PROTON-PUMP INHIBITORS ARE ASSOCIATED WITH AN INCREASED RISK OF MICROSCOPIC COLITIS: A POPULATION-BASED STUDY AND REVIEW OF THE LITERATURE.

BACKGROUND: •The study evaluated the risk of developing microscopic colitis and its subtypes in patients on PPI therapy. BACKGROUND: •Using a large multicenter database, a retrospective cohort analysis was conducted, excluding patients with autoimmune diseases, and adjusting for confounders. BACKGROUND: •An increased risk of developing microscopic colitis was associated with female gender, smoking, and the use of PPI, SSRI, and NSAIDs. BACKGROUND: •The use of PPI represented the highest odds of developing microscopic colitis. BACKGROUND: Microscopic colitis is a relatively new diagnosis that was first described in the 1980s. Patients usually present with chronic watery and non-bloody diarrhea and are typically characterized by an unremarkable gross appearance of the colon on lower endoscopy while having evidence of lymphocytic infiltration of the lamina propria and the epithelium on histology. Two subtypes have been described in the literature: Collagenous colitis, with marked thickening of the subepithelial layer, and Lymphocytic colitis. Multiple risk factors such as female gender, older age and celiac disease have been associated with this entity. A few studies have found an association between microscopic colitis and proton-pump inhibitor (PPI). The aim of our study was to evaluate the risk of developing microscopic colitis and its subtypes for patients who are on PPI therapy. METHODS: A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States from 1999 to September 2022 was utilized to construct this study. Patients aged 18 years and above were included. Individuals who have been diagnosed with any autoimmune disease have been excluded. A multivariate regression analysis was performed to assess risk of developing microscopic, lymphocytic, and collagenous colitis by accounting for potential confounders including female gender, smoking history, and the use of proton pump inhibitor, nonsteroidal anti-inflammatory drugs, and selective serotonin receptor inhibitors. A two-sided P value <0.05 was considered as statistically significant, and all statistical analyses were performed using R version 4.0.2 (R Foundation for Statistical Computing, Vienna, Austria, 2008). RESULTS: 78,256,749 individuals were screened in the database and 69,315,150 were selected in the final analysis after accounting for inclusion and exclusion criteria. The baseline characteristics of patients with microscopic, lymphocytic, and collagenous colitis is seen in table 1. Using a multivariate regression analysis, the risk of developing microscopic, lymphocytic, and collagenous colitis was calculated and illustrated in table 2. DISCUSSION: Our study showed that the risk of microscopic colitis, lymphocytic colitis and collagenous colitis was higher in females and smokers. Although medications like SSRI and NSAIDs showed a positive correlation with colitis, the highest likelihood of developing this disease was associated with PPIs. Lansoprazole has been documented to be associated with microscopic colitis as it is believed to inhibit colonic proton pumps, and subsequently promote diarrhea and inflammation. Interestingly, the prevalence of lymphocytic colitis and collagenous colitis was similar in the cohort of patients treated with PPIs, indicating no specific predisposition to either subtype. This study further confirms the risk factors associated with microscopic colitis. It can help guide physicians to recognize and eliminate these risk factors prior to initiating treatment for this disease. Future studies can focus on identifying the incidence of microscopic colitis with the different types of PPIs in the market.

•The study evaluated the risk of developing microscopic colitis and its subtypes in patients on PPI therapy. •Using a large multicenter database, a retrospective cohort analysis was conducted, excluding patients with autoimmune diseases, and adjusting for confounders. •An increased risk of developing microscopic colitis was associated with female gender, smoking, and the use of PPI, SSRI, and NSAIDs. •The use of PPI represented the highest odds of developing microscopic colitis.

ANTIDEPRESSANT MEDICATIONS ARE ASSOCIATED WITH INCREASED RISK OF HOSPITAL-ACQUIRED CLOSTRIDIOIDES DIFFICILE INFECTION: A POPULATION-BASED STUDY.

WHAT IS ALREADY KNOWN: •The rate and severity of Clostridioides difficile infection (CDI) has increased throughout North America, the United Kingdom, and Europe. •Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. What are the new findings: •The risk of Clostridioides difficile infection is higher in patients who are on mirtazapine, nortriptyline, or trazodone. •The prevalence rate of Clostridioides difficile infection in patients who were using antidepressant medications and the ones who did not, increased with age. Background - During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications.Methods - Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results - The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion - In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.

INCREASED RISK OF COLORECTAL CANCER IN PATIENTS WITH CHRONIC TOPHACEOUS GOUT: A POPULATION-BASED STUDY.

•The study aims to investigate the risk of developing Colorectal cancer in patients with a history of chronic tophaceous gout. •A retrospective cohort analysis of adults extracted from a validated multicenter and research platform database from hospitals in the United States was utilized. •The risk of Colorectal cancer was statistically significantly increased in male gender, smokers, alcoholics, obese, type 2 Diabetic, and chronic tophaceous gout patients. •The risk of developing Colorectal cancer was significantly higher in patients who have a history of Chronic tophaceous gout while accounting for potential confounding variables. Background - Colorectal cancer is the third most common type of cancer in both men and women and ranks second as the most common cause of cancer death in the United States. Classic risk factors include tobacco smoking, high alcohol consumption, physical inactivity and excess body weight. A prospective study found that an elevated serum uric acid was associated with higher rates of cancer-associated polyps. Interestingly, other studies found an association between elevated levels of serum uric acid and other types of cancer including colorectal cancer. Objective - Our study aimed to evaluate whether patients with chronic tophaceous gout had an increased risk of developing colorectal cancer. Methods - A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States was utilized to construct this study. Patients aged 18 years and above were included. Individuals who have had a history of familial adenomatous polyposis, a family history of colon cancer, and those diagnosed with inflammatory bowel disease were excluded from the analysis. The risk of developing colon cancer was calculated using a multivariate regression analysis to account for potential confounders. Results - 80,927,194 individuals were screened in the database and 70,177,200 were selected in the final analysis after accounting for inclusion and exclusion criteria. Type 2 diabetics (28.57%), smokers (10.98%), obese individuals (18.71%), alcoholics (3.13%), and patients who have had a diagnosis of chronic tophaceous gout were more common in the colon cancer group compared to those without the malignancy. Using multivariate regression analysis, risk of colon cancer was calculated for male gender (OR: 1.02; 95%CI: 1.01-1.03), smokers (OR: 1.54; 95%CI: 1.52-1.56), alcoholics (OR: 1.40; 95%CI: 1.37-1.43), obese patients (OR: 1.52; 95%CI: 1.50-1.54), type 2 diabetic individuals (OR: 3.53; 95%CI: 3.50-3.57), and those who have had a diagnosis of chronic tophaceous gout (OR: 1.40; 95%CI: 2.48-3.23). Conclusion - As expected, patients with colon cancer were found to have a higher prevalence in males, obese, tobacco and alcohol users. We also demonstrated that patients with gout have a significantly higher prevalence of CRC than those who do not before and after adjusting for metabolic risk factors. In fact, uric acid was found to induce production of reactive oxygen species, thus potentially promoting tumorigenesis. It would be interesting to assess the prevalence of colon cancer in patients with gout who have a serum uric acid that is less than 7 mg/dL. This might promote a tighter control of serum uric acid levels in this population in order to decrease the risk of colon cancer.

Risco aumentado de câncer colorretal em pacientes com gota tofácea crônica: um estudo populacional / Increased risk of colorectal cancer in patients with chronic tophaceous gout: a population-based study

ABSTRACT Background: Colorectal cancer is the third most common type of cancer in both men and women and ranks second as the most common cause of cancer death in the United States. Classic risk factors include tobacco smoking, high alcohol consumption, physical inactivity and excess body weight. A prospective study found that an elevated serum uric acid was associated with higher rates of cancer-associated polyps. Interestingly, other studies found an association between elevated levels of serum uric acid and other types of cancer including colorectal cancer. Objective: Our study aimed to evaluate whether patients with chronic tophaceous gout had an increased risk of developing colorectal cancer. Methods: A validated multicenter and research platform database of more than 360 hospitals from 26 different healthcare systems across the United States was utilized to construct this study. Patients aged 18 years and above were included. Individuals who have had a history of familial adenomatous polyposis, a family history of colon cancer, and those diagnosed with inflammatory bowel disease were excluded from the analysis. The risk of developing colon cancer was calculated using a multivariate regression analysis to account for potential confounders. Results: 80,927,194 individuals were screened in the database and 70,177,200 were selected in the final analysis after accounting for inclusion and exclusion criteria. Type 2 diabetics (28.57%), smokers (10.98%), obese individuals (18.71%), alcoholics (3.13%), and patients who have had a diagnosis of chronic tophaceous gout were more common in the colon cancer group compared to those without the malignancy. Using multivariate regression analysis, risk of colon cancer was calculated for male gender (OR: 1.02; 95%CI: 1.01-1.03), smokers (OR: 1.54; 95%CI: 1.52-1.56), alcoholics (OR: 1.40; 95%CI: 1.37-1.43), obese patients (OR: 1.52; 95%CI: 1.50-1.54), type 2 diabetic individuals (OR: 3.53; 95%CI: 3.50-3.57), and those who have had a diagnosis of chronic tophaceous gout (OR: 1.40; 95%CI: 2.48-3.23). Conclusion: As expected, patients with colon cancer were found to have a higher prevalence in males, obese, tobacco and alcohol users. We also demonstrated that patients with gout have a significantly higher prevalence of CRC than those who do not before and after adjusting for metabolic risk factors. In fact, uric acid was found to induce production of reactive oxygen species, thus potentially promoting tumorigenesis. It would be interesting to assess the prevalence of colon cancer in patients with gout who have a serum uric acid that is less than 7 mg/dL. This might promote a tighter control of serum uric acid levels in this population in order to decrease the risk of colon cancer.

RESUMO Contexto: O câncer colorretal é o terceiro tipo mais comum de câncer em homens e mulheres e ocupa o segundo lugar como a causa mais comum de morte por câncer nos EUA. Os fatores de risco clássicos incluem tabagismo, alto consumo de álcool, inatividade física e excesso de peso corporal. Um estudo prospectivo descobriu que um ácido úrico sérico elevado estava associado a taxas mais altas de pólipos associados ao câncer. Curiosamente, outros estudos encontraram uma associação entre níveis elevados de ácido úrico sérico e outros tipos de câncer, incluindo o câncer colorretal. Objetivo: Nosso estudo teve como objetivo avaliar se os pacientes com gota tofácea crônica tinham um risco aumentado de desenvolver câncer colorretal. Métodos: Utilizou-se um banco de dados validado multicêntrico e de plataforma de pesquisa de mais de 360 hospitais de 26 diferentes sistemas de saúde nos Estados Unidos para a construção deste estudo. Foram incluídos pacientes com 18 anos ou mais. Indivíduos com histórico de polipose adenomatosa familiar, histórico familiar de câncer de cólon e aqueles diagnosticados com doença inflamatória intestinal foram excluídos da análise. O risco de desenvolver câncer de cólon foi calculado usando uma análise de regressão multivariada para contabilizar possíveis confusões. Resultados: 80.927.194 indivíduos foram rastreados no banco de dados e 70.177.200 foram selecionados na análise final após considerar critérios de inclusão e exclusão. Diabéticos tipo 2 (28,57%), fumantes (10,98%), indivíduos obesos (18,71%), alcoólatras (3,13%) e pacientes que tiveram diagnóstico de gota tofácea crônica foram mais comuns no grupo de câncer de cólon em comparação com aqueles sem a malignidade. Usando a análise de regressão multivariada, o risco de câncer de cólon foi calculado para o sexo masculino (OR: 1,02; IC95%: 1,01-1,03), fumantes (OR: 1,54; IC95%: 1,52-1,56), alcoólatras (OR: 1,40; IC95%: 1,37-1,43), pacientes obesos (OR: 1,52; IC95%: 1,50-1,54), indivíduos diabéticos tipo 2 (OR: 3,53; IC95%: 3,50-3,57), e aqueles que tiveram diagnóstico de gota tofácea crônica (OR: 1,40; IC95%: 2,48-3,23). Conclusão: Como esperado, os pacientes com câncer de cólon foram encontrados com maior prevalência em homens, obesos, usuários de tabaco e álcool. Demonstramos também que os pacientes com gota têm uma prevalência significativamente maior de câncer colorretal do que aqueles que não a têm, antes e após o ajuste para fatores de risco metabólicos. De fato, descobriu-se que o ácido úrico induz a produção de espécies reativas de oxigênio, promovendo assim potencialmente a tumorigênese. Seria interessante avaliar a prevalência de câncer de cólon em pacientes com gota que têm um ácido úrico sérico inferior a 7 mg/dL. Isso poderia promover um controle mais rígido dos níveis de ácido úrico sérico nesta população para diminuir o risco de câncer de cólon.

Medicamentos antidepressivos estão associados a um risco aumentado de infecção hospitalar por Clostridioides difficile: um estudo populacional / Antidepressant medications are associated with increased risk of hospital-acquired clostridioides difficile infection: a population-based study

ABSTRACT Background: During the past decade, Clostridioides difficile infection (CDI) has become the most common cause of antibiotic-associated diarrhea. Several risk factors have been implicated. Scattered evidence about the association of CDI with antidepressant medications use exists in the literature so far. Therefore, we aim to investigate whether the risk of developing CDI is increased in hospitalized patients using antidepressant medications. Methods: Patients who were hospitalized were included in our cohort. We excluded individuals aged less than 18 years. A multivariate regression analysis was performed to calculate the risk of CDI accounting for potential confounders. Results: The risk of CDI in hospitalized patients was increased in individuals diagnosed with inflammatory bowel disease (OR: 4.44; 95%CI: 4.35-4.52), and in patients using clindamycin (OR: 1.55; 95%CI: 1.53-1.57), beta-lactam antibiotics (OR: 1.62; 95%CI: 1.60-1.64), PPI (OR: 3.27; 95%CI: 3.23-3.30), trazodone (OR: 1.31; 95%CI: 1.29-1.33), nortriptyline (OR: 1.25; 95%CI: 1.21-1.28), and mirtazapine (OR: 2.50; 95%CI: 2.46-2.54). After controlling for covariates, the risk of CDI was not increased in patients who were taking fluoxetine (OR: 0.94; 95%CI: 0.92-0.96). Conclusion: In contrary to fluoxetine; mirtazapine, nortriptyline, and trazodone were associated with increased risk of CDI in hospitalized patients.

RESUMO Contexto: Na última década, a infecção por Clostridioides difficile (ICD) tornou-se a causa mais comum de diarreia associada a antibióticos. Vários fatores de risco foram implicados. Existem evidências dispersas na literatura sobre a associação da ICD com o uso de medicamentos antidepressivos. Portanto, pretendemos investigar se o risco de desenvolver infecção adquirida na comunidade por Clostridioides difficile aumenta em pacientes que usam medicamentos antidepressivos. Métodos: Pacientes que foram hospitalizados foram incluídos em nossa coorte. Indivíduos com menos de 18 anos foram excluídos. Uma análise de regressão multivariada foi realizada para calcular o risco de ICD, considerando possíveis confusões. Resultados: O risco de ICD em pacientes hospitalizados foi maior em indivíduos diagnosticados com doença inflamatória intestinal (OR: 4,44; IC95%: 4,35-4,52) e em pacientes que usavam clindamicina (OR: 1,55; IC95%: 1,53-1,57), antibióticos beta-lactâmicos (OR: 1,62; IC95%: 1,60-1,64), PPI (OR: 3,27; IC95%: 3,23-3,30), trazodona (OR: 1,31; IC95%: 1,29-1,33), nortriptilina (OR: 1,25; IC95%: 1,21-1,28) e mirtazapina (OR: 2,50; IC95%: 2,46-2,54). Depois de controlar as covariáveis, o risco de ICD não aumentou em pacientes que estavam tomando fluoxetina (OR: 0,94; IC95%: 0,92-0,96). Conclusão: Em contrário à fluoxetina; mirtazapina, nortriptilina e trazodona foram associados a um risco aumentado de ICD em pacientes hospitalizados.

Non-alcoholic steatohepatitis is independently associated with a history of gestational diabetes mellitus.

BACKGROUND AND AIM: A recent study has demonstrated that women with gestational diabetes mellitus (GDM) are more likely to develop non-alcoholic fatty liver disease than those without GDM. In contrary to non-alcoholic fatty liver, the association of GDM with non-alcoholic steatohepatitis (NASH) has still not been well established in the current literature. Therefore, we aim to evaluate the association of a history of GDM and the development of NASH throughout their lives independently of type 2 diabetes mellitus (T2DM). METHODS: A validated research database of more than 360 hospitals was utilized to construct this study. Adult females included were divided into two groups: those with NASH (case) and individuals without NASH (control). Regression analysis was performed to account for potential cofounders. RESULTS: There were 70 632 640 individuals above the age of 18 years screened in the database. In patients with a history of GDM, NASH was most prevalent in middle age people compared with NASH alone, which was more prevalent in people aged 65 years and above. Compared with those without, patients with NASH tend to be Caucasian (odds ratio [OR]: 2.13), obese (OR: 4.83), have a history of GDM (OR: 1.23), diagnosed with hyperlipidemia (OR: 2.59), T2DM (OR: 4.52), metabolic syndrome (OR: 3.07), polycystic ovaries disease (OR: 1.72), and hypothyroidism (OR: 1.59). CONCLUSION: We demonstrated for the first time an increased odd of developing NASH in women who have had a diagnosis of gestational diabetes mellitus throughout their lives independently of any other factors that could interfere with the results.