Evaluation of self-reported and registry-based influenza vaccination status in a Wisconsin cohort

We evaluated influenza vaccination status as determined by self-report and a regional, real-time immunization registry during two influenza seasons when subjects were enrolled in a study to estimate vaccine effectiveness. We enrolled 2907 patients during the two consecutive seasons. The sensitivity and specificity of self-reported influenza vaccination when compared to immunization registry records were 95% and 90%, respectively. The positive predictive value of self-reported vaccination was 89% and negative predictive value was 96%. In our study population, self-reported influenza vaccine status was a sensitive and fairly specific indicator of actual vaccine status. Misclassification was more common among young children.     

Variation and information in white blood cell differential counts

The magnitude and sources of variation in the white blood cell (WBC) count and differential count affect their information content and clinical value. This study describes components of variation in the WBC count and differential, estimates the magnitude of each component, and uses computer simulations to compare the information conveyed by the total WBC count and by the WBC differential count, expressed as the number of each type of cell and as the percentage of each cell type. Biologic variation is much greater than statistical sampling variation in differential WBC counts, even when a relatively small number of cells is classified. The commonly reported neutrophil percentage is inferior both to the neutrophil count and to the total WBC count in its ability to detect neutrophilia and to detect recovery from elevated levels. This conclusion holds for single as well as for sequential WBC differential determinations and regardless of the level of test result at which the clinician considers disease to be present. The total WBC count and the neutrophil count differ little in performance, so a neutrophilic patient's return to normal levels can safely be detected and monitored by relying on the less expensive total WBC count and foregoing repeated requests for differential counts.     

Influenza vaccination status is not associated with influenza testing among children: implications for observational studies of vaccine effectiveness

Estimates of influenza vaccine effectiveness from observational studies that rely on physician-ordered influenza tests may be biased if physician testing behavior is influenced by patient vaccination status. To assess the potential for differential diagnostic testing of children by vaccine status, we examined the association between receipt of a commercial influenza diagnostic test and influenza vaccination among children aged 6-59 months who sought care at the Marshfield Clinic for acute respiratory or febrile illnesses during the 2004-05 through 2007-08 influenza seasons. There was no significant association between prior influenza vaccination and receipt of a diagnostic test for influenza. These findings suggest that estimates of vaccine effectiveness derived from observational studies among children are unlikely to be biased due to differential diagnostic testing.     

Relationship between the white blood cell count and development of electrocardiographic ST-T abnormalities. Insights from annual health examinations of urban residents

OBJECTIVE: Inflammation has been shown to play a role in atherosclerosis and coronary heart disease. This study was designed to examine the relationship between the baseline white blood cell (WBC) count and development of electrocardiographic ST-T abnormalities. METHODS: The results of annual health examinations conducted in the city of A, Osaka Prefecture, from 1985 to 1997 were evaluated. At the initial examination, carried out during the period 1985-1988, 1,213 women and 201 men, who were current non-smokers without hypertension, were free from ST-T abnormalities. We focused on cases with new ST-T abnormalities identified during the 12-year period. WBC counts were categorized as low (< 50th percentile) or high (> or = 50th percentile), and were divided into quintiles. Cox proportional hazards models were used to test for correlations. RESULTS: The age-adjusted mean WBC count in both men and women were higher for cases with new ST-T abnormalities than for those with normal ECG findings. For men, the percentage of positive cases with a high WBC count was significantly greater. Multivariate models showed that the relative risk (RR) of new ST-T abnormalities for cases with a high WBC count as compared with those with a low WBC count was 7.16 (P<0.001) for men and 1.50 (P< 0.001) for women. The quintiles for men showed a step-wise increment in the rate per 1,000 person-years but no such tendency was observed for women. The higher the quintile in men, the higher the RR was, and the RR in the highest quintile was approximately ten times that in the lowest quintile. For women, a similar trend was observed, but the association between the RR and the WBC count was weaker. CONCLUSIONS: These results confirm that the WBC count is significantly associated with development of ST-T abnormalities, and that an elevated WBC count is a marker for an increased risk of ST-T abnormalities. In women, this relationship appears less prevalent than in men.     

Influenza vaccine effectiveness against hospitalisation with influenza in adults in Australia in 2014

We provide estimates of the influenza vaccine protection against hospitalisation with laboratory-confirmed influenza in the 2014 Australian season where the A/H1N1/pdm09 strain predominated. This was performed using a case-test negative study design as part of a national sentinel surveillance system in Australia. Vaccine effectiveness was estimated as (1-OR) × 100% where the odds ratio of vaccination in cases vs test negative participants was estimated from a conditional logistic regression. Between April and November, 1692 adult patients were admitted with laboratory-confirmed influenza. Vaccine effectiveness was estimated from 1283 patients with influenza and 1116 test negative patients where vaccination status was ascertained. Vaccination was associated with a reduction in the risk of hospitalisation with influenza of 51.5% (95% CI: 41.6%, 59.7%) in all patients, and a reduction of 50.7% (95% CI: 40.1%, 59.3%) in the target population for vaccination. We estimate that the influenza vaccine was moderately protective against hospitalisation with laboratory-confirmed influenza during the 2014 influenza season in Australia.     

The effect of misclassification on evaluating the effectiveness of influenza vaccines

Misclassification is a measurement error and can be considered a type of information bias. Misclassification can occur at both exposure and outcome levels. Nondifferential misclassification causes only a dilution effect leading to underestimation, whereas differential misclassification can have more complicated and serious consequences. To avoid nondifferential diagnosis misclassification, it is necessary to use highly specific diagnostic examinations or criteria such as virus detection to exclude 'false positive' cases, and to limit the observation period to an intensive epidemic period if using less specific diagnostic criteria such as symptoms of influenza-like illness (ILI) or absence from school or workplace. To avoid differential diagnosis misclassification, vaccinated and unvaccinated groups must be equally scrutinized, and such scrutiny is more important than the specificity of diagnosis. So, passive findings from patients with influenza at clinics can cause complicated differential misclassification despite use of highly specific diagnostic procedures because vaccinated and unvaccinated patients may participate differently. Also important is standardization of diagnostic procedure that vaccination anamnesis does not influence diagnosis of influenza, or examination of the influence. Exposure misclassification would mainly underestimate vaccine effectiveness in most situations. Consequently, misclassification of diagnosis, especially differential misclassification, affects evaluation of influenza vaccine effectiveness.     

Accuracy of influenza vaccination status in a computer-based immunization tracking system of a managed care organization

Influenza vaccine safety and effectiveness studies conducted using electronic medical records rely on accurate assessment of influenza vaccination status. However, influenza immunization in non-traditional settings (e.g., the workplace) may not be captured in patient immunization tracking systems. We compared influenza vaccination status from electronic records with self-reported vaccination status for five hundred and two 50–79 years olds enrolled in a large managed care organization. Influenza vaccination status in the medical record had a high positive predictive value and specificity (both >99%). The negative predictive value was 80% and sensitivity was 78%. These data suggest that an electronic record of influenza vaccination reliably indicates immunization, while the absence of such a record is only moderately accurate, partly due to vaccines received in non-traditional settings.     

GPA基因突变与慢性苯中毒的关系

目的探讨外周血红细胞血型糖蛋白A(glycophorin A,GPA)基因突变与慢性苯中毒的关系。方法用荧光标记单克隆抗体和流式细胞术,检测63名慢性苯中毒工人和45名同期接苯但无苯中毒表现的同工种对照工人外周血红细胞GPA基因突变频率。结果苯中毒组的白细胞、中性粒细胞计数明显低于对照组,差异有统计学意义(P<0.01);随着GPA-NN、GPA-Nφ突变频率增加,白细胞及中性粒细胞计数相应减少,两者间的趋势关系均有统计学意义(P<0.05)。GPA-NN突变频率随着累积接触评分增加而增加,两者间的趋势关系有统计学意义(P<0.05)。GPA-Nφ突变频率与累积接触评分间的趋势关系不明显(P>0.05)。结论苯中毒所表现的外周血白细胞、中性粒细胞数的降低,可能来源于骨髓干细胞的遗传损伤,即GPA-MN基因的纯合型(NN)基因突变。GPA-NN基因突变在慢性苯中毒的发病过程中起着重要作用。     

Bacille Calmette-Guérin vaccination at birth and differential white blood cell count in infancy. A randomised clinical trial

BackgroundThe Bacille Calmette-Guérin (BCG) vaccine against tuberculosis (TB) may have beneficial non-specific effects (NSEs) beyond the protection against TB. This may be related to modifications of the innate immune system. We investigated the effect of BCG at birth on differential white blood cell (WBC) count in healthy, Danish infants.MethodThe Danish Calmette Study randomised newborns to BCG at birth (Danish strain 1331, Statens Serum Institut) or no intervention. A sub-group of infants had blood samples collected 4 days after randomisation (n = 161), and at age 3 months (n = 152) and 13 months (n = 300). We evaluated the effect of BCG on WBC differential count (total leucocytes, lymphocytes, monocytes, eosinophil, neutrophil and basophil granulocytes (10⁹ cells/L)) measured in peripheral blood.ResultsOverall, we found no effect of BCG on differential WBC counts at any time point.ConclusionBCG at birth did not affect WBC count in our cohort of healthy, Danish infants.     

Effectiveness of pandemic and seasonal influenza vaccines in preventing pandemic influenza-associated hospitalization

Vaccines are leading pharmacological measures for limiting the impact of pandemic influenza in the community. The objective of this study was to investigate the effectiveness of influenza (pandemic and seasonal) vaccines in preventing pandemic influenza-associated hospitalization. We conducted a multicenter matched case-control study in 36 Spanish hospitals. Patients hospitalized with confirmed pandemic influenza between November 2009 and February 2010 and two hospitalized controls per case, matched according to age, date of hospitalization and province of residence, were selected. Multivariate analysis was performed using conditional logistic regression. Subjects were considered vaccinated if they had received the vaccine >14 days (seasonal influenza vaccine) or >7 days (pandemic influenza vaccine) before the onset of symptoms (cases) or the onset of symptoms of the matched case (controls). For the pandemic influenza vaccine, vaccination effectiveness (VE) was estimated taking into account only patients recruited from November 23, 2009, seven days after the beginning of the pandemic influenza vaccination campaign. 638 cases and 1250 controls were included. The adjusted VE of the pandemic vaccine in the ≥18 years age group was 74.2% (95% CI, 29-90) and that of the influenza seasonal vaccine 15.0% (-34 to 43). The recommendation of influenza vaccination should be reinforced as a regular measure to reduce influenza-associated hospitalization during pandemics and seasonal epidemics.     

105例儿童甲型H1N1流感病例流行病学与临床特征分析

目的探讨甲型H1N1流感患儿的流行特点及临床特征,为甲型H1N1流感的诊疗和预防提供依据。方法 以湖南省儿童医院2009年10月27日-2010年2月27日收治的105例实验室确诊甲型H1N1流感病例为研究对象,回顾性分析其流行病学和临床特征。结果1.105例甲型H1N1流感患儿以男性为主,高发年龄为0~5岁,大部分来自城镇,50.5%有接触史,90.5%患儿入院时间集中在11月、12月份。34例（32.4%）以其它疾病入院。2.临床表现无特异性。咳嗽、发热为其普遍症状,部分患儿出现呕吐、腹泻及头痛症状。24例（22.9%）患儿存在基础疾病。3.白细胞下降主要发生在婴儿;WBC升高主要见于1岁以上患儿。ESR、CRP、PCT等炎性指标及CK、AST、BAMS等酶学指标异常广泛。早期胸片改变较临床明显。4.重症及危重症病例占到71.5%。肺炎为最常见并发症,发生率为80.0%,呼吸衰竭为最严重并发症,发生率为18.1%。结论儿童甲型H1N1流感无特异表现,病情相对温和;但在部分儿童,特别是有基础病史者可表现为重症;门诊血常规、胸片检查有助于早期发现重症。     

司他夫定、拉米夫定联合奈韦拉平治疗艾滋病患者12例效果评估

目的观察2种核苷类逆转录酶抑制剂（NRTI）联合1种非核苷类逆转录酶抑制剂（NNRTI）抗逆转录病毒方法治疗艾滋病的效果和不良反应,为艾滋病治疗提供依据。方法用3TC、D4T联合NVP治疗12例艾滋病患者,随访1年。随访指标为定期检测CD4T淋巴细胞计数,常规生化检查和不良反应。结果12例患者在治疗1年后临床症状明显改善,CD4细胞计数和CD4/CD8比例逐渐升高,且差异有统计学意义。治疗初期不良反应有胃肠道反应、中枢神经系统症状及周围神经病变,一般可自行缓解。结论该药物组合疗效显著,能降低艾滋病患者的机会性感染,提高其生活质量,并能使部分免疫功能得以重建,具有较高的安全性和耐受性。     

流感样症状患者临床特征分析

目的分析中山大学孙逸仙纪念医院急诊留观区2018年9月至2019年1月接诊的流感样症状患者的临床特征,为流感患者诊治提供依据。 方法选择2018年9月至2019年1月中山大学孙逸仙纪念医院急诊接诊的180例流感样症状患者,比较不同月份的发病例数。按流感快速抗原检测结果分为流感组与非流感组,流感组为临床诊断为流行性感冒的患者90例,其中男性31例,女性59例;年龄15～94岁,平均(36.82±16.43)岁。非流感组按照与流感组相同的性别年龄比例选取90例有流感症状但不符合临床诊断标准的患者,其中男性32例,女性58例;年龄17～89岁,平均(37.35±15.59)岁。两组患者的性别年龄组成比例差异无统计学意义。分析比较2组的血常规白细胞计数、淋巴细胞计数、嗜酸性粒细胞计数及临床症状,并比较各种观察指标之间的流感快速抗原检出率。 结果流感在12月及1月发病例数高于其他月份。流感组的白细胞及淋巴细胞计数低于非流感组[(6.71±2.40)×10⁹/L vs (9.08±4.91)×10⁹/L,(0.97±0.49)×10⁹/L vs (1.29±0.75)×10⁹/L];常见临床症状中流感快速抗原检测阳性率分别为：低热13例(40.60%),中度热46例(54.80%),高度热42例(56.0%),不同体温的患者之间的流感病毒检出率差异无统计学意义(P>0.05)。肌痛45例(50.00%),头痛29例(39.20%),乏力13例(50.00%),咽痛40例(47.10%),咳嗽60例(45.80%)。除头痛外,其他各种症状的患者流感检出率差异无统计学意义(P>0.05)。 结论流感冬春季节发病率较高,流感患者感染指标低于非流感患者。流感快速抗原检测敏感性较低,头痛有可能是比较有特异性的临床表现。     

Influenza vaccine effectiveness for hospital and community patients using control groups with and without non-influenza respiratory viruses detected,Auckland, New Zealand 2014

BackgroundWe aimed to estimate the protection afforded by inactivated influenza vaccine, in both community and hospital settings, in a well characterised urban population in Auckland during 2014.MethodsWe used two different comparison groups, all patients who tested negative for influenza and only those patients who tested negative for influenza and had a non-influenza respiratory virus detected, to calculate the vaccine effectiveness in a test negative study design. Estimates were made separately for general practice outpatient consultations and hospitalised patients, stratified by age group and by influenza type and subtype. Vaccine status was confirmed by electronic record for general practice patients and all respiratory viruses were detected by real time polymerase chain reaction.Results1039 hospitalised and 1154 general practice outpatient consultations met all the study inclusion criteria and had a respiratory sample tested for influenza and other respiratory viruses. Compared to general practice patients, hospitalised patients were more likely to be very young or very old, to be Māori or Pacific Islander, to have a low income and to suffer from chronic disease. Vaccine effectiveness (VE) adjusted for age and other participant characteristics using all influenza negative controls was 42% (95% CI: 16 to 60%) for hospitalised and 56% (95% CI: 35 to 70%) for general practice patients. The vaccine appeared to be most effective against the influenza A(H1N1)pdm09 strain with an adjusted VE of 62% (95% CI:38 to 77%) for hospitalised and 59% (95% CI:36 to 74%) for general practice patients, using influenza virus negative controls. Similar results found when patients testing positive for a non-influenza respiratory virus were used as the control group.ConclusionThis study contributes to validation of the test negative design and confirms that inactivated influenza vaccines continue to provide modest but significant protection against laboratory-confirmed influenza.     

Is influenza-like illness a useful concept and an appropriate test of influenza vaccine effectiveness?

Purpose

To assess the utility of “influenza-like illness” (ILI) and whether it appropriately tests influenza vaccine effectiveness.

Principal results

The WHO and CDC definitions of “influenza-like illness” are similar. However many studies use other definitions, some not specifying a temperature and requiring specific respiratory and/or systemic symptoms, making many samples non-comparable. Most ILI studies find less than 25% of cases are RT-PCR-positive, those which test for other viruses and bacteria usually find multiple other pathogens, and most identify no pathogen in about 50% of cases. ILI symptom and symptom combinations do not have high sensitivity or specificity in identifying PCR-positive influenza cases. Rapid influenza diagnostic tests are increasingly used to screen ILI cases and they have low sensitivity and high specificity when compared to RT-PCR in identifying influenza.

Main conclusions

The working diagnosis of ILI presumes influenza may be involved until proven otherwise. Health care workers would benefit by renaming the WHO and CDC ILI symptoms and signs as “acute respiratory illness” and also using the WHO acute severe respiratory illness definition if the illness is severe and meets this criterion. This renaming would shift attention to identify the viral and bacterial pathogens in cases and epidemics, identify new pathogens, implement vaccination plans appropriate to the identified pathogens, and estimate workload during the viral season. Randomised controlled trials testing the effectiveness of influenza vaccine require all participants to be assessed by a gold standard (RT-PCR). ILI has no role in measuring influenza vaccine effectiveness. ILI is well established in the literature and in the operational definition of many surveillance databases and its imprecise definition may be inhibiting progress in research and treatment. The current ILI definition could with benefit be renamed “acute respiratory illness,” with additional definitions for “severe acute respiratory illness” (SARI) with RT-PCR testing for pathogens to facilitate prevention and treatment.     

甲型H1N1流行性感冒病毒裂解疫苗的安全性研究

目的评价甲型H1N1流行性感冒裂解疫苗(简称甲流疫苗)的安全性。方法设立主动监测点,通过全国疑似预防接种异常反应信息管理系统,收集全市接种甲流疫苗和主动监测点接种季节性流感疫苗后的AEFI个案信息,采用描述性方法对相关指标进行流行病学分析。结果邯郸市常规报告接种甲流疫苗后AEFI发生率14.64/10万,以一般反应为主,占88.57%,症状主要为38.5℃以下的低热,无严重不良反应和接种事故发生。主动监测点接种甲流疫苗后AEFI发生率752.63/10万,全部为一般反应,以发热为主。主动监测点接种季节性流感疫苗后AEFI发生率203.14/10万,全部为一般反应,均为发热。结论甲流疫苗接种后AEFI发生率高于季节性流感疫苗,但低于欧盟流感疫苗评价指标。甲流疫苗接种后AEFI反应类型以一般反应为主,且多为低热。甲流疫苗是安全的。     

甲型H1N1流感57例临床分析

目的 分析甲型H1N1流感临床特点,探讨治疗方法,以期及早地控制病情,提高生存率.方法 回顾性分析57例甲型H1N1流感病例的临床资料.结果 57例甲型H1N1流感病例中轻症病例占89.47%,男女之比为2.16∶1;以青少年居多,30岁以下占87.72%.所有患者均有发热、全身酸痛等全身症状,具有季节性流感特征,但较季节性流感病程长.X线示肺纹理增粗为66.67%,10.53%患者合并肺炎.43.86%表现为心电图异常;部分有心肌酶学指标升高,尤以危重病例明显.26.32%患者有肝功能异常.40.35%的患者外周血象表现为白细胞降低,少数有血小板下降.17.54%患者伴有消化道症状.6例重症、危重症病例3岁以下2例,40岁以上3例,均并发肺炎、心肌炎,2例危重症病例并发Ⅰ型呼吸衰竭、低氯低钠血症等.本组病例经中西医结合治疗预后好,无后遗症及死亡病例.结论 甲型H1N1流感临床表现特异性不强,但有其特点,儿童及老年人易重症的高危人群;掌握临床特点,早期识别重症病例,有助于提高生存率.     

White blood cell count: an independent predictor of coronary heart disease mortality among a national cohort

An association between elevated white blood cell (WBC) count and coronary heart disease (CHD) mortality has been previously observed. However, the relationship between WBC count and CHD mortality independent of cigarette smoking and the possible interaction between WBC count and smoking remains unclear. We examined the association between WBC count and CHD mortality with Cox regression analyses of data from 8914 adults, aged 30-75, in the NHANES II Mortality Study (1976-1992). Covariates included age, sex, race, education, physical activity, smoking status, hypertensive status, total serum cholesterol, body mass index, hematocrit, and history of cardiovascular disease, stroke, and diabetes. During 17 follow-up years, there were 548 deaths from CHD (ICD-9 410-414) and 782 deaths from diseases of the heart (ICD-9 390-398, 402, 404, 410-414, 415-417, 420-429). Mean WBC count (x10(9) cells/L) was greater among persons who died from CHD (7.6 vs 7.2, P <.001). Compared to persons with a WBC count <6.1, persons with a WBC count > 7.6 were at increased risk of death from CHD (relative risk = 1.4, 95% confidence interval = 1.1-1.8) after adjustment for smoking status and other CVD risk factors. Similar results were observed among nonsmokers (RR = 1.4, 95% CI = 0.9-2.0). These results suggest that higher WBC counts are a predictor of CHD mortality independent of the effects of smoking and other traditional CVD risk factors, which may indicate a role for inflammation in the pathogenesis of CHD. Additional studies are needed to determine whether interventions to decrease inflammation can reduce the risk for CHD associated with elevated WBC.     

呼吸道反复感染患儿接种不同疫苗后血清免疫水平与效果观察

目的观察肺炎球菌疫苗与流感疫苗联合接种对反复呼吸道感染(RRTI)患儿体液免疫及疗效的影响。方法80例RRTI患儿随机分为4组：对照组(仅使用安慰剂) 肺炎球菌疫苗组、流感疫苗组,联合疫苗接种组(接种肺炎球菌疫苗1月后再行流感疫苗接种),每组20例。末次接种后治疗12周后,测定患儿体液免疫功能指标,6月后观察临床疗效。同时选取2013年2月-2014年5月在本院治疗的非RRTI的急性呼吸道感染患儿30例。结果治疗12周后,RRTI组血清IgG、IgA和IgM水平明显低于非RRTI组(P<0.01)。治疗12周后,与对照组比较,肺炎球菌疫苗组、流感疫苗组和联合接种组患儿血清IgG、IgA和IgM水平、治疗总有效率明显上升 (P<0.01),并且联合接种组明显优于单纯肺炎球菌疫苗组、流感疫苗组(P<0.05)。肺炎球菌疫苗组与流感疫苗组比较,无统计学意义(P>0.05),治疗期间无药物不良反应事件。结论肺炎球菌疫苗与流感疫苗联合接种可更有效地改善RRTI患儿的体液免疫功能。     

健康体检人群白细胞计数与非酒精性脂肪肝的关联性研究

目的 探讨健康体检人群白细胞计数与非酒精性脂肪肝(non-alcoholic fatty liver disease, NAFLD)的关联性。 方法 对象为2016年1—12月中国医科大学附属第一医院健康体检中心的体检人群,对其临床资料进行回顾性分析。最终纳入29 729人,其中NAFLD 12 191例。采用Logistic回归模型评估白细胞计数不同四分位数水平与NAFLD患病之间的关系。 结果 调整混杂因素的影响后,以白细胞计数第一四分位数为参考,第二、三、四分位数组NAFLD患病的比值比(95%CI)分别为1.190(1.084,1.307),1.260(1.075,1.476)和1.430(1.221,1.675)(P_趋势性值<0.001)。 结论 健康体检人群白细胞计数与NAFLD存在相关关系。