Search

Hypochlorite (ClO

Solute carrier (SLC) transporters meditate many essential physiological functions, including nutrient uptake, ion influx/efflux, and waste disposal. In its protective role against tumors and infections, the mammalian immune system coordinates complex signals to support the proliferation, differentiation, and effector function of individual cell subsets. Recent research in this area has yielded surprising findings on the roles of solute carrier transporters, which were discovered to regulate lymphocyte signaling and control their differentiation, function, and fate by modulating diverse metabolic pathways and balanced levels of different metabolites. In this review, we present current information mainly on glucose transporters, amino-acid transporters, and metal ion transporters, which are critically important for mediating immune cell homeostasis in many different pathological conditions., Graphical abstract Solute carrier (SLC) transporters meditate many essential physiological functions. In this review, we present current information mainly on glucose transporters, amino-acid transporters, and metal ion transporters, which are critically important for mediating immune cell homeostasis in many different pathological conditions.Image 1

Background:Patients with rheumatoid arthritis (RA) who have received multiple biologics or targeted therapies over time tend to have more refractory and more severe disease, which may lead to worse clinical response to treatment.Objectives:We used data from the ACR RISE registry to assess whether disease severity was greater in those who received sarilumab shortly after its FDA approval (May 2017) than in subsequent time periods and to evaluate the effectiveness of sarilumab in populations with various degrees of disease severity.Methods:Patients with RA who initiated sarilumab treatment in the period 2017-2020 were identified in the ACR RISE registry and divided into Cohort 1 (2017, year of the FDA approval) and the calendar year-based Cohorts 2-4 (2018-2020). Patient demographics, RA-related features, and comorbidities were determined using data prior to sarilumab initiation. The cohorts were compared using chi-square test (categorical variables) and a nonparametric test (continuous variables). Sarilumab effectiveness was assessed using 3 cohorts assembled based on progressively restrictive criteria: Active Disease cohort (Clinical Disease Activity Index [CDAI] >10 or Routine Assessment of Patient Index Data 3 [RAPID3] >6, and C-reactive protein, if measured, ≥8 mg/L), TARGET Eligibility cohort (patients who satisfied enrolment criteria for TARGET,1 a Phase 3 sarilumab trial in patients with RA and an inadequate response to TNF inhibitors), and TARGET Baseline cohort (patients from TARGET Eligibility cohort with characteristics weighted to match those from the TARGET trial baseline,1 using the matching-adjusted indirect comparison method2). In all 3 effectiveness cohorts, mean changes in CDAI and RAPID3 at 6 and 12 months post-initiation of sarilumab were evaluated using a model adjusted for baseline score, age, sex, race, calendar year, and seropositivity.Results:A total of 2949 patients, treated by 585 rheumatologists, initiated sarilumab treatment in the period 2017–2020. The 4 yearly cohorts were relatively similar in terms of patients’ age, sex, race, and most clinical characteristics. However, patients receiving sarilumab shortly after FDA approval (Cohort 1) had more ambulatory visits, a greater number of previously used non-TNFi biologics (particularly tocilizumab), and a higher comorbidity burden, and were more likely to be current users of glucocorticoids or opioids than sarilumab initiators in the subsequent 3 years. In the 3 cohorts used to assess sarilumab effectiveness, the greatest improvement was observed in the TARGET Baseline cohort, which also had the greatest mean baseline CDAI score (43), compared with the other two (24 both).Conclusion:In this real-world cohort, we observed modest evidence for channeling of patients with greater RA severity and greater prior exposure to non-TNFi biologics to sarilumab shortly after its FDA approval. This cohort effect did not diminish the effectiveness of sarilumab. All cohorts showed improvement, with the greatest clinical improvement observed in the cohort with the highest baseline CDAI score who most closely resembled those enrolled in a phase 3 trial of patients with an inadequate response to TNF inhibitors.References:[1]Fleischmann R, et al. Arthritis Rheumatol 2017;69:277-290.[2]Signorovitch JE et al. Value Health 2012;15:940-7.Figure 1.Adjusted improvements in CDAI and RAPID3Acknowledgements:This study was sponsored by Sanofi. Medical writing support was provided by Vojislav Pejović, PhD (Eloquent Medical Affairs, division of Envision Pharma Group) and funded by Sanofi.Disclosure of Interests:Stefano Fiore Employee of: Sanofi, Lang Chen: None declared, Cassie Clinton Consultant of: Information available in profile, Huifeng Yun Grant/research support from: Research support for Pfizer, Amy Praestgaard Employee of: Sanofi, Kerri Ford Employee of: Sanofi, Jeffrey Curtis Consultant of: Received consulting and research grants from AbbVie, Amgen, BMS, Lilly, Gilead, GSK, Janssen, Myriad, Pfizer, Roche, Samsung, Sandoz, Sanofi, UCB, Grant/research support from: Received consulting and research grants from AbbVie, Amgen, BMS, Lilly, Gilead, GSK, Janssen, Myriad, Pfizer, Roche, Samsung, Sandoz, Sanofi, UCB

Catalytic amination of diols with dimethylamine is a promising approach for the preparation of tetramethyl diamines. In this work, a series of Cu/ZnO/γ-Al2O3 catalysts were developed by co-precipitation and employed in the amination of 1,6-hexanediol (HDO) with dimethylamine (DMA) to N, N, N’, N’-tetramethyl-1,6-hexanediamine (TMHDA) in a fixed-bed reactor. Cu/ZnO/γ-Al2O3–20 exhibited remarkable catalytic performance. Nearly complete conversion of HDO was reached and 93% selectivity of TMHDA was obtained at 180 °C. The excellent catalytic performance was attributed to the highly dispersion of Cu, which was promoted by doped ZnO. The results of characterizations (TEM, H2-TPR, XRD, XPS, etc.) indicated that doped ZnO could efficiently decrease the average particle size and improve the dispersion of Cu. The promoting effect could be ascribed to strong interaction between Cu and ZnO. The availability and effectiveness of Cu/ZnO/γ-Al2O3 catalyst offer a prospective way for the industrial production of tertiary diamines through amination of diols.

Three series of D-π-A 2,6-dimethyl-4-pyrone-cored derivatives were designed and synthesized. Evaluation by spectroscopic methods indicated that all the compounds exhibited aggregation-induced emission enhancement (AIEE) effect and solvatochromism. The experimental results revealed that the restriction of intramolecular rotation is the key element for showcasing the AIEE phenomenon. Moreover, all of the compounds presented red-shifted mechanochromic behavior, the extent of the red-shift was mainly dependent on the position and length of alkoxyl group. The PXRD and DSC profiles demonstrated a transformation from crystalline to amorphous state upon grinding. The D-A strategy introduced in this work could facilitate the development and application of ingenious mechanochromic materials.

Porcine circovirus-associated disease (PCVAD) caused by porcine circovirus type 2 (PCV2) is an important disease in the global pig industry. Dendritic cells (DCs) are the primary immune cells capable of initiating adaptive immune responses as well as major target cells of PCV2. To determine whether PCV2 affects the immune functions of DCs, we evaluated the expression of endocytosis and co-stimulatory molecules on DCs (CD11c+) from PCV2-infected mouse spleen by flow cytometry (FCM). We also analyzed the main cytokines secreted by DCs (CD11c+) and activation of CD4+ and CD8+ T cells by DCs (CD11c+) through measurement of cytokine secretion, using ELISA. Compared with control mice, PCV2 did not affect the endocytic activity of DCs but it significantly enhanced TNF-α secretion and markedly decreased IFN-α secretion. Subsets of CD40+, MHCII+ CD40+ and CD137L+ CD86+ DCs did not increase obviously, but MHCII+ CD40- and CD137L- CD80+/CD86+ DCs increased significantly in PCV2-infected mouse spleen. Under the stimulation of DCs from PCV2-infected mouse, secretion of IFN-γ by CD4+ and CD8+ T cells and of IL-12 by CD8+ T cells was significantly lower than in control mice, while secretion of IL-4 by CD4+ T cells was remarkably higher. These results indicate that PCV2 modulates cytokine secretion and co-stimulatory molecule expression of DCs, and alters activation of CD4+ and CD8+ T cells by DCs. The immunomodulatory effects of PCV2 on DCs might be related to the host's immune dysfunction and persistent infection with this virus.

The goal of the study was to characterize risk pertaining to seafood consumption patterns following the Deepwater Horizon oil spill, among school children (K to 4th grade) residing in close proximity to the Gulf of Mexico in Mobile County, Alabama.Responses on seafood consumption pattern including the type of seafood and intake rate during the pre and post oil spill periods, from parents of 55 school children from three schools located20mile radius from the Gulf of Mexico shoreline (coastal group) were compared with those from parents of 55 children from three schools located ≥20miles away from the shoreline (inland group). We also estimated levels of concern (LOCs) in seafood for selected chemicals found in crude oil including heavy metals, and polycyclic aromatic hydrocarbons (PAH), and dioctyl sodium sulfosuccinate (DOSS), the primary compound in dispersants.The coastal group ate more seafood consisting primarily of crustaceans (62% vs. 42%, p=0.04) and fin fish (78% vs. 58%, p=0.02) from the Gulf of Mexico compared to the inland group, while the inland group ate more fin fish not found in the Gulf of Mexico (62% vs. 33%, p0.01). In the post-oil spill time period, both groups substantially reduced their consumption of sea food. On average, the coastal group ate ≥2 seafood meals per week, while the inland group ate ≤1 meal per week; these frequency patterns persisted in the post oil-spill period. Comparison of the estimated LOCs with contaminant levels detected in the seafood tested by the Food and Drug Administration and National Oceanic and Atmospheric Administration, post-oil spill, found that the levels of PAHs, arsenic, and DOSS in seafood were 1-2 orders of magnitude below the LOCs calculated in our study. Levels of methyl mercury (MeHg) in the seafood tested pre- and post- oil spill were higher than the estimated LOCs suggesting presence of higher levels of MeHg in seafood independent of the oil spill.In sum, the study found higher than average seafood consumption among children along the Mobile coastal area when compared to the inland children and the National Health and Nutrition Examination Survey (NHANES) estimates. Risk characterization based on the LOCs indicated no increase in risk of exposure despite higher seafood consumption rates among the study population compared to the general population.

Herein, a series of 3D nitrogen-doped graphene gels (NG) were synthesized for the removal of dyes from wastewater. Their structures were characterized by XRD, SEM, TEM, elemental analysis, BET analysis, and XPS. It was found that the distribution of functional groups on the NG surface could be significantly affected using different nitrogen sources, which could further influence their adsorption behaviors. Among them, the hybrid prepared from hexamethylenediamine as the nitrogen source shows best adsorbability for acidic dyes, whereas the hybrid obtained from ethylenediamine displays largest adsorption capacity for basic dyes. Adsorption isotherms and kinetics were also investigated. The results indicate that the best interpretation is provided by the Langmuir isotherm equation, and the adsorption dynamic behavior is fit for the pseudo-first-order model. In addition, intra-particle diffusion kinetics manifest rate-controlling steps including external diffusion and intra-particle diffusion. Moreover, all adsorbents exhibit excellent reusability. Therefore, NG adsorbents show potential applicative value in the treatment of dye wastewater.

Pesticide exposure has been associated with acute and chronic adverse health effects. DNA methylation (DNAm) may mediate these effects. We evaluated the association between experiencing unusually high pesticide exposure events (HPEEs) and DNAm among pesticide applicators in the Agricultural Health Study (AHS), a prospective study of applicators from Iowa and North Carolina. DNA was extracted from whole blood from male AHS pesticide applicators (n = 695). Questionnaire data were used to ascertain the occurrence of HPEEs over the participant's lifetime. Pyrosequencing was used to quantify DNAm in CDH1, GSTp1, and MGMT promoters, and in the repetitive element, LINE-1. Linear and robust regression analyses evaluated adjusted associations between HPEE and DNAm. Ever having an HPEE (n = 142; 24%) was associated with elevated DNAm in the GSTp1 promoter at CpG7 (chr11:67,351,134; P 59 years and those with plasma folate levels ≤16.56 ng/mL (p-interaction 59 years and reduced LINE-1 DNAm (P = 0.05) among applicators with ≤16.56 ng/mL plasma folate. Non-specific HPEEs may contribute to increased DNAm in GSTp1, and in some groups, reduced DNAm in MGMT and LINE-1. The impacts of these alterations on disease development are unclear, but elevated GSTp1 promoter DNAm and subsequent gene inactivation has been consistently associated with prostate cancer. Environ. Mol. Mutagen. 58:19–29, 2017. © 2016 Wiley Periodicals, Inc.

An efficient synthetic route for moxifloxacin chiral intermediate via five steps was established. Firstly, dehydration, N-acylation and cyclization were combined in one pot to meet the industrial requirement. Then relatively low hydrogen pressure was employed in the catalytic hydrogenation reaction with high yield. Isopropanol/water system was used in resolution which guaranteed high yield and perfect optical purity. The racemic process conducted by manganese dioxide and Pd/C successfully converted the undesired enantiomer into the racemate and hence the total yield increased remarkably. Furthermore, mild hydrogen transfer catalytic hydrogenation method was utilized in debenzylation process instead of high-pressure hydrogenation. Total yield of 39.0% was achieved which was much higher than that of 29.0% in literature.

A heptamethine cyanine-based near-infrared (NIR) fluorescent probe Cy-1 for hydrosulfide detection was developed, with the response mechanism based on nucleophilic substitution of acryloyl moiety by HS−. Upon addition of NaHS, Cy-1 displayed a rapid fluorescence quenching (excited at 700 nm) and a quick fluorescence enhancement (excited at 544 nm) as well as obvious changes in absorption spectra and color. The response was fast within tens of seconds and could be observed by naked eyes. By contrasting Cy-1 with the reported probe CyAC, the superiority of Cy-1 in selectivity over Cys was demonstrated. Besides, it also exhibited excellent selectivity and sensitivity to HS− over various anions (0.33-μM detection limit). Additionally, this probe was successfully applied in fetal bovine serum samples and imaging of hydrosulfide in living cells.

A novel and efficient five-step synthetic route, including a Biginelli reaction, dehydrogenation, chlorination, sulfonamidation, and reduction, for the core of Rosuvastatin was established. All steps were systematically studied. Tert-butylhydroperoxide aqueous solution was applied in the dehydrogenation instead of nitric acid. N,N-dimethylaniline was employed as a catalyst to accelerate the chlorination proceeding smoothly, and its catalytic mechanism is discussed. In the sulfonamidation, the conversion of compound 5 was obviously improved by use of NaH and acetonitrile. In addition, two sulfonamidation side products 6 and 7 were detected and isolated. Thus, under the optimized reaction conditions, the target product was obtained in 60.4% total yield, much higher than the reported yield (36.4%).

// Changjiang Huang 1, 2 , Xiulin Yi 2 , Dexin Kong 3 , Ligong Chen 1 , Gong Min 3, 4 1 School of Chemical Engineering and Technology, Tianjin University, Tianjin, China 2 Tianjin Institute of Pharmaceutical Research, Tianjin, China 3 School of Pharmacy, Tianjin Medical University, Tianjin, China 4 Department of Oncology, University of Oxford, Oxford, UK Correspondence to: Gong Min, email: kahongmg@163.com Ligong Chen, email: lgchen@tju.edu.cn Keywords: matrix metalloproteinase, tumor targeting peptide, drug conjugate, paclitaxel, tumor metastasis Received: April 25, 2016 Accepted: May 29, 2016 Published: July 20, 2016 ABSTRACT Peptide drug conjugates offer a novel strategy to achieve controlled drug release. This approach avoids the clinical obstacles of non-specific toxicity and overall drug resistance of conventional cytotoxic agents, such as paclitaxel. MMP2 plays important functions in tumour proliferation and metastasis. Herein, we conjugated the paclitaxel with a hexapeptide which is specific recognized by MMP2 protein. The conjugate is dissociated upon the MMP2 specific proteolysis at COOH terminal of hexapeptide, PVGLIG. The results clearly indicated that the PVGLIG-paclitaxel conjugate significantly enhanced the tumor specificity against HT-1080 and U87-MG tumour cells. Our finding suggested that the hexapeptide PVGLIG is capable to act as a controlled and sustained drug carrier of paclitaxel for the treatment against tumour proliferation and metastasis with high MMP2 expression.

A scalable and facile synthetic process for N-(pyridin-4-yl)piperazine-1-carboxamide hydrochloride, a novel Rho kinase inhibitor with an unsymmetrical urea structure currently under investigation for the treatment of central nervous system disorders, was established. After optimisation of the reaction conditions, N-(pyridin-4-yl)piperazine-1-carboxamide hydrochloride was synthesised from 4-aminopyridine and N,N′-carbonyldiimidazole through acylation, deprotection and salt formation. This new procedure affords the product in 53% overall yield with high purity and it can be easily scaled up for production.

Five cyano-functionalized 1,4-bis(( E )-2-(1 H -indol-3-yl)vinyl)benzene derivatives with a donor-acceptor-acceptor-donor structure have been designed and synthesized. All the luminophores exhibit both twisted intramolecular charge transfer and aggregation induced emission characteristics. Meanwhile, significant fluorescence changes (up to 74–77 nm) were observed during their tandem photoluminescence experiments in cyclohexane/THF and THF/water systems. Most importantly, the constructed dyes present chain length-dependent thermochromic behaviour: (1) almost no thermochromism is observed for the three luminophores with relatively short alkyl chains; (2) as for the luminophore with N -tetradecyl groups, it initially exhibits greenish-yellow fluorescence which turns to orange upon heating and the orange emission is retained after cooling; (3) the luminophore with N -hexadecyl groups extraordinarily displays three-colour emissions including greenish-yellow, orange and salmon pink fluorescence in initial, heated and cooled states, respectively. Additionally, the three luminophores with poor thermochromic performance show optical waveguide properties, demonstrated by their fluorescence microscopy images.

Two α-cyanostilbene derivatives NCS1 and NCS2 were designed and synthesized. Both two compounds exhibited AIE properties. Solid compounds showed excellent mechanochromism with 29/26 nm redshift and distinct acid-base vapor chromotropism, which could be applied for relevant sensors. XRSD and PXRD spectra revealed the intrinsic relationship between mechanochromism and molecular packing mode. The twisted molecular conformation became more planar with an increase in conjugation after grinding, resulting in the redshift in fluorescence spectra. Moreover, the emission spectra of NCSs showed obvious fluorescence quenching for p-nitroaniline (PNA) with excellent selectivity. The fluorescence intensity showed better linear relationship at low concentration of PNA. The limit of detections were as low as 0.42 μmol L−1 and 0.60 μmol L−1, respectively. DFT theory proved that this sensing mechanism was attributed to the process of photoinduced electron transfer (PET). Importantly, NCSs were successfully used for PNA detection in real environments. We provide the working basis for developing high-performance multi-functional materials.

Background:Comorbidities and extra-articular manifestations (EAMs) substantially increase disease burden and mortality risk in patients (pts) with ankylosing spondylitis (AS).1,2Tumour necrosis factor inhibitors (TNFi) are highly efficacious and effective in AS treatment (tx), and are used after inadequate response to non-steroidal anti-inflammatory drugs.3,4However, the impact of TNFi on the incidence of comorbidities and EAMs in pts with AS is unknown.5Objectives:To determine the incidence of comorbidities and EAMs in TNFi vs non-TNFi treated pts with AS in the US.Methods:This was a retrospective, observational cohort study using data from 3 healthcare insurance claims databases: Multi-Payer Claims Database (MPCD Optum Insight; 2007–2010), Truven MarketScan®(2010–2014) and US Medicare Fee-for-Service Claims database (2006–2014). Eligible pts: ≥20 years (yrs) for MarketScan/MPCD or ≥65 yrs for Medicare, had an AS diagnosis (≥2 International Classification of Disease, 9thversion [ICD-9] diagnosis codes of 720.0 from a rheumatologist) and ≥12 months’ continuous medical and pharmacy enrolment prior to AS diagnosis (AS index date). Pts with AS not receiving tx were excluded. Tx exposure was reported from the first date of a new prescription/administration of an AS tx (no prior exposure) after the AS index date. Crude incidence rates (IR; shown as cases/100 pt-yrs) were calculated for EAMs (uveitis, psoriasis [PSO], psoriatic arthritis [PsA], inflammatory bowel disease [IBD]), with follow-up until the earliest of: death, lost medical/pharmacy coverage, study period end, first outcome occurrence, tx switch/discontinuation. Hazard ratios (HRs) of comorbidities (hospitalised infection, solid cancers) and EAMs for propensity score (PS)-matched pt groups were calculated using Cox proportional hazard regression models. Pts with the specific comorbidity/EAM of interest prior to AS index date were excluded. PS analyses assessed probability of TNFi initiation vs non-TNFi tx and adjusted for factors including comorbidities and demographics. HRs with confidence intervals crossing 1 are not reported.Results:20,460 pts with AS were eligible (MPCD: 2,384; MarketScan: 9,032; Medicare: 9,044). In all databases, crude IR of EAMs were higher for TNFi vs non-TNFi treated pts (Figure 1). In the PS-matched cohort, incidences of hospitalised infections were lower in TNFi vs non-TNFi treated pts from the MarketScan and Medicare databases (Figure 2). Higher incidences of solid cancers and EAMs were observed in TNFi vs non-TNFi treated pts; Medicare data (Figure 2). A higher risk of PsA and PSO was seen in TNFi vs non-TNFi treated pts; MarketScan data (Figure 2). PS-matched cohort data from the MPCD database were non-significant.Conclusion:Despite strong efficacy in treating AS-related signs and symptoms, similar incidence of comorbidities and increased incidence of some EAMs (IBD, PSO/PsA, uveitis) was seen in TNFi vs non-TNFi treated pts in the PS-matched analyses. This may be due to channelling of pts with more severe AS to receive TNFi, despite the PS-matched analysis aiming to overcome this. Moreover, prior medical history of Medicare pts may not be captured in the database, as pts are typically older with longer disease durations. While these results confirm previous findings,6a prospective observational study is required to generalise to pts outside the US.References:[1]Stolwijk C. Ann Rheum Dis 2015;74:1373–8;[2]Bremander A. Arthritis Care Res 2011;63:550–6;[3]Braun J. Scand J Rheumatol 2005;34:178–90;[4]Ji X. Front Pharmacol 2019;10:1476;[5]Maxwell LJ. Cochrane Database Syst Rev 2015:CD005468;[6]Walsh J. J Pharm Health Serv Res 2018;9:115–21.Acknowledgments:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Rhonda Bohn Consultant of: UCB Pharma, Benjamin Chan: None declared, Robert Suruki Employee of: UCB Pharma, Jeffrey Stark Employee of: UCB Pharma, Huifeng Yun Grant/research support from: Bristol-Myers Squibb and Pfizer, Sarah Siegel: None declared, Lang Chen: None declared, Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corona, Crescendo, Genentech, Janssen, Pfizer, Roche and UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corona, Crescendo, Genentech, Janssen, Pfizer, Roche and UCB Pharma

Background:Axial spondyloarthritis (axSpA) is a chronic inflammatory disease that affects the axial skeleton and sacroiliac joints, and can be classified as ankylosing spondylitis (AS) or non-radiographic (nr)-axSpA.1A 2016 analysis estimated the US diagnostic prevalence of axSpA to be 0.2% and AS to be 0.1%.2Previous studies use disparate populations and diagnostic definitions;3,4it is therefore unclear how AS prevalence has changed over time.Objectives:To investigate the annual diagnostic prevalence of AS in US healthcare insurance claims databases.Methods:A retrospective, observational cohort study was conducted using 2006–2014 data from US Medicare Fee-for-Service Claims (5% random sample of all enrolled patients [pts]) and Truven MarketScan®. Eligible pts were ≥20 years (yrs) and had ≥6 months of continuous medical and pharmacy enrolment prior to diagnosis. Diagnoses used relevant International Classification of Disease, 9thversion (ICD-9) diagnosis codes: ICD-9 720.x [x=any number] for “AS and other inflammatory spondylopathies [SpA]” or 720.0 for “AS”. Two diagnosis definitions were used: Definition 1, ≥1 relevant ICD-9 code from hospital discharge or ≥2 from rheumatologist visit; Definition 2, ≥1 relevant ICD-9 code from hospital discharge or rheumatologist visit. Annual diagnostic prevalence of SpA/AS was calculated as “number of enrolled pts who met the definition of SpA/AS within each calendar yr and had full insurance coverage (medical and pharmacy)”, divided by “total number of pts with full insurance coverage in the same yr”. A primary analysis of SpA prevalence rates used Definitions 1 and 2, followed by a sensitivity analysis for AS prevalence rates using only Definition 2. All prevalence rates are shown per 10,000 pts enrolled.Results:The annual diagnostic prevalence of SpA appeared to increase from 2006–2014 (Table). Similarly, the sensitivity analysis showed the annual diagnostic prevalence of AS appeared to increase during the period from 2006 (Medicare: 2.87/10,000 pts [n=501,031]; MarketScan: 1.37/10,000 pts [n=17,562,637]) to 2014 (Medicare: 4.77/10,000 pts [n=1,046,107]; MarketScan: 2.14/10,000 pts [n=34,553,135];Figure).Conclusion:The apparent increase in diagnostic prevalence of SpA and AS during the period from 2006–‍2014 may be a consequence of increased awareness and availability of effective treatments. Furthermore, the 2009 Assessment of SpondyloArthritis international Society development of the axSpA classification criteria to include pts with both established AS and nr-axSpA may have accelerated this increase.5References:[1]Strand V. Mayo Clin Proc 2017;92:555–64;[2]Curtis J. Perm J 2016;20:15–151;[3]Reveille J. Arthritis Care Res (Hoboken) 2012;64:905–10;[4]Danve A. Clin Rheumatol 2019;38:625–34;[5]Rudwaleit M. Ann Rheum Dis 2009;68:777–83.Table.Prevalence of SpA by calendar year and data sourceMedicare (5% random sample)MarketScanCalendar yrTotal number of eligible ptsPrevalence/10,000 ptsTotal number of eligible ptsPrevalence/10,000 ptsDefinition 1Definition 2Definition 1Definition 22006501,0314.397.6217,562,6371.332.172007816,9705.258.7219,518,0661.472.372008825,4454.898.7828,603,5251.582.532009830,9675.229.2131,757,0691.903.092010844,5285.499.9031,126,1721.963.172011879,9966.3010.7138,295,1211.943.112012921,9946.1710.8840,320,4371.913.0420131,032,8276.7410.8233,826,0412.003.1920141,046,1076.5210.8534,553,1352.213.51Medicare data included a 5% random sample of all enrolled pts age ≥20 yrs. pts: patients; SpA: ankylosing spondylitis and other inflammatory spondylopathies; yr: year.Acknowledgments:This study was funded by UCB Pharma. Editorial services were provided by Costello Medical.Disclosure of Interests:Jeffrey Curtis Grant/research support from: AbbVie, Amgen, Bristol-Myers Squibb, Corona, Crescendo, Genentech, Janssen, Pfizer, Roche and UCB Pharma, Consultant of: AbbVie, Amgen, Bristol-Myers Squibb, Corona, Crescendo, Genentech, Janssen, Pfizer, Roche and UCB Pharma, Kevin Winthrop Grant/research support from: Bristol-Myers Squibb, Consultant of: AbbVie, Bristol-Myers Squibb, Eli Lilly, Galapagos, Gilead, GSK, Pfizer Inc, Roche, UCB, Benjamin Chan: None declared, Sarah Siegel: None declared, Jeffrey Stark Employee of: UCB Pharma, Robert Suruki Employee of: UCB Pharma, Rhonda Bohn Consultant of: UCB Pharma, Fenglong Xie: None declared, Huifeng Yun Grant/research support from: Bristol-Myers Squibb and Pfizer, Lang Chen: None declared, Atul Deodhar Grant/research support from: AbbVie, Eli Lilly, GSK, Novartis, Pfizer, UCB, Consultant of: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB, Speakers bureau: AbbVie, Amgen, Boehringer Ingelheim, Bristol Myer Squibb (BMS), Eli Lilly, GSK, Janssen, Novartis, Pfizer, UCB

Heteroatom-doped porous carbon materials have exhibited promising applications in various fields. In this work, sulfur, nitrogen co-doped carbon materials (SNCs) with abundant pore structure were prepared by pyrolysis of sulfur, nitrogen-containing porous organic polymers (POPs) mixed with nano-CaCO

PurposeWe described medication use patterns among REasons for Geographic And Racial Differences in Stroke (REGARDS) participants hospitalized for heart failure with preserved ejection fraction (HFpEF) (152 hospitalizations, 101 unique individuals).MethodsMedication data were obtained from medical record review and Medicare Part D pharmacy claims. We compared discharge medication prescriptions between patients with and without chronic kidney disease (CKD), coronary heart disease (CHD), chronic obstructive pulmonary disease (COPD), and diabetes.ResultsThe mean age was 74.8 years, 53.3% were black and 73.7% were female. Hypertension (97.2%), diabetes (65.1%), COPD (51.3%), CKD (41.1%) and history of CHD (60.9%) were common. On admission and discharge, respectively, beta-blockers (66.4%, 72.7%), angiotensin converting enzyme inhibitors or angiotensin receptor blockers (42.8%, 51.7%), diuretics (61.2%, 80.9%), loop diuretics (55.9%, 78.3%), calcium channel blockers (41.0%, 41.2%) and statins (44.7%, 50.3%) were commonly used. Spironolactone, digoxin, hydralazine plus isosorbide dinitrate (HISDN), isosorbide dinitrate alone and aldosterone receptor antagonists were used by ConclusionBeta-blockers and diuretics were commonly prescribed at admission and discharge among HFpEF, but pharmacy claims for these medications within one-year were substantially less common. The comorbidities CHD, CKD, and diabetes were associated with prescriptions of statins at discharge.

Hierarchical hollow bimetallic NiCo/MgxNiyO catalysts were constructed by assembling NiMgCo layered double hydroxide (LDH) platelets on zeolitic imidazolate framework-67 (ZIF-67), followed by subsequent calcination and reduction. The three-level hierarchical structure of NiCo/MgxNiyO catalysts, including the hollow structure, nanolamellar structure and NiCo alloy particles, showed a significant enhancement on the catalytic activity of NiCo/MgxNiyO in the hydrogenation of phenol to cyclohexanol. The confined environment of the lamellar structure may strengthen the interaction between the active species and support, avoiding the agglomeration, sintering and leaching of the NiCo active species, thus facilitating the stability. The optimal catalyst NiCo/MgxNiyO(10) showed an excellent catalytic performance with 99.9 % conversion and 99.9 % selectivity for cyclohexanol, and featured with a highest TOF value of 588 h−1 compared with the reported Ni-based catalysts. Detailed characterizations have demonstrated that the combination of the hollow structure and the confined effect would benefit the catalytic performance. Moreover, this non-precious metal catalyst can be magnetically separated, and recycled for at least 6 times. This approach provides a valuable guidance for the design and preparation of the non-precious metal catalysts for industrial applications.

A novel multifunctional D-A type triphenylamine derivative (CPA-TPA) was designed and synthesized via Knoevenagel condensation reaction. It was found with distinct aggregation-induced enhanced emission (AEE) characteristics and solvatochromic performance. Interestingly, its crystals showed distinct luminescent responses to anisotropic grinding and isotropic compression. Upon grinding, its orange emission was changed into yellow fluorescence (blue-shift 17 nm from 592 nm), while the orange emission was changed into a red fluorescence upon 30 GPa pressure (red-shift 9 nm). Significantly, both the maximum emission wavelength and fluorescence intensity of the crystalline solid displayed nice linear relationships to pressure. Thus it offered a promising candidate for mechanical stimuli sensing in practical applications. The mechanism of its distinct MFC was discussed by PXRD, DSC and XRSD experiments. Furthermore, it was found that CPA-TPA presented a hypersensitive response to viscosity, so an efficient quantitative determination method for total polar materials (TPM) in frying oil was established.

Medication regimens in adults with heart failure (HF) are complex which can complicate patient adherence. Individuals with HF frequently use beta blockers (BBs) for multiple indications, including hypertension and HF, but BBs can have significant side effects that may affect their use. We examined medication-taking behaviors and perceptions in individuals with HF with a particular focus on BBs. A mailed survey on medication use was administered to US adults with HF enrolled in the REasons for Geographic And Racial Differences in Stroke study. Among 518 respondents, 357 (69%) reported taking a BB. Nearly half (42%) reported taking ≥10 medications per day. However, 45% indicated that they did not miss any days taking medications, and over 85% reported willingness to take additional medications to prevent further healthcare encounters. Participants' perceptions of BB symptoms varied, but 56% of those who reported experiencing symptoms did not discuss this with their healthcare providers. Adults who experienced HF hospitalization had higher odds of reporting taking BBs to treat HF (odds ratio 1.51, 95% confidence interval 1.19, 1.91). Adults with hypertension were also likely to report taking BBs to treat high blood pressure (odds ratio 2.42, 95% confidence interval 1.79, 3.26). In conclusion, despite extensive medication regimens, individuals with HF were willing to take additional medications for their disease. Participant recognition of BB use for treating HF and co-morbidities was high, yet many do not report side effects to healthcare providers. In conclusion, better understanding of patients' medication-taking behaviors and perceptions may facilitate optimization of HF treatments.

Background HIV is associated with an increased risk for atherosclerotic cardiovascular disease, which may result in many people living with HIV taking a statin. Some statins are contraindicated with certain antiretroviral therapies ( ART ) and other medications commonly used by HIV ‐infected patients. Methods and Results We analyzed trends in the use of statins, including contraindicated statins, between 2007 and 2015 among HIV ‐infected patients aged ≥19 years taking ART who had employer‐sponsored or Medicare supplemental health insurance in the Marketscan database (n=186 420). Statin use was identified using pharmacy claims. Contraindicated statin use was defined by a pharmacy claim for HIV protease inhibitors, cobicistat, hepatitis C protease inhibitors, anti‐infectives, calcium channel blockers, amiodarone, gemfibrozil, or nefazodone followed by a fill for a contraindicated statin type and dosage within 90 days. The percentage of beneficiaries with HIV taking a statin remained unchanged between 2007 (24.6%) and 2015 (24.7%). Among those taking a statin, the percentage taking a contraindicated statin declined from 16.3% in 2007 to 9.0% in 2014 and then increased to 9.8% in 2015. The proportion of contraindicated statin fills attributable to HIV protease inhibitors declined from 63.9% in 2007 to 51.0% in 2015, while those attributable to cobicistat increased from 0% before 2012 to 20.6% in 2015. Conclusions Changes in ART regimens resulted in a decline in contraindicated statin use from 2007 to 2014, but this favorable trend was attenuated in 2015 because of increased use of cobicistat‐containing ART regimens.

Compare medical expenditures among adults with statin-associated adverse effects (SAAE) and high statin adherence (HSA) following myocardial infarction (MI). We analyzed expenditures in 2016 US dollars among Medicare beneficiaries with SAAE (n = 1741) and HSA (n = 55,567) who were ≥ 66 years of age and initiated moderate/high-intensity statins following an MI in 2007–2013. SAAE were identified through a claims-based algorithm, which included down-titrating statins and initiating ezetimibe, switching to ezetimibe monotherapy, having a rhabdomyolysis or antihyperlipidemic adverse event followed by statin down-titration or discontinuation, or switching between ≥ 3 statin types within 365 days following MI. HSA was defined by having a statin available to take for ≥ 80% of the days in the 365 days following MI. Expenditures among beneficiaries with SAAE and HSA were $40,776 (95% CI $38,329–$43,223) and $26,728 ($26,482–$26,974), respectively, in the 365 days following MI, and $34,238 ($31,396–$37,080) and $29,053 ($28,605–$29,500), respectively, for every year after the first 365 days. Multivariable-adjusted ratios comparing expenditures among beneficiaries with SAAE versus HSA in the first 365 days and after the first 365 days following MI were 1.51 (95% CI 1.43–1.59) and 1.23 (1.12–1.34), respectively. Inpatient and outpatient expenditures were higher among beneficiaries with SAAE versus HSA during and after the first 365 days following MI. Compared to beneficiaries with HSA, medication expenditures among those with SAAE were similar in the 365 days following MI, but higher afterwards. Other medical expenditures were higher among beneficiaries with SAAE versus HSA. SAAE are associated with increased expenditures following MI compared with HSA.

Catalysts with Co nanoparticles (NPs) entrapped in N,S-codoped carbon shells were successfully fabricated by pyrolysis of porous organic polymers (POPs) with cobalt salts. The encapsulated structure consisting of Co NPs and N,S-codoped carbon layers was verified by TEM, XRD, and X-ray photoelectron spectroscopy. The catalysts displayed excellent activity and stability for the catalytic transfer hydrogenation (CTH) of nitrobenzene with formic acid under base-free conditions. Furthermore, the resultant catalysts allowed for highly efficient and selective transfer hydrogenation of various functionalized nitroarenes to the corresponding anilines. Through control experiments, the covered Co NPs were identified as active sites for CTH. The incorporation of S into the N-doped carbon lattice promoted the electron transfer from metallic cobalt NPs to their shells, which played a significant role in the acceleration of CTH. Moreover, the Co-NSPC-850 catalyst pyrolyzed at 850 °C showed excellent stability in the recycling experiments.

Zinc levels are high in pancreatic β-cells, and zinc is involved in the synthesis, processing and secretion of insulin in these cells. However, precisely how cellular zinc homeostasis is regulated in pancreatic β-cells is poorly understood. By screening the expression of 14 Slc39a metal importer family member genes, we found that the zinc transporter Slc39a5 is significantly down-regulated in pancreatic β-cells in diabetic db/db mice, obese ob/ob mice and high-fat diet-fed mice. Moreover, β-cell-specific Slc39a5 knockout mice have impaired insulin secretion. In addition, Slc39a5-deficient pancreatic islets have reduced glucose tolerance accompanied by reduced expression of Pgc-1α and its downstream target gene Glut2. The down-regulation of Glut2 in Slc39a5-deficient islets was rescued using agonists of Sirt1, Pgc-1α and Ppar-γ. At the mechanistic level, we found that Slc39a5-mediated zinc influx induces Glut2 expression via Sirt1-mediated Pgc-1α activation. These findings suggest that Slc39a5 may serve as a possible therapeutic target for diabetes-related conditions. Electronic supplementary material The online version of this article (10.1007/s13238-018-0580-1) contains supplementary material, which is available to authorized users.

Background Patients with RA undergoing major surgery are at high risk for infection. Different biologic DMARDs may be associated with different infection risks.1 Objectives Goals were 1) to compare post-operative infection risk after arthroplasty in patients with RA exposed to different biologics, and 2) examine associations between glucocorticoid use and post-operative infection. Methods A retrospective cohort study using U.S. Medicare data from 2006-September 2015 evaluated adults with ≥2 ICD9 codes for RA undergoing elective inpatient primary or revision total knee or hip arthroplasty. Eligible patients received an infusion or prescription for abatacept, adalimumab, etanercept, infliximab, or tocilizumab within 8 weeks or a rituximab infusion within 16 weeks of surgery. Patients with hip fracture, malignancy, pre-existing infection, or non-elective surgery were excluded. Average glucocorticoid dose in the 3 months before surgery was calculated from oral prescriptions. Logistic or Cox regression evaluated associations between biologic exposure and post-operative outcomes: 1) hospitalised infection within 30 days (from discharge diagnoses, PPV >80%), 2) rate of prosthetic joint infection (PJI, ICD9 996.66) within 1 year, and 3) 30 day readmission among patients with discharge to home, skilled nursing facility, or inpatient rehab. Propensity scores based on the probability of receiving a specific biologic treatment were used to balance confounders across treatment groups using inverse probability weighting. Similar analyses were used to evaluate associations between glucocorticoid dose and outcomes in the same cohort, using inverse probability weighted analyses based on the probability of being in each glucocorticoid treatment category. Results Among 7929 surgeries in 7138 patients, there were 717 (9.0%) hospitalised infections within 30 days of surgery (most commonly urinary, skin/soft tissue, and pneumonia), 192 (2.8/100 person-years) PJI within 1 year, and 465/7554 (6.2%) 30 day readmissions. There was no significant difference in the risk of hospitalised infection, PJI, or 30 day readmission across biologic treatment groups (table 1). Glucocorticoid dose >10 mg/day (mean 13.5±3.5 mg/day) was associated with a significantly greater risk of hospitalised infection [aOR 2.37 (1.63–3.44)] and prosthetic joint infection [aHR 2.04 (1.09–3.84)] compared to no glucocorticoid use (table 1). Patients with glucocorticoid dose >10 mg also had a numerically greater risk of 30 day readmission that did not reach statistical significance [aOR 1.61 (0.99–2.61)] (table 1). Conclusions Risk of hospitalised infection, prosthetic joint infection, and readmission after arthroplasty was similar in patients with RA treated with different biologics. In contrast, glucocorticoid use, especially >10 mg/day, was associated with greater risk of hospitalised infection and PJI. Reference [1] Yun H, et al. Comparative risk of hospitalized infection associated with biologic agents in rheumatoid arthritis patients enrolled in medicare. Arthritis & Rheumatology2016;68:56–66. Disclosure of Interest M. George Grant/research support from: Bristol Myers Squibb, J. Baker: None declared, K. Winthrop Grant/research support from: Abbvie, Astellis, Galapagos, Eli Lilly, Pfizer, BMS, Roche, UCB, Consultant for: Abbvie, Astellis, Galapagos, Eli Lilly, Pfizer, BMS, Roche, UCB, E. Alemao Employee of: Bristol Myers Squibb, L. Chen: None declared, S. Connolly Employee of: Bristol Myers Squibb, T. Simon Employee of: Bristol Myers Squibb, Q. Wu: None declared, F. Xie: None declared, S. Yang: None declared, J. Curtis Grant/research support from: Pfizer, Amgen, UCB, Myriad genetics, Bristol Myers Squibb, Consultant for: Pfizer, Amgen, UCB, Myriad genetics, Bristol Myers Squibb, Janssen

Background Methotrexate (MTX) has been associated with reduced risk for CVD in several studies conducted among rheumatoid arthritis (RA) patients never exposed to biologic disease-modifying antirheumatic drugs (bDMARDS). Effect of concomitant MTX use on CVD risk among RA patients initiating bDMARDS remains unknown. Objectives The objective of this study was to assess the CVD risk associated with MTX use among RA patients initiate bDMARDS, overall, and by each bDMARDS initiated. Methods A retrospective cohort study was conducted using 2006–2015 Medicare claims data for RA patients. Follow up started at initiation (index date) and ended at earliest of 1) end of exposure of the specific bDMARDS agent (days of supply plus 90 days extension), 2) switched to other bDMARDS or tofacitinib, 3) CVD event, 4) death date, 5) loss of Medicare coverage, 6) end of study (September 30, 2015). MTX use was defined as 1) concomitant MTX use, with prescription for MTX within 120 days after index date and 2) time varying MTX, defined as prescription date to prescription date plus days of supply without extension. For sensitivity analysis, a 90 day extension was added to days of supply. The primary outcome was composite of incident MI, incident stroke and fatal CVD. Fatal CVD were identified by a claims based algorithm with PPV ≥80%. Incidence rates (IR) and 95% confidence intervals (CI) were calculated using Poisson regression. Overall association between MTX use (versus no MTX) and risk of CVD were assessed using Cox regression. Given that the interactions between MTX and background bDMARDs was significant, we performed contrast (MTX Yes vs No) to examine the association between MTX and risk for CVD for each underlying bDMARDS in one model. A subgroup analysis limited the cohort to RA patients with previous exposure to MTX was conducted to ensure consistency of findings. Results A total of 88,255 DMARDS initiations (64 218 patients) were included in this study. The average age at initiation was 64.6 (12.3) years, 84.0% were female, 68.2% were non-Hispanic white. The crude IRs for CVD were 13.1 (95% CI: 12.2 to 14.0) and 18.7 (95% CI: 17.6 to 19.9) events per 1000 person years for RA patients with and without concomitant MTX respectively. The crude IRs for CVD were 12.1 (95% CI: 11.1 to 13.2) and 17.9 (95% CI: 16.9 to 18.8) events per 1000 person years for RA patients with and without time varying MTX respectively. IRs for individual bDMARDS are shown in figure. P-value for interaction between concomitant MTX and background bDMARDS was 0.0189 and p-value for interaction between time varying MTX and background bDMARDS was 0.0030. The contrast HRs for concomitant MTX ranged from 0.61 (0.37, 1.01) for golimumab initiators to 0.97 (0.74, 1.26) for adalimumab initiators (figure 1). The contrast HRs for time varying MTX ranged from 0.58 (0.35, 0.96) for certolizumab initiators to 0.90 (0.68, 1.18) for adalimumab initiators. Results were robust in sensitivity and subgroup analyses. Conclusions Our observational study suggests an overall 23% reduction of CVD risk associated with concomitant MTX use. The effect sizes vary among background bDMARDS. Disclosure of Interest F. Xie: None declared, L. Chen: None declared, H. Yun Grant/research support from: BMS, E. Levitan Grant/research support from: Amgen, Consultant for: Amgen, Novartis, P. Muntner: None declared, J. Curtis Grant/research support from: AbbVie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB

Background The ACC/AHA recommends preventive strategies for patients with a high predicted risk of atherosclerotic cardiovascular disease (CVD). RA patients are at higher risk for CVD events, yet the role of systemic inflammation and the influence of traditional CVD risk factors is unclear with respect to risk prediction in RA. Objectives A simple and accurate algorithm for predicting CVD event risk that includes systemic inflammation might help risk assessment for RA patients and optimise preventive care. Methods We derived a U.S. cohort of RA patients with multi-biomarker disease activity (MBDA) test results linked to Medicare claims data. Patients had to have ≥1 year baseline with Medicare coverage prior to the first MBDA test. Exclusions were past MI, PCI/CABG, stroke, or cancer. Follow-up ended at the earliest of 1) CVD event; 2) other than CVD cause of death; 3) loss of coverage; or 4) 12/31/2014. The composite CVD event comprised of incident MI, stroke or fatal CVD event, using validated algorithms. MBDA scores were grouped as low ( 44). Other predictors included demographics, healthcare utilisation, and comorbidities. Three separate models were developed using Cox regression. Model 1 included age, sex and race. Model 2 included age, sex race, 9 comorbidities and CVD medication classes, plus interaction terms. Model 3 included age, sex, and race plus categorised MBDA score. We calculated the net reclassification index (NRI) for model 2 and 3 compared to model 1. We also plotted the observed vs. predicted probability of CVD event for each model, with risk categorised as low ( Results A total of 15,757 RA patients were included; mean (SD) age 68.6 (10.8) years, 80% female, 80% white. A total 209 CVD events occurred in 14 843 person years (1.41/100 py). The median (IQR) follow up time was 0.84 (0.41, 1.27) year. The maximum event time was at 2.7 year. All models had reasonable discrimination and calibration; model 3 was better than models 1 and 2 and observed vs predicted risk is shown (figure 1). The sum of the absolute difference between observed and predicted probability was 0.56, 0.57 and 0.33 for models 1, 2 and 3 respectively. Compared to model 1, model 2 resulted in a positive overall NRI of 0.214 (non-event NRI=0.173, event NRI=0.041); model 3 resulted in positive overall NRI of 0.279 (non-event NRI=0.092, event NRI=0.187), consistent with more accurate CVD event classification. Conclusions Preliminary results from this analysis suggest that a simple algorithm consisting only of age, sex and race plus a multi-biomarker score can provide an accurate method to predict short term CVD risk in RA. Further validation with more extended time frames should improve the utility of this approach. Acknowledgements This work was supported by the Patient Centred Outcomes Research Institute (PCORI) and Myriad Genetics. Disclosure of Interest F. Xie: None declared, L. Chen: None declared, H. Yun Grant/research support from: BMS, J. Curtis Grant/research support from: AbbVie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB

Background: The multi-biomarker disease activity (MBDA) score is a validated test used to assess disease activity for patients with rheumatoid arthritis (RA). How it is used in clinical practice in the U.S. is unclear. Objectives: We evaluated the likelihood that rheumatologists would add or switch biologic therapies based on the MBDA test result. Methods: Using previously published methods, we linked results of MBDA tests obtained as part of routine clinical care to 2012–2014 Medicare fee for service claims data for RA patients. We characterized patients as being on a biologic or targeted synthetic DMARD in the 90 days prior to the MBDA test and evaluated biologic/to facitinib treatment changes in the 90 days following the MBDA test. MBDA test scores were classified as low ( 44). The unit of analysis was the 90-day interval before and after each MBDA test score. Alternating logistic regression was used to compute odds ratios (OR) to quantify the likelihood that patients made any change (add or switch), accounting for the clustered nature of the data (intervals nested within patients, and patients nested within doctor practices) and physician-level variability, controlling for patient age and sex. Sensitivity analyses used a 6-month interval for outcome ascertainment after the MBDA test. Results: Using previously validated methods, a total of 27,621 unique RA patients were linked to 44,438 MBDA test scores. For the 27,256 intervals where RA patients were not on biologic therapy when the MBDA score was obtained, a total of 13.2% of patients added a biologic. Patients with high MBDA scores were significantly more likely to add a biologic (table 1). For the 17,182 intervals where RA patients were already on a biologic, a total of 19.1% of patients switched or stopped the biologic that they were taking. Patients with lower MBDA scores were significantly more likely to stay on their therapy, whereas those with higher scores were more likely to stop and/or switch biologics. After adjustment, results from the regression analyses showed that patients with moderate MBDA scores were 1.47 (95% 1.29–1.67)-fold more likely to add or switch biologics, and those with high MBDA scores were 2.54 (95% CI 2.19–2.94)-fold more likely to add or switch biologics. Men (OR=0.90, 95% 0.82–0.98) and older patients (OR=0.92 per 5 year increment, 95% CI 0.91–0.93) were less likely to add or switch therapy, even after controlling for variability between physicians (OR=1.10, 95% CI 1.02–1.19). These results were robust and ORs were numerically larger when extending the interval to 6 months. Conclusions: Results from the MBDA score were significantly associated with the likelihood that a physician added or switched biologic therapies, with either type of change being more frequent when the MBDA score was high. Further evaluation of outcomes after switching, conditional on the MBDA score, is warranted. Acknowledgements: Financial support provided by Crescendo Bioscience Inc. Disclosure of Interest: J. Curtis Grant/research support from: AbbVie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, Consultant for: AbbVie, Amgen, BMS, Corrona, Janssen, Lilly, Myriad, Pfizer, Roche/Genentech, UCB, K. Ford Employee of: Myriad Genetics, Inc., L. Chen: None declared, H. Yun Grant/research support from: BMS, F. Xie: None declared

Background Anti-tumour necrosis factor (anti-TNF) treatment has led to reduction in signs and symptoms, and improvements in physical function and quality of life in ankylosing spondylitis (AS) patients (pts). Whether anti-TNFs impact the incidence of AS-related comorbidities and extra-articular manifestations (EAMs) is not known. Objectives To evaluate the incidence and prevalence of AS-related comorbidities and EAMs in AS pts in the US. Methods This was a retrospective cohort study of 3 commercial insurance claims databases (Multi-Payer Claims Database [MPCD 2007–2010], Truven MarketScan [2010–2014], and US Medicare Fee-for-Service Claims [2006–2014]) to evaluate EAMs (uveitis, psoriasis, inflammatory bowel disease) and physician-diagnosed comorbidities (cardiac, renal, pulmonary, neurologic) in AS pts diagnosed by a rheumatologist (index date), having 6 months’ baseline data prior to the index date, and drug-specific exposures after AS diagnosis (ICD-9 720.0). Three mutually exclusive hierarchical exposure groups were examined (low to high): 1 no therapy or prescription NSAIDs; 2 conventional DMARDs; 3 anti-TNFs. Prevalence of comorbidities was ascertained in a 12 month period (6 months pre- and post-index date). Incidence of comorbidities and EAMs was assessed during the period between treatment initiation and the earliest of death, loss of medical coverage, end of study, first outcome occurrence, treatment discontinuation or initiation of therapy at a higher level in exposure hierarchy. Pts with a history of prior events (except infections) were excluded from the incidence assessment for that event. Hazard ratios comparing anti-TNFs vs DMARDs and NSAIDs/no therapy were estimated using inverse probability treatment weighted Cox proportional hazards models. Results A total of 37,566 AS pts were included. Prevalence of AS in the MPCD population was 0.26% and in the Medicare population was 1.21%. As expected, comorbidities were more common in Medicare AS pts vs those in MPCD or MarketScan databases in all exposure groups. The propensity score-weighted incidences of solid cancers, myocardial infarction, conduction block, cord compression and vertebral fractures were lower in anti-TNF treated pts vs those treated with NSAIDs or DMARDs alone, although anti-TNF treated Medicare pts had a higher incidence of EAMs such as psoriatic arthritis, uveitis and ulcerative colitis (figure 1) . Conclusions This investigation of the prevalence and incidence of comorbidities and EAMs of AS in US pts suggests that anti-TNF use is associated with a lower incidence of some comorbidities, and a trend of higher incidence of EAMs, which may reflect channelling of more severe AS pts to anti-TNFs. Although results vary somewhat by data source and may be explained by different baseline characteristics (e.g. Medicare pts were older), our results suggest that anti-TNF use is associated with lower incidence of those comorbidities that confer substantial morbidity in AS. Acknowledgements This study was undertaken in conjunction with UCB Pharma. Editorial services were provided by Costello Medical. Disclosure of Interest A. Deodhar Grant/research support from: Amgen, Eli Lilly, GSK, Janssen, Novartis, UCB Pharma, Speakers bureau: Eli Lilly, Janssen, Novartis, UCB Pharma, K. Winthrop Grant/research support from: BMS, Consultant for: AbbVie, BMS, Galapagos, GSK, Eli Lilly, Pfizer, Roche, UCB Pharma, R. Bohn Employee of: Bohn Epidemiology, LLC and UCB Pharma, B. Chan: None declared, R. Suruki Employee of: UCB Pharma, J. Stark Employee of: UCB Pharma, H. Yun Grant/research support from: BMS, S. Siegel: None declared, L. Chen: None declared, M. Yassine Employee of: UCB Pharma, J. Curtis Grant/research support from: Amgen, BMS, Janssen, Eli Lilly, Myriad Genetics, Novartis, Pfizer, Roche, UCB Pharma, Consultant for: Amgen, BMS, Janssen, Eli Lilly, Myriad Genetics, Novartis, Pfizer, Roche, UCB Pharma

Background Guidelines recommend holding biologic DMARDs before major surgery, but few studies have examined perioperative timing of individual biologic therapies.1 Objectives We aimed to determine whether holding abatacept infusions before elective hip or knee arthroplasty is associated with lower risk of adverse post-operative outcomes. Methods This retrospective cohort study using U.S. Medicare claims data from 2006-September 2015 evaluated adults with ≥2 ICD9 codes for RA who received abatacept by infusion within 6 months of inpatient primary or revision total hip or knee arthroplasty. Infusions were selected as these procedures can be precisely dated in claims data. Patients with hip fracture, malignancy, pre-existing infection, non-elective procedures, or surgery after hospital day 3 were excluded. Logistic and Cox regression were used to assess associations between abatacept stop timing (time between most recent infusion and surgery in 4 week intervals based on dosing interval) and adverse outcomes: 1) hospitalised infection within 30 days (from discharge diagnoses, PPV >80%), 2) rate of prosthetic joint infection (PJI, ICD9 996.66) within 1 year, and 3) 30 day readmission (among patients with discharge to home, rehabilitation facility, or skilled nursing facility). Propensity scores based on the probability of being in each abatacept stop timing group were used to balance confounders across exposure groups using inverse probability weighting. Risk of hospitalised infection associated with methotrexate or with average glucocorticoid dose in the 3 months prior to surgery was assessed in abatacept treated patients using a reduced multivariable logistic regression model. Results Among 1537 surgeries in 1410 patients, there were 158 (10.3%) hospitalised infections within 30 days (most commonly urinary, skin/soft tissue, and pneumonia), 34 (2.6/100 person-years) PJI within 1 year, and 108/1448 (7.5%) 30 day readmissions. There were no significant differences in the rates of hospitalised infection, prosthetic joint infection, or 30 day readmission in patients who received abatacept within 4 weeks of surgery vs patients with longer stop timing (table 1). Among abatacept treated patients, glucocorticoid use (vs. none) was associated with a dose-dependent increase in the risk of hospitalised infection:≤5 mg [aOR 1.32 (0.88–1.98)], 5–10 mg [aOR 2.40 (1.54–3.73)],>10 mg [aOR 1.73 (0.74–4.06)]. Concomitant use of methotrexate was not associated with hospitalised infection risk [aOR 0.97 (0.68–1.38)] (table 2). Conclusions Holding intravenous abatacept for ≥4 weeks (one dosing interval) was not associated with a lower risk of hospitalised infection, prosthetic joint infection, or 30 day readmission. Glucocorticoid use even at 5–10 mg per day was associated with significantly greater risk of post-operative infection. Reference [1] Goodman SM, et al. ACR/AAHKS Guideline for the Perioperative Management of Antirheumatic Medication in Patients With Rheumatic Diseases Undergoing Elective Total Hip or Total Knee Arthroplasty. Arthritis & Rheum2017;69:1538–1551. Disclosure of Interest M. George Grant/research support from: Bristol Myers Squibb, J. Baker: None declared, K. Winthrop Grant/research support from: Abbvie, Astellis, Galapagos, Eli Lilly, Pfizer, BMS, Roche, UCB, Consultant for: Abbvie, Astellis, Galapagos, Eli Lilly, Pfizer, BMS, Roche, UCB, E. Alemao Employee of: Bristol Myers Squibb, L. Chen: None declared, S. Connolly Employee of: Bristol Myers Squibb, T. Simon Employee of: Bristol Myers Squibb, Q. Wu: None declared, F. Xie: None declared, S. Yang: None declared, J. Curtis Grant/research support from: Pfizer, Amgen, UCB, Myriad genetics, Bristol Myers Squibb, Consultant for: Pfizer, Amgen, UCB, Myriad genetics, Bristol Myers Squibb, Janssen

Background Many patients with RA do not achieve guideline-recommended treat-to-target (T2T) goals in clinical practice. Little is known about the challenges that patients and rheumatologists face when attempting to achieve better control of RA disease activity. Objectives To identify and prioritise patient- and rheumatologist-perceived barriers to achieving RA disease activity control. Methods Participants were recruited from the Consortium of Rheumatology Researchers of North America (Corrona) registry and invited to participate in nominal groups (NGs), 4 with patients and 3 with rheumatologists. Each group generated a list of barriers to reaching RA disease control (patients) and T2T goals (rheumatologists). Two separate lists containing the generated items were created and were subjected to a card sort procedure to create common themes. A random sample of Corrona RA patients were invited by email to complete a compensated online survey and asked to rank their top 3 barriers. A weighted score was assigned for each barrier by considering the number of respondents who ranked it and the priority rank they assigned. The barriers/themes were sorted into domains. The patient survey also included knowledge items about T2T strategy and attitudes about RA treatment. Results Nominal groups with 37 RA patients identified 17 themes to achieving control of RA activity. Similarly, 8 themes emerged from the physician NGs, 7 of which were also found in the patient NGs (table 1). Cost of RA care was ranked highest by both patients and physicians, while medication risk aversion ranked second and third among the physician- and patient-generated barriers, respectively. We sent 1694 invitations to complete the survey and 450 patients with RA for whom clinical data was available responded within 3 weeks. There were no differences in age, sex, or disease duration between survey- respondents and non-respondents. A higher proportion of respondents were college-educated. A total of 344 (77%) respondents considered RA to be a high priority for their health, 225 (51%) reported being familiar with T2T as a treatment strategy, and 312 (85%) displayed core beliefs favouring medications. Among the challenges to controlling RA disease activity, the domain that received the highest score was unpredictability of RA and its treatment (figure 1). Symptoms and illness burden domain received the second highest score, followed by the health system factors domain (figure 1). Conclusions There are common patient- and physician-perceived barriers to achieving RA disease control. From the patient perspective important barriers are unpredictability of how RA may progress, medication risk aversion and cost of RA care. Addressing these barriers, when possible, may improve goal-directed RA care. Acknowledgements Pfizer IGLC, Corrona Disclosure of Interest None declared

Background Contact with the healthcare system represents an opportunity for individuals who discontinue statins to re‐initiate treatment. To help identify opportunities for healthcare providers to emphasize the risk‐lowering benefits accrued through restarting statins, we determined the types of healthcare utilization associated with statin re‐initiation among patients with history of a myocardial infarction. Methods and Results Medicare beneficiaries with a statin pharmacy fill claim within 30 days of hospital discharge for a myocardial infarction in 2007 to 2012 (n=158 795) were followed for 182 days postdischarge to identify treatment discontinuation, defined as 60 continuous days without statins (n=24 461). Re‐initiation was defined as a statin fill within 365 days of the discontinuation date (n=13 136). Using a case‐crossover study design and each beneficiary as their own control, healthcare utilization during 0 to 14 days before statin re‐initiation (case period) was compared with healthcare utilization 30 to 44 days before statin re‐initiation (control period). The mean age of beneficiaries was 75.4 years; 52.8% were women and 81.9% were white. For routine healthcare utilization, the odds ratio (95% confidence interval) for statin re‐initiation associated with lipid panel testing was 2.65 (1.93–3.65), outpatient primary care was 1.31 (1.23–1.40), and outpatient cardiologist care was 1.38 (1.28–1.50). For acute healthcare utilization, the odds ratio (95% confidence interval) for statin re‐initiation associated with emergency department visits was 1.77 (1.31–2.40), coronary heart disease ( CHD ) hospitalizations was 3.16 (2.41–4.14) and non–coronary heart disease hospitalizations was 1.73 (1.49–2.01). Conclusions The weaker association of routine versus acute healthcare utilization with statin re‐initiation suggests missed opportunities to reinforce the importance of statin therapy for secondary prevention.

Background It is unknown whether causes and temporal patterns of 30‐day readmission vary between heart failure (HF) with preserved ejection fraction ( HF p EF ) and HF with reduced ejection fraction ( HF r EF ). We sought to address this question by examining a 5% national sample of Medicare beneficiaries. Methods and Results We included individuals who experienced a hospitalization for HF p EF or HF r EF between 2007 and 2013. We identified causes of 30‐day readmission based on primary discharge diagnosis and further classified causes of readmission as HF ‐related, non– HF cardiovascular‐related, and non–cardiovascular‐related. We calculated the cumulative incidence of these classifications for HF p EF and HF r EF in a competing risks model and calculated subdistribution hazard ratios of these classifications by comparing those with HF p EF and those with HF r EF . Among 60 640 Medicare beneficiaries, we identified 13 785 unique older adults hospitalized with HF p EF and 15 205 who were hospitalized with HF r EF . Noncardiovascular diagnoses represented the most common causes of 30‐day readmission ( HF p EF : 59%; HF r EF : 47%), a pattern that was observed for each week of the 30‐day study period for both HF p EF and HF rEF participants. In comparing readmission diagnoses in an adjusted model, non–cardiovascular‐related diagnoses were more common and HF ‐related diagnoses were less common in HF pEF participants. Conclusions Non–cardiovascular‐related diagnoses represented the most common causes of 30‐day readmission following HF hospitalization for each week of the 30‐day postdischarge period. HF diagnoses were less common among those with HF p EF compared with HF r EF . Future interventions aimed at reducing 30‐day readmissions following an HF hospitalization would benefit from an increased focus on noncardiovascular comorbidity and interventions that target HF p EF and HF r EF separately.

Asymmetric transformations arising from iminium activation of aromatic aldehydes are uncommon. In this work, an enantioselective organocatalytic domino aza-Michael–Henry reaction between N-(2-formylphenyl)sulfonamides and trans-β-nitro olefins through iminium activation has been presented. This reaction proceeded smoothly to give chiral 3-nitro-1,2-dihydroquinolines in high yields with up to 88 % ee under mild conditions. Furthermore, a preliminary study showed that 2-mercaptobenzaldehyde derivatives could participate in a thia-Michael–Henry reaction with trans-β-nitro olefins to yield chiral 3-nitro-2H-thiochromenes.

Fully biobased chemically crosslinked anisotropic carboxymethyl cellulose (CMC)/cellulose nanofibril (CNF) aerogels were prepared using an environmentally friendly directional freeze-drying method. The resulting cellulose aerogels were characterized using various techniques. It was found that the CMC/CNF aerogel exhibited a honeycomb structure, and thus possessed anisotropic properties. Moreover, the fully biobased crosslinked organic aerogel possessed excellent mechanical properties based on both compression and three-point bending tests. For instance, it exhibited a remarkable compressive modulus (up to 10 MPa) along the vertical direction (parallel to the freezing direction) as well as a high flexural modulus (up to 54 MPa) perpendicular to the freezing direction. The effects of different aerogel densities and CNF contents on the mechanical properties of CMC/CNF aerogels have been studied. With increasing aerogel density or CNF content, the modulus and strength of the CMC/CNF aerogel increased in both compression and three-point bending tests. In addition, these cellulose aerogels also exhibited relatively low thermal conductivities (

A near-infrared heptamethine indocyanine probe was successfully synthesized and demonstrated to be a colorimetric and fluorescent probe for F− with high selectivity and sensitivity. In the presence of F−, the probe shows a new prominent absorption peak at 942 nm, accompanied by a remarkable solution color change from pale red to colorless in a few seconds, which provides a way for the ‘naked-eye’ detection of fluoride anions. These responses were attributed to the deprotonation of the –NH fragment of an indolyl unit, and the 1H NMR study and density functional theory (DFT) calculations are in agreement with them. Moreover, the probe can be employed to detect F− quantitatively within a certain concentration range, and the limit of detection could be as low as 1.3 μM.

A series of Pd/γ-Al2O3 catalysts modified by potassium salts were prepared and evaluated in the reductive cyclization of 2-nitro-2′-hydroxy-5′-methylazobenzene without additional base. These solid base-hydrogenation bifunctional catalysts were characterized and the results demonstrated that potassium salts could have an important impact on the properties and catalytic performance of Pd/γ-Al2O3.

An efficient synthetic route for the parent nucleus of atorvastatin calcium was successfully established through the modification of the related reactions. Under the optimized conditions, compound 1 was obtained in 61.2% yield (lit. 51.4%) from methyl isopropyl ketone via five steps. Two impurities generated by the aldol condensation of methyl isopropyl ketone were identified by gas chromatography–mass spectrometry and their generation can be inhibited by reducing the mixing time of methyl isopropyl ketone and NaH. One oxybromination protocol with hydrogen peroxide was employed to make the best of bromine. A debromination by-product was isolated and confirmed by 1H NMR, 13C NMR, and high-resolution mass spectrometry and its generation mechanism was discussed. The impurity can be inhibited by protecting the reaction from light and easily removed by recrystallization.

The extraction of base oil from waste lubricating oil is becoming the preferred way of handling used oil to protect the environment and conserve petroleum resources. Supercritical carbon dioxide extraction has become a potential technology for the regeneration of waste lubricant oil because carbon dioxide has high dissolving power, is nontoxic, nonflammable, and inexpensive. Since the equilibrium solubility data are important for supercritical extraction processes, in this study the equilibrium solubilities for one of the synthetic ester lubricant oils, diisooctyl sebacate [bis (2-ethylhexyl) sebacate], in supercritical carbon dioxide (sc-CO2) were obtained at 313.2 K, 328.2 K, 343.2 K, 358.2 K and in a pressure range from 7.24 MPa up to 15.96 MPa. Oil solubility increased with pressure but decreased with temperature, providing sc-CO2 with the highest oil solubility (82.1959 g/L) at 313.2 K and 13.96 MPa, which showed that the solubility is strongly dependent on the density of CO2. The experimental solubi...

A series of metal chlorides supported solid catalysts were prepared by simple wet impregnation method. Their catalytic performances for Friedel-Crafts acylation of toluene with benzoyl chloride were evaluated and the excellent results were obtained over FeCl3/SiO2. These catalysts were characterized by BET, NH3-TPD and FT-IR of pyridine adsorption to clarify the structure-activity relationship. It was found that FeCl3/SiO2 has larger pore size and pore volume than other catalysts, which increased the accessibility of the catalyst. In addition, FeCl3/SiO2 exhibited higher molar ratio of Lewis acid sites and Brφnsted acid sites, which might be another reason for the increase of toluene conversion. Furthermore, the reaction parameters, including temperature, time and molar ratio, were optimized. Under the optimized conditions, 91.2%, conversion and 82.0%, selectivity were obtained. Meanwhile, the generality of the catalyst was demonstrated by the acylations of alkyl substituted aromatics. Finally, the catalyst was reused for four runs with slight loss in catalytic activity, which attributed to the drain of the active component.

Background Simplified measures to quantify rheumatoid arthritis (RA) disease activity are increasingly used. The minimally clinically important differences (MCID) for some measures, such as the clinical disease activity index (CDAI), have not been well-defined in real-world clinic settings, especially for early RA patients with low/moderate disease activity.

The Friedel–Craft acylation of m-xylene with benzoyl chloride over iron-modified tungstophosphoric acid supported on titania was investigated. It was found that FeTPA/TiO2 catalyst displayed excellent catalytic performance for this reaction. Furthermore, a series of catalysts were prepared and characterized by FT-IR, XRD, BET, NH3-TPD, and Py-IR. The results indicated that both the Lewis acidity and the textural properties presented significant influences on their catalytic performance. Moreover, the influence of catalyst calcination temperature to the above reaction was also studied. The reaction parameters, including reaction temperature, catalyst dose, and molar ratio of m-xylene to benzoyl chloride, were optimized, and a 95.1% yield of 2,4-dimethylbenzophenone was obtained under optimal conditions. Finally, the kinetics of the benzoylation of m-xylene over 30% FeTPA/TiO2 was established.

RO8191 represents a newly discovered small-molecule IFN-like agent that displays potent anti-HCV activity. With it as lead, a series of compounds bearing an imidazo[1,2-α][1,8]naphthyridine core and an amide bond-linked side chain were designed and synthesized. These compounds were evaluated on HCV cell culture system (HCVcc-hRluc-JFH1), and some of them exhibited remarkable anti-HCV activity (EC50 = 0.017-0.159 μM) and low toxicity (CC50 > 25 μM). Moreover, it was revealed that these newly identified anti-HCV agents exert their antiviral effect through a distinct mechanism of action from that of RO8191 by targeting the viral entry process. Thus, our study provides a starting point for the development of potential HCV entry inhibitor.

An efficient and mild synthetic method was developed for tofacitinib citrate from 3-amino-4-methylpyridine and 4-chloro-7H-pyrrolo[2,3-d]pyrimidine. The related reactions were systematically optimized. Sodium hydride instead of potassium tert-butoxide employed in the methoxycarbonylation reaction of compound made the reaction proceed effectively to present compound in a better yield. The replacement of benzaldehyde with benzyl bromide simplified the protection process of amino group. Red-Al provided a cost-effective method for the reduction of amides. The introduction of tosyl group into compound enhanced the nucleophilic substitution of with compound dramatically. Thus, under the optimized conditions, tofacitinib citrate was obtained in 13.3% yield (based on compound ) with a purity of 99.9%, much better than the reported yield 8.6%. This cost-effective and environmental friendly process is more suitable for scale-up production.

The synthesis of 2-(2′-hydroxy-5′-methylphenyl)benzotriazole from 2-nitro-2′-hydroxy-5′-methylazobenzene over Pd/γ-Al2O3 in a fixed-bed reactor was investigated. Pd/γ-Al2O3 catalysts were prepared by two methods and characterized by XRD, TEM, H2-TPR, and N2 adsorption–desorption. Employed in the above reaction, the palladium catalyst impregnated in hydrochloric acid exhibited much better catalytic performance than that impregnated in ammonia–water, which was possibly attributed to the better dispersion of palladium crystals on γ-Al2O3. This result demonstrated that the preparation process of the catalyst was very important. Furthermore, the reaction parameters were optimized. Under the optimized conditions (toluene, NAB/triethylamine molar ratio 1:2, 60 °C, 2.5 MPa hydrogen pressure, 0.23 h–1 liquid hourly space velocity), about 90% yield of 2-(2′-hydroxy-5′-methylphenyl)benzotriazole was obtained. Finally, the time on stream performance of the catalyst was evaluated, and the reaction could proceed effect...

Anthrax Vaccine Adsorbed (AVA, BioThrax®) is approved for use in humans as a priming series of 3 intramuscular (i.m.) injections (0, 1, 6 months; 3-IM) with boosters at 12 and 18 months, and annually thereafter for those at continued risk of infection. A reduction in AVA booster frequency would lessen the burden of vaccination, reduce the cumulative frequency of vaccine associated adverse events and potentially expand vaccine coverage by requiring fewer doses per schedule. Because human inhalation anthrax studies are neither feasible nor ethical, AVA efficacy estimates are determined using cross-species bridging of immune correlates of protection (COP) identified in animal models. We have previously reported that the AVA 3-IM priming series provided high levels of protection in non-human primates (NHP) against inhalation anthrax for up to 4 years after the first vaccination. Penalized logistic regressions of those NHP immunological data identified that anti-protective antigen (anti-PA) IgG concentration measured just prior to infectious challenge was the most accurate single COP.In the present analysis, cross-species logistic regression models of this COP were used to predict probability of survival during a 43 month study in humans receiving the current 3-dose priming and 4 boosters (12, 18, 30 and 42 months; 7-IM) and reduced schedules with boosters at months 18 and 42 only (5-IM), or at month 42 only (4-IM). All models predicted high survival probabilities for the reduced schedules from 7 to 43 months. The predicted survival probabilities for the reduced schedules were 86.8% (4-IM) and 95.8% (5-IM) at month 42 when antibody levels were lowest. The data indicated that 4-IM and 5-IM are both viable alternatives to the current AVA pre-exposure prophylaxis schedule.