Rivaroxaban Failure Presenting With Renal Infarction in a Patient With Persistent Atrial Fibrillation: A Case Report.

Direct oral anticoagulants (DOAC) are the preferred choice of anticoagulation for patients with atrial fibrillation. DOACs are always preferred over vitamin K antagonists due to their better safety profile in terms of life-threatening bleeding and decreased need for INR (international normalised ratio) monitoring. Although the most commonly used anticoagulation, failure to DOAC has been reported. Here we present a rare case of rivaroxaban failure presenting with left renal infarction in a patient who had dense spontaneous echocardiographic contrast in the left atrium visualised by transthoracic echocardiography.

Preschool teachers' knowledge, beliefs, and self-efficacy concerning autism: A parallel mixed-methods study of an intervention to improve autism identification.

LAY ABSTRACT: Preschool teachers can play a critical role in early detection of autism. Equipping preschool teachers with prerequisite knowledge and skills would allow them to identify children with probable autism and referral to diagnostic services. This study aimed to investigate the impact of an educational module (EMiASD) that prepared preschool teachers to identify autism symptoms. The sample included 144 preschool teachers, of which 120 were stratified and randomly assigned to an intervention arm receiving training in EMiASD (n = 60) or a comparison arm receiving standard training (n = 60) using a parallel mixed-methods design. Responses to open-ended questions about video case studies revealed improvement in the identification of autism symptoms in preschool teachers in the intervention arm, in contrast to preschool teachers in the comparison arm. Moreover, significant changes in knowledge, belief, and self-efficacy about autism favoured EMiASD. Overall, these results demonstrate the influence of EMiASD in the Yemeni cultural context.

Efficacy of Pemafibrate Versus Fenofibrate Administration on Serum Lipid Levels in Patients with Dyslipidemia: Network Meta-Analysis and Systematic Review.

BACKGROUND: Pemafibrate is a novel fibrate class drug that is a highly potent and selective agonist of peroxisome proliferator-activated receptor α (PPARα). We performed the first ever network meta-analysis containing the largest ever group of patients to test the efficacy of pemafibrate in improving lipid levels compared with fenofibrate and placebo in patients with dyslipidemia. METHODS: Potentially relevant clinical trials were identified in Medline, PubMed, Embase, clinicaltrials.gov, and Cochrane Controlled Trials registry. Nine randomized controlled trials met the inclusion criteria out of 40 potentially available articles. The primary effect outcome was a change in the levels of triglycerides (TG), high-density lipoproteins (HDL), or low-density lipoproteins (LDL) before and after the treatment. RESULTS: A total of 12,359 subjects were included. The mean patient age was 54.73 (years), the mean ratio for female patients was 18.75%, and the mean examination period was 14.22 weeks. The dose for pemafibrate included in our study was 0.1, 0.2, or 0.4 mg twice daily, whereas the dose for fenofibrate was 100 mg/day. Data showed a significant reduction in TG and a mild increase in HDL levels across the pemafibrate group at different doses and fenofibrate 100 mg group (with greatest effect observed with pemafibrate 0.1 mg twice daily). A mild increase in LDL was also observed in all groups, but the increase in LDL in the 0.1 mg twice daily dose group was statistically insignificant. CONCLUSION: Pemafibrate 0.1 mg twice daily dose led to highest reduction in TG levels and the highest increase in HDL levels compared with other doses of pemafibrate, fenofibrate, and placebo.

Pre- and post-COVID-19 antimicrobial resistance profile of bacterial pathogens, a comparative study in a tertiary hospital.

INTRODUCTION: Antimicrobial resistance (AMR) is a natural evolutionary process in bacteria that is accelerated by selection pressure from the frequent and irrational use of antimicrobial drugs. This study aimed to determine the variations in AMR patterns of priority bacterial pathogens at a tertiary care hospital in the Gaza Strip during pre- and post-COVID-19 pandemic. METHODOLOGY: This is a retrospective observational study to determine the AMR patterns of bacterial pathogens at a tertiary hospital in the Gaza Strip in the post-COVID-19 pandemic period compared to the pre-COVID-19 period. Positive-bacterial culture data of 2039 samples from pre-COVID-19 period and 1827 samples from post-COVID-19 period were obtained from microbiology laboratory records. These data were analysed and compared by Chi square test using Statistical Package for Social Sciences (SPSS) Program. RESULTS: Gram-positive and Gram-negative bacterial pathogens were isolated. Escherichia coli was the most prevalent in both study periods. The overall AMR rate was high. There was a statistically significant increase in resistance to cloxacillin, erythromycin, cephalexin, co-trimoxazole and amoxicillin/clavulanic acid in the post-COVID-19 period compared to pre-COVID-19 period. There was also a significant decrease in resistance to cefuroxime, cefotaxime, gentamicin, doxycycline, rifampicin, vancomycin and meropenem in the post-COVID-19 period. CONCLUSIONS: During the COVID-19 pandemic, the AMR rates of restricted and noncommunity-used antimicrobials declined. However, there was an increase in AMR to antimicrobials used without medical prescription. Therefore, restriction on the sale of antimicrobial drugs by community pharmacies without a prescription, hospital antimicrobial stewardship and awareness about the dangers of extensive use of antibiotics are recommended.

Diabetic striatopathy unusual presentation with ischemic stroke-A case report and literature review.

Diabetic striatopathy (DS) is a rare condition present as a combination of hemichorea or hemiballismus with striatal computed tomography (CT) or magnetic resonance imaging (MRI) changes in the presence of a severely hyperglycemic state. Varying severity and manifestations of DS were reported throughout the literature. However, the exact pathogenesis and mechanism remain unclear. In this case report, we are presenting an unusual case of DS combined with acute ischemic stroke. A 74-year-old male presented with the main complaint of acute left arm and leg weakness, and was found to have significantly high blood sugar and evidence of DS in combination with stroke on CT and MRI. Eventually, he was labeled as a case of combined DS and ischemic stroke.

Positive rate and quality assessment of CT pulmonary angiography in sickle cell disease: a case‒control study.

BACKGROUND: Pulmonary complications are common in sickle cell disease (SCD) and can mimic pulmonary embolisms (PEs), leading to potential overuse of computed tomography pulmonary angiography (CTPA). Maximizing the quality of CTPA is essential for its diagnostic accuracy. However, little is known about the positive rate and quality of CTPA in SCD. METHODS: This retrospective case‒control study aimed to determine the positive rate and quality of CTPA studies performed to rule out PE in SCD (HbSS genotype) patients compared to a control group. Logistic regression analysis was used to identify independent factors associated with suboptimal CTPA studies, defined as a mean enhancement of < 210 HU in the pulmonary artery. RESULTS: The study included 480 patients, consisting of 240 SCD patients and 240 controls. The positive rate of PE was 4.0%, with a similar rate in both SCD patients and the control group (4.2% vs. 3.8%, p = 0.08). However, SCD patients had significantly lower contrast enhancement of the pulmonary artery than the control group (266.1 ± 90.5 HU vs. 342.2 ± 116.1 HU, p < 0.01). Notably, 25.4% of SCD patients had suboptimal scans. The logistic regression model demonstrated that SCD was significantly associated with suboptimal pulmonary arterial contrast enhancement compared to the control group (OR = 4.4; 95% CI: 2.4-8.3). CONCLUSIONS: This study revealed a relatively low positive rate of CTPA in both SCD patients and the control group. However, SCD was significantly associated with suboptimal image quality due to inadequate contrast enhancement of the pulmonary artery. Further research is needed to identify measures that can enhance the quality of CTPA studies in SCD patients and to establish a specific imaging protocol for this patient population.

Accelerated cell culture process development and characterization for cilgavimab/tixagevimab (AZD7442) for the prevention and treatment of COVID-19.

The global COVID-19 pandemic ignited an unprecedented race to develop vaccines and antibody therapeutics. AstraZeneca's pursuit to provide AZD7442 (EVUSHELD), two long-acting, SARS-CoV-2 spike receptor binding domain-specific neutralizing monoclonal antibodies, to individuals at risk on highly accelerated timelines challenged our traditional ways of process development and spurred the rapid adoption of novel approaches. Conventional upstream development processes were replaced by agile strategies that combined technological advances and highly accelerated workflows. With calculated business risks and close cross-functional collaborations, this process paved the way for hyper accelerated antibody development from discovery through manufacturing, process validation, emergency use authorization filing, and global regulatory approvals. The result was initiation of commercial manufacturing at a contract manufacturing organization less than 6 months from the selection of cilgavimab and tixagevimab-a process that historically has taken close to 10 years.

A Multifaceted Review of Eurycoma longifolia Nutraceutical Bioactives: Production, Extraction, and Analysis in Drugs and Biofluids.

Eurycoma longifolia Jack (known as Tongkat Ali) is a popular traditional herbal medicine, native to southeast Asia, that is well-known for its aphrodisiac as well as several other effects. Mostly, the root extract of E. longifolia is used as a folk medicine for sexual dysfunction, aging, anxiety, exercise recovery, fever, increased energy, and osteoporosis. These health effects led to the inclusion of E. longifolia in dietary supplements, particularly for bodybuilding purposes. These effects are mediated by a myriad of bioactive compounds belonging to quassinoids, canthin-6-one alkaloids, tirucallane triterpenes, squalene derivatives, and bioactive steroids. Among these phytoconstituents, quassinoids account for a large portion of E. longifolia root phytochemicals. Of these ingredients, eurycomanone, the major quassinoid in E. longifolia extract, accounts to a large extent for its health effects. This review capitalizes on the novel trends toward the production of E. longifolia bioactives using biotechnology and extraction optimization for best yields and recovery. Alongside, novel extraction methods, i.e., green techniques, of E. longifolia bioactives are described. Further, an overview of the different analytical approaches for the quality control assessment of E. longifolia plant material and nutraceuticals is presented alongside studies in body fluids to determine its pharmacokinetics and efficacy level. Such a compilation of analytical methods will help ensure safety and efficacy of that major drug.

A CABG Complication - LIMA Graft to Cardiac Venous System Anastomosis Rescued by Percutaneous Coronary Intervention.

Inadvertent graft anastomosis to the great anterior cardiac vein is a known but rare complication of coronary artery bypass graft surgery (CABG). This is usually managed with percutaneous embolization of the inadvertently anastomosed graft with stenting of underlying atherosclerotic coronary artery disease (CAD) or by surgical correction. We present a similar case of the inadvertent left internal mammary artery (LIMA) graft anastomosis to the cardiac venous system, managed with the less complicated percutaneous coronary intervention of the underlying coronary artery disease due to anginal symptoms without the need for surgical correction or embolization of the graft.

Comparison of In-Hospital Outcomes After Insertion of Watchman Device in Men Versus Women (from the National Inpatient Data).

Left atrial appendage occlusion with the Watchman device is approved to manage nonvalvular atrial fibrillation and prevent stroke in patients with contraindications to anticoagulation. This study aimed to analyze the National Inpatient Sample (NIS) data to evaluate gender disparities and further assess its impact on medical decision-making. The NIS data for 16,505 patients who underwent left atrial appendage occlusion with the Watchman device from 2016 to 2017 was used to perform a cross-sectional analysis. The primary end point was risk-adjusted in-hospital mortality. The study included 9,825 men and 6,680 women. Male patients were younger than female patients (mean age of 75.3 years vs 76.3 years, p <0.001). The observed in-hospital mortality was higher in female patients (0.3% vs 0.1%, p = 0.003). This remained significant after adjustment for baseline confounders (adjusted odds ratio 2.9, 95% confidence interval 1.4 to 6.3, p = 0.005). In conclusion, analysis of the large pool of NIS data reveals that female patients have relatively worse in-hospital outcomes in terms of mortality, length of stay, and total hospitalization cost than male patients who underwent Watchman device implantation. However, these disparities are not enough to impact the medical decision-making process and to defer the use of the Watchman device in female patients.

Job insecurity, fear of litigation, and mental health among expatriate nurses.

The objective was to assess whether job insecurity and fear of litigation were correlates of depression, anxiety, and stress among expatriate nurses in Saudi Arabia. The participants included 977 expatriate nurses working in Al-Qassim, Saudi Arabia who completed an online survey that assessed depression, anxiety, and stress (using DASS-21) as well as demography, lifestyle, and job characteristics. Mean age was 32 years and 60% of nurses were from India/Pakistan. Twenty-four percent of nurses reported job insecurity, and 18% reported a fear of litigation. Severe depression, anxiety, and stress were significantly higher among nurses who always felt insecure about their job (compared to never) and among those who always feared litigation (compared to never). We concluded that job insecurity and fear of litigation were significant correlates of severe depression, anxiety, and stress among expatriate nurses.

Origanum vulgare L. Essential Oil as a Potential Anti-Acne Topical Nanoemulsion-In Vitro and In Vivo Study.

Antibiotics are often prescribed in acne treatment; however, Propionibacterium acnes and Staphylococcus epidermidis, the two of the major acne-associated bacteria, developed antibiotic resistance. Essential oils (EOs) present a natural, safe, efficacious and multifunctional alternative treatment. This study aimed to assess the potential anti-acne activity of selected seven EOs commonly used in Mediterranean folk medicine. Antimicrobial activity screening of these oils showed oregano to exhibit the strongest antimicrobial activity with minimum inhibitory concentration (MIC) of 0.34 mg/mL and minimum bactericidal concentration (MBC) of 0.67 mg/mL against P. acnes; and MIC of 0.67 mg/mL and MBC of 1.34 mg/mL against S. epidermidis. The composition of the most effective EOs (oregano and thyme) was determined using gas chromatography-mass spectrometry (GC-MS). Monoterpenoid phenols predominated oregano and thyme EO with thymol percentile 99 and 72, respectively. Thymol showed MIC 0.70 mg/mL against both P. acnes and S. epidermidis whereas MBC was 1.40 and 2.80 mg/mL against P. acnes and S. epidermidis, respectively. Moreover, oregano exhibited the strongest anti-biofilm effect against S. epidermidis with MBIC 1.34 mg/mL and killing dynamic time of 12 and 8 h against P. acnes and S. epidermidis, respectively. Oregano, the most effective EO, was formulated and tested as a nanoemulsion in an acne animal mouse model. The formulation showed superior healing and antimicrobial effects compared to the reference antibiotic. Collectively, our data suggested that oregano oil nanoemulsion is a potential natural and effective alternative for treating acne and overcoming the emerging antibiotic resistance.

Identification and Ablation of Dormant Conduction in Atrial Fibrillation Using Adenosine.

BACKGROUND: Ablation is used for treatment of atrial fibrillation (AF) but recurrence is common. Dormant conduction is hypothesized to be responsible for these recurrences, and the role of adenosine in identification and ablation of these pathways is controversial with conflicting results on AF recurrence. MATERIALS AND METHODS: We conducted a meta-analysis for studies evaluating AF ablation and adenosine use. Included in the meta-analysis were human studies that compared ablation using adenosine or adenosine triphosphate (ATP) and reported freedom from AF in patients beyond a minimum follow-up of 6 months. RESULTS: Our analysis suggests that the use of adenosine leads to a decrease in recurrence of AF compared to the cohort which did not utilize adenosine. Subgroup analysis showed no difference in the recurrence of AF with the modality used for ablation (cryoablation vs. radiofrequency ablation) or with the preparation of adenosine used (ATP vs. adenosine). There was a significant benefit in delayed administration of ATP over early administration. Pooling results of only randomized control trials did not show any significant difference in AF recurrence. CONCLUSIONS: Adenosine-guided identification and ablation of dormant pathways may lead to a decrease in recurrence of AF.

Evidence for rangewide panmixia despite multiple barriers to dispersal in a marine mussel.

Oceanographic features shape the distributional and genetic patterns of marine species by interrupting or promoting connections among populations. Although general patterns commonly arise, distributional ranges and genetic structure are species-specific and do not always comply with the expected trends. By applying a multimarker genetic approach combined with Lagrangian particle simulations (LPS) we tested the hypothesis that oceanographic features along northeastern Atlantic and Mediterranean shores influence dispersal potential and genetic structure of the intertidal mussel Perna perna. Additionally, by performing environmental niche modelling we assessed the potential and realized niche of P. perna along its entire native distributional range and the environmental factors that best explain its realized distribution. Perna perna showed evidence of panmixia across >4,000 km despite several oceanographic breaking points detected by LPS. This is probably the result of a combination of life history traits, continuous habitat availability and stepping-stone dynamics. Moreover, the niche modelling framework depicted minimum sea surface temperatures (SST) as the major factor shaping P. perna distributional range limits along its native areas. Forthcoming warming SST is expected to further change these limits and allow the species to expand its range polewards though this may be accompanied by retreat from warmer areas.

An Infrequent Cause of Apical Ventricular Aneurysm in the United States.

Chronic Chagas cardiomyopathy (CCC) is a late complication of Chagas disease with various manifestations including arrhythmia, heart failure, thromboembolism, and stroke. In a patient with symptoms of heart failure and left ventricular apical aneurysm unexplained by structural heart or coronary vascular abnormalities, CCC should be strongly considered and inquiry made about exposure status. Typical electrocardiographic findings of bundle branch block, complete heart blocks, and ventricular arrhythmia are helpful clues. A positive trypanosomal immunoglobulin G antibody is supportive. Initiation of stage appropriate guideline-recommended heart failure regimen is the goal with careful attention paid to prevention of sudden cardiac death from ventricular arrhythmias.

A meta-analysis of antibacterial envelope use in prevention of cardiovascular implantable electronic device infection.

OBJECTIVES: Cardiac implantable electronic device (CIED) infection has been a major clinical problem in addition to being a major financial burden. In spite of antimicrobial prophylaxis, CIED infection rates have been increasing disproportionately. We therefore conducted this meta-analysis to assess the role of TYRX antibiotic envelope for the prevention of CIED infection. METHODS: Using extensive online search, we conducted a meta-analysis of studies reporting CIED infections with versus without the use of TYRX antibiotic envelope. A random-effect model was used, and between studies heterogeneity was estimated with I2. All analyses were performed with RevMan (version 5.0.20). RESULTS: Five cohort studies were included in this meta-analysis. The pooled odds ratio (OR) of included studies was 0.29 [95% confidence interval (CI): 0.09-0.94; p < 0.004]. There was evidence of heterogeneity with I2 of 58%. There was also evidence of publication bias on funnel plot analysis. On sensitivity analysis, no statistically significant difference was noted when stratified by study design or duration of follow-up. CONCLUSION: The results of our study demonstrate a significant beneficial effect of TYRX antibiotic envelope for the prevention of CIED infections.

Egg Consumption and Incidence of Heart Failure: A Meta-Analysis of Prospective Cohort Studies.

INTRODUCTION: Heart failure (HF) remains a major health problem affecting 5.7 million adults in USA. Data on the association of egg consumption with incident HF have been inconsistent. We, therefore, conducted this meta-analysis of prospective cohort studies to assess the relation of egg consumption with incident HF in the general population. METHODS: Using extensive online search, we conducted a meta-analysis of new onset HF following exposure to egg consumption. A random effects model was used and between studies heterogeneity was estimated with I2. Publication bias was assessed graphically using a funnel plot. All analyses were performed with Comprehensive Meta-Analysis (version 2.2.064). RESULTS: We identified four prospective cohorts for a total of 105,999 subjects and 5,059 cases of new onset HF. When comparing the highest (≥1/day) to the lowest category of egg consumption, pooled relative risk of HF was 1.25 (95% confidence interval = 1.12-1.39; p = 0.00). There was no evidence for heterogeneity (I2 = 0%) nor publication bias. On sensitivity analysis, stratification by gender differences, follow-up duration, and region where study was conducted did not alter the main conclusion. CONCLUSION: Our meta-analysis suggests an elevated risk of incident HF with frequent egg consumption.

Isolated rupture of bicuspid aortic valve following blunt chest trauma: a case report and systematic review of literature.

Blunt trauma to chest cause injury to various cardiac structures. Isolated rupture of aortic valve without aortic dissection is rare complication of blunt chest trauma and can be caused by a tear or avulsion of the valve. We report a case of a 35-year-old male who presented with severe aortic insufficiency due to rupture of a non-infected congenital bicuspid aortic valve following non-penetrating chest trauma. The diagnosis was suggested by echocardiography and was confirmed by intra-operative and histological findings. The patient was successfully treated with surgical valve replacement with uneventful postoperative course and recovery. We describe patho-physiology, clinical manifestations, management and the literature review of traumatic rupture of bicuspid aortic valve.

Clinical outcomes associated with per-operative discontinuation of aspirin in patients with coronary artery disease: A systematic review and meta-analysis.

BACKGROUND: Postoperative state is characterized by increased thrombotic risk by virtue of platelet activation. Whether aspirin ameliorates this risk in patients with established coronary artery disease undergoing cardiac or noncardiac surgery is unknown. We conducted a systematic review and meta-analysis to compare the risk of major adverse cardiac events (MACE) and the risk of bleeding in patients with early (3-5 or more days before surgery) vs. late discontinuation(<3-5 days)/no discontinuation of aspirin. METHODS: Multiple databases were searched from inception of these databases until March 2015 to identify studies that reported discontinuation of aspirin in patients undergoing surgery. The outcomes measured were all cause mortality, nonfatal myocardial infarction and other relevant thrombotic events (MACE) which also may include, fatal and nonfatal MI, stent thrombosis and restenosis, stroke, perioperative cardiovascular complications (heart failure, MI, VTE, acute stroke) and perioperative bleeding during the perioperative period to up to 30 days after surgery. RESULTS: A total of 1,018 titles were screened, after which six observational studies met the inclusion criteria. Our analysis suggests that there is no difference in MACE with planned discontinuation of aspirin (OR = 1.17, 95% CI = 0.76-1.81; P = 0.05; I2 = 55%). Early discontinuation of aspirin showed a decreased risk of peri-operative bleeding (OR 0.82, 95% CI = 0.67-0.99; P = 0.04; I2 = 42%). CONCLUSION: Our analysis suggests that planned short-term discontinuation in the appropriate clinical setting appears to be safe in the correct clinical setting with no increased risk of thrombotic events and with a decreased risk of bleeding. © 2016 Wiley Periodicals, Inc.

Genetics and psychotic disorders: A fresh look at consanguinity.

Consanguineous unions refer to marriages between related individuals who share a common ancestor. These unions are still commonplace in certain regions of the world such as the southern coast of the Mediterranean, throughout the Middle East and South-East Asia. According to available data, couples of second cousins or closer and their offspring currently represent 10.4% of the world's population, thus resulting in increased frequencies of autosomal recessive disorders. Furthermore, consanguinity may be implicated in the increased frequency of multifactorial pathologies such as mental disorders. The few existing epidemiological studies in consanguineous and/or geographically isolated populations confirm that there is a significant association between consanguinity and mental disorders and a higher risk of schizophrenia or bipolar disorders among offspring from consanguineous couples. There exists a strong and complex genetic component in the predisposition to psychotic disorders that has been confirmed in numerous studies. However, the genetic basis of these disorders remains poorly understood. GWAS studies (Genome Wide Association Studies) over the past 10 years have identified a few weak associations, thus refuting the "common diseases-common variants" hypothesis. A model implicating numerous rare variants has been supported by the recent discovery of CNVs (Copy Number Variants) and their statistically significant association with psychiatric disorders such as schizophrenia, bipolar disorders and autism. The study of consanguineous families may contribute to identifying rare variants in homogenous populations who have conserved certain alleles. Major developments in molecular biology techniques would facilitate these studies as well as contributing to identifying major genes. These results emphasize the need for genetic counseling in high-risk communities and the importance of implementing preventive actions and raising awareness concerning the risk of consanguineous unions.