The efficacy and safety of influenza vaccination in older people: An umbrella review of evidence from meta-analyses of both observational and randomized controlled studies

Vaccination is the main public health intervention to prevent influenza. We aimed to evaluate the efficacy and safety of influenza vaccination including systematic reviews and meta-analyses of observational studies and randomized controlled trials (RCTs). Peer-reviewed systematic reviews with meta-analyses of prospective studies that investigated the association of influenza vaccination with any health-related outcome, as well as RCTs that investigated the efficacy and safety of influenza vaccination, were included. Among 1240 references, 6 meta-analyses were included. In cohort studies of community-dwelling older people influenza vaccination was associated with a lower risk of hospitalization for heart disease and for influenza/pneumonia (strength of evidence: convincing). Evidence in lowering the risk of mortality in community-dwelling older people, of all deaths/severe respiratory diseases in high risk community-dwelling older people and of hospitalization for influenza/pneumonia in case-control studies, was highly suggestive. In RCTs, influenza vaccination, compared to placebo/no intervention, was associated to higher risk of local tenderness/sore arm and to a reduced risk of influenza like-illness. Both these associations showed moderate evidence using the GRADE (Grading of Recommendations Assessment, Development and Evaluation). In conclusion, influenza vaccination in older people seems safe and effective. Further, the evidence on safety and efficacy of vaccines in this population might benefit by an extension of the follow-up period both in RCTs and in longitudinal studies, beyond the usual 6-month period, in order to be able to evaluate the impact of vaccination on long term outcomes.     

sFlt-1、IGFBP-3、PAPP-A在稽留流产中的表达及意义

目的研究可溶性FMS样酪氨酸激酶-1(sFlt-1)、胰岛素样生长因子结合蛋白3(IGFBP-3)、妊娠相关血浆蛋白A(PAPP-A)在稽留流产中的表达及意义。方法选取2015年6月至2017年6月在重庆市两江新区第一人民医院接受治疗的稽留流产患者40例纳入稽留流产组;早期流产患者40例纳入早期流产组;另外选取进行体检的健康妊娠期产妇20例作为正常组。收集3组研究对象的绒毛组织,采用免疫组化染色处理,酶联免疫吸附测定sFlt-1、IGFBP-3、PAPP-A表达,并在显微镜下观察其阳性表达情况。结果正常组sFlt-1表达水平显著低于早期流产组和稽留流产组(P<0.05);稽留流产组sFlt-1表达水平低于早期流产组(P<0.05)。正常组IGFBP-3、PAPP-A表达水平显著高于早期流产组和稽留流产组(P<0.05);稽留流产组患者IGFBP-3、PAPP-A表达水平高于早期流产患者(P<0.05)。sFlt-1、IGFBP-3、PAPP-A三项联合检测敏感度、准确度高于sFlt-1、IGFBP-3、PAPP-A单一检测,特异度低于sFlt-1、IGFBP-3、PAPP-A单一检测(P<0.05)。结论sFlt-1、IGFBP-3、PAPP-A联合检测对稽留流产的诊断价值较高,sFlt-1、IGFBP-3、PAPP-A的异常表达参与了稽留流产的发展,为稽留流产的治疗提供一定的理论基础。     

联合检测C反应蛋白和降钙素原在创伤后脓毒症患者早期预警中的作用

目的评估血清C反应蛋白(CRP)和降钙素原(PCT)联合检测对创伤后脓毒症患者的预警价值。方法纳入严重创伤患者235例,其中110例脓毒症患者和125例非脓毒症患者。采集入院24 h内血样,检测血清中CRP和PCT。采用ROC曲线比较CRP和PCT对创伤后脓毒症的预警价值,同时采用NRI和IDI分析联合使用后的提高能力。结果脓毒症患者血清CRP和PCT水平均显著高于非脓毒症患者(P<0.001),ROC分析显示血清CRP和PCT的AUC分别为0.766(0.707~0.819)和0.744(0.684~0.799);将CRP和PCT联合较单指标预警创伤脓毒症的AUC提高了5.1%,7.3%。NRI和IDI分析结果证实PCT和CPR的联合使用较单独使用的预警效能显著提高(P<0.001)。结论CRP和PCT对严重创伤后脓毒症发生风险具有早期预警作用,二者联合能够显著提高早期预警能力。     

Quadrivalent versus trivalent influenza vaccine: clinical outcomes in two influenza seasons,historical cohort study

ObjectivesThe quadrivalent influenza vaccine (QIV) contains two influenza B antigens (one of each B lineage), while the trivalent vaccine (TIV) contains solely one. As a result, a mismatch between the circulating B lineage and the lineage in the TIV occurs frequently. We aimed to compare the frequency of clinically significant outcomes in a large cohort of vaccinees receiving either TIV or QIV.MethodsHistorical cohort study of all inactivated influenza vaccinees (aged 3 years and older) in a Health Maintenance Organization insuring 1.2 million individuals, over two influenza seasons in which both vaccines were provided non-selectively. Primary outcome was hospital admissions during the influenza season. Multivariate analysis was performed using logistic regression to adjust for relevant covariates.ResultsOur cohort included 150 518 and 168 296 vaccinees in the first (S1) and second season (S2), respectively. The two influenza seasons were characterized by high Influenza B activity. Of those vaccinated with QIV, 2074 of 49 726 (4.2%) and 6563 of 121 741 (5.4%) were hospitalized compared with 7378 of 100 792 (7.3%) and 3372 of 46 555 (7.2%) of those vaccinated with TIV (S1 and S2, respectively). After multivariate analysis adjusting for several covariates (gender, age, socioeconomic status, chronic morbidity, timing of vaccination), compared with TIV recipients, QIV vaccinees had lower odds for hospitalization (OR = 0.92, 95% CI 0.87–0.98 and OR = 0.89, 95% CI 0.85–0.93) or emergency department visit (OR = 0.91, 95% CI 0.87–0.95 and OR = 0.84, 95% CI 0.81–0.87) in S1 and S2, respectively (p < 0.001). Lower odds of mortality and influenza-like illness were also observed in S2 (OR = 0.61, 95% CI 0.50–0.75 and OR = 0.92, 95% CI 0.90–0.95, respectively).ConclusionsIn seasons with relatively high influenza B activity, QIV appeared more protective than TIV in Israel.     

Characterization of antibody and memory T-cell response in H7N9 survivors: a cross-sectional analysis

ObjectivesDespite the importance of immunological memory for protective immunity against viral infection, whether H7N9-specific antibodies and memory T-cell responses remain detectable years after the original infection is unknown.MethodsA cross-sectional study was conducted to investigate the immune memory responses of H7N9 patients who contracted the disease and survived during the 2013–2016 epidemics in China. Sustainability of antibodies and T-cell memory to H7N9 virus were examined. Healthy individuals receiving routine medical examinations in a physical examination centre were recruited as control.ResultsA total of 75 survivors were enrolled and classified into four groups based on the time elapsed from illness onset to specimen collection: 3 months (n = 14), 14 months (n = 14), 26 months (n = 28) and 36 months (n = 19). Approximately 36 months after infection, the geometric mean titres of virus-specific antibodies were significantly lower than titres in patients 3 months after infection, but 16 of 19 (84.2%) survivors in the 36-month interval had microneutralization (MN) titres ≥40. Despite the overall declining trend, the percentages of virus-specific cytokine-secreting memory CD4⁺ and CD8⁺ T cells remained higher in survivors at nearly all time-points in comparison with control individuals. Linear regression analysis showed that severe disease (mean titre ratio 2.77, 95% CI 1.17–6.49) was associated with higher haemagglutination inhibition (HI) titre and female sex for both HI (1.92, 1.02–3.57) and MN (3.33, 1.26–9.09) antibody, whereas female sex (mean percentage ratio 1.69, 95% CI 1.08–2.63), underlying medical conditions (1.94, 95% CI 1.09–3.46) and lack of antiviral therapy (2.08, 95% CI 1.04–4.17) were predictors for higher T-cell responses.ConclusionsSurvivors of H7N9 virus infection produced long-term antibodies and memory T-cell responses. Our findings warrant further serological investigation in general and high-risk populations and have important implications for vaccine design and development.     

Autonomic nervous system functioning in early childhood: Responses to cognitive and negatively valenced emotional challenges

Although autonomic nervous system (ANS) functioning is “context-dependent,” few studies examined children's normative sympathetic and parasympathetic autonomic responses to distinct challenges in early childhood years. Examining children's ANS responsivity to distinct challenges is important for understanding normative autonomic responses toward everyday life stressors and identifying paradigms that effectively elicit a “stress response.” We examined children's (N = 278) sympathetic (preejection period [PEP]) and parasympathetic (respiratory sinus arrhythmia [RSA]) responses to cognitive (i.e., problem-solving and cognitive control) and negatively valenced emotional (i.e., blocked goal and unfairness) challenges in preschool, kindergarten, and grade 1. Children, on average, demonstrated parasympathetic inhibition (RSA withdrawal) in response to all challenges but the magnitude of these responses depended on the task. Children showed sympathetic activation (PEP shortening) toward the problem-solving task at each assessment and there was no sample-level change in the magnitude of this response over time. Children showed greater sympathetic responsivity toward the cognitive control task over time, with evidence for a sympathetic activation response only in grade 1. Children experienced sympathetic inhibition (PEP lengthening) toward the unfairness tasks but did not experience significant sympathetic responsivity toward the blocked goal tasks. Parasympathetic responsivity to most challenges were modestly stable but there was no stability in sympathetic responsivity across time.     

Associative binding in early childhood: Evidence from a preferential looking paradigm

Relational memory processes are responsible for forming representations that bind together the co-occurring elements of an experience. These processes provide a foundation of episodic memory, the capacity to remember specific events about one's past. In the present research, we used a visual comparison paradigm to determine whether toddlers can form memories for the relation between co-occurring items. In Experiment 1, 66 2-year-olds viewed pairs of cartoon faces (AB; CD) and did not show a significant novelty preference for the violated associations (i.e., did not look longer at AD rearranged pair than old AB pair when exposed to AD-AB). However, toddlers looked longest at the individual face (i.e., D) violating a studied pair, which appeared to be supported by visual preference for centrally located stimuli. In Experiment 2, 46 2-year-olds participated in a similar procedure, but faces violating the pair during test were located to the periphery (e.g., AB-AC). Under these conditions, toddlers looked longer at recombined pair AC. Overall, our results show that toddlers show some ability to make item-item associations but may need to overcome preferential looking biases to demonstrate this capacity. Furthermore, looking behaviors beyond overall novelty preference may be informative even when overall novelty preference is not found.