Difference of Cerebrospinal Fluid Biomarkers and Neuropsychiatric Symptoms Profiles among Normal Cognition, Mild Cognitive Impairment, and Dementia Patient.

The delineation of biomarkers and neuropsychiatric symptoms across normal cognition, mild cognitive impairment (MCI), and dementia stages holds significant promise for early diagnosis and intervention strategies. This research investigates the association of neuropsychiatric symptoms, evaluated via the Neuropsychiatric Inventory (NPI), with cerebrospinal fluid (CSF) biomarkers (Amyloid-ß42, P-tau, T-tau) across a spectrum of cognitive states to enhance diagnostic accuracy and treatment approaches. Drawing from the National Alzheimer's Coordinating Center's Uniform Data Set Version 3, comprising 977 individuals with normal cognition, 270 with MCI, and 649 with dementia. To assess neuropsychiatric symptoms, we employed the NPI to understand the behavioral and psychological symptoms associated with each cognitive category. For the analysis of CSF biomarkers, we measured levels of Amyloid-ß42, P-tau, and T-tau using the enzyme-linked immunosorbent assay (ELISA) and Luminex multiplex xMAP assay protocols. These biomarkers are critical in understanding the pathophysiological underpinnings of Alzheimer's disease and its progression, with specific patterns indicative of disease stage and severity. This study cohort consists of 1896 participants, which is composed of 977 individuals with normal cognition, 270 with MCI, and 649 with dementia. Dementia is characterized by significantly higher NPI scores, which are largely reflective of mood-related symptoms (p < 0.001). In terms of biomarkers, normal cognition shows median Amyloid-ß at 656.0 pg/mL, MCI at 300.6 pg/mL, and dementia at 298.8 pg/mL (p < 0.001). Median P-tau levels are 36.00 pg/mL in normal cognition, 49.12 pg/mL in MCI, and 58.29 pg/mL in dementia (p < 0.001). Median T-tau levels are 241.0 pg/mL in normal cognition, 140.6 pg/mL in MCI, and 298.3 pg/mL in dementia (p < 0.001). Furthermore, the T-tau/Aß-42 ratio increases progressively from 0.058 in the normal cognition group to 0.144 in the MCI group, and to 0.209 in the dementia group (p < 0.001). Similarly, the P-tau/Aß-42 ratio also escalates from 0.305 in individuals with normal cognition to 0.560 in MCI, and to 0.941 in dementia (p < 0.001). The notable disparities in NPI and CSF biomarkers among normal, MCI and Alzheimer's patients underscore their diagnostic potential. Their combined assessment could greatly improve early detection and precise diagnosis of MCI and dementia, facilitating more effective and timely treatment strategies.

Time-dependent risk of atopic dermatitis following nontyphoidal Salmonella infection.

BACKGROUND: The pathogenesis of atopic dermatitis (AD) remains unclear. Nontyphoidal Salmonella (NTS) infection might trigger immune-mediated reactions. We aimed to examine NTS and the risk of subsequent AD. METHODS: From 2002 to 2015, eligible patients (aged 0-100 years) with NTS were identified. NTS and non-NTS groups were matched at a 1:10 ratio on age and sex. We utilized conditional multivariable Cox proportional hazard models to estimate the adjusted hazard ratio (aHR) and 95% confidence interval (CI) for AD development. Subgroup analyses were conducted based on age, sex, and severity of NTS infection. We utilized landmark analysis to explore the time-dependent hazard of AD following NTS. RESULTS: In the NTS group (N = 6624), 403 developed AD. After full adjustment of demographics and comorbidities, the NTS group had a higher risk of AD than the reference group (aHR = 1.217, 95% CI = 1.096-1.352). Age-stratified analysis revealed that NTS group exhibited an elevated risk compared to the reference group, particularly among those aged 13-30 years (aHR = 1.25, 95% CI = 1.017-1.559), individuals aged 31-50 years (aHR = 1.388, 95% CI = 1.112-1.733), those aged 51-70 years (aHR = 1.301, 95% CI = 1.008-1.679), and individuals aged 71 years and over (aHR = 1.791, 95% CI = 1.260-2.545). Severe NTS was associated with a higher risk of AD than the reference group (aHR = 2.411, 95% CI = 1.577-3.685). Landmark analysis showed generally consistent findings. CONCLUSIONS: Minimizing exposure to NTS infection may represent a prospective strategy for averting the onset and progression of atopic dermatitis.

Tooth Loss and Chronic Pain: A Population-based Analysis of the National Health and Nutrition Examination Survey.

Poor oral health conditions in adults are associated to chronic pain. A nationwide cross-sectional study was conducted to investigate the link between tooth loss and chronic pain. The study involved 8,662 participants from the National Health and Nutrition Examination Survey (NHANES). Tooth count was categorized into four groups and chronic pain was defined as persistent pain lasting over three months despite treatment. Location of the chronic pain, demographics, comorbidities, lifestyle determinants, and dietary intake were retrieved. Univariate and multivariate logistic regression were used to explore cross-sectional associations between tooth count and chronic pain. Compared to participants with more than 20 teeth, those with severe tooth loss presented with greater odds of chronic pain (adjusted odds ratio (aOR)=2.111, 95%CI=1.213-3.676 f for patients with 1-8 teeth). Edentulous participants presented with significant higher odds of chronic pain in lower extremities (78.4%) and buttocks (49.5%). In the multivariate model, apart from rheumatic arthritis (aOR=4.004, 95%CI=2.766-5.798), variables of higher chronic pain included smoking (aOR=1.518, 95%CI=1.228-1.878), and hypertension (aOR=1.463, 95%CI=1.013-2.112). On the contrary, being Mexican American (aOR=0.603, 95%CI=0.414-0.880) was associated with lower odds of chronic pain. The findings suggested a significant link between chronic pain and tooth loss, independent of ethnicity, lifestyle determinants, and immune-mediated inflammatory diseases including rheumatoid arthritis. PERSPECTIVE: A US nationwide study examined tooth loss and chronic pain. Those with severe tooth loss had increased odds of chronic pain. Edentulous individuals presented higher odds of pain in lower extremities and buttocks. This study highlighted the link between tooth loss and chronic pain, independent of comorbidities and lifestyle factors.

Maternal human papillomavirus infection and the risk of congenital malformations: A nationwide population-based cohort study.

Previous research has explored theories regarding the vertical transmission of human papillomavirus (HPV) infection and its association with adverse pregnancy and perinatal outcomes. However, the impact of maternal HPV infection on congenital anomalies (CAs) in offspring remains relatively understudied. We conducted a population-based cohort study linking the Taiwan Birth Registry, Taiwan Death Registry, and National Health Insurance Research Database, in which newborns born in Taiwan between 2009 and 2015 were included. We established a maternal HPV infection cohort comprising 37 807 newborns and matched them with a comparison group of 151 228 newborns at a 1:4 ratio based on index year, age, and sex. The study examined a composite outcome and subgroups of different types of congenital malformations. Differences in cumulative incidence of CAs were assessed using Kaplan-Meier curves and log-rank tests. Adjusted hazard ratios (aHRs) were estimated using Cox proportional hazard regressions. No significant association was found between HPV infection and the broad spectrum of CAs (aHR: 1.04, 95% confidence interval [CI]: 0.98-1.10; log-rank test p = 0.14). However, we observed a 19% increased risk of musculoskeletal CAs in the maternal HPV infection group (aHR: 1.19; 95% CI: 1.05-1.34) compared to those without maternal HPV exposure. Other factors, including the type of HPV (aHR: 0.65; 95% CI: 0.16-2.63), the timing of exposure (during or before pregnancy), and maternal age (aHR for <30 years: 1.02, 95% CI: 0.94-1.1; aHR for 30-39 years: 1.05, 95% CI: 0.99-1.11; aHR for ≥40 years: 0.88, 95% CI: 0.67-1.17), did not significantly affect the risk for any CA. In conclusion, gestation detection of HPV infection was associated with musculoskeletal CAs but not other major CAs. Prospective studies are warranted to elucidate the necessity of prenatal screening in populations at risk.

Paxlovid use is associated with lower risk of cardiovascular diseases in COVID-19 patients with autoimmune rheumatic diseases: a retrospective cohort study.

BACKGROUND: Paxlovid has been shown to be effective in reducing mortality and hospitalization rates in patients with coronavirus disease 2019 (COVID-19). It is not known whether Paxlovid can reduce the risk of cardiovascular diseases (CVD) in COVID-19-surviving patients with autoimmune rheumatic diseases (AIRDs). METHODS: TriNetX data from the US Collaborative Network were used in this study. A total of 5,671,395 patients with AIRDs were enrolled between January 1, 2010, and December 31, 2021. People diagnosed with COVID-19 were included in the cohort (n = 238,142) from January 1, 2022, to December 31, 2022. The Study population was divided into two groups based on Paxlovid use. Propensity score matching was used to generate groups with matched baseline characteristics. The hazard ratios (HRs) and 95% confidence intervals of cardiovascular outcomes, admission rate, mortality rate, and intensive care unit (ICU) admission rate were calculated between Paxlovid and non-Paxlovid groups. Subgroup analyses on sex, age, race, autoimmune diseases group, and sensitivity analyses for Paxlovid use within the first day or within 2-5 days of COVID-19 diagnosis were performed. RESULTS: Paxlovid use was associated with lower risks of cerebrovascular complications (HR = 0.65 [0.47-0.88]), arrhythmia outcomes (HR = 0.81 [0.68-0.94]), ischemic heart disease, other cardiac disorders (HR = 0.51 [0.35-0.74]) naming heart failure (HR = 0.41 [0.26-0.63]) and deep vein thrombosis (HR = 0.46 [0.24-0.87]) belonging to thrombotic disorders in AIRD patients with COVID-19. Compared with the Non-Paxlovid group, risks of major adverse cardiac events (HR = 0.56 [0.44-0.70]) and any cardiovascular outcome mentioned above (HR = 0.76 [0.66-0.86]) were lower in the Paxlovid group. Moreover, the mortality (HR = 0.21 [0.11-0.40]), admission (HR = 0.68 [0.60-0.76]), and ICU admission rates (HR = 0.52 [0.33-0.80]) were significantly lower in the Paxlovid group than in the non-Paxlovid group. Paxlovid appears to be more effective in male, older, and Black patients with AIRD. The risks of cardiovascular outcomes and severe conditions were reduced significantly with Paxlovid prescribed within the first day of COVID-19 diagnosis. CONCLUSIONS: Paxlovid use is associated with a lower risk of CVDs and severe conditions in COVID-19-surviving patients with AIRD.

Association between Cholecystectomy and the Incidence of Pancreaticobiliary Cancer after Endoscopic Choledocholithiasis Management.

(1) Background: Previous studies have raised concerns about a potential increase in pancreaticobiliary cancer risk after cholecystectomy, but few studies have focused on patients who undergo cholecystectomy after receiving endoscopic retrograde cholangiopancreatography (ERCP) for choledocholithiasis. This study aims to clarify cancer risks in these patients, who usually require cholecystectomy, to reduce recurrent biliary events. (2) Methods: We conducted a nationwide cohort study linked to the National Health Insurance Research Database, the Cancer Registry Database, and the Death Registry Records to evaluate the risk of pancreaticobiliary cancers. All patients who underwent first-time therapeutic ERCP for choledocholithiasis from 2011 to 2017 in Taiwan were included. We collected the data of 13,413 patients who received cholecystectomy after endoscopic retrograde cholangiopancreatography and used propensity score matching to obtain the data of 13,330 patients in both the cholecystectomy and non-cholecystectomy groups with similar age, gender, and known pancreaticobiliary cancer risk factors. Pancreaticobiliary cancer incidences were further compared. (3) Results: In the cholecystectomy group, 60 patients had cholangiocarcinoma, 61 patients had pancreatic cancer, and 15 patients had ampullary cancer. In the non-cholecystectomy group, 168 cases had cholangiocarcinoma, 101 patients had pancreatic cancer, and 49 patients had ampullary cancer. The incidence rates of cholangiocarcinoma, pancreatic cancer, and ampullary cancer were 1.19, 1.21, and 0.3 per 1000 person-years in the cholecystectomy group, all significantly lower than 3.52 (p < 0.0001), 2.11 (p = 0.0007), and 1.02 (p < 0.0001) per 1000 person-years, respectively, in the non-cholecystectomy group. (4) Conclusions: In patients receiving ERCP for choledocholithiasis, cholecystectomy is associated with a significantly lower risk of developing pancreaticobiliary cancer.

General anesthesia is not associated with dementia in older adults with osteoarthritis for hip/knee replacements, a national population-based nested case-control study.

BACKGROUND: Dementia is a prevalent neurological condition, yet the relationship between dementia and general anesthesia remains uncertain. The study aimed to explore the association between general anesthesia and dementia using a nationwide population-based database. METHODS: The study extracted data from Taiwan's national health insurance, which encompassed the records of one million insured residents. A total of 59,817 patients aged 65 years and above, diagnosed with osteoarthritis between 2002 and 2010, were included. Among these patients, 3277 individuals with an initial diagnosis of dementia between 2004 and 2013 were matched with non-dementia patients based on age, gender, and the date of osteoarthritis diagnosis. Following a 1:2 random matching, the case group included 2171 patients with dementia, while the control group consisted of 4342 patients without dementia. The data was analyzed using conditional and unconditional logistic regressions. RESULTS: No significant differences in the odds of dementia were found between individuals exposed to general and regional anesthesia during hip/knee replacement surgeries (OR = 1.11; 95%CI: 0.73-1.70), after adjusting for age, sex, and co-morbidities. Similarly, there were no significant differences in the odds of dementia based on different durations of anesthesia exposure (General: <2 h: OR = 0.91, 95%CI = 0.43-1.92; 2-4 h: OR = 1.21, 95%CI = 0.82-1.79; >4 h: OR = 0.39, 95%CI = 0.15-1.01; compared to no exposure. Regional: <2 h: OR = 1.18, 95%CI = 0.85-1.62; 2-4 h: OR = 0.9, 95%CI = 0.64-1.27; >4 h: OR = 0.55, 95%CI = 0.15-1.96; compared to no exposure). Likewise, no significant differences were observed in the odds of dementia based on the number of replacement surgeries (twice: OR = 0.74, 95%CI = 0.44-1.23, compared to once). CONCLUSION: Neither general anesthesia nor regional anesthesia in hip/knee surgery was associated with dementia. Different numbers and durations of anesthesia exposure showed no significant differences in the odds for dementia.

Hydroxychloroquine had neutral effect on long-term risk of malignancy in rheumatoid arthritis patients: A population-based retrospective cohort study.

BACKGROUND: The cancer risk in rheumatoid arthritis (RA) patients has been discussed. Hydroxychloroquine (HCQ) may exert protective effects against malignancy. The study investigated the association between HCQ use and the risk of subsequent malignancy in RA patients. METHODS: Catastrophic illness certificated RA patients were extracted from the National Health Insurance Research Database. The index date was set 180 days after the RA diagnosis date to avoid immortal time bias. Two groups were matched in a 1-to-1 ratio by propensity score regarding age, gender, index date, relevant comorbidities, and comedication. HCQ users prior to the diagnosis of RA were exempted to ensure compliance with the new-user design. Cancers diagnosed before or less than 180 days after the index date were excluded to mitigate protopathic bias. The study adopted the Kaplan-Meier curve and Cox proportional hazards model to examine the association between HCQ use and cancer risk. The assumption of proportional hazard was also tested. RESULTS: Based on strict criteria, we included 492 eligible RA patients and divided them into study and control groups (N = 246 in each group). HCQ users exhibited a neutral risk of cancer relative to the controls (adjusted hazard ratio, 0.99; 95% CI, 0.44-2.21, p > .05). The assumption of proportional hazard was not violated. CONCLUSION: This study does not observe the effect of using HCQ as a primary regimen to prevent cancer in RA patients. We are assured that HCQ is not associated with an increased risk of subsequent malignancy in RA patients. Further mechanistic research is needed.

Risk of uveitis in autoimmune diseases patients treated with hydroxychloroquine: A population-based retrospective cohort study.

OBJECTIVE: Uveitis is a common manifestation of various autoimmune diseases and can lead to severe visual impairment. Hydroxychloroquine (HCQ) is an antimalarial drug that is also used to treat autoimmune diseases. The aim of this study was to investigate the association between HCQ use and the incidence of uveitis in patients with autoimmune diseases, as well as to identify potential risk factors for the development of uveitis in this study. METHODS: We conducted a population-based cohort study using a nationwide database to investigate the incidence of uveitis in patients with autoimmune diseases who received HCQ treatment. We selected non-HCQ comparison cohort at a 1:1 ratio by propensity score matching on age, sex, index date, urbanization, income, comorbidities, and medications. The data were analyzed using Cox proportional hazards models, and propensity score matching (PSM) was used to reduce selection bias. RESULTS: Our study included 15 822 patients with autoimmune diseases. After 1:1 PSM, there were 4555 individuals in both the HCQ group (n = 4555) and the non-HCQ group (n = 4555). The multiple Cox proportional hazard regression analysis was used for the estimation of adjusted hazard ratios on uveitis. After PSM, the adjusted hazard ratio for the HCQ group was 0.74 (95% CI = 0.58-0.95). These findings suggest that HCQ may play a protective role in reducing the risk of uveitis in patients with autoimmune diseases, including rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus groups. The Kaplan-Meier survival curves also showed a significantly lower incidence of uveitis in the HCQ group (log-rank = 0.0229) after PSM. CONCLUSION: HCQ use is associated with a lower incidence of uveitis in patients with autoimmune diseases. Further studies are needed to confirm this association and to investigate the underlying mechanisms.

Using ChatGPT-Like Solutions to Bridge the Communication Gap Between Patients With Rheumatoid Arthritis and Health Care Professionals.

The communication gap between patients and health care professionals has led to increased disputes and resource waste in the medical domain. The development of artificial intelligence and other technologies brings new possibilities to solve this problem. This viewpoint paper proposes a new relationship between patients and health care professionals-"shared decision-making"-allowing both sides to obtain a deeper understanding of the disease and reach a consensus during diagnosis and treatment. Then, this paper discusses the important impact of ChatGPT-like solutions in treating rheumatoid arthritis using methotrexate from clinical and patient perspectives. For clinical professionals, ChatGPT-like solutions could provide support in disease diagnosis, treatment, and clinical trials, but attention should be paid to privacy, confidentiality, and regulatory norms. For patients, ChatGPT-like solutions allow easy access to massive amounts of information; however, the information should be carefully managed to ensure safe and effective care. To ensure the effective application of ChatGPT-like solutions in improving the relationship between patients and health care professionals, it is essential to establish a comprehensive database and provide legal, ethical, and other support. Above all, ChatGPT-like solutions could benefit patients and health care professionals if they ensure evidence-based solutions and data protection and collaborate with regulatory authorities and regulatory evolution.

Safety and efficacy of peficitinib in Asian patients with rheumatoid arthritis who had an inadequate response or intolerance to methotrexate: results of a multicenter, randomized, double-blind, placebo-controlled phase 3 study.

Background: The efficacy and safety of the oral Janus kinase inhibitor peficitinib were investigated in Asian patients with rheumatoid arthritis (RA). Methods: In this double-blind, phase 3 study, patients from mainland China, Korea, and Taiwan with RA and an inadequate response/intolerance to methotrexate were randomized (1:1:1) to once-daily placebo (N = 128), peficitinib 100 mg (N = 129), or 150 mg (N = 128) in combination with non-biologic DMARDs. At Week 24, patients receiving placebo switched to peficitinib 100 mg or 150 mg. American College of Rheumatology (ACR) 20 response at Week 24/early termination (ET) was the primary endpoint. Adverse events (AEs) were assessed. The study was registered at ClinicalTrials (NCT03660059). Findings: 385 patients were included in the analysis. ACR20 responses were statistically significantly higher in both peficitinib 100 mg (56.6%) and 150 mg (56.3%) groups versus placebo (24.2%); Odds Ratio (95% confidence interval, CI) 4.14 (2.42, 7.08) and 4.07 (2.38, 6.96), respectively (both P < 0.001) at Week 24/ET. The incidence rate of herpes zoster related disease (herpes zoster and varicella) was higher in patients who received peficitinib versus placebo, but no dose dependency was observed (incidence rate/100 patient-years (95% CI): peficitinib 6.7 (4.32, 10.37); placebo 3.7 (0.93, 14.88). Interpretation: In Asian patients with RA and an inadequate response/intolerance to methotrexate, peficitinib 100 mg and 150 mg demonstrated superiority to placebo in the reduction of RA symptoms and was well tolerated. No additional benefit was observed with use of the higher peficitinib dose in this study population of predominantly Chinese patients. Funding: Astellas Pharma.

Metformin and the risks of cellulitis, foot infections, and amputation in patients with type 2 diabetes.

BACKGROUND: Patients with diabetes tend to have cellulitis, foot infections, and amputation. We conducted this research to compare the risks of cellulitis, foot infections, and amputation between metformin no-use and use in persons with type 2 diabetes. METHODS: Using propensity score matching, we identified 23 234 pairs of metformin nonusers and users from the National Health Insurance Research Database of Taiwan, since January 1, 2000, to December 31, 2017. Cox proportional hazards models were adopted to examine the risks of incident cellulitis, recurrent cellulitis, foot infections, and amputation between metformin use and no-use. RESULTS: The mean follow-up period of metformin use and no-use was 6.31 (3.93) and 5.54 (3.97) years, respectively. Compared with metformin no-use, the adjusted hazard ratio and 95% confidence interval for metformin use in cellulitis development, recurrent cellulitis, foot infections, and amputation were 1.08 (1.04-1.12), 1.33 (1.14-1.55), 1.91 (1.75-2.09), and 1.88 (1.35-2.62), respectively. The longer cumulative duration of metformin usage had association with higher risks of these outcomes than metformin no-use. CONCLUSION: This population-based cohort study revealed that metformin use had association with significantly higher risks of incident cellulitis, recurrent cellulitis, foot infections, and amputation than metformin no-use in patients with type 2 diabetes.