Effects of esketamine nasal spray on depressive symptom severity in adults with treatment-resistant depression and associations between the Montgomery-Åsberg Depression Rating Scale and the 9-item Patient Health Questionnaire.

OBJECTIVE: To examine the effect of esketamine nasal spray (ESK) plus newly initiated oral antidepressant (OAD) versus OAD plus placebo nasal spray (PBO) on the association between Montgomery-Åsberg Depression Rating Scale (MADRS) and 9-item Patient Health Questionnaire (PHQ-9) scores in adults with treatment-resistant depression (TRD). METHODS: Data from TRANSFORM-1 and TRANSFORM-2 (two similarly designed, randomized, active-controlled TRD studies) and SUSTAIN-1 (relapse prevention study) were analyzed. Group differences for mean changes in PHQ-9 total score from baseline were compared using analysis of covariance. Associations between MADRS and PHQ-9 total scores from TRANSFORM-1/TRANSFORM-2 were assessed using simple parametric, nonparametric, and multiple regression models. RESULTS: In TRANSFORM-1/TRANSFORM-2 (ESK + OAD, n = 343; OAD + PBO, n = 222), baseline PHQ-9 mean scores were 20.4 for ESK + OAD and 20.6 for OAD + PBO (severe depression). At day 28, significant group differences were observed in least squares mean change (SE) in PHQ-9 scores from baseline (-12.8 [0.46] vs -10.3 [0.53], P < .001) and in clinically substantial change in PHQ-9 scores (≥6 points; 77.1% vs 64%, P < .001) in ESK + OAD and OAD + PBO groups, respectively. A nonlinear relationship between MADRS and PHQ-9 was observed; total scores demonstrated increased correlation over time. In SUSTAIN-1, 57.3% of patients receiving ESK + OAD (n = 89) versus 44.2% receiving OAD + PBO (n = 86) retained remission status (PHQ-9 score ≤4) at maintenance treatment end point (P = .044). CONCLUSIONS: In adults with TRD, ESK + OAD significantly improved severity of depressive symptoms, and more patients achieved clinically meaningful changes in depressive symptoms based on PHQ-9, versus OAD + PBO. PHQ-9 outcomes were consistent with those of clinician-rated MADRS. TRIAL REGISTRATION: ClinicalTrials.gov: NCT02417064, NCT02418585, NCT02493868.

The buffering effects of psychological capital on the relationship between physical violence and mental health issues of nurses and personal care assistants working in aged care facilities.

PURPOSE: The purpose of this study was to examine the effects of psychological capital on the relationship between physical violence and mental health issues of nurses and personal care assistants (PCAs) working in aged care using the job demands-resources theory. METHODOLOGY: Data were collected from 254 nurses and PCAs of the Australian Nursing Midwifery Federation located in Victoria, Australia. The study takes a quantitative approach and tests the hypotheses through regression analyses. FINDINGS: The results indicate that experiencing physical violence increases levels of stress, depression, and anxiety. This, in turn, increases nurses' and PCAs' intention to leave. However, increased psychological capital can assist nurses and PCAs in dealing with physical violence. RESEARCH IMPLICATIONS: The study acknowledges that physical violence is a factor in nurses' intention to leave. The significant finding is that psychological capital plays a protective role in ameliorating the negative impact of physical violence on individual well-being and intentions to leave. We note, however, that this is a cross-section study, and more longitudinal research needs to be undertaken. PRACTICAL IMPLICATIONS: There are clear implications for managers to create a supportive organization that cultivates hope, self-efficacy, and resilience, thereby increasing psychological capital. Leadership development programs could build a supportive foundation for nurses to seek support and build resilience. Job construction should be focused on protecting nurses from risk by utilizing manageable workloads to limit stress, depression, and anxiety. ORIGINALITY: Our study extends research on retention of these skilled and important health care workers in a demanding environment that has largely been absent from the literature. Specifically, physical violence is often considered part of nursing work, but its impact on mental health, well-being, and intention to leave are underexplored in this sector, as well as the effectiveness of specific measures that bolster the negative impact of physical violence on nurses.

Culturally appropriate health solutions: Aboriginal men 'thriving' through activities in Men's Sheds/groups.

This study examines social determinants impacting the health and wellbeing of Aboriginal and Torres Strait Islander men in Australia. Social determinants prevent many men from thriving in community environments which also impacts on their social, work and family lives. We examine the impact on men's health and identify how men who participate in Men's Sheds/groups engage in learning about health interventions. Our study extends the work of Percival et al. and their Indigenous health promotion model. A qualitative case study approach conducted 'gatherings' and 'yarning circles' (focus groups) with men from urban, regional and remote areas of the country. We argue that men's groups can serve as a central intervention to support men to build their confidence to learn about health and wellbeing and how to thrive through activities in community life. Findings support health interventions delivered through training and mentoring around various health and other services, healthy eating, sport and fathering programmes (to name a few) to enhance awareness and men's vitality for learning. There are implications for our healthcare system to better understand the conditions of Aboriginal men's health and support these vulnerable groups. Our study proposes men's groups as culturally safe environments to promote and deliver central health promotion interventions that support men to thrive in all facets of their lives.

[Major depressive disorder and treatment-resistant depression: an epidemiological analysis in Argentina of the Study of Treatment-Resistant Depression in Latin America]. / Trastorno depresivo mayor y depresión resistente al tratamiento: un análisis epidemiológico en Argentina del estudio de Depresión resistente al tratamiento en América Latina.

Treatment-Resistant Depression (TRD) prevalence varies considerable between regions and epidemiology of TRD in Argentina is lacking. Based on the Treatment-Resistant Depression in America Latina (TRAL) study, epidemiology and burden of TRD in MDD patients from Argentina is reported in this paper. A sample of adult MDD patients (n=396) from 5 sites in Argentina, with clinical diagnosis were included. Patients with psychosis, schizophrenia, bipolar disorder, schizoaffective disorder, dementia, with severe chemical dependence or currently participating in another clinical trial were excluded. Patient reported outcomes and clinical assessment scales were used as outcomes. The prevalence of TRD in MDD patients in Argentina is 33.2%, based on TRAL data. Patients in TRD are older compared to those without TRD, and was more evident in married/consensual union MDD patients. Higher suicidality, greater comorbidity based on MINI, and worse scores in MADRS and PHQ-9 were identified in TRD patients. The prevalence identified in TRAL study for Argentina is substantial comparing with other Latin American countries and worldwide prevalence. TRD represents a disproportional burden to society, and efforts should be placed on reducing the burden of MDD and TRD in Argentina by improving early diagnosis, therapeutic management and ensuring that all patients have better access to mental healthcare.

Mapping the Patient-Oriented Prostate Utility Scale From the Expanded Prostate Cancer Index Composite and the Short-Form Health Surveys.

OBJECTIVES: This study aimed to develop mapping algorithms from the Expanded Prostate Cancer Index Composite (EPIC) and the Short-Form (SF) Health Surveys to the Patient-Oriented Prostate Utility Scale (PORPUS), an econometric instrument specifically developed for patients with prostate cancer. METHODS: Data were drawn from 2 cohorts concurrently administering PORPUS, EPIC-50, and SF-36v2. The development cohort included patients who had received a diagnosis of localized or locally advanced prostate cancer from 2017 to 2019. The validation cohort included men who had received a diagnosis of localized prostate cancer from 2014 to 2016. Linear regression models were constructed with ln(1 - PORPUS utility) as the dependent variable and scores from the original and brief versions of the EPIC and SF as independent variables. The predictive capacity of mapping models constructed with all possible combinations of these 2 instruments was assessed through the proportion of variance explained (R2) and the agreement between predicted and observed values. Validation was based on the comparison between estimated and observed utility values in the validation cohort. RESULTS: Models constructed with EPIC-50 with and without SF yielded the highest predictive capacity (R2 = 0.884, 0.871, and 0.842) in comparison with models constructed with EPIC-26 (R2 = 0.844, 0.827, and 0.776). The intraclass correlation coefficient was excellent in the 4 models (>0.9) with EPIC and SF. In the validation cohort, predicted PORPUS utilities were slightly higher than those observed, but differences were not statistically significant. CONCLUSIONS: Mapping algorithms from both the original and the abbreviated versions of the EPIC and the SF Health Surveys allow estimating PORPUS utilities for economic evaluations with cost-utility analyses in patients with prostate cancer.

Workplace health promotion interventions for Australian workers with intellectual disability.

Workplace health promotion (WHP) and the general wellbeing of workers in the Australian workforce should be a priority for all management. Our study argues that management support for workers with an intellectual disability (WWID) can make a difference to their health promotion and ultimately their participation in the workforce. We adopt a qualitative approach, through semi-structured interviews with 22 managers, across various organizations, to examine their perspectives around the WHP of WWID. We integrate the key values of WHP; rights for health, empowerment for health and participation for health (Spencer, Corbin and Miedema, Sustainable development goals for health promotion: a critical frame analysis, Health Promot Int 2019;34:847-58) into the four phases of WHP interventions; needs assessment, planning, implementation and evaluation (Bortz and Döring, Research Methods and Evaluation for Human and Social Scientists, Heidelberg: Springer, 2006) and examine management perspectives (setting-based approach) on WHP of WWID. Where this integration had taken place, we found some evidence of managers adopting more flexible, innovative and creative approaches to supporting the health promotion of WWID. This integration seemed to drive continuous improvement for WWID health promotion at the workplace. We also found evidence that some organizations, such an exemplar film company, even over deliver in terms of supporting WWID needs by encouraging their capabilities in film making interventions, whilst others are more direct in their support by matching skills to routine jobs. Our approach demonstrates that incorporating key WHP values into the four-phase WHP framework is critical for the effective health promotion of WWID.

Prevalence and Impact of Treatment-Resistant Depression in Latin America: a Prospective, Observational Study.

Approximately one-third of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD). The TRAL study will evaluate the prevalence and impact of TRD among patients with MDD in four Latin American countries. In this multicenter, prospective, observational study, patients with MDD were recruited from 33 reference sites in Mexico, Colombia, Brazil, and Argentina. Patients were assessed for TRD, defined as failure to respond to ≥ 2 antidepressant medications of adequate dose and duration. Demographics, previous/current treatments, depressive symptoms, functioning, healthcare resource utilization, and work impairment were also collected and evaluated using descriptive statistics, chi-square test, Fisher exact test, t-test for independent samples, or the Mann-Whitney nonparametric test, as appropriate. 1475 patients with MDD were included in the analysis (mean age, 45.6 years; 78% women); 89% were receiving relevant psychiatric treatment. 429 patients met criteria for TRD, and a numerically higher proportion of patients with TRD was present in public versus private sites of care (31% vs 27%). The mean Montgomery-Asberg Depression Rating Scale score was 25.0 among all MDD patients and was significantly higher for patients with TRD versus non-TRD (29.4 vs 23.3; P < 0.0001). Patients with TRD, versus those with non-TRD, were significantly more likely to be older, have a longer disease duration, have more comorbidities, be symptomatic, have a higher median number of psychiatric consultations, and report greater work impairment. Patients with TRD have a disproportionate burden of disease compared to those with non-TRD. Appropriate treatment for TRD is a substantial unmet need in Latin America. https://www.ClinicalTrials.gov identifier NCT03207282, 07/02/2017.

Workplace violence against nurses in health care and the role of human resource management: A systematic review of the literature.

AIM: To provide insights into how workplace violence has an impact on nurses and to inform human resource management about developing comprehensive strategies to manage and mitigate violence. DESIGN: A systematic review of the literature to appraise contemporary studies, source data and synthesize findings for human resource management to implement practices to mitigate violence against nurses in the healthcare sector. DATA SOURCES: Searches were conducted using ProQuest, Business Source Complete (EBSCO), Emerald Insight, PsycINFO (ProQuest), ScienceDirect, and Google Scholar. Our search was delimited to refereed journal articles and government reports over the last 15 years from 2004-2019 and included a total of 71 articles. REVIEW METHODS: The research team systematically reviewed each article and relative reports, eliminating any not considered relevant to nurses. This systematic review is associated with and reflects contemporary issues around nurses, violence, and human resource management practice. RESULTS: In the studies we found high incidents of violence against nurses in the workplace. However, human resource management fundamentally services as an administrator, managing compliance and does not do enough to methodically mitigate and manage acts of violence in the workplace and its effects on nurses' mental health. CONCLUSIONS: This systematic review contributes to the literature on violence in health care and proposes that human resource management must explore and implement practices towards mitigating violence against nurses. IMPACT: This systematic review will influence how human resource management currently manages violence against nurses and the increasing number of persons requiring health care due to the ageing population and decline in the number of nurses. It will also have an impact on action research to engage in a cycle of continuous improvement that supports eliminating violence against nurses (and all others) in the healthcare sector.

Ahead of time: Early sentence slow cortical modulations associated to semantic prediction.

According to prediction-based accounts of language comprehension, incoming contextual information is constantly used to guide the pre-activation of the most probable continuations to the unfolding sentences. However, there is still scarce evidence of the build-up of these predictions during sentence comprehension. Using event-related brain potentials, we investigated sustained processes associated to semantic prediction during online sentence comprehension. To address this, participants read sentences with varying levels of contextual constraint one word at a time. A 1000 ms interval preceded the final word, which could be congruent or incongruent. A slow sustained negativity developed gradually over the course of sentences, showing differences across conditions, with increasingly larger amplitudes for high than low levels of constraint. The effect was maximal in the interval preceding the closing word. This interval elicited a left-dominant slow negative potential with a graded amplitude modulation to contextual constraint, replicating previous results in speech comprehension. We argue that these slow potentials index the engagement of cognitive operations associated to semantic prediction. In addition, we replicated the finding of an earlier onset of the N400 effect (incongruent minus congruent) for high relative to low contextual constraint, suggesting facilitated processing for contextually-supported and highly expected words. Altogether, these results are consistent with prediction-based models of language comprehension and they also strengthen the value of investigating slow components as potential indices of mechanisms linked to language prediction.

Neurophysiological signatures of prediction in language: A critical review of anticipatory negativities.

Recent event-related potential (ERP) studies in language comprehension converge in finding anticipatory negativities preceding words or word segments that can be pre-activated based on either sentence contexts or phonological cues. We review these findings from different paradigms in the light of evidence from other cognitive domains in which slow negative potentials have long been associated with anticipatory processes and discuss their potential underlying mechanisms. We propose that this family of anticipatory negativities captures common mechanisms associated with the pre-activation of linguistic information both within words and within sentences. Future studies could utilize these anticipatory negativities in combination with other, well-established ERPs, to simultaneously track prediction-related processes emerging at different time intervals (before and after the perception of pre-activated input) and with distinct time courses (shorter-lived and longer-lived cognitive operations).

Can the knight capture the queen? The role of supramarginal gyrus in chess rule-retrieval as evidenced by a novel combined awake brain mapping and fMRI protocol.

Brain tumours represent a burden for society, not only due to the risks they entail but also because of the possibility of losing relevant cognitive functions for the patient's life after their resection. In the present study, we report how we monitored chess performance through a multimodal Electrical Stimulation Mapping (ESM) - functional Magnetic Resonance Imaging (fMRI) combined protocol. The ESM was performed under a left parietal lobe tumour resection surgery on a patient that expressed the desire to preserve his chess playing ability post-operative. We designed an ad-hoc protocol to evaluate processes involved in chess performance that could be potentially affected by the tumour location: (i) visual search, (ii) rule-retrieval, and (iii) anticipation of checkmate. The fMRI study reported functional regions for chess performance, some of them proximal to the lesion in the left parietal lobe. The most relevant result was a positive eloquent point encountered in the vicinity of the left supramarginal gyrus while performing the rule-retrieval task in the ESM. This functional region was convergent with the activations observed in the pre-operative fMRI study for this condition. The behavioural assessment comparison revealed post-operative an increase in reaction time in some tasks but correctness in performance was maintained. Finally, the patient maintained the ability to play chess after the surgery. Our results provide a plausible protocol for future interventions and suggest a role of the left supramarginal gyrus in chess cognitive operations for the case presented.

Philippine retinoblastoma initiative multi-eye center study 2010-2020.

AIM: To provide a comprehensive and more representative national data on the disease, especially on treatment options and outcomes, and to determine access of retinoblastoma patients from Luzon, Visayas and Mindanao to eye care, and determine if access is associated with delay in consultation, staging and outcomes. METHODS: Cohort study of retinoblastoma patients seen in eleven institutions located in the three major areas of the Philippines namely Luzon, Vizayas and Mindanao from 2010-2020. RESULTS: Totally 636 patients, involving 821 eyes, were included. Majority (57%) were from Luzon and were seen in institutions in Luzon (72%). Annually, 58±10 new cases were seen with 71% having unilateral disease. Median delay of consultation remained long at 9 (3, 17)mo, longest in patients with unilateral disease (P<0.02) and those from the Visayas (P<0.003). Based on the International Retinoblastoma Staging System, only 35% of patients had Stage 1 while 47% already had extraocular disease. Enucleation was the most common treatment received by 484 patients while intravenous chemotherapy was received by 469. There were 250 (39%) patients alive, 195 (31%) dead, 85 (13%) abandoned, 17 (3%) refused and 89 (14%) with no data. CONCLUSION: This study presents the largest cohort of retinoblastoma patients in the Philippines in terms of patients' and participating institutions' number and geographical location and type of institution (private and public). It also presents more comprehensive data on the treatments used and outcomes (survival, globe salvage, and vision retention rates). Delay in consultation was still long among patients leading to advanced disease stage and lower survival rate. Despite increasing capacity to diagnose and manage retinoblastoma in the country, the delay of consultation remains long primarily due to accessibility issues to eye care institutions especially in the Visayas and financial concerns. The delay was still significant that overall survival rate remain low.

Efficacy and Safety of Esketamine Nasal Spray in Patients with Treatment-Resistant Depression Who Completed a Second Induction Period: Analysis of the Ongoing SUSTAIN-3 Study.

BACKGROUND: Treatment-resistant depression (TRD) is a chronic illness requiring long-term treatment. Esketamine nasal spray (ESK) has been studied in several long-term trials of patients with TRD, including SUSTAIN-1 (NCT02493868) and SUSTAIN-3 (NCT02782104). This subgroup analysis of SUSTAIN-3 evaluated patients with TRD who received a second induction (IND) and maintenance treatment with ESK plus oral antidepressant (AD) after a relapse in SUSTAIN-1. METHODS: Patients aged 18-64 years who achieved stable remission or response with ESK and subsequently relapsed after randomization to continue ESK or switch to placebo nasal spray (PBO) in SUSTAIN-1 and entered the IND phase of SUSTAIN-3 were included in this interim analysis. Response (≥50% improvement in total score from baseline for Montgomery-Åsberg Depression Rating Scale [MADRS] and Patient Health Questionnaire 9-item [PHQ-9]), remission (MADRS score ≤12; PHQ-9 total score <5), changes in depression rating scores (measured as mean change from baseline), and safety were evaluated (incidence of treatment-emergent and serious adverse events [AE]). RESULTS: Of the 96 eligible patients who entered IND in SUSTAIN-3, 32 (33.3%) were taking ESK+AD at the time of relapse in SUSTAIN-1 and 64 (66.7%) were taking AD+PBO. Substantial improvements in depressive symptoms were observed over the second IND phase in both groups and were maintained over the optimization/maintenance (OP/M) phase. MADRS response rates following a second IND were 71.9% and 73.4% for previously relapsed (PR) ESK+AD and PR-AD+PBO, respectively; remission rates were 62.5% and 60.9%, respectively. During the IND and OP/M phases, 58.3% and 83.3% of patients experienced a treatment-emergent AE, respectively. No patients discontinued due to an AE during the second IND. CONCLUSIONS: Patients with TRD benefitted from receiving a second IND and maintenance treatment with ESK and no new safety signals were identified.

Depression and suicidality severity among TRD patients after 1-year under standard of care: Findings from the TRAL study, a multicenter, multinational, observational study in Latin America.

INTRODUCTION: Treatment resistant depression (TRD) is one of the most pressing issues in mental healthcare in LatAm. However, clinical data and outcomes of standard of care (SOC) are scarce. The present study reported on the Treatment-Resistant Depression in America Latina (TRAL) project 1-year follow-up of patients under SOC assessing clinical presentation and outcomes. MATERIALS AND METHODS: 420 patients with clinical diagnoses of TRD from Argentina, Brazil, Colombia and Mexico were included in a 1-year follow-up to assess clinical outcomes of depression (MADRS) and suicidality (C-SSRS), as well as evolution of clinical symptoms of depression. Patients were assessed every 3 months and longitudinal comparison was performed based on change from baseline to each visit and end of study (12 months). Socio demographic characterization was also performed. RESULTS: Most patients were female (80.9%), married (42.5%) or single (34.4%), with at least 10 years of formal education (71%). MDD diagnosis was set at 37.29 (SD=14.00) years, and MDD duration was 11.11 years (SD=10.34). After 1-year of SOC, 79.1% of the patients were still symptomatic, and 40% of the patients displayed moderate/severe depression. Only 44.1% of the patients achieved a response (≥50% improvement in MADRS), and 60% of the sample failed to achieve remission. Suicidal ideation was reported by more than half of the patients at the end of study. CONCLUSIONS: Depression and suicidality symptoms after a 1-year of SOC is of great concern. Better therapeutic options are needed to tackle this debilitating and burdensome disease.

Survivorship care planning in colorectal cancer: feedback from survivors & providers.

The Institute of Medicine recommended that all patients receive survivorship care plans (SCPs) post-treatment to improve quality of follow-up care. However, little is known regarding how survivors utilize SCPs and the congruency between providers' and survivors' perspectives. Feedback from colorectal cancer survivors (in receipt of a personalized/individualized SCP) and oncology providers was obtained via interviews. Survivors noted SCPs benefits of reduced duplicative procedures and cancer worry with the synthesized treatment information. Providers noted billing/reimbursement and time investiture (for form completion) as potential barriers. Further investigation of SCPs is warranted regarding utility prior to widespread adoption in follow-up care.

Montgomery-Åsberg Depression Rating Scale factors in treatment-resistant depression at onset of treatment: Derivation, replication, and change over time during treatment with esketamine.

OBJECTIVE: Derive and confirm factor structure of the Montgomery-Åsberg Depression Rating Scale (MADRS) in patients with treatment-resistant depression (TRD) and evaluate how the factors evident at baseline change over 4 weeks of esketamine treatment. METHODS: Two similarly-designed, short-term TRANSFORM trials randomized adults to esketamine or matching placebo nasal spray, each with a newly-initiated oral antidepressant, for 4 weeks (TRANSFORM-1: N = 342 patients; TRANSFORM-2: N = 223 patients). The factor structure of MADRS item scores at baseline was determined by exploratory factor analysis in TRANSFORM-2 and corroborated by confirmatory factor analysis in TRANSFORM-1. Change in MADRS factor scores from baseline (day 1) to the end of the 28-day double-blind treatment phase of TRANSFORM-2 was analyzed using a mixed-effects model for repeated measures (MMRM). RESULTS: Three factors were identified based on analysis of MADRS items: Factor 1 labeled affective and anhedonic symptoms (apparent sadness, reported sadness, lassitude, inability to feel), Factor 2 labeled anxiety and vegetative symptoms (inner tension, reduced sleep, reduced appetite, concentration difficulties), and Factor 3 labeled hopelessness (pessimistic thoughts, suicidal thoughts). The three-factor structure observed in TRANSFORM-2 was verified in TRANSFORM-1. Treatment benefit at 24 h with esketamine versus placebo was observed on all 3 factors and continued throughout the 4-week double-blind treatment period. CONCLUSIONS: A three-factor structure for MADRS appears to generalize to TRD. All three factors improved over 4 weeks of treatment with esketamine nasal spray.

Suicidality and Quality of Life in Treatment-Resistant Depression Patients in Latin America: Secondary Interim Analysis of the TRAL Study.

Background: A large proportion of patients with major depressive disorder (MDD) have treatment-resistant depression (TRD). The TRAL study examines the impact of TRD on suicidality and health-related quality of life (HRQoL) among MDD patients in 4 Latin American countries. Methods: In this multicenter, prospective, observational study, MDD patients were recruited from 33 sites in Mexico, Colombia, Brazil, and Argentina. Patients were assessed for TRD, defined as failure to respond to ≥2 antidepressant medications of adequate dose and duration. Other assessments included current disease status, Mini International Neuropsychiatric Interview (MINI), Columbia-Suicide Severity Rating Scale (C-SSRS), 5 Level EQ-5D (EQ-5D-5L), Patient Health Questionnaire-9 (PHQ-9), and Sheehan Disability Scale (SDS). Results: 1,475 MDD patients were included in the analysis (mean age, 45.6 years; 78% women), and 429 met criteria for TRD. Thoughts of suicide and suicide attempts were more common among TRD patients (38.7%) compared with non-TRD patients (24.9%; P < 0.0001), according to the current disease status questionnaire. The C-SSRS showed that lifetime suicidal behavior was significantly more common among TRD patients than non-TRD patients (13.8 vs. 10.0%; P = 0.0384). Compared with non-TRD patients, TRD patients showed significantly greater adverse impacts on QoL (EQ-5D-5L), more severe depression (PHQ-9), and greater functional impairment (SDS). Conclusion: TRD patients in clinical sites from Mexico, Colombia, Brazil, and Argentina were more likely to experience suicidality and negative effects on HRQoL than non-TRD patients.

Alpha power decreases associated with prediction in written and spoken sentence comprehension.

Alpha and beta power decreases have been associated with prediction in a variety of cognitive domains. Recent studies in sentence comprehension have also reported alpha and/or beta power decreases preceding contextually predictable words, albeit with remarkable spatiotemporal variability across reports. To contribute to the understanding of the mechanisms underlying this phenomenon, and the sources of variability, the present study explored to what extent these prediction-related alpha and beta power decreases might be common across different modalities of comprehension. To address this, we re-analysed the data of two EEG experiments that employed the same materials in written and in spoken comprehension. Sentence contexts were weakly or strongly constraining about a sentence-final word, which was presented after a 1 s delay, either matching or mismatching the expectation. In written comprehension, alpha power (8-12 Hz) decreased before final words appearing in strongly (relative to weakly) constraining contexts, in line with previous reports. Furthermore, a similar oscillatory phenomenon was evidenced in spoken comprehension, although with relevant spatiotemporal differences. Altogether, the findings agree with the involvement of both modality-specific and general-domain mechanisms in the elicitation of prediction-related alpha power decreases in sentence comprehension. Specifically, we propose that this phenomenon might partly reflect richer and more precise information representation when linguistic contexts afford prediction.

Mortality and biochemical recurrence after surgery, brachytherapy, or external radiotherapy for localized prostate cancer: a 10-year follow-up cohort study.

To compare the effectiveness at ten years of follow-up of radical prostatectomy, brachytherapy and external radiotherapy, in terms of overall survival, prostate cancer-specific mortality and biochemical recurrence. Cohort of men diagnosed with localized prostate cancer (T1/T2 and low/intermediate risk) from ten Spanish hospitals, followed for 10 years. The treatment selection was decided jointly by patients and physicians. Of 704 participants, 192 were treated with open radical retropubic prostatectomy, 317 with 125I brachytherapy alone, and 195 with 3D external beam radiation. We evaluated overall survival, prostate cancer-specific mortality, and biochemical recurrence. Kaplan-Meier estimators were plotted, and Cox proportional-hazards regression models were constructed to estimate hazard ratios (HR), adjusted by propensity scores. Of the 704 participants, 542 patients were alive ten years after treatment, and a total of 13 patients have been lost during follow-up. After adjusting by propensity score and Gleason score, brachytherapy and external radiotherapy were not associated with decreased 10-year overall survival (aHR = 1.36, p = 0.292 and aHR = 1.44, p = 0.222), but presented higher biochemical recurrence (aHR = 1.93, p = 0.004 and aHR = 2.56, p < 0.001) than radical prostatectomy at ten years of follow-up. Higher prostate cancer-specific mortality was also observed in external radiotherapy (aHR = 9.37, p = 0.015). Novel long-term results are provided on the effectiveness of brachytherapy to control localized prostate cancer ten years after treatment, compared to radical prostatectomy and external radiotherapy, presenting high overall survival, similarly to radical prostatectomy, but higher risk of biochemical progression. These findings provide valuable information to facilitate shared clinical decision-making.Study identifier at ClinicalTrials.gov: NCT01492751.

Role of radiation therapy in the multidisciplinary management of Ewing's Sarcoma of bone in pediatric patients: An effective treatment for local control.

BACKGROUND: Radiotherapy (RT) plays an important role in the multidisciplinary management of Ewing's Sarcoma (ES), especially in unresectable cases. AIM: Assessment of efficacy of RT in terms of local control in pediatric patients with primary ES of bone. MATERIALS AND METHODS: Thirty-six patients younger than 17 years old with ES treated with combined RT and chemotherapy with (N = 14) or without (N = 22) prior surgery from 1981 to 2008 were retrospectively reviewed. Since 1995, they were all treated according to the Spanish Society of Pediatric Oncology protocol (55.5% cases). Those patients received vincristine, ifosfamide, doxorubicin and etoposide. The TNM classification was as follows: 17 T1, 18 T2 and 1 T3; 36 N0; 29 M0, 5 M1a and 2 M1b. Analysis was stratified by treatment: definitive RT or pre/postoperative RT. RESULTS: The 36 patients (21 male; 15 female) had a median age of 10 years (range 2-17 years). Median follow-up of living patients was 105 months. The 2-year local control (LC) rate for all patients was 88%. Five-year LC rates for patients treated with definitive and pre/postoperative RT were 91% and 86%, respectively. Two-year overall survival and disease-free survival rates for all patients were 68% and 66%, respectively. Low phosphatase alkaline levels and local and distant recurrences were significantly predictive of worse prognosis (P = 0.021, P = 0.011, P = 0.007, respectively). CONCLUSION: Radiotherapy with and without surgery is a highly effective local treatment option in the multidisciplinary management of ES in pediatric patients.