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No evidence-based therapy for borderline personality disorder (BPD) exhibits a clear superiority. However, BPD is highly heterogeneous, and different patients may specifically benefit from the interventions of a particular treatment.
From a randomized trial comparing a year of dialectical behavior therapy (DBT) to general psychiatric management (GPM) for BPD, long-term (2-year-post) outcome data and patient baseline variables (n = 156) were used to examine individual and combined patient-level moderators of differential treatment response. A two-step bootstrapped and partially cross-validated moderator identification process was employed for 20 baseline variables. For identified moderators, 10-fold bootstrapped cross-validated models estimated response to each therapy, and long-term outcomes were compared for patients randomized to their model-predicted optimal v. non-optimal treatment.
Significant moderators surviving the two-step process included psychiatric symptom severity, BPD impulsivity symptoms (both GPM > DBT), dependent personality traits, childhood emotional abuse, and social adjustment (all DBT > GPM). Patients randomized to their model-predicted optimal treatment had significantly better long-term outcomes (d = 0.36, p = 0.028), especially if the model had a relatively stronger (top 60%) prediction for that patient (d = 0.61, p = 0.004). Among patients with a stronger prediction, this advantage held even when applying a conservative statistical check (d = 0.46, p = 0.043).
Patient characteristics influence the degree to which they respond to two treatments for BPD. Combining information from multiple moderators may help inform providers and patients as to which treatment is the most likely to lead to long-term symptom relief. Further research on personalized medicine in BPD is needed.
The development of oceanography and meteorology has greatly benefited from satellite-based data of Earth’s atmosphere and ocean. Traditional Earth observation missions have utilised Sun-synchronous orbits with repeat ground tracks due to their advantages in visible and infrared wavelengths. However, diversification of observation wavelengths and massive deployment of miniaturised satellites are both enabling and necessitating new kinds of space missions. This paper proposes several unconventional satellite orbits intended for use in, but not limited to, Earth observation. This ‘toolbox’ of orbits and taxonomy thereof will thus support the definition of design requirements for the individual satellites in nano-satellite constellations developed by national space agencies, industries and academia.
Studies suggest that alcohol consumption and alcohol use disorders have distinct genetic backgrounds.
We examined whether polygenic risk scores (PRS) for consumption and problem subscales of the Alcohol Use Disorders Identification Test (AUDIT-C, AUDIT-P) in the UK Biobank (UKB; N = 121 630) correlate with alcohol outcomes in four independent samples: an ascertained cohort, the Collaborative Study on the Genetics of Alcoholism (COGA; N = 6850), and population-based cohorts: Avon Longitudinal Study of Parents and Children (ALSPAC; N = 5911), Generation Scotland (GS; N = 17 461), and an independent subset of UKB (N = 245 947). Regression models and survival analyses tested whether the PRS were associated with the alcohol-related outcomes.
In COGA, AUDIT-P PRS was associated with alcohol dependence, AUD symptom count, maximum drinks (R2 = 0.47–0.68%, p = 2.0 × 10−8–1.0 × 10−10), and increased likelihood of onset of alcohol dependence (hazard ratio = 1.15, p = 4.7 × 10−8); AUDIT-C PRS was not an independent predictor of any phenotype. In ALSPAC, the AUDIT-C PRS was associated with alcohol dependence (R2 = 0.96%, p = 4.8 × 10−6). In GS, AUDIT-C PRS was a better predictor of weekly alcohol use (R2 = 0.27%, p = 5.5 × 10−11), while AUDIT-P PRS was more associated with problem drinking (R2 = 0.40%, p = 9.0 × 10−7). Lastly, AUDIT-P PRS was associated with ICD-based alcohol-related disorders in the UKB subset (R2 = 0.18%, p < 2.0 × 10−16).
AUDIT-P PRS was associated with a range of alcohol-related phenotypes across population-based and ascertained cohorts, while AUDIT-C PRS showed less utility in the ascertained cohort. We show that AUDIT-P is genetically correlated with both use and misuse and demonstrate the influence of ascertainment schemes on PRS analyses.
There is controversy over the extent to which the new International Classification of Diseases (ICD-11) diagnosis of complex posttraumatic stress disorder (CPTSD) is distinct from posttraumatic stress disorder (PTSD). This study aimed to conduct the first investigation of distinctive neural processes during threat processing in CPTSD relative to PTSD.
This cross-sectional functional magnetic resonance study included 99 participants who met criteria for PTSD (PTSD = 32, CPTSD = 28) and 39 trauma-exposed controls. PTSD was assessed with the Clinician-Administered PTSD Scale (CAPS). CPTSD was assessed with an adapted version of the International Trauma Questionnaire. Neural responses were measured across the brain while threat or neutral faces were presented at both supraliminal and subliminal levels.
During supraliminal presentations of threat stimuli, there was greater bilateral insula and right amygdala activation in CPTSD participants relative to PTSD. Reduced supraliminal right dorsolateral prefrontal cortex activation and increased subliminal amygdala and insula activation were observed as common dysfunction for both CPTSD and PTSD groups relative to trauma controls. There were no significant differences in terms of subliminal presentations and no differences in functional connectivity. Dissociative responses were positively associated with right insula activation (r = 0.347, p < 0.01).
These results provide the first evidence of distinct neural profiles of CPTSD and PTSD during threat processing. The observation of increased insula and right amygdala activation in CPTSD accords with the proposal that CPTSD is distinguished from PTSD by disturbances in emotion regulation and self-concept.
To investigate the association between parity and the risk of incident dementia in women.
We pooled baseline and follow-up data for community-dwelling women aged 60 or older from six population-based, prospective cohort studies from four European and two Asian countries. We investigated the association between parity and incident dementia using Cox proportional hazards regression models adjusted for age, educational level, hypertension, diabetes mellitus and cohort, with additional analysis by dementia subtype (Alzheimer dementia (AD) and non-Alzheimer dementia (NAD)).
Of 9756 women dementia-free at baseline, 7010 completed one or more follow-up assessments. The mean follow-up duration was 5.4 ± 3.1 years and dementia developed in 550 participants. The number of parities was associated with the risk of incident dementia (hazard ratio (HR) = 1.07, 95% confidence interval (CI) = 1.02–1.13). Grand multiparity (five or more parities) increased the risk of dementia by 30% compared to 1–4 parities (HR = 1.30, 95% CI = 1.02–1.67). The risk of NAD increased by 12% for every parity (HR = 1.12, 95% CI = 1.02–1.23) and by 60% for grand multiparity (HR = 1.60, 95% CI = 1.00–2.55), but the risk of AD was not significantly associated with parity.
Grand multiparity is a significant risk factor for dementia in women. This may have particularly important implications for women in low and middle-income countries where the fertility rate and prevalence of grand multiparity are high.
We aimed to investigate the heterogeneity of seasonal suicide patterns among multiple geographically, demographically and socioeconomically diverse populations.
Weekly time-series data of suicide counts for 354 communities in 12 countries during 1986–2016 were analysed. Two-stage analysis was performed. In the first stage, a generalised linear model, including cyclic splines, was used to estimate seasonal patterns of suicide for each community. In the second stage, the community-specific seasonal patterns were combined for each country using meta-regression. In addition, the community-specific seasonal patterns were regressed onto community-level socioeconomic, demographic and environmental indicators using meta-regression.
We observed seasonal patterns in suicide, with the counts peaking in spring and declining to a trough in winter in most of the countries. However, the shape of seasonal patterns varied among countries from bimodal to unimodal seasonality. The amplitude of seasonal patterns (i.e. the peak/trough relative risk) also varied from 1.47 (95% confidence interval [CI]: 1.33–1.62) to 1.05 (95% CI: 1.01–1.1) among 12 countries. The subgroup difference in the seasonal pattern also varied over countries. In some countries, larger amplitude was shown for females and for the elderly population (≥65 years of age) than for males and for younger people, respectively. The subperiod difference also varied; some countries showed increasing seasonality while others showed a decrease or little change. Finally, the amplitude was larger for communities with colder climates, higher proportions of elderly people and lower unemployment rates (p-values < 0.05).
Despite the common features of a spring peak and a winter trough, seasonal suicide patterns were largely heterogeneous in shape, amplitude, subgroup differences and temporal changes among different populations, as influenced by climate, demographic and socioeconomic conditions. Our findings may help elucidate the underlying mechanisms of seasonal suicide patterns and aid in improving the design of population-specific suicide prevention programmes based on these patterns.
Individuals with posttraumatic stress disorder (PTSD) are at increased risk of various chronic diseases. One hypothesized pathway is via changes in diet quality. This study evaluated whether PTSD was associated with deterioration in diet quality over time.
Data were from 51 965 women in the Nurses' Health Study II PTSD sub-study followed over 20 years. Diet, assessed at 4-year intervals, was characterized via the Alternative Healthy Eating Index-2010 (AHEI). Based on information from the Brief Trauma Questionnaire and Short Screening Scale for DSM-IV PTSD, trauma/PTSD status was classified as no trauma exposure, prevalent exposure (trauma/PTSD onset before study entry), or new-onset (trauma/PTSD onset during follow-up). We further categorized women with prevalent exposure as having trauma with no PTSD symptoms, trauma with low PTSD symptoms, and trauma with high PTSD symptoms, and created similar categories for women with new-onset exposure, resulting in seven comparison groups. Multivariable linear mixed-effects spline models tested differences in diet quality changes by trauma/PTSD status over follow-up.
Overall, diet quality improved over time regardless of PTSD status. In age-adjusted models, compared to those with no trauma, women with prevalent high PTSD and women with new-onset high PTSD symptoms had 3.3% and 3.6% lower improvement in diet quality, respectively, during follow-up. Associations remained consistent after adjusting for health conditions, sociodemographics, and behavioral characteristics.
PTSD is associated with less healthy changes in overall diet quality over time. Poor diet quality may be one pathway linking PTSD with a higher risk of chronic disease development.
Research participants want to receive results from studies in which they participate. However, health researchers rarely share the results of their studies beyond scientific publication. Little is known about the barriers researchers face in returning study results to participants.
Using a mixed-methods design, health researchers (N = 414) from more than 40 US universities were asked about barriers to providing results to participants. Respondents were recruited from universities with Clinical and Translational Science Award programs and Prevention Research Centers.
Respondents reported the percent of their research where they experienced each of the four barriers to disseminating results to participants: logistical/methodological, financial, systems, and regulatory. A fifth barrier, investigator capacity, emerged from data analysis. Training for research faculty and staff, promotion and tenure incentives, and funding agencies supporting dissemination of results to participants were solutions offered to overcoming barriers.
Study findings add to literature on research dissemination by documenting health researchers’ perceived barriers to sharing study results with participants. Implications for policy and practice suggest that additional resources and training could help reduce dissemination barriers and increase the return of results to participants.
Item 9 of the Patient Health Questionnaire-9 (PHQ-9) queries about thoughts of death and self-harm, but not suicidality. Although it is sometimes used to assess suicide risk, most positive responses are not associated with suicidality. The PHQ-8, which omits Item 9, is thus increasingly used in research. We assessed equivalency of total score correlations and the diagnostic accuracy to detect major depression of the PHQ-8 and PHQ-9.
We conducted an individual patient data meta-analysis. We fit bivariate random-effects models to assess diagnostic accuracy.
16 742 participants (2097 major depression cases) from 54 studies were included. The correlation between PHQ-8 and PHQ-9 scores was 0.996 (95% confidence interval 0.996 to 0.996). The standard cutoff score of 10 for the PHQ-9 maximized sensitivity + specificity for the PHQ-8 among studies that used a semi-structured diagnostic interview reference standard (N = 27). At cutoff 10, the PHQ-8 was less sensitive by 0.02 (−0.06 to 0.00) and more specific by 0.01 (0.00 to 0.01) among those studies (N = 27), with similar results for studies that used other types of interviews (N = 27). For all 54 primary studies combined, across all cutoffs, the PHQ-8 was less sensitive than the PHQ-9 by 0.00 to 0.05 (0.03 at cutoff 10), and specificity was within 0.01 for all cutoffs (0.00 to 0.01).
PHQ-8 and PHQ-9 total scores were similar. Sensitivity may be minimally reduced with the PHQ-8, but specificity is similar.
Norovirus, a major cause of gastroenteritis in people of all ages worldwide, was first reported in South Korea in 1999. The most common causal agents of pediatric acute gastroenteritis are norovirus and rotavirus. While vaccination has reduced the pediatric rotavirus infection rate, norovirus vaccines have not been developed. Therefore, prediction and prevention of norovirus are very important. Norovirus is divided into genogroups GI–GVII, with GII.4 being the most prevalent. However, in 2012–2013, GII.17 showed a higher incidence than GII.4 and a novel variant, GII.P17-GII.17, appeared. In this study, 204 stool samples collected in 2013–2014 were screened by reverse transcriptase-polymerase chain reaction; 11 GI (5.39%) and 45 GII (22.06%) noroviruses were identified. GI.4, GI.5, GII.4, GII.6 and GII.17 were detected. The whole genomes of the three norovirus GII.17 were sequenced. The whole genome of GII.17 consists of three open reading frames of 5109, 1623 and 780 bp. Compared with 20 GII.17 strains isolated in other countries, we observed numerous changes in the protruding P2 domain of VP1 in the Korean GII.17 viruses. Our study provided genome information that might aid in epidemic prevention, epidemiology studies and vaccine development.
Given the challenges in accurately identifying unexposed controls in case–control studies of diarrhoea, we examined diarrhoea incidence, subclinical enteric infections and growth stunting within a reference population in the Global Enteric Multicenter Study, Kenya site. Within ‘control’ children (0–59 months old without diarrhoea in the 7 days before enrolment, n = 2384), we examined surveys at enrolment and 60-day follow-up, stool at enrolment and a 14-day post-enrolment memory aid for diarrhoea incidence. At enrolment, 19% of controls had ⩾1 enteric pathogen associated with moderate-to-severe diarrhoea (‘MSD pathogens’) in stool; following enrolment, many reported diarrhoea (27% in 7 days, 39% in 14 days). Controls with and without reported diarrhoea had similar carriage of MSD pathogens at enrolment; however, controls reporting diarrhoea were more likely to report visiting a health facility for diarrhoea (27% vs. 7%) or fever (23% vs. 16%) at follow-up than controls without diarrhoea. Odds of stunting differed by both MSD and ‘any’ (including non-MSD pathogens) enteric pathogen carriage, but not diarrhoea, suggesting control classification may warrant modification when assessing long-term outcomes. High diarrhoea incidence following enrolment and prevalent carriage of enteric pathogens have implications for sequelae associated with subclinical enteric infections and for design and interpretation of case–control studies examining diarrhoea.
Toca 511 (vocimagene amiretrorepvec) is an investigational, conditionally lytic, retroviral replicating vector (RRV). RRVs selectively infect cancer cells due to innate and adaptive immune response defects in cancers that allow virus replication, and the requirement for cell division for virus integration into the genome. Toca 511 spreads through tumors, stably delivering an optimized yeast cytosine deaminase gene that converts the prodrug Toca FC (investigational, extended-release 5-FC) into 5-FU within the tumor microenvironment. 5-FU kills infected dividing cancer cells and surrounding tumor, myeloid derived suppressor cells, and tumor associated macrophages, resulting in long-term tumor immunity in preclinical models. Data from a Phase 1 resection trial showed six durable CRs and extended mOS compared to historical controls. The FDA granted Breakthrough Therapy Designation for Toca 511 & Toca FC in the treatment of patients with rHGG. Toca 5 is an international, randomized, open-label Phase 3 trial (NCT02414165) of Toca 511 & Toca FC versus SOC in patients undergoing resection for first or second recurrence of rHGG. Patients will be stratified by IDH1 status, KPS, and geographic region. Primary endpoint is OS, and secondary endpoints are durable response rate, durable clinical benefit rate, duration of durable response, and 12-month survival rate. Key inclusion criteria are histologically proven GBM or AA, tumor size ≥1cm and ≤5cm, and KPS ≥70. Immune monitoring and molecular profiling will be performed. Approximately 380 patients will be randomized. An IDMC is commissioned to review the safety and efficacy data which includes 2 interim analyses. Enrollment is ongoing.
Different diagnostic interviews are used as reference standards for major depression classification in research. Semi-structured interviews involve clinical judgement, whereas fully structured interviews are completely scripted. The Mini International Neuropsychiatric Interview (MINI), a brief fully structured interview, is also sometimes used. It is not known whether interview method is associated with probability of major depression classification.
To evaluate the association between interview method and odds of major depression classification, controlling for depressive symptom scores and participant characteristics.
Data collected for an individual participant data meta-analysis of Patient Health Questionnaire-9 (PHQ-9) diagnostic accuracy were analysed and binomial generalised linear mixed models were fit.
A total of 17 158 participants (2287 with major depression) from 57 primary studies were analysed. Among fully structured interviews, odds of major depression were higher for the MINI compared with the Composite International Diagnostic Interview (CIDI) (odds ratio (OR) = 2.10; 95% CI = 1.15–3.87). Compared with semi-structured interviews, fully structured interviews (MINI excluded) were non-significantly more likely to classify participants with low-level depressive symptoms (PHQ-9 scores ≤6) as having major depression (OR = 3.13; 95% CI = 0.98–10.00), similarly likely for moderate-level symptoms (PHQ-9 scores 7–15) (OR = 0.96; 95% CI = 0.56–1.66) and significantly less likely for high-level symptoms (PHQ-9 scores ≥16) (OR = 0.50; 95% CI = 0.26–0.97).
The MINI may identify more people as depressed than the CIDI, and semi-structured and fully structured interviews may not be interchangeable methods, but these results should be replicated.
Declaration of interest
Drs Jetté and Patten declare that they received a grant, outside the submitted work, from the Hotchkiss Brain Institute, which was jointly funded by the Institute and Pfizer. Pfizer was the original sponsor of the development of the PHQ-9, which is now in the public domain. Dr Chan is a steering committee member or consultant of Astra Zeneca, Bayer, Lilly, MSD and Pfizer. She has received sponsorships and honorarium for giving lectures and providing consultancy and her affiliated institution has received research grants from these companies. Dr Hegerl declares that within the past 3 years, he was an advisory board member for Lundbeck, Servier and Otsuka Pharma; a consultant for Bayer Pharma; and a speaker for Medice Arzneimittel, Novartis, and Roche Pharma, all outside the submitted work. Dr Inagaki declares that he has received grants from Novartis Pharma, lecture fees from Pfizer, Mochida, Shionogi, Sumitomo Dainippon Pharma, Daiichi-Sankyo, Meiji Seika and Takeda, and royalties from Nippon Hyoron Sha, Nanzando, Seiwa Shoten, Igaku-shoin and Technomics, all outside of the submitted work. Dr Yamada reports personal fees from Meiji Seika Pharma Co., Ltd., MSD K.K., Asahi Kasei Pharma Corporation, Seishin Shobo, Seiwa Shoten Co., Ltd., Igaku-shoin Ltd., Chugai Igakusha and Sentan Igakusha, all outside the submitted work. All other authors declare no competing interests. No funder had any role in the design and conduct of the study; collection, management, analysis and interpretation of the data; preparation, review or approval of the manuscript; and decision to submit the manuscript for publication.
Coinfection with human immunodeficiency virus (HIV) and viral hepatitis is associated with high morbidity and mortality in the absence of clinical management, making identification of these cases crucial. We examined characteristics of HIV and viral hepatitis coinfections by using surveillance data from 15 US states and two cities. Each jurisdiction used an automated deterministic matching method to link surveillance data for persons with reported acute and chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infections, to persons reported with HIV infection. Of the 504 398 persons living with diagnosed HIV infection at the end of 2014, 2.0% were coinfected with HBV and 6.7% were coinfected with HCV. Of the 269 884 persons ever reported with HBV, 5.2% were reported with HIV. Of the 1 093 050 persons ever reported with HCV, 4.3% were reported with HIV. A greater proportion of persons coinfected with HIV and HBV were males and blacks/African Americans, compared with those with HIV monoinfection. Persons who inject drugs represented a greater proportion of those coinfected with HIV and HCV, compared with those with HIV monoinfection. Matching HIV and viral hepatitis surveillance data highlights epidemiological characteristics of persons coinfected and can be used to routinely monitor health status and guide state and national public health interventions.
Whether monozygotic (MZ) and dizygotic (DZ) twins differ from each other in a variety of phenotypes is important for genetic twin modeling and for inferences made from twin studies in general. We analyzed whether there were differences in individual, maternal and paternal education between MZ and DZ twins in a large pooled dataset. Information was gathered on individual education for 218,362 adult twins from 27 twin cohorts (53% females; 39% MZ twins), and on maternal and paternal education for 147,315 and 143,056 twins respectively, from 28 twin cohorts (52% females; 38% MZ twins). Together, we had information on individual or parental education from 42 twin cohorts representing 19 countries. The original education classifications were transformed to education years and analyzed using linear regression models. Overall, MZ males had 0.26 (95% CI [0.21, 0.31]) years and MZ females 0.17 (95% CI [0.12, 0.21]) years longer education than DZ twins. The zygosity difference became smaller in more recent birth cohorts for both males and females. Parental education was somewhat longer for fathers of DZ twins in cohorts born in 1990–1999 (0.16 years, 95% CI [0.08, 0.25]) and 2000 or later (0.11 years, 95% CI [0.00, 0.22]), compared with fathers of MZ twins. The results show that the years of both individual and parental education are largely similar in MZ and DZ twins. We suggest that the socio-economic differences between MZ and DZ twins are so small that inferences based upon genetic modeling of twin data are not affected.
We have previously shown that the minor alleles of vascular endothelial growth factor A (VEGFA) single-nucleotide polymorphism rs833069 and superoxide dismutase 2 (SOD2) single-nucleotide polymorphism rs2758331 are both associated with improved transplant-free survival after surgery for CHD in infants, but the underlying mechanisms are unknown. We hypothesised that one or both of these minor alleles are associated with better systemic ventricular function, resulting in improved survival.
This study is a follow-up analysis of 422 non-syndromic CHD patients who underwent neonatal cardiac surgery with cardiopulmonary bypass. Echocardiographic reports were reviewed. Systemic ventricular function was subjectively categorised as normal, or as mildly, moderately, or severely depressed. The change in function was calculated as the change from the preoperative study to the last available study. Stepwise linear regression, adjusting for covariates, was performed for the outcome of change in ventricular function. Model comparison was performed using Akaike’s information criterion. Only variables that improved the model prediction of change in systemic ventricular function were retained in the final model.
Genetic and echocardiographic data were available for 335/422 subjects (79%). Of them, 33 (9.9%) developed worse systemic ventricular function during a mean follow-up period of 13.5 years. After covariate adjustment, the presence of the VEGFA minor allele was associated with preserved ventricular function (p=0.011).
These data support the hypothesis that the mechanism by which the VEGFA single-nucleotide polymorphism rs833069 minor allele improves survival may be the preservation of ventricular function. Further studies are needed to validate this genotype–phenotype association and to determine whether this mechanism is related to increased vascular endothelial growth factor production.
Introduction: The majority of syncope patients transported to the emergency department (ED) by emergency medical services (EMS) are low-risk with very few suffering serious adverse events (SAE) within 30-days and over 50% are diagnosed with vasovagal syncope. These patients can potentially be diverted by EMS to alternate pathways of care (primary care or syncope clinic) if appropriately identified. We sought to identify high-risk factors associated with SAE within 30-days of ED disposition as a step towards developing an EMS clinical decision tool. Methods: We prospectively enrolled adult syncope patients who were transported to 5 academic EDs by EMS. We collected standardized variables at EMS presentation from history, clinical examination and investigations including ECG and ED disposition. We also collected concerning symptoms identified and EMS interventions. Adjudicated SAE included death, myocardial infarction, arrhythmia, structural heart disease, pulmonary embolism, hemorrhage and procedural interventions. Multivariable logistic regression was used for analysis. Results: 990 adult syncope patients (mean age 58.9 years, 54.9% females and 16.8% hospitalized) were enrolled with 137 (14.6%) patients suffering SAE within 30-days of ED disposition. Of 42 candidate predictors, we identified 5 predictors that were significantly associated with SAE on multivariable analysis: ECG abnormalities [OR=1.77; 95%CI 1.36-2.48] (non-sinus rhythm, high degree atrioventricular block, left bundle branch block, ST-T wave changes or Q waves), cardiac history [OR=2.87; 95%CI 1.86-4.41] (valvular or coronary heart disease, cardiomyopathy, congestive heart failure, arrhythmias or device insertions), EMS interventions or concerning symptoms [OR=4.88; 95%CI 3.13- 7.62], age >50 years [OR=3.18; 95%CI 1.68-6.02], any abnormal vital signs [OR=1.58; 95%CI 1.03-2.42] (any EMS systolic blood pressure >180 or <100 mmHg, heart rate <50 or >100/minute, respiratory rate >25/minute, oxygen saturation <91%). [C-statistic: 0.81; Hosmer Lemeshow p=0.30]. Conclusion: We identified high-risk factors that are associated with 30-day SAE among syncope patients transported to the ED by EMS. This will aid in the development of a clinical decision tool to identify low-risk patients for diversion to alternate pathways of care.
Introduction: A recent cross-sectional study reported a 17.3% prevalence of pulmonary embolism (PE) among patients with syncope. However, the study had several flaws including spectrum and work-up bias with over-diagnosis due to excessive investigations. We sought to evaluate the prevalence of PE among Canadian emergency department (ED) patients presenting with syncope. Methods: We enrolled adults with syncope at 5 EDs and collected demographics, proportion of patients evaluated for suspected PE, their Wells PE score values and results of investigations [d-dimer, computed angiography (CT) of chest or ventilation-perfusion (VQ) scan]. 30-day adjudicated outcome included diagnosis of PE requiring treatment. We used descriptive statistics to report the results. Results: 4,739 patients [mean age 54.3 years, 54.4% females, and 587 (12.4%) hospitalized] were enrolled. 323 patients (6.8%) had further evaluation and investigations performed for suspected PE: 255 patients had D-dimer performed, 140 had CT chest and 17 had VQ performed. Of the 323 patients, 300 patients were low risk (Wells score ≤4) and 23 were high-risk (score >4). A total of 16 patients (0.3%) in the study cohort were diagnosed with PE: 10 patients were diagnosed in the ED, 5 patients were diagnosed while hospitalized as inpatient, and 1 patient was diagnosed on a return ED visit. Overall the prevalence of PE was 0.3% among all ED patients with syncope; and a 0.9% among those hospitalized for syncope. Conclusion: Our study shows that the prevalence of PE is very low among all patients presenting to the ED with syncope. The prevalence is also very low among those hospitalized for syncope than previously reported. While PE should be suspected and further investigations performed among syncope patients if clinically appropriate, caution should also be taken against indiscriminate over-investigations for PE.
Introduction: Syncope is a common emergency department (ED) presentation and constitutes 1% of all ED visits, approximately 160,000 visits annually across Canada. Lack of standardized syncope care has economic and cost implications. Currently, emergency medical services (EMS) is over utilized, variations in ED management exist and a substantial proportion (46.5%) are hospitalized for cardiac monitoring. Our previous studies have proposed ways to reduce health care utilization through development of EMS clinical decision tool, ED risk scores and remote cardiac monitoring. We sought to: 1) Estimate costs associated with syncope care in the pre-hospital, ED and inpatient settings; and 2) Determine potential cost savings if the proposed alternate strategies were adopted. Methods: A prospective cohort study was conducted in five Canadian EDs from 2010-2014. We enrolled adult (≥16 years) syncope patients and excluded those with prolonged loss of consciousness, mental status changes, seizure, significant trauma, or alcohol/illicit drug abuse. Demographics, medical history, mode of arrival, EMS time points, reasons for hospitalization, ED and inpatient length of stay, final ED diagnosis and any serious adverse event within 30 days of index visit were collected. Descriptive and inferential statistics were used. Results: Out of 4,064 patients enrolled, 67.3% were transported to the ED by EMS and the average cost per event was $262.78 (range at study sites: $156.43-$553.03). The average cost per ED visit was $267.98 (range: $174.66-$374.95). 12.9% of the patients were admitted and the average of cost per admission was $9,886.15 (range: $9,715.23-$10,277.98). Syncope is associated with an estimated total annual cost of $257 million. In Canada, we estimate that diverting low-risk patients will save $5 million in the pre-hospital setting and $15 million in the ED annually, and implementing a remote cardiac monitoring strategy will save $50 million annually. Conclusion: It is estimated that the proposed strategies will save $70 million annually. This is likely an underestimation as cost savings due to reduction in investigations related to diversion of ED patients, reduction in ED length of stay and hospitalization are unaccounted. Adoption of similar strategies will likely lead to significantly higher cost savings in countries with higher resource utilization for syncope management.