Biguanide Pharmaceutical Formulations and the Applications of Bile Acid-Based Nano Delivery in Chronic Medical Conditions

Biguanides, particularly the widely prescribed drug metformin, have been marketed for many decades and have well-established absorption profiles. They are commonly administered via the oral route and, despite variation in oral uptake, remain commonly prescribed for diabetes mellitus, typically type 2. Studies over the last decade have focused on the design and development of advanced oral delivery dosage forms using bio nano technologies and novel drug carrier systems. Such studies have demonstrated significantly enhanced delivery and safety of biguanides using nanocapsules. Enhanced delivery and safety have widened the potential applications of biguanides not only in diabetes but also in other disorders. Hence, this review aimed to explore biguanides’ pharmacokinetics, pharmacodynamics, and pharmaceutical applications in diabetes, as well as in other disorders.

The Impact of COVID-19 on Healthy Related Issues, A structured Review

Coronavirus: (COVID-19) is a recently discovered viral disease caused by a new strain of coronavirus. The majority of patients with corona-virus infections will have a mild-moderate respiratory disease that recovers without special care. Most often, the elderly, and others with chronic medical conditions such as asthma, coronary disease, respiratory illness, and malignancy are seriously ill. COVID-19 is spread mostly by salivary droplets or nasal secretions when an infected person coughs or sneezes. COVID-19 causes severe acute respiratory illness (SARS-COV-2). The first incidence was recorded in Wuhan, China, in 2019. Since then it spreads leading to a pandemic. The typical incubation time for COVID-19 infection is 2-14 days (normally 5). The common features include fever, cough, tiredness, difficulty in breathing, loss of smell or taste. Occasionally, signs are absent. COVID-19 complications include renal failure, syndrome of cytokine release, pneumonia, respiratory failure, lung fibrosis.

Telemedicine Readiness Across Medical Conditions in a US National Representative Sample of Older Adults

Telemedicine has provided older adults the ability to seek care remotely during the coronavirus disease (COVID-19) pandemic. However, it is unclear how diverse medical conditions play a role in telemedicine uptake. A total of 3379 participants (≥65 years) were interviewed in 2018 as part of the National Health and Aging Trends Study. We assessed telemedicine readiness across multiple medical conditions. Most chronic medical conditions and mood symptoms were significantly associated with telemedicine unreadiness, for physical or technical reasons or both, while cancer, hypertension, and arthritis were significantly associated with telemedicine readiness. Our findings suggest that multiple medical conditions play a substantial role in telemedicine uptake among older adults in the US. Therefore, comorbidities should be taken into consideration when promoting and adopting telemedicine technologies among older adults.

Prevalence of MCI and Dementia Prior to Incarceration

As the number of older, incarcerated persons increases, prevalence of dementia and mild cognitive impairment (MCI) in this population will likely grow, with implications for healthcare costs and advance care planning within the prison setting. This study is the first to determine the prevalence of dementia or MCI in later-life adults prior to incarceration. We leveraged a national cohort of Veterans aged 50+ whose most recent incarceration was ≤10 years in length and who were released between 10/1/2012 and 9/30/2018 (N=17,962). We linked VA and CMS healthcare records to determine diagnosis of dementia or MCI within 3 years prior to incarceration. The overall sample had a mean age of 62.4 (±7.6) years at the start of their incarceration, were largely male (97%), and were 65% White and 30% Black. Before incarceration, 445 (2.5%) and 152 (0.8%) Veterans were diagnosed with dementia and MCI, respectively. Compared to those without a diagnosis of dementia or MCI prior to incarceration, those with dementia or MCI were older at incarceration start (66.1 [±8.3] vs. 62.3 [±7.9]), had more chronic medical conditions (4.0 [±2.2] vs. 2.2 [±1.9]), were more likely to experience homelessness (21.6% vs. 9.1%), have a TBI (24.5% vs. 9.1%), and have serious mental illness (81.7% vs. 49.1%). All comparisons were significant (p<.001). Our findings indicate that later-life adults with dementia or MCI are being incarcerated. Improved understanding of pathways linking cognitive impairment to later-life incarceration is needed to both prevent unnecessary incarceration and to help provide appropriate healthcare for this vulnerable group.

Redeployment of psychiatrist trainees during the COVID-19 pandemic: evaluation of attitude and preparedness

Background: The coronavirus disease-2019 (COVID-19) pandemic has imposed an unprecedented strain on healthcare systems worldwide. In response, psychiatrist trainees were redeployed from their training sites to help manage patients with COVID-19. This study aimed to examine the attitude of psychiatrist trainees toward redeployment to COVID-19 sites and their perceived preparedness for managing physical health conditions during redeployment. Methods: A cross-sectional researcher-developed online survey was administered among psychiatrist trainees in May 2020 at the Department of Psychiatry, Hamad Medical Corporation, Qatar. Results: Of the 45 psychiatrist trainees, 40 (88.9%) responded to the survey. Most trainees reported being comfortable dealing with chronic medical conditions, but less so with acute life-threatening medical conditions. Half reported feeling anxious about redeployment, and most felt the need for additional training. We found that trainees’ perceived redeployment preparedness was significantly associated with their level of postgraduate training and the time since and duration of their last medical or surgical training. Conclusion: Adequate preparation and training of psychiatrist trainees is important before redeployment to COVID-19 sites to ensure that they can effectively and safely manage patients with COVID-19.

Technical Challenges to the Delivery of Quality Radiation Therapy During the COVID-19 Unlock Period: Medical Physics Perspective

The Covid-19 onset was very pandemic for all of society all over the world. To overcome this state of affairs, the country’s government had done the lockdown in their respective countries. The lockdown helped the people from spreading the Covid-19 virus among people, however, it affected another part of life such as people becoming unemployed. The health care sector was affected a lot by the lockdown as the patient faced lots of problems such as reaching the hospital, meeting the concerned staff, getting the treatment on time, etc. Covid-19 affected the cancer patients most, during the lockdown. After awareness of Covid-19, when the world has started towards the unlock down. With the little negligence of people, the world has started facing the peak of Covid-19. And, there was more crowd in the health care sectors, therefore the hospital staff got infected a lot, as the patient treatment cannot be carried out from home. Cancer patient treatment, which comes under radiotherapy, has already existed in chronic medical conditions, such as lung cancer patients, esophagus cancer patients, heart disease patients, etc, has a higher risk of Covid-19 infection. During treatment, when such a patient comes in contact with a radiation oncologist, medical physicist, and radiation technologist, then some of the staff get infected through patients. To prevent such spread, all the medical staff should strictly follow the rules made for staff. In this article, we are sharing the challenges for the medical physics team and some suggestions during patient care.

Adverse Childhood Experiences (ACEs) in Newly-Diagnosed Childhood and Adolescent/Young Adult (AYA) Cancer Patients with Hematologic Malignancies

Background and Aims: Childhood and adolescent/young adult (AYA) cancer survivors are at increased risk for emotional distress, chronic health conditions, and premature mortality compared to peers with no cancer history. Some, but not all, of this increased risk is explained by cancer- and treatment-related exposures. Because cancer treatment remains necessary to achieve cure, it is critical to identify and target other factors to reduce sub-optimal outcomes. Adverse Childhood Experiences (ACEs) are traumatic events occurring during childhood, such as experiencing violence and/or neglect, which are associated with poor mental health, chronic health conditions, and premature mortality in the adult general population. Little is known on how ACEs impact health in children and AYAs with cancer. Research indicates that otherwise healthy individuals exposed to ACEs experience fewer adverse health outcomes if they possess resilience, which can be learned. This provides a potential target for intervention. This pilot study aimed to identify demographic characteristics associated with ACEs and resilience as well as associations between ACEs, resilience, and the presence of chronic medical conditions, mental health issues, and substance abuse in children and AYAs with cancer. Methods: Childhood and AYA leukemia and lymphoma patients undergoing cancer treatment at the University of Chicago were included for analysis (N=38, 55.26% female, 50% non-Hispanic white, mean age at assessment 14.74±6.97 years). Participants ≤17 years old completed the study with one parent/caregiver. ACEs were measured using age-specific instruments adapted from the original ACEs study by Kaiser Permanente and the Centers for Disease Control and Prevention. Resilience was analyzed using age-specific instruments provided by the Resilience Research Centre, and resilience scores were categorized as low (≤62), moderate (63-70), high (71-76), and exceptional (≥77). For participants 0-11 years old, a parent/guardian completed the study on their behalf. 12-17 year old participants and their parent/guardian both completed the study, and participants over 18 completed the study alone. Descriptive statistics characterized demographic, biologic, treatment, and health behavior variables. The association between total scores for ACEs and resilience were measured using Pearson's correlation. Regression analysis assessed ACEs (logistic model) and resilience scores (linear model) adjusting for age, sex, race/ethnicity, household income, and insurance type. Participants were then stratified, and two sample t-tests compared potential outcomes based on ACE exposures. Results: 23 participants (60.53%) reported prior ACEs (mean total number of ACEs 1.45±1.77; range 1-7), and the mean resilience score for participants was 73.76±9.61 (range 49-85) indicating high resilience overall. Regression analyses showed the odds of reporting ACEs increased with age (OR: 1.18; 95% CI: 1.02-1.37), while resilience scores decreased with age (β=0.76; t(32)=-2.74, p=0.01) holding other variables constant. Sex, race/ethnicity, household income, and insurance type were not associated with ACEs or resilience scores. There was a strong negative correlation between the total number of ACEs and resilience, r(36)=-0.57, p<0.01; the total number of ACEs explained 32% of the variation in resilience scores. Compared to participants who did not report prior ACEs, those with ACEs were more likely to report chronic medical conditions, t(31.41)=-2.47, p=0.02, prior psychiatric diagnoses or mental health issues, t(34.16)=-2.13, p=0.04, as well as substance abuse t(31.41)=-2.47, p=0.02. Conclusions: ACEs were associated with endorsement of chronic medical conditions, mental health issues, and substance abuse in our sample of childhood and AYA patients currently receiving cancer treatment. As the total number of ACEs increased, resilience scores decreased for participants. The results of this study provide the groundwork for further investigations of ACEs and resilience in large cohorts of childhood and AYA cancer patients and survivors. This future work could provide valuable information for creating and implementing interventions designed for childhood and AYA cancer patients and survivors who have experienced ACEs, thus potentially reducing additional morbidity and premature mortality for these high-risk patients. Disclosures No relevant conflicts of interest to declare.

Validating Direct Oral Anticoagulants (DOAC) for Use in Children By the Throm-PED Doac Registry of the International Pediatric Thrombosis Network

Background: A growing number of randomized clinical trials (RCTs) provide promising data on pharmacokinetics/ pharmacodynamics, efficacy and safety of DOAC in children and the first DOACs have recently been approved for treatment of thromboembolism in children. Based on the risk benefit profiles published so far, we expect DOACs to be widely used for treatment and prophylaxis of thrombosis in children. The strict inclusion criteria for participation in the RCTs limit their generalizability, particularly to those with more serious acute and chronic medical conditions that account for a significant proportion of pediatric VTE patients in clinical practice. Real world data complements evidence from randomized clinical trials, and is urgently needed to improve patient care. Aim: To obtain efficacy and safety data of DOACs in a large and heterogeneous pediatric patient collectives. To expand the knowledge on treatment strategies and outcomes across different risk profiles and comorbidities including cancer and renal disease. Study Design: An international, multicentre, prospective observational cohort study imbedded in the Throm-PED Registry of the International Pediatric Thrombosis Network (IPTN). Parameters included at baseline are age, gender, height, weight, thrombosis type, thrombosis location, risk factors, underlying medical conditions and comedication. Primary outcomes include 1) thrombus progression or recurrence and 2) bleeding (major, clinically relevant non major including menorrhagia) and 3) mortality. Outcomes are assessed every 3 months for a total of 12 months. Additional variables include self-reported adherence, comedication, chemotherapy, DOAC drug levels, measures of renal function and dose adjustments on children with chronic medical conditions including renal disease and cancer. Study population : Patients from 0-21 years with thromboembolic disease treated with DOACs who are enrolled in the IPTN Throm-PED Registry. Results: As of June 30, 2021 82 patients from 10 centers have been enrolled. The majority of patients were at least 12 years old (Figure 1). 66% suffered from venous thrombosis. With about 30% each, pulmonary embolism or thrombosis of the lower extremities were reported most commonly. In this cohort the majority of patients received Rivaroxaban (80%), followed by Apixaban and Edoxaban. Risk factors were manifold, including patients with cancer (13%) and renal disease (4%). Of the 33 patients with follow-up reported at 3 months, bleeding was reported in 3 (9%) of patients during treatment with a DOAC, and thrombosis progression was reported in 2 (6%) (Table 1). Summary: This initial real world data, as expected, demonstrates reduced efficacy and more bleeding than noted in published trials, however numbers are small. Further real world data collection is essential to identify specific patient groups at risk of worse outcome with DOACs and to understand drug interactions and dose adjustments. Data on younger age groups are required. IPTN registry is an important framework to collect real world data that can then be explored in clinical trials. Figure 1 Figure 1. Disclosures Raffini: CSL Behring: Consultancy; Genentech: Consultancy; HEMA Biologics: Consultancy; Bayer: Consultancy; XaTek: Consultancy.