Therapeutic Advances in Chronic Disease最新文献

Type 2 diabetes mellitus (T2DM) is a chronic metabolic condition marked by insulin resistance, decreased insulin production, and persistent low-grade inflammation. The prevalence of T2DM has increased significantly in recent decades; as a result, it is now regarded as one of the fastest-growing public health concerns worldwide. Long-term micro- and macrovascular problems such as nephropathy, retinopathy, neuropathy, and cardiovascular disease can be caused by poor blood glucose control. Therefore, developing reliable diagnostic indicators for early diagnosis and investigating new treatment targets are critical for addressing the increasing prevalence of T2DM. Several novel diagnostic approaches have been created by targeting endogenous proteins, with fetuin-A being one of the most promising targets. Human fetuin-A, also referred to as alpha-2-Heremans Schmid glycoprotein, is a liver-produced glycoprotein that is abundantly secreted into the bloodstream and seems to be involved in insulin resistance, metabolic syndrome, and inflammation. Clinical studies have shown that circulating fetuin-A levels are closely associated with T2DM and its complications, underscoring its potential as both a biomarker and a therapeutic target. This narrative review provides a detailed overview of the evolving role of fetuin-A in the development of T2DM and its associated complications, as well as its future perspectives.

What is this summary about? • This is a summary of a research article published in a medical journal that describes the main results from two studies called TRuE-V1 and TRuE-V2 • These studies looked at the use of ruxolitinib cream to treat vitiligo, a long-term condition where white patches develop on the skin • Ruxolitinib belongs to a group of medicines called Janus kinase (JAK) inhibitors, which have been shown to restore the skin color (also known as skin pigment) of some people with the most common form of vitiligo (non-segmental vitiligo, also known as generalized vitiligo or bilateral vitiligo) What happened in the studies? • Researchers who designed the TRuE-V1 and TRuE-V2 studies wanted to understand if ruxolitinib cream helped to restore the skin color of people with non-segmental vitiligo, compared with an identical cream that did not contain ruxolitinib. This is called a vehicle cream • In the studies, people aged 12 years and older with non-segmental vitiligo were randomly chosen to apply either ruxolitinib cream or vehicle cream to the parts of their body affected by vitiligo twice a day for 6 months. For every one person that used the vehicle cream, two people used the ruxolitinib cream • The main goal of the studies was to find out how many people had a 75% improvement in their facial vitiligo after 6 months ○ This meant that three-quarters of the white patches on the face returned to normal skin color • Other goals included measuring: ○ How many people had a 50% improvement in the vitiligo on their whole body after 6 months ■ This meant that half of the white patches on the whole body returned to normal skin color ○ How many people felt their vitiligo was less noticeable after 6 months • The study also looked at the side effects of ruxolitinib cream and the vehicle cream What do the results mean? • In both the TRuE-V1 and TRuE-V2 studies, people who used ruxolitinib cream for 6 months had greater improvements in their vitiligo compared with those who used the vehicle cream • The most common side effects were acne (red pimples located mainly on the face) and itchy skin where ruxolitinib cream was applied • Results from the studies suggest that ruxolitinib cream helps to restore the color of the skin over time in people with non-segmental vitiligo.

Currently, the diagnosis of Parkinson's disease (PD), Parkinson's disease dementia (PDD), and Lewy body dementia (DLB) relies on clinical symptoms, with Lewy body (LB) pathology serving as the gold standard. The co-pathology associated with Alzheimer's disease (AD) contributes to the clinical heterogeneity and rapid progression seen in Lewy body disorders (LBD). The AT(N) classification system may help identify the distinct biochemical, neuro-radiological, and clinical characteristics of both pure LB and PD. Recent advancements in biomarkers have improved the precise identification of pathological α-synuclein (i.e., misfolded and aggregated) in cerebrospinal fluid (CSF) through the seed amplification assay. Consequently, the Neuronal α-synuclein Integrated Staging System (NSD-ISS) has reclassified PD as a neuronal α-synuclein disease, rather than just a clinical syndrome. Although some debate the necessity of a biological definition for clinical diagnosis, biomarker-based systems continue to serve as diagnostic tools for these disorders. This narrative review will explain the definitions of the AT(N) and NSD-ISS systems and provide an updated list of research that supports the proposed biological definitions and staging systems. Additionally, it will discuss how the combination of LB-AD pathology, along with the neuronal concept of the disease, significantly influences the clinical phenotype, progression, and overall prognosis of PD. Finally, this review will overview current advancements in blood-based AD biomarkers that could facilitate faster screening of LBD patients for AD co-pathologies, thereby enhancing the diagnostic sensitivity of LBD-AD and its potential for prognostic, research, and diagnostic applications.

Glatiramer acetate (GA) has been a pivotal therapy for relapsing multiple sclerosis (MS) due to its favorable safety profile. Long-term data spanning decades demonstrate its continued use in diverse patient populations. Adverse events include manageable localized injection site reactions, lipoatrophy or necrosis, and rare cases of liver injury. GA has minimal effects on immune function, and does not increase the risk of opportunistic infections, making it suitable for MS patients at risk for infections or reactivation of latent infections. GA's immunomodulatory properties may pose a lower infection risk than other disease-modifying treatments. Progressive multifocal leukoencephalopathy risk with GA is low, and screening for latent infection is unnecessary before treatment. Vaccination is important for preventing infections in MS patients. GA does not compromise vaccine efficacy and is compatible with both inactivated and live attenuated vaccines. Special populations that may benefit from the characteristics of GA include older adults and patients with comorbidities and/or polypharmacy. MS patients often have comorbidities, necessitating careful management of potential drug interactions and side effects. Drug interactions with GA are not predicted, and clinical data suggest that the risk is low. GA is not contraindicated during pregnancy and exhibits a reassuring safety profile during breastfeeding, with no increased risk of adverse outcomes identified. Regulatory restrictions on GA use during breastfeeding have been removed. In summary, GA remains a safe and well-established therapy for MS patients, including those in special populations. Its favorable safety profile, compatibility with vaccination, and reassuring outcomes solidify its role in MS treatment.

Background: Ketamine, an N-methyl-D-aspartate antagonist, has been used for decades as an anesthetic agent, but more recently it has been studied in psychiatric illness. Though ketamine has been investigated for use in the general population, fewer studies have investigated the efficacy and tolerability of this treatment for older (age >60) adults.

Objectives: This review sought to compile the randomized controlled trials (RCTs) investigating the evidence for ketamine treatment in older adults with psychiatric disorders.

Eligibility criteria: Only RCTs published in English language journals, or with official English language translations, and human studies were included.

Sources of evidence: Our team searched PubMed, Cochrane Database, and Ovid with the terms ketamine, depression, suicidal ideation, bipolar disorder, mania, anxiety, schizophrenia, psychotic disorders, dementia, delirium, and post-traumatic stress disorder.

Charting methods: Covidence was used to extract and organize included studies.

Results: Our review yielded 14 RCTs and 2 post-hoc analyses evaluating ketamine treatment in older patients. Eight of these studies examined ketamine for the treatment of delirium, while the remaining eight examined its use in depression. The studies had significant heterogeneity so direct comparisons of the results were challenging. However, five studies showed no significant impact of ketamine on delirium incidence. Two studies showed a lower incidence of delirium in the ketamine group, but another study showed a higher incidence of delirium with ketamine. Four studies showed improvement in depressive symptoms with ketamine treatment, while the others showed a lack of improvement. Most reported side effects were mild.

Conclusion: Several studies have investigated ketamine for depression and delirium in older adults and show mixed results. This review reveals the paucity of current data on ketamine for other psychiatric conditions in older adults. It reaffirms that use of ketamine in older adults with psychiatric illness, including depression and delirium, remains an individual risk versus benefit analysis using shared decision making.

Background: Optimal use of renin-angiotensin system (RAS) modulators plays a crucial role in improving the outcomes for chronic heart failure (CHF) patients with reduced ejection fraction (rEF). Despite their established benefits, there is limited evidence regarding real-world prescribing patterns, dose optimization, and factors influencing RAS modulator use in this population.

Objective: This study aimed to evaluate the patterns of use, dose optimization, and associated factors affecting the administration of RAS modulators among CHF patients with rEF at Public Comprehensive Specialized Hospitals (PCSHs).

Design: A hospital-based, multicenter cohort study was conducted from February 1, 2020, to May 31, 2024, at PCSHs among CHF patients with rEF.

Methods: A total sample size of 385 patients was determined using a systematic random sampling technique at the Northwest Ethiopian PCSHs during the study period. Data were collected from medical records and interviews using standardized questionnaires. Data analysis was performed using SPSS version 27.0, and binary logistic regression analysis was employed to identify factors associated with the use and optimization of RAS modulators. The study strictly adhered to the most recent guideline recommendations from the American Heart Association (2022) and the European Society of Cardiology (2021).

Results: Of 385 patients, 263 (68.3%) were prescribed RAS modulators; however, only 86 (32.7%) of these patients were receiving an optimal dose. Predictors significantly associated with the use of RAS modulators included a duration of CHF with rEF of ⩾3 years (AOR: 1.79, 95% CI: 1.02-3.15), the presence of ischemic heart disease (AOR: 8.23, 95% CI: 4.23-16), hypertension (AOR: 2, 95% CI: 1.09-3.69), diabetes mellitus (AOR: 7.34, 95% CI: 1.48-36.34), chronic kidney disease (AOR: 4.35, 95% CI: 1.32-14.34), and a furosemide dose of ⩾40 mg (AOR: 0.26, 95% CI: 0.013-0.49). Regarding suboptimal RAS modulator dosing, significant predictors identified were age ⩾65 years (AOR: 2.83, 95% CI: 1.46-5.50), a previous history of hospitalization (AOR: 2.05, 95% CI: 1.07-3.95), the use of diuretics (AOR: 5.34, 95% CI: 2.73-10.44), a furosemide dose of ⩾40 mg (AOR: 3.88, 95% CI: 1.89-7.97), and CHF with rEF for ⩾3 years (AOR: 0.31, 95% CI: 0.16-0.63).

Conclusions: The majority of CHF patients with rEF received suboptimal doses of RAS modulators, with only one-third receiving optimal therapy. This highlights a critical gap in treatment that must be urgently addressed. Targeted interventions are needed to identify and mitigate modifiable predictors contributing to suboptimal dosing, thereby improving therapeutic outcomes and reducing the burden of CHF with rEF.

Background: Antilipidemic therapy adherence to medication among patients with dyslipidemia and type 2 diabetes mellitus (T2DM) remains suboptimal, particularly in developing countries. Poor adherence to lipid-lowering therapy is associated with a significantly higher risk of major adverse cardiovascular outcomes in this population than in the general population.

Objectives: This study aimed to assess the level of non-adherence to antilipidemic medications and associated socio-demographic and clinical factors among patients attending comprehensive specialized hospitals (CSHs) in Northwest Ethiopia.

Design: This multicenter, prospective, cross-sectional study was conducted at CSHs in Northwest Ethiopia from November 10, 2023 to January 30, 2024.

Methods: Data were entered using EpiData version 4.6.0.0 and analyzed using STATA version 17.0. The Adherence in Chronic Diseases Scale was used to assess medication adherence. Multinomial logistic regression analysis was used to identify factors associated with non-adherence, and model fitness was checked before interpretation.

Results: The study included 398 patients, yielding a response rate of 98.76%. Of these patients, 290 (72.9%) were classified as non-adherent to their antilipidemic medications. Factors significantly associated with medium and low medication adherence included female sex (adjusted odds ratio (AOR) for medium: 2.94, 95% confidence interval (CI): 1.61-5.38; AOR for low: 3.09, 95% CI: 1.66-5.76), unmarried status (AOR for medium: 2.83, 95% CI: 1.52-5.27; AOR for low: 2.72, 95% CI: 1.43-5.17), current smoking (AOR for medium: 3.25, 95% CI: 1.20-8.82; AOR for low: 6.54, 95% CI: 2.46-17.36), presence of comorbidities (AOR for medium: 3.01, 95% CI: 1.65-5.49; AOR for low: 2.41, 95% CI: 1.29-4.47), and polypharmacy (⩾5 medications) (AOR for medium: 3.00, 95% CI: 1.60-5.63; AOR for low: 4.87, 95% CI: 2.56-9.24).

Conclusion: This study revealed a high prevalence of medication non-adherence among patients with T2DM with dyslipidemia in Northwest Ethiopia. Non-adherence was significantly associated with female gender, unmarried status, smoking, comorbid conditions, and polypharmacy. These findings emphasize the need for targeted strategies to improve adherence in high-risk populations to enhance lipid control and lower the likelihood of cardiovascular complications.

Background: Insulin pump therapy improves glycemic control in children with type 1 diabetes but is associated with technical and dermatological complications that can impact adherence. Research on these adverse effects in pediatric populations is limited.

Objectives: This study aimed to evaluate short- and long-term complications of insulin pump therapy in pediatric patients in Saudi Arabia, focusing on technical malfunctions, dermatological issues, and patient satisfaction.

Design: A cross-sectional survey-based study conducted in multiple centers in Taif, Saudi Arabia.

Methods: Fifty-nine parents of children with type 1 diabetes who used insulin pumps provided data for the study. Participants reported technical issues, skin-related complications, and overall satisfaction. IBM SPSS Statistics version 27.0.1 was used to conduct the statistical analysis.

Results: Technical complications were frequent, with 64.4% experiencing tube blockages, 39.0% reporting needle dislodgment, and 39.0% observing air bubbles in the tubing. Dermatological issues included discomfort at the infusion site (54.2%), skin pigmentation (45.8%), and scarring (55.9%), with lipohypertrophy (22.0%) posing a concern for insulin absorption. Longer pump use was significantly associated with increased complications, particularly tube blockages and skin pigmentation. Despite these challenges, 84.7% of participants recommended insulin pumps over multiple daily injections.

Conclusion: Technical and dermatological complications were common, increasing with longer pump use. Proper infusion site rotation, infusion set management, and improved patient education are key to reducing adverse effects. To improve safety and efficacy, future studies should concentrate on infusion set change patterns, newer pump technologies, and standardized guidelines.

Background: Obesity is a significant public health concern linked to various health complications, including periodontitis. This study uniquely integrates multiple obesity indicators (body mass index (BMI), waist circumference (WC), and waist-to-hip ratio (WHR)) alongside clinical periodontal parameters and considers sociodemographic factors to provide a comprehensive analysis of the relationship between obesity and periodontitis.

Objectives: To determine the association between BMI, WC, and WHR with periodontal clinical parameters, and to explore the role of sociodemographic and behavioral factors.

Design: Transversal study.

Methods: A total of 1000 adults (579 males and 421 females) with ⩾15 teeth were enrolled using systematic random sampling. Sociodemographic variables (age, sex, marital status, income, education level), behavioral factors (brushing frequency, smoking status), and anthropometric measurements (BMI, BP, WHR) were considered. Clinical periodontal parameters included probing pocket depth (PPD), bleeding on probing, clinical attachment loss (CAL), plaque index, and gingival index. Associations were assessed using multivariate regression models adjusted for age, sex, education, income, and oral hygiene habits.

Results: The study population comprised 579 males and 421 females, predominantly aged 19-30 years. BMI classifications were 46.2% normal, 30.5% overweight, and 4.5% obese. Elevated BMI and WC were significantly associated with increased PPD and CAL (p < 0.001*). In univariate analysis, overweight (odds ratio (OR) = 2.28, p < 0.001*) and obesity (OR = 6.46, p < 0.001*) were significantly associated with periodontitis. In multivariate analysis, obesity remained significantly associated with periodontitis (adjusted OR = 3.42, p < 0.01*), as did WC (adjusted OR = 1.84, p < 0.01*). The WHR was associated with periodontitis in univariate but not in multivariate analysis.

Conclusion: Obesity, as measured by BMI and central adiposity indicators, is independently positively associated with greater periodontitis severity. The findings highlight the importance of assessing obesity in estimating periodontal risk and structuring targeted interventions that consider both metabolic status and sociodemographic factors to optimize periodontal health benefits.

Background: Cardiovascular disease (CVD) has emerged as the most significant complication and leading cause of death among metabolic-associated fatty liver disease (MAFLD).

Objectives: This study aims to investigate the CVD risk among MAFLD subgroups.

Design: Data of participants from June 2017 to January 2023 in the Physical Examination Center of the Third Hospital of Hebei Medical University were collected. MAFLD were divided into four subgroups: metabolic healthy lean/normal weight MAFLD (MHL), metabolic healthy overweight/obese MAFLD (MHO), metabolic dysfunctional lean/normal weight MAFLD (MDL), and metabolic dysfunctional overweight/obese MAFLD (MDO).

Methods: The risk assessment for atherosclerotic CVD was performed based on the flowchart for primary prevention risk assessment in Chinese adults.

Results: The proportions of MHL, MHO, MDL, and MDO were 0.77% (n = 185), 10.05% (n = 2406), 1.29% (n = 310), and 16.86% (n = 4038), respectively. After adjustment for gender, age, smoking history, drinking history, and significant liver fibrosis, the subgroup of MAFLD was still an independent risk factor for high adverse cardiovascular events (HACE). Compared with the MHL, the MDL had the highest risk, followed by MDO (all p < 0.05), and there was no significant difference between MHO and MHL. We performed regression analysis according to age (65 years) and gender (male or female), respectively, and the results were similar to those of the total population.

Conclusion: MAFLD is associated with a higher risk of CVD, especially in MDO. Classification of MAFLD based on body mass index and metabolic status helps in risk stratification, which will mitigate or prevent the development of CVD.