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Introduction: Hyperkalemia is a common electrolyte disturbance associated with morbidity and mortality. Commonly used therapies for hyperkalemia include IV calcium, sodium bicarbonate, insulin, beta-adrenergic agents, ion-exchange resins, diuretics and hemodialysis. This study aims to evaluate which treatments are more commonly used to treat hyperkalemia and to examine factors which influence those clinical decisions. Methods: This is a retrospective chart review of all cases of hyperkalemia encountered in 2017 at a Canadian adult ED. Potassium values were classified as mild (5.5 - 6.5 mEq/L), moderate (>6.5 - 7.5 mEq/L) and severe (>7.5 mEq/L). Treatment choices were then recorded and matched to hemodynamic stability, degree of hyperkalemia and ECG findings. More statistical methods to test correlation between treatment and specific variables will be performed over the next 2 months, including logistic regression to highlight potential determinants of treatment and Chi-square tests to verify randomness and to construct 95% confidence intervals. Results: 1867 ED visits were identified, of which 479 met the inclusion criteria. 89.1% of hyperkalemia cases were mild, 8.2% were moderate, and 2.7% were severe. IV insulin was used in 22.1% of cases, followed by Kayexalate in 20.5%, sodium bicarbonate in 12.3%, IV calcium in 9.4%, frusemide in 7.3%, salbutamol in 2.7%, and dialysis in 1.9%. Moderate and severe hyperkalemia were associated with higher use of insulin (79.5% and 64.3% respectively), IV calcium (41% and 64.3% respectively), sodium bicarbonate (56.4% and 85.7% respectively). Bradycardia was associated with higher insulin and IV calcium use (46.7% and 33.3% respectively). Hypotension was associated with a similar increase in use of insulin and IV calcium (34.2% and 23.7% respectively). There were only 15 cases of cardiac arrest in which sodium bicarbonate and IV calcium were more frequently used (80% and 60% respectively). Conclusion: This study demonstrates variability in the ED management of hyperkalemia. We found that Insulin and Kayexalate were the 2 most common interventions, with degree of hyperkalemia, bradycardia and hypotension influencing rates of treatment. Overuse of kayexalate for emergent treatment of hyperkalemia is evident despite weak supporting evidence. Paradoxically, beta adrenergic agents were underutilized despite their rapid effect and safer profile. The development of a widely accepted guideline may help narrow the differences in practice and potentially improve outcomes.
Introduction: CAEP recently developed the acute atrial fibrillation (AF) and flutter (AFL) [AAFF] Best Practices Checklist to promote optimal care and guidance on cardioversion and rapid discharge of patients with AAFF. We sought to assess the impact of implementing the Checklist into large Canadian EDs. Methods: We conducted a pragmatic stepped-wedge cluster randomized trial in 11 large Canadian ED sites in five provinces, over 14 months. All hospitals started in the control period (usual care), and then crossed over to the intervention period in random sequence, one hospital per month. We enrolled consecutive, stable patients presenting with AAFF, where symptoms required ED management. Our intervention was informed by qualitative stakeholder interviews to identify perceived barriers and enablers for rapid discharge of AAFF patients. The many interventions included local champions, presentation of the Checklist to physicians in group sessions, an online training module, a smartphone app, and targeted audit and feedback. The primary outcome was length of stay in ED in minutes from time of arrival to time of disposition, and this was analyzed at the individual patient-level using linear mixed effects regression accounting for the stepped-wedge design. We estimated a sample size of 800 patients. Results: We enrolled 844 patients with none lost to follow-up. Those in the control (N = 316) and intervention periods (N = 528) were similar for all characteristics including mean age (61.2 vs 64.2 yrs), duration of AAFF (8.1 vs 7.7 hrs), AF (88.6% vs 82.9%), AFL (11.4% vs 17.1%), and mean initial heart rate (119.6 vs 119.9 bpm). Median lengths of stay for the control and intervention periods respectively were 413.0 vs. 354.0 minutes (P < 0.001). Comparing control to intervention, there was an increase in: use of antiarrhythmic drugs (37.4% vs 47.4%; P < 0.01), electrical cardioversion (45.1% vs 56.8%; P < 0.01), and discharge in sinus rhythm (75.3% vs. 86.7%; P < 0.001). There was a decrease in ED consultations to cardiology and medicine (49.7% vs 41.1%; P < 0.01), but a small but insignificant increase in anticoagulant prescriptions (39.6% vs 46.5%; P = 0.21). Conclusion: This multicenter implementation of the CAEP Best Practices Checklist led to a significant decrease in ED length of stay along with more ED cardioversions, fewer ED consultations, and more discharges in sinus rhythm. Widespread and rigorous adoption of the CAEP Checklist should lead to improved care of AAFF patients in all Canadian EDs.
The uncertainty surrounding high intakes of folic acid and associations with cognitive decline in older adults with low vitamin B12 status has been an obstacle to mandatory folic acid fortification for many years. We estimated the prevalence of combinations of low/normal/high vitamin B12 and folate status and compared associations with global cognitive function using two approaches, of individuals in a population-based study of those aged ≥50 years in the Republic of Ireland. Cross-sectional data from 3781 men and women from Wave 1 of The Irish Longitudinal Study on Ageing were analysed. Global cognitive function was assessed by the Mini Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA). Prevalence estimates for combinations of vitamin B12 (plasma vitamin B12 < or ≥258 pmol/l) and folate (plasma folate ≤ or >45·3 nmol/l) concentrations were generated. Negative binomial regression models were used to investigate the associations of vitamin B12 and folate status with global cognitive function. Of the participants, 1·5 % (n 51) had low vitamin B12 (<258 pmol/l) and high folate (>45·3 nmol/l) status. Global cognitive performance was not significantly reduced in these individuals when compared with those with normal status for both B-vitamins (n 2433). Those with normal vitamin B12/high folate status (7·6 %) had better cognitive performance (MMSE: incidence rate ratio (IRR) 0·82, 95 % CI 0·68, 0·99; P = 0·043, MoCA: IRR 0·89, 95 % CI 0·80, 0·99; P = 0·025). We demonstrated that high folate status was not associated with lower cognitive scores in older adults with low vitamin B12 status. These findings provide important safety information that could guide fortification policy recommendations in Europe.
The endothelial glycocalyx layer (EGL) is a brush-like layer that lines the internal surfaces of blood vessels. It is thought to serve a number of physiological functions, including as a mechanotransducer of fluid loadings to the vessel wall. However, the fragility of the EGL makes it difficult to examine experimentally, and so there is much value in theoretical models that can help to explain the dynamical behaviour of the EGL. Most previous models have employed mixture theory to mechanically describe the layer, which treats the EGL as a isotropic linearly poroelastic layer. However, there is increasing experimental evidence to suggest that the EGL has a well-defined organisational structure that might not necessarily be well captured by such mixture theory descriptions. We therefore employ homogenisation theory to incorporate into the models some of the possible EGL microstructure suggested by the current biological literature. We explore how mechanotransduction varies under the different possible EGL microstructures, which potentially has important consequences to our understanding of how structural changes to the EGL might affect a vessel’s ability to respond to hemodynamical cues. We also find that, whereas mechanotransduction through the solid components of the EGL is dominated by the fluid tractions applied at the lumen–EGL interface, the component carried through its fluid phase is most sensitive to pressure gradients within the bulk EGL. This is relevant, since it is known that the underlying endothelial cells respond differently to these two different forms of mechanical loading.
Bipolar disorder (BD) is associated with impaired psychosocial behaviours. Little is known about deficits in neurocognitive functions like decision-making possibly related both to these behaviours and to the nature of the disorder.
To determine whether decision-making impairments exist in manic (M), depressed (D) and euthymic (E) bipolar patients (BP) and to determine whether illness and course-of-illness characteristics can predict participants’ performance
A power analysis was conducted. A total of 315 subjects, including 45 M and 32 D inpatients and 90 E outpatients with BD I, medicated, and 150 Healthy Controls (HC), age, IQ and gender-matched, were included. Decision-making ability and sensitivity to punishment frequency were assessed with the Iowa Gambling Task (IGT).
On the IGT, MBP (p< 0.001), DBP (p< 0.01) and EBP (p< 0.05) selected significantly more cards from the risky decks than HC with no significant differences between BP groups. Unlike HC, MBP (p< 0.001), DBP (p< 0.05) and EBP (p< 0.05) showed little capacity to learn from incurred losses with no significant differences between BP groups, but, like HC, BP preferred decks that yielded infrequent penalties over those decks that yielded frequent penalties. In a multivariate analysis, decision-making impairment in the BP was significantly (p=0.001) predicted by low level of education, high total number of admissions and family history of BD.
BP clearly show defects in decision-making predicted by course-of-illness illness characteristics. Impaired decision-making might be a trait-related neurocognitive deficit in BD and partly explain impaired psychosocial behaviours of BP.
Previous research in clinical, community, and school settings has demonstrated positive outcomes for the Secret Agent Society (SAS) social skills training program. This is designed to help children on the autism spectrum become more aware of emotions in themselves and others and to ‘problem-solve’ complex social scenarios. Parents play a key role in the implementation of the SAS program, attending information and support sessions with other parents and providing supervision, rewards, and feedback as their children complete weekly ‘home mission’ assignments. Drawing on data from a school-based evaluation of the SAS program, we examined whether parents’ engagement with these elements of the intervention was linked to the quality of their children’s participation and performance. Sixty-eight 8–14-year-olds (M age = 10.7) with a diagnosis of autism participated in the program. The findings indicated that ratings of parental engagement were positively correlated with children’s competence in completing home missions and with the quality of their contribution during group teaching sessions. However, there was a less consistent relationship between parental engagement and measures of children’s social and emotional skill gains over the course of the program.
Cognitive impairment associated with lifetime major depressive disorder (MDD) is well-supported by meta-analytic studies, but population-based estimates remain scarce. Previous UK Biobank studies have only shown limited evidence of cognitive differences related to probable MDD. Using updated cognitive and clinical assessments in UK Biobank, this study investigated population-level differences in cognitive functioning associated with lifetime MDD.
Associations between lifetime MDD and cognition (performance on six tasks and general cognitive functioning [g-factor]) were investigated in UK Biobank (N-range 7,457–14,836, age 45–81 years, 52% female), adjusting for demographics, education, and lifestyle. Lifetime MDD classifications were based on the Composite International Diagnostic Interview. Within the lifetime MDD group, we additionally investigated relationships between cognition and (a) recurrence, (b) current symptoms, (c) severity of psychosocial impairment (while symptomatic), and (d) concurrent psychotropic medication use.
Lifetime MDD was robustly associated with a lower g-factor (β = −0.10, PFDR = 4.7 × 10−5), with impairments in attention, processing speed, and executive functioning (β ≥ 0.06). Clinical characteristics revealed differential profiles of cognitive impairment among case individuals; those who reported severe psychosocial impairment and use of psychotropic medication performed worse on cognitive tests. Severe psychosocial impairment and reasoning showed the strongest association (β = −0.18, PFDR = 7.5 × 10−5).
Findings describe small but robust associations between lifetime MDD and lower cognitive performance within a population-based sample. Overall effects were of modest effect size, suggesting limited clinical relevance. However, deficits within specific cognitive domains were more pronounced in relation to clinical characteristics, particularly severe psychosocial impairment.
A developing application of laser-driven currents is the generation of magnetic fields of picosecond–nanosecond duration with magnitudes exceeding
. Single-loop and helical coil targets can direct laser-driven discharge currents along wires to generate spatially uniform, quasi-static magnetic fields on the millimetre scale. Here, we present proton deflectometry across two axes of a single-loop coil ranging from 1 to 2 mm in diameter. Comparison with proton tracking simulations shows that measured magnetic fields are the result of kiloampere currents in the coil and electric charges distributed around the coil target. Using this dual-axis platform for proton deflectometry, robust measurements can be made of the evolution of magnetic fields in a capacitor coil target.
The most frequently asked questions about Chlamydia trachomatis, commonly known as “chlamydia,” are (1) what is it? and (2) where did it come from? The capricious and cryptic nature of genital infections caused by C. trachomatis and the difficulties in isolating the pathogen have led to many misconceptions about its origins and how infection occurs. The first question is now easy to answer. There is no doubt: chlamydiae are not viruses, nor are they protozoan parasites; they are bacteria. However, they are not free-living bacteria and so cannot be cultivated on conventional media such as agar plates. Chlamydiae are highly specialized bacteria, which can be grown only within living cells; thus they are obligate intracellular pathogens.
Chlamydiae also have a complex developmental cycle. The name is derived from Chlamydozoa, which means “cloaked organisms,” because they develop within an inclusion membrane within the cytoplasm of the cell and initially in the infection process are not visible. These gram-negative bacteria have a unique development cycle that includes the repeated division of a replicating stage, called an RB, or reticulate body. RBs increase in number to a point where they can be seen under the microscope as moving specks within a defined membrane structure known as an inclusion in the host cell's cytoplasm. With time the inclusion ruptures out of the cell and releases the smaller nonreplicating infectious forms called “elementary bodies.”
The genus is also known as Chlamydia; it is a proper noun written in italics, with no plural. The genus Chlamydia currently contains nine species and no doubt, more will be added. The species C. trachomatis, the focus of our discussion, is made up of a number of serovars, differentiated by surface antigens that induce specific antibodies. It has four ocular serovars that cause blinding endemic trachoma, A, B, Ba, and C and at least eight serovars, D to K, which typically cause genital tract infections. There are additionally the three L serovars that cause the condition known as lymphogranuloma venerum. Closely related species are C. muridarum, which infects mice and hamsters, and C. suis, which is endemic in pigs.
Subcutaneous adipose tissue (scAT) and peripheral blood mononuclear cells (PBMC) play a significant role in obesity-associated systemic low-grade inflammation. High-fat diet (HFD) is known to induce inflammatory changes in both scAT and PBMC. However, the time course of the effect of HFD on these systems is still unknown. The aim of the present study was to determine the time course of the effect of HFD on PBMC and scAT. New Zealand white rabbits were fed HFD for 5 or 10 weeks (i.e. HFD-5 and HFD-10) or regular chow (i.e. control (CNT)-5 and CNT-10). Thereafter, metabolic and inflammatory parameters of PBMC and scAT were quantified. HFD induced hyperfattyacidaemia in HFD-5 and HFD-10 groups, with the development of insulin resistance in HFD-10, while no changes were observed in scAT lipid metabolism and inflammatory status. HFD activated the inflammatory pathways in PBMC of HFD-5 group and induced modified autophagy in that of HFD-10. The rate of fat oxidation in PBMC was directly associated with the expression of inflammatory markers and tended to inversely associate with autophagosome formation markers in PBMC. HFD affected systemic substrate metabolism, and the metabolic, inflammatory and autophagy pathways in PBMC in the absence of metabolic and inflammatory changes in scAT. Dietary approaches or interventions to avert HFD-induced changes in PBMC could be essential to prevent metabolic and inflammatory complications of obesity and promote healthier living.
Additional crystallographic data are given for the recently reported mineral middlebackite, which has been described for discoveries at Iron Knob in South Australia and Passo di San Lugano near Trento, Italy. The material examined in the present study was from a third finding of the mineral, viz. from a quartz outcrop at Mooloo Downs Station in Western Australia within which it was co-located with the chemically- and structurally-related mineral moolooite, CuIIC2O4·nH2O, reported by Clarke and Williams (1986). In this study, the crystal structure was elucidated independently of the other studies using a combination of the a priori charge flipping and simulated annealing methods with synchrotron radiation diffraction (SRD) powder data. The principal crystal data for the Mooloo Downs material are: space group P21/c with lattice parameters a = 7.2659(18) Å, b = 5.7460(11) Å, c = 5.6806(11) Å, β = 104.588(3)°; Vc = 229.46(18) Å3; empirical formula CuII2C2O4(OH)2 with 2 formula units per unit cell; and calculated density = 3.605 g cm−3. The lattice parameters agree approximately with values given for the other studies, but not within the reported error estimates. The atom coordinates, interatomic distances, and angles for the Mooloo Downs material are compared with those from the other studies using single crystal data, with the values from all three studies agreeing approximately, but again not within the reported uncertainties. The crystal chemistry found for middlebackite received strong confirmation through the synthesis for the first time of di-copper oxalate di-hydroxide. Laboratory X-ray diffraction powder data for the synthetic form of the mineral from this study agree closely with the SRD data for the natural mineral.
Refractory depression is a major contributor to the economic burden of depression. Radically open dialectical behaviour therapy (RO DBT) is an unevaluated new treatment targeting overcontrolled personality, common in refractory depression, but it is not yet known whether the additional expense of RO DBT is good value for money.
To estimate the cost-effectiveness of RO DBT plus treatment as usual (TAU) compared with TAU alone in people with refractory depression (trial registration: ISRCTN85784627).
We undertook a cost-effectiveness analysis alongside a randomised trial evaluating RO DBT plus TAU versus TAU alone for refractory depression in three UK secondary care centres. Our economic evaluation, 12 months after randomisation, adopted the perspective of the UK National Health Service (NHS) and personal social services. It evaluated cost-effectiveness by comparing the net cost of RO DBT with the net gain in quality-adjusted life-years (QALYs), estimated using the EQ-5D-3L measure of health-related quality of life.
The additional cost of RO DBT plus TAU compared with TAU alone was £7048 and was associated with a difference of 0.032 QALYs, yielding an incremental cost-effectiveness ratio (ICER) of £220 250 per QALY. This ICER was well above the National Institute for Health and Care Excellence (NICE) upper threshold of £30 000 per QALY. A cost-effectiveness acceptability curve indicated that RO DBT had a zero probability of being cost-effective compared with TAU at the NICE £30 000 threshold.
In its current resource-intensive form, RO DBT is not a cost-effective use of resources in the UK NHS.
Declaration of interest
R.H. is co-owner and director of Radically Open Ltd, the RO DBT training and dissemination company. D.K. reports grants outside the submitted work from the National Institute for Health Research (NIHR). T.L. receives royalties from New Harbinger Publishing for sales of RO DBT treatment manuals, speaking fees from Radically Open Ltd, and a grant outside the submitted work from the Medical Research Council. He was co-director of Radically Open Ltd between November 2014 and May 2015 and is married to Erica Smith-Lynch, the principal shareholder and one of two directors of Radically Open Ltd. H.O'M. reports personal fees outside the submitted work from the Charlie Waller Institute and Improving Access to Psychological Therapy. S.R. provides RO DBT supervision through her company S C Rushbrook Ltd. I.R. reports grants outside the submitted work from NIHR and Health & Care Research Wales. M. Stanton reports personal fees outside the submitted work from British Isles DBT Training, Stanton Psychological Services Ltd and Taylor & Francis. M. Swales reports personal fees outside the submitted work from British Isles DBT Training, Guilford Press, Oxford University Press and Taylor & Francis. B.W. was co-director of Radically Open Ltd between November 2014 and February 2015.
Individuals with depression often do not respond to medication or psychotherapy. Radically open dialectical behaviour therapy (RO DBT) is a new treatment targeting overcontrolled personality, common in refractory depression.
To compare RO DBT plus treatment as usual (TAU) for refractory depression with TAU alone (trial registration: ISRCTN 85784627).
RO DBT comprised 29 therapy sessions and 27 skills classes over 6 months. Our completed randomised trial evaluated RO DBT for refractory depression over 18 months in three British secondary care centres. Of 250 adult participants, we randomised 162 (65%) to RO DBT. The primary outcome was the Hamilton Rating Scale for Depression (HRSD), assessed masked and analysed by treatment allocated.
After 7 months, immediately following therapy, RO DBT had significantly reduced depressive symptoms by 5.40 points on the HRSD relative to TAU (95% CI 0.94–9.85). After 12 months (primary end-point), the difference of 2.15 points on the HRSD in favour of RO DBT was not significant (95% CI –2.28 to 6.59); nor was that of 1.69 points on the HRSD at 18 months (95% CI –2.84 to 6.22). Throughout RO DBT participants reported significantly better psychological flexibility and emotional coping than controls. However, they reported eight possible serious adverse reactions compared with none in the control group.
The RO DBT group reported significantly lower HRSD scores than the control group after 7 months, but not thereafter. The imbalance in serious adverse reactions was probably because of the controls' limited opportunities to report these.
Substantial clinical heterogeneity of major depressive disorder (MDD) suggests it may group together individuals with diverse aetiologies. Identifying distinct subtypes should lead to more effective diagnosis and treatment, while providing more useful targets for further research. Genetic and clinical overlap between MDD and schizophrenia (SCZ) suggests an MDD subtype may share underlying mechanisms with SCZ.
The present study investigated whether a neurobiologically distinct subtype of MDD could be identified by SCZ polygenic risk score (PRS). We explored interactive effects between SCZ PRS and MDD case/control status on a range of cortical, subcortical and white matter metrics among 2370 male and 2574 female UK Biobank participants.
There was a significant SCZ PRS by MDD interaction for rostral anterior cingulate cortex (RACC) thickness (β = 0.191, q = 0.043). This was driven by a positive association between SCZ PRS and RACC thickness among MDD cases (β = 0.098, p = 0.026), compared to a negative association among controls (β = −0.087, p = 0.002). MDD cases with low SCZ PRS showed thinner RACC, although the opposite difference for high-SCZ-PRS cases was not significant. There were nominal interactions for other brain metrics, but none remained significant after correcting for multiple comparisons.
Our significant results indicate that MDD case-control differences in RACC thickness vary as a function of SCZ PRS. Although this was not the case for most other brain measures assessed, our specific findings still provide some further evidence that MDD in the presence of high genetic risk for SCZ is subtly neurobiologically distinct from MDD in general.
The diurnal feeding patterns of dairy cows affects the 24 h robot utilisation of pasture-based automatic milking systems (AMS). A decline in robot utilisation between 2400 and 0600 h currently occurs in pasture-based AMS, as cow feeding activity is greatly reduced during this time. Here, we investigate the effect of a temporal variation in feed quality and quantity on cow feeding behaviour between 2400 and 0600 h as a potential tool to increase voluntary cow trafficking in an AMS at night. The day was allocated into four equal feeding periods (0600 to 1200, 1200 to 1800, 1800 to 2400 and 2400 to 0600 h). Lucerne hay cubes (CP = 19.1%, water soluble carbohydrate = 3.8%) and oat, ryegrass and clover hay cubes with 20% molasses (CP = 11.8%, water soluble carbohydrate = 10.7%) were offered as the ‘standard’ and ‘preferred’ (preference determined previously) feed types, respectively. The four treatments were (1) standard feed offered ad libitum (AL) throughout 24 h; (2) as per AL, with preferred feed replacing standard feed between 2400 and 0600 h (AL + P); (3) standard feed offered at a restricted rate, with quantity varying between each feeding period (20:10:30:60%, respectively) as a proportion of the (previously) measured daily ad libitum intake (VA); (4) as per VA, with preferred feed replacing standard feed between 2400 and 0600 h (VA + P). Eight non-lactating dairy cows were used in a 4 × 4 Latin square design. During each experimental period, treatment cows were fed for 7 days, including 3 days habituation and 4 days data collection. Total daily intake was approximately 8% greater (P < 0.001) for the AL and AL + P treatments (23.1 and 22.9 kg DM/cow) as compared with the VA and VA + P treatments (21.6 and 20.9 kg DM/cow). The AL + P and VA treatments had 21% and 90% greater (P < 0.001) dry matter intake (DMI) between 2400 and 0600 h, respectively, compared with the AL treatment. In contrast, the VA + P treatment had similar DMI to the VA treatment. Our experiment shows ability to increase cow feeding activity at night by varying feed type and quantity, though it is possible that a penalty to total DMI may occur using VA. Further research is required to determine if the implementation of variable feed allocation on pasture-based AMS farms is likely to improve milking robot utilisation by increasing cow feeding activity at night.
Observation of the ion source generated background has been an area of focus during our routine analytical work. It is noted that the results of very-low-ratio samples are dependent upon the particular procedures for measurement using the present-day Cs+ sputter ion sources. When measured without excessive Cs+ fluxes and without interleafing with other higher-ratio samples and references, the accelerator mass spectrometry (AMS) sensitivity can be somewhat improved. In some cases, it appears possible to assess old radiocarbon (14C) samples to beyond the long-standing 60 kyr limit. A number of observational studies are made for the sole purpose of minimizing the final contamination to the rare isotopes that is generated within the ion source.
Introduction: Hypotension is known to be associated with increased mortality in severe traumatic brain injury (TBI) patients. Systolic blood pressure (SBP) of <90 mmHg is the threshold for hypotension in consensus TBI treatment guidelines; however, evidence suggests hypotension should be defined at higher levels for these patients. Our objective was to determine the influence of hypotension on mortality in TBI patients requiring ICU admission using different thresholds of SBP on arrival at the emergency department (ED). Methods: Retrospective cohort study of patients with severe TBI (Abbreviated Injury Scale Head score ≥3) admitted to ICU at the QEII Health Sciences Centre (Halifax, Canada) between 2002 and 2013. Patients were grouped by SBP on ED arrival ( <90 mmHg, <100 mmHg, <110 mmHg). We performed multiple logistic regression analysis with mortality as the dependent variable. Models were adjusted for confounders including age, gender, Injury Severity Score (ISS), injury mechanism, and trauma team activation (TTA). Results: A total of 1233 patients sustained a severe TBI and were admitted to the ICU during the study period. The mean age was 43.4 ± 23.9 years and most patients were male (919/1233; 74.5%). The most common mechanism of injury was motor vehicle collision (491/1233; 41.2%) followed by falls (427/1233; 35.8%). Mean length of stay in the ICU was 6.1 ± 6.4 days, and the overall mortality rate was 22.7%. SBP on arrival was available for 1182 patients. The <90 mmHg group had 4.6% (54/1182) of these patients; mean ISS was 20.6 ± 7.8 and mortality was 40.7% (22/54). The <100 mmHg had 9.3% (110/1182) of patients; mean ISS was 19.3 ± 7.9 and mortality was 34.5% (38/110). The <110 mmHg group had 16.8% (198/1182) of patients; mean ISS was 17.9 ± 8.0 and mortality was 28.8% (57/198). After adjusting for confounders, the association between hypotension and mortality was 2.22 (95% CI 1.19-4.16) using a <90 mmHg cutoff, 1.79 (95% CI 1.12-2.86) using a <100 mmHg cutoff, and 1.50 (95% CI 1.02-2.21) using a <110 mmHg cutoff. Conclusion: While we found that TBI patients with a SBP <90 mmHg were over 2 times more likely to die, patients with an SBP <110 mmHg on ED arrival were still 1.5 times more likely to die from their injuries compared to patients without hypotension. These results suggest that establishing a higher threshold for clinically meaningful hypotension in TBI patients is warranted.
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.
The last shot of Season One of Les Revenants/The Returned (Canal+, 2012–15) finds the hit French television show's nameless mountain town suddenly, mysteriously, catastrophically flooded. Water has rushed in to a place that, for the past eight episodes, has been the site of another unruly invasion: of the dead, les revenants, come back to life. They are not violent. They just want to resume the lives they lost months or years earlier. By the beginning of Season Two, the army has come to take control, managing the double catastrophe caused by a dam that cannot hold back water and the town's returned dead.
When the show first aired, it brought the French past itself into the present, for the image of a mountain community in the Haute-Savoie threatened by water, almost vacant, and under state control recalls similar historical events of more than 50 years earlier. In March 1952, the valley containing the mountain village of Tignes was flooded to make way for a new hydroelectric dam on the Isère River. Four hundred CRS were called in to remove resisting residents and dynamite their homes to prevent them from returning. These actions were the culmination of one of the most contentious and visible battles between state technocrats and the opponents – one might say victims – of modernisation that animated the early years of France's Trente Glorieuses (Fourastié 2000; Frost 1985). Although never explicitly identified, this is the same dam that appears throughout Les Revenants. Its return to French screens underpins a broader allegory about state-sponsored modernisation and its legacy, a once-‘glorious’ project returned as a story of failure and unintended consequences.
For critics and industry professionals, the returned dead of the show represented another level of allegory: the return of French dramatic television to a level of quality it had not enjoyed for decades. LesRevenants was one of the first French shows to garner public interest and critical accolades during what critics have dubbed ‘the golden age of television’. Its first season attracted record audiences and critical praise in France before being picked up for diffusion by Swedish, British, Dutch, and American channels and winning a 2013 International Emmy for Best Dramatic Series.