Early goal enteral nutrition associated with decreased in-hospital death in mechanically ventilated critically ill adults: a retrospective cohort study.

INTRODUCTION: Early enteral nutrition (EN) in critically ill adult patients is thought to improve mortality and morbidity; expert guidelines recommend early initiation of EN in critically ill adults. However, the ideal schedule and dose of EN remain understudied. STUDY OBJECTIVE: Our objective was to evaluate the relationship between achieving 70% of recommended EN within 2 days of intubation ('early goal EN') and clinical outcomes in mechanically ventilated medically critically ill adults. We hypothesised that early goal EN would be associated with reduced in-hospital death. METHODS: We conducted a retrospective cohort study of mechanically ventilated adult patients admitted to our medical intensive care unit during 2013-2019. We assessed the proportion of recommended total EN provided to the patient each day following intubation until extubation, death or 7 days whichever was shortest. Patients who received 70% or more of their recommended total daily EN within 2 days of intubation (ie, 'baseline period') were considered to have achieved 'early goal EN'; these patients were compared with patients who did not ('low EN'). The primary outcome was in-hospital death; secondary outcomes were successful extubation and discharge alive. RESULTS: 938 patients met eligibility criteria and survived the baseline period. During the 7-day postintubation period, 64% of all patients reached 70% of recommended daily calories; 33% of patients achieved early goal EN. In unadjusted and adjusted models, early goal EN versus low EN was associated with a lower incidence of in-hospital death (subdistribution HR (SHR) unadjusted=0.63, p=0.0003, SHR adjusted=0.73, p=0.02). Early goal EN was also associated with a higher incidence of successful extubation (SHR unadjusted=1.41, p<0.00001, SHR adjusted=1.27, p=0.002) and discharge alive (SHR unadjusted=1.54, p<0.00001, SHR adjusted=1.24, p=0.02). CONCLUSIONS: Early goal EN was associated with significant improvement in clinical metrics of decreased in-hospital death, increased extubation and increased hospital discharge alive.

Association Between Daily Average of Mobility Achieved During Physical Therapy Sessions and Hospital-Acquired or Ventilator-Associated Pneumonia among Critically Ill Patients.

PURPOSE: Hospital-acquired and ventilator-associated pneumonias (HAP and VAP) are associated with increased morbidity and mortality. Immobility is a risk factor for developing ICU-acquired weakness (ICUAW). Early mobilization is associated with improved physical function, but its association with hospital-acquired (HAP) and ventilator-associated pneumonias (VAP) is unknown. The purpose of this study is to evaluate the association between daily average of highest level of mobility achieved during physical therapy (PT) and incidence of HAP or VAP among critically ill patients. MATERIALS AND METHODS: In a retrospective cohort study of progressive mobility program participants in the medical ICU, we used a validated method to abstract new diagnoses of HAP and VAP. We captured scores on a mobility scale achieved during each inpatient physical therapy session and used a Bayesian, discrete time-to-event model to evaluate the association between daily average of highest level of mobility achieved and occurrence of HAP or VAP. RESULTS: The primary outcome of HAP/VAP occurred in 55 (26.8%) of the 205 participants. Each increase in the daily average of highest level of mobility achieved during PT (0-6 mobility scale) exhibited a protective association with occurrence of HAP or VAP (adjusted hazard ratio [HR] 0.61; 95% CI 0.44, 0.85). Age, baseline ambulatory status, Acute Physiology and Chronic Health Evaluation (APACHE) II, and previous day's mechanical ventilation (MV) status were not significantly associated with the occurrence of HAP/VAP. CONCLUSIONS: Among critically ill patients in a progressive mobility program, a higher daily average of highest level of mobility achieved during PT was associated with a decreased risk of HAP or VAP.

Enhancing cosinor analysis of circadian phase markers using the gamma distribution.

The cosinor model, in which a cosine curve is fitted to periodic data within a regression model, is a frequently used method for describing patterns of cyclical activity such as circadian rhythms. For circadian variables of interest (eg, melatonin and heart rate) that do not take on negative values, the assumption of normally distributed residuals required by the general linear model, which is most commonly used for cosinor analysis, may not be appropriate. Alternatively, a generalized linear model with the gamma distribution (GZLM-gamma) is specifically defined to accommodate non-negative outcomes. Herein, we demonstrate the improved fit and gains of efficiency in detection of circadian rhythm afforded by using the GZLM-gamma in cosinor models of heart rate, actigraphic activity, and urinary 6-sulfatoxymelatonin. Notably, this improved detection of circadian rhythm allows retention of additional patients for downstream analyses, further improving study power.

A SAS macro for modelling periodic data using cosinor analysis.

BACKGROUND AND OBJECTIVE: Cosinor analysis, developed by Franz Hallberg and colleagues in the 1960s, allows for the fitting of a cosine curve to data of a known period. Cosinor analysis is frequently used in the analysis of biological rhythm data. While software exists to perform these analyses, we are not aware of any published SAS procedures or macros which would facilitate them. METHODS: To meet this gap, we herein describe SAS macros which perform cosinor analyses that assume either normally or gamma distributed outcomes and fixed period. The macros can 1) produce datasets with cosinor parameters including acrophase, mesor, amplitude, nadir and test for rhythmicity 2) output datasets with fitted and observed values from the model, and 3) plot the resulting curve and underlying data. RESULTS: We demonstrate the use of these macros with data from our research on circadian rhythms of heart rate and sleep in critically ill patients. CONCLUSIONS: Cosinor analysis provides a parsimonious and intuitive set of estimates to summarize periodic data. We are hopeful that the publication of our macro will allow a wider spectrum of users to avail themselves of this technique.

Pilot Observational Study to Detect Diurnal Variation and Misalignment in Heart Rate Among Critically Ill Patients.

Circadian disruption is common in critically ill patients admitted to the intensive care unit (ICU). Understanding and treating circadian disruption in critical illness has significant potential to improve critical illness outcomes through improved cognitive, immune, cardiovascular, and metabolic function. Measurement of circadian alignment (i.e., circadian phase) can be resource-intensive as it requires frequent blood or urine sampling over 24 or more hours. Less cumbersome methods of assessing circadian alignment would advance investigations in this field. Thus, the objective of this study is to examine the feasibility of using continuous telemetry to assess diurnal variation in heart rate (HR) among medical ICU patients as a proxy for circadian alignment. In exploratory analyses, we tested for associations between misalignment of diurnal variation in HR and death during hospital admission. This was a prospective observational cohort study embedded within a prospective medical ICU biorepository. HR data were continuously collected (every 5 s) via telemetry systems for the duration of the medical ICU admission; the first 24 h of this data was analyzed. Patients were extensively characterized via medical record chart abstraction and patient interviews. Of the 56 patients with complete HR data, 48 (86%) had a detectable diurnal variation. Of these patients with diurnal variation, 39 (81%) were characterized as having the nadir of their HR outside of the normal range of 02:00-06:00 ("misalignment"). Interestingly, no deaths occurred in the patients with normally aligned diurnal variation; in contrast, there were seven deaths (out of 39 patients) in patients who had misaligned diurnal variation in HR. In an exploratory analysis, we found that the odds ratio of death for misaligned vs. aligned patients was increased at 4.38; however, this difference was not statistically significant (95% confidence interval 0.20-97.63). We conclude that diurnal variation in HR can be detected via continuous telemetric monitoring of critically ill patients. A majority of these patients with diurnal variation exhibited misalignment in their first 24 h of medical ICU admission. Exploratory analyses suggest possible associations between misalignment and death.

Quasi-Experimental Evaluation of the Effectiveness of a Large-Scale Readmission Reduction Program.

IMPORTANCE: Feasibility, effectiveness, and sustainability of large-scale readmission reduction efforts are uncertain. The Greater New Haven Coalition for Safe Transitions and Readmission Reductions was funded by the Center for Medicare & Medicaid Services (CMS) to reduce readmissions among all discharged Medicare fee-for-service (FFS) patients. OBJECTIVE: To evaluate whether overall Medicare FFS readmissions were reduced through an intervention applied to high-risk discharge patients. DESIGN, SETTING, AND PARTICIPANTS: This quasi-experimental evaluation took place at an urban academic medical center. Target discharge patients were older than 64 years with Medicare FFS insurance, residing in nearby zip codes, and discharged alive to home or facility and not against medical advice or to hospice; control discharge patients were older than 54 years with the same zip codes and discharge disposition but without Medicare FFS insurance if older than 64 years. High-risk target discharge patients were selectively enrolled in the program. INTERVENTIONS: Personalized transitional care, including education, medication reconciliation, follow-up telephone calls, and linkage to community resources. MEASUREMENTS: We measured the 30-day unplanned same-hospital readmission rates in the baseline period (May 1, 2011, through April 30, 2012) and intervention period (October 1, 2012, through May 31, 2014). RESULTS: We enrolled 10 621 (58.3%) of 18 223 target discharge patients (73.9% of discharge patients screened as high risk) and included all target discharge patients in the analysis. The mean (SD) age of the target discharge patients was 79.7 (8.8) years. The adjusted readmission rate decreased from 21.5% to 19.5% in the target population and from 21.1% to 21.0% in the control population, a relative reduction of 9.3%. The number needed to treat to avoid 1 readmission was 50. In a difference-in-differences analysis using a logistic regression model, the odds of readmission in the target population decreased significantly more than that of the control population in the intervention period (odds ratio, 0.90; 95% CI, 0.83-0.99; P = .03). In a comparative interrupted time series analysis of the difference in monthly adjusted admission rates, the target population decreased an absolute -3.09 (95% CI, -6.47 to 0.29; P = .07) relative to the control population, a similar but nonsignificant effect. CONCLUSIONS AND RELEVANCE: This large-scale readmission reduction program reduced readmissions by 9.3% among the full population targeted by the CMS despite being delivered only to high-risk patients. However, it did not achieve the goal reduction set by the CMS.

Too good to treat? Outcomes in patients not receiving thrombolysis due to mild deficits or rapidly improving symptoms.

INTRODUCTION: Among ischemic stroke patients arriving within the treatment window, rapidly improving symptoms or having a mild deficit (i.e. too good to treat) is a common reason for exclusion. Several studies have reported poor outcomes in this group. We addressed the question of early neurological deterioration in too good to treat patients in a larger prospective cohort study. METHODS: Admission and discharge information were collected prospectively in acute stroke patients who presented to the emergency room within three-hours from onset. The primary outcome measure was change in the National Institutes of Health Stroke Scale from baseline to discharge. Secondary outcomes were discharge National Institutes of Health Stroke Scale >4, not being discharged home, and discharge modified Rankin scale. RESULTS: Of 355 patients who presented within three-hours, 127 (35·8%) had too good to treat listed as the only reason for not receiving thrombolysis, with median admission National Institutes of Health Stroke Scale = 1 (range = 0 to 19). At discharge, seven (5·5%) showed a worsening of National Institutes of Health Stroke Scale ≥1, and nine (7·1%) had a National Institutes of Health Stroke Scale >4. When excluding prior stroke (remaining n = 97), discharge status was even more benign: only five (5·2%) had a discharge National Institutes of Health Stroke Scale >4, and two (2·1%) patients were not discharged home. CONCLUSION: We found that a small proportion of patients deemed too good to treat will have early neurological deterioration, in contrast to other studies. Decisions about whether to treat mild stroke patients depend on the outcome measure chosen, particularly when considering discharge disposition among patients who have had prior stroke. The decision to thrombolyze may ultimately rest on the nature of the presentation and deficit.

Common predictors of cigarette smoking, alcohol use, aggression, and delinquency among inner-city minority youth.

The present study examined the prevalence rates and common predictors of substance use, aggression, and delinquency among inner-city minority youth entering middle school. A survey was administered to sixth grade students (N=5442) from 42 New York City schools. Aggressive behaviors were reported most frequently, followed by delinquent behaviors, alcohol use, and cigarette smoking. Across all behavioral outcomes, social and environmental influences explained the largest proportion of variance, followed by individual characteristics and skills, bonding to conventional institutions, and demographic variables. For the majority of predictor variables, there was substantial overlap in patterns of prediction across outcomes. These findings indicate that several factors that correspond to the predominant psychosocial theories of adolescent development explain variation across different problem behavior outcomes among inner-city minority youth.

Effectiveness of a universal drug abuse prevention approach for youth at high risk for substance use initiation.

BACKGROUND: Universal school-based prevention programs for alcohol, tobacco, and other drug use are typically designed for all students within a particular school setting. However, it is unclear whether such broad-based programs are effective for youth at high risk for substance use initiation. METHOD: The effectiveness of a universal drug abuse preventive intervention was examined among youth from 29 inner-city middle schools participating in a randomized, controlled prevention trial. A subsample of youth (21% of full sample) was identified as being at high risk for substance use initiation based on exposure to substance-using peers and poor academic performance in school. The prevention program taught drug refusal skills, antidrug norms, personal self-management skills, and general social skills. RESULTS: Findings indicated that youth at high risk who received the program (n = 426) reported less smoking, drinking, inhalant use, and polydrug use at the one-year follow-up assessment compared to youth at high risk in the control condition that did not receive the intervention (n = 332). Results indicate that a universal drug abuse prevention program is effective for minority, economically disadvantaged, inner-city youth who are at higher than average risk for substance use initiation. CONCLUSIONS: Findings suggest that universal prevention programs can be effective for a range of youth along a continuum of risk.

Personal competence skills, distress, and well-being as determinants of substance use in a predominantly minority urban adolescent sample.

Several previous studies have investigated the relationship between psychological distress and substance use among youth. However, less research has investigated the potentially protective role of psychological well-being on adolescent substance use, and the extent to which personal competence skills may promote well-being. The present study examined personal competence skills, psychological distress and well-being, and adolescent substance use over a 3-year period in a predominantly minority sample of urban students (N = 1,184) attending 13 junior high schools in New York City. Structural equation modeling indicated that greater competence skills predicted less distress and greater well-being over time. Although psychological well-being was associated with less subsequent substance use, distress did not predict later substance use. Findings indicate that competence skills promote resilience against early stage substance use in part by enhancing psychological well-being, and suggest that school-based prevention programs should include competence enhancement components in order to promote resilience.

Estimates of intragroup dependence for drug use and skill measures in school-based drug abuse prevention trials: an empirical study of three independent samples.

Group-randomized drug abuse prevention trials customarily designate schools as the unit of assignment to experimental condition; however, students within schools remain the unit of observation. Students nested within schools may show some resemblance based on common (peer) selection or school climate factors (i.e., disciplinary practices, group norms, or rules). Appropriate analyses of any treatment effects must be statistically correct for the magnitude of clustering within these intact social units (i.e., intraclass correlation coefficient [ICC]). There is little reported evidence, however, of variation in ICCs that might occur with studies of racially or geographically diverse populations. The purpose of this study was to generate estimates of intragroup dependence for drug use and psychosocial measures (hypothesized mediators) from three separate drug abuse prevention trials. Clustering for the drug use measures averaged .02 across study and age-groups (range = .002 to .053) and was equivalently small for the psychosocial measures (averaging .03 across studies and age-groups; range = .001 to .149). With few exceptions and across different samples, clustering decreased in magnitude over time. Clustering was largest for peer smoking and drinking norms among white, suburban youth and smallest for alcohol expectancies among urban black youth. Findings are discussed with respect to the influence of social climate factors and group norms in the design and analysis of school-based, drug abuse, prevention programs.