Alergia e intolerancia a antiinflamatorios no esteroideos en pediatría / Allergy and intolerance to nonsteroidal anti-inflammatory drugs in children

Los antiinflamatorios no esteroideos son ampliamente recetados en niños. Constituyen la segunda causa de reacciones a medicamentos en pediatría después de los antibióticos betalactámicos; sin embargo, solo una parte de estas son reacciones de hipersensibilidad. La prevalencia de dichas reacciones a antiinflamatorios no esteroideos en niños es del 0,3 % y aumenta al 5 % en asmáticos.Los mecanismos fisiopatológicos involucrados (inhibición de la ciclooxigenasa, hipersensibilidad mediada por inmunoglobulina E, linfocitos T reactivos y/o afectación de la inmunidad innata) darán lugar a diferentes entidades clínicas con sintomatología dispar.La confusión con síntomas propios de procesos virales y la variabilidad clínica hacen del diagnóstico de certeza un verdadero desafío. Una historia clínica detallada, análisis de laboratorio, pruebas cutáneas y de provocación controlada permitirán definir estrategias para cada paciente en particular sin etiquetar como alérgico a un niño que no lo es ni exponer a riesgos innecesarios a quien está sensibilizado.

Nonsteroidal anti-inflammatory drugs are widely prescribed in children. They are the second cause of drug ́s reactions in pediatrics after beta-lactam antibiotics, however only a part of them are hypersensitivity reactions. The prevalence of these reactions to nonsteroidal anti-inflammatory drugs in children is 0.3 %, increasing to 5 % in asthmatics.The different physiopathological mechanisms involved (inhibition of cyclooxygenase, immunoglobulin E-mediated hypersensitivity, reactive T lymphocytes and/or disturbance of innate immunity) will cause different clinical entities with diverse symptoms.The confusion between the common symptoms of a viral infection and a hypersensitivity reaction, and the variability of the clinical presentations make diagnosis a real challenge.A detailed clinical history, laboratory, skin and controlled provocation tests will provide strategies for each patient, without labeling a child who is not an allergic one, or taking unnecessary risks with those who are sensitized.

A comprehensive review and the pharmacologic management of primary dysmenorrhea

Dysmenorrhea is the most common gynecologic condition in women during the reproductive period. Severe dysmenorrhea pain affects their social activities, sleep, and quality of life. Nevertheless, the proportion of women with dysmenorrhea do not receive adequate medical counseling or pharmacological treatments. Primary dysmenorrhea is diagnosed clinically, and the secondary causes that can cause pelvic pain should be identified. The treatment of choice for primary dysmenorrhea is non-steroidal anti-inflammatory drugs (NSAIDs). In order to maximize the therapeutic effect, it is necessary to ensure that the appropriate medication is administered in a proper way. NSAIDs can cause adverse effects, including gastrointestinal disorders. If side effects occur or are anticipated with NSAIDs, the use of hormonal contraceptives may be recommended when contraception is considered. In addition to these pharmacological treatments, heat, dietary, and behavioral therapies have been tried and reported to have some effects. However, further research is required for robust conclusions.

The effect of naproxen patches on relieving orthodontic pain by evaluation of VAS and IL-1β inflammatory factor: a split-mouth study

ABSTRACT Introduction: Pain related to orthodontic tooth movement is common and cause dissatisfaction and discomfort. Objective: The present study aimed to compare the efficacy of naproxen patches in pain control during orthodontic tooth separation, by means of visual analogue scale (VAS) and interleukin 1β (IL-1β) levels in gingival crevicular fluid (GCF). Methods: In this split-mouth triple-blind clinical trial, with 40 patients following separation, 5% naproxen or placebo patches were randomly placed on the upper right or left first molars every 8 hours. Pain intensity scores were determined after 2 and 6 hours, sleep time, 24 hours, days 2, 3 and 7 by the patients using a 100-mm VAS ruler. IL-1β levels in GCF were evaluated by ELISA at baseline, 1 and 24 hours and 7 days. Paired samples t-tests and two-way repeated measures ANOVA analysis of variance with a significance level of 0.05 were applied. Results: A total number of 30 patients (13 males and 17 females) finished the trial. Significant differences were found in pain scores (p< 0.0001) and IL-1β levels (p= 0.047) between naproxen and placebo groups. Lower pain scores were reported for the patients using naproxen patches at all time points, except 1 hour after separation. IL-1β levels were lower for the patients using naproxen patches only 1 hour after separation (p= 0.047). The peak of pain scores and IL-1β levels were calculated at 24 hours. Conclusion: In the light of VAS scores and IL-1β levels, naproxen patches reduced the pain caused by separator placement.

RESUMO Introdução: a dor relacionada à movimentação dentária ortodôntica é comum e causa insatisfação e desconforto. Objetivo: o presente estudo teve como objetivo avaliar a eficácia de curativos de naproxeno no controle da dor durante a separação ortodôntica dos dentes, por meio de escalas visuais analógicas (EVA) e dos níveis de interleucina 1β (IL-1β) no fluido crevicular gengival (FCG). Métodos: neste ensaio clínico, triplo-cego, boca dividida, com 40 pacientes após a separação dos dentes, foram aplicados, de forma aleatória, curativos com naproxeno a 5% ou placebo, nos primeiros molares superiores, direito ou esquerdo, a cada 8 horas. Os escores de intensidade da dor foram registrados pelos pacientes após 2 e 6 horas, durante o sono, após 24 horas, 2, 3 e 7 dias, usando uma EVA de 100 mm. Os níveis de IL-1β no FCG foram avaliados pelo ELISA no momento inicial, e após 1 e 24 horas e 7 dias. Foram aplicados testes t para amostras pareadas e ANOVA de duas vias para medidas repetidas, com nível de significância de 0,05. Resultados: no total, 30 pacientes (13 homens e 17 mulheres) terminaram o ensaio clínico. Diferenças significativas foram encontradas nos escores de dor (p< 0,0001) e níveis de IL-1β (p= 0,047) entre os grupos naproxeno e placebo. Índices mais baixos de dor foram relatados pelos pacientes que usaram curativos de naproxeno em todos os tempos avaliados, com exceção de 1 hora após a separação. Os níveis de IL-1β foram menores nos pacientes que usaram os curativos de naproxeno apenas 1 'hora após a separação (p= 0,047). Os picos dos escores de dor e dos níveis de IL-1β foram registrados 24 horas após a separação. Conclusão: considerando-se os escores das EVAs e os níveis de IL-1β, pode-se concluir que os curativos de naproxeno reduziram a dor causada pela instalação dos separadores ortodônticos.

Tolerância ao paracetamol em crianças com hipersensibilidade não seletiva aos anti-inflamatórios não esteroidais / Tolerance to paracetamol in children with non-selective hypersensitivity to non-steroidal anti-inflammatory drugs

Introdução: Os anti-inflamatórios não esteroidais (AINEs) estão envolvidos na maior parte das reações de hipersensibilidade a drogas na América Latina. Objetivos: Avaliar a tolerância ao paracetamol em crianças com história sugestiva de hipersensibilidade não seletiva aos AINEs. Métodos: Estudo retrospectivo de análise de dados de pacientes pediátricos atendidos em ambulatório especializado no período de julho de 2011 a julho de 2017. Os dados foram analisados e registrados em questionário padronizado adaptado. As reações foram classificadas como seletivas ou não seletivas. Pacientes com história clínica a um único AINE foram submetidos a teste de provocação oral (TPO) com o ácido acetilsalicílico para definição da seletividade ou não da reação. TPO com paracetamol foi realizado em todos os que relataram reação ao mesmo. Resultados: A maior parte dos pacientes tinha hipersensibilidade não seletiva a AINEs. A dipirona foi implicada em todos os casos, seguida do ibuprofeno (78%) e do paracetamol (51%). Todos os pacientes com história de hipersensibilidade seletiva foram provocados com outro AINE inibidor forte de COX-1, que não aquele implicado em sua história, e todos demonstraram tolerância. Os 22 pacientes cuja história apontava envolvimento do paracetamol foram submetidos a TPO e todas as provocações resultaram negativas. O etoricoxibe foi testado como droga alternativa em oito pacientes e se demonstrou ser uma opção segura (todas as provocações negativas). Conclusão: Apesar da elevada frequência de relato de reações ao paracetamol, a maioria das crianças tolera o composto que é, sem dúvida alguma, alternativa segura frente à hipersensibilidade não seletiva aos AINEs.

Introduction: Non-steroidal anti-inflammatory drugs (NSAIDs) are the group of drugs most frequently involved in hypersensitivity reactions in Latin America. Objectives: To evaluate tolerance to paracetamol in children with non-selective hypersensitivity reactions to NSAIDs. Methods: Clinical records of children treated at a specialized outpatient clinic from July 2011 to July 2017 were retrospectively analyzed. The data were registered in a specific questionnaire and reactions were defined as selective or non-selective. The diagnosis was confirmed by oral drug provocation test with acetylsalicylic acid in patients with only one NSAID implicated in clinical history to confirm whether the hypersensitivity reaction was selective. Tolerance to paracetamol was also evaluated through drug provocation tests. Results: Most of the cases were classified as non-selective hypersensitivity reactions. Dipirone was implicated in all the cases, followed by ibuprofen (78%) and paracetamol (51%). All patients with selective hypersensitivity reactions to NSAIDs underwent a drug provocation test with an alternative COX-1 inhibitor and all of them tolerated it. Twenty-two patients were tested with paracetamol and all of them had negative results. Tolerance to etoricoxib was also evaluated through drug provocation tests, all negative. Conclusion: Paracetamol can be considered a great alternative drug in children with non-selective hypersensitivity reactions to NSAIDs.

Clinical Implications of Single Nucleotide Polymorphisms in Diagnosis of Asthma and its Subtypes

For the past three decades, a large number of genetic studies have been performed to examine genetic variants associated with asthma and its subtypes in hopes of gaining better understanding of the mechanisms underlying disease pathology and to identify genetic biomarkers predictive of disease outcomes. Various methods have been used to achieve these objectives, including linkage analysis, candidate gene polymorphism analysis, and genome-wide association studies (GWAS); however, the degree to which genetic variants contribute to asthma pathogenesis has proven to be much less significant than originally expected. Subsequent application of GWAS to well-defined phenotypes, such as occupational asthma and non-steroidal anti-inflammatory drugexacerbated respiratory diseases, has overcome some of these limitations, although with only partial success. Recently, a combinatorial analysis of single nucleotide polymorphisms (SNPs) identified by GWAS has been used to develop sets of genetic markers able to more accurately stratify asthma subtypes. In this review, we discuss the implications of the identified SNPs in diagnosis of asthma and its subtypes and the progress being made in combinatorial analysis of genetic variants.

Eperisone-Induced Anaphylaxis: Pharmacovigilance Data and Results of Allergy Testing

PURPOSE: Eperisone is an oral muscle relaxant used in musculoskeletal disorders causing muscle spasm and pain. For more effective pain control, eperisone is usually prescribed together with nonsteroidal anti-inflammatory drugs (NSAIDs). As such, eperisone may have been overlooked as the cause of anaphylaxis compared with NSAIDs. This study aimed to analyze the adverse drug reaction (ADR) reported in Korea and suggest an appropriate diagnostic approach for eperisone-induced anaphylaxis. METHODS: We reviewed eperisone-related pharmacovigilance data (Korea Institute of Drug Safety-Korea Adverse Event Reporting System [KIDS-KAERS]) reported in Korea from 2010 to 2015. ADRs with causal relationship were selected. Clinical manifestations, severity, outcomes, and re-exposure information were analyzed. For further investigation, 7-year ADR data reported in a single center were also reviewed. Oral provocation test (OPT), skin prick test (SPT) and basophil activation test (BAT) were performed in this center. RESULTS: During the study period, 207 patients had adverse reactions to eperisone. The most common ADRs were cutaneous hypersensitive reactions (30.4%) such as urticaria, itchiness or angioedema. Fifth common reported ADR was anaphylaxis. There were 35 patients with anaphylaxis, comprising 16.9% of the eperisone-related ADRs. In the single center study, there were 11 patients with eperisone-induced anaphylaxis. All the patients underwent OPT and all the provoked patients showed a positive reaction. Four of the 11 patients with anaphylaxis also underwent SPT and BAT, which were all negative. CONCLUSIONS: Incidence of eperisone-induced anaphylaxis calculated from the KIDS-KAERS database was 0.001%. Eperisone can cause hypersensitive reactions, including anaphylaxis, possibly by inducing non-immunoglobulin E-mediated immediate hypersensitivity.

Comparison of Preoperative and Postoperative Parecoxib Administration for Pain Control Following Major Spine Surgery

STUDY DESIGN: Prospective randomized, double-blind controlled trial. PURPOSE: Here, we aim to compare the efficacy and safety of pain control between pre- and postoperative parecoxib administration in patients who have undergone major spine surgery. OVERVIEW OF LITERATURE: Several studies have compared the efficacy of pre- and postoperative administration of parecoxib, which led to inconclusive results owing to variation in operative time. Preincisional parecoxib administration reduces inflammatory response in major spine surgery requiring longer operative time; however, it may not reduce pain as much as parecoxib administration immediately after surgery would. METHODS: Totally, 127 patients who underwent major spine surgery were randomly divided into three groups: pre-group, which received 40 mg parecoxib before skin incision and at 12 and 24 hours after the first dose; post-group, which received the same dose at wound closure and at 12 and 24 hours after the first dose; and control group, which did not receive any parecoxib. Efficacy and safety of parecoxib were measured based on pain score, morphine consumption, and side effects from both morphine and parecoxib at 24 hours after surgery. RESULTS: Initial postoperative pain score, postoperative pain score at rest, and accumulative morphine consumption at 24 hours after surgery were similar between the pre- and post-groups. Despite the significantly lower pain score and morphine consumption in both pre- and post-groups compared with the control group, cumulative morphine consumption at 24 hours after surgery was reduced by approximately 50% in the pre-group and 46% in the post-group compared. Analgesic-related complication incidence was similar in all groups. CONCLUSIONS: The timing of parecoxib administration, either before or after major spinal surgery, did not affect the safety and analgesic efficacy of pain management.

Effect of Non-Steroidal Anti-Inflammatory Drug Mouthwash on Post-Tonsillectomy Pain: Randomized, Controlled Study / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: Altough tonsillectomy is one of the most common otolaryngological procedures, a highly reliable and effective method for reducing postoperative pain has yet to be identified. This study evaluated the efficacy of a non-steroidal anti-inflammatory drug (NSAID) mouthwash on postoperative pain in tonsillectomy patients. SUBJECTS AND METHOD: A total of 64 patients who underwent tonsillectomy were randomly assigned to one of two groups (32 patients each). One group received the NSAID mouthwash and the other a distilled water mouthwash. Postoperative pain in the two groups was compared by assessing pain severity 1-9 days postoperatively using a visual analog scale. RESULTS: Compared to the distilled water mouthwash group, patients using the NSAID mouthwash showed a statistically significant decrease in postoperative pain over the first 9 postoperative days. CONCLUSION: A NSAID mouthwash may be a simple and effective method for controlling post-tonsillectomy pain when administered in conjunction with routine medications.

Early Clinical Outcomes after Subacromial Injection of Ketorolac in Patients with Shoulder Impingement Syndrome: A Comparison with Steroid Injection / 대한정형외과학회잡지

PURPOSE: The purpose of this study was to compare the clinical results between the subacromial injection of the ketorolac and that of the corticosteroid in patients with subacromial shoulder impingement syndrome. MATERIALS AND METHODS: Twenty patients with shoulder impingement syndrome received an injection of 60 mg ketorolac and were evaluated in terms of visual analogue scale (VAS), range of motion (ROM) and Constant-Murley score. The outcomes are compared with the data of patients treated by 40 mg triamcinolone injection, retrospectively. RESULTS: There was no significant difference in the demographics, VAS, ROM, and Constan-Murley score between the two groups before the injection. At the 4 weeks follow-up, pain improvement was significantly greater in the corticosteroid group (2.7±1.53) than in the ketorolac group (4.9±2.08; p=0.001). However 12 weeks after the injection, there was no significant difference in pain improvement between the two groups (ketorolac: 2.9±2.32, corticosteroid: 2.6±1.82; p=0.707). The Constant-Murley score at the final follow-up improved from 33.5 to 52.1 in the corticosteroid group, and from 39.0 to 56.6 in the ketorolac group (p=0.677). ROM was increased in both groups, and external rotation was significantly greater in the ketorolac group than in the corticosteroid group at the final follow-up (ketorolac: 29.3°±9.90°, corticosteroid: 20.8°±7.99°; p=0.005). CONCLUSION: In this study, ketolorac provided an effect equivalent to triamcinolone in the treatment of subacromial shoulder impingement syndrome at 12 weeks after the injection. This result could offer better opportunities to manage patients with diabetes or local and systemic side effects of repetitive use of corticosteroids.

Acute kidney injury caused by administration of zaltoprofen in a cat

A 5-year-old, 2.7 kg, spayed female Scottish Fold cat presented with hematemesis after administration of oral zaltoprofen, a non-steroidal anti-inflammatory drug, by the owner. Diagnostic imaging and blood analyses indicated development of acute kidney injury (AKI) resulting from zaltoprofen ingestion. To correct dehydration and anemic conditions, the cat received intravenous fluid therapy with whole blood transfusion and peroral N-acetylcysteine. Clinical signs resolved, but persistent azotemia was unresolved indicating that AKI could progress to chronic kidney disease. This case suggests that although zaltoprofen may have low adverse effects on humans, administration of zaltoprofen in cats can have serious adverse effects.

ADMINISTRATION OF H2 BLOCKERS IN NSAID INDUCED GASTROPATHY IN RATS: effect on histopathological changes in gastric, hepatic and renal tissues

ABSTRACT Background Nonsteroidal anti-inflammatory drugs induces gastric mucosal lesions because of its acidic properties. Ranitidine, an H2 receptor antagonist, has proved beneficial in patients with gastric ulcers. Objective The present study was performed to assess the effect of administering ranitidine in Nonsteroidal anti-inflammatory drugs (diclofenac, nimesulide) induced gastropathy, and their effect on the histopathology of stomach, kidney and liver. Methods Diclofenac, nimesulide, and ranitidine were administered in doses of 2, 4, and 6 mg/kg, p.o. once daily for 14 days, and their effect on gastric volume, acidity, mean ulcer number, and gastric pH. In addition, histopathological examination was also performed on sections of stomach, kidney and liver. Results Following the administration of diclofenac or nimesulide, all the gastric parameters were significantly altered as well as the histopathology of stomach, liver and kidney. In the control group, the renal sections showed normal glomeruli with no thickening of glomerular basement membrane, while in diclofenac alone, nimesulide alone, and ranitidine with nimesulide groups, the thickening of glomerular basement membrane was observed. These alterations were observed to be reversed in the ranitidine with diclofenac group. In the sections from the liver, the control group showed anastomosing plates and cords of cuboidal hepatocytes with round well stained nuclei and abundant cytoplasm. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, mild dilatation of sinusoids is seen coupled with prominence of central vein. In the diclofenac alone and nimesulide alone groups, the proximal and distal convoluted tubules show mild focal tubular necrosis. In the gastric sections, the control group showed several folds forming villi, and the epithelial lining surface of the mucosa. In the ranitidine with diclofenac, and ranitidine with nimesulide groups, the duodenum showed scattered inflammatory cells composed predominantly of lymphocytes. In diclofenac alone and nimesulide alone group, the sections from the gastric areas showed partial necrosis and mild chronic inflammation respectively. Conclusion The study, therefore, has provided therapeutic rationale towards simultaneous administration of H2 receptor blocker ranitidine with diclofenac to be more beneficial as compared to ranitidine with nimesulide, to minimise the gastric intolerance of diclofenac in long term treatment of inflammatory conditions.

RESUMO Contexto Anti-inflamatórios não esteroidais induzem lesões da mucosa gástrica devido às suas propriedades ácidas. Ranitidina, um antagonista dos receptores H2, revelou-se benéfico em pacientes com úlceras gástricas. Objetivo - O presente estudo foi realizado para avaliar o efeito da administração de ranitidina em gastropatia induzida por anti-inflamatórios não esteroidais (diclofenaco, nimesulida) e seu efeito sobre a histopatologia do estômago, dos rins e fígado. Métodos Diclofenaco, nimesulida e ranitidina foram administradas em doses de 2, 4 e 6 mg/kg, p.o. uma vez diariamente por 14 dias e seu efeito sobre o volume gástrico, acidez, significam o número de úlcera e o pH gástrico. Além disso, o exame histopatológico também foi realizado em seções do estômago, dos rins e fígado. Resultados Após a administração de diclofenaco ou nimesulida, todos os parâmetros gástricos foram significativamente alterados assim como a histopatologia do estômago, fígado e rim. No grupo controle, as seções renais mostraram glomérulos normais sem espessamento da membrana basal glomerular, enquanto em diclofenaco isolado, nimesulida isolado e grupos com ranitidina e nimesulida, foi observado espessamento da membrana basal glomerular. Estas alterações observou-se serem revertidas no grupo ranitidina com diclofenaco. As seções do fígado, o grupo controle mostrou placas e cordões de hepatócitos cuboidais anastomosados com núcleos bem demarcados e citoplasma abundante. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, leve dilatação dos sinusoides é vista acoplados com proeminência de veia central. Nos grupos diclofenaco e nimesulida sozinhos, túbulos proximais e distais contorcidos mostram necrose tubular focal leve. Nas secções gástricas, o grupo controle mostrou várias dobras formando vilosidades e a superfície do revestimento epitelial da mucosa. Nos grupos ranitidina com diclofenaco e ranitidina com nimesulida, o duodeno mostrou dispersas células inflamatórias predominantemente compostas por linfócitos. Nos grupos diclofenaco e nimesulida sozinhos, as secções de áreas gástricas mostraram necrose parcial e inflamação crônica moderada respectivamente. Conclusão - O estudo, portanto, forneceu o fundamento terapêutico para administração simultânea de bloqueador de receptor H2 (ranitidina) com diclofenaco, sendo mais benéfica em comparação com ranitidina com nimesulida para minimizar a intolerância gástrica de diclofenaco no tratamento a longo prazo de condições inflamatórias.

Gastrointestinal Risk Factors and Non-steroidal Anti-inflammatory Drugs Use in Rheumatoid Arthritis and Osteoarthritis Patients in Korea

OBJECTIVE: The aim of this study was to examine and compare the gastrointestinal (GI) risk factors and treatment patterns of rheumatoid arthritis (RA) and osteoarthritis (OA) patients in Korea. METHODS: This was a cross-sectional, observational study on RA and OA patients taking non-steroidal anti-inflammatory drugs (NSAIDs) for at least 1 month. A total of 1,896 patients (981 RA patients, 915 OA patients) were recruited from 20 university hospitals. Data were collected through medical records and patient surveys. GI risk factors included age, prolonged (over 3 months) or high-dose use of NSAIDs, alcohol drinking, smoking, use of aspirin, anticoagulants or glucocorticoids, comorbidities, and history of Helicobacter pylori infection or other GI complications. Treatment patterns were classified according to groups using, selective cyclooxygenase (COX)-2 inhibitors+/-gastro-protective agents, non-selective COX-2 inhibitors+proton pump inhibitor, or non-selective COX-2 inhibitors+/-other gastro-protective agents. RESULTS: GI risk factors were highly present in both RA and OA patients. The proportion of prolonged use of NSAIDs, smoking, and glucocorticoid use were higher in RA patients (p<0.001). The proportion of comorbidities and use of aspirin were higher in OA patients (p<0.001). The remaining GI risk factors were present in similar proportions in both groups. Use of selective COX-2 inhibitors or gastro-protective agents was higher in RA patients. CONCLUSION: Prolonged use of NSAIDs and concomitant glucocorticoid use were higher in RA patients, while comorbidities and concomitant aspirin use were predominant in OA patients. These results will provide insights for use in development of future guidelines for proper selection of NSAIDs and effective prevention of GI complications in arthritis patients.

Nonsteroidal Anti-inflammatory Drug and Aspirin-induced Peptic Ulcer Disease / 대한소화기학회지

Despite decreasing Helicobacter pylori prevalence, the prevalence of peptic ulcer disease is increasing in the aged population, mainly due to increasing use of NSAIDs to manage pain and inflammation. In addition, low dose aspirin is employed as an anti-coagulant for those who have suffered or are at high risk of ischemic stroke and cardiovascular disease. However, NSAIDs and aspirin are injurious to mucosa of stomach and duodenum. NSAID-induced inhibition of mucosal prostaglandin synthesis is thought to be a major mechanism of gastrointestinal mucosal injury. The proportion of elderly has increased rapidly in Korea, with the proportion over 65 years old expected to be 24.3% in 2030. In this higher-risk population, the strategy to reduce the incidence of NSAID-related peptic ulcers and complications such as bleeding, obstruction and perforation is very important. Proton pump inhibitors (PPIs) with cyclooxygenase-2 inhibitor can be used for reducing the risk of NSAID-related ulcers and upper gastrointestinal (GI) complications. However, continuous use of PPI has several problems. In addition, NSAID-related problems in the lower GI tract have increased, in contrast to the decrease of NSAID-related upper GI disease. The aim of this review is to provide an evidence-based knowledge regarding the mechanism, complications of treatment, and prevention strategies for NSAID- or aspirin-related peptic ulcer disease in Korea.

Peptic ulcer frqquency differences related to h. pylori or aines / Diferentes frequências da úlcera péptica relacionadas com H. pylori ou AINES

Background Peptic ulcer etiology has been changing because of H. pylori decline. Objectives To estimate peptic ulcer prevalence in 10 years-interval and compare the association with H. pylori and use of non-steroidal anti-inflammatory drugs. Methods Records assessment in two periods: A (1997-2000) and B (2007-2010), searching for peptic ulcer, H. pylori infection and non-steroidal anti-inflammatory drugs use. Results Peptic ulcer occurred in 30.35% in A and in 20.19% in B. H. pylori infection occurred in 73.3% cases in A and in 46.4% in B. Non-steroidal anti-inflammatory drugs use was 3.5% in A and 13.3% in B. Neither condition occurred in 10.4% and 20.5% in A and B respectively. Comparing both periods, we observed reduction of peptic ulcer associated to H. pylori (P=0.000), increase of peptic ulcer related to non-steroidal anti-inflammatory drugs (P=0.000) and idiopathic peptic ulcer (P=0.002). The concurrent association of H. pylori and non-steroidal anti-inflammatory drugs was also higher in B (P=0.002). Rates of gastric ulcer were higher and duodenal ulcer lower in the second period. Conclusions After 10 years, the prevalence of peptic ulcer decreased, as well as ulcers related to H. pylori whereas ulcers associated to non-steroidal anti-inflammatory drugs increased. There was an inversion in the pattern of gastric and duodenal ulcer and a rise of idiopathic peptic ulcer. .

Contexto A etiologia da úcera péptica vem apresentando mudanças devido à redução da infecção pelo H. pylori. Objetivos Estimar a prevalência da úlcera péptica em dois períodos com intervalo de 10 anos e comparar a associação com a infecção pelo H. pylori com o uso de anti-inflamatórios não esteroides. Métodos Revisão de prontuários em dois períodos: A (1997-2000) e B (2007-2010), com busca por úlcera péptica, H. pylori e uso de anti-inflamatórios não esteroides (AINE). Resultados Úcera péptica apresentou frequência de 30,35% em A e 20,19% em B. Infecção por H. pylori ocorreu em 73,3% em A e em 46,4% em B. Uso de anti-inflamatórios não esteroides ocorreu em 3,5% em A e em 13,3% em B. Nenhuma dessas condições esteve associada em 10,4% e 20,5% das úlceras em A e B, respectivamente. Comparando os dois períodos, houve redução da úlcera péptica associada à H. pylori (P=0,000), aumento das úlceras associadas ao uso de anti-inflamatórios não esteroides (P=0,000) e aumento de úlceras idiopáticas (P=0,002). A associação concomitante de H. pylori e anti-inflamatórios não esteroides foi também mais alta em B (P=0,002). Úlceras gástricas aumentaram e úlceras duodenais diminuíram em B. Conclusões No intervalo de 10 anos, a prevalência de úlcera péptica diminuiu assim como as úlceras relacionadas com H. pylori e houve um aumento das úlceras associadas ao uso de anti-inflamatórios não esteroides. Houve inversão na frequência das lesões gástricas e duodenais e aumento da prevalência da úlcera idiopática. .

An Analysis on the Effect of Patient-controlled Analgesia Performed by Orthopaedic Department or Postoperative Pain Control after Shoulder and Elbow Surgery

BACKGROUND: We investigated the effectiveness of pain management and the adverse events of intravenous (IV) patient-controlled analgesia (PCA) after orthopedic surgery. METHODS: From September 2014 and August 2015, we performed a retrospective analysis of 77 patients who underwent orthopedic surgery of the shoulder or the elbow in our hospital. The composition of the intravenous PCA administered to the patients was as follows: 250 mg of dexketoprofen trametamol, 70 mg of oxycodone, and 0.6 mg of ramosetron, which were made up to 79 ml of normal saline. We evaluated and statistically analyzed the difference in the visual analogue scale (VAS) scores for pain at immediate postoperation, at 24 hours of PCA, at 72 hours of PCA, and after discontinuation of PCA and in the incidence of adverse events. RESULTS: We found that VAS score decreased for 3 postoperative days and that with discontinuation of IV PCA a meaningful change in VAS score was no longer seen. Of the 77 patients, 22 presented with adverse events (28.6%). We terminated IV PCA temporarily in the 21 patients who presented with adverse events; we terminated analgesia permanently in one patient (1.2%). Consequently, 76 of 77 patients carried out IV PCA till the designated period. CONCLUSIONS: Intravenous PCA after orthopedic surgery of the shoulder or the elbow may be accompanied with adverse events. Careful assessment of the patient and treatment of the adverse outcomes are key to a successful maintenance of PCA and to a successful management of postoperative pain.

An Analysis on the Effect of Patient-controlled Analgesia Performed by Orthopaedic Department or Postoperative Pain Control after Shoulder and Elbow Surgery

BACKGROUND: We investigated the effectiveness of pain management and the adverse events of intravenous (IV) patient-controlled analgesia (PCA) after orthopedic surgery. METHODS: From September 2014 and August 2015, we performed a retrospective analysis of 77 patients who underwent orthopedic surgery of the shoulder or the elbow in our hospital. The composition of the intravenous PCA administered to the patients was as follows: 250 mg of dexketoprofen trametamol, 70 mg of oxycodone, and 0.6 mg of ramosetron, which were made up to 79 ml of normal saline. We evaluated and statistically analyzed the difference in the visual analogue scale (VAS) scores for pain at immediate postoperation, at 24 hours of PCA, at 72 hours of PCA, and after discontinuation of PCA and in the incidence of adverse events. RESULTS: We found that VAS score decreased for 3 postoperative days and that with discontinuation of IV PCA a meaningful change in VAS score was no longer seen. Of the 77 patients, 22 presented with adverse events (28.6%). We terminated IV PCA temporarily in the 21 patients who presented with adverse events; we terminated analgesia permanently in one patient (1.2%). Consequently, 76 of 77 patients carried out IV PCA till the designated period. CONCLUSIONS: Intravenous PCA after orthopedic surgery of the shoulder or the elbow may be accompanied with adverse events. Careful assessment of the patient and treatment of the adverse outcomes are key to a successful maintenance of PCA and to a successful management of postoperative pain.

COMPARISON OF SELECTIVE AND NON SELECTIVE CYCLO-OXYGENASE 2 INHIBITORS IN EXPERIMENTAL COLITIS EXACERBATION: role of leukotriene B4 and superoxide dismutase / Comparação dos inibidores seletivos e não seletivos da ciclo-oxigenage 2 na exacerbação da colite experimental: papel do leucotrieno B4 e superóxido dismutase

Context Nonsteroidal anti-inflammatory drugs are considered one of the most important causes of reactivation of inflammatory bowel disease. With regard to selective cyclo-oxygenase 2 inhibitors, the results are controversial in experimental colitis as well as in human studies. Objectives The aim this study is to compare nonsteroidal anti-inflammatory drugs effects, selective and non selective cyclo-oxygenase 2 inhibitors, in experimental colitis and contribute to the understanding of the mechanisms which nonsteroidal anti-inflammatory drugs provoke colitis exacerbation. Methods Six groups of rats: without colitis, with colitis, and colitis treated with celecoxib, ketoprofen, indometacin or diclofenac. Survival rates, hemoglobin, plasmatic albumin, colonic tissue of interleukin-1ß, interleukin-6, tumor necrosis factor alpha, prostaglandin E2, catalase, superoxide dismutase, thiobarbituric acid-reactive substances, chemiluminescence induced by tert-butil hydroperoxides, and tissue and plasmatic leukotriene B4 were determined. Results The groups treated with diclofenac or indometacin presented lower survival rates, hemoglobin and albumin, higher tissue and plasmatic leukotriene B4 and tissue superoxide dismutase than the group treated with celecoxib. Ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib, concerning to survival rate and albumin. The groups without colitis, with colitis and with colitis treated with celecoxib showed leukotriene B4 and superoxide dismutase lower levels than the groups treated with nonselective cyclo-oxygenase 2 inhibitors. Conclusions Diclofenac and indometacin presented the highest degree of induced colitis exacerbation with nonsteroidal anti-inflammatory drugs, celecoxib did not show colitis exacerbation, and ketoprofen presented an intermediary behavior between diclofenac/indometacin and celecoxib. These results suggest that leukotriene B4 and superoxide ...

Contexto Os anti-inflamatórios não-esteróides são considerados uma das mais importantes causas de reativação da doença inflamatória intestinal. Em relação aos inibidores seletivos da ciclo-oxigenase 2, os resultados são controversos tanto em estudos envolvendo humanos como na colite experimental. Objetivos Comparar os efeitos dos anti-inflamatórios não-esteróides, seletivos e não seletivos da ciclo-oxigenase 2, na colite experimental e, contribuir para o entendimento do mecanismo no qual os anti-inflamatórios não-esteróides provocam a exacerbação da colite. Métodos Seis grupos de ratos foram estudados: sem colite, com colite e com colite e tratados com celecoxib, cetoprofeno, indometacina ou diclofenaco. Foram determinadas a taxa de sobrevida, as concentrações de hemoglobina e albumina plasmática, as concentrações teciduais na mucosa colônica de interleucina-1ß, interleucina-6, fator de necrose tumoral alfa, prostaglandina E2, catalase, superóxido dismutase, substâncias reativas ao ácido tiobarbitúrico e quimiluminescência estimulada por hidroperóxido de tert-butil, e as concentraçãos plasmática e tecidual de leucotrieno B4. Resultados O grupo tratado com diclofenaco ou indometacina apresentaram as menores taxas de sobrevida, concentrações de hemoglobina e albumina, e as maiores concentrações plasmática e tecidual de leucotrieno B4 e tecidual de superóxido dismutase do que os groupos tratados com celecoxib. O grupo tratado com cetoprofeno apresentou um comportamento intermediário entre diclofenaco/indometacina e celecoxib, em relação a taxa de sobrevida e albumina. Os grupos sem colite, colite e colite tratado com celecoxib apresentaram menores concentrações de leucotrieno B4 e superóxido ...

A Case of Lithium Toxicity within Normal Creatinine Range during Lithium Maintenance Treatment / 신경정신의학

Lithium is a widely used drug for treatment of bipolar disorder. Because of its narrow therapeutic range and renal toxicity, most clinical guidelines recommend regular monitoring of serum lithium level and kidney function for patients taking lithium. We report on a case of a 20 year-old man with occurrence of lithium toxicity after more than one year of lithium maintenance therapy with daily lithium intake of 900 mg. His serum creatinine level was within normal range at admission and elevated compared to his baseline, but still within normal range when lithium toxicity occurred. Acute kidney injury associated with dehydration, analgesics, and nephrotoxic effect of lithium might be a risk factor of lithium toxicity. This case showed the importance of thorough monitoring of serum creatinine level change even if its elevated result is within normal range in observing renal function of patients treated with lithium.

A Comparison of the Efficacy and Safety of Non-Steroidal Anti-Inflammatory Drugs versus Acetaminophen in Symptom Relief for the Common Cold: A Meta-Analysis of Randomized Controlled Trial Studies / 가정의학회지

BACKGROUND: Non-steroidal anti-inflammatory drugs (NSAIDs) and acetaminophen are widely used for common cold symptom relief. The objective of this study was to evaluate and compare the efficacy and safety of acetaminophen and NSAIDs in common cold symptom relief using meta-analysis of randomized controlled trial. METHODS: We searched MEDLINE (PubMed), Cochrane, EMBASE, CINAHL, KMbase, KoreaMed, National Assembly Library, and Riss4u for studies released through June 2012. Two authors independently extracted the data. To assess the risk of bias, the Cochrane Collaborations risk of bias tool was used. The Review Manager ver. 5.1 (RevMan) was used for statistics. RESULTS: We identified 5 studies. The relative benefit for participants with pain relief was 1.00 (95% confidence interval [CI], 0.96 to 1.05) and I2 = 0%. The existence of the heterogeneity between studies was not important in this study, thus subgroup analysis was not implemented. The relative benefit for participants with rhinorrhea was 1.02 (95% CI, 0.77 to 1.35) and I2 = 0%, which also indicates the existence of heterogeneity was not important. The relative risk of adverse events was 1.14 (95% CI, 0.93 to 1.40), I2 = 0%. There was no apparent asymmetry in the funnel plot. CONCLUSION: There was no difference between NSAIDs and acetaminophen in common cold symptom relief.

Advent of Novel Phosphatidylcholine-Associated Nonsteroidal Anti-Inflammatory Drugs with Improved Gastrointestinal Safety

The mucosa of the gastrointestinal (GI) tract exhibits hydrophobic, nonwettable properties that protect the underlying epithelium from gastric acid and other luminal toxins. These biophysical characteristics appear to be attributable to the presence of an extracellular lining of surfactant-like phospholipids on the luminal aspects of the mucus gel layer. Phosphatidylcholine (PC) represents the most abundant and surface-active form of gastric phospholipids. PC protected experimental rats from a number of ulcerogenic agents and/or conditions including nonsteroidal anti-inflammatory drugs (NSAIDs), which are chemically associated with PC. Moreover, preassociating a number of the NSAIDs with exogenous PC prevented a decrease in the hydrophobic characteristics of the mucus gel layer and protected rats against the injurious GI side effects of NSAIDs while enhancing and/or maintaining their therapeutic activity. Bile plays an important role in the ability of NSAIDs to induce small intestinal injury. NSAIDs are rapidly absorbed from the GI tract and, in many cases, undergo enterohepatic circulation. Thus, NSAIDs with extensive enterohepatic cycling are more toxic to the GI tract and are capable of attenuating the surface hydrophobic properties of the mucosa of the lower GI tract. Biliary PC plays an essential role in the detoxification of bile salt micelles. NSAIDs that are secreted into the bile injure the intestinal mucosa via their ability to chemically associate with PC, which forms toxic mixed micelles and limits the concentration of biliary PC available to interact with and detoxify bile salts. We have worked to develop a family of PC-associated NSAIDs that appear to have improved GI safety profiles with equivalent or better therapeutic efficacy in both rodent model systems and pilot clinical trials.