Real-world evidence of epidemiology, patient characteristics, and mortality in people with drug-resistant epilepsy in the United Kingdom, 2011-2021.

BACKGROUND: A third of people with epilepsy are drug resistant. People with drug-resistant epilepsy (DRE) have a higher risk of mortality and physical injuries than those who respond to anti-seizure medication (ASM). This study describes patient characteristics, comorbidities, and mortality in people with DRE in the UK. METHODS: The Clinical Practice Research Datalink was utilised to select people with DRE prescribed a third ASM between 1 January 2011 and 31 March 2021. Annual incidence and prevalence of DRE, patient characteristics, comorbidities, and mortality rates were analysed. Subgroup analysis was performed by age, sex, presence of intellectual disabilities and time from epilepsy diagnosis to DRE. RESULTS: A total of 34,647 people with DRE were included (mean ± SD age 42.68 ± 23.59 years, 52.6% females). During the study period, annual DRE incidence ranged from 1.99% to 3.12%. As of 31 March 2021, DRE prevalence was 26.6% (95% confidence interval [CI] 26.3%-26.8%). A greater proportion of people with DRE resided in the most deprived regions, with 21.1% and 16.7% in the top two quintiles of the Index of Multiple Deprivation respectively, compared to < 15% in the three less deprived regions. All-cause mortality ranged from 3,687 to 4,802 per 100,000 persons with DRE, four times higher than that in the general population in the UK. Variations existed across subgroups. CONCLUSIONS: Considerable disease burden was observed in people with DRE in the UK. The findings emphasise the importance of early DRE diagnosis and appropriate disease management in people who develop DRE.

Opicapone versus entacapone: Head-to-head retrospective data-based comparison of healthcare resource utilization in people with Parkinson's disease new to catechol-O-methyltransferase (COMT) inhibitor treatment.

BACKGROUND AND PURPOSE: Motor fluctuations are a significant driver of healthcare resource utilization (HCRU) in people with Parkinson's disease (pwPD). A common management strategy is to include catechol-O-methyltransferase (COMT) inhibition with either opicapone or entacapone in the levodopa regimen. However, to date, there has been a lack of head-to-head data comparing the two COMT inhibitors in real-world settings. The aim of this study was to evaluate changes in HCRU and effect on sleep medications when opicapone was initiated as first COMT inhibitor versus entacapone. METHODS: In this retrospective cohort study, we assessed HCRU outcomes in pwPD naïve to COMT inhibition via UK electronic healthcare records (Clinical Practice Research Datalink and Hospital Episodes Statistics databases, June 2016 to December 2019). HCRU outcomes were assessed before (baseline) and after COMT inhibitor prescription at 0-6 months, 7-12 months and 13-18 months. Opicapone-treated pwPD were algorithm-matched (1:4) to entacapone-treated pwPD. RESULTS: By 6 months, treatment with opicapone resulted in 18.5% fewer neurology outpatient visits compared to entacapone treatment; this effect was maintained until the last follow-up (18 months). In the opicapone group, the mean levodopa equivalent daily dose decreased over the first year and then stabilized, whereas the entacapone-treated group showed an initial decrease in the first 6 months followed by a dose increase between 7 and 18 months. Neither COMT inhibitor had a significant impact on sleep medication use. CONCLUSIONS: This head-to-head study is the first to demonstrate, using 'real-world' data, that initiating COMT inhibition with opicapone is likely to decrease the need for post-treatment HCRU versus initiation of COMT inhibition with entacapone.

Anticoagulant Treatment Adherence and Persistence in German Patients with Atrial Fibrillation.

INTRODUCTION: Treatment adherence and persistence impact the effectiveness of edoxaban for the prevention of thromboembolism in patients with atrial fibrillation (AF). The objective of this analysis was to assess adherence and persistence of edoxaban vs. other non-vitamin K antagonist oral anticoagulants (NOACs) and vitamin K antagonists (VKAs). METHODS: Utilizing a German claims database, adults with AF with the first pharmacy claim identified for edoxaban, apixaban, dabigatran, rivaroxaban, or VKAs from January 2013 to December 2017 were included in a propensity score-matched analysis. The first pharmacy claim was the index claim. Adherence (i.e., proportion of days covered [PDC]) and persistence (proportion of patients who continued therapy) were compared between edoxaban and other therapies. Patients receiving once-daily (QD) vs. twice-daily (BID) NOAC were also analyzed. RESULTS: Overall, 21,038 patients were included (1236 edoxaban, 6053 apixaban, 1306 dabigatran, 7013 rivaroxaban, and 5430 VKA). After matching, baseline characteristics were well balanced across cohorts. Adherence was significantly higher for edoxaban vs. apixaban, dabigatran, and VKAs (all P < 0.0001). Significantly more edoxaban patients continued therapy vs. rivaroxaban (P = 0.0153), dabigatran (P < 0.0001), and VKAs (P < 0.0001). Time to discontinuation was significantly longer for edoxaban vs. dabigatran, rivaroxaban, and VKAs (all P < 0.0001). More patients receiving NOACs QD had a PDC ≥ 0.8 compared with those receiving NOACs BID (65.3 vs. 49.6%, respectively; P < 0.05); persistence rates were comparable between QD and BID groups. CONCLUSIONS: Patients with AF receiving edoxaban had significantly higher adherence and persistence compared with those receiving VKAs. This trend was also seen in NOAC QD regimens vs. NOAC BID regimens for adherence. These results provide insight into how adherence and persistence may contribute to the effectiveness of edoxaban for stroke prevention in patients with AF in Germany.

Real-world economic and clinical outcomes associated with current hemostatic matrix use in spinal surgery.

Aim: Bleeding during spine surgery is controlled using topical hemostatic agents. Studies have reported outcomes between Surgiflo® and Floseal, the most widely used flowable hemostatic matrices, but have not included the latest Surgiflo formulation which is more adherent to the bleeding surface than prior formulations. Materials & methods: A propensity score-matched analysis was conducted using the Premier Healthcare Database to compare economic and clinical outcomes of adults undergoing inpatient spinal surgery between 2013 and 2018 receiving current Surgiflo or Floseal. Results: This retrospective study included 28,910 patients in each group and found comparable outcomes for bleeding events, overall transfusion rate, inpatient mortality and readmissions between Surgiflo and Floseal. Surgiflo was associated with $430 (USD) lower hospitalization costs, shorter length of stay and shorter operating room time than Floseal.

Topical hemostatic agents such as Surgiflo^® and Floseal are used during invasive surgery to manage bleeding. We compared outcomes of spine surgeries that used either of two most frequently used topical hemostatic agents, Surgiflo or Floseal. This is the largest retrospective study presenting economic and clinical outcomes of patients receiving Surgiflo versus Floseal during spine surgery using the latest product formulations. The study suggests that clinical outcomes are comparable between Surgiflo and Floseal groups and that Surgiflo is associated with lower hospitalization costs, slightly shorter hospital stay and shorter operating room time among patients undergoing spine surgery.

VPS4B mutation impairs the osteogenic differentiation of dental follicle cells derived from a patient with dentin dysplasia type I / 国际口腔科学杂志·英文版

A splicing mutation in VPS4B can cause dentin dysplasia type I (DD-I), a hereditary autosomal-dominant disorder characterized by rootless teeth, the etiology of which is genetically heterogeneous. In our study, dental follicle cells (DFCs) were isolated and cultured from a patient with DD-I and compared with those from an age-matched, healthy control. In a previous study, this DD-I patient was confirmed to have a loss-of-function splicing mutation in VPS4B (IVS7 + 46C > G). The results from this study showed that the isolated DFCs were vimentin-positive and CK14-negative, indicating that the isolated cells were derived from the mesenchyme. DFCs harboring the VPS4B mutation had a significantly higher proliferation rate from day 3 to day 8 than control DFCs, indicating that VPS4B is involved in cell proliferation. The cells were then replenished with osteogenic medium to investigate how the VPS4B mutation affected osteogenic differentiation. Induction of osteogenesis, detected by alizarin red and alkaline phosphatase staining in vitro, was decreased in the DFCs from the DD-I patient compared to the control DFCs. Furthermore, we also found that the VPS4B mutation in the DD-I patient downregulated the expression of osteoblast-related genes, such as ALP, BSP, OCN, RUNX2, and their encoded proteins. These outcomes confirmed that the DD-I-associated VPS4B mutation could decrease the capacity of DFCs to differentiate during the mineralization process and may also impair physiological root formation and bone remodeling. This might provide valuable insights and implications for exploring the pathological mechanisms underlying DD-I root development.

Online survey of family physician′s contract service and its influencing factors in Luohu District, Shenzhen / 中华健康管理学杂志

Objective:To identify the current situation of contract signing for family physician services in Luohu District, Shenzhen, and to explore the associated factors with contract signing and access to services.Methods:Using the WeChat official account of"People′s Hospital of Luohu", an online survey was conducted to investigate the status of family physician′s contract services for residents in Luohu District from May 19th to 25th, 2019. A total of 14 487 valid responses were received. Chi-square test and Logistic regression models were used to analyze the contract signing of family physician services and the related factors.Results:8 560 (59.09%) of the participants had signed with a family physician, and 12 696 of them had learnt about the service before. The awareness rate of family doctor services was 87.64%. The contract signing rate of those unemployed, who living or working in Luohu less than 5 years, who living alone, having no Shenzhen medical insurance, or having not heard of family physicians signing services were less than 50%. The signing rate was positively correlated with the awareness of family physician contract service, as well as the possibility of accepting signed medical examination, traditional Chinese medicine services and health information. Only 9.70% of the contractors received health services information.Conclusions:The contract Signing rates and awareness rate of family physicians among young and middle-aged residents in Luohu District are relatively high. However, access to contract services varies considerably. The signing rate and accepted services are mainly affected by job, length of residence in Shenzhen, type of medical insurance, and understanding of contract.

Clinical distribution and antibiotic resistance of Streptococcus pneumonia isolated from pediatric patients in Guangzhou / 国际检验医学杂志

Objective To explore the sample type and drug resistance characteristics of Streptococcus pneu-monia(Spn)isolated from pediatric patients in Guangzhou district,and their age distribution to offer instruc-tions for prevention and clinical treatment.Methods Spn isolates were cultured and identified according to the national standard procedure for clinical laboratory operation,followed by analysis of sample type and age dis-tribution of pediatric patients with positive isolates of Spn in Guangzhou Women and Children′s Medical Cen-ter from 2013 Jan 1st to 2015 Dec 31st,drug resistance status was determined by MIC test.Results Totally, 1 243 strains of Spn were isolated,which were mainly from pediatric patients under 1 year old(42.80%).Spn isolates were mainly isolated from respiratory tract(72.81%),ear secretions(15.37%),blood(5.63%),cere-brospinal fluid(3.06%)and hydrothorax(2.01%).For all Spn isolates,the resistance rate to erythromycin, tetracycline and sulfamethoxazole was especially high as 94.93%,85.76%,73.53% respectively,with relative high resistance to penicillin G(24.70%),amoxicillin(39.59%),ceftriaxone(24.05%),meropenem(22.85%) and cefotaxime(19.89%),low resistance to quinolone antibiotics(<10.00%),and no resistance to vancomycin and linezolid.Conclusion The major age group of children with Spn infection is infants under one year old in Guangzhou,clinicians should be serious about the high resistant rate of Spn to erythromycin,tetracycline and sulfamethoxazole,the significantly increased resistant rate to penicillin,amoxicillin and ceftriaxone.Clinicians should choose antibiotics rationally according to the characteristics of drug sensitivity for better treatment.

Analysis of DSPP gene mutation in a Chinese pedigree affected with hereditary dentinogenesis imperfecta / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze the clinical phenotype of a Chinese pedigree affected with hereditary dentinogenesis imperfecta and mutation of dentin sialophosphoprotein (DSPP) gene.</p><p><b>METHODS</b>Affected members underwent intraoral photography, dental film and panoramic radiography. Genomic DNA was extracted from peripheral venous blood samples. Coding regions of the DSPP gene were subjected to PCR amplification and Sanger sequencing. Functional effect of the mutation was predicted with SIFT and PolyPhen-2. The tertiary structure of wild type and mutant proteins were predicted by Swiss-Port.</p><p><b>RESULTS</b>A heterozygous c.50C to T (p.P17L) mutation was identified in exon 2 of the DSPP gene in the proband and her father. The same mutation was not found among 200 unrelated healthy controls. The Pro-17 residues and its surrounding positions in DSPP are highly conserved across various species. The mutation was predicted to be damaging to the structure of DSPP protein.</p><p><b>CONCLUSION</b>The c.50C to T (p.P17L) mutation of the DSPP gene probably underlies the disease in this pedigree. Above finding has expanded the spectrum of DSPP gene mutations and provided a basis for genetic counseling and prenatal diagnosis for this family.</p>

Omics of vector mosquitoes: a big data platform for vector biology and vector-borne diseases / 南方医科大学学报

Recently the studies on mosquito genomics, transcriptomics and small RNAomics developed rapidly with the novel biotechnologies of the next generation sequencing techniques. The genome sequences of several important vector mosquitoes including Anopheles gambiae, Culex quinquefasciatus, and Aedes aegypti have been published. The genome sizes vary among the different species of mosquitoes and are consistent with the number of the repeat regions. The released genome sequences facilitate gene cloning and identification as for OBP, OR and dsx genes. Transcriptomics provides a useful tool for functional analyses of the mosquito genes, and using this technique, the molecular basis of mosquito blooding, gland proteins and diapauses have been explored. Studies on small RNAomics suggest important roles of miRNAs and piRNAs in ovary development, blood digestion, and immunity against virus infection. The studies on mosquito omics have generated a big data platform for investigation of vector biology and vector-transmitted disease prevention.

Analysis of population genetic structure of Anopheles sinensis based on mitochondrial DNA cytochrome oxidase subunit I gene fragment / 南方医科大学学报

<p><b>OBJECTIVE</b>To study the population genetic variation, genetic diversity and phylogenesis of Anopheles sinensis in China.</p><p><b>METHODS</b>Anopheles sinensis samples collected from Shandong, Anhui, Jiangsu, Guizhou, and Yunnan Provinces and Guangxi Zhuang Autonomous Region with different geographical conditions between 2010 and 2012 were analyzed by mitochondrial DNA cytochrome oxidase subunit I (mtDNA-COI) gene amplification and sequencing. Bioedit 7.0 and DnaSP 5.0 software was used to compare the gene sequences and analyze the population genetic structure, respectively. Arlequin 3.1 was used to calculate the genetic distance and parameters of population differentiation. The relationship between the geographic and genetic distances was analyzed using IBD Web Service. PHYLIP 3.6 was used to construct the phylogenetic tree.</p><p><b>RESULTS</b>PCR amplification and sequencing was performed successfully for 6 Anopheles sinensis populations containing 123 female mosquitoes. The length of mtDNA-COI gene fragment was 841 bp with an average A+T content of 71.2% and G+C content of 28.8%. High nucleotide diversity and genetic differentiation were observed among the Anopheles sinensis populations based on mtDNA-COI gene. Analysis of the molecular variance revealed a greater variation between populations than that within populations with isolation by distance between the populations. The Anopheles sinensis populations appeared to have undergone expansion, but the Yunnan population constituted an isolated branch in the phylogenetic tree.</p><p><b>CONCLUSION</b>mtDNA-COI can serve as the molecular marker to analyze population genetic variation and phylogenesis of Anopheles sinensis. The Yunnan population shows a phylogenetic difference from the other populations analyzed in this study.</p>

Bone marrow-derived endothelial progenitor cells in diabetic rats：study of biological activity in vitro / 介入放射学杂志

Objective To study the defects of bone marrow-derived endothelial progenitor cells (EPCs) in number ratio and biological abilities (proliferation, adhesion and migration) in diabetic rats. Methods (1) Establishment of diabetic rat model:1%STZ solution was quickly injected into the abdominal cavity of the male SD rats with the dose of 60 mg/kg. (2). Isolation, culture and identification of bone marrow-derived EPCs in diabetic and normal rats. Bone marrow mononuclear cells were isolated from diabetic and normal rats by density gradient centrifugation methods and cultured by EGM-2 MV medium. The cells were identified by morphological observation, FITC-UEA-1 binding and Dil-Ac-LDL uptake assay, and fluorescent immunocytochemistry was used for detection of CD34 , CD133 and VEGFR-2 expression. CCK-8 method and Transwell kit method were used to determine biological activities of EPCs. Results (1) When cultured in vitro, both bone marrow-derived EPCs in diabetic and normal rats were fusiform in shape, the cells snuggled up to the wall. The expression of CD34, CDl33, VEGFR-2 could be detected in these cells, and the cells could uptake Dil-Ac-LDL and bind FITC-UEA-1, which proved that these cells were EPCs. (2) No significant difference in the number of EPCs derived from bone marrow existed between diabetic rats and normal rats, but the proliferation ability, migration ability and adhesion ability of bone marrow-derived EPCs in diabetic rats were obviously lower than those in normal rats. Conclusion The number of bone marrow-derived EPCs in diabetic rats is not obviously different from that in normal rats, but the biologic activity of EPCs derived from bone marrow in diabetic rats is degraded, which is manifested as weakened abilities of the proliferation, adhesion and migration.