controls. CONCLUSIONS: The results raise concerns about the use of direct single-item utility measures or utility measures derived from generic health status measures in effectiveness studies for depression. Choice of measure may lead to different conclusions about the benefit and CE of treatment. Utility measures that capture the mental health and non-health outcomes associated with treatment for depression are needed.

What should be reported in a methods section on utility assessment?

BACKGROUND: The measurement of utilities, or preferences, for health states may be affected by the technique used. Unfortunately, in papers reporting utilities, it is often difficult to infer how the utility measurement was carried out. PURPOSE: To present a list of components that, when described, provide sufficient detail of the utility assessment. METHODS: An initial list was prepared by one of the authors. A panel of 8 experts was formed to add additional components. The components were drawn from 6 clusters that focus on the design of the study, the administration procedure, the health state descriptions, the description of the utility assessment method, the description of the indifference procedure, and the use of visual aids or software programs. The list was updated and redistributed among a total of 14 experts, and the components were judged for their importance of being mentioned in a Methods section. RESULTS: More than 40 components were generated. Ten components were identified as necessary to include even in an article not focusing on utility measurement: how utility questions were administered, how health states were described, which utility assessment method(s) was used, the response and completion rates, specification of the duration of the health states, which software program (if any) was used, the description of the worst health state (lower anchor of the scale), whether a matching or choice indifference search procedure was used, when the assessment was conducted relative to treatment, and which (if any) visual aids were used. The interjudge reliability was satisfactory (Cronbach's alpha = 0.85). DISCUSSION: The list of components important for utility papers may be used in various ways, for instance, as a checklist while writing, reviewing, or reading a Methods section or while designing experiments. Guidelines are provided for a few components.

Utility elicitation using single-item questions compared with a computerized interview.

BACKGROUND: The use of a simpler procedure for the measurement of utilities could affect primarily the variance or both the mean and the variance of measurements. In the former case, simpler methods would be useful for population studies of preferences; however, in the latter, their use for such studies might be problematic. PURPOSE: The purpose of this study was to compare the results of utility elicitation using single-item questions to computer elicitation using the Ping-Pong search procedure. METHODS: In a convenience sample of 149 primary care patients with symptoms of depression, the authors measured and compared standard gamble (SG) utilities elicited using a single-item "open question" to SG elicitations performed using a computerized interview procedure. Elicitations were performed 1 to 2 weeks apart to minimize memory effects. RESULTS: More than 90% of persons with utilities of 1.0 to the single-item standard gamble had utilities of less than 1.0 on the computer SG instrument. Consistent with this finding, the mean utilities were lower in computer interviews (0.80 vs. 0.90; P < 0.0001 for differences). Within subjects, utility measures had only a fair degree of correlation (r = 0.54). CONCLUSIONS: Use of single-item questions to elicit utilities resulted in less precise estimates of utilities that were upwardly biased relative to those elicited using a more complex search procedure.

Utility of B-type natriuretic peptide in the diagnosis of congestive heart failure in an urgent-care setting.

OBJECTIVES: The goal of this study was to evaluate the utility of a rapid "bedside" technique for measurement of B-type natriuretic peptide (BNP) in the diagnosis of congestive heart failure (CHF) in an urgent-care setting. BACKGROUND: B-type natriuretic peptide is a protein secreted from the cardiac ventricles in response to pressure overload. One potential application of measurements of BNP in blood is distinguishing dyspnea due to CHF from other causes. METHODS: B-type natriuretic peptide concentrations were measured in a convenience sample of 250 predominantly male (94%) patients presenting to urgent-care and emergency departments of an academic Veteran's Affairs hospital with dyspnea. Results were withheld from clinicians. Two cardiologists retrospectively reviewed clinical data (blinded to BNP measurements) and reached a consensus opinion on the cause of the patient's symptoms. This gold standard was used to evaluate the diagnostic performance of the BNP test. RESULTS: The mean BNP concentration in the blood of patients with CHF (n = 97) was higher than it was in patients without (1,076 +/- 138 pg/ml vs. 38 +/- 4 pg/ml, p < 0.001). At a blood concentration of 80 pg/ml, BNP was an accurate predictor of the presence of CHF (95%); measurements less than this had a high negative predictive value (98%). The overall C-statistic was 0.97. In multivariate analysis, BNP measurements added significant, independent explanatory power to other clinical variables in models predicting which patients had CHF. The availability of BNP measurements could have potentially corrected 29 of the 30 diagnoses missed by urgent-care physicians. CONCLUSIONS: B-type natriuretic peptide blood concentration measurement appears to be a sensitive and specific test to diagnose CHF in urgent-care settings.

A rapid bedside test for B-type peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study.

OBJECTIVES: The goal of this study was to determine if B-type natriuretic peptide (BNP) levels predict outcomes of patients admitted with decompensated heart failure. BACKGROUND: Treatment of decompensated congestive heart failure (CHF) has often been based on titration of drugs to relieve patient's symptoms, a case that could be made for attempting to also treat neurohormonal abnormalities. Because BNP reflects both elevated left ventricular pressure as well as neurohormonal modulation, we hypothesized that BNP might be useful in assessing outcomes in patients admitted with decompensated CHF. METHODS: We followed 72 patients admitted with decompensated New York Heart Association class III to IV CHF, measuring daily BNP levels. We then determined the association between initial BNP measurement and the predischarge or premoribund BNP measurement and subsequent adverse outcomes (death and 30-day readmission). RESULTS: Of the 72 patients admitted with decompensated CHF, 22 end points occurred (death: n = 13, readmission: n = 9). In these patients, BNP levels increased during hospitalization (mean increase, 233 pg/ml, p < 0.001). In patients without end points, BNP decreased (mean decrease 215 pg/ml). Univariate analysis revealed that the last measured BNP was strongly associated with the combined end point. In patients surviving hospitalization, BNP discharge concentrations were strong predictors of subsequent readmission (area under the receiver operator curve of 0.73). CONCLUSIONS: In patients admitted with decompensated CHF, changes in BNP levels during treatment are strong predictors for mortality and early readmission. The results suggest that BNP levels might be used successfully to guide treatment of patients admitted for decompensated CHF.

Acceptability of computerized visual analog scale, time trade-off and standard gamble rating methods in patients and the public.

One technique to enhance patient participation in clinical decision making is formal measurement of preferences and values. Three commonly applied methods are a visual analog scale(VAS), the standard gamble(SG), and the time trade-off(TTO). We studied participants subjective experience using computer implementations these methods using scale we call the VIBE (for Value Instrument Battery--Evaluation) that measures four aspects of user acceptance (clarity, difficulty, reasonableness, and comfort level) Studies were performed in two groups: patients with HIV infection (n=75) and a convenience sample of the general public(n=640). In the patient study, VIBE scores appeared reliable (Cronbach s alpha of 0.739, 0.826, and 0.716, for VAS, SG, and TTO ratings, respectively.) Patients acceptance of the VAS the highest, followed by the TTO and the SG method (p<0.05 for all comparisons). Despite significant enhancements in computer software for measuring SG preferences, observed differences in acceptance between SG and VAS methods were replicated in the general public study (p<0.0001 for differences). The results suggest developers of clinical decision support systems should use VAS and TTO rating methods where these methods are theoretically appropriate.

What is the next step in patient decision support?

Patient decision support systems have a promising role in the delivery of health care. However, the best approach for further development of these systems is a matter of speculation. To help chart a course for further development of decision support systems, we consider the four traditional roles that patients play in the medical decision making process, the limitations that patients face in participating in each role and describe how contemporary systems address can facilitate successful decision making for each role. Because patients have a diversity of preferences for the role they play in decision making, we believe that the critical research question is how to make decision support systems robust enough to support a patient's desired role, whatever that role might be. By directing research in decision support systems in this fashion, we believe that they will achieve a larger patient audience and have increased value in the delivery of clinical care.

Differences in health values among patients, family members, and providers for outcomes in schizophrenia.

OBJECTIVE: The objectives of this study were to determine whether there are important differences in how patients, family members, and health care providers (HCPs) value health outcomes in schizophrenia and to assess the degree to which such differences, if they exist, could adversely affect clinical and policy decision making. METHODS: Participants viewed videotaped depictions of simulated patients with mild and moderate symptoms of schizophrenia, with and without a common adverse drug effect (pseudoparkinsonism), and then provided standard gamble and visual analog scale ratings of desirability of these states. SUBJECTS: A convenience sample of unrelated patients (n = 148), family members of patients (n = 91), and HCPs (nurses, psychologists, doctors of pharmacy, and doctors of medicine; n = 99) was drawn from geographically and clinically diverse environments. RESULTS: Patients' and family members' utilities for health states averaged 0.1 to 0.15 units higher than those of HCPs (P <0.002 for differences between groups, ANOVA for multiple observations). The disutility of adverse drug effects was less for health professionals than patients and family members (P = 0.008). Health professionals tended to prefer states with mild symptoms with extrapyramidal side effects to states with moderate symptoms. Patients and family members found these states equally preferable (P <0.007 for differences between groups). CONCLUSIONS: There are systematic differences in values for health outcomes between patients and HCPs with regard to states with adverse effects of antipsychotic drugs. Family members of patients in general had values that were more similar to those of patients than were those of health professionals. The results emphasize the importance of participation by patients (or family member proxies) in clinical decision making and guideline development.

Validity and interpretation of preference-based measures of health-related quality of life.

Utilities are numeric measurements that reflect an individual's beliefs about the desirableness of a health condition, willingness to take risks to gain health benefits, and preferences for time. This report discusses the approaches to assess and compare the validity of methods used to assign utilities for cost-utility analysis. Threats to validity include construct underrepresentation and construct-irrelevant variance. Construct underrepresentation occurs when a stimulus presented to a judge fails to fully represent the depth and complexity of information required in actual judgments. Construct-irrelevant variation occurs when factors irrelevant to preferences influence measurements of utilities. Among several factors that cause construct-irrelevant variation are cognitive abilities, numeracy skills, emotions and prejudices, and the elicitation procedure. Commonly used elicitation methods (visual-analog scales, time tradeoff, and standard gamble) capture different facets of utilities (desirableness of states, time preferences, and risk attitude) to different degrees. The validity of an elicitation protocol depends (1) on the degree to which its scaling method captures the relevant facets of utility and (2) on the degree to which measurements are influenced by construct-irrelevant variation. Discrete-state health index models provide an alternative to direct elicitation of utilities and work by attaching fixed preference weights to observable health states. The creation of discrete-state models with current technologies requires the adoption of strong assumptions about the scaling properties of utilities. Future research must refine methods of eliciting utilities and identify sources of construct-irrelevant variability that reduce the validity of utility assessments. Because of the impact of variation in techniques on measurements, we do not recommend the combination of utilities elicited with different protocols in cost-utility analysis and do not recommend the display of cost-utility ratios from different studies in comparison or "league" tables.

Estimation of utilities for the effects of depression from the SF-12.

BACKGROUND: Utilities for health conditions, including major depressive disorder, have a theoretical relationship to health-related quality of life (HRQOL). Because of the complexity of utility measurement and the existence of large numbers of completed studies with HRQOL data but not utility data, it would be desirable to be able to estimate utilities from measurements of HRQOL. OBJECTIVE: The objective of this study was to estimate utility for remission in major depression by use of information on associated variation in Short Form 12 (SF-12) scores. DESIGN: A mapping function for SF-12 scores (based on a 6-health-state model with patient-weighted preferences) was applied to longitudinal data from a large naturalistic study to estimate changes in utilities. SUBJECTS: Preference ratings for states were performed in a convenience sample of depressed primary care patients (n = 140). Outcomes were evaluated in patients in the Course of Depression Study (n = 295) with a DSM III diagnosis of depression at the onset of the study. MEASURES: From clinical interview data, differences in utilities and global physical and mental health-related quality of life at 1- and 2-year follow-up were compared for patients who did and did not experience remission as determined by the Course of Depression Interview. RESULTS: Remission of depression resulted in health status improvement, as measured by the SF-12, equivalent to a gain of 0.11 quality-adjusted life-years over 2 years. CONCLUSIONS: Utilities for changes in health status, associated with a clinical change in depression, can be modeled from the SF-12 scales, which results in utilities within the range of estimates described in the literature.

Quality Enhancement Research Initiative for human immunodeficiency virus/acquired immunodeficiency syndrome: framework and plan. HIV-QUERI Executive Committee.

The Veterans Health Administration (VHA) sees approximately equal to 17,000 human immunodeficiency virus (HIV)-infected patients each year, which makes it the largest provider of HIV care in the United States. HIV causes chronic progressive disease that leads to early death. Newer combination antiretro viral treatments are effective but expensive and difficult to use. The HIV Quality Enhancement Research Initiative (HIV-QUERI) uses the QUERI process to identify high-risk and high-volume populations (step 1), which includes those already under VHA care for HIV, those who do not know of their infection, and those at risk for HIV. In identifying best practices (step 2), the HIV-QUERI will benefit greatly from existing guidelines for the care of established HIV infection, but gaps in knowledge regarding adherence to medication regimens and cost-effective screening are large. To identify existing practice patterns (step 3), the HIV-QUERI will develop a clean analytic data set based on Immunology Case Registry files and expand it through a survey of veterans. Interventions to improve care (step 4) will include national, regional, and site-specific feedback on performance relative to quality standards, as well as patient-level and provider-level interventions to improve adherence and support medical decision-making. To document that best practices improve outcomes and quality of life (steps 5 and 6), HIV-QUERI will track indicators on an ongoing basis by use of the Immunology Case Registry database and possible future waves of the survey. In addition, we will require that these issues be addressed in evaluations of HIV-QUERI interventions. In the present article, we present these steps within a framework and plan.