BACKGROUND:Tracer antibiotic algorithms using administrative data were investigated to estimate mortality attributable to extensively drug-resistant gram-negative infections (GNIs).METHODS:Among adult inpatients coded for GNIs, colistin cases and 2 comparator cohorts (non-carbapenem β-lactams or carbapenems) treated for ≥4 consecutive days, or died while receiving the antibiotic, were separately propensity score-matched (1:2). Attributable mortality was the in-hospital mortality difference among propensity-matched groups. Infection characteristics and sepsis severity influences on attributable mortality were examined. Algorithm accuracy was assessed by chart review.RESULTS:Of 232,834 GNIs between 2010 and 2013 at 79 hospitals, 1,023 per 3,350 (30.5%) colistin and 9,188 per 105,641 (8.7%) β-lactam (non-carbapenem) comparator cases died. Propensity-matched colistin and β-lactam case mortality was 29.2% and 16.6%, respectively, for an attributable mortality of 12.6% (95% confidence interval 10.8-14.4%). Attributable mortality varied from 11.0% (7.5%-14.7%) for urinary to 15.5% (12.6%-18.4%) for respiratory (P < .0001), and 4.6% (2.1%-7.4%) for early (≤4 days) to 16.6% (14.3%-18.9%) for late-onset infections (P < .0001). Attributable mortality decreased to 7.5% (5.6%-9.4%) using a carbapenem comparator cohort but increased 9-fold in patients coded for severe sepsis or septic shock (P < .0001). Our colistin algorithm had a positive predictive value of 60.4% and sensitivity of 65.3%.CONCLUSIONS:Mortality attributable to treatment-limiting resistance during GNIs varied considerably by site, onset, and severity of infection.

Meta-analysis has become a popular approach for summarizing a large number of clinical trials and resolving discrepancies raised by these trials. In this chapter, we introduce the general procedures for meta-analysis: formulating the question, defining eligibility, identifying studies, abstracting data, statistical analysis, and reporting the results. One key issue determining whether studies can be combined is the extent of heterogeneity among individual studies. We review graphical and statistical tools for assessing heterogeneity, describing the fixed-effect and random-effect models commonly used in meta-analysis, and providing some general recommendations regarding when fixed-effect or random-effect approach is appropriate. Publication bias is an inherent issue with meta-analysis, since studies (especially smaller ones) with "negative" results are frequently unpublished. Funnel plot, Begg and Mazumdar's rank correlation, and Egger regression are useful tools for assessing publication bias. As an illustration of the concepts discussed, we apply meta-analysis techniques to studies examining the use of antiinflammatory therapies in sepsis.

Tracheostomy remains one of the most commonly performed surgical procedures in the setting of acute respiratory failure. Tracheostomy literature focuses on 2 aspects of this procedure: when (timing) and how (technique). Recent trials have failed to demonstrate an effect of tracheostomy timing on most clinically important endpoints. Nonetheless, relative to continued translaryngeal intubation, studies suggest that tracheostomy use is associated with less need for sedation and enhanced patient comfort. Evidence likewise suggests that percutaneous dilational tracheostomy is advantageous with respect to cost and complication profile and should be considered the preferred approach in appropriately selected patients.

Each year, thousands of medical school graduates fail to secure postgraduate training through the National Resident Matching Program.1 To date, job opportunities for these individuals who would like direct involvement in patient care have been limited. They cannot work as medical practitioners because their lack of postgraduate training renders them ineligible for licensure in any state.2 US graduates may pursue health care–related employment with the intent of reapplying for residency training, or pursue a nonclinical career path altogether. Additionally, foreign medical graduates may practice in certain countries outside of the United States indefinitely while attempting to obtain a residency position.Recently, Missouri created another option for those lacking residency training. Legislation enacted in 2014 established the position of “assistant physician,” defined as an individual who may be licensed to function as a primary care provider following a brief apprenticeship.3 This novel approach may draw the interest of stakeholders in other states. However, the consequences of the assistant physician legislation for patient safety and health care quality should be addressed before this approach is considered for broader adoption.The main intent of the law is to increase the availability of primary care providers in Missouri. Like many parts of the country, the number of primary care practitioners in the state is not adequate, despite the presence of several medical schools in addition to programs dedicated to the training of advanced practice nurses and physician assistants.4 This shortage in Missouri may be exacerbated by its state legislature's reluctance to expand Medicaid coverage under the Affordable Care Act.5 A possible intent of the legislation is that the additional providers made available by the assistant physician legislation may rectify this problem. In addition, assistant physicians may be less expensive to employ than either fully trained physicians or midlevel providers, so this approach may have appeal to legislators, policymakers, and health care administrators.Briefly, the assistant physician law will apply to graduates of US and the international medical schools listed in the World Directory of Medical Schools and will limit practice to providing primary care services to underserved rural and urban locales. As defined, these services include prescribing controlled substances, “performing routine therapeutic procedures,” “assisting in surgery,” and “other tasks not prohibited by law”3 (box). Assistant physicians will be required to maintain a collaborative practice agreement with a supervising physician. For the first month of practice, the supervising physician must be continuously present; thereafter, the assistant physician can practice within a 50-mile radius of his or her supervisor. A supervising physician may enter into such collaborative practice agreements with as many as 3 assistant physicians. Finally, the statute directs that educational programs be put in place to “facilitate the advancement of the assistant physician's knowledge and capabilities, and which may lead to credit toward a future residency program.”3 As the details of operationalizing the law are being finalized, it is anticipated that individuals can apply for licensure as an assistant physician as early as 2016.Medical school graduates lacking additional “graduate” training are not typically viewed as possessing the knowledge and skills necessary to practice independently. Thus, the principal barrier to implementing the assistant physician law centers on how these individuals would be trained and supervised. Traditional residency programs in primary care specialties (ie, internal medicine, family medicine, or pediatrics) are 3 years in duration, are highly structured to provide a well-rounded and rigorous clinical and educational experience, and are based in environments that have clinical education as a core mission.6 The goals and objectives of these programs are established by the Accreditation Council for Graduate Medical Education.7 Trainees achieve educational milestones by providing care under the supervision of physician educators, attending educational conferences, and engaging in independent reading and self-study. Standard approaches to assessment (such as in-service examinations and rotation evaluations completed by faculty) are used not only to examine the trainees' knowledge base, clinical skills, and professionalism, but also to identify trainees in need of additional training and remediation. With progression through residency, trainees are afforded greater autonomy, based in part on these assessments.8 Board certification is conferred on those who successfully complete residency training and meet performance benchmarks on a certifying examination.6 Accumulating evidence suggests that the quality of care provided by board-certified physicians is superior to that of physicians who have not attained this benchmark, including individuals who have not completed residency training.9–11In contrast, there is no infrastructure in place for training or supervising assistant physicians, or for monitoring the quality of care those individuals deliver. The 1-month period of direct supervision provided by the law appears arbitrary, and no standard assessment tools are used to determine whether assistant physicians are competent to practice autonomously. Aside from maintaining active licensure, supervising physicians are not required to possess any specific credential, such as board certification in a primary care specialty.3 These individuals may have completed as little as 1 year of postgraduate training themselves (the minimum required for independent licensure in Missouri), and most will lack expertise as an educator.2 Finally, while 1 intent of the law is ostensibly to serve as a pathway for medical school graduates to enter residency training, it is unclear how serving as an assistant physician would be of educational value or otherwise further the career prospects of these individuals.Additional concerns exist. Medical school graduates who are not successful at securing a residency position may not possess the same academic credentials, clinical skills, and interpersonal qualities as those who secure a position. Similarly, the quality of education provided by some international medical schools may be inferior to education available at universities in the United States. Both groups may be grossly unprepared for the rapid transition into independent practice and would particularly benefit from the highly structured environment residency training provides. The foregoing arguments notwithstanding, it might be argued that assistant physicians possess training equal to, if not exceeding that of, advanced nurse practitioners who are allowed to practice independently in many locations. Conceivably, assistant physician–styled laws might be a strategy on the part of organized medicine to counter the growing independence of this nursing specialty.12,13Advanced practice nurses are certified in 1 of several areas (eg, acute care, gerontology, etc) after completion of master's or doctoral level training in accredited programs, which involve a minimum of 500 hours of supervised clinical care.14 Their scope of practice is defined in all 50 states. The training of physician assistants is similarly rigorous.15 Accumulating evidence suggests that midlevel providers deliver high-quality, cost-effective care.16,17 Thus, while an assistant physician license might be granted to inadequately trained individuals to practice in settings in which they have little expertise, midlevel providers are specifically educated and credentialed in a narrowly defined focus.Missouri's assistant physician law is a public response designed to bridge critical gaps in the health care workforce. This is to be achieved by disregarding established approaches to medical education developed over decades at substantial expense. At the same time, the passage of this law emphasizes the need for greater social accountability on the part of training institutions. Furthermore, the Missouri legislation also illustrates the need for dialogue between the academic community, state legislatures, and professional societies regarding issues that directly affect physician training. Finally, while the assistant physician model may have appeal as a strategy to expand primary care services, its effects on the health care workforce and patient outcomes should be understood before broad implementation.

Department of Surgery, Washington University School of Medicine, St. Louis, MO *See also p. 1506. The author has disclosed that he does not have any potential conflicts of interest.

Department of Surgery, Washington University School of Medicine, St. Louis, MO *See also p. 617. The author has disclosed that he does not have any potential conflicts of interest.

BACKGROUND: Mortality after smoke inhalation-associated acute lung injury (SI-ALI) remains substantial. Age and burn surface area are risk factors of mortality, whereas the impact of patient-and center-level variables and treatments on survival are unknown.METHODS: We performed a retrospective cohort study of burn and non-burn centers at 68 US academic medical centers between 2011 and 2014. Adult inpatients with SI-ALI were identified using an algorithm based on a billing code for respiratory conditions from smoke inhalation who were mechanically ventilated by hospital day 4, with either a length-of-stay >= 5 days or death within 4 days of hospitalization. Predictors of in-hospital mortality were identified using logistic regression. The primary outcome was the odds ratio for in-hospital mortality.RESULTS: A total of 769 patients (52.9 +/- 18.1 years) with SI-ALI were analyzed. In-hospital mortality was 26% in the SI-ALI cohort and 50% in patients with >= 20% surface burns. In addition to age > 60 years (OR 5.1, 95% CI 2.53-10.26) and >= 20% burns (OR 8.7, 95% CI 4.55-16.75), additional risk factors of in-hospital mortality included initial vasopressor use (OR 5.0, 95% CI 3.16-7.91), higher diagnostic-related group-based risk-of-mortality assignment and lower hospital bed capacity (OR 2.3, 95% CI 1.23-4.15). Initial empiric antibiotics (OR 0.93, 95% CI 0.58-1.49) did not impact survival. These new risk factors improved mortality prediction by 9.9% (P < .001).CONCLUSIONS: In addition to older age and major surface burns, mortality in SI-ALI is predicted by initial vasopressor use, higher diagnostic-related group-based risk-of-mortality assignment, and care at centers with < 500 beds, but not by initial antibiotic therapy.

PURPOSE:Individuals who struggle to provide substitute judgment for the critically ill often find it challenging to engage in decision making for therapeutic interventions. Although essential to the conduct of research, how these individuals respond to requests for clinical trial participation is poorly understood.METHODS:Survey data collected to examine surrogate attitudes toward research provided the conceptual framework to explore influences on decision making. Path analysis was used to derive the final model (nonlatent, fully recursive, 1 indicator/variable).RESULTS:Surrogates with list-wise complete records (406) were analyzed. The following variables were not retained in the final model: education, income, religiosity, decision-making experience, discussion of patient's wishes, number of individuals assisting with decision making, trust in care providers, difficulty making decisions, and responsibility for decision making. Being white and having experience making treatment decisions for the patient during the current intensive care unit encounter affected the likelihood the surrogate would permit participation in research positively (parameter estimates, 0.281 and 0.06, respectively). No variable reflecting difficulty functioning in the surrogate role was associated with permitting research participation.CONCLUSIONS:We were unable to demonstrate a relationship between perceived difficulty in decision making in the surrogate role and receptivity to clinical trial participation.

Approaches to postgraduate medical training have evolved substantially in recent years, reflecting the complexity of the educational mission. Residency programs seek to produce clinicians who achieve board certification as an attestation of their competency. Certification criteria are established by the American Board of Medical Specialties, are consistent from state to state, and include periods of supervised instruction ranging from as few as three years (for primary care specialties) to much longer for selected disciplines. In contrast, minimum postgraduate training criteria necessary for licensure as an independent practitioner are established by state medical boards and vary significantly among and within jurisdictions. In most states, licenses can be granted to individuals who have completed as little as one year of postgraduate training. The discrepancy between the minimum time commitment necessary to become a competent physician and that to be licensed as an independent practitioner has implications for health care quality and safety. Data are lacking as to the number of licenses issued nationally to individuals who have only partially completed residency training and the nature of practices they pursue. Extrapolating from available evidence, these individuals may very well provide care inferior to those who have satisfied training requirements for certification eligibility and be more prone to problematic behavior resulting in disciplinary action. Efforts to establish more rigorous licensure criteria will require dialog between members of the academic community, professional organizations, state medical boards, and legislatures. The recently proposed Interstate Medical Licensure Compact may serve as a prototype for achieving this goal.

Background Many research studies conducted today in critical care have a genomics component. Patients' surrogates asked to authorize participation in genomics research for a loved one in the intensive care unit may not be prepared to make informed decisions about a patient's participation in the research.Objectives To examine the effectiveness of a new, computer-based education module on surrogates' understanding of the process of informed consent for genomics research.Methods A pilot study was conducted with visitors in the waiting rooms of 2 intensive care units in a Midwestern tertiary care medical center. Visitors were randomly assigned to the experimental (education module plus a sample genomics consent form; n = 65) or the control (sample genomics consent form only; n = 69) group. Participants later completed a test on informed genomics consent.Results Understanding the process of informed consent was greater (P=.001) in the experimental group than in the control group. Specifically, compared with the control group, the experimental group had a greater understanding of 8 of 13 elements of informed consent: intended benefits of research (P=.02), definition of surrogate consenter (P=.001), withdrawal from the study (P=.001), explanation of risk (P=.002), purpose of the institutional review board (P=.001), definition of substituted judgment (P=.03), compensation for harm (P=.001), and alternative treatments (P=.004).Conclusions Computer-based education modules may be an important addition to conventional approaches for obtaining informed consent in the intensive care unit. Preparing patients' family members who may consider serving as surrogate consenters is critical to facilitating genomics research in critical care.

BACKGROUND:Critical illness research is challenging due to disease severity and because patients are frequently incapacitated. Surrogates called upon to provide consent might not accurately represent patient preferences. Though commonplace, genetic data collection adds complexity in this context. We undertook this investigation to understand whether surrogate decision makers would be receptive to permitting participation in a critical illness genetics study and whether their decision making was consistent with that of the patient represented.METHODS:We invited individuals identified as surrogates for critically ill adults, if required, as well as patients once recovered to participate in a survey designed to understand attitudes about genetic research. Associations between dependent (receptivity to participation, concordance of responses) and independent variables were tested using bivariate and multivariate logistic regression analyses.RESULTS:Most of the entire surrogate sample (n=439) reported familiarity with research, including genetic research; tended to view research as useful; and were receptive to allowing their family member participate (with 39.6% and 38.1% stating that this would be "very" and "somewhat likely," respectively) even absent direct benefit. Willingness to participate was similar comparing genetic and non-genetic studies (χ2 [1,n=439]=0.00127, p=0.972), though respondents expressed worry regarding lack of confidentiality of genetic data. Responses were concordant in 70.8% of the 192 surrogate-patient pairs analyzed. In multivariate analysis, African American race was associated with less receptivity to genetic data collection (p<0.05). No factors associated with concordance of surrogate-patient response were identified.CONCLUSIONS:Surrogates' receptivity to critical illness research was not influenced by whether the study entailed collection of genetic data. While more than two-thirds of surrogate-patient responses for participation in genetics research were concordant, concerns expressed regarding genetic data often related to breach of confidentiality. Emphasizing safeguards in place to minimize such breeches might prove an effective strategy for enhancing recruitment.

BACKGROUND: Obese patients are more prone to post-injury multiple organ failure (MOF). Obesity pathophysiology includes an adipose-tissue-derived, renin-angiotensin-aldosterone system affecting inflammatory responses via leukocyte angiotensin receptors. We hypothesized that obese patients receiving pre-injury angiotensin-converting enzyme inhibitor (ACE) or angiotensin receptor blocker (ARB) therapy would have decreased MOF and differences in immune cell frequencies.STUDY DESIGN: We analyzed the Inflammation and the Host Response to Injury trauma-related database. Patients receiving pre-injury ACE or ARB were stratified as obese (BMI > 30 kg/m(2)) or nonobese (BMI < 30 kg/m(2)). Groups were age, sex, and Injury Severity Score matched against patients not receiving this therapy. Primary end points were Marshall Multiple Organ Dysfunction Score, Denver-2 Postinjury MOF Score, leukocyte markers on T cells, and monocytes measured by flow cytometry.RESULTS: We evaluated 1,932 patients. One hundred and ten were receiving pre-injury ACE/ARB; 94 patients had data available to calculate BMI. Obese patients receiving ACE/ARB showed maximum Marshall (5.83 +/- 2.87) and Denver-2 (2.45 +/- 2.32) scores similar to nonobese patients receiving or not receiving ACE/ARB, and obese patients not receiving ACE/ARB had significantly higher Marshall (6.49 +/- 2.57; p = 0.009) and Denver-2 (3.33 +/- 2.21; p = 0.006) scores. Leukocyte analysis suggested improved T-cell function and monocyte maturation in obese patients on ACE/ARB.CONCLUSIONS: Obese patients receiving preinjury ACE/ARB therapy demonstrate post-injury MOF scores similar to nonobese patients; obese patients not receiving these medications have greater postinjury MOF. Leukocyte analysis demonstrates improved immune regulation. Modulation of the renin-angiotensin-aldosterone system pathway might represent a novel therapeutic target in severely injured obese patients. (C) 2015 by the American College of Surgeons

BACKGROUNDCollection of genetic biospecimens as part of critical illness investigations is increasingly commonplace. Oversight bodies vary in restrictions imposed on genetic research, introducing inconsistencies in study design, potential for sampling bias, and the possibility of being overly prohibitive of this type of research altogether. We undertook this study to better understand whether restrictions on genetic data collection beyond those governing research on cognitively intact subjects reflect the concerns of surrogates for critically ill patients.METHODSWe analyzed survey data collected from 1,176 patients in nonurgent settings and 437 surrogates representing critically ill adults. Attitudes pertaining to genetic data (familiarity, perceptions, interest in participation, concerns) and demographic information were examined using univariate and multivariate techniques.RESULTSWe explored differences among respondents who were receptive (1,333) and nonreceptive (280) to genetic sample collection. Whereas factors positively associated with receptivity to research participation were "complete trust" in health-care providers (OR, 2.091; 95% CI, 1.544-2.833), upper income strata (OR, 2.319; 95% CI, 1.308-4.114), viewing genetic research "very positively" (OR, 3.524; 95% CI, 2.122-5.852), and expressing "no worry at all" regarding disclosure of results (OR, 2.505; 95% CI, 1.436-4.369), black race was negatively associated with research participation (OR, 0.410; 95% CI, 0.288-0.585). We could detect no difference in receptivity to genetic sample collection comparing ambulatory patients and surrogates (OR, 0.738; 95% CI, 0.511-1.066).CONCLUSIONSExpressing trust in health-care providers and viewing genetic research favorably were associated with increased willingness for study enrollment, while concern regarding breach of confidentiality and black race had the opposite effect. Study setting had no bearing on willingness to participate.

This article is an exploratory data analysis of the determinants of confidence in a surrogate decision maker who has been asked to permit an intensive care unit (ICU) patient's participation in genetic research. We pursue the difference between surrogates' and patients' confidence that the surrogate can accurately represent the patient's wishes. The article also explores whether greater confidence leads to greater agreement between patients and surrogates. Our data come from a survey conducted in three hospital ICUs. We interviewed 445 surrogates and 214 patients. The only thing that influences patients' confidence in their surrogate's decision is whether they had prior discussions with him or her; however, there are more influences operating on the surrogate's self-confidence. More confident surrogates are more likely to match their patients' wishes. Patients are more likely to agree to research participation than their surrogates would allow. The surrogates whose response did not match as closely were less trusting of the hospital staff, were less likely to allow patient participation if there were no direct benefits to the patient, had given less thought about the way genetic research is conducted, and were much less likely to have a person in their life who they would trust to make decisions for them if they were incapacitated.

Department of Surgery, Washington University School of Medicine, St. Louis, MO * See also p. 413. The author has disclosed that he does not have any potential conflicts of interest.

ObjectivesThis study explores surrogate decision-makers’ (SDMs) challenges making decisions related to the care of patients in critical care, to (1) characterise the SDM stress, (2) identify personal, social, care-related factors influencing stress and (3) consider implications of findings to improving critical care practice.MethodologySemi-structured interviews were conducted with SDMs of critically ill patients receiving care in two tertiary care institutions. Transcripts were analysed using a grounded theory approach. Domains explored were: stress characteristics, stress mitigators, coping strategies, social networks, SDM decision-making role, decision-making concordance, knowledge of patient's preferences, experience with provider team, SDM-provider communication, patient outcome certainty.Main outcomesWe interviewed 34 SDMs. Most were female and described long-term relationships with patients. SDMs described the strain of uncertain outcomes and decision-making without clear, consistent information from providers. Decision-making anxiety was buffered by SDMs’ active engagement of social networks, faith and access to clear communication from providers.ConclusionStress is a very real factor influencing SDMs confidence and comfort making decisions. These findings suggest that stress can be minimised by improving communication between SDMs and medical providers. Nurses’ central role in the ICU makes them uniquely poised to spearhead interventions to improve provider-SDM communication and reduce SDM decision-making anxiety.

Critical illness clinical trials that entail genomic data collection pose unique challenges. In this qualitative study, we found that surrogate decision makers (SDMs) for critically ill individuals, such as those who would be approached for study participation, appeared to have a limited grasp of genomic principles. We argue that low levels of genomic literacy should neither preclude nor be in conflict with the conduct of ethically rigorous clinical trials.

BACKGROUND: Tracheostomy practice in patients with acute respiratory failure (ARF) varies greatly among institutions. This variability has the potential to be reflected in the resources expended providing care. In various healthcare environments, increased resource expenditure has been associated with a favorable effect on outcome. OBJECTIVE: To examine the association between institutional resource expenditure and mortality in ARF patients managed with tracheostomy. METHODS: We developed analytic models employing the University Health Systems Consortium (Oakbrook, Illinois) database. Administrative coding data were used to identify patients with the principal diagnosis of ARF, procedures, complications, post-discharge destination, and survival. Mean resource intensity of participating academic medical centers was determined using risk-adjusted estimates of costs. Mortality risk was determined using a multivariable approach that incorporated patient-level demographic and clinical variables and institution-level resource intensity. RESULTS: We analyzed data from 44,124 ARF subjects, 4,776 (10.8%) of whom underwent tracheostomy. Compared to low-resource-intensity settings, treatment in high-resource-intensity academic medical centers was associated with increased risk of mortality (odds ratio 1.11, 95% CI 1.05–1.76), including those managed with tracheostomy (odds ratio high-resource-intensity academic medical center with tracheostomy 1.10, 95% CI 1.04–1.17). We examined the relationship between complication development and outcome. While neither the profile nor number of complications accumulated differed comparing treatment environments (P > .05 for both), mortality for tracheostomy patients experiencing complications was greater in high-resource-intensity (95/313, 30.3%) versus low-resource-intensity (552/2,587, 21.3%) academic medical centers (P < .001). CONCLUSIONS: We were unable to demonstrate a positive relationship between resource expenditure and outcome in ARF patients managed with tracheostomy.

Department of Pulmonary and Critical Care Medicine, The Johns Hopkins Medical Institution, Baltimore, MD Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins Medical Institution, Baltimore, MD, on behalf of The Johns Hopkins University Multidisciplinary Percutaneous Tracheostomy Team Authors belonging to The Johns Hopkins University Multidisciplinary Percutaneous Tracheostomy Team: Vinciya Pandian, CRNP; Nasir Bhatti, MD; Elliott R. Haut, MD; Athir Morad, MD; Adil Haider, MD; Adam Schiavi, MD, PhD; David Efron, MD; Kent A. Stevens, MD; David Feller-Kopman, MD; Christina A. Miller, MD; Amy P. Rushing, MD; Albert Chi, MD; John Ulatowski, MD, PhD, MBA. Dr. Mirski has received book royalties from Humana Press. Dr. Yarmus has disclosed that he does not have any potential conflicts of interest.