Development of Pediatric Dosage Preparation for CVD 103-HgR Live Oral Cholera Vaccine.

PXVX0200 is an oral cholera vaccine that is approved for use by the U.S. Food and Drug Administration and European Medicines Agency under the tradename Vaxchora. The vaccine is supplied as two packets, one containing buffer component and the other the active component, that are mixed with water and ingested. The aim of this study was to develop vaccine preparation methods that are appropriate for administering PXVX0200 to children. Developing oral liquid medication for children has unique challenges, including administration volume and palatability. These challenges were addressed by preparing PXVX0200 in different volumes and testing the potency of the vaccine in the presence of sweeteners, flavorings, and food and drinks. Vaccine potency, defined as colony-forming units/dose, was used to determine the compatibility of PXVX0200 with different vaccine preparation methods. We found that the reconstitution volume can be reduced from 100 to 50 mL to accommodate children aged 2 to 6 years and to 10 mL for children aged 6 months to 2 years, as long as the buffer concentration is the same as for the approved (100 mL) dose. Sucrose or stevia sweeteners may also be added without affecting the vaccine potency. Reconstitution in juices or foods was challenging because of effervescence caused by bicarbonate in the buffer component. An alternate preparation method was developed for reconstitution in baby formula. Vaccine preparation methods to make PXVX0200 appropriate for pediatric administration will facilitate administration of the vaccine to improve compliance and protect children from cholera infection while traveling.

CVD 103-HgR live, attenuated cholera vaccine strain viability in drinking waters from the US and Europe.

CVD 103-HgR live, attenuated oral cholera vaccine strain is indicated for single dose immunization against Vibrio cholerae, the causative agent for cholera. The vaccine packets containing buffer powder and lyophilized CVD 103-HgR are reconstituted in water and consumed. Studies were performed to explore the viability of CVD 103-HgR in drinking waters from common sources. CVD 103-HgR vaccine was reconstituted in bottled and tap waters from the United States and Europe, and viability was measured via colony forming units assay. Chemical analysis of select water samples was used to identify chemicals that have a negative effect on CVD 103-HgR viability. CVD 103-HgR titers were stable in all bottled waters tested, including purified bottled water, bottled spring water, and sparkling waters. However, tap water from certain cities in the US and Europe affected viability and are not compatible with vaccine. Water chemistry revealed that these tap waters contained copper, likely leached from copper plumbing. These studies give high confidence in the stability of CVD 103-HgR reconstituted in a variety of bottled waters. Waters containing copper, including tap water, should not be used to reconstitute CVD 103-HgR strain oral vaccine due to the common use of copper plumbing.

Home Administration of CVD 103-HgR: A Live Attenuated Oral Cholera Vaccine.

Vaccination is a well-established means for prevention and spread of disease in people traveling abroad. Although vaccines to diseases such as cholera are recommended by world health agencies, they are seldom required even when traveling to endemic regions. Consequences of noncompliance can affect traveler's health and spread diseases to new regions, as occurred in Haiti in 2010 when United Nations peacekeepers from Nepal, where a cholera outbreak was underway, introduced the disease to the region. Steps to increase vaccine recommendation compliance should therefore be an integral part of vaccine development. PXVX0200 contains Center for Vaccine Development 103-HgR live, attenuated recombinant Vibrio cholerae vaccine strain, and is indicated for single-dose immunization against the bacteria that causes cholera. It is supplied as one buffer and one active component packet to be mixed into water and ingested. Administration instructions are designed to be "user friendly" with flexibility for self-administration, thus promoting compliance. Studies to support self-administration were conducted to cover stability of the vaccine outside of normal storage conditions, potency in case of misadministration, and disposal procedures to minimize environmental impact. The principal findings showed that the stability of vaccine was maintained under conditions allowing for transport times and temperature conditions as well as when misadministration errors were made. Finally, the vaccine was effectively neutralized with hot water and soap to prevent bacterial environmental contamination in the event of an accidental spill. The conclusion is that PXVX0200 oral vaccine is stable, easy to formulate and dispose of, and is amenable to self-administration.

Coronary Artery Disease in Patients with HIV Infection: An Update.

Premature cardiovascular disease among the HIV-infected population is of great concern among clinicians. The increased life expectancy of HIV-infected individuals is mainly due to the early detection of infection and the advent of antiretroviral therapy. Once known as a deadly disease, HIV infection has transitioned into a chronic condition. Cardiovascular disease in this population is thought to progress early due to traditional and non-traditional risk factors. Early detection of subclinical atherosclerosis has become a center of focus in research as our complete understanding of this process it not yet well known. Advancements in cardiac computed tomography angiography has enabled the exploration of coronary artery disease by further evaluation of coronary stenosis and plaque analysis. An increase in cardiovascular event rates in this population is currently thought to be linked to antiretroviral therapy, Framingham risk factors, and HIV. We sought to present an updated comprehensive review of the available literature on HIV related to atherosclerosis and cardiovascular risk.

Radiation exposure and coronary artery calcium scans in the society for heart attack prevention and eradication cohort.

Coronary artery calcium (CAC) scoring is used in asymptomatic patients to improve their clinically predicted risk for future cardiovascular events. Current CT protocols seek to reduce radiation exposure without diminishing image quality. Reported radiation exposure remains widely variable (0.8-5 mSv) depending on the type of protocol. In this study, we report the radiation exposure of CAC scoring from the Society for Heart Attack Prevention and Eradication (SHAPE) early detection program cohort sites, which spanned multiple centers using 64-MDCT (multi-detector computed tomography) scanners. We reviewed radiation exposure in milliSieverts (mSv) for 82,214 participants from the SHAPE early detection program cohort who underwent CAC scoring. This occurred over a 2.5-year period (2012-2014) divided among 33 sites in 7 countries with four different types 64-MDCT scanners. The effective radiation dose was reported as mSv. Mean radiation dosing amongst all 82,214 participants was 1.03 mSv, a median dose of 0.94 mSv. The mean radiation dose ranged from 0.76 to 1.31 mSv across the 33 sites involved with the SHAPE program cohort. Subgroup analysis by age, gender or body mass index (BMI) less than 30 kg/m2 showed no variability. Radiation dose in patients with BMI > 30 kg/m2 were significantly greater than other subgroups (µ = 1.96 mSv, p < 0.001). The use of 64-MDCT scanners and protocols provide the effective radiation dose for CAC scoring, which is approximately 1 mSv. This is consistently lower than previously reported for CAC scanning, regardless of scanner type, age or gender. In contrast, a greater BMI influenced mean radiation doses.

Effects of eicosapentaenoic acid and docosahexaenoic acid on lipoproteins in hypertriglyceridemia.

PURPOSE OF REVIEW: The treatment of hypertriglyceridemia (HTG) with ω-3 fatty acid preparations adds a novel therapy to reduce cardiovascular disease. This review examines the effects of eicosapentaenoic acid (EPA) and docosahexaenoic acid on lipoproteins and the cardioprotective effects in HTG. RECENT FINDINGS: The evidence that ω-3 fatty acid therapy at prescription strength is effective and safe at lowering triglyceride levels is growing. Although EPA/docosahexaenoic acid formulations did lower triglyceride levels, an increase in low-density lipoproteins was observed and outcome data were mixed. More recent trials have shown that decreased levels of low-density lipoprotein can be achieved with EPA preparations. Although the cardiovascular outcomes data are not fully available, meta-analysis of available data reports protection against vascular disease. SUMMARY: The addition of ω-3 fatty acid treatment should be considered in patients with severe HTG as well as high-risk patients for atherosclerotic disease. Emerging data are supportive, but long-term outcome studies are still underway.

Coronary artery disease in patients with HIV infection.

HIV-infected patients are known to be at risk for premature coronary artery disease. This emerging paradigm is a rising concern for clinicians. Due to advances in the treatment of HIV, this once fatal infection has been transformed into a chronic illness. Traditional risk factors paired with the long-term use of antiretroviral therapy (ART) and chronic inflammation leads to premature atherosclerosis, particularly progression of atherosclerotic plaque. This population of patients requires early recognition of subclinical atherosclerosis, as well aggressive primary and secondary prevention strategies among the multi-disciplinary team of physicians caring for them. We sought to present a comprehensive review of the available literature related to HIV and atherosclerosis and cardiovascular risk.

Botulinum injection for the management of myofascial pain in the masticatory muscles. A prospective outcome study.

We prospectively analysed the outcome after botulinum injection in patients who did not recover after conservative measures to manage masticatory myofascial pain, and who were not willing to take low dose tricyclic antidepressants as a muscle relaxant. We prospectively 62 patients were assessed with visual analogue scores (VAS) for pain on the affected side before, and 6 weeks after botulinum injection(s) (50 units Dysport in up to 3 sites), and measured mouth opening in mm. Of those treated 49 (79%) showed at least some improvement (pain reduced by more than 25%). Patients reported more than a 90% reduction in the VAS for 25 (30%) of the 84 sides of the face treated. Only 22 of the 62 patients had more than one course of treatment to the same side. Interincisal distance improved by a mean/median of 0.9 mm (p<0.03) after treatment. Side effects included 3 cases of temporary weakness of a facial muscle. Ranking the VAS pain scores using the Wilcoxon test before and after injection showed a significant reduction in pain (median change -29.5, interquartile range -53 to -16, p<0.0001). The treatment significantly improved patients' pain scores and the overall mean/median reduction in pain was 57%. Botulinum injection does not guarantee complete resolution of myofascial pain, but it usually has some beneficial effect in improving the symptoms, and should be considered as an alternate treatment for masticatory myofascial pain if conservative methods have failed.

A meandering mesenteric artery.

An 83-year-old woman with a history of peripheral vascular disease presented for evaluation of lower left extremity discomfort. A peripheral multidetector CT angiography showed a dilated inferior mesenteric artery acting as an important source of retrograde collateral perfusion secondary to a celiac axis stenosis.

Screening for heart disease: C-reactive protein versus coronary artery calcium.

The Framingham model has become the standard to assess future risk of coronary artery disease. Several nontraditional risk factors have been suggested to improve risk stratification to provide a new algorithm for predicting coronary heart disease (CHD). Two factors with the most available data include C-reactive protein (CRP) and coronary artery calcification (CAC). CRP, a well-established biomarker of inflammation, has shown very inconsistent data to predict CHD, and no study to date shows improvement in the C-statistic; in addition, reclassification is modest (<10% of patients are reclassified to higher or lower risk categories). CAC seems to hold a greater promise in the prediction of CHD and demonstrates a stronger relationship to future cardiac events, with all studies demonstrating improvement in the C-statistic when added to the Framingham risk score. Measurement of CAC consistently provides reclassification of patients more accurately to the Framingham risk model. Only four studies have evaluated both CAC and CRP in the same cohort for future cardiovascular events, but all of these showed significant prediction for coronary artery disease using CAC and no significant prediction ability for CRP. Current review of the literature available suggests CAC to be more relevant in evaluating CHD in a clinical setting. Given the higher cost of CAC scanning compared with CRP, cost-effectiveness studies are still needed.

Layer-by-Layer assembly of TiO2 nanoparticles for stable hydrophilic biocompatible coatings.

Stable, super-hydrophilic (water contact angle approximately equal to 0 degrees) titanium dioxide nanoparticle thin films have been obtained on substrates with different initial wettability such as glass, poly(methyl methacrylate) and poly(dimethyl siloxane) using layer-by-layer nano-assembly method. Titanium dioxide nanoparticles were alternated with poly(styrene sulfonate) to form films of thickness ranging from 11 nm to 220 nm. The hydrophilicity of these thin films increases with increasing number of deposited PSS/TiO2 bilayers. It was found that 2, 5 and 20 layers were needed to form super-hydrophilic TiO2 coating on glass, PMMA and PDMS respectively. Oxygen plasma treatment of substrate surfaces enhanced the formation of homogeneous TiO2 films and accelerated the formation of hydrophilic layers. Super-hydrophilicity has been shown to be unique to PSS/TiO2 films as compared with other polyelectrolyte/nanoparticle layers, and UV irradiation may restore hydrophilicity even after months of storing of the samples. Biocompatibility of TiO2 nanoparticle films has been demonstrated by the successful cell culture of human dermal fibroblast.

Nanoassembly of biodegradable microcapsules for DNA encasing.

A new microcontainer for DNA delivery based on biocompatible poly[beta-glucuronic acid-(1 --> 3)-N-acetyl-beta-galactosamine-6-sulfate-(1 --> 4)](chondroitin sulfate)/poly(-l-arginine) microcapsules with 40 nm thick molecularly organized shell was proposed. DNA molecules were deposited as DNA/sperimidine complex on the surface of template 4 mum core particles followed by layer-by-layer nanoassembly of protective chondroitin sulfate/poly(-l-arginine) shell. After template core dissolution, DNA molecules were captured inside microcapsules retaining a natural double-helix structure. The developed DNA encapsulation approach can be employed for targeted delivery of plasmid DNA in living cells.