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Major depressive disorder (MDD) and bipolar disorder (BD) are likely to be etiologically diverse, resulting from the contributions of multiple pathophysiologic processes present in affected individuals to varying degrees. In MDD, there is abundant evidence that alterations in serotonin and other monoamines (1) and glutamatergic signaling (2) are implicated in its pathogenesis, and most available treatments target these pathways.
While network research often focuses on social integration as a predictor of health, a less-explored idea is that connections to dissimilar others may benefit well-being. As such, this study investigates whether network diversity is associated with changes in four health outcomes over a 3-year period of time in the U.S.A. Specifically, we focus on how an underexplored measure of network diversity—educational attainment assortativity—is associated with common self-reported outcomes: propensity to exercise, body-mass index, mental health, and physical health. We extend prior research by conducting multilevel analyses using this measure of diversity while adjusting for a range of socio-demographic and network confounders. Data are drawn from a longitudinal probability sample of U.S. adults (n=10.679) in which respondents reported information about themselves and eight possible alters during three yearly surveys (2013–2015). We find, first, that higher educational attainment is associated with more educationally insular networks, while less-educated adults have more educationally diverse networks. Results further suggest that having educationally similar networks is associated with higher body-mass index among the less educated. Further exploration of the relationship between ego network diversity, tie strength, and health is warranted.
Introduction: Each year, 3/1000 Canadians sustain a mild traumatic brain injury (mTBI). Many of those mTBI are accompanied by various co-injuries such as dislocations, sprains, fractures or internal injuries. A number of those patients, with or without co-injuries will suffer from persistent post-concussive symptoms (PPCS) more than 90 days post injury. However, little is known about the impact of co-injuries on mTBI outcome. This study aims to describe the impact of co-injuries on PPCS and on patient return to normal activities. Methods: This multicenter prospective cohort study took place in seven large Canadian Emergency Departments (ED). Inclusion criteria: patients aged ≥ 14 who had a documented mTBI that occurred within 24 hours of ED visit, with a Glasgow Coma Scale score of 13-15. Patients who were admitted following their ED visit or unable to consent were excluded. Clinical and sociodemographic information was collected during the initial ED visit. A research nurse then conducted three follow-up phone interviews at 7, 30 and 90 days post-injury, in which they assessed symptom evolution using the validated Rivermead Post-concussion Symptoms Questionnaire (RPQ). Adjusted risk ratios (RR) were calculated to estimate the influence of co-injuries. Results: A total of 1674 patients were included, of which 1023 (61.1%) had at least one co-injury. At 90 days, patients with co-injuries seemed to be at higher risk of having 3 symptoms ≥2 points according to the RPQ (RR: 1.28 95% CI 1.02-1.61) and of experiencing the following symptoms: dizziness (RR: 1.50 95% CI 1.03-2.20), fatigue (RR: 1.35 95% CI 1.05-1.74), headaches (RR: 1.53 95% CI 1.10-2.13), taking longer to think (RR: 1.50 95% CI 1.07-2.11) and feeling frustrated (RR: 1.45 95% CI 1.01-2.07). We also observed that patients with co-injuries were at higher risk of non-return to their normal activities (RR: 2.31 95% CI 1.37-3.90). Conclusion: Patients with co-injuries could be at higher risk of suffering from specific symptoms at 90 days post-injury and to be unable to return to normal activities 90 days post-injury. A better understanding of the impact of co-injuries on mTBI could improve patient management. However, further research is needed to determine if the differences shown in this study are due to the impact of co-injuries on mTBI recovery or to the co-injuries themselves.
Introduction: Mild traumatic brain injury (mTBI) is a serious public health issue and as much as one third of mTBI patients could be affected by persistent post-concussion symptoms (PPCS) three months after their injury. Even though a significant proportion of all mTBIs are sports-related (SR), little is known on the recovery process of SR mTBI patients and the potential differences between SR mTBI and patients who suffered non-sports-related mTBI. The objective of this study was to describe the evolution of PPCS among patients who sustained a SR mTBI compared to those who sustained non sport-related mTBI. Methods: This Canadian multicenter prospective cohort study included patients aged ≥ 14 who had a documented mTBI that occurred within 24 hours of Emergency Department (ED) visit, with a Glasgow Coma Scale score of 13-15. Patients who were hospitalized following their ED visit or unable to consent were excluded. Clinical and sociodemographic information was collected during the initial ED visit. Three follow-up phone interviews were conducted by a research nurse at 7, 30 and 90 days post-injury to assess symptom evolution using the validated Rivermead Post-concussion Symptoms Questionnaire (RPQ). Adjusted risk ratios (RR) were calculated to demonstrate the impact of the mechanism of injury (sports vs non-sports) on the presence and severity of PPCS. Results: A total of 1676 mTBI patients were included, 358 (21.4%) of which sustained a SR mTBI. At 90 days post-injury, patients who suffered a SR mTBI seemed to be significantly less affected by fatigue (RR: 0.70 (95% CI: 0.50-0.97)) and irritability (RR: 0.60 (95% CI: 0.38-0.94)). However, no difference was observed between the two groups regarding each other symptom evaluated in the RPQ. Moreover, the proportion of patients with three symptoms or more, a score ≥21 on the RPQ and those who did return to their normal activities were also comparable. Conclusion: Although persistent post-concussion symptoms are slightly different depending on the mechanism of trauma, our results show that patients who sustained SR-mTBI could be at lower risk of experiencing some types of symptoms 90 days post-injury, in particular, fatigue and irritability.
Pemphigus is a rare autoimmune dermatological disease, whose onset and course depend on the interaction between predisposing severed and inducing factors. Psychological stress has been suggested to be a potential triggering factor of pemphigus. However, this hypothesis has not been thoroughly investigated. To this purpose, we explored recent stressful life events and personality disorders in 25 consecutive subjects with pemphigus. Baseline information was collected on demographic characteristics, family history, presence of psychopathology, the impact of stressful life events occurring within one year prior to onset of pemphigus, presence of Axis I and Axis II diagnosis, using standardized instruments. Patients affected by pemphigus were matched for number, age and gender with subjects with other skin diseases and with healthy volunteers. All pemphigus patients had a negative anamnesis for Axis I diagnosis. Pemphigus patients showed a significantly higher Comprehensive Psychopathological Rating Scale (CPRS) and depression and anxiety with Montgomery-Asberg Depression Rating Scale (MADRS) total scores than controls. Cases and controls did not differ regarding the total number of stressful events experienced. The uncontrollable events and undesiderable events had occurred more frequently among pemphigus patients than controls. In 68% of pemphigus patients at least one personality disorder was diagnosed; there was a high prevalence of obsessive-compulsive and avoidant personality disorder. These findings suggest that stressful life events might increase vulnerability to pemphigus and that personality features might modulate individual susceptibility to illness.
The aim of this study was to evaluate the clinical characteristics of OCD patients with poor insight, and the predictive value of poor insight with respect to response to treatment with serotonin reuptake inhibitors (SRIs). One hundred ten patients fulfilling DSM-IV criteria for OCD were included in the study and assessed by standardized instruments. Seventy-nine patients were treated with SRIs and followed prospectively for 3 years. During the follow-up period, the clinical status of each patients was evaluated monthly during the first year and bimonthly thereafter by means of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Hamilton Rating Scale for Depression (HDRS). Twenty-one percent of the patients did not recognize obsessive-compulsive symptoms as unreasonable or senseless. Patients with poor insight had a earlier age at onset, a greater severity of obsessive-compulsive symptoms at intake, a higher rate of schizophrenia spectrum disorders in first-degree relatives and a higher comorbidity rate of schizotypal or obsessive-compulsive personality disorders. At the end of the study, 62% percent of the patients with normal insight responded to SRIs, whereas none of the patients with poor insight was found to be responder. The study provides evidence that poor insight is associated with specific clinical characteristics and treatment failure in OCD. Further studies should aim at identifying additional treatment strategies that are effective in OCD patients with poor insight.
This study aimed to evaluate the long-term course of obsessive-compulsive disorder (OCD) in patients treated with serotonin reuptake inhibitors (SRIs) and to identify predictors of clinical outcome. Seventy-nine patients fulfilling DSM-IV criteria for OCD were followed prospectively for 3 years. Baseline information was collected on demographic and clinical characteristics, using standardized instruments. During the follow-up period, the clinical status of each patient was evaluated monthly in the first year and bimonthly thereafter by means of the Yale-Brown Obsessive Compulsive Scale (Y-BOCS) and the Hamilton Rating Scale for Depression (HDRS). The cumulative probability of achieving an at least partial remission from obsessive-compulsive (OC) symptoms during the 3-year period was 65%. The probability of full remission was 38%. In subjects who achieved an at least partial remission, the probability of subsequent relapse was 60%. Significant predictors of poor outcome included a longer duration of illness, a greater severity of OC symptoms at intake, and the presence of comorbid schizotypal personality disorder. The findings confirm that the course of illness in OCD is usually continuous with fluctuations in the intensity of OC symptoms. Despite adequate SRI therapy, relatively few patients achieve a completely asymptomatic state and, of those who achieve at least a partial remission, a substantial proportion subsequently relapse. One third of OCD patients is treatment-resistant. Further studies with large samples are required to adequately identify predictors of long-term outcome of OCD in order to optimize the choice among the existing treatment modalities.
Blood dyscrasias, other than agranulocytosis, have received little attention in clozapine-treated patients. The aim of the present study was to shed more light on the incidence and course of clozapine-induced blood dyscrasias that occur during the first eighteen weeks of treatment with the antipsychotic. The study included 135 patients (M 75 and F 60), with a mean age of 33.1±10.4 years. The blood dyscrasias appeared in 88.1% of the total sample and were divided, on the basis of their duration, into transient and persistent. The analysis of data revealed that persistent dyscrasias had a higher incidence (56.2%) when compared to transient ones (11%). Persistent anemia was more common in female patients (F 52.5% vs M 11.2%), while male patients had a higher frequency of eosinophilia (M 26.2% vs F 21.2%), neutrophilia (M 18.7% vs F 15.0%) and leucocytosis (M 21.2% vs 8.7% F). The correlation between clinical response and blood dyscrasias revealed a statistically significant positive effect for male patients with eosinophilia (p< .05) and a negative correlation for male patients who presented persistent leucocytosis (p< .05). Our data could be offered to alert clinicians to the possibility that hematologic complications, other than agranulocytosis, may be common in clozapine-treated patients.
Many published studies underlined the relationship between Atypical Antipsychotic treatment and Metabolic Syndrome (MS) onset, but only few have compared the effects of Typical and Atypical Antipsychotics to this respect. The present study examined in schizophrenic and bipolar patients the impact of haloperidol (mean dose 3.37±2.28 mg and 2.51±1.48 mg, respectively) and olanzapine treatment (mean dose 12.42±6.53 mg and 9.97±5.36 mg, respectively) on glycemia, blood pressure, BMI, triglycerides and HDL cholesterol. A higher prevalence and a different time of appearance of Metabolic Syndrome was observed in Bipolar patients when treated with olanzapine. Moreover, weight increase was greater in bipolar patients treated with olanzapine (p< .000) when compared to schizophrenic treated with both Antipsychotics. These findings suggest a shared susceptibility to antipsychotic- related metabolic disregulations in both schizophrenic and bipolar patients for SGAs, but not for FGAs. Moreover, the effects of olanzapine in bipolar patients support the development and testing of interventions specifically designed for preventing and treating the metabolic syndrome and its components.
Only few studies have compared the effects of Typical and Atypical Antipsychotics on Metabolic Syndrome (MS) onset. The present study examined in schizophrenic and bipolar patients the impact of haloperidol (mean dose 3.37±2.28 mg and 2.51±1.48 mg, respectively) and olanzapine treatment (mean dose 12.42±6.53 mg and 9.97±5.36 mg, respectively) on glycemia, blood pressure (BP), BMI, triglycerides, HDL cholesterol, fasting cholesterol and body weight (BW). Our data disclosed significant time x diagnosis x drug treatment interactions for fasting cholesterol (p<.005), systolic BP (p<.003), BW (p<.005) and BMI (p<.02) suggesting that these parameters differently changed overtime in the two groups in relation to the 2 drug treatments. Indeed, increases in fasting cholesterol, systolic BP, BW and BMI were significantly higher in olanzapine-treated patients as compared to haloperidol-treated ones and these effects were more pronounced in bipolar patients as compared to schizophrenic ones. Significant time x drug treatment interactions were found for fasting glucose and triglycerides (p<.0001), indicating that these parameters differently changed after the 2 drug treatments irrespective of the diagnostic group. Indeed, plasma levels of glucose and triglycerides significantly increased after olanzapine treatment but not after haloperidol in both patients groups.
Metabolic profile of olanzapine as compared to haloperidol has been evaluated much less comprehensively in bipolar than in schizophrenic patients. Medical records of 343 patients who completed a 3-year treatment with haloperidol or olanzapine were retrospectively reviewed, and metabolic outcomes were evaluated. Twenty-three percent of patients fulfilled MetS criteria with a point prevalence of 25.3% in bipolar and 21.2% in schizophrenic group; 20.3% of schizophrenics treated with haloperidol and 22.4% of those treated with olanzapine developed MetS, which was detected, instead, in 17.1% of haloperidol-treated bipolar patients and 32.9% of those treated with olanzapine. Significant changes were detected overtime in fasting cholesterol, systolic BP, BW and BMI; some of these parameters at the 3-year follow-up presented more severe changes with olanzapine than haloperidol in both diagnostic groups. Overall, a significant number of subjects fulfilled MetS criteria in the first month of treatment, but only in schizophrenics olanzapine was faster than haloperidol in inducing such an effect. These data suggest that haloperidol and olanzapine increase the risk for MetS in both schizophrenic and bipolar patients with a higher prevalence for olanzapine only in bipolar patients. Morever, as compared to haloperidol, olanzapine has a faster dismetabolic action in schizophrenic but not in bipolar patients.
Blood dyscrasias induced by clozapine treatment and other Typical and Atypical Antipsychotics have received little attention. The aim of the present study was to shed more light on the incidence and course of clozapine-induced blood dyscrasias that occour during the first eighteen weeks of treatment compared to dyscrasias induced by other Typical and Atypical Antipsychotics. The study included 135 clozapine-treated patients (M 75 and F 60), 75 patients treated with other Atypical (M 35 and F 40), and 75 treated with Typical (M 39 and F 36). Persistent eosinophilia appeared in 36.8% of clozapine-treated patients, in 4%, (p<.05) and 2.7%, (p<.05), respectively, of patients treated with Atipical and Typical Antipychotics; persistent leukocytosis, instead, appeared in 26.5% of patients treated with clozapine, 13.3% and 18.7% treated, respectively, with Atypical and Typical. Moreover, persistent neutrophilia appeared in 27.2% of subjects treated with clozapine, 12.0% with Atypical and 10.7%, (p<.027) with Typical. Our data report an incidence of persistent anemia in clozapine-treated patients of 45.6% (62/136) with respect to 8% (6/75), (p<.05) of patients treated with Atypical and 12% (9/75), (p<.05) with Typical. Our study report sex-correlated differences in clozapine-treated patients, with a major incidence of persistent anemia among female patients (p<.001). Our data could be offered to alert clinicians to the possibility that hematologic complications may be more common in patients treated with clozapine than in patients treated with other antipsychotics.
Blood dyscrasias, other than agranulocytosis, have received little attention in clozapine-treated patients. The aim of the study was to shed more light on the incidence and course of clozapine-induced blood dyscrasias that occur during the first eighteen weeks of treatment with the antipsychotic. These dyscrasias have been characterized on the basis of different variables (patient gender, age, number of previous hospitalizations; time of appearance and disappearance, dose of clozapine when blood dyscrasias appeared and at the end of the 18th week of treatment, drugs used before and concomitantly to clozapine treatment, correlation with clinical response). The study included 135 patients (M 75 and F 60), with a mean age of 33.1 ± 10.4 years. The blood dyscrasias appeared in 88.1% of the total sample and were divided, on the basis of their duration, into transient and persistent. The analysis of data revealed that persistent dyscrasias had a higher incidence (56.2%) when compared to transient ones (11%). Persistent anemia was more common in female patients (F 52.5% vs M 11.2%), while male patients had a higher frequency of eosinophilia (M 26.2% vs F 21.2%), neutrophilia (M 18.7% vs F 15.0%) and leucocytosis (M 21.2% vs 8.7% F). Correlation between clinical response and blood dyscrasias revealed a statistically significant positive effect for male patients with eosinophilia (p < .05) and a negative correlation for male patients who presented persistent leucocytosis (p < .05). Our data could be offered to alert clinicians to the possibility that hematologic complications, other than agranulocytosis, may be common in clozapine-treated patients.
The duration of untreated illness (DUI), defined as the interval between the onset of a disorder and the first adequate treatment, has been increasingly investigated as a predictor of outcome in psychotic disorders. However, few data are available on the impact of DUI on the outcome of the obsessive-compulsive disorder.
This study aimed at investigating: 1) patients'socio-demographic and clinical characteristics which influence duration of untreated illness in OCD; 2) the effect of duration of untreated illness on outcome.
Eighty-three outpatients fulfilling DSM-IV criteria for OCD were recruited and prospectively followed up for 3 years. Baseline information, demographic and clinical characteristics, were collected by standardized instruments. Obsessive-compulsive symptoms were assessed using Yale-Brown Obsessive Compulsive Scale (Y-BOCS). Fifty-nine patients completed the follow-up.
Recruited patients were predominantly male (52%), with a mean age of 31.5 (SD = 10.2) years, 11.2 (SD = 3.9) years spent in general education. Fifty-two per cent of them were married and 50.6% were employed. The mean DUI was 7.3 (SD = 5.8) years. Patients with a DUI > 2 years had a later onset of OCD, a familiarity for affective disorders, and showed an higher frequency of aggressive obsessions. At completion of the follow-up, these patients showed a worse clinical outcome and more frequently did not achieve remission.
DUI has a considerable impact on outcome of obsessive-compulsive disorder. Being DUI a modifiable prognostic factor, programs aimed to early detection and treatment of OCD could substantially reduce personal, social and economical burden related to this disorder.
Different studies have identified specific clinical characteristics of patients with obsessive-compulsive disorder (OCD) in comorbidity with schizotypal personality disorder (SPD), although no perspective evaluations of prognosis and response to treatment have been conducted so far. The aims of the present study were to evaluate: (1) the clinical and demographic correlates of OCD patients with comorbid SPD (OCD-SPD) using standardized instruments; (2) the response of OCD-SPD patients to long-term naturalistic pharmacological treatment. Socio-demographic and clinical characteristics of patients with OCD-SPD were compared to patients with “pure OCD”. OCD-SPD patients were characterized by a greater severity of obsessive-compulsive symptomatology, earlier age at onset, a higher rate of schizophrenia spectrum disorders in their first-degree relatives and a poorer insight. During the observational period, OCD-SPD patients were less likely to achieve remission of their symptomatology and required a greater number of trials with different antipsychotic drugs or received more frequently augmentation with antipsychotics. Our findings suggested that comorbidity with SPD is correlated to a poor treatment response in OCD patients and a reduced likelihood to recover from OCD symptoms, following standard pharmacological treatments. Further research is needed to identify alternative strategies for the management of this cohort of patients.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
Duration of untreated illness (DUI) is a predictor of outcome in psychotic and affective disorders. Data available on DUI and its relationship with outcome in obsessive-compulsive disorder (OCD) suggest an association between longer DUI and poorer treatment response. The present study investigated socio-demographic and clinical predictors of DUI and its association with long-term outcome in OCD patients. Eighty-three OCD outpatients were treated with serotonin reuptake inhibitors (SRIs) and prospectively followed-up for 3 years. Baseline information was collected on demographic and clinical characteristics using standard assessments. Each patient was assessed through the structured clinical interview for DSM-IV axis I disorders (SCID-I), the structured clinical interview for DSM-IV axis II personality disorders (SCID-II), the Yale-Brown obsessive–compulsive scale (Y-BOCS) and the 17-item Hamilton rating scale for depression (HDRS). The DUI was explored by interviewing patients, family caregivers and clinicians. OCD subjects had a mean DUI of 7.3 (5.8) years. A younger age at onset and a greater severity of OCD symptoms at baseline were associated with a longer DUI. The DUI of patients with a “good outcome” was shorter than that of patients with a “poor outcome”. Logistic regression analysis revealed indeed a possible association between longer DUI and “poor outcome”. In the logistic multivariable model, the association of DUI with treatment outcome held true whilst controlling for socio-demographic and clinical variables.
Disclosure of interest
The authors have not supplied their declaration of competing interest.
The deviation from thermodynamic equilibrium of the ion velocity distribution functions (VDFs), as measured by the Magnetospheric Multiscale (MMS) mission in the Earth’s turbulent magnetosheath, is quantitatively investigated. Making use of the unprecedented high-resolution MMS ion data, and together with Vlasov–Maxwell simulations, this analysis aims at investigating the relationship between deviation from Maxwellian equilibrium and typical plasma parameters. Correlations of the non-Maxwellian features with plasma quantities such as electric fields, ion temperature, current density and ion vorticity are found to be similar in magnetosheath data and numerical experiments, with a poor correlation between distortions of ion VDFs and current density, evidence that questions the occurrence of VDF departure from Maxwellian at the current density peaks. Moreover, strong correlation has been observed with the magnitude of the electric field in the turbulent magnetosheath, while a certain degree of correlation has been found in the numerical simulations and during a magnetopause crossing by MMS. This work could help shed light on the influence of electrostatic waves on the distortion of the ion VDFs in space turbulent plasmas.
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.