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Effect of the probiotic strain, Lactiplantibacillus plantarum P9, on chronic constipation: A randomized, double-blind, placebo-controlled study.
Ma, T, Yang, N, Xie, Y, Li, Y, Xiao, Q, Li, Q, Jin, H, Zheng, L, Sun, Z, Zuo, K, et al
Pharmacological research. 2023;191:106755
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Plain language summary
Chronic constipation (CC) is a common gastroenterological problem encountered in clinical practice, and it negatively impacts patients’ quality of life. Growing evidence indicates that the occurrence of CC is closely linked to gut dysbiosis. Several main probiotics have been used to relieve constipation. The main aim of this study was to systematically evaluate the beneficial effects of Lactiplantibacillus plantarum P9 (P9) administration on alleviating CC and impact on the host gut microbiota and its metabolites. This study was a 42-day longitudinal double-blind randomised controlled trial which enrolled a total of 181 patients with CC. Subjects were randomly assigned to the probiotic or placebo group. Subjects in P9 group received one sachet of P9 powder per day after meal. Results show that P9 administration significantly improved patients’ defecation frequency. In fact, P9 administration effectively alleviated constipation, and the symptom relief effects were linked to desired changes and interactions with different types of host microbes. Authors conclude that administering P9 could effectively relieve chronic constipation in adults and improve some aspects of their quality of life.
Expert Review
Conflicts of interest:
None
Take Home Message:
- This study suggested that P9-associated constipation symptom relief was not attributed to macroscopic changes in the host gut bacteriome and phageome
- However, results supported that taking P9 could alleviate constipation, with the symptom relief effects linked to desired changes and interactions with different types of host microbes, including the gut commensal bacteria (L. plantarum, Ruminococcus_B gnavus, Oscillospiraceae sp., Lachnospiraceae sp.) and the bacteriophage family, Herelleviridae.
Evidence Category:
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X
A: Meta-analyses, position-stands, randomized-controlled trials (RCTs)
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B: Systematic reviews including RCTs of limited number
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C: Non-randomized trials, observational studies, narrative reviews
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D: Case-reports, evidence-based clinical findings
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E: Opinion piece, other
Summary Review:
Introduction
This study investigated the effect of a specific probiotic strain in alleviating Chronic Constipation (CC).
Methods
- The study employed a 42-day randomised control trial (RTC) double-blind, placebo-controlled design, with 163 patients, (mean age =22.68 ±5.66 years for the probiotic group and 21.59 ±4.59 years for the placebo group), diagnosed with CC (Rome IV criteria)
- The male to female ratio was 15–63 and 17–68 in probiotic and placebo groups respectively
- Groups were standardised with no differences observed in baseline age, gender ratio, drug treatment, high-fibre diet and smoking between the two groups (P >0.18)
- Participants were randomly assigned to the probiotic Lactiplantibacillis plantarum P9 (n=78; 2 g per sachet, 1 ×1011 CFU/day) or the placebo (n =85; maltodextrin powder) groups.
Results
Primary outcomes: weekly mean complete spontaneous bowel movements (CSBMs):
- At 28-days CSBM was 28% higher in the P9 group (P=0.039) compared with the placebo group
- At 42-days CSBM remained significantly higher in the P9 group (P=0.026) compared with the placebo group, and increased 2-fold compared with baseline (P <0.05)
- Authors noted that the CSBM benefits were maintained even after 14 days of not taking the supplement.
Secondary outcomes: The effects of P9 supplementation on constipation-related parameters, including the weekly mean frequency of spontaneous bowel movements (SBMs) demonstrated:
- After 28-days of P9 supplementation, SBMs were 12% higher than the placebo group (P=0.039)
- No differences were observed in the weekly mean stool consistency and straining scores between groups (P>0.05).
Patients’ quality of life and psychological state, using a PAC-QOL questionnaire related to: worries and concerns (WO), physical discomfort, psychosocial discomfort, and satisfaction and found:
- At day 14 WO in the P9 group was 1.22-fold lower than those in the placebo group (P <0.05)
- No differences in the other 3 items between P9 and placebo groups (P >0.05) were observed
- Supplementation resulted in a significant change in relative abundance of the P9 genome (≥0.01%)
- However, no differences were observed in alpha diversity after P9 consumption compared with placebo.
Conclusion
- The results indicated that P9 administration alleviated patients’ constipation symptoms and improved their quality of life but did not impact on gut bacteria or phageome
- Lactiplantibacillis plantarum P9 supplementation impacted several beneficial bacteria species (e.g. (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), and reduced levels of other bacteria and phage taxa (e.g. Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae) which may be implicated in constipation relief mechanisms.
Clinical practice applications:
- In this study, the use of P9 administration significantly improved patients’ defecation frequency which could have beneficial implications for patients suffering from chronic constipation
- Probiotic effects are known to be strain- and host-specific, and based on this study P9 administration for relief of constipation needs to be taken for at least two weeks to improve aspects of patients’ quality of life and 4 weeks for improvements in constipation.
Considerations for future research:
- Future trials should include factors that impact gut motility and constipation symptoms, such as: a detailed daily diet (dietary composition, fibre content, and water intake) and physical activity scale (intensity and duration), and longer term use of P9 or comparison across strains
- The relatively small study size and short duration of this study, as well as the younger age groups included may be pertinent when considering future research.
Abstract
Chronic constipation (CC) is a common gastrointestinal condition associated with intestinal inflammation, and the condition considerably impairs patients' quality of life. We conducted a large-scale 42-day randomized, double-blind, placebo-controlled trial to investigate the effect of probiotics in alleviating CC. 163 patients diagnosed with CC (following Rome IV criteria) were randomly divided into probiotic (n = 78; received Lactiplantibacillus plantarum P9 [P9]; 1 ×1011 CFU/day) and placebo (n = 85; received placebo material) groups. Ingesting P9 significantly improved the weekly mean frequency of complete spontaneous bowel movements (CSBMs) and spontaneous bowel movements (SBMs), while significantly reducing the level of worries and concerns (WO; P < 0.05). Comparing with the placebo group, P9 group was significantly enriched in potentially beneficial bacteria (Lactiplantibacillus plantarum and Ruminococcus_B gnavus), while depriving of several bacterial and phage taxa (Oscillospiraceae sp., Lachnospiraceae sp., and Herelleviridae; P < 0.05). Interesting significant correlations were also observed between some clinical parameters and subjects' gut microbiome, including: negative correlation between Oscillospiraceae sp. and SBMs; positive correlation between WO and Oscillospiraceae sp., Lachnospiraceae sp. Additionally, P9 group had significantly (P < 0.05) more predicted gut microbial bioactive potential involved in the metabolism of amino acids (L-asparagine, L-pipecolinic acid), short-/medium-chain fatty acids (valeric acid and caprylic acid). Furthermore, several metabolites (p-cresol, methylamine, trimethylamine) related to the intestinal barrier and transit decreased significantly after P9 administration (P < 0.05). In short, the constipation relief effect of P9 intervention was accompanied by desirable changes in the fecal metagenome and metabolome. Our findings support the notion of applying probiotics in managing CC.
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Clinical efficacy of weight loss herbal intervention therapy and lifestyle modifications on obesity and its association with distinct gut microbiome: A randomized double-blind phase 2 study.
Cao, MZ, Wei, CH, Wen, MC, Song, Y, Srivastava, K, Yang, N, Shi, YM, Miao, M, Chung, D, Li, XM
Frontiers in endocrinology. 2023;:1054674
Abstract
GOALS To assess the efficacy and safety of Chinese Medicine Prescription "W-LHIT" in subjects with simple obesity, and to explore its potential mechanism of action. METHODS Thirty-seven patients aged 18 to 60 from Wei-En hospital (Weifang City, Shandong, China), participated in a double blinded, placebo-controlled study. Subjects were randomly divided into 2 groups, 18 in treatment and 19 in placebo group. The treatment group took the "W-LHIT" capsules for two months, while the control group received placebo capsules. Both groups accepted healthy lifestyle education materials. After a 2-month treatment, the placebo group transferred to open-label treatment after unblinding. RESULTS 72.22% participants in the treatment group lost more than 5% of their body weight, compared with 36.84% in the placebo group (p < 0.001). Body weight loss and body mass index reduction of the treatment group were also significantly higher than those of the placebo group (p < 0.05). These changes were accompanied by increased abundance of Akkermansia muciniphila and Enterococcus faecium, and decreased abundance of Proteobacteria in gut microbiota. Furthermore, the treatment group also showed improvement in obesity-related comorbidities such as hypertension and elevation of liver enzymes. No serious adverse reactions were found during the study period. Weight did not rebound at a follow-up visit 2 months after treatment. CONCLUSION W-LHIT significantly improved body weight and comorbid conditions without obvious adverse reaction or rebound weight gain. These effects were associated with increased abundance of probiotics in gut microbiota. W-LHIT may have a potential for treating obesity in conjunction with healthy lifestyle modifications.
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Prolonged Glycemic Adaptation Following Transition From a Low- to High-Carbohydrate Diet: A Randomized Controlled Feeding Trial.
Jansen, LT, Yang, N, Wong, JMW, Mehta, T, Allison, DB, Ludwig, DS, Ebbeling, CB
Diabetes care. 2022;(3):576-584
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Abstract
OBJECTIVE Consuming ≥150 g/day carbohydrate is recommended for 3 days before an oral glucose tolerance test (OGTT) for diabetes diagnosis. For evaluation of this recommendation, time courses of glycemic changes following transition from a very-low-carbohydrate (VLC) to high-carbohydrate diet were assessed with continuous glucose monitoring (CGM). RESEARCH DESIGN AND METHODS After achieving a weight loss target of 15% (±3%) on the run-in VLC diet, participants (18-50 years old, BMI ≥27 kg/m2) were randomly assigned for 10 weeks to one of three isoenergetic diets: VLC (5% carbohydrate and 77% fat); high carbohydrate, high starch (HC-Starch) (57% carbohydrate and 25% fat, including 20% refined grains); and high carbohydrate, high sugar (HC-Sugar) (57% carbohydrate and 25% fat, including 20% sugar). CGM was done throughout the trial (n = 64) and OGTT at start and end (n = 41). All food was prepared in a metabolic kitchen and consumed under observation. RESULTS Glucose metrics continued to decline after week 1 in the HC-Starch and HC-Sugar groups (P < 0.05) but not VLC. During weeks 2-5, fasting and 2-h glucose (millimoles per liter per week) decreased in HC-Starch (fasting -0.10, P = 0.001; 2 h -0.10, P = 0.04). During weeks 6-9, 2-h glucose decreased in HC-Starch (-0.07, P = 0.01) and fasting and 2-h glucose decreased in HC-Sugar (fasting -0.09, P = 0.001; 2 h -0.09, P = 0.003). The number of participants with abnormal glucose tolerance by OGTT remained 10 (of 16) in VLC at start and end but decreased from 17 to 9 (of 25) in both high-carbohydrate groups. CONCLUSIONS Physiological adaptation from a low- to high-carbohydrate diet may require many weeks, with implications for the accuracy of diabetes tests, interpretation of macronutrient trials, and risks of periodic planned deviations from a VLC diet.
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A Low-Carbohydrate Diet Realizes Medication Withdrawal: A Possible Opportunity for Effective Glycemic Control.
Han, Y, Cheng, B, Guo, Y, Wang, Q, Yang, N, Lin, P
Frontiers in endocrinology. 2021;12:779636
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Many studies have shown that diet restrictions can help glycemic control and reduce metabolic risks in patients with type 2 diabetes mellitus (T2DM). The aim of this study was to look at the efficacy of two diets, the LCD and the low-fat diet (LFD), on glycemic control and clinical treatment. The study was a prospective, open-label, double-arm, randomized controlled trial conducted from March 2019 to December 2020 in China. 134 T2DM participants took part and they were randomly assigned to the LCD group or the low -fat diet (LFD) group. The following were measured at the beginning and end of each intervention: weight, fasting blood glucose (FBG), postprandial 2-h blood glucose (PPG), glycosylated haemoglobin (HbA1c), antiglycemic medications, and medications for other diseases and emerging diseases. The effect of decreasing blood glucose control with the LCD is superior to that of the LFD for Chinese patients with T2DM. It also led to a lower medication effects score (MES). It can reduce body weight, BMI, and lipid-lowering agents. Strict diet control and monitoring are the keys to managing diabetes. Further larger scale studies are needed to obtain more evidence.
Abstract
Objective: Multiple studies have confirmed that diet restrictions can effectively realize glycemic control and reduce metabolic risks in patients with type 2 diabetes mellitus (T2DM). In 2018, the American Diabetes Association (ADA) and European Association for the Study of Diabetes (EASD) stated that individuals can select a low-carbohydrate diet (LCD) according to their needs and preferences. Owing to the influence of Chinese traditional eating habits, only a small portion of patients in China have achieved their blood glucose goals. As a result, the Chinese government will incur huge expenditures. Method: This study recruited 134 T2DM participants and randomly assigned them to the LCD group (n = 67) or the low-fat diet (LFD) group (n = 67). All of the patients had a fixed amount of exercise and were guided by clinicians. After a period of dietary washout, all of the patients received corresponding dietary education according to group. The follow-up time was 6 months. The indicators for anthropometry, glycemic control, and medication application parameters were collected and compared between the two groups. Results: There were 121 participants who finally entered the study. The proportions of calories from three major nutrients the participants consumed met the requirements of LCD and LFD. Compared with baseline, the pre-postdifferences of body weight, BMI, and several other indicators were significant except for dosages of insulin used in the LCD group and MES in the LFD group. After the intervention, body weight, body weight index (BMI), fasting blood glucose (FBG), postprandial 2-h blood glucose (PPG), and glycosylated hemoglobin (HbA1c) levels in the LCD group decreased significantly (p < 0.05) compared with the LFD group. The number of patients using lipid-lowering agents was significant higher in the LCD group and lower in the LFD group. However, there was no significant difference between the two groups for antihypertensive, hormone-replacement, and other agents. Conclusions: The LCD diet can decrease body weight, glycemic levels, MES, and lipid-lowering agents more than the LFD diet, thus decreasing cost burden in Chinese patients with T2DM. Strict diet control and monitoring are the keys to managing diabetes.
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Efficacy and safety of weekly paclitaxel with or without ramucirumab as second-line therapy for the treatment of advanced gastric or gastroesophageal junction adenocarcinoma (RAINBOW-Asia): a randomised, multicentre, double-blind, phase 3 trial.
Xu, RH, Zhang, Y, Pan, H, Feng, J, Zhang, T, Liu, T, Qin, Y, Qin, S, Yin, X, Liu, B, et al
The lancet. Gastroenterology & hepatology. 2021;(12):1015-1024
Abstract
BACKGROUND In the global phase 3 RAINBOW study, ramucirumab plus paclitaxel significantly improved overall survival compared with placebo plus paclitaxel in patients with advanced gastric or gastro-oesophageal junction (GEJ) adenocarcinoma. RAINBOW-Asia, a bridging study with similar design to RAINBOW, aimed to evaluate the efficacy and safety of ramucirumab plus paclitaxel for advanced gastric or GEJ adenocarcinoma in Asian, predominantly Chinese, patients. METHODS RAINBOW-Asia was a randomised, double-blind, placebo-controlled, phase 3 trial done at 32 centres in China, Malaysia, the Philippines, and Thailand. Adult patients (≥18 years) with metastatic or locally advanced, unresectable gastric or GEJ adenocarcinoma who previously received fluoropyrimidine-platinum-based chemotherapy were randomly assigned with a centralised interactive web response system in a 2:1 ratio to receive ramucirumab 8 mg/kg or placebo intravenously on days 1 and 15 plus paclitaxel 80 mg/m2 intravenously on days 1, 8, and 15 of every 28-day cycle. Randomisation was stratified by Eastern Cooperative Oncology Group performance status and presence of peritoneal metastases. The co-primary endpoints were progression-free survival and overall survival. Efficacy analyses were done in the intention-to-treat population, and safety analysis included patients who received at least one dose of study treatment. This trial is registered with ClinicalTrials.gov, NCT02898077, and has been completed. FINDINGS Between March 2, 2017, and June 30, 2020, 440 patients were randomly assigned to receive ramucirumab plus paclitaxel (n=294) or placebo plus paclitaxel (n=146). Median progression-free survival was 4·14 months (95% CI 3·71-4·30) in the ramucirumab plus paclitaxel group compared with 3·15 months (2·83-4·14) in the placebo plus paclitaxel group (hazard ratio [HR] 0·765, 95% CI 0·613-0·955, p=0·0184). Median overall survival was 8·71 months (95% CI 7·98-9·49) in the ramucirumab plus paclitaxel group and 7·92 months (6·31-9·10) in the placebo plus paclitaxel group (HR 0·963, 95% CI 0·771-1·203, p=0·7426). The most common grade 3 or worse treatment-emergent adverse events were decreased neutrophil count (159 [54%] of 293 patients in the ramucirumab plus paclitaxel group vs 56 [39%] of 145 in the placebo plus paclitaxel group), decreased white blood cell count (127 [43%] vs 42 [29%]), anaemia (46 [16%] vs 24 [17%]), hypertension (21 [7%] vs nine [6%]), and febrile neutropenia (18 [6%] vs one [<1%]). INTERPRETATION These findings, along with the results from RAINBOW, support the use of ramucirumab plus paclitaxel as second-line therapy in a predominantly Chinese population with advanced gastric or GEJ adenocarcinoma. FUNDING Eli Lilly and Company, USA. TRANSLATION For the Chinese translation of the abstract see Supplementary Materials section.
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Effects of an Omaha system-based continuing nursing program on nutritional status in patients undergoing peritoneal dialysis: a randomized controlled trial.
Zhao, X, Dong, Q, Zhao, G, Liu, X, Zhang, Y, Hui, R, Sun, X, Yang, N, Li, Z, Jin, G
International urology and nephrology. 2020;(5):981-989
Abstract
PURPOSE This study was aimed to develop and conduct an Omaha system-based continuing nursing program for chronic kidney disease (CKD) patients undergoing peritoneal dialysis (PD) and to explore its effect on patients' nutritional status. METHODS A randomized controlled trial was performed in a teaching hospital in China between June 2017 and July 2018. A total of 203 eligible patients were included and then randomly assigned to the study group (n = 101) or the control group (n = 102). In the study group, health education, treatments and procedures, case management, and surveillance based on the Omaha system were used. In the control group, only common outpatient nursing intervention was given to the patients. Changes in subjective global assessment (SGA), anthropometric measurements including body mass index (BMI), triceps skin-fold thickness (TSF), mid-arm muscle circumference (MAMC), and handgrip strength (HGS), and biochemical parameters (hemoglobin, albumin, pre-albumin, total cholesterol, and creatinine) were evaluated before the intervention and 6 months after the intervention and differences in measurements were analyzed. RESULTS After intervention, the proportion of well-nourished patients in the study group was significantly improved from 6.19 to 29.90% ([Formula: see text]2 = 18.441, P < 0.001), and after 6 months, this was higher in the study group than that in the control group (29.90% vs 9.28%, [Formula: see text]2 = 13.090, P < 0.001). Also, mean TSF, MAMC, and HGS were significantly improved in the study group and after 6 months, these levels were higher in the study group than those in the control group (P < 0.05). In addition, levels of hemoglobin, albumin, and pre-albumin in patients in the study group were significantly increased and after 6 months, these levels were higher in the study group than those in the control group (P < 0.05). CONCLUSIONS The continuing nursing program based on the Omaha system improved patients' nutritional status and should be further examined in future studies.
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Pharmacokinetic and bioequivalence study of new S-1 capsule in Chinese cancer patients.
Chen, Y, Jiang, Y, Qu, J, Wang, Q, Bai, Y, Shi, J, Shi, Y, Chen, X, Yang, N, Heng, J, et al
European journal of pharmaceutical sciences : official journal of the European Federation for Pharmaceutical Sciences. 2020;:105384
Abstract
S-1 is a multicomponent capsule containing tegafur, gimeracil, and oteracil potassium that has shown anticancer activity against numerous tumor types. However, S-1 capsules from different manufacturing companies have shown variations in pharmacokinetics and safety. Therefore, this multicenter, single-dose, randomized-sequence, open-label, two-way, self-crossover study was conducted to evaluate the bioequivalence of a newly developed generic S-1 (New Times Pharmaceutical Co., Ltd., Shandong, China) and the original brand-name S-1 capsule (Taiho Pharmaceutical Co., Ltd., Japan). Furthermore, the safety profiles of both products were compared. A total of 70 patients with 18 types cancer including breast, lung, gastric, and colorectal recruited at 5 hospitals who were randomly and alternatively administered 50 mg of the reference and test S-1 with a 7-day interval. Plasma concentrations of tegafur, 5-chloro-2,4-dihydroxypyridine (CDHP), oteracil potassium, and 5-fluorouracil were detected using liquid chromatography-tandem mass spectrometry (LC-MS/MS). Pharmacokinetic parameters, including maximum drug concentration (Cmax), time to achieve Cmax (Tmax), half-life (t1/2, area under the concentration-time curve from 0-time t (AUC0-t), and AUC from 0-infinity (AUC0-∞) were determined using non-compartmental analysis with DAS2.0 software. Bioequivalence of the reference and test S-1 was evaluated according to 90% confidence intervals (CIs) for ratios of AUC and Cmax of S-1. Adverse events were evaluated by monitoring symptoms, physical and laboratory examinations, electrocardiogram, and subject interviews. No significant difference was observed in plasma concentrations and pharmacokinetic profiles of tegafur, CDHP, oteracil potassium, or 5-fluorouracil (p > 0.05) among cancer patients treated with the reference or test S-1 formulation. The 90% CIs of Cmax, AUC0-t, and AUC0-∞ ratios were within the 80%-125% limit. The generic S-1 caused eight mild adverse events including liver dysfunction, diarrhea, nausea, fatigue, abnormal blood electrolytes, hyperglycemia, and dermal toxicity. Similarly, 18 mild adverse events were observed including dysarteriotony, diarrhea, nausea, fatigue, fever, hematotoxicity, abnormal blood electrolytes, hyperglycemia, dermal toxicity, and joint pain. There were no differences in the adverse event incidence between the two formulations. In conclusion, the newly developed generic S-1 showed similar pharmacokinetics to those of an original brand-name S-1 in cancer patients, thereby indicating bioequivalence. Furthermore, both treatments were well tolerated, suggesting that the cost-effective generic S-1 should be considered as a feasible option when treating patients.
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A comparison of the quality of hypertension management in primary care between Shanghai and Shenzhen: a cohort study of 3196 patients.
Li, H, Wei, X, Wong, MC, Yang, N, Wong, SY, Lao, X, Griffiths, SM
Medicine. 2015;(5):e455
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Abstract
Strong primary care is in urgent need for the management and control of hypertension. This study aimed to compare the quality of hypertensive care delivered by community health centers (CHCs) in Shanghai and Shenzhen. Multistage random sampling method was used to select 4 CHCs in each city as study settings. A cohort of hypertensive patients under the hypertensive management program in the CHCs was selected from the electronic information system by using a systematic random sampling method. Binary logistic regression models were constructed for comparison between the 2 cities. A total of 3196 patients' records were assessed. The proportions of hypertensive patients who received advice on smoking cessation (33.8 vs 7.7%, P < 0.001), increasing physical activity (52.4 vs 16.8%, P < 0.001), low-sodium diet (72.0 vs 64.1%, P < 0.001), and regular follow-up (37.8 vs 8.6%, P < 0.001) were higher in Shenzhen than in Shanghai. However, the drug treatment rate in Shenzhen was lower than that in Shanghai (74.2 vs 95.2%, P < 0.001). The hypertension control rate in Shenzhen was lower than that in Shanghai (76.3 vs 83.2%, P < 0.001). Better performance in the process of hypertensive care in terms of increasing physical activity advice, low-sodium diet advice, regular follow-up, and drug prescription was associated with a higher rate of hypertension control. The study indicates that primary care is effective in managing hypertension irrespective of management and operation models of CHCs in urban China. Our study suggests that improvements in the process of hypertensive care may lead to better hypertension control.
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MARCH2: comparative assessment of therapeutic effects of acarbose and metformin in newly diagnosed type 2 diabetes patients.
Wang, G, Liu, J, Yang, N, Gao, X, Fan, H, Xu, Y, Yang, W
PloS one. 2014;(8):e105698
Abstract
BACKGROUND The data of MARCH (Metformin and AcaRbose in Chinese as the initial Hypoglycaemic treatment) trial demonstrated that acarbose and metformin have similar efficacy as initial therapy for hemoglobin A1c (HbA1c) reduction in Chinese patients with newly diagnosed type 2 diabetes. We investigated whether the therapeutic efficacy was diversified under different body mass index (BMI) status. METHODS All 784 subjects were divided into normal-weight group (BMI<24 kg/m2), overweight group (BMI 24-28 kg/m2) and obese group (BMI≥28 kg/m2). Patients were assigned to 48 weeks of therapy with acarbose or metformin, respectively. The clinical trial registry number was ChiCTR-TRC-08000231. RESULTS The reduction of HbA1c levels and the proportion of patients with HbA1c of 6.5% or less were similar in the three groups after acarbose and metformin treatment. In overweight group, fasting blood glucose (FBG) after metformin treatment showed greater decline compared to acarbose group at 48 weeks [-1.73 (-1.99 to -1.46) vs. -1.37 (-1.61 to -1.12), P<0.05), however the decrease of 2 h post-challenge blood glucose (PBG) after acarbose treatment at 48 weeks was bigger compared to metformin group [-3.34 (-3.83 to-2.84) vs. -2.35 (-2.85 to -1.85), P<0.01]. Both acarbose and metformin treatment resulted in a significant decrease in waist circumference, hip circumference, weight and BMI in the three groups (all P<0.05). CONCLUSION Acarbose and metformin decreased HbA1c levels similarly regardless of BMI status of Chinese type 2 diabetic patients. Acarbose and metformin resulted in a significant and modest improvement of anthropometric parametres in different BMI status. Thus, acarbose treatment may contribute a similar effect on plasma glucose control compared to metformin, even in obesity patients. TRIAL REGISTRATION ChiCTR.org ChiCTR-TRC-08000231.
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The relative bioavailability and fasting pharmacokinetics of three formulations of olmesartan medoxomil 20-mg capsules and tablets in healthy Chinese male volunteers: An open-label, randomized-sequence, single-dose, three-way crossover study.
Li, KY, Liang, JP, Hu, BQ, Qiu, Y, Luo, CH, Jiang, Y, Lin, XP, Yang, N
Clinical therapeutics. 2010;(9):1674-80
Abstract
BACKGROUND Olmesartan medoxomil is an angiotensin II-receptor antagonist used in the treatment of hypertension. It is a prodrug and is converted to the pharmacologically active compound on de-esterification by arylesterase in the gastrointestinal tract. OBJECTIVE This study investigated the relative bioavailability and fasting pharmacokinetic properties of olmesartan after single doses of a 20-mg test tablet, a 20-mg test capsule, and a commercially available 20-mg reference tablet in healthy Chinese male volunteers. The study was conducted to satisfy Chinese State Food and Drug Administration regulatory requirements for approval of a generic formulation of olmesartan medoxomil. METHODS This study had an open-label, randomized-sequence, single-dose, 3-treatment, 3-period crossover design. Healthy volunteers were randomly assigned in a 1:1:1 ratio to receive a single 20-mg dose of the test tablet, test capsule, or reference tablet, each administered after a 12-hour overnight fast, followed by a 1-week washout period and administration of the alternate formulation. Blood samples were obtained at baseline and at 0.5, 1, 1.5,2,2.5,3,4,6,8,12,24,36, and 48 hours after dosing. Tolerability was assessed based on vital signs and laboratory values obtained before and after administration of study drug. The formulations were assumed to be bioequivalent if the 90% CIs for the log-transformed ratios of C(max), AUC(0-t), and AUC(0-∞) were within the predetermined equivalence range (70%-143% for C(max); 80%-125% for AUC(0-t) and AUC(0-∞)), as established by the Chinese State Food and Drug Administration. RESULTS Twenty-one healthy male subjects (mean age, 21 years [range, 18-25 years]; weight, 62.1 kg [range, 54.0-80.0 kg]) were enrolled in and completed the study. No period or sequence effect was observed. The mean AUC(0-∞) values for the test tablet, test capsule, and reference tablet were 3993 (1070), 3567 (850), and 3849 (872) ng/mL/h, respectively. The 90% CIs for the log-transformed ratios of test tablet to reference tablet for C(max), AUC(0-48), and AUC(0-∞) were 103.9 to 124.9, 94.0 to 111.5, and 94.4 to 111.7, respectively (all, P = NS). The corresponding 90% CIs for the log-transformed ratios of test capsule to reference tablet were 90.8 to 109.2, 84.9 to 107.9, and 85.1 to 100.7 (all, P = NS). Ten adverse events were reported during the study; 7 subjects complained of pain during blood sampling, and 3 had a blocked venous catheter. No treatment-related adverse events were reported or observed. CONCLUSIONS In this single-dose crossover study in healthy Chinese male volunteers, the test and reference formulations of olmesartan medoxomil 20-mg capsules and tablets met the regulatory criteria for assuming bioequivalence. The 3 formulations were well tolerated.