Sarcopenia, adiposity and large discordance between cystatin C and creatinine-based estimated glomerular filtration rate in patients with cancer.

BACKGROUND: Creatinine-based estimated glomerular filtration rate (eGFRCRE) may overestimate kidney function in patients with sarcopenia. While cystatin C-based eGFR (eGFRCYS) is less affected by muscle mass, it may underestimate kidney function in patients with obesity. We sought to evaluate the relationship between body composition defined by computed tomography (CT) scans and discordance between creatinine, eGFRCRE and eGFRCYS in adult patients with cancer. METHODS: This study is a cross-sectional study of consecutive adults with cancer with an abdominal CT scan performed within 90 days of simultaneous eGFRCRE and eGFRCYS measurements between May 2010 and January 2022. Muscle and adipose tissue cross-sectional areas were measured at the level of the third lumbar vertebral body using a validated deep-learning pipeline. CT-defined sarcopenia was defined using independent sex-specific cut-offs for skeletal muscle index (<39 cm2/m2 for women and <55 cm2/m2 for men). High adiposity was defined as the highest sex-specific quartile of the total (visceral plus subcutaneous) adiposity index in the cohort. The primary outcome was eGFR discordance, defined by eGFRCYS > 30% lower than eGFRCRE; the secondary outcome was eGFRCYS > 50% lower than eGFRCRE. The odds of eGFR discordance were estimated using multivariable logistic regression modelling. Unadjusted spline regression was used to evaluate the relationship between skeletal muscle index and the difference between eGFRCYS and eGFRCRE. RESULTS: Of the 545 included patients (mean age 63 ± 14 years, 300 [55%] females, 440 [80.7%] non-Hispanic white), 320 (58.7%) met the criteria for CT-defined sarcopenia, and 136 (25%) had high adiposity. A total of 259 patients (48%) had >30% eGFR discordance, and 122 (22.4%) had >50% eGFR discordance. After adjustment for potential confounders, CT-defined sarcopenia and high adiposity were both associated with >30% eGFR discordance (adjusted odds ratio [aOR] 1.90, 95% confidence interval [CI] 1.12-3.24; aOR 2.01, 95% CI 1.15-3.52, respectively) and >50% eGFR discordance (aOR 2.34, 95% CI 1.21-4.51; aOR 2.23, 95% CI 1.19-4.17, respectively). A spline model demonstrated that as skeletal muscle index decreases, the predicted difference between eGFRCRE and eGFRCYS widens considerably. CONCLUSIONS: CT-defined sarcopenia and high adiposity are both independently associated with large eGFR discordance. Incorporating valuable information from body composition analysis derived from CT scans performed as a part of routine cancer care can impact the interpretation of GFR estimates.

Estimating Vitamin K Antagonist Anticoagulation Benefit in People With Atrial Fibrillation Accounting for Competing Risks: Evidence From 12 Randomized Trials.

BACKGROUND: Patients with atrial fibrillation have a high mortality rate that is only partially attributable to vascular outcomes. The competing risk of death may affect the expected anticoagulant benefit. We determined if competing risks materially affect the guideline-endorsed estimate of anticoagulant benefit. METHODS: We conducted a secondary analysis of 12 randomized controlled trials that randomized patients with atrial fibrillation to vitamin K antagonists (VKAs) or either placebo or antiplatelets. For each participant, we estimated the absolute risk reduction (ARR) of VKAs to prevent stroke or systemic embolism using 2 methods-first using a guideline-endorsed model (CHA2DS2-VASc) and then again using a competing risk model that uses the same inputs as CHA2DS2-VASc but accounts for the competing risk of death and allows for nonlinear growth in benefit. We compared the absolute and relative differences in estimated benefit and whether the differences varied by life expectancy. RESULTS: A total of 7933 participants (median age, 73 years, 36% women) had a median life expectancy of 8 years (interquartile range, 6-12), determined by comorbidity-adjusted life tables and 43% were randomized to VKAs. The CHA2DS2-VASc model estimated a larger ARR than the competing risk model (median ARR at 3 years, 6.9% [interquartile range, 4.7%-10.0%] versus 5.2% [interquartile range, 3.5%-7.4%]; P<0.001). ARR differences varied by life expectancies: for those with life expectancies in the highest decile, 3-year ARR difference (CHA2DS2-VASc model - competing risk model 3-year risk) was -1.3% (95% CI, -1.3% to -1.2%); for those with life expectancies in the lowest decile, 3-year ARR difference was 4.7% (95% CI, 4.5%-5.0%). CONCLUSIONS: VKA anticoagulants were exceptionally effective at reducing stroke risk. However, VKA benefits were misestimated with CHA2DS2-VASc, which does not account for the competing risk of death nor decelerating treatment benefit over time. Overestimation was most pronounced when life expectancy was low and when the benefit was estimated over a multiyear horizon.

Use of Lecanemab for Patients With Cardiovascular Disease: The Challenge of Uncertainty.

This Viewpoint discusses lecanemab use and the risk of cerebral macrohemorrhage for patients with mild cognitive impairment or early dementia.

Hazardous Alcohol Use Among Community-Dwelling Older Adults With Persistent or Recurrent Pain: Findings From the Health and Retirement Study.

BACKGROUND: Although pain and alcohol use are highly prevalent and associated with deleterious health outcomes among older adults, a paucity of literature has examined hazardous drinking among older adults with pain. We aimed to examine the prevalence of hazardous drinking among a nationally representative sample of older adults with persistent or recurrent pain. METHODS: We conducted cross-sectional analyses of data collected from the 2018 wave of the Health and Retirement Study. Participants included 1  549 community-dwelling adults aged ≥65 with persistent or recurrent pain (ie, clinically significant pain present at 2 consecutive survey waves). RESULTS: More than one-quarter of older adults with persistent or recurrent pain reported regular alcohol use (≥weekly), nearly half of whom reported hazardous patterns of drinking. Specifically, 32% reported excessive drinking (ie, >2 drinks per day for older men; >1 drink per day for older women), and 22% reported binge drinking (ie, ≥4 drinks on one occasion). Exploratory analyses revealed a high prevalence of hazardous drinking among the subsample of older adults who used opioids (47%). CONCLUSIONS: Hazardous alcohol use-including both excessive and binge drinking-is common among older adults with persistent or recurrent pain, including those who take opioids. Given that hazardous drinking can complicate pain management and increase the risk for adverse opioid effects (eg, overdose), the current findings underscore the importance of assessing and addressing hazardous patterns of alcohol use among older adults with persistent or recurrent pain.

Impact of standardized, language-concordant hospital discharge instructions on postdischarge medication questions.

Written instructions improve patient comprehension of discharge instructions but are often provided only in English even for patients with a non-English language preference (NELP). We implemented standardized written discharge instructions in English, Spanish, and Chinese for hospital medicine patients at an urban academic medical center. Using an interrupted time series analysis, we assessed the impact on medication-related postdischarge questions for patients with English, Spanish, or Chinese language preferences. Of 4013 patients, ∼15% had NELP. Preintervention, Chinese-preferring patients had a 5.6 percentage point higher probability of questions (adjusted odds ratio [aOR] = 1.55, 95% confidence interval [CI]: 1.08, 2.21) compared to English-preferring patients; Spanish-preferring and English-preferring patients had similar rates of questions. Postintervention, English-preferring and Spanish-preferring patients had no significant change; Chinese-preferring patients had a significant 10.9 percentage point decrease in the probability of questions (aOR = 0.38, 95% CI: 0.21, 0.69) thereby closing the disparity. Language-concordant written discharge instructions may reduce disparities in medication-related postdischarge questions for patients with NELP.

Development and applicability of a risk assessment tool for hospital-acquired mobility impairment in ambulatory older adults.

BACKGROUND: Mobility loss is common in hospitalized older adults, and resources to prevent mobility impairment are finite. Our goal was to use routinely collected data to develop a risk assessment tool that identifies individuals at risk of losing the ability to walk during hospitalization on the first hospital day. Second, we determined if the tool could inform the use of mobility-preserving interventions. METHODS: We included patients admitted to a general medical service, aged ≥65 years, who walked occasionally or frequently on admission (Braden Scale Activity subset > = 3). Patients were considered to have a new mobility impairment if, at discharge, their ability to walk was severely limited or nonexistent or they were confined to bed (Braden Scale Activity subset <3). We used predictors available on the first hospital day to develop (2017-18 cohort) and validate (2019 cohort) a risk assessment tool. We determined the association between predicted risk and therapy use in the validation cohort to highlight the model's clinical utility. RESULTS: 5542 patients were included (median age 76 years, 48% women); 7.6% were discharged unable to walk. The model included 5 predictors: age, medication administrations, Glasgow Coma Scale verbal score, serum albumin, and urinary catheter presence. In the validation cohort, the model discriminated well (c-statistic 0.75) and was strongly associated with hospital-acquired mobility impairment (lowest decile 1%, highest decile 25%). In the validation cohort, therapy consultation ordering increased linearly with predicted risk; however, observed mobility impairment increased exponentially. CONCLUSION: The tool assesses the risk of mobility impairment in all ambulatory hospitalized older adults on the first hospital day. Further, it identifies at-risk older adults who may benefit from mobility interventions.

Overestimation of anticoagulant benefit in patients with atrial fibrillation and low life expectancy: evidence from 12 randomized trials.

Background: Patients with atrial fibrillation (AF) have a high rate of all-cause mortality that is only partially attributable to vascular outcomes. While the competing risk of death may affect expected anticoagulant benefit, guidelines do not account for it. We sought to determine if using a competing risks framework materially affects the guideline-endorsed estimate of absolute risk reduction attributable to anticoagulants. Methods: We conducted a secondary analysis of 12 RCTs that randomized patients with AF to oral anticoagulants or either placebo or antiplatelets. For each participant, we estimated the absolute risk reduction (ARR) of anticoagulants to prevent stroke or systemic embolism using two methods. First, we estimated the ARR using a guideline-endorsed model (CHA 2 DS 2 -VASc) and then again using a Competing Risk Model that uses the same inputs as CHA 2 DS 2 -VASc but accounts for the competing risk of death and allows for non-linear growth in benefit over time. We compared the absolute and relative differences in estimated benefit and whether the differences in estimated benefit varied by life expectancy. Results: 7933 participants had a median life expectancy of 8 years (IQR 6, 12), determined by comorbidity-adjusted life tables. 43% were randomized to oral anticoagulation (median age 73 years, 36% women). The guideline-endorsed CHA 2 DS 2 -VASc model estimated a larger ARR than the Competing Risk Model (median ARR at 3 years, 6.9% vs. 5.2%). ARR differences varied by life expectancies: for those with life expectancies in the highest decile, 3-year ARR difference (CHA 2 DS 2 -VASc model - Competing Risk Model 3-year risk) was -1.2% (42% relative underestimation); for those with life expectancies in the lowest decile, 3-year ARR difference was 5.9% (91% relative overestimation). Conclusion: Anticoagulants were exceptionally effective at reduced stroke risk. However, anticoagulant benefits were misestimated with CHA 2 DS 2 -VASc, which does not account for the competing risk of death nor decelerating treatment benefit over time. Overestimation was most pronounced in patients with the lowest life expectancy and when benefit was estimated over a multi-year horizon.

Social Frailty Index: Development and validation of an index of social attributes predictive of mortality in older adults.

While social characteristics are well-known predictors of mortality, prediction models rely almost exclusively on demographics, medical comorbidities, and function. Lacking an efficient way to summarize the prognostic impact of social factor, many studies exclude social factors altogether. Our objective was to develop and validate a summary measure of social risk and determine its ability to risk-stratify beyond traditional risk models. We examined participants in the Health and Retirement Study, a longitudinal, survey of US older adults. We developed the model from a comprehensive inventory of 183 social characteristics using least absolute shrinkage and selection operator, a penalized regression approach. Then, we assessed the predictive capacity of the model and its ability to improve on traditional prediction models. We studied 8,250 adults aged ≥65 y. Within 4 y of the baseline interview, 22% had died. Drawn from 183 possible predictors, the Social Frailty Index included age, gender, and eight social predictors: neighborhood cleanliness, perceived control over financial situation, meeting with children less than yearly, not working for pay, active with children, volunteering, feeling isolated, and being treated with less courtesy or respect. In the validation cohort, predicted and observed mortality were strongly correlated. Additionally, the Social Frailty Index meaningfully risk-stratified participants beyond the Charlson score (medical comorbidity index) and the Lee Index (comorbidity and function model). The Social Frailty Index includes age, gender, and eight social characteristics and accurately risk-stratifies older adults. The model improves upon commonly used risk prediction tools and has application in clinical, population health, and research settings.

Development and validation of novel multimorbidity indices for older adults.

BACKGROUND: Measuring multimorbidity in claims data is used for risk adjustment and identifying populations at high risk for adverse events. Multimorbidity indices such as Charlson and Elixhauser scores have important limitations. We sought to create a better method of measuring multimorbidity using claims data by incorporating geriatric conditions, markers of disease severity, and disease-disease interactions, and by tailoring measures to different outcomes. METHODS: Health conditions were assessed using Medicare inpatient and outpatient claims from subjects age 67 and older in the Health and Retirement Study. Separate indices were developed for ADL decline, IADL decline, hospitalization, and death, each over 2 years of follow-up. We validated these indices using data from Medicare claims linked to the National Health and Aging Trends Study. RESULTS: The development cohort included 5012 subjects with median age 76 years; 58% were female. Claims-based markers of disease severity and disease-disease interactions yielded minimal gains in predictive power and were not included in the final indices. In the validation cohort, after adjusting for age and sex, c-statistics for the new multimorbidity indices were 0.72 for ADL decline, 0.69 for IADL decline, 0.72 for hospitalization, and 0.77 for death. These c-statistics were 0.02-0.03 higher than c-statistics from Charlson and Elixhauser indices for predicting ADL decline, IADL decline, and hospitalization, and <0.01 higher for death (p < 0.05 for each outcome except death), and were similar to those from the CMS-HCC model. On decision curve analysis, the new indices provided minimal benefit compared with legacy approaches. C-statistics for both new and legacy indices varied substantially across derivation and validation cohorts. CONCLUSIONS: A new series of claims-based multimorbidity measures were modestly better at predicting hospitalization and functional decline than several legacy indices, and no better at predicting death. There may be limited opportunity in claims data to measure multimorbidity better than older methods.

Can markers of disease severity improve the predictive power of claims-based multimorbidity indices?

BACKGROUND: Claims-based measures of multimorbidity, which evaluate the presence of a defined list of diseases, are limited in their ability to predict future outcomes. We evaluated whether claims-based markers of disease severity could improve assessments of multimorbid burden. METHODS: We developed 7 dichotomous markers of disease severity which could be applied to a range of diseases using claims data. These markers were based on the number of disease-associated outpatient visits, emergency department visits, and hospitalizations made by an individual over a defined interval; whether an individual with a given disease had outpatient visits to a specialist who typically treats that disease; and ICD-9 codes which connote more versus less advanced or symptomatic manifestations of a disease. Using Medicare claims linked with Health and Retirement Study data, we tested whether including these markers improved ability to predict ADL decline, IADL decline, hospitalization, and death compared to equivalent models which only included the presence or absence of diseases. RESULTS: Of 5012 subjects, median age was 76 years and 58% were female. For a majority of diseases tested individually, adding each of the 7 severity markers yielded minimal increase in c-statistic (≤0.002) for outcomes of ADL decline and mortality compared to models considering only the presence versus absence of disease. Gains in predictive power were more substantial for a small number of individual diseases. Inclusion of the most promising marker in multi-disease multimorbidity indices yielded minimal gains in c-statistics (<0.001-0.007) for predicting ADL decline, IADL decline, hospitalization, and death compared to indices without these markers. CONCLUSIONS: Claims-based markers of disease severity did not contribute meaningfully to the ability of multimorbidity indices to predict ADL decline, mortality, and other important outcomes.

Long-term functional outcomes and mortality after hospitalization for extracranial hemorrhage.

BACKGROUND: The effects of extracranial hemorrhage (ECH), or bleeding outside the brain, are often considered transient. Yet, there are few data on the long-term and functional consequences of ECH. OBJECTIVE: Define the association of ECH hospitalization with functional independence and survival in a nationally representative cohort of older adults. DESIGN: Longitudinal cohort study. SETTINGS AND PARTICIPANTS: Data from the Health and Retirement Study from 1995 to 2016, a nationally representative, biennial survey of older adults. Adults aged 66 and above with Medicare linkage and at least 12 months of continuous Medicare Part A and B enrollment. INTERVENTION: Hospitalization for ECH. MAIN OUTCOMES AND MEASURES: Adjusted odds ratios and predicted likelihood of independence in all activities of daily living (ADLs), independence in all instrumental activities of daily living (IADLs) and extended nursing home stay. Adjusted hazard ratio and predicted likelihood for survival. RESULTS: In a cohort of 6719 subjects (mean age 77, 59% women) with average follow-up time of 8.3 years (55,767 person-years), 736 (11%) were hospitalized for ECH. ECH was associated with a 15% increase in ADL disability, 15% increase in IADL disability, 8% increase in nursing home stays, and 4% increase in mortality. After ECH, subjects became disabled and died at the same annual rate as pre-ECH but never recovered to pre-ECH levels of function. In conclusion, hospitalization for ECH was associated with significant and durable declines in independence and survival. Clinical and research efforts should incorporate the long-term harms of ECH into decision-making and strategies to mitigate these effects.

Association of Social Support With Functional Outcomes in Older Adults Who Live Alone.

Importance: Older adults who live alone are at risk for poor health outcomes. Whether social support mitigates the risk of living alone, particularly when facing a sudden change in health, has not been adequately reported. Objective: To assess if identifiable support buffers the vulnerability of a health shock while living alone. Design, Setting, and Participants: In this longitudinal, prospective, nationally representative cohort study from the Health and Retirement Study (enrollment March 2006 to April 2015), 4772 community-dwelling older adults 65 years or older who lived alone in the community and could complete activities of daily living (ADLs) and instrumental ADLs independently were followed up biennially through April 2018. Statistical analysis was completed from May 2020 to March 2021. Exposures: Identifiable support (ie, can the participant identify a relative/friend who could help with personal care if needed), health shock (ie, hospitalization, new diagnosis of cancer, stroke, heart attack), and interaction (multiplicative and additive) between the 2 exposures. Main Outcomes and Measures: The primary outcomes were incident ADL dependency, prolonged nursing home stay (≥30 days), and death. Results: Of 4772 older adults (median [IQR] age, 73 [68-81] years; 3398 [71%] women) who lived alone, at baseline, 1813 (38%) could not identify support, and 3013 (63%) experienced a health shock during the study. Support was associated with a lower risk of a prolonged nursing home stay at 2 years (predicted probability, 6.7% vs 5.2%; P = .002). Absent a health shock, support was not associated with a prolonged nursing home stay (predicted probability over 2 years, 1.9% vs 1.4%; P = .21). However, in the presence of a health shock, support was associated with a lower risk of a prolonged nursing home stay (predicted probability over 2 years, 14.2% vs 10.9%; P = .002). Support was not associated with incident ADL dependence or death. Conclusions and Relevance: In this longitudinal cohort study among older adults who live alone, identifiable support was associated with a lower risk of a prolonged nursing home stay in the setting of a health shock.

Do Anticoagulants Preserve Function and Quality of Life in Older Adults with Atrial Fibrillation?

Anticoagulants in Older Adults with Atrial FibrillationAn 82-year-old woman with hypertension and diabetes is seen in the clinic for newly diagnosed atrial fibrillation. She uses a walker and fell twice last year. She completes activities of daily living independently. Should she be prescribed an anticoagulant?

Disparities After Discharge: The Association of Limited English Proficiency and Postdischarge Patient-Reported Issues.

BACKGROUND: The transition from hospital to home is a vulnerable period for all patients, particularly for those who have limited English proficiency (LEP). METHODS: The research team retrospectively studied adults discharged home from a hospital in 2018-2019 to determine the association of LEP with (1) reach of a care transitions outreach program phone call (automated call within three days after discharge or a subsequent manual phone call) and (2) postdischarge issues reported on the phone calls. All results were adjusted for measured confounders; associations using predicted probabilities and average marginal effects were described. RESULTS: A total of 13,860 patients were included, and 11.3% had LEP. After adjustment, the program reached most patients regardless of LEP status; automated calls were more likely to reach English proficient patients (81.1% vs. 75.6%, p < 0.01), and when the automated call was unsuccessful, manual calls were more likely to reach LEP patients (47.8% vs. 28.3%, p < 0.001). After adjustment, patients with LEP reported more difficulty with all measured issues: understanding discharge instructions (11.3% vs. 6.5%), obtaining prescriptions (8.3% vs. 5.5%), medication concerns (12.9% vs. 10.6%), follow-up questions (16.1% vs. 13.3%), new or worsening symptoms (15.1% vs. 11.9%), and any other clinical issues (16.6% vs. 13.0%); p < 0.05 for all comparisons. CONCLUSION: Although reach was high for the care transitions program, among patients with LEP, important disparities exist in patient-reported postdischarge issues. These results indicate the need for better discharge processes that focus on communication quality and health equity.

Long-term individual and population functional outcomes in older adults with atrial fibrillation.

BACKGROUND: Older adults with atrial fibrillation (AF) have multiple risk factors for disablement. Long-term function and the contribution of strokes to disability have not been previously characterized. Our objective was to determine long-term function among older adults with AF and the relative contribution of stroke. METHODS: We used data from the nationally representative Health and Retirement Study (1992-2014) with participants ≥65 years with incident AF. We examined the association of incident stroke with three outcomes: independence with activities of daily living (ADL), instrumental activities of daily living (IADL), and residence outside a nursing home (community-dwelling). We fit logistic regression models with repeated measures adjusting for comorbidities and demographics to estimate the effect of stroke on function. We estimated the contribution of strokes to the overall population burden of disability using the method of recycled predictions. RESULTS: Among 3530 participants (median age 79 years, 53% women), 262 had a stroke over 17,396 person-years. Independent of stroke and accounting for comorbidities, annually, ADL independence decreased by 4.4%, IADL independence decreased by 3.9%, and community dwelling decreased by 1.2% (p < 0.05 for all). Accounting for comorbidities, of those who experienced a stroke, 31.9% developed new ADL dependence, 26.5% developed new IADL dependence, and 8.6% newly moved to a nursing home (p < 0.05 for all). Considering all causes of function loss, 1.7% of ADL disability-years, 1.2% of IADL disability-years, and 7.3% of nursing home years could be attributed to stroke over 7.4 years. CONCLUSION: Older adults lose substantial function over time following AF diagnosis, independent of stroke. Stroke was associated with a significant functional decline and increase in the likelihood of nursing home move, but stroke did not accelerate subsequent disability accrual. Because of the high background rate of disability, stroke was not the dominant determinant of population-level disability in older adults with AF.

Geriatric Syndromes and Atrial Fibrillation: Prevalence and Association with Anticoagulant Use in a National Cohort of Older Americans.

BACKGROUND: Although guidelines recommend focusing primarily on stroke risk to recommend anticoagulants in atrial fibrillation (AF), physicians report that geriatric syndromes (e.g., falls and disability) are important when considering anticoagulants. Little is known about the prevalence of geriatric syndromes in older adults with AF or the association with anticoagulant use. METHODS: We performed a cross-sectional analysis of the 2014 Health and Retirement Study, a nationally representative study of older Americans. Participants were asked questions to assess domains of aging, including function, cognition, and medical conditions. We included participants 65 years and older with 2 years of continuous Medicare enrollment who met AF diagnosis criteria by claims codes. We examined five geriatric syndromes: one or more falls within the last 2 years, receiving help with activities of daily living (ADLs) or instrumental ADLs (IADL), experienced incontinence, and cognitive impairment. We determined the prevalence of geriatric syndromes and their association with anticoagulant use, adjusting for ischemic stroke risk (i.e., CHA2 DS2 -VASc score [congestive heart failure, hypertension, age, diabetes mellitus, stroke, vascular disease, and sex]). RESULTS: In this study of 779 participants with AF (median age = 80 years; median CHA2 DS2 -VASc score = 4), 82% had one or more geriatric syndromes. Geriatric syndromes were common: 49% reported falls, 38% had ADL impairments, 42% had IADL impairments, 37% had cognitive impairments, and 43% reported incontinence. Overall, 65% reported anticoagulant use; guidelines recommend anticoagulant use for 97% of participants. Anticoagulant use rate decreased for each additional geriatric syndrome (average marginal effect = -3.7%; 95% confidence interval = -1.4% to -5.9%). Lower rates of anticoagulant use were reported in participants with ADL dependency, IADL dependency, and dementia. CONCLUSION: Most older adults with AF had at least one geriatric syndrome, and geriatric syndromes were associated with reduced anticoagulant use. The high prevalence of geriatric syndromes may explain the lower than expected anticoagulant use in older adults.

Evaluation of a novel metric for personalized opioid prescribing after hospitalization.

BACKGROUND: The duration of an opioid prescribed at hospital discharge does not intrinsically account for opioid needs during a hospitalization. This discrepancy may lead to patients receiving much larger supplies of opioids on discharge than they truly require. OBJECTIVE: Assess a novel discharge opioid supply metric that adjusts for opioid use during hospitalization, compared to the conventional discharge prescription signature. DESIGN, SETTING, & PARTICIPANTS: Retrospective study using electronic health record data from June 2012 to November 2018 of adults who received opioids while hospitalized and after discharge from a single academic medical center. MEASURES & ANALYSIS: We ascertained inpatient opioids received and milligrams of opioids supplied after discharge, then determined days of opioids supplied after discharge by the conventional prescription signature opioid-days ("conventional days") and novel hospital-adjusted opioid-days ("adjusted days") metrics. We calculated descriptive statistics, within-subject difference between measurements, and fold difference between measures. We used multiple linear regression to determine patient-level predictors associated with high difference in days prescribed between measures. RESULTS: The adjusted days metric demonstrates a 2.4 day median increase in prescription duration as compared to the conventional days metric (9.4 vs. 7.0 days; P<0.001). 95% of all adjusted days measurements fall within a 0.19 to 6.90-fold difference as compared to conventional days measurements, with a maximum absolute difference of 640 days. Receiving a liquid opioid prescription accounted for an increased prescription duration of 135.6% by the adjusted days metric (95% CI 39.1-299.0%; P = 0.001). Of patients who were not on opioids prior to admission and required opioids during hospitalization but not in the last 24 hours, 325 (8.6%) were discharged with an opioid prescription. CONCLUSIONS: The adjusted days metric, based on inpatient opioid use, demonstrates that patients are often prescribed a supply lasting longer than the prescription signature suggests, though with marked variability for some patients that suggests potential under-prescribing as well. Adjusted days is more patient-centered, reflecting the reality of how patients will take their prescription rather than providers' intended prescription duration.

Upper airway gene expression reveals suppressed immune responses to SARS-CoV-2 compared with other respiratory viruses.

SARS-CoV-2 infection is characterized by peak viral load in the upper airway prior to or at the time of symptom onset, an unusual feature that has enabled widespread transmission of the virus and precipitated a global pandemic. How SARS-CoV-2 is able to achieve high titer in the absence of symptoms remains unclear. Here, we examine the upper airway host transcriptional response in patients with COVID-19 (n = 93), other viral (n = 41) or non-viral (n = 100) acute respiratory illnesses (ARIs). Compared with other viral ARIs, COVID-19 is characterized by a pronounced interferon response but attenuated activation of other innate immune pathways, including toll-like receptor, interleukin and chemokine signaling. The IL-1 and NLRP3 inflammasome pathways are markedly less responsive to SARS-CoV-2, commensurate with a signature of diminished neutrophil and macrophage recruitment. This pattern resembles previously described distinctions between symptomatic and asymptomatic viral infections and may partly explain the propensity for pre-symptomatic transmission in COVID-19. We further use machine learning to build 27-, 10- and 3-gene classifiers that differentiate COVID-19 from other ARIs with AUROCs of 0.981, 0.954 and 0.885, respectively. Classifier performance is stable across a wide range of viral load, suggesting utility in mitigating false positive or false negative results of direct SARS-CoV-2 tests.