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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.
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.
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 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.
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.
Environmental risk factors for dementia are poorly understood. Aluminium and fluorine in drinking water have been linked with dementia but uncertainties remain about this relationship.
In the largest longitudinal study in this context, we set out to explore the individual effect of aluminium and fluoride in drinking water on dementia risk and, as fluorine can increase absorption of aluminium, we also examine any synergistic influence on dementia.
We used Cox models to investigate the association between mean aluminium and fluoride levels in drinking water at their residential location (collected 2005–2012 by the Drinking Water Quality Regulator for Scotland) with dementia in members of the Scottish Mental Survey 1932 cohort who were alive in 2005.
A total of 1972 out of 6990 individuals developed dementia by the linkage date in 2012. Dementia risk was raised with increasing mean aluminium levels in women (hazard ratio per s.d. increase 1.09, 95% CI 1.03–1.15, P < 0.001) and men (1.12, 95% CI 1.03–1.21, P = 0.004). A dose-response pattern of association was observed between mean fluoride levels and dementia in women (1.34, 95% CI 1.28–1.41, P < 0.001) and men (1.30, 95% CI 1.22–1.39, P < 0.001), with dementia risk more than doubled in the highest quartile compared with the lowest. There was no statistical interaction between aluminium and fluoride levels in relation with dementia.
Higher levels of aluminium and fluoride were related to dementia risk in a population of men and women who consumed relatively low drinking-water levels of both.
OBJECTIVES/SPECIFIC AIMS: The objective of this project is to determine whether HRV, collected peri-operatively, is predictive of cognitive decline among older adults who undergo elective surgery/anesthesia. METHODS/STUDY POPULATION: This project is a part of the ongoing INTUIT/PRIME study, which is collecting pre- and post-operative cognitive testing, fMRI imaging, CSF samples, and EEG recordings from 200 older adults (age ≥ 60) undergoing elective non-cardiac/non-neurologic surgery scheduled to last > 2 hours at Duke University Medical Center and Duke Regional Hospital. This project utilizes data from the first 60 INTUIT participants who contributed continuous heart rate data before and during surgery. Participants undergo cognitive testing prior to surgery (baseline) and at 6 weeks after surgery. Our primary dependent variable is the change in the composite score from baseline to 6-weeks. Delirium is assessed in the hospital with the twice daily 3D-CAM tool, so we will report the proportion of individuals with 6-week cognitive decline who exhibited delirium in the days following surgery. Participants’ echocardiogram (ECG) recordings are extracted pre- and intraoperatively from B650/B850 patient monitors with VSCapture software. HRV is defined as the variability between successive R-spikes or inter-beat-intervals on ECG. RESULTS/ANTICIPATED RESULTS: We anticipate that lower intraoperative HRV is associated with worse cognitive decline at 6 weeks after surgery. As secondary objectives, we will determine whether pre-operative HRV or change in HRV (from pre-operative to intra-operative measures) are predictive of cognitive decline after surgery. We expect that in-hospital delirium will be detected in a higher proportion of those with 6-week cognitive decline, compared to those with stable or improved cognition at 6 weeks. DISCUSSION/SIGNIFICANCE OF IMPACT: HRV may address the present need for pre- and intra-operative cognitive risk stratification in the elderly. Physiological indices like HRV have the potential to dramatically change our understanding of CI in older adults undergoing surgery, as they offer an accessible, cost-effective, and non-invasive means whereby clinicians, particularly those unfamiliar with the nuances of geriatric and CI/dementia-related care, can monitor patients and refer those at high-risk of CI after surgery for early intervention.
Healthcare organizations are required to provide workers with respiratory protection (RP) to mitigate hazardous airborne inhalation exposures. This study sought to better identify gaps that exist between RP guidance and clinical practice to understand issues that would benefit from additional research or clarification.
Current work in multicultural competency has emphasized factors such as race and ethnicity, age, disability status, socioeconomic status, sexual orientation and gender. For those clinicians who work with military and veteran populations, grounding in military cultural competence is also critical as a prerequisite for providing quality care. We believe that engaging these populations from a specifically cognitive behavioural orientation allows bridging of cultural gaps and that there is a natural alignment between cognitive behavioural therapy (CBT) and many aspects of warrior culture. This paper outlines several factors related to the values of military culture and strategies of the CBT therapist to better understand and use these values effectively in clinical practice, including lessons learned from an intensive outpatient program providing speciality care to veterans and military service members.
Middle-third helical rim defects may arise from trauma or oncological resection, and pose a challenging reconstructive problem. Reconstructing defects larger than 2 cm using traditional methods commits patients to the inconvenience of staged procedures.
This paper describes a single-stage helical rim reconstruction technique using a post-auricular bipedicled flap and ipsilateral conchal cartilage graft for delayed middle-third helical rim reconstruction.
Two examples of this technique used in post-trauma and oncological reconstruction cases are presented, with pre- and post-operative photographs provided for demonstration.
Contralateral graft harvest and staged operations for helical rim reconstruction are associated with donor site morbidity and the inconvenience of multiple operations to achieve the desired reconstructive outcome. Our single-stage helical rim reconstruction technique was well tolerated by patients, and showed satisfactory aesthetic results in terms of size and symmetry.
The value of the nosological distinction between non-affective and affective psychosis has frequently been challenged. We aimed to investigate the transdiagnostic dimensional structure and associated characteristics of psychopathology at First Episode Psychosis (FEP). Regardless of diagnostic categories, we expected that positive symptoms occurred more frequently in ethnic minority groups and in more densely populated environments, and that negative symptoms were associated with indices of neurodevelopmental impairment.
This study included 2182 FEP individuals recruited across six countries, as part of the EUropean network of national schizophrenia networks studying Gene–Environment Interactions (EU-GEI) study. Symptom ratings were analysed using multidimensional item response modelling in Mplus to estimate five theory-based models of psychosis. We used multiple regression models to examine demographic and context factors associated with symptom dimensions.
A bifactor model, composed of one general factor and five specific dimensions of positive, negative, disorganization, manic and depressive symptoms, best-represented associations among ratings of psychotic symptoms. Positive symptoms were more common in ethnic minority groups. Urbanicity was associated with a higher score on the general factor. Men presented with more negative and less depressive symptoms than women. Early age-at-first-contact with psychiatric services was associated with higher scores on negative, disorganized, and manic symptom dimensions.
Our results suggest that the bifactor model of psychopathology holds across diagnostic categories of non-affective and affective psychosis at FEP, and demographic and context determinants map onto general and specific symptom dimensions. These findings have implications for tailoring symptom-specific treatments and inform research into the mood-psychosis spectrum.
The role that vitamin D plays in pulmonary function remains uncertain. Epidemiological studies reported mixed findings for serum 25-hydroxyvitamin D (25(OH)D)–pulmonary function association. We conducted the largest cross-sectional meta-analysis of the 25(OH)D–pulmonary function association to date, based on nine European ancestry (EA) cohorts (n 22 838) and five African ancestry (AA) cohorts (n 4290) in the Cohorts for Heart and Aging Research in Genomic Epidemiology Consortium. Data were analysed using linear models by cohort and ancestry. Effect modification by smoking status (current/former/never) was tested. Results were combined using fixed-effects meta-analysis. Mean serum 25(OH)D was 68 (sd 29) nmol/l for EA and 49 (sd 21) nmol/l for AA. For each 1 nmol/l higher 25(OH)D, forced expiratory volume in the 1st second (FEV1) was higher by 1·1 ml in EA (95 % CI 0·9, 1·3; P<0·0001) and 1·8 ml (95 % CI 1·1, 2·5; P<0·0001) in AA (Prace difference=0·06), and forced vital capacity (FVC) was higher by 1·3 ml in EA (95 % CI 1·0, 1·6; P<0·0001) and 1·5 ml (95 % CI 0·8, 2·3; P=0·0001) in AA (Prace difference=0·56). Among EA, the 25(OH)D–FVC association was stronger in smokers: per 1 nmol/l higher 25(OH)D, FVC was higher by 1·7 ml (95 % CI 1·1, 2·3) for current smokers and 1·7 ml (95 % CI 1·2, 2·1) for former smokers, compared with 0·8 ml (95 % CI 0·4, 1·2) for never smokers. In summary, the 25(OH)D associations with FEV1 and FVC were positive in both ancestries. In EA, a stronger association was observed for smokers compared with never smokers, which supports the importance of vitamin D in vulnerable populations.
The role of vegetable and fruit intake in reducing falls risk in elderly populations is uncertain. This study examined the associations of vegetable and fruit intake with falls-related hospitalisations in a prospective cohort study of elderly women (n 1429, ≥70 years), including effects on muscular function, which represented a potential causal pathway. Muscular function, measured using grip strength and timed-up-and-go (TUG), and vegetable and fruit intake, quantified using a validated FFQ, were assessed at baseline (1998). Incident falls-related hospitalisation over 14·5-year follow-up was captured by the Hospital Morbidity Data Collection, linked via the Western Australian Data Linkage System. Falls-related hospitalisation occurred in 568 (39·7 %) of women. In multivariable-adjusted models, falls-related hospitalisations were lower in participants consuming more vegetables (hazard ratio (HR) per 75 g serve: 0·90 (95 % CI 0·82, 0·99)), but not fruit intake (per 150 g serve: 1·03 (95 % CI 0·93, 1·14)). Only total cruciferous vegetable intake was inversely associated with falls-related hospitalisation (HR: per 20 g serve: 0·90 (95 % CI 0·83, 0·97)). Higher total vegetable intake was associated with lower odds for poor grip strength (OR: 0·87 (95 % CI 0·77, 0·97)) and slow TUG (OR: 0·88 (95 % CI 0·78, 0·99)). Including grip strength and TUG in the multivariable-adjusted model attenuated the association between total vegetable intake and falls-related hospitalisations. In conclusion, elderly women with higher total and cruciferous vegetable intake had lower injurious falls risk, which may be explained in a large part by better physical function. Falls reduction may be considered an additional benefit of higher vegetable intake in older women.
The ideal sampling method and benefit of qualitative versus quantitative culture for carbapenem-resistant Enterobacteriaceae (CRE) recovery in hospitalized patient rooms and bathrooms is unknown. Although the use of nylon-flocked swabs improved overall gram-negative organism recovery compared with cellulose sponges, they were similar for CRE recovery. Quantitative culture was inferior and unrevealing beyond the qualitative results.