Current Therapeutic Research-clinical and Experimental最新文献

Background

Portugal has among the highest rates of dependency among older adults in Europe. Older adults with aging-related comorbidities are prone to the use of potentially inappropriate medication (PIM).

Objective

The aim of this study was to analyze PIM prescriptions in older Portuguese adults, as well as the change rate of PIM prescriptions over time, and assess the geographical variability between the different regions of mainland Portugal.

Methods

Using a national database, PIM prescriptions were analyzed for older adults (aged 65 years and older) between 2019 and 2021 from 2 perspectives: PIM-defined daily dose (DDD) frequency (%) and DDD per 1000 inhabitants per day (DID).

Results

Overall, mainland Portugal presented a PIM DDD frequency of 9.20%, which was relatively higher in Alentejo and Centro and lower in the North. Alprazolam, fluoxetine, and rivaroxaban were PIM with higher DDD frequency values. Over the years, the DID change rates for these three PIM were –3.80%, –14.86%, and +18.54%, respectively, depending on the geographic region. Alprazolam and fluoxetine were mostly prescribed to older women, whereas rivaroxaban was mostly prescribed to older men.

Conclusions

These results emphasize the need to implement initiatives and interventions to decrease PIM prescriptions in older adults.

Background

Diabetic foot ulcer is a major public health problem, and among the leading causes of this complication in Ethiopian patients with diabetes. Despite the magnitude of this problem, data regarding the determinants of diabetic foot ulcers are limited.

Objective

This study aimed to assess the determinants of diabetic foot ulcers among adults attending follow-up visits in diabetes clinics in the Wolaita Zone, southern Ethiopia.

Methods

An institution-based case-control study was done from September 10 to December 28, 2020, in southern Ethiopia. We recruited 137 patients with diabetic foot ulcers and 408 patients without any diabetic foot ulcers using a consecutive sampling method. EpiData version 3.1.1 (EpiData Association, Odense, Denmark) and SPSS version 25 (IBM-SPSS Inc, Armonk, New York) were used for data entry and analysis. Descriptive statistics were calculated followed by a multivariate logistic regression analysis.

Results

Having a low wealth index (adjusted odds ratio [AOR] = 2.6; 95% CI, 1.177–5.662); being obese (AOR = 3.6; 95% CI, 1.380–9.547; P = 0.003), being overweight (AOR = 3.1; 95% CI, 1.480–6.436; P = 0.009), having peripheral neuropathy (AOR = 3.9; 95% CI, 1.641–9.430; P = 0.002), living with diabetes for >10 years (AOR = 2.3; 95% CI, 1.191–4.475; P = 0.013), and practicing poor diabetic foot self-care (AOR = 6.0; 95% CI, 3.156–11.312; P = 0.000) were significantly associated with having a diabetic foot ulcer.

Conclusions

This study suggests there is a need for education and counseling of patients on decreasing weight and improving foot-care practice, especially in those who are economically disadvantaged, have peripheral neuropathy, and have lived with diabetes for more than 10 years. (Curr Ther Res Clin Exp. 2022; 83:XXX–XXX)

Background

During 2020, the Food and Drug Administration approved 53 novel drugs.

Objective

Biomarkers, surrogate endpoints and dosing regimens used in early and pivotal clinical stages are evaluated.

Methods

Information on various efficacy end points of 2020 Food and Drug Administration approved novel drugs was gathered from the Drug Approvals and Databases page of the Food and Drug Administration website. Endpoint data from efficacy end points for the 2019 approved novel drugs by Tong and Wang are used as a comparison.

Results

Among the 53 drugs approved during 2020, 49 were for treatment of various diseases and 4 were for diagnostics. Twenty-five drug approvals (51%, relative to 49 drugs for treatment of diseases) were based on surrogate end points, consisting of 12 accelerated approvals and 13 regular approvals. There were 19 drug approvals for cancer treatments (39%, relative to 49 drugs for treatment of diseases). During 2019, there were 48 drugs approved. Forty-four were for treatment of various diseases and 4 were for diagnostics. Fourteen drug approvals (32%, relative to 44 drugs for treatment of diseases) were based on surrogate end points, consisting of 9 accelerated approvals and 5 regular approvals. There were 10 drug approvals for cancer treatments (23%, relative to 44 drugs for treatment of diseases).

The approved doses were usually much closer to the highest dose tested in clinical trials (about 2-fold lower) compared with the lower dose tested in clinical trials (about 11-fold higher). Large and variable distances between the starting low dose in humans and the final approved doses indicate that finding the optimal dose in clinical trials is still a time-consuming and costly process. Further dose analysis for cancer drugs approved during 2020 showed that the distances between the starting dose in human beings and the final approved doses of cancer drugs were still large and variable, similar to distances in noncancer drugs. Stratification of drugs approved in 2020 by molecular weights shows that small molecular weights (<1000 Daltons) appeared to be smaller and less variable than those for drugs with large molecules (>1000 Daltons). (Curr Ther Res Clin Exp. 2022; 83:XXX–XXX)

Conclusions

Surrogate end points with accelerated approval have been widely used for approvals, with an increasing trend from 2019 to 2020 (32% vs. 51%). The approved doses usually were much higher (10-fold) than the lowest tested dose in first-in-human trials, while much closer (2-fold lower) to the highest dose tested in clinical trials.

Background

Diarrheal disease is among the leading causes of morbidity and mortality among children younger than age 5 years in Bangladesh.

Objective

The objective of this study is to assess the prevalence of diarrhea among children younger than age 5 years and its associated risk factors.

Methods

Data were sourced from the Bangladesh Demographic and Health Survey, a nationally representative study conducted in 2014. We used multilevel logistic regression models to identify factors associated with diarrheal disease.

Results

Children aged 6 to11 months (odds ratio = 2.26; 95% CI, 1.50–3.42), and 12 to 23 months (odds ratio = 2.31; 95% CI, 1.62–3.31) were more likely to have diarrhea than older children. Other significant risk factors for diarrheal infection included households without access to drinking water (odds ratio = 1.39; 95% CI, 1.03–1.88) and mothers lacking mass media access (odds ratio = 1.32; 55% CI, 1.01–1.73).

Conclusions

Childhood diarrhea in Bangladesh was associated with individual- and community-level factors. The finding of this study suggests that diarrhea prevention programs in the country can effectively be delivered by targeting young children through expanding community-based education and increasing access to health information through mass media.

Background

Endothelial inflammation triggered by oxidized LDL (ox-LDL) is a crucial mechanism involved in atherosclerosis. Triptolide (TP), a primary active ingredient of the traditional Chinese medicine Tripterygium wilfordii Hook F, possesses antioxidant and anti-inflammatory properties in vivo. However, limited information is available regarding these effects on endothelial inflammation occurring in atherosclerosis.

Objectives

This study investigated the effects and possible mechanisms of action of TP on ox–LDL-induced inflammatory responses in human umbilical vein endothelial cells.

Methods

Human umbilical vein endothelial cells were preincubated with TP at the indicated concentrations for 1 hour and then incubated with ox-LDL (50 µg/mL) for the indicated times.

Results

Preincubation of cultured human umbilical vein endothelial cells with TP inhibited ox–LDL-induced cytokine and chemokine production, adhesion molecule expression, and monocyte adhesion in a concentration-dependent manner. The concentrations of 8-isoprostane, malondialdehyde, and superoxide increased after human umbilical vein endothelial cells were exposed to ox-LDL, which were associated with decreased activities of total superoxide dismutase and its isoenzyme (ie, CuZn- superoxide dismutase). Preincubation with TP reversed ox–LDL-induced effects in all events. Moreover, preincubation with TP also attenuated ox–LDL-induced nuclear factor-kappa B transcriptional activation in a concentration-dependent manner, via the suppression of inhibitor of kappa Balpha (IκBα) phosphorylation and subsequent nuclear factor-kappa B DNA binding.

Conclusions

These data indicate that TP inhibits ox–LDL-induced endothelial inflammation, possibly via suppression of the oxidative stress-dependent activation of the nuclear factor-kappa B signaling pathway.

Background

An increasing number of studies on dexmedetomidine use in adults have been published, but the effectiveness of dexmedetomidine remains contentious.

Objective

This study aimed to describe the changing trends and structural relationships of scientific achievements regarding dexmedetomidine over the past 2 decades and provide researchers with information to help them explore better research opportunities.

Methods

Quantitative data of publications were retrieved from the Scopus database. Analyses of co-occurrence and collaboration among authors, countries, and key words were conducted using VOSviewer 1.6.17 software. Weighted occurrence and average publications per year were calculated.

Results

The 1868 publications retrieved showed an increasing trend of annual publications on dexmedetomidine use in adults between 2001 and 2021. China accounted for the largest contribution to publications in the world (n = 577 [30.89%]). Four key word clusters indicating research hotspots were identified using VOSviewer. The number of articles published in the top 10% of journals in the United States was the highest among all publications from the country (97 out of 201 [48.26%]). Journals from the United Kingdom obtained the highest CiteScore (16.56). Journal of Anaesthesiology Clinical Pharmacology published the highest number of articles on this topic (n = 56). Wang authored the highest number of published articles (n = 42). Recent publications focused on the theme of cytokines and immunomodulation. Sufentanil attracted particular interest as a drug-related key word. Moreover, meta-analysis is becoming an increasingly popular research method in this field.

Conclusions

The increasing number of publications on dexmedetomidine use reflects growing interest in this topic. Future research should focus on meta-analyses to identify the most effective therapeutic methods. The immunomodulatory effect of dexmedetomidine on health and disease is of particular interest.

Background

Coronavirus disease 2019 (COVID-19), an acute, sometimes severe respiratory illness caused by a novel coronavirus has led to a vast pandemic with an astonishing spread rate. Its treatment is unknown, its mortality is significant, and its socioeconomic complications are uncontrollable. Although there is still little known about the pathogenesis of the disease, severe cases of COVID-19 are usually associated with cytokine release syndrome and high serum levels of inflammatory cytokines, which are believed to be a major cause of mortality in these patients. Different pathways cause inflammation and the release of cytokines. One of these pathways is the Bruton tyrosine kinase (BTK) pathway, which is essential for the production of several anti-inflammatory cytokines. Theoretically, the inhibition of BTK signaling can reduce cytokine levels and subsequent anti-inflammatory effects.

Objective

This review aims to investigate the role of the BTK pathway in the pathogenesis of COVID-19 and the possible effects of its inhibition in the treatment of this disease.

Methods

This narrative review provides information regarding the use of BTK inhibitors in patients with COVID-19 and discusses whether clinicians should consider these medications while managing their patients based on the literature. Data were gathered using the PubMed, Scopus, and Web of Science databases.

Results

Some data support the use of BTK inhibitors for treating COVID-19.

Conclusions

It is recommended that patients continue their medications in this class if they develop COVID-19 and were receiving these agents before the disease developed. The use of BTK inhibitors might enable patients to experience less severe immune responses to the COVID-19. Well-designed studies are needed to evaluate the effectiveness of BTKis in the management of COVID-19. (Curr Ther Res Clin Exp. 2022; 82:XXX–XXX) © 2022 Elsevier HS Journals

Background

The presence of left atrial/left atrial appendage thrombosis is associated with a higher risk of thromboembolic events in patients with atrial fibrillation. The optimal antithrombotic strategy is not established to date.

Objective

Our aim was to compare the efficacy and safety profile of novel oral anticoagulants with warfarin in the treatment of left atrial/left atrial appendage thrombosis.

Methods

We conducted a systematic search in PubMed, Embase, Cochrane Library, ClinicalTrials.gov, and 3 Chinese databases for all randomized controlled trials and cohort studies (PROSPERO, CRD42021238952) from inception to 7 May 2021. Two authors independently performed the articles selection, data extraction, and quality assessment. The efficacy outcome was the resolution of left atrial/left atrial appendage thrombosis, and the safety outcomes were bleeding and stroke/transient ischemic attack.

Results

One randomized controlled trial and 5 cohort studies were included, with a total of 353 patients. Compared with warfarin, novel oral anticoagulants were associated with increased probability of left atrial/left atrial appendage thrombosis resolution (OR = 2.20; 95% CI, 1.35–3.60; I² = 0%). Compared with warfarin, novel oral anticoagulants had a similar risk of bleeding (OR = 0.91; 95% CI, 0.39–2.13; I² = 0%). There was no evidence of increased risk of stroke/transient ischemic attack (OR = 0.42; 95% CI, 0.12–1.45; I² = 0%).

Conclusions

Novel oral anticoagulants were more effective than warfarin in promoting the resolution of left atrial/left atrial appendage thrombosis, without increased risks of bleeding and stroke/transient ischemic attack. Our study provides valuable insight into clinical practice. Further well-designed randomized controlled trials are needed to fully evaluate the benefits and risks in these patients. PROSPERO Registration No.: CRD42021238952.