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To compare rates of clinical response in children with Clostridioides difficile infection (CDI) treated with metronidazole vs vancomycin.
Design:
Retrospective cohort study was performed as a secondary analysis of a previously established prospective cohort of hospitalized children with CDI. For 187 participants 2–17 years of age who were treated with metronidazole and/or vancomycin, the primary outcome of clinical response (defined as resolution of diarrhea within 5 days of treatment initiation) was identified retrospectively. Baseline variables associated with the primary outcome were included in a logistic regression propensity score model estimating the likelihood of receiving metronidazole vs vancomycin. Logistic regression using inverse probability of treatment weighting (IPTW) was used to estimate the effect of treatment on clinical response.
Results:
One hundred seven subjects received metronidazole and 80 subjects received vancomycin as primary treatment. There was no univariable association between treatment group and clinical response; 78.30% (N = 83) of the metronidazole treatment group and 78.75% (N = 63) of the vancomycin group achieved clinical response (P = 0.941). After adjustment using propensity scores with IPTW, the odds of a clinical response for participants who received metronidazole was 0.554 (95% CI: 0.272, 1.131) times the odds of those who received vancomycin (P = 0.105).
Conclusions:
In this observational cohort study of pediatric inpatients with CDI, the rate of resolution of diarrhea after 5 days of treatment did not differ among children who received metronidazole vs vancomycin.
Lewy body dementias (LBD) are the second most common dementia. Several genes have been associated with LBD, but little is known about their contributions to LBD pathophysiology. Each gene may transcribe multiple RNA, and LBD brains have extensive RNA splicing dysregulation. Hence, we completed the first transcriptome-wide transcript-level differential expression analysis of post-mortem LBD brains for gaining more insights into LBD molecular pathology that are essential for facilitating discovery of novel therapeutic targets and biomarkers for LBD. We completed transcript-level quantification of next-generation RNA-sequencing data from post-mortem anterior cingulate (ACC) and dorsolateral prefrontal cortices (DLPFC) of people with pathology-verified LBD (LBD = 14; Controls = 7) using Salmon. We identified differentially expressed transcripts (DET) using edgeR and investigated their functional implications using DAVID. We performed transcriptome-wide alternative splicing analysis using DRIMseq. We identified 74 DET in ACC and 96 DET in DLPFC after Benjamini-Hochberg false discovery rate (FDR) correction (5%). There were 135 and 98 FDR-corrected alternatively spliced genes in ACC and DLPFC of LBD brains, respectively. Identified DET may contribute to LBD pathology by altering DNA repair, apoptosis, neuroplasticity, protein phosphorylation, and regulation of RNA transcription. We confirm widespread alternative splicing and absence of chronic neuroinflammation in LBD brains. Transcript-level differential expression analysis can reveal specific DET that cannot be detected by gene-level expression analyses. Therapeutic and diagnostic biomarker potential of identified DET, especially those from TMEM18, MICB, MPO, and GABRB3, warrant further investigation. Future LBD blood-based biomarker studies should prioritise measuring the identified DET in small extracellular vesicles.
This constructivist grounded theory study aimed to (1) explore patients’ experiences of and roles in interprofessional collaborative practice for chronic conditions in primary care and (2) consider the relevance and alignment of an existing theoretical framework on patients’ roles and based on the experiences of patient advocates.
Background:
High-quality management of chronic conditions requires an interprofessional collaborative practice model of care considering an individual’s mental, physical, and social health situation. Patients’ experiences of this model in the primary care setting are relatively unknown.
Methods:
A constructivist grounded theory approach was taken. Interview data were collected from primary care patients with chronic conditions across Australia in August 2020 – February 2022. Interviews were recorded, transcribed verbatim, and thematically analysed by (1) initial line-by-line coding, (2) focused coding, (3) memo writing, (4) categorisation, and (5) theme and sub-theme development. Themes and sub-themes were mapped against an existing theoretical framework to expand and confirm the results from a previous study with a similar research aim.
Findings:
Twenty adults with chronic conditions spanning physical disability, diabetes, heart disease, cancer, autoimmune, and mental health conditions participated. Two themes were developed: (1) Adapting to Change with two sub-themes describing how patients adapt to interprofessional team care and (2) Shifting across the spectrum of roles, with five sub-themes outlining the roles patients enact while receiving care. The findings suggest that patients’ roles are highly variable and fluid in interprofessional collaborative practice, and further work is recommended to develop a resource to support greater patient engagement in interprofessional collaborative practice.
We examined whether cannabis use contributes to the increased risk of psychotic disorder for non-western minorities in Europe.
Methods
We used data from the EU-GEI study (collected at sites in Spain, Italy, France, the United Kingdom, and the Netherlands) on 825 first-episode patients and 1026 controls. We estimated the odds ratio (OR) of psychotic disorder for several groups of migrants compared with the local reference population, without and with adjustment for measures of cannabis use.
Results
The OR of psychotic disorder for non-western minorities, adjusted for age, sex, and recruitment area, was 1.80 (95% CI 1.39–2.33). Further adjustment of this OR for frequency of cannabis use had a minimal effect: OR = 1.81 (95% CI 1.38–2.37). The same applied to adjustment for frequency of use of high-potency cannabis. Likewise, adjustments of ORs for most sub-groups of non-western countries had a minimal effect. There were two exceptions. For the Black Caribbean group in London, after adjustment for frequency of use of high-potency cannabis the OR decreased from 2.45 (95% CI 1.25–4.79) to 1.61 (95% CI 0.74–3.51). Similarly, the OR for Surinamese and Dutch Antillean individuals in Amsterdam decreased after adjustment for daily use: from 2.57 (95% CI 1.07–6.15) to 1.67 (95% CI 0.62–4.53).
Conclusions
The contribution of cannabis use to the excess risk of psychotic disorder for non-western minorities was small. However, some evidence of an effect was found for people of Black Caribbean heritage in London and for those of Surinamese and Dutch Antillean heritage in Amsterdam.
Background: Saskatchewan’s Rural and Remote Memory Clinic (RRMC) has provided post-diagnostic virtual dementia care for approximately 19 years. In response to the COVID-19 pandemic and a new need for remote dementia diagnosis, we developed a virtual, team-based, interdisciplinary (neurology, neuropsychology, nursing), diagnostic memory clinic (vRRMC). We evaluated patient and caregiver satisfaction with the new virtual clinic. Methods: Semi-structured telephone interviews were conducted with rural vRRMC patients (n=7), caregivers (n= 13), and one patient/caregiver dyad. Ages of respondents ranged from 40 to 70 years old (60% female). Level of diagnosed cognitive dysfunction ranged from subjective cognitive impairment to major neurocognitive disorder. Respondents saved an average of 460 km of travel compared to a trip to Saskatoon. Results: Thematic analysis of responses revealed universal satisfaction with the virtual model. The technology training sessions, offered prior to the first vRRMC visit, was described as important for satisfaction. Analysis of preference for future visits revealed more nuance; some preferred in-person visits and planned to travel for future appointments post-pandemic, while others preferred to maintain the virtual model due to perceived travel burden (cost, time, and inconvenience). Conclusions: When clinically appropriate, virtual diagnostic memory clinics should persist as an option post pandemic for families who experience high travel burden.
Tobacco is a highly prevalent substance of abuse in patients with psychosis. Previous studies have reported an association between tobacco use and schizophrenia. The aim of this study was to analyze the relationship between tobacco use and first-episode psychosis (FEP), age at onset of psychosis, and specific diagnosis of psychosis.
Methods
The sample consisted of 1105 FEP patients and 1355 controls from the European Network of National Schizophrenia Networks Studying Gene–Environment Interactions (EU-GEI) study. We assessed substance use with the Tobacco and Alcohol Questionnaire and performed a series of regression analyses using case-control status, age of onset of psychosis, and diagnosis as outcomes and tobacco use and frequency of tobacco use as predictors. Analyses were adjusted for sociodemographic characteristics, alcohol, and cannabis use.
Results
After controlling for cannabis use, FEP patients were 2.6 times more likely to use tobacco [p ⩽ 0.001; adjusted odds ratio (AOR) 2.6; 95% confidence interval (CI) [2.1–3.2]] and 1.7 times more likely to smoke 20 or more cigarettes a day (p = 0.003; AOR 1.7; 95% CI [1.2–2.4]) than controls. Tobacco use was associated with an earlier age at psychosis onset (β = −2.3; p ⩽ 0.001; 95% CI [−3.7 to −0.9]) and was 1.3 times more frequent in FEP patients with a diagnosis of schizophrenia than in other diagnoses of psychosis (AOR 1.3; 95% CI [1.0–1.8]); however, these results were no longer significant after controlling for cannabis use.
Conclusions
Tobacco and heavy-tobacco use are associated with increased odds of FEP. These findings further support the relevance of tobacco prevention in young populations.
While unobscured and radio-quiet active galactic nuclei are regularly being found at redshifts
$z > 6$
, their obscured and radio-loud counterparts remain elusive. We build upon our successful pilot study, presenting a new sample of low-frequency-selected candidate high-redshift radio galaxies (HzRGs) over a sky area 20 times larger. We have refined our selection technique, in which we select sources with curved radio spectra between 72–231 MHz from the GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) survey. In combination with the requirements that our GLEAM-selected HzRG candidates have compact radio morphologies and be undetected in near-infrared
$K_{\rm s}$
-band imaging from the Visible and Infrared Survey Telescope for Astronomy Kilo-degree Infrared Galaxy (VIKING) survey, we find 51 new candidate HzRGs over a sky area of approximately
$1200\ \mathrm{deg}^2$
. Our sample also includes two sources from the pilot study: the second-most distant radio galaxy currently known, at
$z=5.55$
, with another source potentially at
$z \sim 8$
. We present our refined selection technique and analyse the properties of the sample. We model the broadband radio spectra between 74 MHz and 9 GHz by supplementing the GLEAM data with both publicly available data and new observations from the Australia Telescope Compact Array at 5.5 and 9 GHz. In addition, deep
$K_{\rm s}$
-band imaging from the High-Acuity Widefield K-band Imager (HAWK-I) on the Very Large Telescope and from the Southern Herschel Astrophysical Terahertz Large Area Survey Regions
$K_{\rm s}$
-band Survey (SHARKS) is presented for five sources. We discuss the prospects of finding very distant radio galaxies in our sample, potentially within the epoch of reionisation at
$z \gtrsim 6.5$
.
Gene x environment (G×E) interactions, i.e. genetic modulation of the sensitivity to environmental factors and/or environmental control of the gene expression, have not been reliably established regarding aetiology of psychotic disorders. Moreover, recent studies have shown associations between the polygenic risk scores for schizophrenia (PRS-SZ) and some risk factors of psychotic disorders, challenging the traditional gene v. environment dichotomy. In the present article, we studied the role of GxE interaction between psychosocial stressors (childhood trauma, stressful life-events, self-reported discrimination experiences and low social capital) and the PRS-SZ on subclinical psychosis in a population-based sample.
Methods
Data were drawn from the EUropean network of national schizophrenia networks studying Gene-Environment Interactions (EU-GEI) study, in which subjects without psychotic disorders were included in six countries. The sample was restricted to European descendant subjects (n = 706). Subclinical dimensions of psychosis (positive, negative, and depressive) were measured by the Community Assessment of Psychic Experiences (CAPE) scale. Associations between the PRS-SZ and the psychosocial stressors were tested. For each dimension, the interactions between genes and environment were assessed using linear models and comparing explained variances of ‘Genetic’ models (solely fitted with PRS-SZ), ‘Environmental’ models (solely fitted with each environmental stressor), ‘Independent’ models (with PRS-SZ and each environmental factor), and ‘Interaction’ models (Independent models plus an interaction term between the PRS-SZ and each environmental factor). Likelihood ration tests (LRT) compared the fit of the different models.
Results
There were no genes-environment associations. PRS-SZ was associated with positive dimensions (β = 0.092, R2 = 7.50%), and most psychosocial stressors were associated with all three subclinical psychotic dimensions (except social capital and positive dimension). Concerning the positive dimension, Independent models fitted better than Environmental and Genetic models. No significant GxE interaction was observed for any dimension.
Conclusions
This study in subjects without psychotic disorders suggests that (i) the aetiological continuum hypothesis could concern particularly the positive dimension of subclinical psychosis, (ii) genetic and environmental factors have independent effects on the level of this positive dimension, (iii) and that interactions between genetic and individual environmental factors could not be identified in this sample.
Caregivers of patients with primary brain tumor (PBT) describe feeling preoccupied with the inevitability of their loved one's death. However, there are currently no validated instruments to assess death anxiety in caregivers. This study sought to examine (1) the psychometric properties of the Death and Dying Distress Scale (DADDS), adapted for caregivers (DADDS-CG), and (2) the prevalence and correlates of death anxiety in caregivers of patients with PBT.
Methods
Caregivers (N = 67) of patients with PBT completed the DADDS-CG, Patient Health Questionnaire (PHQ-9), Generalized Anxiety Disorder (GAD-7), Fear of Cancer Recurrence (FCR-7), and God Locus of Health Control (GLHC). Caregivers’ sociodemographic information and patients’ medical characteristics were also collected. Preliminary examination of the psychometric properties of the DADDS-CG was conducted using exploratory factor analysis, Cronbach's alpha, and correlations. The prevalence and risk factors of death anxiety were assessed using frequencies, pair-wise comparisons, and correlations.
Results
Factor analysis of the DADDS-CG revealed a two-factor structure consistent with the original DADDS. The DADDS-CG demonstrated excellent internal consistency, convergent validity with the PHQ-9, GAD-7, and FCR-7, and discriminant validity with the GLHC. Over two-thirds of caregivers reported moderate-to-severe symptoms of death anxiety. Death anxiety was highest in women and caregivers of patients with high-grade PBT.
Significance of results
The DADDS-CG demonstrates sound psychometric properties in caregivers of patients with PBT, who report high levels of death anxiety. Further research is needed to support the measure's value in clinical care and research — both in this population and other caregivers — in order to address this unmet, psychosocial need.
Lower parental education has been linked to adverse youth mental health outcomes. However, the relationship between parental education and youth suicidal behaviours remains unclear. We explored the association between parental education and youth suicidal ideation and attempts, and examined whether sociocultural contexts moderate such associations.
Methods
We conducted a systematic review and meta-analysis with a systematic literature search in PubMed, PsycINFO, Medline and Embase from 1900 to December 2020 for studies with participants aged 0–18, and provided quantitative data on the association between parental education and youth suicidal ideation and attempts (death included). Only articles published in English in peer-reviewed journals were considered. Two authors independently assessed eligibility of the articles. One author extracted data [e.g. number of cases and non-cases in each parental education level, effect sizes in forms of odds ratios (ORs) or beta coefficients]. We then calculated pooled ORs using a random-effects model and used moderator analysis to investigate heterogeneity.
Results
We included a total of 59 articles (63 study samples, totalling 2 738 374 subjects) in the meta-analysis. Lower parental education was associated with youth suicidal attempts [OR = 1.12, 95% Confidence Interval (CI) = 1.04–1.21] but not with suicidal ideation (OR = 1.05, 95% CI = 0.98–1.12). Geographical region and country income level moderated the associations. Lower parental education was associated with an increased risk of youth suicidal attempts in Northern America (OR = 1.26, 95% CI = 1.10–1.45), but with a decreased risk in Eastern and South-Eastern Asia (OR = 0.72, 95% CI = 0.54–0.96). An association of lower parental education and increased risk of youth suicidal ideation was present in high- income countries (HICs) (OR = 1.14, 95% CI = 1.05–1.25), and absent in low- and middle-income countries (LMICs) (OR = 0.91, 95% CI = 0.77–1.08).
Conclusions
The association between youth suicidal behaviours and parental education seems to differ across geographical and economical contexts, suggesting that cultural, psychosocial or biological factors may play a role in explaining this association. Although there was high heterogeneity in the studies reviewed, this evidence suggests that the role of familial sociodemographic characteristics in youth suicidality may not be universal. This highlights the need to consider cultural, as well as familial factors in the clinical assessment and management of youth's suicidal behaviours in our increasingly multicultural societies, as well as in developing prevention and intervention strategies for youth suicide.
The GaLactic and Extragalactic All-sky Murchison Widefield Array (GLEAM) is a radio continuum survey at 76–227 MHz of the entire southern sky (Declination $<\!{+}30^{\circ}$) with an angular resolution of ${\approx}2$ arcmin. In this paper, we combine GLEAM data with optical spectroscopy from the 6dF Galaxy Survey to construct a sample of 1 590 local (median $z \approx 0.064$) radio sources with $S_{200\,\mathrm{MHz}} > 55$ mJy across an area of ${\approx}16\,700\,\mathrm{deg}^{2}$. From the optical spectra, we identify the dominant physical process responsible for the radio emission from each galaxy: 73% are fuelled by an active galactic nucleus (AGN) and 27% by star formation. We present the local radio luminosity function for AGN and star-forming (SF) galaxies at 200 MHz and characterise the typical radio spectra of these two populations between 76 MHz and ${\sim}1$ GHz. For the AGN, the median spectral index between 200 MHz and ${\sim}1$ GHz, $\alpha_{\mathrm{high}}$, is $-0.600 \pm 0.010$ (where $S \propto \nu^{\alpha}$) and the median spectral index within the GLEAM band, $\alpha_{\mathrm{low}}$, is $-0.704 \pm 0.011$. For the SF galaxies, the median value of $\alpha_{\mathrm{high}}$ is $-0.650 \pm 0.010$ and the median value of $\alpha_{\mathrm{low}}$ is $-0.596 \pm 0.015$. Among the AGN population, flat-spectrum sources are more common at lower radio luminosity, suggesting the existence of a significant population of weak radio AGN that remain core-dominated even at low frequencies. However, around 4% of local radio AGN have ultra-steep radio spectra at low frequencies ($\alpha_{\mathrm{low}} < -1.2$). These ultra-steep-spectrum sources span a wide range in radio luminosity, and further work is needed to clarify their nature.
This SHEA white paper identifies knowledge gaps and challenges in healthcare epidemiology research related to coronavirus disease 2019 (COVID-19) with a focus on core principles of healthcare epidemiology. These gaps, revealed during the worst phases of the COVID-19 pandemic, are described in 10 sections: epidemiology, outbreak investigation, surveillance, isolation precaution practices, personal protective equipment (PPE), environmental contamination and disinfection, drug and supply shortages, antimicrobial stewardship, healthcare personnel (HCP) occupational safety, and return to work policies. Each section highlights three critical healthcare epidemiology research questions with detailed description provided in supplementary materials. This research agenda calls for translational studies from laboratory-based basic science research to well-designed, large-scale studies and health outcomes research. Research gaps and challenges related to nursing homes and social disparities are included. Collaborations across various disciplines, expertise and across diverse geographic locations will be critical.
Optical tracking systems typically trade off between astrometric precision and field of view. In this work, we showcase a networked approach to optical tracking using very wide field-of-view imagers that have relatively low astrometric precision on the scheduled OSIRIS-REx slingshot manoeuvre around Earth on 22 Sep 2017. As part of a trajectory designed to get OSIRIS-REx to NEO 101955 Bennu, this flyby event was viewed from 13 remote sensors spread across Australia and New Zealand to promote triangulatable observations. Each observatory in this portable network was constructed to be as lightweight and portable as possible, with hardware based off the successful design of the Desert Fireball Network. Over a 4-h collection window, we gathered 15 439 images of the night sky in the predicted direction of the OSIRIS-REx spacecraft. Using a specially developed streak detection and orbit determination data pipeline, we detected 2 090 line-of-sight observations. Our fitted orbit was determined to be within about 10 km of orbital telemetry along the observed 109 262 km length of OSIRIS-REx trajectory, and thus demonstrating the impressive capability of a networked approach to Space Surveillance and Tracking.
Epidemiological studies have reported that the increased risk of developing psychosis in cannabis users is dose related. In addition, experimental research has shown that the active constituent of cannabis responsible for its psychotogenic effect is Delta-9-Tetrahydrocannabinol (THC) (Murray et al, 2007). Recent evidence has suggested an increased in potency (% TCH) in the cannabis seized in the UK (Potter et al, 2007).
Hypothesis:
We predicted that first episode psychosis patients are more likely to use higher potency cannabis and more frequently than controls.
Methods:
We collected information concerning socio-demographic, clinical characteristics and cannabis use (age at first use, frequency, length of use, type of cannabis used) from a sample of 191 first-episode psychosis patients and 120 matched healthy volunteers. All were recruited as part of the Genetic and Psychosis (GAP) study which studied all patients who presented to the South London and Maudsley Trust.
Results:
There was no significant difference in the life-time prevalence of cannabis use or age at first use between cases and controls. However, cases were more likely to be regular users (p=0.05), to be current users (p=0.04) and to have smoked cannabis for longer (p=0.01). Among cannabis users, 86.8% of 1st Episode Psychosis Patients preferentially used Skunk/Sinsemilla compared to 27.7% of Controls. Only 13.2 % of 1st Episode psychosis Patients chose to use Resin/Hash compared to 76.3% of controls. The concentration of TCH in these in South East London, ranges between 8.5 and 14 % (Potter et al, 2007). Controls (47%) were more likely to use Hash (Resin) whose average TCH concentration is 3.4% (Potter et al, 2007).
Conclusions:
Patients with first episode psychosis have smoked higher potency cannabis, for longer and with greater frequency, than healthy controls.
Extended-release formulations of antidepressants have been marketed as a strategy to increase patient adherence. Changes in the formulation of drugs, however, could be related to changes in efficacy and tolerability. Among second-generation antidepressants, bupropion, fluoxetine, mirtazapine, paroxetine, and venlafaxine are available in immediate- and extended-release formulations.
Objectives
To compare the efficacy, tolerability, and adherence of immediate- versus extended-release formulations of second-generation antidepressants for the treatment of major depressive disorder (MDD) in adults.
Aim
To provide an evidence base for clinicians when choosing immediate- or extended-release formulations of antidepressants for the treatment of MDD.
Methods
We conducted a comparative effectiveness review for the U.S. Agency for Healthcare Research and Quality searching PubMed, EMBASE, The Cochrane Library, and the International Pharmaceutical Abstracts up to May 2010. Two people independently reviewed the literature, abstracted data, and rated the risk of bias.
Results
Six RCTs and one observational study provided evidence about the comparative efficacy, tolerability, and adherence of bupropion SR (sustained release) versus bupropion XL (extended release), fluoxetine daily vs. fluoxetine weekly, paroxetine IR (immediate release) versus paroxetine CR (continuous release), and venlafaxine IR versus venlafaxine XR (extended release). Overall, no substantial differences in efficacy and safety could be detected. Open-label and observational evidence indicated better adherence for bupropion XL and fluoxetine weekly than for immediate-release medications. No differences in adherence could be detected between paroxetine IR and paroxetine CR.
Conclusions
Our findings indicate similar efficacy and tolerability between immediate- and extended-release formulations. Whether extended-release formulations lead to better adherence remains unclear.
Evidence indicates that migrant and ethnic minority groups have an elevated risk of psychosis in a number of countries. Social disadvantage is one of the hypotheses put forward to explain these findings. The aim of this study is to investigate main effects, association and synergism between social disadvantage and migration on odds of psychotic experiences. We collected information on social disadvantage and migration from 332 patients and from 301 controls recruited from the local population in South London. Two indicators of social disadvantage in childhood and six indicators of social disadvantage in adulthood were analyzed. We found evidence that the odds of reporting psychotic experience were higher in those who experienced social disadvantage in childhood (OR= 2.88, 95% CI 2.03-4.06), social disadvantage in adulthood (OR= 9.06, 95% CI 5.21–15.74) and migration (OR = 1.46, 95% CI 1.05–2.02). When both social disadvantage and migration were considered together, the association with psychosis was slightly higher for social disadvantage in childhood and migration (OR 3.46, 95% CI 2.12–5.62) and social disadvantage in adulthood and migration (OR 9.10, 95% CI 4.63-17.86). Migrant cases were not more likely than non-migrant cases to report social disadvantage (p = 0.71) and no evidence of an additive interaction between migration and social disadvantage was found (ICR 0.32 95% CI -4.04–4.69). Preliminary results support the hypothesis that the association between social disadvantage and psychosis is independent of migration status.
Disclosure of interest
The authors have not supplied their declaration of competing interest.