Hazardous cosleeping environments and risk factors amenable to change: case-control study of SIDS in south west England

Objectives: To investigate the factors associated with sudden infant death syndrome (SIDS) from birth to age 2 years, whether recent advice has been followed, whether any new risk factors have emerged, and the specific circumstances in which SIDS occurs while cosleeping (infant sharing the same bed or sofa with an adult or child). Design: Four year population based case-control study. Parents were interviewed shortly after the death or after the reference sleep (within 24 hours) of the two control groups. Setting: South west region of England (population 4.9 million, 184 800 births). Participants: 80 SIDS infants and two control groups weighted for age and time of reference sleep: 87 randomly selected controls and 82 controls at high risk of SIDS (young, socially deprived, multiparous mothers who smoked). Results: The median age at death (66 days) was more than three weeks less than in a study in the same region a decade earlier. Of the SIDS infants, 54% died while cosleeping compared with 20% among both control groups. Much of this excess may be explained by a significant multivariable interaction between cosleeping and recent parental use of alcohol or drugs (31% v 3% random controls) and the increased proportion of SIDS infants who had coslept on a sofa (17% v 1%). One fifth of SIDS infants used a pillow for the last sleep (21% v 3%) and one quarter were swaddled (24% v 6%). More mothers of SIDS infants than random control infants smoked during pregnancy (60% v 14%), whereas one quarter of the SIDS infants were preterm (26% v 5%) or were in fair or poor health for the last sleep (28% v 6%). All of these differences were significant in the multivariable analysis regardless of which control group was used for comparison. The significance of covering the infant’s head, postnatal exposure to tobacco smoke, dummy use, and sleeping in the side position has diminished although a significant proportion of SIDS infants were still found prone (29% v 10%). Conclusions: Many of the SIDS infants had coslept in a hazardous environment. The major influences on risk, regardless of markers for socioeconomic deprivation, are amenable to change and specific advice needs to be given, particularly on use of alcohol or drugs before cosleeping and cosleeping on a sofa

Responding to unexpected infant deaths : experience in one English region

New national procedures for responding to the unexpected death of a child in England require a joint agency approach to investigate each death and support the bereaved family. As part of a wider population-based study of sudden unexpected deaths in infancy (SUDI) we evaluated the implementation of this approach. Methods: A process evaluation using a population-based study of all unexpected deaths from birth to 2 years in the South West of England between January 2003 and December 2006. Local police and health professionals followed a standardised approach to the investigation of each death, supported by the research team set up to facilitate this joint approach as well as collect data for a wider research project. Results: We were notified of 155/157 SUDI, with a median time to notification of 2 hours. Initial multi-agency discussions took place in 93.5% of cases. A joint home visit by police officers with health professionals was carried out in 117 cases, 75% within 24 hours of the death. Time to notification and interview reduced during the 4 years of the study. Autopsies were conducted on all cases, the median time to autopsy being 3 days. At the conclusion of the investigation, a local multi-agency case discussion was held in 88% of cases. The median time for the whole process (including family support) was 5 months. Conclusions: This study has demonstrated that with appropriate protocols and support, the joint agency approach to the investigation of unexpected infant deaths can be successfully implemented

The Anticonvulsant Ethosuximide Disrupts Sensory Function to Extend C. elegans Lifespan

Ethosuximide is a medication used to treat seizure disorders in humans, and we previously demonstrated that ethosuximide can delay age-related changes and extend the lifespan of the nematode Caenorhabditis elegans. The mechanism of action of ethosuximide in lifespan extension is unknown, and elucidating how ethosuximide functions is important for defining endogenous processes that influence lifespan and for exploring the potential of ethosuximide as a therapeutic for age-related diseases. To identify genes that mediate the activity of ethosuximide, we conducted a genetic screen and identified mutations in two genes, che-3 and osm-3, that cause resistance to ethosuximide-mediated toxicity. Mutations in che-3 and osm-3 cause defects in overlapping sets of chemosensory neurons, resulting in defective chemosensation and an extended lifespan. These findings suggest that ethosuximide extends lifespan by inhibiting the function of specific chemosensory neurons. This model is supported by the observation that ethosuximide-treated animals displayed numerous phenotypic similarities with mutants that have chemosensory defects, indicating that ethosuximide inhibits chemosensory function. Furthermore, ethosuximide extends lifespan by inhibiting chemosensation, since the long-lived osm-3 mutants were resistant to the lifespan extension caused by ethosuximide. These studies demonstrate a novel mechanism of action for a lifespan-extending drug and indicate that sensory perception has a critical role in controlling lifespan. Sensory perception also influences the lifespan of Drosophila, suggesting that sensory perception has an evolutionarily conserved role in lifespan control. These studies highlight the potential of ethosuximide and related drugs that modulate sensory perception to extend lifespan in diverse animals

Development of a questionnaire to evaluate patients’ awareness of cardiovascular disease risk in England’s National Health Service Health Check preventive cardiovascular programme

Background The National Health Service (NHS) Health Check is a CVD risk assessment and management programme in England aiming to increase CVD risk awareness among people at increased risk of CVD. There is no tool to assess the effectiveness of the programme in communicating CVD risk to patients. Aims The aim of this paper was to develop a questionnaire examining patients’ CVD risk awareness for use in health service research evaluations of the NHS Health Check programme. Methods We developed an 85 item questionnaire to determine patients’ views of their risk of CVD. The questionnaire was based on a review of the relevant literature. After review by an expert panel and focus group discussion, 22 items were dropped and 2 new items were added. The resulting 65 item questionnaire with satisfactory content validity (content validity indices >=0.80) and face validity was tested on 110 NHS Health Check attendees in primary care in a cross sectional study between May 21 and July 28, 2014. Results Following analyses of data, we reduced the questionnaire from 65 to 26 items. The 26 item questionnaire constitutes 4 scales: Knowledge of CVD Risk and Prevention, Perceived Risk of Heart Attack/Stroke, Perceived Benefits and Intention to Change Behaviour and Healthy Eating Intentions. Perceived Risk (Cronbach’s α = 0.85) and Perceived Benefits and Intention to Change Behaviour (Cronbach’s α = 0.82) have satisfactory reliability (Cronbach’s α >=0.70). Healthy Eating Intentions (Cronbach’s α = 0.56) is below minimum threshold for reliability but acceptable for a three item scale. Conclusions The resulting questionnaire, with satisfactory reliability and validity, may be used in assessing patients’ awareness of CVD risk among NHS Health Check attendees

Rapid discrimination between methicillin-sensitive and methicillin-resistant Staphylococcus aureus by intact cell mass spectrometry

Rapid, accurate discrimination between methicillin-sensitive Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) strains is essential for appropriate therapeutic management and timely intervention for infection control. A rapid method involving intact cell mass spectrometry (ICMS) is presented that shows promise for identification, discrimination of MSSA from MRSA and typing. In ICMS, cells from a bacterial colony are emulsified in a chemical matrix, added to a sample slide, dried and analysed by matrix-assisted laser desorption ionisation time-of-flight mass spectrometry (MALDI-TOF-MS). This technique examines the chemistry of the intact bacterial cell surface, yielding spectra consisting of a series of peaks from 500 to 10 000, which represent the mass:charge (m:z) ratios. Each peak corresponds to a molecular fragment released from the cell surface during laser desorption. Specimens can be prepared in a few seconds from plate cultures and a spectrum can be obtained within 2 min. ICMS spectra for 20 staphylococcal isolates showed characteristic peaks, some of which were conserved at species level, some at strain level and some were characteristic of the methicillin susceptibility status of the strain. ICMS may have potential for MRSA identification and typing, and may improve infection control measures

Selenoprotein H is an essential regulator of redox homeostasis that cooperates with p53 in development and tumorigenesis

Selenium, an essential micronutrient known for its cancer prevention properties, is incorporated into a class of selenocysteine-containing proteins (selenoproteins). Selenoprotein H (SepH) is a recently identified nucleolar oxidoreductase whose function is not well understood. Here we report that seph is an essential gene regulating organ development in zebrafish. Metabolite profiling by targeted LC-MS/MS demonstrated that SepH deficiency impairs redox balance by reducing the levels of ascorbate and methionine, while increasing methionine sulfoxide. Transcriptome analysis revealed that SepH deficiency induces an inflammatory response and activates the p53 pathway. Consequently, loss of seph renders larvae susceptible to oxidative stress and DNA damage. Finally, we demonstrate that seph interacts with p53 deficiency in adulthood to accelerate gastrointestinal tumor development. Overall, our findings establish that seph regulates redox homeostasis and suppresses DNA damage. We hypothesize that SepH deficiency may contribute to the increased cancer risk observed in cohorts with low selenium levels.National Cancer Institute (U.S.) (Grant R01 DK090311)National Cancer Institute (U.S.) (Grant R24OD017870

Antidepressants of the Serotonin-Antagonist Type Increase Body Fat and Decrease Lifespan of Adult Caenorhabditis elegans

It was recently suggested that specific antidepressants of the serotonin-antagonist type, namely mianserin and methiothepin, may exert anti-aging properties and specifically extend lifespan of the nematode C.elegans by causing a state of perceived calorie restriction (Petrascheck M, Ye X, Buck LB: An antidepressant that extends lifespan in adult Caenorhabditis elegans; Nature, Nov 22, 2007;450(7169):553–6, PMID 18033297). Using the same model organism, we instead observe a reduction of life expectancy when employing the commonly used, standardized agar-based solid-phase assay while applying the same or lower concentrations of the same antidepressants. Consistent with a well-known side-effect of these compounds in humans, antidepressants not only reduced lifespan but also increased body fat accumulation in C. elegans reflecting the mammalian phenotype. Taken together and in conflict with previously published findings, we find that antidepressants of the serotonin-antagonist type not only promote obesity, but also decrease nematode lifespan

Quality of investigations into unexpected deaths of infants and young children in England after implementation of national child death review procedures in 2008: a retrospective assessment

Objectives In 2008, new statutory national procedures for responding to unexpected child deaths were introduced throughout England. There has, to date, been no national audit of these procedures. Study design Families bereaved by the unexpected death of a child under 4 years of age since 2008 were invited to participate. Factors contributing to the death and investigations after the death were explored. Telephone interviews were conducted, and coroners’ documents were obtained. The nature and quality of investigations was compared with the required procedures; information on each case was reviewed by a multiagency panel; and the death was categorised using the Avon clinicopathological classification. Results Data were obtained from 91 bereaved families (64 infant deaths and 27 children aged 1–3 years); 85 remained unexplained after postmortem examination. Documentation of multiagency assessments was poorly recorded. Most (88%) families received a home visit from the police, but few (37%) received joint visits by police and healthcare professionals. Postmortem examinations closely followed national guidance; 94% involved paediatric pathologists; 61% of families had a final meeting with a paediatrician to explain the investigation outcome. There was no improvement in frequency of home visits by health professionals or final meetings with paediatricians between 2008–2013 and 2014–2017 and no improvement in parental satisfaction with the process. Conclusions Statutory procedures need to be followed more closely. The implementation of a national child mortality database from 2019 will allow continuing audit of the quality of investigations after unexpected child deaths. An important area amenable to improvement is increased involvement by paediatricians

An Integrated TCGA Pan-Cancer Clinical Data Resource to Drive High-Quality Survival Outcome Analytics

For a decade, The Cancer Genome Atlas (TCGA) program collected clinicopathologic annotation data along with multi-platform molecular profiles of more than 11,000 human tumors across 33 different cancer types. TCGA clinical data contain key features representing the democratized nature of the data collection process. To ensure proper use of this large clinical dataset associated with genomic features, we developed a standardized dataset named the TCGA Pan-Cancer Clinical Data Resource (TCGA-CDR), which includes four major clinical outcome endpoints. In addition to detailing major challenges and statistical limitations encountered during the effort of integrating the acquired clinical data, we present a summary that includes endpoint usage recommendations for each cancer type. These TCGA-CDR findings appear to be consistent with cancer genomics studies independent of the TCGA effort and provide opportunities for investigating cancer biology using clinical correlates at an unprecedented scale. Analysis of clinicopathologic annotations for over 11,000 cancer patients in the TCGA program leads to the generation of TCGA Clinical Data Resource, which provides recommendations of clinical outcome endpoint usage for 33 cancer types