Factors associated with influenza vaccine receipt in community dwelling adults and their children

Background

Factors associated with influenza vaccine receipt are well studied in healthcare personnel, pregnant women, and the elderly. There has been substantially less research in community dwelling adults and children, and none among entire households. Many studies determine vaccination status by self-report or behavioral intention, outcomes susceptible to misclassification. Given that vaccine is recommended for everyone over six months, re-evaluating these factors is warranted.

Methods

The Household Influenza Vaccine Effectiveness (HIVE) study is a prospective cohort of households with children. In 2010–2011, 549 adults representing 312 households completed surveys evaluating knowledge, attitudes, and practices regarding influenza vaccination for themselves and their children. Using the health belief model (HBM) as a framework, we examined factors associated with documented seasonal influenza vaccine receipt using log-binomial regression models.

Results

In multivariate models, cues to action such as doctor recommendation, (RR 1.62, 95% CI: 1.25–2.10), perceived benefits (RR 1.25, 95% CI: 1.04–1.50), and perceived susceptibility (RR 1.21, 95% CI: 1.03–1.42) were significantly associated with increased likelihood of vaccine receipt among adults while high perceived barriers were associated with decreased likelihood (RR 0.38, 95% CI: 0.25–0.59). Similarly, parents reporting higher barriers were less likely (RR 0.58, 95% CI: 0.42–0.79) and those perceiving greater benefits (RR 4.16, 95% CI: 2.28–7.59) and severity (RR 1.13, 95% CI: 1.00–1.27 were more likely to vaccinate their children. The observed effects of perceptions of susceptibility, severity, and benefits were more pronounced at low cues to action for children, as were the effects of perceptions of barriers and severity among adults.

Conclusion

Perceived benefits and barriers are most strongly associated with vaccine receipt. However, the effects of various factors were most pronounced in the absence of cues to action, which may be an important component of targeted interventions.     

DNA methylation-independent loss of RARA gene expression in acute myeloid leukemia

The retinoic acid receptor (RAR) alpha gene (RARA) encodes 2 major isoforms and mediates positive effects of all-trans retinoic acid (ATRA) on myelomonocytic differentiation. Expression of the ATRA-inducible (RARalpha2) isoform increases with myelomonocytic differentiation and appears to be down-regulated in many acute myeloid leukemia (AML) cell lines. Here, we demonstrate that relative to normal myeloid stem/progenitor cells, RARalpha2 expression is dramatically reduced in primary AML blasts. Expression of the RARalpha1 isoform is also significantly reduced in primary AML cells, but not in AML cell lines. Although the promoters directing expression of RARalpha1 and RARalpha2 are respectively unmethylated and methylated in AML cell lines, these regulatory regions are unmethylated in all the AML patient cell samples analyzed. Moreover, in primary AML cells, histones associated with the RARalpha2 promoter possessed diminished levels of H3 acetylation and lysine 4 methylation. These results underscore the complexities of the mechanisms responsible for deregulation of gene expression in AML and support the notion that diminished RARA expression contributes to leukemogenesis.     

Pharmacokinetics of antimony in children treated for leishmaniasis with meglumine antimoniate

BACKGROUND: In some settings, the response to pentavalent antimonial therapy for leishmaniasis may be lower in children than in adults. We hypothesized that there are age-dependent pharmacokinetic differences of potential clinical relevance. METHODS: We compared the pharmacokinetics of antimony (Sb) in adults and 2 groups of children 3-6 years old who had cutaneous leishmaniasis treated with intramuscular meglumine antimoniate. Adults (n=9) and the first group of children (n=9) received 20 mg Sb/kg/day for 20 days; the second group of children (n=6) received 20 mg Sb/kg for 19 days and 30 mg Sb/kg on day 20. Drug exposure was assessed by the area under the 24-h time-concentration curve (AUC(0-24)) in plasma. RESULTS: Children (vs. adults) who received 20 mg/kg had a 42% lower AUC(0-24) (mean +/- SE, 111+/-7 vs. 190+/-10 mg x h/L, compared with adults; P<.001), a 16% lower peak concentration (32.7+/-0.9 vs. 38.8+/-2.1 mg/L; P=.04), and a 75% higher weight-adjusted clearance (0.185+/-0.013 vs. 0.106+/-0.006 L/h/kg; P<.001). The 30 mg/kg dose in children increased the AUC(0-24) to 164+/-10 mg x h/L and the peak concentration to 43.8+/-2.3 mg/L. CONCLUSIONS: Drug exposure is significantly lower in children than in adults treated with the same weight-adjusted regimen of meglumine antimoniate, which primarily stems from a higher antimony clearance rate.     

Broken pump or leaky filter? Renal dysfunction in heart failure a contemporary review

Renal dysfunction is a frequent and progressive complication of chronic heart failure and is a powerful predictor of cardiovascular mortality. It is intimately associated with cardiovascular disease even in its earliest stages. Although cardiovascular and renal disease share many risk factors, the prognostic implications do not simply reflect widespread atherosclerotic vascular disease as this appears to be as important in those with heart failure secondary to idiopathic dilated cardiomyopathy as it is in those with coronary artery disease. There may be a role in the progression of heart failure, as the deleterious effects of even “mild” renal impairment seem to be borne out in predicting outcome, in a broad range of heart failure patients including those with heart failure and preserved systolic function. Renal dysfunction is both an indication for, as well as frequently limiting intervention with intensive disease modifying therapy. Although renal impairment is common in heart failure and these patients are at higher risk for adverse events including death, they are under represented in clinical trials.     

应用非甾体抗炎药对高血压合并冠状动脉疾病患者的有害作用

慢性疼痛综合征患者常应用非甾体抗炎药( non-steroidal anti-inflammatory drugs,NSAID).许多这类患者有潜在的高血压和冠状动脉疾病.临床试验和系统性分析显示,选择性环氧化酶2抑制剂增加心肌梗死的风险[J].该发现可能导致更普遍地应用非选择性NSAID作为治疗慢性疼痛综合征的替代手...     

A Preclinical Animal Model to Assess the Effect of Pre-existing Immunity on AAV-mediated Gene Transfer

Hepatic adeno-associated virus (AAV)-serotype 2–mediated gene transfer results in sustained transgene expression in experimental animals but not in human subjects. We hypothesized that loss of transgene expression in humans might be caused by immune memory mechanisms that become reactivated upon AAV vector transfer. Here, we tested the effect of immunological memory to AAV capsid on AAV-mediated gene transfer in a mouse model. Upon hepatic transfer of an AAV2 vector expressing human factor IX (hF.IX), mice immunized with adenovirus (Ad) vectors expressing AAV8 capsid before AAV2 transfer developed less circulating hF.IX and showed a gradual loss of hF.IX gene copies in liver cells as compared to control animals. This was not observed in mice immunized with an Ad vectors expressing AAV2 capsid before transfer of rAAV8-hF.IX vectors. The lower hF.IX expression was primarily linked to AAV-binding antibodies that lacked AAV-neutralizing activity in vitro rather than to AAV capsid–specific CD8⁺ T cells.     

Anti-arrhythmic effects of lidocaine metabolites

Patients on lidocaine infusions for the control of arrhythmias accumulate significant concentrations of lidocaine metabolites. The potency of lidocaine in suppressing digitalis-induced arrhythmias in guinea pig atria was compared to that of two of the metabolites of lidocaine monoethyglycinexylidide (MEGX), and glycinexylidide (GX). The potency of MEGX relative to lidocaine was 0.833. GX was only $\text{1}\text{10}$ as potent. Thus, it would seem that MEGX may contribute to the total anti-arrhythmic effect of a lidocaine infusion.     

Current Smoking and Prognosis After Acute ST-Segment Elevation Myocardial Infarction: New Pathophysiological Insights

ObjectivesThe aim of this study was to mechanistically investigate associations among cigarette smoking, microvascular pathology, and longer term health outcomes in patients with acute ST-segment elevation myocardial infarction (MI).BackgroundThe pathophysiology of myocardial reperfusion injury and prognosis in smokers with acute ST-segment elevation MI is incompletely understood.MethodsPatients were prospectively enrolled during emergency percutaneous coronary intervention. Microvascular function in the culprit artery was measured invasively. Contrast-enhanced magnetic resonance imaging (1.5-T) was performed 2 days and 6 months post-MI. Infarct size and microvascular obstruction were assessed using late gadolinium enhancement imaging. Myocardial hemorrhage was assessed with T2* mapping. Pre-specified endpoints included: 1) all-cause death or first heart failure hospitalization; and 2) cardiac death, nonfatal MI, or urgent coronary revascularization (major adverse cardiovascular events). Binary logistic regression (odds ratio [OR] with 95% confidence interval [CI]) with smoking status was used.ResultsIn total, 324 patients with ST-segment elevation MI were enrolled (mean age 59 years, 73% men, 60% current smokers). Current smokers were younger (age 55 ± 11 years vs. 65 ± 10 years, p < 0.001), with fewer patients with hypertension (52 ± 27% vs. 53 ± 41%, p = 0.007). Smokers had better TIMI (Thrombolysis In Myocardial Infarction) flow grade (≥2 vs. ≤1, p = 0.024) and ST-segment resolution (none vs. partial vs. complete, p = 0.010) post–percutaneous coronary intervention. On day 1, smokers had higher circulating C-reactive protein, neutrophil, and monocyte levels. Two days post-MI, smoking independently predicted infarct zone hemorrhage (OR: 2.76; 95% CI: 1.42 to 5.37; p = 0.003). After a median follow-up period of 4 years, smoking independently predicted all-cause death or heart failure events (OR: 2.20; 95% CI: 1.07 to 4.54) and major adverse cardiovascular events (OR: 2.79; 95% CI: 2.30 to 5.99).ConclusionsSmoking is associated with enhanced inflammation acutely, infarct-zone hemorrhage subsequently, and longer term adverse cardiac outcomes. Inflammation and irreversible myocardial hemorrhage post-MI represent mechanistic drivers for adverse long-term prognosis in smokers. (Detection and Significance of Heart Injury in ST Elevation Myocardial Infarction. [BHF MR-MI]; NCT02072850)     

Increased plasma norepinephrine response to yohimbine in elderly men

BACKGROUND: The effects of aging on sympathetic nervous system and adrenomedullary outflow were estimated by the measurement of plasma norepinephrine (NE) and epinephrine (EPI) responses to yohimbine and clonidine in healthy young and healthy older subjects. METHODS: Yohimbine (0.65 mg/kg), clonidine (5 microg/kg), and placebo were administered on separate days in random order to 5 healthy older men (age 74 +/- 1 years) and 18 healthy young men (age 26 +/- 1 years). NE and EPI were measured by radioenzymatic assay in plasma samples obtained before and 30, 60, and 90 minutes after drug administration. RESULTS: Plasma NE increases after yohimbine were greater in older men than in young men. but plasma NE decreases following clonidine did not differ between groups. Plasma NE and systolic blood pressure were higher in older men than in young men at baseline but no longer differed 90 minutes after clonidine. Plasma EPI increases after yohimbine and decreases after clonidine did not differ between groups. CONCLUSIONS: These results suggest increased sympathetic nervous system outflow in human aging that is not a function of reduced responsiveness of alpha-2 adrenoreceptor-mediated feedback inhibition.