莫沙必利治疗餐后不适综合征和上腹痛综合征随机、双盲、安慰剂对照研究

背景：莫沙必利作为一种促胃肠动力药早已被推荐用于治疗功能性消化不良（FD），然而目前遵循罗马Ⅲ标准FD诊断分型和症状评估原则进行的莫沙必利治疗FD的临床研究尚不多见。目的：评估莫沙必利改善餐后不适综合征（PDS）和上腹痛综合征（EPS）症状的疗效和安全性。方法：病例连续选自2006年12月-2007年9月在上海仁济医院消化内科门诊就诊、符合罗马ⅢFD诊断标准中PDS和EPS诊断的患者。先经1周安慰剂筛选期，无安慰剂治疗反应者随机进入治疗流程组合A或B，给予莫沙必利5mg tid×1周或安慰剂1片tid×1周，然后进入1周药物清洗期（安慰剂1片tid），最后给予安慰剂或莫沙必利继续治疗1周。各阶段治疗前和治疗后分别行FD症状评估。结果：共纳入FD患者83例，安慰剂总有效率为19．3％，67例对安慰剂无治疗反应者进入莫沙必利疗效观察研究．随机进入治疗流程组合A或B者分别为34例和33例。与安慰剂治疗相比，莫沙必利可显著降低患者的总症状积分（14．4±6．8对1．4±1．3，P〈0．05），对PDS的餐后饱胀不适、早饱症状和EPS的上腹部疼痛和烧灼感症状均有显著治疗作用。莫沙必利对PDS和EPS治疗的总有效率分别为79．4％和60．6％，差异有统计学意义（P〈0．05）。结论：莫沙必利可明显改善FD患者的临床症状，对PDS和EPS均有治疗效果，对PDS的有效率优于EPS，是安全、有效的FD治疗药物。     

健脾消胀颗粒治疗功能性消化不良脾虚气滞证痞满临床研究

[目的]评价健脾消胀颗粒对功能性消化不良(FD)脾虚气滞证痞满患者的治疗效果和安全性.[方法]176例FD患者随机分为治疗组和对照组,治疗组100例服健脾消胀颗粒;对照组76例服多潘立酮.观察症状、舌象、脉象及钡条胃排空率.[结果]治疗组治疗后症状及胃排空率较治疗前明显好转,与对照组比较差异无统计学意义.两组均未发现不良反应.[结论]健脾消胀颗粒治疗FD脾虚气滞证痞满患者临床疗效与多潘立酮作用相近.     

铝碳酸镁咀嚼片治疗功能性消化不良上腹痛综合征的多中心、随机、开放、平行阳性对照临床研究

目的 评价铝碳酸镁咀嚼片治疗功能性消化不良上腹痛综合征的有效性及安全性,并探讨其在首次服药后的起效时间和药物经济学.方法 采用多中心、随机、开放、平行阳性对照设计.将240例功能性消化不良上腹痛综合征患者随机分为铝碳酸镁组和奥美拉唑组,各组连续服药2周.观察治疗后临床症状的改善情况和铝碳酸镁组服药后症状消失时间.同时比较两组药物的成本效应.结果 治疗1周及2周后两组患者的临床症状均得到显著改善.治疗2周后,铝碳酸镁片组总有效率为85.71%;奥美拉唑组总有效率为90.43%.两组间差异无统计学意义(P＞0.05).患者在上腹痛发生后,首次服用铝碳酸镁后上腹痛缓解的中位起效时间估计值为0.417 h.铝碳酸镁组平均每治疗1例有效患者的费用为122.29元,奥美拉唑组为242.95元.不良反应主要为腹泻、口干、腹胀、头痛和打嗝等,两组均未发生严重不良事件.结论 铝碳酸镁咀嚼片能通过多种作用途径快速缓解功能性消化不良患者上腹痛综合征的临床症状,且安全有效,其成本效应比显著优于奥美拉唑肠溶胶囊.     

莫沙必利和泮托拉唑治疗功能性消化不良的对照研究

关于促胃肠动力药和质子泵抑制剂（PPI）改善功能性消化不良（FD）症状的疗效,国内外临床试验多为安慰剂对照研究,比较促胃肠动力药与PPI疗效的研究尚少.目的：比较莫沙必利与泮托拉唑治疗餐后不适综合征（PDS）和上腹痛综合征（EPS）的疗效和安全性.方法：采用随机、非盲试验设计.连续纳入2009年12月-2010年12月宁波市第一医院符合罗马ⅢPDS和EPS诊断标准的患者,经一周安慰剂筛选后,PDS和EPS患者分别随机接受莫沙必利（5 mg tid）或泮托拉唑（40 mg qd）治疗2周.治疗前后行FD症状评估.结果：148例患者进入治疗期,其中PDS 78例,EPS 70例.莫沙必利和泮托拉唑均能显著降低FD患者的总症状积分（P〈0.05）,但两组间总症状积分下降值（14.4±6.8对13.6±5.3）和总有效率（70.3%对67.6%）差异无统计学意义.按PDS和EPS分别评估,莫沙必利组与泮托拉唑组间PDS症状（餐后饱胀不适、早饱）,EPS症状（上腹部疼痛、烧灼感）积分下降值和总有效率差异亦无统计学意义.结论：莫沙必利和泮托拉唑均能明显改善FD患者的临床症状,是安全、有效的FD治疗药物,两者对PDS和EPS的疗效无明显差异.     

气滞胃痛颗粒的临床应用3例

气滞胃痛颗粒是全国著名中医专家李乾构教授在“四逆散”基础上结合多年治疗脾胃病临床经验的结晶。全方以柴胡疏肝解郁为君药；枳壳理气和中，与柴胡同用，一升一降，共奏升清降浊之功，与具有理气之功的香附共为臣药；白芍柔肝敛阴，缓急止痛，与同样具有止痛功效的延胡索共为佐药；炙甘草一方面具有补脾益气之功，同时具有缓急止痛之效为使药。此药自问世以来疗效突出，不仅成为治疗胃痛的良药，也逐渐延伸成为各科杂症的常用药，受到临床医家的重视和患者好评，现仅举数则病案，以为例证。     

氟哌噻吨美利曲辛片联合常规治疗对功能性消化不良疗效的临床研究

目的 选择常规促胃肠动力剂、PPI治疗效果不佳的患者,给予氟哌噻吨美利曲辛片联合治疗,评价联合治疗的临床疗效.方法 病例选自2011年10月～2012年8月在北京友谊医院消化内科门诊就诊的功能性消化不良(FD)患者,根据FD临床亚型分为餐后不适综合征(PDS)和上腹痛综合征(EPS),分别给予莫沙必利和奥美拉唑治疗4周.对于治疗效果不佳的患者随机分为继续莫沙必利或奥美拉唑常规治疗组和氟哌噻吨美利曲辛片联合莫沙必利或奥美拉唑治疗组,比较常规治疗组和联合治疗组的症状改善情况和治疗有效率.结果 共纳入200名患者,男性89例,女性111例,PDS组92例,EPS组108例.PDS组莫沙必利治疗的总有效率63.0％,EPS组奥美拉唑治疗的有效率为70.3％.PDS组和EPS组中分别有34例和32例患者治疗效果不佳,随机进入治疗的第二阶段.PDS组中氟哌噻吨美利曲辛片联合治疗的总有效率为52.9％.EPS组中氟哌噻吨美利曲辛片联合治疗的总有效率为50.0％.结论 对于常规治疗效果不佳的患者联合应用氟哌噻吨美利曲辛片,可以改善患者的焦虑抑郁情绪,从而改善患者的临床症状.     

ghrelin与功能性消化不良

功能性消化不良（FD）患者尽管未发现胃肠道器质性病变,但是研究提示FD可能存在胃动力、胃排空、胃十二指肠神经调节或内脏敏感性等胃肠道功能的改变。ghrelin作为主要由胃X／A样细胞产生的一种多肽,影响胃的动力、排空和分泌功能。最近的研究表明血清中的ghrelin水平与FD有一定的关系,提示其可能在FD的发病机制中起一定的作用,值得深入的研究。     

消痞止痛方治疗脾虚气滞证功能性消化不良的随机、双盲、对照研究

目的:评价消痞止痛方治疗功能性消化不良(脾虚气滞证)的临床疗效和安全性。方法:采用多中心、随机、双盲、阳性药物和安慰剂平行对照的方法,把117例功能性消化不良患者随机分为试验组、对照组和安慰剂组,分别予消痞止痛方、香砂六君子汤和安慰剂治疗4周。主要疗效指标为总体症状应答率,次要疗效指标为总体症状积分改善率和单项症状有效率。疗效分析分为全分析集(FAS)以及符合方案集(PPS)分析。结果:试验组、对照组和安慰剂组总体症状应答率的PPS集分析分别为76.9%、42.4%和27.8%(P<0.01),FAS集分析分别为75.6%、36.8%和26.3%(P<0.01);3组总体症状改善率的PPS集分析分别为41.1%、30.1%和24.1%(P<0.05),FAS集分析分别为41.1%、25.5%和22.9%(P<0.05);试验组各单项症状有效率在FAS和PPS分析集中均显著优于安慰剂组,试验组的早饱感和上腹烧灼感的有效率在FAS分析集中显著优于对照组(P<0.05)。3组患者不良反应发生率比较差异无统计学意义(P>0.05)。结论:消痞止痛方能安全有效...     

功能性消化不良患者不同亚型与焦虑和抑郁的关系

目的观察功能性消化不良患者不同亚型与焦虑和抑郁的关系,探讨功能性消化不良患者不同亚型的发病机制,并为功能性消化不良的治疗提供依据。方法采用焦虑自评量表（SAS）及抑郁自评量表（SDS）,通过问卷的方法,对功能性消化不良餐后不适综合征和上腹疼痛综合征各40例患者进行焦虑和抑郁评分。结果餐后不适综合征组SAS平分平均为（53．72±11．21）分,SDS评分平均为（49．48±9．03）分,SAS评分明显高于SDS评分（P〈0．05）;上腹疼痛综合征组SAS评分平均为（49．03±9．04）分,SDS评分平均为（55．034-14．03）分,SDS评分明显高于SAS评分（P〈0．05）。两组间比较,餐后不适综合征组SAS评分明显高于上腹疼痛综合征组（P〈0．05）,上腹疼痛综合征组SDS评分明显高于餐后不适综合征组（P〈0．05）;两组患者各自症状评分与SAS和SDS评分呈显著正相关;两组间精神异常发生率、焦虑发生率、抑郁发生率比较无明显差异（P〉0．05）。结论两种功能性消化不良亚型与焦虑和抑郁均存在密切联系,重视焦虑和抑郁在功能性消化不良发病中的作用及临床表现,对于改善功能性消化不良患者生活质量有着重要的临床意义。     

胃黏膜肥大细胞与功能性消化不良罗马Ⅲ分型的相关性研究

目的研究胃黏膜肥大细胞(mastcell,MC)与功能性消化不良罗马Ⅲ分型的关系。方法对65例功能性消化不良(functional dyspepsia,FD)患者及30例健康志愿者胃黏膜MC进行免疫组化染色,对胃黏膜MC及其脱颗粒细胞进行计数。结果 FD组胃黏膜MC计数及其脱颗粒率较对照组明显增多,差异有显著性(P<0.05),FD分型中上腹痛(EPS)及餐后不适(EDS)两组间差异不显著,EPS组VAS疼痛评分与MC计数有相关性(r=0.657,P<0.05)。结论胃黏膜MC可能参与了FD的形成机制,并与腹痛关系密切。     

Large-scale randomized clinical study on functional dyspepsia treatment with mosapride or teprenone: Japan Mosapride Mega-Study (JMMS)

Background and Aim: Functional dyspepsia (FD) is a common condition seen in primary gastroenterology practice. The present study was conducted to compare the clinical effectiveness of mosapride and teprenone in patients with FD. Methods: Prospective clinical comparative study with random allocation of open labeled medications was performed as a multicenter trial in Japan. 1042 patients presenting symptoms of FD, either with gastric stasis (GSS) and/or epigastric pain (EPS), were enrolled. After initial endoscopic evaluation, medication either with mosapride 5 mg tid or teprenone 50 mg tid was started. Severity and frequency of GSS and EPS, health‐related quality of life (HR‐QOL) by the SF‐36 Japanese version, and patients' compliance to medication was evaluated. Results: Organic lesions were found in 90 patients (9%) in the 1027 patients examined by endoscopy. Among those without any specific lesions detected by endoscopy, gastrointestinal symptoms were resolved within one week after the endoscopy in 264 (28%) patients before initiating medication. 618 patients who remained symptomatic were randomized to medication either with mosapride (n = 311) or teprenone (n = 307). Two‐week treatment with mosapride significantly improved GSS and EPS, while teprenone tended to improve only GSS. Mosapride also improved HR‐QOL. 91% of patients treated with mosapride favored their medication, while only 52% of patients treated with teprenone favored their medication. Conclusions: Endoscopic evaluation at patients' presentation was effective to find active lesions and to improve FD symptoms. Mosapride was more favorably accepted than teprenone by the patients with sufficient safety and efficacy.     

Effect of cisapride on functional dyspepsia in patients with and without histological gastritis: A double-blind placebo-controlled trial

In the present double-blind placebo-controlled study the effect of cisapride on functional dyspepsia was evaluated in patients with and without histological gastritis. Patients with functional dyspepsia and whose symptoms persisted after a 2 week run-in period with antacid treatment were randomized to receive cisapride (10 mg) or matching placebo three times daily for 4 weeks. Symptoms of epigastric pain, bloating, nausea, belching, early satiety and heartburn were graded on a four-point scale based on patients’ feedback and diary card recording. A global response was also formulated by the investigators. One hundred and four patients entered the study and 76 completed the trial, comprising 36 patients with histological gastritis and 40 patients without gastritis. Symptom scores in both gastritis and non-gastritis groups were significantly improved by both cisapride and placebo; however, the improvement was not statistically different between the two treatment groups. Cisapride produced a good or better global response in 58% of subjects with histological gastritis and in 53% of subjects without gastritis compared with 47% and 52%, respectively, of patients on placebo; this difference was not statistically significant. Gastric histology did not influence the effect of cisapride on the symptoms of functional dyspepsia.     

Helicobacter pylori eradication versus prokinetics in the treatment of functional dyspepsia: a randomized, double-blind study

Background This randomized, double-blind study compared the efficacy of Helicobacter pylori eradication against prokinetics in H. pylori-infected functional dyspepsia patients. Methods Patients with moderately severe or severe dyspepsia fulfilling the Rome II criteria were randomized to either H. pylori eradication for 1 week and 6 weeks of placebo prokinetics or 6 weeks of prokinetics and placebo H. pylori eradication in the first week. Symptoms were assessed at baseline and at 6 and 12 months using the Glasgow Dyspepsia Severity Score (GDSS). Global response to treatment was assessed at 12 months. Results Altogether 130 patients were enrolled (H. pylori eradication, 71; prokinetics, 59). The mean baseline GDSS was 9.3 for the H. pylori eradication group and 8.9 for the prokinetic group. At 6 months, the score was 3.6 and 4.1, respectively, and it remained at 3.5 and 3.8, respectively, at 12 months. With H. pylori eradication, 31.0% had complete symptom resolution (GDSS 0 or 1) at 12 months compared with 23.7% with prokinetics (a nonsignificant difference). At 12 months, global symptomatic improvement was seen in 62.0% of the H. pylori eradication group compared with 67.8% of the prokinetics group. Conclusions Both H. pylori eradication and prokinetic therapy resulted in symptom improvement in two-thirds of dyspeptic patients at 1 year. More patients tended to achieve complete symptom relief with H. pylori eradication.     

Functional dyspepsia: past, present, and future

Functional dyspepsia (FD) is a highly prevalent gastrointestinal disorder characterized by symptoms originating from the gastroduodenal region in the absence of underlying organic disease that readily explains the symptoms. The Rome II consensus, which defined FD as the presence of unexplained pain or discomfort in the epigastrium, had a number of drawbacks, including an unjustified focus on pain, inclusion of a large number of nonspecific symptoms, and an unclear position on overlap with gastroesophageal reflux disease (GERD) and irritable bowel syndrome (IBS). The Rome III consensus redefined FD as the presence of epigastric pain or burning, postprandial fullness or early satiation in the absence of underlying organic disease. Frequent overlap with GERD and IBS is acknowledged but does not exclude a diagnosis of FD. A subgroup classification into postprandial distress syndrome and epigastric pain syndrome was proposed. Ongoing studies will clarify the impact of this subdivision on clinical management and treatment outcomes.     

Therapeutic strategies for functional dyspepsia and the introduction of the Rome III classification

Although placebo response rates in clinical trials for functional dyspepsia (FD) are more than 30%, a recent meta-analysis based on randomized controlled trials (RCTs) showed that antisecretory drugs were more or less superior to placebos. On the other hand, large-scale RCTs on the efficacy of treatment with prokinetics on FD are still needed. Indications for antibiotic eradication therapy for Helicobacter pylori-positive FD are still controversial, but there seems to be a small but significant therapeutic gain achieved with H. pylori eradication. Since preprandial and postprandial symptomatic disturbances are very important targets for FD treatment, ghrelin, a novel appetite-promoting gastrointestinal peptide that also promotes gastric motility or basal acid secretion can be expected to be a therapeutic target. In the recently published Rome III classification, FD is redefined for patients with symptoms thought to originate from the gastroduodenal region, specifically epigastric pain or burning, postprandial fullness, or early satiation, and it is divided into the subcategories postprandial distress syndrome and epigastric pain syndrome. These new criteria are of value in clinical practice, for epidemiological, pathophysiological, and clinical research, and for the development of new therapeutic strategies.     

Effect of profound acid suppression in functional dyspepsia: a double-blind,randomized, placebo-controlled trial

BACKGROUND: Functional dyspepsia (FD) is defined as persistent or recurrent pain/discomfort centred in the upper abdomen, where no structural explanation for the symptoms is found. The role of drug treatment remains controversial. The aim in this study was to evaluate the effect of omeprazole 20 mg twice daily (b.i.d) and to test methods for symptom assessment. METHODS: 197 patients fulfilling the criteria for FD were randomly allocated to double-blind treatment with omeprazole 20 mg b.i.d (n = 100) or placebo (n = 97) for 14 days. Patients with a known gastrointestinal disorder or with main symptoms indicating gastro-oesophageal reflux disease or irritable bowel syndrome were excluded. Helicobacter pylori testing and 24-h intra-oesophageal 24-h pH-metry were performed before randomization. The patients recorded dyspeptic symptoms on diary cards. RESULTS: A stringent endpoint, 'complete symptom relief on the last day of treatment', was the primary efficacy variable. For the APT cohort, this was achieved in 29.0% and 17.7% on omeprazole and placebo, respectively (95% CI of difference (11.3%): -0.4%-23.0%, P = 0.057). Similar figures in the PP cohort were 31.0% and 15.5%, respectively (95% Cl of difference (15.5%): 3.2%-27.7%, P = 0.018). The benefit of omeprazole in the PP cohort was confirmed by secondary endpoints such as, no dyspeptic symptoms on the last 2 days of treatment and overall treatment response. H. pylori status and the level of oesophageal acid exposure did not significantly influence the response to therapy. CONCLUSION: A subset of patients with FD will respond to therapy with omeprazole.