Andre Williams

Postextubation dysphagia is persistent and associated with poor outcomes in survivors of critical illness

IntroductionDysphagia is common among survivors of critical illness who required mechanical ventilation during treatment. The risk factors associated with the development of postextubation dysphagia, and the effects of dysphagia on patient outcomes, have been relatively unexplored.MethodsWe conducted a retrospective, observational cohort study from 2008 to 2010 of all patients over 17 years of age admitted to a university hospital ICU who required mechanical ventilation and subsequently received a bedside swallow evaluation (BSE) by a speech pathologist.ResultsA BSE was performed after mechanical ventilation in 25% (630 of 2,484) of all patients. After we excluded patients with stroke and/or neuromuscular disease, our study sample size was 446 patients. We found that dysphagia was present in 84% of patients (n = 374) and classified dysphagia as absent, mild, moderate or severe in 16% (n = 72), 44% (n = 195), 23% (n = 103) and 17% (n = 76), respectively. In univariate analyses, we found that statistically significant risk factors for severe dysphagia included long duration of mechanical ventilation and reintubation. In multivariate analysis, after adjusting for age, gender and severity of illness, we found that mechanical ventilation for more than seven days remained independently associated with moderate or severe dysphagia (adjusted odds ratio (AOR) = 2.84 [interquartile range (IQR) = 1.78 to 4.56]; P < 0.01). The presence of severe postextubation dysphagia was significantly associated with poor patient outcomes, including pneumonia, reintubation, in-hospital mortality, hospital length of stay, discharge status and surgical placement of feeding tubes. In multivariate analysis, we found that the presence of moderate or severe dysphagia was independently associated with the composite outcome of pneumonia, reintubation and death (AOR = 3.31 [IQR = 1.89 to 5.90]; P < 0.01).ConclusionsIn a large cohort of critically ill patients, long duration of mechanical ventilation was independently associated with postextubation dysphagia, and the development of postextubation dysphagia was independently associated with poor patient outcomes.

Cluster analysis in the COPDGene study identifies subtypes of smokers with distinct patterns of airway disease and emphysema

Background There is notable heterogeneity in the clinical presentation of patients with COPD. To characterise this heterogeneity, we sought to identify subgroups of smokers by applying cluster analysis to data from the COPDGene study. Methods We applied a clustering method, k-means, to data from 10 192 smokers in the COPDGene study. After splitting the sample into a training and validation set, we evaluated three sets of input features across a range of k (user-specified number of clusters). Stable solutions were tested for association with four COPD-related measures and five genetic variants previously associated with COPD at genome-wide significance. The results were confirmed in the validation set. Findings We identified four clusters that can be characterised as (1) relatively resistant smokers (ie, no/mild obstruction and minimal emphysema despite heavy smoking), (2) mild upper zone emphysema-predominant, (3) airway disease-predominant and (4) severe emphysema. All clusters are strongly associated with COPD-related clinical characteristics, including exacerbations and dyspnoea (p<0.001). We found strong genetic associations between the mild upper zone emphysema group and rs1980057 near HHIP, and between the severe emphysema group and rs8034191 in the chromosome 15q region (p<0.001). All significant associations were replicated at p<0.05 in the validation sample (12/12 associations with clinical measures and 2/2 genetic associations). Interpretation Cluster analysis identifies four subgroups of smokers that show robust associations with clinical characteristics of COPD and known COPD-associated genetic variants.

Post-extubation dysphagia is associated with longer hospitalization in survivors of critical illness with neurologic impairment

IntroductionCritically ill patients can develop acute respiratory failure requiring endotracheal intubation. Swallowing dysfunction after liberation from mechanical ventilation, also known as post-extubation dysphagia, is common and deleterious among patients without neurologic disease. However, the risk factors associated with the development of post-extubation dysphagia and its effect on hospital lengthofstay in critically ill patients with neurologic disorders remains relatively unexplored.MethodsWe conducted a retrospective, observational cohort study from 2008 to 2010 of patients with neurologic impairment who required mechanical ventilation and subsequently received a bedside swallow evaluation (BSE) by a speech-language pathologist.ResultsA BSE was performed after mechanical ventilation in 25% (630/2,484) of all patients. In the 184 patients with neurologic impairment, post-extubation dysphagia was present in 93% (171/184), and was classified as mild, moderate, or severe in 34% (62/184), 26% (48/184), and 33% (61/184), respectively. In univariate analyses, statistically significant risk factors for moderate/severe dysphagia included longer durations of mechanical ventilation and the presence of a tracheostomy. In multivariate analysis, adjusting for age, tracheostomy, cerebrovascular disease, and severity of illness, mechanical ventilation for >7 days remained independently associated with moderate/severe dysphagia (adjusted odds ratio = 4.48 (95%confidence interval = 2.14 to 9.81), P<0.01). The presence of moderate/severe dysphagia was also significantly associated with prolonged hospital lengthofstay, discharge status, and surgical placement of feeding tubes. When adjusting for age, severity of illness, and tracheostomy, patients with moderate/severe dysphagia stayed in the hospital 4.32 days longer after their initial BSE than patients with none/mild dysphagia (95% confidence interval = 3.04 to 5.60 days, P <0.01).ConclusionIn a cohort of critically ill patients with neurologic impairment, longer duration of mechanical ventilation is independently associated with post-extubation dysphagia, and the development of post-extubation dysphagia is independently associated with a longer hospital length of stay after the initial BSE.

Diagnosis and treatment of post-extubation dysphagia: Results from a national survey

PURPOSE This study sought to determine the utilization of speech-language pathologist (SLPs) for the diagnosis and treatment of post-extubation dysphagia in survivors of mechanical ventilation. METHODS We designed, validated, and mailed a survey to 1,966 inpatient SLPs who routinely evaluate patients for post-extubation dysphagia. RESULTS Most SLP diagnostic evaluations (60%; 95% CI, 59%-62%) were performed using clinical techniques with uncertain accuracy. Instrumental diagnostic tests (such as fluoroscopy and endoscopy) are more likely to be available at university than community hospitals. After adjusting for hospital size and academic affiliation, instrumental test use varied significantly by geographical region. Treatments for post-extubation dysphagia usually involved dietary adjustment (76%; 95% CI, 73-79%) and postural changes/compensatory maneuvers (86%; 95% CI, 84-88%), rather than on interventions aimed to improve swallowing function (24%; 95% CI, 21-27%). CONCLUSIONS SLPs frequently evaluate acute respiratory failure survivors. However, diagnostic evaluations rely mainly upon bedside techniques with uncertain accuracy. The use of instrumental tests varies by geographic location and university affiliation. Current diagnostic practices and feeding decisions for critically ill patients should be viewed with caution until further studies determine the accuracy of bedside detection methods.

The Association of Adiponectin with Computed Tomography Phenotypes in Chronic Obstructive Pulmonary Disease

RATIONALE Chronic obstructive pulmonary disease (COPD) is a heterogeneous disorder associated with systemic manifestations that contribute to its morbidity and mortality. Recent work suggests that biomarker signatures in the blood may be useful in evaluating COPD phenotypes and may provide insight into the pathophysiology of systemic manifestations. Adiponectin, primarily produced by fat cells, has been implicated in the pathophysiology of emphysema. OBJECTIVES To investigate the association of adiponectin with clinical and radiologic COPD phenotypes. METHODS Adiponectin levels were determined in 633 individuals, including 432 individuals with COPD from a cohort of former or current smokers enrolled in the COPDGene study. Univariate and multiple regression analysis were used to examine the association of adiponectin with clinical and physiologic data together with quantitative high-resolution computed tomography parameters. MEASUREMENTS AND MAIN RESULTS Multiple regression analysis confirmed that higher plasma adiponectin levels were independently associated with emphysema, decreasing body mass index, female sex, older age, and lower percentage change in prebronchodilator/post-bronchodilator FEV1. CONCLUSIONS The association between plasma adiponectin and computed tomography-assessed emphysema suggests a contribution of adiponectin to the development of emphysema and highlights a role for metabolic derangements in the pathophysiology of emphysema.

Surrogate and patient discrepancy regarding consent for critical care research.

Objective:Critically ill patients frequently display impaired decision-making capacity due to their underlying illness and the use of sedating medications. Healthcare providers often rely on surrogates to make decisions for medical care and participation in clinical research. However, the accuracy of surrogate decisions for a variety of critical care research studies is poorly understood. Design:Cross-sectional observational study. Setting:Academic medical center. Patients:Medical intensive care unit patients and their designated surrogates. Intervention:Patients were asked whether they would consent to participate in hypothetical research studies of increasing complexity, and surrogates independently indicated whether they would consent to enroll the patient in the same scenarios. Results:Overall, 69 medical intensive care unit patients were enrolled into the study. The majority of surrogates were either the spouse (58%) or parent (22%) of the patient. The percentage of patients that would agree to participate in a research study and the percentage of surrogates that would agree to have the patient enrolled into a research study both declined as the risk of the study increased (p < .001 for both analyses). In addition, the overall discrepancy, the false-negative rates, and the false-positive rates between patient and surrogates were greater as the risk of the study increased (p < .001, p < .001, and p = .049, respectively). &kgr; values for all seven scenarios demonstrated less-than-moderate agreement (range 0.03–0.41). Conclusions:There are significant discrepancies in the willingness to participate in various types of clinical research proposals between critically ill patients and their surrogate decision makers. The results of this study raise concerns about the use of surrogate consent for inclusion of critically ill patients into research protocols.

Alcohol screening scores and 90-day outcomes in patients with acute lung injury

Objectives:The effects of excess alcohol consumption (alcohol misuse) on outcomes in patients with acute lung injury have been inconsistent, and there are no studies examining this association in the era of low tidal volume ventilation and a fluid conservative strategy. We sought to determine whether validated scores on the Alcohol Use Disorders Identification Test that correspond to past-year abstinence (zone 1), low-risk drinking (zone 2), mild to moderate alcohol misuse (zone 3), and severe alcohol misuse (zone 4) are associated with poor outcomes in patients with acute lung injury. Design:Secondary analysis. Setting:The Acute Respiratory Distress Syndrome Network, a consortium of 12 university centers (44 hospitals) dedicated to the conduct of multicenter clinical trials in patients with acute lung injury. Subjects:Patients meeting consensus criteria for acute lung injury enrolled in one of three recent Acute Respiratory Distress Syndrome Network clinical trials. Interventions:None. Measurements and Main Results:Of 1,133 patients enrolled in one of three Acute Respiratory Distress Syndrome Network studies, 1,037 patients had an Alcohol Use Disorders Identification Test score available for analysis. Alcohol misuse was common with 70 (7%) of patients having Alcohol Use Disorders Identification Test scores in zone 3 and 129 (12%) patients in zone 4. There was a U-shaped association between validated Alcohol Use Disorders Identification Test zones and death or persistent hospitalization at 90 days (34% in zone 1, 26% in zone 2, 27% in zone 3, 36% in zone 4; p < 0.05 for comparison of zone 1 to zone 2 and zone 4 to zone 2). In a multiple logistic regression model, there was a significantly higher odds of death or persistent hospitalization in patients having Alcohol Use Disorders Identification Test zone 4 compared with those in zone 2 (adjusted odds ratio 1.70; 95% confidence interval 1.00, 2.87; p = 0.048). Conclusions:Severe but not mild to moderate alcohol misuse is independently associated with an increased risk of death or persistent hospitalization at 90 days in acute lung injury patients.

Healthcare Utilization in Medical Intensive Care Unit Survivors with Alcohol Withdrawal

BACKGROUND Rehospitalization is an important and costly outcome that occurs commonly in several diseases encountered in the medical intensive care unit (ICU). Although alcohol use disorders are present in 40% of ICU survivors and alcohol withdrawal is the most common alcohol-related reason for admission to an ICU, rates and predictors of rehospitalization have not been previously reported in this population. METHODS We conducted a retrospective cohort study of medical ICU survivors with a primary or secondary discharge diagnosis of alcohol withdrawal using 2 administrative databases. The primary outcome was time to rehospitalization or death. Secondary outcomes included time to first emergency department or urgent care clinic visit in the subset of ICU survivors who were not rehospitalized. Cox proportional hazard models were adjusted for age, gender, race, homelessness, smoking, and payer source. RESULTS Of 1,178 patients discharged from the medical ICU over the study period, 468 (40%) were readmitted to the hospital and 54 (4%) died within 1 year. Schizophrenia (hazard ratio 2.23, 95% CI 1.57, 3.34, p < 0.001), anxiety disorder (hazard ratio 2.04, 95% CI 1.30, 3.32, p < 0.01), depression (hazard ratio 1.62, 95% CI 1.05, 2.40, p = 0.03), and Deyo comorbidity score ≥3 (hazard ratio 1.43, 95% CI 1.09, 1.89, p = 0.01) were significant predictors of time to death or first rehospitalization. Bipolar disorder was associated with time to first emergency department or urgent care clinic visit (hazard ratio 2.03, 95% CI 1.24, 3.62, p < 0.01) in the 656 patients who were alive and not rehospitalized within 1 year. CONCLUSIONS The presence of a psychiatric comorbidity is a significant predictor of multiple measures of unplanned healthcare utilization in medical ICU survivors with a primary or secondary discharge diagnosis of alcohol withdrawal. This finding highlights the potential importance of targeting longitudinal multidisciplinary care to patients with a dual diagnosis.

Current Smoking Status Is Associated With Lower Quantitative CT Measures of Emphysema and Gas Trapping

Purpose: The purposes of this study were to evaluate the effect of smoking status on quantitative computed tomography CT measures of low-attenuation areas (LAAs) on inspiratory and expiratory CT and to provide a method of adjusting for this effect. Materials and Methods: A total of 6762 current and former smokers underwent spirometry and volumetric inspiratory and expiratory CT. Quantitative CT analysis was completed using open-source 3D Slicer software. LAAs were defined as lung voxels with attenuation values ⩽−950 Hounsfield units (HU) on inspiratory CT and ⩽−856 HU on expiratory CT and were expressed as percentage of CT lung volume (%LAAI-950 and %LAAE-856). Multiple linear regression was used to determine the effect of smoking status on %LAAI-950 and %LAAE-856 while controlling for demographic variables, spirometric lung function, and smoking history, as well as total lung capacity (%LAAI-950) or functional residual capacity (%LAAE-856). Quantile normalization was used to align the %LAAI-950 distributions for current and former smokers. Results: Mean %LAAI-950 was 4.2±7.1 in current smokers and 7.7±9.7 in former smokers (P<0.001). After adjusting for confounders, %LAAI-950 was 3.5 percentage points lower and %LAAE-856 was 6.0 percentage points lower in current smokers than in former smokers (P<0.001). After quantile normalization, smoking status was an insignificant variable in the inspiratory regression model, with %LAAI-950 being 0.27 percentage points higher in current smokers (P=0.13). Conclusions: After adjusting for patient demographics and lung function, current smokers display significantly lower %LAAI-950 and %LAAE-856 than do former smokers. Potential methods for adjusting for this effect would include adding a fixed value (eg, 3.5%) to the calculated percentage of emphysema in current smokers, or quantile normalization.

Surrogate Consent for Genetic Testing, the Reconsent Process, and Consent for Long-Term Outcomes in Acute Respiratory Distress Syndrome Trials

To the Editor: Advancing critical care research is necessary to improve patient outcomes and has been defined as a priority for our healthcare system (1). However, most critically ill patients are initially incapacitated due to their acute illness, and are unable to participate in informed consent for research participation decisions (2). Therefore, surrogates make decisions for patients and often do so without a priori knowledge of the patients’ wishes. The surrogate consent process to enroll critically ill patients into research studies is complex. During the initial consent for a clinical trial, surrogates may also be asked to consent for the collection of biospecimens from the patient, including genetic material. Though consent rates for most genetic studies are generally high, individuals who are able to consent for themselves often have concerns regarding the use of their genetic material (3). In addition, racial and ethnic disparities have been reported in the willingness of individuals to consent to their own participation in genetic studies (4–6). However, whether surrogates are willing to consent for the collection of genetic material from critically ill patients has not been previously determined. When a surrogate provides consent for a research study, surviving patients who regain decisional capacity should be reconsented for their prior and continued participation. This reconsent process is unique to critical care research, as other incapacitated research participants, such as those with dementia, usually do not regain consent capacity. A better understanding of this reconsent process may provide insight into the patient’s perception of the burden of participating in clinical research. Finally, multicenter clinical trials of critically ill patients are recommended to include assessment of long-term outcomes (LTO) (7). However, it is presently unclear whether critical care survivors are willing to participate in LTO assessments. Therefore, using 1,164 patients enrolled into three Acute Respiratory Distress Syndrome Network trials (ALTA, OMEGA, and EDEN) (8–10), we sought to better understand the surrogate consent for genetic studies, the reconsent process, and the willingness of critical care survivors to participate in subsequent LTO studies. At the time of consent for these three clinical trials, surrogates were asked to provide consent for the collection of the patient’s genetic material for three types of ancillary studies: (1) genetic studies related to the parent study only (n = 1164), (2) future genetic studies for any acute respiratory distress syndrome (ARDS)-related research (n = 1164), and (3) future genetic studies for non–ARDS-related research (n = 1059). Patient race was categorized as white, African American, other, or not reported. Patient ethnicity was defined as Hispanic or not Hispanic; thus, study patients could be coded as being any race and also Hispanic. When they regained decisional capacity sufficient to provide informed consent, surviving patients underwent reconsent for their study participation. In regard to LTO, surrogates were initially consented for subject participation in assessments at 6 and 12 months after ARDS onset. Patients meeting eligibility criteria and not reconsented by hospital discharge were reconsented for LTO participation when subsequently contacted by telephone. Some of the results of these studies have been previously reported in the form of abstracts (11, 12). Overall, surrogates were generally willing to consent to the collection of the patient’s genetic material for all three types of ancillary studies (type 1, 92.0%, 95% CI = 90.3–93.4%; type 2, 90.5%, 95% CI = 88.7–92.1%; and type 3, 84.6%, 95% CI = 82.3–86.7%). However, surrogates were statistically less likely to provide consent for genetic studies when the future use of the material was not related to the parent study or ARDS research in general (P < 0.05). In univariate and multivariate analyses, surrogates of African Americans and other races were less likely to consent for each of the three different genetic studies when compared with surrogates of white patients (Tables 1 and ​and2).2). Surrogates of Hispanic patients were less likely to consent for genetic testing related to the parent study and genetic testing for future ARDS research not related to the parent study (Tables 1 and ​and22). TABLE 1. SURROGATE CONSENT FOR ANCILLARY GENETIC SUBSTUDIES BY PATIENT RACE/ETHNICITY TABLE 2. SURROGATE CONSENT FOR ANCILLARY GENETIC SUBSTUDIES BY PATIENT RACE/ETHNICITY: MULTIVARIABLE ANALYSES Of the 946 surviving patients, 407 (43%, 95% CI = 40–46%) were not reconsented due to either not being assessed for regaining consent capacity (n = 165) or a perceived lack of decisional capacity upon assessment (n = 242) (Figure 1). Of patients who survived and regained decisional capacity sufficient to provide reconsent, 522 of 539 (97%, 95% CI = 96–98%) affirmed their study participation. A total of 659 surviving patients met eligibility criteria for LTO assessments. The majority, 440 (67%, 95% CI = 63–70%), had provided reconsent for participation prior to hospital discharge. The remaining 219 (33%, 95% CI = 29–37%) were either not assessed for reconsent or lacked reconsent capacity in the hospital. Subsequently, they were consented for LTO assessment at the time of the initial follow-up telephone call conducted as part of the LTO assessment protocol. Overall, 211 of 219 (96%, 95% CI = 93–99%) were willing to consent to ongoing LTO study participation. Figure 1. Diagram of the reconsent process. Optimizing the surrogate consent process for critical care research is imperative to both protect the rights of vulnerable patients and increase study enrollment. To our knowledge, this is the first investigation examining the willingness of surrogates to provide informed consent for the collection of biospecimen samples from critically ill patients. In our study, surrogates were less willing to provide consent for future non–ARDS-related genetic research studies. Patients are generally willing to consent broadly to the use of biospecimens, but desire information regarding the type of research performed on their specimens before providing consent (3, 4). Similarly, our results demonstrate that surrogates are also less willing to provide consent for the collection of genetic material from patients when there is uncertainty regarding the use of the genetic material. Higher rates of study participation from surrogates may occur with enhanced communication concerning the actual use of the biospecimen material. In general, individuals of racial and ethnic minorities are less willing to agree to participate in clinical research studies (3–6). The lower consent rates for genetic studies in surrogates of underrepresented minorities highlights potential concerns regarding cultural differences and disparities in medical research (13, 14). Future prospective studies should examine the role of racial and ethnic disparities of surrogates in providing consent for a critically ill patient’s participation in research. In 2008, the Office for Human Research Participations Subcommittee for the Inclusion of Individuals with Impaired Decision Making in Research recommended that incapacitated research participants who are anticipated to regain consent capacity be evaluated for reconsent (15). Our high rates of reconsent may indicate that subjects agreed with their surrogates’ consent decision; however, this would be an oversimplification of a complex consent process. Previous studies have shown that significant discrepancies exist between critically ill patients and their surrogates regarding willingness to participate in hypothetical critical care research studies (16). A complete understanding of the reconsent process is also inherently hampered by the inability to include patients who died before they could be reconsented (i.e., survivorship bias). Furthermore, reconsent rates may be influenced by the magnitude of burden from continued study participation at the time of reconsent. As 43% of the surviving patients were not able to be reconsented, our results raise important concerns about the feasibility of conducting these assessments. To improve the conduct of the reconsent process, specific tools to assess decision-making capacity exist and should be used, and research personnel should be properly trained to reliably conduct competency assessments (17–19). Although obtaining LTO assessments of critical care survivors is important, concerns have been raised regarding feasibility of these studies and cohort retention (20). Our study demonstrates that subjects are willing to be contacted for LTO assessments, and therefore, high rates of cohort retention are possible in studies of critical care survivors. In conclusion, our study begins to examine the nuances of the surrogate consent and reconsent process, and demonstrates the need for future investigation in this area.