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Background Early prediction of therapeutic response can optimize treatment strategies in atopic dermatitis (AD). Baricitinib is approved for moderate-to-severe AD in Europe, Japan and other countries. Objectives To identify early clinical improvements that can reliably predict a later clinical response to baricitinib in adults with moderate-to-severe AD. Methods Using data from one topical corticosteroid combination study [BREEZE-AD7 (NCT03733301)] and data pooled from two monotherapy studies [(BREEZE-AD1 (NCT03334396) and BREEZE-AD2 (NCT03334422)], we calculated the sensitivity and specificity, along with the positive predictive value (PPV) and negative predictive value (NPV), of predefined changes in single and combined clinical scores at weeks 2, 4 and 8, to predict clinical response at week 16. Clinical response was defined as ≥ 75% improvement in Eczema Area and Severity Index (EASI 75), ≥ 4-point improvement in Itch Numeric Rating Scale (Itch NRS ≥ 4), or a combination of both. Results Composite predictors had higher predictive accuracy for week 16 response outcomes than did single parameters. This was evident as early as week 4 for the combination of EASI 50 or Itch NRS ≥ 3 and of validated Investigator Global Assessment for AD (vIGA-AD) score ≤ 2 or Itch NRS ≥ 3 (sensitivity 87–100%; NPV 68–100%). The predictive accuracy of these composite clinical predictors for week 16 response outcomes was highest at week 8 (sensitivity 92–100%; NPV 80–100%). At both weeks 4 and 8, EASI 50 or Itch NRS ≥ 3 had higher sensitivity and NPV than did vIGA-AD score ≤ 2 or Itch NRS ≥ 3. Conclusions Improvement in signs and symptoms early during treatment with baricitinib 4 mg once daily predicts clinical response at week 16, providing a tool for dermatologists when choosing treatment strategies for patients with moderate-to-severe AD.

Background: Baricitinib demonstrated efficacy in treating adults with moderate-to-severe atopic dermatitis (AD) in Phase 3 clinical trials. Objective: To examine long-term efficacy of baricitinib combined with topical corticosteroids (TCS) in adult patients from a Phase 3 study, BREEZE-AD7 (NCT03733301), enrolled in ongoing extension study, BREEZE-AD3 (NCT03334435). Methods: Upon BREEZE-AD7 completion, responders or partial responders (RPR [vIGA-AD™ ≤2]) receiving baricitinib 2-mg or 4-mg + TCS maintained their original treatment doses in BREEZE-AD3. Nonresponders (NR; vIGA-AD 3,4) receiving baricitinib 2-mg were rerandomized 1:1 to baricitinib 2-mg or 4-mg; NR receiving baricitinib 4-mg remained on same dose. Integrated data from all patients (RPR + NR = baricitinib 4-mg intent-to-treat [ITT] cohort) receiving continuous baricitinib 4-mg in BREEZE-AD7 through BREEZE-AD3 were analysed, along with baricitinib 4-mg or 2-mg RPR cohorts. Primary endpoint was proportion of patients with vIGA-AD (0,1) at Weeks 16, 36 and 52 (Weeks 32, 52 and 68 of continuous therapy). Additional outcomes included improvement in EASI75 and Itch NRS (up to Week 32). Missing data were imputed by last observation carried forward. Results: In baricitinib 4-mg ITT cohort (N = 102), proportions of patients achieving vIGA-AD (0,1) at Week 32, Week 52, and Week 68 were 21.6%, 26.5% and 23.5%; EASI75 were 46.1%, 40.2% and 43.1%, respectively. Itch NRS ≥4-point improvement (Itch ≥4) were 47.3% at Week 16 and 40.6% at Week 32. In baricitinib 4-mg RPR cohort (N = 63), proportions of patients achieving vIGA-AD (0,1) at Week 32, Week 52 and Week 68 were 31.7%, 33.3% 34.9%, respectively; EASI75 were 57.1%, 49.2% and 49.2%, respectively. Itch ≥4 were 53.6% at Week 16 and 46.4% at Week 32. Corresponding proportions for baricitinib 2-mg RPR cohort (N = 53) for vIGA-AD (0,1) were 39.6%, 45.3% and 30.2%; EASI75 were 77.4%, 69.8% and 58.5%, respectively. Itch ≥4 were 56.3% at Week 16 and 47.9% at Week 32. Conclusion: Baricitinib 4-mg and 2-mg combined with TCS maintained clinically meaningful sustained efficacy over 68 weeks of continuous treatment.

Cong Wang,1,* Wen-lin Xu,1,* Guan-wu Li,2 Cong Fu,1 Jin-jin Li,1 Jing Wang,1 Xin-yu Chen,3 Zhen Liu,1 Yun-fei Chen1 1Department of Acupuncture and Moxibustion, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 2Department of Radiology, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, Shanghai, People’s Republic of China; 3Acupuncture and Tuina Academy, Beijing University of Chinese Medicine Dongfang College, Hebei, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yun-fei Chen; Zhen LiuDepartment of Acupuncture and Moxibustion, Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine, No. 110 Ganhe Road, Hongkou District, Shanghai, 200437, People’s Republic of ChinaTel/Fax +86-21-65162628Email icyf1968@163.com; liuzhen8918@163.comStudy Objectives: To evaluate the efficacy and safety of acupuncture at HT 7 (Shenmen) and KI 7 (Fuliu) on sleep and comorbid symptoms for chronic insomnia.Methods and Design: A randomized, single-blind, parallel and sham-controlled trial consisted of an acupuncture group (n = 41) and a sham acupuncture group (n = 41). Setting: a tertiary hospital of integrated Chinese and Western medicine. Participants: 82 subjects with chronic insomnia based on the International Classification of Sleep Disorders, Third Edition (ICSD-3). Interventions: a 10-session acupuncture treatment at bilateral HT 7 and KI 7 or sham acupoints with shallow needling was performed over 3 weeks. Measurements: the Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI) were evaluated at baseline, posttreatment, and at two follow-ups as the primary outcome measures. Polysomnography (PSG) on two consecutive nights, the Beck anxiety inventory (BAI), the Beck depression inventory (BDI) fatigue severity scale (FSS) and the Epworth sleepiness scale (ESS) were evaluated at baseline and posttreatment as the secondary outcome measures.Results: After the treatments, PSQI scores decreased by 5.04 in the acupuncture group and 2.92 in the sham acupuncture group. ISI scores decreased by 7.65 in the acupuncture group and 5.05 in the sham acupuncture group. The between-group differences in the primary outcome measures posttreatment were statistically significant. However, no differences were found between the two groups during the two follow-ups. Regarding the PSG data, there were significantly lower levels of sleep onset latency (SOL), a lower percentage of sleep stage N1 and a higher percentage of sleep stage N3 in the acupuncture group than in the sham acupuncture group. After treatment, there were lower levels of comorbid symptoms (BAI, BDI, FSS and ESS) in both groups. However, no significant differences were observed between the groups.Conclusion: Acupuncture at HT 7 and KI 7 is an effective and safe nonpharmacologic intervention option for chronic insomnia.Clinical Trial Registration: The study was registered at the Chinese Clinical Trial Registry, registration ID: ChiCTR1900023787, China.Keywords: acupuncture, chronic insomnia, sleep and comorbid symptoms, randomized clinical trial

In adults with atopic dermatitis (AD), head and/or neck involvement is frequent, bothersome, and impacts quality of life, however, long-term topical corticosteroids (TCS) are contraindicated for this difficult-to-treat region. Baricitinib, an oral, selective, reversible inhibitor of Janus kinase 1/2 has demonstrated efficacy in adult patients with moderate-to-severe AD.For this post hoc analysis, data from five Phase III trials were used to investigate the efficacy of baricitinib in patients with head and neck involvement.Data were obtained from BREEZE-AD1, -AD2, -AD4, -AD5, and -AD7; Phase III, multicenter, randomized, double-blind, placebo-controlled studies conducted in patients ≥18 years with moderate-to-severe AD. BREEZE-AD1, -AD2, and -AD5 evaluated baricitinib as monotherapy, and BREEZE-AD4 and -AD7 evaluated baricitinib in combination with TCS, topical calcineurin inhibitors, or topical PDE-4 inhibitors, where available. The proportion of patients with improvement of Eczema Area and Severity Index (EASI) total score from baseline of ≥50% (EASI50) and ≥75% (EASI75), as well as head/neck EASI50 and EASI75 and erythema head/neck EASI50 and EASI75 response rates were assessed up to Week 16.Across the studies, 93-98% of patients had head/neck involvement at baseline (EASI head/neck score ≥1). Baricitinib was similarly effective based on EASI total score for the entire body in all studies. In the monotherapy studies, the proportion of patients achieving head/neck EASI50 and EASI75 scores was significantly higher for baricitinib 2-mg and 4-mg versus placebo at Weeks 1 and 16.Baricitinib 2-mg and 4-mg treatment showed rapid and substantial reduction in AD head and neck severity, including erythema.

Background. Insomnia is often related to stressful events. The hypothalamus-pituitary-adrenal (HPA) axis is related to stress, and dopamine (DA) and DA receptors are involved in the regulation of HPA axis. Electroacupuncture (EA) can improve sleep in individuals with insomnia, but the mechanism is unclear. We demonstrated that EA can improve sleep in rats after cage change through DA and the DA receptors in the HPA axis. Methods. A rat model of insomnia was established by cage change to a dirty cage. The rats in treatment groups were intervened by EA and D1R (or D2R) antagonists. Electroencephalography (EEG) and electromyogram (EMG) were recorded to compare the changes in sleep. The DA, corticotropin-releasing hormone (CRH), adrenocorticotropic hormone (ACTH), and cortisol (CORT) levels in the plasma and hypothalamus were measured by ELISAs, and the D1R and D2R levels were measured by RT-PCR and immunohistochemistry. Results. The dirty group showed a significant increase in the amount of wakefulness and decrease in the amount of NREM sleep, with decreased numbers of long NREM sleep bouts and REM sleep bouts and increased mean duration of wakefulness during the light period. EA and D1R (or D2R) antagonists intervention could improve sleep disturbance by decreasing wakefulness in the light period after cage change, EA and D1R (or D2R) antagonists could increase the hypothalamus DA, CRH, ACTH, CORT level, and the D1R and D2R mRNA levels in the HPA axis, and the effect of EA plus D1R (or D2R) antagonist was not superior to that of EA or D1R (or D2R) antagonists alone. Conclusions. EA can improve the sleep of rats after cage change, and the mechanism may be related to the regulation of DA and D1R or D2R in the HPA axis.

To address the need for long-term efficacy and patient-reported outcomes (PROs) data for patients with atopic dermatitis (AD) treated with baricitinib 2 mg, a study was conducted to evaluate the efficacy of baricitinib 2 mg in adult patients with moderate-to-severe AD. Data presented here provided efficacy and outcomes data for patients treated for 52 weeks. Patients who participated in the originating study, BREEZE-AD5 (NCT03435081), and met additional eligibility criteria could enroll in the multicenter, open-label, Phase 3, long-term extension study BREEZE-AD6 (NCT03559270). Patients received baricitinib 2 mg for the duration of BREEZE-AD6. In BREEZE-AD6, the proportion of patients who achieved a 75% improvement in the Eczema Area and Severity Index (EASI75) and validated Investigator Global Assessment for AD (vIGA-AD™) of 0 (clear) or 1 (almost clear) were assessed through 52 weeks, in addition to several PROs. At week 52, the proportion of patients treated with baricitinib 2 mg daily achieving EASI75 was 48.6% (70/144), and 31.3% (45/144) of patients achieved a vIGA-AD score of 0 or 1 (clear or almost clear). Improvements in PROs such as SCORing Atopic Dermatitis (SCORAD, itch and sleep) scores, Dermatology Life Quality Index (DLQI) total score, and DLQI ≤5 response were observed, and these responses were sustained through 52 weeks. Long-term efficacy of baricitinib in patients with AD was demonstrated by both clinician and patient-reported outcome measures.

AIM: To investigate the relationship between neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR) and type 2 diabetic retinopathy (DR). METHODS: A total of 200 cases with type 2 diabetes mellitus were involved. All patients were divided into three groups according to the fundus examination: diabetes mellitus (DM, n=100), non-proliferative diabetic retinopathy (NPDR, n=62) and proliferative diabetic retinopathy (PDR, n=38). 100 healthy persons were selected as the normal control group (NCG, n=100). The related indicators, such as neutrophil count, lymphocyte count and platelet count, were measured. RESULTS: The value of NLR was significantly higher in PDR group patients than in NC group (1.81), DM group (1.76) and NPDR group (1.85) (P

Since the power unbundling reform in 2002, China's power industry has been a typical sector moving towards marketization. The supply-side structural reform that began in 2015 has intensified the competition among China's power generation enterprises. In this context, this paper combines a data envelopment analysis (DEA) game cross-efficiency model with the Malmquist index approach to investigate the dynamic environmental efficiency of China's power generation enterprises in a competitive market. Furthermore, the system generalized method of moments (SYS-GMM) is employed to analyze the influences of factors on the dynamic environmental efficiency. The results show that: (1) Compared with the basic DEA Charnes-Cooper-Rhodes (CCR)-Malmquist index model, the DEA game cross-Malmquist index approach can enhance the discrimination among the decision making units (DMUs). (2) The change in the overall dynamic environmental efficiency of China's power generation enterprises mainly comes from the catch-up effect, while technological progress has not played a role as significant as expected. (3) The installed capacity growth rate, implementation of carbon emission trading pilots, economic growth rate, and enterprise ownership all affect the dynamic environmental performance of China's power generation enterprises during the study period.

International audience; Searching for eco-friendly and earth-abundant materials to supersede traditional high-cost bismuth telluride for fabricating wearable devices is of great significance in thermoelectrics. In this work, promising flexible Cu2Se based thin films with high thermoelectric performance is successfully fabricated via a facile co-sputtering method. Experimental results indicate that excess Cu in Cu2Se films leads to the decrease of carrier concentration by suppressing the formation of Cu vacancies and donating electrons, benefiting to achieve high Seebeck coefficient. Moreover, Cu-excess Cu2Se films have highly (0l0) preferred orientation and extra high carrier mobility, maintaining the decent electrical conductivity in the whole measurement temperature range. Combined with the low thermal conductivity, a maximum ZT of 0.42 is obtained at 275 °C from the Cu-excess Cu2Se due to the simultaneous optimization both of electrical and heat transport. Subsequently, a flexible thermoelectric device assembled with high performance Cu2Se films exhibits a maximum power density of 4.28 Wm-2 at a temperature difference of 50 °C, which thermal stability is greatly improved after introducing a molybdenum buffer layer into electrode layer. Therefore, this work demonstrates that rational microstructure manipulations and connection technology improvement can achieve high performance in the flexible thermoelectric device, which possess potential in wearable applications.

To investigate the factors affecting the chronicity of childhood primary immune thrombo-cytopenia (ITP) and compare the efficiency of different first-line treatment regimens.Children with ITP hospitalized in our hospital from September 2013 to October 2018 were retrospectively analyzed.Three hundred and one children (150 males and 151 females) were included in this study, with a median age of 8 (0.17-17) years old, and 110 (36.5%), 92 (30.6%), and 99 (32.9%) cases were grouped into newly diagnosed, persistent, and chronic ITP, respectively. The median of follow-up was 41.92 (1.07-74.03) months. At the end of the follow-up (October 2019), among the 202 newly diagnosed/persistent ITP children, 79 cases (59 newly diagnosed and 20 persistent ITP) achieved remission within 1 year after initial diagnosis, with a remission rate of 39.3%; 122 cases (50 newly diagnosed and 72 persistent ITP) developed chronic disease, with a chronicity rate of 60.7%; one case underwent splenectomy. In 99 cases with chronic ITP, 5 cases underwent splenectomy. Multivariable logistic regression analysis showed that, the insidious onset of symptoms (OR=3.754, 95%CI: 1.882-7.488, P=0.000) increased the risk of chronicity, while the positive antibody to anti-platelet membrane glycoprotein (OR=0.446, 95%CI: 0.224-0.888, P=0.021) might reduce the risk of chronicity. And no difference was found by the analysis of subtype of anti-platelet membrane glycoprotein (P=0.305). The efficacy of the first-line treatment of intravenous immunoglobulin (IVIG) alone or combined with steroid was better than that of steroid alone (P=0.028, 0.028), however, the efficiency was not significantly different between IVIG alone and combined with steroid (P=0.086).Insidious onset of symptoms in pediatric ITP increases the risk of chronicity, while the positive titer of anti-platelet membrane glycoprotein may reduce the risk. In the first-line treatment for the newly diagnosed/persistent children. The efficacy of IVIG alone or combined with steroid is better than that of steroid alone.原发免疫性血小板减少症住院患儿临床分析.研究儿童原发免疫性血小板减少症（ITP）慢性化的影响因素，比较不同一线治疗方案的疗效.回顾性分析2013年9月至2018年10月于本院住院治疗的ITP患儿的临床资料.共计301例ITP患儿纳入研究。男150例，女151例，中位年龄8（0.17-17）岁。新诊断ITP 110例（36.5%），持续性ITP 92例（30.6%），慢性ITP 99例（32.9%）。中位随访时间41.92（1.07-74.03）个月。截至随访终点（2019年10月），202例新诊断/持续性ITP患儿中，79例（59例新诊断ITP，20例持续性ITP）在初诊后1年内获得缓解，缓解率39.3%；122例（50例新诊断ITP，72例持续性ITP）进展为慢性ITP，慢性化率60.7%；1例行脾切除。99例慢性ITP患儿中，5例行脾切除。多因素Logistic回归分析显示，隐匿起病(OR=3.754,95%CI:1.882-7.488,P=0.000)增加疾病慢性化风险，而血小板膜糖蛋白抗体阳性(OR=0.446,95%CI:0.224-0.888,P=0.021)降低慢性化风险，抗体类型的亚组分析无差异（P=0.305）。新诊断和持续性ITP仅接受一线治疗的患儿，单独应用静脉注射免疫球蛋白（IVIG）或IVIG联合激素疗效均优于激素单药治疗（P=0.028，0.028），而单独应用IVIG与IVIG联合激素比较疗效无差异（P=0.086）.儿童ITP隐匿起病慢性化风险升高，血小板膜糖蛋白抗体阳性降低慢性化风险。儿童新诊断和持续性ITP的一线治疗，单独应用IVIG或IVIG联合激素疗效均优于激素单药治疗.

In order to expand the application in the medical field and enhance pharmacological effects, casein-myricetin nanomicelles were prepared by the self-assembly method and characterised by ultraviolet-visible spectroscopy and Fourier transform infrared spectroscopy. The parameters in self-assembly were optimised according to the factors of particle size, encapsulation yield, and drug loading. The result showed a pH of 5.5, a casein concentration of 2 mg/ml, a mass ratio of casein to myricetin of 8:1, ultrasonic power of 300 W, ultrasonic time of 5 min and ethanol volume of 7 ml were the optimal conditions. The situ cycle intestinal perfusion methods indicated that casein-myricetin nanomicelles can be more easily absorbed by small intestine than myricetin standard sample. Therefore, casein micelles are effective for improving the water solubility of myricetin.

We investigated if corilagin can ameliorate or reverse atherosclerotic development via the toll-like receptor 4 (TLR4) signaling pathway in vitro and in vivo. Ana-1 cells or mouse peritoneal macrophages (MPMs) were stimulated with oxidized low-density lipoprotein followed by corilagin treatment. TLR4 expression in Ana-1 cells was upregulated by lentiviral transduction and downregulated by small interfering RNA. Peripheral blood mononuclear cells (PBMCs), plasma samples, and femoral arteries were collected from rats exhibiting peripheral artery disease (PAD). mRNA and protein expression of TLR4 and downstream molecules were decreased significantly by corilagin treatment in Ana-1 cells, MPMs, and rat PBMCs, and the reduction remained irrespective of downregulation or upregulation of TLR4 expression in Ana-1 cells. Corilagin also exerted a prominent effect on changes in plasma levels of cytokines and the pathologic manifestation of atherosclerosis in femoral arteries. Corilagin could ameliorate the development of atherosclerotic plaques by inhibiting the TLR4 signaling pathway in monocyte/macrophages and reduce the release of proinflammatory cytokines. This study provides a new therapeutic target and new niche targeting drug to oppose atherosclerosis and reveals the enormous potential of corilagin for control of PAD in humans.

Background In this post hoc analysis, we assessed relationship between pain improvement and disease activity and evaluated whether baricitinib (BARI) provided additional pain improvement vs. PBO and adalimumab (ADA) across levels of disease activity. Methods 1,305 patients on stable background MTX were randomized 3:2:3 (PBO:40-mg subcutaneous ADA every other week:daily, oral 4-mg BARI). Pain was assessed with 0-100-mm VAS; pain improvement (baseline to Week 12) was grouped by ≤ 30%, >30% to ≤ 50%, >50% to ≤ 70%, >70%. Disease activity was measured with CDAI, SDAI, DAS28 with CRP, and DAS28 with ESR. To evaluate change in pain with disease activity, regression was used with continuous change in pain VAS score from baseline to Week 12 as outcome and continuous CDAI/SDAI/DAS28-CRP/DAS28-ESR values, treatment, and interaction term between treatment and disease activity as explanatory variables. Last observation carried forward was used to impute missing values. Pain VAS change (Week 12) was estimated if patients achieved remission (REM)/low disease activity (LDA)/moderate disease activity (MDA) as defined by the corresponding clinical measure. Analyses were not adjusted for multiplicity. Data visualization (percentage of pain VAS improvement vs. disease activity) was created to examine pain improvement with treatment over time. Results With CDAI, 91%/9% of patients had high disease activity/MDA across all treatments (baseline). Percentage of patients achieving REM with PBO, ADA, and BARI were 2%, 7%, 8%; for LDA: 15%, 27%, 33%; for MDA: 33%, 40%, 38%. At all CDAI values, estimated change in pain VAS for BARI was greater vs. PBO and ADA (Week 12). Similar trends were observed with other measures (Table). BARI demonstrated greater pain improvement vs. ADA and PBO in percentage of patients with ≤30%, >30% to ≤ 50%, >50% to ≤ 70%, and >70% pain improvement from baseline at Week 12. . With CDAI/SDAI, greater differentiation between BARI and ADA was observed as CDAI/SDAI values increased. Conclusion BARI provided additional pain improvement vs. PBO and ADA when disease activity was controlled, across all levels of disease activity, measured by CDAI, SDAI, DAS28-CRP, or DAS28-ESR (Week 12). Disclosures P.C. Taylor (Presenter): Consultancies; PCT has been a consultant and/or received research support from: AbbVie, Eli Lilly and Company, Galapagos, and Pfizer. J. Pope: Consultancies; JP has been a consultant and/or has received grant/research support from: AbbVie, Amgen, Bayer, BMS, Eli Lilly and Company, Merck, Novartis, Pfizer, Roche, Sanofi, Sandoz, and UCB. K. Ikeda: Consultancies; KI has been a consultant and/or received research support and/or honoraria from: AbbVie, Astellas Pharma, Bristol-Myers K.K., Chugai Pharmaceutical, Eisai, Eli Lilly and Company, Kyowa Hakko Kir. X. Zhang: Corporate appointments; XZ is an employee of Eli Lilly and Company. Shareholder/stock ownership; XZ is a shareholder of Eli Lilly and Company. B. Jia: Corporate appointments; BJ is an employee of Eli Lilly and Company. Shareholder/stock ownership; BJ is a shareholder of Eli Lilly and Company. H. Zhang: None. A. Quebe: Corporate appointments; AQ is an employee of Eli Lilly and Company. Shareholder/stock ownership; AQ is a shareholder of Eli Lilly and Company. Y. Chen: Corporate appointments; Y-FC is an employee of Eli Lilly and Company. Shareholder/stock ownership; Y-FC is a shareholder of Eli Lilly and Company. C.L. Kannowski: Corporate appointments; CLK is an employee of Eli Lilly and Company. Shareholder/stock ownership; CLK is a shareholder of Eli Lilly and Company. T. Holzkaemper: Corporate appointments; TH is an employee of Eli Lilly and Company. Shareholder/stock ownership; TH is a shareholder of Eli Lilly and Company. A. Cardoso: Corporate appointments; AC is an employee of Eli Lilly and Company. Shareholder/stock ownership; AC is a shareholder of Eli Lilly and Company. A. Sebba: Consultancies; AS has been a consultant and/or speaker for: Eli Lilly and Company, Genentech, and Novartis.

IntroductionInsomnia with short sleep duration has a more serious negative impact on patient health. The existing literature suggests that medication therapy is more effective for this phenotype of insomnia compared with cognitive–behavioural therapy. However, the potential side effects of hypnotic medications hinder their clinical application. Acupuncture has been widely used in the treatment of insomnia, but it remains unclear whether it has therapeutic efficacy for insomnia with short sleep duration. The purpose of this trial is to evaluate the efficacy and safety of acupuncture for insomnia with short sleep duration.Methods and analysisThis study is designed as a randomised, single-centre, single-blinded, placebo acupuncture controlled trial involving 152 participants. Eligible patients will be divided into two groups according to the objective total sleep time: insomnia with normal sleep duration group and insomnia with short sleep duration group. Then, patients in each group will be randomly assigned to two subgroups, the treatment group (acupuncture) and the control group (placebo acupuncture), in a 1:1 ratio with 38 subjects in each subgroup. The primary outcome is the Pittsburgh Sleep Quality Index and the Insomnia Severity Index. Secondary outcomes are actigraphy, the Beck Anxiety Inventory, the Beck Depression Inventory and the Fatigue Severity Scale. All adverse effects will be assessed by the Treatment Emergent Symptom Scale. Outcomes will be evaluated at baseline, post treatment, as well as at 1-week and 1-month follow-up.Ethics and disseminationThis protocol has been approved by the ethics committee of Yueyang Hospital of Integrated Traditional Chinese and Western Medicine (no. 2019-17). Written informed consent will be obtained from all participants. The results will be disseminated through peer-reviewed journals for publications.Trial registration numberChiCTR1900023473; Pre-results.

The unbundling policy reform of power industry has become a worldwide trend since 1980s. There are quite many studies focusing on the efficiency changes of transmission and distribution sectors in European and Latin American countries while few reports on China's issues have been found. This paper employs a nonparametric frontier estimation combined with meta-frontier and bootstrapping method to measure the productive efficiency and changes in the decomposition index for China's 31 grid companies from 2004 to 2013. In addition, it further employs Tobit regression model to analyze the influences of relevant policies and heterogeneity factors, such as natural conditions and economic development. The results indicate that the grouping approach extends the application of non-parametric data envelopment analysis, which may decrease the assumption of homogeneity for the decision making units and provide better efficiency estimates by increasing the credibility of the evaluation results. Overall productive efficiency increased during the whole study period, with technology progress the main contributor to this improvement. Efficiency trends fluctuated with changes in economic development and power supply situation, and the economics and customer density had positive effects on productive efficiency while the influence of clean power proportion is negative.

Introduction In clinical trials of Alzheimer's disease, a mixed-model repeated measure approach often serves as the primary analysis when evaluating disease progression; a slope model may be secondary. Methods Longitudinal change from baseline (14-item version of Alzheimer's Disease Assessment Scale–Cognitive Subscale) was simulated for treatment/placebo from multivariate normal distributions with the variance-covariance matrix estimated from solanezumab trial data. Type I error, power, and bias were based on 18-month treatment contrast. Sample sizes included 500 and 1000 patients/arm. Results The slope model was more powerful in most scenarios. Mixed-model repeated measure was relatively unbiased in parameter estimation. The slope model yielded unbiased estimates whenever the underlying trajectory was not detectably different from linear. Both methods led to similar type I error. Discussion In clinical trials of Alzheimer's disease, mixed-model repeated measure analysis with relaxed assumptions on disease progression seems to be preferred. The slope model might be more powerful if the trajectory has little departure from linearity.

Background:Reducing structural damage is an important treatment goal for rheumatoid arthritis (RA). Demonstrating a clinically meaningful, statistically significant difference in radiographic progression (assessed by van der Heijde modified total Sharp score, mTSS) is a common objective in trials for RA treatments.Complete collection of radiographic data is challenging, especially in long term follow-up and pediatric studies. Therefore, scores for individual joints or entire patients are regularly missing. A frequently used analysis method for mTSS is the analysis of covariance model, in which missing data are imputed using linear extrapolation (ANCOVA+LE). However, other ways to deal with missing information have also been proposed.Objectives:To evaluate robust analysis methods for mTSS data.Methods:Simulated data were used to compare a random coefficient model (RC) without imputation, ANCOVA+LE and ANCOVA with last observation carry forward imputation (LOCF).A log-normal distribution was used to generate baseline patient level data to simulate a 2-arm clinical trial using baseline mTSS and rate of change in mTSS from recently completed trials. Changes in mTSS (12, 28 and 44 week timepoints) were generated under linear, concave quadratic (fast progression then slow progression), and convex quadratic (slow progression then fast progression) assumptions, with the proportion of change forced to be 0 (a proportion of simulated patients do not have progression). A monotone missing pattern was assumed to generate a data set with missing data (the ‘observed’ dataset).ANCOVA analyses were performed using baseline and treatment as predictors. The RC model was applied using baseline, treatment, time, and time-by-treatment interactions as fixed effect and time as a random effect. Bias (difference between average of simulation sample mean and true value, the smaller the better), root mean square error (RMSE, a measure of variation among simulation samples, the smaller the better), power and type I error rate were compared between methods.Results:The random coefficient model provided better or at least similar results in bias, RMSE, power and type I error rate as ANCOVA+LE under evaluated scenarios (Table 1).Progression assumptionSimulation parameters(Number of simulations = 500; common sample size=300, baseline mTSS=~11.7)ModelBiasPowerRMSELinearppbo= 0.6, rpbo= 0.065ptrt= 0.68 rpbo= 0.046Δwk44= −0.49ANCOVA + Full0.0020.9240.140ANCOVA + LE0.0030.8660.155ANCOVA+LOCF0.1540.8440.190RC + FULL0.0010.920.139RC + OBS−0.0020.8720.156Concaveppbo= 0.6, rpbo= −0.0009, qpbo= 0.11ptrt= 0.68, rtrt= −0.0011, qtrt= 0.093Δwk44= −0.611ANCOVA + Full0.0020.9820.141ANCOVA + LE−0.0020.9260.180ANCOVA+LOCF0.1880.940.222RC + FULL0.0020.9780.141RC + OBS−0.0050.9240.174Convexppbo=0.6, rpbo= 0.0037, qpbo=−0.09ptrt= 0.68, rtrt= 0.003, qtrt= −0.1Δwk44= −0.83ANCOVA + Full0.00310.139ANCOVA + LE0.3430.9480.368ANCOVA+LOCF0.3910.9740.405RC + FULL−0.00410.140RC + OBS0.1990.9880.249Abbreviations: FULL = complete dataset with no missing values trt = active treatment, OBS = the ‘observed’ dataset, pbo = placebo, p= proportion of patients with no progression, r = linear progression rate (mTSS units per week), q = quadratic term coefficient. Δ = active treatment progression – placebo rConclusion:RC is a robust analysis method for mTSS. We recommend its use in primary analyses, especially for long-term extension and pediatric studies with a higher likelihood of missing data. This method can also provide reference for time points when no data are collected via estimated slope. ANCOVA+LE can be used for sensitivity analysis.References:None.Disclosure of Interests:Robert B.M. Landewé Consultant of: AbbVie; AstraZeneca; Bristol-Myers Squibb; Eli Lilly & Co.; Galapagos NV; Novartis; Pfizer; UCB Pharma, Luna Sun Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Yun-Fei Chen Shareholder of: Own shares in Eli Lilly and Company., Employee of: Employee of Eli Lilly and Company, Douglas Schlichting Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Désirée van der Heijde Consultant of: AbbVie, Amgen, Astellas, AstraZeneca, BMS, Boehringer Ingelheim, Celgene, Cyxone, Daiichi, Eisai, Eli-Lilly, Galapagos, Gilead Sciences, Inc., Glaxo-Smith-Kline, Janssen, Merck, Novartis, Pfizer, Regeneron, Roche, Sanofi, Takeda, UCB Pharma; Director of Imaging Rheumatology BV

We use 3487 surface soil samples, 35 soil profile samples, and 93 agricultural products and root soil samples obtained from the southeastern Tarim basin, Xinjiang, northwestern China (Ruoqiang County and Qiemo County, Bayingguo Mongolia Autonomous Prefecture, and Minfeng County and Yutian County, Hetian Prefecture) to assess As contamination. Multivariate statistical analysis, geostatistics, and global information system (GIS) techniques are used to study:the spatial distribution characteristics of soil As, the effects of various agricultural products on As enrichment, and to compare the characteristics of the As content of agricultural products and root soils in spatially significantly and non-significantly autocorrelated regions. The As content of soil samples were relatively low, and the average As contents determined for agricultural land and non-agricultural land were 9.81 mg·kg

Since the 1990s, microfluidic technology has developed rapidly. However, subject to the limitations of traditional microfluidic device manufacturing methods, traditional microfluidic devices have long manufacturing cycles and high manufacturing costs. Micro-nano additive manufacturing is an important direction to break through the limitations of traditional microfluidic device manufacturing. In this paper, the micropump in the microfluidic device is taken as an example. By using the innovative design method of analog design, the "Automobile engine type micropump system" is proposed in this paper. Through the analysis of the relevant simulation results, the following conclusions can be drawn. The "Automobile engine type micropump structure" can significantly improve the smoothness of the output flow of the micropump. It is composed of basic structural units. By turning on or off the independent drive voltage, this micropump can generate seven different flow rates as outputs, thereby improving the compatibility of the micropump structure.

To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) and "Xuanzhong" (GB39) on joint inflammatory reactions and serum matrix metalloproteinase-3 (MMP-3) and MMP-9 contents in rats with adjuvant arthritis (AA), so as to explore its mechanism underlying improvement of AA.Forty male SD rats were randomly divided into control, model, acupoint and non-acupoint groups (The arthritis index score and serum concentrations of MMP-3 and MMP-9 were significantly increased in the model group relevant to the control group (acupoint EA intervention can significantly alleviate the inflammatory reaction of AA rats, which may be related to its effects in reducing the levels of serum MMP-3 and MMP-9.