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There is increasing evidence that smoking is a risk factor for severe mental illness, including bipolar disorder. Conversely, patients with bipolar disorder might smoke more (often) as a result of the psychiatric disorder.
We conducted a bidirectional Mendelian randomisation (MR) study to investigate the direction and evidence for a causal nature of the relationship between smoking and bipolar disorder.
We used publicly available summary statistics from genome-wide association studies on bipolar disorder, smoking initiation, smoking heaviness, smoking cessation and lifetime smoking (i.e. a compound measure of heaviness, duration and cessation). We applied analytical methods with different, orthogonal assumptions to triangulate results, including inverse-variance weighted (IVW), MR-Egger, MR-Egger SIMEX, weighted-median, weighted-mode and Steiger-filtered analyses.
Across different methods of MR, consistent evidence was found for a positive effect of smoking on the odds of bipolar disorder (smoking initiation ORIVW = 1.46, 95% CI 1.28–1.66, P = 1.44 × 10−8, lifetime smoking ORIVW = 1.72, 95% CI 1.29–2.28, P = 1.8 × 10−4). The MR analyses of the effect of liability to bipolar disorder on smoking provided no clear evidence of a strong causal effect (smoking heaviness betaIVW = 0.028, 95% CI 0.003–0.053, P = 2.9 × 10−2).
These findings suggest that smoking initiation and lifetime smoking are likely to be a causal risk factor for developing bipolar disorder. We found some evidence that liability to bipolar disorder increased smoking heaviness. Given that smoking is a modifiable risk factor, these findings further support investment into smoking prevention and treatment in order to reduce mental health problems in future generations.
Declaration of interest
W.v.d.B received fees in the past 3 years from Indivior, C&A Pharma, Opiant and Angelini. G.M.G. is a National Institute for Health Research (NIHR) Emeritus Senior Investigator, holds shares in P1vital and has served as consultant, advisor or CME speaker in the past 3 years for Allergan, Angelini, Compass Pathways, MSD, Lundbeck (/Otsuka and /Takeda), Medscape, Minervra, P1Vital, Pfizer, Sage, Servier, Shire and Sun Pharma.
We analyzed antibiotic use data from 29 southeastern US hospitals over a 5-year period to determine changes in antibiotic use after the fluoroquinolone US Food and Drug Administration (FDA) advisory update in 2016. Fluoroquinolone use declined both before and after the FDA announcement, and the use of select, alternative antibiotics increased after the announcement.
Fluoroquinolones are among the 4 most commonly prescribed antibiotic classes.1,2 Postmarketing reports of serious adverse events linked to fluoroquinolones include tendonitis, neuropathy, hypoglycemia, psychiatric side effects, and possible aortic vessel rupture, leading to safety label changes in July 2008 and August 2013.3 In July 2016, the US Food and Drug Administration (FDA) strengthened the “black box” warning following an initial safety announcement in May 2016, recommending avoidance of fluoroquinolones for uncomplicated infections such as acute exacerbation of chronic bronchitis, uncomplicated urinary tract infections, and acute bacterial sinusitis.4 Concerns over safety and the association with Clostridiodes difficile infection have led inpatient antimicrobial stewardship programs (ASPs) to develop initiatives to promote avoidance of quinolones. The objective of this study was to quantify the effect of the 2016 FDA “black box” update on inpatient antibiotic use among a cohort of southeastern US hospitals.
We describe the case of an 11-month-old girl with a rare cerebellar glioblastoma driven by a NACC2-NTRK2 (Nucleus Accumbens Associated Protein 2-Neurotrophic Receptor Tyrosine Kinase 2) fusion. Initial workup of our case demonstrated homozygous CDKN2A deletion, but immunohistochemistry for other driver mutations, including IDH1 R132H, BRAF V600E, and H3F3A K27M were negative, and ATRX was retained. Tissue was subsequently submitted for personalized oncogenomic analysis, including whole genome and whole transcriptome sequencing, which demonstrated an activating NTRK2 fusion, as well as high PD-L1 expression, which was subsequently confirmed by immunohistochemistry. Furthermore, H3 and IDH demonstrated wildtype status. These findings suggested the possibility of treatment with either NTRK- or immune checkpoint- inhibitors through active clinical trials. Ultimately, the family pursued standard treatment that involved Head Start III chemotherapy and proton radiotherapy. Notably, at most recent follow upapproximately two years from initial diagnosis, the patient is in disease remission and thriving, suggesting favorable biology despite histologic malignancy. This case illustrates the value of personalized oncogenomics, as the molecular profiling revealed two actionable changes that would not have been apparent through routine diagnostics. NTRK fusions are known oncogenic drivers in a range of cancer types, but this is the first report of a NACC2-NTRK2 fusion in a glioblastoma.
This presentation will enable the learner to:
1.Explore the current molecular landscape of pediatric high grade gliomas
2.Recognize the value of personalized oncogenomic analysis, particularly in rare and/or aggressive tumors
3.Discuss the current status of NTRK inhibitor clinical trials
Analysis of a recent surge of Morsnevbreen, Svalbard, is used to test predictions of the enthalpy balance theory of surging. High-resolution time series of velocities, ice thickness and crevasse distribution allow key elements of the enthalpy (internal energy) budget to be quantified for different stages of the surge cycle. During quiescence (1936–1990), velocities were very low, and geothermal heat slowly built-up enthalpy at the bed. Measurable mass transfer and frictional heating began in 1990–2010, then positive frictional heating-velocity feedbacks caused gradual acceleration from 2010 to 2015. Rapid acceleration occurred in summer 2016, when extensive crevassing and positive air temperatures allowed significant surface to bed drainage. The surge front reached the terminus in October 2016, coincident with a drop in velocities. Ice plumes in the fjord are interpreted as discharge of large volumes of supercooled water from the bed. Surge termination was prolonged, however, indicating persistence of an inefficient drainage system. The observations closely match predictions of the theory, particularly build-up of enthalpy from geothermal and frictional heat, and surface meltwater, and the concomitant changes in ice-surface elevation and velocity. Additional characteristics of the surge reflect spatial processes not represented in the model, but can be explained with respect to enthalpy gradients.
The sternocleidomastoid can be used as a pedicled flap in head and neck reconstruction. It has previously been associated with high complication rates, likely due in part to the variable nature of its blood supply.
To provide clinicians with an up-to-date review of clinical outcomes of sternocleidomastoid flap surgery in head and neck reconstruction, integrated with a review of vascular anatomical studies of the sternocleidomastoid.
A literature search of the Medline and Web of Science databases was conducted. Complications were analysed for each study. The trend in success rates was analysed by date of the study.
Reported complication rates have improved over time. The preservation of two vascular pedicles rather than one may have contributed to improved outcomes.
The sternocleidomastoid flap is a versatile option for patients where prolonged free flap surgery is inappropriate. Modern vascular imaging techniques could optimise pre-operative planning.
Space Infrared Telescope for Cosmology and Astrophysics (SPICA), the cryogenic infrared space telescope recently pre-selected for a ‘Phase A’ concept study as one of the three remaining candidates for European Space Agency (ESA's) fifth medium class (M5) mission, is foreseen to include a far-infrared polarimetric imager [SPICA-POL, now called B-fields with BOlometers and Polarizers (B-BOP)], which would offer a unique opportunity to resolve major issues in our understanding of the nearby, cold magnetised Universe. This paper presents an overview of the main science drivers for B-BOP, including high dynamic range polarimetric imaging of the cold interstellar medium (ISM) in both our Milky Way and nearby galaxies. Thanks to a cooled telescope, B-BOP will deliver wide-field 100–350
m images of linearly polarised dust emission in Stokes Q and U with a resolution, signal-to-noise ratio, and both intensity and spatial dynamic ranges comparable to those achieved by Herschel images of the cold ISM in total intensity (Stokes I). The B-BOP 200
m images will also have a factor
30 higher resolution than Planck polarisation data. This will make B-BOP a unique tool for characterising the statistical properties of the magnetised ISM and probing the role of magnetic fields in the formation and evolution of the interstellar web of dusty molecular filaments giving birth to most stars in our Galaxy. B-BOP will also be a powerful instrument for studying the magnetism of nearby galaxies and testing Galactic dynamo models, constraining the physics of dust grain alignment, informing the problem of the interaction of cosmic rays with molecular clouds, tracing magnetic fields in the inner layers of protoplanetary disks, and monitoring accretion bursts in embedded protostars.
Clinical Enterobacteriacae isolates with a colistin minimum inhibitory concentration (MIC) ≥4 mg/L from a United States hospital were screened for the mcr-1 gene using real-time polymerase chain reaction (RT-PCR) and confirmed by whole-genome sequencing. Four colistin-resistant Escherichia coli isolates contained mcr-1. Two isolates belonged to the same sequence type (ST-632). All subjects had prior international travel and antimicrobial exposure.
To examine the association between parenting styles and overall child dietary quality within households that are low-income and food-insecure.
Child dietary intake was measured via a 24 h dietary recall. Dietary quality was assessed using the Healthy Eating Index-2005 (HEI-2005). Parenting styles were measured and scored using the Parenting Styles and Dimensions Questionnaire. Linear regressions were used to test main and interaction associations between HEI-2005 scores and parenting styles.
Non-probability sample of low-income and food-insecure households in South Carolina, USA.
Parent–child dyads (n 171). Parents were ≥18 years old and children were 9–15 years old.
We found a significant interaction between authoritative and authoritarian parenting style scores. For those with a mean authoritarian score, each unit increase in authoritative score was associated with a higher HEI-2005 score (b = 3·36, P < 0.05). For those with an authoritarian score that was 1 sd above the mean authoritarian score, each unit increase in authoritative score was associated with a higher HEI-2005 score (b = 8.42, P < 0.01). For those with an authoritarian score that was −1 sd below the mean authoritarian score, each unit increase in authoritative score was associated with a lower HEI-2005 score; however, this was not significant (b = −1·69, P > 0·05). Permissive parenting style scores were negatively associated with child dietary quality (b = −2·79, P < 0·05).
Parenting styles should be considered an important variable that is associated with overall dietary quality in children living within low-income and food-insecure households.
Starting in 2016, we initiated a pilot tele-antibiotic stewardship program at 2 rural Veterans Affairs medical centers (VAMCs). Antibiotic days of therapy decreased significantly (P < .05) in the acute and long-term care units at both intervention sites, suggesting that tele-stewardship can effectively support antibiotic stewardship practices in rural VAMCs.
Young people with 22q11.2 deletion syndrome (22q11.2DS) are at high risk for neurodevelopmental disorders. Sleep problems may play a role in this risk but their prevalence, nature and links to psychopathology and cognitive function remain undescribed in this population.
Sleep problems, psychopathology, developmental coordination and cognitive function were assessed in 140 young people with 22q11.2DS (mean age = 10.1, s.d. = 2.46) and 65 unaffected sibling controls (mean age = 10.8, s.d.SD = 2.26). Primary carers completed questionnaires screening for the children's developmental coordination and autism spectrum disorder.
Sleep problems were identified in 60% of young people with 22q11.2DS compared to 23% of sibling controls (OR 5.00, p < 0.001). Two patterns best-described sleep problems in 22q11.2DS: restless sleep and insomnia. Restless sleep was linked to increased ADHD symptoms (OR 1.16, p < 0.001) and impaired executive function (OR 0.975, p = 0.013). Both patterns were associated with elevated symptoms of anxiety disorder (restless sleep: OR 1.10, p = 0.006 and insomnia: OR 1.07, p = 0.045) and developmental coordination disorder (OR 0.968, p = 0.0023, and OR 0.955, p = 0.009). The insomnia pattern was also linked to elevated conduct disorder symptoms (OR 1.53, p = 0.020).
Clinicians and carers should be aware that sleep problems are common in 22q11.2DS and index psychiatric risk, cognitive deficits and motor coordination problems. Future studies should explore the physiology of sleep and the links with the neurodevelopment in these young people.
To identify, in caregivers of patients with Alzheimer’s disease (AD) dementia, factors associated with subjective (personal, physical, emotional, and social) and objective (informal caregiver time and costs) caregiver burden.
Prospective longitudinal European observational study: post-hoc analysis.
Community-dwelling patients in France and Germany aged ≥ 55 years (n = 969) with probable AD and their informal caregivers.
Mini-Mental State Examination (MMSE), Alzheimer’s Disease Cooperative Study—Activities of Daily Living (ADCS-ADL), 12-item Neuropsychiatric Inventory (NPI-12), Zarit Burden Interview (ZBI), informal caregiver basic and instrumental ADL hours (Resource Utilization in Dementia instrument), and informal caregiver costs. Mixed-effect models of repeated measures (MMRM) were run, including baseline and time-dependent covariates (change from baseline [CFB] to 18 months in MMSE, ADCS-ADL, and NPI-12 scores) associated with CFB in ZBI score/informal caregiver time over 36 months (analyzed using linear regression models) and informal caregiver costs over 36 months (analyzed using generalized linear models).
Greater decline in patient function (ADCS-ADL) over 18 months was associated with increased subjective caregiver burden (ZBI), hours, and costs over 36 months. Increased behavioral problems (NPI-12) over 18 months also negatively impacted ZBI. Cognitive decline (MMSE) over 18 months did not affect change in caregiver burden.
Long-term informal caregiver burden was driven by worsening functional abilities and behavioral symptoms but not cognitive decline, over 18 months in community-dwelling patients with AD dementia. Identifying the drivers of caregiver burden could highlight areas in which interventions may benefit both caregivers and patients.
We explored how positive and negative life experiences of caregivers are associated with household food insecurity.
The Midlands Family Study (MFS) was a cross-sectional study with three levels of household food security: food secure, food insecure without child hunger and food insecure with child hunger. Ordinal logistic regression analysis was used for analyses of negative and positive life experiences (number, impact, type) associated with food insecurity.
An eight-county region in South Carolina, USA, in 2012–2013.
Caregivers (n 511) in households with children.
Caregivers who reported greater numbers of negative life experiences and greater perceived impact had increased odds of household food insecurity and reporting their children experienced hunger. Each additional negative life experience count of the caregiver was associated with a 16 % greater odds of food insecurity without child hunger and a 28 % greater odds of child hunger. Each one-unit increase in the negative impact score (e.g. a worsening) was associated with 8 % higher odds of food insecurity without child hunger and 12 % higher odds of child hunger. Negative work experiences or financial instability had the strongest association (OR = 1·8; 95 % CI 1·5, 2·2) with child hunger. Positive life experiences were generally not associated with food security status, with one exception: for each unit increase in the number of positive experiences involving family and other relationships, the odds of child hunger decreased by 22 %.
More research is needed to understand approaches to build resilience against negative life experiences and strengthen positive familial, community and social relationships.
Introduction: Elder abuse is infrequently detected in the emergency department (ED) and less than 2% are reported to proper law authorities by ED physicians. This study aims to examine the characteristics of community-dwelling older adults who screened positive for elder abuse during home care assessments and the epidemiology of ED visits by these patients relative to other home care patients. Methods: This study utilized a population-based retrospective cohort study of home care patients in Canada between April 1, 2007 and March 31, 2015. Standardized, comprehensive home care assessments were extracted from the Home Care Reporting System. A positive screen for elder abuse was defined as at least one these criteria: fearful of a caregiver; unusually poor hygiene; unexplained injuries; or neglected, abused, or mistreated. Home care assessments were linked to the National Ambulatory Care Reporting System in the regions and time periods in which population-based estimates could be obtained to identify all ED visits within 6 months of the home care assessment. Results: A total of 30,413 from the 2,401,492 patients (1.3%) screened positive for elder abuse during a home care assessment. They were more likely to be male (40.5% versus 35.3%, p < 0.001), to have a cognitive impairment (82.9% versus 65.3%, p < 0.001), a higher frailty index (0.27 versus 0.22, p < 0.001) and to exhibit more depressive symptoms (depression rating scale 1 or more: 68.7% versus 42.7%, p < 0.001). Patient who screened positive for elder abuse were less likely to be independent in activities of daily living (41.9% versus 52.7%, p < 0.001) and reported having fallen more frequently (44.2% versus 35.5%, p < 0.001). Caregiver expressing distress was associated with elder abuse (35.3% versus 18.3%, p < 0.001) but not a higher number of hours caring for the patient. Victims of elder abuse were more likely to attend the ED for low acuity conditions (Canadian triage and acuity scale (CTAS) 4 or 5). Diagnosis at discharge from ED were similar with the exception of acute intoxication that was more frequent in patients who are victims of abuse. Conclusion: Elder abuse is infrequently detected during home care assessments in community-dwelling older adults. Higher frailty index, cognitive impairment, depressive symptoms were associated with elder abuse during homecare assessments. Patients who are victims of elder abuse are attending EDs more frequently for low acuity conditions but ED diagnosis at discharge, except for acute intoxication, are similar.
Children with congenital heart disease are at high risk for malnutrition. Standardisation of feeding protocols has shown promise in decreasing some of this risk. With little standardisation between institutions’ feeding protocols and no understanding of protocol adherence, it is important to analyse the efficacy of individual aspects of the protocols.
Adherence to and deviation from a feeding protocol in high-risk congenital heart disease patients between December 2015 and March 2017 were analysed. Associations between adherence to and deviation from the protocol and clinical outcomes were also assessed. The primary outcome was change in weight-for-age z score between time intervals.
Increased adherence to and decreased deviation from individual instructions of a feeding protocol improves patients change in weight-for-age z score between birth and hospital discharge (p = 0.031). Secondary outcomes such as markers of clinical severity and nutritional delivery were not statistically different between groups with high or low adherence or deviation rates.
High-risk feeding protocol adherence and fewer deviations are associated with weight gain independent of their influence on nutritional delivery and caloric intake. Future studies assessing the efficacy of feeding protocols should include the measures of adherence and deviations that are not merely limited to caloric delivery and illness severity.
Laser–solid interactions are highly suited as a potential source of high energy X-rays for nondestructive imaging. A bright, energetic X-ray pulse can be driven from a small source, making it ideal for high resolution X-ray radiography. By limiting the lateral dimensions of the target we are able to confine the region over which X-rays are produced, enabling imaging with enhanced resolution and contrast. Using constrained targets we demonstrate experimentally a
X-ray source, improving the image quality compared to unconstrained foil targets. Modelling demonstrates that a larger sheath field envelope around the perimeter of the constrained targets increases the proportion of electron current that recirculates through the target, driving a brighter source of X-rays.
A new deep level transient spectroscopy (DLTS) technique is described, called half-width at variable intensity analysis. This method utilizes the width and normalized intensity of a DLTS signal to determine the activation energy and capture cross section of the trap that generated the signal via a variable, kO. This constant relates the carrier emission rates giving rise to the differential capacitance signal associated with a given trap at two different temperatures: the temperature at which the maximum differential capacitance is detected, and an arbitrary temperature at which some nonzero differential capacitance signal is detected. The extracted activation energy of the detected trap center is used along with the position of the peak maximum to extract the capture cross section of the trap center.