Associations of genetic variations in pyroptosis related genes with acute adverse events in postoperative rectal cancer patients receiving concurrent chemoradiotherapy / 中华肿瘤杂志

Objective: This study aims to investigate the associations between genetic variations of pyroptosis pathway related key genes and adverse events (AEs) of postoperative chemoradiotherapy (CRT) in patients with rectal cancer. Methods: DNA was extracted from the peripheral blood which was collected from 347 patients before CRT. Sequenom MassARRAY was used to detect the genotypes of 43 haplotype-tagging single nucleotide polymorphisms (htSNPs) in eight pyroptosis genes, including absent in melanoma 2 (AIM2), caspase-1 (CASP1), caspase-4(CASP4), caspase-5 (CASP5), caspase-11 (CASP11), gasdermin D (GSDMD), gasdermin E (GSDME) and NLR family pyrin domain containing 3 (NLRP3). The associations between 43 htSNPs and AEs were evaluated by the odd ratios (ORs) and 95% confidence intervals (CIs) by unconditional logistic regression models, adjusted for sex, age, clinical stage, tumor grade, Karnofsky performance status (KPS), surgical procedure, and tumor location. Results: Among the 347 patients with rectal cancer underwent concurrent CRT with capecitabine after surgery, a total of 101(29.1%) occurred grade ≥ 2 leukopenia. rs11226565 (OR=0.41, 95% CI: 0.21-0.79, P=0.008), rs579408(OR=1.54, 95% CI: 1.03-2.29, P=0.034) and rs543923 (OR=0.63, 95% CI: 0.41-0.98, P=0.040) were significantly associated with the occurrence of grade ≥ 2 leukopenia. One hundred and fifty-six (45.0%) had grade ≥ 2 diarrhea, two SNPs were significantly associated with the occurrence of grade ≥ diarrhea, including CASP11 rs10880868 (OR=0.55, 95% CI: 0.33-0.91, P=0.020) and GSDME rs2954558 (OR=1.52, 95% CI: 1.01-2.31, P=0.050). In addition, sixty-six cases (19.0%) developed grade ≥2 dermatitis, three SNPs that significantly associated with the risk of grade ≥2 dermatitis included GSDME rs2237314 (OR=0.36, 95% CI: 0.16-0.83, P=0.017), GSDME rs12540919 (OR=0.52, 95% CI: 0.27-0.99, P=0.045) and NLRP3 rs3806268 (OR=1.51, 95% CI: 1.03-2.22, P=0.037). There was no significant difference in the association between other genetic variations and AEs of rectal cancer patients (all P>0.05). Surgical procedure and tumor location had great impacts on the occurrence of grade ≥2 diarrhea and dermatitis (all P<0.01). Conclusion: The genetic variants of CASP4, CASP11, GSDME and NLRP3 are associated with the occurrence of AEs in patients with rectal cancer who received postoperative CRT, suggesting they may be potential genetic markers in predicting the grade of AEs to achieve individualized treatment of rectal cancer.

Segurança e tolerabilidade de Nintedanibe em pacientes com fibrose pulmonar idiopática no Brasil / Safety and tolerability of nintedanib in patients with idiopathic pulmonary fibrosis in Brazil

RESUMO Objetivo Ensaios clínicos mostraram que 150 mg de Nintedanibe duas vezes ao dia reduzem a progressão da doença em pacientes com Fibrose Pulmonar Idiopática (FPI), com um perfil de efeitos adversos que é controlável para a maioria dos pacientes. Antes da aprovação do Nintedanibe como tratamento para a FPI no Brasil, um Programa de Acesso Expandido (PEA) foi iniciado para fornecer acesso precoce ao tratamento e avaliar a segurança e a tolerância do Nintedanibe para este grupo de pacientes. Métodos Foram elegíveis para participar da PEA pacientes com diagnóstico de FPI nos últimos 5 anos, com capacidade vital forçada (CVF) ≥ 50% do previsto e capacidade de difusão dos pulmões para monóxido de carbono (DLco) 30%-79% do previsto. Os pacientes receberam Nintedanibe 150 mg, 2 vezes ao dia (bid). As avaliações de segurança incluíram eventos adversos que levaram à suspensão permanente do Nintedanibe e eventos adversos graves. Resultados O PEA envolveu 57 pacientes em 8 centros. A maioria dos pacientes era do sexo masculino (77,2%) e brancos (87,7%). No início do estudo, a média de idade foi de 70,7 (7,5) anos e a CVF foi de 70,7 (12,5%) do previsto. A média de exposição ao Nintedanibe foi de 14,4 (6,2) meses; a exposição máxima foi de 22,0 meses. Os eventos adversos frequentemente relatados pelo pesquisador como relacionados ao tratamento com Nintedanibe foram diarreia (45 pacientes, 78,9%) e náusea (25 pacientes, 43,9%). Os eventos adversos levaram à suspensão permanente do Nintedanibe em 16 pacientes (28,1%) que passaram por um evento adverso grave. Conclusões No PEA brasileiro, o Nintedanibe apresentou um perfil aceitável de segurança e tolerância em pacientes com FPI, condizendo com dados de ensaios clínicos.

ABSTRACT Objective Clinical trials have shown that nintedanib 150 mg twice daily (bid) reduces disease progression in patients with idiopathic pulmonary fibrosis (IPF), with an adverse event profile that is manageable for most patients. Prior to the approval of nintedanib as a treatment for IPF in Brazil, an expanded access program (EAP) was initiated to provide early access to treatment and to evaluate the safety and tolerability of nintedanib in this patient population. Methods Patients with a diagnosis of IPF within the previous five years, forced vital capacity (FVC) ≥ 50% predicted and diffusing capacity of the lungs for carbon monoxide (DLco) 30% to 79% predicted were eligible to participate in the EAP. Patients received nintedanib 150 mg bid open-label. Safety assessments included adverse events leading to permanent discontinuation of nintedanib and serious adverse events. Results The EAP involved 57 patients at eight centers. Most patients were male (77.2%) and white (87.7%). At baseline, mean (SD) age was 70.7 (7.5) years and FVC was 70.7 (12.5) % predicted. Mean (SD) exposure to nintedanib was 14.4 (6.2) months; maximum exposure was 22.0 months. The most frequently reported adverse events considered by the investigator to be related to nintedanib treatment were diarrhea (45 patients, 78.9%) and nausea (25 patients, 43.9%). Adverse events led to permanent discontinuation of nintedanib in 16 patients (28.1%). Sixteen patients (28.1%) had a serious adverse event. Conclusion In the Brazilian EAP, nintedanib had an acceptable safety and tolerability profile in patients with IPF, consistent with data from clinical trials.

Evaluation of growth performance and gastro-intestinal parameters on the response of weaned piglets to dietary organic acids

ABSTRACT Two experiments (E) were carried out to evaluate the effects of fumaric acid and an acidifier blend [composed by calcium formate, calcium lactate and medium-chain fatty acids (capric and caprylic)] in piglet diets containing colistin (40 ppm) or halquinol (120 ppm) on performance, diarrhea incidence (E1), organs relative weight, pH values, intestinal morphometry and microbiota (E2). In E1, 192 and E2, 24 piglets weaned at 21-day-old were randomly assigned to blocks with 2x2 factorial arrangement of treatments [absence or presence of fumaric acid x absence or presence of acidifier blend], six replicates of eight (E1) and one piglet per pen (E2). For E1, the treatments were control (CD): no acidifier product + 40 ppm of colistin, FA: fumaric acid in absence of acidifier blend, AB: acidifier blend in absence of fumaric acid and, AF+AB: presence of fumaric acid and acidifier blend. For E2, the pre-starter I diet were used and the same treatments as E1 evaluated. No treatment effects (P>0.05) were observed on performance, diarrhea incidence (E1), gut pH values and duodenum morphometry of piglets (E2). However, the addition of AB increased (P<0.05) large intestine relative weight and, FA addition decreased (P<0.05) pancreas relative weight, jejunum villi height and, total coliform and E. coli counts in cecum. The inclusion of FA and AB in diets containing colistin or halquinol did not improve performance, although FA exerted an inhibitory effect on cecum microbiota.

Pharmacovigilance of patients with multiple myeloma being treated with bortezomib and/or thalidomide

In order to evaluate the main adverse effects of drug protocols using bortezomib and/or thalidomide for the treatment of multiple myeloma, we conducted a prospective study. Data were collected through interviews, clinical observation, and from hospital records. A total of 59 patients were included. There was a predominance of females, 36 (61%) vs 23 (39%) males, and of whites, 49 (83.1%) vs 10 (16.9%) blacks. Age ranged from 40 to 94 years, with a median of 65 years (SD=11.6). Regarding staging at diagnosis, 27 (45.7%) patients were in stage III-A, with 12 (20.3%) patients having serum creatinine ≥2 mg/dL. The main adverse effects in the bortezomib treatment group (n=40) were: neutropenia (42.5%), diarrhea (47.5%), and peripheral neuropathy in 60% of cases, with no difference between the iv (n=26) and sc (n=14) administration routes (P=0.343). In the group treated with thalidomide (n=19), 31.6% had neutropenia, 47.4% constipation, and 68.4% peripheral neuropathy. Neutropenia was associated with the use of alkylating agents (P=0.038). Of the 3 patients who received bortezomib in combination with thalidomide, only 1 presented peripheral neuropathy (33.3%). Peripheral neuropathy was the main adverse effect of the protocols that used bortezomib or thalidomide, with a higher risk of neutropenia in those using alkylating agents. Improving the identification of adverse effects is critical in multiple myeloma patient care, as the patient shows improvements during treatment, and requires a rational and safe use of medicines.

Diarrea asociada a antibióticos / Antibiotic associated diarrhea

La diarrea asociada a antibióticos es una entidad clínica que ha aumentado de manera considerable los últimos años a nivel mundial. Lo anterior se ha visto favorecido por el incremento en el uso de antibióticos de amplio espectro, los que fundamentalmente alteran la flora intestinal habitual, actuando también por otros mecanismos como la alteración de la motilidad intestinal y acción tóxica directa sobre la mucosa intestinal. La presentación clínica varía desde un cuadro leve hasta de mayor gravedad, llegando incluso a la muerte. Lo anterior dependerá de algunas variables, siendo fundamental el estado inmunitario del paciente. La diarrea asociada a antibióticos por Clostridium Difficile tiene mayor relevancia dado su mayor morbimortalidad. Se han utilizado diversos métodos diagnósticos para evaluar esta patología como así también, diferentes estrategias terapéuticas de enfrentamiento, las que se exponen en la presente revisión

Antibiotic-associated diarrhea is a clinical entity showing a significantly greater presence in past years worldwide. These has been favored by the intensification of treatments based on the use of broad-spectrum antibiotics, which alter intestinal flora and act through other mechanisms like alteration of intestinal motility and direct toxic action on the intestinal mucosa. Clinical symptoms vary from mild to severe and may even cause death. The severity of this condition depends on different variables, mainly the immune status of the patient. Clostridum difficile antibiotic-associated diarrhea is the most relevant since it causes greater mobility and mortality. This article is a review of various diagnostic methods used to evaluate this pathology and multiple therapeutical strategies for management of same.

Trasplante de microbiota fecal en infección recurrente por Clostridium difficile: Experiencia local a partir de un caso clínico / Fecal microbiota transplantation in recurrent Clostridium difficile infection: Report of one case

Fecal microbiota transplantation (FMT) has an incomparable efficacy to treat recurrent Clostridium difficile infection, with near 90% of success. We report a 57 years old woman who developed an antibiotic associated diarrhea with a positive polymerase chain reaction test for Clostridium Difficile toxin. She was successfully treated with Vancomycin trice but diarrhea recurred. Therefore a fecal microbiota transplant was performed using solid stools from a relative, diluted in saline and instilled in the distal ileon, with a good clinical response, without recurrence of diarrhea, during a 6-month follow-up.

Factors Predictive of Treatment-Emergent Adverse Events of Prucalopride: An Integrated Analysis of Four Randomized, Double-Blind, Placebo-Controlled Trials

BACKGROUND/AIMS: This integrated analysis aimed to identify the factors associated with the most frequently reported treatment-emergent adverse events (TEAEs) in Asian and non-Asian patients with chronic constipation (CC) who receive prucalopride or placebo over 12 weeks. METHODS: Pooled data from four randomized, double-blind, placebo-controlled, multicenter, phase III studies (NCT00488137, NCT00483886, NCT00485940, and NCT01116206) on patients treated with prucalopride 2 mg or placebo were analyzed. The associations between predictors and TEAEs were evaluated based on a logistic regression model. RESULTS: Overall, 1,821 patients (Asian, 26.1%; non-Asian, 73.9%) were analyzed. Prucalopride treatment was significantly associated with diarrhea, headache, and nausea (p<0.001), but not with abdominal pain, compared with placebo. Differences in the prevalence of TEAEs between prucalopride and placebo decreased greatly after the first day of treatment. Compared with non-Asians, Asians were more likely to experience diarrhea and less likely to develop abdominal pain, headache, and nausea. Prior laxative use, CC duration, and body weight were not predictive of any of these TEAEs. CONCLUSIONS: Prucalopride treatment was positively associated with diarrhea, headache, and nausea. Asian patients tended to have a higher frequency of diarrhea but lower frequencies of headache, abdominal pain, and nausea compared with non-Asians.

Factors Predictive of Treatment-Emergent Adverse Events of Prucalopride: An Integrated Analysis of Four Randomized, Double-Blind, Placebo-Controlled Trials

BACKGROUND/AIMS: This integrated analysis aimed to identify the factors associated with the most frequently reported treatment-emergent adverse events (TEAEs) in Asian and non-Asian patients with chronic constipation (CC) who receive prucalopride or placebo over 12 weeks. METHODS: Pooled data from four randomized, double-blind, placebo-controlled, multicenter, phase III studies (NCT00488137, NCT00483886, NCT00485940, and NCT01116206) on patients treated with prucalopride 2 mg or placebo were analyzed. The associations between predictors and TEAEs were evaluated based on a logistic regression model. RESULTS: Overall, 1,821 patients (Asian, 26.1%; non-Asian, 73.9%) were analyzed. Prucalopride treatment was significantly associated with diarrhea, headache, and nausea (p<0.001), but not with abdominal pain, compared with placebo. Differences in the prevalence of TEAEs between prucalopride and placebo decreased greatly after the first day of treatment. Compared with non-Asians, Asians were more likely to experience diarrhea and less likely to develop abdominal pain, headache, and nausea. Prior laxative use, CC duration, and body weight were not predictive of any of these TEAEs. CONCLUSIONS: Prucalopride treatment was positively associated with diarrhea, headache, and nausea. Asian patients tended to have a higher frequency of diarrhea but lower frequencies of headache, abdominal pain, and nausea compared with non-Asians.

Antidiarrhoeal evaluation of rhizomes of Cryptocoryne spiralis Fisch. ex Wydler: Antimotility and antisecretory effects.

The antidiarrhoeal activity of Cryptocoryne spiralis rhizomes extract (250, 500, 750 mg/kg, po) was evaluated using faecal excretion, castor oil-induced diarrhoea, small intestinal transit, intestinal fluid accumulation, gastric emptying and PGE2 induced enteropooling models in rats. In addition, various biochemical estimations, histopathological studies and antibacterial evaluations on strains responsible for diarrhoea were also performed. The results illustrated a significant reduction in normal faecal output rate after 5th and 7th h of treatment, while castor oil-induced diarrhoea model depicted a protection of 55.44% at same dose level from diarrhoea. The other models except, gastric emptying test demonstrated more pronounced effect at same dose level. A significant inhibition in nitric oxide, increase in carbohydrates, protein, DNA, Na+ and K+ level with minimum degeneration of colonic fibrous tissues and potent antibacterial activity were also observed. The antidiarrhoeal potential of C. spiralis may be as a result of antimotility and antisecretory type effect mediated through nitric oxide pathway.

Practical Effect of Sorafenib Monotherapy on Advanced Hepatocellular Carcinoma and Portal Vein Tumor Thrombosis

BACKGROUND/AIMS: We investigated the effects of sorafenib monotherapy on advanced hepatocellular carcinoma (HCC) and portal vein tumor thrombosis (PVTT) in a clinical setting. METHODS: In total, 143 consecutive patients with unresectable HCC were treated with sorafenib. Among these patients, 30 patients with advanced HCC and PVTT (Vp3 or 4) were treated with sorafenib monotherapy. RESULTS: All patients had a performance status of 1 to 2 (Eastern Cooperative Oncology Group 1/2, 20/10) and Child-Pugh class A or B (A/B, 17/13). Eleven patients had modified Union for International Cancer Control stage IVA tumors, whereas 19 had stage IVB tumors. All patients had PVTT (Vp3, 6; Vp4, 24). Following sorafenib monotherapy, three patients (10.0%) had a partial response with PVTT revascularization, and nine (30.0%) had stable disease, with a disease control rate of 33.3%. The median overall survival was 3.1 months (95% confidence interval [CI], 2.70 to 3.50), and the median progression-free survival was 2.0 months (95% CI, 1.96 to 2.05). Fatigue and hand-foot skin reactions were the most troublesome side effects. CONCLUSIONS: A limited proportion of patients with advanced HCC and PVTT exhibited a remarkable outcome after sorafenib monotherapy, although the treatment results in this type of patient is extremely poor. Further studies to predict good responders to personalized therapy are warranted.

Secondary Prophylaxis of Docetaxel Induced Diarrhea with Loperamide: Case Report

Diarrhea is a common adverse event of docetaxel with 20%-40% of incidence and severe diarrhea occurs in 5%-6%. Several treatment guidelines for chemotherapy induced diarrhea (CID) exist, however the prophylaxis for that is not well known. We describe a new prophylactic approach for the CID with loperamide. A 72-yr-old male patient with stage IV non-small-cell lung cancer developed diarrhea repeatedly after docetaxel-cisplatin chemotherapy. His diarrhea persisted despite treatment including loperamide and fasting. However, the diarrhea was successfully prevented when loperamide was given before and after the chemotherapy. To our knowledge, this is the first report of prophylactic approach for the CID with loperamide.

The effect of Lactobacillus casei and Bifidobacterium breve on antibiotic-associated diarrhea treatment: randomized double-blind clinical trial / Efeito de Lactobacillus casei e Bifidobacterium breve na diarréia associada ao uso de antimicrobiano: estudo clínico randomizado duplo cego

INTRODUCTION: Antibiotic-associated diarrhea (AAD) is an important side effect of this specific class of drugs. The objective of this study was to investigate the effect of the use of probiotics in the treatment of AAD. METHODS: A group of hospitalized patients, who contracted diarrhea during or after 7 days of suspension of antimicrobial medication, was blindly randomized to receive a standardized diet associated with the use of the probiotics (Lactobacillus casei and Bifidobacterium breve) or its corresponding placebo, three times a day. RESULTS: Seventy patients were studied. For the experimental (n=35) and control (n=35) groups, respectively, the average time of treatment was 5.06±2.18 and 5.49±3.17 days (p=0.95), and the average duration of diarrhea, among those who were healed, was 4.87±2.13 and 4.52±2.55 days (p=0.36). Four (11.4 percent) patients who received probiotics and ten (28.6 percent) who received the placebo were not cured (p=0.13), and relapse rates were similar between both groups. Seven patients from each group, in addition to diarrhea, presented cases of bloating and/or abdominal cramps and/or vomiting (p=1.00). CONCLUSIONS: In this light, it is concluded that L. casei associated with B. breve, in the administered dosage and frequency, has no effect on the antibiotic-associated diarrhea. Similar studies need to be conducted with higher doses of these or other probiotics.

INTRODUÇÃO: A diarréia associada ao uso de antimicrobiano (DAA) é um importante efeito colateral dessa classe de fármacos. O objetivo do presente trabalho é investigar o efeito do uso de probióticos no tratamento da DAA. MÉTODOS: Pacientes hospitalizados em um hospital universitário com diarréia, que se desenvolveu durante o uso ou até sete dias após a suspensão de antimicrobianos, foram randomizados, de forma cega, para receberem dieta padronizada associada, três vezes ao dia, ao uso de probiótico (Lactobacillus casei e Bifidobacterium breve) ou placebo. RESULTADOS: Foram estudados um total de setenta pacientes. Para o grupo experimento (n=35) e controle (n=35), respectivamente, o tempo médio de tratamento foi de 5,06 ± 2,18 e 5,49 ± 3,17dias (p=0,95) e o tempo médio de duração da diarréia, entre aqueles que se curaram, foi de 4,87 ± 2,13 e 4,52 ± 2,55 dias (p=0,36). Quatro (11,4 por cento) pacientes que receberam probióticos e dez (28,6 por cento) que receberam placebo não foram curados (p=0,13) e a frequência de recidiva foi similar entre os grupos. Sete pacientes de cada grupo, além da diarréia, apresentaram distensão e/ou cólica abdominal e/ou vômito (p=1,00). CONCLUSÕES: L. casei associado a B. breve, na dosagem e frequência administradas, não demonstraram qualquer efeito no tratamento da diarréia associada a antimicrobiano. Estudos similares merecem ser realizados com doses maiores destes ou de outros probióticos.

Clinical applications of probiotics in gastrointestinal disorders in children.

Probiotics are widely used in promoting human health and adjunctive therapy of human disease. Many clinical trials and research studies have shown benefits of probiotics. We review the literature associated with the clinical applications of probiotics in paediatric diseases, including necrotizing enterocolitis, infantile colic, infectious diarrhoea or gastrointestinal infection, antibiotic-associated diarrhoea, constipation, lactose intolerance, inflammatory bowel disease, irritable bowel syndrome and functional abdominal pain. We also summarize the representative probiotics that are commonly used in paediatric diseases.

Efficacy of Levofloxacin and Rifaximin based Quadruple Therapy in Helicobacter pylori Associated Gastroduodenal Disease: A Double-Blind, Randomized Controlled Trial

The aim of this study was to evaluate the efficacy of levofloxacin and rifaximin based quadruple regimen as first-line treatment for Helicobacter pylori infection. A prospectively randomized, double-blinded, parallel group, comparative study was performed. Three hundred consecutive H. pylori positive patients were randomized to receive: omeprazole, amoxicillin, clarithromycin (OAC); omeprazole, amoxicillin, levofloxacin (OAL); and omeprazole, amoxicillin, levofloxacin, rifaximin (OAL-R). The eradication rates in the intention to treat (ITT) and per protocol (PP) analyses were: OAC, 77.8% and 85.6%; OAL, 65.3% and 73.6%; and OAL-R, 74.5% and 80.2%. The eradication rate achieved with OAC was higher than with OAL on the ITT (P = 0.05) and PP analysis (P = 0.04). OAL-R regimen was not inferior to OAC. The frequency of moderate to severe adverse effects was significantly higher in OAC treatment group. Especially, diarrhea was most common complaint, and there was a significantly low rate of moderate to severe diarrhea with the rifaximin containing regimen. In conclusion, the levofloxacin and rifaximin based regimen comes up to the standard triple therapy, but has a limited efficacy in a Korean cohort. The rifaximin containing regimen has a very high safety profile for H. pylori eradication therapy.

Assessment of antidiarrhoeal activity of Desmostachya bipinnata L. (Poaceae) root extracts / Evaluación de la actividad de antidiarreica de extractos de la raíz de Desmostachya bipinnata L. (Poaceae)

Desmostachya bipinnata root has been used in the Indian traditional system of medicine for treatment of diarrhoea and dysentery. The antidiarrhoeal effect of both alcoholic and aqueous extracts of the roots of Desmostachya bipinnata were studied in rats against castor oil induced diarrhoea and charcoal meal test at the doses of 200 and 400 mg/kg body weight. The alcoholic extract and to a lesser extent aqueous extract significantly reduced the weight of the faces and decreased the propulsion of charcoal meal through the gastrointestinal tract. The phytochemical screening of the extracts showed the presence of alkaloids, glycosides, flavonoids, tannins, phytosterol, terpenoids, polyphenolics, protein and carbohydrates. These results may support the fact that this plant is used traditionally to cure diarrhoea.

La raíz de Desmostachya bipinnata ha sido utilizada en el sistema tradicional de medicina Hindú para el tratamiento de diarrea y disentería. El efecto antidiarreico de los extractos alcohólicos y acuosos de los extractos de la raíz de Desmostachya bipinnata fueron estudiados en ratas, utilizando la diarrea inducida por aceite de castor y el ensayo de la prueba por carbón en dosis de 200 y 400 mg/kg de peso corporal. El extracto alcohólico y en menor grado, el extracto acuoso, redujeron significativamente la propulsión de carbón a través del tracto gastrointestinal. El análisis de los extractos mostrarón la presencia de alcaloides, glicósidos, flavonoides, taninos, fitoesterol, terpenoides, polifenoles, proteínas y carbohidratos. Estos resultados pueden apoyar el hecho de que esta planta sea usada tradicionalmente para curar la diarrea.

Antibiotics-associated Diarrhea and Other Gastrointestinal Abnormal Responses Regarding Helicobacter pylori Eradication / 대한소화기학회지

BACKGROUND/AIMS: Helicobacter pylori (H. pylori) is closely related with a wide range of gastrointestinal disease. One-week triple therapy is currently considered as the golden standard for the treatment of H. pylori infection. However, gastrointestinal abnormal responses are major pitfalls in such regimen. The aim of this study was to identify symptoms, frequency and severity of antibiotics-associated gastrointestinal abnormal responses during H. pylori eradication therapy. METHODS: Sixty-seven patients with H. pylori infection between September 2005 and March 2006 were included. After 1 week of H. pylori eradication triple therapy (rabeprazol 10 mg, clarithromycin 500 mg, amoxicillin 1 g bid), we evaluated gastrointestinal abnormal responses (diarrhea, bloating, constipation, abdominal pain, borborygmus, flatulence, stool frequency, belching, and nausea) and severities every week for 4 weeks. RESULTS: The incidence of diarrhea was the highest in week 1, which was 41.28% (n=28) and the lowest in week 4, which was 9.52% (n=6) and decreased from week 1 to week 4 with statistical significance (p<0.0001). The most common gastrointestinal abnormal responses were associated with flatulence in week 1 (n=21, 31.34%), week 2 (n=21, 33.33%) and abdominal distention in week 3 (n=16, 25.40%), week 4 (n=15, 23.81%). Most of gastrointestinal abnormal responses were mild, and the most common symptom with higher than moderate grade was abdominal pain (n=4, 40.00%) in week 1. Alcohol consumption and coexisting medical illness were not associated with diarrhea (p=0.0852, 0.9009 respectively). CONCLUSIONS: H. pylori eradication therapy is commonly associated with antibiotics-associated gastrointestinal abnormal responses, which may result in antibiotics intolerance and H. pylori eradication failure. Even though those symptoms are not so severe, we have to consider the gastrointestinal abnormal responses associated with H. pylori eradication, especially diarrhea.

Effect of Probiotic Lactobacillus (Lacidofil(R) Cap) for the Prevention of Antibiotic-associated Diarrhea: A Prospective, Randomized, Double-blind, Multicenter Study

Antibiotic-associated diarrhea (AAD) is a common complication of antibiotic use. There is growing interest in probiotics for the treatment of AAD and Clostridium difficile infection because of the wide availability of probiotics. The aim of this multicenter, randomized, placebo-controlled, double-blind trial was to assess the efficacy of probiotic Lactobacillus (Lacidofil(R) cap) for the prevention of AAD in adults. From September 2008 to November 2009, a total of 214 patients with respiratory tract infection who had begun receiving antibiotics were randomized to receive Lactobacillus (Lacidofil(R) cap) or placebo for 14 days. Patients recorded bowel frequency and stool consistency daily for 14 days. The primary outcome was the proportion of patients who developed AAD within 14 days of enrollment. AAD developed in 4 (3.9%) of 103 patients in the Lactobacillus group and in 8 (7.2%) of 111 patients in the placebo group (P=0.44). However, the Lactobacillus group showed lower change in bowel frequency and consistency (50/103, 48.5%) than the placebo group (35/111, 31.5%) (P=0.01). Although the Lacidofil(R) cap does not reduce the rate of occurrence of AAD in adult patients with respiratory tract infection who have taken antibiotics, the Lactobacillus group maintains their bowel habits to a greater extent than the placebo group.

Antibiotic associated diarrhea in children.

Context: Keeping in view the recent flooding of the Indian market with antibiotic and probiotic combinations, we decided to look at the prevalence of antibiotic associated diarrhea (AAD) and Clostridium difficile infection (CDI) in children and reviewed evidence available for use of probiotics in the prevention of AAD. Evidence acquisition: We did a PubMed, Medline and Cochrane libary search for literature available in last 25 years. Results: Prevalence of antibiotic associated diarrhea (AAD) is around 11%. Children younger than 2 years and type of antibiotics are the two risk factors identified for AAD. For the pediatric population, CDI reportedly decreased in a tertiary care hospital in India, though number of suspected samples tested increased. The incidence of community acquired CDI is increasing in the pediatric population also. Detection of toxin A and B by enzyme linked immunosorbent assay (ELISA) and detection of toxin B by tissue culture form the mainstay in the diagnosis of C. difficile. Most of the AAD would respond to only discontinuation or change of the antibiotic. Oral metronidazole or oral vancomycin are drugs of choice for CDI. Probiotics reduce the risk of AAD in children and for every 7-10 patients one less would develop AAD. Conclusion: Prevalence of AAD is low and majority will respond to discontinuation of antibiotic. CDI is uncommon in children. Probiotics will prevent AAD in only 1 in 7 children on antibiotics. We need cost effectiveness studies to decide the issue of needing a probiotic antibiotic combination to prevent AAD.

Adherence and side effects of three ferrous sulfate treatment regimens on anemic pregnant women in clinical trials / Adesão e efeitos colaterais em ensaio clínico comparando três esquemas de tratamento com sulfato ferroso em gestantes anêmicas

The objective of this study was to analyze adherence and side effects of three iron supplement regimens (ferrous sulfate) on anemic pregnant women. The clinical trial involved 150 women between the 16th and 20th gestational weeks, at low obstetric risk and with hemoglobin concentration of between 8.0 and 11.0g/dL. Treatment was provided by ferrous sulfate with 60mg of elemental iron during 16 (± 1) weeks, in three regimens: single tablet a week (n = 48); single tablet twice a week (n = 53) or single tablet a day (n = 49). The outcomes were adherence, assessed through interviews and by counting tablets, and side effects, according to patient information. The adherence showed a declining trend (92 percent, 83 percent and 71 percent; p = 0.010) and the side effects revealed a growing trend (40 percent, 45 percent and 71 percent; p = 0.002) as the dosage increased. Diarrhea and epigastric pain were significantly associated with the dose administered (p = 0.002). These results suggest that in anemic pregnant women, complaints are directly proportional and the compliance is inversely proportional to the amount of medicinal iron.

O objetivo deste estudo foi analisar a adesão e os efeitos colaterais de três esquemas de suplementação com sulfato ferroso em gestantes anêmicas. O ensaio clínico incluiu 150 mulheres entre a 16ª e 20ª semanas de gestação, de baixo risco obstétrico e com concentração de hemoglobina entre 8,0 e 11,0g/dL. A intervenção foi realizada com 60mg de ferro elementar, durante 16 (±1) semanas, em três esquemas: uma drágea semanal (n = 48); uma drágea duas vezes por semana (n = 53) ou uma drágea diariamente (n = 49). Os desfechos foram adesão, verificada por entrevista e contagem das drágeas, e efeitos colaterais auto-relatados pelas pacientes. A adesão apresentou tendência declinante (92 por cento, 83 por cento e 71 por cento; p = 0,010) e os efeitos colaterais, ascendente (40 por cento, 45 por cento e 71 por cento; p = 0,002) com o aumento da dose prescrita. Diarréia e dor epigástrica estiveram significativamente associadas à dose administrada (p = 0,002). Os resultados sugerem que em gestantes anêmicas as queixas e a adesão ao tratamento com sulfato ferroso são, respectivamente, direta e inversamente proporcionais à quantidade do ferro medicamentoso.