Extracorporeal Membrane Oxygenation in the Context of the 2009 H1N1 Influenza A Pandemic

Background: Extracorporeal membrane oxygenation (ECMO) incorporates surgical techniques as adjuncts in the management of refractory respiratory dysfunction. For many years, its primary application was for support of neonatal infants in cardiorespiratory failure. As the 2009 H1N1 influenza A pandemic developed, more reports came in of severe respiratory dysfunction and even death that seemed to be occurring preferentially in younger adults. Centers with the capability began to use ECMO to salvage these patients. Results: The H1N1 virus is a subtype of influenza A. The hemagglutinin receptor binding is similar to that of the seasonal influenza virus, but 2009 H1N1 also binds to •2,3-linked receptors, which are found in the conjunctivae, distal airways, and alveolar pneumocytes. Influenza viruses elude host immune responses through drift and shift in the hemagglutinin (HA) and neuraminidase (NA) proteins. The incubation period ranges from 1-7 days. The majority of patients present with fever and cough, but a broad spectrum of clinical syndromes has been reported, and laboratory testing remains the mainstay of diagnosis. Most patients recover within a week without treatment. The H1N1 virus remains largely sensitive to the NA inhibitors but is resistant to the matrix protein-2 inhibitors. Extracorporeal membrane oxygenation provides continuous pulmonary (and sometimes cardiac) support and minimizes ventilator-induced lung injury. The potential for life-threatening complications is high. In 2009, in the Conventional Ventilation or ECMO for Severe Adult Respiratory Failure (CESAR) randomized trial of ECMO, the overall survival rate was 63% in the ECMO group compared with 47% in the control group (p = 0.03). Similar studies have been reported from Australia and New Zealand, Canada, and France. Conclusions: Supportive management is continued along with ECMO. Antiviral drugs and antimicrobial agents should be given as appropriate, as should nutritional support. Volume management should be used. Ventilator settings should be reduced as ECMO support allows, with a goal of reducing airway pressures, ventilator rate, and FiO2. Complications of ECMO are common. Bleeding, the most common, can result in death, especially if it occurs intracranially.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90458/1/sur-2E2010-2E082.pd

Dental students' knowledge of and attitudes towards prescribing medication in Western Australia

ACKNOWLEDGEMENTThe authors would like to acknowledge UWA dental students for their time and valuable input. Open access publishing facilitated by The University of Western Australia, as part of the Wiley - The University of Western Australia agreement via the Council of Australian University Librarians. [Correction added on 14 May 2022, after first online publication: CAUL funding statement has been added.]Peer reviewedPublisher PD

Pharmacokinetics of Oseltamivir and Oseltamivir Carboxylate in Critically I ll Patients Receiving Continuous Venovenous Hemodialysis and/or Extracorporeal Membrane Oxygenation

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/94511/1/phar1151.pd

Lung Injury Prevention with Aspirin (LIPS-A): a Protocol for a Multicentre Randomised Clinical Trial in Medical Patients at High Risk of Acute Lung Injury

Introduction: Acute lung injury (ALI) is a devastating condition that places a heavy burden on public health resources. Although the need for effective ALI prevention strategies is increasingly recognised, no effective preventative strategies exist. The Lung Injury Prevention Study with Aspirin (LIPS-A) aims to test whether aspirin (ASA) could prevent and/or mitigate the development of ALI. Methods and analysis LIPS-A is a multicentre, double-blind, randomised clinical trial testing the hypothesis that the early administration of ASA will result in a reduced incidence of ALI in adult patients at high risk. This investigation will enrol 400 study participants from 14 hospitals across the USA. Conditional logistic regression will be used to test the primary hypothesis that early ASA administration will decrease the incidence of ALI. Ethics and dissemination Safety oversight will be under the direction of an independent Data and Safety Monitoring Board (DSMB). Approval of the protocol was obtained from the DSMB prior to enrolling the first study participant. Approval of both the protocol and informed consent documents were also obtained from the institutional review board of each participating institution prior to enrolling study participants at the respective site. In addition to providing important clinical and mechanistic information, this investigation will inform the scientific merit and feasibility of a phase III trial on ASA as an ALI prevention agent. The findings of this investigation, as well as associated ancillary studies, will be disseminated in the form of oral and abstract presentations at major national and international medical specialty meetings. The primary objective and other significant findings will also be presented in manuscript form. All final, published manuscripts resulting from this protocol will be submitted to Pub Med Central in accordance with the National Institute of Health Public Access Policy

Utilization of Intensive Care Unit Nutrition Consultation Is Associated With Reduced Mortality

BackgroundThe aim of this project was to investigate the prevalence of nutrition consultation (NC) in U.S. intensive care units (ICUs) and to examine its association with patient outcomes.MethodsData from the Healthcare Cost and Utilization Project’s state inpatient databases was utilized from 2010 â 2014. A multilevel logistic regression model was used to evaluate the relationship between NC and clinical outcomes.ResultsInstitutional ICU NC rates varied significantly (mean: 14%, range: 0.1%â 73%). Significant variation among underlying disease processes was identified, with burn patients having the highest consult rate (P < 0.001, mean: 6%, range: 2%â 25%). ICU patients who received NC had significantly lower inâ hospital mortality (odds ratio [OR] 0.59, 95% confidence interval [CI] 0.48â 0.74, P < 0.001), as did the subset with malnutrition (OR 0.72, 95% CI 0.53â 0.99, P = 0.047) and the subset with concomitant physical therapy consultation (OR 0.53, 95% CI 0.38â 0.74, P < 0.001). NC was associated with significantly lower rates of intubation, pulmonary failure, pneumonia, and gastrointestinal bleeding (P < 0.05). Furthermore, patients who received NC were more likely to receive enteral or parenteral nutrition (ENPN) (OR 1.8, 95% CI 1.4â 2.3, P < 0.001). Patients who received followâ up NC were even more likely to receive ENPN (OR 3.0, 95% CI 2.1â 4.2, P < 0.001).ConclusionsRates of NC were low in critically ill patients. This study suggests that increased utilization of NC in critically ill patients may be associated with improved clinical outcomes.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154413/1/jpen1534_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154413/2/jpen1534.pd

Prevention of Catheter-Related Blood Stream Infection: Back to Basics?

Background: Central venous catheter (CVC)-related infections are a substantial problem in the intensive care unit (ICU). Our infection control team initiated the routine use of antiseptic-coated (chlorhexidine-silver sulfadiazine; Chx-SS) CVCs in our adult ICUs to reduce catheter-associated (CA) and catheter-related (CR) blood stream infection (BSI) as we implemented other educational and best practice standardization strategies. Prior randomized studies documented that the use of Chx-SS catheters reduces microbial colonization of the catheter compared with an uncoated standard (Std) CVC but does not reduce CR-BSI. We therefore implemented the routine use of uncoated Std CVCs in our surgical ICU (SICU) and examined the impact of this change. Hypothesis: The use of uncoated Std CVCs does not increase CR-BSI rate in an SICU. Methods: Prospective evaluation of universal use of uncoated Std CVCs, implemented November 2007 in the SICU. The incidences of CA-BSI and CR-BSI were compared during November 2006-October 2007 (universal use of Chx-SS CVCs) and November 2007-October 2008 (universal use of Std CVCs) by t-test. The definitions of the U.S. Centers for Disease Control and Prevention were used for CA-BSI and CR-BSI. Patient data were collected via a dedicated Acute Physiology and Chronic Health Evaluation (APACHE) III coordinator for the SICU. Results: Annual use of CVCs increased significantly in the last six years, from 3,543 (2001) to 5,799 (2006) total days. The APACHE III scores on day 1 increased from a mean of 54.4 in 2004 to 55.6 in 2008 (p = 0.0010; 95% confidence interval [CI] 1.29-5.13). The mean age of the patients was unchanged over this period, ranging from 58.2 to 59.6 years. The Chx-SS catheters were implemented in the SICU in 2002. Data regarding the specific incidence of CR-BSI were collected beginning at the end of 2005, with mandatory catheter tip cultures when CVCs were removed. Little difference was identified in the incidence of BSI between the interval with universal Chx-SS use and that with Std CVC use. (Total BSI 0.7 vs. 0.8 per 1,000 catheter days; CA-BSI 0.5 vs. 0.8 per 1,000 catheter days; CR-BSI 0.2 vs. 0 per 1,000 catheter days.) No difference was seen in the causative pathogens of CA-BSI or CR-BSI. Conclusion: Eliminating the universal use of Chx-SS-coated CVCs in an SICU with a low background incidence of CR-BSIs did not result in an increase in the rate of CR-BSIs. This study documents the greater importance of adherence to standardization of the processes of care related to CVC placement than of coated CVC use in the reduction of CR-BSI.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90456/1/sur-2E2009-2E082.pd

Olfactory and gustatory sensory changes to tobacco smoke in pregnant smokers

Models of smoking behavior change include addiction, social, and behavioral concepts. The purpose of this study was to explore the prevalence of two biologic factors, olfactory and gustatory responses to tobacco smoke, as potentially powerful contributors to smoking behavior change among pregnant women. Data were obtained from 209 pregnant smokers. The majority of women reported olfactory (62%) and gustatory (53%) aversions to tobacco. Aversions first appeared during the first trimester of pregnancy. Women who experienced olfactory aversions were more likely also to experience gustatory aversions. Olfactory aversions were associated with women smoking less. Aversions to tobacco smoke are common among pregnant smokers, are associated with women smoking less, and could help explain pregnant women’s smoking patterns

Early High-Dose Vitamin D3 for Critically Ill, Vitamin D-Deficient Patients

BACKGROUND: Vitamin D deficiency is a common, potentially reversible contributor to morbidity and mortality among critically ill patients. The potential benefits of vitamin D supplementation in acute critical illness require further study. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality. RESULTS: A total of 1360 patients were found to be vitamin D-deficient during point-of-care screening and underwent randomization. Of these patients, 1078 had baseline vitamin D deficiency (25-hydroxyvitamin D level,[50 nmol per liter]) confirmed by subsequent testing and were included in the primary analysis population. The mean day 3 level of 25-hydroxyvitamin D was 46.9±23.2 ng per milliliter (117±58 nmol per liter) in the vitamin D group and 11.4±5.6 ng per milliliter (28±14 nmol per liter) in the placebo group (difference, 35.5 ng per milliliter; 95% confidence interval [CI], 31.5 to 39.6). The 90-day mortality was 23.5% in the vitamin D group (125 of 531 patients) and 20.6% in the placebo group (109 of 528 patients) (difference, 2.9 percentage points; 95% CI, -2.1 to 7.9; P = 0.26). There were no clinically important differences between the groups with respect to secondary clinical, physiological, or safety end points. The severity of vitamin D deficiency at baseline did not affect the association between the treatment assignment and mortality. CONCLUSIONS: Early administration of high-dose enteral vitamin D3 did not provide an advantage over placebo with respect to 90-day mortality or other, nonfatal outcomes among critically ill, vitamin D-deficient patients. METHODS: We conducted a randomized, double-blind, placebo-controlled, phase 3 trial of early vitamin D3 supplementation in critically ill, vitamin D-deficient patients who were at high risk for death. Randomization occurred within 12 hours after the decision to admit the patient to an intensive care unit. Eligible patients received a single enteral dose of 540,000 IU of vitamin D3 or matched placebo. The primary end point was 90-day all-cause, all-location mortality

Research Staff COVID-19 Pandemic Survey-Results from the Prevention and Early Treatment of Acute Lung Injury (PETAL) Network

Objectives: There is a lack of knowledge about the challenges of researchers who continued in-person research during the early phases of the COVID-19 pandemic. Design: Electronic survey assessing work-related exposure to COVID-19, logistical challenges, and procedural changes during the first year of the COVID-19 pandemic on clinical research. Setting: National Heart, Lung, and Blood Institute-sponsored Prevention and Early Treatment of Acute Lung Injury Clinical Trial Network Centers. Subjects: Research staff at research Network Sites. Measurements and Main Results: The 37-question survey was completed by 277 individuals from 24 states between 29 September 2020, and 12 December 2020, yielding a response rate of 37.7%. Most respondents (91.5%) indicated that non-COVID-19 research was affected by COVID-19 research studies. In response to the COVID-19 pandemic, 20% of respondents were reassigned to different roles at their institution. Many survey takers were exposed to COVID-19 (56%), with more than 50% of researchers requiring a COVID-19 test and 8% testing positive. The fear of infection was 2.7-times higher compared to pre-COVID-19 times. Shortages of personal protective equipment were encountered by 34% of respondents, primarily due to lack of access to N95 masks, followed by gowns and protective eyewear. Personal protective equipment reallocation from research to clinical use was reported by 31% of respondents. Most of the respondents (88.5%), despite these logistical challenges, indicated their willingness to enroll COVID-19 patients. Conclusions: During the first year of the COVID-19 pandemic, members of the research network were engaged in COVID-19 research despite logistical challenges, limited access to personal protective equipment, and fear of exposure. The research network’s survey experience can inform ongoing policy discussions to create research enterprises that can dexterously refocus research to address the knowledge gaps associated with novel public health emergencies while mitigating the effect of pandemics on existing research projects and research personnel

Circulating senescent myeloid cells drive blood brain barrier breakdown and neurodegeneration

Neurodegenerative diseases (ND) are characterized by progressive loss of neuronal function. Mechanisms of ND pathogenesis are incompletely understood, hampering the development of effective therapies. Langerhans cell histiocytosis (LCH) is an inflammatory neoplastic disorder caused by hematopoietic progenitors expressing MAPK activating mutations that differentiate into senescent myeloid cells that drive lesion formation. Some patients with LCH subsequently develop progressive and incurable neurodegeneration (LCH-ND). Here, we show that LCH-ND is caused by myeloid cells that are clonal with peripheral LCH cells. We discovered that circulating BRAF V600E $^{+}$ myeloid cells cause the breakdown of the blood-brain barrier (BBB), enhancing migration into the brain parenchyma where they differentiate into senescent, inflammatory CD11a $^{+}$ macrophages that accumulate in the brainstem and cerebellum. Blocking MAPK activity and senescence programs reduced parenchymal infiltration, neuroinflammation, neuronal damage and improved neurological outcome in preclinical LCH-ND. MAPK activation and senescence programs in circulating myeloid cells represent novel and targetable mechanisms of ND