Intake Of Non-steroidal Anti-inflammatory Drugs Research Articles

Genotype of Helicobacter pylori and non-steroidal anti-inflammatory drugs

Studying strains of Helicobacter pylori in a mucous membrane of a stomach in adult patients taking non-steroidal anti-inflammatory drugs was carried out. Helicobacter pylori genotyping was performed by technique of polymerase chain reaction. Results of the conducted research, despite some heterogeneity, show existence of statistically significant differences depending on existence of erosive and ulcer changes and a factor of non-steroidal anti-inflammatory drugs intake.

Proinflammatory Dietary Intake is Associated with Increased Risk of Colorectal Cancer: Results of a Case-Control Study in Argentina Using a Multilevel Modeling Approach

ABSTRACTLittle evidence regarding the inflammatory potential of diet and its effect on colorectal cancer exists in Latin American countries. The aim of the present study was to evaluate the association between the Dietary Inflammatory Index (DII®) and colorectal cancer (CRC) risk in Córdoba, Argentina. A frequency-matched case-control study (N = 446, including 144 (32.3%) CRC cases and 302 (67.7%) controls was conducted in Córdoba (Argentina) from 2008 through 2015. DII® scores were computed based on dietary intake assessed by a validated food frequency questionnaire (FFQ). Multilevel logistic regression models were fit to evaluate the association between DII scores and CRC, following adjustment for age, body mass index, sex, energy intake, smoking habits, socio-economic status, physical activity, and use of nonsteroidal anti-inflammatory drugs as first-level covariates and level of urbanization as the contextual variable. Odds of colorectal cancer increased linearly with increasing DII scores (ORcontinuous 1.34; 95%CI 1.07 to 1.69 and ORtertile3 vs. tertile1 1.21; 95%CI 1.01 to 1.44). The association was stronger among men than women (ORcontinuous 1.29; 95%CI 1.21 to 1.37 vs. ORcontinuous 1.05; 95%CI 0.83 to 1.33, respectively). A proinflammatory diet, reflected by higher DII scores, was positively associated with colorectal cancer occurrence, mainly in men.

The effects of nonsteroidal anti-inflammatory drugs in the incident and recurrent risk of hepatocellular carcinoma: a meta-analysis.

BackgroundRecent studies have showed that nonsteroidal anti-inflammatory drugs (NSAIDs) could reduce the risk of several types of cancer. However, epidemiological evidence of the association between NSAIDs intake and the risk of hepatocellular carcinoma (HCC) remains controversial.MethodsTo assess the preventive benefit of NSAIDs in HCC, we simultaneously searched the databases of PubMed, EmBase, Web of Science, and Scopus and screened eligible publications.ResultsA total of twelve articles (published from 2000 to 2017) from five countries were identified by retrieval. We observed a significantly lower risk of HCC incidence among users of NSAIDs than among those who did not use NSAIDs (pooled hazard ratio [HR] value =0.81, 95% confidence interval [CI]: 0.69–0.94). No evidence of publication bias was observed (Begg’s test, P=0.755; Egger’s test, P=0.564). However, when stratified according to the categories of NSAIDs, users of non-aspirin NSAIDs (HR =0.81, 95% CI: 0.70–0.94), but not aspirin (HR =0.77, 95% CI: 0.58–1.02), showed a statistically significant reduced HCC incidence. We also found that NSAIDs use significantly reduced the recurrent risk of HCC, with a HR value of 0.79 (95% CI: 0.75–0.84), whereas there was no statistically significant association between NSAIDs use and HCC mortality, with a HR value 0.65 (95% CI: 0.40–1.06).ConclusionTaken together, our meta-analysis demonstrates that NSAIDs significantly reduce the incident and recurrent risk of HCC.

Role of Sulforaphane in Protection of Gastrointestinal Tract Against H. pylori and NSAID-Induced Oxidative Stress.

Background: Sulforaphane (SFN), a phytochemical found in abundance in broccoli sprouts, potently induces a variety of antioxidant enzymes, and thereby protects cells from injury induced by various kinds of oxidative stresses. It has been suggested that both H. pylori infection and intake of non-steroidal anti-inflammatory drugs (NSAIDs) induce chronic oxidative stress in gastrointestinal (GI) mucosa, thereby causing mucosal injury in the GI tract. Therefore, it would be a reasonable assumption that SFN protects GI mucosa against oxidative injury induced by H. pylori or NSAIDs.Methods: We examined the effects of SFN on H. pylori viability in vitro, levels of gastritis in H.pylori-infected mice in vivo, and in H.pylori-infected human subjects. We also examined the effects of SFN on NSAID-induced small intestinal injury in mice.Results: Our data from the H. pylori infection study clearly demonstrated that SFN inhibited H. pylori viability both in vitro and in vivo, and mitigated H. pylori-induced gastritis in mice and humans. Similar-ly, our study on NSAID-induced small intestinal injury showed that SFN not only mitigated aspirin-induced injury of small intestinal epithelial cells in vitro, but also ameliorated indomethacin-induced small intestinal injury in mice in vivo.Conclusions: These data strongly suggest that SFN contributes to the protection of GI mucosa against oxidative injury induced by H. pylori or NSAIDs.

Abstract NTOC-081: PHARMACOLOGIC ANALYSIS OF HIGH–GRADE SEROUS OVARIAN CANCER TCGA DATASET IDENTIFIES A NOVEL CHEMO–ADJUVANT ROLE FOR NON–STEROIDAL ANTI–INFLAMMATORY DRUGS (NSAIDS)

Abstract Computation-based drug repositioning approaches that automatically search vast amounts of genomic-chemical-phenotypic data for tens of thousands of drugs and diseases can greatly speed up the traditional drug-discovery process. To date, systematic and comprehensive computation-based approaches to identify and validate drug repositioning candidates for High-grade serous ovarian cancer (HGSOC) have not been undertaken. Using a novel computational drug-repositioning platform (Drug-Predict) with HGSOC gene expression dataset from The Cancer Genome Atlas (TCGA) as the input, we have uncovered that Non-steroidal anti-inflammatory drugs (NSAIDs) could be potential candidates for Drug repositioning in HGSOC. Given that numerous epidemiological studies have shown that regular intake of NSAIDs in women is associated with decreased incidence of ovarian cancer, we assessed whether NSAIDs could have chemo-adjuvant applications in HGSOC and have identified Indomethacin as a novel chemo-adjuvant in HGSOC. Indomethacin decreased survival of primary HGSOC tumor cells and interestingly, cisplatin resistant ovarian tumor cells (derived from primary HGSOC PDX models) exhibited significantly higher cell death upon Indomethacin treatment suggesting that Indomethacin could exert chemo-adjuvant effects in HGSOC. Accordingly, Indomethacin treatment induced chemo-sensitivity in cisplatin resistant HGSOC tumor cells and combo treatment with Indomethacin and cisplatin exerted synergistic cell death as compared to individual drugs alone. Furthermore, Indomethacin decreased stem-like properties and induced chemo-sensitivity in ALDHhigh cisplatin-resistant tumor-initiating cells (TICs) thus suggesting that the chemo-adjuvant effect of the drug is mediated by decrease in TIC properties in HGSOC cells. Mechanistically, we found that Indomethacin inhibits Wnt/β-catenin signaling by degrading β-catenin and β-catenin modulation inversely affected Indomethacin functioning in HGSOC. Our study is the first report describing functional effects of an NSAID in patient-derived HGSOC models and demonstrates that combining novel computational predictions with experimental validation has potential in identifying viable drug candidates and moving them into patient trials efficiently and cost-effectively. Since NSAIDs are in routine clinical use in gynecological settings and have acceptable safety profile, this discovery provides with a potentially rapid and cost-effective translational opportunity for testing NSAIDs as chemo-adjuvants in patient trials in HGSOC. Citation Format: Anil Belur Nagaraj, QuanQiu Wang, Olga Kovalenko, Peronne Joseph, Yang Chen, Rong Xu and Analisa DiFeo. PHARMACOLOGIC ANALYSIS OF HIGH–GRADE SEROUS OVARIAN CANCER TCGA DATASET IDENTIFIES A NOVEL CHEMO–ADJUVANT ROLE FOR NON–STEROIDAL ANTI–INFLAMMATORY DRUGS (NSAIDS) [abstract]. In: Proceedings of the 11th Biennial Ovarian Cancer Research Symposium; Sep 12-13, 2016; Seattle, WA. Philadelphia (PA): AACR; Clin Cancer Res 2017;23(11 Suppl):Abstract nr NTOC-081.

Quercetin attenuates, indomethacin-induced acute gastric ulcer in rats.

Peptic ulcer diseases are common and are induced by many factors, including stress, smoking, and ingestion of non-steroidal anti-inflammatory drugs. Quercetin is considered to be an anti-oxidant with healing effects on many experimental toxic injuries. The present study aimed to explore the possible effect of quercetin on acute gastric ulcer induced by indomethacin in rats. Three groups received indomethacin (30 mg/kg body weight) orally by orogastric gavage on two consecutive days. The rats received famotidine (50 mg/kg body weight), quercetin (50 mg/kg body weight), or vehicle alone for 15 consecutive days by oral gavage. The control group received no indomethacin but received vehicle for 15 days by oral gavage. The ulcer index, volume, and pH of gastric juice were measured, and the stomachs were examined by routine light microscopy. Compared with the control group, the indomethacin-treated rats showed a marked damage of the gastric mucosal surface and a high ulcer index. In the famotidine- and quercetin-treated groups, significantly increased antioxidant enzyme activities were observed. The congestion, erosions, and necrosis were reduced with mild inflammatory cell infiltration while no major damage of endothelial cells was observed in the treated rats. The findings of the study show that quercetin had antioxidant effect and can protect gastric mucosa against indomethacin-induced gastric ulceration than famotidine.

Protocolo diagnóstico del angioedema

IntroductionAngioedema (AE) is a local swelling in the subcutaneous/submucosal tissue produced by a transient increase of vascular permeability. ClassificationIt is classified into histaminergic AE (H-AE) and bradykinergic AE (BK-AE). There is another type of AE were leukotrienes are involved together with histamine as the mediators, and it is related to the intake of nonsteroidal anti-inflammatory drugs (NSAID-AE). AE is also divided into hereditary forms (HAE) and acquired (AAE). Diagnostic protocolsWhen facing an AE case it is important to conduct an approximative diagnosis that allows to classify the AE as histaminergic or bradykinergic to apply the most appropriate treatment. H-AE is usually erythematosus, pruritic, and hot, can have associated urticaria and responds to treatment with H1 antihistamines. Conversely, BK-AE is not erythematous, itchy or hot, it is not associated to urticaria and does not respond to H1 antihistamines. This protocol presents some diagnostic algorithms for the emergency room or outpatient consultations.

Natural evolution in patients with nonsteroidal anti-inflammatory drug-induced urticaria/angioedema.

Nonsteroidal anti-inflammatory drugs (NSAIDs) are the most frequent triggers of drug hypersensitivity with NSAIDs-induced urticaria/angioedema (NIUA) the most common phenotype. Loss of hypersensitivity has been reported for IgE-mediated reactions; however, it has not been assessed in nonimmunological reactions such as NIUA. We evaluated NSAID-hypersensitivity over time in NIUA patients. Patients confirmed as NIUA by positive drug provocation test (DPT) with acetylsalicylic acid (ASA) during 2005-2012 (V1) were included (n=38). Subjects were prospectively re-evaluated by DPT with ASA/other NSAIDs at two time points between 2013 and 2015 (V2 and V3). Atopy was assessed by skin prick test (SPT) using inhalant and food allergens. Patients were evaluated at V1 and re-evaluated after 60 months (V2; IR:48-81) and a further 18 months (V3; IR:14-24). At V2, the majority (24; 63.15%) tolerated ASA and other NSAIDs (Group A) while 14 (36.84%) still reacted (Group B). At V3, all Group A patients remained tolerant; all Group B patients remained hypersensitive. The number of previous episodes reported at V1 and the percentage of reactions induced by ASA/ibuprofen were significantly lower in Group A (P=.005 and P=.006, respectively). Group A patients developed tolerance 72 months (IR:45-87) after their last evaluated reaction (V1); this interval was shorter in nonatopics (P=.003), patients who experienced reactions over 1 hour after NSAIDs administration (P=.001), and those who experienced isolated urticaria after NSAID intake (P=.024). NIUA patients may develop tolerance to NSAIDs over time, a process that seems to be influenced by atopy and type of clinical reaction.

ω-3 polyunsaturated fatty acids use for optimization of children inflammatory joints diseases treatment

The use of additional treatment methods in inflammatory joints disease therapy is very important. But the main principles of diet therapy for patients with rheumatoid joint inflammation and reactive arthritis and possibility of focused impact on disease activity by means of alimentary factors have not still been formed out. The aim of the investigation was to study the effect of diet therapy including ω-3 polyunsaturated fatty acids (PUFAs) on joint syndrome evidence and on bone turnover markers of children with inflammatory joint diseases. With parents' agreement children aged 5-16 hospitalized with inflammatory joint diseases (53 with juvenile rheumatoid arthritis and 35 with reactive arthritis) were enrolled in this research. According to the treatment mode 2 subgroups were separated in each group: the first subgroup underwent backbone therapy, the second - backbone therapy along with ω-3 PUFAs (cod liver oil 1000 mg containing 115 mg of docosahexaenoic and 23 mg of eicosapentaenoic acids). Children aged 3-5 years received 1 capsule 2 times a day, over 6 years old - 1 capsule 3 times per day with meals for 3 months. Disease activity, joint syndrome evidence (counting of joint pain, Ritchie index, number of inflammatory joints, morning stiffness duration) and biochemical values of connective tissue metabolism were estimated while being introduced into research and at the end of treatment. More apparent improvement of joint syndrome indexes at the end of supervision was diagnosed in the groups undergoing backbone therapy along with ω-3 PUFAs. Statistically significant (p<0.05) reduce of morning stiffness time by 3 fold vs 2 fold in children treated with basic therapy, reduce of joint index by 2.9-5.7 fold vs 2.0-3.8 fold, the number of inflammatory joints by 4.5-5.8 fold vs 2.0-2.3 fold, blood serum level of hydroxyl proline and antibodies to rumalon were observed in main groups of patients. Disease activity index DAS 4 decreased in the group undergoing backbone therapy by 0.44 (p<0.05) and in the group undergoing modified therapy - by 1.20 (p<0.05). No adverse effects of PUFAs have been observed. It was concluded that ω-3 PUFAs increased the action of basic therapy favoring advances in inflammatory process activity control, provided decrease of non-steroidal antiinflammatory drugs (NSAID) intake and proved to be an important supplement in diet therapy of children inflammatory joints diseases.

Features of inflammatory and regenerative reaction to excimer laser refractive keratectomy with photoprotection

Aim. To study the features of inflammatory and regenerative reaction to excimer laser refractive keratectomy with photoprotection.Methods. Clinical cases of 560 excimer laser refractive keratectomies with photoprotection in 280 patients with myopia and myopic astigmatism of different severity. The observation period varied from 1 month to 2.5 years.Results. The study showed that intensity of aseptic inflammation and the type of regenerative response are influenced by the amount of evaporated corneal tissue, which correlates with the severity of myopia. Moreover, in case of equal severity of myopia and amount of evaporated tissue inflammatory and regenerative response was less prominent if excimer laser ablation was performed under the superficial corneal flap. In this case epithelial stromal corneal flap allowed reducing the negative effect of ultraviolet exposure and interaction between proinflammatory epithelial and stromal cytokines. At photorefractive ablation of corneal stroma saturated with 0.25% isotonic riboflavin solution aseptic inflammatory and regenerative response, intensity and duration of corneal syndrome decreased. Due to such technique of photorefractive keratectomy stromal layers saturated with riboflavin absorbed the secondary ultraviolet induced by ablation. Clinical observation demonstrated the need for additional photoprotection by glasses from external unltraviolet in all types of photorefractive surgeries on cornea up to full recovery of visual and optometric parameters. Use of photoprotection during excimer laser refractive ablation allowed achieving early stabilization of vision and refraction, decreasing the duration of postoperative steroidal and nonsteroidal anti-inflammatory drugs intake by one third in average.Conclusion. Local photoprotection with riboflavin during excimer laser refractive keratectomy and photoprotection by glasses from external ultraviolet reduce the risk of oxidative stress in the cornea, postoperative aseptic inflammatory and regenerative reactions, promote stabilization of visual, optic refractive parameters and improve their predictability.

AN OPEN-LABEL MULTICENTER OBSERVATIONAL STUDY OF THE EFFICACY, TOLERABILITY, AND SAFETY OF THE NONSTEROIDAL ANTI-INFLAMMATORY DRUG AMTOLMETIN GUACIL IN PATIENTS WITH KNEE OSTEOARTHRITIS AND DYSPEPSIA

Objective: to investigate the efficacy and tolerability of amtolmetin guacil (AMG; Niselat®, Dr. Reddy's Laboratories Ltd, India) versus previous therapy with nonsteroidal anti-inflammatory drugs (NSAIDs) in patients with knee osteoarthritis (OA) and signs of dyspepsia.Subjects and methods. The open-label observational study included 220 patients aged 30–65 years who suffered from knee OA and intense pain during NSAID intake and had symptoms of dyspepsia in the absence of contraindications to the use of AMG. Among the comorbidities that generally occurred in 68% of the patients, there was a preponderance of hypertension (42%), lower extremity varicose veins (6.4%), and diabetes mellitus (6%). Treatment efficacy was evaluated using three domains of the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), by also taking into account pain intensity and general health assessment on the visual analogue scale. A Severity of Dyspepsia Assessment (SODA) scale was used to rate dyspepsia.Results and discussion. AMG had a marked analgesic effect confirmed by 40% or more pain reduction that occurred in 72.5% of the patients. The high analgesic effect of AMG was confirmed by a statistically significant (p &lt;0.001) reduction in the WOMAC index (pain and stiffness) and by an increase in functional activity. There was a significant decrease in painless and painful signs of dyspepsia, as well as positive changes in the measures “overall assessment of dyspepsia severity” (p &lt; 0.001) and “satisfaction with treatment”. Overall assessment of AMG tolerability was only positive: excellent (33%), good (56%), and satisfactory (11%). There were no serious adverse events (AE). AE were graded as moderate and mild in 8 and 82% of cases, respectively. AE were recorded in 7.7% of the patients. Conclusion. The findings suggest that AMG offers good prospects for knee OA treatment.

A COMMON PATHOLOGY, A RARE CAUSE - A CASE REPORT OF CANDIDIAL GASTRIC PERFORATION

Peritonitis due to peptic ulcer perforation is a frequently encountered surgical emergency. Intake of non steroidal anti inflammatory drugs (NSAIDs), Helicobacter pylori infection and neoplastic etiology are the common causes documented. Uncommonly peptic perforation can be due to fungal infection. If it occurs; it is associated with significantly increased morbidity and mortality. This case report emphasize on considering fungal infection as etiology of gastric perforation, even when other common causes like NSAIDs intake are present. An early diagnosis can prevent fatal complications like shock, fever, wound complications and multiorgan failure. Knowledge of such case reports can help a surgeon in dealing with common pathology but rare etiology.

TREATMENT OF PATIENT SYNDROME AT THE AMBULATORY-POLYCLINIC STAGE. SELECTION OF THE ANALGETIC FROM THE POSITIONS OF COMORBIDITY AND DRUG SAFETY: IN FOCUS DEXKETOPROFEN

Pain is one of the most common symptoms in modern clinical practice and one of the most common reasons why patients seek medical care at an outpatient clinic. Traditionally, nonsteroidal anti-inflammatory drugs (NSAIDs) are the leading means of protecting peripheral pain receptors. However, with the intake of NSAIDs, a whole range of different complications is associated. Comorbidity and drug safety are closely related to the use of NSAIDs. In the presented review, domestic and foreign studies of dexketoprofen for the treatment of pain syndrome in the outpatient and polyclinic stage were analyzed. The emergence of the domestic brand-generic dexketoprofen, the drug Flamadex®, in the Russian pharmaceutical market increases the availability of effective and safe therapy of pain syndrome in patients with comorbid pathology at the outpatient and polyclinic stage.

OA04.05 Chronic Inflammation, NSAIDS and the Risk of Lung Cancer Death

Chronic inflammation appears to heighten the risk of lung cancer and, reciprocally, agents that reduce inflammation have been found to reduce this risk. Nevertheless, few prospective studies have examined associations between lung cancer and the intake of nonsteroidal anti-inflammatory drugs (NSAIDs). In the current study, we examined associations between fatal lung cancer and NSAIDs using prospective data from the Third National Health and Nutrition Examination Study. Baseline data on smoking, NSAIDs and other lifestyle variables were collected for 10,735 participants during 1988-1994, and cause-specific mortality status was ascertained through probabilistic record matching using the National Death Index through 2006. Cox proportional hazards regression models were used to estimate hazard ratios (HRs) to quantify associations between NSAID use and lung cancer death, with adjustment for current smoking and other variables. During 18 years of follow-up, 269 individuals died from lung cancer of which 252 (93.6%) reported a history of cigarette smoking. Since all but 17 of the 269 fatal lung cancer cases occurred among current or former smokers, estimates of NSAID effects were ascertained from a sub-cohort of 5,882 individuals who reported a history of past or current cigarette smoking. Multivariate regression models revealed that regular use of ibuprofen reduced the risk of lung cancer death by 48% (HR=0.52, 95% CI=0.33-0.82, P<0.01). Main effects of other compounds tested (aspirin or acetaminophen) were not statistically significant. Prospective data from NHANES III showed that among adults with a history of past or current smoking, ibuprofen intake was associated with a substantial (48%) reduction in the risk of dying from lung cancer. Effects of aspirin and acetaminophen were not statistically significant. These results suggest that regular use of certain NSAIDs may be beneficial for high-risk subgroups of smokers as a lung cancer prevention strategy.

RENAL-ASSOCIATED ESCAPE EFFECT OF ANTIHYPERTENSIVE THERAPY IN HYPERTENSIVE PATIENTS RECEIVING NONSTEROIDAL ANTI-INFLAMMA‑ TORY DRUGS (“PANDA” TRIAL)

Objective. The subanalysis of the study “PANDA” (the study of renal function in patients with acute nonspecific pain in lower back during therapy with nonsteroidal anti-inflammatory drugs (NSAID)) is the study of renal-associated escape effect of antihypertensive therapy in patients with arterial hypertension (HTN) receiving NSAID. Design and methods. We included 407 patients receiving one of the following NSAIDs for 14 days: meloxicam (15 mg/day), etoricoxib (60 mg/day), nimesulide (200 mg/day) or celecoxib (200 mg/day). Five visits were performed. During the visits blood pressure (BP), glomerular filtration rate (GFR), blood levels of cystatin C were assessed. Results. At first step, all parameters were evaluated in the whole group (n = 407). As the second step, we analyzeds the indicators in 4 groups depending on the NSAID type. At the third stage (subanalysis) we allocated 3 groups of patients: 1 group (n = 62) — patients with a history of HTN and diabetes mellitus, group 2 (n = 173) patients with HTN, and group 3 (n = 172) — patients without HTN and diabetes mellitus. Conclusions . In patients with acute nonspecific back pain, with a history of HTN, NSAID intake is associated with the certain changes in BP, GFR and cystatin-С. Therefore, we can discuss a renal-associated escape effect of antihypertensive therapy. It is the most evident on the 7th day of NSAID therapy. All changes of the studied parameters should be considered as a class-effect adverse reactions of NSAIDs, without any benefits in relation to specific medications.

Antiinflammatory treatment in patients with chronic back pain

We analyzed the peculiarities of treatment of CBP in 250 patients at baseline and after 1 and 2 years. The features of drug therapy, the reasons for therapy cancellation were evaluated. 52 (20.8%) of patients with CBP were not treated with NSAIDs, 38 (15.2%) recieved NSAIDs in 4 and > days per week, 44 (17.6%) - 3 and < days a week, 62 (24.8%) took NSAID in 7-14 day 2-5 times per year, 54 (21.6%) - in on-demand mode. Absence of NSAIDs administration in CBP was associated with older age, the presence of comorbidites, with non-alcoholic fatty liver disease and obesity. The cancelletion of previously initiated NSAID was equally associated with the resolution of pain and with the failure to respond to therapy, with the presence of obesity and with the intake of nonselective NSAIDs. Continuation of the initiated effective anti-inflammatory therapy was associated with the use of coxibs, complex treatment with the use of neirobion, with the presence of normal body weight, and with the achievement of a decrease in the severity of the pain syndrome even in the absence of its complete resolution. Increased adherence to treatment with NSAIDs in CBP patients can be achieved by increasing of its effectiveness through the use of NSAIDs (especially coxibs) with B group vitamins (B1, B6, B12), by normalizing of BMI and effectively controlling liver function.

Non-steroidal Anti-inflammatory Drugs may Worsen the Course of Community-Acquired Pneumonia: A Cohort Study.

Non-steroidal anti-inflammatory drugs (NSAIDs) are frequently prescribed or used as self-medication in cases of community-acquired pneumonia (CAP). Nevertheless, the consequences of such medication on the risk of pleuroparenchymal complications are not well known. The aim was to investigate whether exposure to NSAIDs prior to hospital admission among patients suffering from CAP is associated with the development of pleural complications or a lung abscess. All consecutive non-immunocompromised patients with CAP and admitted to a university hospital were prospectively included (2-year period). The risk of pleuropulmonary complications was analyzed according to previous exposure to NSAIDs. Of the 221 included patients, 40 (18.1%) had developed a pleuropulmonary complication. NSAIDs intake prior to admission was reported for 24 patients (10.9%) who were younger (50.6±18.5 vs. 66.5±16.4years; p=0.001), had less comorbidities (60 vs. 25.1%; p=0.001), had a longer duration between the first symptoms of CAP and the start of an antibiotic therapy (6.1±7.6 vs. 2.8±3.8days; p=0.001), and who had a higher incidence of pleuropulmonary complications (33.3 vs. 16.2%; p=0.048). In multivariate analyses, two factors were independently associated with the development of pleuroparenchymal complications: NSAIDs intake [Odds Ratio (OR)=2.57 [1.02-6.64]; p=0.049] and alcohol abuse (OR=2.68 [1.27-5.69]; p=0.01). Our findings suggest that NSAIDs, often taken by young and healthy patients, may worsen the course of CAP with delayed therapy and a higher rate of pleuropulmonary complications.

Association of interleukin-25 levels with development of aspirin induced respiratory diseases

BackgroundAspirin-exacerbated respiratory diseases (AERD) are caused by ingestion of non-steroidal anti-inflammatory drugs and are characterized by acute bronchospasms and marked infiltration of eosinophils, the latter being attributable to altered synthesis of cysteinyl leukotrienes (LT) and prostaglandins (PG). Recently, the innate Th2 response is revealed to induce eosinophil infiltration in allergic inflammation, however the role of the innate Th2 response has not been studies in AERD. Thus, we evaluated the relationship between the innate Th2 cytokines including IL-25, thymic stromal lymphopoietin (TSLP) and IL-33 and the development of AERD. Methods and materialsPlasma IL-25, IL-33, and TSLP levels were measured before and after aspirin challenge in subjects with AERD (n = 25) and aspirin-tolerant asthma (ATA, n = 25) by enzyme-linked immunosorbent assay (ELISA). Pre and post-aspirin challenge levels of LTC4 and PGD2 were measured using ELISA. ResultsBasal plasma IL-25 levels were significantly higher in AERD group than in normal controls and in ATA group (p = 0.025 and 0.031, respectively). IL-33 and TSLP levels were comparable in the AERD and ATA groups. After the aspirin challenge, the IL-25 levels were markedly decreased in the ATA group (p = 0.024), while not changed in the AERD group. The post-challenge IL-25 levels of all asthmatic subjects were significantly correlated with aspirin challenge - induced declines in FEV1 (r = 0.357, p = 0.011), but not with basal and post challenge LTC4 and PGD2 levels. ConclusionsIL-25 is associated with bronchospasm after aspirin challenge, possibly via mechanisms other than altered LTC4 and PGD2 production.

Symptom-modifying effects of oral avocado/soybean unsaponifiables in routine treatment of knee osteoarthritis in Poland. An open, prospective observational study of patients adherent to a 6-month treatment.

ObjectivesObservational studies provide insights into real-life situations. Therefore, we assessed the effects of oral avocado/soybean unsaponifiable (ASU) capsules on pain relief and functional ability in patients, while they were receiving a routine treatment for knee osteoarthritis (OA).Material and methodsAn open, prospective, observational 6-month study was conducted in 99 centers in Poland in a group of 4822 patients with symptomatic knee OA receiving one 300 mg ASU capsule/day as a routine medication. The patients had no diagnoses of other rheumatic diseases and were not treated with other symptomatic slow-acting drugs for osteoarthritis (SYSADOAs). Data on OA symptoms and therapy were collected from the initiation of ASU treatment (visit 0) and during 3 consecutive control visits performed every 2 months (visits 1–3). Functional Lequesne index, severity of joint pain of one symptomatic knee (Laitinen index and VAS), use of analgesics and non-steroidal anti-inflammatory drugs (NSAIDs), adherence to treatment and adverse events were evaluated and recorded using electronic Case Report Forms.ResultsFour thousand one hundred and eighty-six patients (86.8%) attended all 4 visits. In 94.2% of patients (mean age 60.7 ±11.6 years SD, 73.4% female) at least one OA risk factor was identified. There was a significant improvement in functional ability between the last and baseline visits as evidenced by the median Lequesne index decreasing from 8 to 4 points (p < 0.001). Measures of pain intensity also fell significantly (p < 0.001) throughout the study: median Laitinen score decreased from 6 to 3 points, median pain at rest VAS – from 1.8 to 0 cm and median pain during walking VAS – from 5.6 to 1.9 cm. The significant differences were also noted between consecutive visits. The proportion of patients using analgesics and NSAIDs declined from 58.8% at the baseline visit to 24.9% at the last visit 3 (p < 0.001). Defined daily dose of NSAIDs decreased significantly from 1 at the baseline visit to 0.67 at the visit 3. Severe adverse events associated with ASU treatment were not observed.ConclusionsIt was the first observational study in Poland evaluating the effects of routine knee OA treatment with oral ASU. Only a small group of patients (13.2%) treated with ASU discontinued the study. The majority of patients adherent to the ASU treatment for 6 months showed gradual alleviation of joint pain, improvement in functional ability and a significant reduction in NSAIDs intake.

Dilemma of Timing of Administration of Non-Steroidal Anti-inflammatory Agents in Relation to Food in the Prevention of Drug Induced Gastritis: Debusting the Myth.

We aimed to identify the signals that indicate the possible benefits of administering Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) at the initiation of meal, compared to immediately after food. This was a randomized, controlled, pilot study in 160 patients who received only NSAIDs for various pain conditions. Patients were randomized to Group I (control group) -NSAID After Food (AF), Group II-NSAID Before Food (BF), Group III-NSAID BF for 2 days and then crossed over to AF for next two days (CO-1) and Group IV-NSAID AF for 2 days and then crossed over to BF for next two days (C0-2 group). Group III & Group IV were given a washout period of 48 hours after the initial two days of treatment. All were followed up for the next 2 drug free days. Patients were observed for the development of gastritis (epigastric distress, epigastric pain, nausea, fullness of stomach, repeated reflux) throughout the study. Symptoms of gastritis were seen in 6.45% (2/31) and 36.11% (13/36) patients in group I and II, respectively. There was no statistically significant difference in the development of gastritis in AF group. However, statistically significant difference (P<0.05) was found between BF group and AF intake of NSAIDs [CO-1 (AF), CO-2 (A.F), AF (control group)] in terms of development of gastritis. Administering NSAIDs at the initiation of meal is better tolerated as indicated by the lower incidence of gastritis. If proved in larger population, routine concurrent administration of medication for prevention of gastritis can be avoided.