Health-state utility of patients with HER2-positive breast cancer in Vietnam: A multicenter cross-sectional study.

BACKGROUND: Patients with human epidermal growth factor receptor 2 (HER2)-positive breast cancer may have poor prognoses and short overall and disease-free survival. Most previous studies focused on assessing the quality of life and health-state utility of the general population of breast cancer patients. The number of studies for HER2-positive breast cancer patients is negligible. This study investigated the health-state utility and its associated factors among Vietnamese patients with HER2-positive breast cancer. METHODS: We conducted face-to-face interviews with 301 HER2-positive breast cancer patients to collect data. Their health-state utility was measured via the EQ-5D-5L instrument. The Mann-Whitney U and Kruskal-Wallis tests were employed to compare the differences in utility scores between two groups and among three groups or more, respectively. Factors associated with patients' heath-state utility were identified via Tobit regression models. RESULTS: Pain/discomfort (56.1%) and anxiety/depression (39.5%) were the two issues that patients suffered from the most, especially among metastatic breast cancer patients. The severity of distress (depression, anxiety, and stress) in patients was relatively mild. Of 301 patients, their average utility score was 0.86±0.17 (range: 0.03-1.00), and the average EQ-visual analogue scale (VAS) score was 69.12±12.60 (range: 30-100). These figures were 0.79±0.21 and 65.20±13.20 for 102 metastatic breast cancer patients, significantly lower than those of 199 non-metastatic cancer patients (0.89±0.13 and 71.13±11.78) (p<0.001), respectively. Lower health-state utility scores were significantly associated with older age (p = 0.002), lower education level (p = 0.006), lower monthly income (p = 0.036), metastatic cancer (p = 0.001), lower EQ-VAS score (p<0.001), and more severe level of distress (p<0.001). CONCLUSIONS: Our findings showed a significant decrement in utility scores among metastatic breast cancer patients. Patients' health-state utility differed by their demographic characteristics (age, education level, and income) and clinical characteristics (stage of cancer and distress). Their utility scores may support further cost-effectiveness analysis in Vietnam.

Experience of Autologous Immunotherapy for Non-Small Cell Lung Cancer Using Zoledronate-Actived Gammadelta T Cells.

BACKGROUND: Several nations around the world have utilized autologous immune enhancement therapy in the treatment of cancer, with initial positive outcomes. This study describes our experience with autologous gamma delta T cell immunotherapy for the treatment of non-small cell lung cancer patients in Vietnam, a developing nation. METHODS: Five patients with non-small cell lung cancer at stages III - IV were enrolled in the study. Each patient received six infusions of autologous γδT cells, separated by two weeks. Before, during, at the end of treatment, and three and six months after treatment, a comprehensive evaluation of clinical, laboratory, quality of life, and adverse events related to the method was conducted. RESULTS: At the time of culture seeding, the total number of cells ranged from 2.9 to 18.2 x 106, with γδT cells ranging in number from 10.7 to 19.6 x 104. On day 14 of the culture, the number of γδT cells ranged from 3.1 to 8.3 x 108. Regarding the safety of therapy in a total of 30 infusions, two (fever), one (myalgia), and one (joint pain) were graded as 1 by CTCAE criteria. After the course, no toxicity was observed in the hematopoietic system, kidney function, or liver function. Evaluation of the patient's response in accordance with the RECIST 1.1 criteria: 20% of patients (one patient) had partial response disease, and 80% of patients (four patients) had stable disease at the end of treatment. During the follow-up period of the study, three patients were still alive, and the disease remained stable. The patient's quality of life improved after treatment in most functional measures (activity, cognitive, and social), but physical and emotional scores decreased slightly. Two patients' fatigue symptoms increased, but after six months of treatment, the average value dropped from 25.3 to 8.3. Dyspnea symptoms decreased gradually from 33.3 at the start of treatment to 8.3 six months later. CONCLUSIONS: The initial results we obtained regarding the efficacy and safety of autologous γδT cell immunotherapy for patients with non-small cell lung cancer are extremely encouraging and comparable to those of previous studies.

Analysis and Visualization of Longitudinal Genomic and Clinical Data from the AACR Project GENIE Biopharma Collaborative in cBioPortal.

International cancer registries make real-world genomic and clinical data available, but their joint analysis remains a challenge. AACR Project GENIE, an international cancer registry collecting data from 19 cancer centers, makes data from >130,000 patients publicly available through the cBioPortal for Cancer Genomics (https://genie.cbioportal.org). For 25,000 patients, additional real-world longitudinal clinical data, including treatment and outcome data, are being collected by the AACR Project GENIE Biopharma Collaborative using the PRISSMM data curation model. Several thousand of these cases are now also available in cBioPortal. We have significantly enhanced the functionalities of cBioPortal to support the visualization and analysis of this rich clinico-genomic linked dataset, as well as datasets generated by other centers and consortia. Examples of these enhancements include (i) visualization of the longitudinal clinical and genomic data at the patient level, including timelines for diagnoses, treatments, and outcomes; (ii) the ability to select samples based on treatment status, facilitating a comparison of molecular and clinical attributes between samples before and after a specific treatment; and (iii) survival analysis estimates based on individual treatment regimens received. Together, these features provide cBioPortal users with a toolkit to interactively investigate complex clinico-genomic data to generate hypotheses and make discoveries about the impact of specific genomic variants on prognosis and therapeutic sensitivities in cancer. SIGNIFICANCE: Enhanced cBioPortal features allow clinicians and researchers to effectively investigate longitudinal clinico-genomic data from patients with cancer, which will improve exploration of data from the AACR Project GENIE Biopharma Collaborative and similar datasets.

Mutation spectrum of retinoblastoma patients in Vietnam.

BACKGROUND: Retinoblastoma (RB), an intraocular malignancy commonly diagnosed in children, is mostly caused by inactivating mutations of both alleles of the RB1 gene. Early genetic screening for RB1 gene mutations would greatly improve treatment outcomes and patient management. METHODS: In this study, both somatic and germline mutations were detected in blood and tumour samples of 42 RB patients using direct sequencing and multiplex ligation-dependent probe amplification. RESULTS: In total, 34 different mutations were found in 36 patients, including 1 SNP, 4 large deletions, 5 splicing sites, 1 missense, 7 frameshifts and 17 nonsense mutations. There were five novel mutations and one unreported which have not been found in large databases such as Leiden Open Variation Database (LOVD) and ClinVar. CONCLUSION: A higher rate of RB patients carrying heterozygous germline mutation and highly prevalent with pathogenic truncated mutation, hence, early detection of RB is essential for vision salvation and genetic counselling.

The GENIE BPC NSCLC Cohort: A Real-World Repository Integrating Standardized Clinical and Genomic Data for 1,846 Patients with Non-Small Cell Lung Cancer.

PURPOSE: We describe the clinical and genomic landscape of the non-small cell lung cancer (NSCLC) cohort of the American Association for Cancer Research (AACR) Project Genomics Evidence Neoplasia Information Exchange (GENIE) Biopharma Collaborative (BPC). EXPERIMENTAL DESIGN: A total of 1,846 patients with NSCLC whose tumors were sequenced from 2014 to 2018 at four institutions participating in AACR GENIE were randomly chosen for curation using the PRISSMM data model. Progression-free survival (PFS) and overall survival (OS) were estimated for patients treated with standard therapies. RESULTS: In this cohort, 44% of tumors harbored a targetable oncogenic alteration, with EGFR (20%), KRAS G12C (13%), and oncogenic fusions (ALK, RET, and ROS1; 5%) as the most frequent. Median OS (mOS) on first-line platinum-based therapy without immunotherapy was 17.4 months [95% confidence interval (CI), 14.9-19.5 months]. For second-line therapies, mOS was 9.2 months (95% CI, 7.5-11.3 months) for immune checkpoint inhibitors (ICI) and 6.4 months (95% CI, 5.1-8.1 months) for docetaxel ± ramucirumab. In a subset of patients treated with ICI in the second-line or later setting, median RECIST PFS (2.5 months; 95% CI, 2.2-2.8) and median real-world PFS based on imaging reports (2.2 months; 95% CI, 1.7-2.6) were similar. In exploratory analysis of the impact of tumor mutational burden (TMB) on survival on ICI treatment in the second-line or higher setting, TMB z-score harmonized across gene panels was associated with improved OS (univariable HR, 0.85; P = 0.03; n = 247 patients). CONCLUSIONS: The GENIE BPC cohort provides comprehensive clinicogenomic data for patients with NSCLC, which can improve understanding of real-world patient outcomes.

Case Report: Novel rare mutation c.6353C > G in the ABCA12 gene causing harlequin ichthyosis identified by whole exome sequencing.

Background: Harlequin ichthyosis (HI) is a severe rare genetic disease that mainly affects the skin. Neonates with this disease are born with thick skin and large diamond-shaped plates covering most of their bodies. Affected neonates lose the ability to control dehydration and regulate temperature and are more susceptible to infections. They also face respiratory failure and feeding problems. These clinical symptoms are factors associated with high mortality rates of neonates with HI. Until now, there are still no effective treatments for HI patients and most patients die in the newborn period. Mutation in the ABCA12 gene, which encodes an adenosine triphosphate-binding cassette (ABC) transporter, has been demonstrated as the major cause of HI. Case presentation: In this study, we report the case who is one infant that was born prematurely at 32 gestational weeks with the whole body covered with thick plate-like scales of skin. The infant was severely infected with mild edema, multiple cracked skins full of the body, yellow discharge, and necrosis of fingers and toes. The infant was suspected to be affected by HI. Whole exome sequencing (WES) was performed as a tool for detecting the novel mutation in one prematurely born Vietnam infant with HI phenotype. And after that, the mutation was confirmed by the Sanger sequencing method in the patient and the members of his family. In this case, one novel mutation c.6353C > G (p.S2118X, Hom) in the ABCA12 gene, was detected in the patient. The mutation has not been reported in any HI patients previously. This mutation was also found in a heterozygous state in the members of the patient's family, including his parents, an older brother, and an older sister who are no symptoms. Conclusions: In this study, we identified a novel mutation in a Vietnamese patient with HI by whole exome sequencing. The results for the patient and the members of his family will be helpful in understanding the etiology of the disease, diagnosing carriers, assisting in genetic counseling, and emphasizing the need for DNA-based prenatal screening for families with a history of the disease.

A case of response to combination treatment with autologous immunotherapy and bevacizumab in advanced non-small cell lung cancer.

Natural killer (NK) cells have developed as a potent tool in cancer immunotherapy. Especially, patients who have failed in the first-line or maintenance treatment received a good response with immunotherapy in association with other approaches. We report the case of a 61-year-old male patient with programmed cell death ligand - 1(PD-L1) expression in advanced non-small cell lung cancer (NSCLC) (stage IV). Even though the patient was treated with standard therapy using keytruda, he still appeared with new lesions. Therefore, the patient was treated in combination with autologous NK cells therapy, gemcitabine, bevacizumab. NK cells were expanded from peripheral blood mononuclear cells (PBMCs) of the patient, and after that, they were transferred back to the patient. After 6 infusions of autologous NK cells in combination with gemcitabine, bevacizumab, the patient decreased significantly the size of primary, metastatic lesions and had a marked improvement in the quality of life. Besides, during combination therapy, no side effects have been reported and there was no toxicity observed in the hematopoietic system, liver as well as kidneys. Our case suggests that this treatment regimen is a potential treatment approach for advanced NSCLC with PD-L1 expression.

Preimplantation genetic testing (PGT) for hemophilia A: Experience from one center.

OBJECTIVE: Hemophilia A (HA) is an X-linked recessive bleeding disease caused by a deficiency or dysfunction of blood coagulation factor VIII (FVIII). Available treatment to replenish the missing factor may not reach a good outcome for all patients because of potential complications that include the development of inhibitor antibodies directed against factor VIII. Therefore, the prevention of transmitting pathogenic mutations to the next generation is the best solution for this disease. Preimplantation genetic testing for a monogenic disorder (PGT-M) has become a standard method to prevent the transmission of monogenic heritable disease. The gold standard of the molecular technique used for PGT-M nowadays is the co-amplification of the polymorphic microsatellite linkage markers that use microsatellite DNA technique that overcomes the limitation of other methods. The important issue of this technique is the definition of markers that are specific for each allele on different loci. Each gene locus needs a characteristic design to allow accurate diagnosis that can be applied on PGT-M due to the limited quantity of DNA available. Here we present our study of four specific self-designed linked polymorphic markers applied on screening the embryos before implantation for hemophilia A families in Vietnam. MATERIAL AND METHODS: In this study, we investigated the feasibility of application and diagnostic value of 4 STR loci (FXS1108, DXS9897, F8int22, DXS9901) in the intragenic or neighbouring regions of the F8 gene. 35 hemophilia A families were recruited for STR analysis to define at least two characteristic heterologous markers for each family and 12 cases of pre-implantation genetic testing (PGT-M) for carrier mothers were performed. RESULT: All 4 of these loci (FXS1108, DXS9897, F8int22, DXS9901) were found practical and useful for preimplantation genetic testing (PGT-M). All 12 cases of PGT-M using the method had informative STR results and correct diagnosis was achieved. 9 out of the 12 mothers (75%) were implanted with 1-2 thawed embryos after the biopsy resulting in the birth of 5 healthy babies (55%). CONCLUSION: We conclude that specific 4 STR markers for rapid pre-implantation genetic testing of hemophilia A can be successfully applied with high confidence and accuracy in clinical settings. The results of the study provide solid evidence confirming that the microsatellite DNA technique is a highly reliable method, suitable for hemophilia A families wishing to determine carrier status or having healthy babies.

Genetic Ancestry Correlates with Somatic Differences in a Real-World Clinical Cancer Sequencing Cohort.

Accurate ancestry inference is critical for identifying genetic contributors of cancer disparities among populations. Although methods to infer genetic ancestry have historically relied upon genome-wide markers, the adaptation to targeted clinical sequencing panels presents an opportunity to incorporate ancestry inference into routine diagnostic workflows. We show that global ancestral contributions and admixture of continental populations can be quantitatively inferred using markers captured by the MSK-IMPACT clinical panel. In a pan-cancer cohort of 45,157 patients, we observed differences by ancestry in the frequency of somatic alterations, recapitulating known associations and revealing novel associations. Despite the comparable overall prevalence of driver alterations by ancestry group, the proportion of patients with clinically actionable alterations was lower for African (30%) compared with European (33%) ancestry. Although this result is largely explained by population-specific cancer subtype differences, it reveals an inequity in the degree to which different populations are served by existing precision oncology interventions. SIGNIFICANCE: We performed a comprehensive analysis of ancestral associations with somatic mutations in a real-world pan-cancer cohort, including >5,000 non-European individuals. Using an FDA-authorized tumor sequencing panel and an FDA-recognized oncology knowledge base, we detected differences in the prevalence of clinically actionable alterations, potentially contributing to health care disparities affecting underrepresented populations. This article is highlighted in the In This Issue feature, p. 2483.

Molecular Characterization and Genotype-Phenotype Correlation of G6PD Mutations in Five Ethnicities of Northern Vietnam.

Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzyme disorder and is caused by G6PD gene mutations. To date, more than 400 variants in the G6PD gene have been discovered, and about 160 identified variants are associated with a significant decrease in the G6PD enzyme activity. However, the molecular characterization and epidemiological study of G6PD deficiency are still limited in Vietnam. Therefore, we conducted this study to determine the G6PD variants among the Vietnamese populations and evaluate their correlation to G6PD enzyme activity. A total of 339 patients (302 males and 37 females) were enrolled in this study. The G6PD variants were identified by Sanger sequencing. Our results indicate that males are more severely deficient in G6PD than females. This enzyme activity in males (1.27 ± 1.06 IU/g·Hb) is significantly lower than in females (2.98 ± 1.57 IU/g·Hb) (p < 0.0001). The enzyme activity of the heterozygous-homozygous females and heterozygous females-hemizygous males was found to be significantly different (p < 0.05), which is interpreted due to random X-inactivation. For G6PD molecular characteristics, Viangchan (c.871G>A), Canton (c.1376G>T) and Kaiping (c.1388G>A) variants were the most dominant, accounting for 24.48%, 17.70%, and 22.42%, respectively, whereas the highest frequency of complex variants was observed in Viangchan/Silent with 20.35%. In terms of G6PD activity, the Union variant presented the lowest mean value (1.03 IU/g·Hb) compared to the other variants (p < 0.05). Computational analysis using Polyphen-2 tool investigated that all variants were relative to G6PD deficiency and separated the levels as benign and damaged. The result will establish effective methods to screen G6PD variants in Vietnam.

Generation of mature compact ventricular cardiomyocytes from human pluripotent stem cells.

Compact cardiomyocytes that make up the ventricular wall of the adult heart represent an important therapeutic target population for modeling and treating cardiovascular diseases. Here, we established a differentiation strategy that promotes the specification, proliferation and maturation of compact ventricular cardiomyocytes from human pluripotent stem cells (hPSCs). The cardiomyocytes generated under these conditions display the ability to use fatty acids as an energy source, a high mitochondrial mass, well-defined sarcomere structures and enhanced contraction force. These ventricular cells undergo metabolic changes indicative of those associated with heart failure when challenged in vitro with pathological stimuli and were found to generate grafts consisting of more mature cells than those derived from immature cardiomyocytes following transplantation into infarcted rat hearts. hPSC-derived atrial cardiomyocytes also responded to the maturation cues identified in this study, indicating that the approach is broadly applicable to different subtypes of the heart. Collectively, these findings highlight the power of recapitulating key aspects of embryonic and postnatal development for generating therapeutically relevant cell types from hPSCs.

Association of the STAT4, CDKN1A, and IRF5 variants with risk of lupus nephritis and renal biopsy classification in patients in Vietnam.

BACKGROUND: Lupus nephritis is a common complication of systemic lupus erythematosus (SLE, OMIM #15200) in the Asian population and a main contributor to mortality and morbidity. In this study, we evaluate the variants on three genes STAT4, CDKN1A, and IRF5 and their association with lupus nephritis. METHOD: One hundred fifty-two SLE patients with confirmed lupus nephritis (through biopsy) and 76 healthy controls were recruited. Genotyping of SNPs on three gene STAT4, CDKN1A, and IRF5, phenotypic, and laboratory assessment were performed; renal biopsy and classification were carried out for the patient group. RESULTS: Carriers of rs7582694 C alleles on STAT4 have higher risk of lupus nephritis (OR 2.0; 95% CI [1.14, 3.19]; p = 0.015), at higher risk of hematuria and higher serum level of dsDNA antibodies compared to controls (p < 0.05) and were more likely to have nephrotic histopathology grading of class III or higher. No association was observed for CDKN1A; and no variation was observed for the IRF5 gene in both the study and control group. CONCLUSION: This study investigates the relationship between STAT4, CDKN1A, and IRF5 gene and SLE in a Vietnamese patient population. Patients with the C allele (STAT4) in rs7582694 were associated with a more severe disease phenotype.

Mechanism for the Binding of Netropsin to Hairpin DNA Revealed Using Nanoscale Ion Emitters in Native Mass Spectrometry.

Netropsin is one of the first ligands to be discovered that selectively binds to the minor groove of DNA and is actively used as a scaffold for developing potential anticancer and antibiotic agents. The mechanism by which netropsin binds to hairpin DNA remains controversial with two competing mechanisms having been proposed. In one mechanism, netropsin binding induces a hairpin-to-duplex DNA transition. Alternatively, netropsin binds in two thermodynamically different modes at a single duplexed AATT site. Here, results from native mass spectrometry (MS) with nanoscale ion emitters indicate that netropsin can simultaneously and sequentially bind to both hairpin and duplex DNA. Duplex DNA was not detected using conventional MS with larger emitters because nanoscale emitters significantly reduce the extent of salt adduction to ligand-DNA complex ions, including in the presence of relatively high concentrations of nonvolatile salts. Based on native MS and polyacrylamide gel electrophoresis results, the abundances of hairpin and duplex DNA are unaffected by the addition of netropsin. By native MS, the binding affinities for five ligand-DNA and DNA-DNA interactions can be rapidly obtained simultaneously. This research indicates a "simultaneous binding mechanism" for the interactions of netropsin with DNA.

Acromesomelic dysplasia Maroteaux-type in patients from Vietnam.

Acromesomelic dysplasias are rare skeletal disorders leading to severe short stature and abnormal skeletal morphology. Acromesomelic dysplasia Maroteaux-type is caused by homozygous or compound heterozygous pathogenic variants in NPR2 that encodes for natriuretic peptide receptor B. Here, we reported the first AMDM case in South East Asia and identified a novel pathogenic variant in NPR2 (c. 152T>C, p. (Leu51Pro)). Further analyses reveal the parents and two other family members were heterozygous for the variant. The clinical report highlights the importance of molecular genetic testing in diagnosing rare hereditable disease affecting skeletal abnormalities.

Genetic analysis of 55 northern Vietnamese patients with Wilson disease: seven novel mutations in ATP7B.

Wilson disease (WD) is an autosomal recessive disorder of copper metabolism. The gene responsible for WD was discovered in 1993 and is located on chromosome 13 at 13q14.3. It encodes a copper-specific transporting P-type ATPase. Early diagnosis can improve treatment outcome and decrease the rate of disability or even mortality.We used Sanger sequencing to identify mutation hot spots in 55 northern Vietnamese with a clinical diagnosis of WD. Mutations were screened and detected by direct DNA sequencing. A total of 26 different ATP7B gene mutations were identified, including seven novel mutations (five nonsense and two missense mutations). The most frequent mutations were p.Ser105Ter (24.55%), p.Arg778Leu (5.45%) and p.Thr850Ile (4.55%). Mutation detection rate in exon 2 was 34.55% and ranked first, followed by exon 8 with 16.36%, and exon 18 with 10.91% each, thus, exons 2, 8 and 18 are the mutation hot spots for northern VietnameseWD patients. These findings were different from previous studies in Asia. Our research established a suitable strategy for ATP7B gene testing in northern Vietnamese WD patients.

The Effectiveness of a Worksite Lifestyle Intervention Program on High-Risk Individuals as Potential Candidates for Bariatric Surgery: My Unlimited Potential (MyUP).

This is a single-arm, pre and post effectiveness study that evaluated the impact of a comprehensive workplace lifestyle program on severe obesity among high cardiovascular disease risk individuals in a large, diverse employee population. Employees of Baptist Health South Florida were considered eligible to participate if they had 2 or more of the following cardiometabolic risk factors: total cholesterol ≥200 mg/dL, systolic blood pressure ≥140 mmHg or diastolic blood pressure ≥90 mmHg, hemoglobin A1c ≥6.5%, body mass index ≥30kg/m(2). Participants received a personalized diet plan and physical activity intervention, and were followed for 1 year. Data on anthropometric measurements, blood pressure, blood glucose, and other biochemical measures were collected. Participants' body mass index was calculated and their eligibility for bariatric surgery (BS) also assessed. A total of 297 persons participated in the program; 160 participants completed all procedures through 12 months of follow-up. At baseline, 34% (n = 100) of all participants were eligible for BS. In an intention-to-treat analysis, 27% (n = 27) of BS eligible participants at baseline became ineligible after 12 months. Considering program completers only, 46% of BS eligible participants at baseline became ineligible. Irrespective of BS eligibility at 12 months, mean values of cardiometabolic risk factors among program completers improved after the follow-up period. Workplace wellness programs provide an important option for weight loss that can obviate the need for BS, reduce cardiovascular disease risk, and potentially reduce costs. However, in designing future worksite lifestyle interventions, measures should be taken to improve participation and retention rates in such programs.

Trends in Ideal Cardiovascular Health Metrics Among Employees of a Large Healthcare Organization (from the Baptist Health South Florida Employee Study).

The American Heart Association (AHA)'s 2020 goal is to improve the cardiovascular health (CVH) of people living in the United States (US) by 20% and reduce mortality from cardiovascular diseases and stroke by 20%. Given that 155 million adults are in the US workforce, and >60% have employee-based insurance, workplace studies provide an important opportunity to assess and potentially advance CVH through the use of comprehensive workplace wellness programs. Among a cohort of employees of the Baptist Health System, CVH was assessed annually during voluntary health fairs and health risk assessments (HRA) from 2011 to 2014 using the AHA's 7 CVH metrics: smoking, body mass index (BMI), physical activity, diet, blood pressure, total cholesterol, and blood glucose. Each metric was categorized as ideal, intermediate, or poor according to the AHA criteria. Cochrane-Armitage test was used to detect trends in CVH by year. Ideal CVH, defined as meeting ideal criteria for all 7 metrics, was assessed and compared across years. The overall cohort was 34,746 with 4,895 employees in 2011, 10,724 in 2012, 9,763 in 2013, and 9,364 in 2014. Mean age (SD) was between 43 (±12) and 46 years (±12). Female to male ratio was 3:1. The prevalence of study participants who met the ideal criteria for diet, physical activity, and blood pressure increased significantly from 2011 to 2014 but for BMI, total cholesterol, and blood glucose, a significant decrease was noticed. In addition, the prevalence of study participants in ideal CVH although low, increased significantly over time (0.3% to 0.6%, p <0.0001). In conclusion, this study shows the trends of the AHA's CVH metrics in a large health care organization. The positive findings noted for the metrics of smoking, physical activity, total cholesterol, and blood glucose should be reinforced. However, the metrics of diet, BMI, and blood pressure need more attention.

Assessment of American Heart Association's Ideal Cardiovascular Health Metrics Among Employees of a Large Healthcare Organization: The Baptist Health South Florida Employee Study.

BACKGROUND: Healthcare organizations and their employees are critical role models for healthy living in their communities. The American Heart Association (AHA) 2020 impact goal provides a national framework that can be used to track the success of employee wellness programs with a focus on improving cardiovascular (CV) health. This study aimed to assess the CV health of the employees of Baptist Health South Florida (BHSF), a large nonprofit healthcare organization. HYPOTHESIS: HRAs and wellness examinations can be used to measure the cardiovascular health status of an employee population. METHODS: The AHA's 7 CV health metrics (diet, physical activity, smoking, body mass index, blood pressure, total cholesterol, and blood glucose) categorized as ideal, intermediate, or poor were estimated among employees of BHSF participating voluntarily in an annual health risk assessment (HRA) and wellness fair. Age and gender differences were analyzed using χ(2) test. RESULTS: The sample consisted of 9364 employees who participated in the 2014 annual HRA and wellness fair (mean age [standard deviation], 43 [12] years, 74% women). Sixty (1%) individuals met the AHA's definition of ideal CV health. Women were more likely than men to meet the ideal criteria for more than 5 CV health metrics. The proportion of participants meeting the ideal criteria for more than 5 CV health metrics decreased with age. CONCLUSIONS: A combination of HRAs and wellness examinations can provide useful insights into the cardiovascular health status of an employee population. Future tracking of the CV health metrics will provide critical feedback on the impact of system wide wellness efforts as well as identifying proactive programs to assist in making substantial progress toward the AHA 2020 Impact Goal.

A systematic review of internet-based worksite wellness approaches for cardiovascular disease risk management: outcomes, challenges & opportunities.

CONTEXT: The internet is gaining popularity as a means of delivering employee-based cardiovascular (CV) wellness interventions though little is known about the cardiovascular health outcomes of these programs. In this review, we examined the effectiveness of internet-based employee cardiovascular wellness and prevention programs. EVIDENCE ACQUISITION: We conducted a systematic review by searching PubMed, Web of Science and Cochrane library for all published studies on internet-based programs aimed at improving CV health among employees up to November 2012. We grouped the outcomes according to the American Heart Association (AHA) indicators of cardiovascular wellbeing--weight, BP, lipids, smoking, physical activity, diet, and blood glucose. EVIDENCE SYNTHESIS: A total of 18 randomized trials and 11 follow-up studies met our inclusion/exclusion criteria. Follow-up duration ranged from 6-24 months. There were significant differences in intervention types and number of components in each intervention. Modest improvements were observed in more than half of the studies with weight related outcomes while no improvement was seen in virtually all the studies with physical activity outcome. In general, internet-based programs were more successful if the interventions also included some physical contact and environmental modification, and if they were targeted at specific disease entities such as hypertension. Only a few of the studies were conducted in persons at-risk for CVD, none in blue-collar workers or low-income earners. CONCLUSION: Internet based programs hold promise for improving the cardiovascular wellness among employees however much work is required to fully understand its utility and long term impact especially in special/at-risk populations.

Preventing AID, a physiological mutator, from deleterious activation: regulation of the genomic instability that is associated with antibody diversity.

Activation-induced cytidine deaminase (AID) is essential and sufficient to accomplish class-switch recombination and somatic hypermutation, which are two genetic events required for the generation of antibody-mediated memory responses. However, AID can also introduce genomic instability, giving rise to chromosomal translocation and/or mutations in proto-oncogenes. It is therefore important for cells to suppress AID expression unless B lymphocytes are stimulated by pathogens. The mechanisms for avoiding the accidental activation of AID and thereby avoiding genomic instability can be classified into three types: (i) transcriptional regulation, (ii) post-transcriptional regulation and (iii) target specificity. This review summarizes the recently elucidated comprehensive transcriptional regulation mechanisms of the AID gene and the post-transcriptional regulation that may be critical for preventing excess AID activity. Finally, we discuss why AID targets not only Igs but also other proto-oncogenes. AID targets many genes but it is not totally promiscuous and the criteria that specify its targets are unclear. A recent finding that a non-B DNA structure forms upon a decrease in topoisomerase 1 expression may explain this paradoxical target specificity determination. Evolution has chosen AID as a mutator of Ig genes because of its efficient DNA cleavage activity, even though its presence increases the risk of genomic instability. This is probably because immediate protection against pathogens is more critical for species survival than complete protection from the slower acting consequences of genomic instability, such as tumor formation.