Target serum concentration of vancomycin may be reached earlier with a loading dose

Background:Vancomycin treatment failure against vancomycin-susceptible gram-positive cocci is not rare in the intensive care unit(ICU).One of the reasons for this is the substandard drug trough concentration.We aimed to examine the hypothesis that the target serum concentration could be reached earlier with a loading dose of vancomycin.Methods:This retrospective cohort study was conducted at our ICU between June 2018 and June 2020 and involved patients who were suspected of having,or confirmed to have,gram-positive cocci infection and treated with vancomycin.One group of the patients was administered a loading dose of vancomycin(loading group)and compared with the group that did not receive a loading dose(control group).The baseline characteristics,vancomycin serum concentrations,and clinical outcomes were collected and analyzed.Results:Fifty-five patients were finally included,of which 29 received a loading dose of vancomycin.The serum concentration of vancomycin before the second dose was significantly higher for the loading group than for the control group(10.3±6.1 mg/Lvs.5.7±4.4 mg/L,P=0.002).The results for both groups were similar before the fifth dose(12.4±7.3 mg/Lvs.10.3±6.3 mg/L in the loading and the control groups,respectively;P=0.251).The 28-day mortality was lower for the loading group than for the control group(6.7%vs.34.6%in the loading and control groups,respectively;P=0.026).No significant differences were observed in serum creatinine(Cr)concentrations of the two groups.Conclusion:With the loading dose of vancomycin,the target serum concentration of vancomycin may be reached earlier without increasing the risk of acute kidney injury.

Comparison of benefit and safety between different loading dose of clopidogrel on elderly patients undergoing primary percutaneous cronary intervention for ST-segment elevation myocardial infarction

Background Despite the proven benefit of 600-mg loading dose of clopidogrel in patients with acute ST- segment elevation myocardial infarction （STEMI） who undergo primary percutaneous cronary intervention （PCI）, there is still concern about its benefit and safety on elderly population. Methods Data of 172 consecutive elderly patients （~〉75 years） with STEMI who underwent primary PCI at Guangdong Provincial Cardiovascular Institute from January 2008 to December 2011 were retrospectively collected. Patients were divided into 600-mg loading clopidogrel group and 300-mg clopidogrel group accoring to the loading dose of clopidogrel before primary percunaeous coronary intervention（PCI）. Enzymatic myocardial infarction size estimated by peak creatine kinase-myocardial band （CK-MB） and patency of the infarct-related artery （IRA） were compared. Thirty-day major adverse cardiac events （MACEs）, which consist of death, nonfatal myocardial infarction （MI）, nonfatal stroke, target vessel revascularization （TVR） or stent thrombosis （ST） were compared to assess the efficacy of different loading dose. Bleeding information was compared as well to assess the safety of different pretreatment stragety before primary PCI. Results 96 patients were adminstered with 600-mg loading clopidogrel before primary PCI while 76 were administered with 300-mg. Patency of the IRA was significantly higher in patients administered with 600-mg loading clopidogrel therapy as compared with those who received 300-mg loading clopidogrel （94.8% vs. 85.5%, P = 0.038）. 600-mg loading dose of clopidogrel was associated with lower incidence of 30-day MACEs compared with 300-mg loading dose of clopidogrel （8.3% vs. 19.7%, P = 0.029） while did not increase the risk of TIMI major （3.1% vs. 3.9%, P = 0.770） and minor bleeding （10.4% vs. 6.6%, P = 0.376）. Conclusion 600-mg loading clopidogrel improves final patency of the IRA and clinical outcome as compared with 300-mg loading clopidogrel without increasing bleeding hazard.

Use of tailored loading-dose clopidogrel in patients undergoing selected percutaneous coronary intervention based on adenosine diphosphate-mediated platelet aggregation

Background Adenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention.Methods A total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel （n=104） served as the Talcom （Taijia）group; others （n=101） received Plavix, the Plavix group, Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% （the primary endpoint） compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months.Results Compared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a ＞50% decrease in adenosine phosphate-mediated platelet aggregation （rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P=0.028）. There was no significant difference in the eligible index between the Talcom and Plavix groups （47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P ＞0.05） based on a standard adenosine diphosphate-mediated platelet aggregation decrease of ＞50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events （2.5% vs. 2.9%, P=5.43）. No acute or subacute stent thrombosis events occurred.Conclusion An adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no increase in bleeding.

Comparison of two different treatment regimens’ efficacy in neovascular age-related macular degeneration in Turkish population—based on real life data-Bosphorus RWE Study Group

AIM: To compare two different anti-vascular endothelial growth factor(anti-VEGF) treatment regimens'-a priori pro re nata(PRN) and PRN regimen following^(th)e loading phaseanatomical and functional results in neovascular agerelated macular degeneration(n AMD) patients. METHODS: Totally 544 n AMD patients followed and treated with aflibercept(n=135) and ranibizumab(n=409)at 9 different centers between 2013 and 2015 were enrolled into^(th)is retrospective multicenter study. Patients with initial best corrected visual acuity(BCVA) interval of 1.3-0.3(log MAR) and a minimum follow-up of 12 mo were included. Patients under two different regimens-a priori pro re nata(1+PRN) or 3 consecutive intravitreal injections followed by a PRN regimen(3+PRN)-were compared in BCVA at 3^(th), 6^(th) and 12^(th) months, and in central macular^(th)ickness(CMT) at 6^(th) and 12^(th) months. The total study group, intravitreal ranibizumab(IVR) and intravitreal aflibercept(IVA) groups were evaluated separately. RESULTS: The mean CMT decreased in^(th)e 1+PRN(n=101) regimen from 407 to 358 and 340 μm and in^(th)e 3+PRN(n=443) group from 398 to 318 and finally to 310 μm at months 6 and 12, respectively. Anatomically,^(th)e CMT reduction at 6^(th) month(48.5 vs 76.4;P<0.05) was statistically significant in favor of 3+PRN group. BCVA changed in 1+PRN group from 0.77 to 0.78, 0.75 and 0.75;in 3+PRN group from 0.81 to 0.69, 0.72, and 0.76 at months 3, 6, and 12, respectively. Visual gain was statistically better in 3+PRN group at 3^(th) month(-0.01 vs 0.12;P<0.001). In IVR group, CMT reduction was in greater in 3+PRN at 6^(th)(44 vs 72) and 12^(th) month(61 vs 84), but statistically insignificant. The 3+PRN group revealed statistically better visual results at 3^(th) month(-0.02 vs 0.11, P<0.05). In IVA group, although statistically insignificant, CMT reduction(61 vs 89, 6^(th) month;85 vs 97, 12^(th) month) and visual gain(0.02 vs 0.16;0.02 vs 0.14;0.05 vs 0.11) was found in favor of 3+PRN group at all visits.CONCLUSION: The loading dose of anti-VEGF treatments in n AMD leads to significantly better anatomical and functional results, regardless of the agent, specially in early follow-up interval.

Clinical significance of human papilloma virus infection in the cervical lesions

Cervical lesions have been regarded as the common and frequently occurring diseases in China.Recently,the morbidity and youth tendency of cervical cancer have gradually increased.Cervical cancer,related with human papilloma virus(HPV)infection,has been one of the severest diseases threatening health and life of women,and is an infectious disease.The universality of HPV infection in the reproductive tract should not be ignored.The well-known risk factors of HPV infection in cervical lesions consist of high-risk sexual behaviors,immunosuppression,age,contraceptive methods,the concurrent infection of other sexually transmitted diseases,etc.The variation of cervical lesions induced by HPV infection is involved in the continuous pathological process,including the subclinical,latent,and persistent infection of high risk(HR)-HPV,chronic cervicitis with abnormal results of cytological examination,cervical intraepithelial neoplasia(CIN),and cervical cancer.The outcome of patients with HPV infection is influenced by many factors,such as HPV subtype dominance,persistent HPV infection,HPV loading dose,and multiple HPV infection.Controlling HR-HPV persistent infection should be an important strategy for reducing cervical lesions.