姜黄素联合吉非替尼对人肺腺癌细胞A549/H1975增殖影响的研究

目的：考察姜黄素与吉非替尼联用对人肺腺癌细胞A549（EGFR野生型;K-ras突变）和H1975（EGFR突变：T790M＋L858R;K-ras野生型）增殖的影响,及姜黄素对吉非替尼在细胞膜内药物浓度的影响。方法：完全培养基稀释姜黄素与吉非替尼分别至5个不同浓度,交叉组合作用于A549/H1975细胞72 h,MTT法检测A549/H1975细胞的增殖。联合指数法（combination index,CI）评价姜黄素和吉非替尼的联合作用效价,当CI〈1时认为方案具有协同效应。HPLC-MS法检测细胞膜内吉非替尼浓度。结果：与单独用药组相比,姜黄素与吉非替尼联用显著提高了对A549细胞增殖的抑制作用,表现出强相加/协同效应;而对于H1975细胞仅仅表现为相加效应。在吉非替尼浓度为1μmol·L-1时,添加姜黄素后A549细胞膜内吉非替尼浓度上升至吉非替尼单独用药组的（1.25±0.26）倍,差异存在统计学意义（P〈0.05）,吉非替尼浓度为10μmol·L-1时则没有明显变化;而当作用细胞为H1975时,是否添加姜黄素对于吉非替尼在细胞膜内的浓度均未见明显变化。结论：姜黄素与小剂量吉非替尼联用可以显著抑制肺腺癌A549细胞的增殖,但对于H1975细胞效果不佳。姜黄素可以提高吉非替尼在A549细胞膜内的浓度是可能的原因之一。     

Hospital recovery following Thermachoice ablation is not dependent on setting (outpatient or daycase) or rescue analgesia: unexpected result

BACKGROUND: Thermal balloon endometrial ablation (TBEA) is increasingly being performed in the outpatient setting under local anaesthesia (LA) rather than in a daycase setting under general anaesthesia (GA). Our aim was to compare the post operative rescue analgesia requirements and duration of hospital stay in women undergoing outpatient (LA) and daycase (GA) TBEA. METHODS: Prospective observational study of consecutively recruited women who underwent outpatient (LA) TBEA (n=51) and daycase (GA) TBEA (n=50) over the same time period. Analgesia that was provided additional to the standard administered analgesic regimen was considered rescue analgesia. The main outcome measures were requirement for rescue analgesia and duration of hospital stay in both cohorts. RESULT(S): LA compared to GA cohorts had shorter hospital stays (11h [95% CI 9-13] vs. 17h [95% CI 14-20]) and lower analgesia requirements. However, multivariate regression, correcting for all known confounders, showed that duration of stay was independent of setting for ablation or amount of rescue analgesia. CONCLUSION(S): Duration of hospital stay is not entirely dependent on whether outpatient or daycase endometrial ablation is considered. This unexpected preliminary finding deserves to be validated in future confirmatory trials that compare outpatient and daycase treatments. We also discuss the confounding factors that should be considered when designing such trials.     

Modification of the vaccine manufacturing process improves the pyrogenicity profile of inactivated influenza vaccines in young children

Background

There were increased reports of fevers and febrile reactions in young children (particularly children aged <5?years) receiving the Seqirus/CSL Southern Hemisphere 2010 trivalent inactivated influenza vaccine (IIV3). Modifying the vaccine manufacturing process by increasing the minimum concentration of splitting agent (sodium taurodeoxycholate [TDOC]) from 0.5% w/v to 1.5% w/v for all strains resolved this issue. The current analysis compared fever rates in three pediatric studies of Seqirus IIV3 (S-IIV3) or quadrivalent inactivated influenza vaccine (S-IIV4), prepared using the modified manufacturing process, with fever rates in three pediatric studies of historical (pre-2010) IIV3 formulations. The historical IIV3 formulations, S-IIV3, and S-IIV4 had 0/3, 2/3, and 4/4 vaccine strains split at 1.5% TDOC, respectively.

MMR vaccine effectiveness in an outbreak that involved day-care and primary schools

Objective

In 2006, a large measles outbreak occurred in Catalonia (Spain), where the immunization schedule included two doses of MMR vaccine at 15 months and 4 years. The aim of this study was to investigate the vaccine effectiveness (VE) of MMR in children attending day-care and pre-school centres and to estimate the number of cases that would have been avoided by administering the first dose of MMR at 12 months.

Methods

A retrospective cohort study was carried out between October 2006 and January 2007 in day-care and pre-school centres with confirmed measles cases. VE was calculated in children aged ≥15 months without previous measles infection. Cases avoided by advancing the first dose of MMR to 12 months were estimated by calculating the basic and effective reproduction number in centres where transmission outside the class was observed.

Results

Fifteen centres and 1394 children were included. There were 77 confirmed cases (attack rate = 5.5%). Vaccination coverage of the 1121 children aged ≥15 months was 91.6% and VE was 96% (95%CI 89-98%).There were 33 (41%) cases in the 81 children aged 12-14 months. Advancing the first dose to 12 months would have prevented 74 cases (91.5%) and lowered the attack rate from 41% to 8.6%.

Conclusions

Over 90% of cases in children aged 12-14 months would have been avoided by MMR administration at 12 rather than 15 months. We strongly recommend advancing the first dose of MMR to 12 months in order to reduce the risk of measles outbreaks.     

Fine particulate matter and incidence of metabolic syndrome in non-CVD patients: A nationwide population-based cohort study

Background

It has been reported that particulate matter (PM) is associated with cardiovascular diseases (CVD) while metabolic syndrome is also an important risk factor for CVD. However, few studies have investigated the epidemiological association between PM and metabolic syndrome.

Prevalence and factors affecting underweight,overweight and obesity using Asian and World Health Organization cutoffs among adults in Nepal: Analysis of the Demographic and Health Survey 2016

ObjectiveThere is a little published data on prevalence and determinants of underweight, overweight and obesity among adults in Nepal. This study analysed the cross-sectional Nepal Demographic and Health Survey (NDHS) 2016 to obtain these using the World Health Organization (WHO) and Asian-specific cutoffs of body mass index (BMI).MethodsThe 2016 NDHS used a multistage cluster-sampling design to obtain data on major health indicators in Nepal. The BMI cutoffs for underweight was <18.5 kg/m². The BMI cutoffs for overweight/obesity as per the Asian and WHO classifications were ≥23, and ≥25 kg/m², respectively. After reporting the prevalence according to sex and background characteristics, multilevel logistic regression was conducted to estimate odds ratios.SubjectsThis analysis included 12,652 adults (5283 males and 7369 females) with a median age of 40 years (interquartile range [IQR]: 28–54).ResultsThe overall median BMI was 21.5 kg/m² (IQR:19.3–24.3). The overall prevalence of underweight was 16.7% (15.1% among males and 17.1% among females). The Asian-specific BMI cutoffs found the prevalence of overweight and obesity as 26.4% (27.4% among males and 25.6% among females) and 11.0% (7.7% among males and 13.3% among females), respectively. The WHO-recommended BMI cutoffs found 18.2% people overweight (16.7% among males and 19.3% among females) and 4.3% (2.5% among males and 5.6% among females) people obese. The prevalence and odds of extreme body weight categories (i.e., underweight, overweight and obesity) varied according to age, sex, education level, household wealth status, place, ecological zone and provinces of residence as per both recommended cutoffs. Overall, higher education level and wealth status were positively associated with overweight/obesity and inversely associated with underweight as per both cutoffs.ConclusionA large proportion Nepalese adults have either underweight, overweight or obesity, and could be at a greater risk of mortality and morbidity due to these extreme body weight categories. It is essential to address the factors or characteristics that are associated with the higher prevalence and likelihood of these extreme body weight categories to reduce the overall burden of underweight and overweight/obesity in Nepal.