Potential Cardiovascular Events Avoided with Bempedoic Acid Plus Ezetimibe Fixed-Dose Combination Compared with Ezetimibe Alone in Patients with Atherosclerotic Cardiovascular Disease Taking Maximally Tolerated Statins.

BACKGROUND: Patients with atherosclerotic cardiovascular disease who require additional low-density lipoprotein cholesterol (LDL-C) lowering despite maximally tolerated statins have a significant unmet medical need and are at increased risk of future cardiovascular events and a reduced quality of life. OBJECTIVE: We aimed to estimate the percentage of cardiovascular events avoided following treatment with a fixed-dose combination of bempedoic acid plus ezetimibe (BA+EZE FDC) versus ezetimibe (EZE) in patients with atherosclerotic cardiovascular disease receiving maximally tolerated statins across a range of baseline LDL-C levels. METHODS: A Markov cohort simulation model estimated major adverse cardiovascular events avoided over a lifetime horizon among patients with atherosclerotic cardiovascular disease and baseline LDL-C levels from 80 to >200 mg/dL. BA+EZE FDC was compared with EZE based on mean percent LDL-C reductions versus placebo reported in a phase III trial. Health outcomes for the average patient were extrapolated to a US population of 100,000 persons using evidence on contemporary LDL-C levels from the National Health and Nutrition Examination Survey. RESULTS: Among patients with atherosclerotic cardiovascular disease not at the LDL-C goal with maximally tolerated statins, the addition of BA+EZE FDC compared with the addition of EZE was predicted to provide incremental absolute reductions in major adverse cardiovascular events dependent on baseline LDL-C levels at the population level. For those with baseline LDL-C of 101-110 mg/dL (n = 15,237), there were 4.9% (744) fewer events predicted, while for patients with baseline LDL-C of > 200 mg/dL (n = 1689), 10.9% (184) fewer events were predicted through the addition of BA+EZE FDC versus EZE. CONCLUSIONS: Further LDL-C reductions through the addition of BA+EZE FDC to maximally tolerated statins are predicted to reduce major adverse cardiovascular events compared with the addition of EZE. Benefits are potentially greater among those with higher starting LDL-C.

Predictors for mucormycosis in COVID era: A case-control study from Gujarat.

Context: Mucormycosis has been increasingly described in the coronavirus disease (COVID-19) era, however, there is a lack of robust epidemiological studies to understand the predictors for the development of mucormycosis from India. Aims: To document the risk factors of mucormycosis with or without COVID-19 and estimate the strength of association of various risk factors. Settings and Design: A case-control study was conducted in the Ahmedabad districts of Gujarat from June to August 2021. Methods and Material: One hundred participants (25 cases with mucor, 75 without mucor) were enrolled in the study. The cases and controls were then matched based on age and gender. Ethical approval was sought from the Institutional Ethics Committee of the Indian Institute of Public Health Gandhinagar, Gujrat, India. Statistical Analysis Used: Data were collected using the Epi Collect 5 application, and the descriptive, inferential analysis was done using the SPSS version 21 statistical software. Results: About 68% of the cases were from a rural area and had past comorbidity conditions. About 80% of the cases reported a previous history of COVID-19, whereas 67% of the controls reported the same. The factors which remained significant after applying the hierarchical model were rural residents (OR = 3.2 [95% CI: 1.05-10.3]) and history of oxygen therapy (OR = 5.42 [95% CI: 1.24-23.8]). Conclusions: This study concludes that mucormycosis is independent of the COVID-19 status. Rural residents and oxygen therapy were found to be the most significant risk factors for mucormycosis. The findings of this study are also not conclusive to establish an association; thus, further exploration and in-depth research with larger samples are recommended.

A US Time and Motion Pilot Study of Nebulized COPD Therapy in an Inpatient and a Long-Term Care Setting.

INTRODUCTION: There is a lack of quantitative data on healthcare professionals' (HCPs) time dedicated to nebulized chronic obstructive pulmonary disease (COPD) therapy in inpatient and long-term care (LTC) settings. Using time and motion methodology, we quantified HCP time and opportunity costs (time and materials) associated with nebulized COPD therapy in inpatient and LTC settings and estimated efficiencies of changing to once-daily therapy. METHODS: A case report form was built to reflect local nebulization workflow. Primary outcomes were mean active HCP time per predefined task and mean total active HCP time associated with short-acting beta agonist (SABA) and SABA/short-acting muscarinic antagonist (SAMA) combination nebulization processes. RESULTS: Twenty observations occurred within each setting. Inpatient observations included three SABA and 17 SABA/SAMA (from 18 different patients), and LTC observations included five SABA and 15 SABA/SAMA (from eight different patients). Mean total process time was 16.12 min in the inpatient setting (95% CI 14.48-17.76) and 21.0 min in the LTC setting (95% CI 18.8-23.2), with the actual nebulization comprising over 50% of process time for both. In LTC, CIs suggest a difference by cognitive impairment status: mean 24.1 min (95% CI 21.3-26.9) if cognitively impaired versus 19.0 min (95% CI 16.1-21.8) if not. In the inpatient setting, the estimated process time/admission was 7.8 h; a once-daily nebulized drug would require only 2.3 h. In LTC, the estimated process time was 32.1 h/month; a once-daily nebulized drug would require only 13.7 h/month. Estimated nebulization cost was $243/admission for current versus $72 for once-daily dosing in inpatient, and $1177/month versus $504 in LTC. CONCLUSIONS: The nebulization process for COPD patients in both inpatient and LTC settings consumes considerable HCP time. A switch from SABA or SABA/SAMA to a drug with a once-daily nebulization frequency could generate substantial time savings depending on the setting and site characteristics.

Sinus node sparing novel hybrid approach for treatment of inappropriate sinus tachycardia/postural sinus tachycardia: multicenter experience.

BACKGROUND: The ideal treatment of inappropriate sinus tachycardia (IST) and postural orthostatic tachycardia syndrome (POTS) still needs to be defined. Medical treatments yield suboptimal results. Endocardial catheter ablation of the sinus node (SN) may risk phrenic nerve damage and open-heart surgery may be accompanied by unjustified invasive risks. METHODS: We describe our first multicenter experience of 255 consecutive patients (235 females, 25.94 ± 3.84 years) having undergone a novel SN sparing hybrid thoracoscopic ablation for drug-resistant IST (n = 204, 80%) or POTS (n = 51, 20%). As previously described, the SN was identified with 3D mapping. Surgery was performed through three 5-mm ports from the right side. A minimally invasive approach with a bipolar radiofrequency clamp was used to ablate targeted areas while sparing the SN region. The targeted areas included isolation of the superior and the inferior caval veins, and a crista terminalis line was made. All lines were interconnected. RESULTS: Normal sinus rhythm (SR) was restored in all patients at the end of the procedure. All patients discontinued medication during the follow-up. After a blanking period of 6 months, all patients presented stable SR. At a mean of 4.07 ± 1.8 years, normal SN reduction and chronotropic response to exercise were present. In the 51 patients initially diagnosed with POTS, no syncope occurred. During follow-up, pericarditis was the most common complication (121 patients: 47%), with complete resolution in all cases. Pneumothorax was observed in 5 patients (1.9%), only 3 (1.1%) required surgical drainage. Five patients (1.9%) required a dual-chamber pacemaker due to sinus arrest > 5 s. CONCLUSIONS: Preliminary results of this multicenter experience with a novel SN sparing hybrid ablation of IST/POTS, using surgical thoracoscopic video-assisted epicardial ablation combined with simultaneous endocardial 3D mapping may prove to be an efficient and safe therapeutic option in patients with symptomatic drug-resistant IST and POTS. Importantly, in our study, all patients had a complete resolution of the symptoms and restored normal SN activity.

Swertisin, a novel SGLT2 inhibitor, with improved glucose homeostasis for effective diabetes therapy.

Failing pancreas and subsequent loss of pancreatic ß cells worsen diabetic conditions which are further alleviated by the mounting up of glucose levels. Inhibition of sodium glucose cotransporter 2 (SGLT2) in the kidney responsible for glucose reabsorption strikingly reduces blood glucose levels. Bioactive swertisin showed a promising glucose-lowering effect. Hence, we aimed to mechanistically dissect the glucose lowering property of swertisin. A systematic in silico, in vitro, and in vivo approach was directed for target analysis of swertisin. Molecular docking was performed with Swertisn-hSGLT2 complex. Glucose uptake assay and protein expression for SGLT2 and regulatory proteins were performed under swertisin effect. Various physiological and metabolic parameters were evaluated in STZ induced BALB/c mice using swertisin treatment. SGLT2 expression was evaluated in the kidney tissue of mice. Swertisn-hSGLT2 molecularly docked complex showed similar binding energy compared to the Canagliflozin-hSGLT2 complex. Swertisin inhibited glucose uptake and decreased expression of SGLT2 in HEK293 cells. Swertisin does not affect GLUT mediated glucose transport. Swertisin treated diabetic mice demonstrated remarkable improvement in overall glucose homeostasis. Reduced expression of SGLT2 was found in kidney tissue along with reduced PKC expression which is one of the key regulators of SGLT2. Our study explored SGLT2 as a selective target of swertisin for its swift glucose-lowering action which not only inhibits SGLT2 but also reduces its expression in diabetic condition. Thus, the potential property of swertisin as a glucose-lowering agent is remarkable which points towards the likelihood of a wider avenue of diabetes therapy.

Current global vaccine and drug efforts against COVID-19: Pros and cons of bypassing animal trials.

COVID-19 has become one of the biggest health concern, along with huge economic burden. With no clear remedies to treat the disease, doctors are repurposing drugs like chloroquine and remdesivir to treat COVID-19 patients. In parallel, research institutes in collaboration with biotech companies have identified strategies to use viral proteins as vaccine candidates for COVID-19. Although this looks promising, they still need to pass the test of challenge studies in animal models. As various models for SARS-CoV-2 are under testing phase, biotech companies have bypassed animal studies and moved to Phase I clinical trials. In view of the present outbreak, this looks a justified approach, but the problem is that in the absence of animal studies, we can never predict the outcomes in humans. Since animal models are critical for vaccine development and SARS-CoV-2 has different transmission dynamics, in this review we compare different animal models of SARS-CoV-2 with humans for their pathogenic, immune response and transmission dynamics that make them ideal models for vaccine testing for COVID-19. Another issue of using animal model is the ethics of using animals for research; thus, we also discuss the pros and cons of using animals for vaccine development studies.

Commercial claims costs related to health care resource use associated with a diagnosis of peanut allergy.

BACKGROUND: Peanut allergy (PA) affects approximately 1.6 million US children. The current standard of care is strict avoidance and prompt reaction treatment. Peanut allergy health care costs and health care resource utilization (HCRU) are poorly understood. OBJECTIVE: To estimate PA health care costs and HCRU using a nationally representative commercial payer database. METHODS: The IBM MarketScan Commercial Claims and Encounters Database was examined for PA diagnosis/reaction codes between January 2010 and October 2016 in patients 64 years of age or younger, with age cohort-matched controls. Outcomes were measured 12 months before and after the first claim date. Health care costs and HCRU were compared using Student's t tests and χ2 tests. RESULTS: Patients with a PA-related diagnostic code (n = 41,675) incurred almost double all-cause health care costs vs controls ($6436 vs $3493, P < .001), mainly from inpatient and outpatient medical costs ($5002 vs $2832, P < .001). More than one third of the PA group patients (36%) had a code indicative of an anaphylactic reaction during follow-up. Mean PA or reaction-related code costs per visit totaled $7921 for hospitalizations and $1115 for emergency department (ED) visits. Costs were 30% lower in patients with asthma codes without PA codes vs those with both codes ($5678 vs $8112, P < .001); all-cause ED costs were more than double in patients with atopic dermatitis codes with PA codes vs those without PA codes ($654 vs $308, P < .001). CONCLUSION: National commercial payer claims data indicate a significant health care burden associated with a PA-related code, including over $6400/patient in annual all-cause costs and increased health care utilization.

The 1-year economic burden of community-acquired pneumonia (CAP) initially managed in the outpatient setting in the USA.

Aim: To assess the annual economic burden of community-acquired pneumonia (CAP) initially managed in the outpatient setting. Patients & methods: Patients with an outpatient diagnosis of CAP between January 2012 and December 2016 were identified from the IQVIA (Danbury, CT & Durham, NC, USA) Real-World Data Adjudicated Claims - US Database. All-cause and CAP-related healthcare resource utilization and costs were assessed over the 1-year follow-up. Generalized linear model examined adjusted total cost. Results: Among 256,916 patients with outpatient CAP, a tenth (10.6%) had ≥1 hospitalization and, of these, 18.7% had ≥1 CAP-related hospitalization. The mean total cost per patient was US$14,372; 10.9% was CAP-related and 26.1% was due to inpatient care. The adjusted mean total all-cause cost was US$13,788. Conclusion: Patients with outpatient CAP incurred a substantial annual economic burden.

The annual economic burden among patients hospitalized for community-acquired pneumonia (CAP): a retrospective US cohort study.

Objective: To assess the 1-year economic burden among patients hospitalized for community-acquired pneumonia (CAP) in the US.Methods: Adult patients hospitalized for CAP between 1/2012 and 12/2016 were identified from the IQVIA hospital charge data master (CDM) linked to the IQVIA Real-World Data Adjudicated Claims - US Database (date of admission = index date). Patients had continuous enrollment 180-days pre- and 360-days post-index, and empiric antimicrobial treatment (monotherapy [EM] or combination therapy [EC]) and chest x-ray on the index date or day after. All-cause and CAP-related healthcare resource utilization and cost were assessed over the 1-year follow-up. Generalized linear models (GLM) examined adjusted total cost.Results: The cohort comprised 1624 patients hospitalized for CAP (mean age 50.3; 52.8% female). The majority (78.2%) initiated EC, most frequently with beta-lactams + macrolides (30.4%). The index hospitalization was associated with a mean length of stay (LOS) of 5.7 days and mean cost of $17,736; 22.7% had a transfer to the intensive care unit (ICU). All-cause readmission rates at 30- and 180-days were 8.8% and 20.1%, respectively. Mean annual all-cause total cost was $61,928; one-third (33.8%, $20,954) was related to CAP. The primary cost driver was inpatient care, which accounted for more than half (56.0%) of total all-cause cost and 94.3% of total CAP-related cost. Mean total inpatient cost was significantly higher among EC versus EM patients ($37,106 versus $25,999, p = .0399). Adjusted mean total all-cause cost was $55,391.Conclusions: Patients hospitalized for CAP incurred a significant annual economic burden, driven substantially by the high cost of hospitalizations.

Metabolic Syndrome Rather than Obesity Alone Is More Significant for Kidney Disease.

INTRODUCTION: Obesity is associated with metabolic syndrome, nonalcoholic steatohepatitis, and kidney disease. BMI may not be the ideal measure of obesity when used to assess its effect on kidney disease as it does not discriminate for age, sex, ethnicity, muscle, bone, or fat mass. OBJECTIVES: To assess the prevalence microalbuminuria and identify independent risk factors for development of kidney disease in the obese Indian population. METHODS: Age, weight, BMI, total body fat percentage, waist-to-hip ratio, hypertension, urinary albumin-to-creatinine ratio (UACR), and HbA1c were collected from 568 obese patients, presenting for bariatric surgery. Multivariate binary logistic regression was used to identify independent risk factors for kidney disease. RESULTS: A total of 114 out of 568 (20.07%) obese patients had microalbuminuria (UACR range 30-283 µg/mg). HbA1C levels ≥ 6 (p = 0.01) and hypertension (p = 0.03) were the strongest independent variables for microalbuminuria. 14.67% with a BMI < 35 kg/m2, 21.30% with a BMI 35-50 kg/m2, and 19.44% with a BMI > 50 kg/m2 had microalbuminuria. Increasing BMI however was not statistically significant (p = 0.75). Total body fat percentage (p = 0.51), waist-to-hip ratio (p = 0.96), age (p = 0.30), sex (p = 0.38), and BMI (p = 0.75) were found to be statistically insignificant. CONCLUSIONS: Kidney disease afflicts 1/5th of the obese Indian patients studied. Diabetes and hypertension remained as the most significant risk factors, while age, weight, increasing BMI, waist-to-hip ratio, or increasing body fat were found to be statistically insignificant for development and progression of kidney disease.

A novel approach to treat peri implantitis with the help of PRF.

A new field of biomédical science, known as tissue engineering, applies the principles of biology and engineering to the development of functional substitutes for tissues and organs. Little is known about the influence of Keratinised Mucosa dimension around implants on the soft and hard tissue health The purpose of this case report is to understand the importance of healthy tissue around the implants for long term success and how biomimetic materials like PRF Membrane can be incorporated in treatment plan as an important modality in selected cases.

Communication aid requirements of intensive care unit patients with transient speech loss.

Alert and transiently nonvocal intensive care unit (ICU) patients are dependent on augmentative and alternative communication (AAC). Unfortunately, the literature demonstrates that existent AAC devices have not been widely adopted, and unaided methods are often the primary modalities used despite being insufficient, and frustrating. We present the results of a qualitative semi-structured interview study with 8 ex-ICU patients, 4 ICU patient relatives, and 6 ICU staff, exploring their AAC needs and requirements. Participants identified important AAC hardware, software, and content requirements. Salient factors impacting on AAC adoption in the ICU setting were also highlighted and included the need for staff training and bedside patient assessment. Based on the study results, we propose a series of recommendations regarding the design and implementation of future AAC tools specifically targeted at this group.

Increased Nonalternans Repolarization Variability Precedes Ventricular Tachycardia Onset in Patients with Implantable Defibrillators.

BACKROUND: T-wave alternans (TWA) is associated with ventricular tachycardia (VT). Nonalternans repolarization variability (NARV) precedes VT in certain experimental models, but its link to clinical arrhythmia is unproven. This study was conducted to determine if NARV increases prior to VT in patients with implantable cardioverter defibrillators (ICDs). METHODS: TWA and NARV were calculated from shock-channel electrograms preceding onset of VT or non-VT events in patients with an ICD. In each patient, presence of both a VT and a non-VT event with the same QRS morphology before the event was required. Mixed linear model was used for data analysis, using heart rate (HR) and the number of analyzed beats as covariates. RESULTS: Five hundred and sixty-eight events from 64 patients (males/females 51/13, 67 ± 13 years) were analyzed. HR preceding non-VT events was higher than before VT events (RR interval 595 ± 159 vs 706 ± 111 ms; P < 0.0001). Both TWA and NARV increased with increasing HR (P < 0.001). TWA decreased with increasing number of analyzed beats. When controlled for number of analyzed beats and HR, both TWA and NARV were higher before VT than before non-VT events (P < 0.002 and P < 0.0005, respectively). CONCLUSIONS: NARV is elevated prior to spontaneous VT onset. Both NARV and TWA increase with HR. The decrease of TWA with increasing number of analyzed beats may indicate contamination with NARV or noise when only a small number of beats is available for analysis. NARV might be useful for VT prediction in the future.

Dermatology - a compulsory part of the UK medical school curriculum?

Dermatological conditions form a significant number of consultations seen by general practitioners on a daily basis. There is a lack of training and formal assessment of dermatology during medical school and we propose that there should be a mandatory component in OSCEs for dermatology during medical school to enhance one's diagnostic and clinical reasoning skills which will ultimately lead to better care for the patient and efficacious use of NHS resources.

Mortality, Hospital Costs, Payments, and Readmissions Associated With Clostridium difficile Infection Among Medicare Beneficiaries.

BACKGROUND: The management of Clostridium difficile infection (CDI) among hospitalized patients is costly, and ongoing payment reform is compelling hospitals to reduce its burden. To assess the impact of CDI on mortality, hospital costs, healthcare use, and Medicare payments for beneficiaries who were discharged with CDI listed as a secondary International Classification of Diseases, Ninth Revision, Clinical Modification claim diagnosis. METHODS: Data were analyzed from the 2009 to 2010 5% random sample Medicare Standard Analytic Files of beneficiary claims. Patients with index hospitalizations with CDI as a secondary diagnosis and no previous hospitalization within 30 days were identified. Outcomes included inpatient and 30-day mortality, inpatient costs, index hospital payments, all-provider payments, net hospital losses, payment to cost ratio, length of stay (LOS), and 30-day readmission; outcomes were each risk adjusted using propensity score matching and regression modeling techniques. RESULTS: A total of 3262 patients with CDI were identified after matching to patients without a CDI diagnosis. After risk adjustment, secondary CDI was associated with statistically significantly (all P < 0.05) greater inpatient mortality (3.1% vs. 1.7%), 30-day mortality (4.1% vs. 2.2%), longer LOS (7.0 days vs. 3.8 days), higher rates of 30-day hospital readmissions (14.8% vs. 10.4%), and greater hospital costs ($16,184 vs. $13,954) compared with the non-CDI cohort. The risk-adjusted payment-to-cost ratio was shown to be lower for patients with CDI than those without (0.76 vs. 0.85). CONCLUSIONS: Secondary CDI is associated with greater adjusted mortality, costs, LOS, and hospital readmissions, while receiving similar hospital reimbursement compared with patients without CDI in a Medicare population.

Cardiac implantable electronic device lead extraction in patients with underlying infection using open thoracotomy or percutaneous techniques.

BACKGROUND: Explanting infected cardiac implantable electronic devices (CIEDs) and extracting their associated leads can be performed percutaneously (EP) or via open-thoracotomy (OR) approach. In this study, we examined the characteristics and outcomes of infected CIED patients undergoing EP vs. OR extraction procedures. METHODS: All patients (EP: n = 329 and OR: n = 24) who received lead extraction in the presence of an infected CIED from 2005 to 2010 at the University of Pittsburgh Medical Center were included in this study. Demographic and clinical characteristics were obtained from the electronic medical records. The Charlson comorbidity index (CCI) was used to adjust for severity of co-morbid conditions. RESULTS: Compared to the EP group, OR patients were more likely to have positive blood cultures, larger vegetations, and worse CCI scores. They also had higher total mortality rates at 1 (p = 0.036), 6 (p = 0.020), and 12 months (p = 0.012) after the procedure. One-year survival after lead extractions was significantly better for the EP compared to the OR group (p = 0.002) even after adjusting for other comorbid illnesses (HR = 2.6, p = 0.010) in a Cox regression model. CONCLUSIONS: Infected CIED patients undergoing open-chest lead extraction are sicker and have higher mortality rates compared to those undergoing percutaneous extraction. Randomized, prospective data are needed to determine whether the procedural strategy for lead extraction accounts in part for the difference in outcome.

QT prolongation and T-wave alternans during catheter ablation of atrial fibrillation: a case report.

We report a case of a 63-year-old woman who developed profound QT prolongation, T-wave alternans, and spontaneous ventricular fibrillation during catheter ablation of atrial fibrillation. A thorough search into the possible mechanisms identified the use of sevoflurane, an inhalational gas anesthetic as the culprit. The patient was converted to propofol anesthesia and her QT interval normalized promptly.

Radiofrequency ablation of post-incisional atrial flutter and high-output heart failure in a patient with interrupted inferior vena cava and hereditary hemorrhagic telangiectasia.

A 61-year-old female with a history of secundum atrial septal defect repair and hereditary hemorrhagic telangiectasia presented with epistaxis. She was found to have atypical atrial flutter with 2:1 atrioventricular conduction. Radiofrequency ablation was planned, but inferior vena cava interruption precluded right atrial (RA) access. The RA was then accessed through both subclavian veins, and activation mapping revealed a dense atriotomy scar in the posterolateral inferior RA. Wavefront propagation proceeded caudally through an area of slow conduction confined by the atriotomy scar. Atypical atrial flutter terminated during a second radiofrequency application to an isthmus confined by 2 regions of dense scar. The arrhythmia did not recur, although the patient later experienced typical atrial flutter and atrial fibrillation. High-output heart failure due to systemic arteriovenous shunt was confirmed by cardiac catheterization and improved markedly with bevacizumab therapy.