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

Variation in Demographic Characteristics, Socioeconomic Status, Clinical Presentation and Selected Treatments in Mortality Among Patients with a Diagnosis of COVID-19 in the United States

Objectives: COVID-19 infected over 150 million people and caused over 1 million deaths in the US. This study evaluates several variables thought to be associated with mortality risk in the COVID-19 population. Method(s): The IQVIA longitudinal medical and pharmacy claims databases identified 17,682,111 patients with a COVID-19 diagnosis between 4/1/2020-4/30/2022 from a population of >277 million patients in the US. Patients were linked to Veritas Data Research fact-of-death records (90% complete compared to CDC reporting) and confirmed deaths were flagged. Confirmed mortality rates (CMR) were evaluated by age group, socioeconomic status (SES) using the Area Deprivation Index (v2.0, University of Wisconsin, 2015), co-morbidities and COVID-specific (approved and unapproved) treatments. Result(s): Of the 563,744 patients (3.2%) identified as dead (3.67% in men, 2.85% in women overall), CMR was lowest in patients aged 0-17 (0.08%), highest in age 65-75 (5.92%) and >75 (16.40%). Patients in the lowest 40% of SES had CMR of 4.43% while in the highest 20% was 1.56%. Respiratory failure, pneumonia and sepsis were the most common acute diagnoses accompanying COVID-19 deaths in all SES. In patients with comorbid dementia or Alzheimer's disease, CMR were 21.62% and 23.40% respectively. Additionally, congestive heart failure (15.79%), atrial fibrillation (15.50%), chronic kidney disease (15.30%) and COPD (12.19%) were associated with high CMR. Among patients receiving approved therapies, casirivimab/imdevimab and remdesivir had CMR of 1.41% and 12.63% respectively, while for those receiving unapproved therapies, ivermectin and hydroxychloroquine had CMR of 2.54% and 2.45%. Conclusion(s): Compared to the 1.1% case-mortality rate (Johns Hopkins 2023) among US COVID-19 patients, we found CMR exceeded 3% among those with a medical claim for COVID-19. Advanced age, dementia, and cardio-renal disease were associated with mortality. Patients with the lowest SES had approximately 3 times the confirmed mortality rate compared to those in the highest SES group.Copyright © 2023

Rapid exchange of a percutaneous gastrostomy tube during an early episode of COVID-19

We retrospectively report a case of rapid exchange of a percutaneous radiologic gastrostomy tube (balloon-occluded type catheter) via off-label use of a pigtail catheter for nutrition supply during a very early episode of coronavirus disease 2019 (COVID-19) in an outpatient clinic. This case demonstrates that minimally invasive percutaneous procedures might be provided safely and effectively under appropriate precautions for preventing COVID-19 transmission during the pandemic.Copyright © 2023, Society of Gastrointestinal Intervention.

Dementia and COVID-19

While both dementia and coronavirus disease 2019 (COVID-19) have differing etiology, there is a complex interplay between the two, especially when looking into their effects on certain sub-populations. Hispanic Americans face a higher burden of dementia and COVID-19 due to both modifiable and unmodifiable risk factors, age-related chronic diseases, and environmental factors. The major unmodifiable risk factors include increasing age and predisposing genetics, while the major modifiable risk factors include income/socioeconomic status, educational attainment, exercise, diet, and smoking/tobacco use. Furthermore, specific age-related chronic diseases such as diabetes, kidney disease, hypercholesterolemia, cardiovascular disease, and chronic lung diseases place Hispanic Americans at high risk for dementia and COVID-19. Lastly, Hispanic Americans face the additional disadvantage of environmental factors, such as social inequalities and lack of access to adequate healthcare resources. Given that Hispanic Americans are the largest racial/ethnic minority group within the United States, this chapter will focus upon the research associated with dementia and COVID-19 within the Hispanic American population of the United States. Furthermore, this chapter will explore the four major risk factor categories (unmodifiable risk factors, modifiable risk factors, age-related chronic diseases, and environmental factors), which contribute to the development of dementia and COVID-19 within the Hispanic American population of the United States. © 2023 Elsevier Inc. All rights reserved.

Women and Alzheimer's disease risk: a focus on gender

A previous chapter highlighted the biological mechanisms by which female sex contributes to Alzheimer's disease (AD) risk and outcomes. However, discussion of AD in women is incomplete without considering the impact of female gender on AD risk, as gender encompasses psychosocial and cultural differences between women and men that also modulate risk for cognitive decline. The current chapter discusses several main social determinants of health and explains how women, as a historically oppressed population, may be particularly vulnerable to the effect of each on cognition. This chapter also considers the disproportionate female burden of dementia caregiving, how associated stresses augment risk for later cognitive decline among caregivers themselves, and how the COVID-19 pandemic may add to this risk. Understanding the gender-specific factors that affect AD risk and disease progression is essential for developing targeted preventative interventions and treatments. Future research is necessary to better characterize how social determinants of health uniquely impact female cognition compared to males. Moreover, future studies focused on gender identities outside of the male–female binary are critical to developing a holistic understanding of how gender may impact late-life cognition. © 2023 Elsevier Inc. All rights reserved.

Women and Alzheimer's disease

Approximately, two-thirds of individuals with Alzheimer's disease (AD) are women. Though previously attributed to differences in lifespan, accumulating evidence suggests that the reasons for the higher prevalence of AD in women are multifactorial and related to differences in risk factors, biomarkers, and neuropathology. Sex also contributes to significant disease heterogeneity, which has important implications for prevention and treatment. This chapter discusses the evidence for sex differences in AD, with an emphasis on disease presentation, biomarkers, pathophysiology, progression, and risk. Women tend to present later in the disease course and with different clinical features, progress faster, and are disproportionately affected by the APOE-ϵ4 risk allele and AD neuropathologic changes. Lifetime estrogen exposure, pregnancy, and menopause also affect a woman's risk for cognitive decline later in life. Despite such differences, women are dramatically underrepresented in pharmacologic randomized control trials, leading to significant gaps in knowledge regarding the most effect AD treatment strategies for women. Both researchers and providers need to be aware of sex differences in AD risk, presentation, and outcomes to develop sex-specific prevention and treatment strategies, as well as provide optimum healthcare to women as they age. © 2023 Elsevier Inc. All rights reserved.

The effects of lifestyle in Alzheimer's disease during the COVID-19 pandemic

Alzheimer's disease (AD) is a multifactorial neurodegenerative disease affected by multiple elements such as exercise, food, and social stimulation. Research has demonstrated the positive effects of exercise such as community-based programs and aerobic activities in reducing rates of decline in cognition. Another protective measure is avoiding red meat and alcohol and instead incorporating a Mediterranean diet to reduce inflammation and inhibit free radicals. Finally, social stimulation can serve to reduce the progression of the disease by increasing a sense of connection and meaningful purpose. COVID-19 has made it difficult for AD patients, especially those living in nursing homes or advanced facilities, to participate in exercise classes due to restrictions, to eat a fresh diet due to resource shortages, and to see friends and family due to social distancing. This chapter delves into the effects of COVID-19 on elements such as physical activity, diet, and social interaction on the disease progression of AD. © 2023 Elsevier Inc. All rights reserved.

A comprehensive review on technological advances in alternate drug discovery process:Drug repurposing

The traditional de novo drug discovery is time consuming, costly and in some instances the drugs will fail to treat the disease which result in a huge loss to the organization. Drug repurposing is an alternative drug discovery process to overcome the limitations of the De novo drug discovery process. Ithelps for the identification of drugs to the rare diseases as well as in the pandemic situationwithin short span of time in a cost-effective way. The underlying principle of drug repurposing is that most of the drugs identified on a primary purpose have shown to treat other diseases also. One such example is Tocilizumab is primarily used for rheumatoid arthritis and it is repurposed to treat cancer and COVID-19. At present, nearly30% of the FDA approved drugs to treat various diseases are repurposed drugs. The drug repurposing is either drug-centric or disease centric and can be studied by using both experimental and in silico studies. The in silico repurpose drug discovery process is more efficient as it screens thousands of compounds from the diverse libraries within few days by various computational methods like Virtual screening, Docking, MD simulations,Machine Learning, Artificial Intelligence, Genome Wide Association Studies (GWAS), etc. with certain limitations.These limitationscan be addressed by effective integration of advanced technologies to identify a novel multi-purpose drug.Copyright © 2023, Association of Biotechnology and Pharmacy. All rights reserved.

Effect of COVID-19 on Alzheimer's and dementia measured through ocular indications

Screening for early detection of Alzheimer's disease (AD) through a comprehensive eye exam appears to be promising and could potentially provide a more sensitive, inexpensive way to visualize early signs of AD for early detection in large populations. Optical coherence tomography (OCT), as well as retinal imaging techniques such as Doppler and fluorescence lifetime imaging ophthalmoscopy (FLIO), can detect signs of early AD such as vascular changes or accumulations of Tau proteins and beta-amyloid proteins. In the age of COVID-19, this screening opportunity is threatened by increased no-show rates leading to decreased early detection of AD. Through the combination of COVID-19 neuroinflammation potentially augmenting AD neurodegeneration, as well as missed opportunity in the use of early ophthalmic detection, the pandemic may have significantly worsened the trajectory of AD. © 2023 Elsevier Inc. All rights reserved.

[COVID-19, neuroCOVID-19 and cognitive impairment in elderly and old patients (literature review).]

The new coronavirus infection COVID-19 causes damage to many organs and systems, is a multi-organ disease. Many researchers are studying the relationship of the new coronavirus infection with polymorbid pathology, frailty, sarcopenia. The SARS-CoV-2 virus has the property of neurotropism, therefore, olfactory, taste disorders, as well as cognitive impairments can join the spectrum of clinical manifestations and consequences of the disease. Alzheimer's disease is the most common cause of dementia in the world. It is of interest that there is a link between the coronavirus infection and the development of cognitive impairment, including Alzheimer's disease.

Alzheimer's disease and COVID-19.

In elderly patients with COVID-19 cognitive functions decline;it has been suggested that SARS-CoV-2 infection may lead to the development of Alzheimer's disease (AD) and other long-term neurological consequences. We review several parallels between AD and COVID-19 in terms of pathogenetic mechanisms and risk factors. Possible mechanisms through which COVID-19 can initiate AD are discussed. These include systemic inflammation, hyperactivation of the renin-angiotensin system, innate immune activation, oxidative stress, and direct viral damage. It has been shown that increased expression of angiotensin-renin receptors (ACE2) may be a risk factor for COVID-19 in patients with AD. When entering the central nervous system, the SARS-CoV-2 virus can directly activate glial cell-mediated immune responses, which in turn can lead to the accumulation of beta-amyloid and the subsequent onset or progression of current AD. The involvement of inflammatory biomarkers, including interleukins (IL): IL6, IL1, as well as galectin-3, as a link between COVID-19 and AD is discussed. The rationale for the use of memantine (akatinol memantine) in patients with COVID-19 in order to prevent the development of cognitive deficits is discussed. Memantine has been shown to have a positive effect on neuroinflammatory processes in the onset or exacerbation of cognitive deficits, in reducing cerebral vasospasm and endothelial dysfunction in viral infections. Memantine therapy may improve everyday activity and reduce the risk of severe SARS-CoV-2 infection.Copyright © 2022 Ima-Press Publishing House. All rights reserved.

Automated Prognosis of Alzheimer's Disease using Machine Learning Classifiers on Spontaneous Speech features

Early prediction of Alzheimer's disease and related Dementia has been a great challenge. Recently, preliminary research has shown that neurological symptoms in Covid-19 patients may accelerate the onset of Alzheimer's disease. With such a further rise in Alzheimer's and related Dementia cases, having an early prediction system becomes vital. Speech can provide a non-invasive diagnostic marker for such neurodegenerative diseases. This work mainly focuses on studying significant temporal speech features extracted directly from the recordings of the Dementia bank dataset and applying Machine Learning algorithms to classify the Alzheimer's disease related Dementia Group and the healthy control group. The result shows that Support Vector Machine outperformed other machine learning algorithms with an accuracy of 87%. Compared to prior research, which used manual transcriptions provided with the dataset, this study used audio recordings from the Dementia bank dataset and an advanced Automatic Speech Recognizer to extract speech features from the audio recordings. Furthermore, this method can be applied to the spoken responses of subjects during a neuropsychological assessment. © 2023, Ismail Saritas. All rights reserved.

Surgical and nonsurgical interventions for Alzheimer's disease

Over the years, many surgical and nonsurgical interventions have been adapted to manage Alzheimer's disease (AD). While many of these tools were developed to primarily treat other neurological conditions, increased understanding of AD pathology has opened up new opportunities to apply established techniques in novel fashions. This chapter discusses neurosurgical interventions for AD especially in the context of the coronavirus pandemic. © 2023 Elsevier Inc. All rights reserved.

QSAR and DFT Studies of Some Tacrine-Hydroxamate Derivatives as Inhibitors of Cholinesterase (AChEs) in the Treatment of Alzheimer's Disease

Introduction: This work was devoted to an in silico investigation conducted on twenty-eight Tacrine-hydroxamate derivatives as a potential treatment for Alzheimer's disease using DFT and QSAR modeling techniques. Method(s): The data set was randomly partitioned into a training set (22 compounds) and a test set (6 compounds). Then, fourteen models were built and were used to compute the predicted pIC50 of compounds belonging to the test set. Result(s): Al built models were individualy validated using both internal and external validation methods, including the Y-Randomization test and Golbraikh and Tropsha's model acceptance criteria. Then, one model was selected for its higher R2, R2test, and Q2cv values (R2 = 0.768, R2adj = 0.713, MSE = 0.304, R2test=0.973, Q2cv = 0.615). From these outcomes, the activity of the studied compounds toward the main protease of Cholinesterase (AChEs) seems to be influenced by 4 descriptors, i.e., the total dipole moment of the molecule (mu), number of rotatable bonds (RB), molecular topology radius (MTR) and molecular topology polar surface area (MTPSA). The effect of these descriptors on the activity was studied, in particular, the increase in the total dipole moment and the topological radius of the molecule and the reduction of the rotatable bond and topology polar surface area increase the activity. Conclusion(s): Some newly designed compounds with higher AChEs inhibitory activity have been designed based on the best-proposed QSAR model. In addition, ADMET pharmacokinetic properties were carried out for the proposed compounds, the toxicity results indicate that 7 molecules are nontoxic.Copyright © 2023 Bentham Science Publishers.

Benefits of Breastfeeding on Child and Postpartum Psychological Health of the Mother

Ab s t r ac t Aim: The aim of this study was to summarize different types of benefits that have been observed in the baby's development and the mother's psychological health during the postpartum period. Background(s): Breastfeeding is a natural process that plays a vital role in the physical as well as mental health of the mother and child. Breast milk is rich in contents such as proteins, fats, and vitamins, which are responsible for building the immune system of the baby. Lactation helps in decreasing the prevalence of infant mortality rate. It enhances the development of the physical health of the children. Breastfeeding protects the mother from many systemic conditions like endometrial cancer, ovarian cancer, breast cancer, etc. It has been observed that with an increase in healthy breastfeeding practices, there is a decline in the cases of maternal mental health issues reported mainly in the postpartum period. Review result: The authors have explained various types of advantages of breastfeeding on the child's and mother's health, their mechanism of action, effects on the baby, and mother-child relationship. Conclusion(s): The mother's mental health plays a crucial role in a healthy infant, and breastfeeding is key to it. The role of breastfeeding is therefore considered a boon for the mother because if there is a decrease in health issues in the child, the mother's mental condition improves automatically. Therefore, breastfeeding should be promoted at the national level. Clinical significance: Breastfeeding not only helps in reducing maternal stress and postpartum depression but also improves the physical health of the child and mother during the postpartum period. The clinicians should teach mothers about the importance and also the correct positions of breastfeeding. "Breastfeeding week" is celebrated every year from August 1 to August 7, as implemented by the Indian government.Copyright © The Author(s). 2023 Open Access.

Blood brain barrier disruption following COVID-19 infection and neurological manifestations

Neurological manifestations have been reported following infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The presence of SARS-CoV-2 in brains of affected individuals has been documented. However, the exact route of entry into the brain and subsequent post-infection consequences are not fully understood. Blood–brain barrier (BBB) is an interface between systemic circulation and central nervous system (CNS) that strictly regulates entry of specific molecules from blood to the brain. The functional component of BBB is neurovascular unit (NVU) and any alterations in the structure or function of BBB is detrimental to the CNS functions. Evidence suggests that SARS-CoV-2 infection disrupts BBB integrity and functions directly or indirectly. This chapter highlights the likely mechanisms involved in entry of SARS-CoV-2 into the brain. Further, the alterations in BBB have been implicated in neurological symptoms observed in SARS-CoV-2 patients. Moreover, systemic inflammation and other peripheral factors post infection also contribute to the disruption of BBB. The key protein of SARS-CoV-2, spike protein (S1) induces significant alterations in BBB properties. Entry of S1 protein into brain triggers a proinflammatory cascade that affects BBB integrity. Therefore, understanding the pathophysiological mechanisms in BBB dysfunction and subsequent neurological manifestations along with long-term effects on brain particularly Alzheimer's disease (AD) following coronavirus disease 2019 (COVID-19) is of utmost importance. © 2023 Elsevier Inc. All rights reserved.

NEI 2022 Abstracts

The proceedings contain 96 papers. The topics discussed include: practical pharmacotherapy for opioid use disorder in the age of fentanyl;can COVID-19 cause acute psychosis in pediatric patients? a case report;a survey of bullying experiences in a child and adolescent psychiatric clinic population;acute emergence of suicidal thoughts following Lemborexant initiation: an adverse reaction case report;assessing the unmet clinical need and opportunity for digital therapeutic intervention in schizophrenia: perspective from people with schizophrenia;rapid antidepressant effects and MADRS item improvements with AXS-05 (DEXTROMETHORPHAN-BUPROPION), an oral NMDA receptor antagonist in major depressive disorder: results from two randomized double-blind, controlled trials;targeting lncRNA NEAT1 impedes Alzheimers disease progression via MicroRNA-193a mediated CREB/BDNF and NRF2/NQO1 pathways;and impact of AXS-05 (DEXTROMETHORPHAN-BUPROPION), an Oral NMDA receptor antagonist, on Anhedonic symptoms in major depressive disorder.

Caregiving for Older Adults With Dementia During the Time of COVID-19: A Multi-State Exploratory Qualitative Study.

This qualitative semi-structured interview study explores how 64 family caregivers for older adults with Alzheimer's Disease and related dementias across eight states experienced and executed caregiving decisions before and during the COVID-19 pandemic. First, caregivers experienced challenges communicating with loved ones and healthcare workers in all care settings. Second, caregivers displayed resilient coping strategies in adapting to pandemic restrictions, finding novel strategies to balance risks while preserving communication, oversight, and safety. Third, many caregivers modified care arrangements, with some avoiding and others embracing institutional care. Finally, caregivers reflected on the benefits and challenges of pandemic-related innovations. Certain policy changes reduced caregiver burden and could improve care access if made permanent. Telemedicine's increasing use highlights the need for reliable internet access and accommodations for individuals with cognitive deficits. Public policies must pay greater attention to challenges faced by family caregivers, whose labor is both essential and undervalued.

Characterizing PRN Use of Psychotropic Medications for Acute Agitation in Canadian Long-Term Care Residents with Dementia Before and During COVID-19.

Background: Agitation is a disabling neuropsychiatric symptom of dementia. Pro re nata (PRN) injections of psychotropics can be administered for severe acute agitation, but little is known about the frequency of their actual use. Objective: Characterize actual use of injectable PRN psychotropics for severe acute agitation in Canadian long-term care (LTC) residents with dementia and compare use before and during the COVID-19 pandemic. Methods: Residents from two Canadian LTC facilities with orders for PRN haloperidol, olanzapine, or lorazepam between January 1, 2018- May 1, 2019 (i.e., pre-COVID-19) and January 1, 2020- May 1, 2021 (i.e., COVID-19) were identified. Electronic medical records were reviewed to document PRN injections of psychotropic medications and collect data on reason and demographic characteristics. Descriptive statistics were used to characterize frequency, dose, and indications of use, and multivariate regression models were used to compare use between time periods. Results: Of the 250 residents, 45 of 103 (44%) people in the pre-COVID-19 period and 85 of 147 (58%) people in the COVID-19 period with standing orders for PRN psychotropics received ≥1 injections. Haloperidol was the most frequently used agent in both time periods (74% (155/209 injections) pre-COVID-19; 81% (323/398 injections) during COVID-19). Residents in the COVID-19 period were almost two times more likely to receive injections compared with those in the pre-COVID-19 period (odds ratio = 1.96; 95% CI = 1.15-3.34; p = 0.01). Conclusion: Our results suggest that use of PRN injections increased in LTC during the pandemic and contribute to the mounting evidence that agitation worsened during that time.

COVID-19 and Alzheimer's Disease: Neuroinflammation, Oxidative Stress, Ferroptosis, and Mechanisms Involved.

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by marked cognitive decline, memory loss, and spatio-temporal troubles and, in severe cases, lack of recognition of family members. Neurological symptoms, cognitive disturbances, and the inflammatory frame due to COVID-19, together with long-term effects, have fueled renewed interest in AD based on similar damage. COVID-19 also caused the acceleration of AD symptom onset. In this regard, the morbidity and mortality of COVID-19 were reported to be increased in patients with AD due to multiple pathological changes such as excessive expression of the viral receptor angiotensin-converting enzyme 2 (ACE2), comorbidities such as diabetes, hypertension, or drug-drug interactions in patients receiving polypharmacy and the high presence of proinflammatory molecules. Furthermore, the release of cytokines, neuroinflammation, oxidative stress, and ferroptosis in both diseases showed common underlying mechanisms, which together worsen the clinical picture and prognosis of these patients.