Design of Treatment Trials for Functional Gastrointestinal Disorders.

This article summarizes recent progress and regulatory guidance on design of trials to assess the efficacy of new therapies for functional gastrointestinal disorders (FGIDs). The double-masked, placebo-controlled, parallel-group design remains the accepted standard for evaluating treatment efficacy. A control group is essential, and a detailed description of the randomization process and concealed allocation method must be included in the study report. The control will most often be placebo, but for therapeutic procedures and for behavioral treatment trials, respectively, a sham procedure and control intervention with similar expectation of benefit, but lacking the treatment principle, are recommended. Investigators should be aware of, and attempt to minimize, expectancy effects (placebo, nocebo, precebo). The primary analysis should be based on the proportion of patients in each treatment arm who satisfy a treatment responder definition or a prespecified clinically meaningful change in a patient-reported outcome measure. Data analysis should use the intention-to-treat principle. Reporting of results should follow the Consolidated Standards for Reporting Trials guidelines and include secondary outcome measures to support or explain the primary outcome and an analysis of harms data. Trials should be registered in a public location before initiation and results should be published regardless of outcome.

Efficacy and Safety of Prucalopride in Chronic Constipation: An Integrated Analysis of Six Randomized, Controlled Clinical Trials.

BACKGROUND: Prucalopride, a selective, high-affinity 5-hydroxytryptamine 4 receptor agonist, stimulates gastrointestinal and colonic motility and alleviates common symptoms of chronic constipation (CC) in adults. The relative efficacy by gender has not been evaluated. AIM: To evaluate the global efficacy and safety of prucalopride 2 mg daily in men and women with CC using data from six large, randomized, controlled clinical trials. METHODS: Data were combined from six phase 3 and 4, double-blind, randomized, placebo-controlled, parallel-group trials. The primary efficacy endpoint was the percentage of patients with a mean of ≥3 spontaneous complete bowel movements (SCBMs) per week over 12 weeks of treatment. Safety was assessed throughout all the trials. RESULTS: Overall, 2484 patients (597 men; 1887 women; prucalopride, 1237; placebo, 1247) were included in the integrated efficacy analysis and 2552 patients were included in the integrated safety analysis. Significantly more patients achieved a mean of ≥3 SCBMs/week over the 12 weeks of treatment in the prucalopride group (27.8 %) than in the placebo group [13.2 %, OR 2.68 (95 % CI 2.16, 3.33), p < 0.001]. Prucalopride had a favorable safety and tolerability profile. Efficacy and safety outcomes were not significantly different between men and women. CONCLUSION: The integrated analysis demonstrates the efficacy and safety of prucalopride in the treatment of CC in men and women.

[Esophageal motility abnormalities and their impact on esophageal acid exposure in patients with gastroesophageal reflux disease].

OBJECTIVE: To identify the characteristics of esophageal motility abnormalities in patients with gastroesophageal reflux disease (GERD) and its influence on esophageal acid exposure. METHODS: Patients with typical reflux symptoms and diagnosis of reflux esophagitis (RE) or non-erosive reflux disease (NERD), and healthy subject were enrolled in this prospective controlled study. The esophageal manometry and esophageal 26 hours pH monitoring were performed. GERD patients were divided into 3 groups according to their esophageal motility abnormalities: ① low lower esophageal sphincter pressure (LESP) group, ② ineffective esophageal motivation (IEM) group, ③ IEM and low LESP group. Esophageal acid exposure was analyzed among different groups. RESULTS: A total of 27 GERD patients (15 RE, 12 NERD) and 10 healthy subjects were enrolled in this study. The esophageal motility abnormalities in GERD patients mainly presented as the decrease of LESP and distal esophageal body pressure. The proportion of 3 kinds of esophageal motility abnormalities has significant difference between RE and NERD patients (P = 0.017). In IEM and low LESP group, all patients suffered from RE, with the total number of acid exposure, the total acid exposure time and the acid exposure time in fasting higher than those in low LESP group [98.0 (63.3, 282.8) times vs 41.0 (25.0, 82.0) times, P = 0.029; 11.7% (4.1%, 30.0%) vs 2.2% (1.4%, 9.6%), P = 0.045; 2.6% (0.9%, 4.9%) vs 0.0 (0.0, 1.2%), P = 0.015]. CONCLUSIONS: Esophageal motility abnormalities in GERD patients are characterized as low LESP and IEM in distal esophagus. The coexistence of low LESP and IEM exacerbates esophageal acid exposure, which might explain the mechanism of esophageal mucosal injury in RE patients.

[Characteristics of esophageal motility in patients with non-erosive reflux disease and reflux esophagitis].

OBJECTIVE: To explore the characteristics of esophageal motility in patients with non-erosive disease (NERD) and reflux esophagitis (RE). METHODS: For this single-blind retrospective study, adult patients with typical reflux symptoms underwent esophageal manometry from January 2008 to December 2011. Their course of disease, age, gender, esophageal manometry, hiatal function and 24 h pH monitoring were analyzed by univariate and binary Logistic regression analyses. RESULTS: A total of 244 adult patients (RE = 85, NERD = 159) were enrolled into this study. Age and course of disease were significantly higher in RE group than those in NERD group ((50.7 ± 1.2) vs (46.5 ± 0.9) yrs,(4.8 ± 0.5) vs (3.4 ± 0.3) yrs, both P < 0.05) while no difference existed in gender (P > 0.05).Lower esophageal sphincter (LES) length, LES pressure, peristaltic contraction amplitude of distal esophageal body and rate of effective peristaltic contraction of distal esophageal body were significantly lower in RE group than those in NERD group ((1.91 ± 0.06) vs (2.19 ± 0.04) cm,(6.98 ± 0.31) vs (8.54 ± 0.31)mmHg,(56.76 ± 3.21) vs (75.57 ± 3.47) mmHg, 54.1% (46/85) vs 76.1% (121/159), all P < 0.05) . However, there was no inter-group difference in LES relaxation rate and upper esophageal sphincter (UES) function (both P > 0.05). Rate of hiatal hernia (HH) and hiatal flabby (HF) in RE group significantly increased versus NERD group (23.5% (20/85) vs 1.9% (3/159), 24.7% (21/85) vs 11.3% (18/159), both P < 0.05) . Positive rate of 24 h esophageal pH monitoring, reflux number and percent of reflux were significantly higher in RE group than those in NERD group (59.1% (26/44) vs 32.5% (38/117), 71.0 (13.5, 119.0) vs 25.0 (8.0, 56.0), 5.0% (0.4%, 10.9%) vs 1.1% (0.2%, 5.0%), all P < 0.05) . Binary Logistic regression analysis showed that LES length, rate of effective peristaltic contraction of distal esophageal body and HH were risk factors for RE (OR = 2.781,0.037, 21.722, 95%CI:1.057-7.313, 0.009-0.152, 5.433-86.845). CONCLUSIONS: Impaired anti-reflux barrier at esophagogastric junction and impaired clearance of esophageal body are important causative factors for RE. And abnormal anatomy in esophagogastric junction should raise alerts.

Temperature can influence gastric accommodation and sensitivity in functional dyspepsia with epigastric pain syndrome.

BACKGROUND: Functional dyspepsia-epigastric pain syndrome (FD-EPS) is characterized pathophysiologically by visceral hypersensitivity, but the effect of the temperature stimulation on gastric function has been seldom studied. AIM: The purpose of this study was to investigate the effects of liquid nutrients at different temperatures on the gastric accommodation, sensitivity, and gastric-wall compliance of healthy subjects (HS) and FD-EPS patients. METHODS: Ten FD-EPS patients (Roma III criteria) and ten HS were recruited into the study. Intragastric pressure (IGP) and gastric perfusion were measured and compared following the administration of liquid nutrients at 37 °C on day 1 and at 8 °C on day 2. RESULTS: Seven patients developed abdominal discomfort or abdominal pain after being given cold liquid nutrient. The administration of liquid nutrient at 8 °C resulted in an increase of IGP in HS (P=0.044), a significant decrease in gastric perfusion (P<0.0001), a marked increase in IGP (P=0.015), and a dramatic reduction in gastric wall compliance (P=0.012) in patients compared to the effects of liquid nutrient at 37 °C. In addition, IGP in patients was lower than that in HS at 37 °C liquid nutrient (P=0.036), and the gastric perfusion volume in patients at maximal satiety was also significantly reduced at 8 °C liquid nutrient compared with HS (P=0.017). CONCLUSIONS: Cold stimulation can increase the IGP in HS and FD-EPS patients, elevate the visceral sensitivity and reduce the gastric volume of FD-EPS patients. FD-EPS patients who are sensitive to cold may develop epigastric discomfort or pain.

[Therapeutic mechanism of diaphragm training at different periods in patients with gastroesophageal reflux disease].

OBJECTIVE: To explore the effects of postprandial diaphragm training (DT) on esophageal acid exposure, esophageal motility and proximal gastric volume at different postprandial periods in patients with gastroesophageal reflux disease (GERD). METHODS: Thirty GERD patients and 9 healthy subjects (HS) with matched demographic characteristics were enrolled from June 2005 to June 2006 at Peking Union Medical College Hospital. Esophageal manometry with a Dent sleeve catheter and simultaneous esophageal pH monitoring were recorded in a 30-min fasting period and a 120-min postprandial period. The GERD patients were divided into 3 groups: 9 patients received diaphragm training at 1(st) hour after meal (group DT1 h) and another 10 at 2(nd) hour after meal (group DT2 h) whereas no diaphragm training after meal in 11 (group NDT). Ultrasonic imaging of proximal gastric volume was undertaken at 0, 30, 60, 90 and 120 min after meal. RESULTS: (1) The percentage time with pH<4 in group DT1 h was lower than that in group NDT in the 120-min postprandial period (0.2% (0-4.1%), 6.6% (2.2%-18.2%), P < 0.05) and no significant difference of esophageal acid exposure was observed between groups DT2 h and NDT (3.7% (0.1%-17.8%), 6.6% (2.2%-18.2%), P > 0.05) . (2) Esophagogastric junction (EGJ) and crural diaphragm pressures at the 1(st) hour after meal in group DT1 h were both significantly higher than those in group NDT during diaphragm training ((44.4 ± 8.1) vs(16.2 ± 4.5) mm Hg, (38.2 ± 4.2) vs (9.8 ± 4.5) mm Hg, 1 mm Hg = 0.133 kPa, both P < 0.05). EGJ and crural diaphragm pressures at the 2(nd) hour after meal in group DT2 h were significantly higher than those in group N-DT during diaphragm training ((53.2 ± 7.5) vs (14.0 ± 3.7) mm Hg, (48.2 ± 6.3) vs (8.9 ± 2.7) mm Hg, both P < 0.05). There was no change of lower esophageal sphincter pressure (all P > 0.05). (3) After test meal, the groups DT1 h, DT2 h and N-DT had similar proximal stomach volume (all P > 0.05). CONCLUSIONS: Diaphragm training at the 1(st) hour after meal might reduce the 120-min postprandial esophageal acid exposure in GERD patients. The reduction in esophageal acid exposure may result from enhanced antireflux barrier of EGJ function. Therefore postprandial diaphragm training provides a new approach to conservative treatment of GERD.

Differences in Dietary and Lifestyle Triggers between Non-Erosive Reflux Disease and Reflux Esophagitis-A Multicenter Cross-Sectional Survey in China.

The occurrence of gastroesophageal reflux disease (GERD) and symptom onset are closely associated with diet. We aimed to compare the dietary and lifestyle triggers between non-erosive reflux disease (NERD) and reflux esophagitis (RE) in Chinese patients and to provide evidence for development of practical dietary modifications for GERD. A multicenter cross-sectional survey was conducted. A total of 396 GERD patients with typical gastroesophageal reflux symptoms who received upper endoscopy in the previous month were enrolled, including 203 cases of NERD patients and 193 cases of RE patients. All participants completed questionnaires including demographic data, reflux symptoms, previous management, dietary and lifestyle habits, triggers of reflux symptoms, psychological status, and quality of life. There were no significant differences in GERD symptom scores between NERD and RE. RE patients had a higher male proportion and smoking/drinking and overeating rates than NERD patients. In the NERD group, more patients reported that fruits, dairy products, yogurt, bean products, cold food, and carbonated beverages sometimes and often induced reflux symptoms and had more triggers compared to RE patients. The number of triggers was positively correlated to GERD symptom score and GERD-HRQL score in both NERD and RE patients. However, 74.0% of GERD patients still often consumed the triggering foods, even those foods that sometimes and often induced their reflux symptoms, which might be related to the reflux relapse after PPI withdrawal considering NERD and RE patients had similar GERD symptom severity. There were some differences in terms of dietary habits, dietary and lifestyle triggers, and related quality of life between NERD and RE, and these results may provide evidence of different approaches toward the dietary modification of NERD and RE patients.

Asian consensus report on functional dyspepsia.

BACKGROUND AND AIM: Environmental factors such as food, lifestyle and prevalence of Helicobacter pylori infection are widely different in Asian countries compared with the West, and physiological functions and genetic factors of Asians may also be different from those of Westerners. Establishing an Asian consensus for functional dyspepsia is crucial in order to attract attention to such data from Asian countries, to articulate the experience and views of Asian experts, and to provide a relevant guide on management of functional dyspepsia for primary care physicians working in Asia. METHODS: Consensus team members were selected from Asian experts and consensus development was carried out by using a modified Delphi method. Consensus teams collected published papers on functional dyspepsia especially from Asia and developed candidate consensus statements based on the generated clinical questions. At the first face-to-face meeting, each statement was reviewed and e-mail voting was done twice. At the second face-to-face meeting, final voting on each statement was done using a keypad voting system. A grade of evidence and strength of recommendation were applied to each statement according to the method of the GRADE Working Group. RESULTS: Twenty-nine consensus statements were finalized, including seven for definition and diagnosis, five for epidemiology, nine for pathophysiology, and eight for management. Algorithms for diagnosis and management of functional dyspepsia were added. CONCLUSIONS: This consensus developed by Asian experts shows distinctive features of functional dyspepsia in Asia and will provide a guide to the diagnosis and management of functional dyspepsia for Asian primary care physicians.

[Symptomatic features and psychosocial factors in patients with belching disorders].

OBJECTIVE: To explore the symptomatic features and psychosocial factors in patients with belching disorders. METHODS: At Peking Union Medical College Hospital Outpatient Clinic from September 2010 to January 2011, 21 consecutive patients with repetitive belching were profiled by symptom questionnaires, including general demographics, spectrum of symptoms, disease course, predisposing factors, previous treatment, psychosocial factors, mental status and personality traits, etc. Pearson's correlation analysis and exact probability were used. RESULTS: Among them, 20 patients fulfilled the Rome III criteria of belching disorders. There were 5 males and 15 females with an age range of (49 ± 10) years. Among them, the belching patterns were daily (n = 18), meal-related (n = 16), spontaneous (n = 15), controllable (n = 16) and symptomatic overlapping (n = 17). The most common symptoms were functional dyspepsia (FD) (n = 13) and gastroesophageal reflux disease (GERD) (n = 11). Sixteen patients experienced mental stimulation/negative events and 13 patients were related to family tension, work stress and overwork. There were 12 patients with anxiety and/or depression and 8 with neurotic personality. The number of overlapping symptoms was related to anxiety states (r = 0.47, t = 2.14, P < 0.05). But the severity of belching was unrelated to with or without depression and anxiety state (P = 0.096). CONCLUSIONS: There are a variety of clinical manifestations in patients with belching disorders. Belching disorders is often related to emotional change and environmental stress and accompanied by abnormal mental and personality characteristics. Belching may be an abnormal behavior reaction to gastrointestinal discomfort symptoms. The psychological and social factors probably play an important role in the pathogenesis of belching disorders.

[Multi-centered stratified clinical studies for psychological and sleeping status in patients with chronic constipation in China].

OBJECTIVE: To survey the emotional and sleeping status of patients with chronic constipation (CC) and analyze the relationship between psychological status and constipated symptoms. METHODS: From January 2009 to April 2010, 5 centers and 25 stratified hospitals were selected as the representatives of different regions of mainland China. The CC questionnaires including constipated symptoms, emotional and sleeping status, previous treatments and self-reported impact of constipation on health status, etc. Questionnaires were completed by well-trained physicians or investigators during face-to-face interviews. CC was diagnosed in accordance with the Rome III criteria. RESULTS: A total of 909 valid questionnaires analyzed. There were 258 males and 651 females with a mean age of (49 ± 19) years. 41.5% (377 cases) reported "tense feelings" and 38.3% (348 cases) "felt downcast" over the past 3 months. The patients feeling tense and(or) downcast "frequently" and "most of time" were around 11.3% (103 cases) and 9.4% (85 cases). And 43.8% (398 cases) patients reported sleeping disorders over the past 3 months. Regional differences existed in the comorbidities of psychological and sleeping disorders in CC patients, especially in those from tertiary hospitals. And it was the highest in Beijing area for tense feelings and downcast. The sleeping disorders were the most common in the patients from secondary hospitals, of which 66.1% (37/56) and 65.0% (39/60) were from Wuhan and Xi'an respectively. They were higher than Beijing and Guangzhou (39.7% (23/58), 29.0% (9/31), all P = 0.001). The patients from rural primary clinics suffered more sleeping disorders than those from urban primary cares (P = 0.026). About 35.0% (318 cases) and 28.4% (258 cases) patients reported their constipation was related with emotional and sleeping disorders. The comorbidities of psychological and sleeping disorders were more common in severe constipated patients than mild and moderate counterparts and resulted in more hospital visits (both P = 0.000). CONCLUSIONS: The CC patients often have the comorbidities of psychological and sleeping disorders with regional differences. The patients from the hospitals at various levels may present different spectrums of comorbidities of psychological and sleeping disorders. And the severity of CC influences the moods, sleeps and hospital visits.

[Clinical application of high resolution manometry for examining esophageal function in neonates].

OBJECTIVE: To examine the esophageal function of neonates by high resolution manometry (HRM), and to provide preliminary data for research on the esophageal function of neonates. METHODS: Esophageal HRM was performed on neonates using a solid-state pressure measurement system with 36 circumference sensors arranged at intervals of 0.75 cm, and ManoView software was used to analyze esophageal peristalsis pattern. RESULTS: Esophageal HRM was performed successfully in 11 neonates, and 126 occurrences of complete esophageal peristalsis were recorded. Complete esophageal peristalsis with pressure increase was recorded in some neonates but most neonates showed a different esophageal peristalsis pattern compared with adults. Some neonates had no relaxation of the upper esophageal sphincter (UES) when pharyngeal muscles contracted in swallowing, some neonates had multiple swallowing without esophageal peristalsis and some neonates had relatively low pressure of esophageal peristalsis. Full-term infants could have relatively low UES pressure and esophageal sphincter (LES) pressure but some preterm infants showed relatively high UES pressure and LES pressure. Longitudinal contraction of the whole esophagus and elevation of LES after swallowing were recorded in some neonates. CONCLUSIONS: Esophageal HRM is safe and tolerable for neonates. HRM shows that esophageal peristalsis after swallowing may not occur or may be incomplete in neonates. The esophageal function of neonates has not yet been developed completely, with large individual differences in esophageal peristalsis. Large sample data are needed for further analysis and research on the esophageal function of neonates.

Are bowel symptoms and psychosocial features different in irritable bowel syndrome patients with abdominal discomfort compared to abdominal pain?

BACKGROUND: The Rome IV criteria eliminated abdominal discomfort for irritable bowel syndrome (IBS), which was previously included in Rome III. There are questions as to whether IBS patients with abdominal discomfort (seen in Rome III but not Rome IV) are different from those with abdominal pain (Rome IV). AIM: To compare bowel symptoms and psychosocial features in IBS patients diagnosed with Rome III criteria with abdominal discomfort, abdominal pain, and pain & discomfort. METHODS: We studied IBS patients meeting Rome III criteria. We administered the IBS symptom questionnaire, psychological status, and IBS quality of life. Patients were classified according to the predominant abdominal symptom associated with defecation into an only pain group, only discomfort group, and pain & discomfort group. We compared bowel symptoms, extraintestinal symptoms, IBS quality of life, psychological status and healthcare-seeking behaviors, and efficacy among the three groups. Finally, we tested risk factors for symptom reporting in IBS patients. RESULTS: Of the 367 Rome III IBS patients enrolled, 33.8% (124 cases) failed to meet Rome IV criteria for an IBS diagnosis. There were no meaningful differences between the pain group (n = 233) and the discomfort group (n = 83) for the following: (1) Frequency of defecatory abdominal pain or discomfort; (2) Bowel habits; (3) Coexisting extragastrointestinal pain; (4) Comorbid anxiety and depression; and (5) IBS quality of life scores except more patients in the discomfort group reported mild symptom than the pain group (22.9% vs 9.0%). There is a significant tendency for patients to report their defecatory and non-defecatory abdominal symptom as pain alone, or discomfort alone, or pain & discomfort (all P < 0.001). CONCLUSION: IBS patients with abdominal discomfort have similar bowel symptoms and psychosocial features to those with abdominal pain. IBS symptoms manifesting abdominal pain or discomfort may primarily be due to different sensation and reporting experience.

Asian consensus on irritable bowel syndrome.

BACKGROUND AND AIMS: Many of the ideas on irritable bowel syndrome (IBS) are derived from studies conducted in Western societies. Their relevance to Asian societies has not been critically examined. Our objectives were to bring to attention important data from Asian studies, articulate the experience and views of our Asian experts, and provide a relevant guide on this poorly understood condition for doctors and scientists working in Asia. METHODS: A multinational group of physicians from Asia with special interest in IBS raised statements on IBS pertaining to symptoms, diagnosis, epidemiology, infection, pathophysiology, motility, management, and diet. A modified Delphi approach was employed to present and grade the quality of evidence, and determine the level of agreement. RESULTS: We observed that bloating and symptoms associated with meals were prominent complaints among our IBS patients. In the majority of our countries, we did not observe a female predominance. In some Asian populations, the intestinal transit times in healthy and IBS patients appear to be faster than those reported in the West. High consultation rates were observed, particularly in the more affluent countries. There was only weak evidence to support the perception that psychological distress determines health-care seeking. Dietary factors, in particular, chili consumption and the high prevalence of lactose malabsorption, were perceived to be aggravating factors, but the evidence was weak. CONCLUSIONS: This detailed compilation of studies from different parts of Asia, draws attention to Asian patients' experiences of IBS.

[Evaluation of gastric sensitivity and accommodation by simultaneous determination of intra-gastric pressure in liquid load test].

OBJECTIVE: To extensively evaluate the method of simultaneous determination of intra-gastric pressure (IGP) in liquid load test (LLT) in healthy subjects (HS) and patients with functional dyspepsia (FD). METHODS: Forty HS and 67 FD patients (Rome III criteria) were recruited. All subjects were surveyed with regards to demographic characteristics, features of FD symptom spectrum and psychological status (Zung anxiety and depression scale). And the test of simultaneous determination of IGP in LLT was conducted. Finally all the data were collected and analyzed. RESULTS: HS group: no statistical difference was found in IGP divided by gender, age and body mass index (P > 0.05). The coefficient of variation of IGP at 15.3% was less than that of maximal intake volume (MIV). Twice repeated studies showed quite similar results and the linear interclass correlation coefficient of IGP was 0.806 (P = 0.002). As to the range of normal value from HS, the proportion of gastric hypersensitivity accounted for 35.0% and impaired accommodation for 25.0%. FD group: no statistical difference was found in IGP and MIV divided by gender, age and FD symptom subtype (P > 0.05). FD patients with abnormal psychological status had a lower IGP (4.2 +/- 1.2 mm Hg vs 4.8 +/- 1.1 mm Hg, P = 0.042) and MIV (450 +/- 138 ml vs 526 +/- 121 ml, P = 0.034) than those with normal status. IGP was not related to epigastric pain, epigastric burning, postprandial fullness or early satiation (F = 1.635, P = 0.190). Early satiation was significantly related to MIV (F = 4.682, P = 0.031; correlation coefficient was -6.8, P = 0.033). No statistical difference was found in gastric compliance among HS, all FD patients, patients with hypersensitivity or impaired accommodation (P > 0.05). The test had an excellent safety and tolerability. CONCLUSIONS: The method of simultaneous determination of IGP in LLT can differentiate gastric hypersensitivity from impaired accommodation. And it has an excellent feasibility, safety and reliability.

[Multi-channel electrogastrography and autonomic nervous system function in patients with non-erosive reflux disease and reflux esophagitis].

OBJECTIVE: To investigate the gastric myoelectrical activity and autonomic nervous system (ANS) function in patients with non-erosive reflux disease (NERD) and reflux esophagitis (RE). METHODS: 42 patients with gastroesophageal reflux disease (GERD), 21 with NERD and 21 with RE, and 20 healthy volunteers (controls) underwent multi-channel electrogastrography (MEGG) and electrocardiography simultaneously for 30 min in the fasting state and 60 min after a standard test meal. The MEGG parameters included dominant frequency (DF), dominant power (DP), normal percentage of 2 - 4 times/min gastric slow waves (N%), and percentage of slow wave coupling (%SWC). ANS was determined according to power spectra analysis of heart rate variability (HRV) which was conducted by using electrocardiogram recording, including the parameters of sympathetic activity, vagal activity, and sympathovagal balance ratio so as to evaluate the ANS function. RESULTS: The DF levels of the NERD and RE patients and healthy volunteers after test meal were all significantly higher than those in fasting state (all P < 0.05). The %SWC levels of the 3 groups after test meal were all significantly lower than those when fasting (all P < 0.05), and the %SWC level of the NERD patients was significantly lower than that of the healthy volunteers in fasting state [70.5% (40.6% - 81.9%, 76.3% (66.4% - 91.4%), P < 0.05]. Test meal significantly increased the sympathetic activity and sympathovagal balance ratio of the NERD and RE patients and healthy volunteers (all P < 0.05), and the vagal activity levels of the 3 groups after test meal were all significantly lower than those when fasting (all P < 0.01). The sympathovagal balance ratio of the NERD group was significantly lower than that of RE group after meal [1.4 (0.8 - 2.5), 2.2 (1.3 - 4.4), P < 0.05]. CONCLUSION: The spatial regularity of gastric slow waves and ANS function in NERD patients are significantly different from those in RE patients.

[Value of computed tomographic colonography in analyzing mechanism of defecation in healthy subjects].

OBJECTIVE: To establish the methodology of 3-dimensional CT reconstruction of colon and rectum in evaluating anorectum and pelvic floor function. METHODS: 19 healthy volunteers, 8 males and 11 females, aged 42.8, received both defecography and 3-dimensional CT reconstruction of colon and rectum. Relevant parameters were compared between the two methods. RESULTS: (1) CT reconstruction showed that the average value of anorectal angle (ARA) was (101 +/- 13) degrees when resting, (83 +/- 12) degrees when squeezing, and (124 +/- 13) degrees when defecating;the average values of the distance between the upper part of anal canal and the pubococcygeal line (DUAC) was (10 +/- 6) mm when resting, -2(-8 - 3) mm when squeezing, and (27 +/- 11) mm when defecating; and the average value of the anal canal length (ACL) was (29 +/- 7) mm when resting, (39 +/- 8) mm when squeezing, and (22 +/- 5) mm when defecating. The change trends of ARA, DUAC, and ACL during squeezing and defecating in CT reconstruction were the same as those in defecography. (2) No significant differences were found in ARA and ACL measured by the two methods; but the DUAC values measured by defecography when resting, squeezing, and defecating were (31 +/- 11)mm, 18(-1 - 26) mm, and (50 +/- 12) mm respectively, all significantly longer those measured by CT reconstruction (all P < 0.01). (3) During defecation, the value changes of ARA was not significantly correlated between these 2 methods (r = 0.315, 0.361, both P > 0.05). CONCLUSION: 3-dimensional CT reconstruction of colon and rectum is helpful in evaluation of anorectum and pelvic floor function.

[Investigation of female chronic constipation: a multi-center cross-sectional clinical study].

OBJECTIVE: To analyze the characteristics of female chronic constipation (CC), contributing factors of severe constipation and the correlation between female CC and pelvic floor dysfunction (PFD) so as to provide references for the diagnosis and treatment of female CC. METHODS: Five hundred and sixty-one CC outpatients meeting Rome III criteria at clinics of gastroenterology from ten Beijing hospitals were recruited during March-May 2007. After data input and verification, formulated the standard of severe CC. RESULTS: The peak age of CC onset was 20 - 29 years in female patients while 60 - 69 years in male patients. F:M = 3.04:1. A wide range of CC symptoms were present and straining was the most common one (381, 76%). However, a significant difference between females and males was shown in defecation by manually pelvic floor supporting (female 26/69, 38%, male 3/20, 15% in manual assisted defecation, P < 0.05) and urinary incontinence when coughing (female 95/422, 22.5%, male 13/139, 9.4%, P < 0.01). Severity of CC, its manifestations and pelvic floor dysfunction were closely correlated with frequencies of pregnancy and delivery. CONCLUSION: Owing to anatomic features of female pelvic floor and physiological nature of pregnancy and delivery, the early onset of CC in female patients should attract sufficient attention of multi-disciplinary clinicians.

[Long-term impact on quality of life in patients with gastroesophageal reflux disease after 52-week rabeprazole treatment].

OBJECTIVE: To investigate the longitudinal changes in quality of life (QoL) for gastroesophageal reflux disease (GERD) treated with 52-week rabeprazole over a period of 2-3 years. METHODS: A multi-center, open-label and randomized 52-week rabeprazole trial was conducted in 67 eosinophilic esophagitis (EE) and 31 non-erosive reflux disease (NERD) patients. The follow-up period is 2-3 years after the treatment. Their QoL were evaluated using SF-36 Health Survey Questionnaire and GERD-HRQL scale. The results were compared with those acquired before and after a 52-week proton pump inhibitor (PPI) treatment. RESULTS: (1) Both EE and NERD patients improved significantly according to GERD-HRQL scale in scores of reflux symptoms as well as overall satisfaction (12.5 vs 3.5, 20.0 vs 14.0, both P < 0.01) versus the pre-therapy baseline. (2) Both EE and NERD patients had no significant difference in the scale of GERD-HRQL (2.0 vs 3.5, 5.0 vs 4.0, both P > 0.05) and most major domains of SF-36 questionnaire versus the post-therapy baseline (53 +/- 17 vs 61 +/- 17, t = -2.143, P = 0.035). (3) The NERD patients had a higher score of reflux symptoms than the EE patients according to the GERD-HRQL Scale (14.0 vs 3.5, Z = 2.377, P = 0.017), however there were no significant differences between NERD and EE in 8 major domains of SF-36 questionnaire (P > 0.05). CONCLUSION: Long-term and low-dose PPI treatment achieves improvement both in reflux symptoms and QoL in GERD patients and such effects last a long time. At follow-ups, the reflux symptoms of NERD patients are more severe than EE patients. However, the overall QoL has shown little differences between these two subtypes.

Gastroesophageal reflux disease and chronic cough: A possible mechanism elucidated by ambulatory pH-impedance-pressure monitoring.

BACKGROUND: The pathophysiological mechanism(s) of gastroesophageal reflux disease (GERD)-related chronic cough (CC) is unclear. We aimed to determine the mechanism of reflux-induced cough by synchronous monitoring of reflux episodes, esophageal motility, and cough. METHODS: Patients with GERD were prospectively enrolled and classified into GERD with CC (GERD-CC) and without CC (GERD) groups. Twenty-four-hour ambulatory pH-impedance-pressure monitoring was performed; the reflux patterns, esophageal motility during prolonged exposure to acid and characteristics of reflux episodes that induced coughing paroxysms were analyzed. KEY RESULTS: Thirty-one patients with GERD-CC and 47 with GERD were enrolled; all of whose monitoring results fulfilled the criteria for diagnosis of GERD. Patients with GERD-CC had higher reflux symptom scores, longer exposure to acid, higher DeMeester scores, and more frequent reflux episodes, proximal extent reflux detected by impedance, and higher percentage of strongly acidic reflux than patients in the GERD group (all P < .05). Of 63 reflux-cough episodes identified in the GERD-CC group, 74.6% of distal reflux and 67.0% of proximal reflux episodes were acidic. More patients had low pan-esophageal pressure in primary peristalsis (48.5% vs 11.8%, P = .000) and synchronous contraction in secondary peristalsis during prolonged exposure to acid in the GERD-CC than in the GERD group (63.9% vs 9.1%, P = .000). CONCLUSIONS & INFERENCES: Proximal acidic reflux and distal reflux-reflex are jointly associated with reflux-induced cough in patients with GERD. Low pan-esophageal pressure in primary peristalsis and synchronous contraction in secondary peristalsis may play important roles in GERD-associated chronic cough.