Citations

The outcome of critical illness depends not only on life threatening pathophysiologic disturbances, but also on several complex “system” dimensions: health care providers’ performance, organizational factors, environmental factors, family preferences and the interactions between each component. Systems engineering tools offer a novel approach which can facilitate a “systems understanding” of patient-environment interactions enabling advances in the science of healthcare delivery. Due to the complexity of operations in critical care medicine, certain assumptions are needed in order to understand system behavior. Patient variation and uncertainties underlying these assumptions present a challenge to investigators wishing to model and improve health care delivery processes. In this chapter we present a systems engineering approach to modeling critical care delivery using sepsis resuscitation as an example condition.

BACKGROUND: Many patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS) have had recent healthcare interventions prior to developing ALI/ARDS. OBJECTIVE: To determine the timing of ALI/ARDS onset in relation to hospital admission and other healthcare interventions. METHODS: We conducted a population-based observational cohort study with a validated electronic surveillance tool, and identified patients with possible ALI/ARDS among critically ill adults at Mayo Clinic hospitals that provide critical care services for Olmsted County, Minnesota, in 2006. Trained investigators independently reviewed electronic medical records and confirmed the presence and timing of ALI/ARDS based on the American-European consensus definition. RESULTS: Of 124 episodes of ALI in 118 patients, only 5 did not fulfill the ARDS criteria. The syndrome developed a median 30 hours (IQR 10–82 h) after hospital admission in 79 patients (67%). ARDS was present on admission in 39 patients (33%), of whom 14 had recent hospitalization, 6 were transferred from nursing homes, and 3 had recent out-patient contact (1 antibiotic prescription, 1 surgical intervention, and 1 chemotherapy). Only 16 ARDS patients (14%) did not have known recent contact with a healthcare system. Compared to ARDS on admission, hospital-acquired ARDS was more likely to occur in surgery patients (54% vs 15%, P < .001), and had longer adjusted hospital stay (mean difference 8.9 d, 95% CI 0.3–17.4, P = .04). CONCLUSIONS: ARDS in the community most often develops either during hospitalization or in patients who recently had contact with a healthcare system. These findings have important implications for potential preventive strategies.

A 15-gene expression signature predicts whether a patient with diffuse large B cell lymphoma will respond to dacetuzumab, a therapeutic antibody.

The epithelial chloride channel CFTR is a glycoprotein that is modified by two N-linked oligosaccharides. The most common mutant CFTR protein in patients with cystic fibrosis, ΔF508, is misfolded and retained by ER quality control. As oligosaccharide moieties of glycoproteins are known to mediate interactions with ER lectin chaperones, we investigated the role of N-linked glycosylation in the processing of wild-type and ΔF508 CFTR. We found that N-glycosylation and ER lectin interactions are not major determinants of trafficking of wild-type and ΔF508 from the ER to the plasma membrane. Unglycosylated CFTR, generated by removal of glycosylation sites or treatment of cells with the N-glycosylation inhibitor tunicamycin, did not bind calnexin, but did traffic to the cell surface and exhibited chloride channel activity. Most importantly, unglycosylated ΔF508 CFTR still could not escape quality control in the early secretory pathway and remained associated with the ER. However, the absence of N-linked oligosaccharides did reduce the stability of wild-type CFTR, causing significantly more-rapid turnover in post-ER compartments. Surprisingly, the individual N-linked carbohydrates do not play equivalent roles and modulate the fate of the wild-type protein in different ways in its early biosynthetic pathway.

This study compared and quantified electromyographic muscle activation of the rotator cuff with the isometric torque generated by performing shoulder rotation in various positions. Twenty healthy volunteers were tested in 29 shoulder positions. Using a Cybex II dy namometer synchronously with electromyography, surface electrodes were placed over the pectoralis major muscle and three parts of the deltoid muscle. Intramuscular wire electrodes were inserted into the four rotator cuff muscles. We found that the greatest external rotation isometric force is generated in the frontal and scapular planes in the neutral or full internal rotation positions. The sagittal, dependent, and the scapular plane with 45° of elevation in rotational posi tions of either full or half external rotation generated the greatest torques for internal rotation isometric force. The rotator cuff muscles generated greatest electro myographic activity in neutral to midrotational posi tions. The scapular plane with 90° of shoulder eleva tion in neutral rotation best isolated the subscapularis muscle. The infraspinatus-teres minor muscles were isolated in the sagittal plane with 90° of shoulder ele vation in a half externally rotated position. We were unable to isolate the supraspinatus muscle in any of these tested positions. These positions are recom mended for manual muscle testing and for strengthen ing these muscles.