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Jun Wu,1 Mary L Davis-Ajami,2 Zhiqiang K Lu3 1Department of Pharmaceutical and Administrative Sciences, Presbyterian College School of Pharmacy, Clinton, SC, USA; 2Department of Science of Nursing Care, School of Nursing, Indiana University, Bloomington, IN, USA; 3Department of Clinical Pharmacy and Outcomes Sciences, College of Pharmacy, University of South Carolina, Columbia, SC, USA Purpose: Migraine prevalence increases in people with obesity, and obesity may contribute to migraine chronicity. Yet, few studies examine the effect of comorbid migraine on health care utilization and expenses in obese US adults. This study aimed to identify risk factors for migraine and compare the use of health care services and expenses between migraineurs and non-migraineurs in obese US adults.Subjects and methods: This 7-year retrospective study used longitudinal panel data from 2006 to 2013 from the Household Component of the Medical Expenditure Panel Survey to identify obese adults reporting migraines. Outcomes compared in migraineurs vs non-migraineurs were as follows: annualized per-person medical care, prescription drug, and total health expenses.Results: In 23,596 obese adults, 4.7% reported migraine (n=1,025) approximating 3 million civilian noninstitutionalized US individuals. Logistic regression showed that the following sociodemographic characteristics increased migraine risk: age (18–45 years), females, White race, poor perceived health status, and greater Charlson comorbidity index. Migraineurs showed US$1,401 (P=0.007), US$813 (P

Background: The toxicity and drug resistance associated with oxaliplatin (L-OHP) limit its long-term use for colorectal cancer (CRC) patients. p53 mutation is a common genetic trait of CRC. PRIMA-1 met (APR-246, eprenetapopt) restores the DNA-binding capacity of different mutant P53 proteins. PRIMA-1 met has progressed to the Phase III clinical trial. Our study explores the combination therapy of PRIMA-1 met and L-OHP for CRC with different p53 status., Methods: Cell viability was assessed with Cell Counting Kit-8 (CCK-8) assay and combination index (CI) was calculated using The Chou-Talalay method. We also employed wound healing assay and colony formation assay to determine the effect of L-OHP, PRIMA-1 met and their combination. Weighted gene co-expression network analysis (WGCNA) of RNA-seq data was conducted to identify key modules and central genes related to different treatment modalities. Xenograft CRC mouse model was used to assess the combination treatment in vivo., Results: Our findings showed heightened cytotoxicity and inhibition of migration, and colony formation in CRC cells treated with both drugs, irrespective of p53 status, presenting a promising avenue for addressing L-OHP resistance and toxicity. RNA-seq analysis revealed differential responses between p53-wide type HCT116 and p53-mutant DLD-1 cells, with pathway alterations implicated in tumorigenesis. WGCNA identified key modules and hub genes associated with combination therapy response. In vivo studies demonstrated enhanced efficacy of combined therapy over PRIMA-1 met alone, while mitigating L-OHP-induced toxicity., Conclusions: In summary, our research reveals the differential molecular mechanisms of combined PRIMA-1 met and L-OHP in CRC with wild type p53 and mutant p53. Our data not only demonstrate that this combined regimen exerts synergistic anti-CRC effect in vitro and in vivo, but also suggest the benefit of PRIMA-1 met on prevention of L-OHP-related side effects. These findings underscore the clinical potential of PRIMA-1 met -L-OHP combination therapy in CRC, offering enhanced efficacy and reduced toxicity, warranting further clinical investigation., (© 2025 The Author(s). Cancer Medicine published by John Wiley & Sons Ltd.)

Background: Pruritus, a common symptom of burn wounds, arises from skin tissue damage and abnormal tissue healing. Chronic post-burn pruritus (CPBP) is defined as itching that persists for six weeks or more. The brain mechanisms underlying CPBP are not understood adequately. This study aims to explore abnormal brain function in CPBP patients and identify potential pathogenesis of pruritus., Materials and Methods: Twenty patients with CPBP and twenty healthy controls (HCs) participated in the study and underwent resting-state functional magnetic resonance imaging (fMRI) scans. Brain activity was evaluated using regional homogeneity (ReHo), amplitude of low-frequency fluctuations (ALFF), and fractional ALFF (fALFF) measures. Preprocessing of fMRI data involved steps such as slice timing correction, motion correction, and nuisance regression to account for physiological noise and head motion. Statistical analyses included two-sample t-tests to compare ReHo, ALFF, and fALFF values between CPBP patients and HCs, with age as a covariate, and Spearman correlation analysis to explore relationships between brain activity measures and clinical characteristics., Results: The study revealed significant differences in brain activity between CPBP patients and HCs. CPBP patients exhibited altered higher ReHo in regions including the bilateral middle frontal gyrus, medial superior frontal gyrus, precuneus, left insula, right caudate, and bilateral cerebellar tonsils, with decreased ReHo in the right precentral gyrus. ALFF analysis showed increased activity in the bilateral middle frontal gyrus, medial superior frontal gyrus, right precuneus, and right inferior frontal gyrus, and decreased ALFF in the left precentral gyrus and right postcentral gyrus. fALFF values were notably higher in the bilateral medial superior frontal gyrus and precuneus. Several brain regions with significant differences in ReHo, ALFF, and fALFF were extensively correlated with the burned area and pruritus scale scores., Conclusion: Our data suggest that patients with CPBP show alterations in ReHo, ALFF, and fALFF values primarily in brain regions associated with the default mode network and sensorimotor areas. These results may provide valuable insights relevant to the neuropathology of CPBP., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. Conflict of Interest The authors claim that the absence of any commercial or financial relationships that could be construed as a potential conflict of interest in this study., (Copyright © 2024 Elsevier Ltd and International Society of Burns Injuries. All rights reserved.)

This study provides a systematic review of existing evidence concerning the efficacy of Jiangzhi Tongluo Soft Capsules(JTSC) in treating hyperlipidemia(syndrome of blood stasis and Qi stagnation), following the Guidelines for clinical evidence and value assessment of drugs. The qualitative and quantitative methods were integrated, including questionnaire surveys, evidence-based medicine, and pharmacoeconomic evaluation. Multi-criteria decision analysis(MCDA) model was used for comprehensive assessment of the clinical evidence and value of JTSC for hyperlipidemia in "6+1" dimensions: safety, effectiveness, cost-effectiveness, innovation, suitability, accessibility, and traditional Chinese medicine(TCM) characteristics. The safety evidence was sufficient and the results of the known risk assessment indicated that JTSC was safe and had a sufficient safety profile. Meta-analysis showed that JTSC recovered patients' triglyceride levels(RR=-0.25, 95%CI[-0.41,-0.10], P=0.001). JTSC had similar efficacy to simvastatin Tablets(RR=1.11, 95%CI[0.96, 1.27], P=0.15) and Zhibituo Tablets(RR=1.07, 95%CI[0.99, 1.16], P=0.10) in restoring blood lipid levels. JTSC outperformed Xuezhikang Capsules in recovering blood lipid levels(RR=1.44, 95%CI[1.17, 1.76], P=0.000 6). According to the Grading of Recommendations Assessment, Development and Evaluation(GRADE) system, the evidence was rated as grade C, and the overall evaluation of the quality and value of the evidence indicated that the effectiveness evidence of this product was fairly sufficient. Markov economic model was established, and the results suggested that JTSC was more economical than Pushen Capsules. Considering the incremental effect and the cost of the intervention scheme, JTSC had good cost effectiveness. The innovation of JTSC was evaluated based on three primary indicators and eighteen secondary indicators, which suggested the evidence of innovation for JTSC was abundant. The information of Chinese patent medicines of JTSC was complete, and the survey results showed that the drug was suitable for clinicians, nurses, pharmacists, and patients. The comprehensive evaluation suggested that JTSC had abundant evidence of suitability. The accessibility of a drug mainly involves the price, availability, and affordability of the drug. The tender price of JTSC was 0.72 yuan/capsule, and the treatment cost after refund accounted for 0.08% of the median household disposable income of urban residents and 0.31% of the median household disposable income of rural residents. The evidence of accessibility was abundant. The TCM characteristics of JTSC were prominent. CSC v2.0 was used to calculate the comprehensive evaluation value in the "6+1" dimensions, which yielded a score of 0.69, indicating sufficient evidence for the clinical comprehensive value of this drug. According to the evaluation results of each dimension and the comprehensive evaluation score, it is believed that the clinical value evidence of JTSC in treatment of hyperlipidemia(syndrome of blood stasis and Qi stagnation) is sufficient. It is suggested that high-quality evidence-based research should be carried out on the treatment of hyperlipidemia with JTSC, and contraindications in pregnant women should be added in the section of contraindications of the product instruction.

There are many kinds and dosage forms of Chinese patent medicines for external use on the market, which are widely used in clinical departments. The common adverse reactions of Chinese patent medicines for external use are skin reactions, and those for the rare severe diseases include palpitation, chest tightness, dyspnea, and anaphylactic shock. At present, World Health Organization(WHO), International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use(ICH),the United States, the European Union, and Asia-Pacific countries(such as Japan and South Korea) have not issued any pharmacovigilance guideline of Chinese patent medicines for external use. China has not issued any pharmacovigilance guideline for these medicines, only releasing the standard Evaluation of skin adverse reactions caused by Chinese patent medicines for external use(T/CACM 005-2017). To standardize the safe and reasonable use of Chinese patent medicines for external use, Pharmacovigilance guidelines for clinical application of Chinese patent medicines for external use was developed with the joint efforts of experts in diverse disciplines. The guideline provides guidance on the monitoring and reporting of adverse reactions/events, identification and assessment of risk signals, and risk control measures in the clinical application of Chinese patent medicines for external use to guide the rational use of these medicines in clinical practice. At the same time, the possible risks and risk control measures in clinical application of Chinese patent medicines for external use are listed for clinical reference. In addition, the guideline provides guidance for risk minimization plans and the standardization of activities related to pharmacovigilance of Chinese patent medicines for external use in China.

Background: Glycogen storage disease type Ib (GSD Ib) is a rare disorder characterized by impaired glucose homeostasis caused by mutations in the SLC37A4 gene. It is a severe inherited metabolic disease associated with hypoglycemia, hyperlipidemia, lactic acidosis, hepatomegaly, and neutropenia. Traditional treatment consists of feeding raw cornstarch which can help to adjust energy metabolism but has no positive effect on neutropenia, which is fatal for these patients. Recently, the pathophysiologic mechanism of the neutrophil dysfunction and neutropenia in GSD Ib has been found, and the treatment with the SGLT2 inhibitor empaglifozin is now well established. In 2020, SGLT2 inhibitor empagliflozin started to be used as a promising efficient remover of 1,5AG6P in neutrophil of GSD Ib patients worldwide. However, it is necessary to consider long-term utility and safety of a novel treatment., Results: In this study, we retrospectively examined the clinical manifestations, biochemical examination results, genotypes, long-term outcomes and follow-up of thirty-five GSD Ib children who visited our department since 2009. Fourteen patients among them underwent empagliflozin treatment since 2020. This study is the largest cohort of pediatric GSD Ib patients in China as well as the largest cohort of pediatric GSD Ib patients treated with empagliflozin in a single center to date. The study also discussed the experience of long-term management on pediatric GSD Ib patients., Conclusion: Empagliflozin treatment for pediatric GSD Ib patients is efficient and safe. Increase of urine glucose is a signal for pharmaceutical effect, however attention to urinary infection and hypoglycemia is suggested., (© 2024. The Author(s).)

Background: A conclusive evidence regarding the optimal concentration and volume of local anesthetic for quadratus lumborum block is lacking., Methods: In this single-center, prospective, randomized, controlled study, 60 patients scheduled for laparoscopic colorectal surgery were randomly assigned to 3 different combinations of volume and concentration of ropivacaine (3 mg/kg) - Group 0.25%, Group 0.375% and Group 0.5%. All subjects received ultrasound-guided posterior quadratus lumborum block prior to the induction. The primary outcome was the complete sensory block rate of surgical site measured at 30 min after quadratus lumborum block, after extubation, at 12, 24, and 48 h after operation. Secondary outcomes were the changes in hemodynamic parameters before and after incision (ΔSBP, ΔDBP and ΔHR), postoperative pain score, the sufentanil consumption after surgery, length of stay and adverse reactions., Results: The sensory block rate of surgical site at 5 time points differed significantly among the three groups ( P  < 0.001). Both Group 0.375% ( P  < 0.001) and Group 0.5% ( P  < 0.001) had a higher sensory block rate than Group 0.25%, but no significant difference was observed between the former two. Group 0.375% and Group 0.5% had lower postoperative pain scores, lower sufentanil consumption after surgery and shorter length of stay. No statistical difference was observed in ΔSBP, ΔDBP, ΔHR and the incidence of adverse reactions., Conclusions: 0.375% and 0.5% ropivacaine in posterior quadratus lumborum block provide better sensory block of surgical site when compared to 0.25% in laparoscopic colorectal surgery., Trial Registration Number: Chinese Clinical Trials Registry (ChiCTR2100043949)., Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (© 2024 The Authors. Published by Elsevier Ltd.)

Universal access to insulin remains a global public health challenge mainly due to its high price. After unsuccessful healthcare reforms attempting to lower insulin prices over the past several decades, the novel pooled procurement-also known as the national volume-based procurement (NVBP)was initiated exclusively for insulin in China. The NVBP exclusively for insulin represents a unique approach to conquering the challenges in the pooled procurement many low-income and middle-income countries face. In this paper, we described how the pooled procurement mechanism was implemented for insulin in China. Forty-two insulin products from 11 companies were procured, with a median price reduction of 42.08%. The procurement price ranged from US$0.35 to US$1.63 (¥2.35-¥10.97) per defined daily dose (DDD). The median procurement price per DDD was US$$0.54 (¥3.63) for human insulins and US$0.92 (¥6.18) for analogue insulin (p<0.001), respectively. A total of 32 000 medical facilities participated in the procurement, and the pooled demand for insulin was 1.61 billion daily doses, with an estimated saving of US$2.85 billion (¥19 billion) for the first year of the procurement agreement. Insulin affordability and accessibility improved substantially. This study reveals that the NVBP exclusively for insulin could effectively reduce insulin prices and improve access to this essential medicine. Even though the pooled procurement option looks efficient, its long-term impacts on the healthcare system should be closely monitored., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: Distinct subtypes of Alzheimer's disease (AD) and related dementias (RD) might have different effects on dental care usage and economic burden. To determine the effects of AD and RD on specific types of dental care usage (preventive and treatment visits) and dental care costs from different payers (total and out-of-pocket costs)., Methods: A cross-sectional study was conducted using the Medicare Current Beneficiary Survey in 2016. This study identified 4268 community dwelling older adults with and without Alzheimer's disease and related dementias (ADRD) from a nationally representative sample of Medicare beneficiaries. Dental care usage and costs are based on self-reported data. Preventive dental events included preventive and diagnosis events. Treatment dental events included restorative, oral surgery and other events., Results: This study identified 4268 (weighted N=30 423 885) older adults, including 94.48% without ADRD, 1.90% with AD and 3.63% with RD. Compared with older adults without ADRD, those with AD had similar dental care usage, but those with RD were 38% less likely to have treatment visit (OR: 0.62; 95% CI: 0.41 to 0.94) and had a 40% reduced number of total treatment visits (incidence rate ratio: 0.60; 95% CI: 0.37 to 0.98). RD was not associated with dental care costs, but AD was associated with higher total costs (β: 1.08; 95% CI: 0.14 to 2.01) and higher out-of-pocket costs (β: 1.25; 95% CI: 0.17 to 2.32)., Conclusions: Patients with ADRD were more likely to have adverse dental care outcomes. Specifically, RD was associated with lower treatment dental care usage and AD was associated with higher total and out-of-pocket dental care costs. Effective patient-centred strategies should be used to improve dental care outcomes in patients with distinct subtypes of ADRD., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2023. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Multiple chronic conditions (MCC) require complex patient-centered approaches with effective provider-patient communication., Objective: To describe trends in patient perceptions of provider-patient communication during non-emergency care and identify associated racial disparities in US older adults with MCC., Design, Setting, Participants: Observational study using pooled US Medical Expenditure Panel Survey (2013-2019) data included adults > 65 with two or more chronic conditions., Main Measures: Provider-patient communication was measured by four indicators (how often their doctor explained things clearly, listened carefully, showed respect, and spent enough time with them). The primary outcomes were the annual rates of reporting "always" for the communication indicators. Cochran-Armitage trend tests examined the trends of reporting "always" and associated racial disparities. Multivariable logistic regression identified racial and other factors associated with respondents choosing "always" for one or more categories for provider-patient communication, defined as positive communication., Results: Among 9758 older adults with MCC, declining trends for positive communication were shown across all provider-patient communication categories during 2013 to 2019 (p<0.001). The greatest decrease occurred in "always listening carefully", from 68.6% in 2013 to 59.1% in 2019 (p<0.001). The declining trends of four communication measures in non-Hispanic Whites with MCC were significant (p<0.001). Older adults from Hispanic or Non-Hispanic Black racial backgrounds were 28 to 51% more likely to report "always" for the four indicators of provider-patient communication than non-Hispanic Whites after adjusting for respondents' characteristics., Conclusion: The rates of "always" reporting positive communication with providers significantly declined from 2013 to 2019 in older adults with MCC, particularly in non-Hispanic Whites. Hispanics and non-Hispanic Blacks were more likely to report positive communication with providers than other races., (© 2022. The Author(s), under exclusive licence to Society of General Internal Medicine.)

Background: Stroke has been the leading cause of death in China for decades. The extremely low intravenous thrombolysis rate is largely due to the prehospital delays that make patients ineligible for the time-sensitive therapy. Limited studies evaluated prehospital delays across China. We investigated prehospital delays in the stroke population across China and the associated age, rurality, and geographic disparities., Methods: A cross-sectional study design was employed using the Bigdata Observatory platform for Stroke of China in 2020, the nationwide, prospective, multicentre registry of patients with acute ischaemic stroke (AIS). Mixed-effect regression models were used to account for the clustered data., Findings: The sample contained 78,389 AIS patients. The median onset-to-door (OTD) time was 24 h, with only 11.79% (95% confidence interval [CI]: 11.56-12.02%) patients arriving at hospitals within 3 h. About 12.43% (95% CI: 12.11-12.74%) of patients 65 years or older arrived at hospitals within 3 h, which was significantly higher than the young and middle-aged patients (11.03%; 95% CI: 10.71-11.36%). After controlling for potential confounders, young and middle-aged patients were less likely to present to hospitals within 3 h (adjusted odds ratio: 0.95; 95% CI: 0.90-0.99) compared to patients 65 years or older. The 3-h hospital arrival rate was the highest in Beijing (18.40%, 95% CI: 16.01-20.79%), which was almost 5 times higher than that in Gansu (3.45%, 95% CI: 2.69-4.20%). The arrival rate in urban areas was almost 2 times higher than that in rural areas (13.35% versus. 7.66%)., Interpretation: We found that the low rates of timely arrival at hospitals after a stroke is more salient in the younger population, rural settings, or those residing in less developed geographic regions. This study calls for more tailored interventions focusing on younger people, rural areas, and less developed geographic regions., Funding: The National Natural Science Foundation of China; CIHR, Grant/Award Number: 81973157, PI: JZ. Natural Science Foundation of Shanghai; CIHR, Grant/Award Number: 17dz2308400, PI: JZ. Funding from the University of Pennsylvania; Grant/Award Number: CREF-030, PI: RL., Competing Interests: There are no financial conflicts of interest to disclose., (© 2023 The Author(s).)

This study aimed to examine the responses of persistent soil seed bank to future precipitation reduction of global climate change in the forest-steppe ecotone of Hulunbuir. Samples of soil seed bank were collected from 0-10 cm soil layer along a precipitation gradient. We examined the density, species composition, diversity of seed bank and their relationship with vegetation. Structural equation model was used to explore the direct impact of annual precipitation on soil seed bank and the indirect impact through vegetation, soil nitrogen, soil phosphorus, and soil pH. The results showed that seed bank density and species richness were negatively correlated with annual precipitation. The species diversity of soil seed banks in grasslands was higher than that in forests. The similarity between soil seed bank and vegetation was generally low. The results of structural equation model showed that the effects of annual precipitation on seed bank density and species richness were negative, with the standard path coefficients of -0.051 and -0.122, respectively. The direct effect of annual precipitation on seed bank density and species richness were positive. Precipitation had indirect and positive effect on seed bank density and species richness through soil nitrogen, a significantly indirect negative effect on seed bank species richness through soil pH and soil available phosphorus, and a significantly indirect negative effect on seed bank density through soil pH. The reduction of precipitation under furture climate change might alter the hedging strategies of plants. The persistent soil seed bank in the forest-steppeecotone had a potential buffering effect against future precipitation reduction.

Introduction: Although persistent inhibition of HBV replication by antiviral therapy has shown to slow disease progression, cost-related access barriers to these essential medicines are becoming salient. The national volume-based procurement (NVBP) was piloted in China and led to substantial reduction in the list price of prescription drugs. To examine the impact of NVBP on selected antiviral medication costs per defined daily dose (DDD), procurement volumes, and spending. Methods: We employed an interrupted time series design to examine changes in cost per defined daily dose (DDD), procurement volumes, and spending for NVBP bid-winning antiviral medications (tenofovir disoproxil fumarate and entecavir) in 11 pilot cities from 2017 to 2020. Procurement transaction data were obtained from 9,454 hospitals in the Chinese Hospital Pharmaceutical Audit (CHPA) database. In the secondary analysis, the control group comprised two non-NVBP drugs (adefovir and lamivudine) procured in 11 cities not exposed to the NVBP. Results: Cost per DDD of the two hepatitis B virus (HBV) antiviral medications reduced by CNY1.598 ( p = 0.002) immediately following the implementation of NVBP, dropping from an average cost of CNY16.483 per DDD at baseline to CNY6.420 at the end of the observation period. NVBP implementation resulted in a substantial reduction in daily costs of antivirals and an increase in monthly procurement volumes by 6.674 million DDDs ( p = 0.017), while monthly spending was reduced by CNY138.26 million ( p = 0.002). In the secondary ITS analysis with a control group, the average cost per DDD of the NVBP bid-winning antivirals declined by CNY4.537 ( p < 0.001), monthly procurement volumes increased by 7.209 million DDDs ( p = 0.002), and monthly spending dropped by CNY138.83 million ( p < 0.001). Conclusion: Volume-based procurement piloted in China may be effective for reducing price and total expenditures and improving drug utilization, which is especially important for HBV patients who need constant access to antiviral therapies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Yuan, Lu, Xiong, Lee, Huang and Jiang.)

Importance: Prehospital delay (time from symptom onset of stroke to the door of a hospital) in patients with stroke is long in China. With the goal of improving public awareness and knowledge of stroke recognition, Stroke 1-2-0 was developed in China as an education program to prompt rapid response to the onset of stroke based on clinical practice in China, and examination of its outcomes is needed., Objective: To investigate the association of the Stroke 1-2-0 educational campaign with prehospital delay for patients with ischemic stroke., Design, Setting, and Participants: In a population-based cross-sectional study, all patients with ischemic stroke events were admitted to the Minhang Hospital, which is the only tertiary care hospital with a stroke center that provides acute stroke care in Xinzhuang county, Shanghai, China. The study period was from January 1, 2016, to December 31, 2019, and data analysis was performed from January 1 to July 31, 2021., Exposures: A multifaceted Stroke 1-2-0 educational campaign comprising slides, videos, brochures, and posters distributed in the community., Main Outcomes and Measures: Proportion of patients with hospital arrival within 3 hours and use of an ambulance to seek medical care, as well as the odds of seeking medical attention within 3 hours after the stroke before vs after initiation of the multifaceted educational campaign., Results: A total of 2857 patients (1774 men [62.1%]; mean [SD] age, 69.83 [12.66] years) with stroke were identified, including 503 in the precampaign period and 2354 in the postcampaign period. Following the multifaceted campaign, the median (IQR) prehospital delay time decreased from 18.72 (7.44-27.84) hours to 6.00 (2.00-16.35) hours (P < .001). After the implementation of the Stroke 1-2-0 campaign, the proportion of patients with hospital arrival time within 3 hours increased from 5.8% to 33.4% (P < .001) and use of an ambulance increased from 3.2% to 30.6% (P < .001). In an interrupted time series analysis, the initiation of the Stroke 1-2-0 campaign was associated with significantly increased odds of arriving at the hospital within 3 hours (odds ratio, 8.01; 95% CI, 7.17-8.95; P < .001) and use of an ambulance (odds ratio, 9.41; 95% CI, 8.24-10.74; P < .001)., Conclusions and Relevance: The persistent multifaceted campaign using the Stroke 1-2-0 program was associated with reduced prehospital delay and improved timely arrival rate and ambulance arrival rate for patients with stroke. These findings suggest that Stroke 1-2-0 can be adopted in other regions of China to possibly improve health outcomes and reduce clinical burdens for all patients with stroke.

Objectives: To summarize the clinical phenotypes and the variation spectrum of ATP7B gene in Chinese children with Wilson's disease (WD) and to investigate their significance for early diagnosis. Methods: Retrospective analysis was performed on the clinical data of 316 children diagnosed as WD in Guangzhou Women and Children's Medical Center during the period from January 2010 to June 2021. The general situations, clinical manifestations, lab test results, imaging examinations, and ATP7B gene variant characteristics were collected. The patients were divided into asymptomatic WD group and symptomatic WD group based on the presence or absence of clinical symptoms at the time that WD diagnosis was made. The χ 2 test, t test or Mann-Whitney U test were used to compare the differences between groups. Results: Among the 316 children with WD, 199 were males and 117 were females, with the age of 5.4 (4.0, 7.6) years at diagnosis; 261 cases (82.6%) were asymptomatic with the age of 4.9 (3.9, 6.4) years; whereas 55 cases (17.4%) were symptomatic with the age of 9.6 (7.3, 12.0) years. The main symptoms invloved liver, kidney, nervous system, or skin damage. Of all the patients, 95.9% (303/316) had abnormal liver function at diagnosis; 98.1% (310/316) had the serum ceruloplasmin lever lower than 200 mg/L; 97.7% (302/309) had 24-hour urine copper content exceeding 40 μg; only 7.4% (23/310) had positive corneal K-F rings, 8.2% (23/281) had abnormal MRI signals in the lenticular nucleus, and all of them had symptoms of damage in liver, kidney or nervous system. Compared with the group of symptomatic WD, asymptomatic group had higher levels of serum alanine aminotransferase and lower levels ceruloplasmin and 24-hour urine copper [(208±137) vs. (72±78) U/L, (55±47) vs. (69±48) mg/L, 103 (72, 153) vs. 492 (230, 1 432) μg; t =9.98, -1.98, Z =-4.89, all P <0.001]. Among the 314 patients completing genetic sequencing, a total of 107 mutations in ATP7B gene were detected, of which 10 are novel variants, and 3 cases (1.0%) had large heterozygous deletion (exons 10 to exon 11) in ATP7B gene. The percentage of missense mutation in asymptomatic WD children was significantly higher than that in symptomatic WD (81.5% (422/518) vs. 69.1% (76/110), χ²=8.47, P <0.05). WD patients carrying homozygous variant of c.2 333G>T had significantly low levels of ceruloplasmin than those not carrying this variant ((23±5) vs. (61±48) mg/L, t =-2.34, P <0.001). Conclusions: The elevation of serum ALT is an important clue for early diagnosis of WD in children, while serum ceruloplasmin and 24-hour urine copper content are specific markers for early diagnosis of WD. In order to confirm the diagnosis of WD, it is necessary to combine the Sanger sequencing with multiplex ligation-dependent probe amplification or other testing technologies.

BACKGROUND: High-deductible health plans (HDHPs) are characterized by higher deductibles and lower monthly premiums compared with a typical health plan. HDHPs may reduce, or delay, needed care, which will ultimately lead to poorer access to care for chronically affected participants. OBJECTIVES: To (1) investigate the HDHP enrollment trend and (2) determine the effects of HDHPs on financial access problems for individuals with self-reported cognitive impairment. METHODS: Data between 2010 and 2018 were obtained from the National Health Interview Survey (NHIS). Individuals with cognitive impairment were identified if they were limited by memory difficulties. Problems regarding financial access to health care were assessed based on 6 survey questions from the Centers for Disease Control and Prevention. Multivariable logistic regressions were implemented to evaluate the effects of HDHPs. RESULTS: This study identified 1,148 individuals with cognitive impairment, representing 3.9 million individuals in the United States from 2010 to 2018. A nearly 2-fold increase in HDHP enrollment with cognitive impairment was observed from 2010 (20.9%) to 2018 (41.9%). This increase is similar to that reported for noncognitively impaired individuals. After controlling for possible confounding variables, cognitively impaired individuals with HDPHs were more likely to have overall financial access difficulties compared with those without HDHPs (OR = 1.17, 95% CI = 0.88-1.56, P = 0.271), but this likelihood was not statistically significant. CONCLUSIONS: HDHPs are intended to support effective care options and reduce health care costs. However, our research found that among individuals with cognitive impairment, those with HDHPs experienced some financial access problems, such as affording medical care, follow-up care, and specialists, than those without HDHPs, indicating that HDHPs might have unintended consequences for health care usage. DISCLOSURES: No outside funding supported this study. The authors have no conflicts of interest or financial interests to disclose.

Objective: This study assessed home health care use associated with Alzheimer's Disease and related dementias (ADRD) in US community dwelling older adults, including workforce, intensity, and cost outcomes., Materials and Methods: Medical Expenditure Panel Survey (2010-2018) household and home care event files were used to identify adults ≥ 65 years with ADRD. Outcomes included home health care provider type, intensity of care use, and annual direct home care cost. All analyses applied person weights for national estimates., Results: Among the 20,443 eligible older adults, 4.2% (n = 843) reported ADRD. Among all professional and non-professional health care workers, nurse practitioners (NPs, 38.5%) and home health care aids (35.6%) were most used. Comparing ADRD vs non-ADRD: the annual per-person average number of days in home care was 110 vs. 64 (p<0.001) and home care costs accounted for 30.8% vs. 7.5% of total health care costs. After adjusting for participants' characteristics, those with ADRD were more likely to use home health care (OR = 4.32, 95% CI=3.29 - 5.68) and showed 229% (95% CI = 175% - 297%) higher associated costs than controls (p<0.001)., Conclusion: The study provides insight into the home care workforce. Of the professional workforce NPs were most often used and home care aides dominated the non-professional workforce. As expected, ADRD increased the likelihood and intensity of home health care utilization and associated direct home care costs significantly., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The use of long-acting lipoglycopeptides (LaLGPs) in serious, deep-seated infections is of increasing interest. The purpose of this study is to evaluate the economic and clinical utility of LaLGPs in patients requiring protracted antibiotic courses who are not ideal candidates for oral transition or outpatient parenteral antibiotic therapy (OPAT). This is a retrospective, observational, matched cohort study of adult patients who received a LaLGP. Patients were matched 1:1 to those who received standard of care (SOC). Cost effectiveness was evaluated as total healthcare-related costs between groups. Clinical failure was a composite endpoint of mortality, recurrence, or need for extended antibiotics beyond planned course within 90 days of initial infection. There was no difference in clinical failure between the two cohorts (22% vs. 30%; p = 0.491). Six patients in the SOC cohort left against medical advice (AMA) prior to completing therapy. Among those who did not leave AMA, receipt of LaLGPs resulted in a decreased hospital length of stay by an average of 13.6 days. The average total healthcare-related cost of care was USD 295,589 in the LaLGP cohort compared to USD 326,089 in the SOC cohort ( p = 0.282). Receipt of LaLGPs may be a beneficial treatment option for patients with deep-seated infections and socioeconomic factors who are not candidates for oral transition or OPAT.

Objective: Benzodiazepines were excluded from Medicare Part D coverage since its introduction in 2006. Part D expanded coverage for benzodiazepines in 2013. The objective was to examine the impact of Medicare Part D coverage expansion on the utilisation and financial burden of benzodiazepines in older adults., Design: Interrupted time series with a control group., Setting: Nationally representative sample., Participants: 53 150 468 users of benzodiazepines and 21 749 749 users of non-benzodiazepines (an alternative therapy) from the Medicare Current Beneficiary Survey between the pre-expansion (2006-2012) and post-expansion (2013-2017) periods., Intervention: Medicare Part D coverage expansion on benzodiazepines., Primary and Secondary Outcome Measures: Annual rate of benzodiazepines and non-benzodiazepines, average number of benzodiazepines and non-benzodiazepines and average cost of benzodiazepines and non-benzodiazepines., Results: After Medicare Part D coverage expansion, the level of the annual rate of benzodiazepines increased by 8.20% (95% CI: 6.07% to 10.32%) and the trend decreased by 1.03% each year (95% CI: -1.77% to -0.29%). The trend of the annual rate of non-benzodiazepines decreased by 0.72% each year (95% CI: -1.11% to -0.33%). For the average number of benzodiazepines, the level increased by 0.67 (95% CI: 0.52 to 0.82) and the trend decreased by 0.10 each year (95% CI: -0.15 to -0.05). For the average number of non-benzodiazepines, the level decreased by 0.11 (95% CI: -0.21 to -0.01) and the trend decreased by 0.04 each year (95% CI: -0.08 to -0.01). No significant level and trend changes were identified for the average cost of benzodiazepines and non-benzodiazepines., Conclusions: After Medicare Part D coverage expansion, there was a sudden increase in the utilisation of benzodiazepines and a decreasing trend in the long-term. The increase in the utilisation of benzodiazepines did not add a financial burden to older adults. As an alternative therapy, the utilisation of non-benzodiazepines decreased following the coverage expansion., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Many patients face a financial burden due to their medications, which may lead to poor health outcomes. The behaviors of non-adherence due to financial difficulties, known as cost-related medication non-adherence (CRN), include taking smaller doses of drugs, skipping doses to make prescriptions last longer, or delaying prescriptions. To date, the prevalence of CRN remains unknown, and there are few studies about the association of CRN on self-reported healthcare utilization (Emergency room (ER) visits and outpatient visits) and self-reported health outcomes (health status and disability status) among older adults taking antidepressants. Objectives: The objectives were to 1) examine the CRN prevalence, and 2) determine the association of CRN on self-reported healthcare utilization and self-reported health outcomes. Methods: This study was a cross-sectional study of a sample of older adults from the Medicare Current Beneficiary Survey (MCBS) who reported having used antidepressants in 2017. Four logistic regressions were implemented to evaluate the association of CRN, and self-reported healthcare utilization and self-reported health outcomes. Results: The study identified 602 participants who were Medicare beneficiaries on antidepressants. The prevalence of CRN among antidepressant users was (16.61%). After controlling for covariates, CRN was associated with poorer self-reported outcomes but not statistically significant: general health status [odds ratio (OR): 0.67; 95% confidence interval (CI): 0.39-1.16] and disability status (OR: 1.34; 95% CI: 0.83-2.14). In addition, CRN was associated with increased outpatient visits (OR: 1.89; 95% CI: 1.19-3.02), but not associated with ER visits (OR: 1.10; 95% CI: 0.69-1.76). Conclusion: For Medicare beneficiaries on antidepressants, CRN prevalence was high and contributed to more outpatient visits. The healthcare provider needs to define the reasoning for CRN and provide solutions to reduce the financial burden on the affected patient. Also, health care providers need to consider the factors that may enhance patient health status and healthcare efficiency., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Alnijadi, Yuan, Wu, Li and Lu.)

Background: Antipsychotics are commonly used in dementia patients but have potential risks that often outweigh clinical benefits. Limited studies have assessed the healthcare utilization and medical costs associated with antipsychotic use, especially those focused on cumulative days of use. Objectives: To examine clinical and economic burdens associated with different cumulative days of antipsychotic use in older adults with dementia in the United States. Methods: This study used Medicare Current Beneficiary Survey (2015-2017). Older (≥65 years) Medicare beneficiaries with dementia, without concurrent schizophrenia, bipolar disorder, Huntingon's disease, or Tourette's syndrome were included. Antipsychotic use was measured using Medicare Part D prescription events. Healthcare utilization was measured as inpatient services, outpatient services, and emergency room (ER) visits. Total medical costs were classified as Medicare and out-of-pocket costs. The logistic regression, negative binomial regression, and generalized linear model with a log link and gamma distribution were used to examine factors, healthcare utilization, and medical costs. Survey sampling weights were applied to generate national estimates. Results: Among older adults with dementia, 13.18% used antipsychotics. Factors associated with antipsychotic use were being Hispanic (OR: 2.90; 95% CI: 1.45, 5.78), widowed (OR: 3.52; 95% CI: 1.46, 8.48), and single (OR: 3.25; 95% CI: 1.53, 6.87). Compared to non-users, antipsychotic use was associated with higher inpatient visits (IRR: 2.11; 95% CI 1.53, 2.90), ER visits (IRR: 1.61; 95% CI: 1.21, 2.13), total costs (β: 0.53; 95% CI: 0.36, 0.71), Medicare costs (β: 0.49; 95% CI 0.26, 0.72), and out-of-pocket costs (β: 0.66; 95% CI: 0.35, 0.97). With the increase in cumulative days of antipsychotic use, the magnitude of clinical and economic burdens was decreased. Conclusion: The significant clinical and economic burdens associated with antipsychotic use, especially with short-term use, provide real-world evidence to inform clinical practice on deprescribing antipsychotics among community-dwelling geriatric dementia patients., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Hsieh, Yuan, Lu and Li.)

Objective: The purpose of this study is to examine the association between delivery of healthcare provider's advice about lifestyle management and lifestyle behavioural change in pre-diabetes management in adults who were overweight or obese., Design: This cross-sectional study included adults with body mass index (BMI) ≥25 kg/m 2 and reporting pre-diabetes in USA. Outcomes included the prevalence of receiving provider's advice on lifestyle management and patterns of practicing lifestyle change. The association between delivery of provider's advice and lifestyle-related behavioural change in pre-diabetes management was examined., Setting: US Continuous National Health and Nutrition Examination Survey (2013-2018)., Participants: A total of 1039 adults with BMI ≥25 kg/m 2 reported pre-diabetes., Results: Of eligible adults with pre-diabetes, 76.8% received provider's advice about lifestyle change. The advice group showed higher proportions of ongoing lifestyle change than no advice group, including weight reduction/control (80.1% vs 70.9%, p=0.018), exercise (70.9% vs 60.9%, p=0.013) and diet modifications (83.8% vs 61.8%, p<0.001). After adjustment, those receiving provider's advice were more likely to increase exercise (OR 1.63, 95% CI 1.12 to 2.38) and modify diet (OR 3.0, 95% CI 1.82 to 4.96)., Conclusion: Over 75% of US adults who were overweight or obese and reported pre-diabetes received healthcare provider's advice about reducing the risk of diabetes through lifestyle change. Provider's advice increased the likelihood of lifestyle-related behavioural change to exercise and diet., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

An increasing number of myocarditis/pericarditis incidences has been reported after coronavirus disease-19 (COVID-19) vaccination in adolescents and young adults. This study was designed to investigate the incidence rate of-and risk for-myocarditis and pericarditis following COVID-19 vaccination in the United States according to age and vaccine type. This study used the Vaccine Adverse Events Reporting System (VAERS) from 11 December 2020 to 13 August 2021. A population-based data mining approach was performed based on the reporting odds ratio (ROR). Adverse events of myocarditis and pericarditis following COVID-19 vaccination were rare, with an incidence rate of 5.98 (95% CI = 5.73-6.24) cases per million doses administered. The incidence rate was higher in adolescents and after the administration of the second dose of messenger RNA (mRNA) vaccines. Overall, two mRNA vaccines were significantly associated with increased risks for myocarditis/pericarditis (mRNA-1273 (Moderna): ROR = 2.91, 95% CI = 2.21-3.83; BNT162b2 (Pfizer-BioNTech): ROR = 5.37, 95% CI = 4.10-7.04) compared to all other vaccines from VAERS. The viral vector vaccine of Ad26.COV2.S (Janssen) was not associated with signals of myocarditis/pericarditis (ROR = 1.39; 95% CI = 0.99-1.97). This study found increased risks for myocarditis/pericarditis following mRNA COVID-19 vaccines. For patients at high risk for myocarditis/pericarditis or with myocardial injuries, the viral vector vaccine may be an alternative for consideration.

Background: Big data and real-world data (RWD) have been increasingly used to measure the effectiveness and costs in cost-effectiveness analysis (CEA). However, the characteristics and methodologies of CEA based on big data and RWD remain unknown. The objectives of this study were to review the characteristics and methodologies of the CEA studies based on big data and RWD and to compare the characteristics and methodologies between the CEA studies with or without decision-analytic models. Methods: The literature search was conducted in Medline (Pubmed), Embase, Web of Science, and Cochrane Library (as of June 2020). Full CEA studies with an incremental analysis that used big data and RWD for both effectiveness and costs written in English were included. There were no restrictions regarding publication date. Results: 70 studies on CEA using RWD (37 with decision-analytic models and 33 without) were included. The majority of the studies were published between 2011 and 2020, and the number of CEA based on RWD has been increasing over the years. Few CEA studies used big data. Pharmacological interventions were the most frequently studied intervention, and they were more frequently evaluated by the studies without decision-analytic models, while those with the model focused on treatment regimen. Compared to CEA studies using decision-analytic models, both effectiveness and costs of those using the model were more likely to be obtained from literature review. All the studies using decision-analytic models included sensitivity analyses, while four studies no using the model neither used sensitivity analysis nor controlled for confounders. Conclusion: The review shows that RWD has been increasingly applied in conducting the cost-effectiveness analysis. However, few CEA studies are based on big data. In future CEA studies using big data and RWD, it is encouraged to control confounders and to discount in long-term research when decision-analytic models are not used., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lu, Xiong, Lee, Wu, Yuan and Jiang.)

To cope with the increasing healthcare costs brought about by the universal health insurance programme, national volume-based procurement (NVBP) was implemented in China to reduce drug prices. However, the impact of NVBP remains unknown. We reported the effects of the NVBP pilot programme on medication affordability and discussed the challenges and recommendations for further reforms. A total of 25 molecules won the bidding in the NVBP pilot programme, and price cuts ranged from 25% to 96%. Medication affordability was measured as the number of days' wages needed to pay for a course of treatment, and the medication was identified as affordable if the cost of a treatment course was less than the average daily wage. After the NVBP, the proportion of affordable drugs increased from 33% to 67%, and the mean affordability improved from 8.2 days' wages to 2.8 days' wages. Specifically, for rural residents, the proportion of affordable drugs increased from 13% to 58%, and the mean affordability improved from 15.7 days' wages to 5.3 days' wages. For urban residents, the proportion of affordable drugs increased from 54% to 71%, and the mean affordability improved from 5.9 days' wages to 2.0 days' wages. Implementing the NVBP substantially improved medication affordability. In future reforms, a multifaceted approach addressing all issues in the health system is needed to enhance medicine access., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Objective: The prevalence of Alzheimer's disease and related dementias (ADRD) in women is higher than men. However, the knowledge of gender disparity in ADRD treatment is limited. Therefore, this study aimed to determine the gender disparities in the receipt of anti-dementia medications among Medicare beneficiaries with ADRD in the U.S. Methods: We used data from the Medicare Current Beneficiary Survey 2016. Anti-dementia medications included cholinesterase inhibitors (ChEIs; including rivastigmine, donepezil, and galantamine) and N-methyl-D-aspartate (NMDA) receptor antagonists (including memantine). Descriptive analysis and multivariate logistic regression models were implemented to determine the possible gender disparities in the receipt of anti-dementia medications. Subgroup analyses were conducted to identify gender disparities among beneficiaries with Alzheimer's disease (AD) and those with only AD-related dementias. Results: Descriptive analyses showed there were statistically significant differences in age, marital status, and Charlson comorbidities index (CCI) between Medicare beneficiaries who received and who did not receive anti-dementia medications. After controlling for covariates, we found that female Medicare beneficiaries with ADRD were 1.7 times more likely to receive anti-dementia medications compared to their male counterparts (odds ratio [OR]: 1.71; 95% confidence interval [CI]: 1.19-2.45). Specifically, among Medicare beneficiaries with AD, females were 1.2 times more likely to receive anti-dementia medications (Odds Radio: 1.20; 95% confidence interval: 0.58-2.47), and among the Medicare beneficiaries with only AD-related dementias, females were 1.9 times more likely to receive anti-dementia medications (OR: 1.90; 95% CI: 1.23-2.95). Conclusion: Healthcare providers should be aware of gender disparities in receiving anti-dementia medications among patients with ADRD, and the need to plan programs of care to support both women and men. Future approaches to finding barriers of prescribing, receiving and, adhering to anti-dementia medications by gender should include differences in longevity, biology, cognition, social roles, and environment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lu, Xiong, Wang and Wu.)

BACKGROUND: Before 2007, erythropoiesis-stimulating agents (ESAs) were the highest-expenditure drug in the Medicare system. In 2007, CMS issued a reimbursement policy change for ESAs used by cancer patients. However, empirical evidence is currently lacking to evaluate medical costs after the policy change, especially by sex and racial/ethnic groups. OBJECTIVE: To examine the impact of the Medicare reimbursement policy change and associated racial/ethnic and sex disparities on medical costs for cancer patients who were new users of ESAs. METHODS: This study was an exploratory retrospective treatment effectiveness study, which used SEER-Medicare linked data. A difference-in-difference design was used that incorporated a control group of patients with chronic kidney disease. A generalized linear model, with a log link and a gamma distribution, was used to examine medical costs. RESULTS: The Medicare reimbursement policy change was statistically significantly associated with an 11% (95% CI = 2%-20%) reduction in anemia-related costs, including a 10% (95% CI = 1%-19%) reduction in Medicare payment and an 18% (95% CI = 10%-26%) reduction in patient cost sharing. For total medical costs, the policy change was statistically significantly associated with a 12% (95% CI = 6%-18%) reduction, including an 11% (95% CI = 5%-18%) reduction in Medicare payment and a 14% (95% CI = 7%-20%) reduction in patient cost sharing. Medical costs were reduced in patients who were male and those who were White but remained the same for patients who were female and those who were Black, Hispanic, and other races or ethnicities. CONCLUSIONS: Anemia-related and total medical costs associated with ESAs used by cancer patients with chemotherapy-induced anemia were reduced after the Medicare reimbursement policy change. However, the policy change was only effective for patients who were male and those who were White. The policy change had no effect on patients who were female and those of racial/ethnic minorities. DISCLOSURES: This study was funded by the SPARC Research Grant. The funder had no role in any part of this study. This study used the linked SEER-Medicare database. The interpretation and reporting of the data are the sole responsibility of the authors. The authors have nothing to disclose.

Background: Two coronavirus disease 2019 (COVID-19) vaccines have received emergency use authorizations in the U.S. However, the safety of these vaccines in the real-world remains unknown. Methods: We reviewed adverse events (AEs) following COVID-19 vaccination among adults in the Vaccine Adverse Event Reporting System (VAERS) from December 14, 2020, through January 22, 2021. We compared the top 10 AEs, serious AEs, along with office and emergency room (ER) visits by age (18-64 years, ≥65 years) and gender (female, male). Results: There were age and gender disparities among adults with AEs following COVID-19 vaccination. Compared to younger adults aged between 18 and 64 years, older adults were more likely to report serious AEs, death, permanent disability, and hospitalization. Males were more likely to report serious AEs, death, and hospitalization compared to females. Conclusions: COVID-19 vaccines are generally safe but possible age and gender disparities in reported AEs may exist., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Xiong, Yuan, Li, Jiang and Lu.)

Background: Cancer survivors are vulnerable to have medication nonadherence. We aimed to estimate the impact of cost-related medication nonadherence on economic burdens, productivity loss, and functional abilities among cancer survivors. Methods: A cross-sectional study was conducted using data from the National Health Interview Survey (NHIS), 2011-2018. Cost-related medication nonadherence was identified based on NHIS prompts. An ordinal logistic regression model was used to determine the impact of cost-related medication nonadherence on survivors' economic burden. Two negative binomial regression models were implemented to estimate the impact on productivity loss. In addition, four logistic regression models were used to determine the impact on functional abilities. The weighted analysis was used to generate national estimates. Results: Among 35, 773, 286 cancer survivors, 15, 002, 192 (41.9%) respondents reported that they experienced cost-related medication nonadherence. Compared to cancer survivors without cost-related medication nonadherence, those with nonadherence were significantly associated with an increased economic burden (OR: 1.89, 95% CI: 1.70-2.11). Also, cancer survivors with cost-related medication nonadherence were significantly more likely to have an increased bed disability day (IRR: 1.46, 95% CI: 1.21-1.76). In terms of the limitations, cancer survivors with nonadherence were significantly more likely to have both activity limitation (OR: 1.42, 95% CI: 1.25-1.60) and functional limitation (OR: 2.12, 95% CI: 1.81-2.49). Conclusion: Cost-related medication nonadherence increased economic burdens, productivity loss, and limitations in functional abilities among cancer survivors. Strategies are needed to help cancer survivors with cost-related medication nonadherence to be adherent to prescriptions., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Lu, Xiong, Brown, Horras, Yuan and Li.)

Background: Several pharmacological agents, such as chloroquine/hydroxychloroquine, have been promoted for COVID-19 treatment or pre-exposure prophylaxis. However, no comprehensive evaluation of the safety of these possible agents is available, and is urgently needed., Objective: The purpose of this study was to investigate the risks of cardiac adverse events associated with the possible pharmacotherapies for COVID-19, including certain antimalarial, antiviral, and antibiotic drugs., Patients and Methods: We conduced retrospective pharmacovigilance analyses of the US Food and Drug Administration Adverse Event Reporting System database. The reporting odds ratio (ROR), a data mining algorithm commonly used in pharmacovigilance assessment, was generated to quantify the detection signal of adverse events., Results: Among individuals without coronavirus infection from 2015 Q1 to 2020 Q1, increased risks for cardiac disorders were found for antiviral agents such as chloroquine/hydroxychloroquine (ROR: 1.68; 95% confidence interval [CI] 1.66-1.70), lopinavir/ritonavir (ROR: 1.52; 95% CI 1.39-1.66), and antibiotics such as azithromycin (ROR: 1.37; 95% CI 1.30-1.44) and ceftriaxone (ROR: 1.92; 95% CI 1.80-2.05). Increased serious cardiac adverse events, including myocardial infarction, arrhythmia, and cardiac arrest, were also reported for these drugs. Further analyses of individuals with coronavirus infections revealed that 40% of individuals receiving chloroquine/hydroxychloroquine reported serious cardiac adverse events. Two cases resulted in QT prolongations and one case resulted in cardiac arrest. Chloroquine/hydroxychloroquine and azithromycin contributed to all the QT prolongation and cardiac arrest cases., Conclusions: The current pharmacotherapies for COVID-19 are associated with increased risks of cardiac adverse events. Variations in the cardiac safety profiles of these pharmacotherapies were also observed. Clinicians should closely monitor patients with COVID-19, especially those at high risk, using chloroquine/hydroxychloroquine and azithromycin.

Background: Since the declaration of COVID-19 as a global pandemic by the World Health Organization, countries are struggling with a shortage of medical capacities. It would be essential if the risk for preventable comorbidities, such as the common cold, can be reduced or prevented, so that the scarce medical resources and facilities can be focused on COVID-19., Purpose: To evaluate the effects of two herbal medicines (Jinhaoartemisia antipyretic granules and Huoxiangzhengqi oral liquids) in reducing the risk of the common cold in community-dwelling residents in China during the COVID-19 outbreak., Study Design: A prospective open-label, parallel-group, cluster-randomized controlled trial (RCT), was conducted in Chengdu, China., Methods: A total of 22,065 participants from 11 communities were recruited during a period of one month. The trial started on 30 January and participants were followed up till 29 February 2020. Participants were randomly assigned to receive either a five-day herbal medicine therapy plus a reference manual or a reference manual only if they were allocated to the control group. The primary endpoint was the occurrence of patient-reported common cold symptoms. The secondary endpoint was the time in days from the receipt of herbal drugs/reference manual and the occurrence of the common cold symptoms., Results: Use of herbal medicine reduced the risk of the common cold by 89.6% (95% CI, 52.9% to 97.7%) in all community-dwelling residents, and by 94.0% (95% CI, 52.1% to 99.2%) in residents aged between 16 and 59 years old. Sensitivity analyses showed similar results., Conclusion: This community-based RCT found that the use of a herbal medicine therapy (Jinhaoartemisia antipyretic granules and Huoxiangzhengqi oral liquids) could significantly reduce the risks of the common cold among community-dwelling residents, suggesting that herbal medicine may be a useful approach for public health intervention to minimize preventable morbidity during COVID-19 outbreak., (Copyright © 2020 Elsevier GmbH. All rights reserved.)

p53‑reactivation and induction of massive apoptosis‑1, APR‑017 methylated (PRIMA‑1 met ; APR246) targets mutant p53 to restore its wild‑type structure and function. It was previously demonstrated that PRIMA‑1 met effectively inhibited the growth of colorectal cancer (CRC) cells in a p53‑independent manner, and distinctly induced apoptosis by upregulating Noxa in p53‑mutant cell lines. The present study including experiments of western blotting, acridine orange staining and transmission electron microscopy revealed that PRIMA‑1 met induced autophagy in CRC cells independently of p53 status. Importantly, PRIMA‑1 met not only promoted autophagic vesicle (AV) formation and AV‑lysosome fusion, but also increased lysosomal degradation. Furthermore, Cell Counting Kit‑8 assay, colony formation assay and small interfering RNA transfection were performed to investigate the underling mechanisms. The study indicated that activation of the mTOR/AMPK‑ULK1‑Vps34 autophagic signaling cascade was key for PRIMA‑1 met ‑induced autophagy. Additionally, autophagy served a crucial role in the inhibitory effect of PRIMA‑1 met in cells harboring wild‑type p53, which was closely associated with the increased expression of Noxa. Taken together, the results determined the effect of PRIMA‑1 met on autophagy, and further revealed mechanistic insights into different CRC cell lines. It was concluded that PRIMA‑1 met ‑based therapy may be an effective strategy for CRC treatment.

Stroke leads to both regional brain functional disruptions and network reorganization. However, how brain functional networks reconfigure as task demand increases in stroke patients and whether such reorganization at baseline would facilitate post-stroke motor recovery are largely unknown. To address this gap, brain functional connectivity (FC) were examined at rest and motor tasks in eighteen chronic subcortical stroke patients and eleven age-matched healthy controls. Stroke patients underwent a 2-week intervention using a motor imagery-assisted brain computer interface-based (MI-BCI) training with or without transcranial direct current stimulation (tDCS). Motor recovery was determined by calculating the changes of the upper extremity component of the Fugl-Meyer Assessment (FMA) score between pre- and post-intervention divided by the pre-intervention FMA score. The results suggested that as task demand increased (i.e., from resting to passive unaffected hand gripping and to active affected hand gripping), patients showed greater FC disruptions in cognitive networks including the default and dorsal attention networks. Compared to controls, patients had lower task-related spatial similarity in the somatomotor-subcortical, default-somatomotor, salience/ventral attention-subcortical and subcortical-subcortical connections, suggesting greater inefficiency in motor execution. Importantly, higher baseline network-specific FC strength (e.g., dorsal attention and somatomotor) and more efficient brain network reconfigurations (e.g., somatomotor and subcortical) from rest to active affected hand gripping at baseline were related to better future motor recovery. Our findings underscore the importance of studying functional network reorganization during task-free and task conditions for motor recovery prediction in stroke.

BACKGROUND: Because of increasing safety concerns related to erythropoiesisstimulating agents (ESAs), the Centers for Medicare & Medicaid Services issued a Medicare reimbursement policy change regarding these medications in cancer patients. However, the policy established an absolute hemoglobin or hematocrit threshold to qualify for reasonable use but did not take the effect of gender and racial/ethnic differences in hemoglobin levels into consideration. OBJECTIVE: To examine disparities in the use of ESAs and blood transfusions after the Medicare policy change. METHODS: This study was an exploratory treatment effectiveness study and used the SEER-Medicare linked database. The treatment group was composed of cancer patients, whereas the control group was composed of chronic kidney disease patients. An interrupted time series design was used to examine the effect of the Medicare policy change on the use of ESAs and blood transfusions in different gender and racial/ethnic groups. RESULTS: The Medicare reimbursement policy change had an immediate effect on reducing the use of ESAs by 50% and increasing the use of blood transfusions by 10%. The immediate effect of the policy change on the monthly utilization of ESAs was 2 times greater in females (60% reduction) than males (30% reduction). Females had a 10% immediate increase in the monthly utilization of blood transfusions after the policy change. The policy change had the same immediate effect of a 50% reduction on the use of ESAs for Whites, African Americans/Blacks, and Latinos. African Americans/Blacks had a 50% immediate increase in the monthly utilization of blood transfusions after the policy change. CONCLUSIONS: Gender and racial/ethnic disparities were associated with the Medicare reimbursement policy change in the use of ESAs and blood transfusions. Thus, future policy considerations should keep biologic differences across gender and racial/ethnic groups in mind. DISCLOSURES: This study was funded by the SPARC Research Grant. The funder had no role in any part of this study. The authors have nothing to disclose.

Objectives: As a global pandemic is inevitable, real-time monitoring of transmission is vital for containing the spread of COVID-19. The main objective of this study was to report the real-time effective reproduction numbers (R(t)) and case fatality rates (CFR) in Europe., Methods: Data for this study were obtained mainly from the World Health Organization website, up to March 9, 2020. R(t) were estimated by exponential growth rate (EG) and time-dependent (TD) methods. 'R0' package in R was employed to estimate R(t) by fitting the existing epidemic curve. Both the naïve CFR (nCFR) and adjusted CFR (aCFR) were estimated., Results: With the EG method, R(t) was 3.27 (95% confidence interval (CI) 3.17-3.38) for Italy, 6.32 (95% CI 5.72-6.99) for France, 6.07 (95% CI 5.51-6.69) for Germany, and 5.08 (95% CI 4.51-5.74) for Spain. With the TD method, the R value for March 9 was 3.10 (95% CI 2.21-4.11) for Italy, 6.56 (95% CI 2.04-12.26) for France, 4.43 (95% CI 1.83-7.92) for Germany, and 3.95 (95% CI 0-10.19) for Spain., Conclusions: This study provides important findings on the early outbreak of COVID-19 in Europe. Due to the recent rapid increase in new cases of COVID-19, real-time monitoring of the transmissibility and mortality in Spain and France is a priority., (Copyright © 2020 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Objectives: There is debate on whether the use of third-generation cephalosporins (3GC) increases the risk of clinical failure in bloodstream infections (BSIs) caused by chromosomally-mediated AmpC-producing Enterobacterales (CAE). This study evaluates the impact of definitive 3GC therapy versus other antibiotics on clinical outcomes in BSIs due to Enterobacter, Serratia, or Citrobacter species., Methods: This multicenter, retrospective cohort study evaluated adult hospitalized patients with BSIs secondary to Enterobacter, Serratia, or Citrobacter species from 1 January 2006 to 1 September 2014. Definitive 3GC therapy was compared to definitive therapy with other non-3GC antibiotics. Multivariable Cox proportional hazards regression evaluated the impact of definitive 3GC on overall treatment failure (OTF) as a composite of in-hospital mortality, 30-day hospital readmission, or 90-day reinfection., Results: A total of 381 patients from 18 institutions in the southeastern United States were enrolled. Common sources of BSIs were the urinary tract and central venous catheters (78 (20.5%) patients each). Definitive 3GC therapy was utilized in 65 (17.1%) patients. OTF occurred in 22/65 patients (33.9%) in the definitive 3GC group vs. 94/316 (29.8%) in the non-3GC group (p = 0.51). Individual components of OTF were comparable between groups. Risk of OTF was comparable with definitive 3GC therapy vs. definitive non-3GC therapy (aHR 0.93, 95% CI 0.51-1.72) in multivariable Cox proportional hazards regression analysis., Conclusions: These outcomes suggest definitive 3GC therapy does not significantly alter the risk of poor clinical outcomes in the treatment of BSIs secondary to Enterobacter, Serratia, or Citrobacter species compared to other antimicrobial agents., Competing Interests: P.B.B.—Speaker’s Bureau: bioMérieux. C.M.B.—Speaker’s Bureau: Merck Pharmaceuticals. Grant Funding: ALK Abello. S.T.K.—Speaker’s Bureau: Melinta Therapeutics. J.A.J.—Speaker’s Bureau: bioMérieux. All other authors report no potential conflicts of interest.

Background: Cancer increases the risk of developing one or more chronic conditions, yet little research describes the associations between health care costs, utilization patterns, and chronic conditions in adults with cancer. The objective of this study was to examine the treated prevalence of chronic conditions and the association between chronic conditions and health care expenses in US adults with cancer., Methods: This retrospective observational study used US Medical Expenditure Panel Survey (MEPS) Household Component (2010-2015) data sampling adults diagnosed with cancer and one or more of 18 select chronic conditions. The measures used were treated prevalence of chronic conditions, and total and chronic condition-specific health expenses (per-person, per-year). Generalized linear models assessed chronic condition-specific expenses in adults with cancer vs. without cancer and the association of chronic conditions on total health expenses in adults with cancer, respectively, by controlling for demographic and health characteristics. Accounting for the complex survey design in MEPS, all data analyses and statistical procedures applied longitudinal weights for national estimates., Results: Among 3657 eligible adults with cancer, 83.9% (n = 3040; representing 16 million US individuals per-year) had at least one chronic condition, and 29.7% reported four or more conditions. Among those with cancer, hypertension (59.7%), hyperlipidemia (53.6%), arthritis (25.6%), diabetes (22.2%), and coronary artery disease (18.2%) were the five most prevalent chronic conditions. Chronic conditions accounted for 30% of total health expenses. Total health expenses were $6388 higher for those with chronic conditions vs. those without (p < 0.001). Health expenses associated with chronic conditions increased by 34% in adults with cancer vs. those without cancer after adjustment., Conclusions: In US adults with cancer, the treated prevalence of common chronic conditions was high and health expenses associated with chronic conditions were higher than those without cancer. A holistic treatment plan is needed to improve cost outcomes.