Targeted Atrial Fibrillation Screening in Older Adults: A Secondary Analysis of the VITAL-AF Trial.

Background: One-time screening trials for atrial fibrillation (AF) have produced mixed results; however, it is unclear if there is a subset of individuals for whom screening would be effective. Identifying such a subgroup would support targeted screening. Methods: We conducted a secondary analysis of VITAL-AF, a randomized trial of one-time, single-lead ECG screening during primary care visits. We tested two approaches to identify a subgroup where screening is effective. First, we developed an effect-based model for heterogeneous screening effects using a T-learner. Specifically, we separately predicted the likelihood of AF diagnosis under screening and usual care conditions using LASSO, a penalized regression method. The difference between these probabilities was the predicted screening effect. Second, we used the CHARGE-AF score, a validated AF risk model, to test for a heterogeneous screening effect. We used interaction testing to determine if observed AF diagnosis rates in the screening and control groups differed when stratified by decile of the predicted screening effect and predicted AF risk. Results: Baseline characteristics were similar between the screening (n=15187) and usual care (n=15078) groups (mean age 74 years, 59% female). On average, screening did not significantly increase the AF diagnosis rate (2.55 vs. 2.30 per 100 person-years, rate difference 0.24, 95%CI -0.18 to 0.67). In the effect-based analysis, in the highest decile of predicted screening efficacy (n=3026), AF diagnosis rates were higher in the screening group (6.50 vs. 3.06 per 100 person-years, rate difference 3.45, 95%CI 1.62 to 5.28). In this group, the mean age was 84 years, 68% were female, and 55% had vascular disease. The risk-based analysis did not identify a subgroup where screening was more effective. Predicted screening effectiveness and predicted baseline AF risk were poorly correlated and demonstrated a U-shaped relationship (Spearman coefficient 0.13). Conclusions: In a secondary analysis of the VITAL-AF trial, we identified a small subgroup where one-time screening was associated with increased AF diagnoses using an effect-based approach. In this study, predicted AF risk was a poor proxy for predicted screening efficacy. These data caution against the assumption that high AF risk is necessarily correlated with high screening efficacy.

Periostin regulates lysyl oxidase through ERK1/2 MAPK-dependent serum response factor in activated cardiac fibroblasts.

Collagen crosslinking, mediated by lysyl oxidase, is an adaptive mechanism of the cardiac repair process initiated by cardiac fibroblasts postmyocardial injury. However, excessive crosslinking leads to cardiac wall stiffening, which impairs the contractile properties of the left ventricle and leads to heart failure. In this study, we investigated the role of periostin, a matricellular protein, in the regulation of lysyl oxidase in cardiac fibroblasts in response to angiotensin II and TGFß1. Our results indicated that periostin silencing abolished the angiotensin II and TGFß1-mediated upregulation of lysyl oxidase. Furthermore, the attenuation of periostin expression resulted in a notable reduction in the activity of lysyl oxidase. Downstream of periostin, ERK1/2 MAPK signaling was found to be activated, which in turn transcriptionally upregulates the serum response factor to facilitate the enhanced expression of lysyl oxidase. The periostin-lysyl oxidase association was also positively correlated in an in vivo rat model of myocardial infarction. The expression of periostin and lysyl oxidase was upregulated in the collagen-rich fibrotic scar tissue of the left ventricle. Remarkably, echocardiography data showed a reduction in the left ventricular wall movement, ejection fraction, and fractional shortening, indicative of enhanced stiffening of the cardiac wall. These findings shed light on the mechanistic role of periostin in the collagen crosslinking initiated by activated cardiac fibroblasts. Our findings signify periostin as a possible therapeutic target to reduce excessive collagen crosslinking that contributes to the structural remodeling associated with heart failure.

Sarcopenia, adiposity and large discordance between cystatin C and creatinine-based estimated glomerular filtration rate in patients with cancer.

BACKGROUND: Creatinine-based estimated glomerular filtration rate (eGFRCRE) may overestimate kidney function in patients with sarcopenia. While cystatin C-based eGFR (eGFRCYS) is less affected by muscle mass, it may underestimate kidney function in patients with obesity. We sought to evaluate the relationship between body composition defined by computed tomography (CT) scans and discordance between creatinine, eGFRCRE and eGFRCYS in adult patients with cancer. METHODS: This study is a cross-sectional study of consecutive adults with cancer with an abdominal CT scan performed within 90 days of simultaneous eGFRCRE and eGFRCYS measurements between May 2010 and January 2022. Muscle and adipose tissue cross-sectional areas were measured at the level of the third lumbar vertebral body using a validated deep-learning pipeline. CT-defined sarcopenia was defined using independent sex-specific cut-offs for skeletal muscle index (<39 cm2/m2 for women and <55 cm2/m2 for men). High adiposity was defined as the highest sex-specific quartile of the total (visceral plus subcutaneous) adiposity index in the cohort. The primary outcome was eGFR discordance, defined by eGFRCYS > 30% lower than eGFRCRE; the secondary outcome was eGFRCYS > 50% lower than eGFRCRE. The odds of eGFR discordance were estimated using multivariable logistic regression modelling. Unadjusted spline regression was used to evaluate the relationship between skeletal muscle index and the difference between eGFRCYS and eGFRCRE. RESULTS: Of the 545 included patients (mean age 63 ± 14 years, 300 [55%] females, 440 [80.7%] non-Hispanic white), 320 (58.7%) met the criteria for CT-defined sarcopenia, and 136 (25%) had high adiposity. A total of 259 patients (48%) had >30% eGFR discordance, and 122 (22.4%) had >50% eGFR discordance. After adjustment for potential confounders, CT-defined sarcopenia and high adiposity were both associated with >30% eGFR discordance (adjusted odds ratio [aOR] 1.90, 95% confidence interval [CI] 1.12-3.24; aOR 2.01, 95% CI 1.15-3.52, respectively) and >50% eGFR discordance (aOR 2.34, 95% CI 1.21-4.51; aOR 2.23, 95% CI 1.19-4.17, respectively). A spline model demonstrated that as skeletal muscle index decreases, the predicted difference between eGFRCRE and eGFRCYS widens considerably. CONCLUSIONS: CT-defined sarcopenia and high adiposity are both independently associated with large eGFR discordance. Incorporating valuable information from body composition analysis derived from CT scans performed as a part of routine cancer care can impact the interpretation of GFR estimates.

Estimating Vitamin K Antagonist Anticoagulation Benefit in People With Atrial Fibrillation Accounting for Competing Risks: Evidence From 12 Randomized Trials.

BACKGROUND: Patients with atrial fibrillation have a high mortality rate that is only partially attributable to vascular outcomes. The competing risk of death may affect the expected anticoagulant benefit. We determined if competing risks materially affect the guideline-endorsed estimate of anticoagulant benefit. METHODS: We conducted a secondary analysis of 12 randomized controlled trials that randomized patients with atrial fibrillation to vitamin K antagonists (VKAs) or either placebo or antiplatelets. For each participant, we estimated the absolute risk reduction (ARR) of VKAs to prevent stroke or systemic embolism using 2 methods-first using a guideline-endorsed model (CHA2DS2-VASc) and then again using a competing risk model that uses the same inputs as CHA2DS2-VASc but accounts for the competing risk of death and allows for nonlinear growth in benefit. We compared the absolute and relative differences in estimated benefit and whether the differences varied by life expectancy. RESULTS: A total of 7933 participants (median age, 73 years, 36% women) had a median life expectancy of 8 years (interquartile range, 6-12), determined by comorbidity-adjusted life tables and 43% were randomized to VKAs. The CHA2DS2-VASc model estimated a larger ARR than the competing risk model (median ARR at 3 years, 6.9% [interquartile range, 4.7%-10.0%] versus 5.2% [interquartile range, 3.5%-7.4%]; P<0.001). ARR differences varied by life expectancies: for those with life expectancies in the highest decile, 3-year ARR difference (CHA2DS2-VASc model - competing risk model 3-year risk) was -1.3% (95% CI, -1.3% to -1.2%); for those with life expectancies in the lowest decile, 3-year ARR difference was 4.7% (95% CI, 4.5%-5.0%). CONCLUSIONS: VKA anticoagulants were exceptionally effective at reducing stroke risk. However, VKA benefits were misestimated with CHA2DS2-VASc, which does not account for the competing risk of death nor decelerating treatment benefit over time. Overestimation was most pronounced when life expectancy was low and when the benefit was estimated over a multiyear horizon.

Use of Lecanemab for Patients With Cardiovascular Disease: The Challenge of Uncertainty.

This Viewpoint discusses lecanemab use and the risk of cerebral macrohemorrhage for patients with mild cognitive impairment or early dementia.

In Vivo Wound-Healing Efficacy of Insulin-Loaded Strontium-Cross-Linked Alginate-Based Hydrogels in Diabetic Rats.

The wound-healing effect of insulin is well studied and reported. However, prolonged topical application of insulin without compromising its biological activity is still a challenge. In this study, the effect of topically delivered insulin on promoting wound healing in diabetic animals was evaluated. Alginate diamine PEG-g-poly(PEGMA) (ADPM2S2) was the material used for the topical delivery of insulin. ADPM2S2 hydrogels release insulin and strontium ions, and they synergistically act to regulate different phases of wound healing. Insulin was released from the ADPM2S2 hydrogel for a period of 48 h, maintaining its structural stability and biological activity. In vitro studies were performed under high-glucose conditions to evaluate the wound-healing potential of insulin. Insulin-loaded ADPM2S2 hydrogels showed significant improvement in cell migration, proliferation, and collagen deposition, compared to control cells under high-glucose conditions. Immunostaining studies in L929 cells showed a reduction in phospho Akt expression under high-glucose conditions, and in the presence of insulin, the expression increased. The gene expression studies revealed that insulin plays an important role in regulating the inflammatory phase and macrophage polarization, which favors accelerated wound closure. In vivo experiments in diabetic rat excision wounds treated with insulin-loaded ADPM2S2 showed 95% wound closure within 14 days compared with 82% in control groups. Thus, both the in vitro and in vivo results signify the therapeutic potential of topically delivered insulin in wound management under high-glucose conditions.

Protective effects of vanillic acid on letrozole-induced polycystic ovarian syndrome: A comprehensive study in female wistar rats.

Background: Polycystic ovarian syndrome (PCOS) is one of the known causes of anovulatory fertility in the world. Previous research has linked oxidative stress could contribute to PCOS, and vanillic acid has shown antioxidant potential. Hence, the present study evaluated the effect of vanillic acid on letrozole-induced polycystic ovarian syndrome in female rats. Materials and methods: PCOS was induced in Wistar female rats with letrozole (1 mg/kg, orally) in carboxymethoxycellulose (1 % w/v), administered for 21 days. After induction, the standard group received clomiphene citrate (1 mg/kg, orally) while other treatment groups were administered with vanillic acid at doses 25, 50, and 100 mg/kg, orally for 15 days, and without treatment was considered a negative control group. Different parameters studied were body weight, ovary weight, blood glucose, lipid profile, hormonal levels [luteinizing hormone (LH), follicle-stimulating hormone (FSH), and testosterone], markers for oxidative stress (superoxide dismutase, reduced glutathione, catalase, and malonaldehyde), and histopathology of the ovary. Statistical analysis was done for the results and p < 0.05 was considered to indicate the significance. Results: Vanillic acid-treated animals showed a concentration-dependent activity on the tested parameters. The highest tested dose (100 mg/kg) produced a more prominent effect in significantly (P < 0.001) decreasing the body weight, and ovary weight and improving the hormonal imbalance. Also, vanillic acid significantly (P < 0.01) reduced elevated blood sugar and lipid levels. Additionally, vanillic acid reduced oxidative stress significantly (P < 0.001) in the ovaries of female rats. Histopathological reports showed a reduction in cystic follicles and appearance of normal healthy follicles at different stages of development after the administration of vanillic acid. Furthermore, these effects were observed to be comparable with those recorded for standard drug, clomiphene. Conclusion: The current study data suggests that vanillic acid has protected the letrozole-induced polycystic ovarian syndrome. In the event of several side effects associated with conventional treatments used for PCOS, the findings of this study suggest the promising role of vanillic acid. More research in this direction might identify the true potency of vanillic acid in the treatment of PCOS.

Hazardous Alcohol Use Among Community-Dwelling Older Adults With Persistent or Recurrent Pain: Findings From the Health and Retirement Study.

BACKGROUND: Although pain and alcohol use are highly prevalent and associated with deleterious health outcomes among older adults, a paucity of literature has examined hazardous drinking among older adults with pain. We aimed to examine the prevalence of hazardous drinking among a nationally representative sample of older adults with persistent or recurrent pain. METHODS: We conducted cross-sectional analyses of data collected from the 2018 wave of the Health and Retirement Study. Participants included 1  549 community-dwelling adults aged ≥65 with persistent or recurrent pain (ie, clinically significant pain present at 2 consecutive survey waves). RESULTS: More than one-quarter of older adults with persistent or recurrent pain reported regular alcohol use (≥weekly), nearly half of whom reported hazardous patterns of drinking. Specifically, 32% reported excessive drinking (ie, >2 drinks per day for older men; >1 drink per day for older women), and 22% reported binge drinking (ie, ≥4 drinks on one occasion). Exploratory analyses revealed a high prevalence of hazardous drinking among the subsample of older adults who used opioids (47%). CONCLUSIONS: Hazardous alcohol use-including both excessive and binge drinking-is common among older adults with persistent or recurrent pain, including those who take opioids. Given that hazardous drinking can complicate pain management and increase the risk for adverse opioid effects (eg, overdose), the current findings underscore the importance of assessing and addressing hazardous patterns of alcohol use among older adults with persistent or recurrent pain.

COVISHIELD vaccine-induced thyroiditis: a case report.

BACKGROUND: The rapid development of coronavirus disease 2019 vaccines during the pandemic has left their long-term effects largely unknown. Instances of autoimmune and subacute thyroiditis showing features of autoimmune/inflammatory syndrome induced by adjuvants have been reported post-vaccination. This case report aims to highlight the autoimmune/inflammatory syndrome induced by adjuvants syndrome after coronavirus disease 2019 vaccination, drawing attention to a possible connection with thyroid dysfunction and urging for further thorough research. CASE PRESENTATION: We present a case of thyroiditis induced by the COVISHIELD vaccine in a 37-year-old Indian woman. An apparently normal and healthy adult woman developed neck pain and easy fatigability 2 weeks after the second dose of COVISHIELD, which gradually increased and was associated with irritability, decreased sleep, excessive sweating, tremor, palpitation, and weight loss. She presented to the outpatient department after 1 week of symptoms and was evaluated with laboratory tests and imaging. She was diagnosed with thyroiditis due to the coronavirus disease 2019 vaccine and was treated with propranolol. CONCLUSION: This case report adds to the growing evidence of coronavirus disease 2019 vaccine-related thyroid issues. The development of thyroiditis is rare and underreported post-coronavirus disease 2019 vaccination; hence, research to evaluate the association of coronavirus disease 2019 vaccines with thyroid dysfunction needs to be done in the future.

Correction: Optically controlled hybrid metamaterial of plasmonic spiky gold inbuilt graphene sheets for bimodal imaging guided multimodal therapy.

Correction for 'Optically controlled hybrid metamaterial of plasmonic spiky gold inbuilt graphene sheets for bimodal imaging guided multimodal therapy' by Ramapurath S. Jayasree et al., Biomater. Sci., 2020, 8, 3381-3391, https://doi.org/10.1039/D0BM00312C.

Mitigation of Fibrosis after Myocardial Infarction in Rats by Using a Porcine Cholecyst Extracellular Matrix.

Fibrosis that occurs after nonfatal myocardial infarction (MI) is an irreversible reparative cardiac tissue remodeling process characterized by progressive deposition of highly cross-linked type I collagen. No currently available therapeutic strategy prevents or reverses MI-associated fibrotic scarring of myocardium. In this study, we used an epicardial graft prepared of porcine cholecystic extracellular matrix to treat experimental nonfatal MI in rats. Graft-assisted healing was characterized by reduced fibrosis, with scanty deposition of type I collagen. Histologically, the tissue response was associated with a favorable regenerative reaction predominated by CD4-positive helper T lymphocytes, enhanced angiogenesis, and infiltration of proliferating cells. These observations indicate that porcine cholecystic extracellular matrix delayed the fibrotic reaction and support its use as a potential biomaterial for mitigating fibrosis after MI. Delaying the progression of cardiac tissue remodeling may widen the therapeutic window for management of scarring after MI.

Near infrared-emitting multimodal nanosystem for in vitro magnetic hyperthermia of hepatocellular carcinoma and dual imaging of in vivo liver fibrosis.

Prolonged usage of traditional nanomaterials in the biological field has posed several short- and long-term toxicity issues. Over the past few years, smart nanomaterials (SNs) with controlled physical, chemical, and biological features have been synthesized in an effort to allay these challenges. The current study seeks to develop theranostic SNs based on iron oxide to enable simultaneous magnetic hyperthermia and magnetic resonance imaging (MRI), for chronic liver damage like liver fibrosis which is a major risk factor for hepatocellular carcinoma. To accomplish this, superparamagnetic iron oxide nanoparticles (SPIONs) were prepared, coated with a biocompatible and naturally occurring polysaccharide, alginate. The resultant material, ASPIONs were evaluated in terms of physicochemical, magnetic and biological properties. A hydrodynamic diameter of 40 nm and a transverse proton relaxation rate of 117.84 mM-1 s-1 pronounces the use of ASPIONs as an efficient MRI contrast agent. In the presence of alternating current of 300 A, ASPIONs could elevate the temperature to 45 °C or more, with the possibility of hyperthermia based therapeutic approach. Magnetic therapeutic and imaging potential of ASPIONs were further evaluated respectively in vitro and in vivo in HepG2 carcinoma cells and animal models of liver fibrosis, respectively. Finally, to introduce dual imaging capability along with magnetic properties, ASPIONs were conjugated with near infrared (NIR) dye Atto 700 and evaluated its optical imaging efficiency in animal model of liver fibrosis. Histological analysis further confirmed the liver targeting efficacy of the developed SNs for Magnetic theranostics and optical imaging as well as proved its short-term safety, in vivo.

Impact of standardized, language-concordant hospital discharge instructions on postdischarge medication questions.

Written instructions improve patient comprehension of discharge instructions but are often provided only in English even for patients with a non-English language preference (NELP). We implemented standardized written discharge instructions in English, Spanish, and Chinese for hospital medicine patients at an urban academic medical center. Using an interrupted time series analysis, we assessed the impact on medication-related postdischarge questions for patients with English, Spanish, or Chinese language preferences. Of 4013 patients, ∼15% had NELP. Preintervention, Chinese-preferring patients had a 5.6 percentage point higher probability of questions (adjusted odds ratio [aOR] = 1.55, 95% confidence interval [CI]: 1.08, 2.21) compared to English-preferring patients; Spanish-preferring and English-preferring patients had similar rates of questions. Postintervention, English-preferring and Spanish-preferring patients had no significant change; Chinese-preferring patients had a significant 10.9 percentage point decrease in the probability of questions (aOR = 0.38, 95% CI: 0.21, 0.69) thereby closing the disparity. Language-concordant written discharge instructions may reduce disparities in medication-related postdischarge questions for patients with NELP.

Development and applicability of a risk assessment tool for hospital-acquired mobility impairment in ambulatory older adults.

BACKGROUND: Mobility loss is common in hospitalized older adults, and resources to prevent mobility impairment are finite. Our goal was to use routinely collected data to develop a risk assessment tool that identifies individuals at risk of losing the ability to walk during hospitalization on the first hospital day. Second, we determined if the tool could inform the use of mobility-preserving interventions. METHODS: We included patients admitted to a general medical service, aged ≥65 years, who walked occasionally or frequently on admission (Braden Scale Activity subset > = 3). Patients were considered to have a new mobility impairment if, at discharge, their ability to walk was severely limited or nonexistent or they were confined to bed (Braden Scale Activity subset <3). We used predictors available on the first hospital day to develop (2017-18 cohort) and validate (2019 cohort) a risk assessment tool. We determined the association between predicted risk and therapy use in the validation cohort to highlight the model's clinical utility. RESULTS: 5542 patients were included (median age 76 years, 48% women); 7.6% were discharged unable to walk. The model included 5 predictors: age, medication administrations, Glasgow Coma Scale verbal score, serum albumin, and urinary catheter presence. In the validation cohort, the model discriminated well (c-statistic 0.75) and was strongly associated with hospital-acquired mobility impairment (lowest decile 1%, highest decile 25%). In the validation cohort, therapy consultation ordering increased linearly with predicted risk; however, observed mobility impairment increased exponentially. CONCLUSION: The tool assesses the risk of mobility impairment in all ambulatory hospitalized older adults on the first hospital day. Further, it identifies at-risk older adults who may benefit from mobility interventions.

Bifunctional cysteine gold nanoclusters for ß-amyloid fibril inhibition and fluorescence imaging: a distinctive approach to manage Alzheimer's disease.

Alzheimer's disease (AD) is a progressive complex neurodegenerative disorder affecting millions of individuals worldwide. Currently, there is no effective treatment for AD. AD is characterized by the deposition of amyloid plaques/fibrils. One major strategy for managing this disease is by slowing the progression of AD using different drugs which could potentially limit free-radical formation, oxidative stress and lipid peroxidation and promote the survival of neurons exposed to ß-amyloid. Inhibition of amyloid fibrillization and clearance of amyloid plaques/fibrils are essential for the prevention and treatment of AD. The thiophilic interaction between the side chain of an aromatic residue in a polypeptide and a sulphur atom of the compound can effectively inhibit amyloid fibril formation. In this work, we have synthesized cysteine-capped gold nanoclusters (Cy-AuNCs) which exhibit inherent red emission and can disintegrate amyloid fibrils through the aforementioned thiophilic interactions. Herein, we also used molecular docking to study the thiophilic interactions between the sulphur atom of Cy-AuNCs and the aromatic rings of the protein. Finally, the gold cluster was functionalized with a brain targeting molecule, Levodopa (AuCs-LD), to specifically target the brain and to facilitate passage through the blood brain barrier (BBB). Both Cy-AuNCs and AuCs-LD showed good biocompatibility and the inherent fluorescence properties of nanoclusters enabled real time imaging. The efficacy of the nanoclusters to disintegrate amyloid fibrils and their ability to cross the BBB were demonstrated both in vitro and in vivo in the BBB model and the AD animal model respectively. Our results imply that nanoparticle-based artificial molecular chaperones may offer a promising therapeutic approach for AD.

Overestimation of anticoagulant benefit in patients with atrial fibrillation and low life expectancy: evidence from 12 randomized trials.

Background: Patients with atrial fibrillation (AF) have a high rate of all-cause mortality that is only partially attributable to vascular outcomes. While the competing risk of death may affect expected anticoagulant benefit, guidelines do not account for it. We sought to determine if using a competing risks framework materially affects the guideline-endorsed estimate of absolute risk reduction attributable to anticoagulants. Methods: We conducted a secondary analysis of 12 RCTs that randomized patients with AF to oral anticoagulants or either placebo or antiplatelets. For each participant, we estimated the absolute risk reduction (ARR) of anticoagulants to prevent stroke or systemic embolism using two methods. First, we estimated the ARR using a guideline-endorsed model (CHA 2 DS 2 -VASc) and then again using a Competing Risk Model that uses the same inputs as CHA 2 DS 2 -VASc but accounts for the competing risk of death and allows for non-linear growth in benefit over time. We compared the absolute and relative differences in estimated benefit and whether the differences in estimated benefit varied by life expectancy. Results: 7933 participants had a median life expectancy of 8 years (IQR 6, 12), determined by comorbidity-adjusted life tables. 43% were randomized to oral anticoagulation (median age 73 years, 36% women). The guideline-endorsed CHA 2 DS 2 -VASc model estimated a larger ARR than the Competing Risk Model (median ARR at 3 years, 6.9% vs. 5.2%). ARR differences varied by life expectancies: for those with life expectancies in the highest decile, 3-year ARR difference (CHA 2 DS 2 -VASc model - Competing Risk Model 3-year risk) was -1.2% (42% relative underestimation); for those with life expectancies in the lowest decile, 3-year ARR difference was 5.9% (91% relative overestimation). Conclusion: Anticoagulants were exceptionally effective at reduced stroke risk. However, anticoagulant benefits were misestimated with CHA 2 DS 2 -VASc, which does not account for the competing risk of death nor decelerating treatment benefit over time. Overestimation was most pronounced in patients with the lowest life expectancy and when benefit was estimated over a multi-year horizon.

Fluorescent carbon dots tailored iron oxide nano hybrid system forin vivooptical imaging of liver fibrosis.

Hybrid nanoparticles are innovative invention of last decade designed to overcome limitations of single-component nanoparticles by introducing multiple functionalities through combining two or more different nanoparticles. In this study, we are reporting development of magneto-fluorescent hybrid nanoparticles by combining iron oxide and carbon nanoparticles to enablein vivofluorescence imaging which also has all the required characteristic properties to use as Magnetic Resonance Imaging (MRI) contrast agent. In order to achieve dual-functional imaging, alginate and pullulan coated super paramagnetic iron oxide nanoparticles (ASPION and PSPION) and Carbon dots (Cdts) were synthesised separately. ASPIONs and PSPIONs were further chemically conjugated with Cdts and developed dual-functional nanohybrid particles ASPION-Cdts and PSPION-Cdts. Subsequently, evaluation of the materials for its size, functionalisation efficiency, fluorescence and magnetic properties, biocompatibility and cellular uptake efficiency has been carried out. Fluorescence imaging of liver fibrosis was performedin vivoin rodent model of liver fibrosis using the two nanohybrids, which is further confirmed by high fluorescence signal from the harvested liver.

Social Frailty Index: Development and validation of an index of social attributes predictive of mortality in older adults.

While social characteristics are well-known predictors of mortality, prediction models rely almost exclusively on demographics, medical comorbidities, and function. Lacking an efficient way to summarize the prognostic impact of social factor, many studies exclude social factors altogether. Our objective was to develop and validate a summary measure of social risk and determine its ability to risk-stratify beyond traditional risk models. We examined participants in the Health and Retirement Study, a longitudinal, survey of US older adults. We developed the model from a comprehensive inventory of 183 social characteristics using least absolute shrinkage and selection operator, a penalized regression approach. Then, we assessed the predictive capacity of the model and its ability to improve on traditional prediction models. We studied 8,250 adults aged ≥65 y. Within 4 y of the baseline interview, 22% had died. Drawn from 183 possible predictors, the Social Frailty Index included age, gender, and eight social predictors: neighborhood cleanliness, perceived control over financial situation, meeting with children less than yearly, not working for pay, active with children, volunteering, feeling isolated, and being treated with less courtesy or respect. In the validation cohort, predicted and observed mortality were strongly correlated. Additionally, the Social Frailty Index meaningfully risk-stratified participants beyond the Charlson score (medical comorbidity index) and the Lee Index (comorbidity and function model). The Social Frailty Index includes age, gender, and eight social characteristics and accurately risk-stratifies older adults. The model improves upon commonly used risk prediction tools and has application in clinical, population health, and research settings.

Can markers of disease severity improve the predictive power of claims-based multimorbidity indices?

BACKGROUND: Claims-based measures of multimorbidity, which evaluate the presence of a defined list of diseases, are limited in their ability to predict future outcomes. We evaluated whether claims-based markers of disease severity could improve assessments of multimorbid burden. METHODS: We developed 7 dichotomous markers of disease severity which could be applied to a range of diseases using claims data. These markers were based on the number of disease-associated outpatient visits, emergency department visits, and hospitalizations made by an individual over a defined interval; whether an individual with a given disease had outpatient visits to a specialist who typically treats that disease; and ICD-9 codes which connote more versus less advanced or symptomatic manifestations of a disease. Using Medicare claims linked with Health and Retirement Study data, we tested whether including these markers improved ability to predict ADL decline, IADL decline, hospitalization, and death compared to equivalent models which only included the presence or absence of diseases. RESULTS: Of 5012 subjects, median age was 76 years and 58% were female. For a majority of diseases tested individually, adding each of the 7 severity markers yielded minimal increase in c-statistic (≤0.002) for outcomes of ADL decline and mortality compared to models considering only the presence versus absence of disease. Gains in predictive power were more substantial for a small number of individual diseases. Inclusion of the most promising marker in multi-disease multimorbidity indices yielded minimal gains in c-statistics (<0.001-0.007) for predicting ADL decline, IADL decline, hospitalization, and death compared to indices without these markers. CONCLUSIONS: Claims-based markers of disease severity did not contribute meaningfully to the ability of multimorbidity indices to predict ADL decline, mortality, and other important outcomes.