盐酸屈他维林治疗肠易激综合征的多中心临床试验

背景:肠易激综合征(IBS)是一种常见的慢性功能性肠病,严重影响患者的生活质量,现有治疗药物多数疗效欠佳。目的:观察盐酸屈他维林对IBS的疗效和安全性。方法:采用前瞻性、自身对照、多中心试验设计。217例IBS患者接受盐酸屈他维林片80 mg tid口服治疗,疗程2周。每天记录腹痛以及排便不尽感、排便费力、排便急迫感等伴随症状及其严重程度,同时记录排便次数和粪便性状。结果:经盐酸屈他维林治疗2周,IBS患者的周平均腹痛评分较治疗前显著减低(0.66±0.59对1.42±0.42,P=0.0000),总有效率达77.9%;便秘型IBS(IBS-C)患者的一周日平均排便次数较治疗前显著增加(0.8+0.3对0.6±0.4,P=0.0004),腹泻型IBS(IBS-D)患者则较治疗前显著减低(1.6+0.8对2.8±1.2,P=0.0000),两组患者的粪便性状以及排便不尽感、排便费力、排便急迫感等亦分别有不同程度的改善。试验中未发生严重不良事件。结论:盐酸屈他维林能有效且安全地治疗各亚型IBS。     

Nonsteroidal Anti-Inflammatory Drugs, Aspirin, and Cognitive Function in the Baltimore Longitudinal Study of Aging

OBJECTIVES: To examine the relations between the use of nonaspirin, nonsteroidal anti-inflammatory drugs (NSAIDs) and aspirin and age-related change in multiple domains of cognitive function in community-dwelling individuals without dementia.
DESIGN: Longitudinal, with measures obtained on one to 18 occasions over up to 45 years.
SETTING: General community.
PARTICIPANTS: A volunteer sample of up to 2,300 participants from the Baltimore Longitudinal Study of Aging free of diagnosed dementia.
MEASUREMENTS: At each visit, reported NSAID or aspirin use (yes/no) and tests of verbal and visual memory, attention, perceptuo-motor speed, confrontation naming, executive function, and mental status.
RESULTS: Mixed-effects regression models revealed that NSAID use was associated with less prospective decline on the Blessed Information-Memory-Concentration (I-M-C) Test, a mental status test weighted for memory and concentration ( P <.001), and Part B of the Trail Making Test, a test of perceptuo-motor speed and mental flexibility ( P <.05). In contrast, aspirin use was related to greater prospective decline on the Blessed I-M-C Test ( P <.05) and the Benton Visual Retention Test, a test of visual memory ( P <.001).
CONCLUSION: Consistent with studies of incident dementia, NSAID users without dementia displayed less prospective decline in cognitive function, but on only two cognitive measures. In contrast, aspirin use was associated with greater prospective cognitive decline on select measures, potentially reflecting its common use for vascular disease prophylaxis. Effect sizes were small, calling into question clinical significance, although overall public health significance may be meaningful.     

风湿性疾病患者非甾体抗炎药胃病的临床分析

非甾体抗炎药（NSAIDs）因具有良好的抗炎、解热、镇痛作用而广泛应用于临床,但胃肠道不良反应较明显。目的：探讨风湿性疾病患者NSAIDs胃病的临床特征。方法：对服用NSAIDs至少2周的风湿性疾病患者行问卷调查和内镜检查。结果：共109例患者纳入研究。52例（47．7％）患者发生胃十二指肠黏膜损伤．其中黏膜糜烂36例（33．0％）,溃疡13例（11．9％）,糜烂和溃疡同时存在3例（2．8％）;29例（26．6％）患者病变位于胃部,11例（10．1％）位于十二指肠球部,12例（11．0％）为复合性损伤。各类风湿性疾病患者间的损伤发生率无明显差异。服用不同种类NSAIDs患者间的损伤发生率有显著差异（P〈0．05）。溃疡发生率随NSAIDs暴露时间的延长而上升（P〈0．05）。高龄（≥60岁）、幽门螺杆菌（H．pylori）感染、联合应用泼尼松可增加NSAIDs胃病发生的风险。结论：风湿性疾病人群中NSAIDs胃病的发生率较高,损伤多发生于胃部,以糜烂为主。传统NSAIDs、高龄（≥60岁）、且pylori感染和联合应用泼尼松是风湿性疾病患者发生NSAIDs胃病的危险因素。     

In Vivo Selectivity of Nonsteroidal Antiinflammatory Drugs and Gastrointestinal Ulcers in Rats

The aim of the present work was to study in vivo COX-2–COX-1 selectivity of 16 nonsteroidal anti-inflammatory drugs (NSAIDs) in equipotent ulcerogenic doses in two in vivo experimental models. Indomethacin, ibuprofen, nimesulide, aceclofenac, aspirin, sodium diclofenac, meloxicam, naproxene, paracetamol, piroxicam, tenoxicam, nabumetone, ketoprofen, mefenamic acid, etodolac, and ketorolac were administered to female Wistar rats (N = 10 each group). In experiment I, solid food plus subcutaneous NSAIDs were given. In experiment II, NSAIDs were given by oral gavage and in bolus. Macroscopic gastric antral ulcer area (30%) and intestinal erosiva area (295 mm2) in experiment I and necrotic gastric fundus area (65%) and erosive intestinal area (182 mm2), in vivo the NSAIDs COX-1 was showed. Neutrofilia assessed in gastric intestinal mucosa where also ibuprofen and paracetamol not given neotrophilic infiltration. In conclusion, COX-2–COX-1 selectivity was demonstrated in vivo with the drugs aceclofenac, nabumetone, meloxicam, nimesulide, and paracetamol.     

Effect of One-Month Treatment with Nonsteroidal Antiinflammatory Drugs (NSAIDs) on Gastric pH of Rheumatoid Arthritis Patients

The use of NSAIDs is strongly associated withpeptic ulceration. The inhibition of prostaglandinsynthesis with the consequent increase of gastricacidity is considered a possible mechanism. Therefore we decided to assess the effect of one-monthtreatment with NSAIDs on the circadian gastric pH ofrheumatoid arthritis (RA) patients. We studied 11consecutive patients (one man and 10 women, median age55, range 26-72 years) with confirmed RA. None wasH. pylori positive. A 24-hr gastric pH recording wasperformed both in basal conditions and after one-monthtreatment with either indomethacin 150 mg/day (eight cases) or ketoprofen 300 mg/day (three cases).Only the 10 female patients were eligible for finalanalysis, and six matched healthy subjects not takingNSAIDs were used as control group. The number of 24-hr pH readings for various pH thresholds wascalculated for both populations. The highest acid levels(pH < 3.0) did not differ between the two pH profilesof the control group (7440 vs 7391, P = NS), while they predominated after the one-month NSAIDtreatment (10,339 vs 11,440, P < 0.001) in RApatients. These findings show that there is an increasedgastric acidity after one-month of treatment with NSAIDs in female patients with RA of recent onset.This may sustain the rationale of using antisecretoryagents to prevent gastroduodenal ulcerations in thesepatients.     

Thermal Behavior of the Nimesulide-Salicylic Acid Eutectic Mixtures Prepared by Mechanosynthesis and Recrystallization

Nimesulide, salicylic acid and their binary mixtures were studied by differential scanning calorimetry (DSC) and Fourier Transform Infrared spectroscopy (FTIR). The study of such systems is a promising and viable approach for solving the problem of poor solubility of materials in general and drug systems in particular. All areas of human activity are inextricably linked to materials, and thus, the study presented in the paper and not reported in the literature is very important and provides useful data for those working in various fields. The eutectic mixtures were obtained by mechanosynthesis and by recrystallization from ethanol over the entire 0–1 range of molar fractions. For both situations at the molar fraction of nimesulide 0.5, the mixture has a eutectic that suggests an increase in solubility at this composition. The interactions that take place between the components were determined with the help of the excess thermodynamic functions (G^E, S^E, µ^E), which highlight the deviation from the ideality of the considered binary systems.     

Cost Effectiveness Associated with Helicobacter pylori Screening and Eradication in Patients Taking Nonsteroidal Anti-Inflammatory Drugs and/or Aspirin

Background/Aims

This study was performed to investigate the cost effectiveness of Helicobacter pylori screening/eradication in South Korean patients treated with nonsteroidal anti-inflammatory drugs (NSAIDs) and/or aspirin.

Methods

A decision Markov model was used to estimate the effectiveness and economic impact of an H. pylori screening/eradication strategy compared to a no-screening strategy among patients who were included in the model at the age of 40 years. Utility weights were applied to four of the health status groups to reflect quality-adjusted life years (QALY). The costs of screening, H. pylori eradication, and managing peptic ulcer and ulcer complications were obtained from South Korea-specific data.

Results

The total costs per patient were US $2,454 for the H. pylori screening/eradication and US $3,182 for the no-screening strategy. The QALYs for the two strategies were 16.05 and 15.73, respectively. The results were robust for the analyses of all different cohort groups who entered the model at the age of 30, 50, or 60 years and for NSAIDs-naïve patients. Through the probabilistic sensitivity analysis, the robustness of our study''s results was also determined.

Conclusions

The H. pylori screening/eradication strategy was found to be less expensive and more effective compared to the no-screening strategy among South Korean patients taking NSAIDs and/or aspirin.     

In Vitro and In Vivo Effects of Nonsteroidal Anti-inflammatory Drugs and Aspirin on Rabbit Esophageal Epithelium

BackgroundGastroesophageal reflux disease has a high incidence of 23%, with 29% of those with gastroesophageal reflux disease consuming nonsteroidal anti-inflammatory drugs. There are insufficient data concerning the effects of nonsteroidal anti-inflammatory drugs on the esophageal tissue. We aimed to examine the effects of well-known nonsteroidal anti-inflammatory drugs using electrophysiologic criteria on the rabbit esophageal epithelium.MethodsEsophageal epithelium mounted on Ussing chambers enabled in vitro investigation of the electrophysiological properties. Doses of 1 mg/mL, 2.5 mg/mL, 5 mg/mL ibuprofen, naproxen, and aspirin were dissolved in dimethyl sulfoxide and added to the luminal side. Esophagi were cannulated from both sides for the administration of high-dose ibuprofen in vivo, and the potential difference was monitored.ResultsIbuprofen and aspirin inhibited tissue transport functions in a dose-dependent manner. pH 4 acid and 0.1 mg/mL ibuprofen alone were not harmful; however, the combination of these agents had an additive and significance effect: 78% decrease in the potential difference and 85% decrease in the short-circuited current (Isc). The change in the potential difference in the in vivo experiments (5 mg/mL ibuprofen) was similar (52 ± 7% decrease) with in vitro experiments in the first 30 minutes.ConclusionNonsteroidal anti-inflammatory drugs were harmful to the rabbit esophageal epithelium in both the in vitro and in vivo experiments. Even though aspirin and ibuprofen affected the transport mechanisms of the esophageal epithelium, the dose-dependent decrease of tissue potential difference and Isc with ibuprofen was more pronounced than those with aspirin. The combination of harmless doses of ibuprofen and acid demonstrated that even low acidic conditions can create a disruptive environment.     

盐酸乌拉地尔对老年重症高血压的降压效果及安全性评价

目的研究盐酸乌拉地尔注射液对老年重症高血压的降压效果及安全性。方法老年重症高血压患者108例,其中男58,女50例。患者均给予盐酸乌拉地尔注射液,用药前用立式水银柱血压计测量右上肢卧位血压、心率,并做心电图、肾功能及血、尿常规。治疗后5、10、20、30、60、90、120、150、180、240min分别测血压、心率,同时记录不良反应与处理措施,次日晨复查肝、肾功能及血、尿常规。结果用药后10min与用药前比较收缩压、舒张压及平均压差异均有统计学意义（P〈0.01）。无明显不良反应,肝、肾功能无变化。结论乌拉地尔连续使用无耐药产生,降压过程平稳,无明显血压波动等优点,这些作用对于具有多脏器功能减退、储备能力差的老年患者尤为适宜。     

丹参川芎嗪注射液联合曲美他嗪治疗不稳定型心绞痛疗效的Meta分析

目的系统评价丹参川芎嗪注射液联合曲美他嗪治疗不稳定型心绞痛的临床疗效。方法通过检索PubMed、Cochrane Library、EMbase、PEDro、NTIS、CNKI、WanFang Data、VIP等数据库,检索所有关于丹参川芎嗪注射液联合曲美他嗪治疗不稳定型心绞痛的随机对照试验(RCTs),采用RevMan5.3软件进行Meta分析。结果纳入12篇文献,1 015例病人。丹参川芎嗪注射液联合曲美他嗪可显著提高不稳定型心绞痛的临床疗效[OR=5.01,95%CI(3.37,7.46)],有效减少心绞痛发作次数[MD=-1.16,95%CI(-1.45,-0.86)],缩短疼痛时间[MD=-4.52,95%CI(-6.35,-2.68)],降低硝酸甘油用量[MD=-0.93,95%CI(-1.49,-0.38)]。结论丹参川芎嗪注射液与曲美他嗪联合用药可显著改善不稳定型心绞痛的治疗效果。     

Impact of Anti-Aggregant,Anti-Coagulant and Non-Steroidal Anti-Inflammatory Drugs on Hospital Outcomes in Patients with Peptic Ulcer Bleeding

Background/Aims:

There are a limited number of studies including the impact of antiplatelet drugs use on hospital outcomes for nonvariceal upper gastrointestinal bleeding. The aim of this study was to determine the effect of anti-aggregant, anti-coagulant and non-steroidal anti-inflammatory drugs upon hospital outcomes in patients with peptic ulcer bleeding.

Materials and Methods:

The patients under treatment with antiaggregant, anticoagulant or non-steroidal anti-inflammatory drugs were categorized as exposed group (n = 118) and the patients who were not taking any of these drugs were categorized as non-exposed group (n = 81). We analyzed the data of drug intake, comorbid disease, blood transfusion, duration of hospital stay, Blatchford/total Rockall score and diagnosis of patients.

Results:

In total, 199 patients were included. Of these 59.3% (exposed group) were taking drugs. The patients in exposed group were significantly older than those in non-exposed group (62.9 ± 17.3 years; 55.5 ± 19.3 years, P = 0.005, respectively). Mean number of red blood cell units transfused (2.21 ± 1.51; 2.05 ± 1.87, P = 0.5), duration of hospital stay (3.46 ± 2.80 days; 3.20 ± 2.30 days, P = 0.532) and gastric ulcer rate (33% vs 23.4%, P = 0.172) were higher in exposed group than in non-exposed group but the differences were not statistically significant. Total Rockall and Blatchford scores of the patients were significantly higher in exposed group than in non-exposed group (3.46 ± 1.72 vs 2.94 ± 1.87, P = 0.045; 10.29 ± 3.15 vs 9.31 ± 3.40, P = 0.038).

Conclusıon:

Our study has shown that anticoagulants, antiaggregants and nonsteroidal anti-inflammatory drugs do not effect duration of hospital stay, red blood cell transfusion requirement and rebleeding for peptic ulcer bleeding.     

Symptoms in Patients with Peptic Ulcer and Hematemesis and/or Melena Related to the Use of Non-Steroid Anti-Inflammatory Drugs

During acidotic periods in a girl with a short small bowel, very high D-lactic acid concentrations were measured in blood and urine; the patient's characteristic faecal flora contained mainly lactobacilli, and during antibiotic cocktail treatment also many yeasts. In this case report we sought to understand the beneficial effect of the antibiotic cocktail. Microbiological analysis was performed in faecal samples. Total lactic acid in serum and urine was studied using capillary gas chromatography-mass spectrometry, and D- and L-lactic acid in serum and urine by enzymatic assay. The results were coupled to patient's condition. Antibiotic cocktail therapy reduced the acidosis-associated symptoms, faecal lactobacilli and D-lactic acid production, but simultaneously the antiobiotic therapy strongly increased the percentage of yeast in the faecal flora. Four to six weeks after each course of treatment the percentage of yeast decreased, whereas the percentage of intestinal lactobacilli increased; D-lactic acid also simultaneously increased in blood and urine. The patient felt well and showed a high percentage of intestinal yeast, but she often suffered from acidosis owing to a high percentage of lactobacilli. The yeast was identified as the pathogenic Candida glabrata. From the mentioned data together with data from the literature it was concluded that during several weeks the selected pathogenic yeast, C. glabrata, acted as a microbiological and metabolic buffer. Shortly after the course of antibiotic treatment this intestinal yeast strongly competed with the intestinal lactobacilli and thus prevented renewed rapid growth, massive D-lactic acid production from glucose and consequently also D-lactic acid-associated acidosis. The emergence of this yeast led us to consider probiotic lactobacilli or yeast for therapeutic use. The lack of knowledge regarding bile acid-deconjugating activity in both lactobacilli and probiotic yeast means that a final recommendation is not yet possible.