“Skills to Enhance Positivity” (STEP) is a two-part positive affect program designed to decrease recurrent suicidal behavior in adolescents hospitalized due to suicide risk. Here, we describe the ...initial pilot phase in which the intervention was developed and modified based on a sample of 20 adolescent participants, aged 12 to 18 years old (Mage = 15.9, SD = 1.5). STEP consisted of an in-person phase (four sessions) and a remote delivery phase (text messaging and phone calls). The inpatient sessions focused on psychoeducation of positive affect, mindfulness meditation, gratitude, and savoring. The remote delivery phase comprised of weekly phone calls and daily text messages to enhance mood monitoring and skills practice reminders. Average session attendance was 81%, and mean daily response rate to text messages was 73.6%, demonstrating high engagement. STEP was described as good or excellent by over 90% of parents and 100% of adolescents. Only one participant had a suicide attempt, and five were readmitted for suicidality in the following 6 months, fewer than comparable naturalistic studies. Although preliminary results are promising, larger randomized trials are needed to determine the efficacy of STEP in reducing suicidal behaviors.
Understanding suicide ideation (SI) in adolescents, especially during the high‐risk time following hospitalization for a suicidal event, is a crucial component of improving risk assessment. Most ...studies rely on single assessments of SI, despite the potential for SI to vary considerably over time. This study examined how indices of SI intensity (mean values) and lability (mean squared successive difference values) over a 6‐month period predict suicide attempts (SAs) and self‐harm, as well as how they relate to psychosocial risk factors and affective functioning, in a sample of 103 adolescents hospitalized for a SA or significant SI. Across the sample, SI intensity, but not lability, was associated with SAs and nonsuicidal self‐injury at 6‐month follow‐up. SI intensity performed similarly to single time point SI assessments, and its relations were not moderated by SI lability. SI intensity was also associated with borderline personality disorder criteria and a history of sexual abuse. In contrast, SI lability was associated with greater negative affect intensity and lability. These findings suggest that intensity of SI may confer more risk posthospitalization, and provide support for using these statistical methods to capture two distinct parameters of SI.
Prospective predictors of persistent nonsuicidal self‐injury (NSSI) were examined in adolescents admitted to an inpatient psychiatric unit for suicidal behaviors and followed naturalistically for ...6 months. Seventy‐one (77%) participants reported NSSI at baseline, and 40 (56%) persisted at the 6 month follow‐up. Those who endorsed automatic positive reinforcement (APR) as the predominant reason for NSSI were more likely to persist in NSSI. Depression over follow‐up, but not at baseline, also predicted persistence. These results suggest that helping high‐risk adolescents to identify alternative ways of generating emotion(s) to counter the effects of APR that may accompany NSSI should be a high priority treatment target.
Understanding suicide ideation (SI) in adolescents, especially during the high risk time following hospitalization for a suicidal event, is a crucial component of improving risk assessment. Most ...studies rely on single assessments of SI, despite the potential for SI to vary considerably over time. The present study examined how indices of SI intensity (mean values) and lability (mean squared successive difference values) over a six-month period predict suicide attempts and self-harm, as well as how they relate to psychosocial risk factors and affective functioning, in a sample of 103 adolescents hospitalized for a suicide attempt or significant suicide ideation. Across the sample, SI intensity, but not lability, was associated with suicide attempts and nonsuicidal self-injury at six-month follow-up. SI intensity performed similarly to single time point SI assessments, and its relations were not moderated by SI lability. SI intensity was also associated with borderline personality disorder criteria and a history of sexual abuse. In contrast, SI lability was associated with greater negative affect intensity and lability. These findings suggest that intensity of SI may confer more risk post-hospitalization, and provide support for using these statistical methods to capture two distinct parameters of suicide ideation.
This study examined prospective predictors of persistent non-suicidal self-injury (NSSI) in adolescents admitted to an inpatient psychiatric unit for suicidal behaviors and followed naturalistically ...for six months. Seventy-one (77%) participants reported NSSI at baseline and 40 (56%) persisted at the six month follow-up. Those who endorsed automatic positive reinforcement (APR) as the predominant reason for NSSI, were more likely to persist in NSSI. Depression over follow-up, but not at baseline, also predicted persistence. These results suggest that helping high risk adolescents to identify alternative ways of generating emotion(s) to counter the effects of APR that may accompany NSSI, should be a high priority treatment target.
Modern Orthodox Judaismoffers an extensive selection of primary texts documenting the Orthodox encounter with American Judaism that led to the emergence of the Modern Orthodox movement. Many texts in ...this volume are drawn from episodes of conflict that helped form Modern Orthodox Judaism. These include the traditionalists' response to the early expressions of Reform Judaism, as well as incidents that helped define the widening differences between Orthodox and Conservative Judaism in the early twentieth century. Other texts explore the internal struggles to maintain order and balance once Orthodox Judaism had separated itself from other religious movements.Zev Eleff combines published documents with seldom-seen archival sources in tracing Modern Orthodoxy as it developed into a structured movement, established its own institutions, and encountered critical events and issues-some that helped shape the movement and others that caused tension within it. A general introduction explains the rise of the movement and puts the texts in historical context. Brief introductions to each section guide readers through the documents of this new, dynamic Jewish expression.
Ensuring that evidence-based interventions for people with alcohol use disorders (AUD) are acceptable, effective, and feasible in different socio-cultural and health system contexts is essential. We ...previously adapted a model of integration of AUD interventions for the Tanzanian primary healthcare system. This pilot study aimed to assess the impact on AUD detection and the acceptability and feasibility of the facility-based components of this model from the perspective of healthcare providers (HCPs).
This mixed-methods study comprised a pre-post quasi-experimental study and a qualitative study. The integrated model included training HCPs in managing AUD, introducing systematic screening for AUD, documentation of AUD service utilization, and supportive supervision. We collected information on the number of people identified for AUD three months before and after piloting the service model. A non-parametric trend test, a distribution-free cumulative sum test, was used to identify a change in the identification rate of AUD beyond that observed due to secular trends or, by chance, three months before and after implementing the integrated AUD facility-based interventions. The Mann-Kendal test was used to assess the statistical significance of the trend. We conducted three focus group discussions exploring the experience of HCPs and their perspectives on facilitators, barriers, and strategies to overcome them. The focus group discussions were analyzed using thematic analysis.
During the pre-implementation phase of the facility-based interventions of the adapted AUD model, HCPs assessed 322 people for AUD over three months, ranging from a minimum of 99 to a maximum of 122 per month. Of these, 77 were identified as having AUD. Moreover, HCPs screened 2058 people for AUD during implementation; a minimum of 528 to a maximum of 843 people were screened for AUD per month for the three months. Of these, 514 screened positive for AUD (AUDIT ≥ 8). However, this change in screening for AUD was not statistically significant (p-value = 0.06). HCPs reported that knowledge and skills from the training helped them identify and support people they would not usually consider having problematic alcohol use. Perceived barriers to implementation included insufficient health personnel compared to needs and inconvenient health management information systems. HCPs proposed strategies to overcome these factors and recommended multisectoral engagement beyond the health system.
Although the change in the trend in the number of people screened for AUD by HCPs post-implementation was not statistically significant, it is still feasible to implement the facility-based components of the adapted integrated AUD model while addressing the identified bottlenecks and strategies for implementation. Therefore, a large-scale, adequately powered implementation feasibility study is needed. Findings from this study will be used to finalize the adapted model for integrating AUD interventions for future implementation and larger-scale evaluation.
Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment of haematological malignancies such as acute lymphoblastic leukaemia, B cell lymphoma and multiple myeloma
, but the ...efficacy of CAR T cell therapy in solid tumours has been limited
. This is owing to a number of factors, including the immunosuppressive tumour microenvironment that gives rise to poorly persisting and metabolically dysfunctional T cells. Analysis of anti-CD19 CAR T cells used clinically has shown that positive treatment outcomes are associated with a more 'stem-like' phenotype and increased mitochondrial mass
. We therefore sought to identify transcription factors that could enhance CAR T cell fitness and efficacy against solid tumours. Here we show that overexpression of FOXO1 promotes a stem-like phenotype in CAR T cells derived from either healthy human donors or patients, which correlates with improved mitochondrial fitness, persistence and therapeutic efficacy in vivo. This work thus reveals an engineering approach to genetically enforce a favourable metabolic phenotype that has high translational potential to improve the efficacy of CAR T cells against solid tumours.
Recent large-scale randomised trials demonstrate that immunomodulators reduce cardiovascular (CV) events among the general population. However, it is uncertain whether these effects apply to ...rheumatoid arthritis (RA) and if certain treatment strategies in RA reduce CV risk to a greater extent.
Patients with active RA despite use of methotrexate were randomly assigned to addition of a tumour necrosis factor (TNF) inhibitor (TNFi) or addition of sulfasalazine and hydroxychloroquine (triple therapy) for 24 weeks. Baseline and follow-up
F-fluorodeoxyglucose-positron emission tomography/CT scans were assessed for change in arterial inflammation, an index of CV risk, measured as an arterial target-to-background ratio (TBR) in the carotid arteries and aorta.
115 patients completed the protocol. The two treatment groups were well balanced with a median age of 58 years, 71% women, 57% seropositive and a baseline disease activity score in 28 joints of 4.8 (IQR 4.0, 5.6). Baseline TBR was similar across the two groups. Significant TBR reductions were observed in both groups-ΔTNFi: -0.24 (SD=0.51), Δtriple therapy: -0.19 (SD=0.51)-without difference between groups (difference in Δs: -0.02, 95% CI -0.19 to 0.15, p=0.79). While disease activity was significantly reduced across both treatment groups, there was no association with change in TBR (β=0.04, 95% CI -0.03 to 0.10).
We found that addition of either a TNFi or triple therapy resulted in clinically important improvements in vascular inflammation. However, the addition of a TNFi did not reduce arterial inflammation more than triple therapy.
NCT02374021.
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