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To determine whether age, gender and marital status are associated with prognosis for adults with depression who sought treatment in primary care.
Medline, Embase, PsycINFO and Cochrane Central were searched from inception to 1st December 2020 for randomised controlled trials (RCTs) of adults seeking treatment for depression from their general practitioners, that used the Revised Clinical Interview Schedule so that there was uniformity in the measurement of clinical prognostic factors, and that reported on age, gender and marital status. Individual participant data were gathered from all nine eligible RCTs (N = 4864). Two-stage random-effects meta-analyses were conducted to ascertain the independent association between: (i) age, (ii) gender and (iii) marital status, and depressive symptoms at 3–4, 6–8,<Vinod: Please carry out the deletion of serial commas throughout the article> and 9–12 months post-baseline and remission at 3–4 months. Risk of bias was evaluated using QUIPS and quality was assessed using GRADE. PROSPERO registration: CRD42019129512. Pre-registered protocol https://osf.io/e5zup/.
There was no evidence of an association between age and prognosis before or after adjusting for depressive ‘disorder characteristics’ that are associated with prognosis (symptom severity, durations of depression and anxiety, comorbid panic disorderand a history of antidepressant treatment). Difference in mean depressive symptom score at 3–4 months post-baseline per-5-year increase in age = 0(95% CI: −0.02 to 0.02). There was no evidence for a difference in prognoses for men and women at 3–4 months or 9–12 months post-baseline, but men had worse prognoses at 6–8 months (percentage difference in depressive symptoms for men compared to women: 15.08% (95% CI: 4.82 to 26.35)). However, this was largely driven by a single study that contributed data at 6–8 months and not the other time points. Further, there was little evidence for an association after adjusting for depressive ‘disorder characteristics’ and employment status (12.23% (−1.69 to 28.12)). Participants that were either single (percentage difference in depressive symptoms for single participants: 9.25% (95% CI: 2.78 to 16.13) or no longer married (8.02% (95% CI: 1.31 to 15.18)) had worse prognoses than those that were married, even after adjusting for depressive ‘disorder characteristics’ and all available confounders.
Clinicians and researchers will continue to routinely record age and gender, but despite their importance for incidence and prevalence of depression, they appear to offer little information regarding prognosis. Patients that are single or no longer married may be expected to have slightly worse prognoses than those that are married. Ensuring this is recorded routinely alongside depressive ‘disorder characteristics’ in clinic may be important.
The first demonstration of laser action in ruby was made in 1960 by T. H. Maiman of Hughes Research Laboratories, USA. Many laboratories worldwide began the search for lasers using different materials, operating at different wavelengths. In the UK, academia, industry and the central laboratories took up the challenge from the earliest days to develop these systems for a broad range of applications. This historical review looks at the contribution the UK has made to the advancement of the technology, the development of systems and components and their exploitation over the last 60 years.
The Rapid ASKAP Continuum Survey (RACS) is the first large-area survey to be conducted with the full 36-antenna Australian Square Kilometre Array Pathfinder (ASKAP) telescope. RACS will provide a shallow model of the ASKAP sky that will aid the calibration of future deep ASKAP surveys. RACS will cover the whole sky visible from the ASKAP site in Western Australia and will cover the full ASKAP band of 700–1800 MHz. The RACS images are generally deeper than the existing NRAO VLA Sky Survey and Sydney University Molonglo Sky Survey radio surveys and have better spatial resolution. All RACS survey products will be public, including radio images (with
15 arcsec resolution) and catalogues of about three million source components with spectral index and polarisation information. In this paper, we present a description of the RACS survey and the first data release of 903 images covering the sky south of declination
made over a 288-MHz band centred at 887.5 MHz.
We have previously shown that higher intake of cruciferous vegetables is inversely associated with carotid artery intima-media thickness. To further test the hypothesis that an increased consumption of cruciferous vegetables is associated with reduced indicators of structural vascular disease in other areas of the vascular tree, we aimed to investigate the cross-sectional association between cruciferous vegetable intake and extensive calcification in the abdominal aorta. Dietary intake was assessed, using a FFQ, in 684 older women from the Calcium Intake Fracture Outcome Study. Cruciferous vegetables included cabbage, Brussels sprouts, cauliflower and broccoli. Abdominal aortic calcification (AAC) was scored using the Kauppila AAC24 scale on dual-energy X-ray absorptiometry lateral spine images and was categorised as ‘not extensive’ (0–5) or ‘extensive’ (≥6). Mean age was 74·9 (sd 2·6) years, median cruciferous vegetable intake was 28·2 (interquartile range 15·0–44·7) g/d and 128/684 (18·7 %) women had extensive AAC scores. Those with higher intakes of cruciferous vegetables (>44·6 g/d) were associated with a 46 % lower odds of having extensive AAC in comparison with those with lower intakes (<15·0 g/d) after adjustment for lifestyle, dietary and CVD risk factors (ORQ4 v. Q1 0·54, 95 % CI 0·30, 0·97, P = 0·036). Total vegetable intake and each of the other vegetable types were not related to extensive AAC (P > 0·05 for all). This study strengthens the hypothesis that higher intake of cruciferous vegetables may protect against vascular calcification.
We evaluated the impact of reflex urine culture screen results on antibiotic initiation. More patients with positive urine screen but negative culture received antibiotics than those with a negative screen (30.5 vs 7.1%). Urine screen results may inappropriately influence antibiotic initiation in patients with a low likelihood of infection.
Introduction: Determining fluid status prior to resuscitation provides a more accurate guide for appropriate fluid administration in the setting of undifferentiated hypotension. Emergency Department (ED) point of care ultrasound (PoCUS) has been proposed as a potential non-invasive, rapid, repeatable investigation to ascertain inferior vena cava (IVC) characteristics. Our goal was to determine the feasibility of using PoCUS to measure IVC size and collapsibility. Methods: This was a planned secondary analysis of data from a prospective multicentre international study investigating PoCUS in ED patients with undifferentiated hypotension. We prospectively collected data on IVC size and collapsibility using a standard data collection form in 6 centres. The primary outcome was the proportion of patients with a clinically useful (determinate) scan defined as a clearly visible intrahepatic IVC, measurable for size and collapse. Descriptive statistics are provided. Results: A total of 138 scans were attempted on 138 patients; 45.7% were women and the median age was 58 years old. Overall, one hundred twenty-nine scans (93.5%; 95% CI 87.9 to 96.7%) were determinate. 131 (94.9%; 89.7 to 97.7%) were determinate for IVC size, and 131 (94.9%; 89.7 to 97.7%) were determinate for collapsibility. Conclusion: In this analysis of 138 ED patients with undifferentiated hypotension, the vast majority of PoCUS scans to investigate IVC characteristics were determinate. Future work should include analysis of the value of IVC size and collapsibility in determining fluid status in this group.
Introduction: Patients presenting to the emergency department (ED) with hypotension have a high mortality rate and require careful yet rapid resuscitation. The use of cardiac point of care ultrasound (PoCUS) in the ED has progressed beyond the basic indications of detecting pericardial fluid and activity in cardiac arrest. We examine if finding left ventricular dysfunction (LVD) on emergency physician performed PoCUS reliably predicts the presence of cardiogenic shock in hypotensive ED patients. Methods: We prospectively collected PoCUS findings performed in 135 ED patients with undifferentiated hypotension as part of an international study. Patients with clearly identified etiologies for hypotension were excluded, along with other specific presumptive diagnoses. LVD was defined as identification of a generally hypodynamic LV in the setting of shock. PoCUS findings were collected using a standardized protocol and data collection form. All scans were performed by PoCUS-trained emergency physicians. Final shock type was defined as cardiogenic or non-cardiogenic by independent specialist blinded chart review. Results: All 135 patients had complete follow up. Median age was 56 years, 53% of patients were male. Disease prevalence for cardiogenic shock was 12% and the mortality rate was 24%. The presence of LVD on PoCUS had a sensitivity of 62.50% (95%CI 35.43% to 84.80%), specificity of 94.12% (88.26% to 97.60%), positive-LR 10.62 (4.71 to 23.95), negative-LR 0.40 (0.21 to 0.75) and accuracy of 90.37% (84.10% to 94.77%) for detecting cardiogenic shock. Conclusion: Detecting left ventricular dysfunction on PoCUS in the ED may be useful in confirming the underlying shock type as cardiogenic in otherwise undifferentiated hypotensive patients.
Craving in negative emotional situations (negative craving) is commonly associated with relapse and heavy alcohol use. Elevated dynorphin levels were associated with negative emotions, while variations in the OPRK1 and PDYN genes encoding OPRK1 receptor and dynorphins were associated with alcohol dependence.
To investigate potential overlap in the genetic factors underlying, negative craving and alcohol dependence.
Examine the association of the negative craving and genetic variation in the OPRK1 and PDYN genes.
13 PDYN and 10 OPRK1 Single Nucleotide Polymorphisms (SNPs), including those previously reported to be associated with alcohol dependence were genotyped in 196 alcohol dependent subjects. The raw scores of the negative subscale of Inventory of Drug Taking Situations (IDTS) were utilized as a quantitative measure of negative craving. Logistic regression models were used to test for associations after controlling for age and gender.
Gene-level haplotype testing demonstrated significant association of negative craving with variation in PDYN (p < 0.05) but not OPRK1 gene. The rs2281285 - rs199794 haplotype showed significant association (p = 0.0236) with negative craving, while rs2235749 - rs10485703 haplotype showed marginally significant association (p = 0.055). This replicates previous findings of association between these haplotypes and alcohol dependence. Negative craving was also associated with PDYN rs2281285 variant (p = 0.012) with estimated effect size of 6.95 (SE = 2.75). This new association finding was not significant after correction for multiple testing (p = 0.18).
Our findings support association of PDYN sequence variation with negative craving in alcohol dependent subjects. Future studies should investigate functional mechanisms of this association.
Depression and obesity are highly prevalent major public health problems that frequently co-occur. Shared aetiological factors have been found between depression and obesity. The role of the fat mass and obesity associated (FTO) gene in body mass index (BMI) and obesity has been confirmed in many independent studies. Recently, we reported the first study implicating FTO in the association between depression and obesity.
We aimed to confirm these findings by investigating the FTO rs9939609 polymorphism in a meta-analysis of 13,701 individuals.
The sample consists of 6,902 depressed cases and 6,799 controls from five studies (Radiant, PsyCoLaus, GSK, MARS and NESDA/NTR). Common inclusion criteria were information available on a lifetime DSM-IV diagnosis of major depressive disorder (MDD), BMI and genotype data. Linear regression models for quantitative traits assuming an additive genetic model were performed to test for association and interaction between rs9939609, BMI and depression. Fixed and random-effects meta-analyses were performed.
Fixed-effects meta-analyses support a significant association between rs9939609 polymorphism and BMI (whole-sample: ß=0.07, p=1.29×10-12, depressive-cases: ß=0.12, p=6.92×10-12). No association was found in controls (ß=0.02, p=0.15). Meta-analyses further support a significant interaction between FTO, BMI and depression (fixed-effects: ß=0.13, p=3.087×10-7; random-effects: ß=0.12, p=0.027), wherein depressed carriers of the risk allele have an additional increase of 2.2% in BMI.
This meta-analysis demonstrates a significant interaction between FTO, depression and BMI, indicating that depression increases the effect of FTO on BMI. Depression-related alterations in key biological processes may interact with the rs9939609 FTO risk allele to increase obesity risk.
Daily use of high-potency cannabis has been reported to carry a high risk for developing a psychotic disorder. However, the evidence is mixed on whether any pattern of cannabis use is associated with a particular symptomatology in first-episode psychosis (FEP) patients.
We analysed data from 901 FEP patients and 1235 controls recruited across six countries, as part of the European Network of National Schizophrenia Networks Studying Gene-Environment Interactions (EU-GEI) study. We used item response modelling to estimate two bifactor models, which included general and specific dimensions of psychotic symptoms in patients and psychotic experiences in controls. The associations between these dimensions and cannabis use were evaluated using linear mixed-effects models analyses.
In patients, there was a linear relationship between the positive symptom dimension and the extent of lifetime exposure to cannabis, with daily users of high-potency cannabis having the highest score (B = 0.35; 95% CI 0.14–0.56). Moreover, negative symptoms were more common among patients who never used cannabis compared with those with any pattern of use (B = −0.22; 95% CI −0.37 to −0.07). In controls, psychotic experiences were associated with current use of cannabis but not with the extent of lifetime use. Neither patients nor controls presented differences in depressive dimension related to cannabis use.
Our findings provide the first large-scale evidence that FEP patients with a history of daily use of high-potency cannabis present with more positive and less negative symptoms, compared with those who never used cannabis or used low-potency types.
The Bulge Asymmetries and Dynamical Evolution (BAaDE) survey aims to explore the complex structure of the inner Galaxy and Galactic Bulge, by using the 43 GHz receivers at the Karl G. Jansky Very Large Array (VLA) and the 86 GHz receivers at the Atacama Large Millimeter/submillimeter Array (ALMA) to observe SiO maser lines in red giant stars. The goal is to construct a sample of stellar point-mass probes that can be used to test models of the gravitational potential, and the final sample is expected to provide at least 20,000 line-of-sight velocities and positions. A possible bias between the VLA and the ALMA SiO maser lines is explored, and the 86 GHz SiO line-peak velocities agree using either of the four sampled lines. Additionally, the SiO maser velocities agree with the OH maser derived velocities.
Background: Biallelic variants in POLR1C are associated with POLR3-related leukodystrophy (POLR3-HLD), or 4H leukodystrophy (Hypomyelination, Hypodontia, Hypogonadotropic Hypogonadism), and Treacher Collins syndrome (TCS). The clinical spectrum of POLR3-HLD caused by variants in this gene has not been described. Methods: A cross-sectional observational study involving 25 centers worldwide was conducted between 2016 and 2018. The clinical, radiologic and molecular features of 23 unreported and previously reported cases of POLR3-HLD caused by POLR1C variants were reviewed. Results: Most participants presented between birth and age 6 years with motor difficulties. Neurological deterioration was seen during childhood, suggesting a more severe phenotype than previously described. The dental, ocular and endocrine features often seen in POLR3-HLD were not invariably present. Five patients (22%) had a combination of hypomyelinating leukodystrophy and abnormal craniofacial development, including one individual with clear TCS features. Several cases did not exhibit all the typical radiologic characteristics of POLR3-HLD. A total of 29 different pathogenic variants in POLR1C were identified, including 13 new disease-causing variants. Conclusions: Based on the largest cohort of patients to date, these results suggest novel characteristics of POLR1C-related disorder, with a spectrum of clinical involvement characterized by hypomyelinating leukodystrophy with or without abnormal craniofacial development reminiscent of TCS.
The BAaDE (Bulge Asymmetries and Dynamical Evolution) project is an SiO maser survey of the Galactic Plane. About 19,000 sources have been observed at 43 GHz with the VLA, and the production of spectra for each of these sources is well underway. The primary goal of the project is to collect line-of-sight velocities for all the detected masers in the sample to probe Galactic dynamics. With an expected detection rate of over 60% we should collect over 11,000 velocities to probe the Galactic potential. The survey is also a large sample of infrared sources to explore the different evolved stellar populations within the Milky Way. So far we discern three distinct groups in the BAaDE sample: the main group containing oxygen-rich, evolved stars with a high SiO maser detection rate, a much smaller population of carbon-rich evolved stars, and finally a group of likely young stellar objects with no maser emission. These populations are separated using 2MASS and MSX color-color diagrams, and we find a particularly useful cut between the young and evolved objects using the MSX [D] –[E] color. Identification of these populations will isolate BAaDE’s evolved star sample, and will more tightly define the region in IR color-color diagrams where SiO masers occur yielding a better understanding of these kinematical probes. Using our color-divisions we can also study the distribution of each of the populations within the Galactic Plane.
The Bulge Asymmetries and Dynamical Evolution (BAaDE) survey aims to use circumstellar SiO maser line-of-sight velocities as probes for the Galactic gravitational potential and dynamical structure. The SiO masers are detected at a high rate in specific color-selected MSX infrared sources. Furthermore, the SiO maser properties and line ratios, in combination with infrared spectral energy distributions and location in the Galaxy, will statistically yield detailed information on population and evolution of low- to intermediate-mass evolved stars in the Galaxy.
Introduction: Although use of point of care ultrasound (PoCUS) protocols for patients with undifferentiated hypotension in the Emergency Department (ED) is widespread, our previously reported SHoC-ED study showed no clear survival or length of stay benefit for patients assessed with PoCUS. In this analysis, we examine if the use of PoCUS changed fluid administration and rates of other emergency interventions between patients with different shock types. The primary comparison was between cardiogenic and non-cardiogenic shock types. Methods: A post-hoc analysis was completed on the database from an RCT of 273 patients who presented to the ED with undifferentiated hypotension (SBP <100 or shock index > 1) and who had been randomized to receive standard care with or without PoCUS in 6 centres in Canada and South Africa. PoCUS-trained physicians performed scans after initial assessment. Shock categories and diagnoses recorded at 60 minutes after ED presentation, were used to allocate patients into subcategories of shock for analysis of treatment. We analyzed actual care delivered including initial IV fluid bolus volumes (mL), rates of inotrope use and major procedures. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: Although there were expected differences in the mean fluid bolus volume between patients with non-cardiogenic and cardiogenic shock, there was no difference in fluid bolus volume between the control and PoCUS groups (non-cardiogenic control 1878 mL (95% CI 1550 – 2206 mL) vs. non-cardiogenic PoCUS 1687 mL (1458 – 1916 mL); and cardiogenic control 768 mL (194 – 1341 mL) vs. cardiogenic PoCUS 981 mL (341 – 1620 mL). Likewise there were no differences in rates of inotrope administration, or major procedures for any of the subcategories of shock between the control group and PoCUS group patients. The most common subcategory of shock was distributive. Conclusion: Despite differences in care delivered by subcategory of shock, we did not find any significant difference in actual care delivered between patients who were examined using PoCUS and those who were not. This may help to explain the previously reported lack of outcome difference between groups.
Introduction: Point of care ultrasound has been reported to improve diagnosis in non-traumatic hypotensive ED patients. We compared diagnostic performance of physicians with and without PoCUS in undifferentiated hypotensive patients as part of an international prospective randomized controlled study. The primary outcome was diagnostic performance of PoCUS for cardiogenic vs. non-cardiogenic shock. Methods: SHoC-ED recruited hypotensive patients (SBP < 100 mmHg or shock index > 1) in 6 centres in Canada and South Africa. We describe previously unreported secondary outcomes relating to diagnostic accuracy. Patients were randomized to standard clinical assessment (No PoCUS) or PoCUS groups. PoCUS-trained physicians performed scans after initial assessment. Demographics, clinical details and findings were collected prospectively. Initial and secondary diagnoses including shock category were recorded at 0 and 60 minutes. Final diagnosis was determined by independent blinded chart review. Standard statistical tests were employed. Sample size was powered at 0.80 (α:0.05) for a moderate difference. Results: 273 patients were enrolled with follow-up for primary outcome completed for 270. Baseline demographics and perceived category of shock were similar between groups. 11% of patients were determined to have cardiogenic shock. PoCUS had a sensitivity of 80.0% (95% CI 54.8 to 93.0%), specificity 95.5% (90.0 to 98.1%), LR+ve 17.9 (7.34 to 43.8), LR-ve 0.21 (0.08 to 0.58), Diagnostic OR 85.6 (18.2 to 403.6) and accuracy 93.7% (88.0 to 97.2%) for cardiogenic shock. Standard assessment without PoCUS had a sensitivity of 91.7% (64.6 to 98.5%), specificity 93.8% (87.8 to 97.0%), LR+ve 14.8 (7.1 to 30.9), LR- of 0.09 (0.01 to 0.58), Diagnostic OR 166.6 (18.7 to 1481) and accuracy of 93.6% (87.8 to 97.2%). There was no significant difference in sensitivity (-11.7% (-37.8 to 18.3%)) or specificity (1.73% (-4.67 to 8.29%)). Diagnostic performance was also similar between other shock subcategories. Conclusion: As reported in other studies, PoCUS based assessment performed well diagnostically in undifferentiated hypotensive patients, especially as a rule-in test. However performance was similar to standard (non-PoCUS) assessment, which was excellent in this study.
Despite established clinical associations among major depression (MD), alcohol dependence (AD), and alcohol consumption (AC), the nature of the causal relationship between them is not completely understood. We leveraged genome-wide data from the Psychiatric Genomics Consortium (PGC) and UK Biobank to test for the presence of shared genetic mechanisms and causal relationships among MD, AD, and AC.
Linkage disequilibrium score regression and Mendelian randomization (MR) were performed using genome-wide data from the PGC (MD: 135 458 cases and 344 901 controls; AD: 10 206 cases and 28 480 controls) and UK Biobank (AC-frequency: 438 308 individuals; AC-quantity: 307 098 individuals).
Positive genetic correlation was observed between MD and AD (rgMD−AD = + 0.47, P = 6.6 × 10−10). AC-quantity showed positive genetic correlation with both AD (rgAD−AC quantity = + 0.75, P = 1.8 × 10−14) and MD (rgMD−AC quantity = + 0.14, P = 2.9 × 10−7), while there was negative correlation of AC-frequency with MD (rgMD−AC frequency = −0.17, P = 1.5 × 10−10) and a non-significant result with AD. MR analyses confirmed the presence of pleiotropy among these four traits. However, the MD-AD results reflect a mediated-pleiotropy mechanism (i.e. causal relationship) with an effect of MD on AD (beta = 0.28, P = 1.29 × 10−6). There was no evidence for reverse causation.
This study supports a causal role for genetic liability of MD on AD based on genetic datasets including thousands of individuals. Understanding mechanisms underlying MD-AD comorbidity addresses important public health concerns and has the potential to facilitate prevention and intervention efforts.