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1.
Oncologist ; 29(1): 36-46, 2024 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-37721546

RESUMO

BACKGROUND: Stool pathogen testing is recommended as part of the initial evaluation for patients with new-onset diarrhea on immune checkpoint inhibitors (ICIs), yet its significance has not been well-studied. We aimed to determine the impact of multiplex gastrointestinal (GI) pathogen PCR testing on the clinical course and use of immunosuppressive therapy in patients who develop diarrhea on ICIs. METHODS: This retrospective cohort included individuals who underwent GI pathogen panel PCR for diarrhea on ICIs at Memorial Sloan Kettering between 7/2015 and 7/2021. The primary outcome was use of immunosuppressive therapy for suspected immunotherapy-related enterocolitis (irEC). Secondary outcomes included diarrhea severity and endoscopic and histologic disease patterns. RESULTS: Among 521 ICI-treated patients tested for GI pathogens, 61 (11.7%) had a positive PCR. Compared to patients without detectable infections, patients with infections had more frequent grades 3-4 diarrhea (37.7% vs. 19.6%, P < .01) and colitis (39.3% vs. 14.7%, P < .01). However, patients with infections did not have higher rates of persistent or recurrent diarrhea and were less likely to receive steroids (P < .01) and second-line immunosuppressive agents (P = .03). In 105 patients with lower endoscopy, similar trends were observed and no differences in endoscopic severity or histologic patterns were noted between groups. CONCLUSIONS: GI infections in ICI-treated patients presenting with diarrhea are linked to more severe but self-limited clinical presentations and may be optimally treated with observation and supportive care alone. Routine and timely stool pathogen testing may help avert unnecessary empiric immunosuppression for suspected irEC, which has been linked to blunted antitumor responses and numerous adverse effects.


Assuntos
Colite , Inibidores de Checkpoint Imunológico , Humanos , Inibidores de Checkpoint Imunológico/uso terapêutico , Estudos Retrospectivos , Prevalência , Colite/tratamento farmacológico , Colite/patologia , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Diarreia/tratamento farmacológico
2.
Int J Mol Sci ; 24(7)2023 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-37047398

RESUMO

Inflammatory bowel disease (IBD) refers to chronic intestinal immune-mediated diseases including two main disease manifestations: ulcerative colitis (UC) and Crohn's disease (CD). Epidemiological, clinical, and preclinical evidence has highlighted the potential anti-inflammatory properties of naturally occurring alkaloids. In the present study, we investigated the potential anti-inflammatory activities of the tobacco alkaloids nicotine and anatabine in a dextran sulfate sodium (DSS)-induced UC mouse model with a fully humanized immune system. Our results show that nicotine significantly reduced all acute colitis symptoms and improved colitis-specific endpoints, including histopathologically assessed colon inflammation, tissue damage, and mononuclear cell infiltration. The tobacco alkaloid anatabine showed similar effectiveness trends, although they were generally weaker or not significant. Gene expression analysis in the context of biological network models of IBD further pinpointed a possible mechanism by which nicotine attenuated DSS-induced colitis in humanized mice. The current study enables further investigation of possible molecular mechanisms by which tobacco alkaloids attenuate UC symptoms.


Assuntos
Alcaloides , Antineoplásicos , Colite Ulcerativa , Colite , Doenças Inflamatórias Intestinais , Animais , Camundongos , Nicotiana/efeitos adversos , Nicotina/efeitos adversos , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite Ulcerativa/induzido quimicamente , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/metabolismo , Doenças Inflamatórias Intestinais/metabolismo , Modelos Animais de Doenças , Anti-Inflamatórios/uso terapêutico , Antineoplásicos/uso terapêutico , Alcaloides/farmacologia , Alcaloides/metabolismo , Sistema Imunitário/metabolismo , Sulfato de Dextrana/toxicidade , Camundongos Endogâmicos C57BL , Colo/metabolismo
3.
Cancer Treat Rev ; 109: 102440, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35917654

RESUMO

BACKGROUND: Immune checkpoint inhibitors (ICIs) have improved cancer outcomes. However, immune-related adverse effects are common. The aim was to investigate the incidence of diarrhea and colitis of ICIs alone and in combination with chemotherapy or tyrosine kinase inhibitors (TKIs), histopathological findings, and management. METHODS: Two separate studies, including meta-analyses, were performed. Key inclusion criteria were for Study I) phase I-IV trials, and data on diarrhea and/or colitis; for Study II) studies describing histopathologic and endoscopic findings and/or biologic treatment for ICI-induced colitis. RESULTS: The incidence of anti-PD-1/PD-L1 antibody-induced diarrhea and colitis was 10% and 2%, respectively, with no clinically relevant differences between the compounds. The CTLA-4 inhibitor, ipilimumab, induced diarrhea and colitis in 33% and 7% of patients, respectively, whereas the incidence of diarrhea and colitis following ipilimumab combined with nivolumab was 21%-37% and 4%-8%, depending on regimen. The incidence of all-grade diarrhea following ICIs combined with chemotherapy or TKIs was high (17%-56%), whereas only 0.5% of patients developed severe (≥grade 3) colitis. The main patterns of histopathologic presentation after PD-1/CTLA-4 inhibitor mono- or combination therapy were acute and chronic active colitis and microscopic colitis-like. Infliximab and vedolizumab were equally effective against ICI-induced colitis. CONCLUSION: Expanding treatment options include combinations of ICIs and chemotherapy/TKI with a high incidence of diarrhea and a low incidence of colitis; thus, a potential risk of overtreatment with corticosteroids exists. We suggest a more tailored approach, particularly for the management of low-grade diarrhea. Prospective clinical trials are needed to refine management.


Assuntos
Colite , Inibidores de Checkpoint Imunológico , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colite/epidemiologia , Diarreia/induzido quimicamente , Diarreia/epidemiologia , Humanos , Incidência , Ipilimumab/efeitos adversos , Estudos Prospectivos
4.
Gut Microbes ; 14(1): 2013764, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35025709

RESUMO

With the rapid development and high therapeutic efficiency and biosafety of gas-involving theranostics, hydrogen medicine has been particularly outstanding because hydrogen gas (H2), a microbial-derived gas, has potent anti-oxidative, anti-apoptotic, and anti-inflammatory activities in many disease models. Studies have suggested that H2-enriched saline/water alleviates colitis in murine models; however, the underlying mechanism remains poorly understood. Despite evidence demonstrating the importance of the microbial hydrogen economy, which reflects the balance between H2-producing (hydrogenogenic) and H2-utilizing (hydrogenotrophic) microbes in maintaining colonic mucosal ecosystems, minimal efforts have been exerted to manipulate relevant H2-microbe interactions for colonic health. Consistent with previous studies, we found that administration of hydrogen-rich saline (HS) ameliorated dextran sulfate sodium-induced acute colitis in a mouse model. Furthermore, we demonstrated that HS administration can increase the abundance of intestinal-specific short-chain fatty acid (SCFA)-producing bacteria and SCFA production, thereby activating the intracellular butyrate sensor peroxisome proliferator-activated receptor γ signaling and decreasing the epithelial expression of Nos2, consequently promoting the recovery of the colonic anaerobic environment. Our results also indicated that HS administration ameliorated disrupted intestinal barrier functions by modulating specific mucosa-associated mucolytic bacteria, leading to substantial inhibition of opportunistic pathogenic Escherichia coli expansion as well as a significant increase in the expression of interepithelial tight junction proteins and a decrease in intestinal barrier permeability in mice with colitis. Exogenous H2 reprograms colonocyte metabolism by regulating the H2-gut microbiota-SCFAs axis and strengthens the intestinal barrier by modulating specific mucosa-associated mucolytic bacteria, wherein improved microbial hydrogen economy alleviates colitis.


Assuntos
Bactérias/metabolismo , Colite/tratamento farmacológico , Colite/microbiologia , Microbioma Gastrointestinal , Hidrogênio/administração & dosagem , Mucosa Intestinal/efeitos dos fármacos , Animais , Bactérias/classificação , Bactérias/efeitos dos fármacos , Bactérias/genética , Colite/induzido quimicamente , Colite/metabolismo , Colo/efeitos dos fármacos , Colo/metabolismo , Colo/microbiologia , Sulfato de Dextrana/efeitos adversos , Ácidos Graxos Voláteis/metabolismo , Microbioma Gastrointestinal/efeitos dos fármacos , Humanos , Hidrogênio/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL
5.
Biomed Pharmacother ; 143: 112148, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34560553

RESUMO

Ulcerative colitis (UC) is a gastrointestinal inflammatory disease with a multifactorial pathophysiology. This study aims to investigate the immunomodulatory effect of Portulaca oleracea leaf ethanolic extract (POE) on acetic acid (AA)-induced UC in mice. Experimental animals received oral doses of POE (200 mg/kg for 7 days) after an induction of colitis by intrarectal AA administration. In mice with AA-induced UC treated with POE, the results revealed a significant modulation in body weight and colon length. Moreover, treatment with POE downregulated the interleukin 1, 6, and 17, tumor necrosis factor-alpha, gamma interferon, and nuclear factor-kappa B levels compared with the colitis group. Furthermore, POE markedly inhibited histological damage, decreased myeloperoxidase activity and reduced fecal calprotectin level compared with the colitis group. These data are consistent with the reduction in total bacterial content in the colon. Taken together, treatment with POE may reduce colonic inflammation by alleviating the immune response and inhibiting the severity of colitis. The HPLC analysis of POE resulted in the identification of seven medicinal compounds comprising two phenolic acids (ferulic and caffeic acids) and five flavonoids (kaempferol, quercetin, rutin, narenginin and hesperidin). Subsequent analysis of POE by GC-MS revealed ten phytocomponents; the major percentages were hexadecenoic acid, methyl ester (29.8119%), α-linolenic acid (25.8431%), 16-octadecenoic acid, methyl ester (15.1578%) and α-tocopherol (10.7848%). Delta-lactams and alkanes were the minor components. Such natural plant-derived substances and their probable synergistic action appear to contribute to a promising therapeutic protocol for colitis.


Assuntos
Colite/tratamento farmacológico , Agentes de Imunomodulação/farmacologia , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Portulaca , Animais , Colite/imunologia , Colite/metabolismo , Colite/microbiologia , Citocinas/metabolismo , Modelos Animais de Doenças , Microbioma Gastrointestinal , Agentes de Imunomodulação/isolamento & purificação , Mediadores da Inflamação/metabolismo , Complexo Antígeno L1 Leucocitário/metabolismo , Masculino , Camundongos , NF-kappa B/metabolismo , Peroxidase/metabolismo , Compostos Fitoquímicos/isolamento & purificação , Extratos Vegetais/isolamento & purificação , Folhas de Planta , Portulaca/química
6.
Future Oncol ; 14(22): 2265-2277, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29569483

RESUMO

AIM: Idelalisib (IDELA) treatment is associated with diarrhea/colitis (incidence of ∼15% grade ≥3). We performed a retrospective analysis of gastrointestinal biopsies from 29 patients treated with IDELA across nine clinical trials. METHODS: A central core laboratory performed histopathologic review, immunohistochemistry, and droplet digital PCR viral studies. These results were correlated with tissue immune profiling data and morphologic features per modified Geboes score. RESULTS: Out of 29 eligible patients with abdominal pain or diarrhea, 24 (82.8%) had reported adverse event terms of diarrhea and/or colitis. Infectious pathogens were detected in 9/29 samples. Most biopsies presented with mixed/inflammatory infiltrates and contained increased numbers of FOXP3+ cells versus normal controls. CONCLUSION: This study revealed evidence of T-cell dysregulation and a substantial infectious component in association with IDELA-related diarrhea/colitis.


Assuntos
Colite/induzido quimicamente , Diarreia/induzido quimicamente , Purinas/efeitos adversos , Quinazolinonas/efeitos adversos , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/efeitos adversos , Biópsia , Colite/tratamento farmacológico , Colite/patologia , Colite/virologia , Colo/patologia , Colo/virologia , Infecções por Citomegalovirus/patologia , Diarreia/tratamento farmacológico , Diarreia/patologia , Feminino , Humanos , Imuno-Histoquímica/métodos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Reto/patologia , Reto/virologia
7.
World J Surg ; 42(1): 246-253, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-28744593

RESUMO

BACKGROUND: C. difficile (CDI) has surpassed methicillin-resistant staph aureus as the most common nosocomial infection with recurrence reaching 30% and the elderly being disproportionately affected. We hypothesized that post-discharge antibiotic therapy for continued CDI treatment reduces readmissions. STUDY DESIGN: We queried a 5% random sample of Medicare claims (2009-2011 Part A and Part D; n = 864,604) for hospitalizations with primary or secondary diagnosis of CDI. We compared demographics, comorbidities, and post-discharge CDI treatment (no CDI treatment, oral metronidazole only, oral vancomycin only, or both) between patients readmitted with a primary diagnosis of CDI within 90 days and patients not readmitted for any reason using univariate tests of association and multivariable models. RESULTS: Of 7042 patients discharged alive, 945 were readmitted ≤90 days with CDI (13%), while 1953 were not readmitted for any reason (28%). Patients discharged on dual therapy had the highest rates of readmission (50%), followed by no post-discharge CDI treatment (43%), vancomycin only (28%), and metronidazole only (19%). Patients discharged on only metronidazole (OR 0.28) or only vancomycin (OR 0.42) had reduced odds of 90-day readmission compared to patients discharged on no CDI treatment. Patients discharged on dual therapy did not vary in odds of readmission. CONCLUSIONS: Thirteen percent of patients discharged with CDI are readmitted within 90 days. Patients discharged with single-drug therapy for CDI had lower readmission rates compared to patients discharged on no ongoing CDI treatment suggesting that short-term monotherapy may be beneficial in inducing eradication and preventing relapse. Half of patients requiring dual therapy required readmission, suggesting patients with symptoms severe enough to warrant discharge on dual therapy may benefit from longer hospitalization.


Assuntos
Clostridioides difficile , Infecções por Clostridium/tratamento farmacológico , Colite/tratamento farmacológico , Infecção Hospitalar/tratamento farmacológico , Readmissão do Paciente , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Quimioterapia Combinada , Feminino , Hospitalização , Humanos , Masculino , Medicare , Metronidazol/uso terapêutico , Recidiva , Estudos Retrospectivos , Estados Unidos , Vancomicina/uso terapêutico
8.
J Infect ; 73(2): 115-22, 2016 08.
Artigo em Inglês | MEDLINE | ID: mdl-27246801

RESUMO

OBJECTIVES: We aim to study the disease burden, risk factors and severity of Clostridium difficile infection (CDI) in Hong Kong. METHODS: We conducted a prospective, case-control study in three acute-care hospitals in Hong Kong. Adult inpatients who developed CDI diarrhoea confirmed by PCR (n = 139) were compared with the non-CDI controls (n = 114). Ribotyping of isolates and antimicrobial susceptibility testing were performed. RESULTS: The estimated crude annual incidence of CDI was 23-33/100,000 population, and 133-207/100,000 population among those aged ≥65 years. The mean age of CDI patients was 71.5. Nursing home care, recent hospitalization, antibiotics exposure (adjusted OR 3.0, 95% CI 1.3-7.1) and proton-pump inhibitors use (adjusted OR 2.2, 95% CI 1.2-3.9) were risk factors. Severe CDI occurred in 41.7%. Overall mortality was 16.5% (among severe CDI, 26.5%). The commonest ribotypes were 002 (22.8%), 014 (14.1%), 012 and 046; ribotype 027 was absent. Ribotype 002 was associated with fluoroquinolone resistance and higher mortality (47.6% vs. 12.7%; adjusted HR 2.8, 95% CI 1.1-7.0). CONCLUSIONS: Our findings show high morbidity and mortality of CDI in the older adults, and identify ribotype 002 as a possible virulent strain causing serious infections in this cohort.


Assuntos
Clostridioides difficile/patogenicidade , Infecções por Clostridium/epidemiologia , Infecções por Clostridium/microbiologia , Infecção Hospitalar/epidemiologia , Ribotipagem , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Clostridioides difficile/classificação , Clostridioides difficile/genética , Clostridioides difficile/isolamento & purificação , Infecções por Clostridium/imunologia , Infecções por Clostridium/mortalidade , Colite/tratamento farmacológico , Colite/microbiologia , Efeitos Psicossociais da Doença , Infecção Hospitalar/microbiologia , Diarreia/epidemiologia , Diarreia/microbiologia , Feminino , Fluoroquinolonas/uso terapêutico , Hong Kong/epidemiologia , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Estudos Prospectivos , Fatores de Risco , Índice de Gravidade de Doença
9.
J Pharm Sci ; 101(8): 2668-74, 2012 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-22573521

RESUMO

There are 94,709 clinical trials across 179 countries. Approximately half (47,467) are related to the three categories within the scope of the free online resource "Drug Delivery Trends in Clinical Trials and Translational Medicine," which are (1) drug delivery technology and systems, (2) biological molecule platforms, and (3) pharmacokinetic and pharmacodynamic interactions. In this commentary, trends in biological molecule platforms and their impacts are discussed. The sales of top 15 biologic drugs have reached over $63 billion in 2010. In the past 10 years, major pharmaceutical companies have acquired biological molecule platforms and have become integrated biopharmaceutical companies, highlighting the role of biotechnology in driving new therapeutic product development. The top three products--Remicade, Enbrel, and Humira--indicated for arthritis and colitis and targeted to tumor necrosis factor-alpha (TNF-α), each generated over $6 billion in annual sales. In addition to TNF-α, biologic candidates targeted to other inflammatory molecules are in clinical development, partly driven by commercial interests and medical need. Although clinical experience indicates that all the anti-TNF-α molecular platforms are effective for rheumatoid arthritis, Crohn's disease, and colitis, whether the new agents can provide additional relief or cures remains to be seen.


Assuntos
Artrite Reumatoide/tratamento farmacológico , Colite/tratamento farmacológico , Doença de Crohn/tratamento farmacológico , Sistemas de Liberação de Medicamentos/métodos , Descoberta de Drogas/métodos , Fator de Necrose Tumoral alfa/antagonistas & inibidores , Ensaios Clínicos como Assunto , Sistemas de Liberação de Medicamentos/economia , Descoberta de Drogas/economia , Humanos , Farmacocinética , Pesquisa Translacional Biomédica
10.
Arch Pharm Res ; 33(7): 1091-101, 2010 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-20661720

RESUMO

Metabolic profiling of the fecal extracts of male mice was carried out to assess the effects of probiotics on colonic inflammation using (1)H NMR spectroscopy coupled with multivariate data analysis. The control group (n = 5) was administered phosphate buffered saline for 14 days. Acute colitis was induced with dextran sulfate sodium (DSS) for 7 days following administration of phosphate buffered saline for 7 days (DSS-treated group, n = 5). LAB + DSS-treated group (n = 5) was administered lactic acid bacteria (LAB) daily for 7 days followed by treatment with DSS for 7 days to investigate protective effect of LAB against DSS-inducible colitis. Histological damage, myeloperoxidase activity, and malondialdehyde content of colon tissue were reduced, whereas colon length increased in LAB + DSS-treated mice compared to those in DSS-treated mice. DSS treatment was associated with fecal excretion of amino acids, short chain fatty acids, and nucleotides, revealing significant decreases of threonine, alanine, glutamate, glutamine, aspartate, lysine, glycine, butyrate, uracil, and hypoxanthine together with increases of monosaccharides, glucose, and trimethylamine in the feces of mice with DSS-induced colitis. Increased levels of acetate, butyrate, and glutamine and decreased levels of trimethylamine were found in the feces of LAB + DSS-treated mice compared to DSS-treated mice alone. The increased short chain fatty acids levels in the feces of mice fed with LAB indicate that the probiotics have protective effects against DSS-induced colitis via modulation of the gut microbiota. This work highlights the possibility for alternative approach of metabonomics in feces for assessing the probiotic effect in an animal model of inflammatory bowel disease.


Assuntos
Colite/tratamento farmacológico , Colite/metabolismo , Modelos Animais de Doenças , Metabolômica/métodos , Probióticos/metabolismo , Probióticos/uso terapêutico , Animais , Colite/microbiologia , Sulfato de Dextrana/toxicidade , Mediadores da Inflamação/metabolismo , Mediadores da Inflamação/uso terapêutico , Ácido Láctico/biossíntese , Ácido Láctico/metabolismo , Ácido Láctico/uso terapêutico , Espectroscopia de Ressonância Magnética/métodos , Masculino , Camundongos , Camundongos Endogâmicos ICR
11.
Pharmacol Res ; 58(3-4): 222-31, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-18812224

RESUMO

The aim of this study was to investigate the relevance of mouse ex vivo cultures as a first screening model for new therapeutic agents of Inflammatory Bowel Disease (IBD). Two murine models (dextran sodium sulphate (DSS)-induced colitis and Galphai2-deficient mice) and two anti-inflammatory agents (methyl-prednisolone and the proteasome inhibitor MG132) were evaluated. The in vivo effects of methyl-prednisolone were assessed in both models. Ex vivo colonic tissue from both mouse models were cultured in the presence or absence of the drugs and TaqMan Low-Density arrays were used to assess the regulation of inflammatory genes before and after drug treatment. Colitis induced a similar inflammatory gene profile in both mouse models in in vivo studies and in ex vivo cultures. The differences encountered reflected the different phases of colitis in the models, e.g. innate cytokine/chemokine profile in the DSS model and T cell related markers in Galphai2-deficient mice. After steroid treatment, a similar pattern of genes was suppressed in the two mouse models. We confirmed the suppression of inflammatory gene expression for IL-1beta, IL-6 and iNOS in ex vivo and in vivo colons from both mouse models by quantitative RT-PCR. Importantly, the inflammatory responses in the murine ex vivo culture system reflected the in vivo response in the inflamed colonic tissue as assessed by changes in inflammatory gene expression, suggesting that the murine culture system can be used for validation of future IBD therapies.


Assuntos
Colite/tratamento farmacológico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Animais , Anti-Inflamatórios/uso terapêutico , Células Cultivadas , Colite/induzido quimicamente , Colite/genética , Primers do DNA , Sulfato de Dextrana , Feminino , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/deficiência , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Doenças Inflamatórias Intestinais/genética , Doenças Inflamatórias Intestinais/patologia , Interleucina-1beta/biossíntese , Interleucina-6/biossíntese , Leupeptinas/farmacologia , Metilprednisolona/uso terapêutico , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/biossíntese , Técnicas de Cultura de Órgãos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
12.
J Pediatr Gastroenterol Nutr ; 42(2): 186-9, 2006 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-16456413

RESUMO

BACKGROUND: The aim of this study was to assess the pediatric population that suffered from inflammatory bowel disease (IBD) in the Czech Republic and to determine the incidence of Crohn disease (CD) in children up to 15 years age between 1990 and 2001. METHODS: Diagnostic criteria for CD, ulcerative colitis (UC), and indeterminate colitis (IC) were defined. Medical records provided a source of basic information about the children. A standardized protocol was filled out and sent to the coordinator of the study. All protocols were checked to see whether the data corresponded to the defined criteria and then were processed further. The study was retrospective in character for the years 1990 to 1999 and prospective for the years 2000 and 2001. RESULTS: Diagnostic criteria were met in 470 patients with IBD; 201 of them turned 18 years old during the study period. CD was diagnosed in 223 patients. The incidence of CD in children up to 15 years of age increased from 0.25/100,000 in 1990 to 1.25/100,000 in 2001. Eighty-two percent of children with CD were treated with aminosalicylates in combination with corticosteroids; 29% of patients received azathioprine. Severe growth retardation was recorded in 6.4% of adolescents with CD at the age of 18. UC was diagnosed in 202 patients. Therapy with aminosalicylates only was sufficient for control of the disease in 23% patients; 68% children were treated with corticosteroids, 15 of them (23% of the whole group) received additional azathioprine. Criteria for IC were met in 9.8% of all patients with IBD. CONCLUSION: This study confirmed an increase in incidence of CD in children younger than 15 years in the Czech Republic.


Assuntos
Corticosteroides/uso terapêutico , Ácidos Aminossalicílicos/uso terapêutico , Azatioprina/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Adolescente , Fatores Etários , Criança , Pré-Escolar , Colite/tratamento farmacológico , Colite/epidemiologia , Colite Ulcerativa/complicações , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/epidemiologia , Doença de Crohn/complicações , Doença de Crohn/tratamento farmacológico , Doença de Crohn/epidemiologia , República Tcheca/epidemiologia , Progressão da Doença , Quimioterapia Combinada , Feminino , Transtornos do Crescimento/etiologia , Humanos , Incidência , Lactente , Doenças Inflamatórias Intestinais/complicações , Masculino , Estudos Prospectivos , Estudos Retrospectivos
14.
Eur J Gastroenterol Hepatol ; 15(1): 69-74, 2003 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-12544697

RESUMO

BACKGROUND: A study on orocaecal transit time (OCTT) in patients with different localizations of Crohn's disease (CD) is not available. Because slow-release drug formulations are increasingly available for the treatment, there is a concrete risk that delayed OCTT may impair the efficacy of these formulations. AIMS: We investigated OCTT before and after therapy using lactulose H2-breath test and we studied whether OCTT can influence the clinical response to therapy with slow-release mesalazine formulations in adult CD patients.(2) PATIENTS AND METHODS: We studied 45 adult patients with non-obstructive CD and Crohn's Disease Activity Index (CDAI) <200 (29 men, 16 women; mean age 42 years, range 22-73 years). Twenty patients had ileocolonic, 16 colonic and 9 ileal localization of CD. The control group consisted of 20 healthy subjects (13 men, seven women; mean age 53 years, range 22-71 years). After OCTT assessment, 29 patients were treated with time-dependent mesalazine 3.6 g/day, while 16 patients were treated with pH-dependent mesalazine 3.6 g/day. If bacterial overgrowth was detected, the patients were also treated with rifaximin 800 mg/day for 7 days. RESULTS: OCTT was delayed (120 min, range 115-210 min) in 30 of the 45 CD patients (67%). Four patients (9%) showed bacterial overgrowth, while OCTT was regular (82.5 min, range 75-90 min) in 11 patients (24%). In the control group, the mean OCTT was 88.2 min (range 75-135 min); (P<0.01). OCTT was more prolonged in ileal localization (182.2 min, range 150-210 min), rather than in patients with ileocolonic (122 min, range 75-180 min) or colonic (106 min, range 75-150 min) localization of CD; (P<0.01). Thirty-nine patients showed normal OCTT after starting therapy (83 min, range 75-105 min), while OCTT remained slightly delayed in the remaining patients (110 min, range 105-115 min); (P<0.01). CDAI was <100 (mean value 83) in all patients with reduction of OCTT to normal value 4 months after starting therapy, while it was >140 (mean value 143) in patients with a slight reduction but not normalization of OCTT respectively (five patients with ileal and one with ileocolonic localization of CD) with a statistically significant correlation between OCTT and CDAI (P<0.01). CONCLUSIONS: This study shows clearly for the first time that OCTT is not only delayed in patients with active CD, but also that it is prolonged in ileal and ileocolonic rather than colonic localization of CD. Moreover we obtained these results using a simple, sensitive, non-invasive and repeatable method, namely, a lactulose hydrogen breath test.


Assuntos
Doença de Crohn/fisiopatologia , Trânsito Gastrointestinal , Adulto , Idoso , Anti-Inflamatórios não Esteroides/uso terapêutico , Testes Respiratórios/métodos , Colite/tratamento farmacológico , Colite/fisiopatologia , Doença de Crohn/tratamento farmacológico , Preparações de Ação Retardada , Feminino , Fármacos Gastrointestinais/uso terapêutico , Trânsito Gastrointestinal/efeitos dos fármacos , Humanos , Ileíte/tratamento farmacológico , Ileíte/fisiopatologia , Lactulose , Masculino , Mesalamina/uso terapêutico , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Resultado do Tratamento
15.
Am J Surg ; 176(1): 81-5, 1998 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-9683140

RESUMO

BACKGROUND: The authors determined the radiological misdiagnosis rate of primary epiploic appendagitis (PEA) and its impact on patient management and hospital resource use. METHODS: A total of 660 computed tomography scans performed for clinically suspected diverticulitis (348 cases) or appendicitis (312 cases) were reviewed for cases meeting strict radiological criteria for PEA. Retrospective interpretations were compared with radiological reports. Medical records and hospital cost data were reviewed to estimate impact on patient management and resource use. RESULTS: Eleven scans (2%) met criteria for PEA. Seven scans were initially misdiagnosed as diverticulitis (6 patients) or appendicitis (1 patient). All misdiagnosed patients were hospitalized (mean 4.3 days); 6 received antibiotic therapy. Average cost per patient was $4,117. Four scans were initially correctly diagnosed as PEA. One patient was hospitalized (1 day); none received antibiotic therapy. Average cost per patient was $1,205. CONCLUSIONS: Radiological misdiagnosis of PEA leads to unnecessary hospitalization, medical treatment, and overuse of hospital resources.


Assuntos
Colite/diagnóstico por imagem , Erros de Diagnóstico , Adulto , Idoso , Antibacterianos/economia , Antibacterianos/uso terapêutico , Apendicite/diagnóstico por imagem , Colite/tratamento farmacológico , Colite/economia , Custos e Análise de Custo , Diagnóstico Diferencial , Doença Diverticular do Colo/diagnóstico por imagem , Feminino , Seguimentos , Preços Hospitalares , Humanos , Tempo de Internação/economia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/economia
16.
Dis Colon Rectum ; 34(3): 244-8, 1991 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-1999131

RESUMO

Clostridium difficile infection manifests as a self-limiting diarrhea, protracted colitis, or toxic pseudomembranous colitis. The incidence of C. difficile in a 514-bed community hospital was studied retrospectively; 155 patients of a total 18,262 admitted during 1988 were identified with C. difficile as an admitting or subsequent diagnosis. The method of diagnosis, mode of therapy, and related costs were analyzed. We have determined that education, with an emphasis on pathogenesis and prevention, is necessary to reduce the incidence in the hospital and the cost to the patient.


Assuntos
Clostridioides difficile , Infecções por Clostridium/economia , Colite/economia , Infecção Hospitalar/economia , Adulto , Antibacterianos/uso terapêutico , Técnicas Bacteriológicas/economia , Infecções por Clostridium/diagnóstico , Infecções por Clostridium/tratamento farmacológico , Infecções por Clostridium/epidemiologia , Colite/diagnóstico , Colite/tratamento farmacológico , Colite/epidemiologia , Custos e Análise de Custo , Infecção Hospitalar/diagnóstico , Infecção Hospitalar/tratamento farmacológico , Infecção Hospitalar/epidemiologia , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
17.
Am J Hosp Pharm ; 45(1): 122-5, 1988 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-3348224

RESUMO

A multidisciplinary cost-containment program for promoting oral metronidazole in place of oral vancomycin as initial therapy of antibiotic-associated colitis (AAC) is described. The pharmacy department and the division of infectious diseases implemented the program in two phases. In the first phase, a one-year retrospective drug-use review in patients with AAC treated with oral vancomycin was conducted to determine the average cost of therapy per treatment course. In the second phase, the use of oral metronidazole instead of oral vancomycin for initial treatment of AAC was promoted using inservice-education programs and distribution of pocket-size brochures containing AAC treatment guidelines to medical staff. The pharmacy and therapeutics committee supported the program by endorsing metronidazole as the drug of choice for AAC and by distributing follow-up progress reports of the program to medical staff. Pharmacists on the nursing units were responsible for enforcing the program stipulations regarding vancomycin and metronidazole use and for collecting data on patient-specific drug use. Six months after implementation of the program, the average cost of drug therapy for AAC had decreased by 89%, from $343.24 per patient to $37.50 per patient. The projected annual savings resulting from the program was $38,829.02. All prescribing physicians and dispensing pharmacists complied 100% with the program stipulations regarding drug use. The multidisciplinary program described here was successful in promoting the use of oral metronidazole for initial therapy of AAC.


Assuntos
Antibacterianos/efeitos adversos , Colite/tratamento farmacológico , Metronidazol/uso terapêutico , Administração Oral , Colite/induzido quimicamente , Colite/economia , Controle de Custos , Humanos , Metronidazol/administração & dosagem , Farmacêuticos , Serviço de Farmácia Hospitalar/economia , Comitê de Farmácia e Terapêutica , Vancomicina/uso terapêutico
18.
Lancet ; 2(8358): 1043-6, 1983 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-6138597

RESUMO

101 patients with Clostridium-difficile-associated diarrhoea or colitis were prospectively randomised to 10-day oral courses of metronidazole, 250 mg four times a day, or vancomycin, 500 mg four times a day. 7 did not complete the protocol and were dropped from analysis. Pseudomembranous colitis (PMC) was diagnosed after endoscopy in 33 patients. Of the remaining patients without PMC, 38 had both C difficile culture and cytotoxin and 23 had only culture evidence of C difficile. 52 evaluable patients received vancomycin and 42 received metronidazole. There were two treatment failures with metronidazole and none with vancomycin (p = 0.20); and two relapses with metronidazole versus six with vancomycin (p = 0.17). Treatment in 1 patient in each group was discontinued because of drug intolerance. Response and relapse rates of the 33 patients with PMC were no different from those of the remaining patients. Pharmacy cost for the dosage used was $387.48 to $520.00 for vancomycin and $11.84 for metronidazole. Metronidazole and vancomycin have equivalent efficacy and relapse rates and are tolerated to a similar extent by patients with C-difficile-related diarrhoea and colitis, but metronidazole is considerably more economical.


Assuntos
Infecções por Clostridium/tratamento farmacológico , Colite/tratamento farmacológico , Diarreia/tratamento farmacológico , Metronidazol/uso terapêutico , Vancomicina/uso terapêutico , Adulto , Idoso , Ensaios Clínicos como Assunto , Colite/etiologia , Custos e Análise de Custo , Diarreia/etiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Distribuição Aleatória
19.
Antibiotiki ; 22(2): 181-4, 1977.
Artigo em Russo | MEDLINE | ID: mdl-324386

RESUMO

Data on the use of bificol, a new Soviet preparation, and its effect on the intestine microflora of patients with chronic colitis occupied in production of penicillin are presented. It was shown that by the 28th day of the preparation use the level of the intestine bacteria in the patients' intestine reliably increased. The number of immobile strains decreased from 67.6 to 36.6 per cent. Bifidoflora normalized by the 14th day of the treatment. Some clinical inprovement, i.e. stool normalization, lessening of the stomach pain, increased appetite were observed by the 4th--5th day of the treatment with bificol. On the basis of the microbiological and clinical data it was shown that treatment of the patients with chronic colitis in antibiotic production should continue for at least 28 days and in individual cases for longer periods of time. It is recommended to use the preparation in 10 doses a day divided into 2 parts.


Assuntos
Antibacterianos/farmacologia , Bacteriocinas/uso terapêutico , Colite/microbiologia , Indústria Farmacêutica , Intestinos/microbiologia , Actinomycetaceae/isolamento & purificação , Doença Crônica , Colite/tratamento farmacológico , Exposição Ambiental , Escherichia coli/isolamento & purificação , Humanos , Lactobacillus , Medicina do Trabalho , Fatores de Tempo
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