Impact of ICER Assessments on Payer Decision Making in the United States

Objectives: To evaluate how payers utilize Institute for Clinical and Economic Review (ICER) assessments to inform coverage or formulary decisions. Method(s): Double-blinded, web-based survey was fielded through Xcenda's research panel, the Managed Care Network, from June to July 2022. Result(s): A total of 51 payers from health plans (n=27), integrated delivery networks (n=12), and pharmacy benefit managers (n=12) participated in the survey. When assessing the usefulness of ICER's value assessment framework (VAF) to inform formulary decisions within their organizations, 57% of payers indicated it was extremely/very useful, 33% indicated somewhat useful, and 10% indicated not at all/not very useful. Most respondents (73%) agreed that ICER assessments are aligned with their organization's internal assessment. Utilization of ICER's VAF was most prevalent in high-cost drug or disease states (78%), rare/orphan disease states (71%), and oncology/hematology disease states (67%). Payers reported less use in primary care disease states (29%), COVID-19 (8%), and digital therapeutics (4%). In the last 24 months, 20% of payers reported ICER's recommendations often influenced coverage decisions, 59% indicated occasional influence, and 22% indicated no influence. In the last 24 months, payers indicated the top 5 ICER assessments that influenced their coverage decisions included high cholesterol (38%), Alzheimer's disease (36%), atopic dermatitis (33%), multiple myeloma (31%), and chemotherapy-induced neutropenia (28%). ICER assessments that were less impactful included beta thalassemia (3%), digital health technologies (3%), and supervised injection facilities (3%). Payers reported using ICER assessments to inform both expanded and restricted coverage decisions. Conclusion(s): Payers find ICER's VAF useful to inform their organization's formulary decisions. ICER's assessments often align with payers' internal assessments and are most frequently utilized for high-cost drugs or disease states. Payers indicate ICER assessments have affected both expansion and restriction in their coverage policies.Copyright © 2023

Enabling mRNA medicine for brain tumors

mRNA is a new class of drugs that has the potential to revolutionize the treatment of brain tumors. Thanks to the COVID-19 mRNA vaccines and numerous therapy-based clinical trials, it is now clear that lipid nanoparticles (LNPs) are a clinically viable means to deliver RNA therapeutics. However, LNP-mediated mRNA delivery to brain tumors remains elusive. Over the past decade, numerous studies have shown that tumor cells communicate with each other via small extracellular vesicles, which are around 100 nm in diameter and consist of lipid bilayer membrane similar to synthetic lipidbased nanocarriers. We hypothesized that rationally designed LNPs based on extracellular vesicle mimicry would enable efficient delivery of RNA therapeutics to brain tumors without undue toxicity. We synthesized LNPs using four components similar to the formulation used in the mRNA COVID19 vaccines (Moderna and Pfizer): ionizable lipid, cholesterol, helper lipid and polyethylene glycol (PEG)-lipid. For the in vitro screen, we tested ten classes of helper lipids based on their abundance in extracellular vesicle membranes, commercial availability, and large-scale production feasibility while keeping rest of the LNP components unchanged. The transfection kinetics of GFP mRNA encapsulated in LNPs and doped with 16 mol% of helper lipids was tested using GL261, U87 and SIM-A9 cell lines. Several LNP formations resulted in stable transfection (upto 5 days) of GFP mRNA in all the cell lines tested in vitro. The successful LNP candidates (enabling >80% transfection efficacy) were then tested in vivo to deliver luciferase mRNA to brain tumors via intrathecal administration in a syngeneic glioblastoma (GBM) mouse model, which confirmed luciferase expression in brain tumors in the cortex. LNPs were then tested to deliver Cre recombinase mRNA in syngeneic GBM mouse model genetically modified to express tdTomato under LoxP marker cassette that enabled identification of LNP targeted cells. mRNA was successfully delivered to tumor cells (70-80% transfected) and a range of different cells in the tumor microenvironment, including tumor-associated macrophages (80-90% transfected), neurons (31- 40% transfected), neural stem cells (39-62% transfected), oligodendrocytes (70-80% transfected) and astrocytes (44-76% transfected). Then, LNP formulations were assessed for delivering Cas9 mRNA and CD81 sgRNA (model protein) in murine syngeneic GBM model to enable gene editing in brain tumor cells. Sanger sequencing showed that CRISPR-Cas9 editing was successful in ~94% of brain tumor cells in vivo. In conclusion, we have developed a library of safe LNPs that can transfect GBM cells in vivo with high efficacy. This technology can potentially be used to develop novel mRNA therapies for GBM by delivering single or multiple mRNAs and holds great potential as a tool to study brain tumor biology.

The factors associated with increased risk of hospitalisation in people with diabetes following SARS-CoV- 2 infection: A national replication study

Aim: People with type 1 or type 2 diabetes have a higher hospital admission rate following Covid-19 infection. This study aims to determine the degree to which the results of a previous study in Greater Manchester (GM) could be replicated in national-level data for England. Method(s): We focussed on the univariable regression analysis, which shows the association between admission and Covid-19 infection in people with diabetes. Modelling was conducted using logistic regression on data from the Covid-IMPACT database. Odds ratios were compared descriptively with the previous study. Result(s): In people with type 2 diabetes, factors associated with an increased risk of hospitalisation similar to the previous study were: older age, male sex, higher social deprivation, higher body mass index (BMI), higher cholesterol, lower eGFR, taking an ACE-inhibitor/ ARB, not taking metformin, and having asthma or hypertension. Patients with COPD, and those taking aspirin or clopidogrel also had increased risk, but the national data showed a greater risk (GM COPD odds ratio 1.89 [1.63-2.19] vs national 2.34 [2.28-2.40] / aspirin 1.49 [1.34-1.66] vs 1.66 [1.63-1.70] / clopidogrel 1.71 [1.47-1.98] vs 1.99 [1.94-2.04]). Similar results were observed in patients with type 1 diabetes. However, due to the increase in sample size, many factors which were previously not statistically significant have become significant, such as in type 2 diabetes BMI, low HDL-cholesterol. Conclusion(s): We have successfully replicated the methods, results and conclusions of our previous study in relation to factors associated with increased risk of hospital admission in diabetes individuals. Regional databases are suitable for large cohort studies, and in this instance produced similar results to a national database, validating our previous findings.

Cardiometabolic and psychocognitive features of the post-COVID period in patients with atrial fibrillation.

The number of people with long-term consequences of COVID-19 is increasing worldwide. The long-term prognosis for patients remains poorly understood. Objective. To study cardiometabolic and psychocognitive features in comorbid elderly patients with atrial fibrillation (AF), de-pending on the presence of post-COVID syndrome (PCS). Material and methods. The observational analytical cohort study included 223 patients with AF and comorbidity (coronary artery disease, hypertension, obesity, type 2 diabetes mellitus) aged 60-74, who were divided into two groups: group 1 included 123 patients without COVID-19 and group 2 included 110 patients with a history of COVID-19 and the presence of PCS. The study evaluated laboratory and instrumental tests, and a general clinical study assessing psychocognitive disorders using the SPMSQ and HADS questionnaires was conducted. Results and discussion. In COVID-19 survivors, compared with patients of group 1, there were more pronounced atherogenic changes in total cholesterol (TC) (p=0.003), low-density lipoprotein cholesterol (p<0.001), and triglycerides (p=0.011). Lower dia-stolic blood pressure was found in COVID-19 survivors (p<0.001). In addition, patients in group 2 had higher median pulse pressure (p<0.001) and heart rate (p<0.001). In group 2 patients, a larger ascending aorta diameter was observed (p<0.001). The anx-iety-depressive syndrome was more common in COVID-19 survivors with comorbidities, and a statistically significant difference was found in clinical anxiety (24%, p=0.041) and subclinical depression (21%, p=0.015). When assessing cognitive function, mod-erate cognitive impairment was detected in 22% (p=0.005) of patients with PCS and severe cognitive impairment in 2% (p=0.007). Conclusion. In comorbid elderly patients with the post-COVID syndrome, a high prevalence of psychocognitive disorders and adverse cardiometabolic changes were observed, supporting the need for long-term monitoring of the general clinical condition and psychocognitive status of COVID-19 survivors.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

Optimization and Characterization of Quercetin Vitamin C Nano-Phytosome Formulation

Objective: To design an optimal formulation for quercetin and vitamin C nano-phytosome. Method(s): Nano-phytosomes are prepared by the thin layer hydration technique using a 2-level-5-factor design experimental. A total of 32 experimental formulas were used for data analysis. The ratio of quercetin: soy lecithin (X1), the ratio of quercetin: cholesterol (X2), stirring speed (X3), stirring temperature (X4), and stirring time (X5) were used as independent factors, while globule size as a dependent factor. Data analysis was carried out by Design Expert12 application. Characterization of the optimal formula included physicochemical evaluation, globule size analysis, zeta potential, polydispersity index, entrapment efficiency, Transition Electron Microscopy (TEM) analysis, and FTIR analysis. Result(s): The optimal formula consisted of quercetin: vitamin C: lecithin: cholesterol ratio of 1: 1: 1.046: 0.105 mol;stirring speed 763.986 rpm;stirring time of 59 min, at temperature 51.73 degreeC which produced 59.26 nm average globule size, PDI value 0.66;zeta potential value-35.93+/-0.95 mV and average SPAN value 0.61. This formulation showed entrapment efficiency of quercetin 91.69+/-0.18 % and vitamin C 90.82+/-0.13 %. The TEM and FITR analysis showed the morphological of the globules and interactions between the drugs, soy lecithin, and cholesterol to form nano-phytosomes. Conclusion(s): The conditions to obtain the optimal formula for quercetin vitamin C nano-phytosome consisted of quercetin: vitamin C: lecithin: cholesterol ratio of 1: 1: 1.046: 0.105 mol;stirring speed 763.986 rpm;stirring time of 59 min, and at temperature 51.73 degreeC.Copyright © 2023 The Authors.

IMPROVING PATIENT SAFETY THROUGH THE ESTABLISHMENT OF A PHARMACIST-LED BLOOD MONITORING CLINIC FOR JAK INHIBITORS IN RHEUMATOLOGY

BackgroundJanus kinase inhibitors drugs (JAKi) are novel small molecule medications known to cause abnormalities such as elevations in hepatic transaminases, decreases in neutrophil and lymphocyte counts and elevations in cholesterol and creatinine kinase. Blood monitoring is recommended and dose adjustments are advised if abnormalities arise. Recent warnings by the EMA and MHRA have highlighted the importance of monitoring these medications.Timely review and management of patients on JAKi drugs is difficult to maintain with increasing workload amongst the rheumatology team. A baseline audit (2020) demonstrated that hospital blood monitoring guidelines for JAKi drugs were not being followed. The rheumatology multidisciplinary team met and utilised Quality Improvement methodology including fish and driver diagrams to address this. This led to the creation of a pharmacist-led JAKi blood monitoring clinic.ObjectivesTo establish a pharmacist-led rheumatology blood monitoring clinic for the JAKi drug class in order to: increase patient safety with increased compliance to blood monitoring, save consultant/nurse time, improve communication with primary care on the frequency of blood testing required, increase patient understanding of the importance of blood monitoring with JAKi drugs, reinforce counselling advice such as risk of infections, shingles and thrombosis and promote medication adherence.MethodsThe clinic was established in March 2021. Patients commencing JAKi drugs are referred to the pharmacist-led clinic by the medical team. The pharmacist contacts the patient by phone following delivery of their medication. The patient is counselled on their new medication and dates for blood checks are agreed. A letter is sent to the patient and their GP providing this information. The patient is booked into virtual telephone appointments and bloods are monitored every month for the first 3 months and every 3 months thereafter. Any change or abnormality in blood results are flagged early in the patient's treatment and if necessary, discussed with the consultant. Adjustments are made to the patient's dose if appropriate.ResultsIn order to evaluate the benefit of the pharmacist clinic a re-audit of compliance with blood monitoring (March 2021- September 2022) was carried out alongside a patient satisfaction postal survey (August 2022).A total of 58 patients were sampled in the re-audit. The re-audit found an increase in compliance in blood monitoring since the introduction of the pharmacist clinic. 98% of patients had their full blood count performed at 3 months compared to 56% in audit 1 and 95% of patients had their lipid profile completed at 3 months compared to 15% in audit 1 (Table 1).A patient satisfaction survey (N=62, response rate 48%) found that 28 (93%) patients either agreed or strongly agreed that they were more aware of the importance of attending for regular blood monitoring when prescribed JAKi therapy as a result of the clinic.The pharmacy team made several significant interventions (self-graded Eadon grade 4 and 5). For example by improving medication adherence, detecting haematological abnormalities that required JAKi dose reduction, identifying patients suffering from infection requiring intervention including shingles and Covid-19.Table 1.Comparison of audit results pre (Audit 1) and post (Audit 2) clinic establishmentAudit 1 (N=48)Audit 2 (N=58)Number of patients with full blood count completed at weeks 4, 8 & 1227 (56%)57 (98%)Number of patients with lipid profile completed at week 127 (15%)55 (95%)Number of patients LFTs completed at weeks 4, 8 & 1226 (54%)54 (93%)ConclusionIntroduction of the pharmacist-led clinic has increased patient safety by ensuring compliance with blood monitoring as per hospital guidelines. The clinic has paved the way for improved communication with primary care teams and has provided patients with extra support during their first months on treatment with their JAKi. It has also expanded the role of the rheumatology pharmacy team and saved nursing and medical time.Acknowled ementsI wish to thank the SHSCT Rheumatology team for all their help, support and guidance with this project.Disclosure of InterestsNone Declared.

Novel Degree-Based Topological Descriptors of Fenofibrate Using M-Polynomial

Chemical graph theory is currently expanding the use of topological indices to numerically encode chemical structure. The prediction of the characteristics provided by the chemical structure of the molecule is a key feature of these topological indices. The concepts from graph theory are presented in a brief discussion of one of its many applications to chemistry, namely, the use of topological indices in quantitative structure-activity relationship (QSAR) studies and quantitative structure-property relationship (QSPR) studies. This study uses the M-polynomial approach, a newly discovered technique, to determine the topological indices of the medication fenofibrate. With the use of degree-based topological indices, we additionally construct a few novel degree based topological descriptors of fenofibrate structure using M-polynomial. When using M-polynomials in place of degree-based indices, the computation of the topological indices can be completed relatively quickly. The topological indices are also plotted. Using M-polynomial, we compute novel formulas for the modified first Zagreb index, modified second Zagreb index, first and second hyper Zagreb indices, SK index, SK1 index, SK2 index, modified Albertson index, redefined first Zagreb index, and degree-based topological indices.

Provision of Diet, Exercise, Cholesterol and Hemoglobin A1C Testing in Office Based Medical Visits Among Normal, Overweight, Obese, and Morbidly Obese Individuals in the US

Objectives: Obesity is a global epidemic and leads to complications such as diabetes and dyslipidemia. The objective of this study was to examine the provision of diet, exercise, cholesterol and HbA1c testing in office based medical visits among normal, overweight, obese, and morbidly obese individuals in the US. Method(s): The 2018 National Ambulatory Medical Care Survey data was used to conduct the study. Main outcome was provision of diet/nutrition, exercise, weight-reduction counseling, cholesterol and HbA1c testing in normal (BMI:18-25), overweight (BMI:25-30), obese (BMI:30 - 40), and morbidly obese (BMI:40+) individuals. A logistic regression model was fit to examine main outcomes by BMI status. Survey weights are assigned to the sample visits to obtain national estimates. All models were adjusted for confounders: race, ethnicity, age, gender, MSA, and insurance status. Odds ratios are reported to describe differences in overweight, obese, and morbidly obese patients compared to normal weight patients. Result(s): The weighted study sample consisted of 496,622,621 outpatient visits primarily white (84%), male (58%), covered by private insurance (57%). Multivariate analysis reveals that overweight, obese, and morbidly obese individuals received more HbA1c tests (OR, 1.02;CI, 1.01-1.03;OR, 3.47;CI, 2.31-5.2;OR, 9.01;CI, 4.88-16.66), and lipid profile tests (OR, 1.56;CI, 1.01-2.41;OR, 1.88;CI, 1.32-2.67;OR, 2.16;CI, 1.20-3.90) compared to normal weight patients. Similar trends were observed in the provision of diet/nutrition, exercise, and weight reduction counseling services (OR, 3.31;CI, 1.49 -7.35;OR, 7.51;CI, 2.85 -19.76;OR, 18.47;CI, 7.40- 46.10). Conclusion(s): Our study findings suggest that at risk individuals receive more weight-related services, such as testing for diabetes, cholesterol, diet, exercise, and weight reduction education compared to normal weight individuals. This study forms a baseline to examine disparity in provision of such services post-Covid (2019 and beyond) era given the disruption in the scarcity of health care professionals for such basic preventive services.Copyright © 2023

A prospective study to evaluate the role of cholesterol metabolism related genes expression in predicting clinical outcome of patients with severe COVID-19

Background/Objectives: Latest studies have stressed the relevance of cholesterol metabolism with susceptibility to COVID-19 and its severity. We have previously shown downregulation of low-density lipoprotein particle receptor pathway in severe COVID-19 patient surviving compared to non-surviving(1). We aimed to assess the over-time expression changes of its relevant genes in severe COVID-19 patients with different outcomes (survivors/ non-survivors). Method(s): Blood samples were taken from 39 severe COVID-19 patients without chronic diseases twice: on the day of admission to the intensive care (T1) and in one week (T2). Within 30-day follow-up 18 patients recovered and 21 patients died. 20 individuals never previously infected with COVID-19 were also enrolled. Expression levels of studied genes in peripheral blood lymphocytes were analyzed by real-time PCR with TaqMan assay. Result(s): Increased expression of STAB1 at T2, PPARgamma at T1 and CD36 at T1 and T2 were revealed in COVID-19 patients regardless of the outcome compared to controls (p < 0.05). Interesting, that in respective groups of COVID-19 patients increased STAB1, decreased PPARgamma and in survivors decreased LRP6 expression were revealed at T2 compared to T1 (p < 0.01). Also, STAB1 expression was decreased in survivors compared to non-survivors at T2 (p=0.017). Conclusion(s): Our study revealed, that patients with severe COVID-19 are characterized by increased expression of cholesterol metabolism related genes, withmore pronounced decrease of expression of these genes over time for survivors. Increased STAB1 expression may be considered as a predictor of poor COVID-19 prognosis.

Telemedicine for Optimizing Secondary Prevention in Coronary Artery Bypass Grafting Patients during COVID-19 Pandemic.

(1) Background: The COVID-19 pandemic has introduced a major disruption to the delivery of secondary prevention measures in patients with established atherosclerotic cardiovascular disease (CVD). It required a rapid and widespread adoption of new medical services, including the use of telemedicine. This study aimed to examine the impact of COVID-19 on secondary prevention in patients with coronary artery bypass grafting (CABG) and to evaluate the effectiveness of the telemedicine application for the implementation of lifestyle change measures, remote monitoring, and treatment regimen adjustment; (2) Methods: This prospective study on 194 CABG patients evaluated three consecutive years between 2019 and 2022 in the pre-pandemic period by face-to-face visits and during the pandemic by teleconsultations or hybrid follow-up. Variables of interest were compared between four periods: pre-pandemic-pre-P (1 March 2019-29 February 2020), lockdown-Lock (1 March-31 August 2020), restrictive-pandemic-Restr-P (1 September 2020-28 February 2021), and relaxed-pandemic-Rel-P (1 March 2021-1 March 2022). (3) Results: The average values of the lipidogram, blood sugar, and uric acid increased during Lock and Restr-P, but, through the use of teleprevention, they returned to the pre-pandemic level or even below this level. The exception was blood sugar, which remained high in Rel-P. The number of newly diagnosed patients with diabetes also increased, with most of them having moderate forms of COVID. During Lock and Res-P, the percentage of obese, smoking, or hypertensive patients increased, but, through the use of teleprevention, we managed to reduce it, although it remained slightly higher than the pre-pandemic level. Physical activity decreased in the first year of the pandemic, but, in Rel-P, CABG patients became more active than before the pandemic (4) Conclusions: The use of telemedicine for cardiovascular secondary prevention allowed us to not only continue seeing CABG patients but, also, to adjust their medication and to expand cardiovascular preventive counseling and testing with favorable results, especially during the second year of the pandemic.

Barriers and shortcomings in access to cardiovascular management and prevention for familial hypercholesterolemia during the COVID-19 pandemic.

Familial hypercholesterolemia (FH) is a hereditary condition caused by mutations in the lipid pathway. The goal in managing FH is to reduce circulating low-density lipoprotein cholesterol and, therefore, reduce the risk of developing atherosclerotic cardiovascular disease (ASCVD). Because FH patients were considered high risk groups due to an increased susceptible for contracting COVID-19 infection, we hypothesized whether the effects of the pandemic hindered access to cardiovascular care. In this review, we conducted a literature search in databases Pubmed/Medline and ScienceDirect. We included a comprehensive analysis of findings from articles in English related and summarized the effects of the pandemic on cardiovascular care through direct and indirect effects. During the COVID-19 pandemic, FH patients presented with worse outcomes and prognosis, especially those that have suffered from early ASCVD. This caused avoidance in seeking care due to fear of transmission. The pandemic severely impacted consultations with lipidologists and cardiologists, causing a decline in lipid profile evaluations. Low socioeconomic communities and ethnic minorities were hit the hardest with job displacements and lacked healthcare coverage respectively, leading to treatment nonadherence. Lock-down restrictions promoted sedentary lifestyles and intake of fatty meals, but it is unclear whether these factors attenuated cardiovascular risk in FH. To prevent early atherogenesis in FH patients, universal screening programs, telemedicine, and lifestyle interventions are important recommendations that could improve outcomes in FH patients. However, the need to research in depth on the disproportionate impact within different subgroups should be the forefront of FH research.

Hydroxypropyl-ß-Cyclodextrin Depletes Membrane Cholesterol and Inhibits SARS-CoV-2 Entry into HEK293T-ACEhi Cells.

Vaccination has drastically decreased mortality due to coronavirus disease 19 (COVID-19), but not the rate of acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Alternative strategies such as inhibition of virus entry by interference with angiotensin-I-converting enzyme 2 (ACE2) receptors could be warranted. Cyclodextrins (CDs) are cyclic oligosaccharides that are able to deplete cholesterol from membrane lipid rafts, causing ACE2 receptors to relocate to areas devoid of lipid rafts. To explore the possibility of reducing SARS-CoV-2 entry, we tested hydroxypropyl-ß-cyclodextrin (HPßCD) in a HEK293T-ACE2hi cell line stably overexpressing human ACE2 and Spike-pseudotyped SARS-CoV-2 lentiviral particles. We showed that HPßCD is not toxic to the cells at concentrations up to 5 mM, and that this concentration had no significant effect on cell cycle parameters in any experimental condition tested. Exposure of HEK293T-ACEhi cells to concentrations of HPßCD starting from 2.5 mM to 10 mM showed a concentration-dependent reduction of approximately 50% of the membrane cholesterol content. In addition, incubation of HEK293T-ACEhi cells with HIV-S-CoV-2 pseudotyped particles in the presence of increasing concentrations of HPßCD (from 0.1 to 10 mM) displayed a concentration-dependent effect on SARS-CoV-2 entry efficiency. Significant effects were detected at concentrations at least one order of magnitude lower than the lowest concentration showing toxic effects. These data indicate that HPßCD is a candidate for use as a SARS-CoV-2 prophylactic agent.

The CH24H metabolite, 24HC, blocks viral entry by disrupting intracellular cholesterol homeostasis.

Cholesterol-24-hydroxylase (CH24H or Cyp46a1) is a reticulum-associated membrane protein that plays an irreplaceable role in cholesterol metabolism in the brain and has been well-studied in several neuro-associated diseases in recent years. In the present study, we found that CH24H expression can be induced by several neuroinvasive viruses, including vesicular stomatitis virus (VSV), rabies virus (RABV), Semliki Forest virus (SFV) and murine hepatitis virus (MHV). The CH24H metabolite, 24-hydroxycholesterol (24HC), also shows competence in inhibiting the replication of multiple viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). 24HC can increase the cholesterol concentration in multivesicular body (MVB)/late endosome (LE) by disrupting the interaction between OSBP and VAPA, resulting in viral particles being trapped in MVB/LE, ultimately compromising VSV and RABV entry into host cells. These findings provide the first evidence that brain cholesterol oxidation products may play a critical role in viral infection.

Acute Pancreatitis Following a Lower Extremity Angioplasty

Introduction: Acute pancreatitis affects a significant population globally. Usual etiologies are gallstones, alcohol, hypertriglyceridemia, medications;less frequent are trauma, hypercalcemia, infections, toxins, ischemia, anatomic anomalies, vasculitis, and idiopathic. Pancreatitis post coronary intervention is an uncommon cause with only 19 published cases in the last two decades. Being cognizant of this etiology is important given the increasing number of patients undergoing angiography. Case Description/Methods: An 81-year-old female with hypertension, diabetes, peripheral arterial disease, prior cholecystectomy underwent left lower extremity angioplasty at an outside center. Within a few hours, she started having severe epigastric pain radiating to her back, nausea, vomiting and loose bloody stool. She presented to the emergency department 24 hours after symptom onset. Epigastric tenderness was present on exam. Labs revealed leukocytosis (24,450/muL), elevated lipase (1410 U/L), elevated creatinine (1.3 mg/dL), lactate (3.1 mmol/L), calcium 9.4 mg/dL and triglycerides 161 mg/dL. Incidentally, found to be positive for COVID-19. Normal common bile duct diameter seen on sonogram. CT angiogram of the abdomen/pelvis showed acute pancreatitis, duodenal and central small bowel enteritis (Figure). She was not on any medications known to cause pancreatitis and denied alcohol use. Patient improved with analgesics and intravenous fluids. She had no recurrence of bloody stools and hemoglobin remained stable. On day 4, she was able to tolerate a regular diet, and leukocyte count and creatinine normalized. Patient did not have any COVID respiratory symptoms, and was discharged. Discussion(s): Given the temporal association to angioplasty and no other identifiable cause, acute pancreatitis was presumed to be due to the contrast used during angioplasty. Other possibilities included cholesterol embolism but no peripheral signs of cholesterol embolism were seen. Patient was an asymptomatic COVID-19 case. Although, there are case series of pancreatitis due to COVID, those were found in very sick symptomatic patients. On review of literature, cholesterol embolism was identified as a definite cause only on autopsy or laparotomy (Table). Other possible mechanisms are: high viscosity of the contrast media leading to ischemia and necrosis, contrast causing NF-kB activation followed by epithelial damage, and vasospasm. Pancreatitis after coronary angiography is rare, nonetheless, an important differential especially if there is a temporal relationship.

Metabolic risks and prognosis of COVID-19: are dietary patterns important?

PurposeThis study aims to identify the dietary patterns of two groups of subjects (with and without COVID-19), and to assess the relationship of findings with the prognosis of COVID-19 and metabolic risk parameters.Design/methodology/approachThis study included 100 individuals in the age range of 19–65 years. The medical history, and data on biochemical, hematological and inflammatory indicators were retrieved from the files. A questionnaire for the 24-h food record and the food intake frequency was administered in face-to-face interviews, and dietary patterns of subjects were assessed.FindingsIn individuals with COVID-19, the hip circumference, the waist-hip ratio and the body fat percentage were significantly higher (p < 0.05), and the muscle mass percentage was significantly lower (p < 0.05). Mediterranean diet adherence screener (MEDAS), dietary approaches to stop hypertension (DASH) and healthy eating ındex-2015 (HEI-2015) scores were low in the two groups. A linear correlation of DASH scores was found with the muscle mass percentage (p = 0.046) and a significant inverse correlation of with the body fat percentage (p = 0.006). HEI-2015 scores were significantly and negatively correlated with body weight, body mass index, waist circumference, hip circumference and neck circumference (p < 0.05). Every one-unit increase in MEDAS, DASH and HEI-2015 scores caused reductions in C-reactive protein levels at different magnitudes. Troponin-I was significantly and negatively correlated with fruit intake (p = 0.044), a component of a Mediterranean diet and with HEI-2015 total scores (p = 0.032).Research limitations/implicationsThe limitation of this study includes the small sample size and the lack of dietary interventions. Another limitation is the use of the food recall method for the assessment of dietary patterns. This way assessments were performed based on participants' memory and statements.Practical implicationsFollowing a healthy diet pattern can help reduce the metabolic risks of COVÍD-19 disease.Originality/valueDespite these limitations, this study is valuable because, to the best of the authors' knowledge, it is the first study demonstrating the association of dietary patterns with disease prognosis and metabolic risks concerning COVID-19. This study suggests that dietary patterns during the COVID-19 process may be associated with several metabolic risks and inflammatory biomarkers.

Comprehensive medication management services provided via telehealth or hybrid models: A scoping review

Comprehensive medication management (CMM) is increasingly provided by health care teams through telehealth or hybrid modalities. The purpose of this scoping literature review was to assess the published literature and examine the economic, clinical, and humanistic outcomes of CMM services provided by pharmacists via telehealth or hybrid modalities. This scoping review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for Scoping Reviews. Randomized controlled trials (RCTs) and observational studies were included if they: reported on economic, clinical, or humanistic outcomes;were conducted via telehealth or hybrid modalities;included a pharmacist on their interprofessional team;and evaluated CMM services. The search was conducted between January 1, 2000, and September 28, 2021. The search strategy was adapted for use in Medline (PubMed);Embase;Cochrane;Cumulative Index to Nursing and Allied Health Literature;PsychINFO;International Pharmaceutical s;Scopus;and grey literature. Four reviewers extracted data using a screening tool developed for this study and reviewed for risk of bias. Authors screened 3500 articles, from which 11 studies met the inclusion criteria (9 observational studies, 2 RCTs). In seven studies, clinical outcomes improved with telehealth CMM interventions compared to either usual care, face-to-face CMM, or educational controls, as shown by the statistically significant changes in chronic disease clinical outcomes. Two studies evaluated and found increased patient and provider satisfaction. One study described a source of revenue for a telehealth CMM service. Overall, study results indicate that telehealth CMM services, in select cases, may be associated with improved clinical outcomes, but the methods of the included studies were not homogenous enough to conclude that telehealth or hybrid modalities were superior to in-person CMM. To understand the full impact on the Quadruple Aim, additional research is needed to investigate the financial outcomes of CMM conducted using telehealth or hybrid technologies.Copyright © 2022 Pharmacotherapy Publications, Inc.

A Case of Ocular Myasthenia Gravis Seen by Rheumatology as Suspected Mononeuritis Multiplex in an Adult Male Shortly after Pfizerbiontech Sars-Cov-2 Vaccination

Background/Aims Myasthenia gravis (MG) is an antibody-mediated autoimmune disease targeting proteins at the postsynaptic membrane of the neuromuscular junction. MG is thought to occur in genetically susceptible individuals following an environmental trigger. SARS-CoV-2 infection has been associated with new-onset autoimmune disease, new-onset MG, and exacerbations of pre-existing MG, with molecular mimicry between SARS-CoV-2 epitopes and autoantigen-induced autoreactivity thought to be part of the underlying mechanism. We report a case of newonset ocular MG following first dose Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination which was referred to rheumatology as suspected mononeuritis multiplex. Methods A 53-year-old man of East Asian ethnicity presented to the emergency department (ED) with sudden onset diplopia and left lateral gaze restriction 7 days after receiving his first dose of the Pfizer-BioNTech BNT162b2 SARS-COV2 vaccination. He had longstanding myopia and dry eyes but no other medical history, no regular medications or significant family history. He was a current smoker, with a 50-pack year history. He did not drink alcohol or use any recreational drugs. He was found to have an isolated left VI cranial nerve (CN) palsy with an otherwise normal ocular and physical examination. Blood tests were unremarkable apart from raised cholesterol, and he was discharged with a suspected self-limiting microvascular CN lesion. Three weeks later he presented to ED with worsening diplopia, increasingly restricted eye movements, headache, nausea, vomiting and blurred vision. Ophthalmology assessment noted new right sided CN III and VI palsy, persistent left CN VI palsy, and vertical diplopia in all fields of gaze. Neurological and physical examination were normal. Bloods including an autoimmune screen were unremarkable. SARS-CoV-2 Spike antibodies were positive consistent with SARS-CoV-2 vaccination but not infection. Intracranial and thoracic imaging were unremarkable. He was referred to and seen by both rheumatology and neurology as a case of suspected mononeuritis multiplex. Results A diagnosis of ocular MG was confirmed with positive serum acetylcholine receptor antibodies, and he was started on prednisolone, and pyridostigmine to good effect. Daily forced vital capacity (FVC) showed no respiratory muscle involvement, and nerve conduction studies and electromyography were normal, excluding secondary generalisation. Conclusion A review of the literature found 14 reported cases of new-onset MG all within 4 weeks following SARS-CoV-2 vaccine. Whilst these cases provide interesting insights into the pathogenesis of autoimmune conditions such as MG, they are not epidemiological studies to inform vaccine safety. Ultimately, current evidence suggests that the risks of SARS-COV-2 infection outweigh the risk of vaccine-related adverse events, therefore we suggest clinicians should be aware of potential new-onset autoimmune conditions, but support the safety of SARSCOV2 vaccination. Further, research into possible immunological mechanisms behind this phenomenon, including identifying potential epitopes inducing molecular mimicry, could help establish the likelihood of a causative link.

Cardiometabolic and psychocognitive features of the post-COVID period in patients with atrial fibrillation

The number of people with long-term consequences of COVID-19 is increasing worldwide. The long-term prognosis for patients remains poorly understood. Objective. To study cardiometabolic and psychocognitive features in comorbid elderly patients with atrial fibrillation (AF), de-pending on the presence of post-COVID syndrome (PCS). Material and methods. The observational analytical cohort study included 223 patients with AF and comorbidity (coronary artery disease, hypertension, obesity, type 2 diabetes mellitus) aged 60-74, who were divided into two groups: group 1 included 123 patients without COVID-19 and group 2 included 110 patients with a history of COVID-19 and the presence of PCS. The study evaluated laboratory and instrumental tests, and a general clinical study assessing psychocognitive disorders using the SPMSQ and HADS questionnaires was conducted. Results and discussion. In COVID-19 survivors, compared with patients of group 1, there were more pronounced atherogenic changes in total cholesterol (TC) (p=0.003), low-density lipoprotein cholesterol (p<0.001), and triglycerides (p=0.011). Lower dia-stolic blood pressure was found in COVID-19 survivors (p<0.001). In addition, patients in group 2 had higher median pulse pressure (p<0.001) and heart rate (p<0.001). In group 2 patients, a larger ascending aorta diameter was observed (p<0.001). The anx-iety-depressive syndrome was more common in COVID-19 survivors with comorbidities, and a statistically significant difference was found in clinical anxiety (24%, p=0.041) and subclinical depression (21%, p=0.015). When assessing cognitive function, mod-erate cognitive impairment was detected in 22% (p=0.005) of patients with PCS and severe cognitive impairment in 2% (p=0.007). Conclusion. In comorbid elderly patients with the post-COVID syndrome, a high prevalence of psychocognitive disorders and adverse cardiometabolic changes were observed, supporting the need for long-term monitoring of the general clinical condition and psychocognitive status of COVID-19 survivors.Copyright © 2023, Media Sphera Publishing Group. All rights reserved.

Collapsing glomerulonephritis in a COVID-19 patient. Case report

Acute renal injury due to collapsing glomerulonephritis is associated with high morbidity and mortality, requiring chronic dialysis, COVID-19 is one of its causes. A 17-year-old male patient presented with a four-month history of edema, foamy urine and reduction in the urine flow;anasarca was observed at physical examination. Laboratory values showed creatinine 4,2 mg/dl;albumin 1,9 gr/dl;cholesterol and triglycerides were high;proteinuria 6,7 gr/24h: leucocyturia and hematuria with negative urine culture. Serologies for HIV, syphilis and hepatitis were negative. Studies for systemic lupus were negative. An antigenic test for SARS-CoV-2 was positive as well as an IgG. Renal Biopsy showed Focal and Segmental Glomerulosclerosis, Collapsing variant. He received corticosteroids and cyclosporine. Creatinine improved;proteinuria remained >3 gr/24 hours.Copyright © Universidad Peruana Cayetano Heredia, Facultad de Medicina Alberto Hurtado. All Rights Reserved.

What the Eye Cannot See: A Case of Persistent Altered Mental Status in a Patient With Cholestatic Liver Disease?

Introduction: Altered mental status (AMS) is a common symptom in patients with liver disease with a wide list of differential diagnoses. Knowledge of etiologies of AMS unique to patients with hepatic dysfunction is vital in order to help recognize, diagnose, and treat the underlying cause in a timely manner. Case Description/Methods: A 46-year-old man with a history of recent COVID infection was transferred to our hospital for further evaluation of acute liver injury and AMS. On arrival, his labs were notable for AST of 408 U/L, ALT of 620 U/L, ALP of 5942 U/L, TB of 11.0 mg/dL, and an INR of 1.1. His work-up included an MRCP that showed segmental biliary ductal dilation with associated restricted diffusion and peribiliary enhancement concerning for sclerosing cholangitis. ERCP revealed a 3cm biliary cast that was removed and noted diffuse rarefaction of ducts throughout the entire biliary tree. A liver biopsy revealed centrizonal cholestasis with portal-based bile ductular reaction and mild bile duct injury. Despite adequate treatment of suspected infection and hepatic encephalopathy, his AMS persisted. His basic metabolic panel (BMP) was notable for Na of 143 mEq/L. A send-out lipid panel that was obtained to work-up his dyslipidemia revealed a total cholesterol of 1018 mg/dL, triglycerides of 420mg/dL, and the presence of lipoprotein X. A venous blood gas (VBG) was obtained showing a Na of 157 mEq/L and serum osmolality was 322 mmol/kg, confirming true hypernatremia. He was slowly treated with hypotonic solutions with significant improvement in his mentation. On follow-up one year later, he has persistent cholestasis and is currently being considered for liver transplant. Discussion(s): The final diagnosis was COVID-related ischemic cholangitis and disappearing bile ducts with persistent cholangiopathy, presenting with severe cholestasis, accumulation of lipoprotein X, and pseudonormonatremia. When faced with severe cholestatic liver disease, clinicians should keep in mind the possibility of accumulation of lipoprotein X and its association with hyperviscosity and spurious electrolyte abnormalities. Clinicians should rely on obtaining blood gas analyses for accurate electrolyte measurement in such cholestatic patients as blood gas analyses utilize direct ion-sensitive electrodes (ISE) to measure electrolytes, whereas routine basic metabolic panels utilize indirect ISE that are liable to spurious results in the presence of hyperlipoproteinemia/lipoprotein X.