Impact of all oral anti-hepatitis C virus therapy:A metaanalysis

AIM:To investigate the efficacy,safety,and cost of treatment of direct acting antivirals(DAAs) with and without peg interferon alfa2a(P),and/or ribavirin(R) in treating hepatitis C virus(HCV) genotype 1 patients.METHODS:MEDLINE was searched for randomized controlled trials(RCT) using DAAs for HCV treatment.Phase 1 trials and studies with investigational drugs on genotype 2 or 3,and on human immunodeficiency virus patients were excluded.Data were pooled for sustained virologic response(SVR),serious adverse effects,and drug discontinuation rate on various treatment arms in trials:P + R;1st generation DAA(telaprevir or boceprevir) + P + R;2nd generation DAA(sofosbuvir or simeprevir) + P + R;2nd generation DAA + R;two 2nd generation DAA + R;and two 2nd gen DAA.Data were analyzed separately for each arm for treatment naive and non-responders(NR) to previous treatment.The cost of treatment with each regimen for achieving one SVR was also compared.RESULTS:Twenty three RCTs(n = 9354,62% male,11% cirrhosis) were analyzed.All oral(P free) regimens with combination of 2 DAA achieved SVR above 95%.The cost of treatment to achieve an SVR with DAA based regimens was lower for NR compared to P+R regimen.However,the cost per SVR remained higher for treatment naive patients.CONCLUSION:Second generation and emerging DAAs are promising agents in HCV treatment,with a very high level of safety and efficacy.An important drawback is their high cost.However,the present meta-analysis shows that the cost per SVR for non responders(but not for naive patients) was lower compared to P + R.This finding together with the superior safety profile and better compliance makes these drugs highly attractive.It is possible that further reduction in treatment duration may make them even more cost effective.

Contrast-enhanced ultrasound using SonoVue mixed with oral gastrointestinal contrast agent to evaluate esophageal hiatal hernia: Report of three cases and a literature review

BACKGROUND Due to a thicker abdominal wall in some patients,ultrasound artifacts from gastrointestinal gas and surrounding tissues can interfere with routine ultrasound examination,precluding its ability to display or clearly show the structure of a hernial sac(HS)and thereby diminishing diagnostic performance for esophageal hiatal hernia(EHH).Contrast-enhanced ultrasound(CEUS)imaging using an oral agent mixture allows for clear and intuitive identification of an EHH sac and dynamic observation of esophageal reflux.CASE SUMMARY In this case series,we report three patients with clinically-suspected EHH,including two females and one male with an average age of 67.3±16.4 years.CEUS was administered with an oral agent mixture(microbubble-based SonoVue and gastrointestinal contrast agent)and identified a direct sign of supradiaphragmatic HS(containing the hyperechoic agent)and indirect signs[e.g.,widening of esophageal hiatus,hyperechoic mixture agent continuously or intermittently reflux flowing back and forth from the stomach into the supradiaphragmatic HS,and esophagus-gastric echo ring(i.e.,the“EG”ring)seen above the diaphragm].All three cases received a definitive diagnosis of EHH by esophageal manometry and gastroscopy.Two lesions resolved upon drug treatment and one required surgery.The recurrence rate in follow-up was 0%.The data from these cases suggest that the new non-invasive examination method may greatly improve the diagnosis of EHH.CONCLUSION CEUS with the oral agent mixture can facilitate clear and intuitive identification of HS and dynamic observation of esophageal reflux.

γ⁃Fe2O3@carboxymethyl Cellulose as Potential Oral Nanomedicine for Iron Deficiency Anemia Treatment on Rats

Oral iron supplements such as ferrous iron salts are major treatment agents for iron deficiency anemia(IDA)due to the convenience of large dose administration and good patient compliance.However,the gastrointestinal adverse impact caused by Fe2+stimulus and low bioavailability severely impedes its therapeutic effects.In recent years,it has been found that nano iron⁃based nanoparticles with high surface⁃to⁃volume ratio and low iron ion leakage can alleviate the toxic effect and improve the gastrointestinal absorbance.For further clinical development,nano materials need to meet the pharmaceutical quality demand.Carboxymethyl cellulose(CMC)is a significant pharmaceutical ingredient applied in approved drug formulations,and polyglucosorbitol carboxymethylether(PSC)has been utilized in iron⁃based nanomedicine ferumoxytol synthesis,both of which can be firmly anchored on iron oxide by carboxyl chelation.In this work,iron oxide nanoparticles(NPs)modified with CMC were designed and synthesized,and the structure composition and physicochemical properties were distinctly characterized.Oral supplement effects on rat IDA were investigated and compared with other recently reported iron supplements including NPs modified with PSC.Results show that the oral nano iron supplement achieved the recovery of hemoglobin and serum iron level in only two weeks with high safety.The nano iron oxide modified with pharmaceutical excipients provides new potential approach for oral iron supplement available in clinics.

Oral Gd-DTPA as a negative gastrointestinal contrast agent in magnetic resonance cholangiopancreatography

Objective: To evaluate the value of oral Gd-DTPA as a negative contrast agent during magnetic resonance cholangiopancreatography (MRCP) to eliminate the high signals of the gastrointestinal tract. Methods: To select the optimal concentration of oral Gd-DTPA for MRCP, a phantom study was performed followed by clinical trial in 15 cases undergoing MRCP before and after oral Gd-DTPA (in a total volume of 250 ml 1∶5 diluted Gd-DTPA, 1.488 g/L). MRCP images were acquired using two-dimensional single slice fast spin-echo (SSTSE) sequence and half-Fourier acquisition single slice fast spin-echo (HASTE) sequence. Results: The phantom study showed that the 1∶5 diluted oral Gd-DTPA was best in decreasing the signal intensity both in T2-weighted imaging (59.5%) and in HASTE sequence (82.45%). The high signal intensity of the stomach and intestinal fluid was completely suppressed in all the cases. The depictions of the common bile duct and pancreatic duct were markedly improved by using the oral contrast agent (P<0.05). Conclusion: Oral Gd-DTPA is effective and safe for eliminating the high signal of the gastrointestinal tract to improve the depiction of the biliary system by MRCP.

Oral contrast agents lead to underestimation of dose calculation in volumetric-modulated arc therapy planning for pelvic irradiation

Background:The effects of oral contrast agents(OCAs)on dosimetry have not been studied in detail.Therefore,this study aimed to examine the influence of OCAs on dose calculation in volumetric-modulated arc therapy plans for rectal cancer.Methods:From 2008 to 2016,computed tomography(CT)images were obtained from 33 rectal cancer patients administered OCA with or without intravenous contrast agent(ICA)and 14 patients who received no contrast agent.CT numbers of organs at risk were recorded and converted to electronic densities.Volumetric-modulated arc therapy plans were designed before and after the original densities were replaced with non-enhanced densities.Doses to the planned target volume(PTV)and organs at risk were compared between the plans.Results:OCA significantly increased the mean and maximum densities of the bowels,while the effects of ICA on these parameters depended on the blood supply of the organs.With OCA,the actual doses for PTV were significantly higher than planned and doses to the bowel increased significantly although moderately.However,the increase in the volume receiving a high-range doses was substantial the absolute change of intestine volume receiving≥52 Gy:1.46[0.05-3.99,cubic centimeter range:-6.74 to 128.12],the absolute change of colon volume receiving≥50 Gy:0.34[0.01-1.53 cc,range:-0.08 to 3.80 cc].Dose changes due to ICA were insignificant.Pearson correlation showed that dose changes were significantly correlated with a high intestinal volume within or near the PTV(ρ>0.5,P<0.05)and with the density of enhanced intestine(ρ>0.3,P<0.05).Conclusions:Contrast agents applied in simulation cause underestimation of doses in actual treatment.The overdose due to ICA was slight,while that due to OCA was moderate.The bowel volume receiving≥50Gy was dramatically increased when OCA within the bowel was absent.Physicians should be aware of these issues if the original plan is barely within clinical tolerance or if a considerable volume of enhanced intestine is within or near the PTV.

Effect of Yanggyuksanhwa-Tang on Non-Insulin-Dependent Diabetes Mellitus Unresponsive to Oral Hypoglycemic Agents:A Case Report

Diabetes mellitus is the fourth leading cause of death worldwide, following cancer, cerebrovascular disease, and heart disease. It is triggered by hyperglycemia and other metabolic disorders. Diabetes is a complex endocrine disease that causes chronic vascular complications such as diabetic nephropathy, retinopathy, and polyneuropathy.

Pharmacotherapy for erectile dysfunction

To review current pharmacologic treatment options for erectile dysfunction Methods Relevant literatures from the past two decades regarding the following treatments were reviewed: intracavernous injection, topical therapy, transurethral therapy and oral drugs Study selection More than 125 originally identified articles were reviewed, and 45 were selected that especially addressed the stated purpose Results Among the pharmacologic treatment options available, intracavernous injection therapy remains the most effective although the drop out rate is high Topical creams and gels have not been very successful Transurethral alprostadil can be more effective if a constriction device is applied at the base of the penis Oral sildenafil has the highest patient acceptance rate although systemic side effects can be a major drawback Conclusions Effective pharmacotherapies for ED of various etiologies are now available However, proper evaluation of every patient should be performed before giving treatment so that a number of potentially life threatening causes of erectile dysfunction would not be missed

Efficacy and safety of metformin and sitagliptin based triple antihyperglycemic therapy(STRATEGY):a multicenter,randomized,controlled,non-inferiority clinical trial

Despite the current guideline's recommendation of a timely stepwise intensification therapy,the "clinical inertia",termed as the delayed treatment intensification,commonly exists in the real world,which may be partly due to the relatively little substantial evidence and no clear consensus regarding the efficacy and safety of triple oral agents in patients inadequately controlled with dual therapy.In this clinical trial performed in 237 centers in China,5,535 type 2 diabetic patients inadequately controlled by previous therapies were treated with a stable metformin/sitagliptin dual therapy for 20 weeks.The patients who did not reach the glycated hemoglobin A1c(HbA1c) goal were then further randomized into glimepiride,gliclazide,repaglinide,or acarbose group for an additional 24-week triple therapy.A mean HbAlc reduction of 0.85%was observed when sitagliptin was added to the patients inadequately controlled with metformin in 16 weeks.Further HbAlc reductions in the 24-week triple therapy stage were 0.65%in glimepiride group,0.70%in gliclazide group,0.61%in repaglinide group,and 0.45%in acarbose group.The non-inferiority criterion for primary hypotheses was met for gliclazide and repaglinide,but not for acarbose,compared with glimepiride,when added to metformin/sitagliptin dual therapy.The incidences of adverse events(AEs) were 29.2%in the dual therapy stage and30.3%in the triple therapy stage.Metformin/sitagliptin as baseline therapy,with the addition of a third oral antihyperglycemic agent,including glimepiride,gliclazide,repaglinide,or acarbose,was effective,safe and well-tolerated for achieving an HbAlc<7.0%goal in type 2 diabetic patients inadequately controlled with previous therapies.The timely augmentation of up to three oral antihyperglycemic agents is valid and of important clinical benefit to prevent patients from exposure to unnecessarily prolonged hyperglycemia.