Standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori eradication

AIM: To compare the effectiveness of standard triple, bismuth pectin quadruple and sequential therapies for Helicobacter pylori (H. pylori ) eradication in a randomized, double-blinded, comparative clinical trial in China. METHODS: A total of 215 H. pylori -positive patients were enrolled in the study and randomly allocated into three groups: group A (n = 72) received a 10-d bismuth pectin quadruple therapy (20 mg rabeprazole bid , 1000 mg amoxicillin bid , 100 mg bismuth pectin qid , and 500 mg levofloxacin qd ); group B (n = 72) received the sequential therapy (20 mg omeprazole bid , 1000 mg amoxicillin bid , in 5 d, followed by 20 mg omeprazole bid , 500 mg tinidazole bid , 500 mg clarithromycin bid , for another 5 d); group C (n = 71) received a standard 1-wk triple therapy (20 mg omeprazole bid , 1000 mg amoxicillin bid , 500 mg clarithromycin bid ). After all these treatments, 20 mg omeprazole bid was administrated for 3 wk. H. pylori status was assessed by histology, 13C-urea breath test and rapid urease test at baseline and 4-6 wk after completion of treatment. Ulcer cicatrization was assessed by gastroscopy. χ 2 test (P < 0.05) was used to compare the eradication rates and ulcer cicatrisation rates among the three groups. RESULTS: The eradication rate was 83.33% (60/72) in group A, 88.89% (64/72) in group B, and 80.56% (58/71) in group C. The ulcer cicatrisation rate was 86.44% (51/59) in group A, 90.16% (55/61) in group B, and 84.91% (45/53) in group C. The sequential therapy yielded a higher eradication rate and ulcer cicatrisation rate than the standard triple and bismuth pectin quadruple therapies. Statistically, the eradication rate of group B was significantly different from groups A and C (P < 0.05), but the difference of ulcer cicatrisation rate and side effects was not statistically significant among the three groups (P > 0.05). The three protocols were generally well tolerated. CONCLUSION: The sequential therapy has achieved a significantly higher eradication rate, and is a more suitable first-line alternative protocol for anti-H. pylori infection compared with the standard triple and bismuth pectin quadruple therapies.

Seven-day triple therapy is a better choice for Helicobacter pylori eradication in regions with low antibiotic resistance

AIM: To investigate whether 7-d triple therapies are still valid in populations with low levels of resistance.METHODS: A total of 1106 Helicobacter pylori(H. pylori)-positive patients were divided into three groups,each of which received one type of 7-d triple therapy. Therapeutic outcomes of the patients were assessed by the 13C-urea breath test at 8 wk after treatment. The susceptibility of H. pylori to antibiotics was determined by an agar-dilution method. Data analysis was performed by χ2 tests.RESULTS: The eradication rates in groups A,B and C were 90.71%(332/366),90.46%(313/346) and 90.87%(189/208),respectively(P = 0.986). The resistance rates were 8.91% for clarithromycin,14.78% for levofloxacin and 0% for amoxicillin. The eradication rate was significantly different between clarithromycin-and levofloxacin-resistant patients(P < 0.05) in group A. Patients whose treatment failed in group A also had a higher clarithromycin resistance rate than did successive patients(P = 0.034). However,levofloxacin resistance had no obvious influence on the eradication rate. Furthermore,three main antibiotics(clarithromycin,levofloxacin and amoxicillin) had lower DID(defined daily dose per 1000 inhabitants per day) in this city.CONCLUSION: Clarithromycin resistance is the main reason for the failure of 7-d triple therapy. In populations with low levels of resistance,a 7-d triple therapy is a viable choice. The choice of therapy should not be influenced by conditions in high antibiotic resistance regions.

Pseudomembranous colitis associated with a triple therapy for Helicobacter pylori eradication

Helicobacter pylori(H.pylori)is one of the most common chronic bacterial infections in humans,affecting half of world’s population.Therapy for H.pylori infection has proven to be both effective and safe.The oneweek triple therapy including proton pump inhibitor,clarithromycin,and amoxicillin or metronidazole is still recommended as a first-line treatment to eradicate H.pylori infection in countries with low clarithromycin resistance.Generally,this therapy is well-tolerated,with only a few and usually minor side effects.However,rare but severe adverse effects such as pseudomembranous colitis have been reported,Clostridium difficile(C.difficile)infection being the main causative factor in all cases.We report the cases of two women who developed pseudomembranous colitis after a 1-wk triple therapy consisting of pantoprazole 20 mg bid,clarithromycin 500 mg bid,and amoxicillin 1 g bid to eradicate H.pylori infection.A limited colonoscopy showed typical appearance of pseudomembranous colitis,and the stool test for C.difficile toxins was positive.Rapid resolution of symptoms and negative C.difficile toxins were obtained in both patients with oral vancomycin.No relapse occurred during a four and eleven-month,respectively,follow up.These cases suggest that physicians should have a high index of suspicion for pseudomembranous colitis when evaluate patients with diarrhea following H.pylori eradication therapy.

H pylori eradication:A randomized prospective study of triple therapy with or without ecabet sodium

AIM: To investigate whether adding ecabet sodium to the standard triple therapy for H pylori infection improve eradication rate. METHODS: Two hundred and fifty-seven H pylori-infected patients were randomly assigned to standard triple therapy (group A, n = 129) or triple therapy plus ecabet sodium (group B, n = 128). Successful eradication was defined as a negative 13C-urea breath test 6-8 wk after completion of treatment. RESULTS: After completion of therapy, 194/257 patients showed negative 13C-urea breath test results. According to intention-to-treat analysis, the infection was eradicated in 93/129 (72.1%) patients in group A and 101/128 (78.9%) in group B (P = 0.204). Per-protocol analysis showed successful eradication in 93/118 (78.8%) patients from group A and 101/114 (88.6%) from group B (P = 0.044). There were no significant differences in the side effects experienced by the patients in the two treatment groups. CONCLUSION: Our results suggest that the addition of ecabet sodium improves the efficacy of the standard triple therapy for H pylori.

Comparison of sequential and 7-,10-,14-d triple therapy for Helicobacter pylori infection

AIM:To compare the effectiveness of sequential therapy for Helicobacter pylori(H.pylori) infection with that of triple therapy of varying durations.METHODS:The 460 patients enrolled in this study had H.pylori-associated gastritis or a gastric or duodenal ulcer.After screening,H.pylori-infected patients were randomly assigned to receive either conventional triple therapy for 7,10 or 14 d,or a new 10-d sequential therapy.Each of the 4 treatment groups included 115 patients.The outcomes of eradication therapy were assessed 4 wk after treatment by the urea breath test and histology.RESULTS:The overall eradication rate was 81.0%,and eradication rates were 75.7% for 7-d conventional triple therapy,81.9% for 10-d conventional triple therapy,84.4% for 14-d conventional triple therapy,and 82.0% for 10-d sequential therapy.Neither intention-to-treat analysis nor per protocol analysis showed significant differences in eradication rates using sequential therapy or the standard triple therapy(P = 0.416 and P = 0.405,respectively).CONCLUSION:There are no significant differences between 10-d sequential eradication therapy for H.pylori and any duration of standard triple treatment in Korean patients.

Eradication of H pylori infection in a rural population: One-day quadruple therapy versus 7-day triple therapy

AIM： To compare the one-day quadruple therapy with a standard 7-d triple therapy for H pylori eradication in a rural population of China. METHODS： A total of 396 patients with 13C-urea breath test positive for H pylori were assigned into two groups： 239 patients received one-day quadruple therapy （amoxicillin 2000 mg qid; metronidazole 500 mg qid; bismuth citrate 900 mg qid and lansoprazole 60 mg once daily） and 157 patients received 7-d standard triple therapy （amoxicillin 1000 mg bid; clarithromycin 500 mg bid and lansoprazole 30 mg bid）. All the patients underwent a 13C-UBT to assess the eradication of Hpylori infection six weeks after treatment. RESULTS： Two hundred and twenty-nine patients completed the one-day therapy （95.8%） and 148 patients completed the 7-d therapy （94.2%）. The oneday therapy eradicated H pylori infection in 64 patients （27.95%）. In contrast, 103 patients （69.59%） were Hpylori negative after the 7-d therapy （P 〈 0.01）. CONCLUSION： This pilot study suggests there is no beneficial effect of the one-day therapy in treatment ofHpylori infection compared with the 7-d standard therapy.

Impact of triple antithrombotic therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention in real-world practice

Objective The optimal antithrombotic regimen for patients on oral anticoagulation （OAC） after acute coronary syndrome （ACS） and percutaneous coronary intervention （PCI） remains debated. This study sought to evaluate the efficacy and safety of OAC plus clopidogrel with or without aspirin in a real-world setting. Methods We retrospectively analyzed data from an international, multi-center registry be- tween 2003 and 2014 （n = 15,401）. Patients with ACS and receiving OAC after PCI were screened. The composite primary endpoint was 1-year all-cause death, re-infarction, or severe bleeding. Results The final analysis enrolled 642 patients including 62 patients （9.7%） with OAC and clopidogrel （dual therapy）, and 580 patients （90.3%） with the combination of aspirin, OAC and clopidogrel （triple therapy）. Pa- tients on triple therapy were more often female and were more likely to have comorbidities. There was no significant difference regarding the primary end point between dual therapy with triple therapy patients [17.74% vs. 17.24%; unadjusted hazard ratio （HR）： 1.035; 95% confi- dence interval （CI）： 0.556-1.929; adjusted HR： 1.026; 95% CI： 0.544-1.937]. However, the re-infarction rate was significantly higher in dual therapy than triple therapy patients （14.52% vs. 5.34%; unadjusted HR： 2.807; 95% CI： 1.329-5.928; adjusted HR： 2.333; 95% CI： 1.078-5.047）. In addition, there was no difference between two regimes in all-cause death and severe bleeding. Conclusions In real-life patients with ACS following PCI and with an indication of OAC, triple therapy was not associated with an increased rate of adverse out- comes compared to dual therapy. Moreover, it decreased risk of re-infarction and did not increase risk of severe bleeding.

Triple, standard quadruple and ampicillin-sulbactam-based quadruple therapies for H pylori eradication:A comparative three-armed randomized clinical trial

AIM： To compare the effectiveness of triple, standard quadruple and ampicillin-sulbactam-based quadruple therapies for Hpylori eradication in a comparative three-armed randomized clinical trial. METHODS： A total of 360 H pylori-positive patients suffering from dyspepsia and aging 24-79 years with a median age of 42 years were enrolled in the study and randomly allocated into the following three groups： group A （n = 120） received a standard 1-wk triple therapy （20 mg omeprazole b.i.d., 1000 mg amoxicillin b.i.d., 500 mg clarithromycin b.i.d.）, group B （n = 120） received a 10-d standard quadruple therapy （20 mg omeprazole b.i.d., 1000 mg amoxicillin b.i.d., 240 mg colloidal bismuth subcitrate b.i.d., and 500 mg metronidazole b.i.d.）, group C （n = 120） received the new protocol, i.e. 375 mg sultamicillin （225 mg ampicillin plus 150 mg sulbactam） b.i.d. （before breakfast and dinner）, instead of amoxicillin in the standard quadruple therapy for the same duration. Chi-square test with the consideration of P 〈 0.05 as significant was used to compare the eradication rates by intention-to-treat and per-protocol analyses in the three groups.RESULTS： The per-protocol eradication rate was 91.81% （101 patients from a total of 110） in group A, 85.84% （97 patients from a total of 113） in group B, and 92.85% （104 patients from a total of 112） in group C. The intention-to-treat eradication rate was 84.17% in group A, 80.83% in group B, and 86.67% in group C. The new protocol yielded the highest eradication rates by both per-protocol and intention-to-treat analyses followed by the standard triple and quadruple regimens, respectively. However, the differences were not statistically significant between the three groups. CONCLUSION： The results of this study provide further support for the equivalence of triple and quadruple therapies in terms of effectiveness, compliance and sideeffect profile when administered as first-line treatment for H pylori infection. Moreover, the new protocol using ampicillin-sulbactam instead of amoxicillin in the quadruple regimen is a suitable first-line alternative to be used in regions with amoxicillin-resistant Hpylori strains.

Omeprazole-based triple therapy with low-versus high-dose of clarithromycin plus amoxicillin for H pylori eradication in Iranian population

AIM： To investigate the efficacy and tolerability of H pylori eradication in an omeprazole-based triple therapy with high and low dose of clarithromycin and amoxicillin. METHODS： One hundred and sixty H pylori positive patients were randomly assigned to two groups based on the following 2 wk investigation; （1） group A or low-dose regimen received omeprazole 20 mg b.i.d, clarithromycin 250 mg b.i.d and amoxicillin 500 mg b.i.d; and （2） group B or high-dose regimen received omeprazole 20 mg b.i.d, clarithromycin 500 mg b.i.d and amoxicillin 1000 mg b.i.d. During the study Hpylori status was assessed by histology and rapid urease test prior and by 13C-urea breath test 6 wk after the therapy. Standard questionnaires were administered to determine the compliance to treatment and possible adverse events of therapy. Data were subject to x^2 to compare the eradication rates in the two groups. The significant level of 95% （P ≤ 0.05） was considered statistically different. RESULTS： We found that the per-protocol eradication rate was 88% （68/77） in group A, and 89% （67/75） in group B. The intension-to-treat eradication rate was 85% （68/80） in group A and 83.75% （67180） in group B. Overall adverse events were 26% in group A and 31% in group B. The adverse events were generally mild in nature and tolerated well in both groups with a compliance of 98% in group A vs 96% in group B. CONCLUSION： The omeprazole-based low dose regimen of darithromycin and amoxicillin for two weeks in Hpylori eradication is as effective as high dose regimen in Iranian population.

The <i>Helicobacter pylori</i>Eradication Rate in a High Prevalence Area (West Africa): Three Triple Therapy Comparative Study

In Western countries, the current trend is to use sequential quadruple therapy or bismuth-based instead of triple therapy for the eradication of Helicobacter pylori (H. pylori). In sub-Saharan Africa, high prevalence area of the H. pylori infection, the effectiveness of these triple therapies widely used in routine has been little evaluated. The purpose of this study was to evaluate and compare the effectiveness of three patterns of first-line triple therapy based on combining a proton pump inhibitors (PPI), and 3 types of antibiotics: omeprazole (O), amoxicillin (A), clarythromycin (C) and metronidazole (M). Patients and Methods: This is a randomized clinical trial opened on 3 parallel arms: OAM (group 1 or G1), OAC (group 2 or G2) or OCM (group 3 or G3). The primary endpoint was H. pylori eradication rate after seven days triple therapy. H. pylori diagnosis infection was based on bacterium detection on the histological examination of the gastric biopsies. Histological control was performed 4 weeks after the end of treatment to assess H. pylori eradication rate. Results: The average age of our 153 patients included in the study (86 men) was 44.33 ± 11.72 years. The main reason of the endoscopy was the dyspeptic syndrome (75.16%). The gastroscopy was normal in 28.76%. A Gastric or duodenal peptic ulcer was found in 17% of cases and gastropathy in 45.75%. Histologically, the GC was active in 90.9% of cases, follicular in 35.3% of cases, atrophic in 22.5% of cases and was associated with intestinal metaplasia (IM) in 5.2% of cases. Patients of these three groups (n = 64 for G1, n = 56 for G2 and n = 33 for G3) were comparable for age, gender, endoscopy indications, alcohol consumption history or smoking, and anti-inflammatory drugs taking. Approximately 23% of patients experienced adverse reactions. The overall H. pylori eradication rate was 22.3%. There was no significant difference H. pylori eradication rate depending on the treatment used (28.1%, 21.4% and 15.1% for G1, G2 and G3, p = 0.34). Conclusion: The H. pylori eradication rate was poor regardless of the triple therapy used. It is desirable in the absence of bacteriological data on the primary and secondary resistance levels to optimize the eradication rate advocating the use of quadruple therapy at outset in first-line.

Treatment of Helicobacter pylori in surgical practice:A randomised trial of triple versus quadruple therapy in a rural district general hospital

AIM: To compare a lansoprazole-based triple versus quadruple therapy for Helicobacter pylori (H pylori) eradication with emphasis on side effect prof ile,patient compliance and eradication rate at a rural district general hospital in Wales,United Kingdom. METHODS: One hundred one patients with H pylori infection were included in the study. Patients were randomised to receive triple therapy comprising of lansoprazole 30 mg,amoxycillin 1 g,clarithromycin 500 mg,all b.d. (LAC),or quadruple therapy comprising of lansoprazole 30 mg b.d.,metronidazole 500 mg t.d.s.,bismuth subcitrate 240 mg b.d.,and tetracycline chloride 500 mg q.d.s. (LMBT). Cure was defi ned as a negative 13C urea breath test 2 mo after treatment. RESULTS: Seven patients were withdrawn after randomisation. Fifty patients were assigned to LAC group and 44 to LMBT group. The intention-to-treat cure rates were 92% and 91%,whereas the per-protocol cure rates were 92% and 97%,respectively. Side effects were common,with 56% experiencingmoderate to severe symptoms in the LAC group and 59% in the LMBT group. Symptoms of vomiting,diarrhoea and black stools were significantly more common in the LMBT group. Patient compliance was 100% for triple therapy and 86% for quadruple therapy (P < 0.01). One-third of patients in both groups were still taking acid-reducing medications at six-month follow-up. CONCLUSION: One-week triple and quadruple therapies have similar intention-to-treat eradication rates. Certain side effects are more common with quadruple therapy,which can compromise patient compliance. Patient education or modifi cations to the regimen are alternative options to improve compliance of the quadruple regimen.

Novel triple therapy for hemorrhagic ascites caused by endometriosis:A case report

BACKGROUND Massive hemorrhagic ascites caused by endometriosis is exceedingly rare,and the treatment strategy remains controversial.Here,we report a case of endometriosis with massive hemorrhagic ascites treated with a novel triple therapy including conservative surgery,gonadotropin-releasing hormone agonist,and then dienogest.CASE SUMMARY A 28-year-old nulliparous patient was admitted to Shengjing Hospital of China Medical University,and exploratory laparoscopy was performed.A total of 9500 mL of brown ascites was aspirated from the pelvic cavity,the bilateral ovaries strongly adhered to the posterior of the uterus and were fixed to the pelvic floor,and endometriotic cysts were not observed in either ovary.The pelvic and abdominal peritonea were covered with patchy red,white,and brown endometriotic lesions and defects.Partial surgical resection of endometriotic lesions on the peritoneum was performed while we simultaneously collected multiple peritoneal biopsies.The final pathological diagnosis was endometriosis coupled with hemorrhagic necrotic tissue.CONCLUSION Postoperative injection of gonadotropin-releasing hormone agonist was provided three times,followed by dienogest administration,and we will continue to follow up with this ongoing treatment.

Capecitabine maintenance therapy for XT chemotherapy-sensitive patients with metastatic triple-negative breast cancer

Objective： To investigate the efficacy and safety of capecitabine maintenance therapy（MT） after initial capecitabine plus docetaxel（XT） chemotherapy in patients with metastatic triple-negative breast cancer（m TNBC）.Methods： Fifty-five m TNBC patients treated with XT chemotherapy between May 2007 and June 2013 were retrospectively analyzed. When initial disease control was achieved by the combination chemotherapy, capecitabine was continued for 32 patients（MT）, while 23 patients remained without any treatment（nonMT）. We compared progression-free survival（PFS） and safety of both groups.Results： The median PFS of 55 patients was 8.1 months, overall median PFS time of 32 patients in the capecitabine MT group and 23 in the non-MT group was 10.1 vs. 6.7 months（P=0.032）, respectively. When compared PFS time of maintenance treatment, single-agent capecitabine prolonged PFS by 7.1 months, for non-MT patients, the PFS without any treatment was 3.1 months, and this between-group difference was statistically significant（P=0.003）. Adverse events, including of hematologic toxicity, gastrointestinal toxicities, hand-foot syndrome and abnormal liver function were not significantly different between two groups.Conclusions： After initial disease control was achieved with the XT combination chemotherapy, capecitabine MT can significantly prolong PFS time with a favorable safety profile in m TNBC patients.

Tumor infiltrating lymphocytes in triple negative breast cancer receiving neoadjuvant chemotherapy

AIM To determine influence of neoadjuvant-chemotherapy(NAC) over tumor-infiltrating-lymphocytes(TIL) intriple-negative-breast-cancer(TNBC).METHODS TILs were evaluated in 98 TNBC cases who came to Instituto Nacional de Enfermedades Neoplasicas from 2005 to 2010. Immunohistochemistry staining for CD3, CD4, CD8 and FOXP3 was performed in tissue microarrays(TMA) sections. Evaluation of H/E in full-face and immunohistochemistry in TMA sections was performed in pre and post-NAC samples. STATA software was used and P value < 0.05 was considered statistically significant. RESULTS Higher TIL evaluated in full-face sections from pre-NAC tumors was associated to pathologic-complete-response(pCR)(P = 0.0251) and outcome(P = 0.0334). TIL evaluated in TMA sections showed low level of agreement with full-face sections(ICC = 0.017-0.20) and was not associated to pCR or outcome. TIL in post-NAC samples were not associated to response or outcome. PostNAC lesions with pC R had similar TIL levels than those without pCR(P = 0.6331). NAC produced a TIL decrease in full-face sections(P < 0.0001). Percentage of TIL subpopulations was correlated with their absolute counts. Higher counts of CD3, CD4, CD8 and FOXP3 in pre-NAC samples had longer disease-free-survival(DFS). Higher counts of CD3 in pre-NAC samples had longer overallsurvival. Higher ratio of CD8/CD4 counts in pre-NAC was associated with pCR. Higher ratio of CD4/FOXP3 counts in pre-NAC was associated with longer DFS. Higher counts of CD4 in post-NAC samples were associated with pCR.CONCLUSION TIL in pre-NAC full-face sections in TNBC are correlated to longer survival. TIL in full-face differ from TMA sections, absolute count and percentage analysis of TIL subpopulation closely related.

One-year follow-up study of Helicobacter pylori eradication rate with ^(13)C-urea breath test after 3-d and 7-d rabeprazole-based triple therapy

AIM: To investigate the long-term role of a 3-d rabeprazole-based triple therapy in patients with Helicobacter pylori (H pylori)-infected active peptic ulcers. METHODS: We prospectively studied 115 consecutive patients with H pylori-infected active peptic ulcers. H pylori infection was confirmed if any two of H pylori DNA, histology, and rapid urease test were positive. Patients were assigned to either an open-labeled 3-d course of oral amoxicillin 1 000 mg b.i.d., clarithromycin 500 mg b.i.d., and rabeprazole 20 mg b.i.d., or 7-d course of oral amoxicillin 1 000 mg b.i.d., clarithromycin 500 mg b.i.d., and rabeprazole 20 mg b.i.d. Subsequently, all patients received oral rabeprazole 20 mg once daily until the 8th wk. Three months after therapy, all patients were followed-up endoscopically for the peptic ulcer, H pylori DNA, histology, and rapid urease test. One year after therapy, H pylori infection was tested using the 13C-urea breath test. RESULTS: The ulcer healing rates 3 mo after therapy were 81.0% vs 75.4% for the 3-d and 7-d groups [intention-to-treat (ITT) analysis, P=0.47] respectively, and 90.4% vs 89.6% for the 3-d and 7-d groups [per-protocol (PP) analysis, P=0.89] respectively. The eradication rates 3 mo after therapy were 75.9% vs 73.7% for the 3-d and 7-d groups (ITT, P=0.79) respectively, and 84.6% vs 87.5% for the 3-d and 7-d groups (PP, P=0.68) respectively. One year after therapy, seventy-five patients returned to receive the 13C-urea breath test, and the eradication rates were 78.4% vs 81.6% in 3-d and 7-d groups (PP, P=0.73) respectively. CONCLUSION: Our study showed the eradication rates against H pylori infection 3 and 12 mo after triple therapy were not different between the 3-d and 7-d rabeprazole-based groups. Therefore, the 3-d rabeprazole-based triple therapy may be an alternative treatment for peptic ulcers with H pylori infection.

Effect of Wei’s triple nine needling therapy on flash visual evoked potentials in rats with traumatic optic neuropathy

Objective:To investigate the effect of Wei’s triple nine needling therapy on the N2-P2 wave of the flash visual evoked potential(FVEP)in rats of the of the transverse directional pulling model.Methods:Thirty-six Wistar rats were randomly grouped,nine were in normal control group without any treatment,and the remaining 27 were surgically modelled in the right eyes.Eighteen of these rats were randomly divided into a Wei’s triple nine needling therapy group and a model group of nine rats each after the TON model was made using the transverse quantitative retraction method.The other 9 rats were sham-operated,and only the optic nerve was exposed without retraction.On the next day of modelling,the Wei’s triple nine needling therapy group was treated with Wei’s triple nine needling therapy for 20 minutes/1 time/1 day for 14 days.The model group,sham-operated group and normal control group were not intervened.Wei's triple nine acupoints were represented as follows:1st link:"Jingming"(BL1)and"Chengqi"(ST1);2nd link:"Sizhukong"(SJ23)penetrating"Taiyang"(EX-HN5);and the third:"Fengchi"(GB 20)and"Taichong"(LV3).The FVEP of each group was observed on 1d,7d and 14d.The FVEP of each group was observed on 1d,7d and 14d.Results:Compared with the model group,the N2 wave latency and P2 wave latency were shortened in the Wei’s triple nine needling therapy on 1d(P<0.05,P<0.01);on 7d,their N2 wave latency was shortened(P<0.01)and the N2-P2 wave amplitude was increased compared with the model group(P<0.05);on 14d,their P2 wave latency was shortened(P<0.05)and the N2-P2 wave amplitude was increased.There was no statistical difference in N2 wave latency,P2 wave latency and N2-P2 wave amplitude in the sham-operated group on 1d,7d and 14d(P>0.05).The delayed N2 and P2 wave latencies in the model group did not improve from 1d to 14d(P>0.05)and the amplitude decreased throughout,showing a significant difference on 14d compared to 1d(P<0.05).In contrast,the N2 wave latency in Wei’s triple nine needling therapy group was not significantly different until 7d to 14d(P<0.05);its P2 wave latency,although significantly delayed from 1d to 7d(P<0.05),recovered on 14d and reached a level that was not statistically different from 1d and 7d(P>0.05).There was also no significant decrease in N2-P2 wave amplitude between 1d and 14d in Wei’s triple nine needling therapy group(P>0.05).Conclusion:In this experiment,the TON rat model was successfully established by the transverse quantitative retraction method,and the treatment of TON rats with Wei’s triple nine needling therapy reduced the P2 wave delay of the FVEP electrophysiological signal and increased the N2-P2 amplitude,which had a certain positive effect on the repair of optic nerve injury,probably related to its effect of improving the conduction function of the optic nerve and protecting the retinal ganglion cells that had not been degenerated and necrosed.

Effects of ganglioside + aspirin + atorvastatin triple therapy on oxidative stress and inflammatory response in patients with cerebral infarction

Objective: To investigate the effects of ganglioside + aspirin + atorvastatin triple therapy on oxidative stress and inflammatory response in patients with cerebral infarction. Methods:A total of 138 patients with acute cerebral infarction between July 2016 and July 2017 were divided into control group (n=69) and triple group (n=69) by random number table method. Control group accepted conventional symptomatic treatment combined with aspirin and atorvastatin therapy, triple group accepted conventional symptomatic treatment combined with ganglioside, aspirin and atorvastatin triple therapy, and both groups were treated for 1 month. The differences in oxidative stress and inflammatory response were compared between the two groups before and after treatment. Results: Immediately after admission, There was no statistically significant difference in serum levels of oxidative stress indexes and inflammatory mediators between the two groups. After 1 week of treatment and after 4 weeks of treatment, serum oxidative stress indexes ROS and AOPPs levels of triple group were lower than those of control group whereas SOD and CAT contents were higher than those of control group;serum inflammatory mediators IL-6, TNF-α and TGF-β levels were lower than those of control group whereas IL-4, IL-10 and IL-13 levels were higher than those of control group. Conclusion: ganglioside + aspirin + atorvastatin triple therapy can effectively inhibit the systemic oxidative stress and inflammatory response in patients with cerebral infarction.

Improving Cost Savings and Patient Outcomes with Hepatitis C Triple Therapy Treatment in the Medicaid Population

One of the major infections that plague our world today, hepatitis C, has been causing liver disease in humans since early history. Over time, human ingenuity has allowed us to develop more effective treatments, but at traditionally massive monetary costs. In order to combat such costs, PerformRx came up with three ways to drive costs downward but also increase different outcomes for the Pennsylvania Medicaid population it serves. By restricting access to drugs via prior authorizations, tracking members within a DTM （drug therapy management） program, and giving members touchscreen tablet devices, there was an observed cost savings and a better ability to service members. Even though there was little impact on overall member outcomes, these initial interventions were the right steps to be innovative and create a beneficial scenario for both members and clients.

Molecular mechanisms of Triple H therapy in the treatment of SAH-induced vasospasm

Objective Cerebral artery vasospasm is a major cause of death and disability in patients experiencing subarachnoid hemorrhage (SAH). Vasospasm typically has been evaluated using angiography to examine narrowing of large diameter (>1 mm) cerebral arteries. Currently, little is known regarding the impact of SAH on small diameter (100～200 μm) cerebral arteries, which play an important role in the autoregulation of cerebral blood flow. The goal of the current study was to examine the influence of SAH on the pressure diameter relationship of these small diameter blood vessels. Methods Small diameter cerebral arteries were obtained from a rabbit SAH model. Isolated artery segments were canulated and placed in a myograph chamber superfused with warmed, oxygenated, physiological saline solution. Diameter measurements were then recorded to step wise increases in intravascular pressure. Results Cerebral arteries from SAH animals exhibited a significant increase in pressure induced constrictions (myogenic tone) at intravascular pressures between 40 mmHg and 120 mmHg. At intravascular pressures above 120 mmHg, myogenic tone began to decrease and was abolished at pressures above 180 mmHg. Conclusion These data suggest that in the days following SAH, myogenic tone is enhanced in small diameter cerebral arteries subjected to physiological levels of intravascular pressure. However, supra physiological intravascular pressures causes vasodilation, suggesting small diameter cerebral arteries may act as therapeutic targets of hypervolemia, hemodilution, and hypertension "Triple H therapy" used in the treatment of cerebral artery vasospasm.

Biological Modulation of Parp Inhibition in Triple Negative Breast Cancer, a Combinational Approach Implementing Multitargeted Epigenetic Therapy (Mtet) with Parp Inhibition, in Advanced Breast Cancer: A Case Study

The introduction of PARP inhibitors as active agents to inhibit the DNA repair was a revolution in the cancer therapeutics, however, such approach only has shown promising results for a short time in majority of cases due to secondary mutations and promoter gene methylation, and most of patients with triple negative breast cancer when treated with such agents only benefit for a short time, until the tumor shows resistance and further the therapy fails [1]. Considering this category of drugs and their mechanism of action in DNA repair [2] [3], several recent studies have focused on combination of PARP inhibitors with chemotherapy, immune therapy and interestingly relevant to this article, epigenetic therapies [4]. That said, to our knowledge the human data in this regard is missing. Here we discuss a case report of a patient with stage four refractory and resistant BRCA1 mutated triple negative breast cancer who responded in matter of two weeks to a combinational therapy, consisting of PARP inhibitor and epigenetic therapies. As the patient already had exhausted the PARP inhibitor by excessive presence of BRCA positive altered circulatory DNA, the response merely reflects the epigenetic therapy as back bone of treatment. The liquid biopsy repeated after two weeks of combination therapy showed complete disappearance (resolution of positive BRCA gene/c DNA), reflecting a synergism by proposed modulation of resistance as mechanism of action. (The initial c DNA showed 93 percent mutation allele fraction of BRCA gene.) To our knowledge, this is the first study on combinational therapy in human. The finding in this case could potentially change the standard of care in treating BRCA positive tumors, by providing a superior treatment to current standards.