All that glisters is not gold: a comparison of electronic monitoring versus filled prescriptions – an observational study

BACKGROUND: Poor compliance with antihypertensive medication is assumed to be an important reason for unsatisfactory control of blood pressure. Poor compliance is difficult to detect. Each method of measuring compliance has its own strengths and weaknesses. The aim of the present study was to compare patient compliance with antihypertensive drugs as measured by two methods, electronic monitoring versus refill compliance. METHODS: 161 patients with a diagnosis of hypertension for at least a year prior to inclusion, and inadequate blood pressure control (systolic blood pressure ≥ 160 mmHg and/or diastolic blood pressure ≥ 95 mmHg) despite the use of antihypertensive drugs, were included. Patients' pharmacy records from 12 months prior to inclusion were obtained. Refill compliance was calculated as the number of days for which the pills were prescribed divided by the total number of days in this period. After inclusion compliance was measured with an electronic monitor that records time and date of each opening of the pillbox. Agreement between both compliance measures was calculated using Spearman's correlation coefficient and Cohen's kappa coefficient. RESULTS: There was very little agreement between the two measures. Whereas refill compliance showed a large range of values, compliance as measured by electronic monitoring was high in almost all patients with estimates between 90% and 100%. Cohen's kappa coefficient was 0.005. CONCLUSION: While electronic monitoring is often considered to be the gold standard for compliance measurements, our results suggest that a short-term electronic monitoring period with the patient being aware of electronic monitoring is probably insufficient to obtain valid compliance data. We conclude that there is a strong need for more studies that explore the effect of electronic monitoring on patient's compliance

Standing orders for influenza and pneumococcal polysaccharide vaccination: Correlates identified in a national survey of U.S. Primary care physicians

<p>Abstract</p> <p>Background</p> <p>Standing orders programs (SOPs) allow non-physician medical staff to assess eligibility and administer vaccines without a specific physician's order. SOPs increase vaccination rates but are underutilized.</p> <p>Method</p> <p>In 2009, correlates of SOPs use for influenza vaccine and pneumococcal polysaccharide vaccination (PPV) were assessed in a nationally representative, stratified random sample of U.S. physicians (n = 880) in family and internal medicine who provided office immunization. The response rate was 67%. Physicians reporting no SOPs, only influenza SOPs, and joint influenza and PPV SOPs were compared using multinomial and logistic regression models to examine individual and practice-level correlates.</p> <p>Results</p> <p>23% reported using SOPs consistently for both influenza vaccine and PPV, and 20% for influenza vaccination only, with the remainder not using SOPs. Practice-level factors that distinguished practices with joint influenza-PPV SOPs included perceived practice openness to change, strong practice teamwork, access to an electronic medical record, presence of an immunization champion in the practice, and access to nurse/physician assistant staff as opposed to medical assistants alone.</p> <p>Discussion</p> <p>Physicians in practices with SOPs for both vaccines reported greater awareness of ACIP recommendations and/or Medicare regulations and were more likely to agree that SOPs are an effective way to boost vaccination coverage. However, implementation of both influenza and PPV SOPs was also associated with a variety of practice-level factors, including teamwork, the presence of an immunization champion, and greater availability of clinical assistants with advanced training.</p> <p>Conclusions</p> <p>Practice-level factors are critical for the adoption of more complex SOPs, such as joint SOPs for influenza and PPV.</p

Inhibitory Receptors Are Expressed by Trypanosoma cruzi-Specific Effector T Cells and in Hearts of Subjects with Chronic Chagas Disease

We had formerly demonstrated that subjects chronically infected with Trypanosoma cruzi show impaired T cell responses closely linked with a process of T cell exhaustion. Recently, the expression of several inhibitory receptors has been associated with T cell dysfunction and exhaustion. In this study, we have examined the expression of the cytotoxic T lymphocyte antigen 4 (CTLA-4) and the leukocyte immunoglobulin like receptor 1 (LIR-1) by peripheral T. cruzi antigen-responsive IFN-gamma (IFN-γ)-producing and total T cells from chronically T. cruzi-infected subjects with different clinical forms of the disease. CTAL-4 expression was also evaluated in heart tissue sections from subjects with severe myocarditis. The majority of IFN-γ-producing CD4+ T cells responsive to a parasite lysate preparation were found to express CTLA-4 but considerably lower frequencies express LIR-1, irrespective of the clinical status of the donor. Conversely, few IFN-γ-producing T cells responsive to tetanus and diphtheria toxoids expressed CTLA-4 and LIR-1. Polyclonal stimulation with anti-CD3 antibodies induced higher frequencies of CD4+CTAL-4+ T cells in patients with severe heart disease than in asymptomatic subjects. Ligation of CTLA-4 and LIR-1 with their agonistic antibodies, in vitro, reduces IFN-γ production. Conversely, CTLA-4 blockade did not improved IFN-γ production in response to T. cruzi antigens. Subjects with chronic T. cruzi infection had increased numbers of CD4+LIR-1+ among total peripheral blood mononuclear cells, relative to uninfected individuals and these numbers decreased after treatment with benznidazole. CTLA-4 was also expressed by CD3+ T lymphocytes infiltrating heart tissues from chronically infected subjects with severe myocarditis. These findings support the conclusion that persistent infection with T. cruzi leads to the upregulation of inhibitory receptors which could alter parasite specific T cell responses in the chronic phase of Chagas disease

cGMP-Phosphodiesterase Inhibition Enhances Photic Responses and Synchronization of the Biological Circadian Clock in Rodents

The master circadian clock in mammals is located in the hypothalamic suprachiasmatic nuclei (SCN) and is synchronized by several environmental stimuli, mainly the light-dark (LD) cycle. Light pulses in the late subjective night induce phase advances in locomotor circadian rhythms and the expression of clock genes (such as Per1-2). The mechanism responsible for light-induced phase advances involves the activation of guanylyl cyclase (GC), cGMP and its related protein kinase (PKG). Pharmacological manipulation of cGMP by phosphodiesterase (PDE) inhibition (e.g., sildenafil) increases low-intensity light-induced circadian responses, which could reflect the ability of the cGMP-dependent pathway to directly affect the photic sensitivity of the master circadian clock within the SCN. Indeed, sildenafil is also able to increase the phase-shifting effect of saturating (1200 lux) light pulses leading to phase advances of about 9 hours, as well as in C57 a mouse strain that shows reduced phase advances. In addition, sildenafil was effective in both male and female hamsters, as well as after oral administration. Other PDE inhibitors (such as vardenafil and tadalafil) also increased light-induced phase advances of locomotor activity rhythms and accelerated reentrainment after a phase advance in the LD cycle. Pharmacological inhibition of the main downstream target of cGMP, PKG, blocked light-induced expression of Per1. Our results indicate that the cGMP-dependent pathway can directly modulate the light-induced expression of clock-genes within the SCN and the magnitude of light-induced phase advances of overt rhythms, and provide promising tools to design treatments for human circadian disruptions

Development of targeted therapy for ovarian cancer mediated by a plasmid expressing diphtheria toxin under the control of H19 regulatory sequences

<p>Abstract</p> <p>Background</p> <p>Ovarian cancer ascites fluid (OCAF), contains malignant cells, is usually present in women with an advanced stage disease and currently has no effective therapy. Hence, we developed a new therapy strategy to target the expression of diphtheria toxin gene under the control of H19 regulatory sequences in ovarian tumor cells. H19 RNA is present at high levels in human cancer tissues (including ovarian cancer), while existing at a nearly undetectable level in the surrounding normal tissue.</p> <p>Methods</p> <p>H19 gene expression was tested in cells from OCAF by the in-situ hybridization technique (ISH) using an H19 RNA probe. The therapeutic potential of the toxin vector DTA-H19 was tested in ovarian carcinoma cell lines and in a heterotopic animal model for ovarian cancer.</p> <p>Results</p> <p>H19 RNA was detected in 90% of patients with OCAF as determined by ISH. Intratumoral injection of DTA-H19 into ectopically developed tumors caused 40% inhibition of tumor growth.</p> <p>Conclusion</p> <p>These observations may be the first step towards a major breakthrough in the treatment of human OCAF, while the effect in solid tumors required further investigation. It should enable us to identify likely non-responders in advance, and to treat patients who are resistant to all known therapies, thereby avoiding treatment failure.</p

Frequent Fires in Ancient Shrub Tundra: Implications of Paleorecords for Arctic Environmental Change

Understanding feedbacks between terrestrial and atmospheric systems is vital for predicting the consequences of global change, particularly in the rapidly changing Arctic. Fire is a key process in this context, but the consequences of altered fire regimes in tundra ecosystems are rarely considered, largely because tundra fires occur infrequently on the modern landscape. We present paleoecological data that indicate frequent tundra fires in northcentral Alaska between 14,000 and 10,000 years ago. Charcoal and pollen from lake sediments reveal that ancient birch-dominated shrub tundra burned as often as modern boreal forests in the region, every 144 years on average (+/− 90 s.d.; n = 44). Although paleoclimate interpretations and data from modern tundra fires suggest that increased burning was aided by low effective moisture, vegetation cover clearly played a critical role in facilitating the paleofires by creating an abundance of fine fuels. These records suggest that greater fire activity will likely accompany temperature-related increases in shrub-dominated tundra predicted for the 21st century and beyond. Increased tundra burning will have broad impacts on physical and biological systems as well as on land-atmosphere interactions in the Arctic, including the potential to release stored organic carbon to the atmosphere