Approved but non-funded vaccines: Accessing individual protection

AbstractFunded immunization programs are best able to achieve high participation rates, optimal protection of the target population, and indirect protection of others. However, in many countries public funding of approved vaccines can be substantially delayed, limited to a portion of the at-risk population or denied altogether. In these situations, unfunded vaccines are often inaccessible to individuals at risk, allowing potentially avoidable morbidity and mortality to continue to occur. We contend that private access to approved but unfunded vaccines should be reconsidered and encouraged, with recognition that individuals have a prerogative to take advantage of a vaccine of potential benefit to them whether it is publicly funded or not. Moreover, numbers of “approved but unfunded” vaccines are likely to grow because governments will not be able to fund all future vaccines of potential benefit to some citizens. New strategies are needed to better use unfunded vaccines even though the net benefits will fall short of those of funded programs.Canada, after recent delays funding several new vaccine programs, has developed means to encourage private vaccine use. Physicians are required to inform relevant patients about risks and benefits of all recommended vaccines, publicly funded or not. Likewise, some provincial public health departments now recommend and promote both funded and unfunded vaccines. Pharmacists are key players in making unfunded vaccines locally available. Professional organizations are contributing to public and provider education about unfunded vaccines (e.g. herpes zoster, not funded in any province). Vaccine companies are gaining expertise with direct-to-consumer advertising. However, major challenges remain, such as making unfunded vaccines more available to low-income families and overcoming public expectations that all vaccines will be provided cost-free, when many other recommended personal preventive measures are user-pay. The greatest need is to change the widespread perception that approved vaccines should be publicly funded or ignored

The Effect of Salsalate Therapy on Endothelial Function in a Broad Range of Subjects

Background: Inflammation is fundamental to the development of atherosclerosis. We examined the effect of anti‐inflammatory doses of salicylate on endothelium‐dependent vasodilation, a biomarker of cardiovascular risk, in a broad range of subjects. Methods and Results: We performed a randomized, double‐blind, placebo‐controlled crossover trial evaluating the effects of 4 weeks of high‐dose salsalate (disalicylate) therapy on endothelium‐dependent flow‐mediated and endothelium‐independent vasodilation. Fifty‐eight subjects, including 17 with metabolic syndrome, 13 with atherosclerosis, and 28 healthy controls, were studied. Among all subjects, endothelium‐dependent flow‐mediated vasodilation decreased after salsalate compared with placebo therapy (P=0.01), whereas nitroglycerin‐mediated, endothelium‐independent vasodilation was unchanged (P=0.97). Endothelium‐dependent flow‐mediated vasodilation after salsalate therapy was impaired compared with placebo therapy in subjects with therapeutic salicylate levels (n=31, P0.2). Conclusions: Salsalate therapy, particularly when therapeutic salicylate levels are achieved, impairs endothelium‐dependent vasodilation in a broad range of subjects. These data raise concern about the possible deleterious effects of anti‐inflammatory doses of salsalate on cardiovascular risk. Clinical Trial Registration URL: www.clinicaltrials.gov. Unique Identifiers: NCT00760019 and NCT00762827

Pharmacological and combined interventions to reduce vaccine injection pain in children and adults systematic review and meta-analysis

Background: This systematic review assessed the effectiveness and safety of pharmacotherapy and combined interventions for reducing vaccine injection pain in individuals across the lifespan. Design/Methods: Electronic databases were searched for relevant randomized and quasi-randomized controlled trials. Self-reported pain and fear as well as observer-rated distress were critically important outcomes. Data were combined using standardized mean difference (SMD) or relative risk with 95% confidence intervals (CI). Results: Fifty-five studies that examined breastfeeding (which combines sweet-tasting solution, holding, and sucking), topical anesthetics, sweet-tasting solutions (sucrose, glucose), vapocoolants, oral analgesics, and combination of 2 versus 1 intervention were included. The following results report findings of analyses of critical outcomes with the largest number of participants. Compared with control, acute distress was lower for infants breastfed: (1) during vaccination (n=792): SMD -1.78 (CI, -2.35, -1.22) and (2) before vaccination (n=100): SMD -1.43 (CI, -2.14, -0.72). Compared with control/placebo, topical anesthetics showed benefit on acute distress in children (n=1424): SMD -0.91 (CI, -1.36, -0.47) and self-reported pain in adults (n=60): SMD -0.85 (CI, -1.38, -0.32). Acute and recovery distress was lower for children who received sucrose (n=2071): SMD -0.76 (CI, -1.19, -0.34) or glucose (n=818): SMD -0.69 (CI, -1.03, -0.35) compared with placebo/no treatment. Vapocoolants reduced acute pain in adults [(n=185), SMD -0.78 (CI, -1.08, -0.48)] but not children. Evidence from other needle procedures showed no benefit of acetaminophen or ibuprofen. The administration of topical anesthetics before and breastfeeding during vaccine injections showed mixed results when compared with topical anesthetics alone. There were no additive benefits of combining glucose and non-nutritive sucking (pacifier) compared with glucose or non-nutritive sucking (pacifier) alone or breastfeeding and sucrose compared with breastfeeding or sucrose alone. Conclusions: Breastfeeding, topical anesthetics, sweet-tasting solutions, and combination of topical anesthetics and breastfeeding demonstrated evidence of benefit for reducing vaccine injection pain in infants and children. In adults, limited data demonstrate some benefit of topical anesthetics and vapocoolants

Implementation Effectiveness of a Parent-Directed YouTube Video ("It Doesn't Have To Hurt") on Evidence-Based Strategies to Manage Needle Pain: Descriptive Survey Study

Background: Despite the availability of high-quality evidence and clinical practice guidelines for the effective management of pediatric pain, this evidence is rarely used in practice for managing children’s pain from needle procedures such as vaccinations. Parents are generally unaware of pain management strategies they can use with their children. Objective: This study aimed to develop, implement, and evaluate the implementation effectiveness of a parent-directed YouTube video on evidence-based strategies to manage needle pain in children. Methods: This was a descriptive study. Analytics were extracted from YouTube to describe video reach. A Web-based survey was used to seek parent and health care professional (HCP) feedback about the video. The 2-minute 18-second video was launched on YouTube on November 4, 2013. In the video, a 4-year-old girl tells parents what they should and should not do to help needles hurt less. The key evidence-based messages shared in the video were distraction, deep breathing, and topical anesthetic creams. A group of parents (n=163) and HCPs (n=278) completed the Web-based survey. Measures of reach included number of unique views, country where the video was viewed, sex of the viewer, and length of watch time. The Web-based survey assessed implementation outcomes of the video, such as acceptability, appropriateness, penetration, and adoption. Results: As of November 4, 2018 (5 years after launch), the video had 237,132 unique views from 182 countries, with most viewers watching an average of 55.1% (76/138 seconds) of the video. Overall, both parents and HCPs reported strong acceptance of the video (ie, they liked the video, found it helpful, and felt more confident) and reported significant improvements in plans to use distraction, deep breathing, and topical anesthetic creams. Conclusions: This parent-directed YouTube video was an acceptable and appropriate way to disseminate evidence about the procedure of pain management to a large number of parents

Density of Bloch Waves after a Quench

Production of Bloch waves during a rapid quench is studied by analytical and numerical methods. The density of Bloch waves decays exponentially with the quench time. It also strongly depends on temperature. Very few textures are produced for temperatures lower than a characteristic temperature proportional to the square of the magnetic field.Comment: 4 pages in RevTex + 3 .ps files; improved presentation; version to appear in PR

A respiratory syncytial virus vaccine based on the small hydrophobic protein ectodomain presented with a novel lipid-based formulation is highly immunogenic and safe in adults : a first-in-humans study

Background: Respiratory syncytial virus infection can cause lower respiratory tract infection in older adults comparable to influenza, but no vaccines are available. Methods: This was a randomized, observer-blinded, first-in-humans study of a novel synthetic RSV antigen based on the ectodomain of the small hydrophobic glycoprotein (SHe) of RSV subgroup A, formulated with either the lipid and oil-based vaccine platform DepoVax (DPX-RSV[A]) or alum (RSV[A]-Alum), in healthy, 50-64-year-old individuals. Two dose levels (10 or 25 mu g) of SHe with each formulation were compared to placebo. A booster dose was administered on day 56. Results: There was no indication that the vaccine was unsafe. Mild pain, drowsiness, and muscles aches were the most common solicited adverse events (AEs), and the frequencies of the AEs did not increase after dose 2. Robust anti-SHe-specific immune responses were demonstrated in the DPX-RSV(A) 10-mu g and 25-mu g groups (geometric mean titer, approximately 10-fold and 100-fold greater than that of placebo at days 56 and 236, respectively), and responses were sustained in the DPX-RSV(A) 25-mu g group at day 421. Responses to the RSV(A)-Alum vaccines were very low. Conclusions: A novel antigen from the SH protein of RSV, formulated in a lipid and oil-based vaccine platform, was highly immunogenic, with sustained antigen-specific antibody responses, and had an acceptable safety profile

Presymptomatic risk assessment for chronic non-communicable diseases

The prevalence of common chronic non-communicable diseases (CNCDs) far overshadows the prevalence of both monogenic and infectious diseases combined. All CNCDs, also called complex genetic diseases, have a heritable genetic component that can be used for pre-symptomatic risk assessment. Common single nucleotide polymorphisms (SNPs) that tag risk haplotypes across the genome currently account for a non-trivial portion of the germ-line genetic risk and we will likely continue to identify the remaining missing heritability in the form of rare variants, copy number variants and epigenetic modifications. Here, we describe a novel measure for calculating the lifetime risk of a disease, called the genetic composite index (GCI), and demonstrate its predictive value as a clinical classifier. The GCI only considers summary statistics of the effects of genetic variation and hence does not require the results of large-scale studies simultaneously assessing multiple risk factors. Combining GCI scores with environmental risk information provides an additional tool for clinical decision-making. The GCI can be populated with heritable risk information of any type, and thus represents a framework for CNCD pre-symptomatic risk assessment that can be populated as additional risk information is identified through next-generation technologies.Comment: Plos ONE paper. Previous version was withdrawn to be updated by the journal's pdf versio

Safety and Efficacy of Rivaroxaban in Patients With Cardiac Implantable Electronic Devices:Observations From the ROCKET AF Trial

Background: Although implantation of cardiac implantable electronic devices (CIEDs) in patients receiving warfarin is well studied, limited data are available on the use of oral factor Xa inhibitors in this setting. Methods and Results: Using data from Rivaroxaban Once Daily Oral Direct Factor Xa Inhibition Compared with Vitamin K Antagonism for Prevention of Stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) (n=14 264), we compared baseline characteristics and clinical outcomes in patients with atrial fibrillation randomized to rivaroxaban versus warfarin who did and did not undergo CIED implantation or revision. In this post‐hoc, postrandomization, on‐treatment analysis, only the first intervention per patient was analyzed. During a median follow‐up of 2.2 years, 453 patients (242 rivaroxaban group; 211 warfarin group) underwent de novo CIED implantation (64.2%) or revision procedures (35.8%). Patients who received CIEDs were older, more likely to be male, and more likely to have past myocardial infarction, but had similar stroke risk compared to patients who did not receive CIEDs. Most patients who received a device had study drug interrupted for the procedure and did not receive bridging anticoagulation. During the 30‐day postprocedural period, 11 patients (4.55%) in the rivaroxaban group experienced bleeding complications compared with 15 (7.13%) in the warfarin group. Thromboembolic complications occurred in 3 patients (1.26%) in the rivaroxaban group and 1 (0.48%) in the warfarin group. Event rates were too low for formal hypothesis testing. Conclusions: Bleeding and thromboembolic events were low in both rivaroxaban‐ and warfarin‐treated patients. Periprocedural use of oral factor Xa inhibitors in CIED implantation requires further study in prospective, randomized trials. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00403767