The purpose of this work was to assess the evidence for effectiveness of acupuncture (AC) treatment in gastrointestinal diseases. A systematic review of the Medline-cited literature for clinical trials was performed...The purpose of this work was to assess the evidence for effectiveness of acupuncture (AC) treatment in gastrointestinal diseases. A systematic review of the Medline-cited literature for clinical trials was performed up to May 2006. Controlled trials assessing acupuncture point stimulation for patients with gastrointestinal diseases were considered for inclusion. The search identified 18 relevant trials meeting the inclusion criteria. Two irritable bowel syndrome (IBS) trials, 1 Crohn's disease and 1 colitis ulcerosa trial had a robust random controlled trial (RCT) design. In regard to other gastrointestinal disorders, study quality was poor. In all trials, quality of life (QoL) improved significantly independently from the kind of acupuncture, real or sham. Real AC was significantly superior to sham acupuncture with regard to disease activity scores in the Crohn and Colitis trials. Efficacy of acupuncture related to QoL in IBS may be explained by unspecific effects. This is the same for QoL in inflammatory bowel diseases (IBD), whereas specific acupuncture effects may be found in clinical scores. Further trials for IBDs and in particular for all other gastrointestinal disorders would be necessary to evaluate the efficacy of acupuncture treatment. However, it must be discussed on what terms patients benefit when this harmless and obviously powerful therapy with regard to QoL is demystified by further placebo controlled trials.展开更多
Over the last several years there has been a growing interest in placebo, not only as an inert control in clinical trials, but also in the placebo effect as a group effect as well as a reaction in individual subjects....Over the last several years there has been a growing interest in placebo, not only as an inert control in clinical trials, but also in the placebo effect as a group effect as well as a reaction in individual subjects. Methodological factors such as regression to the mean and natural history of the disease play a role in the evaluation of a possible placebo effect. In this report, we discuss several factors including PavIovian conditioning, beliefs outcome, expectations, and other factors as potential mediators of the placebo response. Placebo effects are common in gastrointestinal diseases and there seems to be no clear difference between placebo effects in functional gastrointestinal diseases (functional dyspepsia and irritable bowel syndrome) and organic gastrointestinal disease (duodenal ulcer and inflammatory bowel disease).展开更多
Objoctive To evaluate the efficacy and safety of defibrase in patients with acute cerebral infarction by a large sample, multicenter, randomized, double-blind, placebo-controlled clinical trial. Mothods Patients with...Objoctive To evaluate the efficacy and safety of defibrase in patients with acute cerebral infarction by a large sample, multicenter, randomized, double-blind, placebo-controlled clinical trial. Mothods Patients with acute cerebral infarction within 12 hours of stroke onset were randomly assigned to receive either an initial intravenous infusion of defibrase 15 U plus normal saline 250 mL or 250 mL of normal saline only. Subsequent infusions of defibrase 5 U or placebo (normal saline) were given on the 3rd, 5th, 7th, and 9th day, respectively. Both groups received standard care of acute cerebral infarction. The primary efficacy outcome was functional status (Barthel Index) at 3 months after treatment. Safety outcome were bleeding events and mortality rate. Secondary outcome included Chinese Stroke Scale (CSS) score at 14 days and recurrence rate of stroke at 1 year. A total of 1053 patients were enrolled at 46 centers from September 2001 to July 2003, and 527 patients were randomly assigned to receive defibrase and 526 to receive placebo. A similar proportion of patients in both groups completed a full course of treatment. There was a significantly greater proportion of favorable functional status (Barthel Index 1≥95) in defibrase group than in placebo group at 3 months (52.2% vs. 42.8%, P 〈 0.01), and the proportion of dependent functional status (Barthel Index ≤60) was a little lower in defibrase group compared with placebo group (27.7% vs. 32.4%). These differences were more obvious among patients who were treated within 6 hours of stroke onset. Patients in defibrase group had better improvement with respect to CSS score than those in placebo group at 14 days (P 〈 0.05). Recurrence rate of stroke at 1 year was lower in the defibrase group compared with placebo group (6.2% vs. 10.1%, P = 0.053). Patients in defibrase group had higher risk of extracranial bleeding events (4.7% vs. 1.5%, P 〈 0.01 ) and a tendency of higher risk of symptomatic intracranial hemorrhage. The hemorrhage incidence was higher in patients with fibrinogen level 〈 130 mg/dL than ≥ 130 mg/dL (10.6% vs. 3.8%, P 〈 0.05). Mortality rate at 3 months were slightly higher in defibrase group than placebo group (5.9% vs. 4.2%). Conclusions The defibrase is effective to improve neurological function and function of daily living for patients with acute cerebral infarction within 12 hours of symptom onset. The efficacy was even better for acute cerebral infarction within 6 hours of onset. The increased risks of intra- and extracranial hemorrhage during defibrase administration were related to the plasma fibrinogen level.展开更多
With great interest we read the recent retrospectice study by Barta et al (1) dealing with the clinical presentation of patients with microscopic colitis. They investigated in a cohort of 53 patients with microscopi...With great interest we read the recent retrospectice study by Barta et al (1) dealing with the clinical presentation of patients with microscopic colitis. They investigated in a cohort of 53 patients with microscopic colitis (46 with collagenous colitis, 7 with lymphocytic colitis) the relationship between microscopic colitis and both constipation and diarrhea. One of their mean finding was that abdominal pain, diarrhea and constipation was a common symptom complex of patients with microscopic colitis, thus the face of microcopic colitis resembles the subgroups of irritable bowel syndrome (IBS).展开更多
AIM:To determine the efficacy of perioperative parecoxib injection on postoperative pain relief after laparoscopic cholecystectomy.METHODS: A prospective, double-blind, randomized, placebo-controlled study was conduct...AIM:To determine the efficacy of perioperative parecoxib injection on postoperative pain relief after laparoscopic cholecystectomy.METHODS: A prospective, double-blind, randomized, placebo-controlled study was conducted on 70 patients who underwent elective laparoscopic cholecystectomy under general anesthesia at Siriraj Hospital, Bangkok, from January 2006 to December 2007. Patients were randomized to receive either 20 mg parecoxib infusion 30 min before induction of anesthesia and at 12 h after the first dose (treatment group), or normal saline infusion, in the same schedule, as a placebo (control group). The degree of the postoperative pain was assessed every 3 h in the first 24 h after surgery, and then every 12 h the following day, using a visual analog scale. The consumption of analgesics was also recorded.RESULTS:There were 40 patients in the treatment group, and 30 patients in the control group. The pain scores at each time point, and analgesic consumption did not differ between the two groups. However,there were fewer patients in the treatment group than placebo group who required opioid infusion within the first 24 h (60% vs 37%, P=0.053).CONCLUSION: Perioperative administration of parecoxib provided no significant effect on postoperative pain relief after laparoscopic cholecystectomy. However, preoperative infusion 20 mg parecoxib could significantly reduce the postoperative opioid consumption.展开更多
Objective To evaluate the efficacy and safety of traditional Chinese medicine(TCM)compounds for the treatment of functional dyspepsia(FD).Methods The Pub Med,Embase,Cochrane Library,Web of Science,Chinese Biomedical D...Objective To evaluate the efficacy and safety of traditional Chinese medicine(TCM)compounds for the treatment of functional dyspepsia(FD).Methods The Pub Med,Embase,Cochrane Library,Web of Science,Chinese Biomedical Database(CBM),Wanfang Data,China National Knowledge Infrastructure(CNKI),and China Science and Technology Journal Database(VIP)were searched to collect randomized,double-blind,and placebo-controlled trials of FD treated with TCM compounds.The search duration was from the establishment of the database to March 2,2021.After two researchers independently screened the literature,extracted the data,and evaluated the bias risk included in the study,they used Rev Man 5.4 software for meta-analysis.Results A total of 23 clinical trials were included,including 2898 patients.Meta-analysis showed that the overall remission rate of FD treated with TCM compounds was significantly higher than that of placebo(73.8%vs.46.2%)[RR=1.50,95%CI(1.29,1.76),P<0.00001].Among the single symptoms,TCM compounds were superior to the placebo in improving epigastric pain[MD=﹣0.99,95%CI(﹣1.37,﹣0.61),P<0.00001],epigastric burning sensation[MD=﹣0.32,95%CI(﹣0.59,﹣0.05),P=0.02],postprandial fullness discomfort[MD=﹣1.59,95%CI(﹣1.96,﹣1.21),P<0.00001],and early satiety symptoms[MD=﹣0.93,95%CI(﹣1.32,﹣0.54),P<0.00001].Compared with the placebo,TCM compounds treatment can obviously improve TCM syndrome in patients with FD[MD=﹣5.58,95%CI(﹣7.55,﹣3.61),P<0.00001],gastric emptying rate[MD=12.22,95%CI(8.90,15.55),P<0.00001],and helped to improve patients’quality of life[MD=11.27,95%CI(0.10,22.43),P=0.05].No severe adverse events were reported between the two groups[RR=1.34,95%CI(0.91,1.96),P=0.14].Conclusion Our results showed that TCM compounds treatment could significantly alleviate FD symptoms,improve gastric emptying in FD patients,and help to improve their quality of life.No severe adverse reactions have been reported in clinical applications.Due to the limitation of the quantity and quality of the included studies,the above conclusions need to be verified by more high-quality studies.展开更多
Background and aim:Newborns with normal evolution have a biological inherited tendency for sucking.The satisfaction of this physiological necessity through excessive use of a pacifier and baby bottle in long time lead...Background and aim:Newborns with normal evolution have a biological inherited tendency for sucking.The satisfaction of this physiological necessity through excessive use of a pacifier and baby bottle in long time leads to multiple probable complications in children.Considering this important fact made the researchers to carry out the present study with the aim of systematic reviews of the disadvantages of the pacifier using on infants by using the texts studying and the writer experiences and the comments of the experts.Methods:All published studies in foreign databases during 2008-2018 were checked by using the key words of pacifier nutrition,non-exclusive nutrition,breastfeeding and human breast milk from Latin databases,such as CINHAL,PubMed,Web of Science and Scopus.Results:Fourteen studies were reviewed,aimed at analyzing the types of drawbacks to use of pacifier in infants.Finally,the types of drawbacks to using the pacifier were discussed in terms of the studies,frequency in the areas of oral and dental disorders,speech disorders,otitis media,sleep disorders,nutritional disorders and cognitive disorders.Conclusion:It seems that appropriate counseling about the way of breastfeeding should be used to replace the negative and false education of associates and informing the parents about the emotional needs of the child,as well as the emphasis on removing the pacifier from the age of one,is one of the things that can be effective in eliminating the factors involved in the aforementioned disorders.展开更多
Placebo has been reported to exert beneficial effects in patients regarding the treatment of pain. Human functional neuroimaging technology can study the intact human brain to elucidate its functional neuroanatomy and...Placebo has been reported to exert beneficial effects in patients regarding the treatment of pain. Human functional neuroimaging technology can study the intact human brain to elucidate its functional neuroanatomy and the neurobiological mechanism of the placebo effect. Blood flow measurement using functional magnetic resonance imaging and positron emission tomography (PET) has revealed that analgesia is related to decreased neural activities in pain-modulatory brain regions, such as the rostral anterior cingulate cortex (rACC), insula, thalamus, and brainstem including periaqueductal gray (PAG) and ventromedial medulla. The endogenous opioid system and its activation of g-opioid receptors are thought to mediate the observed effects of placebo. The μ-opioid receptor-selective radiotracer-labeled PET studies show that the placebo effects are accompanied by reduction in activation of opioid neural transmission in pain-sensitive brain regions, including rACC, prefrontal cortex, insula, thalamus, amygdala, nucleus accumbens (NAC) and PAG. Further PET studies with dopamine D2/D3 receptor-labeling radiotracer demonstrate that basal ganglia including NAC are related to placebo analgesic responses. NAC dopamine release induced by placebo analgesia is related to expectation of analgesia. These data indicate that the aforementioned brain regions and neurotransmitters such as endogenous opioid and dopamine systems contribute to placebo analgesia.展开更多
Aiming at the conclusion that "there is no difference in efficacy between acupuncture and sham-acupuncture" in clinical research field of migraine in foreign countries in recent years, through the discussions on the...Aiming at the conclusion that "there is no difference in efficacy between acupuncture and sham-acupuncture" in clinical research field of migraine in foreign countries in recent years, through the discussions on the definition of sham acupuncture (placebo acupuncture), the principles required to be obey in satisfactory placebo acupuncture, the definition, location, function as well as clinical results of shallow puncture, the authors probed into whether shallow puncture could be the control method of sham acupuncture (placebo acupuncture) in clinical research of acupuncture. It was demonstrated in the results that "acupuncture with minimal stimulation on skin superficial layer of meridian points or non-meridian points", the so-called control method of "sham acupuncture (placebo acupuncture)" excited holistic regulation of human body quite probably through "shallow puncture on cutaneous region of meridians" to achieve therapeutic effects. Hence, this method is not the appropriate control method of placebo acupuncture and cannot be the control method of sham acupuncture (placebo acupuncture) in clinical research of acupuncture. Therefore, it is naturally to repudiate the conclusion that "there is no difference in efficacy between acupuncture and sham acupuncture" in the research where this method is taken as the control of placebo acupuncture.展开更多
Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down ef...Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article exam- ined (a) willed determination, (b) distraction, (c) placebo, (d) hypnosis, (e) meditation, (f) qi-gong, (g) belief, and (h) emotions, respectively, in the brain function for pain modulation. In each, the operational definition, cortical processing, neuroimaging, and pain modulation were systematically deliberated. However, not all studies had featured the brain modulation processing but rather demonstrated potential effects on human pain. In our own studies on the emotional modulation on human pain, we observed that emotions could be induced from music melodies or pictures perception for reduction of tonic human pain, mainly in potentiation of the posterior alpha EEG fields, likely resulted from underneath activities of precuneous in regulation of consciousness, including pain perception. To sum, higher brain functions become the leading edge research in all sciences. How to solve the information bit of thinking and feeling in the brain can be the greatest challenge of human intelligence. Application of higher cortical modulation of human pain and suffering can lead to the progress of social humanity and civilization.展开更多
Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patien...Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical studies.This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone.Eligible patients were randomly assigned to receive chiglitazar 32 mg(n=167),chiglitazar 48 mg(n=166),or placebo(n=202)once daily.The primary endpoint was the change in glycosylated hemoglobin A_(1c)(HbA_(1c))at week 24 with superiority of chiglitazar over placebo.The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA_(1c),and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were-0.87%(95%confidential interval(CI):-1.10 to-0.65;P<0.0001)and-1.05%(95%CI:-1.29 to-0.81;P<0.0001),respectively.Secondary efficacy parameters including glycemic control,insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar groups.The overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the groups.Low incidences of mild edema and body weight gain were reported in the chiglitazar dose groups.The results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.展开更多
With the current limited drug therapy for the core symptoms of autism spectrum disorder(ASD),we herein report a randomized,double-blind,placebo-controlled trial to investigate the efficacy,safety,and potential neural ...With the current limited drug therapy for the core symptoms of autism spectrum disorder(ASD),we herein report a randomized,double-blind,placebo-controlled trial to investigate the efficacy,safety,and potential neural mechanism of bumetanide in children with ASD aged 3-6 years old.A total of 120 children were enrolled into the study and randomly assigned to either 0.5 mg bumetanide or placebo.In the final sample,119 children received at least one dose of bumetanide(59 children) or placebo(60 children) were included in the final analysis.The primary outcome was a reduction in the Childhood Autism Rating Scale(CARS) score,and the secondary outcomes were the Clinical Global Impressions Scale(CGI)-Global Improvement(CGI-I) score at 3 months and the change from baseline to 3-month in the Autism Diagnostic Observation Schedule(ADOS).Magnetic resonance spectroscopy(MRS) was used to measure y-aminobutyric acid(GABA) and glutamate neurotransmitter concentrations in the insular cortex(IC) before and after the treatment.As compared with the placebo,bumetanide treatment was significantly better in reducing the severity.No patient withdrew from the trial due to adverse events.The superiority of bumetanide to placebo in reducing insular GABA,measured using MRS,was demonstrated.The clinical improvement was associated with a decrease in insular GABA in the bumetanide group.In conclusion,this trial in a large group of young children with predominantly moderate and severe ASD demonstrated that bumetanide is safe and effective in improving the core symptoms of ASD.However,the clinical significance remains uncertain,and future multi-center clinical trials are required to replicate these findings and confirm the clinical significance using a variety of outcome measures.展开更多
Background:Patients with inflammatory bowel diseases frequently require surgery,but immunotherapies used in disease management may increase the risk of post-operative complications.We investigated frequencies of post-...Background:Patients with inflammatory bowel diseases frequently require surgery,but immunotherapies used in disease management may increase the risk of post-operative complications.We investigated frequencies of post-operative complications in patients who received vedolizumab—a gut-selective antibody approved for the treatment of moderately to severely active ulcerative colitis and Crohn’s disease—in clinical-trial and post-marketing settings.Methods:This post hoc analysis of safety data from GEMINI 1,GEMINI 2,and long-term safety studies included patients who had had colectomy or bowel surgery/resection.Data from the post-marketing Vedolizumab Global Safety Database were also analysed(data cutoff point:19 May 2016).Adverse events relating to post-operative complications were identified using Medical Dictionary for Regulatory Activities preferred terms.Results:Of 58 total surgeries in patients included in GEMINI 1 and GEMINI 2,post-operative complications were reported for 3/51 vedolizumab-treated patients(5.9%)and 1/7 placebo-treated patients(14.3%).In the long-term safety study,157/2,243 patients(7%)had colectomy or bowel surgery/resection;of these 157 patients who underwent surgery,11(7%)experienced a post-operative complication.Median time between last pre-operative vedolizumab dose and surgery was 23 days in GEMINI 1,20 days in GEMINI 2,and 39–40 days in the long-termsafety study.In the post-marketing setting,based on data covering approximately 46,978 patient-years of vedolizumab exposure,post-operative complications were reported in 19 patients.Conclusions:In clinical trials,complications of colectomy and bowel surgery/resection appeared infrequent,with minimal difference between vedolizumab and placebo.The frequency of post-operative complications in the post-marketing setting appears low.展开更多
Objective: Different kinds of sham acupuncture are widely applied in randomized controlled trials (RCTs) to explore whether acupuncture has intrinsic therapeutic effects beyond the placebo effects for certain indic...Objective: Different kinds of sham acupuncture are widely applied in randomized controlled trials (RCTs) to explore whether acupuncture has intrinsic therapeutic effects beyond the placebo effects for certain indication. To make conclusions of trials more comparable and convincing, it is of great necessity to unify the sham acupuncture procedure. Methods: RCTs of acupuncture with high quality in the recent 14 years were reviewed, and the appropriateness of the sham acupuncture procedures was assessed. Results: The sham acupuncture procedures were mainly classified into five kinds according to their administered sites, penetrating, and intervention apparatus. Conclusion: Among the sham acupuncture procedures, needling near the selected acupoints, needling at a distant non-acupoints, and non-penetrating sham acupuncture are most commonly used. Sham acupuncture performed at distant site belongs to non-meridian and non-acupoint may be an ideal control for the study of the intrinsic therapeutic effects of acupuncture. Besides, the selection of controls must focus on the design and aim of RCTs, such as non-inferiority, equivalence and superiority trials.展开更多
The aim of this article was to assess the clinical evidence for or against the blinding effect of non-penetrating sham needle as placebo needle. This systematic review included randomized controlled trials(RCTs) of ac...The aim of this article was to assess the clinical evidence for or against the blinding effect of non-penetrating sham needle as placebo needle. This systematic review included randomized controlled trials(RCTs) of acupuncture taking non-penetrating sham acupuncture as placebo needle. Systematic searches were conducted in 13 electronic databases up to July 2012: Medline, PubMed, the Cochrane Library, CINAHL, EMBASE, a Chinese medical database. All parallel or cross-over RCTs of acupuncture for the blinding effect of non-penetrating needle were chosen without language restrictions. Finally, totally 7 RCTs met the inclusion criteria. In conclusion, our systematic review and meta-analysis demonstrate that the non-penetrating needle is an effective instrument for placebo control in the acupuncture RCTs.展开更多
文摘The purpose of this work was to assess the evidence for effectiveness of acupuncture (AC) treatment in gastrointestinal diseases. A systematic review of the Medline-cited literature for clinical trials was performed up to May 2006. Controlled trials assessing acupuncture point stimulation for patients with gastrointestinal diseases were considered for inclusion. The search identified 18 relevant trials meeting the inclusion criteria. Two irritable bowel syndrome (IBS) trials, 1 Crohn's disease and 1 colitis ulcerosa trial had a robust random controlled trial (RCT) design. In regard to other gastrointestinal disorders, study quality was poor. In all trials, quality of life (QoL) improved significantly independently from the kind of acupuncture, real or sham. Real AC was significantly superior to sham acupuncture with regard to disease activity scores in the Crohn and Colitis trials. Efficacy of acupuncture related to QoL in IBS may be explained by unspecific effects. This is the same for QoL in inflammatory bowel diseases (IBD), whereas specific acupuncture effects may be found in clinical scores. Further trials for IBDs and in particular for all other gastrointestinal disorders would be necessary to evaluate the efficacy of acupuncture treatment. However, it must be discussed on what terms patients benefit when this harmless and obviously powerful therapy with regard to QoL is demystified by further placebo controlled trials.
文摘Over the last several years there has been a growing interest in placebo, not only as an inert control in clinical trials, but also in the placebo effect as a group effect as well as a reaction in individual subjects. Methodological factors such as regression to the mean and natural history of the disease play a role in the evaluation of a possible placebo effect. In this report, we discuss several factors including PavIovian conditioning, beliefs outcome, expectations, and other factors as potential mediators of the placebo response. Placebo effects are common in gastrointestinal diseases and there seems to be no clear difference between placebo effects in functional gastrointestinal diseases (functional dyspepsia and irritable bowel syndrome) and organic gastrointestinal disease (duodenal ulcer and inflammatory bowel disease).
文摘Objoctive To evaluate the efficacy and safety of defibrase in patients with acute cerebral infarction by a large sample, multicenter, randomized, double-blind, placebo-controlled clinical trial. Mothods Patients with acute cerebral infarction within 12 hours of stroke onset were randomly assigned to receive either an initial intravenous infusion of defibrase 15 U plus normal saline 250 mL or 250 mL of normal saline only. Subsequent infusions of defibrase 5 U or placebo (normal saline) were given on the 3rd, 5th, 7th, and 9th day, respectively. Both groups received standard care of acute cerebral infarction. The primary efficacy outcome was functional status (Barthel Index) at 3 months after treatment. Safety outcome were bleeding events and mortality rate. Secondary outcome included Chinese Stroke Scale (CSS) score at 14 days and recurrence rate of stroke at 1 year. A total of 1053 patients were enrolled at 46 centers from September 2001 to July 2003, and 527 patients were randomly assigned to receive defibrase and 526 to receive placebo. A similar proportion of patients in both groups completed a full course of treatment. There was a significantly greater proportion of favorable functional status (Barthel Index 1≥95) in defibrase group than in placebo group at 3 months (52.2% vs. 42.8%, P 〈 0.01), and the proportion of dependent functional status (Barthel Index ≤60) was a little lower in defibrase group compared with placebo group (27.7% vs. 32.4%). These differences were more obvious among patients who were treated within 6 hours of stroke onset. Patients in defibrase group had better improvement with respect to CSS score than those in placebo group at 14 days (P 〈 0.05). Recurrence rate of stroke at 1 year was lower in the defibrase group compared with placebo group (6.2% vs. 10.1%, P = 0.053). Patients in defibrase group had higher risk of extracranial bleeding events (4.7% vs. 1.5%, P 〈 0.01 ) and a tendency of higher risk of symptomatic intracranial hemorrhage. The hemorrhage incidence was higher in patients with fibrinogen level 〈 130 mg/dL than ≥ 130 mg/dL (10.6% vs. 3.8%, P 〈 0.05). Mortality rate at 3 months were slightly higher in defibrase group than placebo group (5.9% vs. 4.2%). Conclusions The defibrase is effective to improve neurological function and function of daily living for patients with acute cerebral infarction within 12 hours of symptom onset. The efficacy was even better for acute cerebral infarction within 6 hours of onset. The increased risks of intra- and extracranial hemorrhage during defibrase administration were related to the plasma fibrinogen level.
文摘With great interest we read the recent retrospectice study by Barta et al (1) dealing with the clinical presentation of patients with microscopic colitis. They investigated in a cohort of 53 patients with microscopic colitis (46 with collagenous colitis, 7 with lymphocytic colitis) the relationship between microscopic colitis and both constipation and diarrhea. One of their mean finding was that abdominal pain, diarrhea and constipation was a common symptom complex of patients with microscopic colitis, thus the face of microcopic colitis resembles the subgroups of irritable bowel syndrome (IBS).
基金Supported by Faculty of Medicine Siriraj Hospital Research Project Grant
文摘AIM:To determine the efficacy of perioperative parecoxib injection on postoperative pain relief after laparoscopic cholecystectomy.METHODS: A prospective, double-blind, randomized, placebo-controlled study was conducted on 70 patients who underwent elective laparoscopic cholecystectomy under general anesthesia at Siriraj Hospital, Bangkok, from January 2006 to December 2007. Patients were randomized to receive either 20 mg parecoxib infusion 30 min before induction of anesthesia and at 12 h after the first dose (treatment group), or normal saline infusion, in the same schedule, as a placebo (control group). The degree of the postoperative pain was assessed every 3 h in the first 24 h after surgery, and then every 12 h the following day, using a visual analog scale. The consumption of analgesics was also recorded.RESULTS:There were 40 patients in the treatment group, and 30 patients in the control group. The pain scores at each time point, and analgesic consumption did not differ between the two groups. However,there were fewer patients in the treatment group than placebo group who required opioid infusion within the first 24 h (60% vs 37%, P=0.053).CONCLUSION: Perioperative administration of parecoxib provided no significant effect on postoperative pain relief after laparoscopic cholecystectomy. However, preoperative infusion 20 mg parecoxib could significantly reduce the postoperative opioid consumption.
基金funding support from the National Natural Science Foundation of China Project(No.81820108033)the Project of Wangjing Hospital,China Academy of Chinese Medical Sciences(No.WJYY2020-18)。
文摘Objective To evaluate the efficacy and safety of traditional Chinese medicine(TCM)compounds for the treatment of functional dyspepsia(FD).Methods The Pub Med,Embase,Cochrane Library,Web of Science,Chinese Biomedical Database(CBM),Wanfang Data,China National Knowledge Infrastructure(CNKI),and China Science and Technology Journal Database(VIP)were searched to collect randomized,double-blind,and placebo-controlled trials of FD treated with TCM compounds.The search duration was from the establishment of the database to March 2,2021.After two researchers independently screened the literature,extracted the data,and evaluated the bias risk included in the study,they used Rev Man 5.4 software for meta-analysis.Results A total of 23 clinical trials were included,including 2898 patients.Meta-analysis showed that the overall remission rate of FD treated with TCM compounds was significantly higher than that of placebo(73.8%vs.46.2%)[RR=1.50,95%CI(1.29,1.76),P<0.00001].Among the single symptoms,TCM compounds were superior to the placebo in improving epigastric pain[MD=﹣0.99,95%CI(﹣1.37,﹣0.61),P<0.00001],epigastric burning sensation[MD=﹣0.32,95%CI(﹣0.59,﹣0.05),P=0.02],postprandial fullness discomfort[MD=﹣1.59,95%CI(﹣1.96,﹣1.21),P<0.00001],and early satiety symptoms[MD=﹣0.93,95%CI(﹣1.32,﹣0.54),P<0.00001].Compared with the placebo,TCM compounds treatment can obviously improve TCM syndrome in patients with FD[MD=﹣5.58,95%CI(﹣7.55,﹣3.61),P<0.00001],gastric emptying rate[MD=12.22,95%CI(8.90,15.55),P<0.00001],and helped to improve patients’quality of life[MD=11.27,95%CI(0.10,22.43),P=0.05].No severe adverse events were reported between the two groups[RR=1.34,95%CI(0.91,1.96),P=0.14].Conclusion Our results showed that TCM compounds treatment could significantly alleviate FD symptoms,improve gastric emptying in FD patients,and help to improve their quality of life.No severe adverse reactions have been reported in clinical applications.Due to the limitation of the quantity and quality of the included studies,the above conclusions need to be verified by more high-quality studies.
文摘Background and aim:Newborns with normal evolution have a biological inherited tendency for sucking.The satisfaction of this physiological necessity through excessive use of a pacifier and baby bottle in long time leads to multiple probable complications in children.Considering this important fact made the researchers to carry out the present study with the aim of systematic reviews of the disadvantages of the pacifier using on infants by using the texts studying and the writer experiences and the comments of the experts.Methods:All published studies in foreign databases during 2008-2018 were checked by using the key words of pacifier nutrition,non-exclusive nutrition,breastfeeding and human breast milk from Latin databases,such as CINHAL,PubMed,Web of Science and Scopus.Results:Fourteen studies were reviewed,aimed at analyzing the types of drawbacks to use of pacifier in infants.Finally,the types of drawbacks to using the pacifier were discussed in terms of the studies,frequency in the areas of oral and dental disorders,speech disorders,otitis media,sleep disorders,nutritional disorders and cognitive disorders.Conclusion:It seems that appropriate counseling about the way of breastfeeding should be used to replace the negative and false education of associates and informing the parents about the emotional needs of the child,as well as the emphasis on removing the pacifier from the age of one,is one of the things that can be effective in eliminating the factors involved in the aforementioned disorders.
文摘Placebo has been reported to exert beneficial effects in patients regarding the treatment of pain. Human functional neuroimaging technology can study the intact human brain to elucidate its functional neuroanatomy and the neurobiological mechanism of the placebo effect. Blood flow measurement using functional magnetic resonance imaging and positron emission tomography (PET) has revealed that analgesia is related to decreased neural activities in pain-modulatory brain regions, such as the rostral anterior cingulate cortex (rACC), insula, thalamus, and brainstem including periaqueductal gray (PAG) and ventromedial medulla. The endogenous opioid system and its activation of g-opioid receptors are thought to mediate the observed effects of placebo. The μ-opioid receptor-selective radiotracer-labeled PET studies show that the placebo effects are accompanied by reduction in activation of opioid neural transmission in pain-sensitive brain regions, including rACC, prefrontal cortex, insula, thalamus, amygdala, nucleus accumbens (NAC) and PAG. Further PET studies with dopamine D2/D3 receptor-labeling radiotracer demonstrate that basal ganglia including NAC are related to placebo analgesic responses. NAC dopamine release induced by placebo analgesia is related to expectation of analgesia. These data indicate that the aforementioned brain regions and neurotransmitters such as endogenous opioid and dopamine systems contribute to placebo analgesia.
基金Academy-rank research project of China Academy of Chinese Medical Sciences:ZZ 2006084
文摘Aiming at the conclusion that "there is no difference in efficacy between acupuncture and sham-acupuncture" in clinical research field of migraine in foreign countries in recent years, through the discussions on the definition of sham acupuncture (placebo acupuncture), the principles required to be obey in satisfactory placebo acupuncture, the definition, location, function as well as clinical results of shallow puncture, the authors probed into whether shallow puncture could be the control method of sham acupuncture (placebo acupuncture) in clinical research of acupuncture. It was demonstrated in the results that "acupuncture with minimal stimulation on skin superficial layer of meridian points or non-meridian points", the so-called control method of "sham acupuncture (placebo acupuncture)" excited holistic regulation of human body quite probably through "shallow puncture on cutaneous region of meridians" to achieve therapeutic effects. Hence, this method is not the appropriate control method of placebo acupuncture and cannot be the control method of sham acupuncture (placebo acupuncture) in clinical research of acupuncture. Therefore, it is naturally to repudiate the conclusion that "there is no difference in efficacy between acupuncture and sham acupuncture" in the research where this method is taken as the control of placebo acupuncture.
基金supported by the National Natural Science Foundation of China (No.30770691),Beijing Municipal Government for Advancement of Sciences,and Capital Medical University for Innovation Awards
文摘Pain perception and its genesis in the human brain have been reviewed recently. In the current article, the reports on pain modulation in the human brain were reviewed from higher cortical regulation, i.e. top-down effect, particularly studied in psychological determinants. Pain modulation can be examined by gene therapy, physical modulation, pharmacological modulation, psychological modulation, and pathophysiological modulation. In psychological modulation, this article exam- ined (a) willed determination, (b) distraction, (c) placebo, (d) hypnosis, (e) meditation, (f) qi-gong, (g) belief, and (h) emotions, respectively, in the brain function for pain modulation. In each, the operational definition, cortical processing, neuroimaging, and pain modulation were systematically deliberated. However, not all studies had featured the brain modulation processing but rather demonstrated potential effects on human pain. In our own studies on the emotional modulation on human pain, we observed that emotions could be induced from music melodies or pictures perception for reduction of tonic human pain, mainly in potentiation of the posterior alpha EEG fields, likely resulted from underneath activities of precuneous in regulation of consciousness, including pain perception. To sum, higher brain functions become the leading edge research in all sciences. How to solve the information bit of thinking and feeling in the brain can be the greatest challenge of human intelligence. Application of higher cortical modulation of human pain and suffering can lead to the progress of social humanity and civilization.
基金grants from Chinese National and Provincial Major Project for New Drug Innovation(National:2008ZX09101-002 and 2013ZX09401301Provincial:2011A080501010)Shenzhen Municipal Major Project(2010-1746)。
文摘Chiglitazar(Carfloglitazar)is a novel non-thiazolidinedione(TZD)structured peroxisome proliferatoractivated receptor(PPAR)pan-agonist that has shown promising effects on glycemic control and lipid regulation in patients with type 2 diabetes in previous clinical studies.This randomized phase 3 trial aimed to compare the efficacy and safety of chiglitazar with placebo in patients with type 2 diabetes with insufficient glycemic control by strict diet and exercise alone.Eligible patients were randomly assigned to receive chiglitazar 32 mg(n=167),chiglitazar 48 mg(n=166),or placebo(n=202)once daily.The primary endpoint was the change in glycosylated hemoglobin A_(1c)(HbA_(1c))at week 24 with superiority of chiglitazar over placebo.The results showed that both chiglitazar 32 and 48 mg resulted in significant and clinically meaningful reductions in HbA_(1c),and placebo-adjusted estimated treatment differences at week 24 for chiglitazar 32 and 48 mg were-0.87%(95%confidential interval(CI):-1.10 to-0.65;P<0.0001)and-1.05%(95%CI:-1.29 to-0.81;P<0.0001),respectively.Secondary efficacy parameters including glycemic control,insulin sensitivity and triglyceride reduction were also significantly improved in the chiglitazar groups.The overall frequency of adverse events and study discontinuation attributable to adverse events were similar among the groups.Low incidences of mild edema and body weight gain were reported in the chiglitazar dose groups.The results from this phase 3 trial demonstrated that the PPAR pan-agonist chiglitazar possesses an overall good efficacy and safety profile in patients with type 2 diabetes inadequately controlled with lifestyle interventions,thereby providing adequate supporting evidence for using this PPAR pan-agonist as a treatment option for type 2 diabetes.
基金the Shanghai Municipal Commission of Health and Family Planning(2018BR33,2017EKHWYX-02,and GWV-10.1-XK07)the Shanghai Shenkang Hospital Development Center(16CR2025B)+9 种基金the Shanghai Clinical Key Subject Construction Project(shslczdzk02902)the National Natural Science Foundation of China(81761128035,81930095,81873909,82001771,and 31860306)the Shanghai Committee of Science and Technology(17XD1403200,20ZR1404900,and 19410713500)Xinhua Hospital of Shanghai Jiao Tong University School of Medicine(2018YJRC03)the National Human Genetic Resources Sharing Service Platform(2005DKA21300)the National Key Research and Development Program of China(2018YFC0910503)111 Project(B18015)the Shanghai Municipal Science and Technology Major Project(2018SHZDZX01)Guangdong Key Project in‘‘Development of New Tools for Diagnosis and Treatment of Autism”(2018B030335001)the Science and Technology Department of Yunnan Province(202001AV070010)。
文摘With the current limited drug therapy for the core symptoms of autism spectrum disorder(ASD),we herein report a randomized,double-blind,placebo-controlled trial to investigate the efficacy,safety,and potential neural mechanism of bumetanide in children with ASD aged 3-6 years old.A total of 120 children were enrolled into the study and randomly assigned to either 0.5 mg bumetanide or placebo.In the final sample,119 children received at least one dose of bumetanide(59 children) or placebo(60 children) were included in the final analysis.The primary outcome was a reduction in the Childhood Autism Rating Scale(CARS) score,and the secondary outcomes were the Clinical Global Impressions Scale(CGI)-Global Improvement(CGI-I) score at 3 months and the change from baseline to 3-month in the Autism Diagnostic Observation Schedule(ADOS).Magnetic resonance spectroscopy(MRS) was used to measure y-aminobutyric acid(GABA) and glutamate neurotransmitter concentrations in the insular cortex(IC) before and after the treatment.As compared with the placebo,bumetanide treatment was significantly better in reducing the severity.No patient withdrew from the trial due to adverse events.The superiority of bumetanide to placebo in reducing insular GABA,measured using MRS,was demonstrated.The clinical improvement was associated with a decrease in insular GABA in the bumetanide group.In conclusion,this trial in a large group of young children with predominantly moderate and severe ASD demonstrated that bumetanide is safe and effective in improving the core symptoms of ASD.However,the clinical significance remains uncertain,and future multi-center clinical trials are required to replicate these findings and confirm the clinical significance using a variety of outcome measures.
基金This work was supported by Takeda Pharmaceutical Company Ltd.
文摘Background:Patients with inflammatory bowel diseases frequently require surgery,but immunotherapies used in disease management may increase the risk of post-operative complications.We investigated frequencies of post-operative complications in patients who received vedolizumab—a gut-selective antibody approved for the treatment of moderately to severely active ulcerative colitis and Crohn’s disease—in clinical-trial and post-marketing settings.Methods:This post hoc analysis of safety data from GEMINI 1,GEMINI 2,and long-term safety studies included patients who had had colectomy or bowel surgery/resection.Data from the post-marketing Vedolizumab Global Safety Database were also analysed(data cutoff point:19 May 2016).Adverse events relating to post-operative complications were identified using Medical Dictionary for Regulatory Activities preferred terms.Results:Of 58 total surgeries in patients included in GEMINI 1 and GEMINI 2,post-operative complications were reported for 3/51 vedolizumab-treated patients(5.9%)and 1/7 placebo-treated patients(14.3%).In the long-term safety study,157/2,243 patients(7%)had colectomy or bowel surgery/resection;of these 157 patients who underwent surgery,11(7%)experienced a post-operative complication.Median time between last pre-operative vedolizumab dose and surgery was 23 days in GEMINI 1,20 days in GEMINI 2,and 39–40 days in the long-termsafety study.In the post-marketing setting,based on data covering approximately 46,978 patient-years of vedolizumab exposure,post-operative complications were reported in 19 patients.Conclusions:In clinical trials,complications of colectomy and bowel surgery/resection appeared infrequent,with minimal difference between vedolizumab and placebo.The frequency of post-operative complications in the post-marketing setting appears low.
基金National Natural Science Foundation of China (No. 30873299, 90409014, 81001548, 30701123)Shanghai Leading Academic Discipline Project (S30304)
文摘Objective: Different kinds of sham acupuncture are widely applied in randomized controlled trials (RCTs) to explore whether acupuncture has intrinsic therapeutic effects beyond the placebo effects for certain indication. To make conclusions of trials more comparable and convincing, it is of great necessity to unify the sham acupuncture procedure. Methods: RCTs of acupuncture with high quality in the recent 14 years were reviewed, and the appropriateness of the sham acupuncture procedures was assessed. Results: The sham acupuncture procedures were mainly classified into five kinds according to their administered sites, penetrating, and intervention apparatus. Conclusion: Among the sham acupuncture procedures, needling near the selected acupoints, needling at a distant non-acupoints, and non-penetrating sham acupuncture are most commonly used. Sham acupuncture performed at distant site belongs to non-meridian and non-acupoint may be an ideal control for the study of the intrinsic therapeutic effects of acupuncture. Besides, the selection of controls must focus on the design and aim of RCTs, such as non-inferiority, equivalence and superiority trials.
基金supported by Traditional Chinese Medicine and Integrated Traditional and Western Medicine Scientific Research Project of Tianjin Municipal Administration of Traditional Chinese Medicine(No.11047)Development Plan of Changjiang Scholars and Innovative Research Team
文摘The aim of this article was to assess the clinical evidence for or against the blinding effect of non-penetrating sham needle as placebo needle. This systematic review included randomized controlled trials(RCTs) of acupuncture taking non-penetrating sham acupuncture as placebo needle. Systematic searches were conducted in 13 electronic databases up to July 2012: Medline, PubMed, the Cochrane Library, CINAHL, EMBASE, a Chinese medical database. All parallel or cross-over RCTs of acupuncture for the blinding effect of non-penetrating needle were chosen without language restrictions. Finally, totally 7 RCTs met the inclusion criteria. In conclusion, our systematic review and meta-analysis demonstrate that the non-penetrating needle is an effective instrument for placebo control in the acupuncture RCTs.