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Second-generation antipsychotic medications (SGAs) have advanced the treatment of schizophrenia over the past 30 years. However, a number of potentially life-threatening cardiac side-effects associated with these treatments concern and can discourage prescribers from administering these evidence-based treatments. This review provides a practical, psychiatrist-oriented understanding of the relative frequencies, mechanisms, investigations and treatments associated with these cardiac toxicities. We aim to highlight that these are relatively rare complications of an effective class of drug and to promote the advantages of early involvement of cardiologists in the psychiatric multidisciplinary team to guide the investigation and management of these conditions.
After reading this article you will be able to:
•understand the relative incidence of cardiotoxic side-effects of the various SGAs
•perform preliminary investigations to diagnose the common cardiotoxic side-effects of SGAs
•understand the treatments for these cardiac side-effects and the role of cardiologists involved the care of these patients.
The first episode of psychosis is a critical period in the emergence of cardiometabolic risk.
We set out to explore the influence of individual and lifestyle factors on cardiometabolic outcomes in early psychosis.
This was a prospective cohort study of 293 UK adults presenting with first-episode psychosis investigating the influence of sociodemographics, lifestyle (physical activity, sedentary behaviour, nutrition, smoking, alcohol, substance use) and medication on cardiometabolic outcomes over the following 12 months.
Rates of obesity and glucose dysregulation rose from 17.8% and 12%, respectively, at baseline to 23.7% and 23.7% at 1 year. Little change was seen over time in the 76.8% tobacco smoking rate or the quarter who were sedentary for over 10 h daily. We found no association between lifestyle at baseline or type of antipsychotic medication prescribed with either baseline or 1-year cardiometabolic outcomes. Median haemoglobin A1c (HbA1c) rose by 3.3 mmol/mol in participants from Black and minority ethnic (BME) groups, with little change observed in their White counterparts. At 12 months, one-third of those with BME heritage exceeded the threshold for prediabetes (HbA1c >39 mmol/mol).
Unhealthy lifestyle choices are prevalent in early psychosis and cardiometabolic risk worsens over the next year, creating an important window for prevention. We found no evidence, however, that preventative strategies should be preferentially directed based on lifestyle habits. Further work is needed to determine whether clinical strategies should allow for differential patterns of emergence of cardiometabolic risk in people of different ethnicities.
Declaration of interest
F.G. has received honoraria for advisory work and lectures or CME activity support from Roche, BMS, Lundbeck, Otsuka, Janssen and Sunovion, is a collaborator on an NHS Innovations project co-funded by Janssen and has a family member with professional links to Lilly and GSK, including shares. R.M.M. has received honoraria for lectures from Lundbeck, Otsuka, Janssen and Sunovian. M.D.F. has received honoraria for lectures from Janssen and Sunovian. Z.A. has received honoraria for advisory work and lectures from Roche, Sanofi, Lilly and Otsuka. O.H. has received investigator-initiated research funding from and/or participated in advisory/speaker meetings organised by Astra-Zeneca, Autifony, Biogen, BMS, Eli Lilly, Heptares, Jansenn, Lundbeck, Lyden-Delta, Otsuka, Servier, Sunovion, Rand and Roche. D.T. has received funding for lectures and research from Janssen, Otsuka, Servier, Lundbeck, Sunovion.
In preparation for a multisite antibiotic stewardship intervention, we assessed knowledge and attitudes toward management of asymptomatic bacteriuria (ASB) plus teamwork and safety climate among providers, nurses, and clinical nurse assistants (CNAs).
Prospective surveys during January–June 2018.
All acute and long-term care units of 4 Veterans’ Affairs facilities.
The survey instrument included 2 previously tested subcomponents: the Kicking CAUTI survey (ASB knowledge and attitudes) and the Safety Attitudes Questionnaire (SAQ).
A total of 534 surveys were completed, with an overall response rate of 65%. Cognitive biases impacting management of ASB were identified. For example, providers presented with a case scenario of an asymptomatic patient with a positive urine culture were more likely to give antibiotics if the organism was resistant to antibiotics. Additionally, more than 80% of both nurses and CNAs indicated that foul smell is an appropriate indication for a urine culture. We found significant interprofessional differences in teamwork and safety climate (defined as attitudes about issues relevant to patient safety), with CNAs having highest scores and resident physicians having the lowest scores on self-reported perceptions of teamwork and safety climates (P < .001). Among providers, higher safety-climate scores were significantly associated with appropriate risk perceptions related to ASB, whereas social norms concerning ASB management were correlated with higher teamwork climate ratings.
Our survey revealed substantial misunderstanding regarding management of ASB among providers, nurses, and CNAs. Educating and empowering these professionals to discourage unnecessary urine culturing and inappropriate antibiotic use will be key components of antibiotic stewardship efforts.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Nature’s optical nanomaterials are poised to form the platform for future optical devices with unprecedented functionality. The brilliant colors of many animals arise from the physical interaction of light with nanostructured, multifunctional materials. While their length scale is typically in the 100-nm range, the morphology of these structures can vary strongly. These biological nanostructures are obtained in a controlled manner, using biomaterials under ambient conditions. The formation processes nature employs use elements of both equilibrium self-assembly and far-from-equilibrium and growth processes. This renders not only the colors themselves, but also the formation processes technologically and ecologically highly relevant. Yet, for many biological nanostructured materials, little is known about the formation mechanisms—partially due to a lack of in vivo imaging methods. Here, we present the toolbox of natural multifunctional nanostructures and the current knowledge about the understanding of their far-from-equilibrium assembly processes.
Inappropriate antibiotic use is associated with increased antimicrobial resistance and adverse events that can lead to further downstream patient harm. Preventative strategies must be employed to improve antibiotic use while reducing avoidable harm. We use the term “antibiotic never events” to globally recognize and define the most inappropriate antibiotic use.
We observed pediatric S. aureus hospitalizations decreased 36% from 26.3 to 16.8 infections per 1,000 admissions from 2009 to 2016, with methicillin-resistant S. aureus (MRSA) decreasing by 52% and methicillin-susceptible S. aureus decreasing by 17%, among 39 pediatric hospitals. Similar decreases were observed for days of therapy of anti-MRSA antibiotics.
In this report, a unique case of a symptomatic vascular ring formed by right aortic arch, aberrant left subclavian artery, and left ligamentum arteriosus in which there is atresia of the proximal left subclavian artery is described. Imaging modalities were non-diagnostic and the patient was sent to surgery based on strong clinical suspicion. Her anatomy was delineated in the operating room and the ring was successfully repaired.
Background: Phantogeusia associated with Parkinson Disease has not heretofore been reported. Methods: A 59 year old right handed female presented with a four year history of a bitter, sour and sweet taste on her entire tongue and roof of her mouth, 8/10 intensity, constant, persistent, without any external stimuli. Drinking water tasted bitter and sour. The phantogeusia was unresponsive to dietary changes, gabapentine, and allergy medications. Results: Abnormalities in Neurological examination: Decreased blink frequency. Hypokinetic. Hypomimetic face. Mood appears sad. Cranial Nerve (CN) examination: CN lll, lV, Vl: Saccadization of horizontal eye movements. Motor Examination: Pill rolling tremor in right hand. 1+ cogwheel rigidity in left upper extremity. Gait: 2+ retropulsion. Chemosensory testing: Olfactory: Alcohol Sniff Test: 6 (anosmia). SNAP Phenylethyl Alcohol Threshold Testing left -2.5 (hyposmia) & right > -2.0 (anosmia). Gustatory testing: Propylthiouracil Disc Taste test: 10 (normogeusia). Taste Testing Threshold: normogeusia to NaCl, Sucrose, HCl, Urea, and PTC. Other: DOPAPET: positive for Parkinson disease. Upper endoscopy: normal. Conclusions: Investigation for the presence of parkinsonian features in those with phantogeusia is warranted and chemosensory dysfunction including phantogeusia in those who presents with Parkinson’s disease is worthy of exploration.
BACKGROUND: Adult medulloblastomas account for less than 1% of adult neoplasms. They are challenging to treat due to their rarity and the heterogeneity of treatment options, all of which have limited evidence. In this retrospective review, we examined cases of adult medulloblastoma diagnosed in Alberta during a 70-year period. METHODS: We reviewed the charts of patients diagnosed with medulloblastoma between 1944 and 2014. We performed Cox and logistic regression analysis to elucidate features that may influence recurrence risk and survival. RESULTS: We found 86 and analyzed 78 cases. The median age at diagnosis was 27 (range 16 to 71). Most were male (68%). Most had surgery (92%). By COG risk stratification, 54% were standard risk while 21% were poor risk. RT was administered to 85% of patients, and craniospinal irradiation (CSI) to 81%. Chemotherapy was administered to 48%. Median survival was 4.4 years from diagnosis (range 0 to 20). At last follow-up, 39% were alive and recurrence-free. Patients who had CSI and posterior fossa boost had longer survival (p=0.047 and<0.01, respectively) and were less likely to recur (p=0.041 and<0.01). Chemotherapy was also associated with decreased recurrence (p=0.025). CONCLUSIONS: Medulloblastomas carry a significant recurrence risk, especially for patients who had subtotal resection. CSI and posterior fossa boost were associated with fewer recurrences and improved survival. COG risk stratification, Chang staging, desmoplastic histology, vermian location, 4th ventricle involvement, tumor enhancement, presence of hydrocephalus and cerebrospinal fluid (CSF) involvement are not significantly prognostic.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Leafy spurge (Euphorbia esula L.) is an invasive perennial weed infesting range and recreational lands of North America. Previous research and omics projects with E. esula have helped develop it as a model for studying many aspects of perennial plant development and response to abiotic stress. However, the lack of an assembled genome for E. esula has limited the power of previous transcriptomics studies to identify functional promoter elements and transcription factor binding sites. An assembled genome for E. esula would enhance our understanding of signaling processes controlling plant development and responses to environmental stress and provide a better understanding of genetic factors impacting weediness traits, evolution, and herbicide resistance. A comprehensive transcriptome database would also assist in analyzing future RNA-seq studies and is needed to annotate and assess genomic sequence assemblies. Here, we assembled and annotated 56,234 unigenes from an assembly of 589,235 RNA-seq-derived contigs and a previously published Sanger-sequenced expressed sequence tag collection. The resulting data indicate that we now have sequence for >90% of the expressed E. esula protein-coding genes. We also assembled the gene space of E. esula by using a limited coverage (18X) genomic sequence database. In this study, the programs Velvet and Trinity produced the best gene-space assemblies based on representation of expressed and conserved eukaryotic genes. The results indicate that E. esula contains as much as 23% repetitive sequences, of which 11% are unique. Our sequence data were also sufficient for assembling a full chloroplast and partial mitochondrial genome. Further, marker analysis identified more than 150,000 high-quality variants in our E. esula L-RNA–scaffolded, whole-genome, Trinity-assembled genome. Based on these results, E. esula appears to have limited heterozygosity. This study provides a blueprint for low-cost genomic assemblies in weed species and new resources for identifying conserved and novel promoter regions among coordinately expressed genes of E. esula.
An onboard automated coronal mass ejections (CMEs) detection algorithm has been developed for Visible Emission Line Coronagraph (VELC) onboard ADITYA-L1. The aim of this algorithm is to reduce the load on telemetry by sending the high spatial (~ 2.51 arcsec pixel−1) and temporal (1 s) resolution images of corona from 1.05 R⊙ to 3 R⊙, containing CMEs and rejecting others. It is based on intensity thresholding followed by an area thresholding in successive running difference images which are re-binned to lower resolution to improve signal to noise. Here we present the results of application of the algorithm on synthetic corona images generated for the VELC field of view (FOV).
We report daptomycin minimum inhibitory concentrations (MICs) for vancomycin-resistant Enterococcus faecium isolated from bloodstream infections over a 4-year period. The daptomycin MIC increased over time hospital-wide for initial isolates and increased over time within patients, culminating in 40% of patients having daptomycin-nonsusceptible isolates in the final year of the study.