Search

Abstract Background Subcutaneous erenumab reduced monthly migraine days and increased the likelihood of achieving a ≥ 50% reduction at all monthly assessment points tested in 2 pivotal trials in episodic migraine (EM) and chronic migraine (CM). Early efficacy of migraine preventive medications is an important treatment characteristic to patients. Delays in achievement of efficacy can result in failed adherence. The objective of these post-hoc analyses were to evaluate efficacy in the first 4 weeks after initial subcutaneous administration of erenumab 70 mg, erenumab 140 mg, or placebo. Methods There is no generally accepted methodology to measure onset of action for migraine preventive medications. We used a comprehensive approach with data from both studies to evaluate change from baseline in weekly migraine days (WMD), achievement of ≥ 50% reduction in WMD, and proportion of patients experiencing migraine measured on a daily basis. The 7-day moving averages were overlaid with observed data. Results In both studies (EM: N = 955; CM: N = 667), there was evidence of onset of efficacy of erenumab vs. placebo during the first week of treatment, which in some cases reached nominal significance. For EM the changes in WMD were (least squares mean [LSM] [95% CI]): placebo, − 0.1 (− 0.3, 0.0); erenumab 70 mg, − 0.3 (− 0.5, − 0.2) p = 0.130; erenumab 140 mg, − 0.6 (− 0.7, − 0.4) p

Context: Trials comparing higher vs lower levels of positive end-expiratory pressure (PEEP) in adults with acute lung injury or acute respiratory distress syndrome (ARDS) have been underpowered to detect small but potentially important effects on mortality or to explore subgroup differences.Objectives: To evaluate the association of higher vs lower PEEP with patient-important outcomes in adults with acute lung injury or ARDS who are receiving ventilation with low tidal volumes and to investigate whether these associations differ across prespecified subgroups.Data Sources: Search of MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials (1996-January 2010) plus a hand search of conference proceedings (2004-January 2010).Study Selection: Two reviewers independently screened articles to identify studies randomly assigning adults with acute lung injury or ARDS to treatment with higher vs lower PEEP (with low tidal volume ventilation) and also reporting mortality.Data Extraction: Data from 2299 individual patients in 3 trials were analyzed using uniform outcome definitions. Prespecified effect modifiers were tested using multivariable hierarchical regression, adjusting for important prognostic factors and clustering effects.Results: There were 374 hospital deaths in 1136 patients (32.9%) assigned to treatment with higher PEEP and 409 hospital deaths in 1163 patients (35.2%) assigned to lower PEEP (adjusted relative risk [RR], 0.94; 95% confidence interval [CI], 0.86-1.04; P = .25). Treatment effects varied with the presence or absence of ARDS, defined by a value of 200 mm Hg or less for the ratio of partial pressure of oxygen to fraction of inspired oxygen concentration (P = .02 for interaction). In patients with ARDS (n = 1892), there were 324 hospital deaths (34.1%) in the higher PEEP group and 368 (39.1%) in the lower PEEP group (adjusted RR, 0.90; 95% CI, 0.81-1.00; P = .049); in patients without ARDS (n = 404), there were 50 hospital deaths (27.2%) in the higher PEEP group and 44 (19.4%) in the lower PEEP group (adjusted RR, 1.37; 95% CI, 0.98-1.92; P = .07). Rates of pneumothorax and vasopressor use were similar.Conclusions: Treatment with higher vs lower levels of PEEP was not associated with improved hospital survival. However, higher levels were associated with improved survival among the subgroup of patients with ARDS. [ABSTRACT FROM AUTHOR]

RATIONALE: Compositional changes in surfactant and/or decreased surfactant content of the lungs are common features in patients with acute respiratory failure. Instillation of exogenous surfactant into the lungs of neonates with respiratory distress syndrome or pediatric patients with acute respiratory distress syndrome (ARDS) has resulted in improved survival. OBJECTIVES: We conducted this trial to determine whether the instillation of exogenous surfactant would improve the Day 28 outcome of adult patients with acute lung injury (ALI) or ARDS. METHODS: A total of 418 patients with ALI and ARDS were included in an international, multicenter, stratified, randomized, controlled, open, parallel-group study. We randomly assigned 418 patients to receive usual care either with or without instillation of exogenous natural porcine surfactant HL 10 as large boluses. MEASUREMENTS AND MAIN RESULTS: The primary endpoint was death rate before or on Day 28. Secondary endpoints were adverse event and death rate on day 180. The 28-day death rate in the usual care group was 24.5% compared with 28.8% in the HL 10 group. The estimated odds ratio for death at Day 28 in the usual care group versus the HL 10 group was 0.75 (95% CI, 0.48-1.18; P = 0.22). The most common adverse events related to HL 10 administration were temporary hypoxemia defined as oxygen saturation less than 88% (51.9% in HL 10 group vs. 25.2% in usual care) and hypotension defined as mean arterial blood pressure less than 60 mm Hg (34.1% in HL 10 group vs. 17.1% in usual care). CONCLUSIONS: In this study, instillation of a large bolus of exogenous natural porcine surfactant HL 10 into patients with acute lung injury and ARDS did not improve outcome and showed a trend toward increased mortality and adverse effects. Clinical trial registered with www.clinicaltrials.gov (NCT 00742482). [ABSTRACT FROM AUTHOR]

Context: In March 2009, novel 2009 influenza A(H1N1) was first reported in the southwestern United States and Mexico. The population and health care system in Mexico City experienced the first and greatest early burden of critical illness.Objective: To describe baseline characteristics, treatment, and outcomes of consecutive critically ill patients in Mexico hospitals that treated the majority of such patients with confirmed, probable, or suspected 2009 influenza A(H1N1).Design, Setting, and Patients: Observational study of 58 critically ill patients with 2009 influenza A(H1N1) at 6 hospitals between March 24 and June 1, 2009. Demographic data, symptoms, comorbid conditions, illness progression, treatments, and clinical outcomes were collected using a piloted case report form.Main Outcome Measures: The primary outcome measure was mortality. Secondary outcomes included rate of 2009 influenza (A)H1N1-related critical illness and mechanical ventilation as well as intensive care unit (ICU) and hospital length of stay.Results: Critical illness occurred in 58 of 899 patients (6.5%) admitted to the hospital with confirmed, probable, or suspected 2009 influenza (A)H1N1. Patients were young (median, 44.0 [range, 10-83] years); all presented with fever and all but 1 with respiratory symptoms. Few patients had comorbid respiratory disorders, but 21 (36%) were obese. Time from hospital to ICU admission was short (median, 1 day [interquartile range {IQR}, 0-3 days]), and all patients but 2 received mechanical ventilation for severe acute respiratory distress syndrome and refractory hypoxemia (median day 1 ratio of Pao(2) to fraction of inspired oxygen, 83 [IQR, 59-145] mm Hg). By 60 days, 24 patients had died (41.4%; 95% confidence interval, 28.9%-55.0%). Patients who died had greater initial severity of illness, worse hypoxemia, higher creatine kinase levels, higher creatinine levels, and ongoing organ dysfunction. After adjusting for a reduced opportunity of patients dying early to receive neuraminidase inhibitors, neuraminidase inhibitor treatment (vs no treatment) was associated with improved survival (odds ratio, 8.5; 95% confidence interval, 1.2-62.8).Conclusion: Critical illness from 2009 influenza A(H1N1) in Mexico occurred in young individuals, was associated with severe acute respiratory distress syndrome and shock, and had a high case-fatality rate. [ABSTRACT FROM AUTHOR]

RATIONALE: It is commonly stated that mortality from acute respiratory distress syndrome (ARDS) and acute lung injury (ALI) is decreasing. OBJECTIVES: To systematically review the literature assessing ARDS mortality over time and to determine patient- and study-level factors independently associated with mortality. METHODS: We searched multiple databases (MEDLINE, EMBASE, CINAHL, Cochrane CENTRAL) for prospective observational studies or randomized controlled trials (RCTs) published during the period 1984 to 2006 that enrolled 50 or more patients with ALI/ARDS and reported mortality. We pooled mortality estimates using random-effects meta-analysis and examined mortality trends before and after 1994 (when a consensus definition of ALI/ARDS was published) and factors associated with mortality using meta-regression models. MEASUREMENTS AND MAIN RESULTS: Of 4,966 studies, 89 met inclusion criteria (53 observational, 36 RCTs). There was a total of 18,900 patients (mean age 51.6 years; 39% female). Overall pooled weighted mortality was 44.3% (95% confidence interval [CI], 41.8-46.9). Mortality decreased with time in observational studies conducted before 1994; no temporal associations with mortality were demonstrated in RCTs (any time) or observational studies (after 1994). Pooled mortality from 1994 to 2006 was 44.0% (95% CI, 40.1-47.5) for observational studies, and 36.2% (95% CI, 32.1-40.5) for RCTs. Meta-regression identified study type (observational versus RCT, odds ratio, 1.36; 95% CI, 1.08-1.73) and patient age (odds ratio per additional 10 yr, 1.27; 95% CI, 1.07-1.50) as the only factors associated with mortality. CONCLUSIONS: A decrease in ARDS mortality was only seen in observational studies from 1984 to 1993. Mortality did not decrease between 1994 (when a consensus definition was published) and 2006, and is lower in RCTs than observational studies. [ABSTRACT FROM AUTHOR]

Rationale: There are conflicting data regarding the safety and efficacy of recruitment maneuvers (RMs) in patients with acute lung injury (ALI). Objectives: To summarize the physiologic effects and adverse events in adult patients with ALI receiving RMs. Methods: Systematic review of case series, observational studies, and randomized clinical trials with pooling of study-level data. Measurements and Main Results: Forty studies (1,185 patients) met inclusion criteria. Oxygenation (31 studies; 636 patients) was significantly increased after an RM (Pa(O(2)): 106 versus 193 mm Hg, P = 0.001; and Pa(O(2))/Fi(O(2)) ratio: 139 versus 251 mm Hg, P < 0.001). There were no persistent, clinically significant changes in hemodynamic parameters after an RM. Ventilatory parameters (32 studies; 548 patients) were not significantly altered by an RM, except for higher PEEP post-RM (11 versus 16 cm H(2)O; P = 0.02). Hypotension (12%) and desaturation (9%) were the most common adverse events (31 studies; 985 patients). Serious adverse events (e.g., barotrauma [1%] and arrhythmias [1%]) were infrequent. Only 10 (1%) patients had their RMs terminated prematurely due to adverse events. Conclusions: Adult patients with ALI receiving RMs experienced a significant increase in oxygenation, with few serious adverse events. Transient hypotension and desaturation during RMs is common but is self-limited without serious short-term sequelae. Given the uncertain benefit of transient oxygenation improvements in patients with ALI and the lack of information on their influence on clinical outcomes, the routine use of RMs cannot be recommended or discouraged at this time. RMs should be considered for use on an individualized basis in patients with ALI who have life-threatening hypoxemia. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To detennine the magnitude, duration, and consistency of the effects of lung recruitment maneuvers (RMs) on oxygenation, lung mechanics, and comfort in patients with acute lung injury (ALI) and acute respiratory distress syndrome (ARDS). METHODS: We conducted a prospective physiologic study at 3 tertiary-care hospitals. We enroUed 28 consecutive eligible patients with ARDS or ALI and a ratio of PaO, to fraction of inspired oxygen (Pao,lF10) ::s 250 mm Hg While receiving F10, ~ 0.50. We performed RMs twice daily for 3 days. The first RM was at 35 cm H20 for 20 s. Ifinitial response was equivocal, the clinician immediately administered another RM at a higher pressure (40 cm H20, then 45 cm H20) or for longer period (30 s, then 40 s), in a randomized order. Each patient had up to 6 sets of up to 3 RMs. RESULTS: Twenty-seven patients met the criteria for ARDS at baseline; 1 had ALI. There was no net effect on oxygenation or pulmonary mechanics foUowing the first or subsequent RMs. The largest rise in PaO, was from 61 mm Hg to 71 mm Hg, and the largest decrease was 6 mm Hg foUowing the first RM. Augmenting the inflation pressure or duration had no significant effect. These findings precluded analyses about predictors of response or consistency of response. Over the entire study of 122 RMs, 5 patients developed ventilator asynchrony, 3 appeared uncomfortable, 2 experienced transient hypotension, and 4 developed barotrauma that required intervention. CONCLUSIONS: These results do not support the addition of scheduled RMs to usual treatment for ALlor ARDS. [ABSTRACT FROM AUTHOR]

OBJECTIVE: Acute respiratory distress syndrome is a common disorder associated with significant mortality and morbidity. The aim of this article is to critically evaluate the definition of acute respiratory distress syndrome and examine the impact the definition has on clinical practice and research. DATA SOURCES: Articles from a MEDLINE search (1950 to August 2007) using the Medical Subject Heading respiratory distress syndrome, adult, diagnosis, limited to the English language and human subjects, their relevant bibliographies, and personal collections, were reviewed. DATA SYNTHESIS: The definition of acute respiratory distress syndrome is important to researchers, clinicians, and administrators alike. It has evolved significantly over the last 40 years, culminating in the American-European Consensus Conference definition, which was published in 1994. Although the American-European Consensus Conference definition is widely used, it has some important limitations that may impact on the conduct of clinical research, on resource allocation, and ultimately on the bedside management of such patients. These limitations stem partially from the fact that as defined, acute respiratory distress syndrome is a heterogeneous entity and also involve the reliability and validity of the criteria used in the definition. This article critically evaluates the American-European Consensus Conference definition and its limitations. Importantly, it highlights how these limitations may contribute to clinical trials that have failed to detect a potential true treatment effect. Finally, recommendations are made that could be considered in future definition modifications with an emphasis on the significance of accurately identifying the target population in future trials and subsequently in clinical care. CONCLUSION: How acute respiratory distress syndrome is defined has a significant impact on the results of randomized, controlled trials and epidemiologic studies. Changes to the current American-European Consensus Conference definition are likely to have an important role in advancing the understanding and management of acute respiratory distress syndrome. [ABSTRACT FROM AUTHOR]

Context: Low-tidal-volume ventilation reduces mortality in critically ill patients with acute lung injury and acute respiratory distress syndrome. Instituting additional strategies to open collapsed lung tissue may further reduce mortality.Objective: To compare an established low-tidal-volume ventilation strategy with an experimental strategy based on the original "open-lung approach," combining low tidal volume, lung recruitment maneuvers, and high positive-end-expiratory pressure.Design and Setting: Randomized controlled trial with concealed allocation and blinded data analysis conducted between August 2000 and March 2006 in 30 intensive care units in Canada, Australia, and Saudi Arabia.Patients: Nine hundred eighty-three consecutive patients with acute lung injury and a ratio of arterial oxygen tension to inspired oxygen fraction not exceeding 250.Interventions: The control strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau airway pressures not exceeding 30 cm H2O, and conventional levels of positive end-expiratory pressure (n = 508). The experimental strategy included target tidal volumes of 6 mL/kg of predicted body weight, plateau pressures not exceeding 40 cm H2O, recruitment maneuvers, and higher positive end-expiratory pressures (n = 475).Main Outcome Measure: All-cause hospital mortality.Results: Eighty-five percent of the 983 study patients met criteria for acute respiratory distress syndrome at enrollment. Tidal volumes remained similar in the 2 groups, and mean positive end-expiratory pressures were 14.6 (SD, 3.4) cm H2O in the experimental group vs 9.8 (SD, 2.7) cm H2O among controls during the first 72 hours (P < .001). All-cause hospital mortality rates were 36.4% and 40.4%, respectively (relative risk [RR], 0.90; 95% confidence interval [CI], 0.77-1.05; P = .19). Barotrauma rates were 11.2% and 9.1% (RR, 1.21; 95% CI, 0.83-1.75; P = .33). The experimental group had lower rates of refractory hypoxemia (4.6% vs 10.2%; RR, 0.54; 95% CI, 0.34-0.86; P = .01), death with refractory hypoxemia (4.2% vs 8.9%; RR, 0.56; 95% CI, 0.34-0.93; P = .03), and previously defined eligible use of rescue therapies (5.1% vs 9.3%; RR, 0.61; 95% CI, 0.38-0.99; P = .045).Conclusions: For patients with acute lung injury and acute respiratory distress syndrome, a multifaceted protocolized ventilation strategy designed to recruit and open the lung resulted in no significant difference in all-cause hospital mortality or barotrauma compared with an established low-tidal-volume protocolized ventilation strategy. This "open-lung" strategy did appear to improve secondary end points related to hypoxemia and use of rescue therapies.Trial Registration: clinicaltrials.gov Identifier: NCT00182195. [ABSTRACT FROM AUTHOR]

We report a case of fatal necrotizing pneumonia and sepsis caused by community-associated methicillin-resistant Staphylococcus aureus (CA-MRSA) in an otherwise well, 48-year-old Canadian man with type 2 diabetes mellitus who had travelled to Texas. Despite therapy that included intravenous antibiotics, intravenous immune globulin and other supportive measures, the patient succumbed to his illness. Recently, CA-MRSA pneumonia has been reported in several countries. The virulence of this organism may in part be related to its ability to produce toxins, such as Panton-Valentine leukocidin. As rates of CA-MRSA increase worldwide, physicians should be aware of the potential for MRSA to cause life-threatening infections in patients presenting to Canadian emergency departments (EDs). Necrotizing pneumonia caused by MRSA must be considered in the differential diagnosis of acute, severe respiratory illness. Early recognition of this syndrome in the ED may help physicians initiate appropriate antibiotic therapy in a timely manner. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVES: To describe the clinical features and outcome of patients with invasive group A streptococcal (GAS) infections admitted to the ICU. DESIGN: Prospective, population-based surveillance for invasive GAS infections was conducted in Ontario from January 1992 until June 2002. All 62 patients meeting clinical and/or histopathologic criteria for invasive GAS who were admitted to the ICUs of four university-affiliated hospitals in Toronto, Canada were included. Demographic and clinical information were obtained retrospectively by chart review. ICU morbidity data included the occurrence of organ dysfunction (renal, hepatic, coagulation, ARDS), treatment, and interventions such as hemodialysis and mechanical ventilation. MEASUREMENTS AND RESULTS: ARDS developed in 34%, renal dysfunction developed in 55%, hepatic dysfunction developed in 64%, and coagulopathy developed in 69% of patients. A total of 56% of patients were treated with IV polyspecific IgG (IVIG), 81% were intubated and placed on mechanical ventilation, and 21% required renal replacement therapy. The median durations of ICU and hospital stay were 5.3 days and 15.0 days, respectively. The overall mortality was 40%. Mortality correlated directly with acute physiology and chronic health evaluation II score and the number of dysfunctional organs. Survivors were younger, had lower severity of illness scores, fewer dysfunctional organs, and were less likely to have shock or to receive treatment with vasopressors, mechanical ventilation, or pulmonary artery catheters. There was no association between the use of IVIG, surgical intervention, or clindamycin, and survival. Variables independently associated with mortality on multivariable analysis were the presence of coagulopathy (p = 0.0005) and liver dysfunction (p = 0.0123). CONCLUSIONS: Patients with invasive GAS infection admitted to the ICU have a high mortality rate. In this group of patients, coagulopathy and liver failure were independently associated with mortality. We did not observe any association between the use of IVIG, surgical intervention, or clindamycin, and survival. [ABSTRACT FROM AUTHOR]

Rationale: Little is known about the long-term outcomes and costs of survivors of acute respiratory distress syndrome (ARDS).Objectives: To describe functional and quality of life outcomes, health care use, and costs of survivors of ARDS 2 yr after intensive care unit (ICU) discharge.Methods: We recruited a cohort of ARDS survivors from four academic tertiary care ICUs in Toronto, Canada, and prospectively monitored them from ICU admission to 2 yr after ICU discharge.Measurements: Clinical and functional outcomes, health care use, and direct medical costs.Results: Eighty-five percent of patients with ARDS discharged from the ICU survived to 2 yr; overall 2-yr mortality was 49%. At 2 yr, survivors continued to have exercise limitation although 65% had returned to work. There was no statistically significant improvement in health-related quality of life as measured by Short-Form General Health Survey between 1 and 2 yr, although there was a trend toward better physical role at 2 yr (p = 0.0586). Apart from emotional role and mental health, all other domains remained below that of the normal population. From ICU admission to 2 yr after ICU discharge, the largest portion of health care costs for a survivor of ARDS was the initial hospital stay, with ICU costs accounting for 76% of these costs. After the initial hospital stay, health care costs were related to hospital readmissions and inpatient rehabilitation.Conclusions: Survivors of ARDS continued to have functional impairment and compromised health-related quality of life 2 yr after discharge from the ICU. Health care use and costs after the initial hospitalization were driven by hospital readmissions and inpatient rehabilitation. [ABSTRACT FROM AUTHOR]

The National Heart, Lung, and Blood Institute, along with the Centers for Disease Control and Prevention and the National Institute of Allergy and Infectious Diseases, convened a panel to develop recommendations for treatment, prevention, and research for respiratory failure from severe acute respiratory syndrome (SARS) and other newly emerging infections. The clinical and pathological features of acute lung injury (ALI) from SARS appear indistinguishable from ALI from other causes. The mainstay of treatments for ALI remains supportive. Patients with ALI from SARS who require mechanical ventilation should receive a lung protective, low tidal volume strategy. Adjuvant treatments recommended include prevention of venous thromboembolism, stress ulcer prophylaxis, and semirecumbent positioning during ventilation. Based on previous experience in Canada, infection control resources and protocols were recommended. Leadership structure, communication, training, and morale are an essential aspect of SARS management. A multicenter, placebo-controlled trial of corticosteroids for late SARS is justified because of widespread clinical use and uncertainties about relative risks and benefits. Studies of combined pathophysiologic endpoints were recommended, with mortality as a secondary endpoint. The group recommended preparation for studies, including protocols, ethical considerations, Web-based registries, and data entry systems. [ABSTRACT FROM AUTHOR]

STUDY OBJECTIVES: To review the clinical experience with high-frequency oscillatory ventilation (HFOV) in three medical-surgical ICUs in Toronto, ON, Canada, and to describe patient characteristics, HFOV strategies, and outcomes. DESIGN AND PATIENTS: Retrospective chart review of all patients treated with HFOV at three academic university-affiliated ICUs since 1998. The data extracted included patient demographics, etiology of respiratory failure, ventilator settings, and gas exchange and cardiovascular data from baseline to 72 h of treatment, as well as at the transition from HFOV to conventional ventilation (CV). Heart rate and BP were recorded at regular intervals in all patients, and hemodynamic data were recorded in 32 patients who had pulmonary artery catheters in place. Cointerventions and ICU mortality were also recorded. MEASUREMENTS AND RESULTS: A total of 156 adults (67 women and 89 men; mean [+/- SD] age, 48 +/- 18 years; mean acute physiology and chronic health evaluation [APACHE] II score, 23.8 +/- 7.5) with severe ARDS (ie, mean Pao(2)/fraction of inspired oxygen [Fio(2)] ratio, 91 +/- 48 mm Hg; mean oxygenation index [OI], 31 +/- 14) who had received CV for a duration of 5.6 +/- 7.6 days underwent 171 trials of HFOV. HFOV was discontinued within 4 h in 19 patients (12%) because of difficulties with oxygenation, ventilation, or hemodynamics. Pao(2)/Fio(2) ratios and OI ([Fio(2) x mean airway pressure x 100]/Pao(2)) improved significantly with the application of HFOV, and this benefit persisted for the 72-h study duration. Significant changes in hemodynamics following HFOV initiation included an increase in central venous pressure and a reduction in cardiac output (throughout the 72 h), and an increase in pulmonary artery occlusion pressure (at 3 and 6 h). Patients were treated with HFOV for 5.1 +/- 6.3 days. The 30-day mortality rate was 61.7%. Pneumothorax occurred in 21.8% of patients, 43.6% of patients were treated with inhaled nitric oxide, and 37.2% of patients were treated with steroids. Independent predictors of mortality on multivariate analysis were older age, higher APACHE II score, lower pH at the initiation of HFOV, and a greater number of days receiving CV prior to HFOV. CONCLUSIONS: HFOV has beneficial effects on Pao(2)/Fio(2) ratios and OI, and may be an effective rescue therapy for adults with severe oxygenation failure. The early institution of HFOV may be advantageous. [ABSTRACT FROM AUTHOR]

Nosocomial transmission of severe acute respiratory syndrome from critically ill patients to healthcare workers has been a prominent and worrisome feature of existing outbreaks. We have observed a greater risk of developing severe acute respiratory syndrome for physicians and nurses performing endotracheal intubation (relative risk [RR], 13.29; 95% confidence interval [CI], 2.99 to 59.04; p = 0.003). Nurses caring for patients receiving noninvasive positive-pressure ventilation may be at an increased risk (RR, 2.33; 95% CI, 0.25 to 21.76; p = 0.5), whereas nurses caring for patients receiving high-frequency oscillatory ventilation do not appear at an increased risk (RR, 0.74; 95% CI, 0.11 to 4.92; p = 0.6) compared with their respective reference cohorts. Specific infection control recommendations concerning the care of critically ill patients may help limit further nosocomial transmission. [ABSTRACT FROM AUTHOR]

OBJECTIVES: To assess the reproducibility of the static pressure-volume curve of the respiratory system by using a 'mini-syringe' technique; to assess the temporal change in upper (UIP) and lower inflection points (LIP) measured from pressure-volume curves of the respiratory system; to assess the inter- and intraobserver variability in detection of the UIP and LIP in patients with acute lung injury (ALI)/acute respiratory distress syndrome (ARDS); and to compare the syringe and multiple occlusion techniques for determining LIP and UIP. DESIGN: Prospective observational study. SETTING: Academic medical-surgical critical care unit. PATIENTS: Consecutive patients with ALI or ARDS. INTERVENTIONS: Static inspiratory pressure-volume curves of the respiratory system were determined twice on day 1 of diagnosis of ALI/ARDS and then once daily for up to 6 days by using the syringe technique. Pressure-volume curves were determined from zero positive end-expiratory pressure. At each time point, three separate measurements of the pressure-volume curve were made to determine reproducibility. A 100-mL graduated syringe was used to inflate patients' lungs with 50- to 100-mL increments up to an airway pressure of 45 cm H2O or a total volume of 2 L; each volume step was maintained for 2-3 secs until a plateau airway pressure was recorded. On day 1, the static pressure-volume curve also was determined by using the multiple occlusion technique. In a random and blinded sequence, the pressure-volume curves were examined visually by three critical care physicians on three different occasions, to determine the intra- and interobserver variability in visual detection of the LIP and UIP. Observers were given objective instructions to visually identify LIP and UIP. MEASUREMENTS AND MAIN RESULTS: Eleven patients were enrolled, with a total of 134 pressure-volume curves generated. LIP and UIP could be detected in 90-94% and 61-68% of curves, respectively. When the three successive pressure-volume curves were compared, both the LIP and UIP were within 3 cm H2O in >65% of curves. The index of reliability (intraclass correlation coefficient) in LIP and UIP was 0.92 and 0.89 for interobserver variability and 0.90 and 0.88 for intraobserver variability. Daily variability was as high as 7 cm H2O for LIP and 5 cm H2O for UIP. When pressure-volume curves obtained by using the multiple occlusion and syringe techniques were compared, LIP was within 2 cm H2O, and UIP was within 4 cm H2O with the two techniques. CONCLUSIONS: The static pressure-volume curve of the respiratory system is reasonably reproducible, thus avoiding the need for multiple measurements at a single time. We found excellent interobserver and intraobserver correlation in manual identification of the LIP and UIP. Both LIP and UIP show appreciable daily variability in patients with ALI/ARDS. The multiple occlusion and syringe techniques generate similar values for LIP and UIP. [ABSTRACT FROM AUTHOR]

Context: The outcome of patients receiving mechanical ventilation for particular indications has been studied, but the outcome in a large number of unselected, heterogeneous patients has not been reported.Objective: To determine the survival of patients receiving mechanical ventilation and the relative importance of factors influencing survival.Design, Setting, and Subjects: Prospective cohort of consecutive adult patients admitted to 361 intensive care units who received mechanical ventilation for more than 12 hours between March 1, 1998, and March 31, 1998. Data were collected on each patient at initiation of mechanical ventilation and daily throughout the course of mechanical ventilation for up to 28 days.Main Outcome Measure: All-cause mortality during intensive care unit stay.Results: Of the 15 757 patients admitted, a total of 5183 (33%) received mechanical ventilation for a mean (SD) duration of 5.9 (7.2) days. The mean (SD) length of stay in the intensive care unit was 11.2 (13.7) days. Overall mortality rate in the intensive care unit was 30.7% (1590 patients) for the entire population, 52% (120) in patients who received ventilation because of acute respiratory distress syndrome, and 22% (115) in patients who received ventilation for an exacerbation of chronic obstructive pulmonary disease. Survival of unselected patients receiving mechanical ventilation for more than 12 hours was 69%. The main conditions independently associated with increased mortality were (1) factors present at the start of mechanical ventilation (odds ratio [OR], 2.98; 95% confidence interval [CI], 2.44-3.63; P<.001 for coma), (2) factors related to patient management (OR, 3.67; 95% CI, 2.02-6.66; P<.001 for plateau airway pressure >35 cm H(2)O), and (3) developments occurring over the course of mechanical ventilation (OR, 8.71; 95% CI, 5.44-13.94; P<.001 for ratio of PaO(2) to fraction of inspired oxygen <100).Conclusion: Survival among mechanically ventilated patients depends not only on the factors present at the start of mechanical ventilation, but also on the development of complications and patient management in the intensive care unit. [ABSTRACT FROM AUTHOR]

Abstract The second most serious neurodegenerative disease is Parkinson’s disease (PD). Over the past several decades, a strong body of evidence suggests that PD can begin years before the hallmark clinical motor symptoms appear. Biomarkers for PD are urgently needed to differentiate between neurodegenerative disorders, screen novel therapeutics, and predict eventual clinical PD before the onset of symptoms. Some clinical evaluations and neuroimaging techniques have been developed in the last several years with some success in this area. Moreover, other strategies have been utilized to identify biochemical and genetic markers associated with PD leading to the examination of PD progression and pathogenesis in cerebrospinal fluid, blood, or saliva. Finally, interesting results are surfacing from preliminary studies using known PD-associated genetic mutations to assess potential premotor PD biomarkers. The current review highlights recent advances and underscores areas of potential advancement.

Objective: High-frequency oscillatory ventilation (HFOV) is an emerging ventilatory strategy for adults that has been used successfully in the neonatal and pediatric population. This modality utilizes high mean airway pressures to maintain an open lung and low tidal volumes at a high frequency that allow for adequate ventilation while at the same time preventing alveolar overdistension. With the current understanding that excessive lung stretch and inadequate end-expiratory ventilatory volume may be injurious to the lungs, HFOV seems to be the ideal lung-protective ventilatory mode. During the past 8 yrs, there have been increasing numbers of studies describing its use in adult patients with acute respiratory distress syndrome. This article aims to review the published studies of HFOV in adults with acute respiratory distress syndrome with regard to its safety and efficacy.Data Source: To assist us with our review, we did a search of MEDLINE (from 1966 to present) and EMBASE (1980 to present) databases to identify adult, clinical, English-language, research articles related to HFOV use. In addition, we reviewed relevant animal and mechanical ventilation studies. We did not perform a formal systematic review.Data Synthesis: The application of HFOV was mainly reported as a rescue ventilatory mode in adult patients with acute respiratory distress syndrome who were thought to have failed conventional ventilation. In these patients, HFOV has consistently been shown to improve oxygenation without obvious increases in complications measured. There was only one randomized, controlled trial comparing HFOV with conventional ventilation. This study showed that there was a nonsignificant trend toward a lower mortality rate in the HFOV group. In addition, HFOV was as effective and safe as conventional ventilation. Although there are limitations, multiple studies have shown that earlier initiation of HFOV in patients with severe acute respiratory distress syndrome may also be associated with a lower mortality.Conclusions: HFOV seems to be safe and effective for adults with severe acute respiratory distress syndrome who have failed conventional ventilation. Further research is needed to determine the ideal patients, timing, and optimal technique with which to provide HFOV. When considering HFOV as an early, lung-protective mode of ventilation, there is still a need to perform an adequately powered, randomized, controlled trial comparing it with the best available form of conventional ventilation. However, we believe that such a trial should wait until we have a better understanding of HFOV in adults. [ABSTRACT FROM AUTHOR]

Background: The 2003 global outbreak of severe acute respiratory syndrome (SARS) provided numerous challenges to the delivery of critical care. The Toronto critical care community has learned important lessons from SARS, which will help in preparation for future disease outbreaks.Objectives: The objectives of this study were to review the epidemiology and clinical characteristics of the Toronto SARS outbreak, the challenges SARS provided to the delivery of critical care, and how we would like to be better organized for a similar challenge in the future.Findings: SARS manifests clinically as atypical pneumonia and ranges in severity from minor nonspecific symptoms to adult respiratory distress syndrome (ARDS). Approximately 20% of patients with SARS will become critically ill and require admission to the intensive care unit. ARDS develops in the majority of these patients. Mortality from ARDS in SARS is high, and outcome is associated with the presence of comorbid disease and the severity of illness at presentation. The influx of critically ill patients and the transmission of SARS to front line workers created a tremendous strain on Toronto's healthcare system. From a critical care perspective, the most important limitation in the response to SARS was the absence of a coordinated leadership and communication infrastructure. Other challenges encountered during SARS include the following: closure of intensive care unit beds and loss of staff through quarantine and illness, implementing novel infection control protocols, educating staff, conducting research to learn about SARS, system planning, and maintaining staff morale during this very difficult period.Conclusions: Communication and leadership strategies were key components in the critical care response to SARS. Ideally, centers should have systems in place to allow for the rapid expansion and modification of critical care services in the event of a disease outbreak. Other critical care communities should consider their crisis response strategies in advance of similar events. [ABSTRACT FROM AUTHOR]

Background: As more patients survive the acute respiratory distress syndrome, an understanding of the long-term outcomes of this condition is needed.Methods: We evaluated 109 survivors of the acute respiratory distress syndrome 3, 6, and 12 months after discharge from the intensive care unit. At each visit, patients were interviewed and underwent a physical examination, pulmonary-function testing, a six-minute-walk test, and a quality-of-life evaluation.Results: Patients who survived the acute respiratory distress syndrome were young (median age, 45 years) and severely ill (median Acute Physiology, Age, and Chronic Health Evaluation score, 23) and had a long stay in the intensive care unit (median, 25 days). Patients had lost 18 percent of their base-line body weight by the time they were discharged from the intensive care unit and stated that muscle weakness and fatigue were the reasons for their functional limitation. Lung volume and spirometric measurements were normal by 6 months, but carbon monoxide diffusion capacity remained low throughout the 12-month follow-up. No patients required supplemental oxygen at 12 months, but 6 percent of patients had arterial oxygen saturation values below 88 percent during exercise. The median score for the physical role domain of the Medical Outcomes Study 36-item Short-Form General Health Survey (a health-related quality-of-life measure) increased from 0 at 3 months to 25 at 12 months (score in the normal population, 84). The distance walked in six minutes increased from a median of 281 m at 3 months to 422 m at 12 months; all values were lower than predicted. The absence of systemic corticosteroid treatment, the absence of illness acquired during the intensive care unit stay, and rapid resolution of lung injury and multiorgan dysfunction were associated with better functional status during the one-year follow-up.Conclusions: Survivors of the acute respiratory distress syndrome have persistent functional disability one year after discharge from the intensive care unit. Most patients have extrapulmonary conditions, with muscle wasting and weakness being most prominent. [ABSTRACT FROM AUTHOR]

Rationale: If the risk of ventilator-induced lung injury in acute respiratory distress syndrome (ARDS) is causally determined by driving pressure rather than by Vt, then the effect of ventilation with lower Vt on mortality would be predicted to vary according to respiratory system elastance (Ers). Objectives: To determine whether the mortality benefit of ventilation with lower Vt varies according to Ers. Methods: In a secondary analysis of patients from five randomized trials of lower- versus higher-Vt ventilation strategies in ARDS and acute hypoxemic respiratory failure, the posterior probability of an interaction between the randomized Vt strategy and Ers on 60-day mortality was computed using Bayesian multivariable logistic regression. Measurements and Main Results: Of 1,096 patients available for analysis, 416 (38%) died by Day 60. The posterior probability that the mortality benefit from lower-Vt ventilation strategies varied with Ers was 93% (posterior median interaction odds ratio, 0.80 per cm H 2 O/[ml/kg]; 90% credible interval, 0.63-1.02). Ers was classified as low (<2 cm H 2 O/[ml/kg], n  = 321, 32%), intermediate (2-3 cm H 2 O/[ml/kg], n  = 475, 46%), and high (>3 cm H 2 O/[ml/kg], n  = 224, 22%). In these groups, the posterior probabilities of an absolute risk reduction in mortality ≥ 1% were 55%, 82%, and 92%, respectively. The posterior probabilities of an absolute risk reduction ≥ 5% were 29%, 58%, and 82%, respectively. Conclusions: The mortality benefit of ventilation with lower Vt in ARDS varies according to elastance, suggesting that lung-protective ventilation strategies should primarily target driving pressure rather than Vt.

Objectives: Surgical trainee burnout has gained attention recently as a significant factor leading to poorer quality of patient care, decreased productivity, and personal dysfunction. As a result, we aimed to determine the prevalence and associated risk factors for burnout among otolaryngology-head and neck surgery (OHNS) trainees in Australia., Study Design: Cross-sectional survey., Setting: National cohort of accredited OHNS trainees in Australia., Subjects and Methods: Participants completed the Maslach Burnout Inventory (MBI). Trainee burnout was defined if any threshold of the 3 MBI domains-emotional exhaustion, depersonalization, or personal accomplishment-reached an established high threshold. Demographic data on potential predictors of burnout, such as stressors, workload, satisfaction, and support systems, were collected from survey responses. Predictors were compared with the burnout status., Results: Of 67 OHNS trainees, 60 responded (66.7% men). Burnout was common among respondents, with 73.3% suffering from burnout in at least 1 of the 3 MBI domains (70.0%, emotional exhaustion; 46.7%, depersonalization; 18.3%, personal accomplishment). Trainee burnout was significantly influenced by training location (chi-square, P = .05), living geographically apart from social supports (odds ratio [OR], 3.49; chi-square, P = .007), number of years trained rurally or away from social supports (Kendall's tau-B, P = .03), difficulty balancing work and nonwork commitments (OR, 10.0; chi-square, P = .03), training negatively affecting their partner or family (OR, 14.30; chi-square, P = .05), and feeling uncomfortable approaching a supervisor (OR, 2.50; chi-square, P < .0001)., Conclusion: Burnout was found to be very common among OHNS trainees in Australia. The statistically significant predictors identified should be addressed to minimize trainee burnout.

Background and Objectives: Allergic rhinitis may contribute to sleep disordered breathing (SDB) in children. Although adenotonsillectomy is commonly performed to treat SDB, some patients will return to their primary practitioners with residual sleep symptoms. The aim of this study was to assess the incidence of allergic rhinitis via radioallergosorbent testing (RAST) in children undergoing adenotonsillectomy who had residual snoring or sleep symptoms., Method: A retrospective analysis of 500 patients post-adenotonsillectomy was undertaken. The incidence of residual snoring, residual sleep symptoms and results of RAST, as well as total immunoglobulin E (IgE) after surgical intervention, were documented., Results: Children with positive RAST results or elevated total IgE had a significantly greater incidence of residual snoring post-adenotonsillectomy (P = 0.049) and residual sleep symptoms after surgery (P <0.0001)., Discussion: A positive RAST or elevated IgE in children with SDB was associated with incomplete resolution of snoring and residual sleep symptoms after adenotonsillectomy. Thus, there should be raised suspicion of allergic rhinitis in this population.

Sea-level rise (SLR) impacts on intertidal habitat depend on coastal topology, accretion, and constraints from surrounding development. Such habitat changes might affect species like Belding's savannah sparrows ( Passerculus sandwichensis beldingi ; BSSP), which live in high-elevation salt marsh in the Southern California Bight. To predict how BSSP habitat might change under various SLR scenarios, we first constructed a suitability model by matching bird observations with elevation. We then mapped current BSSP breeding and foraging habitat at six estuarine sites by applying the elevation-suitability model to digital elevation models. To estimate changes in digital elevation models under different SLR scenarios, we used a site-specific, one-dimensional elevation model (wetland accretion rate model of ecosystem resilience). We then applied our elevation-suitability model to the projected digital elevation models. The resulting maps suggest that suitable breeding and foraging habitat could decline as increased inundation converts middle- and high-elevation suitable habitat to mudflat and subtidal zones. As a result, the highest SLR scenario predicted that no suitable breeding or foraging habitat would remain at any site by 2100 and 2110. Removing development constraints to facilitate landward migration of high salt marsh, or redistributing dredge spoils to replace submerged habitat, might create future high salt marsh habitat, thereby reducing extirpation risk for BSSP in southern California.

The top-down effects of consumers, such as predators, are known to affect abundances, size structure, and species composition in aquatic ecosystems. Parasites are also important in shaping the ecology of free-living species; however, their effects are often overlooked because parasites can be difficult to detect. Parasites can be particularly challenging to observe in zooplankton hosts because of their small size and ephemeral infection periods. To overcome these challenges, we used a quarantine approach combined with high-magnification microscopy to increase detection of parasites of the tropical Cladoceran, Ceriodaphnia cornuta, in Lake Gatun, Panamá. Using this approach, we were able to demonstrate that competing morphs of Ceriodaphnia experience differential rates of infection, where the subordinate competitor suffered higher parasite prevalence than did the dominant morph. Predation by fishes on the dominant morph is considered the principal mechanism for their coexistence, but we hypothesize that parasites may also play a role in maintaining morphotype diversity of Ceriodaphnia.

Early-life adversity can have long-lasting effects on physiological, behavioural, cognitive, and somatic processes. Consequently, these effects may alter an organism's life-history strategy and reproductive tactics.In response to early-life immune activation, we quantified levels of the acute phase protein haptoglobin (Hp) during development in male zebra finches ( Taeniopygia guttata ). Then, we examined the long-term impacts of early-life immune activation on an important static sexual signal, song complexity, as well as effects of early-life immune activation on the relationship between song complexity and a dynamic sexual signal, beak colouration. Finally, we performed mate-choice trials to determine if male early-life experience impacted female preference.Challenge with keyhole limpet hemocyanin (KLH) resulted in increased song complexity compared to lipopolysaccharide (LPS) treatment or the control. Hp levels were inversely correlated with song complexity. Moreover, KLH-treatment resulted in negative associations between the two sexual signals (beak colouration and song complexity). Females demonstrated some preference for KLH-treated males over controls and for control males over LPS-treated males in mate choice trials.Developmental immune activation has variable effects on the expression of secondary sexual traits in adulthood, including enhancing the expression of some traits. Because developmental levels of Hp and adult song complexity were correlated, future studies should explore a potential role for exposure to inflammation during development on song learning.Early-life adversity may differentially impact static versus dynamic signals. The use of phenotypic correlations can be a powerful tool for examining the impact of early-life experience on the associations among different traits, including sexual signals.

Most species aggregate in local patches. High host density in patches increases contact rate between hosts and parasites, increasing parasite transmission success. At the same time, for environmentally transmitted parasites, high host density can decrease infection risk to individual hosts, because infective stages are divided among all hosts in a patch, leading to safety in numbers. We tested these predictions using the California horn snail, Cerithideopsis californica (=Cerithidea californica), which is the first intermediate host for at least 19 digenean trematode species in California estuaries. Snails become infected by ingesting trematode eggs or through penetration by free-swimming miracidia that hatch from trematode eggs deposited with final-host (bird or mammal) feces. This complex life cycle decouples infective-stage production from transmission, raising the possibility of an inverse relationship between host density and infection risk at local scales. In a field survey, higher snail density was associated with increased trematode (infected snail) density, but decreased trematode prevalence, consistent with either safety in numbers, parasitic castration, or both. To determine the extent to which safety in numbers drove the negative snail-density-trematode-prevalence association, we manipulated uninfected snail density in 83 cages at eight sites within Carpinteria Salt Marsh (California, USA). At each site, we quantified snail density and used data on final-host (bird and raccoon) distributions to control for between-site variation in infective-stage supply. After three months, overall trematode infections per cage increased with snail biomass density. For egg-transmitted trematodes, per-snail infection risk decreased with snail biomass density in the cage and surrounding area, whereas per-snail infection risk did not decrease for miracidium-transmitted trematodes. Furthermore, both trematode recruitment and infection risk increased with infective-stage input, but this was significant only for miracidium-transmitted species. A model parameterized with our experimental results and snail densities from 524 field transects estimated that safety in numbers, when combined with patchy host density, halved per capita infection risk in this snail population. We conclude that, depending on transmission mode, host density can enhance parasite recruitment and reduce per capita infection risk., (© 2017 by the Ecological Society of America.)

Objectives: A recent individual patient data (IPD) meta-analysis suggested that patients with moderate or severe acute respiratory distress syndrome (ARDS) benefit from higher positive end-expiratory pressure (PEEP) ventilation strategies. However, thresholds for continuous variables (eg, hypoxaemia) are often arbitrary and linearity assumptions in regression approaches may not hold; the multivariable fractional polynomial interaction (MFPI) approach can address both problems. The objective of this study was to apply the MFPI approach to investigate interactions between four continuous patient baseline variables and higher versus lower PEEP on clinical outcomes., Setting: Pooled data from three randomised trials in intensive care identified by a systematic review., Participants: 2299 patients with acute lung injury requiring mechanical ventilation., Interventions: Higher (N=1136) versus lower PEEP (N=1163) ventilation strategy., Outcome Measures: Prespecified outcomes included mortality, time to death and time-to-unassisted breathing. We examined the following continuous baseline characteristics as potential effect modifiers using MFPI: PaO2/FiO2 (arterial partial oxygen pressure/ fraction of inspired oxygen), oxygenation index, respiratory system compliance (tidal volume/(inspiratory plateau pressure-PEEP)) and body mass index (BMI)., Results: We found that for patients with PaO2/FiO2 below 150 mm Hg, but above 100 mm Hg or an oxygenation index above 12 (moderate ARDS), higher PEEP reduces hospital mortality, but the beneficial effect appears to level off for patients with very severe ARDS. Patients with mild ARDS (PaO2/FiO2 above 200 mm Hg or an oxygenation index below 10) do not seem to benefit from higher PEEP and might even be harmed. For patients with a respiratory system compliance above 40 mL/cm H2O or patients with a BMI above 35 kg/m(2), we found a trend towards reduced mortality with higher PEEP, but there is very weak statistical confidence in these findings., Conclusions: MFPI analyses suggest a nonlinear effect modification of higher PEEP ventilation by PaO2/FiO2 and oxygenation index with reduced mortality for some patients suffering from moderate ARDS., Study Registration Number: CRD42012003129., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Ankle instantaneous axis of rotation (IAR) measurements represent a more complete parameter for characterizing joint motion. However, few studies have implemented this measurement to study normal, injured, or pathological foot ankle biomechanics. A novel testing protocol was developed to simulate aspects of in vivo foot ankle mechanics during mid-stance gait in a human cadaveric specimen. A lower leg was mounted in a robotic testing platform with the tibia upright and foot flat on the baseplate. Axial tibia loads (ATLs) were controlled as a function of a vertical ground reaction force (vGRF) set at half body weight (356 N) and a 50% vGRF (178 N) Achilles tendon load. Two specimens were repetitively loaded over 10 degrees of dorsiflexion and 20 degrees of plantar flexion. Platform axes were controlled within 2 microns and 0.008 degrees resulting in ATL measurements within ±2 N of target conditions. Mean ATLs and IAR values were not significantly different between cycles of motion, but IAR values were significantly different between dorsiflexion and plantar flexion. A linear regression analysis showed no significant differences between slopes of plantar flexion paths. The customized robotic platform and advanced testing protocol produced repeatable and accurate measurements of the IAR, useful for assessing foot ankle biomechanics under different loading scenarios and foot conditions.

Background: The current climate of increasing patient complexity coupled with rising costs have prompted the need for adaptive innovation. There are limited data describing inpatient interventions targeting improvements in both communication and transitional care., Objective: Evaluate the patient navigator (PN) program, an innovative inpatient intervention intended to enhance navigation through the complexity of hospital admissions for patients and providers., Intervention: PNs were dedicated patient-care facilitators without clinical responsibilities integrated as full members of the inpatient care team responsible for enhancing communication between and among patients and providers., Design: Observational retrospective cohort study., Patients: All patients admitted to the general medical service between July 2010 and March 2014., Setting: Academic medical center., Measurements: Primary outcomes were hospital length of stay (LOS) and 30-day readmission rate matched by case mix group, age category, and resource intensity weight., Results: Our matched cohort included 5628 admissions (4592 patients) exposed and 2213 admissions (1920 patients) not exposed to PNs. Admissions with PNs were 1.3 days (21%) shorter than admission without PNs (6.2 vs 7.5 days, P < 0.001). Thirty-day readmission rate was not different between the 2 groups (13.1 vs 13.8%, P = 0.48)., Conclusion: Implementation of this intervention was associated with a reduction in LOS without an increase in 30-day readmission., (© 2015 Society of Hospital Medicine.)

Background: Exertional heat stroke is a potentially life-threatening disease with varying clinical presentations and severity. Given the severe morbidity that can accompany the disease, the immediate management often begins in the prehospital setting. It is important to have not only a comprehensive understanding of the prehospital cooling methods in addition to hospital management strategies, but an understanding of their potential complications as well., Case Report: A 32-year-old male presented to a San Antonio hospital in March 2014 with progressive confusion, nausea, nonbloody emesis, and ataxia. Initial presentation was concerning for exertional heat stroke, as the patient was recorded in the field to have a temperature of 42.1°C (106.2°F). The patient, on arrival to the emergency department, was found to have a core body temperature of 38.1°C (100.6°F). All active cooling measures were terminated and active rewarming was initiated. Despite adequate resuscitation and rapid identification of the patient's overcorrection in core body temperature, the lowest recorded temperature was 36.0°C (96.8°F). Why Should an Emergency Physician Be Aware of This? This case represents the dangers associated with exertional heat stroke, overcorrection of core body temperature, and the potentially lethal complication of afterdrop. It also represents the need for immediate recognition of the condition and initiation of appropriate medical care. Although this patient's clinical outcome was good, the event could have caused serious morbidity or could have potentially been fatal., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Acute supraglottitis is a medical emergency as it can rapidly lead to airway compromise. With routine pediatric immunization for Hemophilus influenzae serotype b, supraglottitis is now more prevalent in adults, with a shift in the causative organisms and a change in the natural history of this disease. Here, we present a case of supraglottitis due to group B streptococcus that occurred in an adult with previously undetected immunoglobulin 4 (IgG4) and complement protein C2 deficiency., (© 2014 The American Laryngological, Rhinological and Otological Society, Inc.)

Background: Shorter resident duty periods are increasingly mandated to improve patient safety and physician well-being. However, increases in continuity-related errors may counteract the purported benefits of reducing fatigue. We evaluated the effects of 3 resident schedules in the intensive care unit (ICU) on patient safety, resident well-being and continuity of care., Methods: Residents in 2 university-affiliated ICUs were randomly assigned (in 2-month rotation-blocks from January to June 2009) to in-house overnight schedules of 24, 16 or 12 hours. The primary patient outcome was adverse events. The primary resident outcome was sleepiness, measured by the 7-point Stanford Sleepiness Scale. Secondary outcomes were patient deaths, preventable adverse events, and residents' physical symptoms and burnout. Continuity of care and perceptions of ICU staff were also assessed., Results: We evaluated 47 (96%) of 49 residents, all 971 admissions, 5894 patient-days and 452 staff surveys. We found no effect of schedule (24-, 16- or 12-h shifts) on adverse events (81.3, 76.3 and 78.2 events per 1000 patient-days, respectively; p = 0.7) or on residents' sleepiness in the daytime (mean rating 2.33, 2.61 and 2.30, respectively; p = 0.3) or at night (mean rating 3.06, 2.73 and 2.42, respectively; p = 0.2). Seven of 8 preventable adverse events occurred with the 12-hour schedule (p = 0.1). Mortality rates were similar for the 3 schedules. Residents' somatic symptoms were more severe and more frequent with the 24-hour schedule (p = 0.04); however, burnout was similar across the groups. ICU staff rated residents' knowledge and decision-making worst with the 16-hour schedule., Interpretation: Our findings do not support the purported advantages of shorter duty schedules. They also highlight the trade-offs between residents' symptoms and multiple secondary measures of patient safety. Further delineation of this emerging signal is required before widespread system change., Trial Registration: ClinicalTrials.gov, no. NCT00679809., (© 2015 Canadian Medical Association or its licensors.)

Background: Mechanical-ventilation strategies that use lower end-inspiratory (plateau) airway pressures, lower tidal volumes (VT), and higher positive end-expiratory pressures (PEEPs) can improve survival in patients with the acute respiratory distress syndrome (ARDS), but the relative importance of each of these components is uncertain. Because respiratory-system compliance (CRS) is strongly related to the volume of aerated remaining functional lung during disease (termed functional lung size), we hypothesized that driving pressure (ΔP=VT/CRS), in which VT is intrinsically normalized to functional lung size (instead of predicted lung size in healthy persons), would be an index more strongly associated with survival than VT or PEEP in patients who are not actively breathing., Methods: Using a statistical tool known as multilevel mediation analysis to analyze individual data from 3562 patients with ARDS enrolled in nine previously reported randomized trials, we examined ΔP as an independent variable associated with survival. In the mediation analysis, we estimated the isolated effects of changes in ΔP resulting from randomized ventilator settings while minimizing confounding due to the baseline severity of lung disease., Results: Among ventilation variables, ΔP was most strongly associated with survival. A 1-SD increment in ΔP (approximately 7 cm of water) was associated with increased mortality (relative risk, 1.41; 95% confidence interval [CI], 1.31 to 1.51; P<0.001), even in patients receiving "protective" plateau pressures and VT (relative risk, 1.36; 95% CI, 1.17 to 1.58; P<0.001). Individual changes in VT or PEEP after randomization were not independently associated with survival; they were associated only if they were among the changes that led to reductions in ΔP (mediation effects of ΔP, P=0.004 and P=0.001, respectively)., Conclusions: We found that ΔP was the ventilation variable that best stratified risk. Decreases in ΔP owing to changes in ventilator settings were strongly associated with increased survival. (Funded by Fundação de Amparo e Pesquisa do Estado de São Paulo and others.).

Some sexually selected signals are thought to convey information about the current condition and genetic/epigenetic quality of the individual signaling, including the ability to resist parasites. However, it is unclear whether semistatic sexual signals that develop periodically and remain stable over protracted periods, such as avian breeding plumage, can relate to measures of current condition and health. We examined a semistatic signal (wing epaulet size) in male red-winged blackbirds (Agelaius phoeniceus) during the breeding season and looked for relationships between this trait and circulating testosterone (T), hematocrit, bacteria-killing ability (BKA) of the blood, and the infection status, richness, and abundance of four functional categories of parasite. We found that epaulet size was positively related to circulating levels of T and ectoparasite infections. We found no relationships between T and parasite infections. In adult males there was a negative relationship between T and BKA, whereas in yearling males there was no relationship. We found no evidence for a general reduction in immunocompetence in males with larger epaulets but rather an increase in susceptibility to specific types of parasites. Our results suggest that semistatic signals can be linked to measures of current condition, and we postulate that these relationships are modulated via activity levels related to breeding-season activities.