Comparative safety and cardiovascular effectiveness of sodium-glucose cotransporter-2 inhibitors and glucagon-like peptide-1 receptor agonists in nursing homes.

AIM: Studies examining the safety and effectiveness of sodium-glucose cotransporter-2 inhibitors (SGLT2is) versus glucagon-like peptide-1 receptor agonists (GLP-1RAs) among community-dwelling adults may not generalize to nursing home (NH) residents, who are typically older and more multimorbid. We compared the safety and cardiovascular effectiveness of SGLT2is and GLP-1RAs among US NH residents. MATERIALS AND METHODS: Eligible individuals were aged ≥66 years with type 2 diabetes mellitus and initiated an SGLT2i or GLP-1RA in an NH between 2013 and 2018. Safety outcomes included fall-related injuries, hypoglycaemia, diabetic ketoacidosis (DKA), urinary tract infection or genital infection, and acute kidney injury in the year following treatment initiation. Cardiovascular effectiveness outcomes included death, major adverse cardiovascular events and hospitalization for heart failure. Per-protocol adjusted hazard ratios (HR) were calculated using stabilized inverse probability of treatment and censoring weighted cause-specific hazard regression models accounting for 127 covariates. RESULTS: The study population included 7710 residents (31.08% SGLT2i, 68.92% GLP-1RA). Compared with GLP-1RA initiators, SGLT2i initiators had higher rates of DKA (HR 1.95, 95% confidence limits 1.27, 2.99) and death (HR 1.18, 95% confidence limits 1.02, 1.36). Rates of urinary tract infection or genital infection, acute kidney injury, major adverse cardiovascular events, and heart failure were also elevated, while rates of fall-related injuries and hypoglycaemia were reduced, but all estimates were imprecise and highly compatible with no difference. CONCLUSIONS: SGLT2is do not have superior, and may have inferior, effectiveness compared with GLP-1RAs for cardiovascular and mortality outcomes in NH residents. Residents initiating SGLT2is should be monitored closely for DKA.

Evaluation of post-acute care and one-year outcomes among Medicare beneficiaries with hip fractures: a retrospective cohort study.

BACKGROUND: Post-acute care (PAC) services after hospitalization for hip fracture are typically provided in skilled nursing facilities (SNFs), inpatient rehabilitation facilities (IRFs), or at home via home health care (HHC). Little is known about the clinical course following PAC for hip fracture. We examined the nationwide burden of adverse outcomes by PAC setting in the year following discharge from PAC for hip fracture. METHODS: This retrospective cohort included Medicare Fee-for-Service beneficiaries > 65 years who received PAC services in U.S. SNFs, IRFs, or HHC following hip fracture hospitalization between 2012 and 2018. Individuals who had a fall-related injury (FRI) during PAC or received PAC services in multiple settings were excluded. Primary outcomes included FRIs, all-cause hospital readmissions, and death in the year following discharge from PAC. Cumulative incidences and incidence rates for adverse outcomes were reported by PAC setting. Exploratory analyses examined risk ratios and hazard ratios between settings before and after inverse-probability-of-treatment-weighting, which accounted for 43 covariates. RESULTS: Among 624,631 participants (SNF, 67.78%; IRF, 16.08%; HHC, 16.15%), the mean (standard deviation) age was 82.70 (8.26) years, 74.96% were female, and 91.30% were non-Hispanic White. Crude incidence rates (95%CLs) per 1000 person-years were highest among individuals receiving SNF care for FRIs (SNF, 123 [121, 123]; IRF, 105 [102, 107]; HHC, 89 [87, 91]), hospital readmission (SNF, 623 [619, 626]; IRF, 538 [532, 544]; HHC, 418 [414, 423]), and death (SNF, 167 [165, 169]; IRF, 47 [46, 49]; HHC, 55 [53, 56]). Overall, rates of adverse outcomes generally remained higher among SNF care recipients after covariate adjustment. However, inferences about the group with greater adverse outcomes differed for FRIs and hospital readmissions based on risk ratio or hazard ratio estimates. CONCLUSIONS: In this retrospective cohort study of individuals hospitalized for hip fracture, rates of adverse outcomes in the year following PAC were common, especially among SNF care recipients. Understanding risks and rates of adverse events can inform future efforts to improve outcomes for older adults receiving PAC for hip fracture. Future work should consider calculating risk and rate measures to assess the influence of differential time under observation across PAC groups.

Therapeutic strategies against potential antibiofilm targets of multidrug-resistant Acinetobacter baumannii.

Acinetobacter baumannii is the causative agent of various hospital-acquired infections. Biofilm formation is one of the various antimicrobial resistance (AMR) strategies and is associated with high mortality and morbidity. Hence, it is essential to review the potential antibiofilm targets in A. baumannii and come up with different strategies to combat these potential targets. This review covers different pathways involved in the regulation of biofilm formation in A. baumannii like quorum sensing (QS), cyclic-di-GMP signaling, two-component system (TCS), outer-membrane protein (ompA), and biofilm-associated protein (BAP). A newly discovered mechanism of electrical signaling-mediated biofilm formation and contact-dependent biofilm modulation has also been discussed. As biofilm formation and its maintenance in A. baumannii is facilitated by these potential targets, the detailed study of these targets and pathways can bring light to different therapeutic strategies such as anti-biofilm peptides, natural and synthetic molecule inhibitors, QS molecule degrading enzymes, and other strategies. These strategies may help in suppressing the lethality of biofilm-mediated infections. Targeting essential proteins/targets which are crucial for biofilm formation and regulation may render new therapeutic strategies that can aid in combating biofilm, thus reducing the recalcitrant infections and morbidity associated with the biofilm of A. baumannii.

Weight Loss as a Nutritional Indicator in Head and Neck Cancer Patients Undergoing Chemoradiotherapy: Contributing Factors and Its Impact on Disease Outcome.

This is a retrospective study carried out at a tertiary care cancer center to assess weight loss in patients of head and neck cancers (HNCs) during treatment with chemoradiotherapy (CRT) and study various factors affecting it. Treatment and follow-up records of 77 patients of HNCs were studied and assessed for demographic, disease-specific variables, treatment parameters, weight loss during CRT, as well as survival at 2 years after treatment completion. A statistical analysis was conducted to assess the association of study variables with weight loss. It was also assessed if a correlation existed between weight loss during treatment and patient survival at 2 years. Of the study patients, 62.3% (48) suffered 5% or more weight loss during CRT while 23.4% (18) suffered a weight loss of 10% or more. No particular factor was identified having a statistically significant association with weight loss. Nutritional impairment is an important factor affecting the morbidity and possibly the mortality of patients of HNCs undergoing CRT. More robust studies are required to identify which factors affect weight loss during treatment and whether weight loss can be used as a parameter to prognosticate patients.

Differences in opioid prescriptions by race among U.S. older adults with a hip fracture transitioning to community care.

BACKGROUND: Appropriate pain management can facilitate rehabilitation after a hip fracture as patients transition back to the community setting. Differences in opioid prescribing by race may exist during this critical transition period. METHODS: We conducted a retrospective cohort study of older adult U.S. Medicare beneficiaries with a hip fracture to examine whether the receipt and dose of opioids differs between Black and White patients as they transitioned back to the community setting. We stratified beneficiaries by whether they received institutional post-acute care (PAC). Outcomes were (1) receipt of an opioid and (2) opioid doses in the first 90 days in the community in milligram morphine equivalents (MMEs; also presented in mg oxycodone). We estimated relative rates and risk differences of opioid receipt and dose differences using Poisson and linear regression models, respectively, using the parametric g-formula to standardize for age and sex. RESULTS: We identified 164,170 older adults with hip fracture (mean age = 82.7 years; 75% female; 72% with PAC; 46% with opioid use after fracture). Overall use of opioids in the community was similar between Black and white beneficiaries. Black beneficiaries had lower average doses in their first 90 days in both total cumulative doses (PAC group: 165 [95% CI -264 to -69] fewer MMEs [-248 mg oxycodone]; no PAC: 167 [95% CI -274 to -62] fewer MMEs [-251 mg oxycodone]) and average MME per days' supply of medication (PAC: -3.0 [-4.6 to -1.4] fewer MMEs per day [-4.5 mg oxycodone]; no PAC: -4.7 [-4.6 to -1.4] fewer MMEs per day [-7.1 mg oxycodone]). In secondary analyses, Asian beneficiaries experienced the greatest differences (e.g., 617-653 fewer cumulative mg oxycodone). CONCLUSION: Racial differences exist in pain management for Medicare beneficiaries after a hip fracture. Future work should examine whether these differences result in disparities in short- and long-term health outcomes.

Association of nursing home antipsychotic reduction policies with antipsychotic use in community dwellers with dementia.

BACKGROUND: Antipsychotic and other psychotropic medication use is prevalent among community-dwelling older adults with dementia despite the potential for adverse effects. Two Centers for Medicare & Medicaid Services (CMS) initiatives, the National Partnership to Improve Dementia Care ("the Partnership") and the Five Star Quality Rating System for antipsychotic use reporting, have been successful in reducing antipsychotic use in nursing home residents. We assessed if these initiatives had a spillover effect in antipsychotic and other psychotropic medication use among community dwellers with dementia due to potential overlap in prescribers across settings. METHODS: Among community-dwelling older adults with dementia, we examined psychotropic medication class use (i.e., antipsychotics, antidepressants, anxiolytics, anticonvulsants/mood stabilizers, antidementia) in 2010-2017 Medicare fee-for-service claims using interrupted time series analyses across three periods ("Pre-Partnership": July 1, 2010 to March 31, 2012; "Post-Partnership": April 1, 2012 to January 31, 2015; "Five Star Quality Rating": February 1, 2015 to December 31, 2017). RESULTS: We included 1,289,401 community dwellers with dementia contributing 26,609,697 person-months. The mean age was 80 years, most were female (70%), approximately 80% were non-Hispanic Whites, 10% were non-Hispanic Blacks, and 5% were Hispanic ethnicity. Antipsychotic use was declining pre-Partnership (ß = -0.06, 95% CI: -0.08, -0.05) and post-Partnership (ß = -0.02, 95% CI: -0.02, -0.01). Post-Five Star Quality Rating, antipsychotic use remained stable with a nearly flat slope (ß = -0.01, 95% CI: -0.01, 0.00). Anticonvulsant and antidepressant use increased and anxiolytic and antidementia medication use decreased among community-dwelling older adults with dementia. CONCLUSIONS: These two CMS policies on antipsychotic use for nursing home residents were not associated with a spillover effect to community-dwelling older adults with dementia. Strategies to monitor the appropriateness of psychotropic medication use may be warranted for community-dwellers with dementia.

Gall bladder carcinoma presenting with spinal metastasis: a rare phenomenon.

Skeletal metastasis as a primary presentation of gall bladder carcinoma is rare. A 50-year-old lady presented with neck pain and weakness in her right upper limb of 3 months duration. Clinical and imaging work-up suggested locally advanced gall bladder carcinoma with metastasis to cervical vertebra and sternum. Only one case till date has been reported where the patient presented with neurological symptoms due to pathological fracture secondary to metastasis from an occult gall bladder carcinoma. Although rare, an occult gall bladder cancer may present with neurological symptoms due to pathological fracture of spine secondary to metastasis. We present a brief review of literature of patients who presented with skeletal metastases in clinically silent gall bladder malignancy. Palliative care issues in advanced gall bladder carcinoma have also been discussed.

Role of 18 F-FDG PET-CT in Urethral Malignant Melanoma and Analysis of the UK Guidelines on Ano-uro-genital Melanomas.

Urethral melanomas are a rare subtype of noncutaneous melanomas. The disease has a tendency to have skip lesions and early metastases as compared with cutaneous melanomas. The role of fluorine-18 fluorodeoxyglucose ( 18 F-FDG) positron emission tomography computed tomography (PET-CT) is well established in cases of cutaneous melanomas and is recommended by the National Comprehensive Cancer Network (NCCN) for stage IIB to IV cancer. There are no established guidelines on the management of noncutaneous melanomas; however, a recently published United Kingdom national guideline aims to streamline the management of ano-uro-genital melanomas. The guideline describes a very limited role in the use of 18 F-FDG PET-CT in this case scenario. The tendency to skip lesions, early metastases, involvement of brain parenchyma, and finally the usage of anti-PD-1 medications are key areas where 18 F-FDG PET-CT has shown superiority over CT scan. With this case report, we aim to highlight the strength of 18 F-FDG PET-CT in the management of urethral melanomas, which can be extrapolated to other ano-uro-genital melanomas.

Coronaviruses spike glycoprotein endodomains: The sequence and structure-based comprehensive study.

Any protein's flexibility or region makes it available to interact with many biomolecules in the cell. Specifically, such interactions in viruses help them to perform more functions despite having a smaller genome. Therefore, these flexible regions can be exciting and essential targets to be explored for their role in pathogenicity and therapeutic developments as they achieve essential interactions. In the continuation with our previous study on disordered analysis of SARS-CoV-2 spike protein's cytoplasmic tail (CTR), or endodomain, here we have explored the endodomain's disordered potential of six other coronaviruses using multiple bioinformatics approaches and molecular dynamics simulations. Based on the comprehensive analysis of its sequence and structural composition, we report the varying disorder propensity in endodomains of spike proteins of coronaviruses. The observations of this study may help to understand the importance of spike glycoprotein endodomain and creating therapeutic interventions against them.

Use of Oral Empagliflozin to Obtain Optimal Blood Sugar Levels for Conducting 18 F-FDG PET-CT in Patients with Hyperglycemia-A Pilot Study.

Background Flourine-18 fluorodeoxyglucose positron emission tomography-computed tomography ( 18 F-FDG PET-CT) is a well-established imaging modality for the evaluation of patients with oncological and nononcological conditions. The underlying principle of imaging is the preferentially increased glucose consumption by cancer cells, due to overexpression of glucose type 1 receptors that are insulin independent. Thus, one of the factors that leads to decreased sensitivity of an 18 F-FDG PET-CT is elevated blood sugar levels, leading to decreased glucose uptake by cancer cells due to competitive inhibition. A significant percentage of patients scheduled for PET-CT scan has diabetes mellitus type II as a comorbid condition and often has elevated random blood sugar (RBS) precluding an upfront PET-CT evaluation. Such cases must be rescheduled. This causes delay in the evaluation and management of such patients. Empagliflozin is a novel sodium glucose type 2 inhibitor that prevents tubular reabsorption of glucose and increases renal glycosuria resulting in decreased blood sugar. This drug does not cause significant hypoglycemia or increase endogenous insulin secretion. This study was undertaken to evaluate a potential role for empagliflozin in facilitating optimal blood sugar control in patients with hyperglycemia on the day of the scheduled PET scan. Methods This is an interventional prospective study and patients detected to have RBS more than 200 mg/dL on the day of the scheduled scan were included in the study. The patients were administered two tablets of 10 mg empagliflozin and kept under observation. Samples for RBS were taken at approximately 2nd and 4th hour post administration by bedside method. These patients underwent scan on the same day after adequate sugar control and when an RBS of less than 200 mg/dL was achieved. The primary outcome studied was change in RBS values in the patient cohort and evaluation of PET SUV (standardized uptake value) compared with the rest of the patients scheduled on the same day. Secondary outcome was assessment of any side effects in the patients. Results Total of 10 patients were found to have elevated blood sugar (RBS > 200 mg/dL; irrespective of being on medication) and did not meet the evaluation criteria for a PET-CT scan on the scheduled day. Following administration of the drug, all 10 patients were able to attain blood sugar levels and fulfill the criteria for undergoing a PET-CT scan. No obvious side effect was noted in any of the patient. The SUV values of the patient cohort were comparable with the rest of the patient scanned on the day. Conclusion In this pilot study, 20 mg of empagliflozin (2 tablets of 10 mg) appears to be a safe and effective method for achieving optimal decrease in the RBS without causing hypoglycemia or hyperinsulinemia. It can be safely employed in the subset of population with RBS between 201 and 300 mg/dL to adequately bring the sugar levels at acceptable levels RBS less than 200 mg/dl and fulfill the FDG PET-CT criteria as per European Association of Nuclear Medicine (EANM) norms.

Post-Acute Care Setting After Hip Fracture Hospitalization and Subsequent Opioid Use in Older Adults.

OBJECTIVE: Pain management in post-acute care (PAC) requires careful balance, with both opioid use and inadequate pain treatment linked to poor outcomes. We describe opioid use among older adults following discharge from PAC for hip fracture in skilled nursing facilities (SNFs) and inpatient rehabilitation facilities (IRFs). DESIGN: Retrospective cohort. SETTING AND PARTICIPANTS: Medicare beneficiaries with Medicare Provider Analysis (MedPAR) claims, aged 66 years and older with a hip fracture hospitalization between 2012 and 2018 followed by PAC in SNFs or IRFs and then discharge to the community. METHODS: Individuals were followed from PAC discharge for up to 1 year to assess opioid use. Covariate-standardized risk ratios (RR) and risk differences (RD) for opioid use within 7 days of PAC discharge were estimated via parametric g-formula with modified Poisson regression, and hazard ratios (HRs) for any post-PAC opioid use and long-term opioid use via Fine-Gray sub-distribution hazards regression. RESULTS: Of 101,021 individuals, 80% (n = 80,495) were discharged from SNFs and 20% (n = 20,526) from IRFs. Opioids were dispensed to 50,433 patients (50%) overall and the 1-year cumulative incidence was notably higher in IRF (68%) than SNF (46%) patients. The adjusted risk of discharge from PAC with an opioid was 41% lower after SNFs versus IRFs [RR: 0.59; 95% confidence limits (CLs): 0.57-0.61; and RD: -0.16; 95% CLs: -0.17 to -0.15]. The adjusted rate of any opioid use in the year after PAC discharge was 44% lower (HR: 0.56; 95% CLs: 0.54-0.57) and of long-term opioid use was 17% lower (HR: 0.83; 95% CLs: 0.80-0.87) after SNFs versus IRFs. CONCLUSIONS AND IMPLICATIONS: Opioid use is highly prevalent upon discharge from PAC after hip fracture, with lower use after SNF versus IRF care. Future research should assess the benefits and harms of post-PAC opioid prescribing and whether care practices during PAC can be improved to optimize long-term opioid use.

Widespread amyloid aggregates formation by Zika virus proteins and peptides.

Viral pathogenesis typically involves numerous molecular mechanisms. Protein aggregation is a relatively unknown characteristic of viruses, despite the fact that viral proteins have been shown to form terminally misfolded forms. Zika virus (ZIKV) is a neurotropic one with the potential to cause neurodegeneration. Its protein amyloid aggregation may link the neurodegenerative component to the pathogenicity associated with the viral infection. Therefore, we investigated protein aggregation in the ZIKV proteome as a putative pathogenic route and one of the alternate pathways. We discovered that it contains numerous anticipated aggregation-prone regions in this investigation. To validate our prediction, we used a combination of supporting experimental techniques routinely used for morphological characterization and study of amyloid aggregates. Several ZIKV proteins and peptides, including the full-length envelope protein, its domain III (EDIII) and fusion peptide, Pr N-terminal peptide, NS1 ß-roll peptide, membrane-embedded signal peptide 2K, and cytosolic region of NS4B protein, were shown to be highly aggregating in our study. Because our findings show that viral proteins can form amyloids in vitro, we need to do a thorough functional study of these anticipated APRs to understand better the role of amyloids in the pathophysiology of ZIKV infection.

State Variation in Antipsychotic Use Among Assisted Living Residents With Dementia.

OBJECTIVES: More than two-thirds of assisted living (AL) residents have dementia or cognitive impairment and antipsychotics are commonly prescribed for behavioral disturbances. As AL communities are regulated by state-level policies, which vary significantly regarding the care for people with dementia, we examined how antipsychotic prescribing varied across states among AL residents with dementia. DESIGN: This was an observational study using 20% sample of national Medicare data in 2017. SETTING AND PARTICIPANTS: The study cohort included Medicare beneficiaries with dementia aged 65 years or older who resided in larger (≥25-bed) ALs in 2017. METHODS: The study outcome was the percentage of eligible AL person-months in which antipsychotics were prescribed for each state. We used a random intercept linear regression model to shrink estimates toward the overall mean use of antipsychotics addressing unstable estimates due to small sample sizes in some states. RESULTS: A total of 20,867 AL residents with dementia were included in the analysis, contributing to 194,718 person-months of observation. On average, AL residents with dementia were prescribed antipsychotics during 12.6% of their person-months. This rate varied significantly by state, with a low of 7.8% (95% CI 5.9%-10.3%) for Hawaii to a high of 20.5% (95% CI 16.4%-25.3%) for Wyoming. CONCLUSIONS AND IMPLICATIONS: We observed significant state variation in the prescribing of antipsychotics among AL residents with dementia using national data. These variations may reflect differences in state regulations regarding the care for AL residents with dementia and suggest the need for further investigation to ensure high quality of care.

Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 Spike ferritin nanoparticle vaccine antigen produced from two different cell lines.

The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells.

Amyloidogenic proteins in the SARS-CoV and SARS-CoV-2 proteomes.

The phenomenon of protein aggregation is associated with a wide range of human diseases. Our knowledge of the aggregation behaviour of viral proteins, however, is still rather limited. Here, we investigated this behaviour in the SARS-CoV and SARS-CoV-2 proteomes. An initial analysis using a panel of sequence-based predictors suggested the presence of multiple aggregation-prone regions (APRs) in these proteomes and revealed a strong aggregation propensity in some SARS-CoV-2 proteins. We then studied the in vitro aggregation of predicted aggregation-prone SARS-CoV and SARS-CoV-2 proteins and protein regions, including the signal sequence peptide and fusion peptides 1 and 2 of the spike protein, a peptide from the NSP6 protein, and the ORF10 and NSP11 proteins. Our results show that these peptides and proteins can form amyloid aggregates. We used circular dichroism spectroscopy to reveal the presence of ß-sheet rich cores in aggregates and X-ray diffraction and Raman spectroscopy to confirm the formation of amyloid structures. Furthermore, we demonstrated that SARS-CoV-2 NSP11 aggregates are toxic to mammalian cell cultures. These results motivate further studies about the possible role of aggregation of SARS proteins in protein misfolding diseases and other human conditions.

Formulation development and comparability studies with an aluminum-salt adjuvanted SARS-CoV-2 spike ferritin nanoparticle vaccine antigen produced from two different cell lines.

The development of safe and effective second-generation COVID-19 vaccines to improve affordability and storage stability requirements remains a high priority to expand global coverage. In this report, we describe formulation development and comparability studies with a self-assembled SARS-CoV-2 spike ferritin nanoparticle vaccine antigen (called DCFHP), when produced in two different cell lines and formulated with an aluminum-salt adjuvant (Alhydrogel, AH). Varying levels of phosphate buffer altered the extent and strength of antigen-adjuvant interactions, and these formulations were evaluated for their (1) in vivo performance in mice and (2) in vitro stability profiles. Unadjuvanted DCFHP produced minimal immune responses while AH-adjuvanted formulations elicited greatly enhanced pseudovirus neutralization titers independent of ∼100%, ∼40% or ∼10% of the DCFHP antigen adsorbed to AH. These formulations differed, however, in their in vitro stability properties as determined by biophysical studies and a competitive ELISA for measuring ACE2 receptor binding of AH-bound antigen. Interestingly, after one month of 4°C storage, small increases in antigenicity with concomitant decreases in the ability to desorb the antigen from the AH were observed. Finally, we performed a comparability assessment of DCFHP antigen produced in Expi293 and CHO cells, which displayed expected differences in their N-linked oligosaccharide profiles. Despite consisting of different DCFHP glycoforms, these two preparations were highly similar in their key quality attributes including molecular size, structural integrity, conformational stability, binding to ACE2 receptor and mouse immunogenicity profiles. Taken together, these studies support future preclinical and clinical development of an AH-adjuvanted DCFHP vaccine candidate produced in CHO cells.

Receipt of Physical Therapy and Chiropractic Care by Adults Diagnosed with Chronic Pain: Analysis of the 2016-2018 Rhode Island All Payer Claims Database.

OBJECTIVE: To examine trends and factors associated with physical therapy (PT) and chiropractic care use among Rhode Islanders with private or publicly-funded health insurance who were diagnosed with chronic pain from 2016-2018. METHODS: We measured monthly PT and chiropractic care use from the RI All Payer Claims Database, and conducted logistic regression to identify factors associated with utilization. RESULTS: There were 284,942 unique adults with chronic pain representing over one-quarter of insured persons in the state. Chiropractic care use remained unchanged but was more prevalent (7.2%) than PT whose use increased minimally from 4.0% (2016) to 4.5% (2018). Traditional Medicare or Medicaid enrollment was associated with lower odds of receiving PT and chiropractic care than in private plans. CONCLUSIONS: PT and chiropractic care use varied across payers; however, there were little to no changes in their use over time despite clinical guidelines that encourage non-pharmacologic options to manage chronic pain.

Psychotropic medication prescribing in assisted living and nursing home residents with dementia after the National Partnership.

BACKGROUND: The Centers for Medicare & Medicaid Services implemented the National Partnership to Improve Dementia Care in Nursing Homes (the Partnership) to decrease antipsychotic use and improve care for nursing home (NH) residents with dementia. We determined whether the extent of antipsychotic and other psychotropic medication prescribing in AL residents with dementia mirrored that of long-stay NH (LSNH) residents after the Partnership. METHODS: Using a 20% sample of fee-for-service Medicare beneficiaries with Part D, we conducted a retrospective cohort study including AL and LSNH residents with dementia. The monthly prevalence of psychotropic medication prescribing (antipsychotics, antidepressants, anxiolytics/sedative-hypnotics, anticonvulsants/mood stabilizers, benzodiazepines, and antidementia medications) was examined. We used an interrupted time-series analysis to compare medication prescribing before (July 1, 2010-March 31, 2012) and after (April 1, 2012-December 31, 2017) the Partnership in both settings. RESULTS: We identified 107,931 beneficiaries with ≥1 month as an AL resident and 323,766 beneficiaries with ≥1 month as a LSNH resident with dementia, including 1,923,867 person-months and 4,984,405 person-months, respectively. Antipsychotic prescribing declined over the study period in both settings. After the launch of the Partnership, the rate of decline in antipsychotic prescribing slowed in AL residents with dementia (slope change = 0.03 [95% CLs: 0.02, 0.04]) while the rate of decline in antipsychotic prescribing increased in LSNH residents with dementia (slope change = -0.12 [95% CLs: -0.16, -0.08]). Antidepressants were the most prevalent medication prescribed, anticonvulsant/mood stabilizer prescribing increased, and anxiolytic/sedative-hypnotic and antidementia medication prescribing declined. CONCLUSIONS: The federal Partnership to reduce antipsychotic prescribing in NH residents did not appear to affect antipsychotic prescribing in AL residents with dementia. Given the increase in the prescribing of mood stabilizers/anticonvulsants that occurred after the launch of the Partnership, monitoring may be warranted for all psychotropic medications in AL and NH settings.

Design of novel hybrid secondary metabolite targets to diguanylate cyclase of Acinetobacter baumannii.

Biofilm formation in bacteria is a resistance determinant and is positively regulated by cyclic diguanylate signaling. This signaling is a near universal signaling, and c-di-GMP produced by diguanylate cyclase (DGC) in this signaling is involved in different bacterial behaviors. The present study aims to find a plant-based novel hybrid therapeutic agent that can target the DGC of Acinetobacter baumannii. In this study, we have tried to design a hybrid molecule from the anti-biofilm plant secondary metabolites and screened its binding with the DGC of A. baumannii. The modeled and validated DGC was used to identify the active site and docking grid. Designed hybrid compounds were analysed for their interaction with the active site residues of DGC of A. baumannii. Further, the binding free energies of the docked complexes obtained from the Generalized Born model and Solvent Accessibility (MMGBSA) were analysed. The results indicated that VR-QEg-180 has a predicted high binding affinity with enzyme DGC as compared to other hybrids, parent secondary metabolites and positive control. Molecular dynamics simulation (MDS) analysis confirmed the interaction of VR-QEg-180 with DGC of the A. baumannii. The designed lead has favorable ADMET properties, has no human off-targets and has no predicted cytotoxicity in cell lines. Therefore, the designed hybrid molecule (VR-QEg-180) targeting the DGC of A. baumannii may play a very significant role in controlling this pathogen.

Fluorodeoxyglucose positron emission tomography-computed tomography in a pregnant woman with carcinoma breast.

A 35-year-old female with a 15-week period of gestation was detected with locally advanced cancer of the left breast. She was suggested to undergo a medical termination of pregnancy (MTP) followed by invasive Oncological imaging - Contrast enhanced computed tomography (CECT) chest-abdomen-pelvis/fluorodeoxyglucose positron emission tomography-CT (FDG PET-CT) for staging the disease. However, to avoid the risk of iatrogenic novel coronavirus 2019 infection to the patient, on her request, the hospital admission was carried out after the oncological workup and thus PET-CT was conducted before the MTP. FDG PET-CT revealed FDG avid primary in the left breast along with extensive metastases to liver and skeletal lesions. The developing fetus also showed physiological FDG uptake. The patient has undergone an MTP and is presently under treatment for metastatic breast cancer. The case report illustrates the radiation safety guidelines on fetal radiation exposure, steps to decrease fetal radiation exposure, and illustration of fetal FDG uptake.