Opt-out testing for hepatitis B and C infections in adults attending the emergency department of a large London teaching hospital.

BACKGROUND: The National Health Service (NHS) in England commissioned opt-out testing in London Emergency Departments (ED) in April 2022 to allow early identification and management of hepatitis B (HBV) and hepatitis C virus (HCV) infection in patients unaware of their infection status. METHODS: All adults over the age of 16 undergoing blood tests in the ED at the Royal Free Hospital were tested for HBV surface antigen and anti-HCV IgG unless they opted out. Data was collected between the 12th of April and 22nd of August 2022. OUTCOME: Of 11,215 patients tested for HCV, 164 patients were found to be anti-HCV IgG positive, giving a seroprevalence rate of 1.46 %. 52 of the anti-HCV IgG positive patients did not have any previous HCV serology result. 23 of the anti-HCV IgG positive patients were also HCV RNA positive giving an RNA seroprevalence of 0.21 %, and 17 of those were new diagnoses of HCV viraemia. For HBV testing, 82 (0.73 %) out of 11,192 patients tested were found to be HBsAg positive, including one patient who presented acutely with a positive HBV core IgM. 39 of the HBsAg positive patients were previously unknown to us; of these, 9 had an HBV viral load of more than 2000 IU/mL, including 3 patients with positive HBV e antigen and one patient with hepatitis D virus co-infection. CONCLUSION: Opt-out screening of HBV and HCV in ED is effective at identifying patients with previously undiagnosed viral hepatitis infection and providing an opportunity to engage them in specialist care.

Commercial Immunoglobulin Products Contain Neutralizing Antibodies Against Severe Acute Respiratory Syndrome Coronavirus 2 Spike Protein.

BACKGROUND: Patients with antibody deficiency respond poorly to coronavirus disease 2019 (COVID-19) vaccination and are at risk of severe or prolonged infection. They are given long-term immunoglobulin replacement therapy (IRT) prepared from healthy donor plasma to confer passive immunity against infection. Following widespread COVID-19 vaccination alongside natural exposure, we hypothesized that immunoglobulin preparations will now contain neutralizing severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) spike antibodies, which confer protection against COVID-19 disease and may help to treat chronic infection. METHODS: We evaluated anti-SARS-CoV-2 spike antibody in a cohort of patients before and after immunoglobulin infusion. Neutralizing capacity of patient samples and immunoglobulin products was assessed using in vitro pseudovirus and live-virus neutralization assays, the latter investigating multiple batches against current circulating Omicron variants. We describe the clinical course of 9 patients started on IRT during treatment of COVID-19. RESULTS: In 35 individuals with antibody deficiency established on IRT, median anti-spike antibody titer increased from 2123 to 10 600 U/mL postinfusion, with corresponding increase in pseudovirus neutralization titers to levels comparable to healthy donors. Testing immunoglobulin products directly in the live-virus assay confirmed neutralization, including of BQ1.1 and XBB variants, but with variation between immunoglobulin products and batches.Initiation of IRT alongside remdesivir in patients with antibody deficiency and prolonged COVID-19 infection (median 189 days, maximum >900 days with an ancestral viral strain) resulted in clearance of SARS-CoV-2 at a median of 20 days. CONCLUSIONS: Immunoglobulin preparations now contain neutralizing anti-SARS-CoV-2 antibodies that are transmitted to patients and help to treat COVID-19 in individuals with failure of humoral immunity.

Persistent SARS-CoV-2 PCR Positivity Despite Anti-viral Treatment in Immunodeficient Patients.

PURPOSE: COVID-19 infection in immunodeficient individuals can result in chronically poor health, persistent or relapsing SARS-CoV-2 PCR positivity, and long-term infectious potential. While clinical trials have demonstrated promising outcomes using anti-SARS-CoV-2 medicines in immunocompetent hosts, their ability to achieve sustained viral clearance in immunodeficient patients remains unknown. We therefore aimed to study long-term virological outcomes in patients treated at our centre. METHODS: We followed up immunocompromised inpatients treated with casirivimab-imdevimab (Ronapreve) between September and December 2021, and immunocompromised patients who received sotrovimab, molnupiravir, nirmatrelvir/ritonavir (Paxlovid), or no treatment from December 2021 to March 2022. Nasopharyngeal swab and sputum samples were obtained either in hospital or in the community until sustained viral clearance, defined as 3 consecutive negative PCR samples, was achieved. Positive samples were sequenced and analysed for mutations of interest. RESULTS: We observed sustained viral clearance in 71 of 103 patients, none of whom died. Of the 32/103 patients where sustained clearance was not confirmed, 6 died (between 2 and 34 days from treatment). Notably, we observed 25 cases of sputum positivity despite negative nasopharyngeal swab samples, as well as recurrence of SARS-CoV-2 positivity following a negative sample in 12 cases. Patients were then divided into those who cleared within 28 days and those with PCR positivity beyond 28 days. We noted lower B cell counts in the group with persistent PCR positivity (mean (SD) 0.06 (0.10) ×109/L vs 0.22 (0.28) ×109/L, p = 0.015) as well as lower IgA (median (IQR) 0.00 (0.00-0.15) g/L vs 0.40 (0.00-0.95) g/L, p = 0.001) and IgM (median (IQR) 0.05 (0.00-0.28) g/L vs 0.35 (0.10-1.10) g/L, p = 0.005). No differences were seen in CD4+ or CD8+ T cell counts. Antiviral treatment did not impact risk of persistent PCR positivity. CONCLUSION: Persistent SARS-CoV-2 PCR positivity is common among immunodeficient individuals, especially those with antibody deficiencies, regardless of anti-viral treatment. Peripheral B cell count and serum IgA and IgM levels are predictors of viral persistence.

Real world use of dolutegravir two drug regimens.

BACKGROUND: Since 2015, we prescribed dolutegravir (DTG)-based two drug regimens (DTG-2DR) for 620 people [total cohort 3133 (19.8%)]. METHOD: Clinic database search 1 January 15 to 31 October 21. Demographic, tolerability and HIV related data analysed. RESULTS: In total, 620 people identified; 561 had complete data. 446 male (79.5%); median age 54 years (interquartile range 46, 59). 343 (61.1%) MSM. Nine people who initiated naïvely achieved viral suppression (100%). 546/552 (99.0%) switched or continued and were suppressed at data censor. 460/552 (83.3%) received DTG-lamivudine (DTG/3TC), 74/552 (13.4%) received DTG-rilpivirine (DTG/RPV) and 18/552 (3.3%) received DTG-emtricitabine (DTG/FTC). 70 (12.5%) switched off DTG-2DR (55 DTG/3TC, 13 DTG/RPV, two DTG/FTC) due to side-effects. 41 episodes of blip (1 off >50 copies/ml) occurred in 30 people (5.3%). 11/41 on DTG-RPV [ n  = 7 multi-tablet regimen (MTR), n  = 4 single tablet regimen (STR)]. 27/41 DTG-3TC, 3/41 DTG/FTC ( n  = 26 MTR, n  = 4 STR). Six people (1.1%) failed (confirmed viral load >200 copies/ml or persistent low level viraemia) ( n  = 4 DTG-3TC STR, n  = 1 DTG-3TC MTR, n  = 1 DTG-RPV MTR). Four failures due to low level viraemia, one due to non-adherence and one due to high viral load. Resistance tests performed for 5/6 - mutations detected only in latter person with high viral load failure (on DTG-3TC MTR) who developed triple class resistance. CONCLUSION: Majority of experience is in DTG/3TC stable switch. Minority of patients developed side-effects. Low number of virological failures, one developed integrase inhibitor resistance. Viral failure associated with MTR, commensurate with trial data showing no failure with resistance if DTG/3TC STR used. Overall DTG-2DR demonstrates high efficacy in real-world setting.

Development of a comprehensive approach to adult hereditary cancer testing in Ontario.

BACKGROUND: Genetic testing for hereditary cancer susceptibility has advanced over time due to the discovery of new risk genes, improved technology and decreased cost. In the province of Ontario, testing eligibility criteria were initially developed to include hereditary breast, ovarian and colorectal cancer syndromes. The rapid evolution of genetic technologies has facilitated the ability to interrogate a large number of genes concurrently. This, coupled with new knowledge about risk genes, necessitated a coordinated approach to expanding the scope of genes and indications tested and synchronisation of access and test utilisation across the province as required in a publicly funded universal healthcare system. METHODS: Ontario Health-Cancer Care Ontario convened expert working groups to develop a standardised and comprehensive cancer gene list for adults and accompanying hereditary cancer testing (HCT) criteria using an evidence-based framework and broad laboratory and clinical genetics engagement. RESULTS: A standardised 76-cancer-gene panel, organised into 13 larger disease site panels and 25 single/small gene panels, was developed and endorsed by the working groups. Provincial genetic testing eligibility criteria were updated to align with the new panels and to guide clinical decision-making. In the first year following the implementation of these changes, 10 564 HCT panels were performed with an overall mutation detection rate of 12.2%. CONCLUSION: Using an evidence framework and broad clinical engagement to develop and endorse an updated guidance document, cancer genetic testing for adults in Ontario is now standardised and coordinated across the province.

Post-Vaccination Coronavirus Disease 2019: A Case-Control Study and Genomic Analysis of 119 Breakthrough Infections in Partially Vaccinated Individuals.

BACKGROUND: Post-vaccination infections challenge the control of the coronavirus disease 2019 (COVID-19) pandemic. METHODS: We matched 119 cases of post-vaccination severe acute respiratory syndrome coronavirus 2 infection with BNT162b2 mRNA or ChAdOx1 nCOV-19 to 476 unvaccinated patients with COVID-19 (September 2020-March 2021) according to age and sex. Differences in 60-day all-cause mortality, hospital admission, and hospital length of stay were evaluated. Phylogenetic, single-nucleotide polymorphism (SNP), and minority variant allele (MVA) full-genome sequencing analysis was performed. RESULTS: Overall, 116 of 119 cases developed COVID-19 post-first vaccination dose (median, 14 days). Thirteen of 119 (10.9%) cases and 158 of 476 (33.2%) controls died (P < .001), corresponding to the 4.5 number needed to treat (NNT). Multivariably, vaccination was associated with a 69.3% (95% confidence interval [CI]: 45.8 to 82.6) relative risk (RR) reduction in mortality. Similar results were seen in subgroup analysis for patients with infection onset ≥14 days after first vaccination and across vaccine subgroups. Hospital admissions (odds ratio, 0.80; 95% CI: .51 to 1.28) and length of stay (-1.89 days; 95% CI: -4.57 to 0.78) were lower for cases, while cycle threshold values were higher (30.8 vs 28.8, P = .053). B.1.1.7 was the predominant lineage in cases (100 of 108, 92.6%) and controls (341 of 446, 76.5%). Genomic analysis identified 1 post-vaccination case that harbored the E484K vaccine-escape mutation (B.1.525 lineage). CONCLUSIONS: Previous vaccination reduces mortality when B.1.1.7 is the predominant lineage. No significant lineage-specific genomic changes during phylogenetic, SNP, and MVA analysis were detected.

Association Between the 5As and Stage of Change Among African American Smokers Eligible for Low-Dose Computed Tomography Screening.

We investigated the association between the 5As (Ask, Advise, Assess, Assist, and Arrange) clinical protocol and stage of change among African American smokers who are eligible for low-dose computed tomography screening. In 2019, 60 African American daily smokers aged 55 years or older were recruited in a large hospital in New Orleans, Louisiana. Smokers who received assistance for smoking cessation were more likely to be in the preparation stage than those who did not receive any assistance. Assistance from health professionals is an essential form of support and may substantially enhance smokers' motivation to quit smoking in this population that is at higher risk for mortality from lung cancer.

Combatting a "Twin-demic": A quantitative assessment of COVID-19 and influenza vaccine hesitancy in primary care patients.

Background: Public health officials anticipate severe health outcomes amidst the circulation of two major viruses, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza. This study investigated intent to be vaccinated against COVID-19 and influenza, and sought to identify attitudes towards vaccines and barriers for vaccine acceptance. Methods: This observational cross-sectional study was conducted in the Louisiana State University Medicine Clinic from September 2020 to December 2020. Intent to be vaccinated against the COVID-19 and influenza virus was assessed through a brief questionnaire. Additionally, hesitancy and attitudes regarding vaccines were ascertained using validated 5-point Likert scales. In total, 280 patients completed the questionnaire. Results: A total of 248 patients were included in the final analysis. Overall 167 (67%, 95% CI = 61.1-73.0%) of patients were unsure or did not intend to be vaccinated against COVID-19, while only 19.3% (95% CI = 14.4-24.5%) were unsure or did not intend to be vaccinated against the influenza vaccine. Reasons for COVID-19 vaccine hesitancy included concern regarding side effects, fear of getting sick from the vaccine, and the absence of vaccine recommendations from their doctor. Concerningly, African American patients demonstrated decreased likelihood of receiving the COVID-19 vaccine. Conclusion: This survey revealed that only 1 in 3 adults intended to be vaccinated against COVID-19, while 8 out of 10 adults intended to receive the influenza vaccine. Patients who intended on getting the COVID-19 vaccine were less likely to be African American. Given the degree of hesitancy against COVID-19 vaccination, a multifaceted approach to facilitate vaccine uptake that includes vaccine education, behavioral change strategies, and health promotion, is paramount.

Developing Leadership Competencies in Midlevel Nurse Leaders: An Innovative Approach.

A pediatric teaching hospital developed a comprehensive leadership training program for midlevel nurse leaders with varying levels of management knowledge and experience. Content was based on American Organization for Nursing Leadership nurse manager competencies and data from a comprehensive needs assessment. Learners identified differentiating between leadership and management, influencing behavior, managing change, and communication as areas of increased confidence. This program is applicable to any hospital with multiple midlevel nurse leaders new to the role.

ClinVar: improvements to accessing data.

ClinVar is a freely available, public archive of human genetic variants and interpretations of their relationships to diseases and other conditions, maintained at the National Institutes of Health (NIH). Submitted interpretations of variants are aggregated and made available on the ClinVar website (https://www.ncbi.nlm.nih.gov/clinvar/), and as downloadable files via FTP and through programmatic tools such as NCBI's E-utilities. The default view on the ClinVar website, the Variation page, was recently redesigned. The new layout includes several new sections that make it easier to find submitted data as well as summary data such as all diseases and citations reported for the variant. The new design also better represents more complex data such as haplotypes and genotypes, as well as variants that are in ClinVar as part of a haplotype or genotype but have no interpretation for the single variant. ClinVar's variant-centric XML had its production release in April 2019. The ClinVar website and E-utilities both have been updated to support the VCV (variation in ClinVar) accession numbers found in the variant-centric XML file. ClinVar's search engine has been fine-tuned for improved retrieval of search results.

Prospective, Randomized, Double-Blind Evaluation of the Efficacy of a Single-Dose Hyaluronic Acid for the Treatment of Patellofemoral Chondromalacia.

BACKGROUND: Patellofemoral pain is common in the young and active populations. Nonoperative management is limited and focuses on physical therapy. Hyaluronic acid (HA) is an injectable device that has been used for the treatment of knee osteoarthritis. HYPOTHESIS: A single injection of HA would reduce pain and improve function in patients with patellofemoral pain who had previously failed conservative management. STUDY DESIGN: Randomized controlled trial; Level of evidence, 2. METHODS: A total of 86 patients with patellofemoral pain (65 females, 21 males; mean ± SD age, 27.0 ± 7.7 years; height, 168.6 ± 8.9 cm; weight, 74.6 ± 17.0 kg; body mass index, 26.2 ± 5.2 kg/m2) enrolled in this study after failing conservative management. Patients were randomly allocated to either 6 mL of HA or a sham injection. All patients were prescribed an additional home exercise program, including lower extremity strengthening and flexibility exercises, and were evaluated at 1, 3, and 6 months. Outcome assessments included patellofemoral pain assessment with a visual analog scale during a single-legged squat, KOOS (Knee injury and Osteoarthritis Outcome Score), Kujala score, Tegner activity rating, and normalized isometric knee extension strength. Group assignment was revealed after the 6-month assessment, and crossover treatment was offered to patients in the sham group who were still symptomatic. Linear mixed models were used to compare outcomes between groups and across time. RESULTS: A total of 45 patients were randomized to HA injection and 41 to sham, with 6 patients lost to follow-up (93% follow-up rate). Patients in both groups experienced a significant reduction in visual analog pain ratings and significant improvements in all domains of the KOOS and in Kujala scores at 6 months when compared with baseline measurement (P < .05); however, there was no significant difference between groups. There were no differences observed over time or between groups for normalized knee extension strength or Tegner activity rating (P > .05). CONCLUSION: HA injection had no clinically meaningful effect on pain or functional outcomes in patients diagnosed with patellofemoral pain. Improvements were observed for both groups in patient-reported pain and function, with no change in quadriceps strength or activity rating. REGISTRATION: NCT01771952 (ClinicalTrials.gov identifier).

ClinGen's GenomeConnect registry enables patient-centered data sharing.

GenomeConnect, the NIH-funded Clinical Genome Resource (ClinGen) patient registry, engages patients in data sharing to support the goal of creating a genomic knowledge base to inform clinical care and research. Participant self-reported health information and genomic variants from genetic testing reports are curated and shared with public databases, such as ClinVar. There are four primary benefits of GenomeConnect: (1) sharing novel genomic data-47.9% of variants were new to ClinVar, highlighting patients as a genomic data source; (2) contributing additional phenotypic information-of the 52.1% of variants already in ClinVar, GenomeConnect provided enhanced case-level data; (3) providing a way for patients to receive variant classification updates if the reporting laboratory submits to ClinVar-97.3% of responding participants opted to receive such information and 13 updates have been identified; and (4) supporting connections with others, including other participants, clinicians, and researchers to enable the exchange of information and support-60.4% of participants have opted to partake in participant matching. Moving forward, ClinGen plans to increase patient-centric data sharing by partnering with other existing patient groups. By engaging patients, more information is contributed to the public knowledge base, benefiting both patients and the genomics community.

ClinVar: improving access to variant interpretations and supporting evidence.

ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) is a freely available, public archive of human genetic variants and interpretations of their significance to disease, maintained at the National Institutes of Health. Interpretations of the clinical significance of variants are submitted by clinical testing laboratories, research laboratories, expert panels and other groups. ClinVar aggregates data by variant-disease pairs, and by variant (or set of variants). Data aggregated by variant are accessible on the website, in an improved set of variant call format files and as a new comprehensive XML report. ClinVar recently started accepting submissions that are focused primarily on providing phenotypic information for individuals who have had genetic testing. Submissions may come from clinical providers providing their own interpretation of the variant ('provider interpretation') or from groups such as patient registries that primarily provide phenotypic information from patients ('phenotyping only'). ClinVar continues to make improvements to its search and retrieval functions. Several new fields are now indexed for more precise searching, and filters allow the user to narrow down a large set of search results.

Manejo do dinheiro pelo casal e infidelidade financeira / Management of money by the couple and financial infidelity / Gestión de dinero por la pareja e infidelidad financiera

O manejo do dinheiro constitui-se como um dos principais motivos de conflito conjugal. Dessa forma, esse artigo teve como objetivo investigar o manejo do dinheiro pelo casal e as situações de infidelidade financeira. Realizou-se um estudo quantitativo com delineamento descritivo, comparativo e correlacional. Participaram 143 casais, casados oficialmente ou morando juntos, entre 19 e 81 anos. Aplicou-se dois questionários, um sociodemográfico e um sobre manejo do dinheiro. Foram feitas análises estatísticas descritivas e inferenciais. Os resultados revelaram que 58% utiliza o sistema de gestão compartilhada do dinheiro. A maioria (93,5%) afirma nunca ter cometido situações de infidelidade financeira. Ao contrário de estudos prévios, não foram evidentes conflitos significativos em relação ao manejo do dinheiro e sim associação entre infidelidade financeira e renda do casal.

The management of money constitutes one of the main reasons for maritalconflict. This paper aimed to investigate the ways couples handle the moneyand the situations of financial infidelity. A quantitative study with a descriptive, comparative and correlational design was conducted. 143 officially married or living together couples participated. Ages ranged between 19 and 81 years. Two questionnaires were applied, one ofsociodemographic data and a questionnaire about management of money. A descriptive and inferential statistics analysis was made. The results revealed that 58% of participants shared management of money. The majority (93.5%) indicated that they have never committed financial infidelity. Contrary to previous studies, the results showed no significant conflict regarding the handling of money, but association between financial infidelity and income of the couple.

La gestión del dinero constituye uno de los principales motivos de conflictomarital. En vista de eso, este artículo ha tenido como objetivo investigar la gestión del dinero por la pareja y las situaciones de infidelidad financiera. Serealizó un estudio cuantitativo con un diseño descriptivo, comparativo ycorrelacional. Participaron 143 parejas oficiales o que viven juntas, entre 19y 81 años. Se aplicó dos cuestionarios, uno sociodemográfico y uno acercade la administración del dinero. Análisis estadísticos descriptivos e inferenciales fueran realizados. Los resultados revelaron que 58% utiliza un sistema compartido de gestión de dinero. La mayoría (93,5%) afirmó nunca haber cometido infidelidad financiera. Contrariamente a los estudios previos,no se identificó significativos conflictos sobre el dinero pero asociación entrela infidelidad financiera y la situación financiera de la pareja.

Manejo do dinheiro pelo casal e infidelidade financeira / Management of money by the couple and financial infidelity / Gestión de dinero por la pareja e infidelidad financiera

O manejo do dinheiro constitui-se como um dos principais motivos de conflito conjugal. Dessa forma, esse artigo teve como objetivo investigar o manejo do dinheiro pelo casal e as situações de infidelidade financeira. Realizou-se um estudo quantitativo com delineamento descritivo, comparativo e correlacional. Participaram 143 casais, casados oficialmente ou morando juntos, entre 19 e 81 anos. Aplicou-se dois questionários, um sociodemográfico e um sobre manejo do dinheiro. Foram feitas análises estatísticas descritivas e inferenciais. Os resultados revelaram que 58% utiliza o sistema de gestão compartilhada do dinheiro. A maioria (93,5%) afirma nunca ter cometido situações de infidelidade financeira. Ao contrário de estudos prévios, não foram evidentes conflitos significativos em relação ao manejo do dinheiro e sim associação entre infidelidade financeira e renda do casal. (AU)

The management of money constitutes one of the main reasons for maritalconflict. This paper aimed to investigate the ways couples handle the moneyand the situations of financial infidelity. A quantitative study with a descriptive, comparative and correlational design was conducted. 143 officially married or living together couples participated. Ages ranged between 19 and 81 years. Two questionnaires were applied, one ofsociodemographic data and a questionnaire about management of money. A descriptive and inferential statistics analysis was made. The results revealed that 58% of participants shared management of money. The majority (93.5%) indicated that they have never committed financial infidelity. Contrary to previous studies, the results showed no significant conflict regarding the handling of money, but association between financial infidelity and income of the couple. (AU)

La gestión del dinero constituye uno de los principales motivos de conflictomarital. En vista de eso, este artículo ha tenido como objetivo investigar la gestión del dinero por la pareja y las situaciones de infidelidad financiera. Serealizó un estudio cuantitativo con un diseño descriptivo, comparativo ycorrelacional. Participaron 143 parejas oficiales o que viven juntas, entre 19y 81 años. Se aplicó dos cuestionarios, uno sociodemográfico y uno acercade la administración del dinero. Análisis estadísticos descriptivos e inferenciales fueran realizados. Los resultados revelaron que 58% utiliza un sistema compartido de gestión de dinero. La mayoría (93,5%) afirmó nunca haber cometido infidelidad financiera. Contrariamente a los estudios previos,no se identificó significativos conflictos sobre el dinero pero asociación entrela infidelidad financiera y la situación financiera de la pareja. (AU)

ClinVar: public archive of interpretations of clinically relevant variants.

ClinVar (https://www.ncbi.nlm.nih.gov/clinvar/) at the National Center for Biotechnology Information (NCBI) is a freely available archive for interpretations of clinical significance of variants for reported conditions. The database includes germline and somatic variants of any size, type or genomic location. Interpretations are submitted by clinical testing laboratories, research laboratories, locus-specific databases, OMIM®, GeneReviews™, UniProt, expert panels and practice guidelines. In NCBI's Variation submission portal, submitters upload batch submissions or use the Submission Wizard for single submissions. Each submitted interpretation is assigned an accession number prefixed with SCV. ClinVar staff review validation reports with data types such as HGVS (Human Genome Variation Society) expressions; however, clinical significance is reported directly from submitters. Interpretations are aggregated by variant-condition combination and assigned an accession number prefixed with RCV. Clinical significance is calculated for the aggregate record, indicating consensus or conflict in the submitted interpretations. ClinVar uses data standards, such as HGVS nomenclature for variants and MedGen identifiers for conditions. The data are available on the web as variant-specific views; the entire data set can be downloaded via ftp. Programmatic access for ClinVar records is available through NCBI's E-utilities. Future development includes providing a variant-centric XML archive and a web page for details of SCV submissions.

Herpes simplex virus and varicella zoster virus: recent advances in therapy.

PURPOSE OF REVIEW: The mainstay of antiviral therapy for the alpha-herpesviruses [herpes simplex virus (HSV)-1, HSV-2, and varicella zoster virus (VZV)] over the past 40 years has been the nucleoside analogues such as aciclovir. Although conventional antiviral therapy has reduced mortality in severe disease, novel agents are needed to address the emergence of resistance and toxicity associated with current second-line therapy. Treatment and prophylaxis of VZV and HSV reactivations remains a challenge. RECENT FINDINGS: A number of compounds have recently been evaluated in human clinical trials, amongst them brincidofovir, an intracellularly acting derivative of cidofovir currently undergoing phase III trials. The helicase-primase inhibitors are a new class of antiviral agent and may circumvent resistance to existing agents. Amenamevir and pritelivir are two examples of these agents that have been evaluated clinically along with novel nucleoside analogues such as valomaciclovir and FV-100. Tenofovir, an agent used in HIV and hepatitis B therapy, may also have a role in the prevention of HSV-2 acquisition and reduce viral shedding. SUMMARY: Although several novel antiviral agents have undergone clinical trials in recent years, all are yet to gain licensure. Brincidofovir appears to be the candidate with most promise for adoption into routine practice in the near future.

Personalized medicine: CCO's vision, accomplishments and future plans.

Personalized medicine is a rapidly expanding field, with the potential to improve patient care. Its benefits include increasing efficiency in cancer screening, diagnosis and treatment through early detection, targeted therapy and identifying individuals with an underlying genetic risk for cancer or adverse outcomes. Through the work of Cancer Care Ontario (CCO)'s Pathology and Laboratory Medicine Program, a number of initiatives have been undertaken to support developments in personalized medicine. In keeping with the momentum of recent accomplishments, CCO has led the formation of the Personalized Medicine Steering Committee to develop a comprehensive provincial genetics strategy for the future of cancer care.

RefSeq: an update on mammalian reference sequences.

The National Center for Biotechnology Information (NCBI) Reference Sequence (RefSeq) database is a collection of annotated genomic, transcript and protein sequence records derived from data in public sequence archives and from computation, curation and collaboration (http://www.ncbi.nlm.nih.gov/refseq/). We report here on growth of the mammalian and human subsets, changes to NCBI's eukaryotic annotation pipeline and modifications affecting transcript and protein records. Recent changes to NCBI's eukaryotic genome annotation pipeline provide higher throughput, and the addition of RNAseq data to the pipeline results in a significant expansion of the number of transcripts and novel exons annotated on mammalian RefSeq genomes. Recent annotation changes include reporting supporting evidence for transcript records, modification of exon feature annotation and the addition of a structured report of gene and sequence attributes of biological interest. We also describe a revised protein annotation policy for alternatively spliced transcripts with more divergent predicted proteins and we summarize the current status of the RefSeqGene project.

Current status and new features of the Consensus Coding Sequence database.

The Consensus Coding Sequence (CCDS) project (http://www.ncbi.nlm.nih.gov/CCDS/) is a collaborative effort to maintain a dataset of protein-coding regions that are identically annotated on the human and mouse reference genome assemblies by the National Center for Biotechnology Information (NCBI) and Ensembl genome annotation pipelines. Identical annotations that pass quality assurance tests are tracked with a stable identifier (CCDS ID). Members of the collaboration, who are from NCBI, the Wellcome Trust Sanger Institute and the University of California Santa Cruz, provide coordinated and continuous review of the dataset to ensure high-quality CCDS representations. We describe here the current status and recent growth in the CCDS dataset, as well as recent changes to the CCDS web and FTP sites. These changes include more explicit reporting about the NCBI and Ensembl annotation releases being compared, new search and display options, the addition of biologically descriptive information and our approach to representing genes for which support evidence is incomplete. We also present a summary of recent and future curation targets.