bluuebunny/crossref_metadata_2025 huggingface dataset:
Routine screening for HLA Antibodies in Heart Transplant patients—Does it affect clinical decision making?
Authors: Clemmensen Tor Skibsted , Hjort Baatrup Johanne , Bjerre Kamilla Pernille , Lichscheidt Emil , Nielsen Pernille Koefoed , Eiskjaer Hans
Published: March 2024

Background

We aimed to assess outcomes in patients with and without donor specific antibodies (DSA) and to evaluate the relationship between DSA presence and graft function, cardiac allograft vasculopathy (CAV), and mortality.

Methods

The study population comprises 193 consecutive long‐term heart transplanted (HTx) patients who underwent DSA surveillance between 2016 and 2022. The patients were prospectively screened for CAV through serial coronary angiograms, graft function impairment through serial echocardiograms, and cardiac biomarkers. The patients were followed from the first DSA measurement until death, 5 years follow‐up or right censuring on the 30th of June 2023.

Results

DSAs were detected in 50 patients using a cut‐off at MFI ≥1000 and 45 patients using a cut‐off at ≥2000 MFI. The median time since HTx was 9.0 years [3.0–14.4]. DSA positive patients had poorer graft function and higher values of NT‐proBNP and troponin T, and more prevalent CAV than DSA negative patients. In total, 25 patients underwent endomyocardial biopsies due to DSA presence while another eight patients underwent endomyocardial biopsies for other reasons. Histological antibody mediated rejection (AMR) signs were seen in three biopsies. During a median follow‐up of five years [4.7–5], a total of 41 patients died. Mortality rates did not differ between DSA positive and DSA negative patients (HR 1.2, 95% CI .6–2.4). DSA positive patients were more likely to experience CAV progression than DSA negative patients (HR 2.7, 95% CI 1.5–4.8)

Conclusions

Routine screening reveals DSA in approximately 25% of long‐term HTx patients but is rarely related to histopathological AMR signs. DSA presence was associated with poorer graft function and more prevalent and progressive CAV. However, DSA positive patients had similar survival rates to DSA negative patients.
Lessons for future clinical trials in adults with Becker muscular dystrophy: Disease progression detected by muscle magnetic resonance imaging, clinical and patient‐reported outcome measures
Authors: De Wel Bram , Iterbeke Louise , Huysmans Lotte , Peeters Ronald , Goosens Veerle , Dubuisson Nicolas , van den Bergh Peter , Van Parijs Vinciane , Remiche Gauthier , De Waele Liesbeth , Maes Frederik , Dupont Patrick , Claeys Kristl G.
Published: March 2024

Background and purpose

Because Becker muscular dystrophy (BMD) is a heterogeneous disease and only few studies have evaluated adult patients, it is currently still unclear which outcome measures should be used in future clinical trials.

Methods

Muscle magnetic resonance imaging, patient‐reported outcome measures and a wide range of clinical outcome measures, including motor function, muscle strength and timed‐function tests, were evaluated in 21 adults with BMD at baseline and at 9 and 18 months of follow‐up.

Results

Proton density fat fraction increased significantly in 10/17 thigh muscles after 9 months, and in all thigh and lower leg muscles after 18 months. The 32‐item Motor Function Measurement (MFM‐32) scale (−1.3%, p = 0.017), North Star Ambulatory Assessment (−1.3 points, p = 0.010) and patient‐reported activity limitations scale (−0.3 logits, p = 0.018) deteriorated significantly after 9 months. The 6‐min walk distance (−28.7 m, p = 0.042), 10‐m walking test (−0.1 m/s, p = 0.032), time to climb four stairs test (−0.03 m/s, p = 0.028) and Biodex peak torque measurements of quadriceps (−4.6 N m, p = 0.014) and hamstrings (−5.0 N m, p = 0.019) additionally deteriorated significantly after 18 months. At this timepoint, domain 1 of the MFM‐32 was the only clinical outcome measure with a large sensitivity to change (standardized response mean 1.15).

Discussion

It is concluded that proton density fat fraction imaging of entire thigh muscles is a sensitive outcome measure to track progressive muscle fat replacement in patients with BMD, already after 9 months of follow‐up. Finally, significant changes are reported in a wide range of clinical and patient‐reported outcome measures, of which the MFM‐32 appeared to be the most sensitive to change in adults with BMD.
Outcomes and outcome measures
Authors: Castaman Giancarlo , Jimenez‐Yuste Victor , Gouw Samanta , D'Oiron Roseline
Published: March 2024

Introduction

Advances in haemophilia treatment have resulted in a near‐normal life expectancy, lower burden of bleeding and treatment, and improved quality of life in high‐income countries. Bleeding rate is approaching zero and novel parameters should be evaluated to assess the efficacy of treatment not only from the clinical point of view by using new methodologies (e.g. joint health assessment), but also from the patient's perspective (e.g. pain, quality of life, treatment satisfaction).

Methods and results

This approach should be aimed at combining objective clinical methodologies and patient‐reported outcomes (PROs). However, some instruments used for assessing PROs are still suboptimal and not properly validated. Recent evidence suggests that these tools can take advantage from a more personalized designed approach and could be effectively improved and serve to facilitate the patient's self‐evaluation. For other congenital bleeding disorders (BDs), a set of patient‐relevant outcomes has been also defined that overlap substantially those of haemophilia, including bleeding, side effects and complications, and PROs, such as pain, physical functioning, impact on daily life including school and work and mental health. There is a growing focus on addressing women‐specific outcomes in BDs, reflecting an increased awareness of the unique challenges faced by women in this context. However, the development of tailored tools is imperative to further advance the progress in managing women with BDs, ensuring more accurate monitoring and personalized care.

Conclusions

How incorporating these outcome measures in the process of approval of novel treatments for these disorders by regulatory authorities remains to be established.
Sialic acid in the regulation of blood cell production, differentiation and turnover
Authors: Irons Eric Edward , Gc Sajina , Lau Joseph T. Y.
Published: March 2024

Sialic acid is a unique sugar moiety that resides in the distal and most accessible position of the glycans on mammalian cell surface and extracellular glycoproteins and glycolipids. The potential for sialic acid to obscure underlying structures has long been postulated, but the means by which such structural changes directly affect biological processes continues to be elucidated. Here, we appraise the growing body of literature detailing the importance of sialic acid for the generation, differentiation, function and death of haematopoietic cells. We conclude that sialylation is a critical post‐translational modification utilized in haematopoiesis to meet the dynamic needs of the organism by enforcing rapid changes in availability of lineage‐specific cell types. Though long thought to be generated only cell‐autonomously within the intracellular ER‐Golgi secretory apparatus, emerging data also demonstrate previously unexpected diversity in the mechanisms of sialylation. Emphasis is afforded to the mechanism of extrinsic sialylation, whereby extracellular enzymes remodel cell surface and extracellular glycans, supported by charged sugar donor molecules from activated platelets.
Does location matter in IS research? A developing country perspective from India
Authors: Seetharaman Priya , Mathew Saji K. , De' Rahul
Published: March 2024

This paper examines the question of doing information systems (IS) research from a location, particularly from a developing country like India. Our analysis reveals that IS publications from India are relatively few in number, though increasing in recent years; hardly focussed on context‐specific issues and concerns; and are largely in lower‐ranked journals. Using neo‐institutional theory, we show that the reasons are dominantly coercive (measuring up to rankings and accreditation agencies) and mimetic (following leaders). Normative (influence of professional bodies) forces appear to counterbalance this by necessitating continuous improvement in research outputs and emphasising location‐specific, impactful research. Institutional responses to these forces manifest in policies and mechanisms to operationalise them, such as resource availability, balancing teaching load with research expectations, promotion and tenure policies amongst others. We examine the paths by which more rigorous and relevant research, responsible to a location can be achieved, based on the insights from a series of talks given by eminent IS scholars. We opine that there is a need to consciously seek out such paths, perhaps by actively seeking collaboration with other disciplines and practitioners; establishing programmes of research; and building contextualised theories. We conclude with a relook at the underlying dynamics of the various institutional responses, recommended paths and some policy implications of our findings.
Peer perspectives on friendships among peers with and without intellectual and developmental disabilities: A pilot mixed methods study
Authors: Shikarpurya Sehrish , Fogarty Melissa , Gilson Carly B. , Benzel Megan , Fletcher Katherine E. , Osburn Courtney , Villarreal Alexis , Tassin Abigail
Published: March 2024

Background

The benefits of friendships among peers with and without intellectual and developmental disabilities are well supported by research. However, little is known about the nature of these inclusive friendships in inclusive college courses.

Method

We explored the perspectives of peers on the development of authentic friendships among peers with and without intellectual and developmental disabilities in inclusive college courses in the United States. We used a sequential, explanatory, transformative mixed methods‐grounded theory research design. We integrated quantitative (N = 44) and qualitative (N = 8) findings using blended analysis to inform a preliminary grounded theory of inclusive and reciprocal friendships.

Results

Quantitative findings suggest two relationships and one predictor of peers' perceived social engagement. Qualitative findings resulted in five themes that promote friendships.

Conclusions

We propose that the context for developing inclusive friendships could be fostered using the preparation and actions stages of the grounded theory model.
Behavioural, developmental and psychological characteristics in children with germline PTEN mutations: a carer report study
Authors: Cummings K. , Dias R. P. , Hart R. , Welham A.
Published: March 2024

Background

PTEN is primarily known as a tumour suppressor gene. However, research describes higher rates of difficulties including intellectual disability and difficulties relating to autism spectrum conditions (ASCs) in people with germline PTEN mutations. Other psychological characteristics/experiences are less often reported and are explored in this study.

Methods

The parents of 20 children with PTEN mutations completed an online survey exploring adaptive behaviour, ASC‐associated behaviours, anxiety, mood, hypermobility, behaviours that challenge, sensory experiences, quality of life and parental wellbeing. Published normative data and data from groups of individuals with other genetic neurodevelopmental conditions were used to contextualise findings.

Results

Overall levels of adaptive behaviour were below the ‘typical’ range, and no marked relative differences were noted between domains. Higher levels of ASC‐related difficulties, including sensory experiences, were found in comparison with ‘typically developing’ children, with a possible peak in restrictive/repetitive behaviour; ASC and sensory processing atypicality also strongly correlated with reported joint hypermobility. A relative preservation of social motivation was noted. Anxiety levels were found to be elevated overall (and to relate to sensory processing and joint hypermobility), with the exception of social anxiety, which was comparable with normative data. Self‐injurious behaviour was common.

Conclusions

Results suggest a wide range of possible difficulties in children with PTEN mutations, including elevated anxiety. Despite elevated ASC phenomenology, social motivation may remain relatively strong. Firm conclusions are restricted by a small sample size and potential recruitment bias, and future research is required to further explore the relationships between such characteristics.
Long‐term effects of environmental dynamic lighting on sleep–wake rhythm, mood and behaviour in older adults with intellectual disabilities
Authors: Böhmer M. N. , Oppewal A. , Bindels P. J. E. , van Someren E. J. W. , Festen D. A. M.
Published: March 2024

Background

Sleep–wake problems and depressive symptoms are common in people with intellectual disabilities (IDs) and are thought to be related to the unstable sleep–wake rhythm in this population. Previously, we showed that after increasing environmental light exposure, mid‐sleep and sleep onset advanced, and mood improved over a period of 14 weeks after installing environmental dynamic light installations in the living room of people with IDs. We invited participants of that short‐term study to take part in the current study on sleep–wake rhythm, mood and behaviour in older adults with IDs 1 year after installing environmental dynamic light installations in the common living rooms of six group homes.

Methods

A pre–post study was performed from October 2017 to February 2019. We included 45 participants (63.5 ± 8.5 years, 67% female) from six group home facilities who provided data at baseline (9, 4 and 1 weeks prior to installing light installations), short term (3, 7 and 14 weeks after installing light installations) and 1 year (54 weeks after installing light installations). Wrist activity was measured with actigraphy (GENEActiv) to derive the primary outcome of interdaily stability of sleep–wake rhythms as well as sleep estimates. Mood was measured with the Anxiety, Depression and Mood Scale. Behaviour was measured with the Aberrant Behaviour Checklist.

Results

One year after installing dynamic lighting, we did not find a change in interdaily stability. Total sleep time decreased (β = −25.40 min; confidence interval: −10.99, −39.82), and sleep onset time was delayed (β = 25.63 min; confidence interval: 11.18, 40.08). No effect on mood or behaviour was found.

Conclusions

We did not find a change in sleep–wake rhythm, mood or behaviour in older persons with IDs living in care facilities 1 year after installing the light. We did find evidence for a long‐term effect on sleep duration and sleep timing. The results have to be interpreted with care as the current study had a limited number of participants. The need for more research on the long‐term effects of enhancing environmental light in ID settings is evident.
Comparison of ovarian reserve after cystectomy of ovarian endometrioma by bipolar coagulation, suture method, or hemostatic sealants: An updated meta‐analysis
Authors: Paik Haerin , Jee Byung Chul
Published: March 2024

Aim

The purpose of the study was to compare the ovarian reserve after cystectomy of ovarian endometrioma by bipolar coagulation, suture method, or hemostatic sealants (HSs).

Methods

We performed a meta‐analysis of studies in which post‐cystectomy serum anti‐Müllerian hormone (AMH) values were compared between bipolar coagulation and suture method or between bipolar coagulation and HSs. Through a literature search, we retrieved 14 articles which met inclusion criteria and were eligible for final analysis. The articles included 10 randomized trials, 3 prospective studies, and 1 retrospective study (n = 1435). The primary outcome was post‐cystectomy serum AMH values.

Results

Both bipolar coagulation and suture methods showed significantly lower post‐cystectomy AMH values at 3, 6, and 12 months. However, post‐cystectomy serum AMH values at 12 months were significantly higher in the suture method group compared to the bipolar coagulation (weighted mean difference [WMD]: −1.10, 95% confidence interval [CI]: −1.83, −0.38, p = 0.003, I2 = 89, n = 3). The suture method also showed a lower decline rate at 3 months post‐cystectomy compared to the bipolar coagulation group (WMD: −25.13%, 95% CI: −49.56 to −0.70, p = 0.04, I2 = 95%, n = 2). Overall, pregnancy rates were similar between the two groups. Between the bipolar coagulation and HSs group, serum AMH values at 3 months post‐cystectomy were similar (WMD: −0.46, 95% CI: −1.04 to 0.13, p = 0.13, I2 = 0%, n = 3). However, the HSs group showed a less decline rate at 3 months post‐cystectomy compared to the bipolar coagulation group (WMD: −17.02%, 95% CI: −22.81, −11.23, p < 0.00001, I2 = 0%, n = 3).

Conclusions

Both the suture method and HSs may have potential benefits in the preservation of ovarian reserve over the bipolar coagulation method when cystectomy for ovarian endometrioma is performed.
A bloody mess? UK regulation of menopause discrimination and the need for reform
Authors: WESTWOOD SUE
Published: March 2024

This article considers the regulation of menopause‐related discrimination in the workplace. Many menopausal women experience profound workplace inequalities, often connected with the intersection of ageism and sexism. The United Kingdom Parliament's Women and Equalities Committee (WEC) recently recommended that the government consult about a new protected characteristic, ‘menopause’, and that Section 14 of the Equality Act 2010 (EqA) on dual discrimination be brought into force. The government has rejected these recommendations, asserting that menopausal women are sufficiently protected under the EqA's existing provision. This article presents an alternative perspective, arguing that there is insufficient legal protection from menopause discrimination, with it fitting poorly within age, sex, and/or disability discrimination, and there being no facility for intersectional claims. The WEC is correct: Section 14 should be implemented, ‘menopause’ should be a protected characteristic, and, beyond that, the EqA needs wider reform to provide greater protections from discrimination, beyond inflexible identity categories that fail to allow for complex intersecting structural oppressions.
Cerebellar phenotypes in germline PTEN mutation carriers
Authors: Gambini Donatella , Ferrero Stefano , Bulfamante Gaetano , Pisani Luigi , Corbo Massimo , Kuhn Elisabetta
Published: March 2024

PTEN hamartoma tumour syndrome (PHTS) comprises different hereditary conditions caused by germline PTEN mutations, predisposing to the development of multiple hamartomas in many body tissues and also increasing the risk of some types of cancer.

Cerebellar involvement in PHTS patients has been long known due to the development of a pathognomonic cerebellar hamartoma (known as dysplastic gangliocytoma of the cerebellum or Lhermitte‐Duclos disease). Recently, a crucial role of the cerebellum has been highlighted in the pathogenesis of autism spectrum disorders, now recognised as a phenotype expressed in a variable percentage of PHTS children. In addition, rare PTEN variants are indeed identified in medulloblastoma as well, even if they are less frequent than other germline gene mutations.

The importance of PTEN and its downstream signalling enzymatic pathways, PI3K/AKT/mTOR, has been studied at different levels in both human clinical settings and animal models, not only leading to a better understanding of the pathogenesis of different disorders but, most importantly, to identify potential targets for specific therapies. In particular, PTEN integrity makes an important contribution to the normal development of tissue architecture in the nervous system, including the cerebellum. Thus, in patients with PTEN germline mutations, the cerebellum is an affected organ that is increasingly recognised in different disorders, whereas, in animal models, cerebellar Pten loss causes a variety of functional and histological alterations.

In this review, we summarise the range of cerebellar involvement observed in PHTS and its relationships with germline PTEN mutations, along with the phenotypes expressed by murine models with PTEN deficiency in cerebellar tissue.
Imagination as a source of empirical justification
Authors: Myers Joshua
Published: March 2024

Traditionally, philosophers have been skeptical that the imagination can justify beliefs about the actual world. After all, how could merely imagining something give you any reason to believe that it is true? However, within the past decade or so, a lively debate has emerged over whether the imagination can justify empirical belief and, if so, how. This paper provides a critical overview of the recent literature on the epistemology of imagination and points to avenues for future research.
Peritoneal Phosphate Clearance: Determinants and Association With Mortality
Authors: Li Jinping , Zhang Wenyu , Wang Xichao , Sun Na , Li Lei , Chang Wenxiu
Published: March 2024

Background

Dialytic phosphate removal is a cornerstone of the management of hyperphosphatemia in peritoneal dialysis (PD) patients, but the influencing factors on peritoneal phosphate clearance (PPC) are incompletely understood. Our objective was to explore clinically relevant factors associated with PPC in patients with different PD modality and peritoneal transport status and the association of PPC with mortality.

Methods

This is a cross‐sectional and prospective observational study. Four hundred eighty‐five PD patients were enrolled and divided into 2 groups according to PPC. All‐cause mortality was evaluated after followed‐up for at least 3 months.

Results

High PPC group showed lower mortality compared with Low PPC group by Kaplan–Meier analysis and log‐rank test. Both multivariate linear regression and multivariate logistic regression revealed that high transport status, total effluent dialysate volume per day, continuous ambulatory PD (CAPD), and protein in total effluent dialysate volume appeared to be positively correlated with PPC; body mass index (BMI) and the normalized protein equivalent of total nitrogen appearance (nPNA) were negatively correlated with PPC. Besides PD modality and membrane transport status, total effluent dialysate volume showed a strong relationship with PPC, but the correlation differed among PD modalities.

Conclusions

Higher PPC was associated with lower all‐cause mortality risk in PD patients. Higher PPC correlated with CAPD modality, fast transport status, higher effluent dialysate volume and protein content, and with lower BMI and nPNA.
Work-related musculoskeletal disorders in oral health professionals: an umbrella review protocol
Authors: Roby Shiba , Morse Zac , Trevelyan Fiona , Boocock Mark
Published: March 2024

Objective:

The objective of this review is to synthesize the evidence on the prevalence, incidence, risk factors, and preventive and management interventions for work-related musculoskeletal disorders (MSD) in oral health professionals.

Introduction:

Oral health professionals face a considerable risk of developing work-related MSD due to the nature of their work. These disorders can lead to loss of employment, reduced job quality, increased occupational injuries, and early retirement. They can also lead to significant financial burdens for employers and society.

Inclusion criteria:

This umbrella review will include systematic reviews and meta-analyses that have oral health professionals as a population group and address at least one of the following topics: the prevalence or incidence, risk factors, and the efficiency or effectiveness of interventions for the prevention or management of work-related MSD.

Methods:

A systematic search will be conducted across CINAHL Complete (EBSCOhost), Dentistry and Oral Sciences Source (EBSCOhost), MEDLINE (EBSCOhost), Cochrane Library (Ovid), Scopus, PsycINFO (Ovid), AMED Allied and Complementary Medicine (Ovid), Epistemonikos, Ergonomics Abstracts Online (EBSCOhost), and Google Scholar (first 200 articles). The search will be limited to articles published in English, with no restrictions on geographical location. Two independent reviewers will screen the titles and abstracts against the inclusion criteria. The reviews will be assessed using the JBI critical appraisal instrument for systematic reviews and research syntheses, and data will be extracted from each review using a modified version of the JBI data extraction tool. A narrative summary and tables will be used to describe the review characteristics and findings. Results will be presented in a table using visual indicators (traffic light system) to represent beneficial, neutral, and negative effects with each risk factor and intervention. The GRADE approach will be used to rate the overall quality and strength of the evidence.

Review registration:

PROSPERO CRD42023388779
A New Iterative Broyden Legendre Wavelet Galerkin Finite Element Method Applied to Unsteady State Model of Two-Dimensional Elliptic Fin
Authors: Upadhyay Subrahamanyam , Sharma Priti , Singh Surjan , Rai K. N.
Published: March 2024

The novelty of this paper is the investigation of numerical study of a mathematical model, which deals with time-dependent heat flow in elliptic fin (dry, wet, and partially wet). In this paper, we developed a nonlinear model of second-order heat equations in unsteady state condition. A new iterative Broyden Legendre Wavelet Galerkin Finite Element Method (BLWGFEM) is used for the solution. The central difference approximation used for discretization of second order derivatives and then utilization of Hadamard, Khatri Rao and Face splitting matrices product with Legendre Wavelet Galerkin Method transfers our main problem into system of nonlinear algebraic equations. The iterative Broyden Method provides the solution for this system. In a particular case, present solution is compared with the exact solution and is approximately the same. Effect of different parameters such as Biot number, Latent heat, Kirpichev number, Fin thickness, Axis ratio, μ, η, and ξ on the temperature distribution are discussed in detail.
Effects of Flow Pulsation and Surface Geometry on Heat Transfer Performance in a Channel With Teardrop-Shaped Dimples Measured by Transient Technique
Authors: Kobayashi Shimpei , Inokuma Kento , Murata Akira , Iwamoto Kaoru
Published: March 2024

This study focuses on the heat transfer performance of a pulsating flow over a channel surface with teardrop-shaped dimples. Heat transfer measurements were performed by a transient technique with compensation of three-dimensional heat conduction under a bulk Reynolds number of 25,000. Seven types of surfaces with the teardrop-shaped dimples were examined, where dimple arrangement (in-line/staggered) and inclination angle (0–60 deg) were varied. A pulsating flow with the Strouhal number of 0.15 was generated by vibrating a rubber film section on the channel wall using a vibration generator. The pulsation amplitude was evaluated by calculating the root-mean-square value of the phase averaged velocity. Two conditions of the pulsation amplitudes were examined (0.09 and 0.12 of mean velocity). The results showed that the surface-averaged Nusselt number and friction factor for the pulsating flow increased from those for the steady flow. The highest increases of the surface-averaged Nusselt number and heat transfer efficiency index appeared in the 30 deg in-line arrangement, and those were 16.1% and 9.8%, respectively, at most as compared with the steady case. Due to the flow pulsation, the local Nusselt number was enhanced at the leading-edge region of the dimples, and supplementary Reynolds averaged Navier–Stokes (RANS)/unsteady RANS (URANS) results showed that the flow separation size was shrunk by the flow pulsation there.
Examining Audiences’ Information-Seeking Behavior Surrounding the Super Bowl and Sex Trafficking: Insights From Google Trends Data
Authors: Wang Wenche , Sant Stacy-Lynn , King Elizabeth
Published: March 2024

Sex trafficking is a prominent human rights issue that has been increasingly associated with the hosting of large-scale sport events. Despite insufficient evidence demonstrating a causal or correlative link, event stakeholders have implemented antitrafficking efforts in attempts to prevent and promote awareness of sex trafficking. Using Google Trends data to measure audiences’ information-seeking behavior online and Twitter data as a proxy for antitrafficking efforts on social media, we employed a difference-in-differences approach to estimate the change in online demand for sex-trafficking information among the residents of Miami-Dade, the host city of Super Bowl LIV (54). Findings highlight an increase in the online demand for sex-trafficking information in the host city during and after the event. This increased demand attributed to the Super Bowl may offer support for host communities utilizing sport events to promote awareness of pressing social issues.
Functional representation of trigeminal nociceptive input in the human periaqueductal gray
Authors: Mehnert Jan , Tinnermann Alexandra , Basedau Hauke , May Arne
Published: March 2024

The periaqueductal gray (PAG) is located in the mesencephalon in the upper brainstem and, as part of the descending pain modulation, is considered a crucial structure for pain control. Its modulatory effect on painful sensation is often seen as a systemic function affecting the whole body similarly. However, recent animal data suggest some kind of somatotopy in the PAG. This would make the PAG capable of dermatome-specific analgesic function. We electrically stimulated the three peripheral dermatomes of the trigemino-cervical complex and the greater occipital nerve in 61 humans during optimized brainstem functional magnetic resonance imaging. We provide evidence for a fine-grained and highly specific somatotopic representation of nociceptive input in the PAG in humans and a functional connectivity between the individual representations of the peripheral nerves in the PAG and the brainstem nuclei of these nerves. Our data suggest that the downstream antinociceptive properties of the PAG may be rather specific down to the level of individual dermatomes.
Outbreak of NDM-5-producing
Klebsiella pneumoniae
ST307: an emerging high-risk antimicrobial resistance clone in Shanghai, China
Authors: Zhu Junying , Wang Guangyu , Li Min
Published: March 2024

The high-risk clone
Klebsiella pneumoniae
ST307, associated with various carbapenem resistance genes, exhibits a global distribution and prevalence. However, in China, it has remained sporadic and has rarely been detected. In this study, we reported an outbreak caused by nine ST307 CRKP isolates harboring
bla
NDM-5
in Shanghai, China, in 2022. We employed antimicrobial susceptibility testing, conjugation assay, whole-genome sequencing (WGS) and comparative genomics, phylogenetic analysis, and fitness and virulence comparison to further characterize the isolates causing the outbreak. Besides
bla
NDM-5
, these nine isolates co-carried
bla
CTX-M-15
and
bla
DHA-1
, exhibiting nearly identical resistance profiles with high-level resistance to carbapenems and ceftazidime/avibactam, while showing susceptibility to colistin and tigecycline.
bla
NDM-5
was located on an IncX3 plasmid of 45,403 bp with a high frequency of conjugative ability. Phylogenetic and single-nucleotide polymorphism (SNP) analysis indicated the nature of clonal transmission with a maximum of five SNPs between these nine isolates, and they were closely related to strains obtained from the United States. ST307 isolates in our study showed a relatively lower virulence but higher growth rates and certain adaptability compared with ST11 isolates. Clinical investigation revealed that shared nursing staff in a mixed emergency intensive care unit ward and doctors’ movement between wards might be responsible for the outbreak. The nonexistence before and sudden emergence of ST307 suggested that the currently circulating ST307 clone was a newly introduced superbug in our hospital. In conclusion, we revealed that
bla
NDM-5
-producing ST307 CRKP isolates, a globally significant high-risk clone, are spreading in China, posing a substantial threat to public health.

IMPORTANCE

The high-risk clone ST307, associated with various carbapenemases, including KPC, NDM, and OXA, has a global distribution. However, it is rarely reported in China, let alone causing outbreaks. Here, we found an outbreak caused by the clonal transmission of nine ST307 CRKP isolates. Clinical investigation revealed that shared nurses in a mixed emergency intensive care unit ward and doctors’ movement between wards might be responsible for the outbreak. In our study, the nine NDM-5-producing ST307 isolates exhibited high-level resistance to carbapenems and ceftazidime-avibactam, high conjugative ability to
Escherichia coli
J53, and certain adaptability to environment, phylogenetically closet to the United States. All these features make ST307 clone the next successful clone comparable to ST11 clone in China. Therefore, it is imperative for us to vigilantly monitor the prevalence of carbapenem-resistant
Klebsiella pneumoniae
and promptly implement measures to control the spread of
K. pneumoniae
ST307 in China.
Severe case of pustular psoriasis during pregnancy
Authors: van Ierland Katherine , Vredevoogd Corla , Roach Rachel , Clahsen Pieter
Published: March 2024

Pustular psoriasis of pregnancy (PPP) is a rare variant of generalised pustular psoriasis occurring during or after pregnancy. PPP can have significant maternal and fetal morbidity if left untreated. In this case report, we present a pregnant woman with this rare cutaneous disorder and how it was treated. Due to the limited available evidence regarding the treatment of PPP, we describe the treatment that was given based on the clinical manifestations and severity of the disease.
Preterm prelabour rupture of membranes before 23 weeks’ gestation: prospective observational study
Authors: Goodfellow Laura , Care Angharad , Curran Ciara , Roberts Devender , Turner Mark A , Knight Marian , Zarko Alfirevic
Published: March 2024

Objective

To describe perinatal and maternal outcomes of preterm prelabour rupture of membranes (PPROM) before 23 weeks' gestation in a national cohort.

Design

Prospective observational study.

Setting

National population based cohort study with the UK Obstetric Surveillance System (UKOSS), a research infrastructure of all 194 obstetric units in the UK, 1 September 2019 to 28 February 2021.

Participants

326 women with singleton and 38 with multiple pregnancies with PPROM between 16+0 and 22+6 weeks+days' gestation.

Main outcome measures

Perinatal outcomes of live birth, survival to discharge from hospital, and severe morbidity, defined as intraventricular haemorrhage grade 3 or 4, or requiring supplemental oxygen at 36 weeks' postmenstrual age, or both. Maternal outcomes were surgery for removal of the placenta, sepsis, admission to an intensive treatment unit, and death. Clinical data included rates of termination of pregnancy for medical reasons.

Results

Perinatal outcomes were calculated with all terminations of pregnancy for medical reasons excluded, and a worst-best range was calculated assuming that all terminations for medical reasons and those with missing data would have died (minimum value) or all would be liveborn (maximum value). For singleton pregnancies, the live birth rate was 44% (98/223), range 30-62% (98/326-201/326), perinatal survival to discharge from hospital was 26% (54/207), range 17-53% (54/326-173/326), and 18% (38/207), range 12-48% (38/326-157/326) of babies survived without severe morbidity. The rate of maternal sepsis was 12% (39/326) in singleton and 29% (11/38) in multiple pregnancies (P=0.004). Surgery for removal of the placenta was needed in 20% (65/326) and 16% (6/38) of singleton and twin pregnancies, respectively. Five women became severely unwell with sepsis; two died and another three required care in the intensive treatment unit.

Conclusions

In this study, 26% of women who had very early PPROM with expectant management had babies that survived to discharge from hospital. Morbidity and mortality rates were high for both mothers and neonates. Maternal sepsis is a considerable risk that needs more research. These data should be used in counselling families with PPROM before 23 weeks' gestation, and currently available guidelines should be updated accordingly.
Tracing Tomorrow: young people’s preferences and values related to use of personal sensing to predict mental health, using a digital game methodology
Authors: Pavarini Gabriela , Lyreskog David M , Newby Danielle , Lorimer Jessica , Bennett Vanessa , Jacobs Edward , Winchester Laura , Nevado-Holgado Alejo , Singh Ilina
Published: March 2024

Background

Use of personal sensing to predict mental health risk has sparked interest in adolescent psychiatry, offering a potential tool for targeted early intervention.

Objectives

We investigated the preferences and values of UK adolescents with regard to use of digital sensing information, including social media and internet searching behaviour. We also investigated the impact of risk information on adolescents’ self-understanding.

Methods

Following a Design Bioethics approach, we created and disseminated a purpose-built digital game (www.tracingtomorrow.org) that immersed the player-character in a fictional scenario in which they received a risk assessment for depression Data were collected through game choices across relevant scenarios, with decision-making supported through clickable information points.

Findings

The game was played by 7337 UK adolescents aged 16–18 years. Most participants were willing to personally communicate mental health risk information to their parents or best friend. The acceptability of school involvement in risk predictions based on digital traces was mixed, due mainly to privacy concerns. Most participants indicated that risk information could negatively impact their academic self-understanding. Participants overwhelmingly preferred individual face-to-face over digital options for support.

Conclusions

The potential of digital phenotyping in supporting early intervention in mental health can only be fulfilled if data are collected, communicated and actioned in ways that are trustworthy, relevant and acceptable to young people.

Clinical implications

To minimise the risk of ethical harms in real-world applications of preventive psychiatric technologies, it is essential to investigate young people’s values and preferences as part of design and implementation processes.
Exploring the barriers to, and importance of, participant diversity in early-phase clinical trials: an interview-based qualitative study of professionals and patient and public representatives
Authors: Chatters Robin , Dimairo Munyaradzi , Cooper Cindy , Ditta Shamila , Woodward Jonathan , Biggs Katie , Ogunleye Della , Thistlethwaite Fiona , Yap Christina , Rothman Alexander
Published: March 2024

Objectives

To explore the importance of, and barriers to achieving, diversity in early-phase clinical trials.

Design

Qualitative interviews analysed using thematic analysis.

Setting and participants

Five professionals (clinical researchers and methodologists) and three patient and public representatives (those with experience of early-phase clinical trials and/or those from ethnic minority backgrounds) were interviewed between June and August 2022. Participants were identified via their institutional web page, existing contacts or social media (eg, X, formerly known as Twitter).

Results

Professionals viewed that diversity is not currently considered in all early-phase clinical trials but felt that it should always be taken into account. Such trials are primarily undertaken at a small number of centres, thus limiting the populations they can access. Referrals from clinicians based in the community may increase diversity; however, those referred are often not from underserved groups. Referrals may be hindered by the extra resources required to approach and recruit underserved groups and participants often having to undertake ‘self-driven’ referrals. Patient and public representatives stated that diversity is important in research staff and that potential participants should be informed of the need for diversity. Those from underserved groups may require clarification regarding the potential harms of a treatment, even if these are unknown. Education may improve awareness and perception of early-phase clinical trials. We provide 14 recommendations to improve diversity in early-phase clinical trials.

Conclusions

Diversity should be considered in all early-phase trials. Consideration is required regarding the extent of diversity and how it is addressed. The increased resources needed to recruit those from underserved groups may warrant funders to increase the funds to support the recruitment of such participants. The potential harms and societal benefits of the research should be presented to potential participants in a balanced but accurate way to increase transparency.
What Matters to Aboriginal and Torres Strait Islander Youth (WM2Y): a study protocol to develop a national youth well-being measure
Authors: Garvey Gail , Howard Kirsten , Garvey Darren , Dickson Michelle , Howell M , Butler Tamara L , Cadet-James Yvonne , Cunningham Joan , Bainbridge Roxanne , McGorry Patrick , Williamson A , Anderson Kate Mallory
Published: March 2024

Introduction

Adolescents face challenges associated with unprecedented environmental, social and technological changes. The impacts of colonisation, intergenerational trauma, racism and socioeconomic disadvantage intensify these challenges for many Aboriginal and Torres Strait Islander adolescents. However, Aboriginal and Torres Strait Islander adolescents also have cultural, spiritual, family and community capital that fosters their well-being.

To date, little research has focused on understanding and appropriately measuring the well-being of Aboriginal and Torres Strait Islander adolescents, a pivotal factor in informing and guiding programmes and interventions that support them. This study will identify the domains of well-being and develop a new preference-based well-being measure based on the values and preferences of Aboriginal and Torres Strait Islander youth (aged 12–17 years).

Methods and analysis

This project will be conducted across three research phases: (1) qualitative exploration of well-being using PhotoYarning and yarns with adult mentors to develop candidate items; (2) Think Aloud study, quantitative survey, psychometric analysis, validity testing of candidate items and finalisation of the descriptive system; and (3) scoring development using a quantitative preference-based approach. A multinomial (conditional) logit framework will be used to analyse responses and generate a scoring algorithm for the new preference-based well-being measure.

Ethics and dissemination

Ethics approvals have been obtained from: the Human Research Ethics Committees for each state and territory where data are being collected, the institutions where the research is being conducted and from the relevant Departments of Education. The new well-being measure will have wide applicability and can be used in assessing the effectiveness of programmes and services. This new national measure will ensure benefit and positive impact through the ability to identify and measure the aspects of well-being important to and valued by Aboriginal and Torres Strait Islander youth. Results will be published in international peer-reviewed journals and presented at conferences, and summaries will be provided to the study partner organisations and other relevant organisations.
Health-related quality of life after 12 months post discharge in patients hospitalised with COVID-19-related severe acute respiratory infection (SARI): a prospective analysis of SF-36 data and correlation with retrospective admission data on age, disease severity, and frailty
Authors: Wright Gavin , Senthil Keerthi , Zadeh-Kochek Amir , Au Jonathan Heung-san , Zhang Jufen , Huang Jiawei , Saripalli Ravi , Khan Mohiuddin , Ghauri Omar , Kim San , Mohammed Zakiuddin , Alves Carol , Koduri Gouri
Published: March 2024

Long-term outcome and ‘health-related quality of life’ (HRQoL) following hospitalisation for COVID-19-related severe acute respiratory infection (SARI) is limited.

Objective

To assess the impact of HRQoL in patients hospitalised with COVID-19-related SARI at 1 year post discharge, focusing on the potential impact of age, frailty, and disease severity.

Method

Routinely collected outcome data on 1207 patients admitted with confirmed COVID-19 related SARI across all three secondary care sites in our NHS trust over 3 months were assessed in this retrospective cohort study. Of those surviving 1 year, we prospectively collected 36-item short form (SF-36) HRQoL questionnaires, comparing three age groups (<49, 49–69, and the over 69-year-olds), the relative impact of frailty (using the Clinical Frailty Score; CFS), and disease severity (using National Early Warning Score; NEWS) on HRQoL domains.

Results

Overall mortality was 46.5% in admitted patients. In our SF-36 cohort (n=169), there was a significant reduction in all HRQoL domains versus normative data; the most significant reductions were in thephysical component(p<0.001) across all ages and theemotional component(p<0.01) in the 49–69 year age group, with age having no additional impact on HRQoL. However, there was a significant correlation between physical well-beingversus CFS (the correlation coefficient=−0.37, p<0.05), though not NEWS, with no gender difference observed.

Conclusion

There was a significant reduction in all SF-36 domains at 1 year. Poor CFS at admission was associated with a significant and prolonged impact on physical parameters at 1 year. Age had little impact on the severity of HRQoL, except in the domains ofphysical functioningand the overallphysical component.
Enablers and barriers to a quaternary prevention approach: a qualitative study of field experts
Authors: Otte Jessica Anneliese , Llargués Pou Maria
Published: March 2024

Objective

There is a growing concern about the sustainability of healthcare and the impacts of ‘overuse’ on patients and systems. Quaternary prevention (P4), a concept promoting the protection of patients from medical interventions in which harms outweigh benefits, is well positioned to stimulate reflection and inspire solutions, yet has not been widely adopted. We sought to identify enablers and barriers to a P4 approach, according to field experts and advocates in one health system.

Design

Qualitative methodology, using semistructured interviews and a grounded theory approach facilitated thematic analysis and development of a conceptual model.

Setting

Virtual interviews, conducted in British Columbia, Canada.

Participants

12 field experts, recruited based on their interest and work related to P4 and related concepts.

Results

Four factors were seen as promoting or hindering P4 efforts depending on context: relationship between patient and clinician, education of clinicians and the public, health system design and influencers. We extracted four broad enablers of P4: evidence-based medicine, personal experiences and questioning attitude, public P4 campaigns and experience in resource-poor contexts. There were six barriers: peer pressure between clinicians, awareness and screening campaigns, cognitive biases, cultural factors, complexity of the problem and industry influence.

Conclusions

Elicited facilitators and impediments to the application of P4 were similar to those seen in existing literature but framed uniquely; our findings place increased emphasis on the clinician–patient relationship as central to decision-making and position other drivers as influencing this relationship. A transition to a model of care that explicitly integrates conscious protection of patients by reducing overtesting, overdiagnosis and overtreatment will require changes across health systems and society.