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Clinical guidelines for personality disorder emphasise the importance of patients being supported to develop psychological skills to help them manage their symptoms and behaviours. But where these mechanisms fail, and hospital admission occurs, little is known about how episodes of acutely disturbed behaviour are managed.
Aims
To explore the clinical characteristics and management of episodes of acutely disturbed behaviour requiring medication in in-patients with a diagnosis of personality disorder.
Method
Analysis of clinical audit data collected in 2024 by the Prescribing Observatory for Mental Health, as part of a quality improvement programme addressing the pharmacological management of acutely disturbed behaviour. Data were collected from clinical records using a bespoke proforma.
Results
Sixty-two mental health Trusts submitted data on 951 episodes of acutely disturbed behaviour involving patients with a personality disorder, with this being the sole psychiatric diagnosis in 471 (50%). Of the total, 782 (82%) episodes occurred in female patients. Compared with males, episodes in females were three times more likely to involve self-harming behaviour or be considered to pose such a risk (22% and 70% respectively: p < 0.001). Parenteral medication (rapid tranquillisation) was administered twice as often in episodes involving females than in males (64 and 34% respectively: p < 0.001).
Conclusions
Our findings suggest that there are a large number of episodes of acutely disturbed behaviour on psychiatric wards in women with a diagnosis of personality disorder. These episodes are characterised by self-harm and regularly prompt the administration of rapid tranquillisation. This has potential implications for service design, staff training, and research.
A comparison of ‘intention’ and its role in criminal law is made extremely difficult by the overlaps and imperfections in terminology, both in common law and German law. There are also significant differences in how courts, academics and laypeople understand and apply the terms. The authors therefore concentrate on the substantive questions behind the legal terms: what makes ‘intentional’ offending more dangerous and more blameworthy than non-intentional causation of similar harm? What types or degrees of intention can be differentiated because they imply more or less intense subjective violations of legal rules? In particular, is there a normative difference between actors who wish to achieve a certain result and those who do not but are reasonably certain that they will bring about this result? How should the law deal with actors who know that they engage in risky behaviour but are unsure about its effect?
Targeting the glutamatergic system is posited as a potentially novel therapeutic strategy for psychotic disorders. While studies in subjects indicate that antipsychotic medication reduces brain glutamatergic measures, they were unable to disambiguate clinical changes from drug effects.
Aims
To address this, we investigated the effects of a dopamine D2 receptor partial agonist (aripiprazole) and a dopamine D2 receptor antagonist (amisulpride) on glutamatergic metabolites in the anterior cingulate cortex (ACC), striatum and thalamus in healthy controls.
Method
A double-blind, within-subject, cross-over, placebo-controlled study design with two arms (n = 25 per arm) was conducted. Healthy volunteers received either aripiprazole (up to 10 mg/day) for 7 days or amisulpride (up to 400 mg/day) and a corresponding period of placebo treatment in a pseudo-randomised order. Magnetic resonance spectroscopy (1H-MRS) was used to measure glutamatergic metabolite levels and was carried out at three different time points: baseline, after 1 week of drug and after 1 week of placebo. Values were analysed as a combined measure across the ACC, striatum and thalamus.
Results
Aripiprazole significantly increased glutamate + glutamine (Glx) levels compared with placebo (β = 0.55, 95% CI [0.15, 0.95], P = 0.007). At baseline, the mean Glx level was 8.14 institutional units (s.d. = 2.15); following aripiprazole treatment, the mean Glx level was 8.16 institutional units (s.d. = 2.40) compared with 7.61 institutional units (s.d. = 2.36) for placebo. This effect remained significant after adjusting for plasma parent and active metabolite drug levels. There was an observed increase with amisulpride that did not reach statistical significance.
Conclusions
One week of aripiprazole administration in healthy participants altered brain Glx levels as compared with placebo administration. These findings provide novel insights into the relationship between antipsychotic treatment and brain metabolites in a healthy participant cohort.
Patients with posttraumatic stress disorder (PTSD) exhibit smaller regional brain volumes in commonly reported regions including the amygdala and hippocampus, regions associated with fear and memory processing. In the current study, we have conducted a voxel-based morphometry (VBM) meta-analysis using whole-brain statistical maps with neuroimaging data from the ENIGMA-PGC PTSD working group.
Methods
T1-weighted structural neuroimaging scans from 36 cohorts (PTSD n = 1309; controls n = 2198) were processed using a standardized VBM pipeline (ENIGMA-VBM tool). We meta-analyzed the resulting statistical maps for voxel-wise differences in gray matter (GM) and white matter (WM) volumes between PTSD patients and controls, performed subgroup analyses considering the trauma exposure of the controls, and examined associations between regional brain volumes and clinical variables including PTSD (CAPS-4/5, PCL-5) and depression severity (BDI-II, PHQ-9).
Results
PTSD patients exhibited smaller GM volumes across the frontal and temporal lobes, and cerebellum, with the most significant effect in the left cerebellum (Hedges’ g = 0.22, pcorrected = .001), and smaller cerebellar WM volume (peak Hedges’ g = 0.14, pcorrected = .008). We observed similar regional differences when comparing patients to trauma-exposed controls, suggesting these structural abnormalities may be specific to PTSD. Regression analyses revealed PTSD severity was negatively associated with GM volumes within the cerebellum (pcorrected = .003), while depression severity was negatively associated with GM volumes within the cerebellum and superior frontal gyrus in patients (pcorrected = .001).
Conclusions
PTSD patients exhibited widespread, regional differences in brain volumes where greater regional deficits appeared to reflect more severe symptoms. Our findings add to the growing literature implicating the cerebellum in PTSD psychopathology.
To evaluate the impact of implementing a multi-step Clostridioides difficile infection (CDI) testing algorithm on hospital-onset (HO)-CDI rates and clinical outcomes.
Two academic hospitals in Pittsburgh, Pennsylvania.
Methods:
In the pre-intervention period, a standalone polymerase chain reaction (PCR) assay was used for diagnosing CDI. In the post-intervention period, positive PCR assays were reflexed to a glutamate dehydrogenase antigen test and an enzyme immunoassay for toxin A/B.
Results:
The implementation of a multi-step testing algorithm resulted in a significant reduction in HO-CDI cases per 10,000 patient days from 5.92 to 2.36 (P < 0.001). Despite the decrease in reportable HO-CDI cases, there were no significant differences in clinical outcomes such as hospital length of stay, intensive care unit admissions, and treatment courses. In addition, there was a significant reduction in all-cause 30-day readmissions in the post-intervention group, though CDI-related readmissions remained similar.
Conclusions:
The multi-step testing algorithm significantly reduced HO-CDI rates without compromising clinical outcomes. The study supports the use of a multi-step CDI testing algorithm to assist healthcare providers with CDI management decisions and potentially to reduce financial penalties burdened on healthcare systems.
Objectives/Goals: Electronic health record (EHR)-based recruitment can facilitate participation in clinical trials, but is not a panacea to trial accrual challenges. We conducted a root cause analysis to identify EHR-based accrual barriers and facilitators in a pragmatic randomized trial of metformin for those with prostate cancer and glucose intolerance. Methods/Study Population: We quantitatively analyzed enrollment drop-offs among eligible patients who either did not complete a consent (with analysis of EHR-embedded consent process) or who completed a consent but were not enrolled (with analysis of EHR implementation of a Best Practice Alert). We summarized data from the EHR by eligibility, provider encounters, and alerts, and generated CONSORT diagrams and tables to trace the enrollment pathway. We supplemented quantitative findings with a thematic analysis of semi-structured individual interviews with eligible patients (n = 10) and study providers (n = 4) to identify systematic barriers to recruitment and enrollment of eligible patients. Results/Anticipated Results: CONSORT diagram analysis found that 24% of potentially eligible patients (268 of 1130) had an eligible study encounter but were not enrolled. Additionally, BPAs were not triggering for some eligible patients. Interviews revealed that study providers wanted more detailed information about which study arm their patient would be assigned to, and about next steps after enrollment, especially relating to additional lab tests and follow-up care needed. Patient interviews suggested that patients often did not remember completing the consent process and felt overwhelmed with appointments and information; patients expected providers to actively bring up research opportunities during appointments. Discussion/Significance of Impact: While pragmatic EHR-embedded trials are often characterized as lower-burden, these trials still require active engagement by providers, as well as ongoing attention from both research and informatics teams to ensure that EHR-embedded processes are functioning as designed, and that they are effective in recruiting study participants.
Forgetting, and having recourse to unremembering the past, is useful for different populations. The modern world has provided a range of examples, but the effectiveness of short-term amnesia has not always been highlighted in archaeological scholarship. In this article, a case study from the Roman-period Netherlands highlights that the significance of memory-making in the past may have been overstated. Especially among those societies living under imperial rule, forgetting played an important role, one that calls for more critical focus and understanding. The utilization of cross-cultural and historical examples provides the background for a close analysis of the remains from a single graveyard. The study brings out the repeated amnesiac changes that indigenous groups underwent to adapt themselves to the continuing fact of occupation.
Vaccines have revolutionised the field of medicine, eradicating and controlling many diseases. Recent pandemic vaccine successes have highlighted the accelerated pace of vaccine development and deployment. Leveraging this momentum, attention has shifted to cancer vaccines and personalised cancer vaccines, aimed at targeting individual tumour-specific abnormalities. The UK, now regarded for its vaccine capabilities, is an ideal nation for pioneering cancer vaccine trials. This article convened experts to share insights and approaches to navigate the challenges of cancer vaccine development with personalised or precision cancer vaccines, as well as fixed vaccines. Emphasising partnership and proactive strategies, this article outlines the ambition to harness national and local system capabilities in the UK; to work in collaboration with potential pharmaceutic partners; and to seize the opportunity to deliver the pace for rapid advances in cancer vaccine technology.
This study sought to assess undergraduate students’ knowledge and attitudes surrounding perceived self-efficacy and threats in various common emergencies in communities of higher education.
Methods
Self-reported perceptions of knowledge and skills, as well as attitudes and beliefs regarding education and training, obligation to respond, safety, psychological readiness, efficacy, personal preparedness, and willingness to respond were investigated through 3 representative scenarios via a web-based survey.
Results
Among 970 respondents, approximately 60% reported their university had adequately prepared them for various emergencies while 84% reported the university should provide such training. Respondents with high self-efficacy were significantly more likely than those with low self-efficacy to be willing to respond in whatever capacity needed across all scenarios.
Conclusions
There is a gap between perceived student preparedness for emergencies and training received. Students with high self-efficacy were the most likely to be willing to respond, which may be useful for future training initiatives.
Highly portable and accessible MRI technology will allow researchers to conduct field-based MRI research in community settings. Previous guidance for researchers working with fixed MRI does not address the novel ethical, legal, and societal issues (ELSI) of portable MRI (pMRI). Our interdisciplinary Working Group (WG) previously identified 15 core ELSI challenges associated with pMRI research and recommended solutions. In this article, we distill those detailed recommendations into a Portable MRI Research ELSI Checklist that offers practical operational guidance for researchers contemplating using this technology.
In response to the COVID-19 pandemic, we rapidly implemented a plasma coordination center, within two months, to support transfusion for two outpatient randomized controlled trials. The center design was based on an investigational drug services model and a Food and Drug Administration-compliant database to manage blood product inventory and trial safety.
Methods:
A core investigational team adapted a cloud-based platform to randomize patient assignments and track inventory distribution of control plasma and high-titer COVID-19 convalescent plasma of different blood groups from 29 donor collection centers directly to blood banks serving 26 transfusion sites.
Results:
We performed 1,351 transfusions in 16 months. The transparency of the digital inventory at each site was critical to facilitate qualification, randomization, and overnight shipments of blood group-compatible plasma for transfusions into trial participants. While inventory challenges were heightened with COVID-19 convalescent plasma, the cloud-based system, and the flexible approach of the plasma coordination center staff across the blood bank network enabled decentralized procurement and distribution of investigational products to maintain inventory thresholds and overcome local supply chain restraints at the sites.
Conclusion:
The rapid creation of a plasma coordination center for outpatient transfusions is infrequent in the academic setting. Distributing more than 3,100 plasma units to blood banks charged with managing investigational inventory across the U.S. in a decentralized manner posed operational and regulatory challenges while providing opportunities for the plasma coordination center to contribute to research of global importance. This program can serve as a template in subsequent public health emergencies.
Tiafenacil is a new nonselective protoporphyrinogen IX oxidase (PPO)–inhibiting herbicide with both grass and broadleaf activity labeled for preplant application to corn, cotton, soybean, and wheat. Early-season corn emergence and growth often coincides in the mid-South with preplant herbicide application in cotton and soybean, thereby increasing opportunity for off-target herbicide movement from adjacent fields. Field studies were conducted in 2022 to identify the impacts of reduced rates of tiafenacil (12.5% to 0.4% of the lowest labeled application rate of 24.64 g ai ha–1) applied to two- or four-leaf corn. Corn injury 1 wk after treatment (WAT) for the two- and four-leaf growth stages ranged from 31% to 6% and 37% to 9%, respectively, whereas at 2 WAT these respective ranges were 21.7% to 4% and 22.5% to 7.2%. By 4 WAT, visible injury following the two- and four-leaf exposure timing was no greater than 8% in all instances except the highest tiafenacil rate applied at the four-leaf growth stage (13%). Tiafenacil had no negative season-long impact, as the early-season injury observed was not manifested in a reduction in corn height 2 WAT or yield. Application of tiafenacil directly adjacent to corn in early vegetative stages of growth should be avoided. In cases where off-target movement does occur, however, affected corn should be expected to fully recover with no impact on growth and yield, assuming adequate growing conditions and agronomic/pest management practices are provided.
Herbicides that persist in the forest litter and soil following their use for managing invasive plant species may negatively affect restoration efforts as well as minimize reinvasion via their residual phytotoxic activity. This study determined the impact of an herbicide mixture comprising triclopyr, dicamba, picloram, and aminopyralid (TDPA) for the control of dense infestations of a woody invader, Pinus contorta Douglas ex Loudon, on the germination of reinvading P. contorta and three New Zealand native species (Chionochloa rubra Zotov, Nothofagus cliffortiodes (Hook. f.) Oerst., and Leptospermum scoparium J.R. Forst. & G. Forst.) used in restoration. Given the essential role of ectomycorrhizal fungi in facilitating conifer reinvasion, the impact of residual herbicides present in mineral soil on the ectomycorrhizal infection of P. contorta seedling roots was also examined. Germination trials were conducted using intact forest litter–soil cores collected at 27, 112 and 480 d (after herbicide spraying) from sprayed and adjacent unsprayed dense P. contorta infestations. At the same time, mineral soil was also collected for the ectomycorrhizal infection study. Post-spray herbicide residue bound in the litter significantly decreased survival, germination rate, root and shoot growth, and also caused malformation of P. contorta seedlings. Similar results were recorded for native species’ germination; however, overall viability of native seed was poor, resulting in low germination rates. There was no difference in levels of ectomycorrhizal infection rates of P. contorta between treatments. Results indicate residual levels of TDPA herbicide in forest floor litter negatively affect P. contorta reinvasion, native recruitment, and active restoration management. Ectomycorrhizal fungi, however, are unaffected by this herbicide mixture and therefore remain a risk to facilitating reinvasion as residual herbicide declines.
The Accelerating COVID-19 Therapeutic Interventions and Vaccines (ACTIV) Cross-Trial Statistics Group gathered lessons learned from statisticians responsible for the design and analysis of the 11 ACTIV therapeutic master protocols to inform contemporary trial design as well as preparation for a future pandemic. The ACTIV master protocols were designed to rapidly assess what treatments might save lives, keep people out of the hospital, and help them feel better faster. Study teams initially worked without knowledge of the natural history of disease and thus without key information for design decisions. Moreover, the science of platform trial design was in its infancy. Here, we discuss the statistical design choices made and the adaptations forced by the changing pandemic context. Lessons around critical aspects of trial design are summarized, and recommendations are made for the organization of master protocols in the future.
To compare rates of Clostridioides difficile infection (CDI) recurrence following initial occurrence treated with tapered enteral vancomycin compared to standard vancomycin.
Design:
Retrospective cohort study.
Setting:
Community health system.
Patients:
Adults ≥18 years of age hospitalized with positive C. difficile polymerase chain reaction or toxin enzyme immunoassay who were prescribed either standard 10–14 days of enteral vancomycin four times daily or a 12-week tapered vancomycin regimen.
Methods:
Retrospective propensity score pair matched cohort study. Groups were matched based on age < or ≥ 65 years and receipt of non-C. difficile antibiotics during hospitalization or within 6 months post-discharge. Recurrence rates were analyzed via logistic regression conditioned on matched pairs and reported as conditional odds ratios. The primary outcome was recurrence rates compared between standard vancomycin versus tapered vancomycin for treatment of initial CDI.
Results:
The CDI recurrence rate at 6 months was 5.3% (4/75) in the taper cohort versus 28% (21/75) in the standard vancomycin cohort. The median time to CDI recurrence was 115 days versus 20 days in the taper and standard vancomycin cohorts, respectively. When adjusted for matching, patients in the taper arm were less likely to experience CDI recurrence at 6 months when compared to standard vancomycin (cOR = 0.19, 95% CI 0.07–0.56, p < 0.002).
Conclusions:
Larger prospective trials are needed to elucidate the clinical utility of tapered oral vancomycin as a treatment option to achieve sustained clinical cure in first occurrences of CDI.
John Selden's 1642 edition and translation of an extract from a chronicle by Eutychius (Said ibn Batriq), the tenth-century Melkite patriarch of Alexandria, can be considered the first Arabic book printed in England. This article examines the early reception of Selden's Eutychius in the European republic of letters, exploring the ways in which its testimony about the early Alexandrian Church contributed to scholarly debates over episcopacy against the backdrop of the English Revolution. In doing so it demonstrates how Selden's edition made Eutychius a touchstone in seventeenth-century confessional disputes over ecclesiastical history while attracting readers in England and abroad.
Postural orthostatic tachycardia syndrome is a debilitating disorder. We compared paediatric patients with this dysautonomia presenting with and without peak upright heart rate > 100 beats per minute.
Materials and Methods:
Subjects were drawn from the Postural Orthostatic Tachycardia Syndrome Program database of the Children’s Hospital of Philadelphia diagnosed between 2007 and 2018. Subjects were aged 12–18 years at diagnosis with demographic data, supine and peak heart rate from 10-minute stand, symptoms, and family history. Patients were divided into “low heart rate” (peak less than 100 beats/minute) and “high heart rate” (peak at least 100 beats/minute) groups.
Results:
In total, 729 subjects were included (low heart rate group: 131 patients, high heart rate group: 598 patients). The low heart rate group had later age at diagnosis (16.1 versus 15.7, p = 0.0027). Median heart rate increase was 32 beats/minute in the low heart rate group versus 40 beats/minute in the high heart rate group (p < 0.00001). Excluding palpitations and tachypalpitations, there were no differences in symptom type or frequency between groups.
Discussion:
Paediatric patients meeting heart rate criteria for postural orthostatic tachycardia syndrome but without peak heart rate > 100 demonstrate no difference in symptom type or frequency versus those who meet both criteria. Differences observed reached statistical significance due to population size but are not clinically meaningful. This suggests that increased heart rate, but not necessarily tachycardia, is seen in these patients, supporting previous findings suggesting maximal heart rate is not a major determinant of symptom prevalence in paediatric postural orthostatic tachycardia syndrome.
We present radio observations of the galaxy cluster Abell S1136 at 888 MHz, using the Australian Square Kilometre Array Pathfinder radio telescope, as part of the Evolutionary Map of the Universe Early Science program. We compare these findings with data from the Murchison Widefield Array, XMM-Newton, the Wide-field Infrared Survey Explorer, the Digitised Sky Survey, and the Australia Telescope Compact Array. Our analysis shows the X-ray and radio emission in Abell S1136 are closely aligned and centered on the Brightest Cluster Galaxy, while the X-ray temperature profile shows a relaxed cluster with no evidence of a cool core. We find that the diffuse radio emission in the centre of the cluster shows more structure than seen in previous low-resolution observations of this source, which appeared formerly as an amorphous radio blob, similar in appearance to a radio halo; our observations show the diffuse emission in the Abell S1136 galaxy cluster contains three narrow filamentary structures visible at 888 MHz, between $\sim$80 and 140 kpc in length; however, the properties of the diffuse emission do not fully match that of a radio (mini-)halo or (fossil) tailed radio source.
Multiple studies have demonstrated that European colonization of the Americas led to the death of nearly all North American dog mitochondrial lineages and replacement with European ones sometime between AD 1492 and the present day. Historical records indicate that colonists imported dogs from Europe to North America, where they became objects of interest and exchange as early as the seventeenth century. However, it is not clear whether the earliest archaeological dogs recovered from colonial contexts were of European, Indigenous, or mixed descent. To clarify the ancestry of dogs from the Jamestown Colony, Virginia, we sequenced ancient mitochondrial DNA from six archaeological dogs from the period 1609–1617. Our analysis shows that the Jamestown dogs have maternal lineages most closely associated with those of ancient Indigenous dogs of North America. Furthermore, these maternal lineages cluster with dogs from Late Woodland, Hopewell, and Virginia Algonquian archaeological sites. Our recovery of Indigenous dog lineages from a European colonial site suggests a complex social history of dogs at the interface of Indigenous and European populations during the early colonial period.