Dropout from psychological treatment for borderline personality disorder: a multilevel survival meta-analysis.

BACKGROUND: Dropout from psychotherapy for borderline personality disorder (BPD) is a notorious problem. We investigated whether treatment, treatment format, treatment setting, substance use exclusion criteria, proportion males, mean age, country, and other variables influenced dropout. METHODS: From Pubmed, Embase, Cochrane, Psycinfo and other sources, 111 studies (159 treatment arms, N = 9100) of psychotherapy for non-forensic adult patients with BPD were included. Dropout per quarter during one year of treatment was analyzed on participant level with multilevel survival analysis, to deal with multiple predictors, nonconstant dropout chance over time, and censored data. Multiple imputation was used to estimate quarter of drop-out if unreported. Sensitivity analyses were done by excluding DBT-arms with deviating push-out rules. RESULTS: Dropout was highest in the first quarter of treatment. Schema therapy had the lowest dropout overall, and mentalization-based treatment in the first two quarters. Community treatment by experts had the highest dropout. Moreover, individual therapy had lowest dropout, group therapy highest, with combined formats in-between. Other variables such as age or substance-use exclusion criteria were not associated with dropout. CONCLUSION: The findings do not support claims that all treatments are equal, and indicate that efforts to reduce dropout should focus on early stages of treatment and on group treatment.

Group schema therapy for cluster-C personality disorders: A multicentre open pilot study.

BACKGROUND: Group schema therapy (GST) is increasingly popular as a treatment for personality disorders (PDs), including Cluster-C PDs. Individual ST has proven to be effective for Cluster-C PD patients, while the evidence for GST is limited. This study aimed to investigate the effectiveness of GST for Cluster-C PD. Moreover, differences between the specific Cluster-C PDs (avoidant PD, dependent PD and obsessive-compulsive PD) were explored. METHODS: A multicentre open trial was conducted, including 137 patients with a Cluster-C PD (avoidant PD: n = 107, dependent PD: n = 11 and obsessive-compulsive PD: n = 19). Patients received 30 weekly GST sessions with a maximum of 180 min of individual ST and five optional monthly booster sessions. Outcome measures including Cluster-C PD severity, general psychopathological symptoms, quality of life, functional impairment, happiness, PD-related beliefs, self-esteem, self-ideal discrepancy, schemas and schema modes were assessed at baseline until 2-year follow-up with semi-structured interviews and self-report measures. Change over time and differences between the specific Cluster-C PDs were analysed with mixed regression analyses. RESULTS: The outcome measures showed significant improvements for all Cluster-C PDs, with medium to large effect sizes after 2 years. A treatment dropout rate of 11.7% was found. There were some indications for differences between the Cluster-C PDs in severity at baseline, change trajectories and effectiveness of GST. CONCLUSIONS: This study demonstrated that GST is a promising treatment for Cluster-C PDs. The following step is a randomized controlled trial to further document the (cost-)effectiveness of GST.

Towards optimal treatment selection for borderline personality disorder patients (BOOTS): a study protocol for a multicenter randomized clinical trial comparing schema therapy and dialectical behavior therapy.

BACKGROUND: Specialized evidence-based treatments have been developed and evaluated for borderline personality disorder (BPD), including Dialectical Behavior Therapy (DBT) and Schema Therapy (ST). Individual differences in treatment response to both ST and DBT have been observed across studies, but the factors driving these differences are largely unknown. Understanding which treatment works best for whom and why remain central issues in psychotherapy research. The aim of the present study is to improve treatment response of DBT and ST for BPD patients by a) identifying patient characteristics that predict (differential) treatment response (i.e., treatment selection) and b) understanding how both treatments lead to change (i.e., mechanisms of change). Moreover, the clinical effectiveness and cost-effectiveness of DBT and ST will be evaluated. METHODS: The BOOTS trial is a multicenter randomized clinical trial conducted in a routine clinical setting in several outpatient clinics in the Netherlands. We aim to recruit 200 participants, to be randomized to DBT or ST. Patients receive a combined program of individual and group sessions for a maximum duration of 25 months. Data are collected at baseline until three-year follow-up. Candidate predictors of (differential) treatment response have been selected based on the literature, a patient representative of the Borderline Foundation of the Netherlands, and semi-structured interviews among 18 expert clinicians. In addition, BPD-treatment-specific (ST: beliefs and schema modes; DBT: emotion regulation and skills use), BPD-treatment-generic (therapeutic environment characterized by genuineness, safety, and equality), and non-specific (attachment and therapeutic alliance) mechanisms of change are assessed. The primary outcome measure is change in BPD manifestations. Secondary outcome measures include functioning, additional self-reported symptoms, and well-being. DISCUSSION: The current study contributes to the optimization of treatments for BPD patients by extending our knowledge on "Which treatment - DBT or ST - works the best for which BPD patient, and why?", which is likely to yield important benefits for both BPD patients (e.g., prevention of overtreatment and potential harm of treatments) and society (e.g., increased economic productivity of patients and efficient use of treatments). TRIAL REGISTRATION: Netherlands Trial Register, NL7699 , registered 25/04/2019 - retrospectively registered.

Design of an RCT on cost-effectiveness of group schema therapy versus individual schema therapy for patients with Cluster-C personality disorder: the QUEST-CLC study protocol.

BACKGROUND: Given the high prevalence of Cluster-C Personality Disorders (PDs) in clinical populations, disease burden, high societal costs and poor prognosis of comorbid disorders, a major gain in health care can be achieved if Cluster-C PDs are adequately treated. The only controlled cost-effectiveness study published so far found Individual Schema Therapy (IST) to be superior to Treatment as Usual (TAU). Group ST (GST) might improve cost-effectiveness as larger numbers can be treated in (>50%) less time compared to IST. However, to date there is no RCT supporting its (cost-) effectiveness. The overall aim of this study is to assess the evidence for GST for Cluster-C PDs and to improve treatment allocation for individual patients. Three main questions are addressed: 1) Is GST for Cluster-C PDs (cost-)effective compared to TAU? 2) Is GST for Cluster-C PDs (cost-) effective compared to IST? 3) Which patient-characteristics predict better response to GST, IST, or TAU? METHODS: In a multicenter RCT, the treatment conditions GST, IST, and TAU are compared in 378 Cluster-C PD patients within 10 sites. GST and IST follow treatment protocols and are completed within 1 year. TAU is the optimal alternative treatment available at the site according to regular procedures. Severity of the Cluster-C PD is the primary outcome, assessed with clinical interviews by independent raters blind for treatment. Functioning and wellbeing are important secondary outcomes. Assessments take place at week 0 (baseline), 17 (mid-GST), 34 (post-GST), 51 (post-booster sessions of GST), and 2 years (FU). Patient characteristics predicting better response to a specific treatment are studied, e.g., childhood trauma, autistic features, and introversion. A tool supporting patients and clinicians in matching treatment to patient will be developed. An economic evaluation investigates the cost-effectiveness and cost-utility from a societal perspective. A process evaluation by qualitative methods explores experiences of participants, loved ones and therapists regarding recovery, quality of life, and improving treatment. DISCUSSION: This study will determine the (cost-)effectiveness of treatments for Cluster-C PDs regarding treatment type as well as optimal matching of patient to treatment and deliver insight into which aspects help Cluster-C-PD patients recover and create a fulfilling life. TRIAL REGISTRATION: Dutch Trial Register: NL9209 . Registered on 28-01-2021.

Moderate acute alcohol use impairs intentional inhibition rather than stimulus-driven inhibition.

Moderate alcohol intake may impair stimulus-driven inhibition of motor actions in go/no-go and stop-signal tasks. Exposure to alcohol-related cues has been found to exacerbate this impairment. By contrast, the effect of alcohol use on intentional inhibition, or the capacity to voluntarily suspend an action, has rarely been investigated. We examined whether and how moderate alcohol intake affects stimulus-driven inhibition (stop-signal task) and intentional inhibition (chasing bottles task), during exposure to alcohol-related stimuli. One hundred and eleven participants were randomly assigned to an alcohol (male: 0.55 g/kg, female: 0.45 g/kg), placebo, or control group. For the stop-signal task, ANOVAs were performed on stop-signal reaction time (SSRT) and go RT with Pharmacological and Expectancy Effects of Alcohol, Stimulus Category (alcohol-related or neutral), and Sex as factors. For the chasing bottles task, multilevel survival analysis was performed to predict whether and when intentional inhibition was initiated, with the same factors. For the stop-signal task, Sex moderated the Pharmacological Effect of Alcohol on SSRT: only for females, alcohol consumption shortened SSRT. In the non-alcohol groups, males had shorter SSRT than females. Concerning intentional inhibition, the alcohol group initiated intentional inhibition less often, especially when stimuli were non-alcohol related. These findings indicate that (1) stimulus-driven inhibition and intentional inhibition reflect different aspects of response inhibition; (2) moderate alcohol intake negatively affects intentional inhibition (but not stimulus-driven inhibition). Speculatively, the observed impairment in intentional inhibition might underlie the lack of control over alcohol drinking behavior after a priming dose. This study highlights the potential role of intentional inhibition in the development of addiction.

Do Lacunar Infarcts Have Different Aetiologies? Risk Factor Profiles of Lacunar Infarcts in Deep White Matter and Basal Ganglia: The Second Manifestations of ARTerial Disease-Magnetic Resonance Study.

BACKGROUND: Evidence suggests that lacunar infarcts have different etiologies, possibly related to their anatomical location and vascular territory. We investigated the risk factor profiles of patients with new lacunar infarcts in the basal ganglia and deep white matter. METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study, a prospective cohort on brain changes on MRI in patients with symptomatic atherosclerotic disease, 679 patients (57 ± 9 years) had vascular screening and MRI at baseline and after a mean follow-up of 3.9 years. We investigated the association between vascular risk factors at baseline and appearance of new lacunar infarcts in the basal ganglia and deep white matter at follow-up. RESULTS: New lacunar infarcts appeared in 44 patients in the basal ganglia and in 37 patients in the deep white matter. In multivariable analysis, older age, history of cerebrovascular disease, and baseline white matter hyperintensity (WMH) volume were associated with increased risk of new lacunar infarcts in both locations. Hyperhomocysteinemia was associated with increased risk of lacunar infarcts in the basal ganglia (relative risk [RR] 2.0; 95% CI 1.0-4.2), whereas carotid stenosis >70% (RR 2.5; 95% CI 1.2-5.0), smoking (per 10 pack-year: RR 1.1; 95% CI 1.0-1.3), hypertension (RR 3.4; 95% CI 1.2-9.7), and progression of WMH volume (RR 2.4; 95% CI 1.1-5.2) were associated with increased risk of lacunar infarcts in the deep white matter. CONCLUSIONS: The different risk factor profiles for new lacunar infarcts in basal ganglia and deep white matter indicate different etiologies. The independent association between progression of WMH and new deep white matter lacunar infarcts suggest a common etiology for these radiological abnormalities.

Cerebellar Cortical Infarct Cavities: Correlation With Risk Factors and MRI Markers of Cerebrovascular Disease.

BACKGROUND AND PURPOSE: Small cerebellar infarct cavities have been recently found on magnetic resonance imaging (MRI) to preferentially involve the cerebellar cortex, but epidemiological studies are lacking. We aimed to determine the prevalence and risk factor profiles of cerebellar cortical infarct cavities (≤1.5 cm) as well as their association with MRI markers of cerebrovascular disease and functioning. METHODS: We analyzed the 1.5 Tesla MRI of 636 patients (mean age, 62±9 years; 81% men) from the Second Manifestations of Arterial Disease-Memory, Depression and Aging (SMART-Medea) study. Logistic regression analyses were performed to estimate the associations of age, sex, vascular risk factors, MRI markers of cerebrovascular disease, and functioning with cerebellar cortical cavities, adjusted for age and sex. RESULTS: Cerebellar cortical infarct cavities occurred on MRI in 10% of patients and were significantly associated with age, intima-media thickness (odds ratio [OR], 2.0; 95% confidence interval [CI], 1.1-3.7), high levels of homocysteinemia (OR, 1.8; 95% CI, 1.0-3.3), cortical infarcts (OR, 2.9; 95% CI, 1.6-5.4), gray matter lacunes of presumed vascular origin (OR, 3.0; 95% CI, 1.6-5.8), brain stem infarcts (OR, 5.1; 95% CI, 1.9-13.6), and decreased brain parenchymal fraction (OR, 0.84; 95% CI, 0.74-0.94), but not with white matter hyperintensities (OR, 1.2; 95% CI, 0.8-1.8) or white matter lacunes of presumed vascular origin (OR, 1.1; 95% CI, 0.5-2.5). They were also associated with worse physical functioning (OR, 0.96; 95% CI, 0.94 to -0.99) [corrected] but not with mental functioning. CONCLUSIONS: Cerebellar cortical infarct cavities are far more common than previously assumed based on symptomatic case series and are associated with markers of atherothromboembolic cerebrovascular disease.

Malignant pleural mesothelioma metastatic to the submandibular salivary gland, simulating glandular hypertrophy, diagnosed by fine-needle aspiration biopsy: a case report and literature review.

BACKGROUND: Malignant mesothelioma is a rare neoplasm that generally develops in the pleural or peritoneal cavity. Distant metastases are common; it rarely metastatizes to the head and neck region. CASE PRESENTATION: A 54-year-old white man, a non-smoker, was treated with chemotherapy, surgery and radiation for a malignant pleural mesothelioma. Seven months after the last treatment, he developed a right submandibular enlargement: clinical examination, ultrasound and computerized tomography scans revealed a salivary gland hypertrophy. Anti-inflammatory and antibiotic treatment was then started, without improvement. An ultrasound (US)-guided fine-needle aspiration biopsy (FNAB) showed atypical mesothelial cells with nuclear enlargement and increased chromatin representation. Immunocytochemistry showed positivity for calretinin and WT-1.A diagnosis of right submandibular salivary gland involvement from mesothelioma was established, allowing an adequate treatment. CONCLUSION: We report a very rare site of metastasis from malignant pleural mesothelioma. We suggest that US-guided FNAB is a useful, quick, and cheap procedure for a definite diagnosis.

Non-fear emotions in changes in posttraumatic stress disorder symptoms during treatment.

BACKGROUND AND OBJECTIVES: Posttraumatic stress disorder (PTSD) is not only associated with fear but also with other emotions. The present study aimed to examine if changes in shame, guilt, anger, and disgust predicted changes in PTSD symptoms during treatment, while also testing if PTSD symptoms, in turn, predicted changes in these emotions. METHODS: Participants (N = 155) with childhood-related PTSD received a maximum of 12 sessions of eye movement desensitization and reprocessing or imagery rescripting. The data was analyzed using Granger causality models across 12 treatment sessions and 6 assessment sessions (up until one year after the start of treatment). Differences between the two treatments were explored. RESULTS: Across treatment sessions, shame, and disgust showed a reciprocal relationship with PTSD symptoms, while changes in guilt preceded PTSD symptoms. Across assessments, anger was reciprocally related to PTSD, suggesting that anger might play a more important role in the longer term. LIMITATIONS: The individual emotion items were not yet validated, and the CAPS was not administered at all assessments. CONCLUSIONS: These findings partly differ from earlier studies that suggested a unidirectional relationship in which changes in emotions preceded changes in PTSD symptoms during treatment. This is in line with the idea that non-fear emotions do play an important role in the treatment of PTSD and constitute an important focus of treatment and further research.

A collaborative backbone resource for comparative studies of subterranean evolution: The World Asellidae database.

Transition to novel environments, such as groundwater colonization by surface organisms, provides an excellent research ground to study phenotypic evolution. However, interspecific comparative studies on evolution to groundwater life are few because of the challenge in assembling large ecological and molecular resources for species-rich taxa comprised of surface and subterranean species. Here, we make available to the scientific community an operational set of working tools and resources for the Asellidae, a family of freshwater isopods containing hundreds of surface and subterranean species. First, we release the World Asellidae database (WAD) and its web application, a sustainable and FAIR solution to producing and sharing data and biological material. WAD provides access to thousands of species occurrences, specimens, DNA extracts and DNA sequences with rich metadata ensuring full scientific traceability. Second, we perform a large-scale dated phylogenetic reconstruction of Asellidae to support phylogenetic comparative analyses. Of 424 terminal branches, we identify 34 pairs of surface and subterranean species representing independent replicates of the transition from surface water to groundwater. Third, we exemplify the usefulness of WAD for documenting phenotypic shifts associated with colonization of subterranean habitats. We provide the first phylogenetically controlled evidence that body size of males decreases relative to that of females upon groundwater colonization, suggesting competition for rare receptive females selects for smaller, more agile males in groundwater. By making these tools and resources widely accessible, we open up new opportunities for exploring how phenotypic traits evolve in response to changes in selective pressures and trade-offs during groundwater colonization.

Homocysteine, progression of ventricular enlargement, and cognitive decline: the Second Manifestations of ARTerial disease-Magnetic Resonance study.

BACKGROUND: Homocysteine may be a modifiable risk factor for cognitive decline and brain atrophy, particularly in older persons. We examined whether homocysteine increased the risk for cognitive decline and brain atrophy, and evaluated the modifying effect of age. METHODS: Within the Second Manifestations of ARTerial disease-Magnetic Resonance study-a prospective cohort study among patients with atherosclerotic disease-longitudinal analyses were performed in 663 patients (mean age: 57 ± 9 years; follow-up: 3.9 ± 0.4 years). At baseline and follow-up, brain segmentation on magnetic resonance imaging was used to quantify relative (%) cortical, ventricular, and global brain volumes, and z-scores of memory and executive functioning were calculated. Linear regression analysis was used to estimate associations of homocysteine (per standard deviation increase) and hyperhomocysteinemia (HHCY) with brain volumes, memory, and executive functioning at follow-up, adjusted for baseline brain volume, memory, and executive functioning, respectively, and age, sex, and vascular risk factors. Furthermore, interaction terms between homocysteine and age (continuous) were added. RESULTS: Significant interactions were observed between total plasma homocysteine (tHcy) and age with cortical, ventricular, and global brain volume (for all three measures: P < .05), and between HHCY and age with executive functioning (P = .04), and results were stratified by age. In patients aged ≥65 years, increasing tHcy level and HHCY were significantly associated with progression of ventricular enlargement (B = 0.07%, 95% confidence interval [CI]: 0.01% to 0.13% and B = 0.16%, 95% CI: 0.01% to 0.31%, respectively) and with a decline in executive function (B = -0.29, 95% CI: -0.54 to -0.04 and B = -0.84, 95% CI: -1.37 to -0.32, respectively). CONCLUSION: Elevated tHcy was related to progression of ventricular enlargement and increased the risk for a decline in executive functioning in older persons.

Identification of mutations in the NUCB2/nesfatin gene in children with severe obesity.

Nesfatin-1 is the N-terminal fragment of nucleobindin-2 (NUCB2) that was identified as a novel satiety molecule in rodents. The protein is reported to exert anorexigenic effects and appears to play an important role in hypothalamic pathways regulating energy homeostasis and food intake. In this study, we hypothesized that mutations in the nesfatin encoding gene NUCB2 might cause obesity in humans. Therefore, we screened the entire coding region of the NUCB2 gene for mutations in a population of 471 obese children and adolescents. Mutation analysis of NUCB2 identified a total of seven sequence variants of which four were previously reported as polymorphisms. The remaining three variants included ex9+6G>C, L125H and K178X and were found in 3 unrelated individuals in the obese population only (0.6%). Biochemical experiments including ELISA and western blot were performed on plasma samples of the obese patient carrying the nonsense mutation K178X. However, neither NUCB2/nesfatin-1 immunoreactive plasma levels of the patient, nor expression of full length NUCB2 differed significantly from matched obese control individuals. In conclusion, we have identified the first genetic variants in the NUCB2 gene in obese individuals, although further functional characterization will be essential to verify disease causality of the mutations.

Surgical demonstration of pressure differential through an optic disc pit.

PURPOSE: To demonstrate intraoperative dynamic flow through an optic disc pit. METHODS: Retrospective interventional case report. RESULTS: Surgical management of an optic disc pit involved standard 25-gauge pars plana vitrectomy, induction of posterior hyaloid separation with triamcinolone stain, temporal peripapillary laser and SF6 gas. Intraoperatively a remnant of stained vitreous at the optic disc head prolapsed into the optic disc pit with higher intraocular pressure but was drawn back into the vitreous cavity as the intraocular pressure was lowered. This clearly demonstrated a pressure differential across the pit. CONCLUSION: Communication between the vitreous cavity and the perineural space of the optic nerve is described histologically. Our case demonstrated dynamic flow through the optic disc pit with intraoperative fluctuation of intraocular pressure.

Postural freezing relates to startle potentiation in a human fear-conditioning paradigm.

Freezing to impending threat is a core defensive response. It has been studied primarily using fear conditioning in non-human animals, thwarting advances in translational human anxiety research that has used other indices, such as skin conductance responses. Here we examine postural freezing as a human conditioning index for translational anxiety research. We employed a mixed cued/contextual fear-conditioning paradigm where one context signals the occurrence of the US upon the presentation of the CS, and another context signals that the CS is not followed by the US. Critically, during the following generalization phase, the CS is presented in a third and novel context. We show that human freezing is highly sensitive to fear conditioning, generalizes to ambiguous contexts, and amplifies with threat imminence. Intriguingly, stronger parasympathetically driven freezing under threat, but not sympathetically mediated skin conductance, predicts subsequent startle magnitude. These results demonstrate that humans show fear-conditioned animal-like freezing responses, known to aid in active preparation for unexpected attack, and that freezing captures real-life anxiety expression. Conditioned freezing offers a promising new, non-invasive, and continuous, readout for human fear conditioning, paving the way for future translational studies into human fear and anxiety.

Threat learning impairs subsequent associative inference.

Despite it being widely acknowledged that the most important function of memory is to facilitate the prediction of significant events in a complex world, no studies to date have investigated how our ability to infer associations across distinct but overlapping experiences is affected by the inclusion of threat memories. To address this question, participants (n = 35) encoded neutral predictive associations (A → B). The following day these memories were reactivated by pairing B with a new aversive or neutral outcome (B → CTHREAT/NEUTRAL) while pupil dilation was measured as an index of emotional arousal. Then, again 1 day later, the accuracy of indirect associations (A → C?) was tested. Associative inferences involving a threat learning memory were impaired whereas the initial memories were retroactively strengthened, but these effects were not moderated by pupil dilation at encoding. These results imply that a healthy memory system may compartmentalize episodic information of threat, and so hinders its recall when cued only indirectly. Malfunctioning of this process may cause maladaptive linkage of negative events to distant and benign memories, and thereby contribute to the development of clinical intrusions and anxiety.

Cannabis adulterated with the synthetic cannabinoid receptor agonist MDMB-4en-PINACA and the role of European drug checking services.

BACKGROUND: European drug checking services exchange information on drug trends within the Trans European Drug Information (TEDI) network, allowing monitoring and coordination of responses. Starting in Spring 2020, several services detected the synthetic cannabinoid receptor agonist MDMB-4en-PINACA in adulterated low-THC cannabis products. METHODS: Cannabis products suspected of adulteration were analyzed for the presence of MDMB-4en-PINACA by 9 services in 8 countries within the TEDI network. If available, phytocannabinoid analysis was also performed. RESULTS: 1142 samples sold as cannabis in herbal, resin and e-liquid form were analyzed, of which 270 were found to contain MDMB-4en-PINACA. All cannabis samples contained low THC (<1%), except the e-liquids which contained no phytocannabinoids. Three serious health incidents requiring hospitalization after use of an adulterated cannabis sample were reported. CONCLUSION: Adulteration of cannabis with synthetic cannabinoid receptor agonists is a new phenomenon that carries risk for people who use it. Given that cannabis consumers are not a usual target group for drug checking services, services and associated harm reduction interventions could be reconfigured to include them.

Cerebral small vessel disease and risk of death, ischemic stroke, and cardiac complications in patients with atherosclerotic disease: the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study.

BACKGROUND AND PURPOSE: Cerebral small vessel disease may be related to vascular and nonvascular pathology. We assessed whether lacunar infarcts and white matter lesions on MRI increased the risk of vascular and nonvascular death and future vascular events in patients with atherosclerotic disease. METHODS: Brain MRI was performed in 1309 patients with atherosclerotic disease from the Second Manifestations of ARTerial disease-Magnetic Resonance (SMART-MR) study. Infarcts were scored visually and volumetric assessment of white matter lesion was performed. Patients were followed for a median of 4.5 years (range, 0.2 to 7.1 years) for death, ischemic stroke, and ischemic cardiac complications. RESULTS: Cox regression models showed that presence of lacunar infarcts (n=229) increased the risk of vascular (hazard ratio, 2.6; 95% CI, 1.4 to 4.9) and nonvascular death (hazard ratio, 2.7; 95% CI, 1.3 to 5.3), adjusted for age, sex, vascular risk factors, nonlacunar infarcts, and white matter lesion. These risks were similar for patients with silent lacunar infarcts. White matter lesion volume (relative to total intracranial volume) increased the risk of vascular death (hazard ratio per milliliter increase, 1.03; 95% CI, 1.01 to 1.05) and white matter lesions in the upper quintile compared with lower quintiles increased risk of ischemic stroke (hazard ratio, 2.6; 95% CI, 1.3 to 4.9). CONCLUSIONS: Cerebral small vessel disease, with or without a history of cerebrovascular disease, is associated with increased risk of death and ischemic stroke in patients with atherosclerotic disease.

Functional connectivity analysis of fMRI data using parameterized regions-of-interest.

Connectivity analysis of fMRI data requires correct specification of regions-of-interest (ROIs). Selection of ROIs based on outcomes of a GLM analysis may be hindered by conservativeness of the multiple comparison correction, while selection based on brain anatomy may be biased due to inconsistent structure-to-function mapping. To alleviate these problems we propose a method to define functional ROIs without the need for a stringent multiple comparison correction. We extend a flexible framework for fMRI analysis (Activated Region Fitting, Weeda et al. 2009) to connectivity analysis of fMRI data. This method describes an entire fMRI data volume by regions of activation defined by a limited number of parameters. Therefore a less stringent multiple comparison procedure is required. The regions of activation from this analysis can be directly used to estimate functional connectivity. Simulations show that Activated Region Fitting can recover the connectivity of brain regions. An application to real data of a Go/No-Go experiment highlights the advantages of the method.

On the Relation Between the Linear Factor Model and the Latent Profile Model.

The relationship between linear factor models and latent profile models is addressed within the context of maximum likelihood estimation based on the joint distribution of the manifest variables. Although the two models are well known to imply equivalent covariance decompositions, in general they do not yield equivalent estimates of the unconditional covariances. In particular, a 2-class latent profile model with Gaussian components underestimates the observed covariances but not the variances, when the data are consistent with a unidimensional Gaussian factor model. In explanation of this phenomenon we provide some results relating the unconditional covariances to the goodness of fit of the latent profile model, and to its excess multivariate kurtosis. The analysis also leads to some useful parameter restrictions related to symmetry.

Subtypes of smokers in a randomized controlled trial of a web-based smoking cessation program and their role in predicting intervention non-usage attrition: Implications for the development of tailored interventions.

INTRODUCTION: Web-based smoking interventions hold potential for smoking cessation; however, many of them report low intervention usage (i.e., high levels of non-usage attrition). One strategy to counter this issue is to tailor such interventions to user subtypes if these can be identified and related to non-usage attrition outcomes. The aim of this study was two-fold: (1) to identify and describe a smoker typology in participants of a web-based smoking cessation program and (2) to explore subtypes of smokers who are at a higher risk for non-usage attrition (i.e., early dropout times). METHODS: We conducted secondary analyses of data from a large randomized controlled trial (RCT) that investigated effects of a web-based Cognitive Bias Modification intervention in adult smokers. First, we conducted a two-step cluster analysis to identify subtypes of smokers based on participants' baseline characteristics (including demographics, psychological and smoking-related variables, N = 749). Next, we conducted a discrete-time survival analysis to investigate the predictive value of the subtypes on time until dropout. RESULTS: We found three distinct clusters of smokers: Cluster 1 (25.2%, n = 189) was characterized by participants being relatively young, highly educated, unmarried, light-to-moderate smokers, poly-substance users, and relatively high scores on sensation seeking and impulsivity; Cluster 2 (41.0%, n = 307) was characterized by participants being older, with a relatively high socio-economic status (SES), moderate-to-heavy smokers and regular drinkers; Cluster 3 (33.8%, n = 253) contained mostly females of older age, and participants were further characterized by a relatively low SES, heavy smoking, and relatively high scores on hopelessness, anxiety sensitivity, impulsivity, depression, and alcohol use. Additionally, Cluster 1 was more likely to drop out at the early stage of the intervention compared to Cluster 2 (adjusted Hazard Ratio (HR adjusted) = 1.51, 95% CI = [1.25, 1.83]) and Cluster 3 (HR adjusted = 1.52, 95% CI = [1.25, 1.86]). CONCLUSIONS: We identified three clusters of smokers that differed on a broad range of characteristics and on intervention non-usage attrition patterns. This highlights the heterogeneity of participants in a web-based smoking cessation program. Also, it supports the idea that such interventions could be tailored to these subtypes to prevent non-usage attrition. The subtypes of smokers identified in this study need to be replicated in the field of e-health outside the context of RCT; based on the smoker subtypes identified in this study, we provided suggestions for developing tailored web-based smoking cessation intervention programs in future research.