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No drugs are currently approved for the treatment of borderline personality disorder (BPD). These studies (a randomised study and its open-label extension) aimed to evaluate the efficacy, safety and tolerability of brexpiprazole for the treatment of BPD.
Methods:
The Phase 2, multicentre, randomised, double-blind, placebo-controlled, parallel-group study enrolled adult outpatients with BPD. After a 1-week placebo run-in, patients were randomised 1:1 to brexpiprazole 2–3 mg/day (flexible dose) or placebo for 11 weeks. The primary endpoint was change in Zanarini Rating Scale for BPD total score from randomisation (Week 1) to Week 10 (timing of randomisation and endpoint blinded to investigators and patients). The Phase 2/3, multicentre, open-label extension study enrolled patients who completed the randomised study; all patients received brexpiprazole 2–3 mg/day (flexible dose) for 12 weeks. Safety assessments included treatment-emergent adverse events (TEAEs).
Results:
Brexpiprazole was not statistically significantly different from placebo on the primary endpoint of the randomised study (N = 324 randomised; N = 110 analysed per treatment group; least squares mean difference −1.02; 95% confidence limits −2.75, 0.70; p = 0.24). Numerical efficacy advantages for brexpiprazole were observed at other time points. The most common TEAE in the randomised study was akathisia (brexpiprazole, 14.0%; placebo, 1.2%); data from the open-label study (N = 199 analysed) suggested that TEAEs were transient.
Conclusion:
The primary endpoint of the randomised study was not met. Further research on brexpiprazole in BPD is warranted based on possible efficacy signals at other time points and its safety profile.
In South Korea, all men at the age of 18 or older are required to serve at military for a certain period as an obligation. These recruits should be able to withstand psychological stress and pressures of rapid adaptation of the unique and new environment in military. The number of military recruits facing adaptation issues has been on the rise, necessitating an evaluation for active service. In our previous study (Park et al., in press 2023), we classified the military recruits with mental issues according to latent profile analysis (LPA) and examined the treatment response during six months.
Objectives
In this study, we further examined clinical characteristics over the next six months.
Methods
Ninety-two participants were analyzed with LPA using MMPI-2 clinical profiles in the previous study. The three classes were identified: mild maladjustment (Class 1, n=14), neurotic depression and anxiety (Class 2, n=36), high vulnerability and hypervigilance (Class 3, n=42). At 12 months, Clinical Global Impression-Severity and Global Assessment of Functioning were assessed to test their long-term changes.
Results
While Class 1 and 2 significantly improved over 6 months, Class 3 showed little or no improvement even with more medications in our previous study. During the 6-month follow-up period, 50% of Class 1, 38.9% of Class 2, and 41.5% of Class 3 were dropped. It was during this period that their level of military service was decided. Class 1 and 2 which showed marked improvement up to initial 6 months, did not demonstrate substantial further improvement during follow-up period with a considerable portion stopped visiting hospital. Subjects in Class 3, who showed little or no improvement during initial 6 months, demonstrated continued improvement in this study, although their symptoms still appeared relatively severe.
Conclusions
This study suggests clinical implications for treatment plan and intervention of each subgroup classified based on MMPI-2 clinical profiles of military recruits who might show maladjustment to serve. The long-term continuous treatment for Class 3 patients will be needed, even after exemption from active duty.
Accordingly, the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) working committee, composed of domestic experts, developed Korea’s first KMAP-BP in 2002 and later in 2006, 2010, and 2010. A revised version of KMAP-BP was announced every four years four times in 2014 and 2018.6-10). The treatment strategy considering the safety and tolerability of KMAP-BP 2022 was developed by collecting opinions from domestic bipolar disorder experts.
Objectives
Safety and tolerability of drugs are very important factors in the treatment of bipolar disorder. An expert opinion survey was conducted on treatment strategies in various special clinical situations, such as significant weight gain, characteristic drug side effects, low drug adherence, pregnant and reproductive women, and genetic counseling.
Methods
A written survey about treatment strategies related to safety and tolerability was prepared and focused on significant weight gain, characteristic drug side effects, low drug adherence, pregnant and reproductive women, and genetic counseling. Ninety-three experts of the review committee completed the survey.
Results
In the case of weight gain occurring during drug treatment, it was preferred to replace it with a drug that caused less weight gain, such as lamotrigine, aripiprazole, or ziprasidone. If there was a significant weight gain due to the treatment drug, it was preferred to intervene as soon as possible. In the case of hyperprolactinemia, it was selected to change the medication and discontinue it for benign rash caused by lamotrigine. In improving drug adherence, the preference for long-acting injections increased. Antipsychotics can be used with great caution in pregnant or reproductive women.
Conclusions
Treatment strategies in various clinical situations related to safety and tolerability in drug treatment for bipolar disorder were described. It is hoped that it will be useful in practical clinical situations.
Majority of international guidelines for bipolar disorders are based on evidences from clinical trials. In contrast, the Korean Medication Algorithm Project for Bipolar Disorder (KMAP-BP) was developed to adopt an expert-consensus paradigm which was more practical and specific to the atmosphere in Korea.
Objectives
In this study, preferred medication strategies for acute mania over six consecutively published KMAP-BP (2002, 2006, 2010, 2014, 2018, and 2022) were investigated.
Methods
A written survey using a nine-point scale was asked to Korean experts about the appropriateness of various treatment strategies and treatment agents. A written survey asked about the appropriateness of various treatment strategies and treatment agents commonly used by clinicians as the first-line.
Results
The most preferred option for the initial treatment of mania was a combination of a mood stabilizer (MS) and an atypical antipsychotic (AAP) in every edition. Preference for combined treatment for euphoric mania increased, peaked in KMAP-BP 2010, and declined slightly. Either MS or AAP monotherapy was also considered a first-line strategy for mania, but not for all types of episodes, including mixed/psychotic mania. Among MSs, lithium and valproate are almost equally preferred except in the mixed subtype where valproate is the most recommended MS. The preference of valproate showed reverse U-shaped curve. This preference change of valproate may indicate the concern about teratotoxicity in women. Quetiapine, aripiprazole, and olanzapine were the preferred AAP for acute mania since 2014. This change might depend on the recent evidences and safety profile. In cases of unsatisfactory response to initial medications, switching or adding another first-line agent was recommended. The most notable changes over time included the increasing preference for AAPs.
Conclusions
The Korean experts have been increasingly convinced of the effectiveness of a combination therapy for acute mania. There have been evident preference changes: increased for AAP and decreased for carbamazepine.
NASA’s all-sky survey mission, the Transiting Exoplanet Survey Satellite (TESS), is specifically engineered to detect exoplanets that transit bright stars. Thus far, TESS has successfully identified approximately 400 transiting exoplanets, in addition to roughly 6 000 candidate exoplanets pending confirmation. In this study, we present the results of our ongoing project, the Validation of Transiting Exoplanets using Statistical Tools (VaTEST). Our dedicated effort is focused on the confirmation and characterisation of new exoplanets through the application of statistical validation tools. Through a combination of ground-based telescope data, high-resolution imaging, and the utilisation of the statistical validation tool known as TRICERATOPS, we have successfully discovered eight potential super-Earths. These planets bear the designations: TOI-238b (1.61$^{+0.09} _{-0.10}$ R$_\oplus$), TOI-771b (1.42$^{+0.11} _{-0.09}$ R$_\oplus$), TOI-871b (1.66$^{+0.11} _{-0.11}$ R$_\oplus$), TOI-1467b (1.83$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-1739b (1.69$^{+0.10} _{-0.08}$ R$_\oplus$), TOI-2068b (1.82$^{+0.16} _{-0.15}$ R$_\oplus$), TOI-4559b (1.42$^{+0.13} _{-0.11}$ R$_\oplus$), and TOI-5799b (1.62$^{+0.19} _{-0.13}$ R$_\oplus$). Among all these planets, six of them fall within the region known as ‘keystone planets’, which makes them particularly interesting for study. Based on the location of TOI-771b and TOI-4559b below the radius valley we characterised them as likely super-Earths, though radial velocity mass measurements for these planets will provide more details about their characterisation. It is noteworthy that planets within the size range investigated herein are absent from our own solar system, making their study crucial for gaining insights into the evolutionary stages between Earth and Neptune.
To provide a systematic synthesis of primary care practice-based interventions and their effect on participation in population-based cancer screening programs.
Background:
Globally, population-based cancer screening programs (bowel, breast, and cervical) have sub-optimal participation rates. Primary healthcare workers (PHCWs) have an important role in facilitating a patient’s decision to screen; however, barriers exist to their engagement. It remains unclear how to best optimize the role of PHCWs to increase screening participation.
Methods:
A comprehensive search was conducted from January 2010 until November 2023 in the following databases: Medline (OVID), EMBASE, and CINAHL. Data extraction, quality assessment, and synthesis were conducted. Studies were separated by whether they assessed the effect of a single-component or multi-component intervention and study type.
Findings:
Forty-nine studies were identified, of which 36 originated from the USA. Fifteen studies were investigations of single-component interventions, and 34 studies were of multi-component interventions. Interventions with a positive effect on screening participation were predominantly multi-component, and most included combinations of audit and feedback, provider reminders, practice-facilitated assessment and improvement, and patient education across all screening programs. Regarding bowel screening, provision of screening kits at point-of-care was an effective strategy to increase participation. Taking a ‘whole-of-practice approach’ and identifying a ‘practice champion’ were found to be contextual factors of effective interventions.
The findings suggest that complex interventions comprised of practitioner-focused and patient-focused components are required to increase cancer screening participation in primary care settings. This study provides novel understanding as to what components and contextual factors should be included in primary care practice-based interventions.
Cave carbonate mineral deposits (speleothems) contain trace elements that are intensively investigated for their significance as palaeoclimate and environmental proxies. However, chlorine, which is abundant in marine and meteoric waters, has been overlooked as a potential palaeo-proxy, while cosmogenic 36Cl could, in principle, provide a solar irradiance proxy. Here, total Cl concentrations analysed from various speleothems were low (3–14 mg/kg), with variations linked to crystal fabrics. High-resolution synchrotron radiation micro X-ray fluorescence (μ-XRF) trace element mapping showed Cl often associated with Na, Si, and Al. We propose that speleothems incorporate Cl in two fractions: (1) water soluble (e.g., fluid inclusions) and (2) water insoluble and strongly bound (e.g., associated with detrital particulates). However, disparities indicated that alternate unidentified mechanisms for Cl incorporation were present, raising important questions regarding incorporation of many trace elements into speleothems. Our first measurements of 36Cl/Cl ratios in speleothems required large samples due to low Cl concentrations, limiting the potential of 36Cl as a solar irradiance proxy. Critically, our findings highlight a knowledge gap into how Cl and other trace elements are incorporated into speleothems, how the incorporation mechanisms and final elemental concentrations are related to speleothem fabrics, and the significance this may have for how trace elements in speleothems are interpreted as palaeoclimate proxies.
Anthropogenic nutrient loading from land use, especially agriculture, is a major threat to waterbodies worldwide. Efforts to govern nutrient pollution are increasingly based on simulation modeling for research, evaluation, and regulation. This study develops a novel approach to simulate nutrient losses from agriculture applied to the Lake Champlain basin in the US state of Vermont. The Vermont Phosphorus-Index—a farm-based empirical model regularly used for site evaluation—is scaled up to the basin level with high-resolution geographic data and probabilistic estimation of unknown parameters and management practices. Results are comparable with analyses using more data and computationally intensive tools. Important insights into basin-wide management include: (1) nutrient-management planning can significantly reduce P losses in a livestock-agriculture-dominated watershed by re-distributing manure applications from areas of high loss to low loss; (2) hotspot identification from geographic data alone may be deeply complicated by high underlying heterogeneity of soil phosphorus; and (3) probabilistic modeling using simple, field-scale models is a potentially useful complement to complex watershed process models. Findings suggest that currently available best-management practices will likely be insufficient to reach reduction targets in the most impaired sub-watersheds. Reductions of agricultural land use and herd size, particularly in intensive dairy operations, may be necessary.
In South Korea, all men at the age of 18 or older are required to serve at military for a certain period as an obligation. These recruits should be able to withstand psychological stress and pressures of rapid adaptation of the unique and new environment in military.
Objectives
The current study attempted to identify distinct subgroups of patients referred for military service suitability and further to investigate whether there is a difference in clinical features such as treatment responsiveness and prognosis among those subgroups.
Methods
Subjects were male patients aged 18 to 28 years who visited the department of psychiatry at the University Hospital for evaluating mental health problems related to military service. We conducted a latent profile analysis (LPA) using 10 clinical scales of MMPI-2 as an indicator variable to investigate the subgroups of subjects. The clinical state of subjects was assessed with CGI-S and GAF scale for three time point (0, 3, and 6 month).
Results
The results showed that the best fitting model corresponded to a three-class model: each class was named ‘Class 1: mild maladjustment’, ‘Class 2: neurotic depression and anxiety’, and ‘Class 3: highly vulnerable and hypervigilant’ respectively. Subsequent analysis was also carried out to identify changes in clinical symptoms and functional level across treatment time of each subgroup identified in LPA. We demonstrated that the three subgroups displayed differential characteristics in treatment responsiveness and clinical course evaluated by CGI-S and GAF over a treatment period of 6 months. Three subgroups indicated significant differences in the number of medications prescribed as well. Class 3 had more antidepressants and anxiolytics on use than Class 1 and 2. Antipsychotic agents and a combination of three antidepressants were prescribed more frequently in Class 3 than in Class 1 and 2.
Conclusions
While Class 1 and 2 significantly improved over 6 months, Class 3 showed little or no improvement in our clinical parameters even with more medications. This study has a clinical significance that it has classified qualitatively different subgroups within the sample by conducting LPA with clinical profiles of MMPI-2 and provides a basis for comprehensively understanding their differentiated clinical features. This study suggests clinical implications for treatment plan and intervention of each subgroup classified based on MMPI-2 clinical profiles of military recruits who might show maladjustment to serve.
Trauma exposure can cause post-traumatic stress symptoms (PTSS), and persistently experiencing PTSS may lead to the development of post-traumatic stress disorder (PTSD). Research has shown that PTSS that emerged within days of trauma was a robust predictor of PTSD development.
Aims
To investigate patterns of early stress responses to trauma and their associations with development of PTSD.
Method
We recruited 247 civilian trauma survivors from a local hospital emergency department. The PTSD Checklist for DSM-5 (PCL-5) and Acute Stress Disorder Scale (ASDS) were completed within 2 weeks after the traumatic event. Additionally, 3 months post-trauma 146 of these participants completed a PTSD diagnostic interview using the Clinician Administered PTSD Scale for DSM-5.
Results
We first used latent profile analysis on four symptom clusters of the PCL-5 and the dissociation symptom cluster of the ASDS and determined that a four-profile model (‘severe symptoms’, ‘moderate symptoms’, ‘mild symptoms’, ‘minimal symptoms’) was optimal based on multiple fit indices. Gender was found to be predictive of profile membership. We then found a significant association between subgroup membership and PTSD diagnosis (χ2(3) = 11.85, P < 0.01, Cramer's V = 0.263). Post hoc analysis revealed that this association was driven by participants in the ‘severe symptoms’ profile, who had a greater likelihood of developing PTSD.
Conclusions
These findings fill the knowledge gap of identifying possible subgroups of individuals based on their PTSS severity during the early post-trauma period and investigating the relationship between subgroup membership and PTSD development, which have important implications for clinical practice.
Gun ownership is a highly consequential political behavior. It often signifies a belief about the inadequacy of state-provided security and leads to membership in a powerful political constituency. As a result, it is important to understand why people buy guns and how shifting purchasing patterns affect the composition of the broader gun-owning community. We address these topics by exploring the dynamics of the gun-buying spike that took place during the COVID-19 pandemic, which was one of the largest in American history. We find that feelings of diffuse threat prompted many individuals to buy guns. Moreover, we show that new gun owners, even more than buyers who already owned guns, exhibit strong conspiracy and anti-system beliefs. These findings have substantial consequences for the subsequent population of gun owners and provide insight into how social disruptions can alter the nature of political groups.
Politics and science have become increasingly intertwined. Salient scientific issues, such as climate change, evolution, and stem-cell research, become politicized, pitting partisans against one another. This creates a challenge of how to effectively communicate on such issues. Recent work emphasizes the need for tailored messages to specific groups. Here, we focus on whether generalized messages also can matter. We do so in the context of a highly polarized issue: extreme COVID-19 vaccine resistance. The results show that science-based, moral frame, and social norm messages move behavioral intentions, and do so by the same amount across the population (that is, homogeneous effects). Counter to common portrayals, the politicization of science does not preclude using broad messages that resonate with the entire population.
As COVID-19 was declared a health emergency in March 2020, there was immense demand for information about the novel pathogen. This paper examines the clinician-reported impact of Project ECHO COVID-19 Clinical Rounds on clinician learning. Primary sources of study data were Continuing Medical Education (CME) Surveys for each session from the dates of March 24, 2020 to July 30, 2020 and impact surveys conducted in November 2020, which sought to understand participants’ overall assessment of sessions. Quantitative analyses included descriptive statistics and Mann-Whitney testing. Qualitative data were analyzed through inductive thematic analysis. Clinicians rated their knowledge after each session as significantly higher than before that session. 75.8% of clinicians reported they would ‘definitely’ or ‘probably’ use content gleaned from each attended session and clinicians reported specific clinical and operational changes made as a direct result of sessions. 94.6% of respondents reported that COVID-19 Clinical Rounds helped them provide better care to patients. 89% of respondents indicated they ‘strongly agree’ that they would join ECHO calls again.COVID-19 Clinical Rounds offers a promising model for the establishment of dynamic peer-to-peer tele-mentoring communities for low or no-notice response where scientifically tested or clinically verified practice evidence is limited.
Major depressive disorder (MDD), bipolar disorder (BD) and schizophrenia-spectrum disorders (SSD) are heterogeneous psychiatric disorders, which place significant burden on patient's well-being and global health. Disruptions in the gut-microbiome may play a role in these psychiatric disorders. This review presents current data on composition of the human gastrointestinal microbiota, and its interaction mechanisms in the gut–brain axis in MDD, BD and SSD. Diversity metrics and microbial relative abundance differed across studies. More studies reported inconsistent findings (n = 7) or no differences (n = 8) than studies who reported lower α-diversity in these psychiatric disorders (n = 5). The most consistent findings across studies were higher relative abundances of the genera Streptococcus, Lactobacillus, and Eggerthella and lower relative abundance of the butyrate producing Faecalibacterium in patients with psychiatric disorders. All three increased genera were associated with higher symptom severity. Confounders, such as medication use and life style have not been accounted for. So far, the results of probiotics trials have been inconsistent. Most traditional and widely used probiotics (consisting of Bifidobacterium spp. and Lactobacillus spp.) are safe, however, they do not correct potential microbiota disbalances in these disorders. Findings on prebiotics and faecal microbiota transplantation (FMT) are too limited to draw definitive conclusions. Disease-specific pro/prebiotic treatment or even FMT could be auspicious interventions for prevention and therapy for psychiatric disorders and should be investigated in future trials.
Behaviors typical of body-focused repetitive behavior disorders such as trichotillomania (TTM) and skin-picking disorder (SPD) are often associated with pleasure or relief, and with little or no physical pain, suggesting aberrant pain perception. Conclusive evidence about pain perception and correlates in these conditions is, however, lacking.
Methods
A multisite international study examined pain perception and its physiological correlates in adults with TTM (n = 31), SPD (n = 24), and healthy controls (HCs; n = 26). The cold pressor test was administered, and measurements of pain perception and cardiovascular parameters were taken every 15 seconds. Pain perception, latency to pain tolerance, cardiovascular parameters and associations with illness severity, and comorbid depression, as well as interaction effects (group × time interval), were investigated across groups.
Results
There were no group differences in pain ratings over time (P = .8) or latency to pain tolerance (P = .8). Illness severity was not associated with pain ratings (all P > .05). In terms of diastolic blood pressure (DBP), the main effect of group was statistically significant (P = .01), with post hoc analyses indicating higher mean DBP in TTM (95% confidence intervals [CI], 84.0-93.5) compared to SPD (95% CI, 73.5-84.2; P = .01), and HCs (95% CI, 75.6-86.0; P = .03). Pain perception did not differ between those with and those without depression (TTM: P = .2, SPD: P = .4).
Conclusion
The study findings were mostly negative suggesting that general pain perception aberration is not involved in TTM and SPD. Other underlying drivers of hair-pulling and skin-picking behavior (eg, abnormal reward processing) should be investigated.
Health technology assessment (HTA) agencies are considering adopting a lifecycle approach to assessments to address uncertainties in the evidence base at launch and to revisit the clinical and economic value of therapies in a dynamic clinical landscape. For reassessments of therapies post launch, HTA agencies are looking to real-world evidence (RWE) to enhance the clinical and economic evidence base, though challenges and concerns in using RWE in decision-making exists. Stakeholders are embarking on demonstration projects to address the challenges and concerns and to further define when and how RWE can be used in HTA decision making. The Institute for Clinical and Economic Review piloted a 24-month observational RWE reassessment. Key learnings from this pilot include identifying the benefits and challenges with using RWE in reassessments and considerations on prioritizing and selecting topics relevant for RWE updates.
Growing attitudinal and affective differences across party lines and increasing social polarization are often attributed to the strengthening of partisanship as a social identity. Scholars have paid less attention to personal preferences as a contributor to these phenomena. Our focus is on how citizens’ policy beliefs—their operational ideologies—are associated with their views of partisan groups. We examine our perspective with two studies. In the first, we find that the attribution of ideologically extreme political views to an individual's peer significantly reduces interest in interpersonal interaction but find limited evidence that partisan group membership alone induces social polarization. In the second, we show that citizens’ policy views are strongly associated with their perceptions of their own partisan group as well as their counterpartisans. Together, our results have important implications for understanding the consequences of increased polarization and partisan antipathy in contemporary politics.
Trichotillomania (TTM) and skin picking disorder (SPD) are common and often debilitating mental health conditions, grouped under the umbrella term of body-focused repetitive behaviors (BFRBs). Recent clinical subtyping found that there were three distinct subtypes of TTM and two of SPD. Whether these clinical subtypes map on to any unique neurobiological underpinnings, however, remains unknown.
Methods
Two hundred and fifty one adults [193 with a BFRB (85.5% [n = 165] female) and 58 healthy controls (77.6% [n = 45] female)] were recruited from the community for a multicenter between-group comparison using structural neuroimaging. Differences in whole brain structure were compared across the subtypes of BFRBs, controlling for age, sex, scanning site, and intracranial volume.
Results
When the subtypes of TTM were compared, low awareness hair pullers demonstrated increased cortical volume in the lateral occipital lobe relative to controls and sensory sensitive pullers. In addition, impulsive/perfectionist hair pullers showed relative decreased volume near the lingual gyrus of the inferior occipital–parietal lobe compared with controls.
Conclusions
These data indicate that the anatomical substrates of particular forms of BFRBs are dissociable, which may have implications for understanding clinical presentations and treatment response.
The American administrative state has, of late, been under siege, attacked on two fronts. The war on one front is somewhat parochial – a pitched battle over US constitutional law. It is waged largely by conservative movement lawyers who view the modern administrative state as an affront to the constitutional separation of powers.
The war on the other front has much greater transnational relevance. This second fight pits defenders of modern bureaucratic governance against those who see public administration as hopelessly inefficient, rigid, and unaccountable. This latter group of critics present themselves as more or less comfortable with the constitutionality of the administrative state – and thus claim to raise only technocratic objections.