Progress of transformational therapy in colorectal liver metastases

Colorectal cancer liver metastases(CLM) treatment is very important given the high incidence of colorectal cancer with liver metastases, which are primarily treated by surgical resection. Transformational therapy such as systemic chemotherapy, hepatic arterial infusion(HAI), portal vein embolization(PVE), ablation therapy, and targeted therapy, should be applied to CLM patients who are unable to undergo immediate surgery to improve patients’ survival and quality of life.     

How Far Have We Come? Challenges to Orphan Drug Access in China, 2011-2017

Rare diseases are an important global public health issue. One significant challenge is to ensure the access to orphan drugs for patients with rare disease. This study aims to evaluate the accessibility of orphan drugs in China. Information pertaining to the availability and costs of each orphan drug in each hospital was obtained from the Chinese Medicine Economic Information database during 2011-2017. We measured the accessibility of orphan drugs from 3 aspects: availability, daily costs, and affordability to patients.The market availability rate of orphan drugs in China was 28.8% by June 30, 2017. The median availability rate at the hospital level was less than 15% but was increasing over time. The cost of a defined daily dose of orphan drugs varied significantly with a decreasing trend in all areas. Less than half of all surveyed orphan drugs had a cost of a defined daily dose no more than residents' average daily income.This study reveals the challenges of access to orphan drugs in China. The availability of marketed orphan drugs in China was relatively low and most orphan drugs placed a heavy financial burden on patients with rare disease. It is necessary to develop legislation for orphan drugs and encourage domestic generics.     

Pulsed-xenon ultraviolet light disinfection in a burn unit: Impact on environmental bioburden,multidrug-resistant organism acquisition and healthcare associated infections

Portable pulsed xenon ultraviolet disinfection (PPX-UVD) may reduce healthcare associated infections (HAI). There is limited data to inform use in burn intensive care units (BICU), where multidrug-resistant organisms (MDRO), especially gram negative rods (GNR), commonly cause disease. We evaluated PPX-UVD effects on environmental bioburden and rates of HAI and MDRO acquisition in a BICU. PPX-UVD was used for 3 months after standard cleaning of patient and operating rooms (ORs). Settle and touch plates in patient rooms and ORs were obtained after standard cleaning, pre-and post-PPX-UVD. HAI and MDRO acquisition were evaluated 1 year prior to and for 3 month periods before, during, and after PPX-UVD. 110 touch and settle plates (33 pre- and 30 post-PPX-UVD) were obtained after standard cleaning, pre- and post-PPX-UVD. After PPX-UVD, environmental samples with any growth decreased (48% vs 31%, p = 0.02), as did mean colony count/sample (2.8 pre- vs 1.6 post-, p = 0.03). The 379 colonies largely represented skin commensals, without identified MDRO. Following PPX-UVD, no changes in device-associated infections, overall MDRO, or MDR GNR were seen, though a prolonged interval without healthcare-associated Clostridium difficile infection was observed. PPX-UVD in a BICU reduced overall environmental bioburden, without a statistically significant impact on HAI or MDRO.     

A chronic oral exposure of pigs with deoxynivalenol partially prevents the acute effects of lipopolysaccharides on hepatic histopathology and blood clinical chemistry

Lipopolysaccharides (LPS), a cell wall component of gram-negative bacteria, and deoxynivalenol (DON), a prevalent Fusarium-derived contaminant of cereal grains, are each reported to have detrimental effects on the liver. A potentiating toxic effect of the combined exposure was reported previously in a mouse model and hepatocytes in vitro, but not in swine as the most DON-susceptible species. Thus, pigs were fed either a control diet (CON) or a Fusarium contaminated diet (DON, 3.1 mg DON/kg diet) for 37 days. At day 37 control pigs were infused for 1 h either with physiological saline (CON_CON), 100 μg/kg BW DON (CON_DON), 7.5 μg/kg BW LPS (CON_LPS), or both toxins (CON_DON/LPS) and Fusarium-pigs with saline (DON_CON) or 7.5 μg/kg BW LPS (DON_LPS). Blood samples were taken before and after infusion (−30, +30, +60, +120, and +180 min) for clinical blood chemistry. Pigs were sacrificed at +195 min and liver histopathology was performed. LPS resulted in higher relative liver weight (p < 0.05), portal, periportal and acinar inflammation (p < 0.05), haemorrhage (p < 0.01) and pathological bilirubin levels (CON_CON 1.0 μmol/L vs. CON_LPS 5.4 μmol/L, CON_DON/LPS 8.3 μmol/L; p < 0.001). DON feeding alleviated effects of LPS infusion on histopathology and blood chemistry to control levels, whereas DON infusion alone had no impact.     

Diminished immunogenicity to pandemic H1N1 2009 influenza vaccine in subjects with severe motor and intellectual disability

Subjects with severe motor and intellectual disability (SMID) are considered to be debilitated and at high risk of influenza infection. However, the safety and immunogenicity of pandemic H1N1 (pH1N1) vaccine in these subjects have not been reported. We measured the hemagglutination inhibition antibody titer and calculated the geometric mean titer ratio (GMTR), seroprotection rate, and seroconversion rate in 104 subjects with SMID (mean age ± standard deviation 40.1 ± 12.9 years), and in 179 healthcare workers (40.7 ± 10.4 years) in a long-term care facility. Antibody responses after the first dose of pH1N1 vaccine among workers were greater than the European Medicines Evaluation Agency criteria and US Food and Drug Administration (FDA) criteria: the seroprotection rate was 79.9% (95% confidence interval (CI) 73.3-85.5), the seroconversion rate was 77.9% (95%CI: 70.8-84.0), and GMTR was 7.3 (95%CI: 6.9-7.8). Responses among subjects with SMID were lower than the FDA criteria: the seroprotection rate was 56.3% (95%CI: 46.2-66.1), the seroconversion rate was 54.1% (95%CI: 43.7-64.2), and GMTR was 5.4 (95%CI: 4.9-5.9). Any additional antibody response induced by the second dose of vaccine among subjects with SMID was limited. Multivariate analysis indicated that subjects with SMID had a significantly lower seroprotection rate (odds ratio (OR) 0.37, 95%CI: 0.20-0.66) and seroconversion rate (OR 0.34, 95%CI: 0.20-0.59) than healthcare workers. No serious adverse reaction was reported in either group. These results indicate that a single dose of pH1N1 vaccine does not induce sufficient immunity among subjects with SMID, and a second dose is likely to be ineffective because of diminished immunogenicity. Further study is required to determine if vaccination over consecutive influenza seasons can improve immunogenicity in subjects with SMID.     

我国部分地区基本药物价格水平实证研究

目的:了解我国基本药物价格水平,针对性提出政策建议.方法:以世界卫生组织和国际健康行动机构提出的标准方法为基础,对其针对我国国情进行改进,分别对我国药品价格与国际参考价格、原研药与仿制药以及公立机构与私立机构药品价格进行比较研究.结果:30种被调查药品的中位价格比为2.97,14种原研药为30.28.在本次调查中,有10.3%的公立医疗机构和46.7%的私立药店药品价格在世界卫生组织推荐的可接受范围内.结论:我国基本药物的价格水平偏高,尤其是原研药.中国公立机构药品价格较私立机构高,原研药价格通常远高于仿制药.     

实验兔出血症病毒检测方法的建立与免疫效果调查

目的检测全省六个实验兔场的兔子所携带的兔出血症病毒(RHDV)情况,调查实验兔RHDV抗体水平,评价不同疫苗的免疫效果,比较HAI与ELISA两种方法的符合率。方法采用HAI、ELISA方法对1168份实验兔RHDV抗体进行了检测,并与RT-PCR方法的检测结果进行对比分析。结果我省实验兔免疫情况较好,不同饲养场的实验兔免疫合格率虽有不同,但未发生疫情。通过比较发现ELISA法检测的抗体合格率明显高于HAI法。结论LISA、HAI和RT-PCR方法均适合实验兔RHDV的检测。     

Phase II trial in adults of concurrent or sequential 2009 pandemic H1N1 and 2009–2010 seasonal trivalent influenza vaccinations

BackgroundDuring the 2009 influenza pandemic both seasonal and 2009 pandemic vaccines were recommended. We conducted a randomized trial of monovalent 2009-H1N1 vaccine and seasonal trivalent inactivated influenza vaccine (IIV3) given sequentially or concurrently to adults.MethodsAdults randomized to 4 study groups and stratified by age (18–64 and ≥65 years) received 1 dose of seasonal IIV3 or placebo and 2 doses of 2009-H1N1 vaccine or placebo in one of 4 combinations, i.e., H1N1 + Placebo/H1N1 + Placebo/IIV3 (HP/HP/V3), H1N1 + IIV3/H1N1 + Placebo/Placebo (HV3/HP/P), H1N1 + Placebo/H1N1 + IIV3/Placebo (HP/HV3/P), and IIV3 + Placebo/H1N1 + Placebo/H1N1 (V3P/HP/H). Intramuscular injections were given three times at 21 day intervals. Sera for antibody assays were obtained prior to and 21 days after each vaccination. Reactogenicity and adverse events were monitored.ResultsEight hundred-five (805) adults were enrolled. All combinations of vaccines were safe and well tolerated. In general, one dose of 2009-H1N1 and one dose of IIV3, regardless of sequence or concurrency of administration, were immunogenic in adults. There were no significant differences in geometric mean titers (GMT) or the proportions of subjects with ≥4-fold rise in antibody responses and titers ≥40 for any vaccine group or between age strata for 2009-H1N1 after the first or second dose, although the vaccine sequence affected the titers to the IIV3 antigens. Hemagglutination inhibition antibody (HAI) GMTs against 2009-H1N1 for the combined age strata 21 days after the first 2009-H1N1 dose were 190.4, 182.1, 232.9 and 157.5 for HP/HP/V3, HV3/HP/P, HP/HV3/P and V3P/HP/H, respectively. While IIV3 GMTs were adequate they were generally lower than the 2009-H1N1 GMTs. In a subset of subjects, there was good correlation between HAI and microneutralization (MN) titers (Spearman's correlation coefficient 0.92).ConclusionsAll vaccine combinations were generally well tolerated. Immune responses to one dose of 2009-H1N1 were adequate regardless of the sequence of vaccination in all age groups, but the sequence affected titers to IIV3 antigens.     

Safety and immunogenicity of a quadrivalent intradermal influenza vaccine in adults

BackgroundAn intradermal (ID) trivalent split-virion influenza vaccine (IIV3-ID) (Fluzone^® Intradermal, Sanofi Pasteur, Swiftwater, PA) has been available in the US since the 2011/2012 influenza season for adults aged 18–64 years. This study examined whether adding a second B-lineage strain affects immunogenicity and safety.MethodsThis randomized, double-blind, multicentre trial evaluated the immunogenicity and safety of an intradermal quadrivalent split-virion influenza vaccine (IIV4-ID) in adults 18–64 years of age in the US during the 2012–2013 influenza season. Participants were randomized 2:1:1 to receive a single injection of IIV4-ID, licensed IIV3-ID, or an investigational IIV3-ID containing the alternate B-lineage strain. Haemagglutination inhibition antibody titres were assessed in two-thirds of participants before vaccination and 28 days after vaccination.Results1672 participants were vaccinated with IIV4-ID, 837 with licensed IIV3-ID, and 846 with an investigational IIV3-ID. For all four vaccine strains, antibody responses to IIV4-ID were statistically non-inferior to the response to the IIV3-ID vaccines containing the matched strains. For both B strains, post-vaccination antibody responses to IIV4-ID were statistically superior to the responses to IIV3-ID lacking the corresponding B strain. Adverse events were similar for IIV4-ID and IIV3-ID. The most commonly reported solicited reactions were pain, pruritus, myalgia, headache, and malaise; and most were grade 1 or 2 and appeared and resolved within 3 days of vaccination. IIV4-ID was statistically non-inferior to the two pooled IIV3-ID vaccines for the proportions of participants with at least one grade 2 or 3 systemic reaction.ConclusionsAntibody responses to the IIV4-ID were non-inferior to IIV3-ID for the A and matched B strains and superior for the unmatched B strains. IIV4-ID was well tolerated without any safety concerns. IIV4-ID may help address an unmet need due to mismatched B strains in previous influenza vaccines.