RESUMO
BACKGROUND: Optimizing second-line biologic therapies for adult ulcerative colitis (UC) post first-line failure is essential. OBJECTIVE: Compare second-line biologic therapy efficacy in adult UC patients with prior treatment failure. METHODS: A comprehensive search of electronic databases up to May 2023 was conducted to assess second-line biologic therapy efficacy using a random effects model. Parameters analyzed included clinical remission rate, clinical response rate, mucosal healing rate, annual discontinuation rate, and colectomy rates. RESULTS: Forty-three research papers were analyzed. Clinical remission rates for second-line biologics were ranked at 6-14 weeks: Infliximab (30%) was followed by Vedolizumab (29%), Ustekinumab (27%), and Adalimumab (19%). At 52-54 weeks, the order shifted, with Vedolizumab (35%) followed by Infliximab (32%), Ustekinumab (31%), and Adalimumab (26%). The mucosal healing rate was 21%, ranked as: Infliximab (31%), Vedolizumab (21%), Adalimumab (21%), and Ustekinumab (14%). The annual discontinuation rate stood at 20%, with Adalimumab (25%), Vedolizumab (18%), Infliximab (17%), and Ustekinumab (16%). Discontinuation rates due to primary failure (PF), secondary failure (SF), and adverse events (AE) were 6%, 12%, and 3%, respectively. The annual colectomy rate was 9%, with Adalimumab (15%) followed by Vedolizumab (10%), Ustekinumab (9%), and Infliximab (5%), and colectomy rates of 10% due to PF, 12% due to SF, and 4% due to AE. CONCLUSION: For UC patients with first-line treatment failure, it is recommended to prioritize infliximab or vedolizumab as second-line biologic therapies, while avoiding adalimumab as the primary choice. Further clinical trials are necessary to assess ustekinumab efficacy accurately.
Assuntos
Colite Ulcerativa , Falha de Tratamento , Humanos , Colite Ulcerativa/tratamento farmacológico , Colite Ulcerativa/cirurgia , Terapia Biológica/métodos , Terapia Biológica/efeitos adversos , Adulto , Produtos Biológicos/uso terapêutico , Produtos Biológicos/efeitos adversos , Fármacos Gastrointestinais/uso terapêutico , Fármacos Gastrointestinais/efeitos adversos , Infliximab/uso terapêutico , Anticorpos Monoclonais HumanizadosRESUMO
CONTEXT: Malignant bowel obstruction (MBO) is a common complication of intra-abdominal cancer, frequently seen in advanced gastrointestinal and gynecologic cancer. Management of MBO can be challenging, particularly if the patient is not a surgical candidate. No consensus exists on how best to manage these patients medically. Retrospective studies suggest that the combination of dexamethasone, octreotide and metoclopramide may lead to relief of obstruction and improvement in symptoms associated with the obstruction. OBJECTIVES: This study seeks to prospectively evaluate the combination of drug "triple therapy" dexamethasone 4 mg BID, metoclopramide 10 mg Q6 and octreotide 300 mcg TID to assess tolerability, safety, and effect on symptoms and deobstruction. METHODS: Adults admitted at Roswell Park Comprehensive Cancer Center with malignant bowel obstruction were eligible. Eligible patients who constented to the study were started on the triple therapy with close monitoring of symptoms and for adverse effects. RESULTS: A total of 15 patients enrolled in the study. Two patients experienced bradycardia as adverse effect and there was no incidence of bowel perforation. All patients who completed the study had complete resolution of their nausea, and improvement in other symptoms including pain, constipation, tolerance of oral intake and resumption of bowel movements. Only two of the 15 patients were alive to complete the six-month post study follow up. CONCLUSION: "Triple therapy" with dexamethasone, metoclopramide, and octreotide for management of nonsurgical MBO in this small sample size appears safe and well tolerated however a diagnosis of inoperable MBO remains associated with poor prognosis and death within months.
Assuntos
Obstrução Intestinal , Neoplasias , Adulto , Humanos , Feminino , Metoclopramida/uso terapêutico , Octreotida/uso terapêutico , Fármacos Gastrointestinais/uso terapêutico , Estudos Retrospectivos , Estudos Prospectivos , Obstrução Intestinal/terapia , Obstrução Intestinal/complicações , Dexametasona/uso terapêutico , Cuidados Paliativos , Neoplasias/complicaçõesRESUMO
Functional dyspepsia(FD) is a prevalent functional gastrointestinal disease characterized by recurrent and long-lasting symptoms that significantly impact the quality of life of patients. Currently, western medicine treatment has not made breakthrough progress and mainly relies on symptomatic therapies such as gastrointestinal motility agents, acid suppressants, antidepressants/anxiolytics, and psychotherapy. However, these treatments have limitations in terms of insufficient effectiveness and safety. Traditional Chinese medicine(TCM) possesses unique advantages in the treatment of FD. Through literature search in China and abroad, it has been found that the mechanisms of TCM in treating FD is associated with various signaling pathways, and research on these signaling pathways and molecular mechanisms has gradually become a focus. The main signaling pathways include the SCF/c-Kit signaling pathway, 5-HT signaling pathway, CRF signaling pathway, AMPK signaling pathway, TRPV1 signaling pathway, NF-κB signaling pathway, and RhoA/ROCK2/MYPT1 signaling pathway. This series of signaling pathways can promote gastrointestinal motility, alleviate anxiety, accelerate gastric emptying, reduce visceral hypersensitivity, and improve duodenal micro-inflammation in the treatment of FD. This article reviewed the research on TCM's regulation of relevant signaling pathways in the treatment of FD, offering references and support for further targeted TCM research in the treatment of FD.
Assuntos
Dispepsia , Humanos , Dispepsia/tratamento farmacológico , Dispepsia/genética , Medicina Tradicional Chinesa , Qualidade de Vida , Fármacos Gastrointestinais/uso terapêutico , Transdução de SinaisRESUMO
Functional dyspepsia is a form of dyspepsia lacking in clear causes following clinical assessment. Dyspepsia is characterized by episodic or persistent abdominal pain or discomfort of the upper gastrointestinal (GI) tract. Its onset has been linked with a deficiency or dysfunction of digestive enzymes. Thus, consumption of digestive multi-enzymatic preparations may be effectively used for the reduction of symptoms. The aim of this study is to assess the effectiveness and tolerability of the supplementation of a normal diet with a multi-enzyme blend obtained from fungal fermentation, in a randomized, placebo-controlled, double-blind, clinical trial. Enrolled subjects (n = 120, male: 63, female: 57), aged 18-59 years, were randomized (allocation ratio 1:1) to receive either 2 capsules per day of the food supplement (containing 200 mg of the multi-enzyme blend/capsule) or placebo, for 2 months. The primary outcome of the study (i.e., improvements in quality of life) was evaluated by the Nepean Dyspepsia Index-SF (NDI-SF) questionnaire, while the secondary outcomes (i.e., severity of pain and the quality of sleep) were assessed through the Visual Analogue Scale (VAS) and Pittsburgh Sleep Quality Index (PSQI) questionnaire. The results showed an improvement in NDI-SF1, NDI-SF2-5, VAS, and PSQI scores in subjects treated with the multi-enzyme blend, indicating an improvement in quality of life and of sleep, and a decreased severity of pain, following the supplementation with digestive enzymes, without side effects. In conclusion, treatment with digestive enzymes was found to be effective in the reduction of functional dyspepsia symptoms and in the improvement of sleep quality, and is well-tolerated.
Assuntos
Dispepsia , Feminino , Humanos , Masculino , Dor Abdominal/tratamento farmacológico , Suplementos Nutricionais , Método Duplo-Cego , Dispepsia/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Qualidade de Vida , Resultado do Tratamento , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-IdadeRESUMO
BACKGROUND: Approximately half the patients with ulcerative colitis who undergo restorative proctocolectomy with ileal pouch-anal anastomosis (IPAA) will subsequently have pouchitis, and among those patients, one fifth will have chronic pouchitis. METHODS: We conducted a phase 4, double-blind, randomized trial to evaluate vedolizumab in adult patients in whom chronic pouchitis had developed after undergoing IPAA for ulcerative colitis. Patients were assigned (in a 1:1 ratio) to receive vedolizumab intravenously at a dose of 300 mg or placebo on day 1 and at weeks 2, 6, 14, 22, and 30. All the patients received concomitant ciprofloxacin from weeks 1 to 4. The primary end point was modified Pouchitis Disease Activity Index (mPDAI)-defined remission (an mPDAI score of ≤4 and a reduction from baseline of ≥2 points in the mPDAI total score; scores range from 0 to 12, with higher scores indicating more severe pouchitis) at week 14. The mPDAI is based on clinical symptoms and endoscopic findings. Other efficacy end points included mPDAI-defined remission at week 34, mPDAI-defined response (a reduction from baseline of ≥2 points in the mPDAI score) at weeks 14 and 34, and PDAI-defined remission (a PDAI score of ≤6 and a reduction from baseline of ≥3 points; scores range from 0 to 18, with higher scores indicating more severe pouchitis) at weeks 14 and 34. The PDAI is based on clinical symptoms, endoscopic findings, and histologic findings. RESULTS: Among the 102 patients who underwent randomization, the incidence of mPDAI-defined remission at week 14 was 31% (16 of 51 patients) with vedolizumab and 10% (5 of 51 patients) with placebo (difference, 21 percentage points; 95% confidence interval [CI], 5 to 38; P = 0.01). Differences in favor of vedolizumab over placebo were also seen with respect to mPDAI-defined remission at week 34 (difference, 17 percentage points; 95% CI, 0 to 35), mPDAI-defined response at week 14 (difference, 30 percentage points; 95% CI, 8 to 48) and at week 34 (difference, 22 percentage points; 95% CI, 2 to 40), and PDAI-defined remission at week 14 (difference, 25 percentage points; 95% CI, 8 to 41) and at week 34 (difference, 19 percentage points; 95% CI, 2 to 37). Serious adverse events occurred in 3 of 51 patients (6%) in the vedolizumab group and in 4 of 51 patients (8%) in the placebo group. CONCLUSIONS: Treatment with vedolizumab was more effective than placebo in inducing remission in patients who had chronic pouchitis after undergoing IPAA for ulcerative colitis. (Funded by Takeda; EARNEST ClinicalTrials.gov number, NCT02790138; EudraCT number, 2015-003472-78.).
Assuntos
Colite Ulcerativa , Fármacos Gastrointestinais , Pouchite , Proctocolectomia Restauradora , Adulto , Humanos , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Ciprofloxacina/administração & dosagem , Ciprofloxacina/uso terapêutico , Colite Ulcerativa/complicações , Colite Ulcerativa/cirurgia , Pouchite/tratamento farmacológico , Pouchite/etiologia , Doença Crônica , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/uso terapêutico , Proctocolectomia Restauradora/efeitos adversos , Método Duplo-Cego , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Administração Intravenosa , Quimioterapia CombinadaRESUMO
Background: The loss of response or failure to achieve remission to vedolizumab in ulcerative colitis (UC) patients is currently a major clinical problem. Recently, Nutritional Risk Index (NRI), Controlling Nutritional Status (CONUT), and Malnutrition Universal Screening Tool (MUST) have been suggested as a new prognostic factor of UC activity. Here, we aimed at confirmation of hypotezis that NRI, CONUT and MUST may be used as inexpensive and efficient predictive biomarkers of response in UC patients treated with vedolizumab. Methods: This study was conducted in retrospective manner in 32 adult patients with UC of Caucasian origin (21 men and 11 women), who were qualified for 52-week therapy with vedolizumab and finished the 14-weeks from January 2020 to March 2022. Our study analyzed the 45 courses of vedolizumab therapy. Nutritional status indicators, i.e., the NRI, CONUT and MUST of each UC patient, were marked at the time of qualifying for biological treatment. Results: In our study, the MUST score was significantly lower in UC patients who positively achieved clinical remission at week 14 during vedolizumab induction therapy (0.33 ± 0.49 vs. 1.37 ± 0.83; p = 0.002). The analysis showed the lower baseline NRI and CONUT scores in patients with positive clinical remission at week 14 (NRI: 96.42 ± 4.29 vs. 101.41 ± 7.09; p = 0.024; CONUT: 1.00 ± 1.08 vs. 2.16 ± 1.46; p = 0.031). Conclusions: Nutritional status indicators (NRI, MUST and CONUT) may become valuable predictor of achieving remission at week 14 during vedolizumab therapy in UC patients.
Assuntos
Colite Ulcerativa , Adulto , Masculino , Humanos , Feminino , Colite Ulcerativa/tratamento farmacológico , Projetos Piloto , Estudos Retrospectivos , Estado Nutricional , Fármacos Gastrointestinais/uso terapêutico , Indução de Remissão , Resultado do TratamentoRESUMO
BACKGROUND: The effectiveness of Ustekinumab (UST) and Vedolizumab (VDZ) in patients with Crohn's disease (CD) as third-line biologic therapies is unclear. AIMS: We performed a multicentre, real-world assessment of the effectiveness of UST and VDZ among highly-refractory patients with CD. METHODS: Data of consecutive patients with CD treated with UST and VDZ as third-line biologic therapy until December 2021 were extracted from the cohort of the Sicilian Network for Inflammatory Bowel Disease (SN-IBD). RESULTS: 143 patients (UST: n = 113; VDZ: n = 30) were included. At the end of induction, the rates of clinical response (CR) were 61.9% for UST and 60.0% for VDZ (p = 1.00), with steroid-free clinical remission (SFCR) achieved in 38.1% of patients in the UST group and 43.3% of patients in the VDZ group (p = 0.75). After 52 weeks of observation, the rates of CR were 65.9% for UST and 71.4% for VDZ (p = 0.77), while the rates of SFCR were 51.8% for UST and 57.1% for VDZ (p = 0.78). At multiple Cox proportional hazard regression model, age (HR 0.98; p = 0.04) and need for systemic steroids at baseline (HR 3.29; p = 0.003) were found to be independent predictors of treatment discontinuation. CONCLUSIONS: Both VDZ and UST showed high effectiveness as third-line biologic therapy in CD, without significant differences between them.
Assuntos
Doença de Crohn , Humanos , Doença de Crohn/tratamento farmacológico , Ustekinumab/uso terapêutico , Estudos Retrospectivos , Indução de Remissão , Fármacos Gastrointestinais/uso terapêutico , Terapia Biológica , Resultado do TratamentoRESUMO
This study aims to investigate the efficacy, safety, and cost-effecctiveness of Qizhi Weitong Granules in the treatment of functional dyspepsia. Specifically, two commonly used clinical protocols for the treatment of functional dyspepsia were selected: Qizhi Weitong Granules+Mosapride vs Mosapride alone(control). Meta-analysis of previous clinical studies was performed to examine the efficacy and safety, and pharmacoeconomic evaluation was carried out according to the results of the Meta-analysis. The cost-effectiveness analysis was carried out to elucidated the incremental cost-effectiveness ratio(ICER), and the sensitivity was analyzed with tornado dia-gram and Monte Carlo simulation. The willingness-to-pay threshold of patients for functional dyspepsia was investigated and compared with the ICER to evaluate whether Qizhi Weitong Granules was cost-effective. The result showed that the effective rate of Qizhi Weitong Granules combined with Mosapride in the treatment of functional dyspepsia was 95.49%, which was higher than that of Mosapride alone(73.30%)(OR=8.52, 95%CI[4.36, 16.64])(P<0.000 1). The two groups showed no significant difference in safety. The price of Qizhi Weitong Granules+Mosapride was higher than that of Mosapride alone. The ICER was 640.29 CNY, 1 506.67 CNY lower than the willingness-to-pay threshold. The sensitivity analysis showed that the analysis results were relatively stable. Thus, Qizhi Weitong Granules+Mosapride is safe, effective, and economical in the treatment of functional dyspepsia, which should be further promoted in clinical settings.
Assuntos
Dispepsia , Benzamidas , Análise Custo-Benefício , Dispepsia/tratamento farmacológico , Farmacoeconomia , Fármacos Gastrointestinais/uso terapêutico , Humanos , Morfolinas , Resultado do TratamentoRESUMO
INTRODUCTION: There are limited data on comparative risk of infections with various biologic agents in older adults with inflammatory bowel diseases (IBDs). We aimed to assess the comparative safety of biologic agents in older IBD patients with varying comorbidity burden. METHODS: We used data from a large, national commercial insurance plan in the United States to identify patients 60 years and older with IBD who newly initiated tumor necrosis factor-α antagonists (anti-TNF), vedolizumab, or ustekinumab. Comorbidity was defined using the Charlson Comorbidity Index (CCI). Our primary outcome was infection-related hospitalizations. Cox proportional hazards models were fitted in propensity score-weighted cohorts to compare the risk of infections between the different therapeutic classes. RESULTS: The anti-TNF, vedolizumab, and ustekinumab cohorts included 2,369, 972, and 352 patients, respectively, with a mean age of 67 years. The overall rate of infection-related hospitalizations was similar to that of anti-TNF agents for patients initiating vedolizumab (hazard ratio [HR] 0.94, 95% confidence interval [CI] 0.84-1.04) and ustekinumab (0.92, 95% CI 0.74-1.16). Among patients with a CCI of >1, both ustekinumab (HR: 0.66, 95% CI: 0.46-0.91, p-interaction <0.01) and vedolizumab (HR: 0.78, 95% CI: 0.65-0.94, p-interaction: 0.02) were associated with a significantly lower rate of infection-related hospitalizations compared with anti-TNFs. No difference was found among patients with a CCI of ≤1. DISCUSSION: Among adults 60 years and older with IBD initiating biologic therapy, both vedolizumab and ustekinumab were associated with lower rates of infection-related hospitalizations than anti-TNF therapy for those with high comorbidity burden.
Assuntos
Terapia Biológica , Infecções , Doenças Inflamatórias Intestinais , Ustekinumab , Idoso , Humanos , Terapia Biológica/efeitos adversos , Comorbidade , Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/complicações , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Estudos Retrospectivos , Resultado do Tratamento , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Ustekinumab/uso terapêutico , Infecções/etiologiaRESUMO
BACKGROUND: Effective prescription drug treatment of constipation-predominant irritable bowel syndrome (IBS-C) requires patients to remain on daily therapy, yet predictive factors to optimize treatment selection are unknown. AIMS: We assessed whether common comorbidities including chronic overlapping pain conditions (COPCs), mood disorders, or concurrent medications influence the risk of discontinuing IBS-C prescription drug therapy. METHODS: We included all IBS-C patients who initiated treatment with the secretagogues linaclotide or lubiprostone across the Michigan Medicine healthcare system between 2012 and 2016. A Cox proportional hazards model was constructed to model time-to-treatment discontinuation as a valid, quantifiable measure of IBS medication persistence using hazards ratios (HR) with 95% confidence intervals (CI). RESULTS: Our cohort included 225 patients on linaclotide and 492 on lubiprostone (mean age 48.3 years, 86.9% women, 46.6% with at least one COPC, 60.3% with at least one mood disorder) with an average follow-up of 2.1 years. Patients with at least one COPC (HR = 0.566; 95%CI = 0.371-0.863) and also women (HR = 0.535; 95%CI = 0.307-0.934) had a lower risk of discontinuing linaclotide, while COPCs predicted a trend toward increased discontinuation of lubiprostone (HR = 1.254; 95%CI = 0.997-1.576). Age, comorbid mood disorders, and baseline use of narcotics or benzodiazepines did not significantly mediate the risk of treatment discontinuation; our findings remained stable in univariate and multivariable analyses. CONCLUSIONS: COPCs and sex appear to influence the likelihood of discontinuation of two commonly prescribed secretagogues, while mood disorders, narcotics, and benzodiazepines may not. Routine assessment for comorbid COPCs prior to initiating therapy may optimize IBS-C treatment selection and outcomes in practice.
Assuntos
Prestação Integrada de Cuidados de Saúde , Síndrome do Intestino Irritável , Medicamentos sob Prescrição , Estudos de Coortes , Constipação Intestinal/tratamento farmacológico , Feminino , Fármacos Gastrointestinais/uso terapêutico , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Masculino , Pessoa de Meia-Idade , Medicamentos sob Prescrição/uso terapêuticoRESUMO
BACKGROUND: The temporal trends in medical treatment and long-term outcomes of patients with Crohn's disease (CD) have not been well elucidated in China over the past 2 decades. Accordingly, we aimed to evaluate the treatment paradigm and long-term clinical course of Chinese patients with CD in a hospital-based cohort. METHODS: All adult patients newly diagnosed with CD (n = 1338) between 1999 and 2019 in the Sir Run Run Shaw Hospital were included in this cohort. Medication utilization, disease outcomes, and risk factors were investigated. RESULTS: Overall, 48.7%, 35.6%, 67.8%, and 61.6% of patients used 5-aminosalicylates (5-ASA), corticosteroids, thiopurines, and infliximab (IFX), respectively. The cumulative risk of 5-ASA and corticosteroid initiation decreased during follow-up, whereas that of IFX initiation increased. Throughout a median follow-up duration of 26.4 (interquartile range, 12.0-49.2) months, a total of 486 and 300 patients underwent hospitalization and surgery, respectively. Of the 1097 patients with B1/B2 disease behavior at diagnosis, 10.3% experienced phenotype progression. The hospitalization rate decreased after 2015; however, surgery and phenotype progression rates did not significantly change. A Cox regression analysis indicated that IFX use since diagnosis was a contributing factor for lower rates of hospitalization and phenotype progression, whereas thiopurine use was associated with a lower surgery rate. CONCLUSIONS: Infliximab use was observed to increase as 5-ASA and corticosteroid use decreased. Additionally, hospitalization rates decreased following temporal changes in IFX management, yet the surgery and phenotype progression rates remained the same.
Assuntos
Doença de Crohn , Mercaptopurina/uso terapêutico , Estudos de Coortes , Doença de Crohn/induzido quimicamente , Doença de Crohn/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Hospitais , Humanos , Fatores Imunológicos/uso terapêutico , Infliximab/uso terapêutico , Prognóstico , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: Irritable bowel syndrome-diarrhoea (IBS-D) and IBS-mixed stool pattern (IBS-M) are disorders of gut-brain interaction characterised by abdominal pain associated with diarrhoea or both diarrhoea and constipation respectively. The pathophysiology of IBS-D/M is multifactorial and not completely understood; thus, treatment is aimed at multiple mechanisms such as altering gut microbiota, visceral hypersensitivity, intestinal permeability, gut-brain interaction and psychological strategies. AIM: The goal of this article was to provide an up-to-date review of the current evidence for both non-pharmacological and pharmacological treatment options in IBS-D and IBS-M. Future treatments for IBS-D and IBS-M will also be discussed. METHODS: Medline and Embase database searches (through April 30 2021) to identify clinical studies in subjects with IBS-D in which dietary modification, alternative treatments (probiotics, acupuncture, exercise) as well as FDA-approved medications were used. RESULTS: Dietary modification is often the first line of therapy. Furthermore, lifestyle treatments include complementary alternative medications (CAM), probiotics and peppermint oil are useful adjuncts but have not specifically been described in IBS-D/M. Evidence strongly supports psychotherapy in the treatment of IBS. Beyond over-the counter anti-diarrhoeals, anti-spasmodics and anti-depressants, pharmacological treatment now includes treating for bile acid malabsorption and the FDA-approved medications rifaximin, eluxadoline and alosetron. CONCLUSIONS: The treatment of IBS-D/M ideally involves a multidisciplinary approach of primary care, gastroenterologist and psychologist. Treatment often involves both non-pharmacological and pharmacological therapies. Future therapies may include faecal microbial transplant, Crofelemer and serotonin antagonists, but further studies are needed.
Assuntos
Síndrome do Intestino Irritável , Constipação Intestinal/tratamento farmacológico , Constipação Intestinal/terapia , Diarreia/tratamento farmacológico , Fármacos Gastrointestinais/uso terapêutico , Humanos , Síndrome do Intestino Irritável/tratamento farmacológico , Síndrome do Intestino Irritável/terapia , Rifaximina/uso terapêuticoRESUMO
BACKGROUND: Infliximab (IFX) and adalimumab (ADA) refer to the classic drugs to treat moderate-severe inflammatory bowel disease (IBD), which have been proven to be effective to control IBD. However, the side effects exerted by IFX and ADA should be monitored in therapies, especially the paradoxical reaction of the skin system (e.g., psoriasis). Psoriasis is recognized as the most common skin lesion, capable of significantly affecting the quality of patients' life. METHODS: This study searched literatures published in English language with the qualifications on PubMed, Embase, Web of Science, Google, and Geenmedical databases. Over 2 co-authors assessed the quality of the articles and extracted the data independently. The data acquired were statistically analyzed with the statistical software of Revman and Stata. RESULTS: The ADA Group achieved a higher incidence of psoriasis (odds ratio [OR]â=â0.658, 95% confidence interval [CI] [0.471-0.919]); Females achieved a higher incidence of psoriasis than males (ORâ=â1.941, 95%CI [1.326-2.843], Pâ<â.05); Smoking up-regulated the incidence of psoriasis (ORâ=â1.679, 95%CI [1.237-2.279], Pâ<â.05); The interval of medication was over 1 year, and the interval of medication applying IFX was longer than that of the ADA Group; most cases could be relieved by using local hormone, phototherapy, or systemic hormone therapy under the strategy of biological agents. CONCLUSIONS: The frequency of reported in IBD exceeds those of other autoimmune diseases, and the ADA treatment for IBD is safer than IFX. Psoriasis is more common in females than in males. Smoking refers to one of risk factors of psoriasis.
Assuntos
Fármacos Gastrointestinais/uso terapêutico , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/epidemiologia , Psoríase/epidemiologia , Fumantes/estatística & dados numéricos , Inibidores do Fator de Necrose Tumoral/uso terapêutico , Adalimumab/uso terapêutico , Fármacos Gastrointestinais/administração & dosagem , Fármacos Gastrointestinais/efeitos adversos , Humanos , Incidência , Infliximab/uso terapêutico , Psoríase/tratamento farmacológico , Fatores de Risco , Distribuição por Sexo , Inibidores do Fator de Necrose Tumoral/administração & dosagem , Inibidores do Fator de Necrose Tumoral/efeitos adversosRESUMO
Hepatic encephalopathy (HE) is a common, incapacitating complication of cirrhosis that affects many patients with cirrhosis. Although several therapies have proven effective in the treatment and prevention of this condition, several patients continue to suffer from covert disease or episodes of relapse. The circadian rhythm has been demonstrated to be pivotal for many body functions, including those of the liver. Here, we explore the impact of circadian rhythm-dependent signaling on the liver and discuss the evidence of its impact on liver pathology and metabolism. We describe the various pathways through which circadian influences are mediated. Finally, we introduce a novel method for improving patient response to drugs aimed at treating HE by utilizing the circadian rhythm. A digital system that introduces a customization-based technique for improving the response to therapies is presented as a hypothetical approach for improving the effectiveness of current medications used for the treatment of recurrent and persistent hepatic encephalopathy.
Assuntos
Sistema Nervoso Autônomo/fisiologia , Ritmo Circadiano , Encefalopatia Hepática/tratamento farmacológico , Fígado/metabolismo , Animais , Fármacos Gastrointestinais/uso terapêutico , Encefalopatia Hepática/metabolismo , Humanos , Fígado/fisiologia , Fígado/fisiopatologiaRESUMO
Postprandial hypotension (PPH) is an important and under-recognised disorder resulting from inadequate compensatory cardiovascular responses to meal-induced splanchnic blood pooling. Current approaches to management are suboptimal. Recent studies have established that the cardiovascular response to a meal is modulated profoundly by gastrointestinal factors, including the type and caloric content of ingested meals, rate of gastric emptying, and small intestinal transit and absorption of nutrients. The small intestine represents the major site of nutrient-gut interactions and associated neurohormonal responses, including secretion of glucagon-like peptide-1, glucose-dependent insulinotropic peptide and somatostatin, which exert pleotropic actions relevant to the postprandial haemodynamic profile. This review summarises knowledge relating to the role of these gut peptides in the cardiovascular response to a meal and their potential application to the management of PPH.
Assuntos
Pressão Sanguínea , Polipeptídeo Inibidor Gástrico/sangue , Fármacos Gastrointestinais/farmacologia , Peptídeo 1 Semelhante ao Glucagon/sangue , Hipotensão , Período Pós-Prandial , Somatostatina/sangue , Acarbose/farmacologia , Acarbose/uso terapêutico , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Fármacos Gastrointestinais/uso terapêutico , Glucagon/sangue , Receptor do Peptídeo Semelhante ao Glucagon 1/sangue , Humanos , Hipotensão/tratamento farmacológico , Hipotensão/fisiopatologia , Insulina/sangue , Peptídeos , Circulação EsplâncnicaRESUMO
BACKGROUND: Ulcerative colitis (UC) is a chronic inflammation of the colon characterised by periods of relapse and remission. It starts in the rectum and can extend throughout the colon. UC and Crohn's disease (CD) are the most common inflammatory bowel diseases (IBDs). However, UC tends to be more common than CD. It has no known cure but can be managed with medication and surgery. However, studies have shown that abdominal pain persists in up to one-third of people with UC in remission. Abdominal pain could be a symptom of relapse of the disease due to adverse effects of medication, surgical complications and strictures or adhesions secondary to UC. OBJECTIVES: To assess the efficacy and safety of interventions for managing abdominal pain in people with ulcerative colitis. SEARCH METHODS: We searched CENTRAL, MEDLINE and five other databases and clinical trials registries on 28 April 2021. We contacted authors of relevant studies and ongoing or unpublished trials that may be relevant to the review. We also searched references of trials and systematic reviews for any additional trials. SELECTION CRITERIA: All published, unpublished and ongoing randomised trials that compared interventions for the management of abdominal pain with other active interventions or standard therapy, placebo or no therapy were included. People with both active and inactive disease were included. We excluded studies that did not report on any abdominal pain outcomes. DATA COLLECTION AND ANALYSIS: Two review authors independently conducted data extraction and 'Risk of bias' assessments. We analysed data using Review Manager 5. We expressed dichotomous and continuous outcomes as risk ratios (RRs) and mean differences (MDs), respectively, with 95% confidence intervals. We assessed the certainty of the evidence using the GRADE methodology. MAIN RESULTS: We included five studies (360 randomised participants). Studies considered mainly participants in an inactive state of the disease. No conclusions could be drawn about the efficacy of any of the interventions on pain frequency, pain intensity, and treatment success. The certainty of the evidence was very low for all comparisons because of imprecision due to sparse data, and risk of bias. One study compared a low FODMAPs diet (n=13) to a sham diet (n=13). The evidence is very uncertain about the effect of this treatment on pain frequency (MD -4.00, 95% CI -20.61 to 12.61) and intensity (MD -9.00, 95% CI -20.07 to 2.07). Treatment success was not reported. One study compared relaxation training (n=20) to wait-list (n=20). The evidence is very uncertain about the effect of this treatment on pain frequency at end of intervention (MD 2.60, 95% CI 1.14 to 4.06) and 6-month follow-up (MD 3.30, 95% CI 1.64 to 4.96). Similarly, the evidence is very uncertain about the effect of this treatment on pain intensity at end of intervention (MD -1.70, 95% CI -2.92 to -0.48) and 6-month follow-up (MD -2.30, 95% CI -3.70 to -0.90). Treatment success was not reported. One study compared yoga (n=30) to no intervention (n=30). The study defined treatment success as the presence or absence of pain; however, the data they provided was unclear. Pain frequency and intensity were not reported. One study compared a kefir diet (Lactobacillus bacteria, n=15) to no intervention (n=15). The evidence is very uncertain about the effect of this treatment on pain intensity (MD -0.17, 95% CI -0.91 to 0.57). Pain frequency and treatment success were not reported. One study compared a stellate ganglion block treatment (n=90) to sulfasalazine treatment (n=30). The study defined treatment success as "stomachache"; however, the data they provided was unclear. Pain frequency and intensity were not reported. Two studies reported withdrawals due to adverse events. One study reported withdrawals due to adverse events as zero. Two studies did not report this outcome. We cannot draw any conclusions about the effects of any of the interventions on withdrawals due to adverse events because of the very limited evidence. The reporting of secondary outcomes was inconsistent. Adverse events tended to be very low or zero. However, we can make no clear judgements about adverse events for any of the interventions, due to the low number of events. Anxiety was measured and reported at end of intervention in only one study (yoga versus no intervention), and depression was not measured in any of the studies. We can therefore draw no meaningful conclusions about these outcomes. AUTHORS' CONCLUSIONS: We found very low-certainty evidence on the efficacy and safety of interventions for the management of abdominal pain in ulcerative colitis. Pervasive issues with very serious imprecision from small samples size and high risk of bias have led to very low-certainty outcomes, precluding conclusions. While few adverse events and no serious adverse events were reported, the certainty of these findings was again very low for all comparisons, so no conclusions can be drawn. There is a need for further research. We have identified eight ongoing studies in this review, so an update will be warranted. It is key that future research addresses the issues leading to reduced certainty of outcomes, specifically sample size and reporting that leads to high risk of bias. It is also important that if researchers are considering pain as a critical outcome, they should report clearly if participants were pain-free at baseline; in that case, data would be best presented as separate subgroups throughout their research.
Assuntos
Dor Abdominal/terapia , Colite Ulcerativa/complicações , Dor Abdominal/etiologia , Adulto , Viés , Dieta com Restrição de Carboidratos , Fármacos Gastrointestinais/uso terapêutico , Humanos , Kefir , Lactobacillus , Pessoa de Meia-Idade , Bloqueio Nervoso , Ensaios Clínicos Controlados Aleatórios como Assunto , Terapia de Relaxamento , Gânglio Estrelado/efeitos dos fármacos , Sulfassalazina/uso terapêutico , Listas de Espera , YogaRESUMO
BACKGROUND: Proton pump inhibitors (PPIs) play an important role in the treatment of nonerosive reflux disease (NERD), but their long-term and excessive uses have been associated with safety concerns. Chinese herbal medicine (CHM) has become a popular alternative treatment for this condition. METHODS: A total of 204 patients were randomly assigned to the combination group or PPI group (1:1 ratio). They were given JianpiQinghua (JQ) granules (34.8 g) plus omeprazole (10 mg) plus dummy omeprazole (10 mg) or dummy JQ granules (34.8 g) plus omeprazole (20 mg) daily for 4 weeks. The primary endpoints were the rate of sufficient relief and complete resolution of GERD Q at week 4. Metabonomics and the gut microbiota were also assessed. RESULTS: Complete resolution was observed in 40.8% of patients in the combination group and 26.8% of patients in the PPI group after 4 weeks (FAS analysis, OR, 1.88; 95% CI, 1.03-3.44; p = 0.039). Sufficient relief was observed in 50% of patients in the combination group and 43.30% of patients in the PPI group after 4 weeks (FAS analysis, OR, 1.31; 95% CI, 0.74-2.30; p = 0.35). Three patients had liver dysfunction, one of whom had a mild case and 2 of whom had moderate-to-severe cases in the combination group. Patients in the combination group showed a significant increase in richness and diversity of their gut microbiota compared with those in the PPI group. Metabonomics showed that the combination therapy could correct the glutamate metabolism pathway. CONCLUSION: Our findings demonstrate the superior efficacy of JQ granules combined with omeprazole (10 mg) vs. omeprazole (20 mg) in terms of symptom relief in patients with NERD. TRIAL REGISTRATION: ClinicalTrials.gov number NCT02892357. Registered on 14 February 2019.