The use of acupuncture for addressing neurological and neuropsychiatric symptoms in patients with long COVID: a systematic review and meta-analysis.

Importance: Acupuncture has been used to treat neurological and neuropsychiatric symptoms in China and other parts of the world. These symptoms, such as fatigue, headache, cognitive impairment, anxiety, depression, and insomnia, are common in people experiencing long COVID. Objective: This study aims to explore the feasibility of acupuncture in the treatment of neurological and neuropsychiatric symptoms in long COVID patients. Data Sources: A systematic search was conducted in four English and four Chinese databases from inception to 23 June 2023. Literature selection and data extraction were conducted by two pairs of independent reviewers. Study Selection: Randomized controlled trials (RCTs) that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included. Data Extraction and Synthesis: RCTs that explored the effect of acupuncture on fatigue, depression, anxiety, cognitive abnormalities, headache, and insomnia were included. A meta-analysis was performed using R software. Heterogeneity was measured using I2. Subgroup analyses were performed focusing on the duration of treatment and acupuncture modalities. The systematic review protocol was registered on PROSPERO (registration number: CRD42022354940). Main outcomes and measures: Widely adopted clinical outcome scales included the Fatigue Scale for assessing fatigue, the Hamilton Depression Rating Scale for evaluating depression, the Mini-Mental State Examination for assessing cognitive impairment, the Visual Analog Scale for headache severity, and the Pittsburgh Sleep Quality Index for measuring insomnia. Results: A total of 110 RCTs were included in the systematic review and meta-analysis. Overall, acupuncture was found to improve the scores of the Fatigue Scale (vs. medication: mean differences (MD): -2.27, P < 0.01; vs. sham acupuncture: MD: -3.36, P < 0.01), the Hamilton Depression Rating Scale (vs. medication: MD: -1.62, 95%, P < 0.01; vs. sham acupuncture: MD: -9.47, P < 0.01), the Mini-Mental State Examination (vs. medication: MD: 1.15, P < 0.01; vs. sham acupuncture: MD: 1.20, P < 0.01), the Visual Analog Scale (vs. medication: MD: -1.05, P < 0.01; vs. waitlist: MD: -0.48, P=0.04), and the Pittsburgh Sleep Quality Index (vs. medication: MD: -2.33, P < 0.01; vs. sham acupuncture: MD: -4.19, P < 0.01). Conclusion and relevance: This systematic review suggested acupuncture as a potentially beneficial approach for the treatment of neurological and neuropsychiatric symptoms, as assessed using clinical scales, and it may have applicability in long COVID patients. Further well-designed clinical studies specifically targeting long COVID patients are needed to validate the role of acupuncture in alleviating long COVID symptoms. Systematic Review Registration: PROSPERO, identifier [CRD42022354940].

Combined clinical, structural, and cellular studies discriminate pathogenic and benign TRPV4 variants.

Dominant mutations in the calcium-permeable ion channel TRPV4 (transient receptor potential vanilloid 4) cause diverse and largely distinct channelopathies, including inherited forms of neuromuscular disease, skeletal dysplasias, and arthropathy. Pathogenic TRPV4 mutations cause gain of ion channel function and toxicity that can be rescued by small molecule TRPV4 antagonists in cellular and animal models, suggesting that TRPV4 antagonism could be therapeutic for patients. Numerous variants in TRPV4 have been detected with targeted and whole exome/genome sequencing, but for the vast majority, their pathogenicity remains unclear. Here, we used a combination of clinical information and experimental structure-function analyses to evaluate 30 TRPV4 variants across various functional protein domains. We report clinical features of seven patients with TRPV4 variants of unknown significance and provide extensive functional characterization of these and an additional 17 variants, including structural position, ion channel function, subcellular localization, expression level, cytotoxicity, and protein-protein interactions. We find that gain-of-function mutations within the TRPV4 intracellular ankyrin repeat domain target charged amino acid residues important for RhoA interaction, whereas ankyrin repeat domain residues outside of the RhoA interface have normal or reduced ion channel activity. We further identify a cluster of gain-of-function variants within the intracellular intrinsically disordered region that may cause toxicity via altered interactions with membrane lipids. In contrast, assessed variants in the transmembrane domain and other regions of the intrinsically disordered region do not cause gain of function and are likely benign. Clinical features associated with gain of function and cytotoxicity include congenital onset of disease, vocal cord weakness, and motor predominant disease, whereas patients with likely benign variants often demonstrated late-onset and sensory-predominant disease. These results provide a framework for assessing additional TRPV4 variants with respect to likely pathogenicity, which will yield critical information to inform patient selection for future clinical trials for TRPV4 channelopathies.

Normotensive metabolic syndrome in Transient Receptor Potential Canonical Channel type 1 Trpc1-/- mice.

Metabolic syndrome has become a global epidemic, affecting all developed countries and communities with growing economies. Worldwide, increasing efforts have been directed at curbing this growing problem. Mice deleted of the gene encoding Type 1 Transient Receptor Potential Canonical Channel (Trpc1) were found to weigh heavier than controls. They had fasting hyperglycemia and impaired glucose tolerance compared with wild-type controls. Beyond 1 year of age, plasma triglyceride level in Trpc1-/- mice was elevated. Plasma cholesterol levels tended to be higher than in controls. The livers of Trpc1-/- mice were heavier, richer in triglyceride, and more echogenic than those of controls on ultrasound evaluation. Hematocrit was lower in Trpc1-/- mice of both genders beginning at the second to third months of age in the absence of bleeding or hemolysis. Measured by the indirect tail-cuff method or by the direct arterial cannulation, blood pressures in null mice were lower than controls. We conclude that TRPC1 gene regulates body metabolism and that except for hypertension, phenotypes of mice after deletion of the Trpc1 gene resemble mice with metabolic syndrome, suggesting that this could be a good experimental model for future investigation of the pathogenesis and management of this disorder.

Pentagonal nanowires from topological crystalline insulators: a platform for intrinsic core-shell nanowires and higher-order topology.

We report on the experimental realization of Pb1-xSnx Te pentagonal nanowires (NWs) with [110] orientation using molecular beam epitaxy techniques. Using first-principles calculations, we investigate the structural stability of NWs of SnTe and PbTe in three different structural phases: cubic, pentagonal with [001] orientation and pentagonal with [110] orientation. Within a semiclassical approach, we show that the interplay between ionic and covalent bonds favors the formation of pentagonal NWs. Additionally, we find that this pentagonal structure is more likely to occur in tellurides than in selenides. The disclination and twin boundary cause the electronic states originating from the NW core region to generate a conducting band connecting the valence and conduction bands, creating a symmetry-enforced metallic phase. The metallic core band has opposite slopes in the cases of Sn and Te twin boundaries, while the bands from the shell are insulating. We finally study the electronic and topological properties of pentagonal NWs unveiling their potential as a new platform for higher-order topology and fractional charge. These pentagonal NWs represent a unique case of intrinsic core-shell one-dimensional nanostructures with distinct structural, electronic and topological properties between the core and the shell region.

Multi-domain neurocognitive impairment following definitive intensity-modulated radiotherapy for nasopharyngeal cancer: A cross-sectional study.

INTRODUCTION: Neurocognitive impairment from inadvertent brain irradiation is common following intensity-modulated radiotherapy (IMRT) for nasopharyngeal carcinoma (NPC). This study aimed to determine the prevalence, pattern, and radiation dose-toxicity relationship of this late complication. MATERIALS AND METHODS: We undertook a cross-sectional study of 190 post-IMRT NPC survivors. Neurocognitive function was screened using the Montreal Cognitive Assessment-Hong Kong (HK-MoCA). Detailed assessments of eight distinct neurocognitive domains were conducted: intellectual capacity (WAIS-IV), attention span (Digit Span and Visual Spatial Span), visual memory (Visual Reproduction Span), verbal memory (Auditory Verbal Learning Test), processing speed (Color Trail Test), executive function (Stroop Test), motor dexterity (Grooved Pegboard Test) and language ability (Verbal Fluency Test). The mean percentiles and Z-scores were compared with normative population data. Associations between radiation dose and brain substructures were explored using multivariable logistic regression. RESULTS: The median post-IMRT interval was 7.0 years. The prevalence of impaired HK-MoCA was 25.3 % (48/190). Among the participants, 151 (79.4 %) exhibited impairments in at least one neurocognitive domain. The predominantly impaired domains included verbal memory (short-term: mean Z-score, -0.56, p < 0.001; long-term: mean Z-score, -0.70, p < 0.001), processing speed (basic: mean Z-score, -1.04, p < 0.001; advanced: mean Z-score, -0.38, p < 0.001), executive function (mean Z-score, -1.90, p < 0.001), and motor dexterity (dominant hand: mean Z-score, -0.97, p < 0.001). Radiation dose to the whole brain, hippocampus, and temporal lobe was associated with impairments in executive function, verbal memory, processing speed, and motor dexterity. CONCLUSIONS: Neurocognitive impairment is prevalent and profound in post-IMRT NPC survivors. Cognitive assessment and rehabilitation should be considered part of survivorship care.

Cerebral hemodynamics and stroke risks in symptomatic intracranial atherosclerotic stenosis with internal versus cortical borderzone infarcts: A computational fluid dynamics study.

There may be different mechanisms underlying internal (IBZ) and cortical (CBZ) borderzone infarcts in intracranial atherosclerotic stenosis. In 84 patients with symptomatic, 50-99% atherosclerotic stenosis of M1 middle cerebral artery (MCA-M1) with acute borderzone infarcts in diffusion-weighted imaging, we classified the infarct patterns as isolated IBZ (n = 37), isolated CBZ (n = 31), and IBZ+CBZ (n = 16) infarcts. CT angiography-based computational fluid dynamics models were constructed to quantify translesional, post-stenotic to pre-stenotic pressure ratio (PR) in the MCA-M1 lesion. Those with IBZ infarcts were more likely to have a low PR (indicating impaired antegrade flow across the lesion) than those without (p = 0.012), and those with CBZ infarcts were more likely to have coexisting small cortical infarcts (indicating possible embolism) than those without (p = 0.004). In those with isolated IBZ or CBZ infarcts, low PR was independently associated with isolated IBZ infarcts (adjusted odds ratio = 4.223; p = 0.026). These two groups may also have different trajectories in the stroke risks under current medical treatment regimen, with a higher risk of same-territory ischemic stroke recurrence within 3 months in patients with isolated IBZ infarcts than isolated CBZ infarcts (17.9% versus 0.0%; log-rank p = 0.023), but similar risks later in 1 year.

Hemodynamic significance of intracranial atherosclerotic disease and ipsilateral imaging markers of cerebral small vessel disease.

INTRODUCTION: Cerebral small vessel disease (CSVD) commonly exists in patients with symptomatic intracranial atherosclerotic disease (sICAD). We aimed to investigate the associations of hemodynamic features of sICAD lesions with imaging markers and overall burden of CSVD. PATIENTS AND METHODS: Patients with anterior-circulation sICAD (50%-99% stenosis) were analyzed in this cross-sectional study. Hemodynamic features of a sICAD lesion were quantified by translesional pressure ratio (PR = Pressurepost-stenotic/Pressurepre-stenotic) and wall shear stress ratio (WSSR = WSSstenotic-throat/WSSpre-stenotic) via CT angiography-based computational fluid dynamics modeling. PR ⩽median was defined as low ("abnormal") PR, and WSSR ⩾ fourth quartile as high ("abnormal") WSSR. For primary analyses, white matter hyperintensities (WMHs), lacunes, and cortical microinfarcts (CMIs) were assessed in MRI and summed up as overall CSVD burden, respectively in ipsilateral and contralateral hemispheres to sICAD. Enlarged perivascular spaces (EPVSs) and cerebral microbleeds (CMBs) were assessed for secondary analyses. RESULTS: Among 112 sICAD patients, there were more severe WMHs, more lacunes and CMIs, and more severe overall CSVD burden ipsilaterally than contralaterally (all p < 0.05). Abnormal PR and WSSR (vs normal PR and WSSR) was significantly associated with moderate-to-severe WMHs (adjusted odds ratio = 10.12, p = 0.018), CMI presence (5.25, p = 0.003), and moderate-to-severe CSVD burden (12.55; p = 0.033), ipsilaterally, respectively independent of contralateral WMHs, CMI(s), and CSVD burden. EPVSs and CMBs were comparable between the two hemispheres, with no association found with the hemodynamic metrics. DISCUSSION AND CONCLUSION: There are more severe WMHs and CMI(s) in the hemisphere ipsilateral than contralateral to sICAD. The hemodynamic significance of sICAD lesions was independently associated with severities of WMHs and CMI(s) ipsilaterally.

Bruton's tyrosine kinase-bearing B cells and microglia in neuromyelitis optica spectrum disorder.

BACKGROUND: Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory autoimmune disease of the central nervous system that involves B-cell receptor signaling as well as astrocyte-microglia interaction, which both contribute to evolution of NMOSD lesions. MAIN BODY: Through transcriptomic and flow cytometry analyses, we found that Bruton's tyrosine kinase (BTK), a crucial protein of B-cell receptor was upregulated both in the blood and cerebrospinal fluid of NMOSD patients. Blockade of BTK with zanubrutinib, a highly specific BTK inhibitor, mitigated the activation and maturation of B cells and reduced production of causal aquaporin-4 (AQP4) autoantibodies. In a mouse model of NMO, we found that both BTK and pBTK expression were significantly increased in microglia. Transmission electron microscope scan demonstrated that BTK inhibitor ameliorated demyelination, edema, and axonal injury in NMO mice. In the same mice colocalization of GFAP and Iba-1 immunofluorescence indicated a noticeable increase of astrocytes-microglia interaction, which was alleviated by zanubrutinib. The smart-seq analysis demonstrated that treatment with BTK inhibitor instigated microglial transcriptome changes including downregulation of chemokine-related genes and genes involved in the top 5 biological processes related to cell adhesion and migration, which are likely responsible for the reduced crosstalk of microglia and astrocytes. CONCLUSIONS: Our results show that BTK activity is enhanced both in B cells and microglia and BTK inhibition contributes to the amelioration of NMOSD pathology. These data collectively reveal the mechanism of action of BTK inhibition and corroborate BTK as a viable therapeutic target.

Prevalence of post-stroke cognitive impairment and associated risk factors in Chinese stroke survivors.

BACKGROUND: Post-stroke cognitive impairment (PSCI) adversely affects survivors' recovery trajectory and overall health outcomes. This study aimed to investigate the prevalence of PCSI and its associated risk factors. METHODS: A cross-sectional study was conducted with stroke survivors recruited from the neurology units of three hospitals in Yunnan, China. Measures included the Frenchay Aphasia Screening Test (FAST), Apathy Evaluation Scale (AES), Fatigue Severity Scale (FSS), Informant Questionnaire for Cognitive Decline in the Elderly (IQCODE), Montreal Cognitive Assessment (MoCA), and Charlson Comorbidity Index (CCI). Logistic regression analysis was carried out to identify risk factors significantly and independently associated with PSCI. RESULTS: Of 389 stroke participants studied, 139 (36%) were found to have PSCI. Every 10-year increase in age [odds ratio (OR) =1.69, 95% confidence interval (CI): 1.27-2.24, p < 0.001], and 1-point increase in the AES (OR = 1.13, 95% CI: 1.07-1.18, p < 0.001) and FSS scores (OR = 1.06, 95% CI: 1.03-1.10, p < 0.001) were significantly associated with higher odds of PSCI. Conversely, a 1-point increase in the MoCA score (OR = 0.91, 95% CI: 0.87-0.95, p < 0.001) and having an undergraduate education (OR = 0.45, 95% CI: 0.24-0.84, p = 0.013) or postgraduate education (OR = 0.18, 95% CI: 0.06-0.50, p = 0.001) were associated with reduced odds of PSCI. CONCLUSIONS: PSCI is prevalent in the Chinese population, with advanced age, lower education levels, lower MoCA scores, and higher fatigue and apathy scores identified as strong risk factors. It is recommended that psychological and cognitive assessment be routinely incorporated into post-stroke rehabilitation pathways to mitigate cognitive decline.

Cerebrospinal fluid oligoclonal bands in Chinese patients with multiple sclerosis: the prevalence and its association with clinical features.

Background: Cerebrospinal fluid oligoclonal band (CSF-OCB) is an established biomarker in diagnosing multiple sclerosis (MS), however, there are no nationwide data on CSF-OCB prevalence and its diagnostic performance in Chinese MS patients, especially in the virtue of common standard operation procedure (SOP). Methods: With a consensus SOP and the same isoelectric focusing system, we conducted a nationwide multi-center study on OCB status in consecutively, and recruited 483 MS patients and 880 non-MS patients, including neuro-inflammatory diseases (NID, n = 595) and non-inflammatory neurological diseases (NIND, n=285). Using a standardized case report form (CRF) to collect the clinical, radiological, immunological, and CSF data, we explored the association of CSF-OCB positivity with patient characters and the diagnostic performance of CSF-OCB in Chinese MS patients. Prospective source data collection, and retrospective data acquisition and statistical data analysis were used. Findings: 369 (76.4%) MS patients were OCB-positive, while 109 NID patients (18.3%) and 6 NIND patients (2.1%) were OCB-positive, respectively. Time from symptom onset to diagnosis was significantly shorter in OCB-positive than that in OCB-negative MS patients (13.2 vs 23.7 months, P=0.020). The prevalence of CSF-OCB in Chinese MS patients was significantly higher in high-latitude regions (41°-50°N)(P=0.016), and at high altitudes (>1000m)(P=0.025). The diagnostic performance of CSF-OCB differentiating MS from non-MS patients yielded a sensitivity of 76%, a specificity of 87%. Interpretation: The nationwide prevalence of CSF-OCB was 76.4% in Chinese MS patients, and demonstrated a good diagnostic performance in differentiating MS from other CNS diseases. The CSF-OCB prevalence showed a correlation with high latitude and altitude in Chinese MS patients.

Tai Chi for the prophylaxis of episodic migraine: protocol of a non-inferiority randomized controlled trial with mechanism exploration.

BACKGROUND: Migraine is a complex neurovascular disorder with considerable clinical, social and economic issues. Tai chi has the potential to be an alternative prophylactic treatment for migraine with high safety since the adverse effects and limited efficacy of available medications. AIMS: The proposed study aims to compare the prophylaxis efficacy of 24-week Tai Chi training on migraine attacks with the standard prophylactic medication; and to explore the mechanism of Tai Chi in preventing migraine attacks by analyzing the associations between changes of migraine attacks and changes of neurovascular functions and inflammatory makers. METHOD: This is a two-arm parallel non-inferiority randomized controlled trial. In total 220 Hong Kong Chinese women aged 18-65 years with diagnosis of episodic migraine will be recruited and randomized to either the Tai Chi training group or the standard prophylactic medication group with 1:1 ratio, and receive the 24 weeks of modified 33-short form Yang-style Tai Chi training and the standard prophylactic medications, respectively. A 24-week follow-up will be implemented for both groups. For efficacy examination, the primary outcome was the frequency of migraine attacks measured by the migraine diary; and for the mechanism exploration, the primary outcome was the volume and number of white matter hyperintensity (WMH) measured by magnetic resonance imaging (MRI). The measurements will be conducted at the baseline, 24th weeks, and 48th weeks. Linear mixed model will be adopted to comprehensively analyze the changes of variables within and between groups. DISCUSSION: Given the importance of reducing disease burden and financial cost of migraine attacks, the findings of this study will provide new insights regarding the role of Tai Chi in alleviating migraine burden and further shed light on the mechanism action of Tai Chi on preventing headache attacks. TRIAL REGISTRATION: ClinicalTrials.gov NCT05690737. Registered on January 28, 2023.

Virtual Multidisciplinary Stroke Care Clinic for Community-Dwelling Stroke Survivors: A Randomized Controlled Trial.

BACKGROUND: Stroke survivors constantly feel helpless and unprepared after discharge from hospitals. More flexible and pragmatic support are needed for their optimized recovery. We examined the effects of a virtual multidisciplinary stroke care clinic on survivors' health and self-management outcomes. METHODS: A randomized controlled trial was conducted. Survivors were recruited from 10 hospitals and randomized at 1:1 ratio into the intervention or the control groups. Intervention group participants received the Virtual Multidisciplinary Stroke Care Clinic service (monthly online consultations with a nurse, follow-up phone calls, and access to an online platform). Control group participants received the usual care. Outcomes of self-efficacy (stroke self-efficacy questionnaire; primary), self-management behaviors (Stroke Self-Management Behaviors Performance Scale), social participation (reintegration to normal living index), and depression (Geriatric Depression Scale; secondary) were measured at baseline, and 3 and 6 months after commencing the intervention (post-randomization). A generalized estimating equations model was used to compare the differential changes in outcomes at 3 and 6 months with respect to baseline between 2 groups. RESULTS: Between July 2019 and June 2022, 335 eligible participants were enrolled in the study. Participants (intervention group; n=166) showed significantly greater improvements in outcomes of self-efficacy (group-by-time interaction regression coefficient, B=4.60 [95% CI, 0.16 to 9.05]), social participation (B=5.07 [95% CI, 0.61 to 9.53]), and depression (B=-2.33 [95% CI, -4.06 to -0.61]), and no significant improvement in performance of self-management behaviors (B=3.45, [95% CI, -0.87 to 7.77]), compared with the control group (n=169) right after the intervention (6 months after its commencement). Hedges' g effect sizes of the intervention on outcomes: 0.19 to 0.36. CONCLUSIONS: The results provide some positive evidence on the usefulness of the Virtual Multidisciplinary Stroke Care Clinic service. The effect sizes are regarded as small to medium, which may not be of clinical relevance. The baseline levels in outcomes were in favor of the control group, the intervention effects might be overestimated. The service must be tested further to determine its effectiveness. REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR1800016101.

Effects of Acupuncture upon cerebral hemodynamics in cerebral small vessel disease: A pilot study.

Background and aims: Recent preclinical studies and meta-analysis of clinical trials suggested that acupuncture may improve cognition in cerebral small vessel disease (CSVD). We investigated the cerebral hemodynamics of acupuncture in subjects with CSVD and compared its impact upon the cerebral hemodynamics in normal elderly subjects. Methods: 10 subjects with CSVD (CSVD group) and 10 aged-matched control subjects who had no or insignificant CSVD (control group) were recruited. A single session of acupuncture was applied for 30 min in both groups. We assessed the effect of our acupuncture intervention on cerebral hemodynamics by transcranial Doppler ultrasound (TCD). Peak systolic velocity (PSV) and pulsatility index (PI) of the middle cerebral artery (MCA) were assessed. Results: We observed that PSV increased by a maximum of 39% at 20 min (p<0.05), while there was no significant change in PI in the CSVD group during the acupuncture session. In the control group, although we observed no significant change in PSV during the acupuncture session, there was a significant decrease in PI by a maximum of 22% at 20 min (p<0.05). No adverse events were reported during or after the procedure. Conclusion: This study suggested that our acupuncture prescription was associated with an increase in cerebral blood flow in subjects with established moderate to severe CSVD yet without apparent impact on distal vascular resistance. While, in subjects with no or insignificant CSVD, it may reduce cerebral small vessel distal vascular resistance. A larger study is needed to confirm our findings.

Acupuncture for post-stroke depression: a systematic review and network meta-analysis.

BACKGROUND: Patients with post-stroke depression (PSD) usually experience anxiety, hopelessness, and insomnia, which have a negative impact on their daily activities and post-stroke rehabilitation. Acupuncture (AC), as a minimally invasive technique, has become a popular choice for improving depression symptoms. However, it is still unclear which therapy is associated with the best outcomes for PSD. In this review, we aimed to explore the impact of AC in alleviating symptoms of PSD and to evaluate the difference in effectiveness between AC combined with pharmacotherapies and various non-pharmacotherapies. METHODS: Six databases and three clinical trials registration platforms were searched from inception to March 2023. Randomized clinical trial comparing needle-based AC with pharmacotherapy, and other non-pharmacotherapy or invalid group were included. Two independent reviewers identified eligible studies, and collected data using a pre-made form. A Bayesian network meta-analysis was conducted to assess and compare different techniques using RStudio 3.6.0 with the package 'GEMTC' V.0.8.1. The primary outcome was the efficacy for PSD assessed by scales measuring depressive symptoms. The secondary outcomes were effectiveness for neurological function and the quality of life. The ranking probabilities for all treatment interventions was performed using the Surface Under the Cumulative Ranking curve (SUCRA). The risk of bias was assessed by using the Revised Cochrane Risk of Bias tool 2. RESULTS: Sixty-two studies, involving 5308 participants published from 2003 to 2022, were included. The results showed that compared with western medicine (WM) (defined as pharmacotherapy for PSD), AC alone or with repetitive transcranial magnetic stimulation (RTMS), Traditional Chinese medicine (TCM) alone or with WM, were superior for alleviating depression symptoms. Compared to Usual Care, AC alone or plus other therapies could significantly decrease scores on the Hamilton Depression Rating scale. According to result of SUCRA, AC plus RTMS had the highest probability of improving depressive symptoms with a probability of 49.43%. CONCLUSIONS: The results of this study indicate that AC alone or combined with other therapies appears to be effective in improving depression symptoms of stroke survivors. Moreover, in comparison to WM, AC alone or plus RTMS, TCM, TCM with WM, or WM, were more effective in improving depression symptoms of PSD. Also, AC with RTMS seems to be the most effective with the highest probability. REGISTRATION: This study was registered in the International Prospective Register of Systematic Reviews (PROSPERO) database in November 2020 and updated in July 2021. The registration number is CRD42020218752.

Comparing machine learning-derived MRI-based and blood-based neurodegeneration biomarkers in predicting syndromal conversion in early AD.

INTRODUCTION: We compared the machine learning-derived, MRI-based Alzheimer's disease (AD) resemblance atrophy index (AD-RAI) with plasma neurofilament light chain (NfL) level in predicting conversion of early AD among cognitively unimpaired (CU) and mild cognitive impairment (MCI) subjects. METHODS: We recruited participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI) who had the following data: clinical features (age, gender, education, Montreal Cognitive Assessment [MoCA]), structural MRI, plasma biomarkers (p-tau181 , NfL), cerebrospinal fluid biomarkers (CSF) (Aß42, p-tau181 ), and apolipoprotein E (APOE) ε4 genotype. We defined AD using CSF Aß42 (A+) and p-tau181 (T+). We defined conversion (C+) if a subject progressed to the next syndromal stage within 4 years. RESULTS: Of 589 participants, 96 (16.3%) were A+T+C+. AD-RAI performed better than plasma NfL when added on top of clinical features, plasma p-tau181 , and APOE ε4 genotype (area under the curve [AUC] = 0.832 vs. AUC = 0.650 among CU, AUC = 0.853 vs. AUC = 0.805 among MCI) in predicting A+T+C+. DISCUSSION: AD-RAI outperformed plasma NfL in predicting syndromal conversion of early AD. HIGHLIGHTS: AD-RAI outperformed plasma NfL in predicting syndromal conversion among early AD. AD-RAI showed better metrics than volumetric hippocampal measures in predicting syndromal conversion. Combining clinical features, plasma p-tau181 and apolipoprotein E (APOE) with AD-RAI is the best model for predicting syndromal conversion.

User Engagement on a Novel Educational Health Intervention Aimed at Increasing HPV Vaccine Uptake in Hong Kong: a Qualitative Study.

HPV vaccine uptake rates are suboptimal in Hong Kong. A multi-disciplinary school-based HPV health-promotion programme (MDL-SHPVP) aimed at raising HPV knowledge levels and increasing vaccine uptake has therefore been developed to address vaccine hesitancy. This qualitative study was conducted to collect user feedback and identify the strengths and limitations of the educational resources developed for the programme among key vaccination stakeholders including adolescent girls and their mothers. Twenty-six participants including eight mother-daughter dyads, four teachers, three social workers, two school principals and one school nurse were recruited. To cater to the diverse audience, ten educational videos, three animations, a digital game and one booklet were developed for the programme and distributed to the participants for viewing. Semi-structured interviews were then conducted to collect feedback on the acceptability and effectiveness of the resources. Interviews were audio-recorded, transcribed verbatim, and resulting data were thematically analysed. Three themes and six sub-themes emerged. The educational materials were well-received and effective in raising HPV-knowledge levels, generating confidence in vaccine safety and effectiveness, and boosting vaccination intention. Some doubts regarding vaccine necessity remained, and recommendations for improving resource presentation and accessibility were provided. Our findings suggest that the MDL-SHPVP has the potential to boost HPV vaccine uptake. Future studies may explore educational interventions which target to increase not only HPV vaccination intention but also the sense of urgency so as to encourage timely vaccination for adolescents at the ideal age. Study findings may also provide directions for the development of future health education interventions.

Messenger RNA Coronavirus Disease 2019 (COVID-19) Vaccination With BNT162b2 Increased Risk of Bell's Palsy: A Nested Case-Control and Self-Controlled Case Series Study.

BACKGROUND: Observable symptoms of Bell's palsy following vaccinations arouse concern over the safety profiles of novel coronavirus disease 2019 (COVID-19) vaccines. However, there are only inconclusive findings on Bell's palsy following messenger (mRNA) COVID-19 vaccination. This study aims to update the previous analyses on the risk of Bell's palsy following mRNA (BNT162b2) COVID-19 vaccination. METHODS: This study included cases aged ≥16 years with a new diagnosis of Bell's palsy within 28 days after BNT162b2 vaccinations from the population-based electronic health records in Hong Kong. Nested case-control and self-controlled case series (SCCS) analyses were used, where the association between Bell's palsy and BNT162b2 was evaluated using conditional logistic and Poisson regression, respectively. RESULTS: Totally 54 individuals were newly diagnosed with Bell's palsy after BNT162b2 vaccinations. The incidence of Bell's palsy was 1.58 (95% confidence interval [CI], 1.19-2.07) per 100 000 doses administered. The nested case-control analysis showed significant association between BNT162b2 vaccinations and Bell's palsy (adjusted odds ratio [aOR], 1.543; 95% CI, 1.123-2.121), with up to 1.112 excess events per 100 000 people who received 2 doses of BNT162b2. An increased risk of Bell's palsy was observed during the first 14 days after the second dose of BNT162b2 in both nested case-control (aOR, 2.325; 95% CI, 1.414-3.821) and SCCS analysis (adjusted incidence rate ratio, 2.44; 95% CI, 1.32-4.50). CONCLUSIONS: There was an overall increased risk of Bell's palsy following BNT162b2 vaccination, particularly within the first 14 days after the second dose, but the absolute risk was very low.

Thromboembolic Risks with Concurrent Direct Oral Anticoagulants and Antiseizure Medications: A Population-Based Analysis.

BACKGROUND AND OBJECTIVE: Drug-drug interactions between direct oral anticoagulants (DOAC) and antiseizure medications via the cytochrome P450 (CYP) or the P-glycoprotein (P-gp) systems may lead to under-anticoagulation. The clinical relevance of these interactions is unclear. We aimed to elucidate the risk of thromboembolism with concurrent DOAC and CYP/P-gp modulating antiseizure medications. METHODS: In this propensity score-weighted population-based retrospective cohort study, we used competing risk regression analyses to determine the risks of ischemic stroke, venous thromboembolism, and death in DOAC recipients taking CYP/P-gp-modulating antiseizure medications (phenytoin, valproate, levetiracetam, carbamazepine, or phenobarbital) versus those taking CYP/P-gp-neutral antiseizure medications (pregabalin, gabapentin, or clobazam). We also performed secondary analyses for the epilepsy and atrial fibrillation subgroups. RESULTS: Among DOAC users, CYP/P-gp-modulating antiseizure medications were collectively associated with an increased risk of ischemic stroke (adjusted hazard ratio 1.28, 95% confidence interval 1.05-1.57, p = 0.017). In addition, phenytoin (adjusted hazard ratio 1.34, 95% confidence interval 1.07-1.68, p = 0.011) and valproate (adjusted hazard ratio 1.38, 95% confidence interval 1.10-1.74, p = 0.006) were associated with increased mortality. In the epilepsy subgroup, the risk of ischemic stroke and venous thromboembolism did not differ between CYP/P-gp-modulating and CYP/P-gp-neutral antiseizure medications. CONCLUSIONS: Although CYP/P-gp-modulating antiseizure medications were associated with an increased risk of ischemic stroke when paired with DOAC in the primary analysis, such a phenomenon was not found among patients with epilepsy who took phenytoin, valproate, or levetiracetam with DOAC. Therefore, these antiseizure medication options among patients with epilepsy with concurrent DOAC should not be restricted solely based on their potential drug-drug interactions. Yet, the increased mortality during concurrent use of DOAC with phenytoin or valproate might call for caution.

A framework on developing integrative medicine clinical practice guideline for stroke management and rehabilitation in Hong Kong.

BACKGROUND: Stroke is the second leading cause of death worldwide. In Hong Kong, the proportion of deaths caused by cerebrovascular disease accounted for approximately 6.8% of total deaths. Although integrative medicine approaches are widely adapted by patients, there is a lack of guideline to support the corresponding clinical practice for stroke management and rehabilitation. Therefore, we design this framework for the development of an integrative medicine clinical practice guideline (CPG) for stroke. METHODS: The framework follows the instructions of World Health Organization (WHO) handbook for guideline development, Guideline International Network (GIN), Appraisal of Guidelines for Research and Evaluation Instrument (AGREE II), and Reporting Items for Practice Guidelines in Healthcare (RIGHT). Three stages with ten steps are conducted. CONCLUSION: Clinical practice guidelines are essential to provide optimal recommendations for patients' prognosis. With proper methodology, this framework will facilitate the formation of clinical practice guideline for stroke through synthesizing evidences in the scope of integrative medicine.