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BACKGROUND AND AIMS: Risk factors for poor outcomes after critical illness are incompletely understood. While nutritional risk is associated with mortality in critically ill patients, its association with disability, cognitive, and health-related quality of life is unclear in survivors of critical illness. This study’s objective was to determine whether greater nutritional risk at ICU admission is associated with greater disability, worse cognition, and worse HRQOL at 3 and 12-month follow-up. METHODS: We enrolled adults (≥ 18 years of age) with respiratory failure or shock treated in medical and surgical intensive care units from two U.S. centers. We measured nutritional risk using the modified Nutrition Risk in Critically Ill (mNUTRIC) score (range 0 to 9 [highest risk]) at intensive care unit admission. We measured associations between mNUTRIC scores and discharge destination, disability in basic activities of daily living (ADLs) using the Katz ADL, instrumental ADLs using the Functional Activities Questionnaire (FAQ), global cognition using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), executive function using the Trail Making Test Part B (Trails B), and health-related quality of life using the SF-36, adjusting for sex, education, BMI, baseline frailty, disability, and cognition, severity of illness, days of delirium, coma, and mechanical ventilation. RESULTS: Of the 821 patients enrolled in the ICU, 636 patients survived to hospital discharge. We assessed outcomes in 448 of 535 survivors (84%) at 3 months and 382 of 476 survivors (80%) at 12 months. Higher mNUTRIC scores predicted greater odds of discharge to an institution (OR 2.0, 95% CI: 1.6 to 2.6; P

Analysis of 2 years of quality improvement data after the implementation of a suicidality screening and treatment protocol in a primary care setting found that among 1,733 patients, 149 had suicidal ideation. Among the 112 of those patients who remained in care, more than half presented with only nonpsychiatric complaints. Primary care practices may be viable tools to combat the nation's suicide epidemic.

Rationale: The biological mechanisms of long-term cognitive impairment and disability after critical illness are unclear.Objectives: To test the hypothesis that markers of acute inflammation and coagulation are associated with subsequent long-term cognitive impairment and disability.Methods: We obtained plasma samples from adults with respiratory failure or shock on Study Days 1, 3, and 5 and measured concentrations of CRP (C-reactive protein), IFN-γ, IL-1β, IL-6, IL-8, IL-10, IL-12, MMP-9 (matrix metalloproteinase-9), TNF-α (tumor necrosis factor-α), soluble TNF receptor 1, and protein C. At 3 and 12 months after discharge, we assessed global cognition, executive function, and activities of daily living. We analyzed associations between markers and outcomes using multivariable regression, adjusting for age, sex, education, comorbidities, baseline cognition, doses of sedatives and opioids, stroke risk (in cognitive models), and baseline disability scores (in disability models).Measurements and Main Results: We included 548 participants who were a median (interquartile range) of 62 (53-72) years old, 88% of whom were mechanically ventilated, and who had an enrollment Sequential Organ Failure Assessment score of 9 (7-11). After adjusting for covariates, no markers were associated with long-term cognitive function. Two markers, CRP and MMP-9, were associated with greater disability in basic and instrumental activities of daily living at 3 and 12 months. No other markers were consistently associated with disability outcomes.Conclusions: Markers of systemic inflammation and coagulation measured early during critical illness are not associated with long-term cognitive outcomes and demonstrate inconsistent associations with disability outcomes. Future studies that pair longitudinal measurement of inflammation and related pathways throughout the course of critical illness and during recovery with long-term outcomes are needed.

Importance Recent reports identify that among hospitalized coronavirus disease 2019 patients, 30% require ICU care. Understanding ICU resource needs remains an essential component of meeting current and projected needs of critically ill coronavirus disease 2019 patients. Objectives This study queried U.S. ICU clinician perspectives on challenging aspects of care in managing coronavirus disease 2019 patients, current and anticipated resource demands, and personal stress. Design, setting, and participants Using a descriptive survey methodology, an anonymous web-based survey was administered from April 7, 2020, to April 22, 2020 (email and newsletter) to query members of U.S. national critical care organizations. Measurements and main results Through a 16-item descriptive questionnaire, ICU clinician perceptions were assessed regarding current and emerging critical ICU needs in managing the severe acute respiratory syndrome coronavirus 2 infected patients, resource levels, concerns about being exposed to severe acute respiratory syndrome coronavirus 2, and perceived level of personal stress. A total of 9,120 ICU clinicians responded to the survey, representing all 50 U.S. states, with 4,106 (56.9%) working in states with 20,000 or more coronavirus disease 2019 cases. The 7,317 respondents who indicated their profession included ICU nurses (n = 6,731, 91.3%), advanced practice providers (nurse practitioners and physician assistants; n = 334, 4.5%), physicians (n = 212, 2.9%), respiratory therapists (n = 31, 0.4%), and pharmacists (n = 30, 0.4%). A majority (n = 6,510, 88%) reported having cared for a patient with presumed or confirmed coronavirus disease 2019. The most critical ICU needs identified were personal protective equipment, specifically N95 respirator availability, and ICU staffing. Minimizing healthcare worker virus exposure during care was believed to be the most challenging aspect of coronavirus disease 2019 patient care (n = 2,323, 30.9%). Nurses report a high level of concern about exposing family members to severe acute respiratory syndrome coronavirus 2 (median score of 10 on 0-10 scale). Similarly, the level of concern reached the maximum score of 10 in ICU clinicians who had provided care to coronavirus disease 2019 patients. Conclusions This national ICU clinician survey identifies continued concerns regarding personal protective equipment supplies with the chief issue being N95 respirator availability. As the pandemic continues, ICU clinicians anticipate a number of limited resources that may impact ICU care including personnel, capacity, and surge potential, as well as staff and subsequent family members exposure to severe acute respiratory syndrome coronavirus 2. These persistent concerns greatly magnify personal stress, offering a therapeutic target for professional organization and facility intervention efforts.

Objectives Little is known about frailty that develops following critical illness. We sought to describe the prevalence of newly acquired frailty, its clinical course, and the co-occurrence of frailty with disability and cognitive impairment in survivors of critical illness. Design Longitudinal prospective cohort study. Setting Medical and surgical ICUs at five U.S. centers. Patients Adult patients treated for respiratory failure and/or shock. Measurements and main results We measured frailty with the Clinical Frailty Scale at baseline (i.e., study enrollment) and at 3 and 12 months postdischarge. We constructed alluvial diagrams to describe the course of frailty and Venn diagrams to describe the overlap of frailty with disability in activities of daily living and cognitive impairment. We included 567 participants a median (interquartile range) of 61 years old (51-70 yr old) with a high severity of illness (Acute Physiology and Chronic Health Evaluation II of 23). Frailty (Clinical Frailty Scale scores ≥ 5) was present in 135 of 567 (24%) at baseline, 239 of 530 (45%) at 3 months, and 163 of 445 (37%) at 12 months. Of those with frailty at 3- or 12-month follow-up, 61% were not frail at baseline. Transition to a worse frailty state occurred in 242 of 530 of patients (46%) between baseline and 3 months and in 179 of 445 of patients (40%) between baseline and 12 months. There were 376 patients with frailty, disability, or cognitive impairment at 3-month follow-up. Of these, 53 (14%) had frailty alone. At 12 months, 276 patients had frailty, disability, or cognitive impairment, 37 (13%) of whom had frailty alone. Conclusions Frailty is common among survivors of critical illness. In the majority, frailty is newly acquired. Roughly one in seven had frailty without co-occurring disability or cognitive impairment. Studies to understand outcomes of frailty that develops as the result of a critical illness and to identify modifiable risk factors for this potentially reversible syndrome are needed.

Background In longitudinal critical care studies, researchers may be interested in summarizing an exposure over time and evaluating its association with a long-term outcome. For example, the number of days a patient has delirium (i.e., brain dysfunction) during their critical care stay is associated with the presence and severity of long-term cognitive problems. In large pragmatic trials and multicenter observational studies, particularly when electronic medical record data is used, the information on daily exposure status may be available at some time points and not at others. Model-based multiple imputation is a well-established, widely adopted method to deal with missing data. But the uncertainty around multiple imputation for summary exposure variables is whether the imputation is to be performed at the summary level or at the daily assessment level. Methods We compare the following approaches to imputing and summarizing partially missing longitudinal data: 1) active imputation, where we impute the summary; 2) passive imputation, where we impute the daily missing data, and then compute the summary; 3) ad hoc methods where we assume all missing time points have the a) most or the b) least extreme value; and 4) complete case analysis where only participants with complete data are analyzed. These methods were applied under different missingness mechanisms, varying proportions of missingness, and association of missingness with an auxiliary variable using simulations that closely mirrors real-life critical care data to be relevant to real-world clinical practice. The performance of the approaches were compared using bias of the estimated coefficients, standard error of the estimate and coverage. We also apply these imputation strategies to two datasets in critical care. Results Simulations show that all methods performed comparably when the proportion of missingness was small, indicating that in such instances, the gain over using any imputation model is minimal. But as the proportion of missingness increases, the passive imputation approach provides efficient and less biased estimates under the missingness at random and missingness completely at random mechanism. Conclusions For longitudinal data where a summary exposure is of interest, we recommend practitioners adopting the passive imputation strategy.

Objective: The purpose of this study was to integrate acupuncture within the standard of care during outpatient opioid tapering and assess impact of this treatment on cumulative withdrawal symptoms, psychologic distress, and pain. Methods: This prospective randomized controlled pilot study administered the National Acupuncture Detoxification Association protocol following monthly opioid tapering. A total of 9 participants were randomized into the intervention group and compared with 6 participants who underwent the standard of care for outpatient opioid tapering. All providers prescribing medication management to both groups were blinded. Psychologic distress was evaluated using the hospital anxiety and depression scale (HADS). The clinical institute narcotic assessment (CINA) measured subjective withdrawal symptoms and pain was assessed using the numerical rating scale (NRS). Results: Overall anxiety appeared slightly higher in the acupuncture group (HADS 7.0 compared with 6.5), however, depression was lower when compared with the standard of care group (HADS 4.0 compared with 6.5). The standard of care group reported more intense withdrawal symptoms (CINA 9.0 compared with 3.5) as well as higher pain scores (NRS 6.5 compared with 5.0). There were no statistically significant differences among the standard of care and acupuncture groups. Conclusions: This study suggests that auricular acupuncture may be implemented within the standard of care for patients undergoing outpatient opioid weaning regimens. Although results were not statistically significant, they support future research and reveal a promising expansion of treatment options for patients physically dependent on opioid medication. Clinical Trials.gov ID: NCT02882048.

Background The impact of specialist palliative care intervention in patients undergoing surgery for cancer has not been studied extensively. The SCOPE randomized controlled trial will investigate the effect of specialist palliative care intervention in cancer patients undergoing surgery for selected abdominal malignancies. The study protocol of the SCOPE Trial was published in December 2019. Methods and design The SCOPE Trial is a single-center, single-blind, prospective, randomized controlled trial that will investigate specialist palliative care intervention for cancer patients undergoing surgery for selected abdominal malignancies. The study plans to enroll 236 patients that will be randomized to specialist palliative care (intervention arm) and usual care (control arm) in a 1:1 ratio. Results The primary outcome of the study is the Functional Assessment of Cancer Therapy-General (FACT-G) Trial Outcome Index (TOI) at 90 days postoperatively. Secondary outcomes of the study include the total FACT-G score at 90 days postoperatively, days alive at home without an emergency room visit within 90 days of operation, and all-cause mortality at 1 year after operation. Time frames for all outcomes will start on the day of surgery. Conclusion This manuscript serves as the formal statistical analysis plan (version 1.0) for the SCOPE randomized controlled trial. The statistical analysis plan was completed on 6 April 2021. Trial registration ClinicalTrials.gov NCT03436290. Registered on 16 February 2018

BACKGROUND: Guidelines currently recommend targeting light sedation with dexmedetomidine or propofol for adults receiving mechanical ventilation. Differences exist between these sedatives in arousability, immunity, and inflammation. Whether they affect outcomes differentially in mechanically ventilated adults with sepsis undergoing light sedation is unknown. METHODS: In a multicenter, double-blind trial, we randomly assigned mechanically ventilated adults with sepsis to receive dexmedetomidine (0.2 to 1.5 μg per kilogram of body weight per hour) or propofol (5 to 50 μg per kilogram per minute), with doses adjusted by bedside nurses to achieve target sedation goals set by clinicians according to the Richmond Agitation–Sedation Scale (RASS, on which scores range from −5 [unresponsive] to +4 [combative]). The primary end point was days alive without delirium or coma during the 14-day intervention period. Secondary end points were ventilator-free days at 28 days, death at 90 days, and age-adjusted total score on the Telephone Interview for Cognitive Status questionnaire (TICS-T; scores range from 0 to 100, with a mean of 50±10 and lower scores indicating worse cognition) at 6 months. RESULTS: Of 432 patients who underwent randomization, 422 were assigned to receive a trial drug and were included in the analyses — 214 patients received dexmedetomidine at a median dose of 0.27 μg per kilogram per hour, and 208 received propofol at a median dose of 10.21 μg per kilogram per minute. The median duration of receipt of the trial drugs was 3.0 days (interquartile range, 2.0 to 6.0), and the median RASS score was −2.0 (interquartile range, −3.0 to −1.0). We found no difference between dexmedetomidine and propofol in the number of days alive without delirium or coma (adjusted median, 10.7 vs. 10.8 days; odds ratio, 0.96; 95% confidence interval [CI], 0.74 to 1.26), ventilator-free days (adjusted median, 23.7 vs. 24.0 days; odds ratio, 0.98; 95% CI, 0.63 to 1.51), death at 90 days (38% vs. 39%; hazard ratio, 1.06; 95% CI, 0.74 to 1.52), or TICS-T score at 6 months (adjusted median score, 40.9 vs. 41.4; odds ratio, 0.94; 95% CI, 0.66 to 1.33). Safety end points were similar in the two groups. CONCLUSIONS: Among mechanically ventilated adults with sepsis who were being treated with recommended light-sedation approaches, outcomes in patients who received dexmedetomidine did not differ from outcomes in those who received propofol. (Funded by the National Institutes of Health; ClinicalTrials.gov number, NCT01739933.)

Background Long-term cognitive impairment frequently occurs after critical illness; no treatments are known to improve long-term cognition. Research Question Does a single high-dose (540,000 International Units) enteral treatment of vitamin D3 given shortly after hospital admission in critically ill patients who are vitamin D deficient improve long-term global cognition or executive function? Study Design and Methods This study evaluated long-term cognitive outcomes among patients enrolled in a multicenter, blinded, randomized clinical trial comparing vitamin D3 treatment vs placebo in critically ill adults with vitamin D deficiency. Global cognition was measured by the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Executive function was measured with a composite score derived from three Delis-Kaplan Executive Function System subscales. Outcomes were assessed at a median of 443 days (interquartile range, 390-482 days) after randomization and were compared using multivariate proportional odds regression. Adjusted ORs of > 1.0 would indicate better outcomes in the vitamin D3 group compared with the placebo group. Results Ninety-five patients were enrolled, including 47 patients randomized to vitamin D3 treatment and 48 patients randomized to placebo. The adjusted median RBANS score at follow-up was 79.6 (95% CI, 73.0-84.0) in the vitamin D3 group and 82.1 (95% CI, 74.7-84.6) in the placebo group (adjusted OR, 0.83; 95% CI, 0.50-1.38). The adjusted median executive function composite scores were 8.1 (95% CI, 6.8-9.0) and 8.7 (95% CI, 7.4-9.3), respectively (adjusted OR, 0.72; 95% CI, 0.36-1.42). Interpretation In vitamin D-deficient, critically-ill adults, a large dose of enteral vitamin D3 did not improve long-term global cognition or executive function. Trial Registry ClinicalTrials.gov; No.: NCT03733418; URL: www.clinicaltrials.gov

Background: To date, 750 000 patients with COVID-19 worldwide have required mechanical ventilation and thus are at high risk of acute brain dysfunction (coma and delirium). We aimed to investigate the prevalence of delirium and coma, and risk factors for delirium in critically ill patients with COVID-19, to aid the development of strategies to mitigate delirium and associated sequelae. Methods: This multicentre cohort study included 69 adult intensive care units (ICUs), across 14 countries. We included all patients (aged ≥18 years) admitted to participating ICUs with severe acute respiratory syndrome coronavirus 2 infection before April 28, 2020. Patients who were moribund or had life-support measures withdrawn within 24 h of ICU admission, prisoners, patients with pre-existing mental illness, neurodegenerative disorders, congenital or acquired brain damage, hepatic coma, drug overdose, suicide attempt, or those who were blind or deaf were excluded. We collected de-identified data from electronic health records on patient demographics, delirium and coma assessments, and management strategies for a 21-day period. Additional data on ventilator support, ICU length of stay, and vital status was collected for a 28-day period. The primary outcome was to determine the prevalence of delirium and coma and to investigate any associated risk factors associated with development of delirium the next day. We also investigated predictors of number of days alive without delirium or coma. These outcomes were investigated using multivariable regression. Findings: Between Jan 20 and April 28, 2020, 4530 patients with COVID-19 were admitted to 69 ICUs, of whom 2088 patients were included in the study cohort. The median age of patients was 64 years (IQR 54 to 71) with a median Simplified Acute Physiology Score (SAPS) II of 40·0 (30·0 to 53·0). 1397 (66·9%) of 2088 patients were invasively mechanically ventilated on the day of ICU admission and 1827 (87·5%) were invasively mechanical ventilated at some point during hospitalisation. Infusion with sedatives while on mechanical ventilation was common: 1337 (64·0%) of 2088 patients were given benzodiazepines for a median of 7·0 days (4·0 to 12·0) and 1481 (70·9%) were given propofol for a median of 7·0 days (4·0 to 11·0). Median Richmond Agitation–Sedation Scale score while on invasive mechanical ventilation was –4 (–5 to –3). 1704 (81·6%) of 2088 patients were comatose for a median of 10·0 days (6·0 to 15·0) and 1147 (54·9%) were delirious for a median of 3·0 days (2·0 to 6·0). Mechanical ventilation, use of restraints, and benzodiazepine, opioid, and vasopressor infusions, and antipsychotics were each associated with a higher risk of delirium the next day (all p≤0·04), whereas family visitation (in person or virtual) was associated with a lower risk of delirium (p

Objective We aimed to identify socioeconomic and clinical risk factors for post-intensive care unit (ICU)-related long-term cognitive impairment (LTCI). Summary background data After delirium during ICU stay, LTCI has been increasingly recognized, but without attention to socioeconomic factors. Methods We enrolled a prospective, multicenter cohort of ICU survivors with shock or respiratory failure from surgical and medical ICUs across 5 civilian and Veteran Affairs (VA) hospitals from 2010 to 2016. Our primary outcome was LTCI at 3- and 12 months post-hospital discharge defined by the Repeatable Battery for Assessment of Neuropsychological Symptoms (RBANS) global score. Covariates adjusted using multivariable linear regression included age, sex, race, AHRQ socioeconomic index, Charlson comorbidity, Framingham stroke risk, Sequential Organ Failure Assessment, duration of coma, delirium, hypoxemia, sepsis, education level, hospital type, insurance status, discharge disposition, and ICU drug exposures. Results Of 1040 patients, 71% experienced delirium, and 47% and 41% of survivors had RBANS scores >1 standard deviation below normal at 3- and 12 months, respectively. Adjusted analysis indicated that delirium, non-White race, lower education, and civilian hospitals (as opposed to VA), were associated with at least a half standard deviation lower RBANS scores at 3- and 12 months (P ≤ 0.03). Sex, AHRQ socioeconomic index, insurance status, and discharge disposition were not associated with RBANS scores. Conclusions Socioeconomic and clinical risk factors, such as race, education, hospital type, and delirium duration, were linked to worse PICS ICU-related, LTCI. Further efforts may focus on improved identification of higher-risk groups to promote survivorship through emerging improvements in cognitive rehabilitation.

Child maltreatment is a global public health issue that has been linked with multiple negative health and life outcomes.This study evaluates the association between children placed in out-of-home care and neighborhood-level factors using eight years of administrative data.Between 2011-2018, 33,890 unique instances of child welfare involvement were captured in a department of child and family services database in a southern state in the United States.Removal addresses were geocoded and linked to the U.S. Census Bureau's American Community Survey to obtain census tract socioeconomic factors. Incidence overall and stratified by individual and neighborhood-level factors was computed. Rate ratios, relative indexes of inequality, and concentration curves quantified disparities in incidence of child welfare involvement by neighborhood-level factors.Incidence of children less than 19 years old placed into out-of-home care was 255 per 100,000 person-years (95 % CI: 252, 258). At the individual level, incidence was highest among children5 and 15-17 years old, comparable between male and female children, and higher among Black children. At the neighborhood level, incidence was highest in census tracts with lower median household incomes, higher percentages of households below poverty or of female-headed or single-parent households, higher unemployment rates, and fewer residents with some college education or health insurance.Incidence of children placed into out-of-home care is disproportionally higher for those who live in disadvantaged communities. Understanding neighborhood-level risk factors that may be linked to child welfare involvement can help inform policy and target prevention efforts.

Background It is not known whether reductions in socioeconomic and racial disparities in incidence of invasive pneumococcal disease (defined as the isolation of Streptococcus pneumoniae from a normally sterile body site) noted after pneumococcal conjugate vaccine (PCV) introduction have been sustained. Methods Individual-level data collected from 20 Tennessee counties participating in Active Bacterial Core surveillance over 19 years were linked to neighborhood-level socioeconomic factors. Incidence rates were analyzed across 3 periods—pre–7-valent PCV (pre-PCV7; 1998–1999), pre–13-valent PCV (pre-PCV13; 2001–2009), and post-PCV13 (2011–2016)—by socioeconomic factors. Results A total of 8491 cases of invasive pneumococcal disease were identified. Incidence for invasive pneumococcal disease decreased from 22.9 (1998–1999) to 17.9 (2001–2009) to 12.7 (2011–2016) cases per 100 000 person-years. Post-PCV13 incidence (95% confidence interval [CI]) of PCV13-serotype disease in high- and low-poverty neighborhoods was 3.1 (2.7–3.5) and 1.4 (1.0–1.8), respectively, compared with pre-PCV7 incidence of 17.8 (15.7–19.9) and 6.4 (4.9–7.9). Before PCV introduction, incidence (95% CI) of PCV13-serotype disease was higher in blacks than whites (17.3 [15.1–19.5] vs 11.8 [10.6–13.0], respectively); after introduction, PCV13-type disease incidence was greatly reduced in both groups (white: 2.7 [2.4–3.0]; black: 2.2 [1.8–2.6]). Conclusions Introduction of PCV13 was associated with substantial reductions in overall incidence and socioeconomic and racial disparities in PCV13-serotype incidence.