The state of the art in secondary pharmacology and its impact on the safety of new medicines.

Secondary pharmacology screening of investigational small-molecule drugs for potentially adverse off-target activities has become standard practice in pharmaceutical research and development, and regulatory agencies are increasingly requesting data on activity against targets with recognized adverse effect relationships. However, the screening strategies and target panels used by pharmaceutical companies may vary substantially. To help identify commonalities and differences, as well as to highlight opportunities for further optimization of secondary pharmacology assessment, we conducted a broad-ranging survey across 18 companies under the auspices of the DruSafe leadership group of the International Consortium for Innovation and Quality in Pharmaceutical Development. Based on our analysis of this survey and discussions and additional research within the group, we present here an overview of the current state of the art in secondary pharmacology screening. We discuss best practices, including additional safety-associated targets not covered by most current screening panels, and present approaches for interpreting and reporting off-target activities. We also provide an assessment of the safety impact of secondary pharmacology screening, and a perspective on opportunities and challenges in this rapidly developing field.

A 36-Year-Old Woman With an Unexpected Cause of Hypokalemia.

A 36-year-old woman complained of bilateral lower limb weakness for the last 3 days. She could move her upper limb, neck, and facial muscles and had no respiratory or swallowing difficulties. About 4 years ago, she complained of sudden weakness involving her lower limbs. Two years later, she had another episode involving only the right upper limb. In both cases, she was hypokalemic and received oral and intravenous potassium. She is a known diabetic and has polycystic ovary disease. Her blood pressure was 150/100 mm Hg, and body mass index was 29. Her serum potassium was 2 mEq/L, plasma renin 5 ng/dL, plasma aldosterone 0.63 µIU/mL, and aldosterone to plasma renin activity ratio 8. Cushing syndrome was considered a possibility. Subsequent analysis indicated a baseline cortisol level of 19.6 µg/dL at 8 Am. A screening overnight 1-mg dexamethasone suppression test (DST) showed 17 µg/dL cortisol. The low-dose DST revealed a cortisol level of 10.8 µg/dL. Adrenocorticotropin level was 196 pg/mL, and 24-hour urinary cortisol level was 1284 mg/dL. A high dose of 8-mg DST at 11 Pm to find the source of hypercortisolism performed yielded 15.9 µg/dL. Magnetic resonance imaging of the pituitary displayed a well-defined, heterogeneously enhanced mass lesion (15 × 13 × 11 mm) in the sella with mild suprasellar extension. Transsphenoidal resection and stereotactic radiosurgery were performed on the tumor with hormone replacement and glycemic control following surgery.

Artificial Intelligence/Machine Learning-Driven Small Molecule Repurposing via Off-Target Prediction and Transcriptomics.

The process of discovering small molecule drugs involves screening numerous compounds and optimizing the most promising ones, both in vitro and in vivo. However, approximately 90% of these optimized candidates fail during trials due to unexpected toxicity or insufficient efficacy. Current concepts with respect to drug-protein interactions suggest that each small molecule interacts with an average of 6-11 targets. This implies that approved drugs and even discontinued compounds could be repurposed by leveraging their interactions with unintended targets. Therefore, we developed a computational repurposing framework for small molecules, which combines artificial intelligence/machine learning (AI/ML)-based and chemical similarity-based target prediction methods with cross-species transcriptomics information. This repurposing methodology incorporates eight distinct target prediction methods, including three machine learning methods. By using multiple orthogonal methods for a "dataset" composed of 2766 FDA-approved drugs targeting multiple therapeutic target classes, we identified 27,371 off-target interactions involving 2013 protein targets (i.e., an average of around 10 interactions per drug). Relative to the drugs in the dataset, we identified 150,620 structurally similar compounds. The highest number of predicted interactions were for drugs targeting G protein-coupled receptors (GPCRs), enzymes, and kinases with 10,648, 4081, and 3678 interactions, respectively. Notably, 17,283 (63%) of the off-target interactions have been confirmed in vitro. Approximately 4000 interactions had an IC50 of <100 nM for 1105 FDA-approved drugs and 1661 interactions had an IC50 of <10 nM for 696 FDA-approved drugs. Together, the confirmation of numerous predicted interactions and the exploration of tissue-specific expression patterns in human and animal tissues offer insights into potential drug repurposing for new therapeutic applications.

Utility of rapid atrial pacing before and after TAVR with balloon-expandable valve in predicting permanent pacemaker implantation.

BACKGROUND: High-grade or complete atrioventricular block (AVB) requiring permanent pacemaker (PPM) implantation is a known complication of transcatheter aortic valve replacement (TAVR). Wenckebach AVB induced by rapid atrial pacing (RAP) after TAVR was previously demonstrated in an observational analysis to be an independent predictor for PPM. We sought to investigate the utility of both pre- and post-TAVR RAP in predicting PPM implantation. METHODS: In a single-center, prospective study, 421 patients underwent TAVR with balloon-expandable valves (BEV) between April 2020 and August 2021. Intraprocedural RAP was performed in patients without a pre-existing pacemaker, atrial fibrillation/flutter, or intraprocedural complete AVB to assess for RAP-induced Wenckebach AVB. The primary outcome was PPM within 30 days after TAVR. RESULTS: RAP was performed in 253 patients, of whom 91.3% underwent post-TAVR RAP and 61.2% underwent pre-TAVR RAP. The overall PPM implantation rate at 30 days was 9.9%. Although there was a numerically higher rate of PPM at 30 days in patients with RAP-induced Wenckebach AVB, it did not reach statistical significance (13.3% vs. 8.4%, p = 0.23). In a multivariable analysis, RAP-induced Wenckebach was not an independent predictor for PPM implantation at 30 days after TAVR. PPM rates at 30 days were comparable in patients with or without pre-TAVR pacing-induced Wenckebach AVB (11.8% vs. 8.2%, p = 0.51) and post-TAVR pacing-induced Wenckebach AVB (10.2% vs. 5.8%, p = 0.25). CONCLUSION: In patients who underwent TAVR with BEV, there were no statistically significant differences in PPM implantation rates at 30 days regardless of the presence or absence of RAP-induced Wenckebach AVB. Due to conflicting results between the present study and the prior observational analysis, future studies with larger sample sizes are warranted to determine the role of RAP during TAVR as a risk-stratification tool for significant AVB requiring PPM after TAVR.

Effects of an 18-Week Integrated Yoga Program on Cardiac Autonomic Function in Breast Cancer Patients Undergoing Adjuvant Chemotherapy: A Randomized Controlled Trial.

BACKGROUND: Cardiotoxicity is a commonly observed adverse effect seen in breast cancer (BC) patients undergoing chemotherapy with attributes toward cardiac autonomic dysfunction (CAD). Yoga, a mind-body system of medicine that has been shown to improve cardiac autonomic nervous system (ANS) activity in various health conditions, could be an effective adjuvant approach in addressing CAD. OBJECTIVE: This study aims to investigate the protective effects of Integrated Yoga Therapy (IYT) on ANS functioning, assessed using Heart rate variability (HRV) in breast cancer patients undergoing chemotherapy. METHODS: A total of 68 (stage I-III) BC patients were randomly assigned into 2 groups: Treatment as Usual group (TAU) and TAU with Yoga Therapy group (TAUYT). All patients underwent anthracycline-based adjuvant chemotherapy for a total of 6 cycles with 21 days/cycle. During chemotherapy, the TAUYT group received IYT 5 days a week for 18 weeks, compared with usual care alone in the TAU group. Resting heart rate (RHR) and HRV, measured in both the time and frequency domains, were used to assess the cardiac ANS function of each patient before and after 6 cycles of chemotherapy. RESULTS: A total of 30 subjects in the TAU group and 29 subjects in the TAUYT group were included in the analysis. At baseline (before chemotherapy), there were no significant differences between the TAU and TAUYT groups in terms of RHR and HRV indices. However, after chemotherapy, patients in the TAU group had a significantly higher average RHR (P < .02) and lower HRV indices with reduced parasympathetic indices: RMSSD (P < .01), pNN50% (P < .04), high-frequency power (P < .001) and increased sympathetic indices: low-frequency power (P < .001) with sympathovagal imbalance: LF/HF (P < .001) compared with patients in the TAUYT group. CONCLUSION: The study showed the protective effects of yoga therapy on CAD in patients receiving anthracycline-based chemotherapy for BC, proposing yoga as a potential adjuvant intervention in improving cardiac health and preventing cardiovascular-related morbidities. TRIAL REGISTRATION: This trial is registered with the Clinical Trials Registry-India (CTRI) database (CTRI/2020/10/028446; October 16, 2020).

Shocked to death: a case report of cardiogenic shock and death following electrocardioversion for atrial fibrillation.

BACKGROUND: Atrial fibrillation (AF) is prevalent, especially in patients with heart failure. Their prevalence increases with age and both conditions are interrelated. Electrocardioversion (ECV) is considered a safe and effective procedure and is among one of the recommended therapies to terminate AF back to normal sinus rhythm. Our study highlights one of the rare complications following ECV. A 71-year-old female with a history of atrial fibrillation underwent electrocardioversion and developed sudden onset of ventricular stunning resulting in refractory cardiogenic shock. She was treated with mechanical cardiac support including IABP and Impella. Both provided minimal support then rapid clinical deterioration happened leading to imminent death. CONCLUSION: Patients with atrial fibrillation and heart failure treated with electrocardioversion might develop refractory cardiogenic shock and death as a complication of this procedure.

AI/ML Models to Predict the Severity of Drug-Induced Liver Injury for Small Molecules.

Drug-induced liver injury (DILI), believed to be a multifactorial toxicity, has been a leading cause of attrition of small molecules during discovery, clinical development, and postmarketing. Identification of DILI risk early reduces the costs and cycle times associated with drug development. In recent years, several groups have reported predictive models that use physicochemical properties or in vitro and in vivo assay endpoints; however, these approaches have not accounted for liver-expressed proteins and drug molecules. To address this gap, we have developed an integrated artificial intelligence/machine learning (AI/ML) model to predict DILI severity for small molecules using a combination of physicochemical properties and off-target interactions predicted in silico. We compiled a data set of 603 diverse compounds from public databases. Among them, 164 were categorized as Most DILI (M-DILI), 245 as Less DILI (L-DILI), and 194 as No DILI (N-DILI) by the FDA. Six machine learning methods were used to create a consensus model for predicting the DILI potential. These methods include k-nearest neighbor (k-NN), support vector machine (SVM), random forest (RF), Naïve Bayes (NB), artificial neural network (ANN), logistic regression (LR), weighted average ensemble learning (WA) and penalized logistic regression (PLR). Among the analyzed ML methods, SVM, RF, LR, WA, and PLR identified M-DILI and N-DILI compounds, achieving a receiver operating characteristic area under the curve of 0.88, sensitivity of 0.73, and specificity of 0.9. Approximately 43 off-targets, along with physicochemical properties (fsp3, log S, basicity, reactive functional groups, and predicted metabolites), were identified as significant factors in distinguishing between M-DILI and N-DILI compounds. The key off-targets that we identified include: PTGS1, PTGS2, SLC22A12, PPARγ, RXRA, CYP2C9, AKR1C3, MGLL, RET, AR, and ABCC4. The present AI/ML computational approach therefore demonstrates that the integration of physicochemical properties and predicted on- and off-target biological interactions can significantly improve DILI predictivity compared to chemical properties alone.

Clopidogrel Vs Aspirin Monotherapy Following Dual Antiplatelet Therapy After Percutaneous Coronary Intervention: A Systematic Review and Meta-analysis.

Current guidelines recommend 6-12 months of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention (PCI) followed by aspirin monotherapy indefinitely. We aimed to assess the efficacy and safety of clopidogrel vs aspirin in the post-PCI population after completing DAPT. We systematically searched 5 electronic databases to identify studies comparing clopidogrel with aspirin following completion of DAPT after PCI. We pooled outcomes for major adverse cardiac events (MACE), cardiac death, all-cause death, major bleeding, myocardial infarction (MI), and stroke. We included 5 studies with 13,850 patients, of whom 5601 (40.4%) received clopidogrel. Mean follow-up was 12-36 months. All patients received drug-eluting stents. Duration of DAPT before antiplatelet monotherapy was 1-18 months. Clopidogrel was associated with reductions in MACE (Risk ratio [RR] 0.77, 95% confidence interval [CI] 0.65-0.91), any stroke (RR 0.51; 95% confidence interval [CI] 0.35-0.76), ischemic stroke (RR 0.55; 95% CI 0.32-0.94), and hemorrhagic stroke (RR 0.24; 95% CI 0.09-0.68) when compared with aspirin. Cardiac death (RR 0.87; 95% CI 0.53-1.41), all-cause death (RR 1.06; 95% CI 0.81-1.39), major bleeding (RR 0.74; 95% CI 0.43-1.29), MI (RR 1.01; 95% CI 0.64-1.60), repeat revascularization (RR 0.88; 95% CI 0.71-1.09), target vessel revascularization (RR 0.76; 95% CI 0.52-1.13), and stent thrombosis (RR 0.96; 95% CI 0.35-2.59) were not significantly different among groups. Compared with aspirin, clopidogrel was associated with reductions in MACE and stroke (ischemic and hemorrhagic) following DAPT completion after PCI. There were no significant differences in mortality, major bleeding, MI, and repeat revascularization between groups.

Cerebral Embolic Protection during Transcatheter Aortic Valve Implantation: Updated Systematic Review and Meta-Analysis.

In patient undergoing transcatheter aortic valve implantation (TAVI), stroke remains a potentially devastating complication associated with significant morbidity, and mortality. To reduce the risk of stroke, cerebral protection devices (CPD) were developed to prevent debris from embolizing to the brain during TAVI. We performed a systematic review and meta-analysis to determine the safety and efficacy of CPD in TAVI. The MEDLINE (PubMed, Ovid) and Cochrane databases were queried with various combinations of medical subject headings to identify relevant articles. Statistical analysis was performed using a random-effects model to calculate unadjusted odds ratio (OR), including subgroup analyses based on follow-up duration, study design, and type of CPD. Using a pooled analysis, CPD was associated with a significant reduction in major adverse cardiovascular events MACE (OR 0.75, 95% CI 0.70-0.81, P < 0.01), mortality (OR 0.65, 95% CI 0.58-0.74, P < 0.01) and stroke (OR 0.84, 95% CI 0.76-0.93, P < 0.01) in patients undergoing TAVI. Similarly, on MRI volume per lesion were lower for patients with CPD use. No significant difference was observed in acute kidney injury (OR 0.75, 95% CI 0.42-1.37, P = 0.68), bleeding (OR 0.92, 95% CI 0.71-1.20, P = 0.55) or vascular complications (OR 0.90, 95% CI 0.62-1.31, P = 0.6) for patients undergoing TAVI with CPD. In conclusion, CPD device use in TAVI is associated with a reduction of MACE, mortality, and stroke compared with patients undergoing TAVI without CPD. However, the significant reduction in mortality is driven mainly by observational studies.

Anterior-Posterior versus anterior-lateral electrodes position for electrical cardioversion of atrial fibrillation: A meta-analysis of randomized controlled trials.

Background: The optimal electrodes position for elective direct current (DC) cardioversion of patients with atrial fibrillation (AF) remains uncertain. Methods: An electronic search of MEDLINE, EMBASE and COCHRANE databases was performed through March 2022 for randomized trials that examined the outcomes of anterior-posterior (AP) versus anterior-lateral (AL) electrodes position during cardioversion of (AF). The main outcome was the success rate of cardioversion. Data were pooled using random effects model. Results: The final analysis included 10 RCTs with a total of 1677 patients. There was no difference in the rate of successful cardioversion between the AP versus AL groups (86.6 vs 87.9 %; RR 1.00; 95 % Confidence Interval (CI) 0.95 to 1.06). Subgroup analysis by the shock waveform showed no significant interaction between monophasic and biphasic waveforms (Pintercation = 0.23). meta-regression analyses showed no effect modification of primary outcome according to body mass index (p = 0.15), left atrial diameter (p = 0.64), valvular heart disease (p = 0.34), lone AF (p = 0.58), or the duration of AF (p = 0.70). There was no significant difference between the AP and AL electrode position groups in successful cardioversion at low energy (RR 0.94; 95 % CI 0.74 to 1.19), the number of the delivered shocks (standardized mean difference [SMD] -0.03; 95 % CI -0.32 to 0.26) or the mean energy of the delivered shocks (SMD -0.11 and 95 % CI -0.30 to 0.07). There was lower transthoracic impedance with AP versus AL electrode position (SMD -0.28; 95 %CI -0.47 to -0.10). Conclusion: Meta-analysis of randomized data showed no difference between AP and AL electrode positions in the success rate of DC cardioversion of AF. Either AP or AL electrode positions should be acceptable approaches for elective DC cardioversion of patients with AF.

In-hospital outcomes of TAVR patients with a bundle branch block: Insights from the National Inpatient Sample 2011-2018.

INTRODUCTION: Data on the outcomes following transcatheter aortic valve replacement (TAVR) in patients with a bundle branch block (BBB) remains limited. METHODS: We studied the outcomes of TAVR patients with a BBB from the National Inpatient Sample (NIS) database between 2011 and 2018 using ICD-9-CM and ICD-10-CM codes. RESULTS: Between 2011 and 2018, 194,237 patients underwent TAVR, where 1.7% (n = 3,232) had a right BBB (RBBB) and 13.7% (n = 26,689) had a left BBB (LBBB). Patients with a RBBB and LBBB had a higher rate of new permanent pacemaker (PPM) implantation (31.5% - RBBB, 15.7% LBBB vs. 10.2% - no BBB). RBBB was associated with a significantly longer median length of stay (5 days) and total hospitalization cost ($53,669) compared with LBBB (3 days and $47,552) and no BBB (3 days and $47,171). Trend analysis revealed lower rates of PPM implantation and reduced lengths of stay and costs across all comparison groups. CONCLUSION: In conclusion, patients undergoing TAVR with a BBB are associated with higher new rates of PPM implantation. RBBB is the strongest independent predictor for new PPM implantation following TAVR. Rates of new PPM implantation in TAVR patients with and without a BBB have improved over time including reductions in length of stay and hospital costs. Further study is needed to reduce the risks of PPM implantation in TAVR patients.

Direct Oral Anticoagulant Versus Warfarin After Left Atrial Appendage Closure With WATCHMAN: Updated Systematic Review and Meta-analysis.

In the pivotal WATCHMAN trials, warfarin was used for post-procedural anticoagulation in the first 45 days after left atrial appendage closure. We aimed to investigate the efficacy and safety of direct oral anticoagulant (DOAC) versus warfarin after WATCHMAN. We performed a literature search of 5 electronic databases to identify studies comparing DOAC with warfarin after WATCHMAN. We pooled outcomes for the efficacy (thromboembolism, device-related thrombus [DRT], peridevice leak [PDL] >5 mm) and safety endpoints (bleeding, mortality). Thromboembolism was defined as ischemic stroke, transient ischemic attack, or systemic embolism. We included 10 cohort studies with 2,440 patients, of whom 1,397 (57.3%) received DOAC. Concerning periprocedural outcomes (within 7 days following implantation), DOAC was associated with a reduction in major bleeding (Risk ratio [RR] 0.32; 95% confidence interval [CI] 0.11-0.92) compared with warfarin, without significant differences in all bleeding (RR 0.46; 95% CI 0.15-1.42) and thromboembolism (RR 0.93; 95% CI 0.21-4.16). On first follow-up transesophageal echocardiography, DRT (RR 0.79; 95% CI 0.39-1.60) and PDL>5 mm (RR 0.44; 95% CI 0.16-1.20) were comparable among groups. With a mean follow-up of 1.5-12 months, DOAC was associated with reductions in major bleeding (RR 0.52; 95% CI 0.30-0.89) and all bleeding (RR 0.38; 95% CI 0.25-0.58) compared with warfarin. The outcomes of thromboembolism (RR 0.79; 95% CI 0.36-1.73) and all-cause mortality (RR 0.49; 95% CI 0.19-1.28) were not significantly different between the 2 groups. Following WATCHMAN implantation, DOAC was associated with reductions in major bleeding and all bleeding compared with warfarin at mid-term follow-up. The outcomes of thromboembolism, all-cause mortality, DRT, and PDL >5 mm were comparable among groups.

Same-Day Discharge After Transcatheter Aortic Valve Implantation: Insights from the Nationwide Readmission Database 2015 to 2019.

Background There is a paucity of data on the feasibility of same-day discharge (SDD) following transcatheter aortic valve implantation (TAVI) at a national level. Methods and Results This study used data from the Nationwide Readmission Database from the fourth quarter of 2015 through 2019 and identified patients undergoing TAVI using the claim code 02RF3. A total of 158 591 weighted hospitalizations for TAVI were included in the analysis. Of the patients undergoing TAVI, 961 (0.6%) experienced SDD. Non-SDDs included 65 814 (41.5%) patients who underwent TAVI who were discharged the next day, and 91 816 (57.9%) discharged on the second or third day. The 30-day readmission rate for SDD after TAVI was similar to non-SDD TAVI (9.8% versus 8.9%, P=0.31). The cumulative incidence of 30-day readmissions for SDD was higher compared with next-day discharge (log-rank P=0.01) but comparable to second- or third-day discharge (log-rank P=0.66). At 30 days, no differences were observed in major or minor vascular complications, heart failure, or ischemic stroke for SDD compared with non-SDD. Acute kidney injury, pacemaker implantation, and bleeding complications were lower with SDD. Predictors associated with SDD included age <85 years, male sex, and prior pacemaker placement, whereas left bundle-branch block, right bundle-branch block, second-degree heart block, heart failure, prior percutaneous coronary intervention, and atrial fibrillation were negatively associated with SDD. Conclusions SDD following TAVI is associated with similar 30-day readmission and complication rates compared with non-SDD. Further prospective studies are needed to assess the safety and feasibility of SDD after TAVI.

Case report: Catheter related blood stream infection caused by Candida vulturna.

Candida vulturna is a newly emerging candida species belong to Candida haemulonii species complex of Metschnikowiaceae family. Numerous clinical samples have been reported to isolate C. vulturna since discovery. We report a case of catheter related blood stream infection in which C. vulturna was isolated from blood in patient after prolong antibiotic therapy for recurrent infection of retroperitoneal cyst. The blood isolate was identified to species level by molecular assay targeting D1/D2 regions of 26s rDNA gene. The patient improved with administration of intravenous micafungin despite lack of antifungal susceptibility breakpoints.

Gender Differences in Age-Stratified Inhospital Outcomes After Transcatheter Aortic Valve Implantation (from the National Inpatient Sample 2012 to 2018).

Contemporary data on gender differences in outcomes after transcatheter aortic valve implantation (TAVI), after stratification by age, remain limited. We studied age-stratified (60 to 70, 71 to 80, and 81 to 90 years) inhospital outcomes by gender after TAVI from the National Inpatient Sample database between 2012 and 2018. We analyzed National Inpatient Sample data using the International Classification of Diseases, Clinical Modification, Ninth Revision, and Tenth Revision claims codes. Between the years 2012 and 2018, a total of 188,325 weighted hospitalizations for TAVI were included in the analysis. A total of 21,957 patients were included in the 60 to 70 age group (44% females), 60,770 (45% females) in the 71 to 80 age group, and 105,580 (50% females) in the 81 to 90 age groups, respectively. Propensity-matched inhospital mortality rates were significantly higher for females than males for the age group of 81 to 90 years (3.0% vs 2.1%, p <0.01). Vascular complications and a need for blood transfusions remained significantly higher for females on propensity-matched analysis across all categories of ages. Conversely, acute kidney injury and the need for pacemaker implantation remained significantly higher for males across all age groups. In conclusion, we report that mortality is higher in female patients who underwent TAVI between the ages of 81 to 90. Moreover, the female gender was associated with higher vascular complications and bleeding requiring transfusions. Conversely, the male gender was associated with higher rates of pacemaker implantation and acute kidney injury.

Outcomes of Cardiac Arrest and Cardiopulmonary Resuscitation in Patients With Left Ventricular Assist Device; an Insight From a National Inpatient Sample.

BACKGROUND: Outcomes of patients with implanted left ventricular assist device (LVAD) implantation experiencing a cardiac arrest (CA) are not well reported. We aimed at defining the in-hospital outcomes of patients with implanted LVAD experiencing a CA. METHODS: The national inpatient sample (NIS) was queried using ICD9/ICD10 codes for patients older than 18 years with implanted LVAD and CA between 2010-2018. We excluded patients with orthotropic heart transplantation, biventricular assist device (BiVAD) implantation and do not resuscitate (DNR) status. RESULTS: A total of 93,153 hospitalisations between 2010 and 2018 with implanted LVAD were identified. Only 578 of these hospitalisations had experienced CA and of those, 173 (33%) hospitalisations underwent cardiopulmonary resuscitation (CPR). The mean age of hospitalisations that experienced a CA was 60.61±14.85 for non-survivors and 56.23±17.33 for survivors (p=0.14). The in-hospital mortality was 60.8% in hospitalisations with CA and 74.33% in hospitalisations in whom CPR was performed. In an analysis comparing survivors with non-survivors, non-survivors had more diabetes mellitus (DM) (p=0.01), and ischaemic heart disease (IHD) (p=0.04). Age, female sex, peripheral vascular disease and history of coronary artery bypass graft (CABG) were independently associated with increased mortality in our cohort. Also, ventricular tachycardia (VT) and CPR were independently associated with in-hospital mortality. During the study period, there was a significantly decreasing trend in performing CPR in LVAD hospitalisations with CA. CONCLUSION: In conclusion, age, female sex, peripheral vascular disease, history of CABG, VT and CPR were independently associated with in-hospital mortality in LVAD hospitalisations who experienced CA.

Evaluation of a new interferon gamma release assay, in comparison to tuberculin skin tests and quantiferon tuberculosis goldplus for the detection of latent tuberculosis infection in children from a high tuberculosis burden setting.

Background: : Detection of latent tuberculosis infection (LTBI) in children, exposed to tuberculosis (TB) infections, followed by appropriate treatment, could be instrumental in reducing TB burden. Interferon Gamma release assays (IGRA) have higher specificity than tuberculin skin tests (TST), hence are more effective option for diagnosis. Hence, the present study was aimed to diagnose the presence of latent TB in children with the help of a new Standard E TB-Feron Enzyme-Linked Immunosorbent Assay (TBF) and evaluating its efficiency as compared to TST and Quantiferon TB Gold plus (QFT Plus). Methods: Diagnosis of LTBI in participants, <18 years old, who were the close household contacts of patients with active TB was carried out employing techniques such as TST, QFT Plus, and TBF. Results: Higher positive results were obtained with IGRA assays QFT Plus and TBF than TST. The perfect agreement was observed between QFT Plus and TBF assays with a Kappa value of 0.9176 whereas TST and TBF assay showed moderate agreement with a Kappa value of 0.42365. The level of cytokines secreted as a result of stimulation by the antigens from QFT Plus tubes was lower in comparison to antigens from TBF tubes. Conclusion: Hence, TBF, which showed similar efficiency as the widely used QFT Plus, can be a useful detection technique for LTBI in children. Moreover, it could prove to be an efficient alternative to expensive IGRAs like QFT Plus.