Current Therapeutic Research-clinical and Experimental最新文献

Background

Current guidelines for the therapeutic monitoring of vancomycin recommend dosing based on the area under the concentration-time curve (AUC) to achieve clinical efficacy while reducing nephrotoxicity. Although a wide range of nephrotoxicity thresholds have been reported, few studies have documented clinical outcomes based on AUC-guided vancomycin dosing in Korea.

Objective

The aim of the study was to evaluate whether a relationship exists between AUC and treatment outcomes in vancomycin treated patients in methicillin-resistant Staphylococcus aureus bacteremia. Furthermore, this study tries to estimate AUC threshold for treatment failure and nephrotoxicity.

Methods

The records of adult patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin for ≥72 hours without dialysis between April 2013 and April 2021, were reviewed retrospectively. Treatment success was defined as defervescence and blood culture sterilization by day 7. Nephrotoxicity was defined as an increase in serum creatinine levels ≥0.3 mg/dL or a 50% increase from baseline on 2 consecutive days. Bayesian estimation was used to predict individual vancomycin AUC. Both classification and regression tree and receiver operating characteristic curve analyses were performed to estimate the optimal AUC thresholds for vancomycin efficacy and nephrotoxicity.

Results

Of 118 patients, 61 (51.7%) experienced treatment failure and 42 (35.6%) developed acute kidney injury. The vancomycin AUC threshold for predicting acute kidney injury was 615.0 mg· hr/L. In the multivariate analysis, AUC ≥615.0 mg· hr/L was a significant risk factor for nephrotoxicity (adjusted odds ratio [aOR] = 5.24; 95% CI, 1.8–14.65). The lower threshold for treatment failure was not defined because it was not statistically significant. Risk factors for treatment failure included low body mass index (aOR = 0.82; 95% CI, 0.70–0.96), severity of acute illness represented by complicated infection (aOR = 77.56; 95% CI, 16.7–359.4) and comorbidities, such as solid organ tumors (aOR = 6.61; 95% CI, 1.19–36.81) and cerebrovascular disease (aOR = 6.05; 95% CI, 1.17–31.23).

Conclusions

Although AUC-guided vancomycin dosing was associated with a reduced risk of acute kidney injury, its ability to predict clinical outcomes was modest. Further studies are needed to define the AUC therapeutic range to maximize efficacy and minimize nephrotoxicity. (Curr Ther Res Clin Exp. 2023; 83:XXX–XXX)

Background

Thyroid hormones are indispensable for organ development and maintaining homeostasis. Thyroid diseases, including thyroiditis and thyroid cancer, affect the normal secretion of hormones and result in thyroid dysfunction.

Objective

This review focuses on therapeutic applications of stem cells for thyroid diseases.

Methods

A literature search of Medline and PubMed was conducted (January 2000–July 2021) to identify recent reports on stem cell therapy for thyroid diseases.

Results

Stem cells are partially developed cell types. They have the capacity to form specialized cells. Besides embryonic stem cells and mesenchymal stem cells, organ resident stem cells and cancer stem cells are recently reported to have important roles in forming organ specific cells and cancers. Stem cells, especially mesenchymal stem cells, have anti-inflammatory and anticancer functions as well.

Conclusions

This review outlines the therapeutic potency of embryonic stem cells, mesenchymal stem cells, thyroid resident stem cells, and thyroid cancer stem cells in thyroid cells’ regeneration, thyroid function modulation, thyroiditis suppression, and antithyroid cancers. Stem cells represent a promising form of treatment for thyroid disorders.

Background

The globalization of clinical research should also benefit the population in developing markets. In this context, the approval of tested medicines and the associated expansion of medical care beyond clinical studies would be desirable as a possible long-term benefit.

Objectives

This study was designed to compare the development of the number of clinical trials with the number of marketing authorizations of medicines on the African continent. To contrast these 2 parameters, the data were analyzed using the model of an ecological study.

Methods

To reflect the broad spectrum of African developing countries with diverse levels of development, the data collection was based on 2 geographically selected sample countries each from Central, North, East, West, and Southern Africa. Based on the ClinicalTrials.gov registry, the first step was to collect trends data on the development of the clinical trials in the 10 selected countries of the country list of the African Region published by the World Health Organization for the period 2015 to 2018. Subsequently, data on the current number of marketing authorizations of medicines in the selected sample countries were identified using the online registries of the national authorities. The data were utilized in comparative analyses.

Results

Eight out of 10 model countries showed an increase in the number of clinical trials, with the exceptions of Cameroon and Libya, which showed an overall decline in research activity over the entire time. In direct comparison with drug registrations, the numbers indicate a similar development. The only exception here is Nigeria, a country with a solid performance in clinical research and yet a decrease in medicine registrations since 2015.

Conclusions

The expected increase in the development of clinical research as result of the globalization trend can basically be observed in most of the model countries. However, this increase does not guarantee an improvement in the number of medicine registrations. Although this is evident in some of the selected model countries, it cannot be projected to the entire African region. This may be linked to the diverse development of the individual countries due to the different political situations and the varying degrees of clinical research infrastructure. (Curr Ther Res Clin Exp. 2022; 82:XXX–XXX)

Background

Docetaxel is a clinically well established antimitotic chemotherapy medication. Labeled docetaxel indications are breast cancer, gastric cancer, head and neck cancer, non–small cell lung cancer, and prostate cancer.

Objective

This is a Phase IV study to evaluate the safety profile of docetaxel (Alvotere; NanoAlvand, Iran) in Iranian patients diagnosed with different types of cancers receiving chemotherapy regimens with docetaxel.

Methods

Patients who received Alvotere as a part of their chemotherapy regimen were enrolled in this Phase IV, observational, multicenter, open-label study. Alvotere was administrated as a single agent or in combination with other chemotherapy agents. Safety parameters in each cycle were assessed, and the related data were recorded in booklets.

Findings

A total of 411 patients with different types of cancers were enrolled from 25 centers in Iran. The most common malignancies among participants were breast cancer (49.88%), followed by gastric cancer (22.63%). Participants’ mean age was 53.33 years, and the mean total dose used in each cycle was 132 mg. According to the results, 341 patients experienced at least 1 adverse event, that the most common was alopecia (41.12%). In total, 92 (22.38%) patients had at least 1 adverse event of grade 3 or 4, and 25 (6.08%) patients showed 54 serious adverse events, which the causality assessment for all was possibly related to Alvotere. There was a significant difference between men and women in the incidence of skin and subcutaneous tissue disorders (55.63% in women vs 41.73% in men; P = 0.009). Also, the incidence of gastrointestinal disorders, nervous system disorders, skin and subcutaneous tissue disorders, hepatic enzymes increase, and fluid retention was significantly higher (P < 0.05) in patients receiving anthracyclines in their chemotherapy regimens.

Conclusions

The findings of this open-label, observational, multicenter, postmarketing surveillance showed that Alvotere appears to have an acceptable safety profile in Iranian cancer patients receiving chemotherapeutic regimens. (Curr Ther Res Clin Exp. 2022; 82:XXX–XXX) © 2022 Elsevier HS Journals, Inc.

Actinic keratoses are keratotic lesions occurring on skin areas extensively damaged by sunlight. Using data from a previously published Phase III randomized, controlled clinical trial in patients with at least 5 actinic keratoses, we explored the potential link between the number of visible actinic keratosis lesions before any treatment and the total number of lesions of the field cancerization as revealed by 5-fluorouracil cream. Our analysis suggests that the baseline number of visible actinic keratoses is a poor indicator of the real number of lesions in the field of cancerization, reinforcing the need to explain the field cancerization concept to patients. (Curr Ther Res Clin Exp. 2022; 82:XXX–XXX) © 2022 Elsevier HS Journals, Inc.

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)