Pathogenesis of HIV-Related Lung Disease: Immunity, Infection, and Inflammation.

Despite anti-retroviral therapy (ART), human immunodeficiency virus-1 (HIV)-related pulmonary disease continues to be a major cause of morbidity and mortality for people living with HIV (PLWH). The spectrum of lung diseases has changed from acute opportunistic infections resulting in death to chronic lung diseases for those with access to ART. Chronic immune activation and suppression can result in impairment of innate immunity and progressive loss of T cell and B cell functionality with aberrant cytokine and chemokine responses systemically as well as in the lung. HIV can be detected in the lungs of PLWH and has profound effects on cellular immune functions. In addition, HIV-related lung injury and disease can occur secondary to a number of mechanisms including altered pulmonary and systemic inflammatory pathways, viral persistence in the lung, oxidative stress with additive effects of smoke exposure, microbial translocation, and alterations in the lung and gut microbiome. Although ART has had profound effects on systemic viral suppression in HIV, the impact of ART on lung immunology still needs to be fully elucidated. Understanding of the mechanisms by which HIV-related lung diseases continue to occur is critical to the development of new preventive and therapeutic strategies to improve lung health in PLWH.

Differentiation of Prior SARS-CoV-2 Infection and Postacute Sequelae by Standard Clinical Laboratory Measurements in the RECOVER Cohort.

BACKGROUND: There are currently no validated clinical biomarkers of postacute sequelae of SARS-CoV-2 infection (PASC). OBJECTIVE: To investigate clinical laboratory markers of SARS-CoV-2 and PASC. DESIGN: Propensity score-weighted linear regression models were fitted to evaluate differences in mean laboratory measures by prior infection and PASC index (≥12 vs. 0). (ClinicalTrials.gov: NCT05172024). SETTING: 83 enrolling sites. PARTICIPANTS: RECOVER-Adult cohort participants with or without SARS-CoV-2 infection with a study visit and laboratory measures 6 months after the index date (or at enrollment if >6 months after the index date). Participants were excluded if the 6-month visit occurred within 30 days of reinfection. MEASUREMENTS: Participants completed questionnaires and standard clinical laboratory tests. RESULTS: Among 10 094 participants, 8746 had prior SARS-CoV-2 infection, 1348 were uninfected, 1880 had a PASC index of 12 or higher, and 3351 had a PASC index of zero. After propensity score adjustment, participants with prior infection had a lower mean platelet count (265.9 × 109 cells/L [95% CI, 264.5 to 267.4 × 109 cells/L]) than participants without known prior infection (275.2 × 109 cells/L [CI, 268.5 to 282.0 × 109 cells/L]), as well as higher mean hemoglobin A1c (HbA1c) level (5.58% [CI, 5.56% to 5.60%] vs. 5.46% [CI, 5.40% to 5.51%]) and urinary albumin-creatinine ratio (81.9 mg/g [CI, 67.5 to 96.2 mg/g] vs. 43.0 mg/g [CI, 25.4 to 60.6 mg/g]), although differences were of modest clinical significance. The difference in HbA1c levels was attenuated after participants with preexisting diabetes were excluded. Among participants with prior infection, no meaningful differences in mean laboratory values were found between those with a PASC index of 12 or higher and those with a PASC index of zero. LIMITATION: Whether differences in laboratory markers represent consequences of or risk factors for SARS-CoV-2 infection could not be determined. CONCLUSION: Overall, no evidence was found that any of the 25 routine clinical laboratory values assessed in this study could serve as a clinically useful biomarker of PASC. PRIMARY FUNDING SOURCE: National Institutes of Health.

The Evolution of Central Venous-to-arterial Carbon Dioxide Difference (PCO2 Gap) during Resuscitation Affects ICU Outcomes: A Prospective Observational Study.

Introduction: The usual methods of perfusion assessment in patients with shock, such as capillary refill time, skin mottling, and serial serum lactate measurements have many limitations. Veno-arterial difference in the partial pressure of carbon dioxide (PCO2 gap) is advocated being more reliable. We evaluated serial change in PCO2 gap during resuscitation in circulatory shock and its effect on ICU outcomes. Materials and methods: This prospective observational study included 110 adults with circulatory shock. Patients were resuscitated as per current standards of care. We recorded invasive arterial pressure, urine output, cardiac index (CI), PCO2 gap at ICU admission at 6, 12, and 24 hours, and various patient outcomes. Results: Significant decrease in PCO2 gap was observed at 6 h and was accompanied by improvement in serum lactate, mean arterial pressure, CI and urine output in (n = 61). We compared these patients with those in whom this decrease did not occur (n = 49). Mortality and ICU LOS was significantly lower in patients with low PCO2 gap, while more patients with high PCO2 gap required RRT. Conclusion: We found that a persistently high PCO2 gap at 6 and 12 h following resuscitation in patients with shock of various etiologies, was associated with increased mortality, need for RRT and increased ICU LOS. High PCO2 gap had a moderate discriminative ability to predict mortality. How to cite this article: Zirpe KG, Tiwari AM, Kulkarni AP, Vaidya HS, Gurav SK, Deshmukh AM, et al. The Evolution of Central Venous-to-arterial Carbon Dioxide Difference (PCO2 Gap) during Resuscitation Affects ICU Outcomes: A Prospective Observational Study. Indian J Crit Care Med 2024;28(4):349-354.

Lung Function in Women With and Without Human Immunodeficiency Virus.

BACKGROUND: Prior studies have found that human immunodeficiency virus (HIV) infection is associated with impaired lung function and increased risk of chronic lung disease, but few have included large numbers of women. In this study, we investigate whether HIV infection is associated with differences in lung function in women. METHODS: This was a cross-sectional analysis of participants in the Women's Interagency HIV Study, a racially and ethnically diverse multicenter cohort of women with and without HIV. In 2018-2019, participants at 9 clinical sites were invited to perform spirometry. Single-breath diffusing capacity for carbon monoxide (DLCO) was also measured at selected sites. The primary outcomes were the post-bronchodilator forced expiratory volume in 1 second (FEV1) and DLCO. Multivariable regression modeling was used to analyze the association of HIV infection and lung function outcomes after adjustment for confounding exposures. RESULTS: FEV1 measurements from 1489 women (1062 with HIV, 427 without HIV) and DLCO measurements from 671 women (463 with HIV, 208 without HIV) met standards for quality and reproducibility. There was no significant difference in FEV1 between women with and without HIV. Women with HIV had lower DLCO measurements (adjusted difference, -0.73 mL/min/mm Hg; 95% confidence interval, -1.33 to -.14). Among women with HIV, lower nadir CD4 + cell counts and hepatitis C virus infection were associated with lower DLCO measurements. CONCLUSIONS: HIV was associated with impaired respiratory gas exchange in women. Among women with HIV, lower nadir CD4 + cell counts and hepatitis C infection were associated with decreased respiratory gas exchange.

Development of a Definition of Postacute Sequelae of SARS-CoV-2 Infection.

Importance: SARS-CoV-2 infection is associated with persistent, relapsing, or new symptoms or other health effects occurring after acute infection, termed postacute sequelae of SARS-CoV-2 infection (PASC), also known as long COVID. Characterizing PASC requires analysis of prospectively and uniformly collected data from diverse uninfected and infected individuals. Objective: To develop a definition of PASC using self-reported symptoms and describe PASC frequencies across cohorts, vaccination status, and number of infections. Design, Setting, and Participants: Prospective observational cohort study of adults with and without SARS-CoV-2 infection at 85 enrolling sites (hospitals, health centers, community organizations) located in 33 states plus Washington, DC, and Puerto Rico. Participants who were enrolled in the RECOVER adult cohort before April 10, 2023, completed a symptom survey 6 months or more after acute symptom onset or test date. Selection included population-based, volunteer, and convenience sampling. Exposure: SARS-CoV-2 infection. Main Outcomes and Measures: PASC and 44 participant-reported symptoms (with severity thresholds). Results: A total of 9764 participants (89% SARS-CoV-2 infected; 71% female; 16% Hispanic/Latino; 15% non-Hispanic Black; median age, 47 years [IQR, 35-60]) met selection criteria. Adjusted odds ratios were 1.5 or greater (infected vs uninfected participants) for 37 symptoms. Symptoms contributing to PASC score included postexertional malaise, fatigue, brain fog, dizziness, gastrointestinal symptoms, palpitations, changes in sexual desire or capacity, loss of or change in smell or taste, thirst, chronic cough, chest pain, and abnormal movements. Among 2231 participants first infected on or after December 1, 2021, and enrolled within 30 days of infection, 224 (10% [95% CI, 8.8%-11%]) were PASC positive at 6 months. Conclusions and Relevance: A definition of PASC was developed based on symptoms in a prospective cohort study. As a first step to providing a framework for other investigations, iterative refinement that further incorporates other clinical features is needed to support actionable definitions of PASC.

Case of Suspected SARS-CoV-2 Vaccine-induced Immune Thrombotic Thrombocytopenia: Dilemma for Organ Donation.

Several vaccines were developed and rolled out at an unprecedented rate in response to the coronavirus disease-2019 (COVID-19) pandemic. Most vaccines approved globally by WHO for emergency use to combat the pandemic were deemed remarkably effective and safe. Despite the safety, rare incidences of vaccine-induced thrombosis and thrombocytopenia (VITT), sometimes known as vaccine-induced prothrombotic thrombocytopenia (VIPIT), have been reported. We report a case of young female with prothrombotic conditions and suspected VITT who developed catastrophic cerebral venous sinus thrombosis (CVST) and progressed to brain death. We highlight hurdles of organ retrieval from a brain-dead patient with suspected SARS-CoV-2 vaccine-induced immune thrombotic thrombocytopenia. There is limited data and lack of substantial evidence regarding transplantation of organs from brain-dead patients with suspected VITT. How to cite this article: Tiwari AM, Zirpe KG, Gurav SK, Bhirud LB, Suryawanshi RS, Kulkarni SS. Case of Suspected SARS-CoV-2 Vaccine-induced Immune Thrombotic Thrombocytopenia: Dilemma for Organ Donation. Indian J Crit Care Med 2022;26(4):514-517.

Use of Baricitinib in Patients With Moderate to Severe Coronavirus Disease 2019.

Hyperinflammation is associated with increased mortality in coronavirus disease 2019 (COVID-19). In this retrospective, uncontrolled patient cohort with moderate -severe COVID-19, treatment with baricitinib plus hydroxychloroquine was associated with recovery in 11 of 15 patients. Baricitinib for the treatment of COVID-19 should be further investigated in randomized, controlled clinical trials.

Age as Maestro or Solo Instrument in Opera of Death.

How to cite this article: Zirpe KG, Nimavat BD, Gurav SK. Age as Maestro or Solo Instrument in Opera of Death. Indian J Crit Care Med 2021;25(6):606-607.

Timing of Invasive Mechanical Ventilation and Mortality among Patients with Severe COVID-19-associated Acute Respiratory Distress Syndrome.

BACKGROUND: Severe acute respiratory distress syndrome associated with coronavirus disease-2019 (COVID-19) (CARDS) pneumonitis presents a clinical challenge as regards to the timing of intubation and ambiguity of outcome. There is a lack of clear consensus on when to switch patients from trials of noninvasive therapies to invasive mechanical ventilation. We investigated the effect of the timing of intubation from the time of admission on the clinical outcome of CARDS. AIM AND OBJECTIVE: The aim and objective was to analyze the effect of timing of intubation early (within 48 hours of admission to critical care unit) versus delayed (after 48 hours of admission to critical care unit) on mortality in severe CARDS patients. MATERIALS AND METHODS: A retrospective observational study performed in a 28-bedded COVID-19 intensive care unit of a tertiary care hospital in Pune, India. All patients admitted between April 1, 2020, and October 15, 2020, with confirmed COVID-19 (RT-PCR positive) requiring mechanical ventilation were included in the study. RESULTS: The primary outcome was in-hospital mortality. Among 2,230 patients that were admitted to the hospital, 525 required critical care (23.5%), invasive mechanical ventilation was needed in 162 patients and 147 (28%) of critical care admission were included in the study cohort after exclusion. Seventy-five patients (51%) were intubated within 48 hours of critical care admission (early group) and 72 (48.9%) were intubated after 48 hours of critical care admission (delayed group). With regards to the total of 147 included patients; male patients were 74.1% with a median age of 59 years (interquartile range, 51-68 years). Diabetes (44.9%) and hypertension (43.5%) were the most common comorbidities. Higher admission acute physiology and chronic health evaluation II scores and lower absolute lymphocyte count were observed in patients intubated within 48 hours. The early intubated group had a mortality of 60% whereas the same was observed as 77.7% in delayed intubation group, and this difference was statistically significant (p = 0.02). CONCLUSION: Current study concludes that early intubation is associated with improved survival rates in severe CARDS patients. HOW TO CITE THIS ARTICLE: Zirpe KG, Tiwari AM, Gurav SK, Deshmukh AM, Suryawanshi PB, Wankhede PP, et al. Timing of Invasive Mechanical Ventilation and Mortality among Patients with Severe COVID-19-associated Acute Respiratory Distress Syndrome. Indian J Crit Care Med 2021;25(5):493-498.

The Second- vs First-wave COVID-19: More of the Same or a Lot Worse? A Comparison of Mortality between the Two Waves in Patients Admitted to Intensive Care Units in Nine Hospitals in Western Maharashtra.

BACKGROUND: India, along with the rest of the world, faced the challenging severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic. The second wave in India lagged behind that in the Western world, due to different timing of seasons. There is scarce data about the differences between the two waves, for intensive care unit (ICU) patients. We present the data of 3,498 patients from 9 ICUs of western Maharashtra. MATERIALS AND METHODS: We collected prospective data of hospitalized, RT-PCR confirmed, coronavirus-2019 (COVID-19) patients, from nine tertiary centers, after institutional ethics committee (IEC) approval. Then, we segregated and analyzed the data of patients admitted to the ICU, for comorbidities, high-resolution computed tomography (HRCT) score, ventilatory support, etc. The primary outcomes were ICU and hospital mortality. We also performed multivariable analysis for predictors of ICU mortality. RESULTS: Overall, there were 3,498 ICU patients. In the first wave, 1,921 patients needed ICU admission, while in the second wave, 1,577 patients. Patients in the second wave had significantly higher ICU (26.1 vs 13.4%, p <0.001) and hospital mortality (29.9 vs 18.2%, p <0.001) and need for ventilatory support of any type. More patients received steroids during the second wave. On multivariable regression, male gender, ICU admission during the second wave, increasing HRCT score, and need for intubation and mechanical ventilation were significant predictors of ICU mortality. CONCLUSION: ICU patients admitted during the two waves were of the similar age, but there were more females, and more patients had comorbidities during the second wave. The ICU and hospital mortality were significantly higher during the second wave. HOW TO CITE THIS ARTICLE: Zirpe KG, Dixit S, Kulkarni AP, Pandit RA, Ranganathan P, Prasad S, et al. The Second- vs First-wave COVID-19: More of the Same or a Lot Worse? A Comparison of Mortality between the Two Waves in Patients Admitted to Intensive Care Units in Nine Hospitals in Western Maharashtra. Indian J Crit Care Med 2021; 25(12):1343-1348.

Twelve tips for developing and implementing a medical education Twitter chat.

Live discussions on the social media site Twitter or Twitter chats are gaining popularity as powerful tools for engaging a broad audience in an interactive discussion. Medical education, in particular, is experiencing an increase in the use of this modality to support informal learning, as a means to encourage collaboration and share best practices, and as a platform for large-scale mentorship. Despite this growth in popularity, there are limited data to guide medical educators on the fundamentals of organizing a Twitter chat. In this Twelve Tips article, we discuss strategies relevant to potential Twitter chat organizers. We have arranged the tips chronologically, beginning with a discussion of initial considerations when planning and formulating a chat topic and publicizing the chat to potentially interested people and groups, followed by practical considerations while hosting the chat, and finally strategies for evaluating and extending a Twitter chat's impact.

Critical Analysis of a Randomized Controlled Trial.

In the era of evidence-based medicine, healthcare professionals are bombarded with plenty of trials and articles of which randomized control trial is considered as the epitome of all in terms of level of evidence. It is very crucial to learn the skill of balancing knowledge of randomized control trial and to avoid misinterpretation of trial result in clinical practice. There are various methods and steps to critically appraise the randomized control trial, but those are overly complex to interpret. There should be more simplified and pragmatic approach for analysis of randomized controlled trial. In this article, we like to summarize few of the practical points under 5 headings: "5 'Rs' of critical analysis of randomized control trial" which encompass Right Question, Right Population, Right Study Design, Right Data, and Right Interpretation. This article gives us insight that analysis of randomized control trial should not only based on statistical findings or results but also on systematically reviewing its core question, relevant population selection, robustness of study design, and right interpretation of outcome. How to cite this article: Nimavat BD, Zirpe KG, Gurav SK. Critical Analysis of a Randomized Controlled Trial. Indian J Crit Care Med 2020;24(Suppl 4):S215-S222.

Incidence of Medication Error in Critical Care Unit of a Tertiary Care Hospital: Where Do We Stand?

BACKGROUND: Medication error in developed countries is of primary concern when there is a question of adversity to a patient's health, but in developing countries like India, it is just a term and its significance is undervalued. The incidence of medication error is essential to estimate the proper medical care provided in the healthcare system. OBJECTIVE: The main objective of the study is to determine the incidences of medication error in critical care unit and to evaluate its risk outcomes. MATERIALS AND METHODS: This is a prospective observational study conducted over a period of 6 months in a critical care unit of a tertiary care hospital. Medication chart review method was opted for data collection. The medication errors were mainly classified as prescription, transcription, indenting, dispensing, and administration error. A total of 6,705 charts were reviewed. The NCCMERP risk index was used to evaluate the outcome of errors. RESULTS: Of the total 6,705 charts, 410 medication errors were found, i.e., 6.11%. The most common error is transcription error that constitutes 44.1% of the total errors, followed by prescription error 40%, and administration error 14%. The frequency of indenting and dispensing errors is negligible with 1.5% and 0.5%, respectively. The main causes of medication errors are due to incomplete prescription 50.2% and wrong doses 22.9%. In drug class, antibiotics and antihypertensive agents are most prone to medication error. About 87.1% errors belonged to the Category B of National Coordinating Council for Medication Error Reporting and Prevention risk index. CONCLUSION: Majority of the errors are transcription errors followed by prescription and administration errors. Consultant doctors have to be more vigilant during prescribing and verifying the medication charts. Clinical pharmacists should act as a checkpoint at each step of medication process to identify and prevent medication errors. HOW TO CITE THIS ARTICLE: Zirpe KG, Seta B, Gholap S, Aurangabadi K, Gurav SK, Deshmukh AM, et al. Incidence of Medication Error in Critical Care Unit of a Tertiary Care Hospital: Where Do We Stand? Indian J Crit Care Med 2020;24(9):799-803.

Impact of "Stroke Code"-Rapid Response Team: An Attempt to Improve Intravenous Thrombolysis Rate and to Shorten Door-to-Needle Time in Acute Ischemic Stroke.

OBJECTIVE: "Stroke code" (SC) implementation in hospitals can improve the rate of thrombolysis and the timeline in care of stroke patient. MATERIALS AND METHODS: A prospective data of patients treated for acute ischemic stroke (AIS) after implementation of "SC" (post-SC era) were analyzed (2015-2016) and compared with the retrospective data of patients treated in the "pre-SC era." Parameters such as symptom-to-door, door-to-physician, door-to-imaging, door-to-needle (DTN), and symptom-to-needle time were calculated. The severity of stroke was calculated using the National Institutes of Health Stroke Score (NIHSS) before and after treatment. RESULTS: Patients presented with stroke symptoms in pre- and post-SC era (695 vs. 610) and, out of these, patients who came in window period constituted 148 (21%) and 210 (34%), respectively. Patients thrombolyzed in pre- and post-SC era were 44 (29.7%) and 65 (44.52%), respectively. Average DTN time was 104.95 min in pre-SC era and reduced to 67.28 min (P < 0.001) post-SC implementation. Percentage of patients thrombolyzed within DTN time ≤60 min in pre-SC era and SC era was 15.90% and 55.38%, respectively. CONCLUSION: Implementation of SC helped us to increase thrombolysis rate in AIS and decrease DTN time.

The Impact of Early Tracheostomy in Neurotrauma Patients: A Retrospective Study.

BACKGROUND: Although majority of neurotrauma patients require long term ventilatory support but the timing of tracheostomy in such patients is controversial. METHOD: This retrospective study was conducted at a Tertiary Care Hospital, Pune, India. Patients >18 years of age, who underwent percutaneous tracheostomy (PCT) from June 2010 to November 2014 at neurotrauma unit (NTU) of hospital, were included. Patients were divided in two groups according to the timing of tracheostomy, early tracheostomy (ET) group (≤5 days; N=100) and late tracheostomy (LT) group (>5 days; N=64). The nonparametric Mann-Whitney test, and Chi-square tests were used to compare these groups. RESULT: There were no significant differences between the groups in terms of age, sex, APACHE II and GCS Score. Patients in the ET group had a significantly shorter stay in the NTU compared to patients in the LT group (mean, 18 vs. 21.2 days, p=0.005), fewer mechanical ventilation days (mean, 8.1 vs. 11.7 days, P=0.000) and shorter length of stay in hospital (mean, 28.8 vs. 34.37 days, P=0.019). There was no difference between ET and LT groups in post PCT ventilator free days (mean, 8.2 vs. 9.4 days; P=0.094). Mortality rates in ET vs. LT groups were also comparable (35% vs. 29.7%; P=0.480). CONCLUSION: Results suggest that ET in neurotrauma patients might be associated with shorter length of stay in NTU and hospital, and shorter duration of mechanical ventilation however there was no mortality difference.

The Impact of Antiretroviral Therapy on Lung Immunology.

Despite the introduction of antiretroviral therapy (ART), human immunodeficiency virus-1 (HIV) continues to cause a major impact worldwide. HIV-induced lung disease continues to represent a significant source of morbidity and mortality, although the spectrum of pulmonary diseases has changed. HIV significantly affects the lung, causing acute and chronic cellular changes in the alveolar space. The impact of ART on lung immunology still needs to be fully elucidated. Similar to the periphery, ART affects HIV viral load and reconstitutes CD4(+) T cells in the lung. ART has been associated with significant decreases in bronchoalveolar lavage lymphocytes and increases in B-cell numbers and functionality, resulting in improved immune responses to vaccinations. There are substantial clinical implications of these ART-induced alterations, including the emergence of immune reconstitution inflammatory syndrome and the increased incidences of noninfectious lung diseases, such as lung cancer and chronic obstructive lung disease. There continues to be many unanswered questions regarding the effects of ART on lung health and, in particular, the immune system. Growing knowledge in this area will hopefully diminish the incidence of these noninfectious lung diseases and further improve the health of individuals living with HIV.

Characteristics and Outcomes of HIV-Infected Patients With Severe Sepsis: Continued Risk in the Post-Highly Active Antiretroviral Therapy Era.

OBJECTIVES: Although highly active antiretroviral therapy has led to improved survival in HIV-infected individuals, outcomes for HIV-infected patients with sepsis in the post-highly active antiretroviral therapy era are conflicting. Access to highly active antiretroviral therapy and healthcare disparities continue to affect outcomes. We hypothesized that HIV-infected patients with severe sepsis would have worse outcomes compared with their HIV-uninfected counterparts in a large safety-net hospital where access to healthcare is low and delivery of critical care is delayed. DESIGN: Secondary analysis of an ongoing prospective observational study between 2006 and 2010. SETTING: Three adult ICUs (medical ICU, surgical ICU, and neurologic ICU) at Grady Memorial Hospital, Atlanta, GA. PATIENTS: Adult patients with severe sepsis in the ICU. INTERVENTIONS: Baseline patient characteristics and clinical outcomes were collected. HIV-infected and HIV-uninfected patients with sepsis were compared using t tests, chi-square tests, and logistic regression; p values less than 0.05 indicated significance. MEASUREMENTS AND MAIN RESULTS: Of 1,095 patients with severe sepsis enrolled, 165 (15%) were positive for HIV, with a median CD4 count of 41 (8-167). Twenty-two percent of HIV-infected patients were on highly active antiretroviral therapy prior to admission, and 80% had a CD4 count less than 200. HIV-infected patients had a greater hospital mortality (50% vs 38%; p < 0.01). HIV infection (odds ratio = 1.78; p = 0.005) was an independent predictor of mortality by multivariate regression modeling after adjusting for age, history of pneumonia, history of hospital-acquired infection, and history of sepsis. CONCLUSIONS: HIV-infected patients with severe sepsis continue to suffer worse outcomes compared with HIV-uninfected patients in a large urban safety-net hospital caring for patients with limited access to medical care. Further studies need to be done to investigate the effect of socioeconomic status and mitigate healthcare disparities among critically ill HIV-infected patients.

Problems and limitations in thrombolysis of acute stroke patients at a tertiary care center.

AIM: (1) To evaluate the number of patients thrombolysed within 1 h of arrival to emergency room (ER) (2) To identify reasons for delay in thrombolysis of acute stroke patients. MATERIALS AND METHODS: All patients admitted to ER with symptoms suggestive of stroke from January 2011 to November 2013 were studied. Retrospective data were collected to evaluate ER to needle (door to needle time [DTNt]) time and reasons for delay in thrombolysis. The parameters studied (1) onset of symptoms to ER time, (2) ER to imaging time (door to imaging time [DTIt]), (4) ER to needle time (door to needle) and (5) contraindications for thrombolysis. RESULTS: A total of 695 patients with suspected stroke were admitted during study period. 547 (78%) patients were out of window period. 148 patients (21%, M = 104, F = 44) arrived within window period (<4.5 h.). 104 (70.27%) were contraindicated for thrombolysis. Majority were intracerebral bleeds. 44 (29.7%) were eligible for thrombolysis. 7 (15.9%) were thrombolysed within 1 h. The mean time for arrival of patients from onset of symptoms to hospital (symptom to door) 83 min (median - 47). The mean door to neuro-physician time (DTPt) was 32 min (median - 15 min). The mean DTIt was 58 min (median - 50 min). The mean DTNt 104 (median - 100 min). CONCLUSION: Reasons for delay in thrombolysis are: Absence of stroke education program for common people. Lack of priority for triage and imaging for stroke patients.

Navigating the institutional review board approval process in a multicenter observational critical care study.

OBJECTIVE: To characterize variation in the institutional review board application process of a multicenter, observational critical care study. DESIGN, SETTING, AND SUBJECTS: Survey analysis of 36 investigators who applied for participation in the United States Critical Illness and Injury Trials Group: Critical Illness and Outcomes Study, an observational study of 69 adult ICUs. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Analysis of investigator-specific characteristics, institutional review board process, application and approval dates, and level of difficulty in obtaining approval. Surveys were analyzed from 36 sites (95%) that applied for institutional review board approval. Level of review ranged from full board, expedited, to exempt. Seventy-five percent of applications were submitted by an experienced investigator while 25% were submitted by a less experienced investigator. Median time to institutional review board approval was 30 days (interquartile range, 14-54) and ranged from 5 days to 5.5 months. Time to approval was 29 days (interquartile range, 17-48) for applications submitted by an experienced investigator compared with 97 days (interquartile range, 25-159) for those submitted by a less experienced investigator (p = 0.08). Subjective level of difficulty was significantly higher for less experienced investigators (4 of 10; interquartile range, 2-8) vs experienced investigators (2 of 10; interquartile range, 1-3) (p = 0.04). Four sites cited institutional review board concern regarding waiver of consent as a major barrier to approval and were required to perform revisions or participate in board meetings regarding this concern. CONCLUSIONS: In a multicenter, observational critical care study, significant variation was observed between sites in all aspects of the institutional review board evaluation and approval process. The level of difficulty was significantly higher for less experienced investigators with a trend toward longer time to institutional review board approval. Variation in institutional review board interpretation of waiver of informed consent regulations was cited as a major barrier to approval.

Effect of reflux time on nanoparticle shape.

In the present work, Pt nanoparticles were produced from a reaction mixture containing a trace amount of cobalt carbonyl salt acting as a shape inducer. Nanoparticle shape evolution during reaction mixture reflux was monitored by characterizing particles extracted from the reaction mixture at different times. It was observed that 5 min of reflux produced spherical nanoparticles, 30 min of reflux produced cube shaped nanoparticles, and 60 min of reflux produced truncated octahedron morphology nanoparticles. It is illustrated that during nanoparticle synthesis the reflux process can provide energy needed for shape transformation from a metastable cube morphology to a truncated octahedron morphology which is thermodynamically the most stable geometry for fcc crystals. An optimization of the reaction reflux is thus needed for isolating metastable shapes.