Venous thromboembolism risk is lower in patients with atopic dermatitis than other immune-mediated inflammatory diseases: A retrospective, observational, comparative cohort study using US claims data.

BACKGROUND: Certain immune-mediated inflammatory diseases (IMIDs) may increase patients' risk for venous thromboembolisms (VTEs), yet how atopic dermatitis (AD) influences VTE risk remains unclear. OBJECTIVE: Describe VTE incidence in patients with AD compared with other IMIDs and unaffected, AD-matched controls. METHODS: This retrospective, observational, comparative cohort study used Optum Clinformatics United States claims data (2010-2019) of adults with AD, rheumatoid arthritis (RA), Crohn's disease (CD), ulcerative colitis (UC), psoriasis (PsO), psoriatic arthritis (PsA), or ankylosing spondylitis (AS). Unaffected control patients were matched 1:1 with patients with AD. RESULTS: Of 2,061,222 patients with IMIDs, 1,098,633 had AD. Patients with AD had a higher VTE incidence (95% CI) than did unaffected, AD-matched controls (0.73 [0.72-0.74] versus 0.59 [0.58-0.60] cases/100 person-years). When controlling for baseline VTE risk factors, however, AD was not associated with increased VTE risk (HR 0.96 [0.90-1.02]). VTE risk was lower in patients with AD versus RA, UC, CD, AS, or PsA; VTE risk was similar to patients with PsO. LIMITATIONS: Disease activity and severity were not accounted for. CONCLUSION: AD did not increase VTE risk when accounting for underlying risk factors. AD was associated with lower VTE risk compared with several rheumatologic and gastrointestinal IMIDs.

A biocompatible NIR-II light-responsive nanoknife for permanent male sterilization.

Nanomaterial-mediated photothermal therapy (PTT) is a promising strategy for permanent male sterilization owing to its easy operation, rapid heating, minimal invasiveness, and high spatiotemporal controllability. However, the currently available PTT for male sterilization utilizes irradiation sources in the first near-infrared window (NIR-I), which may suffer from incomplete sterilization due to the insufficient penetration depth of NIR-I light. Herein, we developed a facile one-pot hydrothermal synthetic method of cysteine-coated copper sulfide (Cys-CuS) nanosheets for the second NIR window (NIR-II) PTT-mediated permanent male sterilization. In this method, Cys acted not only as a template but also as a sulfur resource in the formation of Cys-CuS nanosheets. The obtained Cys-CuS nanosheets possessed good photothermal properties and satisfied deep-tissue light response capacity under 1064 nm laser exposure. Given this, the permanent male sterilization in vivo was readily achieved by Cys-CuS nanosheets in a rapid manner (only 40 s). To the best of our knowledge, it is the first time that nanomaterial-mediated NIR-II PTT is applied for permanent male sterilization. We believe that the facilely prepared biocompatible Cys-CuS nanosheets can serve as a promising NIR-II light-responsive nanoknife to control the overpopulation of domestic pets and stray animals.

Factors Associated with Severe COVID-19 Among Patients with Rheumatoid Arthritis: A Large, Nationwide Electronic Health Record Cohort Study in the United States.

INTRODUCTION: To evaluate factors associated with severe coronavirus disease 2019 (COVID-19) among patients with rheumatoid arthritis (RA) in the US. METHODS: Adults with RA who had a severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, based on molecular or antigen test or clinical diagnosis, were identified from the Optum® COVID-19 Electronic Health Record dataset (March 1, 2020-April 28, 2021). The primary outcome was the occurrence of severe COVID-19 (hospitalization or death) within 30 days from SARS-CoV-2 infection. Adjusted odds ratios (aOR) and 95% confidence intervals (CI) were estimated using multivariable logistic regression models to assess the association between severe COVID-19 and patient characteristics, including demographics, baseline comorbidities, and recent RA treatments. RESULTS: During the study period, 6769 SARS-CoV-2 infections were identified in patients with RA, among whom 1460 (22%) developed severe COVID-19. Multivariable logistic regression analysis showed that being older, male, and non-White and having diabetes and cardiovascular conditions are associated with greater odds of severe COVID-19. In addition, compared with no use, the adjusted odds of severe COVID-19 were lower with recent use of tumor necrosis factor inhibitors (aOR 0.60, 95% CI 0.41-0.86) and higher with recent use of corticosteroids (aOR 1.38, 95% CI 1.13-1.69) or rituximab (aOR 2.87, 95% CI 1.60-5.14), respectively. CONCLUSION: Nearly one in five patients with RA developed severe COVID-19 disease within 30 days after SARS-CoV-2 infection. In patients with RA, recent use of corticosteroids and rituximab were two factors associated with a greater risk of severe COVID-19 in addition to the risk factors among demographics and comorbidities previously identified in the general population.

Impact of Season and Other Factors on Initiation, Discontinuation, and Switching of Systemic Drug Therapy in Patients with Psoriasis: A Retrospective Study.

This study investigated whether systemic drug prescribing for psoriasis varies by season and other exacerbating factors. Eligible patients with psoriasis were assessed for each season for initiation, discontinuation, and switching of systemic drugs. A total of 360,787 patients were at risk of initiating any systemic drugs in 2016‒2019; 39,572 patients and 35,388 patients were at risk of drug discontinuation or switching to a biologic and a nonbiologic systemic drug, respectively. The initiation of biologic therapy in 2016‒2019 peaked in spring (1.28%), followed by summer (1.11%), fall (1.08%), and winter (1.01%). Nonbiologic systemic drugs followed a similar pattern. Those aged 30‒39 years, male, those with psoriatic arthritis, those who live in the South region, those who live in areas with lower altitudes, and those who live in areas with lower humidity had higher initiation with the same seasonality pattern. Discontinuation of biologic drugs peaked in summer, and switching of biologics was highest in spring. Season is associated with initiation, discontinuation, and switching, although seasonality pattern is less clear for nonbiologic systemic drugs. Approximately 14,280 more patients with psoriasis in the United States are estimated to initiate a biologic in spring than in other seasons, and over 840 more biologic users switched in spring than in winter. The findings may provide evidence for healthcare resource planning in psoriasis management.

Outcomes of coronavirus disease 2019 (COVID-19) and risk factors associated with severe COVID-19 in patients with mature B-cell non-Hodgkin lymphomas: A US electronic health record cohort study.

OBJECTIVES: The objectives of this study were to assess the risk of severe coronavirus disease 2019 (COVID-19) outcomes in patients with mature B-cell non-Hodgkin lymphoma (mature B-cell NHL) compared with other cancers and to identify risk factors associated with severe COVID-19. METHODS: This study used Optum's electronic health record database. Risk factors were evaluated using multivariable logistic regression. RESULTS: Patients with mature B-cell NHL were more likely to be hospitalized or die from COVID-19 (age- and sex-standardized risk: 15.6%, 2.1%, respectively) than those without cancer (9.5%, 1.2%), or with solid tumors (9.7%, 1.3%). In patients with mature B-cell NHL, factors associated with severe COVID-19 outcomes included: greater age (75-84 years, adjusted odds ratio, 1.6 [95% CI, 1.3-2.0]; ≥85, 2.6 [2.0-3.4]), male sex (1.4 [1.2-1.6]), chronic kidney disease (1.4 [1.1-1.7]), chronic obstructive pulmonary disease (1.3 [1.0-1.6]), type 2 diabetes (1.3 [1.1-1.5]), and receiving treatment for NHL (1.5 [1.1-2.1]). CONCLUSIONS: These data suggest that patients with mature B-cell NHL are at a higher risk of severe COVID-19 than patients with solid tumors or without cancer and that risk factors are largely consistent with those in the general population.

Risk of Severe COVID-19 Outcomes Among Patients with Immune-Mediated Inflammatory Diseases or Malignancies: A Retrospective Analysis of Real-World Data in the United States.

INTRODUCTION: There are concerns that patients in an immunocompromised state may be at risk for increased coronavirus disease 2019 (COVID-19) severity. The aim of this study was to describe the characteristics of patients with COVID-19 and immune-mediated inflammatory diseases (IMIDs) or malignancies and evaluate their risk of developing severe COVID-19. METHODS: Cases of COVID-19 (ICD-10 code U07.1 or U07.2, or positive polymerase chain reaction or antigen test) among patients with IMIDs or malignancies were identified in the US-based Optum® Electronic Health Records database between 1 February 2020 and 3 March 2021. Age- and sex-standardized risks of severe COVID-19 were calculated by condition of interest. The risks were further adjusted by multiple covariates, and 95% confidence intervals were estimated. RESULTS: A total of 499,772 patients with COVID-19 were identified (mean [SD] age, 46.9 [20.7] years; 57.0% female). Patients with hematologic cancers (adjusted risk ratio [aRR] 2.0, 1.8-2.1), solid tumors (aRR 1.1, 1.1-1.1), or rheumatoid arthritis (aRR 1.2, 1.1-1.3) had a significantly higher risk of severe COVID-19 compared to the general population of patients with COVID-19. Patients with systemic lupus erythematosus (aRR 1.1, 0.9-1.2), psoriasis (aRR 1.0, 0.7-1.2), ulcerative colitis (aRR 0.9, 0.8-1.1), Crohn's disease (aRR 0.9, 0.7-1.0), or ankylosing spondylitis (aRR 0.8, 0.5-1.0) showed a comparable risk of severe COVID-19. Patients with atopic dermatitis (aRR 0.8, 0.7-0.9) or psoriatic arthritis (aRR 0.8, 0.6-1.0) showed a lower risk of severe COVID-19. CONCLUSIONS: The risk of developing severe COVID-19 varied between the studied IMIDs and malignancies. Patients with hematologic cancers, solid tumors, or rheumatoid arthritis had significantly increased risk for severe COVID-19 compared to the general population. These findings highlight the need to protect and monitor immunocompromised patients such as those with IMIDs or malignancies as part of the strategy to control the pandemic worldwide.

Safety and cost-effectiveness of ponatinib versus other tyrosine kinase inhibitors as second-line therapy in patients with chronic myeloid leukemia in the United States.

To evaluate the cost-effectiveness of ponatinib compared with second-line TKIs in the treatment of adult patients with CML who failed, or were intolerant to, first-line TKIs. A Markov state transition model was conducted. Model transition, adverse-effect probabilities, utility data and medical costs were obtained from clinical trials and literature. Measurements included medications, follow-ups, adverse events, allogeneic stem cell transplantation and quality-adjusted life years (QALYs). Univariable and Bayesian multivariable probabilistic sensitivity analyses were conducted using Monte Carlo simulations. Dasatinib resulted in an ICER of $79,086/QALY compared to nilotinib. Ponatinib yielded an ICER of $176,278/QALY and $141,563/QALY compared to dasatinib and nilotinib, respectively. Dasatinib was the optimal treatment at a $100,000/QALY threshold. The probability (36%-40%) for ponatinib or dasatinib optimal treatment was associated with thresholds of $160,000-$180,000/QALY. Dasatinib and ponatinib can be considered cost-effective options and provide clinical benefits compared to other second-line TKIs for CML in the US.

Plasma membrane-localized protein BcHIPP16 promotes the uptake of copper and cadmium in planta.

Cadmium (Cd) is one of the toxic heavy metals in soil, which not only suppresses crop production but also threatens human health. In this study, we aim to clarify the biological function of Cd-related gene BcHIPP16, so as to provide potential genetic solutions to decrease the Cd levels of pak choi. Tissue expression analysis showed that BcHIPP16 expressed in almost all the plant bodies. The transcriptional level of BcHIPP16 in roots was higher than that in shoots, which was significantly induced by copper (Cu) deficiency and Cd exposure conditions. Subcellular localization revealed that BcHIPP16 localized in plasma membrane. Expressing BcHIPP16 in yeast cells improved the sensitivity to Cu and Cd and improved their accumulation in yeast. Furthermore, the Cu and Cd content of Arabidopsis seedlings were increased and complemented, respectively when expressing BcHIPP16 in wild type (WT) and hip16 mutants. Non-invasive Micro-test Technology (NMT) was used to measure the real-time Cd2+ influx from the root surface of BcHIPP16 transgenic Arabidopsis lines, and the result demonstrated that BcHIPP16 promoted Cd2+ influx into Arabidopsis root cells. Taken together, our study showed that BcHIPP16 contributed to absorbing nutrient metal Cu and heavy metal Cd in planta.

Comparative effectiveness and persistence of TNFi and non-TNFi in juvenile idiopathic arthritis: a large paediatric rheumatology centre in the USA.

OBJECTIVE: To evaluate the persistence and effectiveness of TNF inhibitors (TNFi) vs non-TNFi among newly diagnosed JIA patients after initiation of biologic DMARD (bDMARD). METHODS: Using longitudinal patient-level data extracted from electronic medical records in a large Midwestern paediatric hospital from 2009 to 2018, we identified JIA patients initiating TNFi and non-TNFi treatment. Treatment effectiveness was assessed based on disease activity. Inverse probability of treatment weighting of propensity score was used to estimate the treatment effectiveness and Kaplan-Meier analyses were conducted to assess persistence. RESULTS: Of 667 JIA patients, most (92.0%) were prescribed one of the class of TNFi as their initial biologic treatment. Etanercept was the most frequently prescribed (67.1%) treatment, followed by adalimumab (27.5%). Only around 5% of patients were prescribed off-label bDMARDs as their first-course treatment; however, >20% were prescribed off-label biologics as their second-course therapy. Some 7.2% of patients received four or more bDMARDs. The median persistence of the first-course bDMARD is 320 days, with TNFi being significantly longer than the non-TNFi (395 vs 320 days, P = 0.010). The clinical Juvenile Disease Activity Score (cJADAS) reduction of TNFi users (6.6, 95% CI 5.7, 7.5) was significant greater compared with non-TNFi users (3.0, 95% CI 1.5, 4.6, P < 0.0001) at 6-month follow-up visit. CONCLUSION: Persistence was significantly longer among patients initiating TNFi as their first biologic therapy than those receiving non-TNFi. Patients receiving TNF therapy had significant greater reduction of cJADAS at the 6-month follow-up visit compared with patients in the non-TNF cohort.

BcNRAMP1 promotes the absorption of cadmium and manganese in Arabidopsis.

Cadmium (Cd) is a toxic nonessential metal that poses a health risk for humans. Cd is easily accumulated in leaf vegetables than in other vegetables. Leafy vegetables are one of the major dietary Cd sources for the human body. In this study, pak choi was used as our experimental material as it is an important leafy vegetable, especially in Asia. A NRAMP transporter - BcNRAMP1 was identified in pak choi, which is involved in manganese (Mn) and Cd uptake in yeast and in planta. BcNRAMP1 is expressed in the whole plant body of pak choi, with a higher abundance in root tissues than in shoots. Mn deficiency and Cd exposure strongly induced BcNRAMP1 transcription levels. Through transient expression of BcNRAMP1-GFP fusion protein in tobacco leaf epidermal cells, BcNRAMP1 was revealed as a plasma membrane protein. Expressing BcNRAMP1 in yeast enhanced yeast cells to absorb Mn, Cd, and iron (Fe). Overexpression of BcNRAMP1 in Arabidopsis wild-type and nramp1 mutant increased and complemented Mn and Cd transportation and accumulation, respectively. Using noninvasive microelectrode ion flux measurements, a direct evidence that BcNRAMP1 acts on Cd influx in Arabidopsis root cells was provided. The results of this study reveal that BcNRAMP1 functions as a NRAMP protein in planta, absorbing nutrient metal Mn and the toxic metal Cd.

Prescribing Patterns and Impact of Factors Associated with Time to Initial Biologic Therapy among Children with Non-systemic Juvenile Idiopathic Arthritis.

OBJECTIVE: The aim of this study was to examine patterns of initial prescriptions, investigate time to initiation of biologic disease-modifying anti-rheumatic drugs (bDMARDs), and evaluate the impact of clinical and other baseline factors associated with the time to first bDMARD in treating children with newly diagnosed non-systemic juvenile idiopathic arthritis (JIA). METHODS: Using longitudinal patient-level data extracted from electronic medical records (EMR) in a large Midwestern pediatric hospital from 2009 to 2018, the initial prescriptions and prescribing patterns of bDMARDs, conventional synthetic disease-modifying anti-rheumatic drugs (csDMARDs), non-steroidal anti-inflammatory drugs (NSAIDs) and glucocorticoids within 3 months of JIA diagnosis were examined. Kaplan-Meier analyses were performed to assess time to initiation of bDMARDs. Cox proportional hazard models were used to identify factors associated with time to first bDMARD. RESULTS: Of 821 children, the proportion of patients with initial csDMARDs increased from 45.3% in 2009 to 60.3% in 2018. Around 57.5% of polyarthritis rheumatoid factor-positive (Poly RF+) patients and 43.2% of polyarthritis rheumatoid factor-negative (Poly RF-) patients received a bDMARD therapy within 3 months of diagnosis, 14.4% as monotherapy and 28.3% in combination with a csDMARD. Among patients who received combination therapy, combination of methotrexate with adalimumab increased from 16.7% in 2009 to 40% in 2018. The proportion of patients treated with adalimumab gradually increased and passed etanercept in 2016. The predictors of earlier initiation of biologic therapy were JIA category enthesitis-related arthritis (ERA) [hazard ratio (HR) vs persistent oligoarthritis 4.82; p < 0.0001], psoriatic arthritis (PsA) (HR 2.46; p = 0.0002), or Poly RF- (HR 2.43; p = 0.0002); the number of joints with limited range of motion (HR 1.02; p = 0.0222), and erythrocyte sedimentation rate (ESR, HR 1.01; p = 0.0033). CONCLUSIONS: There was a substantial increase in the proportion of patients receiving the combination of methotrexate and adalimumab among patients receiving combination therapy. Adalimumab overtook etanercept as the most frequently prescribed bDMARD. Multiple factors affect the time to biologic initiation, including the number of joints with limited range of motion, ESR, and JIA category.

The cost-effectiveness of once-weekly semaglutide compared with other GLP-1 receptor agonists in type 2 Diabetes: a systematic literature review.

Introduction: As a novel glucagon-like peptide-1receptor agonist (GLP-1 RA) for type 2 diabetes (T2D) treatment, the economic value of once-weekly semaglutide had been assessed in several country settings. The authors' objective was to systematically review the existing pharmacoeconomic literature evaluating the cost-effectiveness associated with once-weekly semaglutide compared with other GLP-1 RAs and provide implications for further researches.Areas covered: We conducted a systematic literature review of cost-effectiveness analysis (CEA) published up to 25 July 2020 in PubMed, web of science, and the ISPOR presentation database, compared once-weekly semaglutide with other GLP-1 RAs in T2D. Nineteen studies were identified, including 8 short-term and 11 long-term studies. General characteristics and main results of the included studies were summarized.Expert opinion: This review provided references for other countries to overview the value of once-weekly semaglutide compared with other GLP-1 RAs in T2D in the healthcare decision-making process and to conduct their CEA studies associated with once-weekly semaglutide. The authors found that the cardiovascular (CV) benefit of once-weekly semaglutide was under-estimated in current studies and suggested that the methods of economic evaluations for novel anti-diabetic drugs with CV benefit should be improved in future researches.

IRT1 and ZIP2 were involved in exogenous hydrogen-rich water-reduced cadmium accumulation in Brassica chinensis and Arabidopsis thaliana.

The results of Cd (cadmium) concentration, Cd2+ fluorescent staining, NMT (non-invasive micro-test technology) analysis of Cd absorption revealed the remarkably positive role of HRW in reducing Cd uptake by root of pak choi seedlings. BcIRT1 (iron-regulated transporter 1) and BcZIP2 (zinc-regulated transporter protein 2) are the main Cd transporters in pak choi, but their roles in the process of HRW-reduced Cd uptake is still far from being answered. In this study, we specifically verified the function of IRT1 and ZIP2 in HRW-reduced Cd absorption in pak choi and Arabidopsis thaliana. Heterologous and homologous expression in Arabidopsis thaliana displayed that Cd concentrations in wild-type (Col-0) and transgenic A. thaliana of IRT1 and ZIP2 were significantly reduced by HRW, except for irt1- and zip2-mutant. NMT detection showed that HRW not only decreased Cd2+ influx in root of WT and transgenic lines, but also enhanced the competition between Zn and Cd. Taken together, the HRW-induced reduction of Cd accumulation in plants may be result from depressing the expression of BcIRT1 and BcZIP2 and affecting the preference of BcIRT1 and BcZIP2 in ion uptake.

Economic burden and treatment patterns of gynecologic cancers in the United States: evidence from the Medical Expenditure Panel Survey 2007-2014.

OBJECTIVE: This study estimated nationally representative medical expenditures of gynecologic cancers, described treatment patterns and assessed key risk factors associated with the economic burden in the United States. METHODS: A retrospective repeated measures design was used to estimate the effect of gynecologic cancers on medical expenditures and utilization among women. Data were extracted from the Medical Expenditure Panel Survey (weighted sample of 609,787 US adults) from 2007 to 2014. Using the behavioral model of health services utilization, characteristics of cancer patients were examined and compared among uterine, cervical, and ovarian cancer patients. Multivariable linear regression models were conducted on medical expenditure with a prior logarithmic transformation. RESULTS: The estimated annual medical expenditure attributed to gynecologic cancers was $3.8 billion, with an average cost of $6,293 per patient. The highest annual cost per person was ovarian cancer ($13,566), followed by uterine cancer ($6,852), and cervical cancer ($2,312). The major components of medical costs were hospital inpatient stays (53%, $2.03 billion), followed by office-based visits (15%, $559 million), and outpatient visits (13%, $487 million). Two key prescription expenditures were antineoplastic hormones (10.3%) and analgesics (9.2%). High expenditures were significantly associated with being a married woman (p<0.001), having private health insurance (p<0.001), being from a low- and middle-income family (p<0.001), or living in the Midwest or the South (p<0.001). CONCLUSION: The key risk factors and components were well described for the economic burden of gynecologic cancers. With a growing population of cancer patients, efforts to reduce the burden of gynecologic cancers are warranted.

Trends in Utilization, Spending, and Prices of Smoking-Cessation Medications in Medicaid Programs: 25 Years Empirical Data Analysis, 1991-2015.

BACKGROUND: Smoking remains the single largest preventable cause of death and disease. Smoking-cessation medications provide patients a multitude of benefits and can prevent certain diseases, including some cancers. Because of the limited amount of studies on smoking-cessation medications, we wanted to find general trends about the use of these medications. OBJECTIVE: To examine trends in the utilization, pharmacy reimbursement, and prices of smoking-cessation medications and nicotine replacement therapy in the US Medicaid-covered population. METHODS: Using national summary files for outpatient drug utilization and expenditure, we extracted data on smoking-cessation medications from the Centers for Medicare & Medicaid Services in the 25 years from January 1991 through June 2015. We conducted a retrospective drug utilization study to examine the annual (or quarterly) trends of the number of prescriptions, reimbursement expenditures, and the prices of smoking-cessation medications. The study drugs included varenicline (Chantix), bupropion (Zyban), and nicotine. We calculated per-prescription pharmacy reimbursement, which was used as a proxy for drug price, as the total quarterly expenditure for the drug, divided by the total number of prescriptions. All expenditures were inflated to 2015 US dollars using the medical services component of the Consumer Price Index. RESULTS: The total number of prescriptions for smoking-cessation medications increased rapidly from 46,396 in 1991 to 942,562 in 2014, an increase of more than 1931%. During the same period, the total pharmacy reimbursement for smoking-cessation medications in Medicaid increased by 3562%, from approximately $2.8 million in 1991 to approximately $101 million in 2014. The use of the nonnicotine prescription drugs varenicline and bupropion also increased rapidly, with a high cost expenditure. The price per nonnicotine prescription drug increased over time, ranging from approximately $169 for bupropion to approximately $251 for varenicline in 2015. CONCLUSIONS: The substantial increase in nonnicotine prescription drugs and nicotine replacement therapy between 2007 and 2015 may be attributed to smoking-cessation participants nationwide. Cost-containment policies might have inadvertently prevented Medicaid-covered smokers from obtaining appropriate pharmacotherapy.