Flu in 15: a novel 15-minute education program to promote acceptance of the influenza vaccine among health care workers.

INTRODUCTION AND RATIONALE: A performance improvement project was undertaken to increase health care worker (HCW) influenza vaccination acceptance rates in the long-term care setting by using a novel 15-minute education intervention called the "Flu in 15." As a core principle, we taught that more Americans die from complications of influenza than hepatitis B, yet there remains individual reluctance and barriers to achieve high acceptance rates of influenza vaccination among HCWs. METHODS: During chance encounters we offered the Flu in 15 in-service to all HCWs at the Johns Hopkins Bayview Care Center including certified nursing assistants (also called geriatric nursing assistants), registered nurses, registered dieticians, environment staff, physical therapists, occupational therapists, speech therapists, respiratory therapists, social workers, and administrators. Of the 106 of 347 HCWs who participated in the Flu in 15 in-service, 58 were by chance encounters selected to be surveyed based on convenience. We surveyed 68 of 241 HCWs who did not attend the Flu in 15 in-service as a comparison. RESULTS: Of the 58 participants who were asked if the in-service helped them understand why a flu vaccine is needed yearly, we found that 15% responded "tremendously," 48% "a lot," 26% "some," 7% "a little," and 2% "no." We had 24% report that the program was effective in changing their behavior to accept the flu vaccination for the first time. We found that 49% responded that the in-service was effective in either changing their behavior to accept the flu vaccination for the first time or reaccept it if recently declined in previous years. With respect to motivation, 42% of the certified nursing assistants stated that the in-service made them think more about returning to school to get a license in some area of health care. Although not cause and effect, we observed an increase in the HCW acceptance rate of the influenza vaccine from 65% in 2006-2007 to 73% in 2007-2008. We noticed a decreased trend in patient deaths attributed to complications of influenza with 4 deaths in 2006-2007 and no deaths in 2007-2008. CONCLUSIONS: The Flu in 15 in-service promoted a better understanding of the importance of the influenza vaccine and demonstrated an associated increase in HCW acceptance of the flu vaccine. Although we cannot claim cause and effect, we noted a decrease in resident mortality in the intervention year compared with the prior year. Now that some medical centers require yearly influenza vaccines among HCWs, the education component remains relevant to provide reason behind the mandate.

In vivo gene transfer of parvalbumin improves diastolic function in aged rat hearts.

OBJECTIVE: Diastolic dysfunction is a characteristic finding of the aged mammalian heart. Parvalbumin acts as a Ca2+ sink and enhances relaxation in skeletal muscle, and overexpression of parvalbumin in myocardium increased cardiac relaxation in vitro as well as in vivo. Therefore, the objective of this study is to test the hypothesis that in vivo gene transfer of parvalbumin will improve diastolic dysfunction in aged rat heart. METHODS: We used adenovirus to transfer parvalbumin into two different rat models of aging: the Fischer 344 (F344) and the Fischer 344 x Brown Norway F1 hybrid (F344 x BN). Cardiac function was measured and compared after gene transfer. RESULTS: In vivo overexpression of parvalbumin in both rat aging models had no effect on systolic parameters but reduced left ventricular diastolic pressure and the time course of pressure decline. Overexpression of parvalbumin also improved the force frequency relationship in senescent rats. CONCLUSION: In vivo overexpression of parvalbumin improves diastolic dysfunction in two rat models of senescence, and this effect is independent of the rat strain investigated. The results show promise that gene therapy of parvalbumin may address the impaired Ca2+ homeostasis and diastolic dysfunction without an increase in energy expenditure.

Gene transfer of parvalbumin improves diastolic dysfunction in senescent myocytes.

BACKGROUND: Impaired relaxation is a cardinal feature of senescent myocardial dysfunction. Recently, adenoviral gene transfer of parvalbumin, a small calcium-buffering protein found exclusively in skeletal muscle and neurons, has been shown to improve cardiomyocyte relaxation in disease models of diastolic dysfunction. The goal of this study was to investigate whether parvalbumin gene transfer could reverse diastolic dysfunction in senescent cardiomyocytes. METHODS AND RESULTS: Myocytes were isolated from senescent (26 months) and adult (6 months) F344/BN hybrid rats and were infected with Ad.Parv.GFP (where GFP is green fluorescent protein) or Ad.betagal.GFP at a multiplicity of infection of 250 for 48 hours. Uninfected senescent and adult myocytes served as controls. After stimulation at a frequency of 0.5 Hz, intracellular calcium transients and myocyte contractility were measured using dual excitation spectrofluorometry and video-edge detection system (Ionoptix). Parvalbumin significantly improved relaxation parameters in senescent myocytes: Both the rate of calcium transient decay and the rate of myocyte relengthening were dramatically increased in senescent cardiac myocytes transduced with parvalbumin compared with nontransduced and GFP-expressing controls, with no effect on myocyte shortening. CONCLUSIONS: Parvalbumin expression corrects impaired relaxation in aging myocytes. Given that abnormalities of myocyte relaxation underlie diastolic dysfunction in a large proportion of elderly patients with heart failure, gene transfer of parvalbumin may thus be a novel approach to target diastolic dysfunction in senescent myocardium.

Apoptosis in heart failure and the senescent heart.

The progressive loss of cardiac myocytes by apoptotic cell death has been discussed as an important pathogenic component in the failing myocardium as well in the aging heart. The degree to which apoptosis contributes to myocyte loss in these conditions, however, is a controversial issue. This review focuses on the regulation of apoptosis, evidence implicating apoptosis as a mechanism for the progression and development of heart failure, the role of apoptotic death in senescent cardiac dysfunction, as well as on the problems of detection of apoptosis.

Telomerase and the aging heart.

Telomeres are highly conserved structures that cap and protect the ends of linear chromosomes. The telomerase enzyme is present in germline cells as well as in many rapidly dividing tissues and serves to maintain chromosome length and integrity during cell division. Telomerase activity is typically reduced as an organism ages, and this phenomenon has been implicated in the aging process. In this Perspective, we focus on the effects of both gene knockout and gene replacement of telomerase in the heart and discuss the implications of these findings for potential cardiovascular therapeutics.

Genetic editing of dysfunctional myocardium.

Ongoing advances in vector technology, cardiac gene delivery, and, most importantly, our understanding of HF pathogenesis, encourage consideration of gene therapy for HF at this time. At the present time, strategies that enhance sarcoplasmic calcium transport are supported by substantial evidence in both cardiomyocytes derived from patients with HF and in animal models. In addition, efforts to promote cardiomyocyte survival and function through modulation of antiapoptotic signaling appear quite promising. In ongoing efforts to target cardiac dysfunction, gene transfer provides an important tool to improve our understanding of the relative contribution of specific pathways. Through such experiments, molecular targets can be validated for therapeutic intervention, whether pharmacologic or genetic. Translating these basic investigations into clinical gene therapy for HF, however, remains a formidable challenge. Further development of concepts established in rodent models will be required in large animal models with clinical grade vectors and delivery systems to evaluate both efficacy and safety of these approaches. Nevertheless, practical advances and our growing understanding of the molecular pathogenesis of HF provide reason for cautious optimism.

Decreased efficiency of adenovirus-mediated gene transfer in aging cardiomyocytes.

BACKGROUND: Aging is an independent risk factor for the development of cardiovascular disease. Clinical application of myocardial gene transfer may be best suited in the elderly. In vivo gene transfer by adenovirus is less efficient in aging myocardium. METHODS AND RESULTS: When infected with adenovirus containing beta-galactosidase (beta-gal) and green fluorescent protein (GFP) driven by cytomegalovirus promoters in vitro, aging rat cardiac myocytes exhibit significantly lower infectivity and delayed transgene expression compared with adult controls. Abnormalities of viral internalization may be one mechanism accounting for this difference. To investigate this, we studied expression levels of the coxsackievirus and adenovirus receptor (CAR) as well as other potential integrins involved in the internalization of adenoviruses. CAR expression tended to be upregulated whereas among potential integrins, alpha(3)beta(1) was downregulated in aging cardiac myocytes. Blocking the beta(1) component of alpha(3)beta(1) further decreased infectivity, suggesting that the interaction between the penton base of the adenovirus and beta(1) maybe a crucial component of the viral entry mechanism. CONCLUSIONS: These results suggest that it is integrin-stimulated internalization rather than the adenovirus-CAR interaction that plays a vital role in adenoviral entry. The downregulation of integrins observed in senescent cells may be a key mechanism accounting for the decrease in viral infectivity seen in these cells. These findings have implications for the gene therapy treatment of myocardial failure in the elderly.

Modulating signaling pathways in hypertrophy and heart failure by gene transfer.

Gene transfer to the heart is a novel concept that holds great promise both as a therapeutic and an experimental tool. With the advent of improved vector technology and new insights into the pathophysiology of heart failure, it is now possible to target specific intracellular signaling pathways by adenoviral gene transfer. By over or under expressing a specific protein, complex pathways can be probed specifically, and the role of various molecular targets within crucial intracellular pathways can be more precisely defined. This review highlights recent advances made in the field of myocardial gene transfer, with an emphasis on how manipulation of signal transduction pathways by adenoviral gene transfer has been used to elucidate the pathophysiology underlying abnormal cardiac phenotypes that lead to cardiac failure, such as hypertrophy, contractile dysfunction, and apoptosis.

Titin--springing back to youth?

Mutations in the muscle protein titin have been linked to dilated cardiomyopathy, a condition in which the heart chambers are enlarged and blood is ineffectively pumped, in humans and in animal models. This protein, which is a component of sarcomeres, provides essential scaffolding for other muscle proteins and acts as a spring to confer passive elasticity on the cardiomyocyte. Several titin isoforms exist, and they display varying size and degrees of elasticity. We review two interesting reports that show how variations in titin isoforms might be implicated in cardiac failure.