Risk of Stroke-Associated Pneumonia With Acid-Suppressive Drugs: A Population-Based Cohort Study

Acid-suppressive drugs, including histamine-2 receptor antagonists (H2RAs) and proton pump inhibitors (PPIs), are common medications used for treating upper gastrointestinal tract disorders. However, acid-suppressive drugs have been reported to increase the risk of pneumonia in numerous disease populations. However, the relationship between acid-suppressive drugs and stroke-associated pneumonia (SAP) remains controversial.The purpose of this study was to investigate the association between acid-suppressive drug usage and pneumonia among patients with stroke by using a nationwide data set.A population-based cohort study was conducted using a data set from the Taiwanese National Health Insurance Research Database. Data on patients with new-onset stroke from 2010 to 2011 were collected. Patients with and without acid-suppressive drug usage were followed up to identify the occurrence of any type of pneumonia. We estimated the adjusted hazard ratios (HRs) by using the Cox proportional hazards model.The study cohort comprised 7965 patients with new-onset stroke. The incidence of pneumonia was 6.9% (552/7965) and more than 40% (225/552) of patients developed pneumonia within 3 months after an acute stroke. Acid-suppressive drug usage was an independent risk factor of pneumonia. The adjusted HR for the risk of pneumonia in patients with new-onset stroke using acid-suppressive drugs was 1.44 (95% confidence interval [CI] = 1.18–1.75, P < 0.01). Only PPI usage increased risk of chronic SAP (adjusted HR = 1.46, 95% CI = 1.04–2.05).Acid-suppressive drug usage was associated with a slightly increased risk of SAP. Physicians should exercise caution when prescribing acid-suppressive drugs to patients with stroke, particularly at the chronic stage.     

Non-steroidal Anti-inflammatory Drugs with Adverse Psychiatric Reactions: Five Case Reports

Adverse drug reactions of non-steroidal anti-inflammatory drugs (NSAIDs) are quite prevalent, but there are few reports about possible adverse psychiatric reactions, which may be ignored or underestimated. We describe here five psychiatric outpatients, two with major depressive disorders, one bipolar disorder, one schizophrenic disorder and one anxiety disorder, who were treated with NSAIDs for pain due to rheumatoid arthritis, osteoarthritis or other painful neuromuscular conditions. All five patients developed a moderate to severe depressive state, three patients became obviously paranoid, and four had either thoughts of suicide or an attempt while undergoing co-administration of NSAIDs. The psychiatric symptoms remitted when the NSAIDs were stopped. The depressive and paranoid symptoms returned on seven occasions of re-use or re-challenge with the same or a different type of NSAID in all five patients. When the NSAIDs were stopped again, the patients had another remission of the adverse psychiatric reactions, and eventually recovered to their baseline mental states in clear temporal relationships. The cases presented suggest that NSAIDs can induce or exacerbate idiosyncratic reproducible adverse psychiatric symptoms in certain vulnerable patients, including those with a variety of psychotic or neurotic disorders, and also in elderly persons, but these undesirable side-effects were generally transient and disappeared on withdrawal of the NSAIDs. Received: 22 June 1998 / Accepted: 14 December 1998     

Comparative Outcome Analysis of Penicillin-Based Versus Fluoroquinolone-Based Antibiotic Therapy for Community-Acquired Pneumonia: A Nationwide Population-Based Cohort Study

Community-acquired pneumonia (CAP) is a common but potentially life-threatening condition, but limited information exists on the effectiveness of fluoroquinolones compared to β-lactams in outpatient settings. We aimed to compare the effectiveness and outcomes of penicillins versus respiratory fluoroquinolones for CAP at outpatient clinics.This was a claim-based retrospective cohort study. Patients aged 20 years or older with at least 1 new pneumonia treatment episode were included, and the index penicillin or respiratory fluoroquinolone therapies for a pneumonia episode were at least 5 days in duration. The 2 groups were matched by propensity scores. Cox proportional hazard models were used to compare the rates of hospitalizations/emergence service visits and 30-day mortality. A logistic model was used to compare the likelihood of treatment failure between the 2 groups.After propensity score matching, 2622 matched pairs were included in the final model. The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy (adjusted odds ratio [AOR], 0.88; 95% confidence interval [95%CI], 0.77–0.99), but no differences were found in hospitalization/emergence service (ES) visits (adjusted hazard ratio [HR], 1.27; 95% CI, 0.92–1.74) and 30-day mortality (adjusted HR, 0.69; 95% CI, 0.30–1.62) between the 2 groups.The likelihood of treatment failure of fluoroquinolone-based therapy was lower than that of penicillin-based therapy for CAP on an outpatient clinic basis. However, this effect may be marginal. Further investigation into the comparative effectiveness of these 2 treatment options is warranted.     

非甾体抗炎药对小肠黏膜的损伤作用

研究显示非甾体抗炎药（NSAIDs）不仅可引起胃十二指肠黏膜损伤，还可引起小肠黏膜损伤。目的：探讨NSAIDs引起小肠黏膜损伤的发病机制及其病理生理变化。方法：50只大鼠随机分为空白对照组和四组模型组，以不同NSAID灌胃14d。另20只大鼠先分别行胆管结扎和假手术。再予吲哚美辛灌胃。观察各组大鼠一般情况和小肠黏膜大体、组织病理学改变，测定小肠组织髓过氧化物酶（MPO）、丙二醛（MDA）、超氧化物歧化酶（SOD）、一氧化氮（NO）含量。结果：四种NSAID均能造成大鼠小肠黏膜损伤，吲哚美辛、布洛芬和塞来昔布组累计损伤深度和面积显著高于空白对照组（P〈0．05），其中以吲哚美辛组损伤最重，阿司匹林组则与空白对照组无明显差异。各模型组小肠组织MPO含量均显著高于空白对照组，SOD活性则显著低于空白对照组（P〈0．05），MDA和NO含量均呈上升趋势，但分别仅吲哚美辛组和布洛芬组与空白对照组相比有显著差异（P〈0．05）。假手术组小肠黏膜损伤显著重于空白对照组（P〈0．05），胆管结扎组与空白对照组相比无明显差异。结论：NSAIDs可通过炎症反应、氧自由基损伤、NO过度产生以及药物的肝肠循环损害小肠上皮屏障，破坏小肠结构的完整性。     

非甾体抗炎药致结肠溃疡合并消化道出血、穿孔1例

<正> 病例:患者男,74岁,因"右半结肠部分切除术后1月余解深褐色成形大便伴乏力3 d"于2007年3月9日拟诊为"下消化道出血"入院。2007年2月1日患者因"1 d内解鲜血便2次,量约100 ml"就诊于本院外科,腹部X线和CT检查示小肠梗阻伴右侧回盲肠肠壁增厚,诊断为"小肠梗阻,回盲部占位可能"。保守治疗无效后行右半结肠部分切除术,术中回盲部触及3 cm×3 cm的肿块,伴穿孔,有脓苔附     

Helicobacter pylori and Bleeding Duodenal Ulcer: Prevalence of the Infection and Role of Non-steroidal Anti-inflammatory Drugs

Background: Several authors have reported low prevalence of Helicobacter pylori infection in patients with upper gastrointestinal bleeding (UGIB). Our aim was to study the prevalence of H. pylori in bleeding duodenal ulcer (DU), with both invasive and non-invasive methods, and to assess the role of non-steroidal anti-inflammatory drugs (NSAIDs). Methods: Ninety-two patients with bleeding DU were prospectively studied. The use of NSAIDs was evaluated by specific questionnaire. As a control group, 428 patients undergoing outpatient evaluation for the investigation of dyspepsia and found to have a DU at endoscopy were included. At endoscopy, two antral biopsies were obtained (H&E stain). A 13C-urea breath test was carried out in all patients. Breath test was repeated in patients treated with omeprazole during the hospitalization if H. pylori was not detected with the first test. Results: Gastric biopsies could be obtained in 39 patients with UGIB. Three patients with UGIB treated with omeprazole and being H. pylori negative with the first breath test were finally considered infected with the second test. Overall, 92.4% (95% CI, 85%-96%) of the patients with UGIB were infected (89.7% with histology and 92.4% with breath test (P = 0.15)). Concordance kappa value for both diagnostic tests was 0.64. NSAID intake was more frequent in patients with UGIB (34%) than in those without UGIB (5.6%) (P &lt; 0.001), while H. pylori infection was less frequent in patients with UGIB (92.4% (85%-96%)) than in those without UGIB (99.1% (98%-100%); P &lt; 0.001). Even in patients with UGIB, NSAID intake was the only risk factor in 5% of cases. The proportion of cases without H. pylori infection and without NSAID intake was very low in both bleeding and non-bleeding ulcers (2% and 0.5%, respectively; P = 0.146). H. pylori prevalence in bleeding ulcers was of 84% (67%-93%) in patients with NSAID intake, and 96.7% (89%-99%) when patients taking NSAIDs were excluded. In the multivariate analysis, NSAID intake (odds ratio, 9.8 (5.2-18.4)) correlated with UGIB; however, neither H. pylori status nor the interaction between H. pylori infection and NSAID intake correlated with UGIB. In the multivariate analysis in the subgroup of patients with UGIB, NSAID use was the only variable which correlated with H. pylori prevalence (odds ratio, 0.18 (0.03-0.97)). Conclusions: The most important factor associated with H. pylori-negative bleeding DU is NSAID use, and if this factor is excluded prevalence of infection is almost 100% (97%), similar to that found in patients with non-bleeding DU (and without NSAID intake). Bleeding DU patients with neither H. pylori infection nor NSAID use are extremely rare (only 2%), which suggests that the pathogenesis of bleeding DU is similar to that of non-complicated DU disease.     

A Predictive Model for the Management of Community-Acquired Pneumonia

Background: Understanding what determines the prognosis of community-acquired pneumonia (CAP) is especially important for decisions on hospitalization and antimicrobial therapy. The objective of the present study was to compare the predictability of mortality in our patients to that of the pneumonia patient outcomes research team (PORT) study. Patients and Methods: Data of 320 patients admitted with CAP were retrospectively evaluated and classified according to the published scheme. Results: One-month mortality was 14.4%; 1-year mortality was 27.8%, two-thirds from new episodes. Univariate logistic regression risk factors for the 1-month mortality rate included leukocytosis, anemia, hypoalbuminemia, elevated blood urea nitrogen, ≥ two comorbidities, tachycardia, tachypnea, acidosis, stupor, age > 65 years and high serum lactic dehydrogenase. These variables, except the last two, plus pleural effusion and bilateral infiltration were also risk factors for 1-year mortality. In the multivariate models, eight of these factors were significant risk factors, four for 1-month mortality and six for 1-year mortality. Our model for prediction of 1-month mortality had a sensitivity of 65%, specificity of 95% and accuracy of 91%. Conclusion: Agreement between predictions by our model and the published model was considerable, showing that most patients in the low score groups should not have been hospitalized. Received: May 5, 2002 · Revision accepted: October 5, 2002 R. Raz (corresponding author)     

小檗碱对非甾体消炎药相关性肠损伤的保护作用及其机制研究

背景：近年非甾体消炎药（NSAIDs）相关性肠损伤的发生率明显升高,但目前尚缺乏有效防治NSAIDs相关性肠损伤的药物。目的：研究中药小檗碱对NSAIDs相关性肠损伤的治疗作用及其机制。方法：将40只大鼠随机分为对照组、模型组以及低、中、高剂量小檗碱干预组（分别为25、50、75mg·kg-1·d-1）。采用7.5mg·kg-1·d-1双氯芬酸制备NSAIDs相关性肠损伤模型。造模第5d处死所有大鼠,行小肠黏膜大体、组织学评分。以ELISA法检测小肠黏膜前列腺素（PG）E2含量,硝酸还原酶法检测小肠黏膜和血清NO含量,免疫组化法检测小肠黏膜环氧合酶（COX）-1、COX-2表达。结果：与对照组相比,模型组大鼠小肠大体评分和组织学评分明显升高（P〈0．05）,小肠黏膜PGE,含量明显降低（P〈0．05）,小肠黏膜和血清NO含量明显升高（P〈0．05）,小肠黏膜COX-1表达明显降低（P〈0．05）,COX-2表达明显升高（P〈0．05）。给予低、中、高剂量小檗碱干预后,上述指标明显改善（P〈0．05）。结论：小檗碱对NSAIDs相关性肠损伤具有保护作用,其机制可能与小檗碱致小肠黏膜PGE：、COX-1表达升高以及组织和血清NO含量、COX-2表达降低有关。     

Helicobacter pylori,Non-steroidal Anti-inflammatory Drugs and Smoking in Risk Pattern of Gastroduodenal Ulcers

Background: Helicobacter pylori , NSAID and cigarette smoking are major risk factors for gastroduodenal ulcers. However, the results of studies on the interaction between these factors on ulcerogenesis are controversial. This study was designed to examine the association between gastroduodenal ulcers and H. pylori infection, NSAID use, smoking and age. Methods: 5967 dyspeptic patients underwent 13 C-urea breath test (UBT) and upper endoscopy, while age and dyspeptic symptoms were reported. Results: Out of 5967 patients, 31.8% were ulcerated; 9.2% had gastric, 17.2% duodenal and 5.4% both gastric and duodenal ulcers. H. pylori was found in 72.5% of gastric ulcer patients, in 83.6% of duodenal ulcer patients, in 76.9% of gastroduodenal ulcer patients and in 64.8% of dyspeptic patients. The gastric, duodenal and gastroduodenal ulcers were related to H. pylori significantly and the respective ORs were: 1.44, 2.77 and 1.81. NSAID alone was used by 6.2%-12.7% of ulcer patients, tending to raise only the risk of gastric ulcer but reducing that of duodenal and gastroduodenal ulcers. The H. pylori prevalence was significantly higher in smokers (76%) than in non-smokers (67%) and the ulcer risk was also significantly higher in smokers than in non-smokers. About 20% of ulcers were 'idiopathic', i.e. without NSAID and H. pylori and the ratio of these ulcers to all ulcers significantly increased during the 5 years of the study. Conclusions: Based on multivariable logistic regression analysis we conclude that: 1) H. pylori infection, NSAID use, smoking and age play major roles in the pathogenesis of peptic ulcerations; 2) there is a negative interaction between H. pylori and NSAID on duodenal ulcers, suggesting that H. pylori reduces the development of these ulcers in NSAID users, and 3) about 20% of peptic ulcers in the Polish population are unrelated to H. pylori and NSAID use (idiopathic ulcers).     

非甾体抗炎药引起小肠黏膜损伤机制及其治疗的研究进展

非甾体抗炎药(NSAIDs)是目前临床应用最广泛的药物之一,具有解热、镇痛、抗炎作用。随着NSAIDs的广泛应用,其胃肠道不良反应的报道日趋增多。目前NSAIDs对小肠黏膜损伤的机制未完全阐明。本文就NSAIDs引起小肠黏膜损伤的机制及其治疗的研究进展作一综述。     

Vulnerable Sites and Changes in Mucin in the Rat Small Intestine After Non-steroidal Anti-inflammatory Drugs Administration

Background and Aims  

The location of mucosal damage and changes in mucin content in the rat small intestine following administration of non-steroidal anti-inflammatory drugs (NSAIDs) have not been well elucidated.     

Gamma-Glutamyltransferase and Future Risk of Pneumonia: A Long-Term Prospective Cohort Study

Serum gamma-glutamyltransferase (GGT) has been linked with the risk of adverse health outcomes. We aimed to assess the prospective association of GGT activity with pneumonia risk. Serum GGT was measured at baseline in 2400 middle-aged men. Within-person variability in GGT values was corrected for using data from repeat measurements. During a median follow-up of 25.3 years, 409 pneumonia cases were recorded. The age-adjusted regression dilution ratio of GGT was 0.68 (95% CI 0.63–0.73). Gamma-glutamyltransferase was approximately log-linearly associated with pneumonia risk. In analysis adjusted for several major pneumonia risk factors, the hazard ratio (95% CI) for pneumonia per 1 standard deviation increase in GGT was 1.14 (1.02–1.28). The association was however attenuated on additional adjustment for high-sensitivity C-reactive protein (hsCRP) 1.08 (0.96–1.22). There is an approximately log-linear positive association between GGT activity and future risk of pneumonia in a middle-aged male population, which is partly dependent on hsCRP.     

Relevant Cytokines in the Management of Community-Acquired Pneumonia

Community-acquired pneumonia (CAP) is the leading cause of infectious death in the world. Immune dysregulation during acute lung infection plays a role in lung injury and the systemic inflammatory response. Cytokines seem to be major players in severe lung infection cases. Here, we present a review of published papers in the last 3 years regarding this topic. The cytokine response during pneumonia is different in bacterial vs viral infections; some of these cytokines correlate with clinical severity scales such as CURB65 or SOFA. Treatment focused in the cytokine environment is an interesting area that could impact the prognosis of CAP. Some of the agents that have been studied as co-adjuvant therapy are corticosteroids, macrolides, and linezolid, but anyone of those have shown a clear or proven efficacy or have been recommended as a part of the standard of care for CAP. More studies designed to define the role of immunomodulatory agents, such as co-adjuvant therapy in pneumonia, are needed.     

Effect of 23-Valent Pneumococcal Polysaccharide Vaccine Inoculated During Anti-Cancer Treatment Period in Elderly Lung Cancer Patients on Community-Acquired Pneumonia Hospitalization: A Nationwide Population-Based Cohort Study

To evaluate effectiveness of 23-valent pneumococcal polysaccharide vaccine (PPSV23) inoculated during defined “vaccination period,” first 6 months post cancer diagnosis (ie, an anti-cancer treatment period), in elderly lung cancer patients on community-acquired pneumonia (CAP) hospitalization incidence.This was a nationwide population-based cohort study of 157 newly diagnosed elderly lung cancer patients receiving PPSV23 during “vaccination period”, and 628 age and sex one-to-one matched controls enrolled in the National Health Insurance Research Database (NHIRD) of Taiwan between 2007 and 2010. All patients were ≥75 years old and still survival post “vaccination period.” Incidence density (ID) of all-cause inpatient CAP and cumulative survival risk were analyzed by multivariate Poisson regression and Kaplan–Meier method, respectively.After a 4-year follow-up, IDs of all-cause inpatient CAP for vaccination and control cohorts were 297 and 444 per 1000 PYs, respectively. Less vaccinated patients had CAP incidence density >1 time per PY (12.7% vs 21.2%) than non-vaccinated patients. After adjusting for potential confounding variables, like influenza vaccination, comorbidities, cancer treatment modalities, and socioeconomic status, adjusted inpatient CAP incidence rate in PPSV23 vaccination cohort was 0.74 times lower than control cohort (incidence rate ratio [IRR] = 0.740, P = 0.0339). Two-year cumulative CAP hospitalization rates and overall survival rates were 37.1% vs. 55.4%, and 46.6% vs. 26.2%, respectively, for lung cancer patients with and without PPSV23 (both P < 0.001). Subgroup analysis showed that for elderly lung cancer patients not ever receiving influenza vaccine, PPSV23 still had trend to reduce all-cause inpatient CAP.For elderly lung cancer patients aged ≥75 years, PPSV23 inoculated during anti-cancer treatment period could reduce CAP hospitalizations and improve survival.