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Post-traumatic stress disorder as a risk factor for major adverse cardiovascular events: a cohort study of a South African medical insurance scheme.
Get PDFAIMS
Prior research, largely focused on US male veterans, indicates an increased risk of cardiovascular disease among individuals with post-traumatic stress disorder (PTSD). Data from other settings and populations are scarce. The objective of this study is to examine PTSD as a risk factor for incident major adverse cardiovascular events (MACEs) in South Africa.
METHODS
We analysed reimbursement claims (2011-2020) of a cohort of South African medical insurance scheme beneficiaries aged 18 years or older. We calculated adjusted hazard ratios (aHRs) for associations between PTSD and MACEs using Cox proportional hazard models and calculated the effect of PTSD on MACEs using longitudinal targeted maximum likelihood estimation.
RESULTS
We followed 1,009,113 beneficiaries over a median of 3.0 years (IQR 1.1-6.0). During follow-up, 12,662 (1.3%) persons were diagnosed with PTSD and 39,255 (3.9%) had a MACE. After adjustment for sex, HIV status, age, population group, substance use disorders, psychotic disorders, major depressive disorder, sleep disorders and the use of antipsychotic medication, PTSD was associated with a 16% increase in the risk of MACEs (aHR 1.16, 95% confidence interval (CI) 1.05-1.28). The risk ratio for the effect of PTSD on MACEs decreased from 1.59 (95% CI 1.49-1.68) after 1 year of follow-up to 1.14 (95% CI 1.11-1.16) after 8 years of follow-up.
CONCLUSION
Our study provides empirical support for an increased risk of MACEs in males and females with PTSD from a general population sample in South Africa. These findings highlight the importance of monitoring cardiovascular risk among individuals diagnosed with PTSD
A Multicenter Long-Term Cohort Study of Eosinophilic Esophagitis Variants and Their Progression to EOE over Time.
Get PDFBACKGROUND
Eosinophilic esophagitis (EoE) variants have been recently characterized as conditions with symptoms of esophageal dysfunction resembling EoE, but absence of significant esophageal eosinophilia. Their disease course and severity have yet to be determined.
METHODS
Patients from six EoE-centers with symptoms of esophageal dysfunction, but peak eosinophil counts of <15/hpf in esophageal biopsies and absence of gastro-esophageal reflux disease with at least one follow-up visit were included. Clinical, (immuno)-histological and molecular features were determined and compared with EoE and healthy controls.
RESULTS
We included 54 patients with EoE variants (EoE-like esophagitis 53.7%; lymphocytic esophagitis 13.0%; non-specific esophagitis 33.3%). In 8 EoE-like esophagitis patients, EoE developed after a median of 14 months (IQR 3.6-37.6). Such progression increased over time (17.6% year 1, 32.0% year 3, 62.2% year 6). Sequential RNA sequencing analyses revealed only seven genes associated with this progression (with TSG6 and ALOX15 among the top three upregulated genes) with upregulation of a previously attenuated Th2 pathway. Immunostaining confirmed the involvement of eosinophil-associated proteins (TSG6, ALOX15) and revealed a significantly increased number of GATA3-positive cells during progression indicating a Th1/Th2 switch. Transition from one EoE variant (baseline) to another variant (during follow-up) was seen in 35.2% (median observation time of 17.3 months).
CONCLUSION
Transition of EoE variants to EoE suggests the presence of a disease spectrum. Few genes appear to be associated with the progression to EoE with upregulation of a previously attenuated Th2 signal. These genes, including GATA3 as a Th1/Th2 switch regulator, may represent potential therapeutic targets in early disease pathogenesis
Interobserver Reliability in the Classification of Thoracolumbar Fractures Using the AO Spine TL Injury Classification System Among 22 Clinical Experts in Spine Trauma Care.
Get PDFSTUDY DESIGN
Reliability study utilizing 183 injury CT scans by 22 spine trauma experts with assessment of radiographic features, classification of injuries and treatment recommendations.
OBJECTIVES
To assess the reliability of the AOSpine TL Injury Classification System (TLICS) including the categories within the classification and the M1 modifier.
METHODS
Kappa and Intraclass correlation coefficients were produced. Associations of various imaging characteristics (comminution, PLC status) and treatment recommendations were analyzed through regression analysis. Multivariable logistic regression modeling was used for making predictive algorithms.
RESULTS
Reliability of the AO Spine TLICS at differentiating A3 and A4 injuries (N = 71) (K = .466; 95% CI .458 - .474; P < .001) demonstrated moderate agreement. Similarly, the average intraclass correlation coefficient (ICC) amongst A3 and A4 injuries was excellent (ICC = .934; 95% CI .919 - .947; P < .001) and the ICC between individual measures was moderate (ICC = .403; 95% CI .351 - .461; P < .001). The overall agreement on the utilization of the M1 modifier amongst A3 and A4 injuries was fair (K = .161; 95% CI .151 - .171; P < .001). The ICC for PLC status in A3 and A4 injuries averaged across all measures was excellent (ICC = .936; 95% CI .922 - .949; P < .001). The M1 modifier suggests respondents are nearly 40% more confident that the PLC is injured amongst all injuries. The M1 modifier was employed at a higher frequency as injuries were classified higher in the classification system.
CONCLUSIONS
The reliability of surgeons differentiating between A3 and A4 injuries in the AOSpine TLICS is substantial and the utilization of the M1 modifier occurs more frequently with higher grades in the system
Reduced SV2A and GABAA receptor levels in the brains of type 2 diabetic rats revealed by [18F]SDM-8 and [18F]flumazenil PET.
No full textPURPOSE
Type 2 diabetes mellitus (T2DM) is associated with a greater risk of Alzheimer's disease. Synaptic impairment and protein aggregates have been reported in the brains of T2DM models. Here, we assessed whether neurodegenerative changes in synaptic vesicle 2 A (SV2A), γ-aminobutyric acid type A (GABAA) receptor, amyloid-β, tau and receptor for advanced glycosylation end product (RAGE) can be detected in vivo in T2DM rats.
METHODS
Positron emission tomography (PET) using [18F]SDM-8 (SV2A), [18F]flumazenil (GABAA receptor), [18F]florbetapir (amyloid-β), [18F]PM-PBB3 (tau), and [18F]FPS-ZM1 (RAGE) was carried out in 12-month-old diabetic Zucker diabetic fatty (ZDF) and SpragueDawley (SD) rats. Immunofluorescence staining, Thioflavin S staining, proteomic profiling and pathway analysis were performed on the brain tissues of ZDF and SD rats.
RESULTS
Reduced cortical [18F]SDM-8 uptake and cortical and hippocampal [18F]flumazenil uptake were observed in 12-month-old ZDF rats compared to SD rats. The regional uptake of [18F]florbetapir and [18F]PM-PBB3 was comparable in the brains of 12-month-old ZDF and SD rats. Immunofluorescence staining revealed Thioflavin S-negative, phospho-tau-positive inclusions in the cortex and hypothalamus in the brains of ZDF rats and the absence of amyloid-beta deposits. The level of GABAA receptors was lower in the cortex of ZDF rats than SD rats. Proteomic analysis further demonstrated that, compared with SD rats, synaptic-related proteins and pathways were downregulated in the hippocampus of ZDF rats.
CONCLUSION
These findings provide in vivo evidence for regional reductions in SV2A and GABAA receptor levels in the brains of aged T2DM ZDF rats
Long-term trajectories of densely reported depressive symptoms during an extended period of the COVID-19 pandemic in Switzerland: Social worries matter.
Get PDFPrevious mental health trajectory studies were mostly limited to the months before access to vaccination. They are not informing on whether public mental health has adapted to the pandemic. The aim of this analysis was to 1) investigate trajectories of monthly reported depressive symptoms from July 2020 to December 2021 in Switzerland, 2) compare average growth trajectories across regions with different stringency phases, and 3) explore the relative impact of self-reported worries related to health, economic and social domains as well as socio-economic indicators on growth trajectories. As part of the population-based Corona Immunitas program of regional, but harmonized, adult cohorts studying the pandemic course and impact, participants repeatedly reported online to the DASS-21 instrument on depressive symptomatology. Trajectories of depressive symptoms were estimated using a latent growth model, specified as a generalised linear mixed model. The time effect was modelled parametrically through a polynomial allowing to estimate trajectories for participants' missing time points. In all regions level and shape of the trajectories mirrored those of the KOF Stringency-Plus Index, which quantifies regional Covid-19 policy stringency. The higher level of average depression in trajectories of those expressing specific worries was most noticeable for the social domain. Younger age, female gender, and low household income went along with higher mean depression score trajectories throughout follow-up. Interventions to promote long-term resilience are an important part of pandemic preparedness, given the observed lack of an adaptation in mental health response to the pandemic even after the availability of vaccines in this high-income context
Effect of Essential Oil Components on the Activity of Steroidogenic Cytochrome P450
Get PDFEndocrine-disrupting chemicals (EDCs) may impact the development of prostate cancer (PCa) by altering the steroid metabolism. Although their exact mechanism of action in controlling tumor growth is not known, EDCs may inhibit steroidogenic enzymes such as CYP17A1 or CYP19A1 which are involved in the production of androgens or estrogens. High levels of circulating androgens are linked to PCa in men and Polycystic Ovary Syndrome (PCOS) in women. Essential oils or their metabolites, like lavender oil and tea tree oil, have been reported to act as potential EDCs and contribute towards sex steroid imbalance in cases of prepubertal gynecomastia in boys and premature thelarche in girls due to the exposure to lavender-based fragrances. We screened a range of EO components to determine their effects on CYP17A1 and CYP19A1. Computational docking was performed to predict the binding of essential oils with CYP17A1 and CYP19A1. Functional assays were performed using the radiolabeled substrates or Liquid Chromatography–High-Resolution Mass Spectrometry and cell viability assays were carried out in LNCaP cells. Many of the tested compounds bind close to the active site of CYP17A1, and (+)-Cedrol had the best binding with CYP17A1 and CYP19A1. Eucalyptol, Dihydro-β-Ionone, and (−)-α-pinene showed 20% to 40% inhibition of dehydroepiandrosterone production; and some compounds also effected CYP19A1. Extensive use of these essential oils in various beauty and hygiene products is common, but only limited knowledge about their potential detrimental side effects exists. Our results suggest that prolonged exposure to some of these essential oils may result in steroid imbalances. On the other hand, due to their effect on lowering androgen output and ability to bind at the active site of steroidogenic cytochrome P450s, these compounds may provide design ideas for novel compounds against hyperandrogenic disorders such as PCa and PCOS
The limited antegrade subintimal tracking technique to retrieve a trapped rotablator burr: a case report.
Get PDFBACKGROUND
Burr entrapment is a rare, but potentially serious complication of rotablation. This report describes the percutaneous options available for Rota burr retrieval.
CASE SUMMARY
A 62-year-old Caucasian man with stable angina presented for percutaneous coronary intervention. Attempted rotablation with a 1.75 mm burr resulted in Rota burr entrapment, in the heavily calcified proximal right coronary artery. A chronic total occlusion angioplasty technique (limited antegrade subintimal tracking) was successfully used to remove the trapped Rota burr, by enabling subintimal dilatation to externally crush plaque and dislodge the burr. The angioplasty procedure was then completed using the wire that had a short subintimal passage, before re-entering the true lumen.
DISCUSSION
The mechanism for Rota burr entrapment, in this case, was initiating rotablation on the heavily calcified lesion and not more proximal to allow a pecking motion. The learning points are (i) to start the rotablator several millimetres proximal to the actual lesion, and (ii) if unable to wire alongside a trapped Rota burr in the true lumen, then subintimal crossing and balloon dilatation in the subintimal space may work to dislodge the burr
Seasonality of mortality under climate change: a multicountry projection study.
Get PDFBACKGROUND
Climate change can directly impact temperature-related excess deaths and might subsequently change the seasonal variation in mortality. In this study, we aimed to provide a systematic and comprehensive assessment of potential future changes in the seasonal variation, or seasonality, of mortality across different climate zones.
METHODS
In this modelling study, we collected daily time series of mean temperature and mortality (all causes or non-external causes only) via the Multi-Country Multi-City Collaborative (MCC) Research Network. These data were collected during overlapping periods, spanning from Jan 1, 1969 to Dec 31, 2020. We projected daily mortality from Jan 1, 2000 to Dec 31, 2099, under four climate change scenarios corresponding to increasing emissions (Shared Socioeconomic Pathways [SSP] scenarios SSP1-2.6, SSP2-4.5, SSP3-7.0, and SSP5-8.5). We compared the seasonality in projected mortality between decades by its shape, timings (the day-of-year) of minimum (trough) and maximum (peak) mortality, and sizes (peak-to-trough ratio and attributable fraction). Attributable fraction was used to measure the burden of seasonality of mortality. The results were summarised by climate zones.
FINDINGS
The MCC dataset included 126 809 537 deaths from 707 locations within 43 countries or areas. After excluding the only two polar locations (both high-altitude locations in Peru) from climatic zone assessments, we analysed 126 766 164 deaths in 705 locations aggregated in four climate zones (tropical, arid, temperate, and continental). From the 2000s to the 2090s, our projections showed an increase in mortality during the warm seasons and a decrease in mortality during the cold seasons, albeit with mortality remaining high during the cold seasons, under all four SSP scenarios in the arid, temperate, and continental zones. The magnitude of this changing pattern was more pronounced under the high-emission scenarios (SSP3-7.0 and SSP5-8.5), substantially altering the shape of seasonality of mortality and, under the highest emission scenario (SSP5-8.5), shifting the mortality peak from cold seasons to warm seasons in arid, temperate, and continental zones, and increasing the size of seasonality in all zones except the arid zone by the end of the century. In the 2090s compared with the 2000s, the change in peak-to-trough ratio (relative scale) ranged from 0·96 to 1·11, and the change in attributable fraction ranged from 0·002% to 0·06% under the SSP5-8.5 (highest emission) scenario.
INTERPRETATION
A warming climate can substantially change the seasonality of mortality in the future. Our projections suggest that health-care systems should consider preparing for a potentially increased demand during warm seasons and sustained high demand during cold seasons, particularly in regions characterised by arid, temperate, and continental climates.
FUNDING
The Environment Research and Technology Development Fund of the Environmental Restoration and Conservation Agency, provided by the Ministry of the Environment of Japan
Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study.
Get PDFBackground: Small, randomized trials of cervical artery dissection (CAD) patients showed conflicting results regarding optimal stroke prevention strategies. We aimed to compare outcomes in patients with CAD treated with antiplatelets versus anticoagulation. Methods: This is a multi-center observational retrospective international study (16 countries, 63 sites) that included CAD patients without major trauma. The exposure was antithrombotic treatment type (anticoagulation vs. antiplatelets) and outcomes were subsequent ischemic stroke and major hemorrhage (intracranial or extracranial hemorrhage). We used adjusted Cox regression with Inverse Probability of Treatment Weighting (IPTW) to determine associations between anticoagulation and study outcomes within 30 and 180 days. The main analysis used an "as treated" cross-over approach and only included outcomes occurring on the above treatments. Results: The study included 3,636 patients [402 (11.1%) received exclusively anticoagulation and 2,453 (67.5%) received exclusively antiplatelets]. By day 180, there were 162 new ischemic strokes (4.4%) and 28 major hemorrhages (0.8%); 87.0% of ischemic strokes occurred by day 30. In adjusted Cox regression with IPTW, compared to antiplatelet therapy, anticoagulation was associated with a non-significantly lower risk of subsequent ischemic stroke by day 30 (adjusted HR 0.71 95% CI 0.45-1.12, p=0.145) and by day 180 (adjusted HR 0.80 95% CI 0.28-2.24, p=0.670). Anticoagulation therapy was not associated with a higher risk of major hemorrhage by day 30 (adjusted HR 1.39 95% CI 0.35-5.45, p=0.637) but was by day 180 (adjusted HR 5.56 95% CI 1.53-20.13, p=0.009). In interaction analyses, patients with occlusive dissection had significantly lower ischemic stroke risk with anticoagulation (adjusted HR 0.40 95% CI 0.18-0.88) (Pinteraction=0.009). Conclusions: Our study does not rule out a benefit of anticoagulation in reducing ischemic stroke risk, particularly in patients with occlusive dissection. If anticoagulation is chosen, it seems reasonable to switch to antiplatelet therapy before 180 days to lower the risk of major bleeding. Large prospective studies are needed to validate our findings
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