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Molecules (Basel, Switzerland) Apr 2019Zeolites are porous minerals with high absorbency and ion-exchange capacity. Their molecular structure is a dense network of AlO and SiO that generates cavities where... (Review)
Review
Zeolites are porous minerals with high absorbency and ion-exchange capacity. Their molecular structure is a dense network of AlO and SiO that generates cavities where water and other polar molecules or ions are inserted/exchanged. Even though there are several synthetic or natural occurring species of zeolites, the most widespread and studied is the naturally occurring zeolite clinoptilolite (ZC). ZC is an excellent detoxifying, antioxidant and anti-inflammatory agent. As a result, it is been used in many industrial applications ranging from environmental remediation to oral applications/supplementation in vivo in humans as food supplements or medical devices. Moreover, the modification as micronization of ZC (M-ZC) or tribomechanically activated zeolite clinoptilolite (TMAZ) or furthermore as double tribomechanically activated zeolite clinoptilolite (PMA-ZC) allows improving its benefits in preclinical and clinical models. Despite its extensive use, many underlying action mechanisms of ZC in its natural or modified forms are still unclear, especially in humans. The main aim of this review is to shed light on the geochemical aspects and therapeutic potentials of ZC with a vision of endorsing further preclinical and clinical research on zeolites, in specific on the ZC and its modified forms as a potential agent for promoting human brain health and overall well-being.
Topics: Dietary Supplements; Humans; Zeolites
PubMed: 30999685
DOI: 10.3390/molecules24081517 -
American Journal of Obstetrics and... Aug 2020Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in... (Review)
Review
Progesterone is essential for the maintenance of pregnancy. Several small trials have suggested that progesterone supplementation may reduce the risk of miscarriage in women with recurrent or threatened miscarriage. Cochrane Reviews summarized the evidence and found that the trials were small with substantial methodologic weaknesses. Since then, the effects of first-trimester use of vaginal micronized progesterone have been evaluated in 2 large, high-quality, multicenter placebo-controlled trials, one targeting women with unexplained recurrent miscarriages (the PROMISE [PROgesterone in recurrent MIScarriagE] trial) and the other targeting women with early pregnancy bleeding (the PRISM [PRogesterone In Spontaneous Miscarriage] trial). The PROMISE trial studied 836 women from 45 hospitals in the United Kingdom and the Netherlands and found a 3% greater live birth rate with progesterone but with substantial statistical uncertainty. The PRISM trial studied 4153 women from 48 hospitals in the United Kingdom and found a 3% greater live birth rate with progesterone, but with a P value of .08. A key finding, first observed in the PROMISE trial, and then replicated in the PRISM trial, was that treatment with vaginal micronized progesterone 400 mg twice daily was associated with increasing live birth rates according to the number of previous miscarriages. Prespecified PRISM trial subgroup analysis in women with the dual risk factors of previous miscarriage(s) and current pregnancy bleeding fulfilled all 11 conditions for credible subgroup analysis. For the subgroup of women with a history of 1 or more miscarriage(s) and current pregnancy bleeding, the live birth rate was 75% (689/914) with progesterone vs 70% (619/886) with placebo (rate difference 5%; risk ratio, 1.09, 95% confidence interval, 1.03-1.15; P=.003). The benefit was greater for the subgroup of women with 3 or more previous miscarriages and current pregnancy bleeding; live birth rate was 72% (98/137) with progesterone vs 57% (85/148) with placebo (rate difference 15%; risk ratio, 1.28, 95% confidence interval, 1.08-1.51; P=.004). No short-term safety concerns were identified from the PROMISE and PRISM trials. Therefore, women with a history of miscarriage who present with bleeding in early pregnancy may benefit from the use of vaginal micronized progesterone 400 mg twice daily. Women and their care providers should use the findings for shared decision-making.
Topics: Abortion, Habitual; Abortion, Threatened; Administration, Intravaginal; Female; Humans; Pregnancy; Pregnancy Trimester, First; Progesterone; Progestins; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 32008730
DOI: 10.1016/j.ajog.2019.12.006 -
The Cochrane Database of Systematic... Apr 2021Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Miscarriage, defined as the spontaneous loss of a pregnancy before 24 weeks' gestation, is common with approximately 25% of women experiencing a miscarriage in their lifetime, and 15% to 20% of pregnancies ending in a miscarriage. Progesterone has an important role in maintaining a pregnancy, and supplementation with different progestogens in early pregnancy has been attempted to rescue a pregnancy in women with early pregnancy bleeding (threatened miscarriage), and to prevent miscarriages in asymptomatic women who have a history of three or more previous miscarriages (recurrent miscarriage).
OBJECTIVES
To estimate the relative effectiveness and safety profiles for the different progestogen treatments for threatened and recurrent miscarriage, and provide rankings of the available treatments according to their effectiveness, safety, and side-effect profile.
SEARCH METHODS
We searched the following databases up to 15 December 2020: Cochrane Central Register of Controlled Trials, Ovid MEDLINE(R), ClinicalTrials.gov and the WHO International Clinical Trials Registry Platform (ICTRP), and reference lists of retrieved studies.
SELECTION CRITERIA
We included all randomised controlled trials assessing the effectiveness or safety of progestogen treatment for the prevention of miscarriage. Cluster-randomised trials were eligible for inclusion. Randomised trials published only as abstracts were eligible if sufficient information could be retrieved. We excluded quasi- and non-randomised trials.
DATA COLLECTION AND ANALYSIS
At least two review authors independently assessed the trials for inclusion and risk of bias, extracted data and checked them for accuracy. We performed pairwise meta-analyses and indirect comparisons, where possible, to determine the relative effects of all available treatments, but due to the limited number of included studies only direct or indirect comparisons were possible. We estimated the relative effects for the primary outcome of live birth and the secondary outcomes including miscarriage (< 24 weeks of gestation), preterm birth (< 37 weeks of gestation), stillbirth, ectopic pregnancy, congenital abnormalities, and adverse drug events. Relative effects for all outcomes are reported separately by the type of miscarriage (threatened and recurrent miscarriage). We used the GRADE approach to assess the certainty of evidence.
MAIN RESULTS
Our meta-analysis included seven randomised trials involving 5,682 women, and all provided data for meta-analysis. All trials were conducted in hospital settings. Across seven trials (14 treatment arms), the following treatments were used: three arms (21%) used vaginal micronized progesterone; three arms (21%) used dydrogesterone; one arm (7%) used oral micronized progesterone; one arm (7%) used 17-α-hydroxyprogesterone, and six arms (43%) used placebo. Women with threatened miscarriage Based on the relative effects from the pairwise meta-analysis, vaginal micronized progesterone (two trials, 4090 women, risk ratio (RR) 1.03, 95% confidence interval (CI) 1.00 to 1.07, high-certainty evidence), and dydrogesterone (one trial, 406 women, RR 0.98, 95% CI 0.89 to 1.07, moderate-certainty evidence) probably make little or no difference to the live birth rate when compared with placebo for women with threatened miscarriage. No data are available to assess the effectiveness of 17-α-hydroxyprogesterone or oral micronized progesterone for the outcome of live birth in women with threatened miscarriage. The pre-specified subgroup analysis by number of previous miscarriages is only possible for vaginal micronized progesterone in women with threatened miscarriage. In women with no previous miscarriages and early pregnancy bleeding, there is probably little or no improvement in the live birth rate (RR 0.99, 95% CI 0.95 to 1.04, high-certainty evidence) when treated with vaginal micronized progesterone compared to placebo. However, for women with one or more previous miscarriages and early pregnancy bleeding, vaginal micronized progesterone increases the live birth rate compared to placebo (RR 1.08, 95% CI 1.02 to 1.15, high-certainty evidence). Women with recurrent miscarriage Based on the results from one trial (826 women) vaginal micronized progesterone (RR 1.04, 95% CI 0.95 to 1.15, high-certainty evidence) probably makes little or no difference to the live birth rate when compared with placebo for women with recurrent miscarriage. The evidence for dydrogesterone compared with placebo for women with recurrent miscarriage is of very low-certainty evidence, therefore the effects remain unclear. No data are available to assess the effectiveness of 17-α-hydroxyprogesterone or oral micronized progesterone for the outcome of live birth in women with recurrent miscarriage. Additional outcomes All progestogen treatments have a wide range of effects on the other pre-specified outcomes (miscarriage (< 24 weeks of gestation), preterm birth (< 37 weeks of gestation), stillbirth, ectopic pregnancy) in comparison to placebo for both threatened and recurrent miscarriage. Moderate- and low-certainty evidence with a wide range of effects suggests that there is probably no difference in congenital abnormalities and adverse drug events with vaginal micronized progesterone for threatened (congenital abnormalities RR 1.00, 95% CI 0.68 to 1.46, moderate-certainty evidence; adverse drug events RR 1.07 95% CI 0.81 to 1.39, moderate-certainty evidence) or recurrent miscarriage (congenital abnormalities 0.75, 95% CI 0.31 to 1.85, low-certainty evidence; adverse drug events RR 1.46, 95% CI 0.93 to 2.29, moderate-certainty evidence) compared with placebo. There are limited data and very low-certainty evidence on congenital abnormalities and adverse drug events for the other progestogens.
AUTHORS' CONCLUSIONS
The overall available evidence suggests that progestogens probably make little or no difference to live birth rate for women with threatened or recurrent miscarriage. However, vaginal micronized progesterone may increase the live birth rate for women with a history of one or more previous miscarriages and early pregnancy bleeding, with likely no difference in adverse events. There is still uncertainty over the effectiveness and safety of alternative progestogen treatments for threatened and recurrent miscarriage.
Topics: Abortion, Habitual; Abortion, Spontaneous; Bias; Birth Rate; Dydrogesterone; Female; Humans; Hydroxyprogesterones; Live Birth; Network Meta-Analysis; Placebos; Pregnancy; Progesterone; Progestins; Randomized Controlled Trials as Topic; Stillbirth
PubMed: 33872382
DOI: 10.1002/14651858.CD013792.pub2 -
Wounds : a Compendium of Clinical... Jul 2020Compression therapy is the gold standard treatment for venous leg ulcers (VLUs); however, with adjunctive pharmacological therapies and poor patient adherence using... (Review)
Review
Compression therapy is the gold standard treatment for venous leg ulcers (VLUs); however, with adjunctive pharmacological therapies and poor patient adherence using compressive dressings, clinicians are looking to find the advantage in treating VLUs. This literature review focuses on the efficacy of pharmacological agents, quality of life using agents in addition to compression therapy, and cost effectiveness to indicate the best outcomes for pharmacological treatment of VLUs. The following available venotonic, hemorheologic, and fibrinolytic agents were reviewed for oral management in treating VLUs: pentoxifylline, flavonoids (diosmin, hidrosmin, rutosides, and micronized purified flavonoid fraction, Vasculera), Red-Vine-Leaf-Extract AS 195, Ruscus, Ginkgo biloba, Centella asiatica, Pycnogenol (French maritime pine bark), escin/horse chestnut extract, nutritional supplements (ie, zinc and magnesium, glycosaminoglycans [sulodexide], mesoglycans), Axaven, cilostazol, fibrinolytic enhancers (stanozolol and defibrotide), calcium dobesilate, aspirin, antibiotics (antimicrobials, doxycycline, levamisole), diuretics, cinnarizine, naftazone, and benzarone. Venous leg ulcer pharmacological treatment options were searched in the English language from February 2020 to March 2020 using numerous databases and sites, such as PubMed. Drugs used adjunctively with compression therapy that facilitate healing in long-standing or large VLUs include micronized purified flavonoid fraction, pentoxifylline, sulodexide, and mesoglycan.
Topics: Bandages; Fibrinolytic Agents; Humans; Leg Ulcer; Quality of Life; Varicose Ulcer; Wound Healing
PubMed: 33166265
DOI: No ID Found -
Advances in Therapy Jan 2023Hemorrhoidal disease (HD) is characterized by prolapse of the inflamed and bleeding vascular tissues of the anal canal. Although HD is associated with a high recurrence... (Review)
Review
INTRODUCTION
Hemorrhoidal disease (HD) is characterized by prolapse of the inflamed and bleeding vascular tissues of the anal canal. Although HD is associated with a high recurrence rate, there is a lack of understanding around interventions that can reduce recurrence and improve outcomes for patients. As such, a systematic literature review (SLR) was conducted to summarize evidence on epidemiology, recurrence, and efficacy of interventions in HD.
METHODS
Real-world evidence (RWE) studies evaluating the incidence, prevalence, or recurrence of HD, as well as SLRs including a meta-analytic component reporting on the efficacy of systemic or topical pharmacological treatments for adults with HD, were included. Systematic searches were conducted in MEDLINE, Embase, Cumulative Index to Nursing and Allied Health Literature, and the Cochrane Database of Systematic Reviews.
RESULTS
The SLR identified 44 eligible publications. Consistent data were limited on the epidemiology of HD or HD recurrence. Specifically, incidence and prevalence reported across geographies were impacted by differences in data collection. Reported risk factors for HD were sedentary behavior, constipation, male gender, and age. Twenty-three RWE studies and one meta-analysis reported HD recurrence rates ranging from 0 to 56.5% following surgery or phlebotonics, with most (n = 19) reporting rates of 20% or less. In addition to time since treatment, risk factors for recurring disease were similar to those for HD in general. With respect to treatment, micronized purified flavonoid fractions significantly improved the main symptoms of HD compared to other pharmacological treatments.
CONCLUSION
The SLRs did not identify any RWE studies reporting recurrence in patients receiving systemic or topical treatments, highlighting the need for future research in this area. Further, more studies are needed to understand the optimum duration of medical treatment to prevent recurrence.
Topics: Adult; Humans; Male; Flavonoids; Hemorrhage; Hemorrhoids; Risk Factors; Meta-Analysis as Topic
PubMed: 36331754
DOI: 10.1007/s12325-022-02351-7 -
Advances in Therapy Nov 2018This study was conducted to determine the frequency of complaints in a cohort of patients with symptomatic hemorrhoidal disease (HD) treated with micronized purified... (Observational Study)
Observational Study
INTRODUCTION
This study was conducted to determine the frequency of complaints in a cohort of patients with symptomatic hemorrhoidal disease (HD) treated with micronized purified flavonoid fraction (MPFF, Detralex). MPFF was selected for conservative treatment in this population owing to its proven effects on hemorrhoidal symptoms in a large number of patients.
METHODS
This multicenter, non-interventional study was part of the international CHORUS survey (Chronic venous and HemORrhoidal diseases evalUation for improvement of Scientific knowledge), conducted in nine centers in different regions of Russia with the participation of 80 coloproctologists. The study enrolled consecutive patients with complaints of hemorrhoids. All were prescribed MPFF-based conservative treatment. The effect of treatment on HD clinical signs and symptoms was assessed at two follow-up visits performed 5-7 days and 25-30 days after enrollment. Surgical and minimally invasive treatment could be performed from day 7 onwards if required.
RESULTS
A total of 1952 patients were enrolled. Over the entire period of observation, MPFF-based conservative treatment was effective in 1489 (76.3%) patients in eliminating the main clinical manifestations of disease, i.e., bleeding and prolapse of internal nodes. Invasive treatment was performed in 68 (3.5%) patients with grade IV hemorrhoids and was combined with MPFF conservative treatment in 395 (20.2%) patients with grades I-III hemorrhoids.
CONCLUSION
Conservative therapy with MPFF was beneficial for relieving hemorrhoidal symptoms in the majority of patients. MPFF-based treatment was most effective in patients with grade I and II hemorrhoids before irreversible degenerative changes in ligaments of the hemorrhoidal plexuses have occurred. It was also beneficial in preventing disease relapse in patients with more advanced HD and for promoting optimal conditions in the postoperative period.
FUNDING
Servier.
Topics: Adult; Chronic Disease; Conservative Treatment; Diosmin; Drug Combinations; Female; Flavonoids; Hemorrhage; Hemorrhoids; Hesperidin; Humans; Male; Middle Aged; Russia; Secondary Prevention; Severity of Illness Index; Symptom Assessment; Treatment Outcome
PubMed: 30276625
DOI: 10.1007/s12325-018-0794-x -
Biomolecules Aug 2022Increasing evidence strongly supports the key role of neuroinflammation in the pathophysiology of neurodegenerative diseases, such as Alzheimer's disease, frontotemporal... (Review)
Review
Increasing evidence strongly supports the key role of neuroinflammation in the pathophysiology of neurodegenerative diseases, such as Alzheimer's disease, frontotemporal dementia, and amyotrophic lateral sclerosis. Neuroinflammation may alter synaptic transmission contributing to the progression of neurodegeneration, as largely documented in animal models and in patients' studies. In the last few years, palmitoylethanolamide (PEA), an endogenous lipid mediator, and its new composite, which is a formulation constituted of PEA and the well-recognized antioxidant flavonoid luteolin (Lut) subjected to an ultra-micronization process (co-ultraPEALut), has been identified as a potential therapeutic agent in different disorders by exerting potential beneficial effects on neurodegeneration and neuroinflammation by modulating synaptic transmission. In this review, we will show the potential therapeutic effects of PEA in animal models and in patients affected by neurodegenerative disorders.
Topics: Alzheimer Disease; Amides; Animals; Ethanolamines; Neurodegenerative Diseases; Palmitic Acids
PubMed: 36009055
DOI: 10.3390/biom12081161 -
Vascular Health and Risk Management 2021Flavonoids are oral venoactive drugs frequently prescribed to relieve the symptoms of chronic venous disorders (CVD). Among venoactive drugs, diosmin is a naturally... (Review)
Review
Is There a Difference in the Clinical Efficacy of Diosmin and Micronized Purified Flavonoid Fraction for the Treatment of Chronic Venous Disorders? Review of Available Evidence.
Flavonoids are oral venoactive drugs frequently prescribed to relieve the symptoms of chronic venous disorders (CVD). Among venoactive drugs, diosmin is a naturally occurring flavonoid glycoside that can be isolated from various plant sources; it can also be obtained after conversion of hesperidin extracted from citrus rinds. Micronized purified flavonoid fraction (MPFF) is a preparation that contains mainly diosmin and a small fraction of hesperidin. We performed a state-of-the-art literature review to collect and analyze well-conducted randomized clinical studies comparing diosmin - also called non-micronized or hemisynthetic diosmin - 600 mg a day and MPFF, 1000 mg a day. Three clinical studies met the criteria and were included for this literature review. These clinical studies showed a significant decrease of CVD symptom intensity (up to approximately 50%) and global patient satisfaction after one-to-six-month treatment with diosmin or MPFF, without statistical differences between these two forms of diosmin. Both treatments were well tolerated with few mild adverse drug reactions reported. Overall, based on this literature review, there is no clinical benefit to increase the dose of diosmin beyond 600 mg per day, to use the micronized form, or to add hesperidin, since clinical efficacy on venous symptomatology is achieved with 600 mg per day of pure non-micronized diosmin. This challenges the status of diosmin - 600 mg a day - in guidelines for the management of CVD, which is currently categorized 2C (weak recommendations for use and poor quality of evidence), while the most widely used and assessed preparation MPFF is rated 1B (strong recommendation for use and moderate quality of evidence).
Topics: Chronic Disease; Diosmin; Flavonoids; Hesperidin; Humans; Randomized Controlled Trials as Topic; Treatment Outcome; Vascular Diseases; Venous Insufficiency
PubMed: 34556990
DOI: 10.2147/VHRM.S324112 -
Micronized Purified Flavonoid Fraction in Hemorrhoid Disease: A Systematic Review and Meta-Analysis.Advances in Therapy Jun 2020Hemorrhoidal disease (HD) is a common and recurrent problem for many adults worldwide. Venoactive drugs, such as micronized purified flavonoid fraction (MPFF; Daflon),... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
Hemorrhoidal disease (HD) is a common and recurrent problem for many adults worldwide. Venoactive drugs, such as micronized purified flavonoid fraction (MPFF; Daflon), have been used to treat HD and their clinical benefits have been demonstrated in previous meta-analyses of clinical trials. The aim of this study was to evaluate the efficacy of MPFF across the broader spectrum of signs and symptoms following treatment of patients with HD.
METHODS
We performed a systematic review of the literature to identify randomized clinical trials in which MPFF treatment was compared to placebo or no treatment for acute HD or for relief of symptoms after patients had undergone medical management or a surgical procedure to remove hemorrhoids. The main endpoints investigated were bleeding, pain, pruritus, discharge or leakage, and overall improvement. There was no limit on treatment duration.
RESULTS
From 351 unique records retrieved, 11 studies reported in 13 articles were included. On the basis of findings from qualitative analysis, MPFF was reported in most studies to be beneficial in treating bleeding, pain, pruritus, anal discharge/leakage, and tenesmus, and in overall improvement. Quantitative meta-analysis of four studies indicated that MPFF treatment provided significant benefits for bleeding (odds ratio [OR] 0.082, 95% confidence interval [CI] 0.027-0.250; P < 0.001), discharge/leakage (OR 0.12, 95% CI 0.04-0.42; P < 0.001), and overall improvement according to patients (OR 5.25, 95% CI 2.58-10.68; P < 0.001) and investigators (OR 5.51, 95% CI 2.76-11.0; P < 0.001). MPFF also tended to decrease pain (OR 0.11, 95% CI 0.01-1.11; P = 0.06).
CONCLUSION
Taken together, these results suggest that MPFF treatment can improve the most important signs and symptoms of HD.
Topics: Adult; Aged; Aged, 80 and over; Diosmin; Female; Hemorrhoids; Humans; Male; Middle Aged; Odds Ratio; Risk Assessment
PubMed: 32399811
DOI: 10.1007/s12325-020-01353-7