Matthew R. Baldwin

A Prognostic Model for 6-Month Mortality in Elderly Survivors of Critical Illness

BACKGROUND Although 1.4 million elderly Americans survive hospitalization involving intensive care annually, many are at risk for early mortality following discharge. No models that predict the likelihood of death after discharge exist explicitly for this population. Therefore, we derived and externally validated a 6-month postdischarge mortality prediction model for elderly ICU survivors. METHODS We derived the model from medical record and claims data for 1,526 consecutive patients aged ≥ 65 years who had their first medical ICU admission in 2006 to 2009 at a tertiary-care hospital and survived to discharge (excluding those patients discharged to hospice). We then validated the model in 1,010 patients from a different tertiary-care hospital. RESULTS Six-month mortality was 27.3% and 30.2% in the derivation and validation cohorts, respectively. Independent predictors of mortality (in descending order of contribution to the models predictive power) were a do-not-resuscitate order, older age, burden of comorbidity, admission from or discharge to a skilled-care facility, hospital length of stay, principal diagnoses of sepsis and hematologic malignancy, and male sex. For the derivation and external validation cohorts, the area under the receiver operating characteristic curve was 0.80 (SE, 0.01) and 0.71 (SE, 0.02), respectively, with good calibration for both (P = 0.31 and 0.43). CONCLUSIONS Clinical variables available at hospital discharge can help predict 6-month mortality for elderly ICU survivors. Variables that capture elements of frailty, disability, the burden of comorbidity, and patient preferences regarding resuscitation during the hospitalization contribute most to this models predictive power. The model could aid providers in counseling elderly ICU survivors at high risk of death and their families.

The feasibility of measuring frailty to predict disability and mortality in older medical intensive care unit survivors

PURPOSE To determine whether frailty can be measured within 4 days prior to hospital discharge in older intensive care unit (ICU) survivors of respiratory failure and whether it is associated with post-discharge disability and mortality. MATERIALS AND METHODS We performed a single-center prospective cohort study of 22 medical ICU survivors age 65 years or older who had received noninvasive or invasive mechanical ventilation for at least 24 hours. Frailty was defined as a score of ≥3 using Frieds 5-point scale. We measured disability with the Katz Activities of Daily Living. We estimated unadjusted associations between Frieds frailty score and incident disability at 1-month and 6-month mortality using Cox proportional hazard models. RESULTS The mean (SD) age was 77 (9) years, mean Acute Physiology and Chronic Health Evaluation II score was 27 (9.7), mean frailty score was 3.4 (1.3), and 18 (82%) were frail. Nine subjects (41%) died within 6 months, and all were frail. Each 1-point increase in frailty score was associated with a 90% increased rate of incident disability at 1-month (rate ratio: 1.9, 95% CI 0.7-4.9) and a threefold increase in 6-month mortality (rate ratio: 3.0, 95% CI 1.4-6.3). CONCLUSIONS Frailty can be measured in older ICU survivors near hospital discharge and is associated with 6-month mortality in unadjusted analysis. Larger studies to determine if frailty independently predicts outcomes are warranted.

Preoperative Serum Albumin Levels Predict 1-Year Postoperative Survival of Patients Undergoing Heart Transplantation

Background—Serum albumin concentration has been recognized as a marker of nutrition, severity of inflammation, and hepatic function in patients with various chronic diseases. The purpose of this study was to investigate the impact of pretransplant serum albumin concentration on post-transplant outcome in heart transplant recipients. Methods and Results—Preoperative laboratory variables, including albumin concentration and donor-related information, were obtained from 822 consecutive patients undergoing heart transplant at Columbia University Medical Center between 1999 and 2010. The association between pretransplant albumin concentration and post-transplant 1-year survival was analyzed. Available data from the United Network for Organ Sharing (n=13 671) were also analyzed to evaluate the impact of preoperative albumin levels on post-transplant outcome. In our cohort, multivariable analysis revealed that preoperative albumin (mg/dL; hazard ratio, 0.46; P<0.0001) and preoperative total bilirubin (mg/dL; hazard ratio, 1.26; P=0.0002) were associated with post-transplant 1-year mortality. This implied that for every 1 mg/dL increase in albumin concentration, the post-transplant 1-year mortality rate decreased by 54%. The Kaplan–Meier analysis based on our patients cohort and the United Network for Organ Sharing dataset showed lower survival rate at 1-year post-transplant in patients with albumin levels ⩽3.5 mg/dL compared with those with >3.5 mg/dL (our patients, 91.3 versus 72.4%; P<0.0001; United Network for Organ Sharing, 88.4 versus 84.8%; P<0.0001). Conclusions—Pretransplant serum albumin concentration is a strong prognostic marker for post-transplant survival in heart transplant recipients.

Donor Age and Early Graft Failure After Lung Transplantation: A Cohort Study

Lungs from older adult organ donors are often unused because of concerns for increased mortality. We examined associations between donor age and transplant outcomes among 8860 adult lung transplant recipients using Organ Procurement and Transplantation Network and Lung Transplant Outcomes Group data. We used stratified Cox proportional hazard models and generalized linear mixed models to examine associations between donor age and both 1‐year graft failure and primary graft dysfunction (PGD). The rate of 1‐year graft failure was similar among recipients of lungs from donors age 18–64 years, but severely ill recipients (Lung Allocation Score [LAS] >47.7 or use of mechanical ventilation) of lungs from donors age 56–64 years had increased rates of 1‐year graft failure (p‐values for interaction = 0.04 and 0.02, respectively). Recipients of lungs from donors <18 and ≥65 years had increased rates of 1‐year graft failure (adjusted hazard ratio [HR] 1.23, 95% CI 1.01–1.50 and adjusted HR 2.15, 95% CI 1.47–3.15, respectively). Donor age was not associated with the risk of PGD. In summary, the use of lungs from donors age 56 to 64 years may be safe for adult candidates without a high LAS and the use of lungs from pediatric donors is associated with a small increase in early graft failure.

Hypoalbuminemia and Early Mortality After Lung Transplantation: A Cohort Study

Hypoalbuminemia predicts disability and mortality in patients with various illnesses and in the elderly. The association between serum albumin concentration at the time of listing for lung transplantation and the rate of death after lung transplantation is unknown. We examined 6808 adults who underwent lung transplantation in the United States between 2000 and 2008. We used Cox proportional hazard models and generalized additive models to examine multivariable‐adjusted associations between serum albumin and the rate of death after transplantation. The median follow‐up time was 2.7 years. Those with severe (0.5–2.9 g/dL) and mild hypoalbuminemia (3.0–3.6 g/dL) had posttransplant adjusted mortality rate ratios of 1.35 (95% CI: 1.12–1.62) and 1.15 (95% CI: 1.04–1.27), respectively. For each 0.5 g/dL decrease in serum albumin concentration the 1‐year and overall mortality rate ratios were 1.48 (95% CI: 1.21–1.81) and 1.26 (95% CI: 1.11–1.43), respectively. The association between hypoalbuminemia and posttransplant mortality was strongest in recipients with cystic fibrosis and interstitial lung disease. Hypoalbuminemia is an independent risk factor for death after lung transplantation.

A score to predict and stratify risk of tuberculosis in adult contacts of tuberculosis index cases: a prospective derivation and external validation cohort study

BACKGROUND Contacts of tuberculosis index cases are at increased risk of developing tuberculosis. Screening, preventive therapy, and surveillance for tuberculosis are underused interventions in contacts, particularly adults. We developed a score to predict risk of tuberculosis in adult contacts of tuberculosis index cases. METHODS In 2002-06, we recruited contacts aged 15 years or older of index cases with pulmonary tuberculosis who lived in desert shanty towns in Ventanilla, Peru. We followed up contacts for tuberculosis until February, 2016. We used a Cox proportional hazards model to identify index case, contact, and household risk factors for tuberculosis from which to derive a score and classify contacts as low, medium, or high risk. We validated the score in an urban community recruited in Callao, Peru, in 2014-15. FINDINGS In the derivation cohort, we identified 2017 contacts of 715 index cases, and median follow-up was 10·7 years (IQR 9·5-11·8). 178 (9%) of 2017 contacts developed tuberculosis during 19 147 person-years of follow-up (incidence 0·93 per 100 person-years, 95% CI 0·80-1·08). Risk factors for tuberculosis were body-mass index, previous tuberculosis, age, sustained exposure to the index case, the index case being in a male patient, lower community household socioeconomic position, indoor air pollution, previous tuberculosis among household members, and living in a household with a low number of windows per room. The 10-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 2·8% (95% CI 1·7-4·4), 6·2% (4·8-8·1), and 20·6% (17·3-24·4). The 535 (27%) contacts classified as high risk accounted for 60% of the tuberculosis identified during follow-up. The score predicted tuberculosis independently of tuberculin skin test and index-case drug sensitivity results. In the external validation cohort, 65 (3%) of 1910 contacts developed tuberculosis during 3771 person-years of follow-up (incidence 1·7 per 100 person-years, 95% CI 1·4-2·2). The 2·5-year risks of tuberculosis in the low-risk, medium-risk, and high-risk groups were, respectively, 1·4% (95% CI 0·7-2·8), 3·9% (2·5-5·9), and 8·6%· (5·9-12·6). INTERPRETATION Our externally validated risk score could predict and stratify 10-year risk of developing tuberculosis in adult contacts, and could be used to prioritise tuberculosis control interventions for people most likely to benefit. FUNDING Wellcome Trust, Department for International Development Civil Society Challenge Fund, Joint Global Health Trials consortium, Bill & Melinda Gates Foundation, Imperial College National Institutes of Health Research Biomedical Research Centre, Foundation for Innovative New Diagnostics, Sir Halley Stewart Trust, WHO, TB REACH, and Innovation for Health and Development.

Refining Low Physical Activity Measurement Improves Frailty Assessment in Advanced Lung Disease and Survivors of Critical Illness

&NA; Rationale: The frail phenotype has gained popularity as a clinically relevant measure in adults with advanced lung disease and in critical illness survivors. Because respiratory disease and chronic illness can greatly limit physical activity, the measurement of participation in traditional leisure time activities as a frailty component may lead to substantial misclassification of frailty in pulmonary and critical care patients. Objectives: To test and validate substituting the Duke Activity Status Index (DASI), a simple 12‐item questionnaire, for the Minnesota Leisure Time Physical Activity (MLTA) questionnaire, a detailed questionnaire covering 18 leisure time activities, as the measure of low activity in the Fried frailty phenotype (FFP) instrument. Methods: In separate multicenter prospective cohort studies of adults with advanced lung disease who were candidates for lung transplant and older survivors of acute respiratory failure, we assessed the FFP using either the MLTA or the DASI. For both the DASI and MLTA, we evaluated content validity by testing floor effects and construct validity through comparisons with conceptually related factors. We tested the predictive validity of substituting the DASI for the MLTA in the FFP assessment using Cox models to estimate associations between the FFP and delisting/death before transplant in those with advanced lung disease and 6‐month mortality in older intensive care unit (ICU) survivors. Results: Among 618 adults with advanced lung disease and 130 older ICU survivors, the MLTA had a substantially greater floor effect than the DASI (42% vs. 1%, and 49% vs. 12%, respectively). The DASI correlated more strongly with strength and function measures than did the MLTA in both cohorts. In models adjusting for age, sex, comorbidities, and illness severity, substitution of the DASI for the MLTA led to stronger associations of the FFP with delisting/death in lung transplant candidates (FFP‐MLTA hazard ratio [HR], 1.42; 95% confidence interval [CI], 0.55‐3.65; FFP‐DASI HR, 2.99; 95% CI, 1.03‐8.65) and with mortality in older ICU survivors (FFP‐MLTA HR, 2.68; 95% CI, 0.62‐11.6; FFP‐DASI HR, 5.71; 95% CI, 1.34‐24.3). Conclusions: The DASI improves the construct and predictive validity of frailty assessment in adults with advanced lung disease or recent critical illness. This simple questionnaire should replace the more complex MLTA in assessing the frailty phenotype in these populations.

A Novel Picture Guide to Improve Spiritual Care and Reduce Anxiety in Mechanically Ventilated Adults in the Intensive Care Unit

RATIONALE Hospital chaplains provide spiritual care that helps patients facing serious illness cope with their symptoms and prognosis, yet because mechanically ventilated patients cannot speak, spiritual care of these patients has been limited. OBJECTIVES To determine the feasibility and measure the effects of chaplain-led picture-guided spiritual care for mechanically ventilated adults in the intensive care unit (ICU). METHODS We conducted a quasi-experimental study at a tertiary care hospital between March 2014 and July 2015. Fifty mechanically ventilated adults in medical or surgical ICUs without delirium or dementia received spiritual care by a hospital chaplain using an illustrated communication card to assess their spiritual affiliations, emotions, and needs and were followed until hospital discharge. Feasibility was assessed as the proportion of participants able to identify spiritual affiliations, emotions, and needs using the card. Among the first 25 participants, we performed semistructured interviews with 8 ICU survivors to identify how spiritual care helped them. For the subsequent 25 participants, we measured anxiety (on 100-mm visual analog scales [VAS]) immediately before and after the first chaplain visit, and we performed semistructured interviews with 18 ICU survivors with added measurements of pain and stress (on ±100-mm VAS). MEASUREMENTS AND MAIN RESULTS The mean (SD) age was 59 (±16) years, median mechanical ventilation days was 19.5 (interquartile range, 7-29 d), and 15 (30%) died in-hospital. Using the card, 50 (100%) identified a spiritual affiliation, 47 (94%) identified one or more emotions, 45 (90%) rated their spiritual pain, and 36 (72%) selected a chaplain intervention. Anxiety after the first visit decreased 31% (mean score change, -20; 95% confidence interval, -33 to -7). Among 28 ICU survivors, 26 (93%) remembered the intervention and underwent semistructured interviews, of whom 81% felt more capable of dealing with their hospitalization and 0% felt worse. The 18 ICU survivors who underwent additional VAS testing during semistructured follow-up interviews reported a 49-point reduction in stress (95% confidence interval, -72 to -24) and no significant change in physical pain that they attributed to picture-guided spiritual care. CONCLUSIONS Chaplain-led picture-guided spiritual care is feasible among mechanically ventilated adults and shows potential for reducing anxiety during and stress after an ICU admission.

The Frailty Phenotype and Palliative Care Needs of Older Survivors of Critical Illness

To assess symptoms in older intensive care unit (ICU) survivors and determine whether post‐ICU frailty identifies those with the greatest palliative care needs.

Initial Right Ventricular Dysfunction Severity Identifies Severe Peripartum Cardiomyopathy Phenotype With Worse Early and Overall Outcomes: A 24‐Year Cohort Study

Background Outcomes in peripartum cardiomyopathy (PPCM) vary. We sought to determine whether severity of left or right ventricular dysfunction (RVD) at PPCM diagnosis differentially associates with adverse outcomes. Methods and Results We conducted a single‐center retrospective cohort study of 53 patients with PPCM. The primary outcome was a composite of left ventricular assist device implantation, cardiac transplantation, or death. We used Kaplan‐Meier curves to examine event‐free survival and Cox proportional hazards models to examine associations of left ventricular (LV) ejection fraction <30%, LV end‐diastolic diameter ≥60 mm, and moderate‐to‐severe RVD at PPCM diagnosis with the primary outcome. Median (interquartile range) follow‐up time was 3.6 (1.4–7.3) years. Seventeen patients (32%) experienced the primary outcome, of whom 11 had moderate‐to‐severe RVD at time of PPCM diagnosis. Overall event‐free survival differed by initial RVD severity and LV ejection fraction <30%, but not by LV end‐diastolic diameter ≥60 mm. In univariable analyses, LV ejection fraction <30% and moderate‐to‐severe RVD were associated with the outcome (hazard ratios [95% confidence intervals] of 4.85 [1.11–21.3] and 4.26 [1.47–11.6], respectively). In a multivariable model with LV ejection fraction <30%, LV end‐diastolic diameter ≥60 mm, and moderate‐to‐severe RVD, only moderate‐to‐severe RVD was independently associated with the outcome (hazard ratio [95% confidence interval], 3.21 [1.13–9.10]). Although most outcomes occurred within the first year, nearly a third occurred years after PPCM diagnosis. Conclusions Initial moderate‐to‐severe RVD is associated with a more advanced cardiomyopathy phenotype and increased risk of adverse outcomes in PPCM, within and beyond the first year of diagnosis. By identifying a worse PPCM phenotype, initial moderate‐to‐severe RVD may prompt earlier consideration of advanced heart replacement therapies.