Comparison of surgery rates in biologic-naïve patients with Crohn's disease treated with vedolizumab or ustekinumab: findings from SOJOURN.

BACKGROUND: Crohn's disease (CD) is a chronic inflammatory bowel disease characterized by relapsing and remitting inflammation that leads to progressive bowel damage. Despite advances in medical treatment for CD, many patients require surgical intervention. Most studies of surgery rates are from patients treated with anti-tumor necrosis factor alpha (anti-TNFα) treatments, with comparatively little data on the surgery rates of patients treated with vedolizumab and ustekinumab. SOJOURN aimed to estimate the hazard rate and incidence of the first CD-related surgery following initiation of treatment with vedolizumab or ustekinumab in biologic-naïve patients with CD. METHODS: SOJOURN was a retrospective, observational cohort study examining administrative claims data from the Optum® Research Database between July 1, 2017 and March 31, 2020. Included participants were adults with a diagnosis of CD and a claim for vedolizumab or ustekinumab (defined as the index treatment) between January 1, 2018 and December 31, 2019, with no claims for a biologic in the 6 months before initiation of this treatment. The variable follow-up started on the day after the index date and continued until whichever came first of discontinuation of the index treatment, surgery event, switching of the index treatment, initiation of combination biologic treatment, disenrollment, or March 31, 2020. The time to the first CD-related surgery on biologic treatment was estimated by Kaplan-Meier analysis. The hazard ratio and incidence rate ratio of CD-related surgery for each treatment cohort was compared using a Cox proportional hazards model and a Poisson regression model, respectively. RESULTS: Of the 1,122 included patients, 578 received vedolizumab and 544 received ustekinumab. After 1 year of the variable follow-up, 7.7% of patients receiving vedolizumab and 11.6% of patients receiving ustekinumab had undergone a CD-related surgery. Vedolizumab was associated with a 34.2% lower hazard rate of surgery (hazard ratio 0.658, 95% confidence interval [CI] 0.436-0.994, p = 0.047) and a 34.5% lower incidence of surgery (rate ratio 0.655, 95% CI 0.434-0.988, p = 0.044) than ustekinumab. CONCLUSIONS: This real-world analysis of biologic-naïve patients with CD suggests that vedolizumab is associated with greater effectiveness in reducing the rate of CD-related surgery than ustekinumab.

Gabapentin-induced myositis in a patient with spinal cord injury - a case report.

Myositis and rhabdomyolysis are the same forms of myopathy, with rhabdomyolysis being a more severe form of myopathy. Gabapentin is frequently used in patients with spinal cord injury for neuropathic pain. We report a case of probable gabapentin-induced myositis in a patient with spinal cord injury who was on an increasing dose of gabapentin. This paraplegic patient was receiving an increasing dose of gabapentin for neuropathic pain in the lower limbs. Gabapentin-induced myositis was diagnosed by a combination of new-onset generalized body pain with tenderness, an increase in creatine kinase, elevated myoglobin levels, and a score of 6 on the Naranjo adverse drug reaction probability scale. Withdrawal of the gabapentin resolved the symptoms completely. Blood parameters became normal within two weeks. We suggest that myopathy, in the form of myositis, should be recognized as a potential side effect of gabapentin in the literature.

Dose Escalation of Biologics in Biologic-Naïve Patients With Ulcerative Colitis: Outcomes From the ODESSA-UC Study.

Background: Dose escalation of biologics may regain treatment response in patients with ulcerative colitis (UC). However, dose escalation rates and associated outcomes and costs are not well characterized in biologic-naïve patients receiving antitumor necrosis factor-alpha (anti-TNF-α) treatments, such as infliximab or adalimumab or vedolizumab. Methods: ODESSA-UC, a retrospective cohort study investigating dose escalation in patients with UC who had received first-line biologics, used data from IBM MarketScan databases. Adults with UC and ≥1 claim for an index drug (adalimumab, infliximab, or vedolizumab) were eligible. A Cox proportional hazards model was used to evaluate the adjusted rate of dose escalation. Logistic regression was used to evaluate the odds of experiencing adverse outcomes (corticosteroid use, infection, sepsis, or inflammatory bowel disease-related hospitalization) and incurring index drug costs. Results: A year after the start of maintenance, a lower proportion of patients experienced dose escalation with vedolizumab (22.3%) than adalimumab (43.0%). The dose escalation risk was significantly higher for infliximab (hazard ratio [HR], 1.894; 95% confidence interval [CI], 1.486-2.413) and adalimumab (HR, 2.120; 95% CI, 1.680-2.675) than for vedolizumab. The odds of experiencing an adverse outcome after dose escalation were higher for anti-TNF-α treatments than for vedolizumab (odds ratio, 2.052; 95% CI, 1.200-3.507). Index drug costs after dose escalation were lowest for vedolizumab. Conclusions: Patients with UC receiving vedolizumab had a lower risk of dose escalation and lower subsequent costs than patients receiving anti-TNF-α treatments. Our study demonstrates the possible clinical and economic implications of dose escalation.

Real-World Persistence of Successive Biologics in Patients With Inflammatory Bowel Disease: Findings From ROTARY.

BACKGROUND: Patients with inflammatory bowel disease (IBD) may receive multiple successive biologic treatments in clinical practice; however, data are limited on the comparative effectiveness of biologics and the impact of treatment sequence on outcomes. METHODS: The ROTARY (Real wOrld ouTcomes Across tReatment sequences in inflammatorY bowel disease patients) study was a retrospective, observational cohort study conducted using data from the Optum Clinical Database between January 1, 2012, and February 29, 2020. Adult patients with Crohn's disease (CD) or ulcerative colitis (UC) who received 2 biologics successively were included. Biologic treatment sequences were analyzed descriptively. Cox proportional hazards models, adjusted for baseline demographics and clinical characteristics, were used to estimate the hazard ratio of switching or discontinuation for each first- and second-line biologic compared with first- and second-line adalimumab, respectively. RESULTS: In total, 4648 patients with IBD (CD, n = 3008; UC, n = 1640) were identified. Most patients received tumor necrosis factor α antagonist (anti-TNFα) treatment followed by another anti-TNFα treatment or vedolizumab. Vedolizumab and infliximab had 39.4% and 34.6% lower rates of switching or discontinuation than adalimumab, respectively, as first-line biologics in patients with CD and 30.8% and 34.3% lower rates as first-line biologics in patients with UC, respectively. Vedolizumab, infliximab, and ustekinumab had 47.2%, 40.0%, and 43.5% lower rates of switching or discontinuation than adalimumab, respectively, as second-line biologics in CD and 56.5%, 43.0%, and 45.6% lower rates as second-line biologics in patients with UC, respectively. CONCLUSIONS: Although anti-TNFα treatments were most commonly prescribed, the adjusted rates of discontinuation for adalimumab as both a first- and second-line biologic were higher than for vedolizumab, infliximab, or ustekinumab.

Patients with inflammatory bowel disease are commonly treated with different sequences of biologics. This study shows that patients who receive adalimumab as their first or second biologic treatment either stop or switch to another biologic at a greater rate than those who are treated with vedolizumab, infliximab, and ustekinumab.

Ecological safety with multifunctional applications of biogenic mono and bimetallic (Au-Ag) alloy nanoparticles.

Recently, the design and biosynthesis of metallic nanoparticles (NPs) have drawn immense interest, but their very specific function and secondary toxic effects are major concern towards commercial application of NPs. That's why environment-friendly (nontoxic) NPs having multiple functions are extremely important. Herein, we report the mechanism of biosynthesis of mono and bimetallic (Au-Ag) alloy NPs and study their multifunctional (antioxidant, antifungal and catalytic) activity and ecotoxicological property. AgNPs exhibit phytotoxicity (at 100 µg/ml) on morphological characteristics of Lentil (during germination), while alloy and AuNPs are non-toxic (up to 100 µg/ml). In-vitro antioxidant response using DPPH methods reveals that alloy NPs (IC50 = 55.8 µg/ml) possesses better antioxidant activity compared to the monometallic NPs (IC50 = 73.6-82.6 µg/ml). In addition, alloy NPs displayed appreciable antifungal efficacy against a plant pathogenic fungus Gloeosporium musarum by structural damage to hyphae and conidia of the fungus. The catalytic performance of NPs for degradation of chlorpyriphos (CP) pesticide reveals that alloy NPs is more efficient in terms of rate constant (k = 0.405 d-1) and half-life (T50 = 1.71 d) compared to the monometallic counterparts (k = 0.115-0.178 d-1; T50 = 3.89-6.04 d). Degradation products of CP (3,5,6-trichloropyridinol and diethyl thiophosphate) are confirmed using mass spectrometry and based on that a degradation pathway has been suggested. Thus, these sustainable and ecological safe biogenic (Au-Ag) alloy NPs promise multiple applications as an antioxidant in the pharmaceutical sector, as a fungicide for disease control in agriculture, as a catalyst for remediation of toxic pollutants and in other pertinent areas.

An Epidemiological Study of Hearing Loss in a Peripheral Tertiary Care Hospital.

The estimated prevalence of adult onset hearing deafness in India is 7.6% and childhood onset hearing loss is 2%. But there are very few studies which highlight the prevalence of various types of hearing loss. So a retrospective, cross-sectional study in a peripheral tertiary care hospital was designed to analyze the different types of hearing loss among patients with complaints of hearing disabilities attending and assess the more prevalent type of hearing loss according to severity. Out of total study population of 14,365 patients, Male patients with Mild hearing loss have the maximum correlation coefficient followed by Moderate, Moderately severe, Profound and Severe hearing loss. In the case of female patients Mild Hearing loss has the maximum correlation coefficient. Result of this study may be helpful in planning and management of different programs related to hearing disability prevention. As most of the hearing loss is mild variety and it slowly progress to other form of severe hearing loss, early intervention is very helpful in reducing the severity thus disability.

Dissipation behaviour and risk assessment of fipronil and its metabolites in paddy ecosystem using GC-ECD and confirmation by GC-MS/MS.

Fipronil -a broad spectrum phenylpyrazole insecticide has high level of toxicity towards environment. Therefore, an easy and reliable analytical method was developed for residue estimation of fipronil to ensure food and environmental safety. A modified QuEChERS technique was followed for estimation of fipronil (5% SC) in paddy ecosystem using GC-ECD and confirmation by GC-MS/MS. The initial residues (0.168-0.794 µg g-1) of total fipronil i.e., sum of fipronil and its metabolites (viz., desulfinyl and sulfone) in leaf and soil were dissipated following first order kinetics. About 92-96% of fipronil residues were degraded after 15 days with half-life of 3.4-4.1 days and pre-harvest interval of 19.4-25.7 days in plant. Residues were below level of quantification (<0.005 µg g-1) in plant and soil at harvest. The fipronil residues in rice grain present low dietary risk (RQd < 1) to human health. However, high risk (RQd > 1) was predicted for cattle health due to fipronil residues in paddy leaf up to 10 days. The residual level in soil was also at highrisk (RQs > 1) for soil ecological health.

A Compressed Sensing Approach to Pooled RT-PCR Testing for COVID-19 Detection.

We propose 'Tapestry', a single-round pooled testing method with application to COVID-19 testing using quantitative Reverse Transcription Polymerase Chain Reaction (RT-PCR) that can result in shorter testing time and conservation of reagents and testing kits, at clinically acceptable false positive or false negative rates. Tapestry combines ideas from compressed sensing and combinatorial group testing to create a new kind of algorithm that is very effective in deconvoluting pooled tests. Unlike Boolean group testing algorithms, the input is a quantitative readout from each test and the output is a list of viral loads for each sample relative to the pool with the highest viral load. For guaranteed recovery of [Formula: see text] infected samples out of [Formula: see text] being tested, Tapestry needs only [Formula: see text] tests with high probability, using random binary pooling matrices. However, we propose deterministic binary pooling matrices based on combinatorial design ideas of Kirkman Triple Systems, which balance between good reconstruction properties and matrix sparsity for ease of pooling while requiring fewer tests in practice. This enables large savings using Tapestry at low prevalence rates while maintaining viability at prevalence rates as high as 9.5%. Empirically we find that single-round Tapestry pooling improves over two-round Dorfman pooling by almost a factor of 2 in the number of tests required. We evaluate Tapestry in simulations with synthetic data obtained using a novel noise model for RT-PCR, and validate it in wet lab experiments with oligomers in quantitative RT-PCR assays. Lastly, we describe use-case scenarios for deployment.

Good research practices for measuring drug costs in cost effectiveness analyses: an industry perspective: the ISPOR Drug Cost Task Force report--Part V.

OBJECTIVES: The industry perspective on drug costs should be framed by the need for decision-makers to use actual and relevant costs, and to inform real-world decisions regarding medication selection and use. The objective of this report is to provide guidance and recommendations on how manufacturers should approach the use of drug costs. METHODS: The Task Force was appointed with the advice and consent of the ISPOR Board of Directors. Members were experienced developers or users of drug cost information working in academia and industry, and came from several countries. Following the core assumptions developed and outlined by the Task Force, a draft report was prepared. Comments were solicited on the outline and several draft reports both from a core group of external reviewers and more broadly from the ISPOR membership of ISPOR via the ISPOR Web site. RESULTS: The industry should always strive for: 1) a focus on drug value and not just cost; 2) credibility-that is correct and consistent costs; 3) transparency-by disclosing the prices and costs, and ensuring that they reflect the actual cost of the drug whenever possible; and 4) providing actionable results that help customers comprehend the value offered by a drug therapy and to use products more efficiently and effectively. CONCLUSIONS: Understanding and accounting for all costs and consequences of the use of a medical treatment is in the best interests of all parties involved in the prescribing, consuming, reimbursement, selling, and manufacturing of bio/pharmaceuticals. Transparency, consistency, and clear communication of costs and value are essential for appropriate decision-making and should be important goals for all parties.

Author Correction: Process optimization for biosynthesis of mono and bimetallic alloy nanoparticle catalysts for degradation of dyes in individual and ternary mixture.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Process optimization for biosynthesis of mono and bimetallic alloy nanoparticle catalysts for degradation of dyes in individual and ternary mixture.

Nanoparticle (NP) catalysts are widely used for removal of dyes for single use, but there is an acute need for developing catalysts with high efficiency and reusability for mixed dyes. Here we first optimized the process (reactant proportion, temperature, time, and pH) for biosynthesis of monometallic Ag, Au and bimetallic Au-Ag alloy NP catalysts using Polyalthia longifolia leaf extract. The biosynthesized NP catalysts were characterized by UV-vis, DLS, Zeta potential, TEM and EDX study while the probable biomolecules responsible for biosynthesis were identified by FTIR and GC-MS/MS analysis. The NPs are found to be mostly spherical in shape (size 5-20 nm) with prolonged stability. We evaluated their chemo-catalytic performance through degradation of dyes (methyl orange, methyl violet, methylene blue) in individual and ternary mixture in presence of NaBH4. The degradation percentage (80.06-96.59% within 5 min), degradation kinetics (k = 0.361-1.518 min-1), half-life (T50 = 0.457-1.920 min) and 80% degradation (T80 = 1.060-4.458 min) of dyes indicated highest catalytic activity of alloy in ternary mixture. Here we report a unique vacuum filtration system using alloy coated beads with excellent catalytic activity which could be reused thrice for removal of hazardous ternary mixed dyes with great promise for environmental remediation.

Health care resource utilization among patients with T2D and cardiovascular-, heart failure-, or renal-related hospitalizations.

OBJECTIVES: In patients with type 2 diabetes (T2D), comorbidity-related hospitalizations can have significant impact on longitudinal care. This study aimed to estimate incremental all-cause health care resource utilization (HCRU) and costs between patients with T2D who experienced cardiovascular (CV)-, heart failure (HF)-, or renal-related hospitalizations vs those who did not. STUDY DESIGN: This was a retrospective cohort study using data from a large national health plan. METHODS: Patients with T2D aged 18 to 90 years with CV, HF, or renal hospitalizations were identified from the Humana claims database from October 1, 2009, to September 30, 2015, and separated into CV, HF, and renal cohorts. Patients had 12 months of continuous enrollment prior to the date of first hospitalization (index) and were followed for up to 12 months. Per-patient per-month (PPPM) all-cause HCRU and costs for hospitalized patients were compared with those of no-CV, no-HF, and no-renal cohorts. Differences in baseline characteristics between cohorts were controlled for using generalized linear models. RESULTS: A total of 221,229, 68,126, and 120,105 patients were included in the CV, HF, and renal cohorts, respectively; these patients were older and had higher Deyo-Charlson Comorbidity Index scores than patients in the no-CV, no-HF, and no-renal cohorts. Adjusted for baseline covariates, they had higher mean PPPM inpatient stays, outpatient visits, emergency department visits, and total health care costs. CONCLUSIONS: Among patients with T2D, concurrent CV, HF, or renal events present significant disease burden leading to poor quality of life. This information can be used to guide disease management strategies and interventions aimed at reducing comorbidity-related hospitalizations and health care costs, thus providing improved quality of life for these patients.

Acoustic cavitation assisted destratified clay tactoid reinforced in situ elastomer-mimetic semi-IPN hydrogel for catalytic and bactericidal application.

Ultrasonicaion is non-chemical process where acoustic waves have been targeted to aqueous medium dispersed precursor materials. In situ synthesis of silver nanoparticles anchored in hydrogel matrix has been opted via ~20 kHz frequency assisted (bath sonication) synthesis having the ultrasonication power intensity (UPI) of ~106 J/m2. Power intensity is inversely proportional to the surface area of the clay tactoids. The hydrogel have been prepared by in situ 20 kHz assisted sonochemical destratification of laponite clay tactoids which could be terminologically stated as 'top-down method'. Silver nanoparticles (AgNPs) have been deposited in the surfaces of the porous matrix of hydrogel via 'soak and irradiate' method. Soaking of silver ions into the gel matrix is welcomed due to their efficient stabilization and fast transformation towards AgNPs. AgNPs played the key role in catalytic reduction and bactericidal activity. Moreover, the prepared hydrogel has enough robust to withstand cyclic stress, uniaxial stress and oscillatory stress which have been extensively justified by the physico-mechanical characterizations. The gel supported catalyst showed first order reaction kinetics and less time consuming period during reduction of 4-nitrophenol as a model pollutant.

A Multifunctional Smart Textile Derived from Merino Wool/Nylon Polymer Nanocomposites as Next Generation Microwave Absorber and Soft Touch Sensor.

In recent times e-textiles have emerged as wonder safeguards due to the great potential background in space, military, healthcare, or portable electronics. As a result, widespread research and development have been done to make significant advancement in this field, but it still remains a key challenge to use one single product with multifunctional attributes with the past performance of key characteristics. In this work, phase-separated PEDOT:PSS ornamented with reduced graphene oxide (rGO) nanosheets, deposited on the newly fabricated ultralightweight, superhydrophobic, and mechanically enriched merino wool/nylon (W-N) composite textile followed by the dipping and drying strategy. The open edges-layered structure of rGO helping uniform deposition of PEDOTs clusters, which allows the formation of a stacked layer of PEDOTs/rGO-PEDOTs/PEDOTs for robust three-dimensional electrical transforming channel network within the W-N textile surface. These dip-coated multifunctional textiles show high electrical conductivities up to 90.5 S cm-1 conjugated with a flexible electromagnetic interference shielding efficiency of 73.8 dB (in X-band) and in-plane thermal conductivity of 0.81 W/mK with a minimum thickness of 0.84 mm. This thin coating maintained the hydrophobicity (water contact angle of ∼150°) leading to an excellent EM protective cloth combined with real-life antenna performance under high mechanical or chemical tolerance. Interestingly, this multiuse textile can also act as an exceptional TASER Proof Textile (TPT) due to a short out of the electrical shock coming from the TASER by its unique conducting network architecture. Remarkably, this coated textile can get a response by the soft touch to lighten up the household bulb and could establish wireless communication via an HC-05 Bluetooth module as a textile-based touch switch. This developed fabric could perform as a new potentially scalable single product in intelligent smart garments, portable next-generation electronics, and the growing threat of EM pollution.

Biocompatible carbon dots derived from κ-carrageenan and phenyl boronic acid for dual modality sensing platform of sugar and its anti-diabetic drug release behavior.

Detection of sugar by enzymatic assay has been suffering from costly, time-taking, instable and denaturation of glucose oxidase. Recently, chemosensors that have affinity towards boronate became the hot topic in the domain of monosaccharide detection. In this work, a novel strategy was addressed to fabricate carbon dots (C-dots) from linear sulfated polysaccharides κ- carrageenan and phenyl boronic acid for nonenzymatic monosaccharide (glucose) detection. The boronic acid group anchored C-dots surface can form assembly by covalently bonded with the cis-diol moiety of the glucose which caused fluorescence quenching of the C-dots. The inert surface nature of the luminescent C-dots enables them to sense as low as 1.7 µM glucose without the interference of other biomolecules. The proposed sensing system was successfully applied for assay of glucose in blood serum. Interestingly, these C-dots were used as a nano vehicle for delivery of anti-diabetic drug Metformin. Good biocompatibility results were found with MTT and hemolysis assay. Owing to its simplicity and effectiveness, the as-prepared C-dots offered great promise for blood sugar diagnosis and treatment.

Differences in All-Cause Health Care Utilization and Costs in a Type 2 Diabetes Mellitus Population with and Without a History of Cardiovascular Disease.

BACKGROUND: Multiple studies have reported that type 2 diabetes mellitus (T2DM) is a major risk factor for cardiovascular diseases (CVD), and presence of T2DM and CVD increases risk of death. There is growing interest in examining the effects of antidiabetic treatments on the reduction of cardiovascular events in T2DM adults with a history of CVD and thus at higher risk of cardiovascular events. OBJECTIVE: To estimate the incremental all-cause health care utilization and costs among adults with T2DM and a history of CVD compared with adults without a history of CVD, using a national linked electronic medical records (EMR) and claims database. METHODS: Adults aged ≥ 18 years with evidence of at least 1 T2DM-related diagnosis code or antidiabetic medication (date of earliest occurrence was defined as the index date) in calendar year 2012 were identified. The population was divided into 2 cohorts (with and without a history of CVD) and followed until the end of their enrollment coverage, death, or 12 months, whichever came first. Multivariable generalized linear models were used to assess differences in health care utilization and per patient per month (PPPM) total costs (plan- and patient-paid amount for health care services) between the 2 groups during the post-index year, while adjusting for an a priori list of demographic and clinical characteristics. RESULTS: A total of 138,018 adults with T2DM was identified, of which 16,547 (12%) had a history of CVD. The unadjusted resource utilization (outpatient: 27.5 vs. 17.8; emergency room [ER]: 0.8 vs. 0.4; inpatient: 0.4 vs. 0.2 days; and total unique drug prescriptions: 10.1 vs. 8.3) and PPPM total health care costs ($2,655.1 vs. $1,435.0) were significantly higher in T2DM adults with a history of CVD versus T2DM adults without a history of CVD. The adjusted models revealed that T2DM adults with a history of CVD had a 31% higher number of ER visits (rate ratio [RR] = 1.31, 95% CI = 1.25-1.37); 27% more inpatient visits (RR = 1.27, 95% CI = 1.21-1.34); 15% longer mean inpatient length of stay (RR = 1.15, 95% CI = 1.06-1.25); and 11% more outpatient visits (RR = 1.11, 95% CI = 1.09-1.13) compared with T2DM adults without a history of CVD. Furthermore, the difference in total PPPM health care cost was found to be 16% ($200) higher in adults with a history of CVD (RR = 1.16, 95% CI = 1.13-1.19). PPPM costs associated with outpatient and ER visits were approximately 21% and 19% higher among adults with a history of CVD, respectively (P < 0.0001), while costs for inpatient visits were similar between the 2 groups. In addition, a subgroup analysis revealed that adjusted differences in PPPM total cost was larger in the younger age group (56% higher cost in those aged < 45 years) and diminished in the older age group (only 2% higher in those aged ≥ 65 years). CONCLUSIONS: Study findings showed that resource utilization and costs remains significantly higher in T2DM patients with a history of CVD compared with patients without a history of CVD even after controlling for significant patient comorbid and demographic characteristics. Also, younger age groups had higher differences in outcomes compared with older age groups. This study underscores the importance of cost-effective interventions that may reduce economic burden in this T2DM population with a history of CVD. DISCLOSURES: This study was funded by Boehringer Ingelheim. At the time of this study, Mehta and Mountford were employed by IQVIA, which received funding from Boehringer Ingelheim to conduct this study. Mountford is employed by Allergan, which has no connection with this study. Ghosh, Sander, and Kuti are employed by Boehringer Ingelheim. Study concept and design were contributed by Mountford, Mehta, and Ghosh, along with Sander and Kuti. Mountford and Mehta collected the data, and data interpretation was performed by all the authors. The manuscript was written by Sander and Kuti, along with the other authors, and revised by Mehta and Gosh, along with the other authors.

Green Reduced Graphene Oxide Toughened Semi-IPN Monolith Hydrogel as Dual Responsive Drug Release System: Rheological, Physicomechanical, and Electrical Evaluations.

Macroporous hydrogel monoliths having tailor-made features, conductivity, superstretchability, excellent biocompatibility, and biodegradability, have become the most nurtured field of interest in soft biomaterials. Green method assisted reduced graphene oxide has been inserted by in situ free radical gelation into semi-IPN hydrogel matrix to fabricate conducting hydrogel. Mechanical toughness has been implemented for the graphene-polymer physisorption interactions with graphene basal planes. Moreover, the as-prepared 3D scaffold type monolith hydrogel has been rheologically superior regarding their high elastic modulus and delayed gel rupturing. κ-Carragenaan, one of the components of the hydrogel, has biodegradable nature. The most significant outcome is their low electrical percolation threshold and reversibly ductile nature. Reversible ductility provides them with rubber-like consistency in flow conditions. Surprising, the hydrogels showed dual stimuli-responsiveness, that is, environmental pH and external electrical stimulation. Electro-stimulation has been adopted here for the first time in semi-IPN systems, which could be an ideal alternative for iontopheretic devices and pulsatile drug release through skin. Regarding this, the hydrogel also has been passed to biocompatibility assay; they are noncytotoxic and show cell proliferation without negligible cell death in live-dead assay. The porosity of the nanocomposite scaffold-like gels was also analyzed by microcomputed tomography (µ-CT), which exhibited their connectivity in cell/voids inside the matrix. Thus, the experimentations are on the support of biocompatible soft material for dual-responsive tunable drug delivery.

Design of psyllium-g-poly(acrylic acid-co-sodium acrylate)/cloisite 10A semi-IPN nanocomposite hydrogel and its mechanical, rheological and controlled drug release behaviour.

Soft biomaterials derived from polysaccharides are generally suffers from lack of mechanical robustness and instability. The naturally occurring highly abundance low cost polysaccharide has immense aspect as biomaterial after functionalization which can be designed as stretchable and rubber-like elastic with reversible ductility. A highly swellable, stretchable, low creep, non-cytotoxic nanocomposite hydrogel has been fabricated by simple one-pot Michael type covalent grafting of acrylic acid based copolymer onto psyllium biomacromolecular chian by free radical gelation technique. The fabricated hydrogel was rheologically tested which implies its viscoelastic and thixotropic like features. The porous morphology of the hydrogel was confirmed by scanning electron micrograph. The cryo-transmission electron micrograph shows the random dispersion of the nanoclay (cloisite 10A) tactoids in exfoliated as well intercalated forms. These random distributions of clay nanosheets also enhance the mechanical toughness and reversible ductility of the hydrogels which was also supported by the mechanical and loading-unloading cycle measurement. Nonetheless, the nanocomposite hydrogel was non-cytotoxic against human cell-line (human osteosarcoma) and shows good cell attachment of live cells in a 5-day 'live-dead' assay with almost negligible quantity of cell death. These attributes can promote this material as a soft biomaterial for controlled release device with mechanical robustness and rubber-like elasticity.

Hospital Admissions, Costs, and 30-Day Readmissions Among Newly Diagnosed Nonvalvular Atrial Fibrillation Patients Treated with Dabigatran Etexilate or Warfarin.

BACKGROUND: Oral anticoagulation such as warfarin and dabigatran is indicated for atrial fibrillation (AF) patients at risk of ischemic stroke. Dabigatran etexilate was developed to address the limitations of warfarin, including the need for regular blood monitoring, which has the potential to lead to higher health care resource use, particularly in hospitalized patients. OBJECTIVE: To evaluate whether hospitalization cost, length of hospital stay (LOS), likelihood of readmission within 30 days, and cost of readmissions differed across inpatient encounters among nonvalvular atrial fibrillation (NVAF) patients that were newly diagnosed and newly treated with either dabigatran or warfarin. METHODS: A retrospective cohort study was conducted using IMS Health's Charge Detail Master (CDM) database. Hospitalizations were identified based on a primary or secondary AF diagnosis, dabigatran or warfarin use, and a discharge date from January 2011 through March 2012. The identified patients without valvular procedures and transient AF were required to have a minimum of 12 months of pharmacy and private practitioner records prior to the inpatient encounter to ensure that they were newly treated on dabigatran or warfarin. Propensity score matching was used to balance baseline characteristics between treatment cohorts. Outcomes assessed were LOS, 30-day readmissions, and costs. Because individual patients could have more than 1 hospital observation, generalized estimating equations (GEE) with a gamma distribution (log link) were used for the analysis of continuous outcome measures (e.g., LOS and costs) and a binominal distribution for dichotomous outcomes (hospital readmissions). RESULTS: Two cohorts were propensity score matched (1:2) on demographic and clinical characteristics. The dabigatran cohort included 646 hospitalizations, and the warfarin cohort included 1,292 hospitalizations. Hospitalizations were on average 13% shorter (4.8 vs. 5.5 days, P less than 0.001) and cost 12% less ($14,794 vs. $16,826, P = 0.007) when dabigatran was used versus warfarin. No differences in 30-day readmissions were observed. CONCLUSIONS: Hospital encounters among newly diagnosed NVAF patients during which warfarin was initiated had longer lengths of stay and incurred higher costs than those during which dabigatran was initiated.

Healthcare utilization and costs associated with dabigatran compared to warfarin treatment in newly diagnosed patients with non-valvular atrial fibrillation.

PURPOSE: Real-world healthcare resource utilization and costs were compared among patients with non-valvular atrial fibrillation (NVAF) receiving either dabigatran or warfarin. METHODS: A retrospective cohort study was conducted using administrative claims data from the United States Department of Defense (DOD) Military Health System. Patients with newly diagnosed AF initiated on dabigatran or warfarin were identified using ICD-9 diagnosis, procedure and drug codes. Patients were observed for 3 months prior to treatment initiation to ascertain a diagnosis of valvular heart disease and 12 months for exclusion of those with a history of anticoagulation therapy. Propensity score matching was used to balance baseline characteristics between the two treatment cohorts. Medical and pharmacy utilization and costs were compared between the dabigatran and warfarin treatment groups for 3 and 12 months following treatment initiation. RESULTS: A total of 1102 patients with newly diagnosed NVAF initiated on dabigatran were matched with corresponding warfarin-treated patients. In the 12 months following initiation of anticoagulation, the mean medical costs for patients initiated on dabigatran were significantly lower than for patients initiated on warfarin (-$6299, p < 0.001), largely due to fewer hospitalizations (-0.162, p = 0.009). While pharmacy costs were higher ($4369, p < 0.001) for dabigatran, overall healthcare costs were significantly lower compared with patients on warfarin (12 months: -$1940, p < 0.001). Mean hospital length of stay between these two groups were similar (6.033 days for dabigatran vs 6.318 days for warfarin, p = 0.139). CONCLUSION: Despite higher pharmacy costs for NVAF patients initiated on dabigatran vs warfarin, this was more than offset by lower utilization of medical care resources.