Chinese Herbal Medicine for Idiopathic Pulmonary Fibrosis: An Overview of Systematic Review.

Objective: To summarize the use of Chinese Herbal Medicines (CHMs) for Idiopathic Pulmonary Fibrosis (IPF) and provide high-level evidence for clinical decisions. Methods: We analyzed systematic reviews (SRs). Two English-language and three Chinese-language electronic databases were searched from inception to July 1, 2019. Published SRs and meta-analyses evaluating CHM use in IPF and reporting clinically-relevant outcomes such as lung function, PO2, and quality of life were eligible for inclusion in this overview. The methodological qualities of the included SRs were assessed by AMSTAR and ROBIS tools. Results: All reviews were published from 2008 to 2019. 15SRs were published in Chinese-language while 2 were in English. A total of 15550 participants were included. All intervention arms received CHM with or without conventional treatment and were compared with control arms with conventional treatment alone, or hormone therapy. Twelve SRs were assessed with low risk of bias while five were assessed high risk by ROBIS. The quality of evidence was assessed to be "moderate" or "low" or "very low" using GRADE. Conclusions: CHM has potential benefits for patients with IPF especially in improving lung function (forced vital capacity (FVC), total lung capacity (TLC), and diffusing capacity of the lungs for carbon monoxide (DLCO)), PO2 level, and the quality of life of patients. Due to the low methodological quality of reviews, our findings should be interpreted with caution.

Association of genetic polymorphisms with mercapturic acids in the urine of young healthy subjects before and after exposure to outdoor air pollution.

We aimed to identify the relationship between variations in metabolic genes and human urinary changes in mercapturic acids (MAs), including CEMA, HMPMA, SPMA, HPMA and HEMA, before and after air pollution exposure. Genotype detection for 47 relevant single nucleotide polymorphisms (SNPs) collected by literature research was performed. Five MAs expression levels in the urinary samples of 50 young healthy individuals with short-term exposure to clean, polluted and purified air at five time points were detected by targeted online solid-phase extraction liquid chromatography tandem mass spectrometry (SPE-LC-MS/MS), followed with associations of SNPs with MAs changes. Difference in MAs between polluted and clean/purified air was significantly associated with 21 SNPs mapped into 9 genes. Five SNPs in GSTP1 showed the most prominent association with the changes in SPMA expression, indicating that those SNPs in GSTP1 and SPMA might serve as biomarkers for susceptibility and the prognosis of lung cancer.

Disposable stainless steel working electrodes for sensitive and simultaneous detection of indole-3-acetic acid and salicylic acid in Arabidopsis thaliana leaves under biotic stresses.

The detection of phytohormones in real time has attracted increasing attention because of their critical roles in regulating the development and signaling of plants, especially in defense against biotic stresses. Herein, stainless steel sheet electrodes modified with carbon cement were coupled with paper-based analysis devices for direct and simultaneous detection of salicylic acid (SA) and indole-3-acetic acid (IAA) in plants. We demonstrated that the excellent conductivity of stainless steel sheet electrodes enabled us to simultaneously differentiate IAA and SA at a level of 10 nM. With our approach, the content of IAA and SA in Arabidopsis thaliana leaves infected or not infected with Pst DC3000 could be rapidly quantified at the same time. Our experimental results on differentiation of IAA and SA at different time points showed that there were antagonistic interactions between the IAA and SA after infection of Arabidopsis leaves with Pst DC3000. By offering a cost-effective approach for rapid and sensitive detection of IAA and SA, this study suggests that electrochemical detection can be used in the study and development of precision agriculture technology.

Experimental Study on Ultrasonic-Assisted End Milling Forces in 2195 Aluminum-Lithium Alloy.

To achieve high-quality machining of the 2195 aluminum-lithium alloy, this paper presents an experimental study on the effect of milling processing parameters on milling forces and surface topography, during which conventional milling and longitudinal-torsional ultrasonic vibration milling of the 2195 Al-Li alloy were performed. The characterization of the tool tip trajectory illustrates some of the advantages of ultrasonic machining, which include variable depth of cut and tool chip pulling. The differences in milling forces between conventional milling and longitudinal-torsional ultrasonic vibration machining were compared using orthogonal tests, and the effect of ultrasonic vibration on milling forces was investigated in detail. The maximum reduction of milling force Fy in the feed direction under the influence of torsional vibration is 62% and 54% for larger feed per tooth and cutting depth, respectively. The high-frequency impact generated by the longitudinal vibration not only reduces the chip accumulation on the surface, but also smooths out the tool-tooth scratches and creates a regular surface profile. In addition, the characteristics of the milling force signals of the two machining methods were analyzed, and the analysis of the spectrum of the collected milling forces revealed that the ultrasonic vibration caused the high-frequency components of the milling forces Fy and Fz. The orthogonal result analysis and single-factor result analysis verified the superiority of ultrasonic machining, provided parameter selection for subsequent aluminum-lithium alloy machining, and bridged the gap of longitudinal torsional ultrasonic vibration machining of 2195 aluminum-lithium alloy in the study of milling force.

Potential urinary biomarkers in young adults with short-term exposure to particulate matter and bioaerosols identified using an unbiased metabolomic approach.

Numerous epidemiological studies have shown a close relationship between outdoor air pollution and increased risks for cancer, infection, and cardiopulmonary diseases. However, very few studies have investigated the potential health effects of coexposure to airborne particulate matter (PM) and bioaerosols through the transmission of infectious agents, particularly under the current circumstances of the coronavirus disease 2019 pandemic. In this study, we aimed to identify urinary metabolite biomarkers that might serve as clinically predictive or diagnostic standards for relevant diseases in a real-time manner. We performed an unbiased gas/liquid chromatography-mass spectroscopy (GC/LC-MS) approach to detect urinary metabolites in 92 samples from young healthy individuals collected at three different time points after exposure to clean air, polluted ambient, or purified air, as well as two additional time points after air repollution or repurification. Subsequently, we compared the metabolomic profiles between the two time points using an integrated analysis, along with Kyoto Encyclopedia of Genes and Genomes-enriched pathway and time-series analysis. We identified 33 and 155 differential metabolites (DMs) associated with PM and bioaerosol exposure using GC/LC-MS and follow-up analyses, respectively. Our findings suggest that 16-dehydroprogesterone and 4-hydroxyphenylethanol in urine samples may serve as potential biomarkers to predict or diagnose PM- or bioaerosol-related diseases, respectively. The results indicated apparent differences between PM- and bioaerosol-associated DMs at five different time points and revealed dynamic alterations in the urinary metabolic profiles of young healthy humans with cyclic exposure to clean and polluted air environments. Our findings will help in investigating the detrimental health effects of short-term coexposure to airborne PM and bioaerosols in a real-time manner and improve clinically predictive or diagnostic strategies for preventing air pollution-related diseases.

Bibliometric Analysis of Birt-Hogg-Dubé Syndrome From 2001 to 2021.

Background: Birt-Hogg-Dubé syndrome (BHD) is a rare autosomal dominant inherited disorder caused by germline mutations in folliculin (FLCN). Despite our significantly evolved understanding of BHD over the past decades, no bibliometric analyses have been conducted in this field. This study aimed to analyze and visualize the characteristics of publication outputs, the research hotspots, and scientific frontiers about BHD using bibliometric analysis. Methods: All relevant literature on BHD was culled from the Web of Science Core Collection (WoSCC) database. Valid data were extracted from the articles and visually analyzed using CiteSpace and VOSviewer. Results: A total of 751 qualifying papers were included. Publication outputs concerning BHD increased over time. The dominant position of the United States and Japan in BHD research field was evident. National Cancer Institute (the USA) and Yokohama City University (Japan) were the two most productive organizations. W. Marston Linehan exerted a considerable publication impact and had made the most remarkable contributions in the field of BHD. Plos One was the journal with the highest publication outputs, and half of the top 10 journals and co-cited journals belonged to Q1 or Q2. Keyword citation bursts revealed that management, tumor suppressor, flcn gene, spectrum, diagnosis, risk, computed tomography were the emerging research hotspots. Conclusion: Research on BHD is prosperous. International cooperation between countries and organizations is also expected to deepen and strengthen in the future. Our results indicated that FLCN-associated pathways involved in the pathogenesis of BHD, specific options for early diagnosis, and molecular-targeting therapies will remain research hotspots in the future.

The Impact of Depression and Anxiety on Chronic Obstructive Pulmonary Disease Acute Exacerbations: A prospective cohort study.

BACKGROUND: To explore the impact of anxiety and depression in chronic obstructive pulmonary disease(COPD) patients on the risk of acute exacerbation. METHODS: 600 COPD patients were recruited and followed in Beijing, China. The demographic data, medical history, smoking history, therapy, assessments for anxiety and depression were completed by our physicians by face-to-face interview. Then the acute exacerbation events during the past one year was derived from their case record. RESULTS: 504 people (295 men and 209 women) were thus included in the final analyses.The patients with anxiety scored more than 50 showed higher risk of acute exacerbation(54.1%) than those who scoring less than 50(39.8%). Similarly, the patients with depression scored more than 53 showed higher risk of acute exacerbation(52.1%) than those who scoring less than 53(40.4%). Eventually, Anxiety and/or depression will increase the risk of acute exacerbation in chronic obstructive pulmonary disease patients(AECOPD) (adjusted OR = 1.60, 95%CI: 1.10-2.31), after adjusting the influence of family history, duration of disease, BMI index and other factors. Besides, the prevalence of acute exacerbation in patients with anxiety and/or depression was higher than those without acute exacerbation (P<0.05). LIMITATIONS: The frequency of AECOPD was limited to self-reported data, recall bias should be reconsidered, and it also may underestimate the association between anxiety and/or depression and AECOPD. Anxiety and depression were assessed by questionnaires rather than by a clinical diagnosis. CONCLUSION: Anxiety and/or depression in stable COPD patients were significantly associated with a higher risk of acute exacerbation. Mental health care should be paid more attention, to decrease the risk of acute exacerbation in COPD patients.

Validation of the NoSAS Score for the Screening of Sleep-Disordered Breathing in a Sleep Clinic.

Background: There is a growing number of patients with sleep-disordered breathing (SDB) referred to sleep clinics. Therefore, a simple but useful screening tool is urgent. The NoSAS score, containing only five items, has been developed and validated in population-based studies. Aim: To evaluate the performance of the NoSAS score for the screening of SDB patients from a sleep clinic in China, and to compare the predictive value of the NoSAS score with the STOP-Bang questionnaire. Methods: We enrolled consecutive patients from a sleep clinic who had undergone apnea-hypopnea index (AHI) testing by type III portable monitor device at the hospital and completed the STOP-Bang questionnaire. The NoSAS score was assessed by reviewing medical records. Sensitivity, specificity, positive predictive value, negative predictive value, and area under the receiver operating characteristic curve (AUC) of both screening tools were calculated at different AHI cutoffs to compare the performance of SDB screening. Results: Of the 596 eligible patients (397 males and 199 female), 514 were diagnosed with SDB. When predicting overall (AHI ≥ 5), moderate-to-severe (AHI ≥ 15), and severe (AHI ≥ 30) SDB, the sensitivity and specificity of the NoSAS score were 71.2, 80.4, and 83.1% and 62.4, 49.3, and 40.7%, respectively. At all AHI cutoffs, the AUC ranged from 0.688 to 0.715 for the NoSAS score and from 0.663 to 0.693 for the STOP-Bang questionnaire. The NoSAS score had the largest AUC (0.715, 95% CI: 0.655-0.775) of diagnosing SDB at AHI cutoff of ≥5 events/h. NoSAS performed better in discriminating moderate-to-severe SDB than STOP-Bang with a marginally significantly higher AUC (0.697 vs. 0.663, P=0.046). Conclusion: The NoSAS score had good performance on the discrimination of SDB patients in sleep clinic and can be utilized as an effective screening tool in clinical practice.

Inhibition of eukaryotic initiation factor 3B suppresses proliferation and promotes apoptosis of chronic myeloid leukemia cells.

BACKGROUND: Eukaryotic translation initiation factor 3B (eIF3b) has been reported to be overexpressed in colon, bladder and prostate cancers as well as in glioblastoma. However, there is no report on any correlation of eIF3b gene expression with cell proliferation and apoptosis in chronic myeloid leukemia (CML). OBJECTIVES: In this study, we evaluated the role of eIF3b in cell proliferation and apoptosis in CML. MATERIAL AND METHODS: Samples from patients with CML and CML cell lines were used. Quantitative RT-PCR, siRNA transfection, flow cytometry, and western blot analysis were performed. RESULTS: Quantitative RT-PCR revealed that the expression of eIF3b mRNA in CML patients was higher than that in the non-malignant controls. The proliferation of CML cells decreased after transfection of the cells with siRNA. The proportion of cells in the G1 and S phases in the experimental group decreased after transfection, while the number of cells in the G2/M phase increased, as compared with the control group. The total cell apoptosis percentage in the sheIF3b group (transduction with lentivirus-anti-eIF3b in K562 cells) was higher than the shCtrl group (transduction with empty-vector lentivirus in K562 cells) after transfection. Caspase 3/7 activity was higher and the expression of anti-apoptotic protein BCL-2 was lower in the sheIF3b group than in the shCtrl group after transfection. CONCLUSIONS: Our results suggest that downregulation of eIF3b expression inhibits proliferation and induces apoptosis in CML cells.

Intermittent hypoxia regulates vasoactive molecules and alters insulin-signaling in vascular endothelial cells.

Vascular dysfunction and insulin resistance (IR) are associated with obstructive sleep apnea (OSA), which is characterized by frequent episodes of nocturnal intermittent hypoxia (IH). While it is recognized that the balance between vasoconstrictive (endothelin-1) and vasodilatory molecules (nitric oxide, NO) determine vascular profile, molecular mechanisms contributing to vascular dysfunction and IR in OSA are not completely understood. Caveolin-1 is a membrane protein which regulates endothelial nitric oxide synthase (eNOS) activity which is responsible for NO generation and cellular insulin-signaling. Hence, we examined the effects of IH on caveolin-1, eNOS, and endothelin-1 in human coronary artery endothelial cells in the context of IR. Chronic 3-day IH exposure up-regulated caveolin-1 and endothelin-1 expression while reducing NO. Also, IH altered insulin-mediated activation of AKT but not ERK resulting in increased endothelin-1 transcription. Similarly, caveolin-1 overexpression attenuated basal and insulin-stimulated NO synthesis along with impaired insulin-dependent activation of AKT and eNOS, with no effect on insulin-stimulated ERK1/2 phosphorylation and endothelin-1 transcription. Our data suggest that IH contributes to a vasoconstrictive profile and to pathway-selective vascular IR, whereby insulin potentiates ET-1 expression. Moreover, IH may partly mediate its effects on NO and insulin-signaling via upregulating caveolin-1 expression.

Apatinib promotes apoptosis of the SMMC-7721 hepatocellular carcinoma cell line via the PI3K/Akt pathway.

The present study investigated the inhibitory effects of apatinib on the proliferation of the SMMC-7721 hepatocellular carcinoma cell line to explore the possible mechanism. The MTT assay was used to detect the inhibitory effects of the different concentrations of apatinib on the proliferation of SMMC-7721 cells. Annexin V/PI double staining was performed to investigate the effects of apatinib on the apoptosis of SMMC-7721 cells. Expression of the apoptosis-related genes Bcl-2, Bax and caspase-9 after apatinib treatment was detected by reverse transcription-quantitative PCR (RT-qPCR) and western blot analysis. Expression of the PI3K, p-PI3K, Akt and p-Akt proteins after apatinib treatment was detected using western blot analysis. The MTT results showed that apatinib inhibited the in vitro proliferation of SMMC-7721 cells. Annexin V/PI double staining showed that apatinib induced the apoptosis of SMMC-7721 cells in a concentration-dependent manner. Results of RT-qPCR and western blot analysis showed that apatinib was able to induce the expression of pro-apoptotic genes Bax and caspase-9 and inhibited the expression of anti-apoptotic gene Bcl-2. In addition, the western blot analysis revealed that p-PI3K and p-Akt was significantly decreased following apatinib treatment, while no significant differences were found in the total protein levels of PI3K and Akt. The results of the present show that apatinib is capable of promoting the apoptosis of SMMC-7721 cells by inhibiting the PI3K/Akt signal transduction pathway, upregulating the expression of pro-apoptotic genes Bax and caspase-9, and downregulating the expression level of the anti-apoptotic gene Bcl-2.

WITHDRAWN: Inhibition of eukaryotic initiation factor 3B suppresses cells proliferation and promotes cells apoptosis in chronic myeloid leukemia.

Ahead of Print article withdrawn by publisher..

Aggressive natural killer cell leukemia or extranodal NK/T cell lymphoma? a case with nasal involvement.

BACKGROUND: Aggressive natural killer cell leukemia/lymphoma (ANKL) is a rare and highly aggressive NK cell neoplasm with a short clinical course and poor prognosis and is often misdiagnosed and confused with NK/T cell lymphoma (NKTL), which has a very different prognosis. Here, we present a case with nasal and bone marrow involvement, provide a literature review and make a differential diagnosis. CASE PRESENTATION: A 41-year-old male presented nasal congestion pharyngalgia, palatal perforation, high fever and multiorgan dysfunction. Our diagnosis primarily relied on clinical features, the morphology and immunophenotype of the neoplastic cells and imaging studies. Characteristic large granular lymphocytes with azurophilic granules were visible in the bone marrow smears. In addition, the neoplastic cells expressed a typical immunophenotype, and the T cell receptor γ (TCR-γ) gene rearrangement analysis and presence of Epstein-Barr virus (EBV) were negative. The patient's symptoms and signs were temporarily relieved after chemotherapy treatment, but after a short time, he underwent a rapid clinical decline and died 8 weeks later after admission due to multiorgan function failure. CONCLUSION: Our case demonstrates that to avoid a misdiagnosis, bone marrow analyses and other examinations should be performed early when a patient initially presents nasal lesions and other systemic symptoms. To the best of our knowledge, this may be the first reported case of ANKL with sternal tenderness.

Intravascular Large B Cell Lymphoma as a Rare Cause of Reversed Halo Sign: A Case Report.

Intravascular large B cell lymphoma (IVLBCL) is a rare type of extranodal diffused large B-cell lymphoma. IVLBCL with primary lung lesion is very rare and it is very difficult to diagnose. Radiographic findings of pulmonary IVLBCL are nonspecific and resembling interstitial lung diseases. Reversed halo sign (RHS) was initially reported in patients diagnosed with cryptogenic organizing pneumonia and then described in a variety of diseases with inflammatory, infectious, autoimmune, and malignant causes. This is the first case of IVLBCL that has presented with RHSs on CT scan.A 59-year-old Chinese man presented with a 4-month history of a nonproductive cough and a weight loss of 5 kg. Physical examination was unremarkable. High-resolution computed tomography scan of the chest showed bilateral patchy ground glass opacities (GGOs) and RHSs. Laboratory tests were unremarkable except elevated serum lactate dehydrogenase (LDH). Surgical lung biopsy was performed. Light microscopic examination of the specimen disclosed diffuse alveolar septal widening caused by neoplastic lymphocytes, which were positive for CD20 and infiltrated in the alveolar capillaries. The patient was diagnosed with IVLBCL and underwent chemotherapy and autologous blood stem cell transplantation. The patient is still alive 5 years after diagnosis.IVLBCL is a rare cause of RHS and should be considered in differential diagnosis of RHS. An increased serum LDH concentration is another important clue.

Complementary and Integrative Medicine at Mayo Clinic.

Complementary and alternative medicine (CAM) has gained acceptance throughout the industrialized world. The present study was performed to provide information about the use of CAM at Mayo Clinic, an academic medical center in Northern Midwest of the US. We retrospectively reviewed the electronic medical records of 2680 patients visiting the CAM program at Mayo Clinic, Rochester, between 1 July 2006 and 31 March 2011. Services provided included acupuncture, massage, integrative medical consultations and executive stress management training. Data including age, gender, race, diagnosis and the number of treatment/consultation sessions were collected to describe the use of CAM in our institute over the last several years. It was found that the mean (standard deviation) age of patient was 52.6 (15.5) years. Of those, 73.1% were female and 26.9% were male. Most patients were white. The number of patients referred to CAM increased significantly from 2007 to 2010. The three most common diagnostic categories were back pain (12.9%), psychological disorders (11.8%), and joint pain (9.6%). Back pain was the most common diagnosis for patients receiving acupuncture, and fibromyalgia was the most common for patients receiving massage therapy. Psychological disorders (i.e., stress) were the major diagnosis referred to both integrative medical consults and executive stress management training. These results suggest that the diseases related to pain and psychological disorders are the main fields of CAM use. It also shows the increasing trend of the use of CAM at an academic medical center in the US.

Development and validation of severe hypoxemia associated risk prediction model in 1,000 mechanically ventilated patients*.

OBJECTIVES: Patients with severe, persistent hypoxemic respiratory failure have a higher mortality. Early identification is critical for informing clinical decisions, using rescue strategies, and enrollment in clinical trials. The objective of this investigation was to develop and validate a prediction model to accurately and timely identify patients with severe hypoxemic respiratory failure at high risk of death, in whom novel rescue strategies can be efficiently evaluated. DESIGN: Electronic medical record analysis. SETTING: Medical, surgical, and mixed ICU setting at a tertiary care institution. PATIENTS: Mechanically-ventilated ICU patients. MEASUREMENTS AND MAIN RESULTS: Mechanically ventilated ICU patients were screened for severe hypoxemic respiratory failure (Murray lung injury score of ≥ 3). Survival to hospital discharge was the dependent variable. Clinical predictors within 24 hours of onset of severe hypoxemia were considered as the independent variables. An area under the curve and a Hosmer-Lemeshow goodness-of-fit test were used to assess discrimination and calibration. A logistic regression model was developed in the derivation cohort (2005-2007). The model was validated in an independent cohort (2008-2010). Among 79,341 screened patients, 1,032 met inclusion criteria. Mortality was 41% in the derivation cohort (n = 464) and 35% in the validation cohort (n = 568). The final model included hematologic malignancy, cirrhosis, aspiration, estimated dead space, oxygenation index, pH, and vasopressor use. The area under the curve of the model was 0.85 (0.82-0.89) and 0.79 (0.75-0.82) in the derivation and validation cohorts, respectively, and showed good calibration. A modified model, including only physiologic variables, performed similarly. It had comparable performance in patients with acute respiratory distress syndrome and outperformed previous prognostic models. CONCLUSIONS: A model using comorbid conditions and physiologic variables on the day of developing severe hypoxemic respiratory failure can predict hospital mortality.

The role of potentially preventable hospital exposures in the development of acute respiratory distress syndrome: a population-based study.

OBJECTIVE: Acute respiratory distress syndrome is a common complication of critical illness, with high mortality and limited treatment options. Preliminary studies suggest that potentially preventable hospital exposures contribute to acute respiratory distress syndrome development. We aimed to determine the association between specific hospital exposures and the rate of acute respiratory distress syndrome development among at-risk patients. DESIGN: Population-based, nested, Matched case-control study. PATIENTS: Consecutive adults who developed acute respiratory distress syndrome from January 2001 through December 2010 during their hospital stay (cases) were matched to similar-risk patients without acute respiratory distress syndrome (controls). They were matched for 6 baseline characteristics. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Trained investigators blinded to outcome of interest reviewed medical records for evidence of specific exposures, including medical and surgical adverse events, inadequate empirical antimicrobial treatment, hospital-acquired aspiration, injurious mechanical ventilation, transfusion, and fluid and medication administration. Conditional logistic regression was used to calculate the risk associated with individual exposures. During the 10-year period, 414 patients with hospital-acquired acute respiratory distress syndrome were identified and matched to 414 at-risk, acute respiratory distress syndrome-free controls. Adverse events were highly associated with acute respiratory distress syndrome development (odds ratio, 6.2; 95% CI, 4.0-9.7), as were inadequate antimicrobial therapy, mechanical ventilation with injurious tidal volumes, hospital-acquired aspiration, and volume of blood products transfused and fluids administered. Exposure to antiplatelet agents during the at-risk period was associated with a decreased risk of acute respiratory distress syndrome. Rate of adverse hospital exposures and prevalence of acute respiratory distress syndrome decreased during the study period. CONCLUSIONS: Prevention of adverse hospital exposures in at-risk patients may limit the development of acute respiratory distress syndrome.

Indicators of central fever in the neurologic intensive care unit.

IMPORTANCE: Fever is common in critically ill neurologic patients. Knowledge of the indicators of central fever may allow greater antibiotic stewardship in this era of rapidly developing super-resistant microorganisms. OBJECTIVE: To develop a model to differentiate central from infectious fever in critically ill neurologic patients with fever of an undetermined cause. DESIGN, SETTING, AND PARTICIPANTS: Retrospective data collection from January 1, 2006, through December 31, 2010, at a 20-bed neurologic intensive care unit of a large teaching hospital. Consecutive patients 18 years and older admitted for 48 hours or longer with a core body temperature higher than 38.3 °C on at least 1 measurement for 2 consecutive days. Patients with alternative identified causes of noninfectious fever were excluded. In total, 526 patients were included in the final analysis. MAIN OUTCOMES AND MEASURES: Percentage incidence and odds ratios of variables associated with central fever. Fever was classified as infectious if there was culture growth of a pathogenic species or documented clinical diagnosis of infection treated with antibiotics. Remaining patients were considered to have central fever. Continuous fever lasting longer than 6 hours for 2 or more consecutive days was considered persistent. RESULTS Fever was central in 246 patients (46.8%). Patients with infectious fever were older (mean, 57.4 vs 53.5 years; P = .01) and had a longer length of stay in the neurologic intensive care unit (mean, 12.1 vs 8.8 days; P < .001). Central fever was more likely to occur within 72 hours of admission to the neurologic intensive care unit (76.4% vs 60.7%; P < .001) and tended to be persistent (26.4% vs 18.6%; P = .04). Blood transfusion (odds ratio [OR], 3.06; 95% CI, 1.63-5.76); absence of infiltrate on chest x-ray (3.02; 1.81-5.05); diagnosis of subarachnoid hemorrhage, intraventricular hemorrhage, or tumor (6.33; 3.72-10.77); and onset of fever within 72 hours of hospital admission (2.20; 1.23-3.94) were independent predictors of central fever on multivariable analysis. The combination of negative cultures; absence of infiltrate on chest radiographs; diagnosis of subarachnoid hemorrhage, intraventricular hemorrhage, or tumor; and onset of fever within 72 hours of admission predicted central fever with a probability of .90. CONCLUSIONS AND RELEVANCE: We provide a reliable model to differentiate central fever from infectious fever in critically ill neurologic patients, allowing clinicians to select patients in whom antibiotics may be safely discontinued despite ongoing fever.

Epidemiology of noninvasive mechanical ventilation in acute respiratory failure--a retrospective population-based study.

BACKGROUND: Noninvasive mechanical ventilation (NIV) is a front-line therapy for the management of acute respiratory failure (ARF) in the intensive care units. However, the data on factors and outcomes associated with the use of NIV in ARF patients is lacking. Therefore, we aimed to determine the utilization of NIV for ARF in a population-based study. METHODS: We conducted a populated-based retrospective cohort study, where in all consecutively admitted adults (≥18 years) with ARF from Olmsted County, Rochester, MN, at the Mayo Clinic medical and surgical ICUs, during 2006 were included. Patients without research authorization or on chronic NIV use for sleep apnea were excluded. RESULTS: Out of 1461 Olmsted County adult residents admitted to the ICUs in 2006, 364 patients developed ARF, of which 146 patients were initiated on NIV. The median age in years was 75 (interquartile range, 60-84), 48% females and 88.7% Caucasians. Eighteen patients (12%) were on Continuous Positive Airway Pressure (CPAP) mode and 128 (88%) were on noninvasive intermittent positive-pressure ventilation (NIPPV) mode. Forty-six (10%) ARF patients were put on NIV for palliative strategy to alleviate dyspnea. Seventy-six ARF patients without treatment limitation were given a trial of NIV and 49 patients succeeded, while 27 had to be intubated. Mortality was similar between the patients initially supported with NIV versus invasive mechanical ventilation (33% vs 22%, P=0.289). In the multivariate analysis, the development of acute respiratory distress syndrome (ARDS) and higher APACHE III scores were associated with the failure of initial NIV treatment. CONCLUSIONS: Our results have important implications for a future planning of NIV in a suburban US community with high access to critical care services. The higher APACHE III scores and the development of ARDS are associated with the failure of initial NIV treatment.

Derivation and validation of automated electronic search strategies to extract Charlson comorbidities from electronic medical records.

OBJECTIVE: To develop and validate automated electronic note search strategies (automated digital algorithm) to identify Charlson comorbidities. PATIENTS AND METHODS: The automated digital algorithm was built by a series of programmatic queries applied to an institutional electronic medical record database. The automated digital algorithm was derived from secondary analysis of an observational cohort study of 1447 patients admitted to the intensive care unit from January 1 through December 31, 2006, and validated in an independent cohort of 240 patients. The sensitivity, specificity, and positive and negative predictive values of the automated digital algorithm and International Classification of Diseases, Ninth Revision (ICD-9) codes were compared with comprehensive medical record review (reference standard) for the Charlson comorbidities. RESULTS: In the derivation cohort, the automated digital algorithm achieved a median sensitivity of 100% (range, 99%-100%) and a median specificity of 99.7% (range, 99%-100%). In the validation cohort, the sensitivity of the automated digital algorithm ranged from 91% to 100%, and the specificity ranged from 98% to 100%. The sensitivity of the ICD-9 codes ranged from 8% for dementia to 100% for leukemia, whereas specificity ranged from 86% for congestive heart failure to 100% for leukemia, dementia, and AIDS. CONCLUSION: Our results suggest that search strategies that use automated electronic search strategies to extract Charlson comorbidities from the clinical notes contained within the electronic medical record are feasible and reliable. Automated digital algorithm outperformed ICD-9 codes in all the Charlson variables except leukemia, with greater sensitivity, specificity, and positive and negative predictive values.