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PURPOSE To assess the safety and effectiveness of the PRESERFLO® MicroShunt (formerly InnFocus MicroShunt) in patients with primary open-angle glaucoma (POAG). DESIGN The MicroShunt, a controlled ab externo glaucoma filtration surgery device, was investigated in a 2-year, multicenter, single-arm study. PARTICIPANTS Eligible patients were aged 18-85 years with POAG inadequately controlled on maximal tolerated medical therapy with intraocular pressure (IOP) ≥18 and ≤35 mmHg or when glaucoma progression warranted surgery. METHODS The MicroShunt was implanted as a stand-alone procedure with adjunctive use of topical mitomycin C (MMC; 0.2-0.4 mg/ml) for 2-3 minutes. MAIN OUTCOME MEASURES The primary effectiveness outcome was IOP reduction and success (not requiring reoperation or pressure failures [IOP > 21 mmHg and < 20% reduction in IOP]) at year 1. Additional end points at year 2 included IOP reduction, success, glaucoma medications, adverse events (AEs), and reoperations. Results are reported in the overall population and subgroups of patients receiving 0.2 or 0.4 mg/ml MMC. RESULTS In 81 patients, mean (± standard deviation [SD]) IOP decreased from 21.7 ± 3.4 mmHg at baseline to 14.5 ± 4.6 mmHg at year 1 and 14.1 ± 3.2 mmHg at year 2 (P < 0.0001). Overall success (with and without supplemental glaucoma medication use) at year 1 was 74.1%. Mean (± SD) number of medications decreased from 2.1 ± 1.3 at baseline to 0.5 ± 0.9 at year 2 (P < 0.0001), and 73.8% of patients were medication free. Most common nonserious AEs were increased IOP requiring medication or selective laser trabeculoplasty (25.9%) and mild-to-moderate keratitis (11.1%). There were 6 (7.4%) reoperations and 5 (6.2%) needlings by year 2. In an analysis (post hoc) according to MMC concentration, overall success was 78.1% (0.2 mg/ml) and 74.4% (0.4 mg/ml; P = 0.710). In the 0.2 and 0.4 mg/ml MMC groups, 51.9% and 90.3% of patients were medication free, respectively (P = 0.001). There was a trend toward lower IOP and higher medication reduction in the 0.4 mg/ml MMC subgroup. CONCLUSIONS In this study, mean IOP and glaucoma medication reductions were significant and sustained over 2 years postsurgery. No long-term, sight-threatening AEs were reported. Further studies may confirm potential risk/benefits of higher MMC concentration.

Bacterial infections are considered as a critical healthcare concern worldwide. Timely infection detection is crucial to effective antibiotic administration which can reduce the severity of infection and the occurrence of antibiotic resistance. We have developed label–free polydiacetylene (PDA) liposome-based colorimetric biosensor to detect and identify bacterial cultures at the genus and species level with naked eyes by simple color change. We found that among the various liposomal systems, moderate concentration of PDA, phospholipids and cholesterol in liposome assemblies can greatly influence the sensitivity to different bacteria, exhibiting unique chromatic properties of each bacterial strain. The strikingly different chromatic color change was due to the various mechanisms of interactions between bacterial toxins and biomimetic lipid bilayers. Furthermore, increase of cholesterol in liposome assemblies greatly enhanced the sensitivity of bacterial strains related to membrane destruction mediated by pore-formation mechanism such as S. aureus and E.coli, whereas the detection of the two bacterial strains was believed to rely on the specific recognition elements coupled with PDA moiety. As a proof of concept, a colorimetric finger-print array for distinguishing 6 bacterial species was studied. Particularly, the proposed bacterial detection platform is achieved through the interaction between bacterially secreted toxins and liposome bilayers instead of specific recognition of receptors-ligands. The results of both response time and sensitivity of label-free-liposome-based system show superior to previous reports on chromatic bacterial detection assays. By combing these results, the label-free-liposome-based colorimetric sensing platform shows great importance as a bacterial-sensing and discrimination platform.

The POPular Risk Score (PRiS), a pharmacogenetic-driven algorithm consisting of CYP2C19 genotype, platelet reactivity, and clinical risk factors, is developed to evaluate ischemic risk and guide dual antiplatelet therapy (DAPT). This study aimed to evaluate the efficacy and safety of DAPT in accordance with the PRiS in patients undergoing drug-eluting stent (DES) implantation. A total of 1757 patients recruited in this cohort study were divided into four groups according to the PRiS and type of P2Y12 receptor inhibitor treatment at discharge. The primary endpoint was major adverse cardiovascular events (MACE, a composite of cardiovascular death, myocardial infarction, stroke, definite or probable stent thrombosis, and target vessel revascularization) during 1-year follow-up. The safety endpoints were defined by Bleeding Academic Research Consortium (BARC) criteria as major bleeding (BARC 3a, 3b, 3c, and 5) and clinically relevant bleeding (BARC 2, 3a, 3b, 3c, and 5). Among 1046 patients with PRiS

Background. In recent years, it has been reported that miRNA can be used as one of the markers of tumor diagnosis, treatment, and prognosis (including liver cancer), and it plays an important role in tumorigenesis. However, there are still very few studies on the mechanism and role of miR-141 in liver cancer. Methods. qRT-PCR was used to test the expressions of miR-141 and STAT4 in collected liver cancer tissues and adjacent tissues, cultured liver cancer cell lines MHCC97H, Hep3B, and Huh7, and normal human liver cells HL7702. After processing the results of the qRT-PCR experiment, liver cancer cell MHCC97H which has the lowest expression level was decided to be taken as the research object. miR-NC, miR-141 mimics, si-NC, si-STAT4, miR-141 mimics and pcDNA-NC, and miR-141 mimics and pcDNA-STAT4 were transfected into MHCC97H cells, respectively. The MTT assay was used to detect the proliferation of each group of cells, and the Transwell test was used to detect the effect of miR-141 on cell proliferation, migration, and invasion. The interaction between miR-141 and STAT4 was verified by the dual-luciferase reporter experiment, and the expression level of Cyclin D1 and MMP2 was detected by the western blot. Results. Compared with normal cell HL7702, the expression level of miR-141 in liver cancer cell lines was relatively low P < 0.05 and the expression level of STAT4 in liver cancer cell lines was relatively high P < 0.05 after testing the expression level of STAT4; transfecting miR-141 mimics or Si-SLBP can inhibit cell proliferation, migration, and invasion; dual-luciferase reporter experiments confirmed that miR-141 can specifically bind to the 3′UTR of STAT4; cotransfection of miR-141 mimics and pcDNA-STAT4 can antagonize the effects of miR-141 mimics on cell proliferation, migration, and invasion. Conclusion. miR-141 can target the STAT4 gene expression to inhibit the proliferation, migration, and invasion of liver cancer cells.

Objective Resin-based dental adhesion is mostly utilized in minimally invasive operative dentistry. However, improving the durability and stability of resin–dentin bond interfaces remain a challenge. Graphene quantum dots (GQDs) reinforced by 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) were introduced to modify the resin–dentin bond interfaces, thereby promoting their durability and stability. Methods GQDs, EDC, and EDC+GQDs groups were designed to evaluate the effects of GQDs and EDC on collagenase activity, the interaction of GQDs with collagen, and the resin–dentin interface. First, the effects of GQDs and EDC on collagenase activity was evaluated by Collagenase (EC 3.4.24.3) reacting with its substrate. The interaction of GQDs and EDC with collagen were evaluated by cross-linking degree analysis, sodium dodecyl sulfate–polyacrylamide gel electrophoresis, attenuated total reflection Fourier transform infrared spectroscopy and enzymatic hydrolysis. Second, the acid-etched and rinse adhesive system was used to evaluate the resin–dentin bond on the basis of microtensile bond strength, in situ zymography and fluorescence confocal laser scanning microscopy. Results GQDs could inhibit collagenase activity. GQDs with the aid of EDC could cross-link collagen via covalent bonds and improve the anti-enzymatic hydrolysis of collagen. In the resin–dentin adhesion model, the μTBS of the EDC+GQDs group was significantly higher than the other control groups after thermocycling. The addition of EDC to GQDs could inhibit matrix metalloproteinase activity and promote the integrity of the bonding interfaces after thermocycling. Significance This study presents a novel strategy to modify the resin–dentin interface and provides a new application for GQDs. This strategy has the potential to improve the durability of resin-based restoration in dentistry.

BACKGROUND Exosomes participate in intercellular communication and act as important molecular vehicles in the regulation of numerous physiological and pathological processes, including autoimmune development. The role of circulating exosomes in the development of autoimmune uveitis is unknown. In this study, using the rat model of experimental autoimmune uveitis, which has clinical and histological features of pan uveitis in man, we evaluated the immunoregulatory function of circulating exosomes. METHODS Experimental autoimmune uveitis was induced in Lewis rats either immunised with interphotoreceptor retinoid-binding protein R16 peptides or injected with activated R16-specific T cells. The disease incidence and severity were examined by indirect fundoscopy and flow cytometry. Circulating exosomes were isolated from peripheral blood of naive and Day 14 R16 immunised Lewis rats. The effect of exosomes on specific T cells was evaluated by R16-specific T cell proliferation, cytokine production and recurrent uveitis induction. RESULTS Circulating exosomes derived from active immunised uveitis rats selectively inhibited immune responses of R16-specific T cells in vitro. Vaccination of naive rats with these exosomes reduced the incidence of recurrent uveitis in an antigen-specific manner. Antigen-specific uveitogenic T cells reduced IFN-γ production and increased IL-10 after vaccination. CONCLUSIONS Circulating exosomes in autoimmune uveitis have the potential to be a novel treatment for recurrent autoimmune uveitis.

Background The difference between the costs of the newer and older glucose-lowering drugs (GLMs) has been steadily increasing since 2010. In 2018, newer drugs cost 8-12 times more than older drugs (except for insulin). This study aimed to understand how the cost change influenced the cost-effectiveness of the newer GLMs. Methods Based on our previous literature review on US-based cost-effectiveness studies comparing newer (i.e., dipeptidyl peptidase-4 inhibitors (DPP4), glucagon-like peptide 1 receptor agonists (GLP1-RA), and sodium-glucose transport protein 2 inhibitors) with older GLMs, we identified 12 studies that reported the cost-effectiveness of newer drugs based on drug costs estimated before 2010. We updated the corresponding cost-effectiveness of each study by replacing the old cost estimates with 2018 estimates from the 2018 IBM® MarketScan® Commercial Claims Databases. The time window and willingness to pay threshold were consistent with the original studies. Results Only 8% of the original studies suggested that the older drugs were cost-effective. However, 58% of studies were in favor of the older drugs after the cost update. Among the four studies comparing newer drugs with thiazolidinediones, all the original results favored newer drugs. However, all studies suggested thiazolidinedione to be cost-effective in the updated analysis. For the four studies comparing newer drugs with sulfonylureas, two studies suggested the sulfonylureas to be cost-effective after the cost update. All four studies suggested newer drugs to be cost-effective when compared with insulin in the original study. Only 1 flipped its conclusion when 2018 costs were used. Our sensitivity analysis shows that our results are robust under a 30% rebate. Conclusion Significant changes in the cost of GLMs have impacted the economic value of different GLM classes substantially. More cost-effectiveness analyses are warranted to support the drug choice in T2DM management.

Jiali Yang,1,&ast; Zhixia Jia,1,&ast; Zhigang Xiao,1 Jing Zhao,2 Ye Lu,2 Li Chu,3 Hui Shao,1,2 Lin Pei,1,2 Shaodan Zhang,4 Yuan Chen4 1School of Integrated Traditional Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 2Hebei Key Laboratory of Turbidity, Hebei Academy of Chinese Medicine Sciences, Shijiazhuang, Hebei, 050011, People’s Republic of China; 3School of Pharmacy, Hebei University of Chinese Medicine, Shijiazhuang, Hebei, 050200, People’s Republic of China; 4Pediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of China&ast;These authors contributed equally to this workCorrespondence: Shaodan Zhang; Lin PeiPaediatrics, The Second Hospital of Hebei Medical University, Shijiazhuang, Hebei, 050051, People’s Republic of ChinaTel/Fax +86 13653115066; +86 13831190309Email 13653115066@163.com; peilin13831190309@126.comPurpose: This study aims to evaluate the beneficial effects of anti-epileptic mechanisms of baicalin (BA) on cognitive dysfunction and neurodegeneration in pentylenetetrazol (PTZ)-induced epileptic rats.Methods: First, PTZ-induced epileptic rats were administered intraperitoneally a sub-convulsive dose of PTZ (40 mg/kg) daily, and the seizure susceptibility (the degree of seizures and latency) was evaluated using Racine’s criterion. Then, classical behavioral experiments were performed to test whether BA ameliorated cognitive dysfunction. Neurodegeneration was assessed using Fluoro Jade-B (FJB), and NeuN staining was used to determine whether BA offered a neuroprotective role. After BA had been proven to possess anti-epileptic effects, its possible mechanisms were analyzed through network pharmacology. Finally, the key targets for predictive mechanisms were experimentally verified.Results: The epileptic model was successfully established, and BA had anti-epileptic effects. Epileptic rats displayed significant cognitive dysfunction, and BA markedly ameliorated cognitive dysfunction. Further, we also discovered that BA treatment mitigated neurodegeneration of the hippocampus CA3 regions, thereby ameliorated cognitive dysfunction of epileptic rats. Subsequent network pharmacology analysis was implemented to reveal a possible mechanism of BA in the anti-epileptic process and the TLR4/MYD88/Caspase-3 pathway was predicted. Finally, experimental studies showed that BA exerted an anti-epileptic effect by activating the TLR4/MYD88/Caspase-3 pathway in PTZ-induced epileptic rats.Conclusion: In conclusion, BA had a protective effect against PTZ-induced seizures. BA improved cognitive dysfunction and exerted a neuroprotective action. The anti-epileptic effects of BA may be potentially through activation of the TLR4/MYD88/Caspase-3 pathway.Keywords: baicalin, pentylenetetrazol, epilepsy, cognitive dysfunction, network pharmacology, TLR4/MYD88/Caspase-3

The androgen receptor (AR) is expressed in prostate fibroblasts in addition to normal prostate epithelial cells and prostate cancer (PCa) cells. Moreover, AR activation in fibroblasts dramatically influences prostate cancer (PCa) cell behavior. Androgen deprivation leads to deregulation of AR downstream target genes in both fibroblasts and PCa cells. Here, we identified LIM domain only 2 (LMO2) as an AR target gene in prostate fibroblasts using ChIP-seq and revealed that LMO2 can be repressed directly by AR through binding to androgen response elements (AREs), which results in LMO2 overexpression after AR deactivation due to normal prostate fibroblasts to cancer-associated fibroblasts (CAFs) transformation or androgen deprivation therapy. Next, we investigated the mechanisms of LMO2 overexpression in fibroblasts and the role of this event in non-cell-autonomous promotion of PCa cells growth in the androgen-independent manner through paracrine release of IL-11 and FGF-9. Collectively, our data suggest that AR deactivation deregulates LMO2 expression in prostate fibroblasts, which induces castration resistance in PCa cells non-cell-autonomously through IL-11 and FGF-9.

Postpartum depression (PPD) is a highly prevalent disorder characterized by increased vulnerability to morbidity and mortality. This study explores the predictors and prevalence of PPD among Taiwanese women. A total of 914 postpartum women was recruited from a mother-child-friendly hospital. These participants completed self-report questionnaires at 1 month postpartum, and their medical records were also examined for relevant information. Multivariate analyses were used to identify independent predictors of PPD. At 1 month postpartum, 18.8% had developed PPD. Multivariate analysis showed that the odds ratios for PPD were significantly lower among women who were breastfeeding, had more family support, and attended a postpartum care center, while those who were younger, primiparous, and who experienced gestational complications had a higher prevalence of PPD. Meanwhile, structural equation modeling showed that family support from partners, parents, and parents-in-law diminished depression scores through direct effects.

A total of 115 convalescent inpatients with COVID-19 were enrolled. According to the results of scans of lung lesions via computed tomography (CT), the patients were divided into mild, moderate, and severe groups. The clinical data of the patients were collected, including age, gender, finger pulse oxygen pressure, ventricular rate, body temperature, etc. The correlation between the clinical indicators and the lesions of high-resolution CT (HRCT) and bronchiectasis was analyzed. Among the 115 patients, 82 had no bronchiectasis and 33 had bronchiectasis. The bronchodilation-prone layers mainly included the left and right lower lobe of the lung. The probability of branching in the inflamed area was greater than that in the noninflamed area in patients with COVID-19. There were significant differences in gender, CT lesion range, and number of incidents of bronchiectasis between noninflamed and inflamed areas (P < 0.05). Moreover, there were significant differences in age, total proportion of CT lesions, volume of CT lesions, and total number of patients with bronchiectasis among the three groups (P < 0.05). CT lesion range was positively correlated with the total number of patients with bronchiectasis and patient age (respectively, r = 0.186, P < 0.05; r = 0.029, P < 0.05). The lesion range in HRCT images of lungs in patients with COVID-19 is correlated with bronchodilation. The larger the lesion, the higher the probability of bronchiectasis and the more incidents of bronchiectasis.

This study aims to estimate the national impact and cost-effectiveness of the 2018 American College of Physicians (ACP) guidance statements compared to the status quo.Survey data from the 2011-2016 National Health and Nutrition Examination were used to generate a national representative sample of individuals with diagnosed type 2 diabetes in the United States. Individuals with A1c6.5% on antidiabetic medications are recommended to deintensify their A1c level to 7.0% to 8.0% (group 1); individuals with A1c 6.5% to 8.0% and a life expectancy of10 years are recommended to deintensify their A1c level8.0% (group 2); and individuals with A1c8.0% and a life expectancy of10 years are recommended to intensify their A1c level to 7.0% to 8.0% (group 3). We used a Markov-based simulation model to evaluate the lifetime cost-effectiveness of following the ACP recommended A1c level.14.41 million (58.1%) persons with diagnosed type 2 diabetes would be affected by the new guidance statements. Treatment deintensification would lead to a saving of $363 600 per quality-adjusted life-year (QALY) lost for group 1 and a saving of $118 300 per QALY lost for group 2. Intensifying treatment for group 3 would lead to an additional cost of $44 600 per QALY gain. Nationally, the implementation of the guidance would add 3.2 million life-years and 1.1 million QALYs and reduce healthcare costs by $47.7 billion compared to the status quo.Implementing the new ACP guidance statements would affect a large number of persons with type 2 diabetes nationally. The new guidance is cost-effective.

Background The effect of type of atrial fibrillation (AF) on adverse outcomes in Chinese patients without oral anticoagulants (OAC) was controversial. Hypothesis The type of AF associated with adverse outcomes in Chinese patients without OAC. Methods A total of 1358 AF patients without OAC from a multicenter, prospective, observational study was included for analysis. Univariable and multivariable Cox regression models were utilized. Net reclassification improvement analysis was performed for the assessment of risk prediction models. Results There were 896(66%) patients enrolled with non‐paroxysmal AF (NPAF) and 462(34%) with paroxysmal AF (PAF). The median age was 70.9 ± 12.6 years, and 682 patients (50.2%) were female. During 1 year of follow‐up, 215(16.4%) patients died, and 107 (8.1%) patients experienced thromboembolic events. Compared with the PAF group, NPAF group had a notably higher incidence of all‐cause mortality (20.2% vs. 9.4%, p

Background It was reported that intravenous amiodarone might induce ventricular fibrillation for acute treatment in patients with atrial fibrillation (AF) and Wolff-Parkinson-White (WPW) syndrome. No study was done to assess its application comprehensively in this population. Methods This study was a retrospective analysis and undertaken by reviewing medical records and electronic databases to search for patients admitted with tachycardia resulting from WPW syndrome and AF, who have intravenously administrated amiodarone at the emergency department from January 2008 to June 2018. Results Thirty patients were involved in this study, of which 27 were males. The mean age of the patients was 47.8 ± 17.0 years. The mean systolic blood pressure and diastolic blood pressure were 111.9 ± 18.3 mmHg and 76.1 ± 14.6 mmHg, respectively. The mean heart rate was 171 (150-189) beats per minute. Half of the patients (53.3%) had no comorbidities, and only one had prior syncope. Nearly 17 patients (56.7%) started with a loading dose of 150 mg. No ventricular acceleration or VF developed. The incidence of hypotension was 3.3% (1/30). Eighteen patients (60.0%) restored to sinus rhythm by amiodarone with the conversion time of 486.0 (229.0-1278.0) minutes. Conclusions Intravenous amiodarone might be an alternative for acute treatment of AF and WPW syndrome in patients characterized by stable hemodynamics, relatively low admission heart rate, few comorbidities, elder age, and no prior syncope. The loading dosage of 150 mg appeared to be preferred, and the maintenance period was better to less than 12 hours. Monitoring and electrolyte correction were also necessary. It is essential to keep a defibrillator nearby during pharmacologic cardioversion.

Background Clinical guidelines recommend a stepped-escalation treatment strategy for type 2 diabetes (T2DM). Across multiple treatment strategies varying in efficacy and costs, no clinical or economic studies directly compared them. This study aims to estimate and compare the cost-effectiveness of 10 commonly used pharmacologic combination strategies for T2DM. Methods Based on Chinese guideline and practice, 10 three-stepwise add-on strategies were identified, which start with metformin, then switch to metformin plus one oral drug (i.e., sulfonylurea, thiazolidinedione, α-glucosidase inhibitor, glinide, or DPP-4 inhibitor) as second line, and finally switch to metformin plus one injection (i.e., insulin or GLP-1 receptor agonist) as third line. A cohort of 10,000 Chinese patients with newly diagnosed T2DM was established. From a healthcare system perspective, the Cardiff model was used to estimate the cost-effectiveness of the strategies, with clinical data sourced from a systematic review and indirect treatment comparison of 324 trials, costs from claims data of 1164 T2DM patients, and utilities from an EQ-5D study. Outcome measures include costs, quality-adjusted life-years (QALYs), incremental cost-effectiveness ratios (ICERs), and net monetary benefits (NMBs). Results Over 40-year simulation, the costs accumulated for a patient ranged from $7661 with strategy 1 to $14,273 with strategy 10, while the QALY gains ranged from 13.965 with strategy 1 to 14.117 with strategy 8. Strategy 7 was dominant over seven strategies (strategies 2~6, 9~10) with higher QALYs but lower costs. Additionally, at a willingness-to-pay threshold of $30,787/QALY (i.e., 3 times GDP/capita for China), strategy 7 was cost-effective compared with strategy 1 (ICER of strategy 7 vs. 1, $3371/QALY) and strategy 8 (ICER of strategy 8 vs. 7, $132,790/QALY). Ranking the strategies by ICERs and NMBs, strategy 7 provided the best value for money when compared to all other strategies, followed by strategies 5, 9, 8, 1, 3, 6, 10, 2, and 4. Scenario analyses showed that patients insist on pharmacologic treatments increased their QALYs (0.456~0.653) at an acceptable range of cost increase (ICERs, $1450/QALY~$12,360/QALY) or even at cost saving compared with those not receive treatments. Conclusions This study provides evidence-based references for diabetes management. Our findings can be used to design the essential drug formulary, infer clinical practice, and help the decision-maker design reimbursement policy.

The outbreak of coronavirus disease 2019 (COVID-19) has spread rapidly around the world. As of May 30, 2020, a total of 84 568 confirmed COVID-19 cases have been recorded in China, with a mortality rate of approximately 5.5%. Taizhou is a prefecture-level city in Zhejiang Province. A total of 146 cases were diagnosed in this epidemic, with a fatality rate of 0%. This condition is due to the establishment of an “Internet +” diagnosis and treatment model based on online medical application (APP), telemedicine, WeChat service, and consultation hotline in Taizhou. Taizhou led in opening the “COVID-19 Prevention and Treatment Special Line” in China, which is conducive to pre-hospital screening, suppressing social panic, and clinical support. Hospitals also carried out related online lectures and popularization of science. We summarize Taizhou’s COVID-19 prevention and control experience with telemedicine features, with a view to providing reference for the control of the epidemic at home and abroad.

Background Lifestyle change interventions (LCI) for prevention of type 2 diabetes are covered by Medicare, but rarely by US Medicaid programs that constitute the largest public payer system in the USA. We estimate the long-term health and economic implications of implementing LCIs in state Medicaid programs. Methods We compared LCIs modeled after the intervention of the Diabetes Prevention Program versus routine care advice using a decision analytic simulation model and best available data from representative surveys, cohort studies, Medicaid claims data, and the published literature. Target population were non-disability-based adult Medicaid beneficiaries aged 19–64 years at high risk for type 2 diabetes (BMI ≥25 kg/m2 and HbA1c ≥ 5.7% or fasting plasma glucose ≥ 110 mg/dl) from eight study states (Alabama, California, Connecticut, Florida, Iowa, Illinois, New York, Oklahoma) that represent around 50% of the US Medicaid population. Incremental cost-effectiveness ratios (ICERs) measured in cost per quality-adjusted life years (QALYs) gained, and population cost and health impact were modeled from a healthcare system perspective and a narrow Medicaid perspective. Results In the eight selected study states, 1.9 million or 18% of non-disability-based adult Medicaid beneficiaries would belong to the eligible high-risk target population – 66% of them Hispanics or non-Hispanic black. In the base-case analysis, the aggregated 5- and 10-year ICERs are US$226 k/QALY and US$34 k/QALY; over 25 years, the intervention dominates routine care. The 5-, 10-, and 25-year probabilities that the ICERs are below US$50 k (US$100 k)/QALY are 6% (15%), 59% (82%) and 96% (100%). From a healthcare system perspective, initial program investments of US$800 per person would be offset after 13 years and translate to US$548 of savings after 25 years. With a 20% LCI uptake in eligible beneficiaries, this would translate to upfront costs of US$300 million, prevent 260 thousand years of diabetes and save US$205 million over a 25-year time horizon. Cost savings from a narrow Medicaid perspective would be much smaller. Minorities and low-income groups would over-proportionally benefit from LCIs in Medicaid, but the impact on population health and health equity would be marginal. Conclusions In the long-term, investments in LCIs for Medicaid beneficiaries are likely to improve health and to decrease healthcare expenditures. However, population health and health equity impact would be low and healthcare expenditure savings from a narrow Medicaid perspective would be much smaller than from a healthcare system perspective. Electronic supplementary material The online version of this article (10.1007/s40258-020-00565-w) contains supplementary material, which is available to authorized users.

Background To investigate the biomechanical properties of the cornea in myopic eyes using corneal visualization Scheimpflug technology (Corvis ST). The relationships between the biomechanical properties of the cornea and the degree of myopia were also investigated. Methods 265 eyes of 265 subjects were included. Based on spherical equivalent (SE) in diopters (D), participants were divided into four groups: low myopia/control (SE: − 0.50 to − 3.00D), moderate myopia (SE: − 3.00 to − 6.00D), high myopia (SE: − 6.00 to − 10.00D) and severe myopia (SE greater than − 10.00D). Axial length (AL), anterior segment parameters, and corneal biomechanical properties were obtained with the Lenstar LS900, Pentacam HR and Corvis ST, respectively. Results Mean (±SD) SE was − 7.29 ± 4.31D (range: − 0.63 to − 25.75D). Mean AL was 26.31 ± 1.82 mm (range: 21.87 to 31.94 mm). Significant differences were detected within the four groups in terms of six corneal biomechanical parameters: deformation amplitude (DA), time from start until second applanation (A2-time), length of flattened cornea at the second applanation (A2-length), corneal velocity during the first and second applanation (A2-velocity), time from start to highest concavity (HC-time), and central curvature at highest concavity (HC radius). AL was positively associated with DA whereas negatively associated with A1-velocity and A2-length. SE was positively associated with A2-time, HC-time and A2-velocity, whereas negatively associated with DA. IOP was positively associated with four corneal biomechanical parameters and negatively associated with three parameters. Conclusions Eyes with severe myopia showed greater DA, lesser A2 time, HC time, and faster A2-velocity compared to low to high myopia. This suggests the cornea becomes weaker and more deformable with elongation of axial length with corresponding increases in myopia. DA, A2-time and A2-velocity could be useful corneal biomechanical indicators in patients with myopia.

Cytochrome P450 (CYP) 2C19 genotype is closely associated with the metabolism and efficacy of clopidogrel, thereby having an important impact on clinical outcomes of patients with acute coronary syndrome (ACS) or undergoing percutaneous coronary intervention (PCI). This study aimed to evaluate the efficacy and safety of CYP2C19 genotype-guided antiplatelet therapy in patients with ACS or undergoing PCI. PubMed, EMBASE, the Cochrane Library and clinicaltrials.gov were searched to identify randomized controlled trials (RCTs) comparing CYP2C19 genotype-guided antiplatelet therapy with conventional therapy in patients with ACS or undergoing PCI. Eight RCTs involving 6708 patients were included in this meta-analysis. CYP2C19 genotype-guided antiplatelet therapy was slightly superior to the conventional antiplatelet therapy in reducing the risk of MACE [RR(95%CI): 0.71(0.51-0.98)

OBJECTIVE This study evaluated the ability of the Building, Relating, Assessing, and Validating Outcomes (BRAVO) risk engine to accurately project cardiovascular outcomes in three major clinical trials—BI 10773 (Empagliflozin) Cardiovascular Outcome Event Trial in Type 2 Diabetes Mellitus Patients (EMPA-REG OUTCOME), Canagliflozin Cardiovascular Assessment Study (CANVAS), and Dapagliflozin Effect on Cardiovascular Events–Thrombolysis in Myocardial Infarction (DECLARE-TIMI 58) trial—on sodium–glucose cotransporter 2 inhibitors (SGLT2is) to treat patients with type 2 diabetes. RESEARCH DESIGN AND METHODS Baseline data from the publications of the three trials were obtained and entered into the BRAVO model to predict cardiovascular outcomes. Projected benefits of reducing risk factors of interest (A1C, systolic blood pressure [SBP], LDL, or BMI) on cardiovascular events were evaluated, and simulated outcomes were compared with those observed in each trial. RESULTS BRAVO achieved the best prediction accuracy when simulating outcomes of the CANVAS and DECLARE-TIMI 58 trials. For EMPA-REG OUTCOME, a mild bias was observed (∼20%) in the prediction of mortality and angina. The effect of risk reduction on outcomes in treatment versus placebo groups predicted by the BRAVO model strongly correlated with the observed effect of risk reduction on the trial outcomes as published. Finally, the BRAVO engine revealed that most of the clinical benefits associated with SGLT2i treatment are through A1C control, although reductions in SBP and BMI explain a proportion of the observed decline in cardiovascular events. CONCLUSIONS The BRAVO risk engine was effective in predicting the benefits of SGLT2is on cardiovascular health through improvements in commonly measured risk factors, including A1C, SBP, and BMI. Since these benefits are individually small, the use of the complex, dynamic BRAVO model is ideal to explain the cardiovascular outcome trial results.

Background Elevated body mass index (BMI) is related with reduced mortality in various cardiovascular diseases. Hypothesis Gender‐specific association between BMI and mortality exists in atrial fibrillation (AF). Methods In this multicenter observational study with a mean follow‐up of 1 year, a total of 1991 AF patients were enrolled and divided into two groups based on the gender. The primary endpoint was all‐cause mortality while the secondary endpoints were defined as cardiovascular mortality, stroke, and major adverse events during 1‐year follow‐up. Cox regression was performed to identify the association between BMI and clinical outcomes according to gender. Results Female patients with AF tended to be older (P = .027) and thinner (P

Background Our objective was to retrospectively analyze the influence of DE-T1, a type of amino-polysaccharide extracted from dandelions, on the rates of blastocysts obtained and live births in women undergoing IVF-ET treatment. Methods This was a retrospective cohort study, conducting a total of 1014 patients over the age of 30, who received IVF treatment at Hanabusa Women’s clinic from Aug. 1, 2012 to Feb. 29, 2020. The patients were divided into two groups, based on their own choice regarding DE-T1 supplementation, which is available as over the counter medicine at the Clinic. The two groups’ overall rates of blastocysts obtained were compared and the rates of blastocysts obtained in patients with different ages and Anti-Mullerian hormone (AMH) levels were also compared using an Intention-to-treat (ITT) analysis. Among the patients who completed embryo transfers (ET), the live birth rate was compared between the supplementation group and the non-supplementation group using a Chi-squared test. Results The blastocyst obtained rate in the supplementation group was 75.98%, which was significantly higher than that of 57.28% in the non-supplementation group (P=2.4×109). The blastocyst obtained rate across the range of ages in the supplementation group were significantly higher than those of the non-supplementation group (≥30 and 5). The blastocyst obtained rate for both AMH levels in the supplementation group were significantly higher than those of the non-supplementation group (AMH≤1.1: 56.47% vs 40.44%, P=0.002; AMH> 1.1: 88.48% vs 71.08%, P=2.52×107). The live birth rate of the supplementation group was significantly higher than that of the non-supplementation group (57.53% vs. 40.0%, P=0.045). Conclusion DE-T1 supplementation might be an influence on improving the blastocyst obtained rate and live birth rates in women receiving IVF-ET treatment. DE-T1 supplementation might be of benefit to women of different ages and AMH levels.

Kallistatin or kallikrein-binding protein (KBP) has been reported to regulate angiogenesis, inflammation and tumor progression. Autoimmune uveitis is a common, sight-threatening inflammatory intraocular disease. However, the roles of kallistatin in autoimmunity and autoreactive T cells are poorly investigated. Compared to non-uveitis controls, we found that plasma levels of kallistatin were significantly upregulated in patients with Vogt-Koyanagi-Harada (VKH) disease, one of the non-infectious uveitis. Using an experimental autoimmune uveitis (EAU) model induced by human interphotoreceptor retinoid-binding protein peptide 651-670 (hIRBP651-670), we examined the effects of kallistatin on the pathogenesis of autoimmune diseases. Compared to wild type (WT) mice, kallistatin transgenic (KS) mice developed severe uveitis with dominant Th17 infiltrates in the eye. In addition, the proliferative antigen-specific T cells isolated from KS EAU mice produced increased levels of IL-17A, but not IFN-γ or IL-10 cytokines. Moreover, splenic CD4+ T cells from naïve KS mice expressed higher levels of Il17a mRNA compared to WT naïve mice. Under Th17 polarization conditions, KS mice exhibited enhanced differentiation of naïve CD4+ T cells into Th17 cells compared to WT controls. Together, our results indicate that kallistatin promotes Th17 differentiation and is a key regulator of aggravating autoinflammation in EAU. Targeting kallistatin might be a potential to treat autoimmune disease.

This study aimed to evaluate the predictive performance of the REACH, PARIS, BleeMACS, and PRECISE-DAPT scores in Chinese patients undergoing coronary drug-eluting stent (DES) implantation. A total of 1911 patients undergoing coronary DES implantation were consecutively recruited and followed up for 1 year. The primary endpoints were BARC type 3 or 5 bleeding and BARC type 2,3, or 5 bleeding. The BleeMACS score and the PRECISE-DAPT score were significantly associated with 1-year incidence of BARC type 3 or 5 bleeding, but not BARC type 2, 3, or 5 bleeding. The discrimination of the PRECISE-DAPT score was moderate for BARC type 3 or 5 bleeding (c-statistic = 0.633), while those of the REACH (c-statistic = 0.533), PARIS (c-statistic = 0.553), and BleeMACS scores (c-statistic = 0.613) were relatively low. However, the analysis of c-statistic, NRI, and IDI detected no significant discrimination improvement of the PRECISE-DAPT score for BARC type 3 or 5 bleeding compared to the other three scores. The calibrations of the PRECISE-DAPT and BleeMACS scores were modest (Hosmer-Lemeshow test p > .05). Decision curve analysis indicated net benefit of the PRECISE-DAPT score in bleeding risk evaluation. In conclusion, the PRECISE-DAPT score performed moderately in predicting BARC type 3 or 5 bleeding, while the discriminative capacities of the REACH, PARIS, BleeMACS scores were relatively low in patients undergoing DES implantation. But no significant discrimination improvement of the PRECISE-DAPT score compared to the other scores could be detected. Further studies are required to develop standardized bleeding risk scores for this population.

Non-infectious autoimmune uveitis (NIU) in man is a heterogeneous group of diseases characterized by inflammation of the uveal tract and adjacent ocular structures.1 The disease course can be acute...

Background: Substantial evidence indicated that absolute income is directly associated with health. Few studies have, however, examined if relative income may be equally associated with health. This study aimed to investigate the association between absolute income/relative deprivation (RD) and self-rated health (SRH). We also investigated whether the urban-rural difference was existing in these associations.Methods: Using cross-sectional data of 7,070 participants in the Shandong Family Health Service Survey of older people, this study applied binary logistic model and semi-parametric model to estimate the effect of absolute income and relative deprivation on SRH of older people. The Kakwani Index was used as a measure of relative deprivation at the individual level.Results: Absolute income has a significant positive effect on the SRH among both urban and rural older people. When considered RD as a variable, both absolute income and RD have negative significant effects on SRH among all older people. In addition, the negative effect of RD on rural elderly is more pronounced than that of urban older populations. Semi-parametric regression results show that there was a complex non-linear relationship between income and SRH. Psychological distress substantially attenuated the association between relative deprivation and SRH.Conclusions: Relative deprivation is negatively associated with self-rated health in both urban and rural older people after controlling the absolute income. RD may partly explain the association between income inequality and worse health status. Compared with the urban elderly, the effect of income-based relative deprivation on SRH was more pronounced among the rural elderly, and more care should be given to the lower income and rural older populations.