Evaluation of the immunogenicity of liposome encapsulated HVR1 and NS3 regions of genotype 3 HCV, either singly or in combination

<p>Abstract</p> <p>Background</p> <p>Hepatitis C virus displays a high rate of mutation and exists as a quasispecies in infected patients. In the absence of an effective universal vaccine, genotype-specific vaccine development represents an alternative. We have attempted to develop a genotype 3 based, liposome encapsulated HCV vaccine with hypervariable region-1 (HVR1) and non-structural region-3 (NS3) components.</p> <p>Results</p> <p>HCV RNA extracted from serum samples of 49 chronically infected patients was PCR amplified to obtain HVR1 region. These amplified products were cloned to obtain 20 clones per sample in order to identify the quasispecies pattern. The HVR1 consensus sequence, along with three variants was reverse transcribed to obtain peptides. The peptides were checked for immunoreactivity individually, as a pool or as a single peptide tetramer interspersed with four glycine residues. Anti-HCV positivity varied from 42.6% (tetramer) to 92.2% (variant-4) when 115 anti-HCV positive sera representing genotypes 1, 3, 4 and 6 were screened. All the 95 anti-HCV negatives were scored negative by all antigens. Mice were immunized with different liposome encapsulated or Al(OH)₃adjuvanted formulations of HVR1 variants and recombinant NS3 protein, and monitored for anti-HVR1 and anti-NS3 antibody titres, IgG isotypes and antigen specific cytokine levels. A balanced Th1/Th2 isotyping response with high antibody titres was observed in most of the liposome encapsulated antigen groups. The effect of liposomes and aluminium hydroxide on the expression of immune response genes was studied using Taqman Low Density Array. Both Th1 (IFN-gamma, Il18) and Th2 (Il4) genes were up regulated in the liposome encapsulated HVR1 variant pool-NS3 combination group. In-vitro binding of the virus to anti-HVR1 antibodies was demonstrated.</p> <p>Conclusion</p> <p>The optimum immunogen was identified to be combination of peptides of HVR1 consensus sequence and its variants along with pNS3 encapsulated in liposomes, which could generate both cellular and humoral immune responses in mice deserving further evaluation in a suitable cell culture system/non-human primate model.</p

Building Consumer Competence and Trust: HRD Professionals as Champions of Change

Despite allocating significant institutional resources to establishing consumer trust, organizations often unintentionally fail to ensure that the social contract between the organization and its customers is upheld and that trust is the center of every transaction. This paper seeks to answer the questions of what role, if any, do organizations play in improving consumer competence and trust, and what substantive role can human resource development professionals play in that effort? Five consumer learning strategies using adult learning principles are set forth along with a decision-making framework that can support an organizational change in the power relationship between vulnerable consumers and organizations. The proposed decision-making framework is intended to serve as a starting point for human resource development professionals and organizations as they examine their strategies to determine how they may be changed to meet the needs of less powerful consumers and build trust

Randomized Clinical Trial of High-Dose Rifampicin With or Without Levofloxacin Versus Standard of Care for Pediatric Tuberculous Meningitis: The TBM-KIDS Trial

Background. Pediatric tuberculous meningitis (TBM) commonly causes death or disability. In adults, high-dose rifampicin may reduce mortality. The role of fluoroquinolones remains unclear. There have been no antimicrobial treatment trials for pediatric TBM. Methods. TBM-KIDS was a phase 2 open-label randomized trial among children with TBM in India and Malawi. Participants received isoniazid and pyrazinamide plus: (i) high-dose rifampicin (30 mg/kg) and ethambutol (R30HZE, arm 1); (ii) high-dose rifampicin and levofloxacin (R30HZL, arm 2); or (iii) standard-dose rifampicin and ethambutol (R15HZE, arm 3) for 8 weeks, followed by 10 months of standard treatment. Functional and neurocognitive outcomes were measured longitudinally using Modified Rankin Scale (MRS) and Mullen Scales of Early Learning (MSEL). Results. Of 2487 children prescreened, 79 were screened and 37 enrolled. Median age was 72 months; 49%, 43%, and 8% had stage I, II, and III disease, respectively. Grade 3 or higher adverse events occurred in 58%, 55%, and 36% of children in arms 1, 2, and 3, with 1 death (arm 1) and 6 early treatment discontinuations (4 in arm 1, 1 each in arms 2 and 3). By week 8, all children recovered to MRS score of 0 or 1. Average MSEL scores were significantly better in arm 1 than arm 3 in fine motor, receptive language, and expressive language domains (P < .01). Conclusions. In a pediatric TBM trial, functional outcomes were excellent overall. The trend toward higher frequency of adverse events but better neurocognitive outcomes in children receiving high-dose rifampicin requires confirmation in a larger trial. Clinical Trials Registration. NCT02958709

Analyzing U.S. Nurse Turnover: Are Nurses Leaving their Jobs or the Profession Itself?

Objective: To examine and compare factors associated with making the decision to vacate a job (organizational turnover) versus leaving the profession (professional turnover) among registered nurses (RN) in the United States (U.S.).Methods: Nationally representative data from the 2008 National Sample Survey of Registered Nurses was used. The sample consisted of 8,796 RNs who held an active RN license as of March 10, 2008, but changed a place of work or left the profession entirely. The analysis has been performed using SAS, version 9.3.Results: The results of binary logistic regression revealed that RNs who reported work-related disability (OR = 14.51; p-value: &lt; .001), illness (OR = 3.32; p-value: &lt; .001), experienced high physical demands (OR = 1.57; p-value: &lt; .001) or burnout (OR = 1.39; p-value: &lt; .001), were unsatisfied with their schedule (OR = 2.16; p-value: &lt; .001), or staffing arrangements (OR = 1.41; p-value: &lt; .001) were more likely to leave the profession. Whereas RNs who reported high levels of stress (OR = 0.59; p-value: &lt; .001) were unsatisfied with the organization’s leadership (OR = 0.22; p-value: &lt; .001), unsatisfied with their opportunity to advance their career (OR = 0.56; p-value: &lt; .001), or were not adequately compensated (OR = 0.63; p-value: &lt; .001), were more likely to leave the organization.Conclusions: Policy makers and health care managers should be aware of the different factors that are associated with RNs’ decision to leave the profession or an organization. Health care managers involved in the development of nurse retention strategies should address organizational leadership and consider development of comprehensive career development programs. Policy makers should consider allocating additional resources to ensure that RN workforce is of adequate size, is qualified, and is able to provide high quality care in the U.S..</jats:p

International Medical Graduates and Health Information Technology Use in the United States

PURPOSE: Health information technology (HIT) holds promise for improving the quality of health care and reducing health care system inefficiencies. Numerous studies have examined HIT availability, specifically electronic health records (EHRs), and utilization among physicians in individual countries. However, no one has examined EHR use among physicians who train in one country and move to practice in another country. In the United States, physicians who complete medical school outside the country but practice within the United States are commonly referred to as International Medical Graduates (IMGs). IMGs have a growing presence in the United States, yet little is known about the availability and use of HIT among these physicians. The purpose of this study is to explore the availability and use of HIT among IMGs practicing in United States. DESIGN/METHODOLOGY/APPROACH: The Health Tracking Physician Survey (2008) was used to examine the relationship between availability and use of HIT and IMG status controlling for several physician and practice characteristics. Our analysis included responses from 4,720 physicians, 20.7% of whom were IMGs. FINDINGS: Using logistic regression, controlling for physician gender, specialty, years in practice, practice type, ownership status and geographical location, we found IMGs were significantly less likely to have a comprehensive EHR in their practices (OR = 0.84; p = 0.005). In addition, findings indicate that IMGs are more likely to have and use several so-called first generation HIT capabilities, such as reminders for clinicians about preventive services (OR = 1.31; p = 0.001) and other needed patient follow-up (OR = 1.26; p = 0.007). ORIGINALITY/VALUE: This study draws attention to the need for further research regarding barriers to HIT adoption and use among IMGs

Patient navigation to improve diabetes outpatient care at a safety-net hospital: a retrospective cohort study

Abstract Background Recent emphasis on value based care and population management, such as Accountable Care Organizations in the United States, promote patient navigation to improve the quality of care and reduce costs. Evidence supporting the efficacy of patient navigation for chronic disease care is limited. The objective of this study was to evaluate the effect of a patient navigation program on medical and administrative outcomes among patients with diabetes in an urban, safety-net hospital clinic setting. Methods A retrospective cohort study with pre- and post-intervention periods was conducted. Eligible patients were those with A1C ≥ 8.5% and at least one appointment no-show in the previous 12 months. The intervention and reference groups were balanced on observed characteristics and baseline outcome levels using propensity score matching. The effect of patient navigation was isolated using the difference-in-differences approach. Primary outcomes were A1C, low-density lipoprotein cholesterol, triglycerides, random urine microalbumin, the number of scheduled appointments, clinic visits, emergency visits, and inpatient stays, and the percentage of arrivals, cancellations, and no-shows to scheduled appointments. Results Of 797 eligible patients, 328 entered the navigation program. Matching reduced the sample size to 392 individuals (196 in each group). Patient navigation resulted in improved A1C (−1.1 percentage points; p < .001), more scheduled appointments (+ 5.3 per year; p < .001), more clinic visits (+6.4 per year; p < .001), more arrivals to scheduled appointments (+7.4 percentage points; p = .009) and fewer no-shows (−9.8 percentage points; p < .001). Conclusions Navigation was associated with improved glycemic control and better clinic engagement among patients with diabetes. Further research is important to identify what features of navigation in diabetes care are critical to achieving success and to understand navigators’ role in other settings

Electronic consultations (e-consults) to improve access to specialty care: A systematic review and narrative synthesis

Background: We define electronic consultations (“e-consults”) as asynchronous, consultative, provider-to-provider communications within a shared electronic health record (EHR) or web-based platform. E-consults are intended to improve access to specialty expertise for patients and providers without the need for a face-to-face visit. Our goal was to systematically review and summarize the literature describing the use and effects of e-consults. Methods: We searched PubMed, EMBASE, the Cochrane Library, and CINAHL for studies related to e-consults published between 1990 through December 2014. Three reviewers identified empirical studies and system descriptions, including articles on systems that used a shared EHR or web-based platform, connected providers in the same health system, were used for two-way provider communication, and were text-based. Results: Our final review included 27 articles. Twenty-two were research studies and five were system descriptions. Eighteen originated from one of three sites with well-developed e-consult programs. Most studies reported on workflow impact, timeliness of specialty input, and/or provider perceptions of e-consults. E-consultations are used in a variety of ways within and across medical centers. They provide timely access to specialty care and are well-received by primary care providers. Discussion E-consults are feasible in a variety of settings, flexible in their application, and facilitate timely specialty advice. More extensive and rigorous studies are needed to inform the e-consult process and describe its effect on access to specialty visits, cost and clinical outcomes