[Clinical research of acupuncture therapy combined with domperidone in treatment of diabetic gastroparesis of liver stagnation and spleen deficiency].

OBJECTIVE: To observe the clinical efficacy of shuanggu yitong acupuncture therapy (the therapy for both replenishment and unblocking) combined with domperidone on diabetic gastroparesis (DGP) of liver stagnation and spleen deficiency pattern and explore its effect mechanism. METHODS: DGP patients differentiated as liver stagnation and spleen deficiency pattern were divided into a control group (n=42) and an observation group (n=42) according to the random number table. The patients in the control group took domperidone tablets orally, 10 mg each time, 3 times a day for 28 days. In the observation group, on the base of the treatment as the control group, shuanggu yitong acupuncture therapy was applied to Baihui (GV20), Shenting (GV24), Zhongwan (CV12), bilateral Zusanli (ST36), Hegu (LI4)and Taichong (LR3), stimulated for 30 min in each treatment. Acupuncture was given once daily, 3 times a weeks for 28 days consecutively. Fasting blood glucose (FBG), 2-hour postprandial blood glucose (2 h PBG) and glycosylated hemoglobin (HbA1c) were detected before and after treatment in the patients of two groups separately. The score of symptom severity index of gastroparesis (GCSI), traditional Chinese medicine (TCM) syndrome score and gastric emptying rate were assessed in the patients of two groups. Using ELISA, radioimmunoassay and colorimentry methods, the contents of motilin in plasma, gastrin, tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß) and interferon-gamma (INF-γ) in serum, as well as the activity of superoxide dismutase (SOD), reactive oxygen species (ROS) and malondialdehyde (MDA) in the serum were determined in the two groups. The clinical curative effect was evaluated. RESULTS: After treatment, the levels of FBG, 2 h PBG and HbA1c, the scores of GCSI and TCM syndrome, the contents of motilin in plasma, gastrin, TNF-α and MDA, as well as the activity of ROS in serum were all reduced when compared with those before treatment in each group (P<0.05, P<0.01), while gastric emptying rate and SOD activity in the serum were higher than those before treatment (P<0.05, P<0.01). After treatment, the serological content of INF-γ was lower than that before treatment in the control group (P<0.05), and the contents of IL-6 and IL-1ß were reduced than those before treatment in the observation group (P<0.05). Compared with the control group, the levels of FBG, 2 h PBG and HbA1c, the scores of GCSI and TCM symptoms, the contents of motilin in plasma, gastrin, TNF-α, MDA, IL-6 and IL-1ß, and the activity of ROS in serum in the observation group were all lower significantly (P<0.05, P<0.01), while the SOD activity and gastric emptying rate in the observation group were higher than those in the control group (P<0.05, P<0.01). The total effective rate was 90.5% (38/42) in the observation group, better than the control group (73.8%, 31/42, P<0.05). CONCLUSION: Shuanggu yitong acupuncture therapy combined with domperidone remarkably relieves the clinical symptoms and improves the gastric emptying rate, effectively reduces motilin and gastrin and regulates oxidative stress and inflammatory responses in the patients with DGP of liver stagnation and spleen deficiency.

[Four Chinese patent medicines for regulating stomach for functional dyspepsia: a rapid health technology assessment].

This study evaluated and compared the efficacy, safety and economy of four Chinese patent medicines(CPMs) in the treatment of functional dyspepsia(FD) using the method of rapid health technology assessment. It aims to provide decision-makers with rapid decision-making information. The eight Chinese and English databases were comprehensively and systematically searched for the relevant clinical research. Studies were screened and evaluated. A total of 110 studies were identified, including 95 randomized controlled trials(RCTs), 7 controlled clinical trials(CCTs), 7 systematic review/Meta-analysis and 1 economic evaluation, among which 28 were Dalitong Granules, 49 were Zhizhu Kuanzhong Capsules, 3 were Biling Weitong Granules and 30 were Qizhi Weitong Granules(Tablets/Capsules). The quality of the included literature was generally low. The efficacy of four CPMs alone or combined with western medicine in the treatment of FD is different. Dalitong Granules was used to treat motility disorder in FD. Zhizhu Kuanzhong Capsules and Qizhi Weitong Granules(Tablets/Capsules) can treat FD patients with anxiety and depression. Qizhi Weitong Granules(Tablets/Capsules) were mainly used in FD for perimenopausal patients. There were no serious adverse reactions in the clinical study of four CPMs in the treatment of FD. Dalitong Granules has better effects than mosapride in the treatment of FD, but the cost is slightly higher. The cost-effectiveness ratio of Zhizhu Kuanzhong Capsules in the treatment of FD patients with anxiety and depression was lower than that of Domperidone. In terms of average daily price, Qizhi Weitong Tablets has the highest price(27.00 yuan per day), Qizhi Weitong Granules has the lowest price(5.04 yuan per day), Biling Weitong Granules has a relatively high price(15.53 yuan per day), followed by Dalitong Granules(13.03 yuan per day). The evidence of Dalitong Granules covered the efficacy, safety and economy, which is relatively complete compared with the other three drugs. It has effective potential in the treatment of motility disorder in FD. Further research in this field in the future is needed.

Preclinical Evaluation of the Effects of Trazpiroben (TAK-906), a Novel, Potent Dopamine D2/D3 Receptor Antagonist for the Management of Gastroparesis.

Current therapies for gastroparesis metoclopramide and domperidone carry risks of extrapyramidal symptoms and life-threatening cardiac arrhythmias. Trazpiroben, a novel, potent dopamine D2/D3 receptor antagonist, has low brain permeation and very low affinity for human ether-à-go-go-related gene (hERG) channel inhibition, potentially improving on safety profiles of existing therapies. Trazpiroben demonstrated the following receptor affinities: high for D2 and D3, moderate for D4, and minimal for D1 and D5 It demonstrated moderate affinity for adrenergic α 1B (α 1B) and 5-hydroxytryptamine (5HT) 2A receptors and low potential for off-target adverse events (AEs). Trazpiroben potently inhibited dopamine-activated D2L receptor activation of cognate G-proteins in human embryonic kidney 293 cell membranes and was a neutral D2L receptor antagonist. In vivo, trazpiroben dose-dependently increased prolactin release in orally dosed rat (0.1-1 mg/kg). Additionally, multiple oral doses in the rat (100 mg/kg) and dog (50 mg/kg) for 3 days produced robust plasma exposures and prolactin increases in both species. Trazpiroben inhibited retching/vomiting in the dog with apomorphine-induced emesis with a potency (0.1-1 mg/kg) like that of trazpiroben-mediated prolactin increases in rat. Oral trazpiroben (1, 10, and 30 mg/kg) did not affect rat rotarod performance, suggesting low brain penetration. Trazpiroben concentrations were low in cerebrospinal fluid versus plasma after multiple oral doses for 4 days in rat and dog. Trazpiroben weakly inhibited the hERG channel current (concentration causing half-maximal inhibition of control-specific binding of 15.6 µM), indicating little potential for disrupting cardiac rhythm. Overall, trazpiroben is a potent D2/D3 receptor antagonist designed to avoid the serious potential AEs associated with current gastroparesis therapies. SIGNIFICANCE STATEMENT: Trazpiroben is a novel, potent dopamine D2/D3 selective receptor antagonist designed to avoid adverse effects associated with the current pharmacological therapies metoclopramide and domperidone. Preclinical studies have demonstrated low brain penetration and weak affinity for the hERG channel, indicating that trazpiroben is not expected to be associated with central nervous system or cardiovascular safety issues. With these pharmacological properties, trazpiroben may represent a viable new treatment option for gastroparesis because of a potentially improved safety profile relative to existing therapies.

[Rational treatment of patients with functional dyspepsia].

Functional dyspepsia is one of the most common functional disorders of the gastrointestinal tract, which resulted from impaired motor skills, visceral hypersensitivity, increased mucosal permeability, disorders of the autonomic nervous system, etc. There is no specific therapy for this disease, which often leads to the irrational use of various groups of drugs. Drug therapy is recommended only during periods of symptoms. The main options of pharmacotherapy include the use of proton pump inhibitors, phytotherapeutic drugs, eradication therapy of Helicobacter pylori. Against the background of possible motor disorders, prokinetics are also one of the possible treatment options, but cisapride has long been withdrawn from sale due to cardiotoxicity, the use of domperidone and metoclopramide is limited due to side effects, especially with long-term therapy, so currently the only prokinetic that can be used in everyday clinical practice is itopride. In refractory cases, tricyclic antidepressants and psychotherapeutic approaches are another effective treatment option.

Influence of domperidone supplementation on short-term changes in C-reactive protein and paraoxonase-1 in dogs with leishmaniasis undergoing meglumine antimoniate and allopurinol therapy.

BACKGROUND: C-reactive protein (CRP) and paraoxonase 1 (PON1) might increase and decrease in canine leishmaniasis (CanL), , and both can rapidly normalize after therapy. Recently, supplementation of domperidone with conventional therapy , increasing the activity of cells involved in acute phase responses in vitro. This combined therapy has been recommended to treat mild forms of CanL; however, no studies have investigated the effects of domperidone supplementation on early CRP or PON1 changes in dogs with CanL. OBJECTIVES: The aim of this study was to evaluate whether domperidone, added to conventional treatments, modifies CRP concentration and PON1 activity kinetics in CanL dogs responsive to conventional therapy. METHODS: Serum CRP concentrations and PON1 activities were measured in dogs with mild CanL before (t-0) and 3 (t-1), 7 (t-2), 14 (t-3), and 21 (t-4) days after treatment with N-methylglucamine antimoniate and allopurinol alone (n = 18) or combined with domperidone (n = 18). RESULTS: C-reactive protein concentrations increased at t-1 in the domperidone group, especially when the CRP concentration at t-0 was normal. However, the concentrations normalized at t-4 in 18/18 dogs compared with 14/18 dogs not receiving domperidone. The median PON1 activity decreased at t-1 in the domperidone group, and this decrease was more significant in dogs with normal PON1 activity at t-0. CONCLUSIONS: Based on these results, transient increases in CRP concentrations or decreases in PON1 activities after domperidone administration should not be erroneously interpreted as signs of a worsening disease process.

Dopamine receptor antagonists as potential therapeutic agents for ADPKD.

Autosomal dominant polycystic kidney disease (ADPKD) is caused mostly by mutations in polycystin-1 or polycystin-2. Fluid flow leads to polycystin-dependent calcium influx and nuclear export of histone deacetylase 5 (HDAC5), which facilitates the maintenance of renal epithelial architecture by de-repression of MEF2C target genes. Here, we screened a small-molecule library to find drugs that promotes nuclear export of HDAC5. We found that dopamine receptor antagonists, domperidone and loxapine succinate, stimulate export of HDAC5, even in Pkd1-/-cells. Domperidone targets Drd3 receptor to modulate the phosphorylation of HDAC5. Domperidone treatment increases HDAC5 phosphorylation likely by reducing protein phosphatase 2A (PP2A) activity, thus shifting the equilibrium towards HDAC5-P and export from the nucleus. Treating Pkd1-/-mice with domperidone showed significantly reduced cystic growth and cell proliferation. Further, treated mice displayed a reduction in glomerular cyst and increased body weight and activity. These results suggest that HDAC5 nucleocytoplasmic shuttling may be modulated to impede disease progression in ADPKD and uncovers an unexpected role for a class of dopamine receptors in renal epithelial morphogenesis.

Acupuncture for symptomatic gastroparesis.

BACKGROUND: Gastroparesis, a state of delayed gastric emptying in the absence of mechanical obstruction of the stomach, has a substantial impact on people's daily function and quality of life when symptomatic. Current treatment options are based on limited evidence of benefits. Acupuncture is widely used to manage gastrointestinal disorders, although its role in people with symptomatic gastroparesis is unclear. We therefore undertook a systematic review of the evidence. OBJECTIVES: To assess the benefits and harms of acupuncture, in comparison with no treatment, sham acupuncture, conventional medicine, standard care, or other non-pharmacological active interventions for symptom management in people with gastroparesis. SEARCH METHODS: On 26 March 2018, we searched the Cochrane Neuromuscular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL Plus, PsycINFO, AMED, Korean medical databases (including Korean Studies Information, DBPIA, Korea Institute of Science and Technology Information, Research Information Centre for Health Database, KoreaMed, and the National Assembly Library), and Chinese databases (including the China Academic Journal). We also searched two clinical trials registries for ongoing trials. We imposed no language limitations. SELECTION CRITERIA: We selected all randomised controlled trials comparing the penetrating type of acupuncture with no treatment, sham acupuncture, conventional medicine, standard care, and other non-pharmacological active interventions for people with symptomatic gastroparesis of any aetiology (i.e. surgical, diabetic, or idiopathic). Trials reporting outcomes at least four weeks from baseline (short-term outcomes) were eligible. We defined long-term outcomes as those measured after 12 weeks from baseline. The primary outcome was improvement of gastroparesis symptoms in the short term. Secondary outcomes were: improvement of symptoms measured after three months, change in the rate of gastric emptying, quality of life, use of medication, and adverse events in the short and long term. DATA COLLECTION AND ANALYSIS: Two review authors independently selected eligible trials based on predefined selection criteria. Two review authors independently extracted data and evaluated the risk of bias. The review authors contacted investigators to obtain missing information wherever possible. MAIN RESULTS: We included 32 studies that involved a total of 2601 participants. Acupuncture was either manually stimulated (24 studies) or electrically stimulated (8 studies). The aetiology of gastroparesis was diabetes (31 studies) or surgery (1 study). All studies provided data on the proportion of people with symptoms 'improved', although the definition or categorisation of improvement varied among the studies. Most measured only short-term outcomes (28 studies), and only one study employed validated instruments to assess subjective changes in symptoms or reported data on quality of life or the use of medication. Reporting of harm was incomplete; minor adverse events were reported in only seven trials. Most studies had unclear risk of bias in terms of allocation concealment (29/32), outcome assessor blinding (31/32) and selective reporting (31/32), as well as high risk of bias in terms of participant/personnel blinding (31/32). Acupuncture was compared with sham acupuncture (needling on non-acupuncture points), three different types of gastrokinetic drugs (domperidone, mosapride, cisapride), and a histamine H2 receptor antagonist (cimetidine).There was low-certainty evidence that symptom scores of participants receiving acupuncture did not differ from those of participants receiving sham acupuncture at three months when measured by a validated scale.There was very low-certainty evidence that a greater proportion of participants receiving acupuncture had 'improved' symptoms in the short term compared to participants who received gastrokinetic medication (4 to 12 weeks) (12 studies; 963 participants; risk ratio (RR) 1.25; 95% confidence interval (CI) 1.17 to 1.33, I² = 8%). Short-term improvement in overall symptom scores favouring acupuncture was also reported in five studies with considerable heterogeneity.Acupuncture in combination with other treatments, including gastrokinetics, non-gastrokinetics and routine care, was compared with the same treatment alone. There was very low-certainty evidence in favour of acupuncture for the proportion of participants with 'improved' symptoms in the short term (4 to 12 weeks) (17 studies; 1404 participants; RR 1.22; 95% CI 1.16 to 1.28; I² = 0%). Short-term improvement in overall symptom scores, favouring acupuncture, were also reported (two studies, 132 participants; MD -1.96, 95% CI -2.42 to -1.50; I² = 0%).Seven studies described adverse events, including minor bleeding and hematoma, dizziness, xerostomia, loose stool, diarrhoea, abdominal pain, skin rash and fatigue. The rest of the trials did not report whether adverse events occurred.Subgroup analyses revealed that short-term benefits in terms of the proportion of people with 'improved' symptoms did not differ according to the type of acupuncture stimulation (i.e. manual or electrical). The sensitivity analysis revealed that use of a valid method of random sequence generation, and the use of objective measurements of gastric emptying, did not alter the overall effect estimate in terms of the proportion of people with 'improved' symptoms. The asymmetric funnel plot suggests small study effects and publication bias towards positive reporting. AUTHORS' CONCLUSIONS: There is very low-certainty evidence for a short-term benefit with acupuncture alone or acupuncture combined with gastrokinetic drugs compared with the drug alone, in terms of the proportion of people who experienced improvement in diabetic gastroparesis. There is evidence of publication bias and a positive bias of small study effects. The reported benefits should be interpreted with great caution because of the unclear overall risk of bias, unvalidated measurements of change in subjective symptoms, publication bias and small study reporting bias, and lack of data on long-term outcomes; the effects reported in this review may therefore differ significantly from the true effect. One sham-controlled trial provided low-certainty evidence of no difference between real and sham acupuncture in terms of short-term symptom improvement in diabetic gastroparesis, when measured by a validated scale. No studies reported changes in quality of life or the use of medication.Due to the absence of data, no conclusion can be made regarding effects of acupuncture on gastroparesis of other aetiologies. Reports of harm have remained largely incomplete, precluding assessments of the safety of acupuncture in this population. Future research should focus on reducing the sources of bias in the trial design as well as transparent reporting. Harms of interventions should be explicitly reported.

Modulation of gastrointestinal motility beyond metoclopramide and domperidone : Pharmacological and clinical evidence for phytotherapy in functional gastrointestinal disorders.

The prokinetic cisapride, an important therapeutic option in functional gastrointestinal (GI) disorders, was withdrawn from the market 15 years ago due to rare severe side effects. Likewise in 2014, the use of metoclopramide (MCP) and domperidone in functional GI disorders (FGID) was restricted, consequently leaving a therapeutic gap in clinical practice. A systematic review revealed that the herbal medicinal product (HMP) STW 5 presents a therapeutic option equivalent to MCP and cisapride. STW 5 is the only HMP for which efficacy has been shown in randomized controlled clinical trials (RCTs) in functional dyspepsia and irritable bowel syndrome, based on its multitarget effect on numerous etiological factors. Due to an outstanding favorable safety profile, STW 5 allows an effective and safe use in FGID without a limitation of the duration of the treatment.

[Elongated needle for post-stroke indigestion].

OBJECTIVE: To observe the clinical efficacy difference among elongated needle, filiform needle and medication for post-stroke indigestion. METHODS: Sixty cases of post-stroke indigestion were randomly assigned into an elongated needle group, a filiform needle group and a medication group, 20 cases in each one. Acupuncture of restoring consciousness and inducing resuscitation and conventional medical treatment were applied in the three groups. 125 mm elongated needles were perpendicularly inserted at Zhongwan (CV 12), Liangmen (ST 21) and Tianshu (ST 25) in the elongated needle group; 20 to 30 mm perpendicular filiform at the same points in the filiform needle group. All the treatment was given for 4 weeks, 6 times a week, 1 time a day. Domperidone was prescribed orally in the medication group for 4 weeks, 3 times a day and once 10 mg. The indexes were dyspepsia TCM symptom score, Liz dyspepsia questionnaire (LDQ), Nepean Dyspepsia Index of quality of life (NDLQI), Safety Data Sheet (SDS) self rating scale and side effect scale (TESS). The effects were evaluated. RESULTS: The scores of TCM symptom, LDQ, SDS scores in the three groups decreased and NDLQI increased after 7-day, 14-day, and 28-day treatment as compared with those before treatment (P<0.05, P<0.01). The TCM symptom score and LDQ score in the elongated needle group after 28-day treatment were lower than those in the filiform needle and medication groups (P<0.05, P<0.01). The SDS score in the medication group was lower than that in the elongated needle and filiform needle group (both P<0.05). There were no significant statistical difference for NDLQI score in the three groups (P>0.05). The total effective rate was 90% (18/20) in the elongated needle group; those in the filiform needle group and medication group were 70% (14/20) and 75% (15/20) respectively, indicating statistical significance (P<0.01). CONCLUSION: Acupuncture with elongated needle can obviously improve symptoms in the patients with post-stroke indigestion, which is better than filiform needle and medication.

Comparison of three preclinical models for nausea and vomiting assessment.

INTRODUCTION: Nausea is a subjective sensation often preceding emesis in humans. Drug-induced nausea remains difficult to predict in preclinical tests. The aim of this study was to compare the effects of emetic agents in rats (pica behavior), ferrets (acute and delayed phases of emesis) or dogs (emesis and cardiovascular endpoints). METHODS: Rats and ferrets were administered cisplatin (±aprepitant/ondansetron or aprepitant) or apomorphine (±domperidone). Telemetered dogs were administered apomorphine (±domperidone). Food and kaolin intake was measured in rats whereas the number of emetic events was counted in ferrets and dogs. Cardiovascular changes were also monitored in dogs. RESULTS: In rats, cisplatin (6mg/kg, i.p.) increased kaolin intake (+2257%, p<0.001). The cisplatin effects were not reversed by the combination of aprepitant/ondansetron (2mg/kg, p.o./2mg/kg, i.p.) or by aprepitant (30mg/kg, p.o.). Apomorphine (10mg/kg, i.p.) did not induce pica behavior. In ferrets, cisplatin (8mg/kg, i.p.) induced acute and delayed emesis (371.8±47.8 emetic events over 72h) which was antagonized by aprepitant (1mg/kg, p.o.). Apomorphine (0.25mg/kg, s.c.) induced acute emesis (38.8±8.7 emetic events over 2h) which was abolished by domperidone (0.1mg/kg, s.c.). In dogs, apomorphine (100µg/kg, s.c.) induced emesis and tachycardia which were decreased by domperidone (0.2mg/kg, i.v.). CONCLUSIONS: The assessment of emesis in the ferret or in the dog displays a strong predictive value. In contrast, assessing nausea remains challenging in all animal species and the use of pica behavior remains questionable in the context of antiemetic drug development.

Cannabinoids for nausea and vomiting in adults with cancer receiving chemotherapy.

BACKGROUND: Cannabis has a long history of medicinal use. Cannabis-based medications (cannabinoids) are based on its active element, delta-9-tetrahydrocannabinol (THC), and have been approved for medical purposes. Cannabinoids may be a useful therapeutic option for people with chemotherapy-induced nausea and vomiting that respond poorly to commonly used anti-emetic agents (anti-sickness drugs). However, unpleasant adverse effects may limit their widespread use. OBJECTIVES: To evaluate the effectiveness and tolerability of cannabis-based medications for chemotherapy-induced nausea and vomiting in adults with cancer. SEARCH METHODS: We identified studies by searching the following electronic databases: Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, PsycINFO and LILACS from inception to January 2015. We also searched reference lists of reviews and included studies. We did not restrict the search by language of publication. SELECTION CRITERIA: We included randomised controlled trials (RCTs) that compared a cannabis-based medication with either placebo or with a conventional anti-emetic in adults receiving chemotherapy. DATA COLLECTION AND ANALYSIS: At least two review authors independently conducted eligibility and risk of bias assessment, and extracted data. We grouped studies based on control groups for meta-analyses conducted using random effects. We expressed efficacy and tolerability outcomes as risk ratio (RR) with 95% confidence intervals (CI). MAIN RESULTS: We included 23 RCTs. Most were of cross-over design, on adults undergoing a variety of chemotherapeutic regimens ranging from moderate to high emetic potential for a variety of cancers. The majority of the studies were at risk of bias due to either lack of allocation concealment or attrition. Trials were conducted between 1975 and 1991. No trials involved comparison with newer anti-emetic drugs such as ondansetron. Comparison with placebo People had more chance of reporting complete absence of vomiting (3 trials; 168 participants; RR 5.7; 95% CI 2.6 to 12.6; low quality evidence) and complete absence of nausea and vomiting (3 trials; 288 participants; RR 2.9; 95% CI 1.8 to 4.7; moderate quality evidence) when they received cannabinoids compared with placebo. The percentage of variability in effect estimates that was due to heterogeneity rather than chance was not important (I(2) = 0% in both analyses).People had more chance of withdrawing due to an adverse event (2 trials; 276 participants; RR 6.9; 95% CI 1.96 to 24; I(2) = 0%; very low quality evidence) and less chance of withdrawing due to lack of efficacy when they received cannabinoids, compared with placebo (1 trial; 228 participants; RR 0.05; 95% CI 0.0 to 0.89; low quality evidence). In addition, people had more chance of 'feeling high' when they received cannabinoids compared with placebo (3 trials; 137 participants; RR 31; 95% CI 6.4 to 152; I(2) = 0%).People reported a preference for cannabinoids rather than placebo (2 trials; 256 participants; RR 4.8; 95% CI 1.7 to 13; low quality evidence). Comparison with other anti-emetics There was no evidence of a difference between cannabinoids and prochlorperazine in the proportion of participants reporting no nausea (5 trials; 258 participants; RR 1.5; 95% CI 0.67 to 3.2; I(2) = 63%; low quality evidence), no vomiting (4 trials; 209 participants; RR 1.11; 95% CI 0.86 to 1.44; I(2) = 0%; moderate quality evidence), or complete absence of nausea and vomiting (4 trials; 414 participants; RR 2.0; 95% CI 0.74 to 5.4; I(2) = 60%; low quality evidence). Sensitivity analysis where the two parallel group trials were pooled after removal of the five cross-over trials showed no difference (RR 1.1; 95% CI 0.70 to 1.7) with no heterogeneity (I(2) = 0%).People had more chance of withdrawing due to an adverse event (5 trials; 664 participants; RR 3.9; 95% CI 1.3 to 12; I(2) = 17%; low quality evidence), due to lack of efficacy (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; very low quality evidence) and for any reason (1 trial; 42 participants; RR 3.5; 95% CI 1.4 to 8.9; low quality evidence) when they received cannabinoids compared with prochlorperazine.People had more chance of reporting dizziness (7 trials; 675 participants; RR 2.4; 95% CI 1.8 to 3.1; I(2) = 12%), dysphoria (3 trials; 192 participants; RR 7.2; 95% CI 1.3 to 39; I(2) = 0%), euphoria (2 trials; 280 participants; RR 18; 95% CI 2.4 to 133; I(2) = 0%), 'feeling high' (4 trials; 389 participants; RR 6.2; 95% CI 3.5 to 11; I(2) = 0%) and sedation (8 trials; 947 participants; RR 1.4; 95% CI 1.2 to 1.8; I(2) = 31%), with significantly more participants reporting the incidence of these adverse events with cannabinoids compared with prochlorperazine.People reported a preference for cannabinoids rather than prochlorperazine (7 trials; 695 participants; RR 3.3; 95% CI 2.2 to 4.8; I(2) = 51%; low quality evidence).In comparisons with metoclopramide, domperidone and chlorpromazine, there was weaker evidence, based on fewer trials and participants, for higher incidence of dizziness with cannabinoids.Two trials with 141 participants compared an anti-emetic drug alone with a cannabinoid added to the anti-emetic drug. There was no evidence of differences between groups; however, the majority of the analyses were based on one small trial with few events. Quality of the evidence The trials were generally at low to moderate risk of bias in terms of how they were designed and do not reflect current chemotherapy and anti-emetic treatment regimens. Furthermore, the quality of evidence arising from meta-analyses was graded as low for the majority of the outcomes analysed, indicating that we are not very confident in our ability to say how well the medications worked. Further research is likely to have an important impact on the results. AUTHORS' CONCLUSIONS: Cannabis-based medications may be useful for treating refractory chemotherapy-induced nausea and vomiting. However, methodological limitations of the trials limit our conclusions and further research reflecting current chemotherapy regimens and newer anti-emetic drugs is likely to modify these conclusions.

Pharmacological treatment of children with gastro-oesophageal reflux.

BACKGROUND: Gastro-oesophageal reflux (GOR) is a common disorder, characterised by regurgitation of gastric contents into the oesophagus. GOR is a very common presentation in infancy in both primary and secondary care settings. GOR can affect approximately 50% of infants younger than three months old (Nelson 1997). The natural history of GOR in infancy is generally that of a functional, self-limiting condition that improves with age; < 5% of children with vomiting or regurgitation continue to have symptoms after infancy (Martin 2002). Older children and children with co-existing medical conditions can have a more protracted course. The definition of gastro-oesophageal reflux disease (GORD) and its precise distinction from GOR are debated, but consensus guidelines from the North American Society of Gastroenterology, Hepatology and Nutrition (NASPGHAN-ESPGHAN guidelines 2009) define GORD as 'troublesome symptoms or complications of GOR.' OBJECTIVES: This Cochrane review aims to provide a robust analysis of currently available pharmacological interventions used to treat children with GOR by assessing all outcomes indicating benefit or harm. SEARCH METHODS: We sought to identify relevant published trials by searching the Cochrane Central Register of Controlled Trials (CENTRAL) (2014, Issue 5), MEDLINE and EMBASE (1966 to 2014), the Centralised Information Service for Complementary Medicine (CISCOM), the Institute for Scientific Information (ISI) Science Citation Index (on BIDS-UK General Science Index) and the ISI Web of Science. We also searched for ongoing trials in the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com).Reference lists from trials selected by electronic searching were handsearched for relevant paediatric studies on medical treatment of children with gastro-oesophageal reflux, as were published abstracts from conference proceedings (published in Gut and Gastroenterology) and reviews published over the past five years.No language restrictions were applied. SELECTION CRITERIA: Abstracts were reviewed by two review authors, and relevant RCTs on study participants (birth to 16 years) with GOR receiving a pharmacological treatment were selected. Subgroup analysis was considered for children up to 12 months of age, and for children 12 months to 16 years of age, and for those with neurological impairment. DATA COLLECTION AND ANALYSIS: Trials were critically appraised and data collected by two review authors. Risk of bias was assessed. Meta-analysis data were independently extracted by two review authors, and suitable outcome data were analysed using RevMan. MAIN RESULTS: A total of 24 studies (1201 participants) contributed data to the review. The review authors had several concerns regarding the studies. Pharmaceutical company support for manuscript preparation was a common feature; also, because common endpoints were lacking, study populations were heterogenous and variations in study design were noted, individual drug meta-analysis was not possible.Moderate-quality evidence from individual studies suggests that proton pump inhibitors (PPIs) can reduce GOR symptoms in children with confirmed erosive oesophagitis. It was not possible to demonstrate statistical superiority of one PPI agent over another.Some evidence indicates that H2antagonists are effective in treating children with GORD. Methodological differences precluded performance of meta-analysis on individual agents or on these agents as a class, in comparison with placebo or head-to-head versus PPIs, and additional studies are required.RCT evidence is insufficient to permit assessment of the efficacy of prokinetics. Given the diversity of study designs and the heterogeneity of outcomes, it was not possible to perform a meta-analysis of the efficacy of domperidone.In younger children, the largest RCT of 80 children (one to 18 months of age) with GOR showed no evidence of improvement in symptoms and 24-hour pH probe, but improvement in symptoms and reflux index was noted in a subgroup treated with domperidone and co-magaldrox(Maalox(®) ). In another RCT of 17 children, after eight weeks of therapy. 33% of participants treated with domperidone noted an improvement in symptoms (P value was not significant). In neonates, the evidence is even weaker; one RCT of 26 neonates treated with domperidone over 24 hours showed that although reflux frequency was significantly increased, reflux duration was significantly improved.Diversity of RCT evidence was found regarding efficacy of compound alginate preparations(Gaviscon Infant(®) ) in infants, although as a result of these studies, Gaviscon Infant(®) was changed to become aluminium-free and has been assessed in its current form in only two studies since 1999. Given the diversity of study designs and the heterogeneity of outcomes, as well as the evolution in formulation, it was not possible to perform a meta-analysis on the efficacy of Gaviscon Infant(®) . Moderate evidence indicates that Gaviscon Infant(®) improves symptoms in infants, including those with functional reflux; the largest study of the current formulation showed improvement in symptom control but was limited by length of follow-up.No serious side effects were reported.No RCTs on pharmacological treatments for children with neurodisability were identified. AUTHORS' CONCLUSIONS: Moderate evidence was found to support the use of PPIs, along with some evidence to support the use of H2 antagonists in older children with GORD, based on improvement in symptom scores, pH indices and endoscopic/histological appearances. However, lack of independent placebo-controlled and head-to-head trials makes conclusions as to relative efficacy difficult to determine. Further RCTs are recommended. No robust RCT evidence is available to support the use of domperidone, and further studies on prokinetics are recommended, including assessments of erythromycin.Pharmacological treatment of infants with reflux symptoms is problematic, as many infants have GOR, and little correlation has been noted between reported symptoms and endoscopic and pH findings. Better evidence has been found to support the use of PPIs in infants with GORD, but heterogeneity in outcomes and in study design impairs interpretation of placebo-controlled data regarding efficacy. Some evidence is available to support the use of Gaviscon Infant(®) , but further studies with longer follow-up times are recommended. Studies of omeprazole and lansoprazole in infants with functional GOR have demonstrated variable benefit, probably because of differences in inclusion criteria.No robust RCT evidence has been found regarding treatment of preterm babies with GOR/GORD or children with neurodisabilities. Initiation of RCTs with common endpoints is recommended, given the frequency of treatment and the use of multiple antireflux agents in these children.

Acupuncture for functional dyspepsia.

BACKGROUND: Functional dyspepsia (FD) has been a worldwide complaint. More effective therapies are needed with fewer adverse effects than are seen with conventional medications. Acupuncture, as a traditional therapeutic method, has been widely used for functional gastrointestinal disorders in the East. Manual acupuncture and electroacupuncture have been recognized treatments for FD, but to date, no robust evidence has been found for the effectiveness and safety of these interventions in the treatment of this condition. OBJECTIVES: This review was conducted to assess the efficacy and safety of manual acupuncture and electroacupuncture in the treatment of FD. SEARCH METHODS: Trials meeting the inclusion criteria were identified through electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, the Allied and Complementary Medicine Database (AMED), Chinese Biology Medicine Disc (CBMdisc), China National Knowledge Infrastructure (CNKI), the Wanfang Database, the VIP Database, and six trial registries. Handsearching was done to screen the reference sections of potential trials and reviews. SELECTION CRITERIA: Randomized controlled trials (RCTs) were included if investigators reported efficacy and safety of manual acupuncture or electroacupuncture for patients with FD diagnosed by Rome II or Rome III criteria, compared with medications, blank control, or sham acupuncture. DATA COLLECTION AND ANALYSIS: Data were extracted by independent review authors. Study limitations were assessed by using the tool of The Cochrane Collabration for assessing risk of bias. For dichotomous data, risk ratios (RRs) and 95% confidence intervals (95% CIs) would be applied, and for continuous data, mean differences (MDs) and 95% CIs. A fixed-effect model was applied in the meta-analysis, or a descriptive analysis was performed. The quality of evidence for the outcome measure was assessed by the Grading of Recommendations Assessment, Development and Evaluation (GRADE) methods. MAIN RESULTS: Seven studies were included in the review, involving 542 participants with FD (212 males and 330 females). These studies generally had an unclear risk of bias based on inadequate descriptions of allocation concealment and a high risk of bias based on lack of blinding. None of the studies reported on outcomes of the Functional Digestive Disorder Quality of Life questionnaire (FDDQL), the Satisfaction With Dyspepsia Related Health scale (SODA), the Digestive Health Status Instrument (DHSI), or effective/inefficient rate and symptom recurrence six months from completion of acupuncture treatment.Four RCTs of acupuncture versus medications (cisapride, domperidone, and itopride) were included in the review. No statistically significant difference was noted in the reduction in FD symptom scores and the frequency of FD attack by manual acupuncture, manual-electroacupuncture, or electroacupuncture compared with medications. In three trials of acupuncture versus sham acupuncture, all descriptive or quantitative analysis results implied that acupuncture could improve FD symptom scores and scores on the Neck Disability Index (NDI), the 36-Item Short Form Health Survey (SF-36), the Self-Rating Anxiety Scale (SAS), and the Self-Rating Depression Scale (SDS) more or as significantly as sham acupuncture. With regard to adverse effects, acupuncture was superior to cisapride treatment (one study; all minor events), but no statistically significant difference was reported between acupuncture and sham acupuncture. No adverse effects data were reported in studies examining manual acupuncture versus domperidone, manual-electroacupuncture versus domperidone, or electroacupuncture versus itopride.Nevertheless, all evidence was of low or very low quality. The body of evidence identified cannot yet permit a robust conclusion regarding the efficacy and safety of acupuncture for FD. AUTHORS' CONCLUSIONS: It remains unknown whether manual acupuncture or electroacupuncture is more effective or safer than other treatments for patients with FD.

Does Braun enteroenterostomy reduce delayed gastric emptying after pancreaticoduodenectomy?

Whether an additional Braun enteroenterostomy is necessary in reducing delayed gastric emptying (DGE) after pancreaticoduodenectomy (PD) has not yet been well investigated. Herein, in this retrospective study, 395 consecutive cases of patients undergoing classic PD from 2009 to 2013 were reviewed. Patients with and without Braun enteroenterostomy were compared in preoperative baseline characteristics, surgical procedure, postoperative diagnosis, and morbidity including DGE. The DGE was defined and classified by the International Study Group of Pancreatic Surgery recommendation. The incidence of DGE was similar in patients with or without Braun enteroenterostomy following PD (37/347, 10.7% vs 8/48, 16.7%, P = 0.220). The patients in the 2 groups were not different in patient characteristics, lesions, surgical procedure, or postoperative complications, although patients without Braun enteroenterostomy more frequently presented postoperative vomiting than those with Braun enteroenterostomy (33.3% vs 15.3%, P = 0.002). Bile leakage, pancreatic fistula, and intraperitoneal abscess were risk factors for postoperative DGE (all P < 0.05). Prokinetic agents and acupuncture were effective in symptom relief of DGE in 24 out of 45 patients and 12 out of 14 patients, respectively.The additional Braun enteroenterostomy following classic PD was not associated with a decreased rate of DGE. Postoperative abdominal complications were strongly correlated with the onset of DGE. Prokinetic agents and acupuncture could be utilized in some patients with DGE.

Acupuncture effectiveness as a complementary therapy in functional dyspepsia patients.

CONTEXT: Functional dyspepsia represents a frequent gastrointestinal disorder in clinical practice. According to the Roma III criteria, functional dyspepsia can be classified into two types as the predominant symptom: epigastric pain and postprandial discomfort. Even though the pathophysiology is still uncertain, the functional dyspepsia seems to be related to multiple mechanisms, among them visceral hypersensitivity, changes in the gastroduodenal motility and gastric accommodation and psychological factors. OBJECTIVE: Evaluate the effectiveness of acupuncture as a complementary to conventional treatment in functional dyspepsia patients. METHODS: Randomized clinical trial in which were enrolled patients with functional dyspepsia patients in according with Rome III criteria. One group was submitted to drug therapy and specific acupuncture (GI) and the other to drug therapy and non-specific acupuncture (GII). The gastrointestinal symptoms, presence of psychiatric disorders and quality of life were evaluated, at the end and three months after treatment. RESULTS: After 4 weeks of treatment there was improvement of gastrointestinal symptoms in Group I (55 ± 12 vs 29 ± 8.8; P = 0.001) and Group II (50.5 ± 10.2 vs 46 ± 10.5; P = 0.001). Quality of life was significantly better in Group I than group II (93.4 ± 7.3 vs 102.4 ± 5.1; P = 0.001). Anxiety (93.3% vs 0%; P = 0.001) and depression (46.7% vs 0%; P = 0.004) were significantly lower in Group I than group II. When comparing the two groups after 4 weeks of treatment, gastrointestinal symptoms (29 ± 8.8 vs 46 ± 10.5; P<0.001) and quality of life (102.4 ± 5.1 vs 96 ± 6.1; P = 0.021) were significantly better in Group I than group II. Three months after the treatment, gastrointestinal symptoms remained better only in Group I, when compared to the pre-treatment values (38 ± 11.3 vs 55 ± 12; P = 0.001). CONCLUSION: In patients with functional dyspepsia the complementary acupuncture treatment is superior to conventional treatment. Further studies with more patients are needed to confirm these findings.

Acupuncture effcctiveness as a complementary therapy in functional dyspepsia patients / Eficacia da acupuntura como terapia complementar em pacientes com dispepsia funcional

Context Functional dyspepsia represents a frequent gastrointestinal disorder in clinical practice. According to the Roma III criteria, functional dyspepsia can be classified into two types as the predominant sympton: epigastric pain and postprandial discomfort. Even though the pathophysiology is still uncertain, the functional dyspepsia seems to be related to multiple mechanisms, among them visceral hypersensitivity, changes in the gastroduodenal motility and gastric accommodation and psychological factors. Objective Evaluate the effectiveness of acupuncture as a complementary to conventional treatment in functional dyspepsia patients. Methods Randomized clinical trial in which were enrolled patients with functional dyspepsia patients in according with Rome III criteria. One group was submitted to drug therapy and specific acupuncture (GI) and the other to drug therapy and non-specific acupuncture (GII). The gastrointestinal symptoms, presence of psychiatric disorders and quality of life were evaluated, at the end and three months after treatment. Results After 4 weeks of treatment there was improvement of gastrointestinal symptoms in Group I (55 ± 12 vs 29 ± 8.8; P = 0.001) and Group II (50.5 ± 10.2 vs 46 ± 10.5; P = 0.001). Quality of life was significantly better in Group I than group II (93.4 ± 7.3 vs 102.4 ± 5.1; P = 0.001). Anxiety (93.3% vs 0%; P = 0.001) and depression (46.7% vs 0%; P = 0.004) were significantly lower in Group I than group II. When comparing the two groups after 4 weeks of treatment, gastrointestinal symptoms (29 ± 8.8 vs 46 ± 10.5; P<0.001) and quality of life (102.4 ± 5.1 vs 96 ± 6.1; P = 0.021) were significantly better in Group I than group II. Three months after the treatment, gastrointestinal symptoms remained better only in Group I, when compared to the pre-treatment values (38 ± ...

Contexto A dispepsia funcional representa uma frequente desordem gástrica da prática clínica. Segundo os critérios de Roma III, pode ser subdividida em dois tipos: do tipo dor epigástrica e tipo desconforto pós prandial, de acordo com o sintoma predominante. Embora de fisiopatologia incerta, a dispepsia funcional parece estar relacionada a múltiplos mecanismos, entre eles: a hipersensibilidade visceral, alterações da motilidade gastroduodenal e acomodação gástrica e participação de fatores psíquicos. Objetivos Avaliar a eficácia da acupuntura como forma complementar ao tratamento medicamentoso em pacientes com dispepsia funcional. Método Ensaio clínico randomizado, com portadores de dispepsia funcional, segundo os critérios de Roma III. Dois grupos foram formados: Grupo I (terapia medicamentosa e acupuntura específica) e; II (terapia medicamentosa e acupuntura não específica). Foram avaliados o índice de sintomas gastrointestinais, a presença de transtornos psíquicos e a qualidade de vida no início, no fim e 3 meses após o tratamento. Resultados Após 4 semanas de tratamento houve melhora dos sintomas gastrointestinais no Grupo I (55 ± 12 vs 29 ± 8,8; P = 0,001) e no Grupo II (50 ± 10 vs 46 ± 10,5; P = 0,001). Na comparação intergrupos, os sintomas gastrintestinais (29 ± 8,8 vs 46 ± 10,5; P<0,001) e os sintomas de ansiedade (0% vs 41,7%; P = 0,003) foram significativamente menores no Grupo I e a qualidade de vida (102,4 ± 5,1 vs 96,4 ± 6,1; P = 0,021) também foi significativamente melhor neste grupo. Três meses após o tratamento, os sintomas gastrointestinais permaneceram melhores no Grupo I, quando comparados aos valores pré-tratamento (38 ± 11,3 vs 55 ...

Therapeutic efficacy of baclofen in refractory gastroesophageal reflux-induced chronic cough.

AIM: To evaluate the efficacy and safety of baclofen for treatment of refractory gastroesophageal reflux-induced chronic cough (GERC) unresponsive to standard anti-reflux therapy. METHODS: Sixteen patients with refractory GERC were given an 8-wk course of baclofen 20 mg three times a day as an add-on therapy to omeprazole. Changes in the cough symptom score, cough threshold to capsaicin, reflux symptom score and possible adverse effects were determined after treatment. The variables of multi-channel intraluminal impedance combined with pH monitoring were compared between responders and non-responders to baclofen. RESULTS: Twelve of 16 patients completed treatment. Cough disappeared or improved in 56.3% (9/16) of patients, including 6 patients with acid reflux-induced cough (66.7%) and 3 patients with non-acid reflux-induced cough (33.3%). With baclofen treatment, the cough symptom score began to decrease at week 2, was clearly decreased at week 6 and reached a minimum at week 8. At the end of therapy, the lowest concentration of capsaicin required for induction of ≥ 2 and ≥ 5 coughs increased from 0.98 (1.46) to 1.95 (6.82) µmol/L (Z = -2.281, P = 0.024) and from 1.95 (7.31) to 7.8 (13.65) µmol/L (Z = -2.433, P = 0.014), respectively, and the reflux symptom score decreased from 8.0 ± 1.6 to 6.8 ± 0.8 (t = 2.454, P = 0.023). The number of acid reflux episodes was significantly lower in responders than in non-responders. The main adverse effects were somnolence, dizziness and fatigue. CONCLUSION: Baclofen is a useful, but suboptimal treatment option for refractory GERC.

[Efficacy controlled observation on acupuncture and western medicine for gastrointestinal dysmotility in liver cirrhosis].

OBJECTIVE: To observe the therapeutic effect of acupuncture on gastrointestinal dysmotility in liver cirrhosis. METHODS: Forty cases of gastrointestinal dysmotility in liver cirrhosis were randomized into an acupuncture group and a motilium group, 20 cases in each one. In the acupuncture group, on the basis of the conventional treatment, electroacupuncture was applied at Zusanli (ST 36), Sanyinjiao (SP 6) and Taichong (LR 3) for 30 min, once a day. In the motilium group, on the basis of the conventional treatment, motilium was taken orally 30 min before meals, 10 mg each time, three times a day. The treatment was required for 2 weeks in both groups. The changes in the digestive tract symptom score and liver function Child-Pugh score were observed and the efficacy was assessed. RESULTS: The total effective rate of digestive tract symptoms was 85.0% (17/20) in the acupuncture group and 70.0% (14/20) in the motilium group. The score improvements in abdominal distention, belching and vomiting in the acupuncture group were superior to those in the motilium group (all P < 0.05). In the acupuncture group, the liver function Child-Pugh total score was 8.40 +/- 0.22 before treatment and reduced to 5.36 +/- 0.17 after treatment, in which the scores for ascites, serum bilirubin and albumin were all reduced (all P < 0.05) and the reducing range was increased in tendency with the improvements in digestive tract symptoms. In the motilium group, Child-Pugh score was not changed obviously as compared with that before treatment. CONCLUSION Acupuncture effectively alleviates digestive tract symptoms and improves liver function for the patients of liver cirrhosis, its efficacy on gastrointestinal dysmotility in liver cirrhosis is superior to motilium.