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The application of intense pulsed light (IPL) to printed copper nanoparticle (CuNP) films enables rapid curing on low temperature substrates in ambient conditions. In this work, we printed CuNP ink on liquid crystal polymer (LCP; Vectra A resin) and then cured the films using a high energy density light pulse. High-resolution SEM images of the cured films revealed that the CuNPs on LCP were fused together. Optimal curing parameters were a 5 ms pulse, 75% duty cycle, and an energy density range of 4.2–5.2 J⋅cm-2. Sheet resistance, Rs, values as low as ~0.1 Ω⋅sq-1were obtained. The LCP substrate took on a yellowed appearance after the application of five pulses and exhibited a surface free energy increase. A filter that blocked wavelengths

The dog rhinarium (naked and often moist skin on the nose-tip) is prominent and richly innervated, suggesting a sensory function. Compared to nose-tips of herbivorous artio- and perissodactyla, carnivoran rhinaria are considerably colder. We hypothesized that this coldness makes the dog rhinarium particularly sensitive to radiating heat. We trained three dogs to distinguish between two distant objects based on radiating heat; the neutral object was about ambient temperature, the warm object was about the same surface temperature as a furry mammal. In addition, we employed functional magnetic resonance imaging on 13 awake dogs, comparing the responses to heat stimuli of about the same temperatures as in the behavioural experiment. The warm stimulus elicited increased neural response in the left somatosensory association cortex. Our results demonstrate a hitherto undiscovered sensory modality in a carnivoran species.

A public health emergency such as an influenza pandemic will lead to shortages of mechanical ventilators, critical care beds, and other potentially life saving treatments. This will raise difficult decisions about who will and will not receive these scarce resources. Existing recommendations reflect a narrow utilitarian perspective in which allocation decisions are based primarily on patients' chances of survival to hospital discharge. Certain patient groups, such as the elderly and those with functional impairment, are denied access to potentially life saving treatments based on selective application of additional allocation criteria. We analyze the ethical principles that could guide allocation and propose an allocation strategy that incorporates and balances multiple morally relevant considerations, including saving the most lives, maximizing the number of “life-years” saved, and prioritizing those who have had the least chance to live through life's stages. We also argue that these principles are relevant to all patients and that justice requires that these principles be applied evenly, rather than selectively to the aged, functionally impaired, and those with certain chronic conditions. We discuss strategies to genuinely engage the public in setting the priorities that will guide allocation of scarce life sustaining treatments during a public health emergency.

Here, we report a previously un-reported printed electronics/additive manufacturing (AM) approach to fabricate conductive/resistive features on novel insulating silver–barium strontium titanate (Ag–BST) printed composite films. Ag–BST composite functional ink was formulated by blending a conductive Ag nanoparticle ink and an insulating BST nanoparticle ink. The blending ratio of Ag and BST inks was optimized to obtain the insulating phase after the initial curing and the conductive/resistive phase following selective laser sintering under ambient conditions. Selective laser sintered Ag–BST resistors showed an ohmic behavior and the resistivity could be adjusted by varying the laser sintering parameters, such as the wavelength, power and the rastering speed/pitch of the laser. This insulator to conductor/resistor transitioning Ag–BST ink paves a new path for direct write printed electronics/AM applications. Proofs of concept for potential applications utilizing this functional ink are demonstrated. Also, this Ag–BST ink can be used as a conventional resistive ink for dispensing printers. Thermally sintered Ag–BST resistors showed less than 8% variation in resistance between −50 °C and 150 °C.

A 13-year-old patient named Jahi McMath was determined to be dead by neurologic criteria following cardiopulmonary arrest and resuscitation at a hospital in Oakland, California. Her family did not agree that she was dead and refused to allow her ventilator to be removed. The family's attorney stated in the media that families, rather than physicians, should decide whether patients are dead and argued in the courts that the families' constitutional rights of religion and privacy would be violated otherwise. Ultimately, a judge agreed that the patient was dead in keeping with California law, but the constitutional issue was undecided. The patient was then transferred to a hospital in New Jersey, a state whose laws allow families to require on religious grounds that death be determined by cardiopulmonary criteria. Although cases such as this are uncommon, they demonstrate public confusion about the concept of neurologic death and the rejection of this concept by some families. The confusion may be caused in part by a lack of uniformity in state laws regarding the legal basis of death, as reflected in the differences between New Jersey and California statutes. Families who reject the determination of death by neurologic criteria on religious grounds should be given reasonable accommodation in all states, but society should not pay for costly treatments for patients who meet these criteria unless the state requires it, as only New Jersey does. Laws that give physicians the right to determine death by neurologic criteria in other states probably can survive a constitutional challenge. Physicians and hospitals faced with similar cases in the future should follow state laws and work through the courts if necessary.

Objectives With increasing rates of infections caused by MDR Gram-negative organisms, clinicians resort to older agents such as colistimethate sodium (CMS) despite a significant risk of nephrotoxicity. Several risk factors for CMS-associated nephrotoxicity have been reported, but they have yet to be validated. We compared the performance of published mathematical models in predicting the risk of CMS-associated nephrotoxicity. Methods In a multicentre, retrospective, cohort study, adult patients (≥18 years of age) were evaluated from five large academic medical centres in the USA. Patients with normal renal function (baseline serum creatinine ≤1.5 mg/dL) who received intravenous CMS for ≥72 h were followed for up to 30 days. The development of nephrotoxicity was as defined by the RIFLE criteria. Each published model was conditioned using patient-specific variables to predict the risk of nephrotoxicity. The predictive performance of the models was evaluated using the observed-to-expected (O/E) ratio. The most significant cut-off threshold for stratifying patients into high and low risk of nephrotoxicity was identified using classification and regression tree analysis. Results A total of 106 patients were examined (mean age 53.3 ± 14.9 years, 66% male); the overall observed nephrotoxicity rate was 52.8%. We identified a simple model demonstrating reasonable overall nephrotoxicity risk assessment [O/E ratio of 1.07 (95% CI = 0.81-1.39)] and high sensitivity (92.9%) in predicting nephrotoxicity development in patients on CMS therapy. Conclusions We identified a model that could be incorporated into patient management strategies to reduce the risk of nephrotoxicity in patients requiring CMS therapy.

Introduction Nous suivons, en dialyse, des patients etrangers en situation irreguliere. La plupart ne parle pas le francais. Cette barriere de la langue est un handicap pour leur prise en charge socio/administrative et medicale. Nous avons donc souhaite organiser des cours de francais pour ces patients. Methodes Nous avons fait appel a Une association loi de 1901, destinee a apprendre le francais aux adultes etrangers, constituee de benevoles. L’enseignement recu est gratuit. Les enseignants de l’association (un ou deux/seance) viennent deux fois par semaine, une heure et demie, pendant la seance d’hemodialyse des patients. Ils sont parfois aides par une aide-soignante de notre service. L’experience a debute en decembre 2018 avec quatre patients : deux armeniens, un soudanais et un mongole. Ils ne beneficiaient pas tous de l’Aide Medicale de l’Etat lors du debut des cours. Les patients ont entre 42 et 54 ans. Leur nephropathie est d’etiologie indeterminee chez trois d’entre eux et un a une nephropathie diabetique. Ils ne presentent pas de trouble cognitif. L’un d’entre eux presente une baisse de l’acuite visuelle. Resultats obtenus ou attendus Apres sept mois de cours, nous observons chez trois des quatre patients : – une amelioration de la maitrise de la langue francaise, et de la communication avec les equipes soignantes, – une modification de leur comportement avec des patients plus ouverts, plus souriants. Conclusion Cette experience a permis d’atteindre son objectif principal chez 3 des 4 patients avec une amelioration de leur niveau de francais. Nous avons egalement assiste a un mieux-etre de trois des quatre patients. Nous poursuivons donc l’experience en incluant nos nouveaux patients migrants. Echec initial chez une patiente, en lien avec une situation sociale encore trop precaire associee a un syndrome depressif.

Increasing numbers of patients survive traumatic brain injury and cardiopulmonary arrest and resuscitation and are admitted to the ICU while in coma. Some of these patients become brain dead; others regain consciousness. Still others become vegetative or minimally conscious, conditions called chronic disorders of consciousness and ultimately can be cared for outside the ICU. Whether these patients would want life-sustaining therapy is difficult to determine because most have not articulated their wishes before becoming comatose. Ethics and law recognize that patients with decision-making capacity have a right to refuse such therapy and that surrogates can exercise this right for them through the principle of substituted judgment as was established by the Supreme Court of New Jersey in the case of Karen Ann Quinlan. In its decision regarding Nancy Cruzan, the US Supreme Court determined that states may require clear and convincing evidence of a vegetative patient's prior wishes before life-sustaining therapy may be withdrawn; this standard has been applied to minimally conscious patients by state supreme courts in some cases. Nevertheless, cases such as these only come to the legal system because end-of-life decisions are contested, which is unusual, and most end-of-life decisions for specific patients with chronic disorders of consciousness are made by surrogates with recommendations from physicians without court involvement. Recent advances in neuroimaging may influence both end-of-life decision-making and legal deliberations. Targeting vegetative and minimally conscious patients in medical resource allocation remains ethically unacceptable and untested in the law.

Although the antistaphylococcal penicillins remain the drugs of choice for methicillin-susceptible Staphylococcus aureus (MSSA) infections, cefazolin and ceftriaxone are often prescribed due to their less frequent dosing and reduced cost. The purpose of this study was to compare clinical outcomes and adverse events in patients receiving outpatient parenteral antimicrobial therapy (OPAT) with ceftriaxone or cefazolin for the treatment of MSSA infections. A retrospective study was carried out of 122 patients evaluated at Ben Taub and Lyndon B. Johnson General Hospitals in Houston, Texas, between January 1, 2006, and March 31, 2012, with a documented MSSA infection who received cefazolin or ceftriaxone as OPAT. A favorable clinical outcome was determined by their primary care physician’s assessment at follow-up in the clinic. Out of 122 patients, 78 (64 %) were treated with cefazolin and 44 (36 %) with ceftriaxone. Patients were predominantly young (median age 46 years), male (54.2 %), and Hispanic (51.2 %). Patients were similar in terms of baseline demographics, types of infections, and management of infections. Favorable clinical outcomes were similar between cefazolin and ceftriaxone (67.9 versus 79.8 %, p = 0.17), along with a similar incidence of adverse events and complications (5.1 versus 2.3 %, p = 0.65, and 26.9 versus 18.2 %, p = 0.38, respectively). OPAT with either cefazolin or ceftriaxone is similar in terms of favorable outcomes, adverse events, and complications when treating MSSA infections. A randomized clinical trial is needed in order to confirm these results.

Importance Misperceptions about prognosis by individuals making decisions for incapacitated critically ill patients (surrogates) are common and often attributed to poor comprehension of medical information. Objective To determine the prevalence of and factors related to physician-surrogate discordance about prognosis in intensive care units (ICUs). Design, Setting, and Participants Mixed-methods study comprising quantitative surveys and qualitative interviews conducted in 4 ICUs at a major US medical center involving surrogate decision makers and physicians caring for patients at high risk of death from January 4, 2005, to July 10, 2009. Main Outcomes and Measures Discordance about prognosis, defined as a difference between a physician’s and a surrogate’s prognostic estimates of at least 20%; misunderstandings by surrogates (defined as any difference between a physician’s prognostic estimate and a surrogate’s best guess of that estimate); differences in belief (any difference between a surrogate’s actual estimate and their best guess of the physician’s estimate). Results Two hundred twenty-nine surrogate decision makers (median age, 47 [interquartile range {IQR}, 35-56] years; 68% women) and 99 physicians were involved in the care of 174 critically ill patients (median age, 60 [IQR, 47-74] years; 44% women). Physician-surrogate discordance about prognosis occurred in 122 of 229 instances (53%; 95% CI, 46.8%-59.7%). In 65 instances (28%), discordance was related to both misunderstandings by surrogates and differences in belief about the patient’s prognosis; 38 (17%) were related to misunderstandings by surrogates only; 7 (3%) were related to differences in belief only; and data were missing for 12. Seventy-five patients (43%) died. Surrogates’ prognostic estimates were much more accurate than chance alone, but physicians’ prognostic estimates were statistically significantly more accurate than surrogates’ (C statistic, 0.83 vs 0.74; absolute difference, 0.094; 95% CI, 0.024-0.163;P = .008). Among 71 surrogates interviewed who had beliefs about the prognosis that were more optimistic than that of the physician, the most common reasons for optimism were a need to maintain hope to benefit the patient (n = 34), a belief that the patient had unique strengths unknown to the physician (n = 24), and religious belief (n = 19). Conclusions and Relevance Among critically ill patients, discordant expectations about prognosis were common between patients’ physicians and surrogate decision makers and were related to misunderstandings by surrogates about physicians’ assessments of patients’ prognoses and differences in beliefs about patients’ prognoses.

We present a fully implemented Infrared (IR) Scanning Near-field Optical Microscopy (SNOM) in spectroscopic mode for tissue imaging and early cancer diagnostics.

Background Studies of cardiac resynchronization therapy in addition to an implantable cardioverter defibrillator in patients with mild to moderate congestive heart failure had not been shown to reduce mortality until the recent RAFT trial (Resynchronization/Defibrillation for Ambulatory Heart Failure Trial). We performed a meta-analysis including the RAFT trial to determine the effect of cardiac resynchronization therapy with or without an implantable defibrillator on mortality. Methods We searched electronic databases and other sources for reports of randomized trials using a parallel or crossover design. We included studies involving patients with heart failure receiving optimal medical therapy that compared cardiac resynchronization therapy with optimal medical therapy alone, or cardiac resynchronization therapy plus an implantable defibrillator with a standard implantable defibrillator. The primary outcome was mortality. The optimum information size was considered to assess the minimum amount of information required in the literature to reach reliable conclusions about cardiac resynchronization therapy. Results Of 3071 reports identified, 12 studies ( n = 7538) were included in our meta-analysis. Compared with optimal medical therapy alone, cardiac resynchronization therapy plus optimal medical therapy significantly reduced mortality (relative risk [RR] 0.73, 95% confidence interval [CI] 0.62–0.85). Compared with an implantable defibrillator alone, cardiac resynchronization therapy plus an implantable defibrillator significantly reduced mortality (RR 0.83, 95% CI 0.72–0.96). This last finding remained significant among patients with New York Heart Association (NYHA) class I or II disease (RR 0.80, 95% CI 0.67–0.96) but not among those with class III or IV disease (RR 0.84, 95% CI 0.69–1.07). Analysis of the optimum information size showed that the sequential monitoring boundary was crossed, which suggests no need for further clinical trials. Interpretation The cumulative evidence is now conclusive that the addition of cardiac resynchronization to optimal medical therapy or defibrillator therapy significantly reduces mortality among patients with heart failure.

The concept of informed consent was applied to clinical research in the United States after research abuses were documented in Nazi Germany and this country. The concept is imbedded in the Nuremberg Code, the Declaration of Helsinki, and the Belmont Report. Federal regulations governing clinical research require both the consent of subjects and peer review of research proposals by institutional review boards (IRBs). Subpart A of the Code of Federal Regulations contains basic provisions for the protection of research subjects and requirements for informed consent by subjects or their surrogates; surrogate consent may or may not be allowed under state law. Other subparts contain further protections for subjects with diminished capacity, such as children, that limit the kind of research in which they can participate. Whether these protections should be extended to decisionally impaired adults, including those who are critically ill, remains to be determined. Consent can be deferred or waived for emergency research only rarely in the United States, in contrast to other countries.

Deaths that occur during medical care for the treatment of a disease are rarely certified as homicides. Some "medical" deaths, however, have been criminally prosecuted for manslaughter, reckless endangerment, or reckless homicide. We describe 5 deaths due to medical complications that underwent criminal prosecution. Three of the deaths were certified as homicides. Deaths certified as homicides due to the actions (or inactions) of a caregiver occur in 3 circumstances. The first is when the medical caregiver intentionally causes the death of the patient. The second is a death due to treatment by an unlicensed fraud or quack. The final circumstance is due to extreme medical negligence that involves a gross and wanton disregard for the well-being of the patient and is the most controversial in the medical community. The law defines reckless endangerment as the conscious disregard of a known substantial likelihood of injury to the patient. Criminal neglect typically is defined as the failure to provide timely, safe, adequate, and appropriate services, treatment, and/or care to a patient. In instances of extreme medical negligence, a homicide manner of death is appropriate because the fatality is due to the criminal acts (or inactions) of another. It also furthers one of the major goals of the medicolegal death investigation system, which is to safeguard the public health.

Because they provide potential benefit at great personal and public cost, the intensive care unit (ICU) and the interventions rendered therein have become symbols of both the promise and the limitations of medical technology. At the same time, the ICU has served as an arena in which many of the ethical and legal dilemmas created by that technology have been defined and debated. This article outlines major events in the history of ethics and law in the ICU, covering the evolution of ICUs, ethical principles, informed consent and the law, medical decision-making, cardiopulmonary resuscitation, withholding and withdrawing life-sustaining therapy, legal cases involving life support, advance directives, prognostication, and futility and the allocation of medical resources. Advancement of the ethical principle of respect for patient autonomy in ICUs increasingly is in conflict with physicians' concern about their own prerogatives and with the just distribution of medical resources.

Background: Respiratory failure remains the leading indication for admission to the intensive care unit (ICU) and a leading cause of death for HIV-infected patients in spite of overall improvements in ICU mortality. It is unclear if these improvements are due to combination anti-retroviral therapy, low tidal volume ventilation for acute lung injury, or both. A study was undertaken to identify therapies and clinical factors associated with mortality in acute lung injury among HIV-infected patients with respiratory failure in the period 1996–2004. A secondary aim was to compare mortality before and after introduction of a low tidal volume ventilation protocol in 2000. Methods: A retrospective cohort study was performed of 148 consecutive HIV-infected adults admitted to the ICU at San Francisco General Hospital with acute lung injury requiring mechanical ventilation. Demographic and clinical information including data on mechanical ventilation was abstracted from medical records and analysed by multivariate analysis using logistic regression. Results: In-hospital mortality was similar before and after introduction of a low tidal volume ventilation protocol, although the study was not powered to exclude a clinically significant difference (risk difference −5.4%, 95% CI −21% to 11%, p = 0.51). Combination antiretroviral therapy was not clearly associated with mortality, except in patients with Pneumocystis pneumonia. Among all those with acute lung injury, lower tidal volume was associated with decreased mortality (adjusted odds ratio 0.76 per 1 ml/kg decrease, 95% CI 0.58 to 0.99, p = 0.043), after controlling for Pneumocystis pneumonia, serum albumin, illness severity, gas exchange impairment and plateau pressure. Conclusions: Lower tidal volume ventilation is independently associated with reduced mortality in HIV-infected patients with acute lung injury and respiratory failure.

Although discussing a prognosis is a duty of physicians caring for critically ill patients, little is known about surrogate decision-makers' beliefs about physicians' ability to prognosticate. We sought to determine: 1) surrogates' beliefs about whether physicians can accurately prognosticate for critically ill patients; and 2) how individuals use prognostic information in their role as surrogate decision-makers.Multicenter study in intensive care units of a public hospital, a tertiary care hospital, and a veterans' hospital. We conducted semistructured interviews with 50 surrogate decision-makers of critically ill patients. We analyzed the interview transcripts using grounded theory methods to inductively develop a framework to describe surrogates' beliefs about physicians' ability to prognosticate. Validation methods included triangulation by multidisciplinary analysis and member checking.Overall, 88% (44 of 50) of surrogates expressed doubt about physicians' ability to prognosticate for critically ill patients. Four distinct themes emerged that explained surrogates' doubts about prognostic accuracy: a belief that God could alter the course of the illness, a belief that predicting the future is inherently uncertain, prior experiences where physicians' prognostications were inaccurate, and experiences with prognostication during the patient's intensive care unit stay. Participants also identified several factors that led to belief in physicians' prognostications, such as receiving similar prognostic estimates from multiple physicians and prior experiences with accurate prognostication. Surrogates' doubts about prognostic accuracy did not prevent them from wanting prognostic information. Instead, most surrogate decision-makers view physicians' prognostications as rough estimates that are valuable in informing decisions, but are not determinative. Surrogates identified the act of prognostic disclosure as a key step in preparing emotionally and practically for the possibility that a patient may not survive.Although many surrogate decision-makers harbor some doubt about the accuracy of physicians' prognostications, they highly value discussions about prognosis and use the information for multiple purposes.

Background: These recommendations have been developed to improve the care of intensive care unit (ICU) patients during the dying process. The recommendations build on those published in 2003 and highlight recent developments in the field from a U.S. perspective. They do not use an evidence grading system because most of the recommendations are based on ethical and legal principles that are not derived from empirically based evidence. Principal Findings: Family-centered care, which emphasizes the importance of the social structure within which patients are embedded, has emerged as a comprehensive ideal for managing end-of-life care in the ICU. ICU clinicians should be competent in all aspects of this care, including the practical and ethical aspects of withdrawing different modalities of life-sustaining treatment and the use of sedatives, analgesics, and nonpharmacologic approaches to easing the suffering of the dying process. Several key ethical concepts play a foundational role in guiding end-oflife care, including the distinctions between withholding and withdrawing treatments, between actions of killing and allowing to die, and between consequences that are intended vs. those that are merely foreseen (the doctrine of double effect). Improved communication with the family has been shown to improve patient care and family outcomes. Other knowledge unique to endof-life care includes principles for notifying families of a patient’s death and compassionate approaches to discussing options for organ donation. End-of-life care continues even after the death of the patient, and ICUs should consider developing comprehensive bereavement programs to support both families and the needs of the clinical staff. Finally, a comprehensive agenda for improving end-of-life care in the ICU has been developed to guide research, quality improvement efforts, and educational curricula. Conclusions: End-of-life care is emerging as a comprehensive area of expertise in the ICU and demands the same high level of knowledge and competence as all other areas of ICU practice. (Crit Care Med 2008; 36:953‐963)

Physicians and nurses sometimes exert pressure on the families of critically ill patients to withhold or withdraw life-sustaining therapy from them. This pressure may stem from prognostic, professional, social, and economic factors. Although the pressure to limit life support may be appropriate in some circumstances, in others it is not justified. The pressure also may damage communications and cause resentment. If communications cannot be improved, and if the pressure cannot be relieved, a due process approach to conflict resolution that involves other parties may be required.

Purpose Although surveying critical care physicians regarding their behaviors and attitudes may usefully inform clinical, ethical, and policy questions, few resources exist for surveying intensivists electronically. We sought to develop an e-mail database for all intensivists associated with US training programs in critical care medicine (academic intensivists) and to determine the feasibility of using this database to survey intensivists. Materials and Methods We obtained e-mail addresses for academic intensivists by consulting each training program's institutional Web site or contacting program directors directly. We sent presumed intensivists up to 3 e-mail invitations to participate in an initial survey. Results We identified 2858 potential intensivists and obtained operative e-mail addresses for 2494 (87%). Only 31 (9%) of the remaining intensivists were members of the Society of Critical Care Medicine, suggesting that most of those without identified addresses were not intensivists. During the conduct of an initial survey, 161 physicians self-identified themselves as nonintensivists; of the remaining 2333 presumed intensivists, 1026 (44%) responded and 44 (2%) opted out. The response rate of 44% is based on the conservative assumptions that the remaining 1263 physicians were intensivists and saw the e-mail invitation. Conclusions This database provides a unique resource for investigators wishing to efficiently identify the views and practice patterns of US academic intensivists and provides a benchmark response rate of approximately 44% for electronic surveys of intensivists.

Consensus on the optimal treatment of Clostridium difficile infection (CDI) is rapidly changing. Treatment with metronidazole has been associated with increased clinical failure rates; however, the reasons for this are unclear. The purpose of this study was to assess age-related treatment response rates in hospitalized patients with CDI treated with metronidazole. This was a retrospective, multicenter cohort study of hospitalized patients with CDI. Patients were assessed for refractory CDI, defined as persistent diarrhea after 7 days of metronidazole therapy, and stratified by age and clinical characteristics. A total of 242 individuals, aged 60 ± 18 years (Charlson comorbidity index, 3.8 ± 2.4; Horn's index, 1.7 ± 1.0) were included. One hundred twenty-eight patients (53%) had severe CDI. Seventy patients (29%) had refractory CDI, a percentage that increased from 22% to 28% and to 37% for patients aged less than 50 years, for patients from 50 to 70 years, and for patients aged >70 years, respectively ( P = 0.05). In multivariate analysis, Horn's index (odds ratio [OR], 2.04; 95% confidence interval [CI], 1.50 to 2.77; P < 0.001), severe CDI (OR, 2.25; 95% CI, 1.15 to 4.41; P = 0.018), and continued use of antibiotics (OR, 2.65; 95% CI, 1.30 to 5.39; P = 0.0072) were identified as significant predictors of refractory CDI. Age was not identified as an independent risk factor for refractory CDI. Therefore, hospitalized elderly patients with CDI treated with metronidazole had increased refractory CDI rates likely due to increased underlying severity of illness, severity of CDI, and concomitant antibiotic use. These results may help identify patients that may benefit from alternative C. difficile treatments other than metronidazole.

Metal nanoshells are a type of nanoparticle composed by a dielectric core and a metallic coating. These nanoparticles have stimulated interest due to their remarkable optical properties. In common with metal colloids, they show distinctive absorpâ^' tion peaks at specific wavelengths due to surface plasmon resonance. However, unlike bare metal colloids, the wavelengths at which resonance occurs can be tuned by changing the core radius and coating thickness. One basic application of such property is in medicine, where it is hoped that nanoshells with absorption peaks in the nearâ^'infrared can be attached to canâ^' cerous tumours. In this paper, we study the changes of optical response in visible and near infrared wavelengths from single to randomly distributed clusters of nanoshells. The results were obtained using a novel formulation of Mie theory in evanesâ^' cent wave conditions, with a finiteâ^'difference timeâ^'domain (FDTD) simulation and experimentally on BaTiO3â^'gold nanoâ^' shells using a scanning nearâ^'optical microscope. The results show that the optical signal of a randomly distributed cluster of nanoshells can be supplementary tuned with respect to the case of single nanoshell depending by the geometric configuration of the clusters.

OBJECTIVE To assess the impact of implementing a low tidal volume ventilation strategy on hospital mortality for patients with acute lung injury or acute respiratory distress syndrome. DESIGN Retrospective, uncontrolled study. SETTING Adult medical-surgical and trauma intensive care units at a major inner city, university-affiliated hospital. PATIENTS A total of 292 patients with acute lung injury or acute respiratory distress syndrome. INTERVENTIONS Between the years 2000 and 2003, 200 prospectively identified patients with acute lung injury/acute respiratory distress syndrome were managed by the ARDS Network low tidal volume protocol. A historical control group of 92 acute respiratory distress syndrome patients managed by routine practice from 1998 to 1999 was used for comparison. MEASUREMENTS AND MAIN RESULTS Patients managed with the ARDS Network protocol had a lower hospital mortality compared with historical controls (32% vs. 51%, respectively; p = .004). Multivariate logistic regression estimated an odds ratio of 0.32 (95% CI, 0.17-0.59; p = .0003) for mortality risk with use of the ARDS Network protocol. Protocol-managed patients had a lower tidal volume (6.2 +/- 1.1 vs. 9.8 +/- 1.5 mL/kg; p < .0001) and plateau pressure (27.5 +/- 6.4 vs. 33.8 +/- 8.9 cm H2O; p < .0001) than historical controls. CONCLUSION Adoption of the ARDS Network protocol for routine ventilator management of acute lung injury/acute respiratory distress syndrome patients was associated with a lower mortality compared with recent historical controls.

Background: Many subjects enrolled in research studies have a limited understanding of the research to which they consented. Objective: To develop recommendations to enhance comprehensiveness and understanding of informed consent forms used in critical care clinical trials. Design: Consensus process. Recommendations: We provide recommendations regarding the U.S. federally required basic and additional elements of informed consent as applied to critical care clinical trials. We also identify issues that investigators need to address, if relevant, in the informed consent forms of critical care clinical trials. These include the description, in understandable language, of complex and detailed experimental protocols that are the focus of the clinical trial, disclosure of death as a risk factor if mortality is an outcome variable, and the identification of who can legally serve as the prospective subject’s surrogate. We also offer suggestions to enhance subjects’ understanding of informed consent forms. Conclusions: The literature on informed consent forms suggest that shorter informed consent forms written at a lower reading level, when read carefully, might provide better subject understanding. Prospective evaluation is needed to determine whether our recommendations enhance the informed consent process.

The concept that critical illness and terminal illness are necessarily distinct entities has given way to the understanding that they often exist on the same spectrum. Consequently, there is growing consensus that palliative treatment must coexist with attempts at restorative treatment in the intensive care unit (ICU). Palliative care in the ICU has evolved from a relatively one-dimensional construct of terminal sedation in dying patients to a multidisciplinary field addressing symptom control, physician-patient-family communication,spiritual needs, and the needs of health care providers. As ongoing research efforts yield new insights, our ability to practice evidence-based palliative care in the ICU will grow, and new avenues for improvement will become evident.

PURPOSE OF REVIEW: The subject of research ethics and informed consent in the ICU has recently received unprecedented attention during the past year, the reasons for which are reviewed herein. RECENT FINDINGS: The controversy over research design and informed consent issues in studies conducted by the Acute Respiratory Distress Syndrome Network in the United States have been responsible for much of the attention on research ethics. So has the draft directive to create a harmonization of the provisions governing clinical trials within the European Union. These and other factors have prompted renewed interest in the proper design of clinical trials, the difficulty of obtaining informed consent for research from critically ill patients and their surrogates, conflicts of interest on the part of investigators and their institutions, the need for improving institutional protections for human subjects, and the desirability of clarifying the investigator-subject relationship. SUMMARY: Clinical trials should compare new therapies with "standard" ones if a standard of care exists. Surrogate consent is required for research involving most critically ill subjects, and state laws in the United States and national statutes in Europe should reflect this requirement. Conflicts of interest should be identified at both the individual and the institutional levels. Institutional review boards should focus on ethical issues after conflicts of interest are evaluated. Making the investigator-subject relationship transparent should help protect subjects.

The primary goal of this study was to address the documented deficiencies in end-of-life care (EOLC) in intensive care unit settings by identifying key EOLC domains and related quality indicators for use in the intensive care unit through a consensus process. A second goal was to propose specific clinician and organizational behaviors and interventions that might be used to improve these EOLC quality indicators.Participants were the 36 members of the Robert Wood Johnson Foundation (RWJF) Critical Care End-of-Life Peer Workgroup and 15 nurse-physician teams from 15 intensive care units affiliated with the work group members. Fourteen adult medical, surgical, and mixed intensive care units from 13 states and the District of Columbia in the United States and one mixed intensive care unit in Canada were represented.An in-depth literature review was conducted to identify articles that assessed the domains of quality of EOLC in the intensive care unit and general health care. Consensus regarding the key EOLC domains in the intensive care unit and quality performance indicators within each domain was established based on the review of the literature and an iterative process involving the authors and members of the RWJF Critical Care End-of-Life Peer Workgroup. Specific clinician and organizational behaviors and interventions to address the proposed EOLC quality indicators within the domains were identified through a collaborative process with the nurse-physician teams in 15 intensive care units.Seven EOLC domains were identified for use in the intensive care unit: a) patient- and family-centered decision making; b) communication; c) continuity of care; d) emotional and practical support; e) symptom management and comfort care; f) spiritual support; and g) emotional and organizational support for intensive care unit clinicians. Fifty-three EOLC quality indicators within the seven domains were proposed. More than 100 examples of clinician and organizational behaviors and interventions that could address the EOLC quality indicators in the intensive care unit setting were identified.These EOLC domains and the associated quality indicators, developed through a consensus process, provide clinicians and researchers with a framework for understanding quality of EOLC in the intensive care unit. Once validated, these indicators might be used to improve the quality of EOLC by serving as the components of an internal or external audit evaluating EOLC continuous quality improvement efforts in intensive care unit settings.

Highly active antiretroviral therapy for human immunodeficiency virus (HIV) infection has produced significant declines in morbidity and mortality from acquired immunodeficiency syndrome (AIDS). Whether this therapy has resulted in changes in epidemiology and outcomes of intensive care among HIV-infected patients is unknown. We performed chart review of all intensive care unit admissions for HIV-infected patients at San Francisco General Hospital from 1996 through 1999. There were an average of 88.5 admissions per year with 71% survival to hospital discharge. Univariate analysis demonstrated that prior highly active antiretroviral therapy (odds ratio [OR] = 1.8, p = 0.04), a non-AIDS-associated admission diagnosis (OR = 3.7, p = 0.001), a lower Acute Physiology and Chronic Health Evaluation II score (OR = 5.4, p = 0.001), and higher serum albumin (OR = 4.4, p = 0.001) predicted improved survival. Pneumocystis carinii pneumonia (OR = 0.24, p = 0.001), mechanical ventilation (OR = 0.19, p = 0.001), or a pneumothorax (OR = 0.08, p = 0.001) were associated with worse survival. In multivariate logistic regression, all variables except prior use of highly active antiretroviral therapy and pneumothorax were significant independent predictors of outcome. At our institution, overall survival for HIV-infected intensive care unit patients has improved, especially among patients receiving highly active antiretroviral therapy. These patients may have an improved survival because of effects of therapy on variables such as likelihood of non-AIDS-associated admission diagnoses and serum albumin levels.

Objective: To illustrate some of the difficulties encountered in the transition from restorative to palliative care and in the pursuit of patient autonomy in the intensive care unit. Design: A review of the cases of three patients who asked that life support be withheld or withdrawn, and a discussion of the legal and ethical implications of these cases. Setting: A surgical intensive care unit in an academically affiliated public hospital serving as a Level I trauma center. Patients: Three adults with severe injuries who lacked legal surrogates and lost the ability to make medical decisions. Interventions: Care from the attending surgery and consultative critical care services, in addition to consultations from the psychiatry service and the hospital ethics committee. Main Results: All three patients died after life support was withheld or withdrawn, but not without conflicts among the various services. In two cases, decisions that the patients may or may not have agreed with were made for them by their physicians. In the third case, the patient was not consulted after his clinical situation changed. Conclusions: Patients' wishes change and are difficult to know, and even when they are known, physicians may have difficulty honoring them. Nevertheless, patient autonomy should be respected whenever possible in the intensive care unit.

In patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS), a recent ARDS Network randomized controlled trial demonstrated that a low tidal volume (VT) mechanical ventilation strategy (6 ml/kg) reduced mortality by 22% compared with traditional mechanical ventilation (12 ml/kg). In this study, we examined the relative efficacy of low VT mechanical ventilation among 902 patients with different clinical risk factors for ALI/ARDS who participated in ARDS Network randomized controlled trials. The clinical risk factor for ALI/ARDS was associated with substantial variation in mortality. The risk of death (before discharge home with unassisted breathing) was highest in patients with sepsis (43%); intermediate in subjects with pneumonia (36%), aspiration (37%), and other risk factors (35%); and lowest in those with trauma (11%) (p < 0.0001). Despite these differences in mortality, there was no evidence that the efficacy of the low VT strategy varied by clinical risk factor (p = 0.76, for interaction between ventilator group and risk factor). There was also no evidence of differential efficacy of low VT ventilation in the other study outcomes: proportion of patients achieving unassisted breathing (p = 0.59), ventilator-free days (p = 0.58), or development of nonpulmonary organ failure (p = 0.44). Controlling for demographic and clinical covariates did not appreciably affect these results. After reclassifying the clinical risk factors as pulmonary versus nonpulmonary predisposing conditions and infection-related versus non-infection-related conditions, there was still no evidence that the efficacy of low VT ventilation differed among clinical risk factor subgroups. In conclusion, we found no evidence that the efficacy of the low VT ventilation strategy differed among clinical risk factor subgroups for ALI/ARDS.

OBJECTIVE: To evaluate the effect of primary care coordination on utilization rates and satisfaction with care among public hospital patients. DESIGN: Prospective randomized gatekeeper intervention, with 1-year follow-up. SETTING: The Adult General Medical Clinic at San Francisco General Hospital, a university-affiliated public hospital. PATIENTS: We studied 2,293 established patients of 28 primary care physicians. INTERVENTION: Patients were randomized based on their primary care physician’s main clinic day. The 1,121 patients in the intervention group (Ambulatory Patient-Physician Relationship Organized to Achieve Coordinated Healthcare [APPROACH] group) required primary care physician approval to receive specialty and emergency department (ED) services; 1,172 patients in the control group did not. MEASUREMENTS AND MAIN RESULTS: Changes in outpatient, ED, and inpatient utilization were measured for APPROACH and control groups over the 1-year observation period, and the differences in the changes between groups were calculated to estimate the effect of the intervention. Acceptability of the gatekeeping model was determined via patient satisfaction surveys. RESULTS: Over the 1-year observation period, APPROACH patients decreased their specialty use by 0.57 visits per year more than control patients did (P=.04; 95% confidence interval [CI] −1.05 to −0.01). While APPROACH patients increased their primary care use by 0.27 visits per year more than control patients, this difference was not statistically significant (P=.14; 95% CI, −0.11 to 0.66). Changes in lowacuity ED care were similar between the two groups (0.06 visits per year more in APPROACH group than control group, P=.42; 95% CI, −0.09 to 0.22). APPROACH patients decreased yearly hospitalizations by 0.14 visits per year more than control patients (P=.02; 95% CI, −0.26 to −0.03). Changes in patient satisfaction with care, perceived access to specialists, and use of out-of-network services between the 2 groups were similar. CONCLUSIONS: A primary care model of health delivery in a public hospital that utilized a gatekeeping strategy decreased outpatient specialty and hospitalization rates and was acceptable to patients.

(1999). The elettra circular polarization beamline and electromagnetic elliptical wiggler insertion device. Synchrotron Radiation News: Vol. 12, No. 4, pp. 34-38.

In some intensive care units (ICUs), fewer patients who die now undergo attempts at cardiopulmonary resuscitation (CPR), and many more have life support actively withdrawn prior to death than did a decade ago. To determine the frequency of withdrawal of life support, we contacted every American postgraduate training program with significant clinical exposure to critical care medicine, asking them prospectively to classify patients who died into one of five mutually exclusive categories. We received data from 131 ICUs at 110 institutions in 38 states. There were 6,303 deaths, of which 393 patients were brain dead. Of the remaining 5,910 patients who died, 1,544 (23%) received full ICU care including failed cardiopulmonary resuscitation (CPR); 1,430 (22%) received full ICU care without CPR; 797 (10%) had life support withheld; and 2,139 (38%) had life support withdrawn. There was wide variation in practice among ICUs, with ranges of 4 to 79%, 0 to 83%, 0 to 67%, and 0 to 79% in these four categories, respectively. Variation was not related to ICU type, hospital type, number of admissions, or ICU mortality. We conclude that limitation of life support prior to death is the predominant practice in American ICUs associated with critical care training programs. There is wide variation in end-of-life care, and efforts are needed to understand practice patterns and to establish standards of care for patients dying in ICUs.

To review acute lung injury (ALI) and the acute respiratory distress syndrome (ARDS) in light of recent information about the definitions, epidemiology, pathophysiology, management, and outcome of these conditions.The author's personal files as well as the computerized MEDLINE database. STUDY SOLUTION: Studies were selected for their relevance to the conditions of ALI and ARDS.The author extracted all applicable data.The diagnostic criteria for ALI and ARDS include a) acute onset; b) bilateral chest radiographic infiltrates; c) a pulmonary artery occlusion pressure ofor =18 mm Hg or no evidence of left atrial hypertension; and d) impaired oxygenation manifested by a PaO2/FIO2 ratio ofor =300 torr (or =40 kPa) for ALI andor =200 torr (or =27 kPa) for ARDS. The incidence of ALI and ARDS are approximately 70 and 7 patients out of 100,000 of the total U.S. population per year, respectively. The conditions result from direct or indirect injury to the pulmonary epithelium and endothelium that causes edema, atelectasis, inflammation, and fibrosis. This "diffuse alveolar damage" is actually patchy in many patients. Therapy of ALI and ARDS is largely supportive, although new approaches in mechanical ventilation, patient positioning, and pharmacologic therapy have been introduced. The mortality rate of ARDS has improved to50%, but the reasons for this improvement are unclear.ALI and ARDS are better defined and understood than ever before, and their outcome has improved for unclear reasons.

The incidence of withholding and withdrawal of life support from critically ill patients has increased to the extent that these practices now precede well over half of all deaths in many intensive care units (ICUs). Although the forgoing of life-sustaining therapy is ethically acceptable and clinically desirable in certain instances, and although physicians do not have a responsibility to provide futile care even if a patient or surrogate insists on it, they must be cautious in exercising their influence, if not authority, over patients and surrogates in prompting the withholding and withdrawal of life support. Such caution is particularly indicated because managed care has made patients suspicious of healthcare institutions and physicians who are rewarded for restricting access to care. Most patients and surrogates agree with reasonable physician recommendations to forgo life-sustaining therapy. When they do not agree, physicians should not limit care on the basis of their own personal notions of futility, but should instead rely on institutional or multiinstitutional futility policies. Such policies should be developed by health professionals, patients, community leaders, and, when appropriate, participants in managed-care organizations. They should specify which ICU interventions are beneficial, address potential conflicts of interest, and be available to persons who could use such information in selecting the source of their care.

T HIS OFFICIAL STATEMENT OF THE A MERICAN T HORACIC S OCIETY WAS ADOPTED BY THE ATS B OARD OF D IRECTORS , M ARCH 1997. SUMMARY American Thoracic Society (ATS) members, as health care practitioners caring for critically ill patients in intensive care units (ICUs) or as ICU directors, commonly must make decisions that allocate ICU resources. Some decisions necessitate prioritization of ICU beds while others limit access to particular scarce resources. Although these decisions arise when providing medical care for ICU patients, they occur in a larger context that includes ethical, economic, social, and legal considerations. In this context health care systems in the United States and in other countries face the consequences of increasing demand for expensive health care services in times of limited financial resources and competing societal needs. If one accepts the premise that demand for health care resources will inevitably outstrip financial constraints, one then must face the basic question of how to allocate those resources fairly. How health care organizations will meet increasing demand for services within financial constraints raises specific questions relating to the fair allocation of ICU resources

To determine whether limits to life-sustaining care are becoming more common, we attempted to quantify the incidence of recommendations to withhold or withdraw life support from critically ill patients, to describe how patients respond to these recommendations, and to examine how conflicts over these recommendations are resolved. In 1992 and 1993 we prospectively enrolled 179 consecutive patients from two intensive care units (ICUs) for whom a recommendation was made to withhold or withdraw life support. Where possible, we compared results with data collected in the same units over a similar time period in 1987 and 1988. Recommendations to withhold or withdraw life support preceded 179 of 200 deaths (90%) in 1992 and 1993, compared with 114 of 224 deaths (51%) in 1987 and 1988 (chi2 = 73.76, p0.001]. Cardiopulmonary resuscitation was initiated in 10% of deaths in 1992 and 1993 as compared with 49% in 1987 and 1988. Ninety percent of patients agreed within less than 5 d, and only eight patients (4%) refused physicians' recommendations to limit life support. In cases of conflict, physicians in 1992 and 1993 deferred to patients with one exception: physicians were willing to refuse surrogate requests for resuscitation of patients they considered hopelessly ill. We conclude that 90% of patients who die in these ICUs now do so following a decision to limit therapy, that this represents a major change in practice in these institutions over a period of 5 yr, that most patients and surrogates accept an appropriate recommendation to withhold or withdraw life support, and that physicians will refuse surrogate requests in certain circumstances.

Advancements were made in the understanding of the human immunodeficiency virus (HIV) and the management of patients with the acquired immunodeficiency syndrome (AIDS) in many parts of the United States after such patients were first identified in 1981. Nevertheless, the relatively small city of San Francisco contributed a disproportionate share of them, due largely to the city's inclusive political and community response to the HIV/AIDS epidemic, including the activities of its Department of Public Health and San Francisco General Hospital (SFGH). San Francisco's colorful history, multicultural character, and tradition of tolerance attracted many patients who would develop HIV/AIDS to the city. The same factors underlaid the community's compassionate response when large numbers of these patients needed medical services. These factors also motivated the physicians, nurses, and other health professionals at SFGH who cared for the patients on the world's first inpatient AIDS ward.