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The Cochrane Database of Systematic... Dec 2020Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer's disease (AD). It has been...
BACKGROUND
Souvenaid is a dietary supplement with a patented composition (Fortasyn Connect™)which is intended to be used by people with Alzheimer's disease (AD). It has been designed to support the formation and function of synapses in the brain, which are thought to be strongly correlated with cognitive function. If effective, it might improve symptoms of Alzheimer's disease and also prevent the progression from prodromal Alzheimer's disease to dementia. We sought in this review to examine the evidence for this proposition.
OBJECTIVES
To assess the effects of Souvenaid on incidence of dementia, cognition, functional performance, and safety in people with Alzheimer's disease.
SEARCH METHODS
We searched ALOIS, i.e. the specialised register of the Cochrane Dementia and Cognitive Improvement Group, MEDLINE (Ovid SP), Embase (Ovid SP), PsycINFO (Ovid SP), Web of Science (ISI Web of Science), Cinahl (EBSCOhost), Lilacs (BIREME), and clinical trials registries up to 24 June 2020. We also reviewed citations of reference lists of landmark papers, reviews, and included studies for additional studies and assessed their suitability for inclusion in the review.
SELECTION CRITERIA
We included randomised, placebo-controlled trials which evaluated Souvenaid in people diagnosed with mild cognitive impairment (MCI) due to AD (also termed prodromal AD) or with dementia due to AD, and with a treatment duration of at least 16 weeks.
DATA COLLECTION AND ANALYSIS
Our primary outcome measures were incidence of dementia, global and specific cognitive function, functional performance, combined cognitive-functional outcomes and adverse events. We selected studies, extracted data, assessed the quality of trials and intended to conduct meta-analyses according to the Cochrane Handbook for Systematic Reviews of Interventions. We rated the quality of the evidence using the GRADE approach. We present all outcomes grouped by stage of AD.
MAIN RESULTS
We included three randomised, placebo-controlled trials investigating Souvenaid in 1097 community-dwelling participants with Alzheimer's disease. One study each included participants with prodromal AD, mild AD dementia and mild-to-moderate AD dementia. We rated the risks of bias of all trials as low. One study (in prodromal AD) was funded by European grants. The other two studies were funded by the manufacturer of Souvenaid. One trial investigated the incidence of dementia in people with prodromal AD at baseline, and found little to no difference between the Souvenaid group and the placebo group after 24 months (RR 1.09, 95% CI 0.82 to 1.43; 1 trial, 311 participants; moderate quality of evidence). In prodromal AD, and in mild and mild-to-moderate Alzheimer's disease dementia, Souvenaid probably results in little or no difference in global or specific cognitive functions (moderate quality of evidence). Everyday function, or the ability to perform activities of daily living, were measured in mild and mild-to-moderate AD dementia. Neither study found evidence of a difference between the groups after 24 weeks of treatment (moderate quality of evidence). Two studies investigated combined cognitive-functional outcomes with the Clinical Dementia Rating Sum of Boxes and observed conflicting results. Souvenaid probably results in slight improvement, which is below estimates of meaningful change, in participants with prodromal Alzheimer's disease after 24 months (moderate quality of evidence), but probably has little to no effect in mild-to-moderate Alzheimer's disease dementia after 24 weeks (moderate quality of evidence). Adverse effects observed were low in all trials, and the available data were insufficient to determine any connection with Souvenaid.
AUTHORS' CONCLUSIONS
Two years of treatment with Souvenaid probably does not reduce the risk of progression to dementia in people with prodromal AD. There is no convincing evidence that Souvenaid affects other outcomes important to people with AD in the prodromal stage or mild-to-moderate stages of dementia. Conflicting evidence on combined cognitive-functional outcomes in prodromal AD and mild AD dementia warrants further investigation. Adverse effects of Souvenaid seem to be uncommon, but the evidence synthesised in this review does not permit us to make a definitive statement on the long-term tolerability of Souvenaid. The effects of Souvenaid in more severe AD dementia or in people with AD at risk of nutritional deficiencies remain unclear.
Topics: Alzheimer Disease; Bias; Cognition; Dementia; Dietary Supplements; Disease Progression; Docosahexaenoic Acids; Eicosapentaenoic Acid; Humans; Phospholipids; Placebos; Prodromal Symptoms; Randomized Controlled Trials as Topic; Time Factors
PubMed: 33320335
DOI: 10.1002/14651858.CD011679.pub2 -
Talanta Feb 2021Stimulated by the increased recognition of phosphatidylethanol (PEth) as sensitive direct marker of alcohol intake, the Ghent University's Laboratory of Toxicology and...
BACKGROUND
Stimulated by the increased recognition of phosphatidylethanol (PEth) as sensitive direct marker of alcohol intake, the Ghent University's Laboratory of Toxicology and the National Institute of Criminalistics and Criminology combined their efforts to develop a quantitative method. To facilitate implementation the focus was on the use of a sampling technique which allows quick and easy blood collection, without the need of dedicated personnel at any place/any time. In the meantime the cooperation of the two labs should also allow to initiate a Belgian network of laboratories capable of quantifying PEth.
METHODS
Dried blood microsamples were collected via volumetric absorptive microsampling (VAMS). PEth 16:0/18:1 was quantified after liquid-liquid extraction using two independent isotope dilution - liquid chromatography - tandem mass spectrometry methods. A systematic review of the entire process at both sites was performed before the final method comparison using samples from 59 routine toxicology cases collected within a one-year time interval.
RESULTS
Initial differences between both laboratories were solved by focusing on important methodological aspects: (i) trueness verification of the calibration protocol focusing on the primary material, preparation of the stock solutions and adequate equilibration of calibrators and QCs, and (ii) verification of comparability of results obtained with different m/z transitions. Several of these aspects could only be verified by critically assessing spiked and native samples. After a final validation good average comparability of the two methods was observed. The average bias was -0.4%, with 85% of the differences within 20%. Moreover, the methods proved to be reproducible and robust within a one-year time interval.
CONCLUSION
This study is the first to develop a quantitative volumetric absorptive microsampling based method for PEth measurements, in addition it is the first to perform a systematic comparison of PEth measurements between two laboratories. From the discussion on the encountered pitfalls it is clear that also on a global scale, more efforts are needed to improve interlaboratory agreement.
Topics: Chromatography, Liquid; Dried Blood Spot Testing; Glycerophospholipids; Humans; Tandem Mass Spectrometry
PubMed: 33303146
DOI: 10.1016/j.talanta.2020.121694 -
World Journal of Clinical Cases Nov 2020Essential phospholipids (EPL) are used for the supportive treatment of non-alcoholic fatty liver disease (NAFLD), but data are mostly from small-scale studies.
BACKGROUND
Essential phospholipids (EPL) are used for the supportive treatment of non-alcoholic fatty liver disease (NAFLD), but data are mostly from small-scale studies.
AIM
To evaluate the efficacy of EPL treatment in adult patients with NAFLD and type 2 diabetes and/or obesity.
METHODS
The MEDLINE, PubMed, Embase, and Cochrane databases were searched up to March 2019 for clinical trials and comparative observational studies. Eligible studies were those published in English or Chinese that enrolled adult patients (≥ 18 years) with NAFLD and type 2 diabetes mellitus and/or obesity receiving EPL as monotherapy or as add-on therapy to existing therapy, and that included at least one of the efficacy outcomes of interest. A variety of studies were identified; thus, direct, indirect and cohort meta-analyses were performed. Mean difference (MD) and 95% confidence interval (CI) were calculated for continuous variables, and relative risk with 95%CI for disease response and recovery. A random-effects model was used to address between-study heterogeneity.
RESULTS
Ten studies met the inclusion criteria ( = 22-324). EPL treatment duration ranged from 4 to 72 wk. In the direct meta-analysis (four randomized controlled trials), compared with antidiabetic therapy alone, EPL plus antidiabetic therapy was associated with a significantly greater reduction in [alanine aminotransferase (ALT); MD: 11.28 U/L (95%CI: -17.33, -5.23), = 0.0003], triglyceride [MD: -49.33 mg/dL (95%CI: -66.43, -32.23), < 0.0001] and total cholesterol levels [MD: -29.74 mg/dL (95%CI: -38.02, -21.45), < 0.0001]. There was also a significant increase in the rate of overall improvement [relative risk 1.50 (95%CI: 1.26-1.79), < 0.0001], and risk of no disease ( = 0.0091), and a reduction in moderate disease ( = 0.0187); there were no significant differences in severe disease, mild disease, or significant improvement. In the cohort meta-analysis of three non-randomized clinical trials, the MD in ALT levels was -16.71 U/L (95%CI: -24.94, -8.49) and 23% of patients had improved disease. In the cohort meta-analysis of five randomized trials, MD in ALT levels was -28.53 U/L (95%CI: -35.42, -21.65), and 87% (95%CI: 81%, 93%) and 58% (95%CI: 46%, 70%) of patients showed clinical improvement and significant clinical improvement.
CONCLUSION
This analysis provides evidence for a benefit of EPL in patients with NAFLD and diabetes and/or obesity. Further large-scale trials are warranted.
PubMed: 33269259
DOI: 10.12998/wjcc.v8.i21.5235 -
Acta Endocrinologica (Bucharest,... 2020The aim of the present study was to systematically review the effects of Realsil (silybin-phospholipid-vitamin E complex) on liver enzymes in patients with NAFLD or NASH. (Review)
Review
THE EFFECTS OF REALSIL (SILYBIN-PHOSPHOLIPID-VITAMIN E COMPLEX) ON LIVER ENZYMES IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE (NAFLD) OR NON-ALCOHOLIC STEATO-HEPATITIS (NASH): A SYSTEMATIC REVIEW AND META-ANALYSIS OF RCTS.
BACKGROUND
The aim of the present study was to systematically review the effects of Realsil (silybin-phospholipid-vitamin E complex) on liver enzymes in patients with NAFLD or NASH.
METHODS
We searched Web of Science, MEDLINE, Google Scholar, Cochrane Library, Science Direct, ProQuest, Scopus, and 1868 articles were found up to December 2018. Four studies that examined the effect of Realsil intake on liver enzymes among NAFLD or NASH patients were included. Exclusion criteria include: animal studies, studies with the design other than clinical trials, studies on non-adult individuals, studies that assess the effect of vitamin E, silybin, or phospholipid solely, studies that examined the effect of Realsil on other outcomes, or studies with insufficient data.
RESULTS
The analysis demonstrated that Realsil intake led to a significant decrease in Gamma-Glutamyl Transpeptidase (GGT) levels (standardized mean difference (SMD) =-0.37; 95% confidence interval (CI]): -0.68 to -0.06). Realsil intake non-significantly decrease alanine transaminase (ALT) levels (SMD=-1.02 U/L; 95% CI: -2.23 to 0.20) and non-significantly increase aspartate aminotransferase (AST) levels (SMD = 0.17 U/L; 95% CI: -0.26-0.61).
CONCLUSION
Realsil intake was associated with a significantly decreased circulating GGT level without any significant effect on AST and ALT levels.
PubMed: 33029240
DOI: 10.4183/aeb.2020.223 -
International Journal of Molecular... Aug 2020The usefulness of polyunsaturated fatty acids on inflammatory, cardiovascular, and the nervous system was studied in the last decades, but the mechanisms underlying...
The usefulness of polyunsaturated fatty acids on inflammatory, cardiovascular, and the nervous system was studied in the last decades, but the mechanisms underlying their benefic properties are still partially unknown. These agents seem to express their action on the membrane phospholipid composition and permeability and modulation of second messenger cascades. In psychiatry, the efficacy and tolerability of omega-3 fatty acids were investigated in several psychiatric disorders, including major depression, bipolar disorder, personality disorders, high-risk conditions to develop psychosis, attention-deficit hyperactivity disorder, and autism spectrum disorders. Initial findings in this field are promising, and some relevant questions need to be addressed. In particular, the effects of these agents on the main symptom dimensions have to be investigated in a trans-diagnostic perspective. The present systematic review is aimed to examine the available data on the efficacy of omega-3 fatty acids on domains of psychotic symptoms, affective symptoms, impulsivity, and aggressiveness, and harmful behaviors, and suicide risk.
Topics: Affective Symptoms; Antipsychotic Agents; Attention Deficit Disorder with Hyperactivity; Autism Spectrum Disorder; Bipolar Disorder; Depressive Disorder, Major; Dietary Supplements; Fatty Acids, Omega-3; Humans; Personality Disorders; Psychopathology; Psychotic Disorders; Randomized Controlled Trials as Topic; Suicidal Ideation
PubMed: 32839416
DOI: 10.3390/ijms21176042 -
Medicina (Kaunas, Lithuania) Aug 2020Liposomal structures are artificial vesicles composed of one or several lamellae of phospholipids which surround an inner aqueous core. Given the amphoteric nature of...
Liposomal structures are artificial vesicles composed of one or several lamellae of phospholipids which surround an inner aqueous core. Given the amphoteric nature of phospholipids, liposomes are promising systems for drug delivery. The present review provides an updated synthesis of the main techniques for the production of liposomes for orthopedic applications, focusing on the drawbacks of the conventional methods and on the advantages of high pressure techniques. Articles published in any language were systematically retrieved from two major electronic scholarly databases (PubMed/MEDLINE and Scopus) up to March 2020. Nine articles were retained based on the "Preferred Reporting Items for Systematic Reviews and Meta-Analyses" (PRISMA) guidelines. Liposome vesicles decrease the rate of inflammatory reactions after local injections, and significantly enhance the clinical effectiveness of anti-inflammatory agents providing controlled drug release, reducing toxic side effects. This review presents an update on the improvement in musculoskeletal ailments using liposome treatment.
Topics: Analgesics; Anti-Inflammatory Agents; Humans; Injections, Intra-Articular; Liposomes; Nanoparticles; Orthopedic Procedures; Orthopedics; Osteoarthritis; Osteomyelitis; Pain, Postoperative
PubMed: 32825518
DOI: 10.3390/medicina56090423 -
Pharmaceuticals (Basel, Switzerland) May 2020Epilepsy is a serious neurological disorder affecting around 70 million people globally and is characterized by spontaneous recurrent seizures. Recent evidence indicates... (Review)
Review
Epilepsy is a serious neurological disorder affecting around 70 million people globally and is characterized by spontaneous recurrent seizures. Recent evidence indicates that dysfunction in metabolic processes can lead to the alteration of neuronal and network excitability, thereby contributing to epileptogenesis. Developing a suitable animal model that can recapitulate all the clinical phenotypes of human metabolic epilepsy (ME) is crucial yet challenging. The specific environment of many symptoms as well as the primary state of the applicable neurobiology, genetics, and lack of valid biomarkers/diagnostic tests are the key factors that hinder the process of developing a suitable animal model. The present systematic review summarizes the current state of available animal models of metabolic dysfunction associated with epileptic disorders. A systematic search was performed by using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) model. A range of electronic databases, including google scholar, Springer, PubMed, ScienceDirect, and Scopus, were scanned between January 2000 and April 2020. Based on the selection criteria, 23 eligible articles were chosen and are discussed in the current review. Critical analysis of the selected literature delineated several available approaches that have been modeled into metabolic epilepsy and pointed out several drawbacks associated with the currently available models. The result describes available models of metabolic dysfunction associated with epileptic disorder, such as mitochondrial respiration deficits, Lafora disease (LD) model-altered glycogen metabolism, causing epilepsy, glucose transporter 1 (GLUT1) deficiency, adiponectin responsive seizures, phospholipid dysfunction, glutaric aciduria, mitochondrial disorders, pyruvate dehydrogenase (PDH) α-subunit gene (PDHA1), pyridoxine dependent epilepsy (PDE), BCL2-associated agonist of cell death (BAD), Kcna1 knock out (KO), and long noncoding RNAs (lncRNA) cancer susceptibility candidate 2 (lncRNA CASC2). Finally, the review highlights certain focus areas that may increase the possibilities of developing more suitable animal models and underscores the importance of the rationalization of animal models and evaluation methods for studying ME. The review also suggests the pressing need of developing precise robust animal models and evaluation methods for investigating ME.
PubMed: 32466498
DOI: 10.3390/ph13060106 -
International Journal of Surgery Case... 2020Mesenteric artery re-vascularization using bypass or angioplasty is a standard of care in atherosclerotic mesenteric vascular disease. However, there are no certain...
INTRODUCTION
Mesenteric artery re-vascularization using bypass or angioplasty is a standard of care in atherosclerotic mesenteric vascular disease. However, there are no certain guidelines for the management of non-atherosclerotic thrombophilic mesenteric vessel disease other than anti-coagulation.
CASE REPORT
We are reporting a case of a 36 years old lady with post-prandial angina and weight loss on the background of anti-phospholipid syndrome having tripple mesentric vessel occlusive disease who underwent 2 vessel aorto-mesenteric bypass. During the post-op course, patient had laparotomy with diversion ileostomy for ischemic perforation of the bowel. At present, after 6 weeks patient is recovering well with improved appetite and resolution of symptoms.
DISCUSSION
There are very few cases reported with acute on chronic mesenteric ischemia in England. Nikolas Melas et al. reported similar history in a 57 yrs old Caucasian female. Morbi AH2 highlights timely diagnosis of acute mesmeric ischemia in a 53 yrs old.
CONCLUSION
This case report is unique in a way that combined mesenteric ischemia and APS is a rare combination in a 36 years old. Mesenteric artery bypass is one of the possible solutions to thrombophilic mesenteric disease, however larger studies with longer follow up are needed.
PubMed: 32446211
DOI: 10.1016/j.ijscr.2020.04.033 -
The Cochrane Database of Systematic... Apr 2020Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. This is... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Studies suggest that a diet rich in omega-3 essential fatty acids may have beneficial anti-inflammatory effects for chronic conditions such as cystic fibrosis. This is an updated version of a previously published review.
OBJECTIVES
To determine whether there is evidence that omega-3 polyunsaturated fatty acid supplementation reduces morbidity and mortality and to identify any adverse events associated with supplementation.
SEARCH METHODS
We searched the Cochrane Cystic Fibrosis and Genetic Disorders Group's Trials Register comprising references identified from comprehensive electronic database searches and handsearches of relevant journals and abstract books of conference proceedings. Date of last search: 01 April 2020. We also searched online study registries and contacted authors. Date of last search: 12 February 2020.
SELECTION CRITERIA
Randomised controlled trials in people with cystic fibrosis comparing omega-3 fatty acid supplements with placebo.
DATA COLLECTION AND ANALYSIS
Two authors independently selected studies for inclusion, extracted data and assessed the risk of bias of the studies. The quality of the evidence was assessed using GRADE.
MAIN RESULTS
The searches identified 23 studies; five studies with 106 participants (children and adults) were included; duration of studies and interventions differed. Two studies compared omega-3 fatty acids to olive oil for six weeks; one study compared omega-3 fatty acids and omega-6 fatty acids to control capsules (customised fatty acid blends) for three months; one study compared a liquid dietary supplement containing omega-3 fatty acids to one without for six months; and one study compared omega-3 fatty acids to a placebo for 12 months. Three studies had a low risk of bias for randomisation, but the risk was unclear in the remaining two studies; all studies had an unclear risk of bias for allocation concealment. Three of the studies adequately blinded participants; the risk of bias for selective reporting was high in one study and unclear for four studies. Two studies reported the number of respiratory exacerbations. At three months, one study (43 participants) reported no change in antibiotic usage. At 12 months the second study (15 participants) reported a reduction in the number of pulmonary exacerbations and cumulative antibiotic days in the supplement group compared to the previous year (no data for the control group); very low-quality evidence means we are unsure whether supplementation has any effect on this outcome. With regards to adverse events, one six-week study (12 participants) reported no difference in diarrhoea between omega-3 or placebo capsules; the very low-quality evidence means we are unsure if supplementation has any effect on this outcome. Additionally, one study reported an increase in steatorrhoea requiring participants to increase their daily dose of pancreatic enzymes, but three studies had already increased pancreatic enzyme dose at study begin so as to reduce the incidence of steatorrhoea. One study (43 participants) reported stomach pains at three months (treatment or control group not specified). One six-week study (19 participants) reported three asthma exacerbations leading to exclusion of participants since corticosteroid treatment could affect affect essential fatty acid metabolism. Four studies reported lung function. One six-week study (19 participants) reported an increase in forced expiratory volume in one second (FEV) (L) and forced vital capacity (FVC) (L), but the very low-quality evidence means we are unsure if supplementation has any effect on lung function. The remaining studies did not report any difference in lung function at three months (unit of measurement not specified) or at six months and one year (FEV % predicted and FVC % predicted). No deaths were reported in any of the five studies. Four studies reported clinical variables. One study reported an increase in Schwachman score and weight alongside a reduction in sputum volume with supplementation compared to placebo at three months (data not analysable). However, three studies reported no differences in either weight at six weeks, in body mass index (BMI) standard deviation (SD) score at six months (very low-quality evidence) or BMI Z score at 12 months. Three studies reported biochemical markers of fatty acid status. One study showed an increase from baseline in both EPA and DHA content of serum phospholipids in the omega-3 group compared to placebo at three months and also a significant decrease in n-6/n-3 ratio in the supplement group compared to placebo; since the quality of the evidence is very low we are not certain that these changes are due to supplementation. One six-month cross-over study showed a higher EPA content of the neutrophil membrane in the supplement group compared to the placebo group, but, no difference in DHA membrane concentration. Furthermore, the leukotriene B to leukotriene B ratio was lower at six months in the omega-3 group compared to placebo. A one-year study reported a greater increase in the essential fatty acid profile and a decrease in AA levels in the treatment arm compared to placebo.
AUTHORS' CONCLUSIONS
This review found that regular omega-3 supplements may provide some limited benefits for people with cystic fibrosis with relatively few adverse effects: however, the quality of the evidence across all outcomes was very low. The current evidence is insufficient to draw firm conclusions or recommend routine use of these supplements in people with cystic fibrosis. A large, long-term, multicentre, randomised controlled study is needed to determine any significant therapeutic effect and to assess the influence of disease severity, dosage and duration of treatment. Future researchers should note the need for additional pancreatic enzymes when providing omega-3 supplementation or olive oil placebo capsules. More research is required to determine the exact dose of pancreatic enzyme required.
Topics: Adult; Bias; Child; Cystic Fibrosis; Dietary Supplements; Disease Progression; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Forced Expiratory Volume; Humans; Olive Oil; Randomized Controlled Trials as Topic; Vital Capacity
PubMed: 32275788
DOI: 10.1002/14651858.CD002201.pub6 -
Journal of Perinatology : Official... Aug 2020Findings from previous meta-analyses of randomized clinical trials (RCTs) in premature infants with respiratory distress syndrome (RDS) varied as to whether clinical... (Review)
Review
Beractant and poractant alfa in premature neonates with respiratory distress syndrome: a systematic review of real-world evidence studies and randomized controlled trials.
Findings from previous meta-analyses of randomized clinical trials (RCTs) in premature infants with respiratory distress syndrome (RDS) varied as to whether clinical outcomes differed by type of animal-derived pulmonary surfactant; real-world evidence (RWE) was excluded. We extracted study characteristics and outcomes from full-text articles from a systematic search for studies that compared beractant with poractant alfa for RDS in preterm infants. RWE data were tabulated; RCT data were subjected to meta-analyses. Designs, patient characteristics, and follow-up durations varied widely among studies (4 RWE, 15 RCT). RWE studies with adjusted odds ratios (ORs) found no statistically significant between-treatment differences in outcomes. In RCT meta-analyses, no statistically significant between-treatment differences were observed for death (OR [95% confidence interval], 1.35 [0.98-1.86]), bronchopulmonary dysplasia (1.25 [0.96-1.62]), pneumothorax (1.21 [0.72-2.05]), and air leak syndrome (2.28 [0.82-6.39]). Collectively, outcomes were similar with beractant and poractant alfa in RWE studies and pooled RCTs.
Topics: Animals; Biological Products; Humans; Infant, Newborn; Phospholipids; Randomized Controlled Trials as Topic; Respiratory Distress Syndrome, Newborn
PubMed: 32051542
DOI: 10.1038/s41372-020-0603-7