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OBJECTIVES: The association between specific types of malignancies and the subsequent risk of dementia remains unknown. DESIGN: A retrospective population-based cohort study based on data from Taiwan National Health Insurance Research Database. SETTING AND PARTICIPANTS: We recruited 32,250 patients who survived malignancies and 322,500 controls between 1998 and 2011 and followed them up until the end of 2013. MEASUREMENTS: Diagnoses of dementia (including Alzheimer's disease (AD), vascular dementia (VaD), and unspecified dementia) was made during the follow-up period. Cox regression analyses were performed after adjusting for potential confounders. A sensitivity analysis was conducted to exclude patients with prodromal dementia. RESULTS: Cancer survivors were more likely to develop AD (hazard ratio [HR]: 1.68, 95% confidence interval [CI]: 1.38-2.06), unspecified dementia (HR: 1.19, 95% CI: 1.07-1.32), and any dementia (HR: 1.26, 95% CI: 1.16-1.37) compared with controls after adjusting for potential confounders. Importantly, cancers of the digestive and genitourinary organs seem to be associated with AD, unspecified dementia, and any dementia, whereas only malignant neoplasms of the brain are more likely to develop into VaD. Sensitivity analyses after exclusion of the first three or five years of observation and after exclusion of case enrollment before 2009 or 2007 showed consistent findings. CONCLUSION: Cancer survivors are at higher risk of subsequent dementia. Different types of cancer survivors may contribute to variable risks of specific dementias. Further studies are necessary to investigate the underlying mechanisms in cancer survivors and patients with dementia.
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Cluster headache (CH) is a debilitating neurological disorder characterized by severe, unilateral pain and ipsilateral autonomic symptoms. Chronic CH is exceedingly rare in Taiwan, constituting approximately 1% of all CH cases. This narrative review provides an up-to-date overview of the acute and preventive treatment strategies for CH in Taiwan, focusing on currently available pharmacological options in the country. The treatment approach for CH in Taiwan involves a stepwise strategy. High-flow oxygen and triptan nasal sprays are the mainstays of acute treatment, providing rapid relief and good tolerability. Transitional treatments, such as oral steroids and suboccipital steroid injections, serve as a crucial bridge between acute and long-term preventive therapies, offering temporary relief while minimizing side effects through a carefully limited duration. For preventive treatment, verapamil is the first-line option, with lithium and topiramate being the second-line alternatives. Among the CGRP monoclonal antibodies, galcanezumab has demonstrated efficacy in the prevention of episodic CH. Preventive treatments are personalized to individual patients, starting with low doses and close monitoring for adverse effects. Neuromodulatory therapies, such as non-invasive vagus nerve stimulation, show promise for chronic and refractory CH but have limited availability in Taiwan. In conclusion, despite the availability of various acute and preventive treatment options, unmet needs in the management of CH in Taiwan remain. In particular, increased awareness and education among healthcare professionals to improve the diagnosis and management of CH in Taiwan should be implemented.
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This study aimed to assess the ability of an artificial intelligence (AI)-based chatbot to generate abstracts from academic psychiatric articles. We provided 30 full-text psychiatric papers to ChatPDF (based on ChatGPT) and prompted generating a similar style structured or unstructured abstract. We further used 10 papers from Psychiatry Research as active comparators (unstructured format). We compared the quality of the ChatPDF-generated abstracts with the original human-written abstracts and examined the similarity, plagiarism, detected AI-content, and correctness of the AI-generated abstracts. Five experts evaluated the quality of the abstracts using a blinded approach. They also identified the abstracts written by the original authors and validated the conclusions produced by ChatPDF. We found that the similarity and plagiarism were relatively low (only 14.07% and 8.34%, respectively). The detected AI-content was 31.48% for generated structure-abstracts, 75.58% for unstructured-abstracts, and 66.48% for active comparators abstracts. For quality, generated structured-abstracts were rated similarly to originals, but unstructured ones received significantly lower scores. Experts rated 40% accuracy with structured abstracts, 73% with unstructured ones, and 77% for active comparators. However, 30% of AI-generated abstract conclusions were incorrect. In conclusion, the data organization capabilities of AI language models hold significant potential for applications to summarize information in clinical psychiatry. However, the use of ChatPDF to summarize psychiatric papers requires caution concerning accuracy.
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Objective: Psilocybin-assisted therapy has shown promising efficacy on clinical depressive symptoms. However, diverse psychological support or psychotherapy was performed with psilocybin treatment. This study aimed to explore the association of psychological protocols with the efficacy of psilocybin-assisted therapy for depressive symptoms. Method: Five major databases were systemic searched for clinical trials addressing psilocybin-assisted therapy for patients with clinical depressive symptoms. A Bayesian random-effects meta-analysis and meta-regression were performed. The effect size was mean difference (with 95% credible interval) measured by 17-Item Hamilton Depression Rating Scale. Results: There were 10 eligible studies including 515 adult patients with clinically diagnosed depression. The psychological protocols could be categorized into four types: (i) manualized directive psychotherapy(k=1); (ii) manualized nondirective psychological support(k=3), (iii) non-manualized nondirective psychological support(k=5); and (iv) non-manualized supportive psychotherapy(k=1). The pooled standard mean difference of psilocybin-assisted therapy was 10.08 (5.03-14.70). Conclusion: Compared with manualized nondirective psychological support, the other three psychological approaches did not differ significantly. The improvement of depressive symptoms was not associated with the psychological protocols in adult patients receiving psilocybin-assisted therapy. Systemic review registration: Open Science Framework: identifier (osf.io/3YUDV).
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OBJECTIVE: To evaluate the comparative effectiveness and acceptability of oral monotherapy using psychedelics and escitalopram in patients with depressive symptoms, considering the potential for overestimated effectiveness due to unsuccessful blinding. DESIGN: Systematic review and Bayesian network meta-analysis. DATA SOURCES: Medline, Cochrane Central Register of Controlled Trials, Embase, PsycINFO, ClinicalTrial.gov, and World Health Organization's International Clinical Trials Registry Platform from database inception to 12 October 2023. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: Randomised controlled trials on psychedelics or escitalopram in adults with depressive symptoms. Eligible randomised controlled trials of psychedelics (3,4-methylenedioxymethamphetamine (known as MDMA), lysergic acid diethylamide (known as LSD), psilocybin, or ayahuasca) required oral monotherapy with no concomitant use of antidepressants. DATA EXTRACTION AND SYNTHESIS: The primary outcome was change in depression, measured by the 17-item Hamilton depression rating scale. The secondary outcomes were all cause discontinuation and severe adverse events. Severe adverse events were those resulting in any of a list of negative health outcomes including, death, admission to hospital, significant or persistent incapacity, congenital birth defect or abnormality, and suicide attempt. Data were pooled using a random effects model within a Bayesian framework. To avoid estimation bias, placebo responses were distinguished between psychedelic and antidepressant trials. RESULTS: Placebo response in psychedelic trials was lower than that in antidepression trials of escitalopram (mean difference -3.90 (95% credible interval -7.10 to -0.96)). Although most psychedelics were better than placebo in psychedelic trials, only high dose psilocybin was better than placebo in antidepression trials of escitalopram (mean difference 6.45 (3.19 to 9.41)). However, the effect size (standardised mean difference) of high dose psilocybin decreased from large (0.88) to small (0.31) when the reference arm changed from placebo response in the psychedelic trials to antidepressant trials. The relative effect of high dose psilocybin was larger than escitalopram at 10 mg (4.66 (95% credible interval 1.36 to 7.74)) and 20 mg (4.69 (1.64 to 7.54)). None of the interventions was associated with higher all cause discontinuation or severe adverse events than the placebo. CONCLUSIONS: Of the available psychedelic treatments for depressive symptoms, patients treated with high dose psilocybin showed better responses than those treated with placebo in the antidepressant trials, but the effect size was small. SYSTEMATIC REVIEW REGISTRATION: PROSPERO, CRD42023469014.
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Banisteriopsis , Teorema de Bayes , Escitalopram , Alucinógenos , Dietilamida do Ácido Lisérgico , Metanálise em Rede , Psilocibina , Humanos , Psilocibina/uso terapêutico , Psilocibina/administração & dosagem , Psilocibina/efeitos adversos , Dietilamida do Ácido Lisérgico/uso terapêutico , Dietilamida do Ácido Lisérgico/administração & dosagem , Dietilamida do Ácido Lisérgico/efeitos adversos , Alucinógenos/uso terapêutico , Alucinógenos/administração & dosagem , Alucinógenos/efeitos adversos , Escitalopram/uso terapêutico , Escitalopram/administração & dosagem , N-Metil-3,4-Metilenodioxianfetamina/administração & dosagem , N-Metil-3,4-Metilenodioxianfetamina/efeitos adversos , N-Metil-3,4-Metilenodioxianfetamina/uso terapêutico , Depressão/tratamento farmacológico , Administração Oral , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do TratamentoRESUMO
BACKGROUND AND PURPOSE: Migraine is a condition that is often observed to run in families, but its complex genetic background remains unclear. This study aimed to identify the genetic factors influencing migraines and their potential association with the family medical history. METHODS: We performed a comprehensive genome-wide association study of a cohort of 1,561 outpatients with migraine and 473 individuals without migraine in Taiwan, including Han Chinese individuals with or without a family history of migraine. By analyzing the detailed headache history of the patients and their relatives we aimed to isolate potential genetic markers associated with migraine while considering factors such as sex, episodic vs. chronic migraine, and the presence of aura. RESULTS: We revealed novel genetic risk loci, including rs2287637 in DEAD-Box helicase 1 and long intergenic non-protein coding RNA 1804 and rs12055943 in engulfment and cell motility 1, that were correlated with the family history of migraine. We also found a genetic location downstream of mesoderm posterior BHLH transcription factor 2 associated with episodic migraine, whereas loci within the ubiquitin-specific peptidase 26 exonic region, dual specificity phosphatase 9 and pregnancy-upregulated non-ubiquitous CaM kinase intergenic regions, and poly (ADP-ribose) polymerase 1 and STUM were linked to chronic migraine. We additionally identified genetic regionsassociated with the presence or absence of aura. A locus between LINC02561 and urocortin 3 was predominantly observed in female patients. Moreover, three different single-nucleotide polymorphisms were associated with the family history of migraine in the control group. CONCLUSIONS: This study has identified new genetic locations associated with migraine and its family history in a Han Chinese population, reinforcing the genetic background of migraine. The findings point to potential candidate genes that should be investigated further.
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OBJECTIVE: To compare the real-world effectiveness and tolerability of calcitonin gene-related peptide (CGRP) monoclonal antibodies (mAbs) and onabotulinumtoxinA in chronic migraine (CM) patients. METHODS: This multicenter study involved retrospective analysis of prospectively collected data of CM patients treated with CGRP mAbs or onabotulinumtoxinA, including difficult-to-treat (DTT) patients (i.e., ≥3 preventive failures). Treatment outcomes were determined at 6 months based on prospective headache diaries and Migraine Disability Assessment (MIDAS). RESULTS: The study included 316 (55 M/261F, mean age 44.4 ± 13.5 years) and 333 (61 M/272F, mean age 47.9 ± 13.4 years) CM patients treated with CGRP mAbs or onabotulinbumtoxinA, respectively. At 6 months, CGRP mAb treatment was associated with a greater decrease in monthly migraine days (MMDs) (-13.0 vs. -8.7 days/month, p < 0.001) and a higher ≥50% responder rate (RR) (74.7% vs. 50.7%, p < 0.001) compared with onabotulinumtoxinA injections. The findings were consistent in DTT patients (-13.0 vs. -9.1 MMDs, p < 0.001; ≥50% RR: 73.9% vs. 50.3%, p < 0.001) or those with medication-overuse headache (MOH) (-13.3 vs. -9.0 MMDs, p < 0.001; ≥50% RR: 79.0% vs. 51.6%, p < 0.001). Besides, patients receiving CGRP mAbs had greater improvement (-42.2 vs. -11.8, p < 0.001) and a higher ≥50% RR (62.0% vs. 40.0%, p = 0.001) in MIDAS scores and a lower rate of adverse events (AEs) (6.0% vs. 21.0%, p < 0.001). However, none of the patients discontinued treatment due to AEs. CONCLUSIONS: In this multicenter, real-world study, CGRP mAbs were more effective than onabotulinumtoxinA in CM patients, even in DTT or MOH patients. All of these injectables were well tolerated. Further prospective studies are needed to verify these findings.
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Anticorpos Monoclonais , Toxinas Botulínicas Tipo A , Peptídeo Relacionado com Gene de Calcitonina , Transtornos de Enxaqueca , Humanos , Toxinas Botulínicas Tipo A/efeitos adversos , Toxinas Botulínicas Tipo A/administração & dosagem , Toxinas Botulínicas Tipo A/uso terapêutico , Transtornos de Enxaqueca/tratamento farmacológico , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Peptídeo Relacionado com Gene de Calcitonina/imunologia , Peptídeo Relacionado com Gene de Calcitonina/antagonistas & inibidores , Estudos Retrospectivos , Taiwan , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/efeitos adversos , Anticorpos Monoclonais/administração & dosagem , Doença Crônica , Resultado do TratamentoRESUMO
Background: Individuals experiencing subjective cognitive decline (SCD) are at an increased risk of developing mild cognitive impairment and dementia. Early identification of SCD and neurodegenerative diseases using biomarkers may help clinical decision-making and improve prognosis. However, few cross-sectional and longitudinal studies have explored plasma biomarkers in individuals with SCD using immunomagnetic reduction. Objective: To identify plasma biomarkers for SCD. Methods: Fifty-two participants [38 with SCD, 14 healthy controls (HCs)] underwent baseline assessments, including measurements of plasma Aß42, Aß40, t-tau, p-tau, and α-synuclein using immunomagnetic reduction (IMR) assays, cognitive tests and the Mini-Mental State Examination (MMSE). Following initial cross-sectional analysis, 39 individuals (29 with SCD, 10 HCs) entered a longitudinal phase for reassessment of these biomarkers and the MMSE. Biomarker outcomes across different individual categories were primarily assessed using the area under the receiver operating characteristic (ROC) curve. The SCD subgroup with an MMSE decline over one point was compared to those without such a decline. Results: Higher baseline plasma Aß1-42 levels significantly discriminated participants with SCD from HCs, with an acceptable area under the ROC curve (AUC) of 67.5% [95% confidence interval (CI), 52.7-80.0%]. However, follow-up and changes in MMSE and IMR data did not significantly differ between the SCD and HC groups (p > 0.05). Furthermore, lower baseline plasma Aß1-42 levels were able to discriminate SCD subgroups with and without cognitive decline with a satisfied performance (AUC, 75.0%; 95% CI, 55.6-89.1%). At last, the changes in t-tau and Aß42 × t-tau could differentiate between the two SCD subgroups (p < 0.05). Conclusion: Baseline plasma Aß42 may help identify people with SCD and predict SCD progression. The role of plasma Aß42 levels as well as their upward trends from baseline in cases of SCD that progress to mild cognitive impairment and Alzheimer's disease require further investigation.
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PURPOSE OF REVIEW: In this narrative review, we aim to summarize recent insights into the complex interplay between environmental and genetic factors affecting the etiology, development, and progression of chronic migraine (CM). RECENT FINDINGS: Environmental factors such as stress, sleep dysfunction, fasting, hormonal changes, weather patterns, dietary compounds, and sensory stimuli are critical triggers that can contribute to the evolution of episodic migraine into CM. These triggers are particularly influential in genetically predisposed individuals. Concurrently, genome-wide association studies (GWAS) have revealed over 100 genetic loci linked to migraine, emphasizing a significant genetic basis for migraine susceptibility. In CM, environmental and genetic factors are of equal importance and contribute to the pathophysiology of the condition. Understanding the bidirectional interactions between these elements is crucial for advancing therapeutic approaches and preventive strategies. This balanced perspective encourages continued research into the complex gene-environment nexus to improve our understanding and management of CM.
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Transtornos de Enxaqueca , Transtornos do Sono-Vigília , Humanos , Estudo de Associação Genômica Ampla , Predisposição Genética para Doença/genética , Fatores Desencadeantes , Transtornos do Sono-Vigília/complicaçõesRESUMO
AIM: This study aimed to examine dose-effects of total pulses on improvement of depressive symptoms in patients with treatment-resistant depression (TRD) receiving repetitive transcranial magnetic stimulation (rTMS) over the left dorsal lateral prefrontal cortex (DLPFC). MATERIALS AND METHODS: The MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), EMBASE, PsycINFO, and ClinicalTrial.gov databases were systematically searched. We included randomized, double-blind, placebo-controlled trials (RCT) that used rTMS over left DLPFC in patients with TRD. Excluded studies were non-TRD, non-RCTs, or combined other brain stimulation interventions. The outcome of interest was the difference between rTMS arms and sham controls in improvement of depressive symptoms in a dose-response manner. A random-effects meta-analysis and dose-response meta-analysis(DRMA) was used to examine antidepressant efficacy of rTMS and association with total pulses. RESULTS: We found that rTMS over left DLPFC is superior to sham controls (reported as standardized mean difference[SMD] with 95% confidence interval: 0.77; 0.56-0.98). The best-fitting model of DRMA was bell-shaped (estimated using restricted cubic spline model; R2 =0.42), indicating that higher doses (>26,660 total pulses) were not associated with increased improvement of depressive symptoms. Stimulation frequency(R2 =0.53) and age(R2 =0.51) were significant moderators for the dose-response curve. Furthermore, 15-20 Hz rTMS was superior to 10 Hz rTMS (0.61, 0.15-1.10) when combining all doses. CONCLUSIONS: Our findings suggest higher doses(total pulses) of rTMS were not always associated with increased improvement of depressive symptoms in patients with TRD, and that the dose-response relationship was moderated by stimulation frequency and age. These associations emphasize the importance of determining dosing parameters to achieve maximum efficacy.
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Transtorno Depressivo Maior , Transtorno Depressivo Resistente a Tratamento , Estimulação Magnética Transcraniana , Humanos , Transtorno Depressivo Resistente a Tratamento/terapia , Estimulação Magnética Transcraniana/métodos , Transtorno Depressivo Maior/terapia , Córtex Pré-Frontal Dorsolateral/fisiologia , Avaliação de Resultados em Cuidados de Saúde , Resultado do Tratamento , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND AND PURPOSE: Differentiating epidural from intrathecal punctures before computed tomography (CT)-guided epidural blood patching (EBP) is subjective, relying on operator experience. This study aimed to investigate CT findings for epidural and intrathecal punctures and identify reliable predictors for successful epidural punctures before targeted CT-guided EBP. MATERIALS AND METHODS: We included 65 patients with low-cerebrospinal fluid (CSF)-pressure headache receiving targeted CT-guided EBP between January 2021 and October 2022 in this retrospective study. We analyzed clinical data, technical information, and CT features before EBP. Fisher's exact test was used for discrete variables, while Mann-Whitney U test was used for continuous variables. Positive (PLR) and negative likelihood ratios (NLR) were calculated to identify predictors for confirming epidural punctures. RESULTS: We confirmed 43 patients as epidural punctures and 22 patients as intrathecal punctures. Before contrast injection, epidural fat at the needle tip in the epidural group was higher than the intrathecal group (37.2 % [16/43] vs. 4.5 % [1/22], p = 0.006). After contrast injection, the "contrast-needle tip connection" sign was mostly observed in the epidural group than the intrathecal group (95.3 % [41/43] vs. 9.1 % [2/22], p < 0.001). Additionally, the epidural group had significantly higher boomerang-shaped contrast morphology than the intrathecal group (65.1 % [28/43] vs. 9.1 % [2/22], p < 0.001). The "contrast-needle tip connection" sign had the highest PLR (10.49) and lowest NLR (0.05). CONCLUSION: Identifying epidural fat at the needle tip, "contrast-needle tip connection" sign, and boomerang-shaped contrast morphology on CT scans are useful for confirming proper placement of the needle tip within the epidural space.
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Placa de Sangue Epidural , Punções , Humanos , Placa de Sangue Epidural/métodos , Estudos Retrospectivos , Cefaleia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND: Conventional epidurography (CE) is thought to have insufficient usefulness on percutaneous epidural adhesiolysis (PEA). We aimed to evaluate the association between the outcome of PEA and cone-beam computed tomography-reformatted epidurography (CBCT-RE). METHODS: After ethics board approval and written informed consent were obtained, we performed 30 PEA in 26 participants, and evaluated their post-PEA image findings. Two independent radiologists categorized and recorded the occurrence of contrast in the intracanal ventral and extraforaminal regions on CE, and in the dorsal canal (DC), ventral canal (VC), dorsal foramen (DF), and ventral foramen (VF) on CBCT-RE. Reproducibility was assessed using intraclass correlation coefficients (ICCs). Baseline characteristics along with contrast distribution patterns of CE and CBCT-RE were analyzed in terms of their association with symptom relief at 1 month after PEA. RESULTS: The rate of patients with symptoms relief >50% after PEA was 63.3%. The inter-reader agreement was higher for CBCT-RE (ICC = 0.955) than for CE (ICC = 0.793). Participants with contrast coexisting in VC and DF adjacent to the irritated nerve root on CBCT-RE ( p = 0.015) had a significantly better response after PEA than those without contrast at these locations on CBCT-RE, independent of baseline characteristics (adjusted odds ratio: 11.414 [ p = 0.012]). CONCLUSION: CBCT-RE with identifying contrast distribution patterns is useful for predicting outcome of PEA.
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Tomografia Computadorizada de Feixe Cônico , Humanos , Projetos Piloto , Reprodutibilidade dos Testes , Tomografia Computadorizada de Feixe Cônico/métodosRESUMO
BACKGROUND: ChatGPT may act as a research assistant to help organize the direction of thinking and summarize research findings. However, few studies have examined the quality, similarity (abstracts being similar to the original one), and accuracy of the abstracts generated by ChatGPT when researchers provide full-text basic research papers. OBJECTIVE: We aimed to assess the applicability of an artificial intelligence (AI) model in generating abstracts for basic preclinical research. METHODS: We selected 30 basic research papers from Nature, Genome Biology, and Biological Psychiatry. Excluding abstracts, we inputted the full text into ChatPDF, an application of a language model based on ChatGPT, and we prompted it to generate abstracts with the same style as used in the original papers. A total of 8 experts were invited to evaluate the quality of these abstracts (based on a Likert scale of 0-10) and identify which abstracts were generated by ChatPDF, using a blind approach. These abstracts were also evaluated for their similarity to the original abstracts and the accuracy of the AI content. RESULTS: The quality of ChatGPT-generated abstracts was lower than that of the actual abstracts (10-point Likert scale: mean 4.72, SD 2.09 vs mean 8.09, SD 1.03; P<.001). The difference in quality was significant in the unstructured format (mean difference -4.33; 95% CI -4.79 to -3.86; P<.001) but minimal in the 4-subheading structured format (mean difference -2.33; 95% CI -2.79 to -1.86). Among the 30 ChatGPT-generated abstracts, 3 showed wrong conclusions, and 10 were identified as AI content. The mean percentage of similarity between the original and the generated abstracts was not high (2.10%-4.40%). The blinded reviewers achieved a 93% (224/240) accuracy rate in guessing which abstracts were written using ChatGPT. CONCLUSIONS: Using ChatGPT to generate a scientific abstract may not lead to issues of similarity when using real full texts written by humans. However, the quality of the ChatGPT-generated abstracts was suboptimal, and their accuracy was not 100%.
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Inteligência Artificial , Pesquisa , Humanos , Estudos Transversais , Pesquisadores , IdiomaRESUMO
OBJECTIVE: Individuals with dementia are at a substantially elevated risk for mortality; however, few studies have examined multimorbidity patterns and determined the inter-relationship between these comorbidities in predicting mortality risk. METHODS: This is a prospective cohort study. Data from 6,556 patients who were diagnosed with dementia between 1997 and 2012 using the Taiwan National Health Insurance Research Database were analyzed. Latent class analysis was performed using 16 common chronic conditions to identify mortality risk among potentially different latent classes. Logistic regression was performed to determine the adjusted association of the determined latent classes with the 5-year mortality rate. RESULTS: With adjustment for age, a three-class model was identified, with 42.7% of participants classified as "low comorbidity class (cluster 1)", 44.2% as "cardiometabolic multimorbidity class (cluster 2)", and 13.1% as "FRINGED class (cluster 3, characterized by FRacture, Infection, NasoGastric feeding, and bleEDing over upper gastrointestinal tract)." The incidence of 5-year mortality was 17.6% in cluster 1, 26.7% in cluster 2, and 59.6% in cluster 3. Compared with cluster 1, the odds ratio for mortality was 9.828 (95% confidence interval [CI]=6.708-14.401; p<0.001) in cluster 2 and 1.582 (95% CI=1.281-1.953; p<0.001) in cluster 3. CONCLUSION: Among patients with dementia, the risk for 5-year mortality was highest in the subpopulation characterized by fracture, urinary and pulmonary infection, upper gastrointestinal bleeding, and nasogastric intubation, rather than cancer or cardiometabolic comorbidities. These findings may improve decision-making and advance care planning for patients with dementia.
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Introduction: Subjective cognitive decline (SCD) and migraine are often comorbid. Hippocampal structural abnormalities have been observed in individuals with both SCD and migraine. Given the known structural and functional heterogeneity along the long axis (anterior to posterior) of the hippocampus, we aimed to identify altered patterns of structural covariance within hippocampal subdivisions associated with SCD and migraine comorbidities. Methods: A seed-based structural covariance network analysis was applied to examine large-scale anatomical network changes of the anterior and posterior hippocampus in individuals with SCD, migraine and healthy controls. Conjunction analyses were used to identify shared network-level alterations in the hippocampal subdivisions in individuals with both SCD and migraine. Results: Altered structural covariance integrity of the anterior and posterior hippocampus was observed in the temporal, frontal, occipital, cingulate, precentral, and postcentral areas in individuals with SCD and migraine compared with healthy controls. Conjunction analysis revealed that, in both SCD and migraine, altered structural covariance integrity was shared between the anterior hippocampus and inferior temporal gyri and between the posterior hippocampus and precentral gyrus. Additionally, the structural covariance integrity of the posterior hippocampus-cerebellum axis was associated with the duration of SCD. Conclusion: This study highlighted the specific role of hippocampal subdivisions and specific structural covariance alterations within these subdivisions in the pathophysiology of SCD and migraine. These network-level changes in structural covariance may serve as potential imaging signatures for individuals who have both SCD and migraine.
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OBJECTIVE: Our study aimed to explore the associative relationship between neurodegenerative diseases and sleep disorders. PATIENTS: This 15-year retrospective longitudinal nationwide population-based matched case-control study used data extracted from the National Health Insurance Research Database. We evaluated 25,589 patients diagnosed with neurodegenerative diseases between 2000 and 2015 and a matched control of 102,356 patients without neurodegenerative diseases. RESULTS: Sleep disorders were an independent risk factor for the development of neurodegenerative diseases (adjusted odds ratio (OR): 1.794, 95% confidence interval (CI): 1.235-2.268, P < 0.001), with a positive dose-effect relationship (adjusted OR (95% CI): <1 year: 1.638 (1.093-2.872), P < 0.001; 1-5 years: 1.897 (1.260-3.135), P < 0.001; >5 years: 2.381 (1.467-3.681), P < 0.001. Moreover, patients with sleep disorder and comorbid depression had a significantly higher risk of neurodegenerative disorders (adjusted OR: 5.874). Subgroup analysis showed that insomnia was associated with Alzheimer's disease, Pick's disease and essential tremor (adjusted OR (95% CI): 1.555 (1.069-1.965), 1.934 (1.331-2.445) and 2.089 (1.439-2.648), respectively). Obstructive sleep apnea was associated with Parkinson's disease, essential tremor, and primary dystonia (adjusted OR (95% CI): 1.801 (1.239-2.275), 5.523 (3.802-6.977), and 4.892 (3.365-6.178), respectively). Other specific sleep disorders were associated with Pick's disease, Parkinson's disease, essential tremor, and primary dystonia (adjusted OR (95% CI): 8.901 (6.101-11.010), 1.549 (1.075-1.986), 2.791 (1.924-3.531), and 9.114 (6.283-10.506), respectively). CONCLUSION: Sleep disorders are associated with the subsequent development of neurodegenerative disorders. Moreover, sleep disorder patients with comorbid depression have a higher risk of neurodegenerative diseases.
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Distúrbios Distônicos , Tremor Essencial , Doenças Neurodegenerativas , Doença de Parkinson , Doença de Pick , Apneia Obstrutiva do Sono , Transtornos do Sono-Vigília , Humanos , Doenças Neurodegenerativas/epidemiologia , Estudos Retrospectivos , Doença de Parkinson/complicações , Doença de Parkinson/epidemiologia , Estudos de Casos e Controles , Doença de Pick/complicações , Tremor Essencial/complicações , Fatores de Risco , Apneia Obstrutiva do Sono/complicações , Distúrbios Distônicos/complicações , Transtornos do Sono-Vigília/complicações , TaiwanRESUMO
Purpose: Fingolimod, an oral treatment for relapsing-remitting multiple sclerosis (RRMS), has been associated with a significant rebound in disease activity after therapy cessation. We described a patient with neuromyelitis optica spectrum disorder (NMOSD) who was previously diagnosed with RRMS and experienced fatal rebound syndrome after cessation of fingolimod. Case report: A 54-year-old woman, previously diagnosed with RRMS, experienced relapse after orthopedic surgery. The diagnosis was later revised to NMOSD based on a positive aquaporin-4 antibody. Three weeks after converting the immunomodulator from fingolimod to azathioprine, severe disease reactivation was observed. Considering the multiple new and enlarging magnetic resonance imaging lesions, the temporal relationship between fingolimod cessation and symptom onset, and the relatively low possibility of disease reactivation within a short time, the diagnosis of fingolimod withdrawal syndrome was proposed. Although immediate steroid pulse therapy and plasma exchange were performed, the patient eventually died owing to a fulminant clinical course. Conclusion: Fingolimod withdrawal syndrome is well known in patients with multiple sclerosis (MS). It can also occur in patients with NMOSD. Recognizing patients with NMOSD who present with MS-like manifestations, and avoiding drugs that may be harmful to patients with NMOSD, are important.
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Esclerose Múltipla Recidivante-Remitente , Esclerose Múltipla , Neuromielite Óptica , Feminino , Humanos , Pessoa de Meia-Idade , Cloridrato de Fingolimode/efeitos adversos , Neuromielite Óptica/diagnóstico , Neuromielite Óptica/tratamento farmacológico , Neuromielite Óptica/patologia , Esclerose Múltipla Recidivante-Remitente/tratamento farmacológico , Esclerose Múltipla/tratamento farmacológico , Fatores Imunológicos/uso terapêuticoRESUMO
Long sit-to-stand (STS) time has been identified as a feature of impaired functional mobility. The changes in biomechanics of STS performance with simultaneous hip adductor contraction have not been studied, which may limit indications for use of hip adductor activation during STS training. Ten individuals with hemiplegia (mean age 61.8 years, injury time 29.8 ± 15.2 months) performed the STS with and without squeezing a ball between two legs. The joint moments, ground reaction force (GRF), chair reaction force and movement durations and temporal index of electromyography were calculated from the control condition for comparison with those from the ball squeezing condition. Under the squeeze condition, reduced peak vertical GRF during the ascension phase with increased loading rate was observed in the nonparetic limb, and the peak knee extensor moment occurred earlier in the paretic. Earlier activation of tibialis anterior and gluteus maximus, and gluteus medius were found in squeeze STS. Squeezing a ball between limbs during STS increased the contraction timing of tibialis anterior, gluteus maximus, gluteus medius, and soleus as well as a more symmetric rising mechanics encourage the use of squeezing a ball between limbs during STS for individuals with hemiparesis.
Assuntos
Movimento , Músculo Esquelético , Humanos , Pessoa de Meia-Idade , Músculo Esquelético/fisiologia , Movimento/fisiologia , Perna (Membro)/fisiologia , Articulação do Joelho/fisiologia , Eletromiografia , Paresia , Fenômenos BiomecânicosRESUMO
Although ramelteon has been examined as a relatively new therapeutic option for delirium prevention, current evidence to evaluate its efficacy is limited. We conducted an updated meta-analysis and examine the reliability of existing evidence regarding the effect of ramelteon on delirium prevention in hospitalized patients. Seven major electronic databases were systematically searched to identify randomized controlled trials examining the efficacy of ramelteon in delirium prevention. Data were pooled using a frequentist-restricted maximum-likelihood random-effects model. A trial sequential analysis was performed using relative risk reduction thresholds of 50%. The primary outcome was the incidence of delirium (reported as odds ratio with 95% confidence intervals). The secondary outcomes were the days of delirium, all-cause mortality, and all-cause discontinuation. Of 187 potentially eligible studies identified, 8 placebo-controlled randomized controlled trials (n = 587) were included. This updated meta-analysis showed that ramelteon was associated with lower odds of delirium occurrence than placebo (0.50; 0.29-0.86; I2 = 17.48%). In trial sequential analysis, the effect of ramelteon across the superiority boundary when using a relative risk reduction threshold ranging from 40% to 60%. In subgroup analyses, ramelteon compared with placebo was associated with lower odds of delirium occurrence in the elderly group (k = 5; 0.28; 0.09-0.85; I2 = 27.93%) and multiple dosage group (k = 5; 0.34; 0.14-0.82; I2 = 44.24%) but not in the non-elderly and non-multiple dosage groups. When considering surgical patients and medical patients separately, ramelteon showed a trend in the treatment of delirium prevention in both groups, while these findings were not statistically significant. No significant between-group differences were found in the secondary outcomes. The current meta-analysis provides updated and reliable evidence that ramelteon, in comparison with placebo, reduces the risk of delirium among hospitalized patients.
Assuntos
Delírio , Melatonina , Humanos , Pessoa de Meia-Idade , Delírio/prevenção & controle , Delírio/tratamento farmacológico , Delírio/epidemiologia , Melatonina/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos TestesRESUMO
OBJECTIVE: To integrate all evidence derived from randomized controlled trials (RCTs) of both pharmacological and nonpharmacological augmentation interventions for clozapine-resistant schizophrenia (CRS). METHODS: Six major electronic databases were systematically searched for RCTs published until July 10, 2021. The primary outcome was change in overall symptoms, and the secondary outcomes were positive and negative symptoms and acceptability. We performed random-effects network meta-analysis. Normalized entropy was calculated to examine the uncertainty of treatment ranking. RESULTS: We identified 35 RCTs (1472 patients with 23 active augmentation treatments) with a mean daily clozapine dose of 440.80 (91.27) mg for 1168.22 (710.28) days. Network meta-analysis of overall symptoms (reported as standardized mean difference; 95 % confidence interval) with consistent results indicated that mirtazapine (-4.41; -5.61, -3.21), electroconvulsive therapy (ECT) (-4.32; -5.43, -3.21), and memantine (-2.02; -3.14, -0.91) were ranked as the best three treatments. For positive symptoms, ECT (-5.18; -5.86, -4.49) was ranked the best with less uncertainty. For negative symptoms, memantine (-3.38; -4.50, -2.26), duloxetine (-3.27; -4.25, -2.29), and mirtazapine (-1.73; -2.71, -0.74) were ranked the best three treatments with less uncertainty. All antipsychotics, N-methyl d-aspartate receptor agonists, and antiepileptics were not associated with more efficacy than placebo. Compared to placebo, only amisulpride had statistically significant lower discontinuation rate (risk ratio: 0.21; 95 % CI: 0.05, 0.93). CONCLUSION: Add-on mirtazapine, ECT, and memantine were the most efficacious augmentation options for CRS. Data on other important outcomes such as cognitive functioning or quality of life were rarely reported, making further large-scale, well-designed RCTs necessary. (PROSPERO number, CRD42021262197.).