The effectiveness and safety of antifibrinolytics in patients with acute intracranial haemorrhage: statistical analysis plan for an individual patient data meta-analysis

Introduction: The Antifibrinolytic Trialists Collaboration aims to increase knowledge about the effectiveness and safety of antifibrinolytic treatment by conducting individual patient data (IPD) meta-analyses of randomised trials. This article presents the statistical analysis plan for an IPD meta-analysis of the effects of antifibrinolytics for acute intracranial haemorrhage. Methods: The protocol for the IPD meta-analysis has been registered with PROSPERO (CRD42016052155). We will conduct an individual patient data meta-analysis of randomised controlled trials with 1000 patients or more assessing the effects of antifibrinolytics in acute intracranial haemorrhage. We will assess the effect on two co-primary outcomes: 1) death in hospital at end of trial follow-up, and 2) death in hospital or dependency at end of trial follow-up. The co-primary outcomes will be limited to patients treated within three hours of injury or stroke onset. We will report treatment effects using odds ratios and 95% confidence intervals. We use logistic regression models to examine how the effect of antifibrinolytics vary by time to treatment, severity of intracranial bleeding, and age. We will also examine the effect of antifibrinolytics on secondary outcomes including death, dependency, vascular occlusive events, seizures, and neurological outcomes. Secondary outcomes will be assessed in all patients irrespective of time of treatment. All analyses will be conducted on an intention-to-treat basis. Conclusions: This IPD meta-analysis will examine important clinical questions about the effects of antifibrinolytic treatment in patients with intracranial haemorrhage that cannot be answered using aggregate data. With IPD we can examine how effects vary by time to treatment, bleeding severity, and age, to gain better understanding of the balance of benefit and harms on which to base recommendations for practice

Purpose in life predicts better emotional recovery from negative stimuli

Purpose in life predicts both health and longevity suggesting that the ability to find meaning from life’s experiences, especially when confronting life’s challenges, may be a mechanism underlying resilience. Having purpose in life may motivate reframing stressful situations to deal with them more productively, thereby facilitating recovery from stress and trauma. In turn, enhanced ability to recover from negative events may allow a person to achieve or maintain a feeling of greater purpose in life over time. In a large sample of adults (aged 36-84 years) from the MIDUS study (Midlife in the U.S., http://www.midus.wisc.edu/), we tested whether purpose in life was associated with better emotional recovery following exposure to negative picture stimuli indexed by the magnitude of the eyeblink startle reflex (EBR), a measure sensitive to emotional state. We differentiated between initial emotional reactivity (during stimulus presentation) and emotional recovery (occurring after stimulus offset). Greater purpose in life, assessed over two years prior, predicted better recovery from negative stimuli indexed by a smaller eyeblink after negative pictures offset, even after controlling for initial reactivity to the stimuli during the picture presentation, gender, age, trait affect, and other well-being dimensions. These data suggest a proximal mechanism by which purpose in life may afford protection from negative events and confer resilience is through enhanced automatic emotion regulation after negative emotional provocation

Do Flexible Administration Procedures Promote Individualized Clinical Assessments?:An Explorative Analysis of How Clinicians Utilize the Funnel Structure of the SCID-5-AMPD Module I: LPFS

The current study examined clinicians' utilization of the SCID-5-AMPD-I funnel structure. Across 237 interviews, conducted as part of the NorAMP study, we found that clinicians administered on average 2-3 adjacent levels under each subdomain, effectively administering only about 50% of available items. Comparing administration patterns of interviews, no two interviews contained the exact same set of administered items. On average, when comparing individual interviews, only about half of the administered items in each interview were administered in both interviews. Cross-classified mixed effects models were estimated to examine the factors affecting item administration. Results indicated that the interplay between patient preliminary scores and item level had a substantial impact on item administration, suggesting clinicians tend to administer items corresponding to expected patient severity. Overall, our findings suggest clinicians utilize the SCID-5-AMPD-I funnel structure to conduct efficient and individually tailored assessments informed by relevant patient characteristics. Adopting similar non-fixed administration procedures for other interviews could potentially provide similar benefits compared to traditional fixed-form administration procedures. The current study can serve as a template for verifying and evaluating future adoptions of non-fixed administration procedures in other interviews.</p

More is more:Evidence for the incremental value of the SCID-II/SCID-5-PD specific factors over and above a general personality disorder factor

Currently, 3 competing conceptualizations of personality dysfunction can be distinguished: the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM–5) categorical model delineating 10 distinct types of personality disorders (PDs); the alternative model for PDs (DSM–5 Section III), which assesses personality functioning and traits separately; and the International Classification of Diseases, 11th Version conceptualization, which provides 1 single code for the presence of a PD (which is based on problems in functioning) as well as codes that specify the level of the disorder (mild/moderate/severe), and prominent trait domains or patterns (5 domains and 1 pattern). The current study aims to assess the incremental value of the DSM–5 PDs over and above a global personality dysfunction factor, using expert ratings obtained with the Structured Clinical Interview for DSM–IV PDs and the Structured Clinical Interview for DSM–5 PDs interview in a large sample of clinical patients (N = 3,851). All estimated bifactor models provided adequate fit to the data. We found a surprisingly low explained common variance for the g-factor (<40%), indicating that ignoring the specific PD factors would lead to a substantial loss of information. The strongest specific PDs in terms of explained common variance were the avoidant, schizotypal, and schizoid PD factors and the conduct disorder criteria set if included. Correlations between our factors and external variables were relatively low, except for the Severity Indices of Personality Problems, which aims to measure personality functioning. Our findings suggest that specific PDs still have an important role to play in the assessment of personality pathology

A Psychometric Analysis of the Structured Clinical Interview for the DSM-5 Alternative Model for Personality Disorders Module I (SCID-5-AMPD-I):Level of Personality Functioning Scale

The current study aims to examine the psychometric properties of the Structured Clinical Interview for the DSM-5 Alternative Model for Personality Disorders Module I (SCID-5-AMPD-I) assessing the Level of Personality Functioning Scale (LPFS) in a heterogeneous sample of 282 nonpsychotic patients. Latent variable models were used to investigate the dimensionality of the LPFS. The results indicate that the LPFS, as assessed by the SCID-5-AMPD-I, can be considered as a unidimensional construct that can be measured reliably across a wide range of the latent trait. Threshold parameters for the 12 indicators of the LPFS increased gradually over the latent scale, indicating that the five LPFS levels were ordered as predicted by the model. In general, the increase of threshold parameters was relatively small for the shift from Level 2 to Level 3. A better distinction among the different severity levels might be obtained by fine-tuning the interview guidelines or the Level 2 indicators themselves

Does heart rate influence CMR image quality of the coronary vessel wall?

Cardiolog

A cross-sectional testing of The Iowa Personality Disorder Screen in a psychiatric outpatient setting

<p>Abstract</p> <p>Background</p> <p>Patients suspected of personality disorders (PDs) by general practitioners are frequently referred to psychiatric outpatient clinics (POCs). In that setting an effective screening instrument for PDs would be helpful due to resource constraints. This study evaluates the properties of The Iowa Personality Disorder Screen (IPDS) as a screening instrument for PDs at a POC.</p> <p>Methods</p> <p>In a cross-sectional design 145 patients filled in the IPDS and were examined with the SCID-II interview as reference. Various case-findings properties were tested, interference of socio-demographic and other psychopathology were investigated by logistic regression and relationships of the IPDS and the concept of PDs were studied by a latent variable path analysis.</p> <p>Results</p> <p>We found that socio-demographic and psychopathological factors hardly disturbed the IPDS as screening instrument. With a cut-off ≥4 the 11 items IPDS version had sensitivity 0.77 and specificity 0.71. A brief 5 items version showed sensitivity 0.82 and specificity 0.74 with cut-off ≥ 2. With exception for one item, the IPDS variables loaded adequately on their respective first order variables, and the five first order variables loaded in general adequately on their second order variable.</p> <p>Conclusion</p> <p>Our results support the IPDS as a useful screening instrument for PDs present or absent in the POC setting.</p

Identifying Predictors for Heart Failure Outcomes in Phospholamban p.(Arg14del)–Positive Individuals

Background: Phospholamban (PLN) p.(Arg14del)–positive individuals are at high risk of developing PLN p.(Arg14del)-related cardiomyopathy, which can lead to progressive heart failure that is poorly amenable to standard heart failure treatment. Genetic therapies for patients with hereditary cardiomyopathy are rapidly advancing, but identifying patients who will benefit from and rely on these therapies is challenging because of reduced penetrance and highly variable expression. Objectives: The aim of this study is to identify clinical predictors of heart failure outcomes in PLN p.(Arg14del)–positive individuals. Methods: Data were collected of 904 PLN p.(Arg14del)–positive individuals from the PLN/ACM Registry. The primary endpoint of the study was a composite endpoint of heart failure outcomes, defined as heart failure hospitalization, left ventricular or biventricular assist device implantation, heart transplantation, or heart failure–related death. Predictors of heart failure outcomes were identified using Least Absolute Shrinkage and Selection Operator Cox regression analyses with different penalization parameters. Results: During a median follow-up of 5.4 years (Q1-Q3: 2.3-9.7 years), 116 study participants (13%) reached the primary endpoint (heart failure hospitalization [75%], heart transplantation [10.3%], left ventricular or biventricular assist device implantation [9.5%], and heart failure–related death [5.2%]). The predictors that remained significant across all analyses were left ventricular ejection fraction, low-voltage electrocardiogram, and NYHA functional class ≥II, measured at first evaluation. Conclusions: This study identified predictors for heart failure outcomes in PLN p.(Arg14del)–positive individuals that can improve risk prediction. Identifying those at risk for heart failure outcomes is of great importance given the rapid advancements in genetic therapies that may offer potential treatments for hereditary cardiomyopathy.</p