Broad-spectrum antibiotic use in febrile neutropenia is often driven by concerns for severe and drug-resistant infections. In select patients who do not have an active infection and improve, their prolonged and unnecessary use contributes to antimicrobial resistance, drug toxicity, and increased healthcare costs. We describe the implementation of an antibiotic de-escalation protocol to reduce inappropriate antibiotic use in febrile neutropenia among hematology patients.

We conducted baseline analysis (January–June 2024) of antibiotic use in febrile neutropenia cases admitted under hematology. Interventions included the (i) development of an antibiotic de-escalation protocol to guide clinical management, (ii) a roadshow to educate and improve uptake of this protocol, and (iii) regular feedback via “report cards” for hematology teams. The primary outcome was the proportion of febrile neutropenia cases with inappropriate antibiotic use, with secondary measures including adverse outcomes (in-hospital mortality, Clostridioides difficile infection, need for intensive care).

Baseline data indicated inappropriate antibiotic use rates of 45.5–66.7% per month from January to June 2024, with 13–28 days of inappropriate therapy. The protocol was developed in July 2024, with a subsequent roadshow to promote its uptake. Regular feedback was provided in the form of “report cards” every 2-monthly thereafter. Post-intervention, inappropriate antibiotic use decreased to a median of 23.35% from July to December 2024, with no observed increase in adverse outcomes.

The implementation of a structured de-escalation protocol, combined with frequent education and feedback, effectively reduced inappropriate antibiotic use in febrile neutropenia without compromising patient safety.

Evidence suggests the crucial role of dysfunctional default mode (DMN), salience and frontoparietal (FPN) networks, collectively termed the triple network model, in the pathophysiology of treatment-resistant depression (TRD).

Using the graph theory- and seed-based functional connectivity analyses, we attempted to elucidate the role of low-dose ketamine in the triple networks, namely the DMN, salience and FPN.

Resting-state functional connectivity magnetic resonance imaging (rs–fcMRI) data derived from two previous clinical trials of a single, low-dose ketamine infusion were analysed. In clinical trial 1 (Trial 1), patients with TRD were randomised to either a ketamine or normal saline group, while in clinical trial 2 (Trial 2) those patients with TRD and pronounced suicidal symptoms received a single infusion of either 0.05 mg/kg ketamine or 0.045 mg/kg midazolam. All participants underwent rs–fcMRI pre and post infusion at Day 3. Both graph theory- and seed-based functional connectivity analyses were performed independently.

Trial 1 demonstrated significant group-by-time effects on the degree centrality and cluster coefficient in the right posterior cingulate cortex (PCC) cortex ventral 23a and b (DMN) and the cluster coefficient in the right supramarginal gyrus perisylvian language (salience). Trial 2 found a significant group-by-time effect on the characteristic path length in the left PCC 7Am (DMN). In addition, both ketamine and normal saline infusions exerted a time effect on the cluster coefficient in the right dorsolateral prefrontal cortex a9-46v (FPN) in Trial 1.

These findings may support the utility of the triple-network model in elucidating ketamine’s antidepressant effect. Alterations in DMN, salience and FPN function may underlie this effect.

The school–vacation cycle may have impacts on the psychological states of adolescents. However, little evidence illustrates how transition from school to vacation impacts students’ psychological states (e.g. depression and anxiety).

To explore the changing patterns of depression and anxiety symptoms among adolescent students within a school–vacation transition and to provide insights for prevention or intervention targets.

Social demographic data and depression and anxiety symptoms were measured from 1380 adolescent students during the school year (age: 13.8 ± 0.88) and 1100 students during the summer vacation (age: 14.2 ± 0.93) in China. Multilevel mixed-effect models were used to examine the changes in depression and anxiety levels and the associated influencing factors. Network analysis was used to explore the symptom network structures of depression and anxiety during school and vacation.

Depression and anxiety symptoms significantly decreased during the vacation compared to the school period. Being female, higher age and with lower mother's educational level were identified as longitudinal risk factors. Interaction effects were found between group (school versus vacation) and the father's educational level as well as grade. Network analyses demonstrated that the anxiety symptoms, including ‘Nervous’, ‘Control worry’ and ‘Relax’ were the most central symptoms at both times. Psychomotor disturbance, including ‘Restless’, ‘Nervous’ and ‘Motor’, bridged depression and anxiety symptoms. The central and bridge symptoms showed variation across the school vacation.

The school–vacation transition had an impact on students’ depression and anxiety symptoms. Prevention and intervention strategies for adolescents’ depression and anxiety during school and vacation periods should be differentially developed.

Fibrosis is a pathological condition that affects various organs by increasing fibrous connective tissue while reducing parenchymal cells. This imbalance can lead to compromised organ function and potential failure, posing significant health risks. The condition’s complexity necessitates the exploration of effective treatments to mitigate its progression and adverse outcomes.

This study aims to investigate the role of ghrelin, a peptide hormone known for its anti-inflammatory and anti-fibrotic properties, in modulating fibrosis across different organs. By binding to the growth hormone secretagogue receptor type 1a (GHSR-1a), ghrelin has shown potential in attenuating the fibrotic process, particularly through its interaction with the TGF-β signalling pathway.

An extensive review of clinical and animal model studies focusing on liver, kidney, lung, and myocardial fibrosis was conducted. The primary focus was on examining how ghrelin influences the TGF-β signalling pathway, with an emphasis on the regulation of TGF-β expression and the suppression of Smad signalling molecules. The methodology involved analysing data from various studies to understand ghrelin’s molecular mechanisms in combating fibrosis.

The findings from the reviewed studies indicate that ghrelin exerts significant anti-fibrotic effects across multiple organ systems. Specifically, ghrelin was found to downregulate TGF-β expression and suppress Smad signalling molecules, leading to a marked reduction in fibrous tissue accumulation and preservation of organ function. In liver fibrosis models, ghrelin reduced TGF-β1 levels and Smad3 phosphorylation, while in kidney and cardiac fibrosis, similar protective effects were observed. The data also suggest that ghrelin’s effects are mediated through both canonical and non-canonical TGF-β pathways.

Ghrelin presents a promising therapeutic agent in the management of fibrosis due to its potent anti-inflammatory and anti-fibrotic actions. Its ability to modulate the TGF-β signalling pathway underscores a vital molecular mechanism through which ghrelin can mitigate fibrotic progression in various organs. Future research should focus on further elucidating ghrelin’s molecular interactions and potential clinical applications in fibrosis treatment, offering new avenues for developing effective anti-fibrotic therapies.

Systemic changes in multiple diseases may influence the onset of dementia. However, the specific temporality between exposure diseases and dementia remains uncertain.

By characterising the full spectrum of temporal disease trajectories before dementia, this study aims to yield a global picture of precursor diseases to dementia and to provide detailed instructions for risk management and primary prevention of dementia.

Using the multicentre, community-based prospective UK Biobank, we constructed disease trajectories before dementia utilising the phenome-wide association analysis, paired directional test and association quantification. Stratified disease trajectories were constructed by dementia subtypes, gender, age of diagnosis and Apolipoprotein E (ApoE) status, respectively.

Our study population comprised 434 266 participants without baseline dementia and 4638 individuals with all-cause dementia. In total, 1253 diseases were extracted as potential components of the disease trajectory before dementia. We identified three clusters of disease trajectories preceding all-cause dementia, initiated by circulatory, metabolic and respiratory diseases occurring approximately 5–15 years before dementia. Cerebral infarction or chronic renal failure following chronic ischaemic heart disease was the specific trajectory before vascular dementia. Apolipoprotein E (ApoE) ε4 non-carriers exhibited more complex trajectories compared with carriers. Lipid metabolism disorders remained in the trajectories regardless of dementia subtypes, gender, age of diagnosis and ApoE status.

This study provides a comprehensive view of the longitudinal disease trajectories before dementia and highlights the potential targets of midlife cardiometabolic dysfunction for dementia screening and prevention.

Despite extensive research into the neural basis of autism spectrum disorder (ASD), the presence of substantial biological and clinical heterogeneity among diagnosed individuals remains a major barrier. Commonly used case‒control designs assume homogeneity among subjects, which limits their ability to identify biological heterogeneity, while normative modeling pinpoints deviations from typical functional network development at individual level.

Using a world-wide multi-site database known as Autism Brain Imaging Data Exchange, we analyzed individuals with ASD and typically developed (TD) controls (total n = 1218) aged 5–40 years, generating individualized whole-brain network functional connectivity (FC) maps of age-related atypicality in ASD. We then used local polynomial regression to estimate a networkwise normative model of development and explored correlations between ASD symptoms and brain networks.

We identified a subset exhibiting highly atypical individual-level FC, exceeding 2 standard deviation from the normative value. We also identified clinically relevant networks (mainly default mode network) at cohort level, since the outlier rates decreased with age in TD participants, but increased in those with autism. Moreover, deviations were linked to severity of repetitive behaviors and social communication symptoms.

Individuals with ASD exhibit distinct, highly individualized trajectories of brain functional network development. In addition, distinct developmental trajectories were observed among ASD and TD individuals, suggesting that it may be challenging to identify true differences in network characteristics by comparing young children with ASD to their TD peers. This study enhances understanding of the biological heterogeneity of the disorder and can inform precision medicine.

Treatment-resistant depression (TRD) is not uncommon in older people. Brain stimulation, such as 4-6 weeks of repetitive transcranial magnetic stimulation (rTMS) or theta burst stimulation (TBS) targeting the left dorsolateral prefrontal cortex, has been evidenced as an essential intervention for adult TRD and also documented in the current international treatment guideline. In 2018, Taiwan Food and Drug Administration cleared the rTMS as a treatment option for TRD and now rTMS is still a treatment at their own expense in Taiwan. Additionally, prolonged intermittent TBS (piTBS) protocol has been proven its similar antidepressant efficacy as standard 4-6 weeks rTMS/iTBS in adult TRD, but in a shorter treatment course of 2 weeks. For older adults with depression, 4-6 weeks of treatment course may burden their caregiver due to their limited ambulation and transportation ability. However, hitherto there was no study to investigate the antidepressant efficacy of left-sided prefrontal piTBS in treating older TRD.

A chart review was performed at a single Taiwan hospital from 2018 to 2020. 17-items Hamilton Depression Rating Scale (HDRS-17) was measured before and after the piTBS intervention. Maudsley Staging Method was used for the depression treatment refractoriness.

We identified 23 old adults with TRD (mean [SD] age, 66.0[5.2]; 78% female) who underwent 10-20 sessions of daily piTBS (1800 pulses/session; 10sessions, n=18, 15sessions,n=4, 20session,n=1). On continuous outcomes, mean(SD) HDRS-17 total scores improved from 20.5(6.62) to 11.8(7.7) after receiving piTBS intervention. The mean percent improvement of HDRS-17 was 46.0%±29.4%. Dichotomous outcomes showed response rate of 43.5% and remission rate of 34.8%. No seizures or other serious adverse events were noted, and no premature discontinuation was noted.

This study is the largest study demonstrating the piTBS protocol provides a comparable reduction in depression symptoms in older adults with TRD, similar to the effectiveness in adult TRD and the efficacy of standard sequential bilateral rTMS/iTBS in older TRD in the FOUR-D trial. Regarding desirable efficiency and effectiveness, piTBS may be an optimal form of rTMS in treating older adults with TRD. Further large comparative effectiveness trials with standard iTBS or high-frequency rTMS in this population are warranted.

National health insurance (NHI) Taiwan has provided additional markups on dental service fees for people with specific disabilities, and the expenditure has increased significantly from TWD473 million (USD15 million) in 2016 to TWD722 million (USD24 million) in 2022. The purpose of this study was to determine oral health risk and to develop a risk assessment model for capitation outpatient dental payments in children with Autism.

Based on the literature and expert opinion, we developed a level of oral health risk model from the claim records of 2019. The model uses oral outpatient claim data to analyze: (i) the degree of caries disease; (ii) the level of dental fear or cooperation; and (iii) the level of tooth structure. Each factor was given a score from zero to four and a total score was calculated. Low-, medium-, and high-risk groups were formed based on the total points. The oral health risk capitation models are estimated by ordinary least squares using an individual’s annual outpatient dental expenditure in 2019 as the dependent variable. For subgroups based on age group and level of disability, expenditures predicted by the models are compared with actual outpatient dental expenditures. Predictive R-squared and predictive ratios were used to evaluate the model’s predictability.

The demographic variables, level of oral health risk, preventive dental care, and the type of dental health care predicted 30 percent of subsequent outpatient dental expenditure in children with autism. For subgroups (age group and disability level) of high-risk patients, the model substantially overpredicted the expenditure, whereas underprediction occurred in the low-risk group.

The risk-adjusted model based on principal oral health was more accurate in predicting an individual’s future expenditure than the relevant study in Taiwan. The finding provides insight into the important risk factor in the outpatient dental expenditure of children with autism and the fund planning of dental services for people with specific disabilities.

Exploring the neural basis related to different mood states is a critical issue for understanding the pathophysiology underlying mood switching in bipolar disorder (BD), but research has been scarce and inconsistent.

Resting-state functional magnetic resonance imaging data were acquired from 162 patients with BD: 33 (hypo)manic, 64 euthymic, and 65 depressive, and 80 healthy controls (HCs). The differences of large-scale brain network functional connectivity (FC) between the four groups were compared and correlated with clinical characteristics. To validate the generalizability of our findings, we recruited a small longitudinal independent sample of BD patients (n = 11). In addition, we examined topological nodal properties across four groups as exploratory analysis.

A specific strengthened pattern of network FC, predominantly involving the default mode network (DMN), was observed in (hypo)manic patients when compared with HCs and bipolar patients in other mood states. Longitudinal observation revealed an increase in several network FCs in patients during (hypo)manic episode. Both samples evidenced an increase in the FC between the DMN and ventral attention network, and between the DMN and limbic network (LN) related to (hypo)mania. The altered network connections were correlated with mania severity and positive affect. Bipolar depressive patients exhibited decreased FC within the LN compared with HCs. The exploratory analysis also revealed an increase in degree in (hypo)manic patients.

Our findings identify a distributed pattern of large-scale network disturbances in the unique context of (hypo)mania and thus provide new evidence for our understanding of the neural mechanism of BD.