Summary Background and aim Fenofibrate is a potential novel therapy for primary biliary cirrhosis (PBC). We performed a systematic review and a meta-analysis of studies of fenofibrate in PBC. Methods ...Electronic database search was performed for relevant studies. A search of abstracts presented in the main scientific meetings in the field and articles in press was also performed. Random effect model was used to pool the effect size across studies for changes in alkaline phosphatase, GGT, bilirubin and IgM levels before and after treatment and the overall rate of complete response to fenofibrate therapy. Results Six studies with 102 patients met the inclusion criteria. All studies were case series and in all, patients who had no or incomplete response to UDCA had fenofibrate added at a dose of 100–200 mg daily. Treatment duration ranged from 8–100 weeks. Treatment with fenofibrate was associated with a significant decrease in alkaline phosphatase (–114 IU/L, 95% CI: –152 to –76, P < 0.0001); a significant decrease in GGT level (–92 IU/L, 95% CI: –149 to –43; P = 0.0004); significant decrease in total bilirubin (–0.11 mg/dL, 95% CI: –0.18 to –0.08; P = 0.0008); and a significant decrease in IgM level (–88 mg/dL, 95% CI: –119 to –58; P < 0.0001). The complete response rate was 69% (95% CI: 53–82%) with an odds ratio of 82.8 (95% CI: 21.6–317.2; P = 0.024) while on fenofibrate. Conclusions Fenofibrate at doses of 100–200 mg daily appears to be effective adjunctive therapy in PBC patients who had no or incomplete response to UDCA. There is a critical need for larger scale randomized trials to determine its effect on liver-related morbidity and mortality (or progression towards end-stage disease).
VSL#3 is a probiotic mix preparation reported to be effective in the treatment of mild to moderately active ulcerative colitis. We aimed to perform a systematic review of the literature and a ...meta-analysis of studies on its efficacy.
The searched databases included PubMed, Scopus, and ScienceDirect. The Mantel-Haenszel method was used to pool the effect- ize across studies, and the odds ratios (ORs) and 95% confidence intervals (CIs) of experiencing a specific outcome were calculated.
Five studies with 441 patients were identified. The pooled remission rate was 49.4% (95% CI, 42.7-56.1). Only 3 low risk of bias studies with 319 patients met the inclusion criteria for further analysis. A total of 162 patients received 3.6 × 10 CFU/d VSL#3, and 157 patients received placebo. A total of 95% of patients received concomitant therapies with 5-ASA and/or immunomodulators. The Ulcerative Colitis Disease Activity Index was used to define response and remission. A >50% decrease in the Ulcerative Colitis Disease Activity Index was achieved in 44.6% of the VSL#3-treated patients versus 25.1% of the patients given placebo (P = 0008; OR, 2.793; 95% CI, 1.375-5.676; number needed to treat = 4-5). The response rate was 53.4% in VSL#3-treated patients versus 29.3% in patients given placebo (P < 0001; OR, 3.03; 95% CI, 1.89-4.83; number needed to treat = 3-4). The remission rate was 43.8% in VSL#3-treated patients versus 24.8% in patients given placebo (P = 0007; OR, 2.4; 95% CI, 1.48-3.88; number needed to treat = 4-5). No serious side effects were reported.
VSL#3, when added to conventional therapy at a daily dose of 3.6 × 10 CFU/d, is safe and more effective than conventional therapy alone in achieving higher response and remission rates in mild to moderately active ulcerative colitis.
Aim
To provide an estimate of the prevalence of celiac disease by race/ethnic origin in large sample of US population.
Methods
Data from the 2009–2010 and 2011–2012 NHANES were combined and analyzed. ...The NHANES is a nationally representative survey with oversampling of certain minorities. Sample-based frequencies were reported and weighted frequencies were used to estimate prevalence.
Results
A total of 14,701 participants were checked for tissue transglutaminase (tTG) and endomysial (EMA) IgA antibodies. Seventy-four participants had positive tTG and/or EMA corresponding to prevalence of 0.79 % (95 % CI 0.54–1.04 %). Non-Hispanic white were more likely to be positive for both compared with other races (72.0 vs 31.7 %;
p
= 0.010) and less likely to be weakly positive for tTG but positive for EMA (3.6 vs 26.4 %;
p
= 0.03). The prevalence of positive serology according to race was as follows: 1.08 % (95 % CI 0.70–1.45 %) in non-Hispanic white, 0.23 % (95 % CI 0.03–0.43 %) in Mexican, 0.22 % (95 % CI 0.01–0.44 %) in non-Hispanic black, 0.38 % (95 % CI 0.00–0.89 %) in “other Hispanic,” and 0.15 % (95 % CI 0.00–0.34 %) in other races including multiracial and undeterminable in non-Hispanic Asian due to the presence of only one positive EMA test. 0.9 % of the NHANES sample participants followed gluten-free diet. Of this group of participants, 85 % were never diagnosed with celiac disease and 99 % of them had negative celiac disease serology.
Conclusions
Potentially 0.79 % of the general US population demonstrate serologic evidence of celiac disease autoimmunity. The prevalence is 4–8 times higher among non-Hispanic white compared with other races. Close to 1 % of the population is electively following gluten-free diet despite having little evidence of the disease.
Liver cirrhosis (LC) is becoming increasingly common among patients presenting with acute coronary syndromes (ACS) and is associated with significant cardiovascular morbidity and mortality. ...Management of such patients is complicated by LC related complications. Literature is scarce on the safety of antithrombotic regimens and invasive strategies for ACS in patients with LC, especially those undergoing liver transplant evaluation. Recently there has been evidence that cirrhosis is an independent risk factor for adverse outcomes in ACS. As patients with LC are generally excluded from large randomized trials, definitive guidelines for the management of ACS in this particular cohort are lacking. Many antithrombotic drugs require either hepatic activation or clearance; hence, an accurate assessment of hepatic function is required prior to initiation and dose adjustment. Despite a demonstrated survival benefit of optimal medical therapy and invasive revascularization techniques in LC patients with ACS, both strategies are currently underutilized in this population. This review aims to present currently available data and provide a practical, clinically oriented approach for the management of ACS in LC. Randomized clinical trials in LC patients with ACS are the need of the hour to further refine their management for favorable outcomes.
Hepatic encephalopathy for the hospitalist Sweigart, Joseph R; Bradley, Bruce; Grigorian, Alla Y
Journal of hospital medicine,
August 2016, Letnik:
11, Številka:
8
Journal Article
The comparative study has been carried out on hypothalamic neurohormone (proline-rich polypeptides-PRP) and synthetic glucocorticoid dexamethasone (DEX) protective properties at the systemic (i/m) ...administration. Both background and evoked electrical activity (on n.ischiadicus stimulation) of single neurons in the lumbo-sacral part (laminae II-VI and VII-VIII by Rexed) and field potentials (FP) of spinal cord were recorded during acute experiments on intact spinal rats, subjected to Vipera Raddei (VR) venom intoxication, and chronic spinal cord trauma (hemisection). The action of PRP was characterized by the pronounced activation of the background activity (BA) with adaptive effect, depending on dose and initial level of BA, by results of the statistical analysis. A high effect is received from comparatively small doses. For comparison it was used strong glucocorticoid DEX, possessing single-directed but less expressed excitative action on investigated spinal cord neurons. The initial increase of BA frequency with subsequent depression was the typical symptom of venom influence. A protective effect of preliminary PRP injection is revealed on the succeeding VR venom influence. Use of PRP and DEX causes the increase of reduced activity of neurons on the injury side of animals with spinal cord hemisection. It provides the possibility of the therapeutic utilization. It was revealed considerably more expressed PRP action on neurodegenerative process connected to spinal cord injury (in comparison with DEX). The influence of hormones was compared in identical conditions of experiments on non-injured (control) and injured sides. Taking into consideration revealed protection characteristic of PRP and also the ability of snake venom to stabilize and to prolong its action combined with these preparations, the assumption is made on prospective use of the specified combination in clinical practice.
A study of separate and combined actions of cobra venom (CV) and a new hypothalamic proline-rich polypeptide (PRP) isolated from magnocellular cells (NPV and NSO) on intoxication- and trauma-induced ...neuronal injury (during 3-4 weeks after hemisection with and without PRP treatment) was carried out. The registration of background and evoked impulse activity flow, changes in spinal cord (SC) inter- and motoneurons, responding to flexor, extensor, and mixed nerve stimulation in both acute and chronic experimental neurodegeneration was performed. The facilitating effect of PRP on the abovementioned neurons was revealed. High doses of CV that evoked the neurodegenerative changes demonstrated an inhibitory effect. In this case PRP treatment both before and after intoxication restored electrical neuronal activity to baseline level and higher. These results are evidence of protective action of PRP. The low doses of CV induced a facilitating effect. The combination of CV and PRP displayed an additive facilitating effect; in a number of cases the repeated administration of CV led to decrease of significant PRP effect till baseline level (for example, the inhibition after primary response prior to secondary late discharge). Greater liability of the secondary early and late long-time discharges of poststimulus responses, differently expressed in various neuron types of SC to chemical influences is of interest. PRP-induced inhibition of the paroxysmal activity related with CV action is also very interesting. Morpho-functional experiments with SC injury demonstrated the abolition of difference in the background and evoked SC neuronal activity below the section and on intact symmetric side after daily PRP administration for 3 weeks. PRP hindered the scar formation and activated neuroglia proliferation; it promoted white matter element growth, hampered the degeneration of cellular elements, and protected against tissue stress. Our results favor the combined use of PRP and CV in clinical practice for the treatment of neurodegeneration of toxic and traumatic origin, as well as specific neurodegenerative diseases such as Alzheimer's.
The action of PRP is characterized by the pronounced activation of the background activity (BA) of the brain spinal cord, and the degree of the activity depends on BA initial level. The typical ...peculiarity of Vipera raddei venom influence is the initial increase in frequency of BA with subsequent depression. A preliminary injection of PRP has a protective effect at subsequent influence of venom. In animals with hemisection the PRP increases the decreased activity of neurons on injury side. Taking into consideration the protective peculiarities of PRP in the relationship to snake venom and the possibility of the latter to stabilize and prolong the action of drugs (in the case of PRP) combined with them, it is supposed that the mentioned use of the combination in clinical practice will be perspective. The data obtained testify the PRP to be a neuroprotector against many toxic compounds formed in organism (glutamate, ceramid, beta-amyloid neurotoxisity, etc.). Investigations in this aspect are still in the process.