Mammographic interpretation in Vietnam: Tailored educational strategies are needed to increase clinicians' expertise.

AIM: Breast cancer incidence is rapidly increasing throughout South East Asia, highlighting the need for high-quality early diagnosis and treatment. This study aims to investigate the efficacy of mammography detection in Hanoi and Ho Chi Minh City (HCMC), Vietnam, using data from Australian radiologists as a benchmark; factors that influence performance will be highlighted. METHODS: A total of 53, 35 and 52 clinicians from Australia, HCMC and Hanoi, respectively, examined and diagnosed a test set of 60 mammograms, 20 of which contained cancers. Each clinician completed an accompanying questionnaire establishing demographic and experiential characteristics. The performance metrics of specificity, sensitivity, area under the receiver operating characteristic curve (AUC), location sensitivity and Jackknife free-response ROC (JAFROC) figure of merit were used to evaluate clinicians performance. Mann-Whitney and Kruskal-Wallis statistical methods were employed to establish significance. RESULTS: Vietnamese radiologists demonstrated significantly lower sensitivity, AUC, lesion sensitivity and JAFROC scores compared to Australian radiologists. There was no difference in performance between clinicians from Hanoi and HCMC. However, certain performance features (older and more experienced clinicians compared with their younger, less experienced counterparts, readers who read more compared with fewer mammograms per week, clinicians with greater radiological experience and clinicians that completed a fellowship) demonstrated significantly better performances. CONCLUSIONS: The significant difference in diagnostic efficacy of mammograms between Vietnam and Australia identifies the need for improvements in breast radiology training, management and practice. Cost-effective solutions are available that can improve the reading efficacy of clinicians, and consequently health outcomes for Vietnamese women.

Patient and caregiver engagement in the Patient-Centered Outcomes Research Institute (PCORI) Health Care Horizon Scanning System (HCHSS) process.

OBJECTIVE: The Patient-Centered Outcomes Research Institute (PCORI) horizon scanning system is an early warning system for healthcare interventions in development that could disrupt standard care. We report preliminary findings from the patient engagement process. METHODS: The system involves broadly scanning many resources to identify and monitor interventions up to 3 years before anticipated entry into U.S. health care. Topic profiles are written on included interventions with late-phase trial data and circulated with a structured review form for stakeholder comment to determine disruption potential. Stakeholders include patients and caregivers recruited from credible community sources. They view an orientation video, comment on topic profiles, and take a survey about their experience. RESULTS: As of March 2020, 312 monitored topics (some of which were archived) were derived from 3,500 information leads; 121 met the criteria for topic profile development and stakeholder comment. We invited fifty-four patients and caregivers to participate; thirty-nine reviewed at least one report. Their perspectives informed analyst nominations for fourteen topics in two 2019 High Potential Disruption Reports. Thirty-four patient stakeholders completed the user-experience survey. Most agreed (68 percent) or somewhat agreed (26 percent) that they were confident they could provide useful comments. Ninety-four percent would recommend others to participate. CONCLUSIONS: The system has successfully engaged patients and caregivers, who contributed unique and important perspectives that informed the selection of topics deemed to have high potential to disrupt clinical care. Most participants would recommend others to participate in this process. More research is needed to inform optimal patient and caregiver stakeholder recruitment and engagement methods and reduce barriers to participation.

Effectiveness of indoor allergen reduction in asthma management: A systematic review.

BACKGROUND: This review will inform updated National Asthma Education and Prevention Program clinical practice guidelines. OBJECTIVE: We sought to evaluate the effectiveness of allergen reduction interventions on asthma outcomes. METHODS: We systematically searched the "gray literature" and 5 bibliographic databases. Eligible studies included systematic reviews, randomized controlled trials, and nonrandomized interventional studies. Risk of bias was assessed by using the Cochrane Risk of Bias instrument and the Newcastle-Ottawa scale. The evidence base was assessed by using the approach of the Agency for Healthcare Research and Quality's Evidence-based Practice Center program. RESULTS: Fifty-nine randomized and 8 nonrandomized trials addressed 8 interventions: acaricide, air purification, carpet removal, high-efficiency particulate air filtration (HEPA) vacuums, mattress covers, mold removal, pest control, and pet removal. Thirty-seven studies evaluated single-component interventions, and 30 studies assessed multicomponent interventions. Heterogeneity precluded meta-analysis. For most interventions and outcomes, the evidence base was inconclusive or showed no effect. No interventions were associated with improvement in validated asthma control measures or pulmonary physiology. Exacerbations were diminished in multicomponent studies that included HEPA vacuums or pest control (moderate strength of evidence [SOE] for both). Quality of life improved in studies of air purifiers (SOE: low) and in multicomponent studies that included HEPA vacuums (SOE: moderate) or pest control (SOE: low). CONCLUSIONS: Single interventions were generally not associated with improvement in asthma measures, with most strategies showing inconclusive results or no effect. Multicomponent interventions improved various outcomes, but no combination of specific interventions appears to be more effective. The evidence was often inconclusive because of a lack of studies. Further research is needed comparing the effect of indoor allergen reduction interventions on validated asthma measures, with sufficient population sizes to detect clinically meaningful differences.

Advances in HTLV-1 peptide vaccines and therapeutics.

In the past two decades a large initiative has been put forth to understand the biological and pathogenic properties of the human T-cell lymphotropic virus type 1 (HTLV-1); this has ultimately led to the development of various experimental vaccination and therapeutic strategies to combat HTLV-1 infection. The focus of this work is to outline key targets for the design of therapeutics for HTLV-1, such as fusion mediated by the envelope glycoprotein, and to discuss reports of novel vaccines or therapeutics. These strategies include peptide, recombinant protein, DNA, and viral vectors. The final focus of this review is to acquaint the reader with vaccine approaches developed in our laboratory over the last decade. These strategies include the development of envelope glycoprotein derived B-cell epitopes for the induction of neutralizing antibodies, as well as a strategy to generate a multivalent cytotoxic T-lymphocyte (CTL) response against the HTLV-1 Tax antigen.

Protective efficacy of multiepitope human leukocyte antigen-A*0201 restricted cytotoxic T-lymphocyte peptide construct against challenge with human T-cell lymphotropic virus type 1 Tax recombinant vaccinia virus.

Human T-cell lymphotropic virus type 1 (HTLV-1) is the causative agent of adult T-cell leukemia. Multiepitope T-cell vaccines are more likely to generate a broad long-lasting immune response than those composed of single epitopes. We recently reported a novel multivalent cytotoxic T-lymphocyte peptide construct derived from the Tax protein of HTLV-1 separated by arginine spacers that elicited high cellular responses against individual epitopes simultaneously in human leukocyte antigen (HLA)-A*0201 transgenic mice. We now report the effect of epitope orientation on the processing of the multiepitope construct by 20s proteasomes and the effect of the processing rates on the immunogenicity of the intended epitopes. A positive correlation was found between processing rates and the immunogenicity of the intended epitopes. The construct with the highest immunogenicity for each epitope was tested for protective efficacy in a preclinical model of infection using HTLV-1 Tax recombinant vaccinia virus and HLA-A*0201 transgenic mice. Mice vaccinated with the multiepitope construct displayed a statistically significant reduction in viral replication that was dependent on CD8 T cells. Reduction in viral replication was also confirmed to be specific to Tax-vaccinia virus. These results demonstrate the activation of Tax-specific CD8+ T cells by vaccination and are supportive of a multivalent peptide vaccine approach against HTLV-1 infections.

De novo design of peptide immunogens that mimic the coiled coil region of human T-cell leukemia virus type-1 glycoprotein 21 transmembrane subunit for induction of native protein reactive neutralizing antibodies.

Peptide vaccines able to induce high affinity and protective neutralizing antibodies must rely in part on the design of antigenic epitopes that mimic the three-dimensional structure of the corresponding region in the native protein. We describe the design, structural characterization, immunogenicity, and neutralizing potential of antibodies elicited by conformational peptides derived from the human T-cell leukemia virus type 1 (HTLV-1) gp21 envelope glycoprotein spanning residues 347-374. We used a novel template design and a unique synthetic approach to construct two peptides (WCCR2T and CCR2T) that would each assemble into a triple helical coiled coil conformation mimicking the gp21 crystal structure. The peptide B-cell epitopes were grafted onto the epsilon side chains of three lysyl residues on a template backbone construct consisting of the sequence acetyl-XGKGKGKGCONH2 (where X represents the tetanus toxoid promiscuous T cell epitope (TT) sequence 580-599). Leucine substitutions were introduced at the a and d positions of the CCR2T sequence to maximize helical character and stability as shown by circular dichroism and guanidinium hydrochloride studies. Serum from an HTLV-1-infected patient was able to recognize the selected epitopes by enzyme-linked immunosorbent assay (ELISA). Mice immunized with the wild-type sequence (WCCR2T) and the mutant sequence (CCR2T) elicited high antibody titers that were capable of recognizing the native protein as shown by flow cytometry and whole virus ELISA. Sera and purified antibodies from immunized mice were able to reduce the formation of syncytia induced by the envelope glycoprotein of HTLV-1, suggesting that antibodies directed against the coiled coil region of gp21 are capable of disrupting cell-cell fusion. Our results indicate that these peptides represent potential candidates for use in a peptide vaccine against HTLV-1.