scholarly journals Clinical studies of drug effects in humans

1996 ◽  
Vol 42 (8) ◽  
pp. 1306-1311 ◽  
Author(s):  
W A Ray
Keyword(s):  
Clinical Studies ◽  
Animal Studies ◽  
Controlled Trial ◽  
Case Series ◽  
Drug Effects ◽  
Study Groups ◽  
Case Control Studies ◽  
Frequent Use ◽  
Outcome Differences

Abstract Many important drug properties cannot be predicted from in vitro or animal studies but must be quantified from studies of clinically relevant endpoints in humans. Clinical study designs include the randomized controlled trial (RCT) and a variety of observational designs. In RCTs, randomization usually ensures treatment group comparability with respect to other factors, so outcome differences reflect treatment differences per se. Properly conducted RCTs thus are the strongest study design, the mainstay of mandatory premarketing studies, and essential for evaluation of therapeutic efficacy. RCT limitations include frequent use of surrogate endpoints, limited power, short-term follow-up, and cross-contamination of study groups. For ethical reasons, some questions cannot be studied with RCTs. The simplest observational design, the case series, has limited value because it lacks a denominator. Limitations of cohort and case-control studies include misclassification, selection bias, and confounding. Despite their limitations, properly conducted experimental and observational clinical studies provide essential data for clinical practice.

An update on cefepime and its future role in combination with novel β-lactamase inhibitors for MDR Enterobacterales and Pseudomonas aeruginosa

2020 ◽  
Author(s):  
Burcu Isler ◽  
Patrick Harris ◽  
Adam G Stewart ◽  
David L Paterson
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Clinical Studies ◽  
Bacterial Infections ◽  
Animal Studies ◽  
Wide Spectrum ◽  
Clinical Development ◽  
Phase Iii ◽  
Lactam Antibiotic ◽  
Tract Infections

Abstract Cefepime, a wide-spectrum β-lactam antibiotic, has been in use for the treatment of serious bacterial infections for almost 25 years. Since its clinical development, there has been a dramatic shift in its dosing, with 2 g every 8 hours being preferred for serious infections to optimize pharmacokinetic/pharmacodynamic considerations. The advent of ESBLs has become a threat to its ongoing use, although future coadministration with β-lactamase inhibitors (BLIs) under development is an area of intense study. There are currently four new cefepime/BLI combinations in clinical development. Cefepime/zidebactam is generally active against MBL-producing Enterobacterales and Pseudomonas aeruginosa, in vitro and in animal studies, and cefepime/taniborbactam has activity against KPC and OXA-48 producers. Cefepime/enmetazobactam and cefepime/tazobactam are potential carbapenem-sparing agents with activity against ESBLs. Cefepime/enmetazobactam has completed Phase III and cefepime/taniborbactam is in Phase III clinical studies, where they are being tested against carbapenems or piperacillin/tazobactam for the treatment of complicated urinary tract infections. While these combinations are promising, their role in the treatment of MDR Gram-negative infections can only be determined with further clinical studies.

scholarly journals Efficacy of Using Probiotics with Antagonistic Activity against Pathogens of Wound Infections: An Integrative Review of Literature

2019 ◽  
Vol 2019 ◽  
pp. 1-21 ◽  
Author(s):  
Sabina Fijan ◽  
Anita Frauwallner ◽  
Tomaž Langerholc ◽  
Bojan Krebs ◽  
Jessica A. ter Haar (née Younes) ◽  
...  
Keyword(s):  
Clinical Studies ◽  
Animal Studies ◽  
Lactobacillus Rhamnosus ◽  
Foot Ulcer ◽  
Surgical Site Infections ◽  
Integrative Review ◽  
Wound Management ◽  
Wound Infections ◽  
Skin Damage

The skin and its microbiota serve as physical barriers to prevent invasion of pathogens. Skin damage can be a consequence of illness, surgery, and burns. The most effective wound management strategy is to prevent infections, promote healing, and prevent excess scarring. It is well established that probiotics can aid in skin healing by stimulating the production of immune cells, and they also exhibit antagonistic effects against pathogens via competitive exclusion of pathogens. Our aim was to conduct a review of recent literature on the efficacy of using probiotics against pathogens that cause wound infections. In this integrative review, we searched through the literature published in the international following databases: PubMed, ScienceDirect, Web of Science, and Scopus using the search terms “probiotic” AND “wound infection.” During a comprehensive review and critique of the selected research, fourteen in vitro studies, 8 animal studies, and 19 clinical studies were found. Two of these in vitro studies also included animal studies, yielding a total of 39 articles for inclusion in the review. The most commonly used probiotics for all studies were well-known strains of the species Lactobacillus plantarum, Lactobacillus casei, Lactobacillus acidophilus, and Lactobacillus rhamnosus. All in vitro studies showed successful inhibition of chosen skin or wound pathogens by the selected probiotics. Within the animal studies on mice, rats, and rabbits, probiotics showed strong opportunities for counteracting wound infections. Most clinical studies showed slight or statistically significant lower incidence of surgical site infections, foot ulcer infection, or burn infections for patients using probiotics. Several of these studies also indicated a statistically significant wound healing effect for the probiotic groups. This review indicates that exogenous and oral application of probiotics has shown reduction in wound infections, especially when used as an adjuvant to antibiotic therapy, and therefore the potential use of probiotics in this field remains worthy of further studies, perhaps focused more on typical skin inhabitants as next-generation probiotics with high potential.

scholarly journals Tumour-on-chip microfluidic platform for assessment of drug pharmacokinetics and treatment response

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Tudor Petreus ◽  
Elaine Cadogan ◽  
Gareth Hughes ◽  
Aaron Smith ◽  
Venkatesh Pilla Reddy ◽  
...  
Keyword(s):  
Animal Studies ◽  
Drug Exposure ◽  
Drug Effects ◽  
Pharmacokinetic Profile ◽  
Microfluidic System ◽  
Drug Dose ◽  
In Vivo Studies ◽  
On Chip

AbstractMicrophysiological in vitro systems are platforms for preclinical evaluation of drug effects and significant advances have been made in recent years. However, existing microfluidic devices are not yet able to deliver compounds to cell models in a way that reproduces the real physiological drug exposure. Here, we introduce a novel tumour-on-chip microfluidic system that mimics the pharmacokinetic profile of compounds on 3D tumour spheroids to evaluate their response to the treatments. We used this platform to test the response of SW620 colorectal cancer spheroids to irinotecan (SN38) alone and in combination with the ATM inhibitor AZD0156, using concentrations mimicking mouse plasma exposure profiles of both agents. We explored spheroid volume and viability as a measure of cancer cells response and changes in mechanistically relevant pharmacodynamic biomarkers (γH2AX, cleaved-caspase 3 and Ki67). We demonstrate here that our microfluidic tumour-on-chip platform can successfully predict the efficacy from in vivo studies and therefore represents an innovative tool to guide drug dose and schedules for optimal efficacy and pharmacodynamic assessment, while reducing the need for animal studies.

scholarly journals Stem Cells as a Model of Study of SARS-CoV-2 and COVID-19: A Systematic Review of the Literature

2021 ◽  
Vol 2021 ◽  
pp. 1-7
Author(s):  
María Verónica Cuevas-Gonzalez ◽  
Álvaro Garcia-Perez ◽  
Álvaro Edgar Gonzalez-Aragon Pineda ◽  
León Francisco Espinosa-Cristobal ◽  
Alejandro Donohue-Cornejo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Trials ◽  
Stem Cell ◽  
Clinical Studies ◽  
Case Series ◽  
In Vitro Studies ◽  
In Vivo Studies

Background. The SARS-CoV-2 virus is the cause of the latest pandemic of the 21st century; it is responsible for the development of COVID-19. Within the multiple study models for both the biology and the treatment of SARS-CoV-2, the use of stem cells has been proposed because of their ability to increase the immune response and to repair tissue. Therefore, the objective of this review is to evaluate the role of stem cells against SARS-CoV-2 and COVID-19 in order to identify their potential as a study model and as a possible therapeutic source against tissue damage caused by this virus. Therefore, the following research question was established: What is the role of stem cells in the study of SARS-CoV-2 and the treatment of COVID-19? Materials and Methods. A search was carried out in the electronic databases of PUBMED, Scopus, and ScienceDirect. The following keywords were used: “SARS-CoV-2,” “COVID-19,” and “STEM CELL,” plus independent search strategies with the Boolean operators “OR” and “AND.” The identified reports were those whose main objective was the study of stem cells in relation to SARS-CoV-2 or COVID-19. For the development of this study, the following inclusion criteria were taken into account: studies whose main objective was the study of stem cells in relation to SARS-CoV-2 or COVID-19 and clinical case studies, case reports, clinical trials, pilot studies, in vitro, or in vivo studies. For assessment of the risk of bias for in vitro studies, the SciRAP tool was used. The data collected for each type of study, clinical or in vitro, were analyzed with descriptive statistics using the SPSS V.22 program. Results. Of the total of studies included ( n = 39 ), 22 corresponded to in vitro investigations and 17 to human studies (clinical cases ( n = 9 ), case series ( n = 2 ), pilot clinical trials ( n = 5 ), clinical trials ( n = 1 )). In vitro studies that induced pluripotent stem cells were the most used ( n = 12 ), and in clinical studies, the umbilical stem cells derived were the most reported ( n = 11 ). The mean age of the study subjects was 58.3 years. After the application of stem cell therapy, the follow-up period was 8 days minimum and 90 days maximum. Discussion. The mechanism by which the virus enters the cell is through protein “S,” located on the surface of the membrane, by recognizing the ACE2 receptor located on the target cell. The evidence that the expression of ACE2 and TMPRSS2 in stem cells indicates that stem cells from bone marrow and amniotic fluid have very little expression. This shows that stem cell has a low risk of infection with SARS-CoV-2. Conclusion. The use of stem cells is a highly relevant therapeutic option. It has been shown in both in vitro studies and clinical trials that it counteracts the excessive secretion of cytokines. There are even more studies that focus on long-term follow-up; thus, the potential for major side effects can be analyzed more clearly. Finally, the ethical use of stem cells from fetal or infant origin needs to be regulated. The study was registered in PROSPERO (no. CRD42021229038). The limitations of the study were because of the methodology employed, the sample was not very large, and the follow-up period of the clinical studies was relatively short.

scholarly journals A randomized, double-blind, placebo-controlled trial to evaluate the hypoglycemic efficacy of the mcIRBP-19-containing Momordica charantia L. fruit extracts in the type 2 diabetic subjects

2022 ◽  
Author(s):  
Yi-Sun Yang ◽  
Nian-Yi Wu ◽  
Edy Kornelius ◽  
Chien-Ning Huang ◽  
Nae-Cherng Yang
Keyword(s):  
Blood Glucose ◽  
Animal Studies ◽  
Controlled Trial ◽  
Fasting Blood Glucose ◽  
Momordica Charantia ◽  
Antidiabetic Drugs ◽  
Bitter Gourd ◽  
Double Blind

Background: The fruits of Momordica charantia L., also named as bitter gourd or bitter melon in popular, is a common tropical vegetable that is traditionally used to reduce blood glucose. A peptide derived from bitter gourd, Momordica charantia insulin receptor binding peptid-19 (mcIRBP-19), had been demonstrated to possess an insulin-like effect in vitro and in the animal studies. However, the benefit of the mcIRBP-19-containing bitter gourd extracts (mcIRBP-19-BGE) for lowering blood glucose levels in humans is unknown. Objective: This aim of this study was to evaluate the hypoglycemic efficacy of mcIRBP-19-BGE in subjects with type 2 diabetes who had taken antidiabetic medications but failed to achieve the treatment goal. Whether glucose lowering efficacy of mcIRBP-19-BGE could be demonstrated when the antidiabetic medications were ineffective was also studied. Design: Subjects were randomly assigned to two groups: mcIRBP-19-BGE treatment group (N = 20) and placebo group (N = 20), and were orally administered 600 mg/day investigational product or placebo for 3 months. Subjects whose hemoglobin A1c (HbA1c) continued declining before the trial initiation with the antidiabetic drugs were excluded from the subset analysis to further investigate the efficacy for those who failed to respond to the antidiabetic medications. Results: The oral administration of mcIRBP-19-BGE decreased with a borderline significance at fasting blood glucose (FBG; P = 0.057) and HbA1c (P = 0.060). The subgroup analysis (N = 29) showed that mcIRBP-19-BGE had a significant effect on reducing FBG (from 172.5 ± 32.6 mg/dL to 159.4 ± 18.3 mg/dL, P = 0.041) and HbA1c (from 8.0 ± 0.7% to 7.5 ± 0.8%, P = 0.010). Conclusion: All of these results demonstrate that mcIRBP-19-BGE possesses a hypoglycemic effect, and can have a significant reduction in FBG and HbA1c when the antidiabetic drugs are ineffective.

scholarly journals In Vitro Cultures of Adipose-Derived Stem Cells: An Overview of Methods, Molecular Analyses, and Clinical Applications

Cells ◽  
2020 ◽  
Vol 9 (8) ◽  
pp. 1783 ◽  
Author(s):  
Maurycy Jankowski ◽  
Claudia Dompe ◽  
Rafał Sibiak ◽  
Grzegorz Wąsiatycz ◽  
Paul Mozdziak ◽  
...  
Keyword(s):  
Stem Cells ◽  
Clinical Studies ◽  
Animal Studies ◽  
Ex Vivo ◽  
Clinical Applications ◽  
In Vitro Cultures ◽  
Adipose Derived Stem Cells ◽  
Molecular Analyses ◽  
Animal Trials

Adipose-derived stem cells (ASCs) exhibiting mesenchymal stem cell (MSC) characteristics, have been extensively studied in recent years. Because they have been shown to differentiate into lineages such as osteogenic, chondrogenic, neurogenic or myogenic, the focus of most of the current research concerns either their potential to replace bone marrow as a readily available and abundant source of MSCs, or to employ them in regenerative and reconstructive medicine. There is close to consensus regarding the methodology used for ASC isolation and culture, whereas a number of molecular analyses implicates them in potential therapies of a number of pathologies. When it comes to clinical application, there is a range of examples of animal trials and clinical studies employing ASCs, further emphasizing the advancement of studies leading to their more widespread use. Nevertheless, in vitro studies will most likely continue to play a significant role in ASC studies, both providing the molecular knowledge of their ex vivo properties and possibly serving as an important step in purification and application of those cells in a clinical setting. Therefore, it is important to consider current methods of ASC isolation, culture, and processing. Furthermore, molecular analyses and cell surface properties of ASCs are essential for animal studies, clinical studies, and therapeutic applications of the MSC properties.

scholarly journals Topiramate reduces nocturnal eating in sleep-related eating disorder

SLEEP ◽  
2020 ◽  
Vol 43 (9) ◽  
Author(s):  
John W Winkelman ◽  
Benjamin Wipper ◽  
Julia Purks ◽  
Leslie Mei ◽  
Laura Schoerning
Keyword(s):  
Clinical Trial ◽  
Eating Disorder ◽  
Side Effects ◽  
Small Sample Size ◽  
Controlled Trial ◽  
Case Series ◽  
Study Groups ◽  
Small Sample ◽  
Drop Out ◽  
Intention To Treat

Abstract Study Objectives Sleep-related eating disorder (SRED) is a parasomnia characterized by partial arousals from sleep with compulsive consumption of food with impaired level of awareness and memory for the event. Small case series’ have demonstrated efficacy of topiramate in SRED. We conducted a placebo-controlled randomized clinical trial of topiramate to assess efficacy in SRED. Methods Thirty-four participants with an ICSD-2/ICSD-3 diagnosis of SRED with >6 months of symptoms and ≥3 sleep-related eating episodes per week were randomized to placebo or topiramate with flexible dosing to a maximum dosage of 300 mg for 13 weeks. Primary outcomes were percentage of nights with eating and Clinician Global Impression-Improvement (CGI-I). Intention-to-treat last observation carried forward (ITT LOCF) analysis was conducted. Results Mean age was 39.5 years, 74% were female, with mean duration of sleep-related eating of 13.7 years. SRED symptoms were significantly reduced with topiramate (74.7% to 33.2% nights/week; n = 15) compared to placebo (77.0% to 57.4%; n = 17) (p = 0.035). There were significantly more CGI-I responders on topiramate (71%) than placebo (27%) (p = 0.016). Level of wakefulness (r = −0.49) and memory for nighttime eating (r = −0.58) at baseline predicted topiramate response. The topiramate group lost significantly more weight than the placebo group (−8.5 lbs vs. +1.0 lbs, p = 0.001). The most common side effects were paresthesias and cognitive dysfunction. Conclusions This first randomized controlled trial demonstrating efficacy for treatment of SRED supports preliminary data on the use of topiramate for SRED. Side effects were prominent for topiramate. Limitations include a small sample size and a high drop-out rate in both study groups. Clinical Trial Information NCT00606411

scholarly journals The fog, the attractive and the addictive: pulmonary effects of vaping with a focus on the contribution of each major vaping liquid constituent

2020 ◽  
Vol 29 (157) ◽  
pp. 200268
Author(s):  
Ariane Lechasseur ◽  
Mathieu C. Morissette
Keyword(s):  
Propylene Glycol ◽  
Clinical Studies ◽  
Animal Studies ◽  
Biological Effects ◽  
Electronic Cigarette ◽  
The Past ◽  
Current State

Vaping has become increasingly popular over the past decade. This pragmatic review presents the published biological effects of electronic cigarette vapour inhalation with a focus on the pulmonary effects. Special attention has been devoted to providing the documented effects specific to each major ingredient, namely propylene glycol/glycerol, nicotine and flavouring agents. For each ingredient, findings are divided according to the methodology used, being in vitro studies, animal studies and clinical studies. Finally, we provide thoughts and insights on the current state of understanding of the pulmonary effects of vaping, as well as novel research avenues and methodologies.

scholarly journals A novel tumour-on-chip microfluidic platform advances assessment of drug pharmacokinetics and treatment response

2021 ◽  
Author(s):  
Tudor Petreus ◽  
Elaine Cadogan ◽  
Gareth Hughes ◽  
Aaron Smith ◽  
Venkatesh Reddy ◽  
...  
Keyword(s):  
Animal Studies ◽  
Drug Exposure ◽  
Drug Effects ◽  
Pharmacokinetic Profile ◽  
Microfluidic System ◽  
Drug Dose ◽  
On Chip ◽  
Cancer Spheroids

Abstract Microphysiological in vitro systems are platforms for preclinical evaluation of drug effects and significant advances have been made in recent years. However, existing microfluidic devices are not yet able to deliver compounds to cell models in a way that reproduces the real physiological drug exposure. Here, we introduce a novel tumour-on-chip microfluidic system that mimics the pharmacokinetic profile of compounds on 3D tumour spheroids to evaluate their response to the treatments. We used this platform to test the response of SW620 colorectal cancer spheroids to irinotecan (SN38) alone and in combination with the ATM inhibitor AZD0156, using concentrations mimicking mouse plasma exposure profiles of both agents. We explored spheroid volume and viability as a measure of cancer cells response and changes in mechanistically relevant pharmacodynamic biomarkers (γH2AX, cleaved-caspase 3 and Ki67). We demonstrate here that our microfluidic tumour-on-chip platform can successfully predict the efficacy from in vivo studies and therefore represents an innovative tool to guide drug dose and schedules for optimal efficacy and pharmacodynamic assessment, while reducing the need for animal studies.

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