DRONet: effectiveness-driven drug repositioning framework using network embedding and ranking learning.

As one of the most vital methods in drug development, drug repositioning emphasizes further analysis and research of approved drugs based on the existing large amount of clinical and experimental data to identify new indications of drugs. However, the existing drug repositioning methods didn't achieve enough prediction performance, and these methods do not consider the effectiveness information of drugs, which make it difficult to obtain reliable and valuable results. In this study, we proposed a drug repositioning framework termed DRONet, which make full use of effectiveness comparative relationships (ECR) among drugs as prior information by combining network embedding and ranking learning. We utilized network embedding methods to learn the deep features of drugs from a heterogeneous drug-disease network, and constructed a high-quality drug-indication data set including effectiveness-based drug contrast relationships. The embedding features and ECR of drugs are combined effectively through a designed ranking learning model to prioritize candidate drugs. Comprehensive experiments show that DRONet has higher prediction accuracy (improving 87.4% on Hit@1 and 37.9% on mean reciprocal rank) than state of the art. The case analysis also demonstrates high reliability of predicted results, which has potential to guide clinical drug development.

Quantum chemical studies of the reaction mechanisms of enzymatic CO2 conversion.

Enzymatic capture and conversion of carbon dioxide (CO2) into value-added chemicals are of great interest in the field of biocatalysis and have a positive impact on climate change. The quantum chemical methods, recognized as valuable tools for studying reaction mechanisms, have been widely employed in investigating the reaction mechanisms of the enzymes involved in CO2 utilization. In this perspective, we review the mechanistic studies of representative enzymes that are either currently used or have the potential for converting CO2, utilizing the quantum chemical cluster approach and the quantum mechanical/molecular mechanical (QM/MM) method. We begin by summarizing current trends in enzymatic CO2 conversion, followed by a brief description of the computational details of quantum chemical methods. Then, a series of representative examples of the computational modeling of biocatalytic CO2 conversion are presented, including the reduction of CO2 to C1 species (carbon monoxide and formate), and the fixation of CO2 to form aliphatic and aromatic carboxylic acids. The microscopic views of reaction mechanisms obtained from these studies are helpful in guiding the rational design of current enzymes and the discovery of novel enzymes with enhanced performance in converting CO2. Additionally, they provide key information for the de novo design of new-to-nature enzymes. To conclude, we present a perspective on the potential combination of machine learning with quantum description in the study of enzymatic conversion of CO2.

Brain metastases from small cell lung cancer and non-small cell lung cancer: comparison of spatial distribution and identification of metastatic risk regions.

PURPOSE: This study aims to investigate the spatial distribution difference of brain metastases (BM) between small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC) and to identify the metastatic risk in brain regions. METHODS: T1-enhanced MR images of 2997 BM from 728 eligible patients with SCLC and NSCLC were retrospectively reviewed by three independent medical institutions in China. All images were spatially normalised according to the Montreal Neurological Institute space, following BM delineation confirmed by three senior radiologists. The brain regions in the normalised images were identified based on the merged Anatomical Automatic Labeling atlas, and all BM locations were mapped onto these brain regions. Two-tailed proportional hypothesis testing was used to compare the BM observed rate with the expected rate based on the region's volume, and metastatic risk regions were finally identified. RESULTS: In SCLC and NSCLC, BM was mainly present in the deep white matter (22.51% and 17.96%, respectively), cerebellar hemisphere (9.84% and 7.46%, respectively) and middle frontal gyrus (6.72% and 7.97%, respectively). The cerebellar hemisphere was a high-risk brain region in the SCLC. The precentral gyrus, middle frontal gyrus, paracentral lobule and cerebellar hemisphere were high-risk BM in the NSCLC. The inferior frontal gyrus and the temporal pole were a low-risk brain region in the SCLC and NSCLC, respectively. CONCLUSION: The spatial BM distribution between SCLC and NSCLC is similar. Several critical brain regions had relatively low BM frequency in both SCLC and NSCLC, where a low-dose radiation distribution can be delivered due to adequate preoperative evaluations.

Efficacy of Acupuncture for Chronic Prostatitis/Chronic Pelvic Pain Syndrome : A Randomized Trial.

BACKGROUND: Acupuncture has promising effects on chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), but high-quality evidence is scarce. OBJECTIVE: To assess the long-term efficacy of acupuncture for CP/CPPS. DESIGN: Multicenter, randomized, sham-controlled trial. (ClinicalTrials.gov: NCT03213938). SETTING: Ten tertiary hospitals in China. PARTICIPANTS: Men with moderate to severe CP/CPPS, regardless of prior exposure to acupuncture. INTERVENTION: Twenty sessions of acupuncture or sham acupuncture over 8 weeks, with 24-week follow-up after treatment. MEASUREMENTS: The primary outcome was the proportion of responders, defined as participants who achieved a clinically important reduction of at least 6 points from baseline on the National Institutes of Health Chronic Prostatitis Symptom Index at weeks 8 and 32. Ascertainment of sustained efficacy required the between-group difference to be statistically significant at both time points. RESULTS: A total of 440 men (220 in each group) were recruited. At week 8, the proportions of responders were 60.6% (95% CI, 53.7% to 67.1%) in the acupuncture group and 36.8% (CI, 30.4% to 43.7%) in the sham acupuncture group (adjusted difference, 21.6 percentage points [CI, 12.8 to 30.4 percentage points]; adjusted odds ratio, 2.6 [CI, 1.8 to 4.0]; P < 0.001). At week 32, the proportions were 61.5% (CI, 54.5% to 68.1%) in the acupuncture group and 38.3% (CI, 31.7% to 45.4%) in the sham acupuncture group (adjusted difference, 21.1 percentage points [CI, 12.2 to 30.1 percentage points]; adjusted odds ratio, 2.6 [CI, 1.7 to 3.9]; P < 0.001). Twenty (9.1%) and 14 (6.4%) adverse events were reported in the acupuncture and sham acupuncture groups, respectively. No serious adverse events were reported. LIMITATION: Sham acupuncture might have had certain physiologic effects. CONCLUSION: Compared with sham therapy, 20 sessions of acupuncture over 8 weeks resulted in greater improvement in symptoms of moderate to severe CP/CPPS, with durable effects 24 weeks after treatment. PRIMARY FUNDING SOURCE: China Academy of Chinese Medical Sciences and the National Administration of Traditional Chinese Medicine.

A network-based machine-learning framework to identify both functional modules and disease genes.

Disease gene identification is a critical step towards uncovering the molecular mechanisms of diseases and systematically investigating complex disease phenotypes. Despite considerable efforts to develop powerful computing methods, candidate gene identification remains a severe challenge owing to the connectivity of an incomplete interactome network, which hampers the discovery of true novel candidate genes. We developed a network-based machine-learning framework to identify both functional modules and disease candidate genes. In this framework, we designed a semi-supervised non-negative matrix factorization model to obtain the functional modules related to the diseases and genes. Of note, we proposed a disease gene-prioritizing method called MapGene that integrates the correlations from both functional modules and network closeness. Our framework identified a set of functional modules with highly functional homogeneity and close gene interactions. Experiments on a large-scale benchmark dataset showed that MapGene performs significantly better than the state-of-the-art algorithms. Further analysis demonstrates MapGene can effectively relieve the impact of the incompleteness of interactome networks and obtain highly reliable rankings of candidate genes. In addition, disease cases on Parkinson's disease and diabetes mellitus confirmed the generalization of MapGene for novel candidate gene identification. This work proposed, for the first time, an integrated computing framework to predict both functional modules and disease candidate genes. The methodology and results support that our framework has the potential to help discover underlying functional modules and reliable candidate genes in human disease.

Electroacupuncture vs Prucalopride for Severe Chronic Constipation: A Multicenter, Randomized, Controlled, Noninferiority Trial.

INTRODUCTION: This multicenter, randomized, noninferiority trial compared electroacupuncture with prucalopride for the treatment of severe chronic constipation (SCC). METHODS: Participants with SCC (≤ 2 mean weekly complete spontaneous bowel movements [CSBMs]) were randomly assigned to receive either 28-session electroacupuncture over 8 weeks with follow-up without treatment over 24 weeks or prucalopride (2 mg/d before breakfast) over 32 weeks. The primary outcome was the proportion of participants with ≥3 mean weekly CSBMs over weeks 3-8, based on the modified intention-to-treat population, with -10% as the noninferior margin. RESULTS: Five hundred sixty participants were randomized, 280 in each group. Electroacupuncture was noninferior to prucalopride for the primary outcome (36.2% vs 37.8%, with a difference of -1.6% [95% confidence interval, -8% to 4.7%], P < 0.001 for noninferiority); almost the same results were found in the per-protocol population. The proportions of overall CSBM responders through weeks 1-8 were similar in the electroacupuncture and prucalopride groups (24.91% vs 25.54%, with a difference of -0.63% [95% confidence interval, -7.86% to 6.60%, P = 0.864]). Except during the first 2-week treatment, no between-group differences were found in outcomes of excessive straining, stool consistency, and quality of life. Adverse events occurred in 49 (17.69%) participants in the electroacupuncture group and 123 (44.24%) in the prucalopride group. One non-treatment-related serious adverse event was recorded in the electroacupuncture group. DISCUSSION: Electroacupuncture was noninferior to prucalopride in relieving SCC with a good safety profile. The effects of 8-week electroacupuncture could sustain for 24 weeks after treatment. Electroacupuncture is a promising noninferior alternative for SCC (see Visual Abstract, http://links.lww.com/AJG/B776).

Hanshiyi Formula, a medicine for Sars-CoV2 infection in China, reduced the proportion of mild and moderate COVID-19 patients turning to severe status: A cohort study.

We formulated a traditional Chinese medicine (TCM) prescription, Hanshiyi Formula (HSYF), which was approved and promoted by the Wuhan Municipal Health Commission for treating mild and moderate coronavirus disease 2019 (COVID-19). We aimed to evaluate the effect of HSYF on the progression to severe disease in mild and moderate COVID-19 patients. We conducted a retrospective cohort study of patients with mild and moderate COVID-19 in a quarantine station in Wuchang District, Wuhan. Using the real-time Internet information collection application and Centers for Disease Control for the Wuchang District, patient data were collected through patient self-reports and follow-ups. HSYF intervention was defined as the exposure. The primary outcome was the proportion of patients who progressed to a severe disease status, and a stratification analysis was performed. Univariate and multivariate regression analyses were performed to identify influencing factors that may affect the outcome. Further, we used propensity score matching (PSM) to assess the effect of HSYF intervention on the conversion of mild and moderate to a severe disease status. Totally, 721 mild and moderate COVID-19 patients were enrolled, including 430 HSYF users (exposed group) and 291 non-users (control group). No cases in the exposed group and 19 (6.5 %, P < 0.001) cases in the control group progressed to severe disease, and the difference between the two groups (exposed group-control group) was -6.5 % [95 % confidence interval (CI): (-8.87 %, -4.13 %)]. Univariate regression analysis revealed sex (male), age, fever, cough, and fatigue as risk factors for progression to severe disease. After PSM, none of the HSYF users and 7 (4.7 %, P = 0.022) non-users transitioned to severe disease, and the difference between the two groups (exposed group-control group) was -4.7 % [95 % CI: (-8.2 %, -1.2 %)]. Multivariate regression analysis revealed that sex (male) [OR: 3.145; 95 % CI: 1.036-9.545; P = 0.043] and age (> 48 years) [odds ratio (OR): 1.044; 95 % CI: 1.001-1.088; P = 0.044] were independent risk factors for conversion to severe disease. Therefore, HSYF can significantly reduce the progression to severe disease in patients with mild and moderate COVID-19, which may effectively prevent and treat the disease. However, further larger clinical studies are required to verify our results.

Integrated network analysis of symptom clusters across disease conditions.

Identifying the symptom clusters (two or more related symptoms) with shared underlying molecular mechanisms has been a vital analysis task to promote the symptom science and precision health. Related studies have applied the clustering algorithms (e.g. k-means, latent class model) to detect the symptom clusters mostly from various kinds of clinical data. In addition, they focused on identifying the symptom clusters (SCs) for a specific disease, which also mainly concerned with the clinical regularities for symptom management. Here, we utilized a network-based clustering algorithm (i.e., BigCLAM) to obtain 208 typical SCs across disease conditions on a large-scale symptom network derived from integrated high-quality disease-symptom associations. Furthermore, we evaluated the underlying shared molecular mechanisms for SCs, i.e., shared genes, protein-protein interaction (PPI) and gene functional annotations using integrated networks and similarity measures. We found that the symptoms in the same SCs tend to share a higher degree of genes, PPIs and have higher functional homogeneities. In addition, we found that most SCs have related symptoms with shared underlying molecular mechanisms (e.g. enriched pathways) across different disease conditions. Our work demonstrated that the integrated network analysis method could be used for identifying robust SCs and investigate the molecular mechanisms of these SCs, which would be valuable for symptom science and precision health.

Effective attention-based network for syndrome differentiation of AIDS.

BACKGROUND: Syndrome differentiation aims at dividing patients into several types according to their clinical symptoms and signs, which is essential for traditional Chinese medicine (TCM). Several previous works were devoted to employing the classical algorithms to classify the syndrome and achieved delightful results. However, the presence of ambiguous symptoms substantially disturbed the performance of syndrome differentiation, This disturbance is always due to the diversity and complexity of the patients' symptoms. METHODS: To alleviate this issue, we proposed an algorithm based on the multilayer perceptron model with an attention mechanism (ATT-MLP). In particular, we first introduced an attention mechanism to assign different weights for different symptoms among the symptomatic features. In this manner, the symptoms of major significance were highlighted and ambiguous symptoms were restrained. Subsequently, those weighted features were further fed into an MLP to predict the syndrome type of AIDS. RESULTS: Experimental results for a real-world AIDS dataset show that our framework achieves significant and consistent improvements compared to other methods. Besides, our model can also capture the key symptoms corresponding to each type of syndrome. CONCLUSION: In conclusion, our proposed method can learn these intrinsic correlations between symptoms and types of syndromes. Our model is able to learn the core cluster of symptoms for each type of syndrome from limited data, while assisting medical doctors to diagnose patients efficiently.

Electroacupuncture for postmenopausal women with stress urinary incontinence: secondary analysis of a randomized controlled trial.

PURPOSE: The efficacy and safety of electroacupuncture was compared to those of sham electroacupuncture for the treatment of postmenopausal women with stress urinary incontinence (SUI). METHODS: This study was a secondary analysis of a multicenter, randomized controlled trial that recruited 504 women with SUI and randomized 349 postmenopausal women to receive 18 treatment sessions of electroacupuncture or sham electroacupuncture over 6 weeks, with a 24-week follow-up assessment. Treatment response was defined as a 50% or greater reduction in urine leakage, as measured by a 1-h pad test at week 6. RESULTS: Of the 349 randomized women, 332 completed the study. The response rate was 61.0% in the electroacupuncture group compared to 18.9% in the sham electroacupuncture group (difference 42.5%; 95% confidence interval, 33.3-51.7; p < 0.001). After 6 weeks of treatment, the mean 72-h urinary incontinence episode frequency, proportion of participants with at least a 50% decrease in mean 72-h incontinence episode frequency, participant-reported SUI severity, International Consultation on Incontinence Questionnaire-Short Form scores, and participants' self-evaluation of therapeutic effects improved in both groups, with significant between-group differences. Treatment-related adverse events occurred in 2.1% of women during the 6-week treatment. CONCLUSION: Electroacupuncture may effectively and safely relieve urinary incontinence symptoms and improve quality of life in postmenopausal women with SUI.

Acupuncture therapy for chronic low back pain: protocol of a prospective, multi-center, registry study.

OBJECTIVE: Acupuncture therapy for chronic low back pain (CLBP) has received increasing attention. Nevertheless, the evidence of efficacy and safety of random controlled trials (RCTs) remains controversial. Acupuncture as a complex intervention influenced by many factors, its effectiveness in treating chronic low back pain in the real world is unknown. We will develop a network-based registry study to evaluate the effectiveness and safety of acupuncture for the treatment of chronic low back pain and explore key factors affecting efficacy in the real world. METHODS: A prospective, multi-center and dynamic registry study. All acupuncture related information will be collected through a high-quality structured network platform. Patients with CLBP included in the study met the following criteria: age from 16 to 80 years, using acupuncture as a main therapy and voluntarily signing the informed consent. At least 2000 patients, 27 acupuncturist, and 9 medical centers will be recruited under actual clinical settings at the first stage. Numeric rating scale (NRS), Oswestry Disability Index (ODI) and Effective rate will be measured in pain and functional disability assessment, respectively, as the primary outcome. Evaluation index will be collected at the baseline and follow-up in 1, 4, 12 weeks after the last visit. Hierarchical models and regression analysis will be used to explore the key factors affecting acupuncture effectiveness. Effects between propensity matching groups (Traditional Chinese acupuncture style vs Microacupuncture style, Local acupoint selection vs Non-local acupoint selection, Single Acupuncture vs Combined therapy) will be compared. DISCUSSION: This study will be conducted based on the characteristics of acupuncture therapy in the "Real World". Fundamental factors affecting the clinical effectiveness of acupuncture and the preferred acupuncture regimen in the treatment of CLBP will be identified. Reliable acupuncture evidence for the treatment of CLBP through the registry will be a significant supplement to the RCTs. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR-OOC-17010751 and Acupuncture-Moxibustion Clinical Trial Registry, AMCTR-OOO-17000045 . Registered date on 3 December 2016.

Treatment satisfaction in Chinese medicine outpatient care: a comparison of patients' and doctors' views.

BACKGROUND: Both doctors' and patients' opinions are important in the process of treatment and healthcare of Chinese medicine. This study is to compare patients' and doctors' treatment satisfaction over the course of two visits in a Chinese medicine outpatient setting, and to explain their respective views. METHODS: Patients' chief complaints were collected prior to the outpatient encounter. The doctor was then asked (through a questionnaire) to state what complaints he or she was prioritizing during the process of diagnosing disease and making a prescription for herbal medicine or acupuncture treatment. On the next visit, both the patient and the doctor completed a questionnaire assessing satisfaction with the treatment of Chinese medicine prescribed in the first visit and administered by the patient at home. A 5-point Likert scales was used to assess the patients' and doctors' satisfaction with treatment. The timing of the follow-up appointment was determined by the doctor. One chief specialist, one associate chief specialist and one attending practitioner in Chinese medicine, and 60 patients having a follow-up appointment with one of the doctors, participated in the study. RESULTS: For 11 patients, their most urgent complaint was different from what the doctor's choose to focus on in his or her treatment. And only one patient refused to comply due to his or her dissatisfaction with the treatment focus of the doctor. Overall, 59 patients completed the satisfaction assessment, and 53 patients visited their doctors for a follow-up appointment. Patients' total satisfaction was higher than their doctors' (mean 3.55 vs. 3.45), and correlation of patients' and doctors' treatment satisfaction was moderate (r = 0.63, P < 0.01). Both of the patients' and doctors' satisfaction ratings were correlated with treatment adherence (P < 0.001). The predictors of their treatment satisfaction were different. Doctors' satisfaction with treatment was a significant factor in the process of making further clinical decisions. CONCLUSION: Patients and doctors form their opinion about the treatment effects in different ways. When evaluating treatment satisfaction, doctor's opinions are also an important indicator of positive or negative clinical effects and affect the subsequent decisions-making.

A protocol for isolation and identification and comparative characterization of primary osteoblasts from mouse and rat calvaria.

Calvaria from neonatal mouse and rat is ideal resource for osteoblasts but can be easily contaminated by other cells such as fibroblasts. Here, we established a protocol for isolation and purification of primary osteoblast by enzyme sequential digestion and differential adhesion. In addition, we compared the phenotypic and functional traits of osteoblasts from mouse and rat which are commonly employed in studies. The method applied equally to rat and mouse in osteoblasts isolation and was corroborated its feasibility and validity. The results also provided us evidences for other experiments such as choosing a certain time point to give intervention and do the relevant tests.

Electroacupuncture for Reflex Sympathetic Dystrophy after Stroke: A Meta-Analysis.

BACKGROUND: Reflex sympathetic dystrophy (RSD) is the common complication among stroke and cerebral injury patients, which is lack of safe and effective treatment. Electroacupuncture (EA) may potentially be a reliably therapy, but the evidence is insufficiency. METHODS: Cochrane Library, MEDLINE, Embase, Chinese National Knowledge Infrastructure, Wan Fang Data, the Chinese Biology Medicine disc, etc., were searched, until July 20, 2018. We included random control trials that contrast EA with conventional rehabilitation therapy for the treatment of RSD. Main outcomes were visual analog scale score and Fugl-Meyer upper limb motor function scoring scale, other outcomes such as Barthel index, and hand swelling score were also collected. Data in included studies were extracted into an excel and pooled by Stata/MP 14.1. RESULTS: We incorporated 13 studies involving 1040 RSD patients and outcomes were from 2 to 6 weeks' follow-up. The analgesic effect between 2 groups had statistically significant difference (weighted mean difference [WMD] = -1.122, 95% confidence interval [CI] [-1.682 to -.562], P = .000], a statistical difference existed in improving dysfunction between 2 groups: (WMD = 6.039, 95% CI [2.231-.916], P = .000). EA groups had a better effect on improving activities of daily life abilities (WMD = 12.170, 95% CI [6.657-17.682], P < .00011] and better detumescence effect (WMD = -.800, 95% CI [-1.972 to -.212], P = .000] contrast to conventional rehabilitation therapy. CONCLUSIONS: This meta-analysis supports that EA has a positive effect on alleviating pain, improving limb dysfunction, and promoting activities of daily living. On account of moderate-quality random control trials and high heterogeneity, further high-quality studies are imperative to optimize the EA treatment program.

Acupuncture for symptoms in menopause transition: a randomized controlled trial.

BACKGROUND: Acupuncture has been used for women during menopause transition, but evidence is limited. OBJECTIVE: We sought to evaluate the efficacy of electroacupuncture on relieving symptoms of women during menopause transition. STUDY DESIGN: We conducted a prospective, multicenter, randomized, participant-blinded trial in China mainland. Subjects were randomized to receive 24 treatment sessions of electroacupuncture at traditional acupoints or sham electroacupuncture at nonacupoints over 8 weeks with 24 weeks' follow-up. Primary outcome was the change from baseline in the total score of Menopause Rating Scale at week 8. Secondary outcomes included the changes from baseline in the average 24-hour hot flash score, the Menopause Rating Scale subscale scores, the total score of Menopause-Specific Quality of Life Questionnaire and its subscales, and serum female hormones. All analyses were performed with a 2-sided P value of < .05 considered significant based on the intention-to-treat principle. RESULTS: A total of 360 women (180 in each group) with menopause-related symptoms during menopause transition were enrolled from June 9, 2013, through Dec 28, 2015. At week 8, the reduction from baseline in the Menopause Rating Scale total score was 6.3 (95% confidence interval, 5.0-7.7) in the electroacupuncture group and 4.5 (95% confidence interval, 3.2-5.8) in the sham electroacupuncture group with a between-group difference of 1.8 (95% confidence interval, 0.9-2.8; P = .0002), less than the minimal clinically important difference of 5 points' reduction. For secondary outcomes, the between-group differences for the decrease in the mean 24-hour hot flash score were significant at weeks 8, 20, and 32, but all were less than the minimal clinically important difference in previous reports. Interestingly, the between-group differences for the Menopause-Specific Quality of Life Questionnaire total score reduction were 5.7 at week 8, 7.1 at week 20, and 8.4 at week 32, greater than the minimal clinically important difference of 4 points. Changes from baseline in follicle-stimulating hormone, luteinizing hormone, and estradiol levels at weeks 8 and 20 (P > .05 for all), with the exception of follicle-stimulating hormone/luteinizing hormone ratios (P = .0024 at week 8 and .0499 at week 20), did not differ between groups. CONCLUSION: Among women during menopause transition, 8 weeks' electroacupuncture treatment did not seem to relieve menopausal symptoms, even though it appeared to improve their quality of life. Generalizability of the trial results may be limited by mild baseline menopausal symptoms in the included participants.

Risk factors associated with 31-day unplanned readmission in 50,912 discharged patients after stroke in China.

BACKGROUND: Unplanned readmission within 31 days of discharge after stroke is a useful indicator for monitoring quality of hospital care. We evaluated the risk factors associated with 31-day unplanned readmission of stroke patients in China. METHODS: We identified 50,912 patients from 375 hospitals in 29 provinces, municipalities or autonomous districts across China who experienced an unplanned readmission after stroke between 2015 and 2016, and extracted data from the inpatients' cover sheet data from the Medical Record Monitoring Database. Patients were grouped into readmission within 31 days or beyond for analysis. Chi-squared test was used to analyze demographic information, health system and clinical process-related factors according to the data type. Multilevel logistic modeling was used to examine the effects of patient (level 1) and hospital (level 2) characteristics on an unplanned readmission ≤31 days. RESULTS: Among 50,912 patients, 14,664 (28.8%) were readmitted within 31 days after discharge. The commonest cause of readmissions were recurrent stroke (34.8%), hypertension (22.94%), cardio/cerebrovascular disease (13.26%) and diabetes/diabetic complications (7.34%). Higher risks of unplanned readmissions were associated with diabetes (OR = 1.089, P = 0.001), use of clinical pathways (OR = 1.174, P < 0.001), and being discharged without doctor's advice (OR = 1.485, P < 0.001). Lower risks were associated with basic medical insurances (OR ranging from 0.225 to 0.716, P < 0.001) and commercial medical insurance (OR = 0.636, P = 0.021), compared to self-paying for medical services. And patients aged 50 years old and above (OR ranging from 0.650 to 0.985, P < 0.05), with haemorrhagic stroke (OR = 0.467, P < 0.001), with length of stay more than 7 days in hospital (OR ranging from 0.082 to 0.566, P < 0.001), also had lower risks. CONCLUSIONS: Age, type of stroke, medical insurance status, type of discharge, use of clinical pathways, length of hospital stay and comorbidities were the most influential factors for readmission within 31 days.

Acupuncture for Chronic Severe Functional Constipation: A Randomized Trial.

BACKGROUND: Acupuncture has been used for chronic constipation, but evidence for its effectiveness remains scarce. OBJECTIVE: To determine the efficacy of electroacupuncture (EA) for chronic severe functional constipation (CSFC). DESIGN: Randomized, parallel, sham-controlled trial. (ClinicalTrials.gov: NCT01726504). SETTING: 15 hospitals in China. PARTICIPANTS: Patients with CSFC and no serious underlying pathologic cause for constipation. INTERVENTION: 28 sessions of EA at traditional acupoints or sham EA (SA) at nonacupoints over 8 weeks. MEASUREMENTS: The primary outcome was the change from baseline in mean weekly complete spontaneous bowel movements (CSBMs) during weeks 1 to 8. Participants were followed until week 20. RESULTS: 1075 patients (536 and 539 in the EA and SA groups, respectively) were enrolled. The increase from baseline in mean weekly CSBMs during weeks 1 to 8 was 1.76 (95% CI, 1.61 to 1.89) in the EA group and 0.87 (CI, 0.73 to 0.97) in the SA group (between-group difference, 0.90 [CI, 0.74 to 1.10]; P < 0.001). The change from baseline in mean weekly CSBMs during weeks 9 to 20 was 1.96 (CI, 1.78 to 2.11) in the EA group and 0.89 (CI, 0.69 to 0.95) in the SA group (between-group difference, 1.09 [CI, 0.94 to 1.31]; P < 0.001). The proportion of patients having 3 or more mean weekly CSBMs in the EA group was 31.3% and 37.7% over the treatment and follow-up periods, respectively, compared with 12.1% and 14.1% in the SA group (P < 0.001). Acupuncture-related adverse events during treatment were infrequent in both groups, and all were mild or transient. LIMITATIONS: Longer-term follow-up was not assessed. Acupuncturists could not be blinded. CONCLUSION: Eight weeks of EA increases CSBMs and is safe for the treatment of CSFC. Additional study is warranted to evaluate a longer-term treatment and follow-up. PRIMARY FUNDING SOURCE: Ministry of Science and Technology of the People's Republic of China through the Twelfth Five-Year National Science and Technology Pillar Program.

Practitioners' perspectives on evaluating treatment outcomes in traditional Chinese medicine.

BACKGROUND: There are no generally accepted standards for evaluation of treatment outcomes in traditional Chinese medicine (TCM). Pattern differentiation and individual treatments are recognized as the most distinguishing features of TCM. Therefore, how practitioners determine curative effects is an issue worthy of research, though little has been done in this area up to this point. This study examines perceptions of the effectiveness of TCM treatments and the means of evaluating clinical outcomes from the practitioners' perspective. METHODS: Qualitative analysis of semi-structured interviews. RESULTS: A total of nine TCM practitioners from three university-affiliated hospitals and two scientific institutions participated in the interviews in August 2013. Participants reported evaluation of periodical treatment as an important part of the process of individual treatment based on pattern differentiation. Themes included (1) ways of evaluating treatment outcomes; (2) relationships between treatment outcomes and pathological transformation; and (3) distinguishing manifestations of the healing process from true adverse reactions. These considerations helped determine the optional treatment principles for further follow-up. An additional theme emerged related to the characteristics of diagnosis and treatment in TCM. CONCLUSIONS: Health professionals considered all of the following as important ways of evaluating TCM treatment outcomes: patients' input and subjective experience, physicians' intake and examination, laboratory tests and medical device measurements. Pathological conditions were determined based on all the above factors, and no single factor determined the effectiveness from the practitioners' perspectives. If the patients felt no significant beneficial effects, then it was necessary to judge the effectiveness from adverse effect. The follow-up measures were usually based on the previous treatment, and physicians' satisfaction with each phase of TCM treatment was a significant factor in the process of making further decisions.

Effect of Electroacupuncture on Urinary Leakage Among Women With Stress Urinary Incontinence: A Randomized Clinical Trial.

Importance: Electroacupuncture involving the lumbosacral region may be effective for women with stress urinary incontinence (SUI), but evidence is limited. Objective: To assess the effect of electroacupuncture vs sham electroacupuncture for women with SUI. Design, Setting, and Participants: Multicenter, randomized clinical trial conducted at 12 hospitals in China and enrolling 504 women with SUI between October 2013 and May 2015, with data collection completed in December 2015. Interventions: Participants were randomly assigned (1:1) to receive 18 sessions (over 6 weeks) of electroacupuncture involving the lumbosacral region (n = 252) or sham electroacupuncture (n = 252) with no skin penetration on sham acupoints. Main Outcomes and Measures: The primary outcome was change from baseline to week 6 in the amount of urine leakage, measured by the 1-hour pad test. Secondary outcomes included mean 72-hour urinary incontinence episodes measured by a 72-hour bladder diary (72-hour incontinence episodes). Results: Among the 504 randomized participants (mean [SD] age, 55.3 [8.4] years), 482 completed the study. Mean urine leakage at baseline was 18.4 g for the electroacupuncture group and 19.1 g for the sham electroacupuncture group. Mean 72-hour incontinence episodes were 7.9 for the electroacupuncture group and 7.7 for the sham electroacupuncture group. At week 6, the electroacupuncture group had greater decrease in mean urine leakage (-9.9 g) than the sham electroacupuncture group (-2.6 g) with a mean difference of 7.4 g (95% CI, 4.8 to 10.0; P < .001). During some time periods, the change in the mean 72-hour incontinence episodes from baseline was greater with electroacupuncture than sham electroacupuncture with between-group differences of 1.0 episode in weeks 1 to 6 (95% CI, 0.2-1.7; P = .01), 2.0 episodes in weeks 15 to 18 (95% CI, 1.3-2.7; P < .001), and 2.1 episodes in weeks 27 to 30 (95% CI, 1.3-2.8; P < .001). The incidence of treatment-related adverse events was 1.6% in the electroacupuncture group and 2.0% in the sham electroacupuncture group, and all events were classified as mild. Conclusions and Relevance: Among women with stress urinary incontinence, treatment with electroacupuncture involving the lumbosacral region, compared with sham electroacupuncture, resulted in less urine leakage after 6 weeks. Further research is needed to understand long-term efficacy and the mechanism of action of this intervention. Trial Registration: clinicaltrials.gov Identifier: NCT01784172.

Real world research: a complementary method to establish the effectiveness of acupuncture.

BACKGROUND: Acupuncture has been widely used in the management of a variety of diseases for thousands of years, and many relevant randomized controlled trials have been published. In recent years, many randomized controlled trials have provided controversial or less-than-convincing evidence that supports the efficacy of acupuncture. The clinical effectiveness of acupuncture in Western countries remains controversial. DISCUSSION: Acupuncture is a complex intervention involving needling components, specific non-needling components, and generic components. Common problems that have contributed to the equivocal findings in acupuncture randomized controlled trials were imperfections regarding acupuncture treatment and inappropriate placebo/sham controls. In addition, some inherent limitations were also present in the design and implementation of current acupuncture randomized controlled trials such as weak external validity. The current designs of randomized controlled trials of acupuncture need to be further developed. In contrast to examining efficacy and adverse reaction in a "sterilized" environment in a narrowly defined population, real world research assesses the effectiveness and safety of an intervention in a much wider population in real world practice. For this reason, real world research might be a feasible and meaningful method for acupuncture assessment. Randomized controlled trials are important in verifying the efficacy of acupuncture treatment, but the authors believe that real world research, if designed and conducted appropriately, can complement randomized controlled trials to establish the effectiveness of acupuncture. Furthermore, the integrative model that can incorporate randomized controlled trial and real world research which can complement each other and potentially provide more objective and persuasive evidence.