274Early adversity scale for schizophrenia (EAS-SZ) constructed and validated using linked register data

Abstract Background A range of adversities have been implicated as risks for schizophrenia. Adversities often cluster, with synergistic impact, which may vary by age of exposure. We expand on current understanding, and propose a method for ranking combinations of adversities associated with risk of schizophrenia, to derive a risk prediction measure. Methods We used prospectively collected data for 430,000 children born 1980–2001 in Western Australia, and their parents. Follow up continued until 2015 using linked State registers, identifying 1,620 children with schizophrenia. Five domains of adversity exposure to age 10 were considered. Using Cox modeling of a 40% training data subset, we categorised adversity exposure by associated rates of schizophrenia. Firstly, for each domain separately, numerous constructs of adversity exposure were screened for independent association with schizophrenia. Those with p < =0.2 were combined, using augmented backwards elimination, to define a minimal domain set of jointly associated constructs. Combination was summarised as the linear predictor corresponding to the optimum Cox model. Secondly, these domain summaries were combined with each other to form a global Cox model, predictive of association with schizophrenia. Harrell’s Concordance was calculated using a 30% assessment sample which did not overlap with our training sample. Prognostic categories were defined and tested. Results Harrell’s Concordance was 0.655. Dose response was observed. Conclusions Our scale combines many adversity measures into a single construct. It displays dose response and predicts association considerably above chance. Key messages EAS-SZ allows a range of adversity exposure profiles to be ranked according to association with schizophrenia.

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Emergency Department Admission and Mortality Rate for Suicidal Behavior

Crisis ◽

10.1027/0227-5910/a000282 ◽

2014 ◽

Vol 35 (6) ◽

pp. 406-414 ◽

Cited By ~ 10

Author(s):

Raimondo Maria Pavarin ◽

Angelo Fioritti ◽

Francesca Fontana ◽

Silvia Marani ◽

Alessandra Paparelli ◽

...

Keyword(s):

Emergency Department ◽

Metropolitan Area ◽

Suicidal Behavior ◽

Mortality Risk ◽

Illicit Drugs ◽

Attempted Suicide ◽

Cox Model ◽

Emergency Department Admission ◽

Completed Suicide

Background: The international literature reports that for every completed suicide there are between 8 and 22 visits to an Emergency Department (ED) for attempted suicide/suicidal behavior. Aims: To describe the characteristics of admission to emergency departments (EDs) for suicide-related presenting complaints in the metropolitan area of Bologna; to estimate the risk for all-cause mortality and for suicide; to identify the profiles of subjects most at risk. Method: Follow-up of patients admitted to the EDs of the metropolitan area of Bologna between January 2004 and December 2010 for attempted suicide. A Cox model was used to evaluate the association between sociodemographic variables and the general mortality risk. Results: We identified 505 cases of attempted suicide, which were more frequent for female subjects, over the weekend, and at night (8:00 p.m./8:00 a.m.). The most used suicide methods were psychotropic drugs, sharp or blunt objects, and jumping from high places. In this cohort, 3.6% of subjects completed suicide (4.5% of males vs. 2.9% of females), 2.3% within 1 year of the start of follow-up. The most common causes of death were drug use and hanging. In the multivariate analysis, those who used illicit drugs 24 hr prior to admission to the ED (hazard ratio [HR] = 3.46, 95% CI = 1.23–9.73) and patients who refused the treatment (HR = 6.74, 95% CI = 1.86–24.40) showed an increased mortality risk for suicide. Conclusion: Deliberate self-harm patients presenting to the ED who refuse treatment represent a specific target group for setting up dedicated prevention schemes.

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Cardiology Fellowship Education in the Era of High-density Training, Data Tracking, and Quality Measures

The American Heart Hospital Journal ◽

10.15420/ahhj.2011.9.2.99 ◽

2011 ◽

Vol 9 (2) ◽

pp. 99

Author(s):

Alex J Auseon ◽

Albert J Kolibash ◽

◽

Keyword(s):

Ohio State University ◽

Training Data ◽

State University ◽

Training Requirements ◽

Healthcare Environment ◽

Medical Centers ◽

Work Hour ◽

The Ohio State University ◽

Data Tracking

Background:Educating trainees during cardiology fellowship is a process in constant evolution, with program directors regularly adapting to increasing demands and regulations as they strive to prepare graduates for practice in todays healthcare environment.Methods and Results:In a 10-year follow-up to a previous manuscript regarding fellowship education, we reviewed the literature regarding the most topical issues facing training programs in 2010, describing our approach at The Ohio State University.Conclusion:In the midst of challenges posed by the increasing complexity of training requirements and documentation, work hour restrictions, and the new definitions of quality and safety, we propose methods of curricula revision and collaboration that may serve as an example to other medical centers.

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Independent Association of a Metabolic Syndrome Severity Score with All-Cause Mortality in Type 1 Diabetes—A 10-Year Follow-Up

Diabetes ◽

10.2337/db18-618-p ◽

2018 ◽

Vol 67 (Supplement 1) ◽

pp. 618-P

Author(s):

GIUSEPPE PENNO ◽

MONIA GAROFOLO ◽

ROSA GIANNARELLI ◽

FABRIZIO CAMPI ◽

DANIELA LUCCHESI ◽

...

Keyword(s):

Metabolic Syndrome ◽

Type 1 Diabetes ◽

Severity Score ◽

All Cause Mortality ◽

Independent Association

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Higher premature atrial complex burden from the Holter examination predicts poor cardiovascular outcome

Scientific Reports ◽

10.1038/s41598-021-91800-4 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Ting-Chun Huang ◽

Po-Tseng Lee ◽

Mu-Shiang Huang ◽

Pei-Fang Su ◽

Ping-Yen Liu

Keyword(s):

Risk Factor ◽

Dose Response ◽

Cox Model ◽

Significant Risk ◽

Significant Risk Factor ◽

Cardiovascular Death ◽

Specific Model ◽

Distribution Model ◽

All Cause Mortality ◽

Quartile Group

AbstractPremature atrial complexes (PACs) have been suggested to increase the risk of adverse events. The distribution of PAC burden and its dose–response effects on all-cause mortality and cardiovascular death had not been elucidated clearly. We analyzed 15,893 patients in a medical referral center from July 1st, 2011, to December 31st, 2018. Multivariate regression driven by ln PAC (beats per 24 h plus 1) or quartiles of PAC burden were examined. Older group had higher PAC burden than younger group (p for trend < 0.001), and both genders shared similar PACs distribution. In Cox model, ln PAC remained an independent risk factor for all-cause mortality (hazard ratio (HR) = 1.09 per ln PAC increase, 95% CI = 1.06‒1.12, p < 0.001). PACs were a significant risk factor in cause-specific model (HR = 1.13, 95% CI = 1.05‒1.22, p = 0.001) or sub-distribution model (HR = 1.12, 95% CI = 1.04‒1.21, p = 0.004). In ordinal PAC model, 4th quartile group had significantly higher risk of all-cause mortality than those in 1st quartile group (HR = 1.47, 95% CI = 1.13‒1.94, p = 0.005), but no difference in cardiovascular death were found in competing risk analysis. In subgroup analysis, the risk of high PAC burden was consistently higher than in low-burden group across pre-specified subgroups. In conclusion, PAC burden has a dose response effect on all-cause mortality and cardiovascular death.

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Interim Estimates of COVID-19 Vaccine Effectiveness in a Mass Vaccination Setting: Data from an Italian Province

Vaccines ◽

10.3390/vaccines9060628 ◽

2021 ◽

Vol 9 (6) ◽

pp. 628

Author(s):

Maria Elena Flacco ◽

Graziella Soldato ◽

Cecilia Acuti Martellucci ◽

Roberto Carota ◽

Rossano Di Luzio ◽

...

Keyword(s):

Adverse Event ◽

Retrospective Cohort ◽

Cox Model ◽

National Health System ◽

Vaccine Dose ◽

Vaccine Hesitancy ◽

Serious Adverse Event ◽

Italian Province ◽

Official Data

This retrospective cohort study compared the rates of virologically-confirmed SARS-CoV-2 infections, symptomatic or lethal COVID-19 among the residents of the Italian province of Pescara who received one or two doses of COVID-19 vaccines, versus the unvaccinated. The official data of the National Health System were used, and a total of 69,539 vaccinated adults were compared with 175,687 unvaccinated. Among the subjects who received at least one vaccine dose, 85 infections (0.12%), 18 severe and 3 lethal COVID-19 cases were recorded after an average follow-up of 38 days. Among the unvaccinated, the numbers were 6948 (4.00%), 933 (0.53%) and 241 (0.14%), respectively. The serious adverse event reports—yet unconfirmed—were 24 out of 102,394 administered doses. In a Cox model, adjusting for age, gender, and selected comorbidities, the effectiveness of either BNT162b2, ChAdOx1 nCoV-19 or mRNA-1273 vaccines was higher than 95% in preventing infections (mostly due to B.1.1.7 variant), symptomatic or lethal COVID-19. No differences were observed across genders, and among the 691 subjects who received the second dose of vaccine later than the recommended date. Although preliminary, these findings support current immunization policies and may help reducing vaccine hesitancy.

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Risk assessment in precapillary pulmonary hypertension: a comparative analysis

Respiratory Research ◽

10.1186/s12931-021-01624-z ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Thomas Sonnweber ◽

Eva-Maria Schneider ◽

Manfred Nairz ◽

Igor Theurl ◽

Günter Weiss ◽

...

Keyword(s):

Risk Assessment ◽

Pulmonary Hypertension ◽

High Risk ◽

Risk Stratification ◽

Risk Prediction ◽

Mortality Risk ◽

Assessment Tool ◽

Risk Models ◽

Non Invasive

Abstract Background Risk stratification is essential to assess mortality risk and guide treatment in patients with precapillary pulmonary hypertension (PH). We herein compared the accuracy of different currently used PH risk stratification tools and evaluated the significance of particular risk parameters. Methods We conducted a retrospective longitudinal observational cohort study evaluating seven different risk assessment approaches according to the current PH guidelines. A comprehensive assessment including multi-parametric risk stratification was performed at baseline and 4 yearly follow-up time-points. Multi-step Cox hazard analysis was used to analyse and refine risk prediction. Results Various available risk models effectively predicted mortality in patients with precapillary pulmonary hypertension. Right-heart catheter parameters were not essential for risk prediction. Contrary, non-invasive follow-up re-evaluations significantly improved the accuracy of risk estimations. A lack of accuracy of various risk models was found in the intermediate- and high-risk classes. For these patients, an additional evaluation step including assessment of age and right atrium area improved risk prediction significantly. Discussion Currently used abbreviated versions of the ESC/ERS risk assessment tool, as well as the REVEAL 2.0 and REVEAL Lite 2 based risk stratification, lack accuracy to predict mortality in intermediate- and high-risk precapillary pulmonary hypertension patients. An expanded non-invasive evaluation improves mortality risk prediction in these individuals.

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A microRNA panel compared to environmental and polygenic scores for colorectal cancer risk prediction

Nature Communications ◽

10.1038/s41467-021-25067-8 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Janhavi R. Raut ◽

Ben Schöttker ◽

Bernd Holleczek ◽

Feng Guo ◽

Megha Bhardwaj ◽

...

Keyword(s):

Colorectal Cancer ◽

Risk Prediction ◽

Risk Score ◽

Characteristic Curve ◽

Predictive Ability ◽

Population Based ◽

Polygenic Risk Score ◽

Nucleotide Polymorphisms ◽

Polygenic Scores

AbstractCirculating microRNAs (miRNAs) could improve colorectal cancer (CRC) risk prediction. Here, we derive a blood-based miRNA panel and evaluate its ability to predict CRC occurrence in a population-based cohort of adults aged 50–75 years. Forty-one miRNAs are preselected from independent studies and measured by quantitative-real-time-polymerase-chain-reaction in serum collected at baseline of 198 participants who develop CRC during 14 years of follow-up and 178 randomly selected controls. A 7-miRNA score is derived by logistic regression. Its predictive ability, quantified by the optimism-corrected area-under-the-receiver-operating-characteristic-curve (AUC) using .632+ bootstrap is 0.794. Predictive ability is compared to that of an environmental risk score (ERS) based on known risk factors and a polygenic risk score (PRS) based on 140 previously identified single-nucleotide-polymorphisms. In participants with all scores available, optimism-corrected-AUC is 0.802 for the 7-miRNA score, while AUC (95% CI) is 0.557 (0.498–0.616) for the ERS and 0.622 (0.564–0.681) for the PRS.

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RNAi inhibition of angiopoietin-like protein 3 (ANGPTL3) with ARO-ANG3 mimics the lipid and lipoprotein profile of familial combined hypolipidemia

European Heart Journal ◽

10.1093/ehjci/ehaa946.3331 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

G.F Watts ◽

C Schwabe ◽

R Scott ◽

P Gladding ◽

D Sullivan ◽

...

Keyword(s):

Adverse Events ◽

Dose Response ◽

Minimal Change ◽

Funding Source ◽

Private Company ◽

Good Tolerability ◽

Duration Of Action ◽

Mixed Dyslipidemia ◽

Genetic Deficiency

Abstract Background Elevated LDL-C and triglyceride rich lipoproteins (TRLs) are independent risk factors for cardiovascular disease (CVD). Genetic deficiency of angiopoietin-like protein 3 (ANGPTL3) is associated with reduced circulating levels of LDL-C, triglycerides (TGs), VLDL-C, HDL-C and reduced CVD risk, with no described adverse phenotype. ARO-ANG3 is a RNA interference drug designed to silence expression of ANGPTL3. Single doses of ARO-ANG3 have been shown to reduce ANGPTL3, TGs, VLDL-C and LDL-C in healthy volunteers (HVs, AHA 2019). We report the effects of multiple doses of ARO-ANG3 in HVs with a focus on the duration of action. Methods ARO-ANG3 was administered subcutaneously to HVs on days 1 and 29 at doses of 100, 200 or 300 mg (n=4 per group). Measured parameters included ANGPTL3, LDL-C, TGs, VLDL-C and HDL-C. Follow up is ongoing. Results All HVs have received both doses and follow-up is currently through week 16 (12 weeks after second dose). Mean nadir for ANGPTL3 levels occurred 2 weeks after the second dose (−83–93%) with minimal change for 200 and 300 mg but 16% recovery for 100 mg at week 16. Mean TGs and VLDL-C reached nadir earlier (3 wks, −61–65%) without apparent dose response and minimal change for any dose at wk 16. LDL-C nadir occurred 4–6 wks after the second dose (−45–54%), again with minimal evidence for dose response or change through wk 16. HDL-C was reduced 14–37% at wk 16. ARO-ANG3 was well tolerated without serious or severe adverse events or dropouts related to drug. The most common adverse events have been headache and upper respiratory infections. Conclusions Genetic deficiency of ANGPTL3 is a cause of familial combined hypolipemia and is associated with a decreased risk of CVD. Using RNAi to selectively suppress ANGPTL3 production reproduces these genetic effects with a duration of at least 12 weeks following a second dose and with good tolerability over 16 wks. ANGPTL3 inhibition results in lowering of LDL-C and TRLs which may confer protection against CVD in patients with atherogenic mixed dyslipidemia. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Arrowhead Pharmaceuticals

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Sleep duration and all-cause mortality in the elderly in China: a population-based cohort study

BMC Geriatrics ◽

10.1186/s12877-020-01962-5 ◽

2020 ◽

Vol 20 (1) ◽

Author(s):

Yanfeng Ren ◽

Maohua Miao ◽

Wei Yuan ◽

Jiangwei Sun

Keyword(s):

Cohort Study ◽

Sleep Duration ◽

Dose Response ◽

Cox Regression ◽

Oldest Old ◽

The Elderly ◽

Response Analysis ◽

Short Sleep Duration ◽

All Cause Mortality

Abstract Background Although a U-shaped association between sleep duration and all-cause mortality has been found in general population, its association in the elderly adults, especially in the oldest-old, is rarely explored. Methods In present cohort study, we prospectively explore the association between sleep duration and all-cause mortality among 15,092 participants enrolled in the Chinese Longitudinal Healthy Longevity Survey (CLHLS) from 2005 to 2019. Sleep duration and death information was collected by using structured questionnaires. Cox regression model with sleep duration as a time-varying exposure was performed to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs). The dose-response association between them was explored via a restricted cubic spline function. Results During an average follow-up of 4.51 (standard deviation, SD: 3.62) years, 10,768 participants died during the follow-up period. The mean (SD) age of the participants was 89.26 (11.56) years old. Compared to individuals with moderate sleep duration (7–8 hours), individuals with long sleep duration (> 8 hours) had a significantly higher risk of all-cause mortality (HR: 1.13, 95%CI: 1.09–1.18), but not among individuals with short sleep duration (≤ 6 hours) (HR: 1.02, 95%CI: 0.96–1.09). Similar results were observed in subgroup analyses based on age and gender. In the dose-response analysis, a J-shaped association was observed. Conclusions Sleep duration was associated with all-cause mortality in a J-shaped pattern in the elderly population in China.

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Reduced Efficacy of the Pipeline Embolization Device in the Treatment of Posterior Communicating Region Aneurysms with Fetal Posterior Cerebral Artery Configuration

Neurosurgery ◽

10.1093/neuros/nyx293 ◽

2017 ◽

Vol 82 (5) ◽

pp. 695-700 ◽

Cited By ~ 14

Author(s):

Anil K Roy ◽

Brian M Howard ◽

Diogo C Haussen ◽

Joshua W Osbun ◽

Sameer H Halani ◽

...

Keyword(s):

Cerebral Artery ◽

Clinical Symptoms ◽

Posterior Cerebral Artery ◽

Neurological Complications ◽

Class I ◽

Class Iii ◽

Pipeline Embolization Device ◽

Independent Association ◽

Incomplete Occlusion

Abstract BACKGROUND Aneurysms at the origin of the posterior communicating artery (PcommA) have been demonstrated to be effectively treated with the pipeline embolization device (PED). Much less is known about the efficacy of the PED for aneurysms associated with a fetal posterior cerebral artery (fPCA) variant. OBJECTIVE To study PED treatment efficacy of PcommA aneurysms, including fPCA aneurysms. METHODS A prospectively maintained university database of aneurysm patients treated with the PED was retrospectively reviewed. Demographics, treatment details, and imaging were reviewed for all PcommA and fPCA aneurysms. RESULTS Out of a total of 285 patients treated with PED, 50 patients (mean age 57.5 ± 12.2 yr, 42 females) with unruptured PcommA (9 fPCA) aneurysms were identified. Mean follow-up duration was 14.0 ± 11.6 mo (48 patients). Roy-Raymond class I occlusion on follow-up magnetic resonance or catheter angiography (mean time 11.7 ± 6.8 mo) was achieved in 30 patients (62.5%), class II occlusion in 11 patients (22.9%) and class III occlusion in 7 patients (14.5%). The PcommA was occluded in 56% of patients without any clinical symptoms. No deaths or permanent neurological complications occurred. In fPCA aneurysms, class I occlusion was seen in 1 patient, class 2 occlusion in 2 patients, and class III occlusion in 6 patients. Multivariate analysis revealed an independent association between incomplete occlusion and fPCA configuration (OR 73.65; 95% CI: 5.84-929.13; P = .001). CONCLUSION The PED is a safe and effective treatment for PcommA aneurysms, although fetal anatomy should increase consideration of traditional endovascular techniques or surgical clipping.

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