Use of inhaled PGE1 to improve diastolic dysfunction, LVEDP, Pulmonary Hypertension and Hypoxia in ARDS—A randomised clinical trial

Introduction: We wished to see the effects of inhaled PGE1 on diastolic dysfunction, left ventricular end diastolic pressure (LVEDP), pulmonary hypertension and hypoxia in ARDS patients. Methods: This is a randomized, prospective, clinical trial conducted in the main adult intensive care unit of a tertiary care University hospital. A total of 67 patients were recruited. Inclusion criteria included all adult patients with a P/F ratio /or Pulmonary Artery systolic (Pa) pressures of \u3e35 mmHg on Pulmonary artery catheter or suspected on clinical grounds. A transthoracic echo was performed to record the diastolic function, LVEDP and Pa pressures. Subsequently patients were randomized by a block computerized randomization to either cases (n = 34) or controls (n = 33). Cases received nebulised PGE1 over 30 minutes in the ICU and normal saline was administered to controls blindly. Following this the echo and arterial blood gases were repeated. Our primary outcomes were an improvement in diastolic function and P/F ratio of greater than 20% and a decrease in pulmonary pressure and LVEDP of \u3e20%. Results: At baseline, mean diastolic dysfunction was grade II, with a mean LVEDP of \u3e15 and the PaO2/FiO2 ratio was 148.38 ± 60.05 with a mean pulmonary artery pressure of 81.35 ± 16.91. Inhaled PGE1 was followed by an improvement in diastolic dysfunction (grade I, p = 0.001) with a resulting improvement in LVEDP (12 +/? 2, p = 0.001) as well as Pa pressures (97.09 ± 30.06, p = 0.04) and a non significant improvement in PaO2/FiO2 ratio (161.45 ± 77.52, p = 0.21). There were no side effects observed in any patients. Conclusion: Our study shows that there is a significant improvement in diastolic dysfunction, LVEDP and Pa pressures after administration of nebulised PGE1, and an improvement although non-significant in hypoxia in ARDS patients. The trial was registered with Clinicaltrials.gov (NCT00314548) and funded by the Pakistan medical research council

Proteomic signature of periodontal disease in pregnancy: Predictive validity for adverse outcomes

The rate of preterm birth is a public health concern worldwide because it is increasing and efforts to prevent it have failed. We report a Clinically Relevant Complex Systematic Review (CSCSR) designed to identify and evaluate the best available evidence in support of the association between periodontal status in women and pregnancy outcome of preterm low birth weight. We hypothesize that the traditional limits of research synthesis must be expanded to incorporate a translational component. As a proof-of-concept model, we propose that this CSCSR can yield greater validity of efficacy and effectiveness through supplementing its recommendations with data of the proteomic signature of periodontal disease in pregnancy, which can contribute to addressing specifically the predictive validity for adverse outcomes. For this CRCSR, systematic reviews were identified through The National Library of MedicinePubmed, The Cochrane library, CINAHL, Google Scholar, Web of Science, and the American Dental Association web library. Independent reviewers quantified the relevance and quality of this literature with R-AMSTAR. Homogeneity and inter-rater reliability testing were supplemented with acceptable sampling analysis. Research synthesis outcomes were analyzed qualitatively toward a Bayesian inference, and converge to demonstrate a definite association between maternal periodontal disease and pregnancy outcome. This CRCSR limits heterogeneity in terms of periodontal disease, outcome measure, selection bias, uncontrolled confounders and effect modifiers. Taken together, the translational CRCSR model we propose suggests that further research is advocated to explore the fundamental mechanisms underlying this association, from a molecular and proteomic perspective

Osteoimmunopathology in HIV/AIDS: A Translational Evidence-Based Perspective

Infection with the human immunodeficiency virus-1 (HIV) and the resulting acquired immune deficiency syndrome (AIDS) alter not only cellular immune regulation but also the bone metabolism. Since cellular immunity and bone metabolism are intimately intertwined in the osteoimmune network, it is to be expected that bone metabolism is also affected in patients with HIV/AIDS. The concerted evidence points convincingly toward impaired activity of osteoblasts and increased activity of osteoclasts in patients with HIV/AIDS, leading to a significant increase in the prevalence of osteoporosis. Research attributes these outcomes in part at least to the ART, PI, and HAART therapies endured by these patients. We review and discuss these lines of evidence from the perspective of translational clinically relevant complex systematic reviews for comparative effectiveness analysis and evidence-based intervention on a global scale

Expanding the Grading of Recommendations Assessment, Development, and Evaluation (Ex-GRADE) for Evidence-Based Clinical Recommendations: Validation Study

Clinicians use general practice guidelines as a source of support for their intervention, but how much confidence should they place on these recommendations? How much confidence should patients place on these recommendations? Various instruments are available to assess the quality of evidence of research, such as the revised Wong scale (R-Wong) which examines the quality of research design, methodology and data analysis, and the revision of the assessment of multiple systematic reviews (R-AMSTAR), which examines the quality of systematic reviews

Pulmonary Dead Space Fraction and Extubation Success In Children Undergoing Cardiac Surgery

A Thesis submitted to The University of Arizona College of Medicine - Phoenix in partial fulfillment of the requirements for the Degree of Doctor of Medicine.Children with prolonged mechanical ventilation after cardiac surgery have a higher risk for poor outcome due to a variety of ventilator‐associated morbidities. It therefore becomes essential to identify these children at higher risk of prolonged mechanical ventilation as well as find methods to identify children ready to be extubated as early as possible to avoid these complications. One physiological variable, the pulmonary dead space fraction (VD/VT), has been suggested as a possible indicator of prolonged mechanical ventilation. VD/VT essentially measures the amount of ventilated air that is unable to participate in gas exchange. Can VD/VT be used successfully in children undergoing cardiac surgery to identify those at risk for prolonged mechanical ventilation and identify those ready for extubation? Retrospective chart review of 461 patients at Phoenix Children’s Hospital in the Pediatric Cardiac Intensive Care Unit since the initiation of standard application of the Philips NM3 monitors in October 2013 through December 2014. From the 461 patients screened, only 99 patients met all the inclusion criteria. These 99 patients consisted of 29 patients with balanced single ventricle physiology and 61 patients with two ventricle physiology. Initial postoperative and pre‐extubation VD/VT values correlated with length of mechanical ventilation for patients with two ventricle physiology but not for patients with single ventricle physiology. Additionally, pre‐extubation VD/VT values of greater than 0.5 indicated higher rates of extubation failure in two ventricle patients. Conclusion: For children with two ventricle physiology undergoing cardiac surgery, VD/VT should be used clinically to estimate the length of mechanical ventilation for these children. VD/VT should also be checked in these patients before attempting to extubate. If VD/VT is found to be higher than 0.5, extubation should not be attempted since the patient is at a much higher risk for extubation failure.This item is part of the College of Medicine - Phoenix Scholarly Projects 2017 collection. For more information, contact the Phoenix Biomedical Campus Library at [email protected]

Proteomic signature of periodontal disease in pregnancy: Predictive validity for adverse outcomes.

The rate of preterm birth is a public health concern worldwide because it is increasing and efforts to prevent it have failed. We report a Clinically Relevant Complex Systematic Review (CSCSR) designed to identify and evaluate the best available evidence in support of the association between periodontal status in women and pregnancy outcome of preterm low birth weight. We hypothesize that the traditional limits of research synthesis must be expanded to incorporate a translational component. As a proof-of-concept model, we propose that this CSCSR can yield greater validity of efficacy and effectiveness through supplementing its recommendations with data of the proteomic signature of periodontal disease in pregnancy, which can contribute to addressing specifically the predictive validity for adverse outcomes. For this CRCSR, systematic reviews were identified through The National Library of MedicinePubmed, The Cochrane library, CINAHL, Google Scholar, Web of Science, and the American Dental Association web library. Independent reviewers quantified the relevance and quality of this literature with R-AMSTAR. Homogeneity and inter-rater reliability testing were supplemented with acceptable sampling analysis. Research synthesis outcomes were analyzed qualitatively toward a Bayesian inference, and converge to demonstrate a definite association between maternal periodontal disease and pregnancy outcome. This CRCSR limits heterogeneity in terms of periodontal disease, outcome measure, selection bias, uncontrolled confounders and effect modifiers. Taken together, the translational CRCSR model we propose suggests that further research is advocated to explore the fundamental mechanisms underlying this association, from a molecular and proteomic perspective

Expanding the Grading of Recommendations Assessment, Development, and Evaluation (Ex-GRADE) for Evidence-Based Clinical Recommendations: Validation Study.

Clinicians use general practice guidelines as a source of support for their intervention, but how much confidence should they place on these recommendations? How much confidence should patients place on these recommendations? Various instruments are available to assess the quality of evidence of research, such as the revised Wong scale (R-Wong) which examines the quality of research design, methodology and data analysis, and the revision of the assessment of multiple systematic reviews (R-AMSTAR), which examines the quality of systematic reviews.The Grading of Recommendation Assessment, Development, and Evaluation (GRADE) Working Group developed an instrument called the GRADE system in order to grade the quality of the evidence in studies and to evaluate the strength of recommendation of the intervention that is proposed in the published article. The GRADE looks at four factors to determine the quality of the evidence: study design, study quality, consistency, and directness. After combining the four components and assessing the grade of the evidence, the strength of recommendation of the intervention is established. The GRADE, however, only makes a qualitative assessment of the evidence and does not generate quantifiable data.In this study, we have quantified both the grading of the quality of evidence and also the strength of recommendation of the original GRADE, hence expanding the GRADE. This expansion of the GRADE (Ex-GRADE) permits the creation of a new instrument that can produce tangible data and possibly bridge the gap between evidence-based research and evidence-based clinical practice

Osteoimmunopathology in HIV/AIDS: A Translational Evidence-Based Perspective.

Infection with the human immunodeficiency virus-1 (HIV) and the resulting acquired immune deficiency syndrome (AIDS) alter not only cellular immune regulation but also the bone metabolism. Since cellular immunity and bone metabolism are intimately intertwined in the osteoimmune network, it is to be expected that bone metabolism is also affected in patients with HIV/AIDS. The concerted evidence points convincingly toward impaired activity of osteoblasts and increased activity of osteoclasts in patients with HIV/AIDS, leading to a significant increase in the prevalence of osteoporosis. Research attributes these outcomes in part at least to the ART, PI, and HAART therapies endured by these patients. We review and discuss these lines of evidence from the perspective of translational clinically relevant complex systematic reviews for comparative effectiveness analysis and evidence-based intervention on a global scale

Prioritization and Timing of Outcomes and Endpoints After Aneurysmal Subarachnoid Hemorrhage in Clinical Trials and Observational Studies: Proposal of a Multidisciplinary Research Group

Introduction: In studies on aneurysmal subarachnoid hemorrhage (SAH), substantial variability exists in the use and timing of outcomes and endpoints, which complicates interpretation and comparison of results between studies. The aim of the National Institute of Health/National Institute of Neurological Disorders and Stroke/National Library of Medicine Unruptured Intracranial Aneurysm (UIA) and SAH common data elements (CDE) Project was to provide a common structure for future UIA and SAH research. Methods: This article summarizes the recommendations of the UIA and SAH CDE Outcomes and Endpoints subgroup, which consisted of an international and multidisciplinary ad hoc panel of experts in clinical outcomes after SAH. Consensus recommendations were developed by review of previously published CDEs for other neurological diseases and the SAH literature. Recommendations for CDEs were classified by priority into “Core,” “Supplemental—Highly Recommended,” “Supplemental,” and “Exploratory.” Results: The subgroup identified over 50 outcomes measures and template case report forms (CRFs) to be included as part of the UIA and SAH CDE recommendations. None was classified as “Core”. The modified Rankin Scale score and Montreal Cognitive Assessment were considered the preferred outcomes and classified as Supplemental—Highly Recommended. Death, Glasgow Outcome Scale score, and Glasgow Outcome Scale-extended were classified as Supplemental. All other outcome measures were categorized as “Exploratory”. We propose outcome assessment at 3 months and at 12 months for studies interested in long-term outcomes. We give recommendations for standardized dichotomization. Conclusion: The recommended outcome measures and CRFs have been distilled from a broad pool of potentially useful CDEs, scales, instruments, and endpoints. The adherence to these recommendations will facilitate the comparison of results across studies and meta-analyses of individual patient data