Self-reported comfort with tracheostomy tube care. cross-sectional survey of non-ear, nose and throat health care professionals

OBJECTIVE: To assess self-reported comfort of non-ear, nose and throat (ENT) health professionals in tracheostomy care and identify its associated factors. METHODS: This was a cross-sectional survey of non-ENT health care professionals, carried out from December 2011 to February 2013 at the Prince Sultan Military Medical City, and King Faisal Specialist Hospital & Research Centre, Riyadh, Kingdom of Saudi Arabia. A self-administered questionnaire was used to collect data on self-rated comfort levels in performing tracheostomy tube change and factors, such as speciality, duration of dedicated ENT rotation in medical school, and years of experience as a practicing consultant. RESULTS: A total of 71 non-ENT health professionals participated in the survey. The response rate was 100%. Overall, one out of every 4 participants (26.8%) rated their comfort level in tracheostomy tube change as \u27fair or poor\u27, 38% as good, and only 35.2% as excellent. Comfort level was the highest among anesthesiologists (94.1%), and intensivists (78.9%). In the multivariate analysis, physicians who reported ever performing tracheostomy tube change as a resident were significantly more likely to report comfort than their counterparts without such exposure (adjusted odds ratio: 7.09; 95% confidence interval: 1.90-26.40; p=0.003). When asked if there should be a mandatory course on tracheostomy care in tertiary care hospitals, most of the participants (60-72%), irrespective of their speciality, training and experience, replied in the affirmative. CONCLUSION: Non-ENT health professionals involved in airway care had a low level of self-rated comfort with tracheostomy tube care suggesting the need for periodic refresher training to address this gap

Therapeutic efficacy of l-ornithine l-aspartate in patients with hepatic encephalopathy

To determine the efficacy of ornithine-aspartate in reducing blood ammonia levels and clinical improvement, as a part of treatment in hepatic encephalopathy. Material & method: A randomized placebo controlled trial was conducted in 2013 in Jinnah medical and dental college hospital Korangi Karachi. One hundred patients with hepatic encephalopathy due to underlying chronic liver disease were randomly assigned into two groups with 50 patients each. One group received three days of ornithine-aspartate infusions (trial-treatment group) and the other group received three days of infusion of placebo (placebo group). Serum ammonia was measured in both groups on day 1 and day 3. Clinical improvement was assessed by West Haven’s grading of hepatic encephalopathy. Result: The patients in trial group showed statistically significant improvement in serum ammonia levels and grading of hepatic encephalopathy as compared to placebo. Conclusion: L -Ornithinie L-Aspartate (LOLA) is effective in decreasing serum ammonia as well as results in clinical improvement in patients with hepatic encephalopathy and may be recommended for use in hepatic encephalopathy

Behaviour and Emotional Health of Adolescent Boys Engaged in Non-Suicidal Self-Injury

Non-suicidal self-injury (NSSI) among adolescents has become a rising concern worldwide and a risk factor for suicide. There is a noticeable rise in number of children who attempted or committed suicide in past few years in Pakistan. However, not much attention has been paid to identify and target risk factors. A preliminary survey was conducted to assess nature of risk factor for NSSI and significance of main study. Participants were 12-17 years old boys (N=104) from schools of Islamabad. The variables of interest were assessed through The Non-Suicidal Self-Injury Assessment Tool (NSSI-AT), Abbreviated Dysregulation Inventory (ADI), Depression Scale for Adolescents (DSA), Peer Relations Questionnaire (PRQ) and Strengths and Difficulties Questionnaire (SDQ). Findings revealed that 34.6% adolescent boys were engaged in NSSI. Participants who reported self-harm had significantly high levels of distress, conduct problems, emotional, and behavioral dysregulation. Findings manifest the need to identify significant risk factors of NSSI among adolescents

Methionine Adenosyltransferase 1a (MAT1A) Enhances Cell Survival During Chemotherapy Treatment and is Associated with Drug Resistance in Bladder Cancer PDX Mice.

Bladder cancer is among the top ten most common cancers, with about ~380,000 new cases and ~150,000 deaths per year worldwide. Tumor relapse following chemotherapy treatment has long been a significant challenge towards completely curing cancer. We have utilized a patient-derived bladder cancer xenograft (PDX) platform to characterize molecular mechanisms that contribute to relapse following drug treatment in advanced bladder cancer. Transcriptomic profiling of bladder cancer xenograft tumors by RNA-sequencing analysis, before and after relapse, following a 21-day cisplatin/gemcitabine drug treatment regimen identified methionine adenosyltransferase 1a (MAT1A) as one of the significantly upregulated genes following drug treatment. Survey of patient tumor sections confirmed elevated levels of MAT1A in individuals who received chemotherapy. Overexpression of MAT1A in 5637 bladder cancer cells increased tolerance to gemcitabine and stalled cell proliferation rates, suggesting MAT1A upregulation as a potential mechanism by which bladder cancer cells persist in a quiescent state to evade chemotherapy

Molecular Speciation of Size Fractionated Particulate Water-Soluble Organic Carbon by Two-Dimensional Nuclear Magnetic Resonance (NMR) Spectroscopy

Particulate matter is associated with increased morbidity and mortality; its effects depend on particle size and chemical content. It is important to understand the composition and resultant toxicological profile of particulate organic compounds, the largest and most complex fraction of particulate matter. The objective of the study was to delineate the nuclear magnetic resonance (NMR) spectral fingerprint of the biologically relevant water-soluble organic carbon (WSOC) fraction of size fractionated urban aerosol. A combination of one and two-dimensional NMR spectroscopy methods was used. The size distribution of particle mass, water-soluble extract, non-exchangeable organic hydrogen functional types and specific biomarkers such as levoglucosan, methane sulfonate, ammonium and saccharides indicated the contribution of fresh and aged wood burning emissions, anthropogenic and biogenic secondary aerosol for fine particles as well as primary traffic exhausts and pollen for large particles. Humic-like macromolecules in the fine particle size range included branched carbon structures containing aromatic, olefinic, keto and nitrile groups and terminal carboxylic and hydroxyl groups such as terpenoid-like polycarboxylic acids and polyols. Our study show that 2D-NMR spectroscopy can be applied to study the chemical composition of size fractionated aerosol

XPO1 inhibition by selinexor induces potent cytotoxicity against high grade bladder malignancies.

Treatment options for high grade urothelial cancers are limited and have remained largely unchanged for several decades. Selinexor (KPT-330), a first in class small molecule that inhibits the nuclear export protein XPO1, has shown efficacy as a single agent treatment for numerous different malignancies, but its efficacy in limiting bladder malignancies has not been tested. In this study we assessed selinexor-dependent cytotoxicity in several bladder tumor cells and report that selinexor effectively reduced XPO1 expression and limited cell viability in a dose dependent manner. The decrease in cell viability was due to an induction of apoptosis and cell cycle arrest. These results were recapitulated in in vivo studies where selinexor decreased tumor growth. Tumors treated with selinexor expressed lower levels of XPO1, cyclin A, cyclin B, and CDK2 and increased levels of RB and CDK inhibitor p27, a result that is consistent with growth arrest. Cells expressing wildtype RB, a potent tumor suppressor that promotes growth arrest and apoptosis, were most susceptible to selinexor. Cell fractionation and immunofluorescence studies showed that selinexor treatment increased nuclear RB levels and mechanistic studies revealed that RB ablation curtailed the response to the drug. Conversely, limiting CDK4/6 dependent RB phosphorylation by palbociclib was additive with selinexor in reducing bladder tumor cell viability, confirming that RB activity has a role in the response to XPO1 inhibition. These results provide a rationale for XPO1 inhibition as a novel strategy for the treatment of bladder malignancies

Effect of angiotensin-converting enzyme inhibitor and angiotensin receptor blocker initiation on organ support-free days in patients hospitalized with COVID-19

IMPORTANCE Overactivation of the renin-angiotensin system (RAS) may contribute to poor clinical outcomes in patients with COVID-19. Objective To determine whether angiotensin-converting enzyme (ACE) inhibitor or angiotensin receptor blocker (ARB) initiation improves outcomes in patients hospitalized for COVID-19. DESIGN, SETTING, AND PARTICIPANTS In an ongoing, adaptive platform randomized clinical trial, 721 critically ill and 58 non–critically ill hospitalized adults were randomized to receive an RAS inhibitor or control between March 16, 2021, and February 25, 2022, at 69 sites in 7 countries (final follow-up on June 1, 2022). INTERVENTIONS Patients were randomized to receive open-label initiation of an ACE inhibitor (n = 257), ARB (n = 248), ARB in combination with DMX-200 (a chemokine receptor-2 inhibitor; n = 10), or no RAS inhibitor (control; n = 264) for up to 10 days. MAIN OUTCOMES AND MEASURES The primary outcome was organ support–free days, a composite of hospital survival and days alive without cardiovascular or respiratory organ support through 21 days. The primary analysis was a bayesian cumulative logistic model. Odds ratios (ORs) greater than 1 represent improved outcomes. RESULTS On February 25, 2022, enrollment was discontinued due to safety concerns. Among 679 critically ill patients with available primary outcome data, the median age was 56 years and 239 participants (35.2%) were women. Median (IQR) organ support–free days among critically ill patients was 10 (–1 to 16) in the ACE inhibitor group (n = 231), 8 (–1 to 17) in the ARB group (n = 217), and 12 (0 to 17) in the control group (n = 231) (median adjusted odds ratios of 0.77 [95% bayesian credible interval, 0.58-1.06] for improvement for ACE inhibitor and 0.76 [95% credible interval, 0.56-1.05] for ARB compared with control). The posterior probabilities that ACE inhibitors and ARBs worsened organ support–free days compared with control were 94.9% and 95.4%, respectively. Hospital survival occurred in 166 of 231 critically ill participants (71.9%) in the ACE inhibitor group, 152 of 217 (70.0%) in the ARB group, and 182 of 231 (78.8%) in the control group (posterior probabilities that ACE inhibitor and ARB worsened hospital survival compared with control were 95.3% and 98.1%, respectively). CONCLUSIONS AND RELEVANCE In this trial, among critically ill adults with COVID-19, initiation of an ACE inhibitor or ARB did not improve, and likely worsened, clinical outcomes. TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT0273570