scholarly journals Review of properties and mechanisms of action of hepatoprotective drugs

2020 ◽  
pp. 36-44
Author(s):  
Е.В. Кардаш ◽  
Е.М. Григорьева ◽  
А.Г. Емельянова ◽  
С.А. Тарасов
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Side Effects ◽  
Randomized Clinical Trials ◽  
Evidence Base ◽  
Mechanisms Of Action ◽  
New Drugs ◽  
Simultaneous Administration ◽  
Essential Phospholipids ◽  
Meta Analyses

В медицинской практике достаточно часто возникает необходимость в одновременном приеме нескольких лекарственных средств. Иногда это оказывается невозможным в силу наличия у препаратов гепатотоксических свойств, поэтому актуальными задачами фармакологии являются как поиск и разработка новых препаратов, так и оптимизация уже существующих с целью уменьшения побочных эффектов при их приеме. В настоящем обзоре были проанализированы данные о фармакологических препаратах класса гепатопротекторов, разобраны механизмы их действия и потенциал поиска новых препаратов. В заключение отмечено, что в настоящее время в клинической практике наибольшей популярностью пользуются препараты, содержащие эссенциальные фосфолипиды и препараты, улучшающие рециркуляцию и выведение желчных кислот. Существуют теоретические обоснования механизмов действия этих препаратов и перспектива накопления доказательной базы для них в виде рандомизированных клинических исследований и мета-анализов. Medical practice quite often requires simultaneous administration of several drugs. Sometimes it is impossible due to their hepatotoxicity; therefore, urgent tasks of pharmacology include searching for and developing new drugs as well as optimizing already existing products in order to reduce side effects during their administration. This review focused on pharmacological drugs of the hepatoprotector class and their mechanisms of action and evaluated the prospects of searching for new medicines. In conclusion, drugs containing essential phospholipids and those improving recirculation and removal of bile acids are currently the most popular agents in clinical practice. Mechanisms of action of these drugs are theoretically justified and there is a prospect for building an evidence base for them by randomized clinical trials and meta-analyses.

Benzodiazepines, Amphetamines, Testosterone and Sildenafil as New Candidates Drugs for Sexual Interest, Desire and/or Arousal Disorder

2021 ◽  
Vol 10 ◽  
Author(s):  
Richard Joseph Wix ◽  
Ezequiel Uribe
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Side Effects ◽  
Sexual Interest ◽  
New Drugs ◽  
Hypoactive Sexual Desire Disorder ◽  
Arousal Disorder ◽  
Approved Drugs ◽  
Fda Approved Drugs ◽  
Desire Disorder

Background: The FDA approved drugs for female sexual interest, desidere and/or arousal disorder (FSIAD), and hypoactive sexual desire disorder (HSDD), however this have low tolerability for patients because its multiple side effects and does not show real therapeutic efficacy. Hypoactive Sexaul Desire affects from 750.000.000 to 1.400.000.000 people worldwide. Methods: In this paper we analyze therapeutic candidate in clinical practice as well as the methodologies clinical trials of possible therapeutic targets of different systems related to the dysfunction. Results: Therefore New Drugs (Benzodiazepines, Amphetamines, Testosterone, Sildenafil or New Compound) Clinical Trials to treat this disorder are necessary.

scholarly journals Opportunities for selective reporting of harms in randomized clinical trials: Selection criteria for nonsystematic adverse events

2019 ◽  
Author(s):  
Evan Mayo-Wilson ◽  
Nicole Fusco ◽  
Hwanhee Hong ◽  
Tianjing Li ◽  
Joseph K. Canner ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Adverse Events ◽  
Selection Criteria ◽  
Randomized Clinical Trials ◽  
Bipolar Depression ◽  
Selective Reporting ◽  
Journal Articles ◽  
Multiple Sources ◽  
Study Results ◽  
Meta Analyses

Abstract Background: Adverse events (AEs) in randomized clinical trials may be reported in multiple sources. Different methods for reporting adverse events across trials, or across sources for a single trial, may produce inconsistent and confusing information about the adverse events associated with interventions Methods: We sought to compare the methods authors use to decide which AEs to include in a particular source (i.e., “selection criteria”) and to determine how selection criteria could impact the AEs reported. We compared sources (e.g., journal articles, clinical study reports [CSRs]) of trials for two drug-indications: gabapentin for neuropathic pain and quetiapine for bipolar depression. We identified selection criteria and assessed how criteria affected AE reporting. Results: We identified 21 gabapentin trials and 7 quetiapine trials. All CSRs (6 gabapentin, 2 quetiapine) reported all AEs without applying selection criteria; by comparison, no other source reported all AEs, and 15/68 (22%) gabapentin sources and 19/48 (40%) quetiapine sources reported using selection criteria. Selection criteria greatly affected the number of AEs that would be reported. For example, 67/316 (21%) AEs in one quetiapine trial met the criterion “occurring in ≥2% of participants in any treatment group,” while only 5/316 (2%) AEs met the criterion, “occurring in ≥10% of quetiapine-treated patients and twice as frequent in the quetiapine group as the placebo group.” Conclusions: Selection criteria for reporting AEs vary across trials and across sources for individual trials. If investigators do not pre-specify selection criteria, they might “cherry-pick” AEs based on study results. Even if investigators pre-specify selection criteria, selective reporting of AEs will produce biased meta-analyses and clinical practice guidelines. Data about all AEs identified in clinical trials should be publicly available; however, sharing data will not solve all the problems we identified in this study. Keywords: Harms, adverse events, clinical trials, reporting bias, selective outcome reporting, data sharing, trial registration

scholarly journals Application of Bee Products for Dermatological Problems

2020 ◽  
Vol 7 (1) ◽  
Author(s):  
Heidrun Männle ◽  
Karsten Münstedt
Keyword(s):  
Clinical Trials ◽  
Atopic Dermatitis ◽  
Randomized Clinical Trials ◽  
Case Control ◽  
Health Claims ◽  
Wound Infections ◽  
Herpes Viruses ◽  
Case Control Studies ◽  
Meta Analyses ◽  
Cutaneous Warts

Context: Bee products are frequently suggested as possible treatments for dermatological problems by protagonists of apitherapy, which is a discipline within the field of complementary and alternative medicine. Unfortunately, apitherapists do not support their health claims. This review was to identify potential uses of bee products in the field of dermatology. Evidence Acquisition: Randomized and non-randomized clinical trials, case-control studies, systematic reviews, and meta-analyses on the topics were identified using various search engines. Results: Evidence suggests that bee products may be a reasonable treatment option for wound infections, burns, radiodermatitis, infections with herpes viruses, atopic dermatitis, rosacea, scars, cutaneous warts, acne, psoriasis, facial wrinkles, and intertrigo. Conclusions: There are several applications for bee products in the field of dermatology, for instance treatment of wound infections with honey and herpes infections with propolis.

scholarly journals Vaccines to prevent COVID-19: a protocol for a living systematic review with network meta-analysis including individual patient data (The LIVING VACCINE Project)

2020 ◽  
Vol 9 (1) ◽  
Author(s):  
Steven Kwasi Korang ◽  
Sophie Juul ◽  
Emil Eik Nielsen ◽  
Joshua Feinberg ◽  
Faiza Siddiqui ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Trials ◽  
Randomized Clinical Trials ◽  
Individual Patient Data ◽  
Viral Vector ◽  
Meta Analysis ◽  
Risk Of Bias ◽  
Serious Adverse Events ◽  
Meta Analyses ◽  
Harmful Effects

Abstract Background Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes coronavirus disease 2019 (COVID-19) which has rapidly spread worldwide. Several human randomized clinical trials assessing potential vaccines are currently underway. There is an urgent need for a living systematic review that continuously assesses the beneficial and harmful effects of all available vaccines for COVID-19. Methods/design We will conduct a living systematic review based on searches of major medical databases (e.g., MEDLINE, EMBASE, CENTRAL) and clinical trial registries from their inception onwards to identify relevant randomized clinical trials. We will update the literature search once a week to continuously assess if new evidence is available. Two review authors will independently extract data and conduct risk of bias assessments. We will include randomized clinical trials comparing any vaccine aiming to prevent COVID-19 (including but not limited to messenger RNA; DNA; non-replicating viral vector; replicating viral vector; inactivated virus; protein subunit; dendritic cell; other vaccines) with any comparator (placebo; “active placebo;” no intervention; standard care; an “active” intervention; another vaccine for COVID-19) for participants in all age groups. Primary outcomes will be all-cause mortality; a diagnosis of COVID-19; and serious adverse events. Secondary outcomes will be quality of life and non-serious adverse events. The living systematic review will include aggregate data meta-analyses, trial sequential analyses, network meta-analyses, and individual patient data meta-analyses. Within-study bias will be assessed using Cochrane risk of bias tool. The Grading of Recommendations, Assessment, Development and Evaluations (GRADE) and Confidence in Network Meta-Analysis (CINeMA) approaches will be used to assess certainty of evidence. Observational studies describing harms identified during the search for trials will also be included and described and analyzed separately. Discussion COVID-19 has become a pandemic with substantial mortality. A living systematic review assessing the beneficial and harmful effects of different vaccines is urgently needed. This living systematic review will regularly inform best practice in vaccine prevention and clinical research of this highly prevalent disease. Systematic review registration PROSPERO CRD42020196492

scholarly journals Case Commentary: the Need for Cefiderocol Is Clear, but Are the Supporting Clinical Data?

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Ryan K. Shields
Keyword(s):  
Clinical Trials ◽  
Clinical Practice ◽  
Salvage Therapy ◽  
Randomized Clinical Trials ◽  
Treatment Options ◽  
Multidrug Resistant ◽  
Gram Negative Bacteria ◽  
Potential Utility ◽  
Gram Negative

ABSTRACT Cefiderocol is a newly approved siderophore cephalosporin that demonstrates expanded in vitro activity against multidrug-resistant Gram-negative bacteria. In two challenging cases reported here, cefiderocol shows potential utility as salvage therapy against difficult-to-treat pathogens with limited or no treatment options; however, two multicenter, randomized clinical trials have yielded mixed results among cefiderocol-treated patients. Taken together, clinicians must balance a clear need for cefiderocol in clinical practice with the uncertainties that have stemmed from the available data.

Impact of Peritoneal Dialysis Dose Guidelines on Clinical Outcomes

2005 ◽  
Vol 25 (3_suppl) ◽  
pp. 95-98 ◽  
Author(s):  
David N. Churchill
Keyword(s):  
Clinical Trials ◽  
Peritoneal Dialysis ◽  
Clinical Practice ◽  
Adverse Effects ◽  
Randomized Clinical Trials ◽  
Intervention Group ◽  
The United States ◽  
Dialysis Dose ◽  
Middle Molecules ◽  
The Impact

The objective was to review the rationale for the Kidney Disease Outcomes Quality Initiative (K/DOQI) recommendations for adequacy of peritoneal dialysis and to evaluate the impact of these recommendations on clinical practice and patient survival. The K/DOQI recommendations were based on large observational studies; the target weekly Kt/V value of 2.0 assumed equivalence of peritoneal and renal clearances. This assumption is no longer considered correct. The impact on clinical practice was evaluated by an examination of temporal trends before and after publication of the guidelines in 1997. In the United States and The Netherlands, there had been a trend toward increased delivered total Kt/V prior to 1997, and there was no acceleration in this trend after 1997. Two randomized clinical trials have implemented these guidelines with increased peritoneal Kt/V (or creatinine clearance) used to achieve the K/DOQI target in the intervention group. This was not associated with improved survival, compared to a lower Kt/V, in either of the randomized clinical trials. Among the explanations for the failure to improve outcome are potential adverse effects of increasing the dialysis dose. These include increased intraperitoneal pressure associated with increased exchange volume, failure to increase clearance of middle molecules, and increased exposure to glucose. Strategies that increase peritoneal clearance without exposure to these potential adverse effects include more-frequent exchanges rather than increased exchange volume, and decreased exposure to glucose and glucose degradation products. Pending such studies, current K/DOQI guidelines should be updated in a timely manner.

Placebo and nocebo effects in randomized double-blind clinical trials for fatigue in advanced cancer patients

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. 9640-9640
Author(s):  
M. de la Cruz ◽  
D. Hui ◽  
H. A. Parsons ◽  
P. Lynn ◽  
C. Parker ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Side Effects ◽  
Cancer Patients ◽  
Advanced Cancer ◽  
Randomized Clinical Trials ◽  
Placebo Response ◽  
Well Being ◽  
Advanced Cancer Patients ◽  
Edmonton Symptom Assessment Scale ◽  
Nocebo Effects

9640 Background: We have previously reported significant placebo response in randomized controlled treatment trials for cancer related fatigue (CRF). We conducted a retrospective study to determine the frequency and predictors of response to placebo and nocebo effect in patients with CRF. Methods: We reviewed patients that received placebo in two previous randomized clinical trials conducted by our group and determined the proportion of patients who demonstrated clinical response to fatigue using an increase (ΔFACIT-F score) > 7 from baseline to day 8, and those with nocebo response as those who reported side effects. Baseline patient characteristics and symptoms recorded from the Edmonton Symptom Assessment Scale (ESAS) were analyzed to determine their association with placebo and nocebo effects. Results: A total of 105 advanced cancer patients received placebo. 59 (56%) patients responded to placebo (median Δ FACIT-F score of 22). Worse baseline anxiety and well-being subscale score (univariate) and well-being (multivariate, MR) were significantly associated with placebo response. Common side effects reported were insomnia (79%), anorexia (53%), nausea (38%) and restlessness (34%). MR analysis showed that worse baseline (ESAS) sleep, appetite, nausea, and restless are associated with increased reporting of these side effects ( Table ). Conclusions: Nearly half of advanced cancer patients enrolled in the fatigue trials responded to placebo. Worse physical well-being score was associated with placebo response. Patients experiencing specific symptoms at baseline were more likely to report these as side effects of the medication. These findings should be considered in fatigue clinical trial design. [Table: see text] No significant financial relationships to disclose.

Treatment-related toxicities in patients with squamous cell carcinoma of the head and neck (SCCHN)

2009 ◽  
Vol 27 (15_suppl) ◽  
pp. e17041-e17041
Author(s):  
M. Ulcickas Yood ◽  
P. Feng Wang ◽  
S. Hensley Alford ◽  
S. Oliveria ◽  
K. Wells ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Clinical Trials ◽  
Clinical Practice ◽  
Health System ◽  
Cell Carcinoma ◽  
Head And Neck ◽  
Medical Record ◽  
Squamous Cell ◽  
Real World ◽  
Randomized Clinical Trials

e17041 Background: Although treatment effects and toxicities have been reported from randomized clinical trials of patients with squamous cell carcinoma of the head and neck (SCCHN), little information is available from real-world clinical practice where heterogeneous treatment patterns and patient populations may lead to different estimates than those observed in clinical trials. Methods: Using a population-based tumor registry at a large, Midwestern integrated health system, we identified all cases of stage III or IV SCCHN diagnosed 2000–2006. The incidence/severity of acute and late toxicities associated with SCCHN treatment was obtained from detailed medical record review of health system encounters, including physician notes. Grading of toxicities (using CTCAE3 criteria), distinction between acute and late toxicity, and analyses by treatment are ongoing. The incidence and severity of toxicities will be presented by treatment regimen, tumor location and tumor stage. We presented here an interim analysis. Results: Among the target population of 194 patients that will ultimately be included in this study, 137 medical record reviews have been completed to date. The percentages of patients with toxicities, including 95% confidence intervals are presented in the table , below. Conclusions: Toxicity in patients with advanced SCCHN is common. Data from clinical practice quantifying the incidence are lacking, these data from an observational real-world study provide important baseline information on the incidence of toxicities in patients with advanced SCCHN and also call for safer effective treatment for SCCHN. [Table: see text] [Table: see text]

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