Objective: Severe diarrhea-predominant irritable bowel syndrome (IBS-D) is associated with decreased health-related quality of life (HRQOL) and increased health care costs. Treatment recommendations for IBS-D often start with traditional pharmacotherapy (TP), with escalation to alosetron, rifaximin or eluxadoline if there is no success. There has been no previous head-to-head clinical trial comparing IBS-D treatment outcome for alosetron versus TP. This study, GSK protocol S3B30020, evaluated resource use, work productivity, health-related quality of life and global symptom response in women with IBS-D who were treated with alosetron or TP.
Methods: A total of 1956 patients who met criteria for severe IBS-D were randomized to treatment with alosetron 1?mg twice daily (BID) or only TP for up to 24 weeks. Work productivity and resource use were evaluated by standard questionnaires, HRQOL by the IBSQOL instrument and IBS symptoms by the Global Improvement Scale (GIS).
Results: Compared to only TP, alosetron-treated patients reported: (1) fewer clinic/office visits for any health problem (p?=?.0181) or for IBS-D (p?=?.0004); (2) reduced use of over-the-counter medications for IBS-D (p < .0001); (3) fewer days of lost work productivity (p < .0001); (4) decreased restriction of social and outdoor activities (p < .0001); and (5) greater global improvement in IBS-D symptoms (p < .0001). Alosetron treatment improved HRQOL scores for all domains (p < .0001). Incidence of adverse events during alosetron use was not remarkable and was similar to that previously reported.
Conclusions: Alosetron 1?mg BID significantly reduced health care utilization and lost productivity, and significantly improved global IBS symptoms, HRQOL, and participation in outdoor and social activities compared with treatment response to TP. 相似文献
OBJECTIVES: There is growing evidence suggesting the mutual link between type 2 diabetes mellitus (T2DM) and hepatitis C virus (HCV) infection. However, the impact of HCV infection on the suite of glucose abnormalities has rarely been investigated. The study aimed to determine the difference regarding the prevalence and the characteristics of glucose abnormalities between chronic hepatitis C (CHC) patients and community-based controls. It also aimed to investigate the related clinical, virological, and histological features of glucose abnormalities in HCV infection. METHODS: Six hundred eighty-three CHC patients and 515 sex-/age-matched controls were included. Oral glucose tolerance test (OGTT) was performed in 522 CHC patients and 447 controls without known T2DM. Clinical data were assessed upon the different stages of glucose abnormalities based on OGTT results. RESULTS: The prevalence of normoglycemia, IGT, and T2DM in 683 CHC patients was 27.7%, 34.6%, and 37.8%, respectively. There was a significant linear trend from normoglycemia to T2DM in terms of age, family history of T2DM, and advanced liver fibrosis in CHC patients. For those CHC patients without fibrosis, the prevalence of glucose abnormalities reached 67.9% high. All CHC patients carried a significantly higher prevalence than controls regarding those aged <65 yr. For those without known DM, there was a 3.5-fold increase in the prevalence of glucose abnormalities in CHC (65.8%) patients in comparison with controls (35.3%) (OR 3.51, 95% CI 2.70–4.56, P < 0.001). CONCLUSIONS: CHC patients carried a high prevalence of glucose abnormalities. Determination of glucose abnormalities by OGTT may be suggested. 相似文献
Evidence suggests that mammalian target of rapamycin activation mediates ketamine’s rapid but transient antidepressant effects and that glycogen synthase kinase-3β inhibits this pathway. However, ketamine has associated psychotomimetic effects and a high risk of abuse. The mood stabilizer lithium is a glycogen synthase kinase-3 inhibitor with strong antisuicidal properties. Here, we used a mouse stress model to investigate whether adjunct lithium treatment would potentiate ketamine’s antidepressant-like effects.
Methods:
Mice received chronic restraint stress and long-term pre- or postketamine lithium treatment in drinking water. The effects of lithium on ketamine-induced antidepressant-like effects, activation of the mammalian target of rapamycin/brain-derived neurotrophic factor signaling pathways, oxidative stress, and dendritic spine density in the brain of mice were investigated.
Results:
Subtherapeutic (600mg/L) lithium-pretreated mice exhibited an antidepressant-like response to an ineffective ketamine (2.5mg/kg, intraperitoneally) challenge in the forced swim test. Both the antidepressant-like effects and restoration of dendritic spine density in the medial prefrontal cortex of stressed mice induced by a single ketamine (50mg/kg) injection were sustained by postketamine treatment with 1200mg/L of lithium for at least 2 weeks. These benefits of lithium treatments were associated with activation of the mammalian target of rapamycin/brain-derived neurotrophic factor signaling pathways in the prefrontal cortex. Acute ketamine (50mg/kg) injection also significantly increased lipid peroxidation, catalase activity, and oxidized glutathione levels in stressed mice. Notably, these oxidative stress markers were completely abolished by pretreatment with 1200mg/L of lithium.
Conclusions:
Our results suggest a novel therapeutic strategy and justify the use of lithium in patients who benefit from ketamine. 相似文献
Retroperitoneal echinococcosis (RE) is a rare condition that is associated with a high mortality and disability rate. It is associated with a high rate of misdiagnosis, a high risk of surgery, and is extremely difficult to manage. There is no uniform standard for determining the exact form of surgical method and the timing of surgery.This was a retrospective analysis of the characteristics and surgical management of patients diagnosed with RE in our hospital between 2012 and 2019.Between 2012 and 2019, 1257 cases of echinococcosis and 121 cases of RE were diagnosed in our hospital. Of these, 68 cases involved surgical treatment, 53 involved non-surgical treatment, and 12 cases were lost to follow-up (4 cases in the surgical group and 8 cases in the non-surgical group). Thus, 109 cases were followed-up. RE cases were divided according to different treatment methods into a radical resection group (Group A, 31 cases), a non-radical resection group (Group B, 37 cases), and a non-surgical group (Group C, 53 cases). We carried out a detailed analysis of the 109 cases experiencing surgical intervention with effective follow-up.Our analysis found that radical resection is the first line of treatment of RE, although non-radical surgery can benefit most patients. It is important to emphasize the importance of the first round of surgery, particularly in cases involving hepatic echinococcosis. If the lesion can be removed radically during the first round of surgery, then radical surgery should be performed. 相似文献