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In RISE, TV46000 once monthly (q1m) or once every 2 months (q2m) significantly extended time to impending schizophrenia relapse. The current study (SHINE, NCT03893825) evaluated the long-term safety, tolerability, and effect of TV46000.
Methods
Patients completing RISE without relapse (rollover) or newly recruited (de novo) were eligible. The de novo and placebo rollover cohorts were randomized 1:1 to q1m or q2m for ≤56 weeks; the TV46000 rollover cohort continued assigned regimen. Exploratory efficacy endpoints included time to impending relapse and patient centered outcomes (PCOs) including Schizophrenia Quality of Life Scale (SQLS).
Results
334 patients were randomized and received TV46000 q1m (n=172) or q2m (n=162), for 202.3 patient-years [PY] of TV-46000 treatment. Treatment-emergent adverse events (AEs) reported for ≥5% of patients were: overall–injection site pain (event rate/100 PY, n [%]; 23.23, 16 [5%]); de novo (n=109)–injection site pain (56.10, 11 [10%]), injection site nodule (16.03, 6 [6%]), blood creatine phosphokinase increased (16.03, 8 [7%]), urinary tract infection (10.69, 7 [6%]); placebo rollover (n=53)–tremor (18.50, 5 [9%]); TV46000 rollover (n=172)–headache (7.97, n=8 [5%]). Serious AEs reported for ≥2 patients were worsening schizophrenia and hyperglycemia. Kaplan– Meier estimates for remaining relapse-free at week 56 were 0.98 (2% risk; q1m) and 0.88 (12%; q2m). SQLS improved for q1m (least-squares mean change [SE], − 2.16 [0.98]) and q2m (− 0.43 [0.98]); other PCOs (5Level EuroQoL 5Dimensions Questionnaire, Personal and Social Performance Scale, Drug Attitudes Inventory 10-item version) remained stable.
Conclusions
TV-46000 had a favorable long-term benefit–risk profile in patients with schizophrenia.
Neoclassical economics (NCE) theory and neoliberal economics practice together form one of the principal driving forces of environmental destruction and social injustice. We critically examine ten key hypotheses that form the foundations of NCE, and four other claims. Each fails to satisfy one or more of the basic requirements of scientific practice. Hence, NCE is fundamentally flawed, is irrational in the common meaning of the word, and should not be used as a guide for government policies. Because NCE is socially constructed, it can be replaced with an interdisciplinary conceptual framework that is compatible with ecological sustainability and social justice.
Technical summary
Neoclassical economics (NCE) is widely regarded as providing theoretical justification for neoliberal notions such as ‘governments should minimize regulation and spending, and hence leave major socioeconomic and environmental decisions to the market’. A large body of literature finds that NCE is largely responsible for environmental destruction and social inequality. As NCE is claimed to be a science and has appropriated terminology (without the content) from physics, we examine critically its basic hypotheses and four other claims from a viewpoint of natural scientists and an ecological economist, each a sustainability researcher. This paper defines NCE in two ways: as a theoretical structure for economics based on (1) the hypotheses of methodological individualism, methodological instrumentalism and methodological equilibration, and (2) the three hypotheses named above together with seven other common hypotheses of NCE. We find that each hypothesis and claim fails to satisfy one or more basic requirements of scientific practice such as empirical confirmation, underlying credible or empirical assumptions, consistency with Earth system science, and internal consistency. Sensitivity analysis is rare and ability to predict is lacking. Therefore, we recommend that neoclassical microeconomics be reformed and neoclassical macroeconomics be abandoned and replaced with a transdisciplinary field such as social ecological economics.
Social media summary
Conventional economics, a driver of environmental damage and social inequality, fails examination by sustainability scientists.
In this chapter, we explore the main themes and ideas emerging from the final six books to be published during Zygmunt Bauman's lifetime: Practices of Selfhood (Bauman and Raud 2015), Of God and Man (Bauman and Obirek 2015a), On the World and Ourselves (Bauman and Obirek 2015b), Liquid Evil (Bauman and Donskis 2016), Babel (Bauman and Mauro 2016) and Strangers at Our Door (Bauman 2016).1 What is immediately striking about these lesser-known books is that five of them follow the format of a conversation. In adopting this format, Bauman is following a form of sociological practice inspired by a method of hermeneutics (Dawson 2015, 2017; Davis 2013, 2020), evident since his earliest works in both Polish and English (Bauman 1962, 1965; Brzezin´ski 2017), as part of a sustained commitment to open and inclusive dialogue as the best solution to society's most urgent problems.
Throughout his long vocation as a sociologist, Bauman chased new ways of unmasking various forms of fundamentalist thinking in order to open up spaces for true dialogue between people who do not begin from a position of agreement. Bauman's thoughts in these later books are not always “new.” Presented in a more accessible style, they are written to engage an educated and curious audience “out there” in civil society, rather than “in here” amongst the Academy. Yet for the rich variety of different topics covered in these books, they remain firmly rooted in his best-known academic insights. First, that today the enduring social ills of rampant individualism and growing social division must be confronted head-on to save democracy and its principle of collective provision against individual misfortune. And second, that the best remedy against these ills remains the pursuit of “true dialogue” by embracing the difficult art of conversation. After all, why privilege the “new” when both the problem and its solution may require repetition rather than novelty? (Tester 2018).
In attempting to understand the richness and complexity of Bauman's writing across more than six decades, it is important to grasp both the breadth of that material and the methodological core that provides it with its sense of coherence.
There is accumulating evidence that distinct forms of domain-general inhibition underlie the selection of lexical candidates from among co-activated representations in single-word production. It is less clear whether similar control processes are engaged in the resolution of syntactic conflict in sentence production. This study assessed the relative contribution of three types of inhibitory control operating at different stages of information processing to syntactic interference resolution in an active-passive voice production task. Inhibition of response execution (the anti-saccade effect) and resolution of representational conflict (the flanker effect) were related to the occurrence of repairs and sentence onset latencies in passive voice trials. The results suggest not only that general-purpose mechanisms may be in place that resolve conflict regardless of whether it stems from syntactic or non-syntactic (non-verbal) representations, but also that they operate at dissociable processing stages.
Depression and anxiety are common and highly comorbid, and their comorbidity is associated with poorer outcomes posing clinical and public health concerns. We evaluated the polygenic contribution to comorbid depression and anxiety, and to each in isolation.
Methods
Diagnostic codes were extracted from electronic health records for four biobanks [N = 177 865 including 138 632 European (77.9%), 25 612 African (14.4%), and 13 621 Hispanic (7.7%) ancestry participants]. The outcome was a four-level variable representing the depression/anxiety diagnosis group: neither, depression-only, anxiety-only, and comorbid. Multinomial regression was used to test for association of depression and anxiety polygenic risk scores (PRSs) with the outcome while adjusting for principal components of ancestry.
Results
In total, 132 960 patients had neither diagnosis (74.8%), 16 092 depression-only (9.0%), 13 098 anxiety-only (7.4%), and 16 584 comorbid (9.3%). In the European meta-analysis across biobanks, both PRSs were higher in each diagnosis group compared to controls. Notably, depression-PRS (OR 1.20 per s.d. increase in PRS; 95% CI 1.18–1.23) and anxiety-PRS (OR 1.07; 95% CI 1.05–1.09) had the largest effect when the comorbid group was compared with controls. Furthermore, the depression-PRS was significantly higher in the comorbid group than the depression-only group (OR 1.09; 95% CI 1.06–1.12) and the anxiety-only group (OR 1.15; 95% CI 1.11–1.19) and was significantly higher in the depression-only group than the anxiety-only group (OR 1.06; 95% CI 1.02–1.09), showing a genetic risk gradient across the conditions and the comorbidity.
Conclusions
This study suggests that depression and anxiety have partially independent genetic liabilities and the genetic vulnerabilities to depression and anxiety make distinct contributions to comorbid depression and anxiety.
Accurate triage is crucial for pediatric patients because their physiological differences make them more vulnerable to traumatic injury and mortality. However, pediatric trauma patients are challenging for EMS personnel for several reasons including infrequent clinical encounters and inadequate training. Despite the need for increased training, little is known about EMS readiness to perform triage and lifesaving interventions during pediatric mass casualty incidents (MCIs). Simulation skills assessment correlates with EMS performance in the field and can be used to determine MCI readiness.Pediatric patients are often omitted from MCI training and protocols. Feedback from EMS clinicians who participate in pediatric MCI simulations may be useful for educators seeking to optimize pediatric mass shooting triage training.
Method:
This was an observational study assessing EMS clinician accuracy in triaging eight children and two adults in a mass shooting simulation involving intimate partner violence (IPV) set at a private residence. Participating EMS clinicians were attendees of continuing education classes at Yale New Haven Health Centers for EMS. Participants worked in pairs, and triage decisions were documented during the simulation with an evaluation tool and video recording. After the simulation, pairs completed the demographic survey and completed a semi-structured debriefing. Facilitator prompts included correct triage level for each patient, the role IPV plays in mass shootings, and the participants feedback. Recordings of the debriefings were transcribed and analyzed using grounded theory. During the evaluation process, the major themes will be identified and coded. The transcriptions will be re-evaluated and any additional sub-themes will be identified and coded.
Results:
As of November 2022, eight paramedics have participated with more sessions scheduled for spring 2023. A preliminary review indicates potential themes will fall under the categories of simulation implementation and clinical approach to triage.
Conclusion:
These findings may assist EMS agencies with their pediatric MCI training and response.
The Affective Neuroscience Personality Scales (ANPS) were designed to provide researchers in the mental sciences with an inventory to assess primary emotional systems according to Pankseppian Affective Neuroscience Theory (ANT). The original ANPS, providing researchers with such a tool, was published in 2003. In the present brief communication, about 20 years later, we reflect upon some pressing matters regarding the further development of the ANPS. We touch upon problems related to disentangling traits and states of the primary emotional systems with the currently available versions of the ANPS and upon its psychometric properties and its length. We reflect also on problems such as the large overlap between the SADNESS and FEAR dimensions, the disentangling of PANIC and GRIEF in the context of SADNESS, and the absence of a LUST scale. Lastly, we want to encourage scientists with the present brief communication to engage in further biological validation of the ANPS.
A unique collaboration between an academic and a practitioner, this book tells the story of money, from ancient Athens to the Bitcoin revolution, to explain how crowdfunding is the way for people to reclaim the power of their money in pursuit of a fairer and greener society.
OBJECTIVES/GOALS: Immunomodulatory drugs (IMiDs) are critical to multiple myeloma (MM) disease control. IMiDs act by inducing Cereblon-dependent degradation of IKZF1 and IKZF3, which leads to IRF4 and MYC downregulation (collectively termed the “Ikaros axis”). We therefore hypothesized that IMiD treatment fails to downregulate the Ikaros axis in IMiD resistant MM. METHODS/STUDY POPULATION: To measure IMiD-induced Ikaros axis downregulation, we designed an intracellular flow cytometry assay that measured relative protein levels of IKZF1, IKZF3, IRF4 and MYC in MM cells following ex vivo treatment with the IMiD Pomalidomide (Pom). We established this assay using Pom-sensitive parental and dose-escalated Pom-resistant MM cell lines before assessing Ikaros axis downregulation in CD38+CD138+ MM cells in patient samples (bone marrow aspirates). To assess the Ikaros axis in the context of MM intratumoral heterogeneity, we used a 35-marker mass cytometry panel to simultaneously characterize MM subpopulations in patient samples. Lastly, we determined ex vivo drug sensitivity in patient samples via flow cytometry. RESULTS/ANTICIPATED RESULTS: Our hypothesis was supported in MM cell lines, as resistant lines showed no IMiD-induced decrease in any Ikaros axis proteins. However, when assessed in patient samples, Pom treatment caused a significant decrease in IKZF1, IKZF3 and IRF4 regardless of IMiD sensitivity. Mass cytometry in patient samples revealed that individual Ikaros axis proteins were differentially expressed between subpopulations. When correlating this with ex vivo Pom sensitivity of MM subpopulations, we observed that low IKZF1 and IKZF3 corresponded to Pom resistance. Interestingly, most of these resistant populations still expressed MYC. We therefore assessed whether IMiD resistant MM was MYC dependent by treating with MYCi975. In 88% (7/8) of patient samples tested, IMiD resistant MM cells were sensitive to MYC inhibition. DISCUSSION/SIGNIFICANCE: While our findings did not support our initial hypothesis, our data suggest a mechanism where MYC expression becomes Ikaros axis independent to drive IMiD resistance, and resistant MM is still dependent on MYC. This suggests targeting MYC directly or indirectly via a mechanism to be determined may be an effective strategy to eradicate IMiD resistant MM.
This chapter provides an overview of the common medicines prescribed within mental health care and explores the ways in which personal narratives and social expectations can influence the experience of taking medicines. The chapter also looks at concepts and practices that influence the management of medicines and encourage safe and high-quality use of medicines. These concepts include consumer experience, concordance, and shared decision-making. Facilitating a positive experience of medicinal use requires quality communication and team work, whereby nurses, psychologists, occupational therapists, dietitians, medical practitioners and pharmacists work in partnership with the consumer and carer.
Assessment in the mental health field is a dynamic process of learning, using experience and applying multiple sources of knowledge and evidence. This chapter presents an overview of assessment practices and processes undertaken within formal mental health care and discusses these within the context of consumer–health practitioner partnerships. We start by considering how assessment practices are a prominent feature of understanding a person’s situation and life context, and how these need to be based on the principles of person-centred, trauma-informed care and cultural safety. We discuss the importance of engagement and therapeutic relationships skills in ensuring consumers, carers and family members are meaningfully connected within a process for identifying the mental health problems the person is experiencing. Part of this awareness is reflecting on what it is like for a person to be assessed, and the power dynamics involved in naming experience, symptoms and diagnosis. The chapter then looks at the paradigm of comprehensive assessment, with specific discussions about strengths-based assessment, mental state examination and the roles of different health professionals.
This chapter introduces the concept of mental illness, how it is diagnosed, and the main diagnostic classification systems used in health practice. The experiences and symptoms of people living with mental illness – according to criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 – are reviewed. It is emphasised that diagnostic criteria can be considered within an overall framework for conversation and engagement between practitioners, consumers, and carers, with the overarching aim of exploring and understanding the best response to distress and treatment approach to promote recovery processes. Criticisms towards diagnostic classification systems are also summarised. Finally, potential effects of the COVID-19 pandemic and its implication for people’s mental health are presented.
Readers of this book will have thought deeply about how to collaborate with and support people with a mental illness, their families and carers. The preceding chapters have given considerable emphasis to a narrative approach. This final chapter discusses leadership, particularly for new entrants into mental health settings.Effective clinical care is person and family centred. It seeks to understand and involve consumers, carers and families in rich discussions about their needs, preferences and values. This understanding and involvement is combined with evidence-based practice to support consumers in their treatment and recovery goals.At the heart of the decision to take this approach has been the fundamental belief in human connectedness. By working through this text, readers have been challenged to think about how and when to move in new ways when working with resilient and vulnerable people, which is helpful across a range of practice settings when seeking to make a difference in the lives of people experiencing a mental illness. While this is important in providing a theoretical and practical basis for care, it is at the point of care that effective leadership is required.
Readers of this book will have thought deeply about how to collaborate with and support people with a mental illness, their families and carers. The preceding chapters have given considerable emphasis to a narrative approach. This final chapter discusses leadership, particularly for new entrants into mental health settings.Effective clinical care is person and family centred. It seeks to understand and involve consumers, carers and families in rich discussions about their needs, preferences and values. This understanding and involvement is combined with evidence-based practice to support consumers in their treatment and recovery goals.At the heart of the decision to take this approach has been the fundamental belief in human connectedness. By working through this text, readers have been challenged to think about how and when to move in new ways when working with resilient and vulnerable people, which is helpful across a range of practice settings when seeking to make a difference in the lives of people experiencing a mental illness. While this is important in providing a theoretical and practical basis for care, it is at the point of care that effective leadership is required.
Assessment in the mental health field is a dynamic process of learning, using experience and applying multiple sources of knowledge and evidence. This chapter presents an overview of assessment practices and processes undertaken within formal mental health care and discusses these within the context of consumer–health practitioner partnerships. We start by considering how assessment practices are a prominent feature of understanding a person’s situation and life context, and how these need to be based on the principles of person-centred, trauma-informed care and cultural safety. We discuss the importance of engagement and therapeutic relationships skills in ensuring consumers, carers and family members are meaningfully connected within a process for identifying the mental health problems the person is experiencing. Part of this awareness is reflecting on what it is like for a person to be assessed, and the power dynamics involved in naming experience, symptoms and diagnosis. The chapter then looks at the paradigm of comprehensive assessment, with specific discussions about strengths-based assessment, mental state examination and the roles of different health professionals.
This chapter introduces the concept of mental illness, how it is diagnosed, and the main diagnostic classification systems used in health practice. The experiences and symptoms of people living with mental illness – according to criteria from the Diagnostic and Statistical Manual of Mental Disorders (DSM)-5 – are reviewed. It is emphasised that diagnostic criteria can be considered within an overall framework for conversation and engagement between practitioners, consumers, and carers, with the overarching aim of exploring and understanding the best response to distress and treatment approach to promote recovery processes. Criticisms towards diagnostic classification systems are also summarised. Finally, potential effects of the COVID-19 pandemic and its implication for people’s mental health are presented.
This chapter provides an overview of the common medicines prescribed within mental health care and explores the ways in which personal narratives and social expectations can influence the experience of taking medicines. The chapter also looks at concepts and practices that influence the management of medicines and encourage safe and high-quality use of medicines. These concepts include consumer experience, concordance, and shared decision-making. Facilitating a positive experience of medicinal use requires quality communication and team work, whereby nurses, psychologists, occupational therapists, dietitians, medical practitioners and pharmacists work in partnership with the consumer and carer.
To improve maternal health outcomes, increased diversity is needed among pregnant people in research studies and community surveillance. To expand the pool, we sought to develop a network encompassing academic and community obstetrics clinics. Typical challenges in developing a network include site identification, contracting, onboarding sites, staff engagement, participant recruitment, funding, and institutional review board approvals. While not insurmountable, these challenges became magnified as we built a research network during a global pandemic. Our objective is to describe the framework utilized to resolve pandemic-related issues.
Methods:
We developed a framework for site-specific adaptation of the generalized study protocol. Twice monthly video meetings were held between the lead academic sites to identify local challenges and to generate ideas for solutions. We identified site and participant recruitment challenges and then implemented solutions tailored to the local workflow. These solutions included the use of an electronic consent and videoconferences with local clinic leadership and staff. The processes for network development and maintenance changed to address issues related to the COVID-19 pandemic. However, aspects of the sample processing/storage and data collection elements were held constant between sites.
Results:
Adapting our consenting approach enabled maintaining study enrollment during the pandemic. The pandemic amplified issues related to contracting, onboarding, and IRB approval. Maintaining continuity in sample management and clinical data collection allowed for pooling of information between sites.
Conclusions:
Adaptability is key to maintaining network sites. Rapidly changing guidelines for beginning and continuing research during the pandemic required frequent intra- and inter-institutional communication to navigate.
Lithium is viewed as the first-line long-term treatment for prevention of relapse in people with bipolar disorder.
Aims
This study examined factors associated with the likelihood of maintaining serum lithium levels within the recommended range and explored whether the monitoring interval could be extended in some cases.
Method
We included 46 555 lithium rest requests in 3371 individuals over 7 years from three UK centres. Using lithium results in four categories (<0.4 mmol/L; 0.40–0.79 mmol/L; 0.80–0.99 mmol/L; ≥1.0 mmol/L), we determined the proportion of instances where lithium results remained stable or switched category on subsequent testing, considering the effects of age, duration of lithium therapy and testing history.
Results
For tests within the recommended range (0.40–0.99 mmol/L categories), 84.5% of subsequent tests remained within this range. Overall, 3 monthly testing was associated with 90% of lithium results remaining within range, compared with 85% at 6 monthly intervals. In cases where the lithium level in the previous 12 months was on target (0.40–0.79 mmol/L; British National Formulary/National Institute for Health and Care Excellence criteria), 90% remained within the target range at 6 months. Neither age nor duration of lithium therapy had any significant effect on lithium level stability. Levels within the 0.80–0.99 mmol/L category were linked to a higher probability of moving to the ≥1.0 mmol/L category (10%) compared with those in the 0.4–0.79 mmol/L group (2%), irrespective of testing frequency.
Conclusion
We propose that for those who achieve 12 months of lithium tests within the 0.40–0.79 mmol/L range, the interval between tests could increase to 6 months, irrespective of age. Where lithium levels are 0.80–0.99 mmol/L, the test interval should remain at 3 months. This could reduce lithium test numbers by 15% and costs by ~$0.4 m p.a.