Current Reviews in Clinical and Experimental Pharmacology最新文献

Background: It has been recognized that patients should be involved in the design of clinical trials. However, there is a lack of agreement on what patient-centricity means.

Methods: In this article, a Patient Motivation Pyramid based on Maslow's theory of human motivation is introduced as a tool to identify patient needs. This pyramid is used to make a comprehensive overview of options to implement a patient-centric trial design. The Pyramid with the described options can help to identify patient-centric activities suitable for given drug development. The current article further describes the potential benefits of patient-centric trial designs with an emphasis on early clinical development. Especially in early clinical development, during which trials have many assessments per patient, and the safety and clinical efficacy are uncertain, patient-centric trial design can improve feasibility. Finally, we present three case examples on patient-centric trial design. The first example is seeking patient input on the trial design for a First-in-Human trial which includes patients with Immune Thrombocytopenic Purpura. The second example is the use of a video-link for home dosing. The final example is the use of digital medicine in a decentralized trial in heart failure patients.

Results: A comprehensive overview of patients' needs can be accomplished by building a Patient Motivation Pyramid as a tool. Patient input can lead to improved endpoints, improved feasibility, better recruitment, less dropout, less protocol amendments, and higher patient satisfaction. The use of digital medicine can lead to a trial design with much less visits to the clinical research center in early clinical development and in a later development phase, even to a complete virtual trial.

Conclusion: We recommend using the Patient Motivation Pyramid as a structural approach for identifying elements of patient-centricity. Secondly, we recommend starting using patient-centric approaches in an early phase of the medicine's lifecycle.

Background: Respiratory tract infections are a primary cause of illness and mortality over the world.

Objective: This study was aimed to investigate the effectiveness of vitamin C supplementation in preventing and treating respiratory tract infections.

Methods: We used the Cochrane, PubMed, and MEDLINE Ovid databases to conduct our search. The inclusion criteria were placebo-controlled trials. Random effects meta-analyses were performed to measure the pooled effects of vitamin C supplementation on the incidence, severity, and duration of respiratory illness.

Results: We found ten studies that met our inclusion criteria out of a total of 2758. The pooled risk ratio (RR) of developing respiratory illness when taking vitamin C regularly across the study period was 0.94 (with a 95% confidence interval of 0.87 to 1.01) which found that supplementing with vitamin C lowers the occurrence of illness. This effect, however, was statistically insignificant (P= 0.09). This study showed that vitamin C supplementation had no consistent effect on the severity of respiratory illness (SMD 0.14, 95% CI -0.02 to 0.30: I2 = 22%, P=0.09). However, our study revealed that vitamin C group had a considerably shorter duration of respiratory infection (SMD -0.36, 95% CI -0.62 to -0.09, P = 0.01).

Conclusion: Benefits of normal vitamin C supplementation for reducing the duration of respiratory tract illness were supported by our meta-analysis findings. Since few trials have examined the effects of therapeutic supplementation, further research is needed in this area.

The use and acceptance of cannabis, either medically or recreationally, has substantially outpaced the collection of data necessary to evaluate it's use in any population. However, the mere widespread availability does not imply the absence of risk or confirmation of efficacy and should not be treated as such. There is enough data to suggest that not only does the potential for pharmacokinetic and metabolic interactions exist, but also that baseline characteristics for a given population could be different in chronic cannabis users. Either or both of these may impact the safety and efficacy profile for any new drug in development. As such, we encourage drug developers to consider that the cannabis user may very well be a special population that warrants its own clinical pharmacology evaluation.

Characterized by small, highly heterogeneous patient populations, rare disease trials magnify the challenges often encountered in traditional clinical trials. In recent years, there have been increased efforts by stakeholders to improve drug development in rare diseases through novel approaches to clinical trial designs and statistical analyses. We highlight and discuss some of the current and emerging approaches aimed at overcoming challenges in rare disease clinical trials, with a focus on the ultimate stakeholder, the patient.

Background: Functional gastrointestinal disorders account for at least a third of visits to gastroenterology clinics. Despite pathophysiological complexity, impaired gut motility may be frequently present in these disorders.

Introduction: Prokinetics are a class of drugs that promote gastrointestinal motility, accelerate transit, and potentially improve digestive symptoms. Several prokinetic agents with a great variety of mechanisms of action are available.

Aim: The purpose of this paper is to update our current knowledge about the efficacy and safety of prokinetics.

Methods: A literature search on efficacy and safety of prokinetics was carried out using the online databases of Pubmed, Medline, and Cochrane.

Results: Based on the action of different receptors, prokinetics mainly comprise dopamine antagonists, 5HT4 agonists, motilin agonists, ghrelin agonists, and cholinergic agonists. Prokinetics have the potential to improve motility function in all segments of the digestive tract, from the esophagus to the colon. In particular, drug international agencies have approved antidopaminergic metoclopramide for the treatment of gastroparesis and serotoninergic prucalopride for chronic constipation not responsive to traditional laxatives. Arrhythmias by QT prolongation and galactorrhea by prolactin stimulation are the more frequent side effects related to prokinetics use.

Conclusion: Old and new prokinetics are effective in ameliorating digestive motility disorders and related symptoms and are widely prescribed. Special attention should be paid to the potential adverse events of these agents.

Background: Treatment with N-Acetyl Cysteine (NAC) in rodenticide poisoning has not been well established due to mixed study results and insufficient evidence. This review aimed to summarize the clinical benefits of NAC in the management of rodenticide poisoning.

Methods: This review follows the PICOS framework and the PRISMA guidelines. Pub- Med/MEDLINE, Scopus, and the Cochrane library were searched to identify the published literature from inception to September 2020, and a reference search was performed for additional relevant studies. The English language studies addressing the use of NAC in rodenticide poisoning were considered for the review. We considered all experimental and observational studies due to the insufficient number of interventional studies.

Results: Ten studies (two RCTs, four observational, and four descriptive) out of 2,178 studies with 492 participants were considered for the review. Only six studies (two RCTs, one prospective, and three retrospective studies) reported recovery and mortality. Pooled results of RCTs (n=2) showed a significant recovery rate (Odds Ratio [OR]: 3.97; 95% Confidence Interval [CI]:1.69-9.30), whereas summary estimates of prospective and retrospective studies recorded a non-significant effect. Metaanalysis of RCTs (OR: 0.25; 95% CI: 0.11-0.59; n=2) and retrospective studies (OR: 0.34; 95% CI: 0.15-0.78; n=3) showed a significant reduction in mortality, whereas pooled analysis of prospective studies recorded a non-significant effect. A significant reduction in intubation or ventilation (OR: 0.25; 95% CI: 0.11-0.60; 2 RCTs) and a non-significant (P=0.41) difference in duration of hospitalization was observed with NAC when compared to the non-NAC treated group. The quality of the included studies appeared to be moderate to high.

Conclusion: Our findings indicate that NAC showed better survival and lower mortality rate when compared to non-NAC treated group; hence NAC can be considered for the management of rodenticide poisoning.

Background: Autism Spectrum Disorders (ASDs) are a group of prevalent neuropsychiatric disorders. They present a complex and unknown etiology, which in most cases includes significant peripheral alterations outside the brain such as in the composition of gut microbiota. Because the gut microbiota is involved in modulating the gut-brain axis, several studies have suggested that the microbiome in the gut can modify metabolites which are able to cross the blood-brain barrier and modulate brain function.

Methods: We reviewed the current evidence regarding microbiota alterations in patients with ASD and the effects of the administration of probiotics and prebiotics in these patients, both in terms of gastrointestinal and behavioural symptoms.

Results: Administration of a probiotic formulation containing different strains of Lactobacillus (L. acidophilus, L. rhamnosus, and others) and Bifidobacteria had beneficial effects upon these aforementioned symptoms and their use is recommended in a subgroup of ASD patients that present gastrointestinal disturbances. Nonetheless, the types of gastrointestinal disturbances that most benefit from such interventions remain to be elucidated in order to personalize the medical approaches.

Conclusion: Recent clinical studies have shown that probiotic treatments can regulate the gut microbiota and may result in improvements in some behavioral abnormalities associated with ASD. Trials using prebiotic fibers or synbiotics preparations are still lacking and necessary in order to deep in such therapeutic strategies in ASD with comorbid gastrointestinal disrturbances.

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