Bradford J. Glavan

Using the medical record to evaluate the quality of end-of-life care in the intensive care unit*

Rationale:We investigated whether proposed “quality markers” within the medical record are associated with family assessment of the quality of dying and death in the intensive care unit (ICU). Objective:To identify chart-based markers that could be used as measures for improving the quality of end-of-life care. Design:A multicenter study conducting standardized chart abstraction and surveying families of patients who died in the ICU or within 24 hrs of being transferred from an ICU. Setting:ICUs at ten hospitals in the northwest United States. Patients:Overall, 356 patients who died in the ICU or within 24 hrs of transfer from an ICU. Measurements:The 22-item family assessed Quality of Dying and Death (QODD-22) questionnaire and a single item rating of the overall quality of dying and death (QODD-1). Analysis:The associations of chart-based quality markers with QODD scores were tested using Mann-Whitney U tests, Kruskal-Wallis tests, or Spearmans rank-correlation coefficients as appropriate. Results:Higher QODD-22 scores were associated with documentation of a living will (p = .03), absence of cardiopulmonary resuscitation performed in the last hour of life (p = .01), withdrawal of tube feeding (p = .04), family presence at time of death (p = .02), and discussion of the patients wish to withdraw life support during a family conference (p < .001). Additional correlates with a higher QODD-1 score included use of standardized comfort care orders and occurrence of a family conference (p ≤ .05). Conclusions:We identified chart-based variables associated with higher QODD scores. These QODD scores could serve as targets for measuring and improving the quality of end-of-life care in the ICU.

Spiritual care of families in the intensive care unit

Objectives:There is growing recognition of the importance of spiritual care as a quality domain for critically ill patients and their families, but there is a paucity of research to guide quality improvement in this area. Our goals were to: 1) determine whether intensive care unit (ICU) family members who rate an item about their spiritual care are different from family members who skip the item or rate the item as “not applicable” and 2) identify potential determinants of higher family satisfaction with spiritual care in the ICU. Design:Cross-sectional study, using data from a cluster randomized trial aimed at improving end-of-life care in the ICU. Setting:ICUs in ten Seattle-area hospitals. Subjects:A total of 356 family members of patients dying during an ICU stay or within 24 hrs of ICU discharge. Intervention:None. Measurements and Main Results:Family members were surveyed about spiritual care in the ICU. Chart abstractors obtained clinical variables including end-of-life care processes and family conference data. The 259 of 356 family members (73%) who rated their spiritual care were slightly younger than family members who did not rate this aspect of care (p = .001). Multiple regression revealed family members were more satisfied with spiritual care if a pastor or spiritual advisor was involved in the last 24 hrs of the patients life (p = .007). In addition, there was a strong association between satisfaction with spiritual care and satisfaction with the total ICU experience (p < .001). Ratings of spiritual care were not associated with any other demographic or clinical variables. Conclusions:These findings suggest that for patients dying in the ICU, clinicians should assess each familys spiritual needs and consult a spiritual advisor if desired by the family. Further research is needed to develop a comprehensive approach to ICU care that meets not only physical and psychosocial but also spiritual needs of patients and their families.

Genetic Variation in the FAS Gene and Associations with Acute Lung Injury

RATIONALE Fas (CD95) modulates apoptosis and inflammation and is believed to play an important role in lung injury. OBJECTIVES To determine if common genetic variation in FAS is associated with acute lung injury (ALI) susceptibility, risk of death, and FAS gene expression. METHODS We genotyped 14 single nucleotide polymorphisms (tagSNPS) in FAS in samples from healthy white volunteers (control subjects, n = 294) and patients with ALI (cases, n = 324) from the ARDSnet Fluid and Catheter Treatment Trial (FACTT). FAS genotypes associated with ALI in the discovery study were confirmed in a nested case-control validation study of critically ill patients at risk for ALI (n = 657). We also tested for associations between selected tagSNPS and FAS mRNA levels in whole blood from healthy control subjects exposed to media alone or LPS ex vivo. MEASUREMENTS AND MAIN RESULTS We identified associations between four tagSNPs in FAS (FAS(-11341A>T) [rs17447140], FAS(9325G>A) [rs2147420], FAS(21541C>T) [rs2234978], and FAS(24484A>T) [rs1051070]) and ALI case status. Haplotype-based analyses suggested that three of the tagSNPs (FAS(9325G>A), FAS(21541C>T), and FAS(24484A>T)) function as a unit. The association with this haplotype and ALI was validated in a nested case-control study of at-risk subjects (P = 0.05). This haplotype was also associated with increased FAS mRNA levels in response to LPS stimulation. There was no association between FAS polymorphisms and risk of death among ALI cases. CONCLUSIONS Common genetic variants in FAS are associated with ALI susceptibility. This is the first genetic evidence supporting a role for FAS in ALI.

Inflammation and immune-related candidate gene associations with acute lung injury susceptibility and severity: a validation study.

Introduction Common variants in genes related to inflammation, innate immunity, epithelial cell function, and angiogenesis have been reported to be associated with risks for Acute Lung Injury (ALI) and related outcomes. We tested whether previously-reported associations can be validated in an independent cohort at risk for ALI. Methods We identified 37 genetic variants in 27 genes previously associated with ALI and related outcomes. We prepared allelic discrimination assays for 12 SNPs from 11 genes with MAF>0.05 and genotyped these SNPs in Caucasian subjects from a cohort of critically ill patients meeting criteria for the systemic inflammatory response syndrome (SIRS) followed for development of ALI, duration of mechanical ventilation, and in-hospital death. We tested for associations using additive and recessive genetic models. Results Among Caucasian subjects with SIRS (n = 750), we identified a nominal association between rs2069832 in IL6 and ALI susceptibility (ORadj 1.61; 95% confidence interval [CI], 1.04–2.48, P = 0.03). In a sensitivity analysis limiting ALI cases to those who qualified for the Acute Respiratory Distress Syndrome (ARDS), rs61330082 in NAMPT was nominally associated with risk for ARDS. In terms of ALI outcomes, SNPs in MBL2 (rs1800450) and IL8 (rs4073) were nominally associated with fewer ventilator-free days (VFDs), and SNPs in NFE2L2 (rs6721961) and NAMPT (rs61330082) were nominally associated with 28-day mortality. The directions of effect for these nominal associations were in the same direction as previously reported but none of the associations survived correction for multiple hypothesis testing. Conclusion Although our primary analyses failed to statistically validate prior associations, our results provide some support for associations between SNPs in IL6 and NAMPT and risk for development of lung injury and for SNPs in IL8, MBL2, NFE2L2 and NAMPT with severity in ALI outcomes. These associations provide further evidence that genetic factors in genes related to immunity and inflammation contribute to ALI pathogenesis.

Long-term outcomes in elderly survivors of cardiac arrest.

n engl j med 368;25 nejm.org june 20, 2013 2437 We also agree that untreated HIV infection is probably a confounder in the recovery of children with severe acute malnutrition.1 For the purposes of our study, we did not perform universal testing of enrolled children for HIV in order to replicate real-world practices in rural health centers in Malawi. At these centers, trained HIV counselors and rapid HIV-antibody test kits are often not available, and the stigma associated with HIV testing often scares caregivers away from bringing their malnourished children to health centers for care. We therefore chose not to conduct universal testing for HIV but instead asked about previous testing at the time of study enrollment and then privately encouraged testing only for those children who were not recovering promptly, a practice that would be part of usual care in this setting. We disagree with the sentiment expressed by Okeke et al. that the risk of antibiotic resistance outweighs the key benefit seen in this study — a 40% reduction in mortality from a disease that affects at least 20 million children annually. Although we certainly do not wish to contribute to the growing plague of antibiotic resistance, it is difficult to ignore the potentially lifesaving benefit proffered by this affordable and readily available adjunct to current therapy; meanwhile, the promotion of breast-feeding and improved sanitation should certainly be pursued simultaneously, as Bowen and Tauxe suggest. The approaches to diagnosis and therapy tested in this study — syndromic, simple, and standardized — are suited to the strategy of integrated community case management,2 which has already been effective in the treatment of other common childhood illnesses when implemented by community health workers. In contrast with the assertion by Okeke et al., a high relapse rate has not been reported after the successful treatment of severe acute malnutrition,3 probiotics have not proved to be of significant benefit in this context,4 and the study they cite by Alcoba et. al, which was conducted before our trial, specifically suggests that a randomized, controlled trial is needed to definitively answer the question about the need for antibiotics as part of the management of severe malnutrition.5 We agree that our results should not be extrapolated to those with moderate malnutrition and that our findings should be implemented judiciously.

Genetic Variation in MAP3K1 Associates with Ventilator-Free Days in Acute Respiratory Distress Syndrome

&NA; Mitogen‐activated protein kinase kinase kinase 1 (MAP3K1) regulates numerous intracellular signaling pathways involved in inflammation and apoptosis. We hypothesized that genetic variation in MAP3K1 might be associated with outcomes in patients with acute respiratory distress syndrome (ARDS), and that these variants would alter MAP3K1‐mediated changes in inflammation and transcriptional regulation. To test this hypothesis, we genotyped single‐nucleotide polymorphisms covering linkage disequilibrium bins in MAP3K1 in 306 subjects with ARDS from the ARDSNet FACTT (Fluid and Catheter Treatment Trial) study, and tested for associations between MAP3K1 single‐nucleotide polymorphisms and ventilator‐free days (VFDs) and mortality. We then validated these associations in a separate cohort of 241 patients with ARDS from Harborview Medical Center (Seattle, WA). We found the variant allele of rs832582 (MAP3K1906Val) was significantly associated with decreased VFDs using multivariate linear regression (−6.1 d, false discovery rate = 0.06) in the FACTT cohort. In the Harborview Medical Center cohort, subjects homozygous for MAP3K1906Val also had decreased VFDs (−15.1 d, false discovery rate < 0.01), and increased 28‐day mortality (all subjects homozygous for the rare allele died). In whole blood stimulated with various innate immune agonists ex vivo, MAP3K1906Val was associated with increased IL‐1&bgr;, IL‐6, IL‐8, monocyte chemoattractant protein 1, and TNF‐&agr; production. Transcriptome analysis of whole blood stimulated with Toll‐like receptor 4 agonist ex vivo demonstrated enrichment of inflammatory gene sets in subjects homozygous for MAP3K1906Val. Our findings show a robust association between the variant allele of rs832582 (MAP3K1906Val) and decreased VFDs in patients with ARDS and suggest that this variant may predispose individuals to a greater inflammatory response.