Comparison of outcomes for elderly patients treated with weekly paclitaxel in combination with carboplatin versus the standard 3-weekly paclitaxel and carboplatin for advanced nonsmall cell lung cancer

BACKGROUND: The purpose of this study was to compare the outcomes between elderly (aged > or = 70 years) patients treated with paclitaxel on a weekly basis and with carboplatin (every 4 weeks) versus the standard 3-weekly regimen of carboplatin and paclitaxel for first-line therapy of advanced nonsmall cell lung cancer. METHODS: Of the 444 patients enrolled, 136 (31%) were aged > or = 70 years. Seventy-two patients were randomized to the weekly schedule (paclitaxel, 100 mg/m(2) weekly for 3 of 4 weeks; carboplatin, area under the curve [AUC] = 6 mg/mL.min on Day 1 every 4 weeks), and 64 patients were randomized to the standard schedule (paclitaxel, 225 mg/m(2); carboplatin, AUC = 6 mg/mL.min on Day 1 every 21 days). Patients with stable disease or objective response after 4 cycles of therapy were eligible for maintenance therapy with weekly paclitaxel (70 mg/m(2), 3 of 4 weeks). RESULTS: The response rate for elderly patients was 26% on the weekly regimen and 19% on the standard schedule. The median survival duration for the weekly and the standard schedules was 37 weeks and 31 weeks, respectively. The 1-year survival rates were similar at 31% and 33%. Grade 3 to 4 anemia was more common on the weekly schedule (16% vs 6%), whereas grade 3 neuropathy was less common (5.5% vs 9.5%). Nausea and emesis were also less frequent on the weekly schedule. CONCLUSIONS: Efficacy was similar between the weekly regimen and the standard regimen of carboplatin and paclitaxel for elderly patients with advanced NSCLC and may be advantageous based on its favorable tolerability profile.     

Health and nutritional status of children of adolescent mothers: experience from a diarrhoeal disease hospital in Bangladesh

AIM: The study aimed at assessing clinical and nutritional features and socioeconomic characteristics of the first birth-order children (1-48 months) of adolescent mothers. METHODS: Five hundred and thirty-nine first birth-order children of both sexes, aged 1-48 month(s) were studied. All study children had adolescent mothers aged < or =19 years (when attending hospital), who attended (as a patient) the Dhaka hospital of ICDDR, B during 2000-2005. A similar group of children (n = 540) of mothers aged 25-29 years (when attending hospital) constituted the comparison group. RESULTS: Malnutrition indicated by underweight [OR 2.3, 95% CI 1.7-3.1, p < 0.001], stunting [OR 2.1, 95% CI 1.5-2.8, p < 0.001], wasting [OR 1.8, 95% CI 1.3-2.7, p = 0.001], infancy (<12 months old) [OR 2.8, 95% CI 2.1-3.9, p < 0.001], duration of hospitalization (> or =48 h) [OR 1.6, 95% CI 1.2-2.2, p = 0.001], DPT immunization [OR 1.8, 95% CI 1.3-2.5, p = 0.001] and maternal illiteracy (no formal schooling) [OR 1.5, 95% CI 1.1-2.0, p = 0.007] were significantly associated with children of adolescent mothers, after adjusting for co-variates in the logistic regression analysis. Similar results were also observed when different indices of malnutrition (stunting, underweight or wasting) were added separately to the different models. CONCLUSION: Children of adolescent mothers are likely to be more malnourished, have lesser opportunities for DPT immunization and have longer duration of hospitalization. Adolescent mothers were also more likely to be illiterate. Therefore, the development of preventive and therapeutic strategies will be required to reduce morbidity and improve the health and nutrition status of both children and their adolescent mothers.     

日本血吸虫嗜肌素样蛋白编码基因的克隆表达及其免疫原性研究

目的克隆和表达日本血吸虫嗜肌素样蛋白(SjcMLP)编码基因,并研究其重组抗原的免疫原性。方法PCR扩增SjcMLP编码基因,并亚克隆人表达载体pQE30。将重组表达质粒pQE 30-SjcMLP转入宿主菌E. coli M15,异丙基-βD-硫代半乳糖苷(IPTG)诱导表达,用金属Ni螯合物亲和层析柱(Ni-NTA)纯化SjcMLP重组蛋白(reSjcMLP)。纯化的reSjcMLP采用十二烷基磺酸钠一聚丙烯酰胺凝胶电泳(SDS-PAGE)和免疫印迹试验(Western blot)作进一步分析。采用酶联免疫吸附试验(ELISA)测定用reSjcMLP免疫C57BL/6小鼠血清中的抗体水平。结果 SDS-PAGE分析表明获得的重组抗原的大小约24.8 kDa,与预的融合蛋白大小相符。Western blot昱示该重组抗原能被日本血吸虫尾蚴感染兔血清识别。用该重组抗原包被进行ELISA检测,免疫血清滴度高达1：12 800。但动物免疫试验结果减虫效果不明显。结论SjcMLP编码基因以可溶性融合蛋白的形式得到表达,动物免疫试验未诱导出明显的保护力     

vJ38gag/IFNα-2b基因共表达核酸疫苗免疫程序的优化

目的　观察国际流行株HIV - 1gag与IFNα - 2b基因共表达颗粒化抗原疫苗与质粒DNA核酸疫苗免疫程序优化的效果。方法　将质粒 pJ38gag/IFNα- 2b经脂质体介导转染RK细胞 ,并在痘苗病毒中共表达HIV - 1gag与IFNα - 2b基因 ,以间接免疫荧光与斑点酶联免疫法鉴定其表达产物。以表达产物与质粒DNA联合免疫小鼠实验 ,检测淋巴细胞转化率、细胞毒性T细胞杀伤活性、CD+ 4 、CD+ 8细胞计数与体液免疫水平。结果　pJ38gag/IFNα - 2b基因表达的颗粒化抗原疫苗具有良好的免疫原性 ,3vJ38gag/IFNα- 2b +pJ38gag/IFNα- 2b联合免疫效果优于vJ38gag/IFNα - 2b单独免疫。 结论　pJ38gag/IFNα- 2b基因表达的颗粒化抗原疫苗能诱导机体产生细胞免疫与体液免疫。     

Compliance with recommended immunizations in adolescents

Introduction Little is known about the completeness and timely administration of recommended standard immunizations in Germany. The goal of this study was to determine compliance with official standard immunization recommendations in adolescents attending secondary schools in the city of Erlangen, Germany.Methods Adolescents who were attending 5th grade (at approximately 11 years of age), 8th grade (14 years), or 10th and 11th grade (16–17 years) classes at any of the 13 of 14 schools that had agreed to participate were eligible to be enrolled.Results While coverage for the primary series of diphtheria, tetanus and poliomyelitis immunizations was satisfactory (98%), coverage for measles-mumps-rubella immunizations (dose 1: 89–96%; dose 2: 60–76%) and hepatitis B (doses 1–3: 61%) was suboptimal. Of note, 39% of students had not received any immunization against pertussis. Completion of immunization series generally was significantly delayed. Furthermore, rates for recommended booster doses in adolescence were disappointingly low with 21% for tetanus component vaccines and <10% for the fifth dose of pertussis.Conclusions Significant immunization gaps for all recommended standard immunizations in adolescents were detected. This puts individuals at risk for serious vaccine-preventable diseases, contributes to suboptimal herd immunity in the population under study leaving the potential for future epidemics, and impedes national and international targets of disease reduction or elimination.This work contains data from the medical thesis of Kerstin Loos at the Medical Faculty, University of Erlangen, Germany.     

Immunization stress-related response – Redefining immunization anxiety-related reaction as an adverse event following immunization

The Council for the International Organizations of Medical Sciences (CIOMS) and WHO working group on pharmacovigilance defines five cause specific AEFI which includes an immunization anxiety-related reaction. Historically this term has been used to describe a range of symptoms and signs that may arise after immunization that are related to “anxiety” about the immunization. However, the term “anxiety” does not adequately capture all the elements of this cause specific AEFI. In 2015, the Global Advisory Committee for Vaccine Safety convened an expert working group with the purpose of redefining, preventing and managing this particular AEFI. The term “Immunization Stress-Related Response” is proposed to replace the former terminology. We present a manual that redefines this AEFI and present a framework for prevention, diagnosis and management in both an individual and also when such events occur as clusters and affect multiple individuals. Since such mass events can result in cessation of immunization programmes and/or a loss of public confidence, a communication response is essential.     

Inactivated influenza vaccine does not reduce all cause respiratory illness in children with pre-existing medical conditions

BackgroundThe effectiveness of inactivated influenza vaccine (IIV) immunization in preventing all cause respiratory illness (RI) in children with pre-existing medical conditions has not been fully established and varies from season to season. This study aims to quantify the overall impact of IIV immunization on primary care attended RI episodes in children with pre-existing medical conditions, using robust observational data spanning twelve influenza seasons.MethodsElectronic records of IIV eligible children aged 6 months to 18 years were extracted from primary care databases over the years 2004–2015. IIV eligibility criteria according to Dutch guidelines included (chronic) respiratory and cardiovascular disease and diabetes mellitus. For each year, information on IIV immunization status, primary care attended RI episodes (including influenza, acute respiratory tract infections and asthma exacerbations) and potential confounders were collected. Generalized estimating equations were used to model the association between IIV status and occurrence of at least one RI episode during the influenza epidemic period with “current year immunized” as reference group. Robustness of findings were assessed by performing various sensitivity analyzes in which (i) seasons with a mismatch between the dominant circulating influenza virus and vaccine strain were excluded, (ii) influenza periods were further restricted to weeks with at least 30% influenza virus positive specimens in sentinel surveillance (instead of 5%), (iii) propensity scores were used to adjust for confounding.ResultsIn total, 11,797 children (follow-up duration: 38,701 child-years) were eligible for IIV for ≥ one season with 29% immunized at least once. The adjusted odds for primary care attended RI episodes during the influenza epidemic period did not differ between current season immunized versus not immunized children (adjusted OR:1.01; 95%CI:0.90–1.13). The various sensitivity analysis showed comparable results.ConclusionsIIV immunization in children with pre-existing medical conditions does not reduce all cause RI episodes encountered in primary care during the influenza season.     

Immunogenicity and safety of a liquid Pentavalent (DTwP-Hb-Hib) combination vaccine manufactured by Human Biologicals Institute in 6–8 weeks old healthy infants: A phase III,randomized, single blind,non-inferiority study

BackgroundA liquid Pentavalent (DTwP-Hb-Hib) combination vaccine, developed by Human Biologicals Institute, underwent a Phase III clinical study in India. In this randomized, single blind, non-inferiority study, the immunogenicity and safety of this Investigational vaccine was compared with Pentavac SD® vaccine in 6–8 weeks old healthy infants.MethodsA total of 405 healthy infants aged 6–8 weeks old were randomized in 2:1 ratio to receive three doses of either the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine or Pentavac SD® vaccine at four to six weeks interval. Immunogenicity was compared by estimation of antibody titers before the first dose and 4–6 weeks after the third dose of vaccination. Safety of each vaccine was assessed and compared by collection of data on solicited and unsolicited adverse events throughout the study period.ResultsOut of a total of 405 enrolled subjects, 387 subjects completed the study. The seroconversion rates, seroprotection rates and geometric mean titres of the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine group were found to be comparable and non-inferior to the Pentavac SD® vaccine group at 4–6 weeks after the third dose of vaccination. Pain, erythema and swelling at the site of injection were found to be the most common local adverse events whereas fever, irritability and unusual crying were found to be the most common systemic adverse events in both the vaccine groups. No vaccine related serious adverse event was reported. In this study, both the Investigational vaccine as well as the Comparator vaccine were found to be immunogenic and well tolerated.ConclusionAfter assessment of the results of the study it was concluded that the Investigational liquid Pentavalent (DTwP-Hb-Hib) combination vaccine developed by Human Biologicals Institute was immunogenic and safe when administered to infants aged 6–8 weeks and was non-inferior in immunogenicity and safety to Pentavac SD® vaccine.Clinical Trial Registry of India Identifier: CTRI/2016/01/006541.