METHOD: We synthesised the evidence from our three previous systematic reviews (covering all literature from inception to 2023 from PubMed, Embase, and PsychInfo) on dementia risk prediction modelling. The aim was to identify models that have been specifically developed and tested specifically in LMICs. There were no language or time restrictions applied.
RESULT: To date, over 50 different dementia risk prediction models have been developed and tested with only 7 models reported from two LMICs including five studies from China and two studies from Mexico. The models incorporated variables typically linked to dementia including demographics (e.g., age, sex, education), health (e.g., diabetes, hypertension, heart disease) and lifestyle (e.g., smoking and alcohol) variables. The 7 models also have varying degrees of predictive accuracy (c-statistic range 0.65 [95%CI: 0.64-0.67] to 0.92 [95%CI: 0.88-0.95]) and none has undergone external validation. These models have been developed using traditional statistical approaches including Cox and Logistic Regression. Further, model development has not considered factors such as socioeconomic status, literacy, access to healthcare, diet, stress, pollution, and workplace hazards that may be crucial in predicting dementia risk in LMICs.
CONCLUSION: There is an urgent need to create context-specific dementia prediction models to inform the development of risk reduction and preventative interventions in LMICs where dementia case numbers are greatest. Dementia risk model development and testing need to be extended to LMICs across different regions (e.g., Asia, Middle East, Global South, Africa) and income levels (e.g., low, lower-middle, and upper-middle income).
RECOMMENDATIONS: Greater investment is needed into understanding dementia, and its risk factors in LMICs to inform the development of risk mitigation programs. Research should focus on developing accurate, resource-conscious models with affordable and obtainable variables for identifying those individuals likely to benefit the most from interventions targeting risk reduction.
METHOD: A scoping review was conducted utilizing the Joanna Briggs Institute guidance. Four databases (OvidMedline, Scopus, PsycINFO, and CINAHL) were searched for eligible studies reporting dementia research priorities in LMICs in Southeast Asian. Comparisons were made to a stakeholders' consultation during a two-day workshop from the 9th to 10th February 2023 in Kuala Lumpur, Malaysia. Participants included the Southeast Asia-Dementia (SEA-Dem) Research Network members key stakeholders from Malaysia, Indonesia, Vietnam, Philippines, Singapore, and Hong Kong (n = 20). Research priorities from each participating country were generated and ranked, harmonized with those from the nominal group technique into tiers of priorities.
RESULT: Only two studies from Malaysia and Vietnam were eligible, reporting unranked research priorities. Nominal group technique ranked outcomes from Malaysia, Vietnam, Indonesia, and the Philippines were included. Top dementia research priorities were (1) local research and data collection capacity, (2) community awareness and engagement, and (3) health policy. Second-tier research priorities included harmonizing guidelines and tools standardization, health inequalities, and availability of carer support. The third tier comprised multisectoral collaboration, integration of care, telemedicine, digital approaches, dementia risk reduction, health economics, and sustainable interventions.
CONCLUSION: Our ranked and harmonized latest dementia research priorities list can serve as a more nuanced and contextually informed dementia research directional guide for countries with similar backgrounds. Collaborative efforts to increase high-quality dementia research capacity in Southeast Asian LMICs should be intensified for better dementia care in the region.
METHOD: Data were obtained from 36 members of COSMIC, representing 28 countries across 6 continents (HICs: Australia, Canada, Faroe Islands, France, Germany, Greece, Italy, Japan, Netherlands, South Korea, Spain, Sweden, & USA; LMICs: Brazil, China, Cuba, Dominican Republic, Ecuador, Indonesia, Malaysia, Mexico, Nigeria, Peru, Philippines, Republic of Congo, & Tanzania). For each member study, we calculated incidence rates for all-cause dementia. Findings from 14 studies, with a consensus diagnosis are presented in the results. Using an Item Response Theory approach, we are currently calculating a comparable incidence rate for those studies without a consensus diagnosis.
RESULT: Consistent with previous trends, incidence rates (per 100 person-years) increased with age, from 65-70 years-old to 85-90 years-old, for both males (i.e., Republic of Congo, 4.41 to 19.57; France, 0.46 to 3.89; USA, 0.17 to 3.22; Spain, 0.31 to 4.22; 65-70 & 85-90 cohorts respectively) and females (i.e., Republic of Congo, 3.57 to 15.31; France, 0.45 to 3.72; USA, 0.22 to 4.25; Spain, 0.36 to 4.96; 65-70 & 85-90 cohorts respectively). There were no sex differences in incidence rates in younger age groups (60-65). Among older age groups, however, women tended to have higher incidence rates than men, in some countries (Faroe Islands, Germany, Sweden, and USA).
CONCLUSION: Geographical differences in dementia incidence rates likely represent inherent variation among countries, beyond methodological considerations. We are working to expand the range of studies and regions for which we calculate dementia incidence rates. This involves the development of approaches to classify and harmonise incident dementia in studies lacking consensus diagnoses. Doing so will bolster LMIC representation.
METHOD: This study was approved by the institutional Ethics Committees. Postmortem nasal mucosa and brain tissues from patients with AD (n = 10) and normal subjects (n = 10) were collected with patient consent at the Fukushimura Brain Bank. Nasal and brain tissue homogenates were added to HEK293 cells expressing tau 3-repeat domain with the L266V and V337M mutations (3RD∗VM) or 4-repeat domain with the P301L and V337M mutations (4RD∗LM), which was fused with GFP at the C-terminus.
RESULT: GFP fluorescence was detected uniformly within the cell bodies of HEK293T cells expressing 3RD∗VM-EGFP and 4RD∗LM-EGFP. There were no changes in the fluorescence after the additions of the brain homogenates from normal subjects. In contrast, a large number of fluorescent puncta was detected both in HEK293T cells expressing 3RD∗VM-EGFP and 4RD∗LM-EGFP at 4 days after the additions of the brain homogenates from patients with AD. Furthermore, the nasal tissue homogenates from patients with AD also induce the formation of fluorescent aggregates in HEK293T cells expressing 3RD∗VM-EGFP and 4RD∗LM-EGFP. Quantitative analysis revealed that the nasal tissue homogenates from AD patients significantly induced the aggregate formation, compared with normal subjects.
CONCLUSION: These results suggest that the nasal tissues from AD patients contain tau seeds with prion activity, similar to the brain. A cellular bioassay using nasal tissues would be great potential as an AD biomarker because of the usefulness of nasal tissue biopsy, and would provide an important contribution to the development of ex vivo diagnosis method for AD using the nasal extracts.
CASE PRESENTATION: An elderly lady with subacute onset and worsening behavioural changes of three months' duration was referred for exclusion of organic brain disease. The neurological and respiratory examination, chest X-ray, electroencephalogram (EEG), and MRI of the brain were normal. She, however, had elevated C-reactive protein, ESR, and raised CSF opening pressure on lumbar puncture. The CSF cell counts, biochemistry, and cultures were within normal limits. Unable to detect a neurological cause for her illness, she was advised to consult a psychiatrist. Two months later she reported to us again, this time essentially for back pain. Investigations for the back pain (including CT spine) revealed a T12 compression fracture with irregularity of the left T12 pedicle and a para-spinal fluid collection. Pus drained from the collection showed mycobacterium tuberculosis bacteria on staining with ZN stain. The CT scan thorax also showed left lower lobe consolidation and a pleural effusion. Contrast CT scan brain revealed subtle meningeal enhancement at the right parietal region. With standard treatment with a four-drug anti-TB regimen (along with a short course of dexamethasone), she improved well. This case report indicates that the initial clinical presentation of TB in general, as well as DTB, can be misleading, resulting in delay in diagnosis and in initiating treatment.
CASE DESCRIPTION: We present a case of tigecycline-induced acute pancreatitis in a 78-year-old man with complex medical conditions, including type 2 diabetes mellitus, chronic renal insufficiency, and triple vessel disease. The patient was initially treated with tigecycline for bilateral dry gangrene of his toes. Six days after initiation of the tigecycline treatment, the patient developed symptoms of acute pancreatitis with electrocardiogram changes. Magnetic resonance imaging confirmed the diagnosis of acute pancreatitis. Tigecycline was stopped promptly, and supportive treatment was initiated. The patient recovered from the acute pancreatitis and was discharged home. He later passed away at home due to his underlying cardiac disease.
CONCLUSIONS: This case highlights the potential complications of tigecycline therapy, particularly in patients with significant comorbidities.
LEARNING POINTS: Elderly patients with complex medical issues, such as diabetes mellitus type 2, chronic renal insufficiency, and cardiovascular disease, are at higher risk for adverse drug reactions. Recognizing these risk factors is important for management.Addressing the use of magnetic resonance imaging for diagnosing acute pancreatitis in this specific patient due to their already compromised kidneys highlights the need for a tailored approach. Most commonly, angiographic transformers or computed tomography scan are used for high-risk patients.The symptoms of acute pancreatitis and the presence of cardiac diseases cause problems in managing patients. Changes on the electrocardiogram may suggest cardiac overload; as a result, constant follow-up is necessary for patients suffering from underlying cardiac conditions.
DESIGN: This study used an interpretive descriptive qualitative design, employing semistructured purposive sampling for focus group discussions. Thematic analysis was conducted on the transcribed interviews and field notes, facilitated by NVivo 12.0 Plus software.
SETTING: Community settings in Zhengzhou City, Henan Province.
PARTICIPANTS: Middle-aged adults (aged 45-59) were identified as at risk of stroke due to the presence of one or more modifiable risk factors.
RESULT: A total of seven focus group discussions were audio recorded. Four main themes emerged, which were: (1) cognitive understanding of a healthy diet; (2) dietary practices; (3) knowledge acquisition and (4) barriers to dietary adherence.
CONCLUSIONS: The middle-aged adults at risk of stroke were generally aware of the risk and attempted to practise healthy eating. The existing educational programmes on following a healthy diet in the prevention of disease need to be made more comprehensible, accessible and equitable, especially for those from socioeconomically disadvantaged communities.
METHODOLOGY: The cross-sectional study retrospectively reviewed certified RTA fatalities from 2018 to 2021, individually counting fatalities in accidents and excluding cases with incomplete death profiles. Data were collected from all Forensic Departments in the government hospitals in Perak. RTA fatalities were confirmed by medical officers/physicians following established procedures during routine procedures. A total of 2517 fatal accident and victim profiles were transcribed into data collection form after reviewing death registration records and post-mortem reports. Inferential analyses were used for comparison between pre- and during COVID-19 pandemic. The standard expected YLL was calculated by comparing the age of death to the external standard life expectancy curve taking into consideration of age and gender in Malaysia.
RESULTS: This study included 2207 (87.7%) of the RTA fatalities in Perak State. The analysis revealed a decreasing trend in RTA deaths from 2018 to 2021, with a remarkable Annual Percent Change (APC) of -25.1% in 2020 compared to the pre-pandemic year in 2019 and remained stable with lower APC in 2021. Comparison between pre-pandemic (2018-2019) and pandemic years (2020-2021) revealed a difference in the fatality distribution with a median age rise during the pandemic (37.7 (IQR: 22.96, 58.08) vs. 41.0 (IQR: 25.08, 61.00), p = 0.002). Vehicle profiles remained consistent, yet changes were observed in the involvement of various road users, where more motorcycle riders and pedestrian were killed during pandemic (p = 0.049). During pandemic, there was a decline in vehicle collisions, but slight increase of the non-collision accidents and incidents involving pedestrians/animals (p = 0.015). A shift in accident from noon till midnight were also notable during the pandemic (p = 0.028). YLL revealed differences by age and gender, indicating a higher YLL for females aged 30-34 during the pandemic.
CONCLUSION: The decline in RTA fatalities during COVID-19 pandemic underscores the influence of pandemic-induced restrictions and reduced traffic. However, demographic shifts, increased accident severity due to risky behaviors and gender-specific impacts on YLL, stress the necessity for improved safety interventions amidst evolving dynamics.
METHOD: The cell viability, sphere-forming and xenografts assay were used to evaluate the ability of ASIV to reverse taxol-resistance. Immunohistochemistry, cytokine application, small-interfering RNA, small molecule inhibitors, and RNA-seq approaches were applied to characterize the molecular mechanism of inhibition of epiregulin (EREG) and downstream signaling by ASIV to reverse taxol-resistance.
RESULTS: ASIV reversed taxol resistance through suppression of the stemness-associated genes of spheres in NSCLC. The mechanism exploration revealed that ASIV promoted the K48-linked polyubiquitination of EREG along with degradation. Moreover, EREG could be triggered by chemo-drug treatment. Consequently, EREG bound to the ErbB receptor and activated the ERK signal to regulate the expression of the stemness-associated genes. Inhibition of EREG/ErbB/ERK could reverse the taxol-resistance by inhibiting the stemness-associated genes. Finally, it was observed that TGFβ and Hedgehog signaling were downstream of EREG/ErbB/ERK, which could be targeted using inhibitors to reverse the taxol resistance of NSCLC.
CONCLUSIONS: These findings revealed that inhibition of EREG by ASIV reversed taxol-resistance through suppression of the stemness of NSCLC via EREG/ErbB/ERK-TGFβ, Hedgehog axis.
METHODS: 160 eyes of 160 healthy children (74 boys, 86 girls) aged 6-18 years (mean: 11.60 ± 3.28 years) were evaluated in this cross-sectional study. The peripapillary retinal nerve fibre layer (pRNFL) and macular thickness were determined for the 1st, 5th, 95th, and 99th percentile points. Cohen's κ value and specific agreement between pediatric data and adult reference database were estimated. The correlation between retinal thickness with age and SE was also determined.
RESULTS: The mean thickness for the total RNFL, average macular, and central macula were 112.05±8.65 μm, 280.24±12.46 μm, and 220.55±17.53 μm, respectively. The overall agreement between the classification of the adult database and pediatric data for pRNFL was ≥90%, with discrepancies in 46 out of 150 eyes (30.67%); for macula, it was above 72%, with discrepancies in 93 out of 153 eyes (60.78%); and for ganglion cell complex and ganglion cell + inner plexiform layer (GCIPL) the agreement was above 84% and 85%, respectively. A significant level of agreement between pediatric data and adult reference data was achieved for temporal RNFL (κ = 0.65), macular perifoveal superior (κ = 0.67), and inferior (κ = 0.63) and inferior GCIPL (κ = 0.67). The correlations between age and retinal thickness were not significant (all p>0.05). Most retinal thickness parameters were positively associated with SE (Pearson's coefficient, r = 0.26 to 0.49, all p<0.05).
CONCLUSIONS: The overall agreement for pRNFL and macular thickness measurements in children with the adult reference database was between 72% and 90%. Children's retinal thickness was not significantly correlated with age but was positively associated with spherical equivalent.