Prescription of potentially inappropriate medications after an intensive care unit stay for acute respiratory failure.

BACKGROUND: Among survivors of critical illness, prescription of potentially inappropriate medications (PIM) at hospital discharge is thought to be an important, modifiable patient safety concern. To date, there are little empirical data evaluating this issue. RESEARCH QUESTION: The objective of this study was to determine the frequency of PIM prescribed to survivors of acute respiratory failure (ARF) at hospital discharge and explore their association with readmissions or death within 90 days of hospital discharge. STUDY DESIGN AND METHODS: Prospective multicenter cohort study of ARF survivors admitted to ICUs and discharged home. Prospective of new PIMs with a high-adverse-effect profile ("high impact") at discharge was the primary exposure. Potential inappropriateness was determined by a structured consensus process using Screening Tool of Older Persons' Prescriptions-Screening Tool to Alert to Right Treatment, Beers' criteria, and clinical context of prescriptions by a multidisciplinary team. Covariate balancing propensity score was used for the primary analysis. RESULTS: Of the 195 Addressing Post Intensive Care Syndrome-01 (APICS-01) patients, 169 (87%) had ≥1 new medications prescribed at discharge, with 154 (91.1%) prescribed with one or more high-impact (HI) medications. Patients were prescribed a median of 5 [3-7] medications, of which 3 [1-4] were HI. Twenty percent of HI medications were potentially inappropriate. Medications with significant central nervous system side-effects were most prescribed potentially inappropriately. Forty-six (30%) patients experienced readmission or death within 90 days of hospital discharge. After adjusting for prespecified covariates, the association between prescription of potentially inappropriate HI medications and the composite primary outcome did not meet the prespecified threshold for statistical significance (risk ratio: 0.54; 0.26-1.13; p = 0.095) or with the constituent endpoints: readmission (risk ratio: 0.57, 0.27-1.11) or death (0.7, 0.05-9.32). CONCLUSION: At hospital discharge, most ARF survivors are prescribed medications with a high-adverse-effect profile and approximately one-fifth are potentially inappropriate. Although prescription of such medications was not associated with 90-day readmissions and mortality, these results highlight an area for additional investigation.

Identifying predictors and determining mortality rates of septic cardiomyopathy and sepsis-related cardiogenic shock: A retrospective, observational study.

INTRODUCTION: Septic shock is a severe form of sepsis that has a high mortality rate, and a substantial proportion of these patients will develop cardiac dysfunction, often termed septic cardiomyopathy (SCM). Some SCM patients may develop frank cardiac failure, termed sepsis-related cardiogenic shock (SeRCS). Little is known of SeRCS. This study describes baseline characteristics of patients with SCM and SeRCS compared to patients with septic shock without cardiac dysfunction. We compare clinical outcomes among SCM, SeRCS, and septic shock, and identify risk factors for the development of SCM and SeRCS. METHODS: Septic patients admitted to the ICU with an echocardiogram obtained within 72 hours were included. Left ventricular ejection fraction of ≤55% was used to define SCM, and cardiac index ≤2.1 L/min/m2 among patients with SCM defined SeRCS. Machine learning was used to identify risk factors for development of SCM and SeRCS. Logistic regression was used to compare mortality among groups. RESULTS: Among 1229 patients, 977 patients had septic shock without cardiac dysfunction, 207 had SCM, and 45 had SeRCS. In patients with septic shock, the strongest predictor for developing SCM and SeRCs was a prior history of cardiac dysfunction. Mortality did not significantly differ among the three groups. CONCLUSIONS: SCM and SeRCS affect a minority of patients with septic shock, disproportionately affecting individuals with a history of cardiac disease. We did not identify a mortality difference associated with SCM or SeRCS. Additional work is needed to define further subtypes and treatment options for this patient population.

Patient experiences with SARS-CoV-2: Associations between patient experience of disease and coping profiles.

INTRODUCTION: Severe acute respiratory syndrome coronavirus 2, (SARS-CoV-2,) caused an influx of patients with acute disease characterized by a variety of symptoms termed COVID-19 disease, with some patients going on to develop post-acute COVID-19 syndrome. Individual factors like sex or coping styles are associated with a person's disease experience and quality of life. Individual differences in coping styles used to manage COVID-19 related stress correlate with physical and mental health outcomes. Our study sought to understand the relationship between COVID-19 symptoms, severity of acute disease, and coping profiles. METHODS: An online survey to assess symptoms, functional status, and recovery in a large group of patients was nationally distributed online. The survey asked about symptoms, course of illness, and included the Brief-COPE and the adapted Social Relationship Inventory. We used descriptive and cluster analyses to characterize patterns of survey responses. RESULTS: 976 patients were included in the analysis. The most common symptoms reported by the patients were fatigue (72%), cough (71%), body aches/joint pain (66%), headache (62%), and fever/chills (62%). 284 participants reported PACS. We described three different coping profiles: outward, inward, and dynamic copers. DISCUSSION: Fatigue, cough, and body aches/joint pains were the most frequently reported symptoms. PACS patients were sicker, more likely to have been hospitalized. Of the three coping profiles, outward copers were more likely to be admitted to the hospital and had the healthiest coping strategies. Dynamic copers activated several coping strategies both positive and negative; they were also younger and more likely to report PACS. CONCLUSION: Cough, fatigue, and body aches/joint pain are common and most important to patients with acute COVID-19, while shortness of breath defined the experience for patients with PACS. Of the three coping profiles, dynamic copers were more likely to report PACS. Additional investigations into coping profiles in general, and the experience of COVID-19 and PACS is needed.

Implementation of Lung-Protective Ventilation in Patients With Acute Respiratory Failure.

OBJECTIVES: We implemented a computerized protocol for low tidal volume ventilation (LTVV) to improve management and outcomes of mechanically ventilated patients with, and without, the acute respiratory distress syndrome (ARDS). DESIGN: Pragmatic, nonrandomized stepped wedge type II hybrid implementation/effectiveness trial. SETTING: Twelve hospitals in an integrated healthcare system over a 2-year period. PATIENTS: Patients greater than or equal to 18 years old who had initiation of mechanical ventilation in the emergency department or ICU. We excluded patients who died or transitioned to comfort care on the day of admission to the ICU. We defined a subgroup of patients with ARDS for analysis. INTERVENTIONS: Implementation of ventilator protocols for LTVV in the ICU. MEASUREMENTS AND MAIN RESULTS: Our primary clinical outcome was ventilator-free days (VFDs) to day 28. Our primary process outcome was median initial set tidal volume. We included 8,692 mechanically ventilated patients, 3,282 (38%) of whom had ARDS. After implementation, set tidal volume reported as mL/kg predicted body weight decreased from median 6.1 mL/kg (interquartile range [IQR], 6.0-6.8 mL/kg) to 6.0 mL/kg (IQR, 6.0-6.6 mL/kg) ( p = 0.009). The percent of patients receiving LTVV (tidal volume ≤ 6.5 mL/kg) increased from 69.8% ( n = 1,721) to 72.5% ( n = 1,846) ( p = 0.036) after implementation. The percent of patients receiving greater than 8 mL/kg initial set tidal volume was reduced from 9.0% ( n = 222) to 6.7% ( n = 174) ( p = 0.005) after implementation. Among patients with ARDS, day 1 positive end-expiratory pressure increased from 6.7 to 8.0 cm H 2 O ( p < 0.001). We observed no difference in VFD (adjusted odds ratio, 1.06; 95% CI, 0.91-1.24; p = 0.44), or in secondary outcomes of length of stay or mortality, either within the main cohort or the subgroup of patients with ARDS. CONCLUSIONS: We observed improved adherence to optimal ventilator management with implementation of a computerized protocol and reduction in the number of patients receiving tidal volumes greater than 8 mL/kg. We did not observe improvement in clinical outcomes.

Association Between Unmet Nonmedication Needs After Hospital Discharge and Readmission or Death Among Acute Respiratory Failure Survivors: A Multicenter Prospective Cohort Study.

OBJECTIVES: To characterize early unmet nonmedication discharge needs (UDNs), classified as durable medical equipment (DME), home health services (HHS), and follow-up medical appointments (FUAs) and explore their association with 90-day readmission and mortality among survivors of acute respiratory failure (ARF) who were discharged home. DESIGN: Prospective multicenter cohort study. SETTING: Six academic medical centers across United States. PARTICIPANTS: Adult survivors of ARF who required an ICU stay and were discharged home from hospital. INTERVENTIONS: None. Exposure of interest was the proportion of UDN for the following categories: DME, HHS, and FUA ascertained within 7-28 days after hospital discharge. MEASUREMENTS AND MAIN RESULTS: Two hundred eligible patients were recruited between January 2019 and August 2020. One-hundred ninety-five patients were included in the analytic cohort: 118 were prescribed DME, 134 were prescribed HHS, and 189 needed at least one FUA according to discharge plans. 98.4% (192/195) had at least one identified nonmedication need at hospital discharge. Median (interquartile range) proportion of unmet needs across three categories were 0 (0-15%) for DME, 0 (0-50%) for HHS, and 0 (0-25%) for FUA, and overall was 0 (0-20%). Fifty-six patients (29%) had 90-day death or readmission. After adjusting for prespecified covariates, having greater than the median level of unmet needs was not associated with an increased risk of readmission or death within 90 days of discharge (risk ratio, 0.89; 0.51-1.57; p = 0.690). Age, hospital length of stay, Acute Physiology and Chronic Health Evaluation II severity of illness score, and Multidimensional Scale Perceived Social Support score were associated with UDN. CONCLUSIONS: UDN were common among survivors of ARF but not significantly associated a composite outcome of 90-day readmission or death. Our results highlight the substantial magnitude of UDN and identifies areas especially vulnerable to lapses in healthcare coordination.

Primary Care Clinicians' Prescribing Patterns of Reduced-Dose Direct Oral Anticoagulants for Extended-Phase Venous Thromboembolism Treatment.

The direct anticoagulants (DOACs), apixaban and rivaroxaban, are used for extended-phase treatment of venous thromboembolism (VTE) and have labeling for dose reduction for this indication. The objective of this study was to better understand primary care clinician prescribing patterns of apixaban and rivaroxaban for extended-phase anticoagulation. We conducted a 21-question survey targeting members of the American College of Physicians and United States Veterans Administration anticoagulation management services. Survey questions covered prescribing behaviors for dose reduction of apixaban and rivaroxaban for extended VTE treatment, as well as questions related to the respondent's practice setting. We used logistic regression to assess associations between demographics and prescribing behaviors. We used k-means clustering to identify distinct groups of prescribing patterns. Among 227 respondents, most were attending physicians (60%) and one-third (34%) practiced in internal medicine or primary care. Most (59%) indicated they dose-reduced DOACs. Hospitalists (no outpatient care) were least likely to dose-reduce (OR 0.09 [95% CI 0.03-0.22]), as well as early-career clinicians (0.53 [0.30-0.91]). Pharmacists and clinicians who treat over 500 VTE patients annually were most likely to dose reduce (6.4 [2.9-16.3]), (2.9 [1.5-6.0]), respectively. We identified five clusters of dosing behaviors and characterized clinician makeup. Clusters were primarily differentiated by frequency of dose reduction, DOAC preference, and temporary re-escalation of doses. We identified clinician characteristics that are associated with dose-reduction prescribing behaviors; these analyses provide insight into where targeted interventions, such as protocolization and education, would be most beneficial.

Physician perceptions and use of reduced-dose direct oral anticoagulants for extended phase venous thromboembolism treatment.

Background: The direct oral anticoagulants (DOACs), apixaban and rivaroxaban, have been studied for extended-phase treatment of venous thromboembolism (VTE). Yet, scant evidence exists surrounding clinician practice and decision-making regarding dose reduction. Aims: Report clinician practice and characteristics surrounding dose reduction of DOACs for extended-phase VTE treatment. Methods: We conducted a 16-question REDCap survey between July 14, 2021, and September 13, 2021, among ISTH 2021 Congress attendees and on Twitter. We explored factors associated with dose reduction using logistic regression. We used k-means clustering to identify distinct groups of dose-reduction decision-making. Random forest analysis explored demographics with respect to identified groups. Results: Among 171 respondents, most were attending academic physicians from North America. Clinicians who treated larger volumes of patients had higher odds of dose reduction. We identified five clusters that showed distinct patterns of behavior regarding dose reduction. Cluster 1 rarely dose reduces and likely prescribes rivaroxaban over apixaban; cluster 2 dose reduces frequently, does not consider age when dose-reducing, is least likely to temporarily reescalate dosing, and prescribes apixaban and rivaroxaban equally; cluster 3 dose reduces <50% of the time, and temporarily reescalates dosing during increased VTE risk; cluster 4 dose reduces frequently, temporarily reescalates dosing, and is most likely to prescribe apixaban over rivaroxaban; and cluster 5 dose reduces most frequently, and takes the fewest risk factors into consideration when deciding to dose reduce. Conclusions: Most clinicians elect to dose-reduce DOACs for extended-phase anticoagulation. The likelihood of a clinician to dose reduce increases with volume of patients treated. Clinician prescribing patterns cluster around VTE risk factors as well as reescalation during high-risk periods.

Order Substitutions and Education for Balanced Crystalloid Solution Use in an Integrated Health Care System and Association With Major Adverse Kidney Events.

Importance: Trials comparing balanced crystalloids with normal saline have yielded mixed results regarding reductions in kidney complications and mortality for hospitalized patients receiving intravenous fluids. Objective: To evaluate the association of a multifaceted implementation program encouraging the preferential use of lactated Ringer solution with patient outcomes and intravenous fluid-prescribing practices in a large, multilevel health care system. Design, Setting, and Participants: This type 2 hybrid implementation and comparative effectiveness study enrolled all patients 18 years or older who received 1 L or more of intravenous fluids while admitted to an emergency department and/or inpatient unit at 1 of 22 hospitals in Idaho and Utah between November 1, 2018, and February 29, 2020. An interrupted time series analysis was used to assess study outcomes before and after interventions to encourage use of lactated Ringer solution. Exposures: Implementation program combining order set modification, electronic order entry alerts, and sequential clinician-targeted education to encourage prescribing of lactated Ringer solution instead of normal saline. Main Outcomes and Measures: The primary implementation outcome was the patient-level proportion of intravenous fluids that was balanced crystalloids. The primary effectiveness outcome was the incidence of major adverse kidney events (MAKE30)-a composite of new persistent kidney dysfunction, new initiation of dialysis, and death-at 30 days. Results: Among 148 423 patients (median [IQR] age, 47 [30-67] years; 91 302 women [61%]), the proportion of total fluids received that was lactated Ringer solution increased from 28% to 75% in the first week vs the last week of the study (immediate implementation effect odds ratio [OR], 3.44; 95% CI, 2.79-4.24). The estimated MAKE30 absolute risk reduction was 2.2% (95% CI, 1.3%-3.3%) based on interrupted time series analysis showing a decrease in the week-on-week trend for MAKE30 (OR difference, 0.03; 95% CI, 0.03-0.03, P < .001). The immediate postimplementation OR for MAKE30 was 0.88 (95% CI, 0.76-1.01), with a decrease in persistent kidney dysfunction (OR, 0.80; 95% CI, 0.69-0.93) and mortality (OR, 0.78; 95% CI, 0.65-0.93) but not dialysis (OR, 1.00; 95% CI, 0.76-1.32). Conclusions and Relevance: In this comparative effectiveness study, an implementation program was associated with an increase in the proportion of fluids administered as lactated Ringer solution compared with normal saline and was associated with a reduction in MAKE30 events among patients treated in a large integrated health care system.

Association between unmet medication needs after hospital discharge and readmission or death among acute respiratory failure survivors: the addressing post-intensive care syndrome (APICS-01) multicenter prospective cohort study.

INTRODUCTION: Survivors of acute respiratory failure (ARF) commonly experience long-lasting physical, cognitive, and/or mental health impairments. Unmet medication needs occurring immediately after hospital discharge may have an important effect on subsequent recovery. METHODS AND ANALYSIS: In this multicenter prospective cohort study, we enrolled ARF survivors who were discharged directly home from their acute care hospitalization. The primary exposure was unmet medication needs. The primary outcome was hospital readmission or death within 3 months after discharge. We performed a propensity score analysis, using inverse probability weighting for the primary exposure, to evaluate the exposure-outcome association, with an a priori sample size of 200 ARF survivors. RESULTS: We enrolled 200 ARF survivors, of whom 107 (53%) were female and 77 (39%) were people of color. Median (IQR) age was 55 (43-66) years, APACHE II score 20 (15-26) points, and hospital length of stay 14 (9-21) days. Of the 200 participants, 195 (98%) were in the analytic cohort. One hundred fourteen (57%) patients had at least one unmet medication need; the proportion of medication needs that were unmet was 6% (0-15%). Fifty-six (29%) patients were readmitted or died by 3 months; 10 (5%) died within 3 months. Unmet needs were not associated (risk ratio 1.25; 95% CI 0.75-2.1) with hospital readmission or death, although a higher proportion of unmet needs may have been associated with increased hospital readmission (risk ratio 1.7; 95% CI 0.96-3.1) and decreased mortality (risk ratio 0.13; 95% CI 0.02-0.99). DISCUSSION: Unmet medication needs are common among survivors of acute respiratory failure shortly after discharge home. The association of unmet medication needs with 3-month readmission and mortality is complex and requires additional investigation to inform clinical trials of interventions to reduce unmet medication needs. Study registration number: NCT03738774 . The study was prospectively registered before enrollment of the first patient.

Evaluating the Balance Between Privacy and Access in Digital Information Sharing.

OBJECTIVES: Access to personal health records in an ICU by persons involved in the patient's care (referred to broadly as "family members" below) has the potential to increase engagement and reduce the negative psychologic sequelae of such hospitalizations. Currently, little is known about patient preferences for information sharing with a designated family member in the ICU. We sought to understand the information-sharing preferences of former ICU patients and their family members and to identify predictors of information-sharing preferences. DESIGN: We performed an internet survey that was developed by a broad, multidisciplinary team of stakeholders. Formal pilot testing of the survey was conducted prior to internet survey administration to study subjects. SETTING: Internet survey. SUBJECTS: Subjects included English-speaking adults who had an ICU experience or a family member with ICU experience between 2013 and 2016. We used panel sampling to ensure an ethnically representative sample of the U.S. population. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One thousand five hundred twenty surveys were submitted, and 1,470 were included in analysis. The majority of respondents (93.6%) stated that they would want to share present and past medical history, either all or that related to their ICU stay, with a designated family member of their choosing. The majority (79%) would also want their designated family member to be able to access that information from a home computer. Although most respondents preferred to share all types of information, they indicated varying levels of willingness to share specific types of more sensitive information. Information-sharing preferences did not differ by age, sex, ethnicity, or type of prior experience in the ICU (i.e., patient or family member). CONCLUSIONS: In the context of an ICU admission, sharing personal health information with a person of the patient's choosing appears desirable for most patients and family members. Policies and implementation of regulations should take this into consideration.

Apixaban compared with warfarin to prevent thrombosis in thrombotic antiphospholipid syndrome: a randomized trial.

Thrombotic antiphospholipid syndrome (TAPS) is characterized by venous, arterial, or microvascular thrombosis. Patients with TAPS merit indefinite anticoagulation, and warfarin has historically been the standard treatment. Apixaban is an oral factor Xa inhibitor anticoagulant that requires no dose adjustment or monitoring. The efficacy and safety of apixaban compared with warfarin for TAPS patients remain unknown. This multicenter prospective randomized open-label blinded endpoint study assigned anticoagulated TAPS patients to apixaban or warfarin (target international normalized ratio 2-3) for 12 months. The primary efficacy outcome was clinically overt thrombosis and vascular death. Apixaban was first given at 2.5 mg twice daily. Two protocol changes were instituted based on recommendations from the data safety monitoring board. After the twenty-fifth patient was randomized, the apixaban dose was increased to 5 mg twice daily, and after the thirtieth patient was randomized, subjects with prior arterial thrombosis were excluded. Primary outcomes were adjudicated by independent experts blinded to treatment allocation. Patients randomized between 23 February 2015 and 7 March 2019 to apixaban (n = 23) or warfarin (n = 25) were similar. Among the components of the primary efficacy outcome, only stroke occurred in 6 of 23 patients randomized to apixaban compared with 0 of 25 patients randomized to warfarin. The study ended prematurely after the forty-eighth patient was enrolled. Conclusions from our study are limited due to protocol modifications and low patient accrual. Despite these limitations, our results suggest that apixaban may not be routinely substituted for warfarin to prevent recurrent thrombosis (especially strokes) among patients with TAPS. This trial was registered at www.clinicaltrials.gov as #NCT02295475.

Learning from past respiratory failure patients to triage COVID-19 patient ventilator needs: A multi-institutional study.

BACKGROUND: Unlike well-established diseases that base clinical care on randomized trials, past experiences, and training, prognosis in COVID19 relies on a weaker foundation. Knowledge from other respiratory failure diseases may inform clinical decisions in this novel disease. The objective was to predict 48-hour invasive mechanical ventilation (IMV) within 48 h in patients hospitalized with COVID-19 using COVID-like diseases (CLD). METHODS: This retrospective multicenter study trained machine learning (ML) models on patients hospitalized with CLD to predict IMV within 48 h in COVID-19 patients. CLD patients were identified using diagnosis codes for bacterial pneumonia, viral pneumonia, influenza, unspecified pneumonia and acute respiratory distress syndrome (ARDS), 2008-2019. A total of 16 cohorts were constructed, including any combinations of the four diseases plus an exploratory ARDS cohort, to determine the most appropriate cohort to use. Candidate predictors included demographic and clinical parameters that were previously associated with poor COVID-19 outcomes. Model development included the implementation of logistic regression and three ensemble tree-based algorithms: decision tree, AdaBoost, and XGBoost. Models were validated in hospitalized COVID-19 patients at two healthcare systems, March 2020-July 2020. ML models were trained on CLD patients at Stanford Hospital Alliance (SHA). Models were validated on hospitalized COVID-19 patients at both SHA and Intermountain Healthcare. RESULTS: CLD training data were obtained from SHA (n = 14,030), and validation data included 444 adult COVID-19 hospitalized patients from SHA (n = 185) and Intermountain (n = 259). XGBoost was the top-performing ML model, and among the 16 CLD training cohorts, the best model achieved an area under curve (AUC) of 0.883 in the validation set. In COVID-19 patients, the prediction models exhibited moderate discrimination performance, with the best models achieving an AUC of 0.77 at SHA and 0.65 at Intermountain. The model trained on all pneumonia and influenza cohorts had the best overall performance (SHA: positive predictive value (PPV) 0.29, negative predictive value (NPV) 0.97, positive likelihood ratio (PLR) 10.7; Intermountain: PPV, 0.23, NPV 0.97, PLR 10.3). We identified important factors associated with IMV that are not traditionally considered for respiratory diseases. CONCLUSIONS: The performance of prediction models derived from CLD for 48-hour IMV in patients hospitalized with COVID-19 demonstrate high specificity and can be used as a triage tool at point of care. Novel predictors of IMV identified in COVID-19 are often overlooked in clinical practice. Lessons learned from our approach may assist other research institutes seeking to build artificial intelligence technologies for novel or rare diseases with limited data for training and validation.

Hydroxychloroquine vs. Azithromycin for Hospitalized Patients with COVID-19 (HAHPS): Results of a Randomized, Active Comparator Trial.

RATIONALE: The COVID-19 pandemic struck an immunologically naïve, globally interconnected population. In the face of a new infectious agent causing acute respiratory failure for which there were no known effective therapies, rapid, often pragmatic trials were necessary to evaluate potential treatments, frequently starting with medications that are already marketed for other indications. Early in the pandemic, hydroxychloroquine and azithromycin were two such candidates. OBJECTIVE: Assess the relative efficacy of hydroxychloroquine and azithromycin among hospitalized patients with COVID-19. METHODS: We performed a randomized clinical trial of hydroxychloroquine vs. azithromycin among hospitalized patients with COVID-19. Treatment was 5 days of study medication. The primary endpoint was the COVID Ordinal Outcomes scale at day 14. Secondary endpoints included hospital-, ICU-, and ventilator-free days at day 28. The trial was stopped early after enrollment of 85 patients when a separate clinical trial concluded that a clinically important effect of hydroxychloroquine over placebo was definitively excluded. Comparisons were made a priori using a proportional odds model from a Bayesian perspective. RESULTS: We enrolled 85 patients at 13 hospitals over 11 weeks. Adherence to study medication was high. The estimated odds ratio for less favorable status on the ordinal scale for hydroxychloroquine vs. azithromycin from the primary analysis was 1.07, with a 95% credible interval from 0.63 to 1.83 with a posterior probability of 60% that hydroxychloroquine was worse than azithryomycin. Secondary outcomes displayed a similar, slight preference for azithromycin over hydroxychloroquine. QTc prolongation was rare and did not differ between groups. The twenty safety outcomes were similar between arms with the possible exception of post-randomization onset acute kidney injury, which was more common with hydroxychloroquine (15% vs. 0%). Patients in the hydroxychloroquine arm received remdesivir more often than in the azithromycin arm (19% vs. 2%). There was no apparent association between remdesivir use and acute kidney injury. CONCLUSIONS: While early termination limits the precision of our results, we found no suggestion of substantial efficacy for hydroxychloroquine over azithromycin. Acute kidney injury may be more common with hydroxychloroquine than azithromycin, although this may be due to the play of chance. Differential use of remdesivir may have biased our results in favor of hydroxychloroquine. Our results are consistent with conclusions from other trials that hydroxychloroquine cannot be recommended for inpatients with COVID-19; azithromycin may merit additional investigation. CLINICAL TRIAL REGISTRATION: This trial was prospectively registered (NCT04329832) before enrollment of the first patient.

Evaluating the association between unmet healthcare needs and subsequent clinical outcomes: protocol for the Addressing Post-Intensive Care Syndrome-01 (APICS-01) multicentre cohort study.

INTRODUCTION: As short-term mortality declines for critically ill patients, a growing number of survivors face long-term physical, cognitive and/or mental health impairments. After hospital discharge, many critical illness survivors require an in-depth plan to address their healthcare needs. Early after hospital discharge, numerous survivors experience inadequate care or a mismatch between their healthcare needs and what is provided. Many patients are readmitted to the hospital, have substantial healthcare resource use and experience long-lasting morbidity. The objective of this study is to investigate the gap in healthcare needs occurring immediately after hospital discharge and its association with hospital readmissions or death for survivors of acute respiratory failure (ARF). METHODS AND ANALYSIS: In this multicentre prospective cohort study, we will enrol 200 survivors of ARF in the intensive care unit (ICU) who are discharged directly home from their acute care hospital stay. Unmet healthcare needs, the primary exposure of interest, will be evaluated as soon as possible within 1 to 4 weeks after hospital discharge, via a standardised telephone assessment. The primary outcome, death or hospital readmission, will be measured at 3 months after discharge. Secondary outcomes (eg, quality of life, cognitive impairment, depression, anxiety and post-traumatic stress disorder) will be measured as part of 3-month and 6-month telephone-based follow-up assessments. Descriptive statistics will be reported for the exposure and outcome variables along with a propensity score analysis, using inverse probability weighting for the primary exposure, to evaluate the relationship between the primary exposure and outcome. ETHICS AND DISSEMINATION: The study received ethics approval from Vanderbilt University Medical Center Institutional Review Board (IRB) and the University of Utah IRB (for the Veterans Affairs site). These results will inform both clinical practice and future interventional trials in the field. We plan to disseminate the results in peer-reviewed journals, and via national and international conferences. TRIAL REGISTRATION DETAILS: ClinicalTrials.gov (NCT03738774). Registered before enrollment of the first patient.

Associations Between the Time in Hypoglycemia and Hypoglycemia Awareness Status in Type 1 Diabetes Patients Using Continuous Glucose Monitoring Systems.

Background: Continuous glucose monitoring (CGM) systems help reduce hypoglycemia in patients with type 1 diabetes (T1D). It remains unclear whether T1D patients with impaired awareness of hypoglycemia (IAH) continue to develop more hypoglycemia than those with normal hypoglycemia awareness (NA) despite CGM use. Materials and Methods: For this cross-sectional observational study, 99 T1D patients using real-time CGMs for ≥86% of time were recruited. Fifty and 49 patients were found to have NA and IAH (based on the Clarke questionnaire), respectively. Two-week CGM hypoglycemia data were collected. Results: IAH was associated with greater percentages of CGM values <70 and <54 mg/dL (P = 0.012, P = 0.004) compared to NA. Clarke scores correlated positively with the percentage of CGM values <70 and <54 mg/dL (P = 0.013, P = 0.004). IAH was also related to more events with glucose <70 and <54 mg/dL determined either with at ≥1 time point (P = 0.048, P = 0.003) or lasting ≥20 min (P = 0.016, P = 0.004). IAH patients presented with more day-time events with glucose <54 mg/dL (P = 0.015), nocturnal events with glucose levels <70 and <54 mg/dL (P = 0.009, P = 0.007) and longer day-time event duration with glucose levels <70 and <54 mg/dL (P < 0.001, P = 0.006), respectively. Conclusions: T1D patients with IAH continue to experience more hypoglycemia despite dedicated CGM use.

Self-Management Behaviors of Patients with Type 1 Diabetes: Comparing Two Sources of Patient-Generated Data.

OBJECTIVES: This article aims to evaluate adult type 1 diabetes mellitus (T1DM) self-management behaviors (SMBs) related to exercise and alcohol on a survey versus a smartphone app to compare self-reported and self-tracked SMBs, and examine inter- and intrapatient variability. METHODS: Adults with T1DM on insulin pump therapy were surveyed about their alcohol, meal, and exercise SMBs. For 4 weeks, participants self-tracked their alcohol, meal, and exercise events, and their SMBs corresponding with these events via an investigator-developed app. Descriptive statistics and generalized linear mixed-effect models were used to analyze the data RESULTS: Thirty-five participants self-tracked over 5,000 interactions using the app. Variability in how participants perceived the effects of exercise and alcohol on their blood glucose was observed. The congruity between SMBs self-reported on the survey and those self-tracked with the app was measured as mean (SD). The lowest congruity was for alcohol and exercise with 61.9% (22.7) and 66.4% (20.2), respectively. Congruity was higher for meals with 80.9% (21.0). There was significant daily intra- and interpatient variability in SMBs related to preprandial bolusing: recommended bolus, p < 0.05; own bolus choice, p < 0.01; and recommended basal adjustment, p < 0.01. CONCLUSION: This study highlights the variability in intra- and interpatient SMBs obtained through the use of a survey and app. The outcomes of this study indicate that clinicians could use both one-time and every-day assessment tools to assess SMBs related to meals. For alcohol and exercise, further research is needed to understand the best assessment method for SMBs. Given this degree of patient variability, there is a need for an educational intervention that goes beyond the traditional "one-size-fits-all" approach of diabetes management to target individualized treatment barriers.

Alarm Settings of Continuous Glucose Monitoring Systems and Associations to Glucose Outcomes in Type 1 Diabetes.

CONTEXT: Little evidence exists regarding the positive and negative impacts of continuous glucose monitor system (CGM) alarm settings for diabetes control in patients with type 1 diabetes (T1D). OBJECTIVE: Evaluate the associations between CGM alarm settings and glucose outcomes. DESIGN AND SETTING: A cross-sectional observational study in a single academic institution. PATIENTS AND MAIN OUTCOME MEASURES: CGM alarm settings and 2-week CGM glucose information were collected from 95 T1D patients with > 3 months of CGM use and ≥ 86% active usage time. The associations between CGM alarm settings and glucose outcomes were analyzed. RESULTS: Higher glucose thresholds for hypoglycemia alarms (ie, ≥ 73 mg/dL vs < 73 mg/dL) were related to 51% and 65% less time with glucose < 70 and < 54 mg/dL, respectively (P = 0.005; P = 0.016), higher average glucose levels (P = 0.002) and less time-in-range (P = 0.005), but not more hypoglycemia alarms. The optimal alarm threshold for < 1% of time in hypoglycemia was 75 mg/dL.Lower glucose thresholds for hyperglycemia alarms (ie, ≤ 205 mg/dL vs > 205 mg/dL) were related to lower average glucose levels and 42% and 61% less time with glucose > 250 and > 320 mg/dL (P = 0.020, P = 0.016, P = 0.007, respectively), without more hypoglycemia. Lower alarm thresholds were also associated with more alarms (P < 0.0001). The optimal alarm threshold for < 5% of time in hyperglycemia and hemoglobin A1c ≤ 7% was 170 mg/dL. CONCLUSIONS: Different CGM glucose thresholds for hypo/hyperglycemia alarms are associated with various hypo/hyperglycemic outcomes. Configurations to the hypo/hyperglycemia alarm thresholds could be considered as an intervention to achieve therapeutic goals.

Data-Driven Diabetes Education Guided by a Personalized Report for Patients on Insulin Pump Therapy.

OBJECTIVE: It is difficult to assess self-management behaviors (SMBs) and incorporate them into a personalized self-care plan. We aimed to develop and apply SMB phenotyping algorithms from data collected by diabetes devices and a mobile health (mHealth) application to create patient-specific SMBs reports to guide individualized interventions. Follow-up interventions aimed to understand patient's reasoning behind discovered SMB choices. METHODS: This study deals with adults on continuous subcutaneous insulin infusion using a continuous glucose monitor (CGM) who self-tracked SMBs with an mHealth application for 1 month. Patient-generated data were quantified and an SMB report was designed and populated for each participant. A diabetes educator used the report to conduct personalized, data-driven educational interventions. Thematic analysis of the intervention was conducted. RESULTS: Twenty-two participants recorded 118 alcohol, 251 exercise, 2,661 meal events, and 1,900 photos. A patient-specific SMB report was created from this data and used to conduct the educational intervention. High variability of SMB was observed between patients. There was variability in the percentage of alcohol events accompanied by a blood glucose check, median 79% (38-100% range), and frequency of changing the bolus waveform, median 11 (7-95 range). Interventions confirmed variability of SMBs. Main emerging themes from thematic analysis were: challenges and barriers, motivators, current SMB techniques, and future plans to improve glycemic control. CONCLUSION: The ability to quantify SMBs and understand patients' rationale may help improve diabetes self-care and related outcomes. This study describes our first steps in piloting a patient-specific diabetes educational intervention, as opposed to the current "one size fits all" approach.

Patient Perception and Satisfaction With Insulin Pump System: Pilot User Experience Survey.

BACKGROUND: The goal of this study was to assess patient perspectives and satisfaction with the MiniMed 670G insulin pump. Those participants who used the pump as part of a hybrid closed loop were also asked to provide their views on the automatic feature (auto mode). METHODS: Adults with type 1 diabetes mellitus using the Medtronic™ 670G pump were asked about their experience with the device using a semi-structured survey developed by the research team. Responses were quantified to identify emergent themes. RESULTS: Seventeen participants used the pump as part of a hybrid closed loop system, while four participants used the pump in combination with a nonintegrated continuous glucose monitoring system. Overall, participants indicated a high level of satisfaction with the pump (14/21) mostly because of improvements in blood glucose (BG) control (15/21). Least liked features were physical design and structure (6/21), frequency of user input (5/21), alert frequency (4/21), and difficulty of use (3/21). Those using the hybrid closed loop were satisfied with the auto mode feature (11/17), mostly because of improvements in BG control (9/17). The least liked features of the auto mode technology were that blood glucose levels remained elevated (5/17) and the frequency of alerts (4/17). CONCLUSION: Participants indicated a high level of satisfaction with the pump and its auto mode featured mostly because of improvements in BG control. They also pointed out some key aspects of the device that are of potential clinical or commercial relevance. Additional research is needed to further evaluate users' perspectives on this new device.