Healthcare-associated outbreak of meticillin-resistant Staphylococcus aureus bacteraemia: role of a cryptic variant of an epidemic clone

BACKGROUND New strains of meticillin-resistant Staphylococcus aureus (MRSA) may be associated with changes in rates of disease or clinical presentation. Conventional typing techniques may not detect new clonal variants that underlie changes in epidemiology or clinical phenotype. AIM To investigate the role of clonal variants of MRSA in an outbreak of MRSA bacteraemia at a hospital in England. METHODS Bacteraemia isolates of the major UK lineages (EMRSA-15 and -16) from before and after the outbreak were analysed by whole-genome sequencing in the context of epidemiological and clinical data. For comparison, EMRSA-15 and -16 isolates from another hospital in England were sequenced. A clonal variant of EMRSA-16 was identified at the outbreak hospital and a molecular signature test designed to distinguish variant isolates among further EMRSA-16 strains. FINDINGS By whole-genome sequencing, EMRSA-16 isolates during the outbreak showed strikingly low genetic diversity (P < 1 × 10(-6), Monte Carlo test), compared with EMRSA-15 and EMRSA-16 isolates from before the outbreak or the comparator hospital, demonstrating the emergence of a clonal variant. The variant was indistinguishable from the ancestral strain by conventional typing. This clonal variant accounted for 64/72 (89%) of EMRSA-16 bacteraemia isolates at the outbreak hospital from 2006. CONCLUSIONS Evolutionary changes in epidemic MRSA strains not detected by conventional typing may be associated with changes in disease epidemiology. Rapid and affordable technologies for whole-genome sequencing are becoming available with the potential to identify and track the emergence of variants of highly clonal organisms

Towards controlled terminology for reporting germline cancer susceptibility variants: an ENIGMA report.

The vocabulary currently used to describe genetic variants and their consequences reflects many years of studying and discovering monogenic disease with high penetrance. With the recent rapid expansion of genetic testing brought about by wide availability of high-throughput massively parallel sequencing platforms, accurate variant interpretation has become a major issue. The vocabulary used to describe single genetic variants in silico, in vitro, in vivo and as a contributor to human disease uses terms in common, but the meaning is not necessarily shared across all these contexts. In the setting of cancer genetic tests, the added dimension of using data from genetic sequencing of tumour DNA to direct treatment is an additional source of confusion to those who are not experienced in cancer genetics. The language used to describe variants identified in cancer susceptibility genetic testing typically still reflects an outdated paradigm of Mendelian inheritance with dichotomous outcomes. Cancer is a common disease with complex genetic architecture; an improved lexicon is required to better communicate among scientists, clinicians and patients, the risks and implications of genetic variants detected. This review arises from a recognition of, and discussion about, inconsistencies in vocabulary usage by members of the ENIGMA international multidisciplinary consortium focused on variant classification in breast-ovarian cancer susceptibility genes. It sets out the vocabulary commonly used in genetic variant interpretation and reporting, and suggests a framework for a common vocabulary that may facilitate understanding and clarity in clinical reporting of germline genetic tests for cancer susceptibility

Virological outcomes of second-line protease inhibitor-based treatment for human immunodeficiency virus type 1 in a high-prevalence rural South African setting: a competing-risks prospective cohort analysis

Background. Second-line antiretroviral therapy (ART) based on ritonavir-boosted protease inhibitors (bPIs) represents the only available option after first-line failure for the majority of individuals living with human immunodeficiency virus (HIV) worldwide. Maximizing their effectiveness is imperative. Methods. This cohort study was nested within the French National Agency for AIDS and Viral Hepatitis Research (ANRS) 12249 Treatment as Prevention (TasP) cluster-randomized trial in rural KwaZulu-Natal, South Africa. We prospectively investigated risk factors for virological failure (VF) of bPI-based ART in the combined study arms. VF was defined by a plasma viral load >1000 copies/mL ≥6 months after initiating bPI-based ART. Cumulative incidence of VF was estimated and competing risk regression was used to derive the subdistribution hazard ratio (SHR) of the associations between VF and patient clinical and demographic factors, taking into account death and loss to follow-up. Results. One hundred one participants contributed 178.7 person-years of follow-up. Sixty-five percent were female; the median age was 37.4 years. Second-line ART regimens were based on ritonavir-boosted lopinavir, combined with zidovudine or tenofovir plus lamivudine or emtricitabine. The incidence of VF on second-line ART was 12.9 per 100 person-years (n = 23), and prevalence of VF at censoring was 17.8%. Thirteen of these 23 (56.5%) virologic failures resuppressed after a median of 8.0 months (interquartile range, 2.8-16.8 months) in this setting where viral load monitoring was available. Tuberculosis treatment was associated with VF (SHR, 11.50 [95% confidence interval, 3.92-33.74]; P < .001). Conclusions. Second-line VF was frequent in this setting. Resuppression occurred in more than half of failures, highlighting the value of viral load monitoring of second-line ART. Tuberculosis was associated with VF; therefore, novel approaches to optimize the effectiveness of PI-based ART in high-tuberculosis-burden settings are needed

Epidemiology and etiology of meningioma.

Although most meningiomas are encapsulated and benign tumors with limited numbers of genetic aberrations, their intracranial location often leads to serious and potentially lethal consequences. They are the most frequently diagnosed primary brain tumor accounting for 33.8% of all primary brain and central nervous system tumors reported in the United States between 2002 and 2006. Inherited susceptibility to meningioma is suggested both by family history and candidate gene studies in DNA repair genes. People with certain mutations in the neurofibromatosis gene (NF2) have a very substantial increased risk for meningioma. High dose ionizing radiation exposure is an established risk factor for meningioma, and lower doses may also increase risk, but which types and doses are controversial or understudied. Because women are twice as likely as men to develop meningiomas and these tumors harbor hormone receptors, an etiologic role for hormones (both endogenous and exogenous) has been hypothesized. The extent to which immunologic factors influence meningioma etiology has been largely unexplored. Growing emphasis on brain tumor research coupled with the advent of new genetic and molecular epidemiologic tools in genetic and molecular epidemiology promise hope for advancing knowledge about the causes of intra-cranial meningioma. In this review, we highlight current knowledge about meningioma epidemiology and etiology and suggest future research directions

Genome sequencing and carrier testing: decisions on categorization and whether to disclose results of carrier testing

We are investigating the use of genome sequencing for preconception carrier testing. Genome sequencing could identify one or more of thousands of X-linked or autosomal recessive conditions that could be disclosed during preconception or prenatal counseling. Therefore, a framework that helps both clinicians and patients understand the possible range of findings is needed to respect patient preferences by ensuring that information about only the desired types of genetic conditions are provided to a given patient

Presented Abstracts from the Thirty Third Annual Education Conference of the National Society of Genetic Counselors (New Orleans, LA, September 2014)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/146864/1/jgc41067.pd

Presented Abstracts from the Thirty Fourth Annual Education Conference of the National Society of Genetic Counselors (Pittsburgh, PA, October 2015)

Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/147137/1/jgc41044.pd

Privacy and Accountability in Black-Box Medicine

Black-box medicine—the use of big data and sophisticated machine learning techniques for health-care applications—could be the future of personalized medicine. Black-box medicine promises to make it easier to diagnose rare diseases and conditions, identify the most promising treatments, and allocate scarce resources among different patients. But to succeed, it must overcome two separate, but related, problems: patient privacy and algorithmic accountability. Privacy is a problem because researchers need access to huge amounts of patient health information to generate useful medical predictions. And accountability is a problem because black-box algorithms must be verified by outsiders to ensure they are accurate and unbiased, but this means giving outsiders access to this health information. This article examines the tension between the twin goals of privacy and accountability and develops a framework for balancing that tension. It proposes three pillars for an effective system of privacy-preserving accountability: substantive limitations on the collection, use, and disclosure of patient information; independent gatekeepers regulating information sharing between those developing and verifying black-box algorithms; and information-security requirements to prevent unintentional disclosures of patient information. The article examines and draws on a similar debate in the field of clinical trials, where disclosing information from past trials can lead to new treatments but also threatens patient privacy

Summaries of plenary, symposia, and oral sessions at the XXII World Congress of Psychiatric Genetics, Copenhagen, Denmark, 12-16 October 2014

The XXII World Congress of Psychiatric Genetics, sponsored by the International Society of Psychiatric Genetics, took place in Copenhagen, Denmark, on 12-16 October 2014. A total of 883 participants gathered to discuss the latest findings in the field. The following report was written by student and postdoctoral attendees. Each was assigned one or more sessions as a rapporteur. This manuscript represents topics covered in most, but not all of the oral presentations during the conference, and contains some of the major notable new findings reported