bluuebunny/crossref_metadata_2025 huggingface dataset:
CLINICAL AND ECONOMIC BURDEN OF MAJOR AND TREATMENT- RESISTANT DEPRESSION IN A POPULATION-BASED STUDY COHORT OF 110.000 PATIENTS
Authors: Pappa *Sofia , Shah Moulesh , Young Sophie , Anwar Tazneem , Ming Timothy
Published: February 2025

Background

Major depressive disorder (MDD) is a leading cause of global disability. Despite availability of effective therapies, many patients with MDD develop treatment-resistant depression (TRD).

Aims

To evaluate and compare treatment outcomes, comorbidities and healthcare resource usage and costs in patients with major depressive disorder (MDD) and treatment-resistant depression (TRD).

Methods

This was a population-based, retrospective analysis of linked primary and secondary care NHS data in the northwest London Discover-NOW dataset. This is the access platform for the longitudinal Whole Systems Integrated Care (WSIC) database, which is hosted by Imperial College Health Partners and contains linked coded primary, acute, mental health, community health, and social care records fed by over 400 provider organisations and covering more than 2.5 million patients. Eligible patients were adults who were registered with a General Practitioner in the area, had diagnostic codes for depression and had been prescribed at least one antidepressant between 2015 and 2020.

Results

A total of 110,406 patients were eligible for inclusion (101,333 [92%] with MDD and 9,073 [8%] with TRD). Mean duration of depression was 52.8 (SD 41.7) months and 70.8 (SD 37.8), respectively. Remission was recorded in 42,348 (42%) patients with MDD and 1,188 (13%) with TRD (p<0.0001) while relapse was seen in 20,970 (21%) and 4,923 (54%), respectively (p<0.0001) during the study period.

Patients with TRD had significantly higher risks of suicidal behaviour and comorbidities such as anxiety, asthma, and alcohol/substance misuse (all p<0.0001). Mean times from diagnosis to first contact with mental health services were 38.9 [SD 33.6] months for MDD and 41.5 [SD 32.0] months for TRD (p<0.0001). Individuals with TRD had considerably higher primary care and emergency attendance rates, more inpatient hospitalizations, longer hospital stays, and greater total healthcare costs than MDD patients. Demand increased with the duration of depression and the number of lines of treatment.

Primary care usage was greatest overall (TRD mean 162 [SD 96] vs. MDD 108 [SD 90] visits per patient, p<0.0001; cost per patient £17,348 [SD £33,040] vs. £12,011 [£25,588], p<0.0001). In secondary care, accident and emergency visits accounted for the highest use (TRD mean 5.5 [10.6] vs. MDD 3.54 [SD 6.0] visits per patient, p<0.0001) while non-elective hospitalisations incurred the highest costs (mean £ 2,518 [£8,064] vs. £1,909 [SD £6,807], p<0.0001).

Conclusions

The study highlights the substantial individual patient and economic burden associated with MDD and particularly TRD in both primary and secondary care settings. Findings suggest that evidence- based treatment optimisation, timely access to newer therapies and the development of stratified care pathways and specialist services could improve patients’ outcomes.
MATERNAL EXPOSURE TO AIR POLLUTANT PM2.5 INDUCES AUTISTIC-LIKE BEHAVIOR IN OFFSPRING
Authors: Yau *Sonata Suk-yu
Published: February 2025

Background

Autism spectrum disorder (ASD) is a devastating neurodevelopmental disorder with increasing prevalence worldwide 1. Existing evidence indicates that environmental factors (particularly in utero or during early life) can increase ASD risk 2,3. Recent meta-analysis and systemic review concluded that exposure to PM2.5 during pregnancy increases risk of ASD in newborns4.We hypothesize that maternal exposure to PM2.5 impairs hippocampal neuroplasticity to induce behavioral deficits that resembles autism-like behavior in the offspring. Aims : Determine whether maternal exposure to PM5 induces autism-like behaviors in mouse offspring, Determine whether maternal exposure to PM5 impairs hippocampal structural and synaptic plasticity in mouse offspring.

Method

Eight to ten-week old female C57 mice will be pair-housed and will be subjected to intratracheal instillation of PM2.5 with PM2.5 suspended in artificial lung fluid at the concentration of 3.5 µg/µl (PM2.5 group) or vehicle as control group. PM2.5 with 30 µl for each mouse, every 3 days will be administered to the female mice continuously for 15 days. After the pre-exposure, a breeder male mouse (6-8 week old) will be introduced to the holding cage for a week leaving them uninterrupted to reduce stress and increase fertility rate during mating period. Intratracheal instillation will then be resumed every three day continuously throughout gestation period. Both female and male offspring at the age of 5-6 week old will be subjected to behavioral tests, biochemical assays, electrophysiology experiments.

Results

Maternal exposure to PM2.5 induced core ASD behavior, including impaired social recognition memory, increased repetitive behavior, and impairment in hippocampal dependent learning and memory performance. The behavioral deficits are concurrent with impaired dendritic branching of immature neurons and long-term potentiation in the hippocampal dentate gyrus, though there were no significant effects on altering hippocampal adult neurogenesis and neuroinflammation.

Discussion & Conclusion

The results have suggested that chronic maternal exposure to PM2.5 could induce behavioral abnormalities in adult offspring, which could be linked to impaired neuroplasticity in the hippocampus.

References

Lyall, K., et al. The Changing Epidemiology of Autism Spectrum Disorders. Annual review of public health 38, 81-102 (2017). Gronborg, T.K., Schendel, D.E. &Parner, E.T. Recurrence of autism spectrum disorders in full- and half-siblings and trends over time: a population-based cohort study.

JAMA pediatrics 167, 947-953 (2013). Hallmayer, J., et al. Genetic heritability and shared environmental factors among twin pairs with autism. Archives of general psychiatry 68, 1095-1102 (2011). Dutheil, F., et al. Autism spectrum disorder and air pollution: A systematic review and meta analysis. Environ Pollut 278, 116856 (2021).
ANTIDEPRESSANT AUGMENTATION STRATEGIES TARGETING SIGNAL TRANSDUCTION PROOF OF CONCEPT IN ANIMAL MODELS
Authors: Tzavara *Eleni T , Gorgievski Victor , Le Marois Marguerite , Belzeaux Raoul , Ibrahim El Cherif
Published: February 2025

Background

Antidepressant (AD) resistant depression is a major cause of disability. We have recently identified a novel AD target, the transcription factor ELK-1. ELK-1 operates inside the cell rather than the synapse, where « classical » ADs act.

Aims & Objectives

We hypothesized that an add-on strategy (classical + ELK-1 modulator) would lead to rapid AD action and/or better efficacy.

Methods

Mice were subjected to social defeat (SD, males) or vicarious social defeat (vSD, females) for 10 days and then, screened in the social interaction test (SI). Susceptible mice (SI<1) were further used in two different sets of experiments. (i) To determine the augmentation effect in the delay of onset of action, mice were treated for 6 days with either desipramine (DES; 15mg/kg), fluoxetine (FLX; 10mg/kg), the ELK-1 modulator (TDE; 2 mg/kg) or in combination (DES + TDE ; FLX + TDE). (ii) To determine the augmentation effect on treatment response, mice were treated for 14 days with desipramine; then stratified for each sex into responders (R=35) and non-responders (NR=19) in the SI. NR were divided into two groups, one treated for an additional week with DES alone (n=10) and one treated with DESI+TDE (n=9). At 21 days mice were rescreened at the SI. Same design was repeated to stratify for each sex mice treated with FLX and subsequently non-responders with FLX alone or FLX+TDE.

Results

The combination of the DESI+TDE resulted in the augmented AD effect, namely (i) a faster onset of action (6 days instead of 14 days) and (ii) a greater proportion of AD-R mice treated with the combination (6/9) as compared to DESI alone (2/10). However, using the same methodoogy, this effect was not found with the SSRI FLX+TDE combination. The augmentation effect and te selectivity for DESI was similar for both sexes. The TDE effect was prevented by the mGluR5 antagonist MPEP.

Conclusion

ELK-1 modulation could represent a promising novel augmentation strategy, most likely via glutamate rigid modulation. However, this effect does not apply to all AD classes, in particular SSRIs.
COMPARISON OF INPATIENT PSYCHIATRIC CARE FOR SARS-COV-2 POSITIVE AND NEGATIVE ADULTS IN VIENNA
Authors: Erfurth Andreas , Sachs *Gabriele
Published: February 2025

Introduction

The structure of psychiatric care has undergone many changes in the last decades. In addition, the SARS-CoV-2 pandemic has posed specific challenges for inpatient psychiatric care. In Vienna, the admission of SARS-CoV-2 positive psychiatric patients has been centralised in one department, the 1st Department of Psychiatry and Psychotherapeutic Medicine, Klinik Hietzing.

Aims

To investigate the extent to which admissions of SARS-CoV-2 positive and negative patients differ with regard to medication, age, sex, diagnosis, need for involuntary admission, duration of treatment, country of birth, and where patients come from and where they are discharged to.

Methods

Between 15 March 2020 and 21 May 2022 (start and end of cohorting of all Vienna SARS-CoV- 2 positive inpatients in one department), 338 SARS-CoV-2 positive and 1312 SARS-CoV-2 negative patients were treated as inpatients at the 1st Department of Psychiatry and Psychotherapeutic Medicine of Klinik Hietzing.

Results

The results of the study are presented.

Conclusions

The SARS-CoV-2 pandemic was a major challenge for inpatient psychiatry. A precise differentiation of the treatment of positive and negative patients is important for the assessment of the impact of the pandemic.
PREDICTION OF CLINICAL RESPONSE TO DONEPEZIL AND MEMANTINE IN PATIENTS WITH ALZHEIMER'S DISEASES BY USING EEG CONNECTIVITY
Authors: Youn *Tak , Park Hae Jeong
Published: February 2025

Background

High doses of acetylcholinesterase (AChE) inhibitor Donepezil and non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptor Memantine are approved for the clinical treatment of mild to severe Alzheimer's disease (AD). However, it is unclear which drug is more appropriate when AD progresses from mild to moderate-severe and thus calls for a neurobiological basis for clinical decisions.

Aims & Objectives

by viewing AD as a disconnection syndrome, we explored brain connectivity as a biomarker for medication choice and to predict the outcomes of both Donepezil and Memantine.

Method

Resting-state EEG was recorded from a total of 54 AD patients (mean age=73.4±6.2, male=18, female=36) at starting medication and after treatment. The mean treatment period is 103.1±58.9 weeks. We divided the patients into two groups according to MMSE score change; a group responds to donepezil alone well(n=26), second group responds to Memantine with high doses of donepezil well(n=28). We analyzed brain connectivity among the 246 cortical regions defined by the Brainnetome atlas using the fieldtrip toolbox by evaluating spectral coherence for five frequency bands (delta, theta, alpha, beta, and gamma). We then analyzed each connectivity between groups using ANCOVA with age, sex, and the initial MMSE scores as covariates. Our study found that Memantine with high doses of donepezil group has reduced and disrupted regional connectivity in the theta and gamma frequency bands, especially between the left fronto-occipitoparietal regions (p<0.001). In the alpha frequency band, reduced regional connectivity between the left frontal and medial temporal areas was also observed(p<0.001).

Discussion & Conclusion

This study suggests the potential of the EEG connectivity as a biomarker to predict treatment response to AchE inhibitor and NMDA antagonist in AD.

References

1)Fan, L., Li, H., Zhuo, J., Zhang, Y., Wang, J., Chen, L., Yang, Z., Chu, C., Xie, S., Laird, A.R., Fox, P.T., Eickhoff, S.B., Yu, C. Jiang, T. The Human Brainnetome Atlas: A New Brain Atlas Based on Connectional Architecture. Cerebral Cortex, 26 (8): 3508-3526,(2016)

2)Eo, J., Kang, J., Youn, T., Park, H.J. Neuropharmacological computational analysis of longitudinal electroencephalograms in clozapine-treated patients with schizophrenia using hierarchical dynamic causal modeling. Neuroimage, 120161.(2023)
ANTI DIABETIC PERIPHERAL NEUROPATHY OF RED FRUIT (PANDANUS CONOIDES LAMK) OIL IN A RAT MODEL: INVOLVEMENT OF OXIDATIVE AND NEUROINFLAMMATORY PATHWAYS
Authors: Anggadiredja *Kusnandar , Lestari Indah Tri , Garmana Afrillia Nuryanti , Utami Ratna Annisa
Published: February 2025

Background

Diabetic peripheral neuropathy (DPN) is the most common cause of neuropathy worldwide, with oxidative and inflammatory being the pathways involved. Red fruit (Pandanus conoides Lamk) is a plant native to Papua, Indonesia. Red fruit oil (RFO) is known to have potent antioxidant and antiinflammatory activities.

Aims and Objective

To evaluate the effects of RFO in a rat model of streptozotocin-induced diabetic neuropathy.

Methods

Male Wistar rats were induced with 55 mg/kg streptozotocin intraperioteally. Rats with fasting blood glucose >200 mg/dL were assigned into groups treated with vehicle, pregabalin, and 0.3, 0.6, or 1.2 mL/kg RFO, respectively. Treatments were given for 3 weeks after a 6-week induction period was completed. Neuropathic pain was evaluated by thermal hyperalgesia testing. Histopathological changes of sciatic the nerve were evaluated by the Gaussian adaptive threshold method. Feed and drinking intake, blood glucose levels, body weight, and the sciatic nerve proinflammatory cytokines were also measured.

Results

There were increases in blood glucose levels, feed and drink intake, MDA, TNF-alfa, IL-6, iNOS, NFkB and the number of damaged nerve cells in the DPN rat model when compared with normal rats (p<0.05). Decreased weight, number of pancreatic B cells, latency time of thermal hyperalgesia were also observed in DPN rats. A decrease in NRF2 and HO was observed in DPN rats but was not different compared with the normal group. RFO improved blood glucose, feed and drink intake, body weight, MDA and IL-6 levels, B-cell counts, the sciatic nerve presentation, and thermal hyperalgesia, although they did not return to normal value. Pregabalin did not affect blood glucose levels, body weight or pancreatic B cells but improved thermal hyperalgesia, the nerve cell counts, TNF-alfa, iNOS, IL-6, dan NFkB.

Discussion and Conclusion

Overall, results of the present work indicate that RFO recovers DPN through the involvement of the oxidative and neuroiflammatory pathways.

References

1.leazu CO, Eleazu KC, Chukwuma S, Essien UN. Review of the mechanism of cell death resulting from streptozotocin challenge in experimental animals, its practical use and potential risk to humans. J Diabetes Metab Disord. 2013;12(1):60.

2.Hiramoto K, Ohkawa T, Oikawa N, Kikugawa K. Is nitric oxide (NO) an antioxidant or a prooxidant for lipid peroxidation? Chem Pharm Bull (Tokyo). 2003;51(9):1046-50.

3.Schirra C, Xia N, Schü ffler A, Heck A, Hasselwander S, Fö rstermann U, Li H. Phosphorylation and activation of endothelial nitric oxide synthase by red fruit (Pandanus conoideus Lam) oil and its fractions. J Ethnopharmacol. 2020;251:112534.
CYCLIC NUCLEOTIDE PHOSPHODIESTERASE 2: A NOVEL TARGET FOR THE TREATMENT OF DEMENTIAS ASSOCIATED WITH ALZHEIMER’ S DISEASE
Authors: Xu *Ying
Published: February 2025

Background

The failure to find effective therapies in the past two decades underscores the challenge and the urgent need for identifying novel targets against Alzheimer's disease (AD). Cyclic nucleotide phosphodiesterase 2 (PDE2) is a "druggable target" which has more advantage than currently developed PDE4 and PDE5 inhibitors due to fewer side effects.

Aims & Objectives

The overall objective of this proposal is to investigate the role of PDE2 in mediating mitochondrial dysfunction and neurodegeneration, which should provide the rationale for future research toward developing potential PDE2 inhibitor, particularly mitochondrial PDE2 inhibitor, for the treatment of AD/ADRD.

Methods

The forebrain PDE2 conditional knockout (PDE2 cKO) mice were crossed with APP/PS1 mice which were routinely generated in our laboratory to investigate the role of PDE2 in mediating mitochondrial dysfunction and neurodegeneration. A functional PDE2A2 conditional knockout mouse model was also used where all PDE2A isoforms were knockout but re-expressed full length PDE2A2 (f2A2). They were crossed with AD mouse models to determine whether mitochondrial defects and AD- related deficits were alleviated. In addition, hippocampal neuronal cells were cultured to explore how aberrant PDE2A signaling mediated Aβ-induced mitochondrial deficits in vitro.

Results

Immunoblot analysis showed that decreased PDE2 expression in the hippocampus of APP/PS1 mice (APS) crossed with PDE2 cKO mice (APS/2KO) along with increased cAMP/cGMP and pDLP1 levels. While amyloid plaque loads as detected by thioflavin-S staining were significantly reduced in both the hippocampus and cortex of the APS/2KO vs. APS mice. Importantly, APS/2KO mice demonstrated improved cognitive function in both male and female mice as measured by the novel object recognition (NOR) test. Further study showed that the increased dendritic lengths and spine density in the APS/2KO mice were reversed by functional PDE2A2 knockin in the forebrain. These results were consistent with the in vitro findings that suggested that PDE2A2 is sufficient to be responsible for mitochondrial cAMP/cGMP signaling in the hippocampal neuronal cells. The in vitro study showed that aberrant PDE2A2 signaling is responsible for regulation of/cGMP mediated Abeta 42-induced mitochondrial deficits.

Discussion &Conclusion

The in vivo studies were consistent with the in vitro findings that suggested that aberrant PDE2A2 mediated Abeta 42-induced mitochondrial dysfunction and neuronal deficits. This provides a means to causally link target engagement of PDE2A2 in mitochondria to its effects on brain function and behavior in AD mouse models. This study likely paves the way for future drug development of PDE2 inhibitors, particularly for the mitochondrial PDE2A2 isoform, as novel therapeutics for AD/ADRD.
ASSOCIATION OF SERUM NARDILYSIN VARIABILITY WITH TREATMENT RESPONSE IN DEPRESSED PATIENTS
Authors: Sudou *Satoshi , Sumi Yukiyoshi , Kaminishi Yuki , Isomura Sadaaki , Fujii Kumiko , Yoshimura Atsushi , Ono Mikiko , Nishi Eiichiro , Ozeki Yuji
Published: February 2025

Background

The cause of depression is still unknown, and no biological markers for pathophysiology or therapeutic response have been found. Nardilysin(NRDC) is a type of metalloendopeptidase that is associated with neurodevelopment, and comprehensive analysis of plasma proteins suggests that it may be a potential biological marker for depression. In the present study, we investigated the variation of NRDC in depressed patients treated with antidepressants and electroconvulsive therapy (ECT). The study was approved by the Ethics Committee of Shiga University of Medical Science.

Aims & Objectives

To search for biological markers of depression.

Methods

15 depressed patients (11 females, mean age 63.2±15.5 years) admitted to the Department of Psychiatry, Shiga University of Medical Science were included in the study. All patients were treated with antidepressants, and 8 of them (6 females, mean age 60.5±17.2 years) were treated with ECT. Serum NRDC, depressive symptoms (assessed by MADRS), and antidepressant dose (imipramine-equivalent dose (IED, mg/day)) at admission and 6 weeks after admission and at discharge were investigated. The correlation between serum NRDC changes at admission and at 6 weeks (ratio of serum NRDC values at 6 weeks and at admission), treatment response (difference in MADRS scores at 6 weeks and at admission), and IEDs at admission and at discharge were analyzed.

Results

MADRS at admission and 6 weeks in 15 patients were 27.7±6.6 and 15.2±6.2, respectively; serum NRDC levels were 1224±746 and 901±279 pg/mL, respectively; and IED at admission and discharge were 123±143 and 142±116 mg/day. MADRS at 6 weeks was significantly lower than admission significantly decreased compared to MADRS (t=4.64, p<0.001). A positive correlation (Spearman's ρ=0.54, p=0.038) was found between changes in serum NRDC levels at admission and at 6 weeks and treatment response. On the other hand, there was no significant correlation between IEDs at admission and discharge, serum NRDC and its fluctuation at admission and 6 weeks, and treatment response.

Discussion

In the treatment of depression, the greater the percentage decrease in serum NRDC from admission to 6 weeks, the greater the decrease in MADRS. Although the number of cases was small, the results suggest that serum NRDC levels may be a potential biological marker for depression treatment.
EFFECTIVENESS AND SAFETY OF BLONANSERIN FOR IMPROVING SOCIAL AND COGNITIVE FUNCTIONS IN PATIENTS WITH FIRST-EPISODE SCHIZOPHRENIA
Authors: Gao *Tianqi , Pu Chengcheng , Li Haiyun , Yu Xin
Published: February 2025

Background

Schizophrenia is a severe and chronic mental disorder affecting approximately 0.5%-1% of the global population. Patients often experience significant impairments or poor in social functioning, which leads to a diminished quality of life. Therefore, improving social functioning has become one of the important targets for intervention.

Aims and Objectives

This prospective, multi-centre, single-arm clinical trial aimed to investigate the effects of blonanserin on social and neurocognitive functioning in patients with first-episode schizophrenia.

Method

Blonanserin treatment (flexible oral dose ranging from 8 - 24 mg/d) was administered for 26 weeks. Outcome measures included the Personal and Social Performance (PSP) scale for evaluating social functioning, the Measurement and Treatment Research to Improve Cognition in Schizophrenia Consensus Cognitive Battery (MCCB) for measuring neurocognitive performance, and the Positive and Negative Syndrome Scale (PANSS) for assessing symptom severity. Incidence of adverse drug reactions (ADRs) were also recorded and analysed.

Results

A total of 96 patients with first-episode schizophrenia were recruited and proceeded to analysis. Following 26 weeks of blonanserin treatment, all outcome measurements demonstrated significant improvement during the follow-up period. Notably, PSP scores exhibited a continuous increase of 68.1% ± 103.73% (46.8±14.47 at baseline, 69.4±17.40 at week 26, p<0.001), indicating positive effects on social functioning that were already noticeable by week 8. Neurocognitive impairment evaluated by MCCB Global Deficit Score (GDS), showed significant improvement (1.6±1.1 at baseline, 1.3±0.9 at week-26, p=0.007). Moreover, PANSS scores consistently decreased, with an overall average reduction of 40.0% ± 18.41% (85.6±13.53 at baseline, 51.3±15.49 at week 26, p<0.001). Impressively, the minimal response to blonanserin treatment was evident as early as week 2. 245 cases of ADRs occurred in 79 (82.3%) patients in this study, with nervous system disorders being the most frequent ADRs (87 cases in 64 (66.7%) patients). Most ADRs relevant to blonanserin treatment were mild to moderate.

Discussion & Conclusion

By intricately modulating both dopamine D2/3 and serotonin 5-HT2A receptor subtypes within the brain, blonanserin targets key elements that are widely recognized to play a crucial role in the pathophysiology of the disorder. In this study, blonanserin treatment exhibited favourable effects on social functioning, neurocognitive performance and symptom severity in individuals with first-episode schizophrenia. And it was also well tolerated. These compelling findings highlight the potential of blonanserin as a viable option for patients with schizophrenia encountering functional and neurocognitive impairment.
THE EFFICACY OF METFORMIN IN COUNTERACTING OLANZAPINE- INDUCED HYPERPROLACTINEMIA: AN OPEN-LABEL PROSPECTIVE STUDY
Authors: Lu *Mong-Liang , Goh Kah Kheng , Wu Tzu-Hua , Chen Chun-Hsin
Published: February 2025

Background

Prolactin elevation, resulting from dopamine D2 receptor antagonism, is a common side effect of antipsychotic medications. Olanzapine, an atypical antipsychotic drug, offers enhanced clinical efficacy and fewer side effects compared to typical antipsychotic drugs. Nevertheless, some studies suggest that olanzapine may still lead to an increase in prolactin levels.

Aims & Objectives

Our study aimed to explore the potential of metformin in managing olanzapine- induced hyperprolactinemia in patients with schizophrenia.

Method

A prospective study was designed to investigate the changes in prolactin levels over an eight- week metformin treatment. We enrolled thirty-one patients with schizophrenia who had been on olanzapine treatment for at least three months. These participants were initiated on metformin therapy at 1500 mg/day for eight weeks. Prolactin levels and metabolic parameters were assessed at baseline and at weeks 2, 4, 6, and 8 of the study.

Results

Results indicated a significant reduction in prolactin levels following eight weeks of metformin treatment, particularly in patients with elevated baseline prolactin levels. Insulin, glucose, and triglyceride levels, as well as insulin resistance, significantly decreased after metformin treatment. No significant gender differences were observed regarding the impact of metformin on prolactin levels and metabolic variables.

Discussion & Conclusion

This study underscores metformin's potential to address antipsychotic-induced side effects, paving the way for further research on its long-term efficacy in managing hyperprolactinemia in patients with psychiatric disorders.
High prevalence of ceftriaxone-resistant Neisseria gonorrhoeae in Hanoi, Vietnam, 2023-2024
Authors: Laumen Jolein Gyonne Elise , Hieu Vu N , Nhung Pham H , Vandelannoote Koen , Tam Nguyen Thi , Trang Nguyen T , Diep Nguyen T N , Kesteman Thomas , van Doorn Rogier H , Chau Tran M , Adamson Paul C
Published: February 2025

Ceftriaxone resistance in Neisseria gonorrhoeae is an escalating global health concern, threatening the efficacy of empiric treatment. In the Asia-Pacific region, a rapid surge in ceftriaxone resistance has been observed, primarily associated with the penA-60.001 allele. This study, conducted in Hanoi, Vietnam between 2023 and 2024, analyzed 352 N. gonorrhoeae isolates and found a 27% prevalence of ceftriaxone resistance. Whole-genome sequencing identified that resistance was predominantly driven by the mosaic penA-237.001 allele, with a smaller contribution from penA-60.001. The high prevalence of resistance and the emergence of new alleles underscore the urgent threat to ceftriaxone as an empiric treatment option.
Urine Metabolites of Suspected Community-Acquired Pneumonia
Authors: Ambroggio Lilliam , Florin Todd A , Williamson Kayla , Bosma Grace , Wagner Brandie D , Yeomans Larisa , Kim Jae Hyun , Sucharew Heidi , Macaluso Maurizio , Ruddy Richard M , Stringer Kathleen A , Shah Samir S
Published: February 2025

Background

Accurate diagnosis of community-acquired pneumonia (CAP) can be challenging. Clinical findings are non-specific, and interpretations of chest radiographs have poor inter-rater reliability. Pilot studies demonstrate the potential for metabolomics to identify metabolite concentrations that differentiate children with CAP from those without. The objective of this study was to expand these findings in a large cohort of children with CAP compared with controls.

Methods

Urine was collected from children, 3 months to 12 years old, with emergency department visits for suspected CAP and community-based controls. Nuclear magnetic resonance spectrometry was used to identify and quantify metabolites. A random forest approach developed three models discriminating cases from community-based controls based on: 1) clinical signs and symptoms; 2) metabolites, and 3) the combination of both. The area under the receiver operating characteristic curve (AUC) was computed for each model.

Results

Included were 253 cases and 122 controls. The metabolite-only model had similar discriminatory ability as the combination model (AUC: 0.97 and 0.99, respectively). The discriminating metabolites in the metabolite-only model were 2-aminobutyrate, fumarate, hypoxanthine, acetone, leucine, quinolinate, valine, O-acetylcarnitine, citrate and trigonelline. In the combined model, discriminatory clinical factors included receipt of corticosteroids, fever, cough, rapid breathing, decreased oral intake, difficulty breathing, receipt of albuterol, abnormal sleepiness, vomiting and wheezing, and included five additional metabolites compared to the metabolite only model (4-hydroxybenzoate, isoleucine, carnitine, 2-hydroxyisovalerate, betaine, succinate).

Conclusions

Urine metabolite concentrations can accurately discriminate healthy children from children with suspected CAP. Metabolites associated with CAP may overcome limitations of prior diagnostic approaches.
SMBH binary candidate PKS J2134−0153: possible multi-band periodic variability and inter-band time lags
Authors: Ren Guo-Wei , Sun Mouyuan , Ding Nan , Yang Xing , Zhang Zhi-Xiang
Published: February 2025

Studying the periodic flux-variation behaviour of blazars is vital for probing supermassive black hole binaries and the kinematics of relativistic jets. In this work, we report the detection of multi-band possible periodic variations of the blazar PKS J2134−0153, including infrared ($1.6(\pm 0.4)\times 10^3$ day) and optical ($1.8(\pm 1)\times 10^3$ day) wavelengths. The periods in the infrared and optical bands are statistically consistent with the period in the radio band ($P_{\mathrm{Radio}} = 1760\pm 33$ days, obtained from our previous work). Moreover, flux variations in different bands are correlated with evident inter-band time delays, and the time lags of infrared and optical emission with respect to radio emission are $(3.3\pm 2.3)\times 10^{2}$ days and $(3.0\pm 2.3)\times 10^{2}$ days, respectively. The cross-correlations indicate a common origin of radio, infrared, and optical emission. The relative positions between emission regions of infrared and optical emission and radio emission are estimated according to the time lags, i.e. $0.37\pm 0.26$ and $0.33\pm 0.26$ pc. The relative distances seem to be quantitatively consistent with the theoretical prediction.
Clinical and Mental Health Characteristics Among Patients Receiving Medications for OUD Treatment vs High-Dose Opioids When Referred for Pain Management
Authors: Yang Jie , Giummarra Melita , Picco Louisa , Arnold Carolyn , Nielsen Suzanne
Published: February 2025

Objective

To examine the demographic and clinical characteristics of patients attending pain management services who were receiving opioid agonist treatment (ie, methadone or buprenorphine for the treatment of opioid use disorder) in comparison to those taking prescription opioid analgesics in oral morphine equivalent daily doses at low (<40 mg) and high doses (>100 mg) using a national database from the electronic Persistent Pain Outcomes Collaboration (ePPOC) in Australia.

Design

A cross-sectional study.

Setting

Australian pain services.

Subjects

Adult patients referred to Australian pain service clinics between 2016 and 2021.

Methods

Multinomial and bivariate logistic regression models were conducted to compare the demographic and clinical characteristics of patients on opioid agonist treatment and those taking other prescription opioid analgesics.

Results

Among 42,182 participants, most were female (56.8%), with a mean age of 51.7 years. People on opioid agonist treatment (n = 1,016) and high-dose opioids (n = 7,122) were similar in that they both had more severe mental health symptoms and longer pain duration, compared with the low-dose group (n = 20,517). Compared to the high-dose group, people on opioid agonist treatment had reduced odds of reporting more severe pain intensity, but increased odds of having multimorbidity, more severe anxiety and pain catastrophising thoughts.

Conclusions

These findings highlight the need for mental health treatment and the necessity of tailored multidisciplinary pain management for people in opioid agonist treatment.
Rational approximation with digit-restricted denominators
Authors: IYER SIDDHARTH
Published: February 2025

We show the existence of ‘good’ approximations to a real number γ using rationals with denominators formed by digits 0 and 1 in base b. We derive an elementary estimate and enhance this result by managing exponential sums.
Big Data Approaches for Novel Mechanistic Insights on Sleep and Circadian Rhythms: a Workshop Summary
Authors: Baizer Lawrence , Bures Regina , Nadkarni Girish , Reyes-Guzman Carolyn , Ladwa Sweta , Cade Brian , Westover M Brandon , Durmer Jeffrey , de Zambotti Massimilliano , Desai Manisha , Parekh Ankit , Si Bing , Fernandez-Mendoza Julio , Minor Kelton , Mazzotti Diego R , Lee Soomi , Katabi Dina , Kiss Orsolya , Spira Adam P , Morris Jonna , Seixas Azizi , Kioumourtzoglou Marianthi-Anna , Bridges John F P , Brown Marishka , Hale Lauren , Purcell Shaun
Published: February 2025

The National Center on Sleep Disorders Research (NCSDR) of the National Heart, Lung, and Blood Institute (NHLBI) at the National Institutes of Health (NIH) hosted a two-day virtual workshop titled Big Data Approaches for Novel Mechanistic Insights on Disorders of Sleep and Circadian Rhythms on May 2nd and 3rd, 2024. The goals of this workshop were to establish a comprehensive understanding of the current state of sleep and circadian rhythms disorders research to identify opportunities to advance the field by using approaches based on artificial intelligence (AI) and machine learning (ML). The workshop showcased rapidly developing technologies for sensitive and comprehensive remote analysis of sleep and its disorders that can account for physiological, environmental and social influences, potentially leading to novel insights on long-term health consequences of sleep disorders and disparities of these health problems in specific populations.
Improving Compassionate Communication Through a Train-the-Trainer Model: Outcomes and Mechanisms for Transformation
Authors: Bintliff Amy V. , Levine Rebecca S. , Kaplan-Liss Evonne , Lantz-Gefroh Valeri
Published: February 2025

Problem

Compassionate communication is an essential component of compassionate care and involves recognizing another person who needs compassion, relating to their suffering, and reacting verbally and/or nonverbally to their needs. Higher-quality compassionate communication facilitates positive patient-clinician relationships, which in turn lead to the development of trust, higher rates of adherence, and reduced health care costs. However, patients report that compassionate communication is lacking across many health care interactions. Research is needed to evaluate innovative educational programs that facilitate improved compassionate communication.

Approach

This report evaluates the Sanford Compassionate Communication Academy Fellowship at UC San Diego Health, a 60-hour arts and humanities fellowship that teaches compassionate communication to clinicians alongside artists using Kirkpatrick’s 4-level evaluation model. At the time of this analysis, 27 fellows participated in the fellowship, using improvisation and theater exercises, role-play, visual thinking strategy, narrative reflection, poetry, literature, and principles drawn from journalism to build personal skills and learn to facilitate a compassionate communication curriculum. This analysis of 30 hours of field notes and 30- to 40-minute interviews conducted from January 2022 to November 2023 was guided by transformative learning theory.

Outcomes

Five themes contributed to improved compassionate communication: empathic listening, pacing, checking for understanding, improved teaching and mentoring, and mechanisms for transformation. In interviews, fellows described how improving these various skills has positively transformed their communication with patients and students. Participants identified 6 innovative mechanisms for transformation: dedicated time and resources, reflective practice, environment of care and safety, arts and humanities integration, colearning between artists and clinicians, and the train-the-trainer model.

Next Steps

Next steps include conducting additional studies to evaluate the fellowship’s effect using mixed methods with added patient and student perspectives. In addition, training will be offered to other institutions, and different delivery modalities and durations of instruction will be compared.
Diagnostic Performance and Impact on Antimicrobial Treatment of a Multiplex Polymerase Chain Reaction in Critically Ill Patients With Pneumonia: A Multicenter Observational Study (The MORICUP-PCR Study: Morocco ICU Pneumonia-PCR study)
Authors: Aissaoui Younes , Derkaoui Ali , Hachimi Abdelhamid , Bouchama Ayoub , Dendane Tarek , Doumiri Mouhssine , ElAidaoui Karim , Ziadi Amra , Essafti Meryem , Oualili Latifa , Khaddouri Mehdi , Mroune Oumaima , Oudrhiri Safiani Mehdi , Khallouki Mohammed , Berdai Adnane , Boukatta Brahim , El Adib Ahmed Rhassane , Madani Naoufel , Soraa Nabila , Belhadj Ayoub , Kohen Jamal Eddine , Abouqal Redouane
Published: February 2025

OBJECTIVES:

Managing severe pneumonia remains a challenge. Rapid diagnostic tests, such as multiplex polymerase chain reaction (mPCR), facilitate quick microorganism identification and may enable timely and appropriate antimicrobial therapy. However, studies from low-income countries are scarce. This study aimed to evaluate the diagnostic characteristics of mPCR and its impact on antibiotic therapy and outcomes in critically ill patients with pneumonia.

DESIGN:

Multicenter observational study.

SETTING:

Twelve ICUs across Morocco.

PATIENTS:

Adult patients with pneumonia requiring invasive mechanical ventilation, including community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), and ventilator-associated pneumonia (VAP).

INTERVENTIONS:

None.

MEASUREMENTS AND MAIN RESULTS:

Respiratory samples were analyzed using both mPCR and conventional microbiological methods. The diagnostic performance of mPCR was evaluated, including its sensitivity and specificity. Additionally, the appropriateness of mPCR-induced modifications in empiric antibiotic therapy and their impact on patient outcomes were assessed. A total of 210 patients were included, with a median age of 50 years (range, 33–67 yr), of whom 66.2% were male. Pneumonia types were distributed as 30% CAP, 58% VAP, and 12% HAP. mPCR demonstrated a sensitivity of 96.9% (95% CI, 92.3–99.2%) and a specificity of 92% (95% CI, 91–93%). Following mPCR, antibiotic therapy modifications were observed in 58% of patients (n = 122), including de-escalation or cessation in 11% (n = 23), escalation in 26.5% (n = 56), adequacy adjustments in 7.5% (n = 16), and initiation of antibiotics in 13% (n = 27). The appropriateness of antibiotic therapy increased significantly from 38.7% (n = 83) to 67% (n = 141; difference, 27.5%; 95% CI, 18.3–36.7; p < 0.0001). Generalized mixed model analysis revealed that appropriate post-mPCR antibiotic therapy was associated with reduced mortality (adjusted odds ratio, 0.37; 95% CI, 0.15–0.93; p = 0.038).

CONCLUSIONS:

Our findings suggest that the use of mPCR is associated with a significant improvement in the appropriateness of empiric antibiotic therapy and is also associated with a positive impact on the outcome of patients with pneumonia.
Blood pressure phenotypes and day-night variability in acute ischemic stroke: is there any cardiovascular mortality link 10 years after?
Authors: Antza Christina , Kotsis Vasilios
Published: February 2025

Objective:

Blood pressure (BP) phenotypes and day–night variability have been associated with acute ischemic stroke (AISTR). The aim of this study was to analyze the BP phenotypes and day–night variability during the first 3 days of an AISTR and their correlation with 10-year cardiovascular death (CVD).

Methods:

Eighty-five volunteers (49.9% men, 77.3 ± 6 years), diagnosed for AISTR, were included in the study. Twenty-four hour ABPM was performed during the first 3 days of AISTR symptoms. A follow-up visit was performed through phone call, 10 years after the AISTR event.

Results:

There is a reproducible nocturnal circadiac rhythm, with the nondipping status to be the most prevalent (89.3%, 89.2%, 88.3% for Days 1, 2, 3 accordingly, P > 0.05), compared to dipping status (P < 0.05), but not a reproducible BP phenotype, except the hypertensive one (50%, 45.8%, 51.6% for Days 1, 2 and 3 accordingly, P > 0.05). The mean follow-up was 509.6 ± 10 weeks. 37.1% had died (41.2% from MACE). Cox regression analysis revealed that age [odds ratio (OR):1.15, confidence interval (CI): 1.01–1.17, P < 0.05], sex (male, OR: 1.92, CI: 1.07–3.82, P < 0.05), diabetes mellitus (OR: 1.55, CI: 1.06–3.14, P < 0.05), early vascular ageing (OR: 2.01, CI: 1.19–3.74, P < 0.05), transient ischemic attack (OR: 2.32, CI: 1.02–5.34, P < 0.05), sustained hypertension (OR: 2.78, CI: 1.13–6.83, P < 0.05), day–night SBP ratio (OR: 0.98, CI: 0.96–0.99, P < 0.05) and day–night DBP ratio (OR: 0.96, CI: 0.94–0.99, P < 0.05) were significant predictors for CVD.

Conclusion:

Hence, patients with AISTR present a reproducible nocturnal circadian rhythm, but not a reproducible BP phenotype, except sustained hypertension. These parameters found also to be determinants for 10-year CVD.
Developing Brain Injury Resource Facilitation for Acquired Brain Injury: Indications and Unmet Needs
Authors: Zhang Bei , Mollayeva Tatyana , Devaraj Srikant , Meixner Cara , Dettmer Judy , Corrigan John D. , Reisher Peggy , Hammond Flora M. , Pollifrone Maria , Backhaus Samantha , Trexler Lance E.
Published: February 2025

Owing to major progress in the survivorship following acquired brain injury (ABI), there exists a pressing need for the development of systems of care and rehabilitation tailored to ABI. One of the supportive systems is brain injury resource facilitation (brain injury RF), which focuses on having therapeutic, social, and financial resources readily available and easily accessible for persons with ABI. Brain injury RF comprises identification of a person’s strengths and challenges, goal setting, resource identification, coordination, access, utilization, monitoring, evaluation, and advocacy. Brain injury RF is critically important in bridging community services for persons with ABI and eliminating disjointed approaches of care that fail to address the full range of the individual’s needs and long-term success. Over recent years, multiple stakeholders in the field of ABI have worked to develop and implement strategies for timely brain injury RF. This white paper aims to provide an overview of the current status of brain injury RF and an analysis on the challenges and opportunities in brain injury RF for ABI. Practical policy recommendations for its implementation are proposed to the potential funders of brain injury RF programs at the national, state, and community levels. We call for attention to this pressing need in society and advocate for a novel, pragmatic, and culturally informed approach in the development of brain injury RF in communities where people with ABI reside.
Co-Occurrence of Traumatic Brain Injury and Post-Traumatic Stress Disorder in a National Sample of UK Police Officers: Impact on Social Well-Being and Employment Outcomes
Authors: Smith Nicholas I. J. , Hogarth Lee , Tonks James , Corrigan John D. , Gilmour Stan , Williams W. Huw
Published: February 2025

Objective:

To determine the lifetime prevalence of traumatic brain injury (TBI) in UK police officers and evaluate associations between mild TBI (mTBI), persistent post-concussion-like symptoms (PPCS), post-traumatic stress disorder (PTSD) and complex PTSD (C-PTSD).

Setting:

Online survey of serving police officers across England, Scotland and Wales.

Participants:

A total of 617 currently serving police officers were eligible for the study and the final sample consisted of 573 participants. Subgroup comparisons were made between individuals with no TBI history (n = 355), a single mTBI (n = 88) and multiple mTBIs (n = 130).

Design:

Cross-sectional survey assessing lifetime history of TBI, PPCS and PTSD symptoms.

Main measures:

Lifetime TBI prevalence was assessed with the Ohio State TBI-Identification Method. Post-concussion-like symptoms were evaluated with the Rivermead Post-Concussion Symptoms Questionnaire (RPQ) and PTSD/C-PTSD were measured using the International Trauma Questionnaire.

Results:

Lifetime prevalence of TBI was 38% (n = 234), with 23% reporting multiple TBIs. One-way ANOVAs demonstrated that individuals with multiple TBIs exhibited significantly greater cognitive (unadjusted R2 = .02, P = .001) and somatic symptoms (unadjusted R2 = .02, P < .001) and reported more severe total RPQ symptoms (unadjusted R2 = .02, P = .009) compared to those without mTBI history. Multiple TBI history was associated with increased severity across all PTSD/C-PTSD domains (P < .004), and a significantly higher C-PTSD prevalence (P = .001). These results remained significant in ANCOVAs, adjusting for demographic, occupational and trauma-exposure variables (P < .04).

Conclusions:

Comorbidity between TBI and C-PTSD is prevalent in this sample of police officers. Symptom endorsement is additive in those with mTBI history, this could lead to risk to employment, relationship breakdown, and further mental health problems. Routine occupational health checks should monitor both TBI and associated symptoms over time. If necessary, police officers with head or neck injuries should follow a graduated return-to-duty protocol, including a gradual increase in activity level and appropriate mental health intervention.
Deformable Biomechanics of DMEK Tissue Scrolls Traveling Through Narrow Lumens II: Double Scrolls Do Not Behave Like Single Scrolls
Authors: Kigin Matthew , Balk Evan , Revis Benjamin , Vigmostad Sarah , Sales Christopher
Published: February 2025

Purpose:

To investigate and compare the dimensional characteristics of Descemet membrane endothelial keratoplasty (DMEK) scrolls in single-scroll and double-scroll conformations at various ages and velocities.

Methods:

DMEK tissues from three donor pairs (ages 47, 62, and 69) were used to compare single-scroll and double-scroll widths under different velocities. Tissues were randomized and manipulated into single-scroll or double-scroll conformation using a syringe pump connected to an hourglass-shaped glass tube. All scrolls were passed through the tube at three different velocities set by syringe pump settings, and high-speed videography at 2000 frames per second captured scroll dimensions. Scroll dimensions were measured using IDT Motion Studio software.

Results:

Single-scrolled DMEK tissue was narrower than double-scrolled tissue across all donor ages. Double-scrolled tissue width remained relatively unchanged regardless of age or velocity. Significant differences in scroll width between single and double scrolls were observed in the 47-year-old donor tissue at all velocities (P <0.001). Significant scroll width differences between single and double scrolls were observed in the 62-year-old donor tissue at medium and high velocities (P = 0.03 and P = 0.01, respectively). In the 69-year-old donor tissue, significant differences in scroll width between single and double scrolls were observed only at high velocities (P = 0.003). Single-scroll width decreased with increasing velocity for 47-year-old and 62-year-old donor tissues (P <0.001, P = 0.03), but not for the 69-year-old donor tissue (P = 1.0).

Conclusions:

There is a significant difference in scroll width between single-scrolled and double-scrolled tissues at high speeds. These differences become less significant as scrolls increase in age and velocity decreases.