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Frontiers in Psychiatry 2021Alterations in the peripheral (e.g., serum, plasma, platelet) concentrations of arginine and its related catabolic products (i.e., ornithine, citrulline) in the urea and...
Alterations in the peripheral (e.g., serum, plasma, platelet) concentrations of arginine and its related catabolic products (i.e., ornithine, citrulline) in the urea and nitric oxide cycles have been reported to be associated with major depressive disorder (MDD). The meta-analysis herein aimed to explore the association between the concentration of peripheral arginine, its catabolic products and MDD, as well as to discuss the possible role of arginine catabolism in the onset and progression of MDD. PubMed, EMBASE, PsycINFO and Web of Science were searched from inception to June 2020. The protocol for the meta-analysis herein has been registered at the Open Science Framework [https://doi.org/10.17605/osf.io/7fn59]. In total, 745 (47.5%) subjects with MDD and 823 (52.5%) healthy controls (HCs) from 13 articles with 16 studies were included. Fifteen of the included studies assessed concentrations of peripheral arginine, eight assessed concentrations of ornithine, and six assessed concentrations of citrulline. Results indicated that: (1) the concentrations of arginine, ornithine, and citrulline were not significantly different between individuals with MDD and HCs when serum, plasma and platelet are analyzed together, (2) in the subgroups of serum samples, the concentrations of arginine were lower in individuals with MDD than HCs, and (3) concurrent administration of psychotropic medications may be a confounding variable affecting the concentrations of arginine, ornithine, and citrulline. Our findings herein do not support the hypothesis that arginine catabolism between individuals with MDD and HCs are significantly different. The medication status and sample types should be considered as a key future research avenue for assessing arginine catabolism in MDD.
PubMed: 34867503
DOI: 10.3389/fpsyt.2021.686973 -
The Cochrane Database of Systematic... 2014With burn injuries involving a large total body surface area (TBSA), the body can enter a state of breakdown, resulting in a condition similar to that seen with severe... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
With burn injuries involving a large total body surface area (TBSA), the body can enter a state of breakdown, resulting in a condition similar to that seen with severe lack of proper nutrition. In addition, destruction of the effective skin barrier leads to loss of normal body temperature regulation and increased risk of infection and fluid loss. Nutritional support is common in the management of severe burn injury, and the approach of altering immune system activity with specific nutrients is termed immunonutrition. Three potential targets have been identified for immunonutrition: mucosal barrier function, cellular defence and local or systemic inflammation. The nutrients most often used for immunonutrition are glutamine, arginine, branched-chain amino acids (BCAAs), omega-3 (n-3) fatty acids and nucleotides.
OBJECTIVES
To assess the effects of a diet with added immunonutrients (glutamine, arginine, BCAAs, n-3 fatty acids (fish oil), combined immunonutrients or precursors to known immunonutrients) versus an isonitrogenous diet (a diet wherein the overall protein content is held constant, but individual constituents may be changed) on clinical outcomes in patients with severe burn injury.
SEARCH METHODS
The search was run on 12 August 2012. We searched the Cochrane Injuries Group's Specialised Register, The Cochrane Library, MEDLINE (OvidSP), Embase (OvidSP), ISI WOS SCI-EXPANDED & CPCI-S and four other databases. We handsearched relevant journals and conference proceedings, screened reference lists and contacted pharmaceutical companies. We updated this search in October 2014, but the results of this updated search have not yet been incorporated.
SELECTION CRITERIA
Randomised controlled trials comparing the addition of immunonutrients to a standard nutritional regimen versus an isonitrogenated diet or another immunonutrient agent.
DATA COLLECTION AND ANALYSIS
Two review authors were responsible for handsearching, reviewing electronic search results and identifying potentially eligible studies. Three review authors retrieved and reviewed independently full reports of these studies for inclusion. They resolved differences by discussion. Two review authors independently extracted and entered data from the included studies. A third review author checked these data. Two review authors independently assessed the risk of bias of each included study and resolved disagreements through discussion or consultation with the third and fourth review authors. Outcome measures of interest were mortality, hospital length of stay, rate of burn wound infection and rate of non-wound infection (bacteraemia, pneumonia and urinary tract infection).
MAIN RESULTS
We identified 16 trials involving 678 people that met the inclusion criteria. A total of 16 trials contributed data to the analysis. Of note, most studies failed to report on randomisation methods and intention-to-treat principles; therefore study results should be interpreted with caution. Glutamine was the most common immunonutrient and was given in seven of the 16 included studies. Use of glutamine compared with an isonitrogenous control led to a reduction in length of hospital stay (mean stay -5.65 days, 95% confidence interval (CI) -8.09 to -3.22) and reduced mortality (pooled risk ratio (RR) 0.25, 95% CI 0.08 to 0.78). However, because of the small sample size, it is likely that these results reflect a false-positive effect. No study findings suggest that glutamine has an effect on burn wound infection or on non-wound infection. All other agents investigated showed no evidence of an effect on mortality, length of stay or burn wound infection or non-wound infection rates.
AUTHORS' CONCLUSIONS
Although we found evidence of an effect of glutamine on mortality reduction, this finding should be taken with care. The number of study participants analysed in this systematic review was not sufficient to permit conclusions that recommend or refute the use of glutamine. Glutamine may be effective in reducing mortality, but larger studies are needed to determine the overall effects of glutamine and other immunonutrition agents.
Topics: Amino Acids, Branched-Chain; Burns; Fatty Acids, Omega-3; Glutamine; Humans; Length of Stay; Malnutrition; Nutrition Therapy; Ornithine; Randomized Controlled Trials as Topic; Soybean Proteins; Vitamins; Wound Infection
PubMed: 25536183
DOI: 10.1002/14651858.CD007174.pub2 -
Clinical and Experimental Hepatology Jun 2023Patients with minimal hepatic encephalopathy (MHE) have no recognizable clinical symptoms of hepatic encephalopathy (HE), but the mild cognitive and psychomotor deficits...
AIM OF THE STUDY
Patients with minimal hepatic encephalopathy (MHE) have no recognizable clinical symptoms of hepatic encephalopathy (HE), but the mild cognitive and psychomotor deficits have been shown to negatively affect their daily functioning and quality of life. Treatment with probiotics has shown benefit in some clinical trials. This review aimed to systematically analyze the efficacy of probiotics in the treatment of MHE.
MATERIAL AND METHODS
A systematic search of the electronic databases PubMed, Science Direct, and Cochrane Library was conducted for randomized controlled trials (RCTs) in adult patients with MHE who had been given probiotics intervention. The primary outcomes were reversal of MHE and improvement of neuropsychometric tests, while the secondary outcome was the reduction of serum ammonia.
RESULTS
Nine RCTs involving 776 MHE patients were included, consisting of 311 patients receiving probiotics and 465 patients receiving comparator (placebo or no treatment, lactulose, L-ornithine L-aspartate [LOLA], or rifaximin). The meta-analysis showed that probiotics significantly reversed MHE (OR = 3.95, < 0.0001, 95% CI: 2.05 to 7.60) compared with placebo or no treatment. Probiotics also significantly reduced serum ammonia compared with placebo (pooled mean difference -25.94, = 0.04, 95% CI: -50.21 to -1.66). However when compared to lactulose and LOLA, probiotics did not show a significant difference in reversal of MHE or reduction of serum ammonia levels.
CONCLUSIONS
Probiotics were more effective in reversal of MHE and reduced serum ammonia levels in patients with MHE compared to placebo or no treatment, but not more effective than lactulose or LOLA.
PubMed: 37502435
DOI: 10.5114/ceh.2023.128768 -
Neuropsychopharmacology Reports Mar 2022Metabolomics has been attracting attention in recent years as an objective method for diagnosing schizophrenia. In this study, we analyzed 378 metabolites in the serum...
Searching for biomarkers in schizophrenia and psychosis: Case-control study using capillary electrophoresis and liquid chromatography time-of-flight mass spectrometry and systematic review for biofluid metabolites.
Metabolomics has been attracting attention in recent years as an objective method for diagnosing schizophrenia. In this study, we analyzed 378 metabolites in the serum of schizophrenia patients using capillary electrophoresis- and liquid chromatography-time-of-flight mass spectrometry. Using multivariate analysis with the orthogonal partial least squares method, we observed significantly higher levels of alanine, glutamate, lactic acid, ornithine, and serine and significantly lower levels of urea, in patients with chronic schizophrenia compared to healthy controls. Additionally, levels of fatty acids (15:0), (17:0), and (19:1), cis-11-eicosenoic acid, and thyroxine were significantly higher in patients with acute psychosis than in those in remission. Moreover, we conducted a systematic review of comprehensive metabolomics studies on schizophrenia over the last 20 years and observed consistent trends of increase in some metabolites such as glutamate and glucose, and decrease in citrate in schizophrenia patients across several studies. Hence, we provide substantial evidence for metabolic biomarkers in schizophrenia patients through our metabolomics study.
Topics: Biomarkers; Case-Control Studies; Chromatography, Liquid; Electrophoresis, Capillary; Humans; Mass Spectrometry; Psychotic Disorders; Schizophrenia
PubMed: 34889082
DOI: 10.1002/npr2.12223 -
Cells Mar 2023Chronic obstructive pulmonary disease (COPD), as the third leading cause of death among adults, is a significant public health problem around the world. However, about... (Review)
Review
Chronic obstructive pulmonary disease (COPD), as the third leading cause of death among adults, is a significant public health problem around the world. However, about 75% of smokers do not develop the disease despite the severe smoking burden. COPD is a heterogeneous disease, and several phenotypes, with differences in their clinical picture and response to treatment, have been distinguished. Metabolomic studies provide information on metabolic pathways, and therefore are a promising tool for understanding disease etiopathogenesis and the development of effective causal treatment. The aim of this systematic review was to analyze the metabolome of the respiratory epithelial lining fluid of patients with COPD, compared to healthy volunteers, refractory smokers, and subjects with other lung diseases. We included observational human studies. Sphingolipids, phosphatidylethanolamines, and sphingomyelins distinguished COPD from non-smokers; volatile organic compounds, lipids, and amino acids distinguished COPD from smokers without the disease. Five volatile organic compounds were correlated with eosinophilia and four were associated with a phenotype with frequent exacerbations. Fatty acids and ornithine metabolism were correlated with the severity of COPD. Metabolomics, by searching for biomarkers and distinguishing metabolic pathways, can allow us to understand the pathophysiology of COPD and the development of its phenotypes.
Topics: Adult; Humans; Volatile Organic Compounds; Pulmonary Disease, Chronic Obstructive; Metabolomics; Smoking; Metabolome
PubMed: 36980173
DOI: 10.3390/cells12060833 -
The Cochrane Database of Systematic... May 2018Hepatic encephalopathy is a common complication of cirrhosis and has high associated morbidity and mortality. The condition is classified as overt if it is clinically... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hepatic encephalopathy is a common complication of cirrhosis and has high associated morbidity and mortality. The condition is classified as overt if it is clinically apparent or minimal if only evident though psychometric testing. The exact pathogenesis of this syndrome is unknown although ammonia is thought to play a key role. L-ornithine L-aspartate has ammonia-lowering properties and may, therefore, benefit people with cirrhosis and hepatic encephalopathy.
OBJECTIVES
To evaluate the beneficial and harmful effects of L-ornithine L-aspartate versus placebo, no intervention, or other active interventions in people with cirrhosis and hepatic encephalopathy.
SEARCH METHODS
We undertook electronic searches of The Cochrane Hepato-Biliary Group Controlled Trials Register, CENTRAL, MEDLINE, Embase, LILACS and Science Citation Index Expanded to December 2017 and manual searches of meetings and conference proceedings; checks of bibliographies; and corresponded with investigators and pharmaceutical companies.
SELECTION CRITERIA
We included randomised clinical trials, irrespective of publication status, language, or blinding. We included participants with cirrhosis who had minimal or overt hepatic encephalopathy or who were at risk for developing hepatic encephalopathy. We compared: L-ornithine L-aspartate versus placebo or no intervention; and L-ornithine L-aspartate versus other active agents such as non-absorbable disaccharides, antibiotics, probiotics, or branched-chain amino acids.
DATA COLLECTION AND ANALYSIS
Two review authors, working independently, retrieved data from published reports and correspondence with investigators and pharmaceutical companies. The primary outcomes were mortality, hepatic encephalopathy, and serious adverse events. We undertook meta-analyses and presented the results as risk ratios (RR) and mean differences (MD) with 95% confidence intervals (CI). We assessed bias control using the Cochrane Hepato-Biliary Group domains; we evaluated the risk of publication bias and other small trial effects in regression analyses; conducted subgroup and sensitivity analyses; and performed Trial Sequential Analyses. We determined the quality of the evidence using GRADE.
MAIN RESULTS
We identified 36 randomised clinical trials, involving at least 2377 registered participants, which fulfilled our inclusion criteria including 10 unpublished randomised clinical trials. However, we were only able to access outcome data from 29 trials involving 1891 participants. Five of the included trials assessed prevention, while 31 trials assessed treatment. Five trials were at low risk of bias in the overall assessment of mortality; one trial was at low risk of bias in the assessment of the remaining outcomes.L-ornithine L-aspartate had a beneficial effect on mortality compared with placebo or no intervention when including all trials (RR 0.42, 95% CI 0.24 to 0.72; I = 0%; 19 trials; 1489 participants; very low quality evidence), but not when the analysis was restricted to the trials at low risk of bias (RR 0.47, 95% CI 0.06 to 3.58; 4 trials; 244 participants). It had a beneficial effect on hepatic encephalopathy compared with placebo or no intervention when including all trials (RR 0.70, 95% CI 0.59 to 0.83; 22 trials; 1375 participants; I = 62%; very low quality evidence), but not in the one trial at low risk of bias (RR 0.96, 95% CI 0.85 to 1.07; 63 participants). The analysis of serious adverse events showed a potential benefit of L-ornithine L-aspartate when including all randomised clinical trials (RR 0.63, 95% CI 0.45 to 0.90; 1 trial; 1489 participants; I = 0%; very low quality evidence), but not in the one trial at low risk of bias for this outcome (RR 0.83, 95% CI 0.15 to 4.65; 63 participants). The Trial Sequential Analyses of mortality, hepatic encephalopathy, and serious adverse events found insufficient evidence to support or refute beneficial effects. Subgroup analyses showed no difference in outcomes in the trials evaluating evaluating the prevention or treatment of either overt or minimal hepatic encephalopathy or trials evaluating oral versus intravenous administration We were unable to undertake a meta-analysis of the three trials involving 288 participants evaluating health-related quality of life. Overall, we found no difference between L-ornithine L-aspartate and placebo or no intervention in non-serious adverse events (RR 1.15, 95% CI 0.75 to 1.77; 14 trials; 1076 participants; I = 40%). In comparison with lactulose, L-ornithine L-aspartate had no effect on mortality (RR 0.68, 95% CI 0.11 to 4.17; 4 trials; 175 participants; I = 0%); hepatic encephalopathy (RR 1.13, 95% CI 0.81 to 1.57); serious adverse events (RR 0.69, 95% CI 0.22 to 2.11); or non-serious adverse events (RR 0.05, 95% CI 0.01 to 0.18). In comparison with probiotics, L-ornithine L-aspartate had no effect on mortality (RR 1.01, 95% CI 0.11 to 9.51); serious adverse events (RR 1.07, 95% CI 0.23 to 4.88); or changes in blood ammonia concentrations from baseline (RR -2.30 95% CI -6.08 to 1.48), but it had a possible beneficial effect on hepatic encephalopathy (RR 0.71, 95% CI 0.56 to 0.90). Finally, in comparison with rifaximin, L-ornithine L-aspartate had no effect on mortality (RR 0.33, 95% CI 0.04 to 3.03; 2 trials; 105 participants); hepatic encephalopathy (RR 1.06, 95% CI 0.57 to 1.96); serious adverse events (RR 0.32, 95% CI 0.01 to 7.42), or non-serious adverse events (RR 0.32, 95% CI 0.01 to 7.42).
AUTHORS' CONCLUSIONS
The results of this review suggest a possible beneficial effect of L-ornithine L-aspartate on mortality, hepatic encephalopathy, and serious adverse events in comparisons with placebo or no-intervention, but, because the quality of the evidence is very low, we are very uncertain about these findings. There was very low quality evidence of a possible beneficial effect of L-ornithine L-aspartate on hepatic encephalopathy, when compared with probiotics, but no other benefits were demonstrated in comparison with other active agents. Additional access to data from completed, but unpublished trials, and new randomised placebo-controlled, double-blind clinical trials are needed.
Topics: Dipeptides; Hepatic Encephalopathy; Humans; Liver Cirrhosis; Quality of Life; Randomized Controlled Trials as Topic
PubMed: 29762873
DOI: 10.1002/14651858.CD012410.pub2 -
Journal of Clinical and Experimental... Sep 2018l-Ornithine l-Aspartate (LOLA) is a mixture of two endogenous amino acids with the capacity to fix ammonia in the form of urea and/or glutamine. Its' efficacy for the...
Efficacy of l-Ornithine l-Aspartate for the Treatment of Hepatic Encephalopathy and Hyperammonemia in Cirrhosis: Systematic Review and Meta-Analysis of Randomized Controlled Trials.
BACKGROUND/OBJECTIVES
l-Ornithine l-Aspartate (LOLA) is a mixture of two endogenous amino acids with the capacity to fix ammonia in the form of urea and/or glutamine. Its' efficacy for the treatment of Hepatic Encephalopathy (HE), a known hyperammonemic disorder, remains the subject of debate. This study quantitatively analyzed the efficacy of LOLA in patients with cirrhosis and HE.
METHODS
Efficacy was defined as the extent of lowering of blood ammonia and improvement of mental state assessed in clinically overt HE (OHE) by Westhaven criteria or psychometric testing for assessment of Minimal HE (MHE). Appropriate keywords were used for electronic and/or manual searches of databases to identify RCTs for inclusion. Study quality and risk of bias were assessed using the Jadad Composite Scale together with The Cochrane Scoring Tool. Random Effects Models were used to express pooled Risk Ratio (RR) or Mean Difference (MD) with associated 95% Confidence Intervals (CI).
RESULTS
10 RCTs (884 patients) were included. Regression analysis showed no evidence of publication bias or other small study effects. Eight RCTs had low risk of bias by Jadad/Cochrane criteria. Comparison with placebo/no intervention controls revealed that LOLA was significantly more effective for improvement of mental state in all types of HE (RR 1.36 (95% CI 1.10-1.69), = 0.005), OHE (RR: 1.19, 95% CI of 1.01-1.39, test for overall effect: = 2.14, = 0.03), MHE (RR: 2.15 (1.48-3.14), < 0.0001) and for lowering of blood ammonia (MD: -17.50 μmol/l (-27.73 to (-7.26)), = 0.0008). Improvement of mental state was greater in trials with low risk of bias. Heterogeneity was reduced in trials from Europe or with >100 participants. Oral LOLA appeared particularly effective for the treatment of MHE.
CONCLUSION
LOLA appears to improve mental state and lower ammonia in patients with HE or MHE. Further studies are required in some subgroups of HE and in the era of HE reclassification.
PubMed: 30302048
DOI: 10.1016/j.jceh.2018.05.004 -
Frontiers in Microbiology 2016The β-lactamase inhibitor, clavulanic acid is frequently used in combination with β-lactam antibiotics to treat a wide spectrum of infectious diseases. Clavulanic acid... (Review)
Review
The β-lactamase inhibitor, clavulanic acid is frequently used in combination with β-lactam antibiotics to treat a wide spectrum of infectious diseases. Clavulanic acid prevents drug resistance by pathogens against these β-lactam antibiotics by preventing the degradation of the β-lactam ring, thus ensuring eradication of these harmful microorganisms from the host. This systematic review provides an overview on the fermentation conditions that affect the production of clavulanic acid in the firstly described producer, Streptomyces clavuligerus. A thorough search was conducted using predefined terms in several electronic databases (PubMed, Medline, ScienceDirect, EBSCO), from database inception to June 30th 2015. Studies must involve wild-type Streptomyces clavuligerus, and full texts needed to be available. A total of 29 eligible articles were identified. Based on the literature, several factors were identified that could affect the production of clavulanic acid in S. clavuligerus. The addition of glycerol or other vegetable oils (e.g., olive oil, corn oil) could potentially affect clavulanic acid production. Furthermore, some amino acids such as arginine and ornithine, could serve as potential precursors to increase clavulanic acid yield. The comparison of different fermentation systems revealed that fed-batch fermentation yields higher amounts of clavulanic acid as compared to batch fermentation, probably due to the maintenance of substrates and constant monitoring of certain entities (such as pH, oxygen availability, etc.). Overall, these findings provide vital knowledge and insight that could assist media optimization and fermentation design for clavulanic acid production in S. clavuligerus.
PubMed: 27148211
DOI: 10.3389/fmicb.2016.00522 -
The Cochrane Database of Systematic... Nov 2016Older people with hip fractures are often malnourished at the time of fracture, and subsequently have poor food intake. This is an update of a Cochrane review first... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Older people with hip fractures are often malnourished at the time of fracture, and subsequently have poor food intake. This is an update of a Cochrane review first published in 2000, and previously updated in 2010.
OBJECTIVES
To review the effects (benefits and harms) of nutritional interventions in older people recovering from hip fracture.
SEARCH METHODS
We searched the Cochrane Bone, Joint and Muscle Trauma Group Specialised Register, CENTRAL, MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, Embase, CAB Abstracts, CINAHL, trial registers and reference lists. The search was last run in November 2015.
SELECTION CRITERIA
Randomised and quasi-randomised controlled trials of nutritional interventions for people aged over 65 years with hip fracture where the interventions were started within the first month after hip fracture.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected trials, extracted data and assessed risk of bias. Where possible, we pooled data for primary outcomes which were: all cause mortality; morbidity; postoperative complications (e.g. wound infections, pressure sores, deep venous thromboses, respiratory and urinary infections, cardiovascular events); and 'unfavourable outcome' defined as the number of trial participants who died plus the number of survivors with complications. We also pooled data for adverse events such as diarrhoea.
MAIN RESULTS
We included 41 trials involving 3881 participants. Outcome data were limited and risk of bias assessment showed that trials were often methodologically flawed, with less than half of trials at low risk of bias for allocation concealment, incomplete outcome data, or selective reporting of outcomes. The available evidence was judged of either low or very low quality indicating that we were uncertain or very uncertain about the estimates.Eighteen trials evaluated oral multinutrient feeds that provided non-protein energy, protein, vitamins and minerals. There was low-quality evidence that oral feeds had little effect on mortality (24/486 versus 31/481; risk ratio (RR) 0.81 favouring supplementation, 95% confidence interval (CI) 0.49 to 1.32; 15 trials). Thirteen trials evaluated the effect of oral multinutrient feeds on complications (e.g. pressure sore, infection, venous thrombosis, pulmonary embolism, confusion). There was low-quality evidence that the number of participants with complications may be reduced with oral multinutrient feeds (123/370 versus 157/367; RR 0.71, 95% CI 0.59 to 0.86; 11 trials). Based on very low-quality evidence from six studies (334 participants), oral supplements may result in lower numbers with 'unfavourable outcome' (death or complications): RR 0.67, 95% CI 0.51 to 0.89. There was very low-quality evidence for six studies (442 participants) that oral supplementation did not result in an increased incidence of vomiting and diarrhoea (RR 0.99, 95% CI 0.47 to 2.05).Only very low-quality evidence was available from the four trials examining nasogastric multinutrient feeding. Pooled data from three heterogeneous trials showed no evidence of an effect of supplementation on mortality (14/142 versus 14/138; RR 0.99, 95% CI 0.50 to 1.97). One trial (18 participants) found no difference in complications. None reported on unfavourable outcome. Nasogastric feeding was poorly tolerated. One study reported no cases of aspiration pneumonia.There is very low-quality evidence from one trial (57 participants, mainly men) of no evidence for an effect of tube feeding followed by oral supplementation on mortality or complications. Tube feeding, however, was poorly tolerated.There is very low-quality evidence from one trial (80 participants) that a combination of intravenous feeding and oral supplements may not affect mortality but could reduce complications. However, this expensive intervention is usually reserved for people with non-functioning gastrointestinal tracts, which is unlikely in this trial.Four trials tested increasing protein intake in an oral feed. These provided low-quality evidence for no clear effect of increased protein intake on mortality (30/181 versus 21/180; RR 1.42, 95% CI 0.85 to 2.37; 4 trials) or number of participants with complications but very low-quality and contradictory evidence of a reduction in unfavourable outcomes (66/113 versus 82/110; RR 0.78, 95% CI 0.65 to 0.95; 2 trials). There was no evidence of an effect on adverse events such as diarrhoea.Trials testing intravenous vitamin B1 and other water soluble vitamins, oral 1-alpha-hydroxycholecalciferol (vitamin D), high dose bolus vitamin D, different oral doses or sources of vitamin D, intravenous or oral iron, ornithine alpha-ketoglutarate versus an isonitrogenous peptide supplement, taurine versus placebo, and a supplement with vitamins, minerals and amino acids, provided low- or very low-quality evidence of no clear effect on mortality or complications, where reported.Based on low-quality evidence, one trial evaluating the use of dietetic assistants to help with feeding indicated that this intervention may reduce mortality (19/145 versus 36/157; RR 0.57, 95% CI 0.34 to 0.95) but not the number of participants with complications (79/130 versus 84/125).
AUTHORS' CONCLUSIONS
There is low-quality evidence that oral multinutrient supplements started before or soon after surgery may prevent complications within the first 12 months after hip fracture, but that they have no clear effect on mortality. There is very low-quality evidence that oral supplements may reduce 'unfavourable outcome' (death or complications) and that they do not result in an increased incidence of vomiting and diarrhoea. Adequately sized randomised trials with robust methodology are required. In particular, the role of dietetic assistants, and peripheral venous feeding or nasogastric feeding in very malnourished people require further evaluation.
Topics: Aftercare; Aged; Cause of Death; Dietary Supplements; Hip Fractures; Humans; Malnutrition; Nutritional Support; Randomized Controlled Trials as Topic
PubMed: 27898998
DOI: 10.1002/14651858.CD001880.pub6 -
The Cochrane Database of Systematic... Apr 2015Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Hirsutism occurs in 5% to 10% of women of reproductive age when there is excessive terminal hair growth in androgen-sensitive areas (male pattern). It is a distressing disorder with a major impact on quality of life. The most common cause is polycystic ovary syndrome. There are many treatment options, but it is not clear which are most effective.
OBJECTIVES
To assess the effects of interventions (except laser and light-based therapies alone) for hirsutism.
SEARCH METHODS
We searched the Cochrane Skin Group Specialised Register, CENTRAL (2014, Issue 6), MEDLINE (from 1946), EMBASE (from 1974), and five trials registers, and checked reference lists of included studies for additional trials. The last search was in June 2014.
SELECTION CRITERIA
Randomised controlled trials (RCTs) in hirsute women with polycystic ovary syndrome, idiopathic hirsutism, or idiopathic hyperandrogenism.
DATA COLLECTION AND ANALYSIS
Two independent authors carried out study selection, data extraction, 'Risk of bias' assessment, and analyses.
MAIN RESULTS
We included 157 studies (sample size 30 to 80) comprising 10,550 women (mean age 25 years). The majority of studies (123/157) were 'high', 30 'unclear', and four 'low' risk of bias. Lack of blinding was the most frequent source of bias. Treatment duration was six to 12 months. Forty-eight studies provided no usable or retrievable data, i.e. lack of separate data for hirsute women, conference proceedings, and losses to follow-up above 40%.Primary outcomes, 'participant-reported improvement of hirsutism' and 'change in health-related quality of life', were addressed in few studies, and adverse events in only half. In most comparisons there was insufficient evidence to determine if the number of reported adverse events differed. These included known adverse events: gastrointestinal discomfort, breast tenderness, reduced libido, dry skin (flutamide and finasteride); irregular bleeding (spironolactone); nausea, diarrhoea, bloating (metformin); hot flushes, decreased libido, vaginal dryness, headaches (gonadotropin-releasing hormone (GnRH) analogues)).Clinician's evaluation of hirsutism and change in androgen levels were addressed in most comparisons, change in body mass index (BMI) and improvement of other clinical signs of hyperandrogenism in one-third of studies.The quality of evidence was moderate to very low for most outcomes.There was low quality evidence for the effect of two oral contraceptive pills (OCPs) (ethinyl estradiol + cyproterone acetate versus ethinyl estradiol + desogestrel) on change from baseline of Ferriman-Gallwey scores. The mean difference (MD) was -1.84 (95% confidence interval (CI) -3.86 to 0.18).There was very low quality evidence that flutamide 250 mg, twice daily, reduced Ferriman-Gallwey scores more effectively than placebo (MD -7.60, 95% CI -10.53 to -4.67 and MD -7.20, 95% CI -10.15 to -4.25). Participants' evaluations in one study with 20 participants confirmed these results (risk ratio (RR) 17.00, 95% CI 1.11 to 259.87).Spironolactone 100 mg daily was more effective than placebo in reducing Ferriman-Gallwey scores (MD -7.69, 95% CI -10.12 to -5.26) (low quality evidence). It showed similar effectiveness to flutamide in two studies (MD -1.90, 95% CI -5.01 to 1.21 and MD 0.49, 95% CI -1.99 to 2.97) (very low quality evidence), as well as to finasteride in two studies (MD 1.49, 95% CI -0.58 to 3.56 and MD 0.40, 95% CI -1.18 to 1.98) (low quality evidence).Although there was very low quality evidence of a difference in reduction of Ferriman-Gallwey scores for finasteride 5 mg to 7.5 mg daily versus placebo (MD -5.73, 95% CI -6.87 to -4.58), it was unlikely it was clinically meaningful. These results were reinforced by participants' assessments (RR 2.06, 95% CI 0.99 to 4.29 and RR 11.00, 95% CI 0.69 to 175.86). However, finasteride showed inconsistent results in comparisons with other treatments, and no firm conclusions could be reached.Metformin demonstrated no benefit over placebo in reduction of Ferriman-Gallwey scores (MD 0.05, 95% CI -1.02 to 1.12), but the quality of evidence was low. Results regarding the effectiveness of GnRH analogues were inconsistent, varying from minimal to important improvements.We were unable to pool data for OCPs with cyproterone acetate 20 mg to 100 mg due to clinical and methodological heterogeneity between studies. However, addition of cyproterone acetate to OCPs provided greater reductions in Ferriman-Gallwey scores.Two studies, comparing finasteride 5 mg and spironolactone 100 mg, did not show differences in participant assessments and reduction of Ferriman-Gallwey scores (low quality evidence). Ferriman-Gallwey scores from three studies comparing flutamide versus metformin could not be pooled (I² = 62%). One study comparing flutamide 250 mg twice daily with metformin 850 mg twice daily for 12 months, which reached a higher cumulative dosage than two other studies evaluating this comparison, showed flutamide to be more effective (MD -6.30, 95% CI -9.83 to -2.77) (very low quality evidence). Data showing reductions in Ferriman-Gallwey scores could not be pooled for four studies comparing finasteride with flutamide as the results were inconsistent (I² = 67%).Studies examining effects of hypocaloric diets reported reductions in BMI, but which did not result in reductions in Ferriman-Gallwey scores. Although certain cosmetic measures are commonly used, we did not identify any relevant RCTs.
AUTHORS' CONCLUSIONS
Treatments may need to incorporate pharmacological therapies, cosmetic procedures, and psychological support. For mild hirsutism there is evidence of limited quality that OCPs are effective. Flutamide 250 mg twice daily and spironolactone 100 mg daily appeared to be effective and safe, albeit the evidence was low to very low quality. Finasteride 5 mg daily showed inconsistent results in different comparisons, therefore no firm conclusions can be made. As the side effects of antiandrogens and finasteride are well known, these should be accounted for in any clinical decision-making. There was low quality evidence that metformin was ineffective for hirsutism and although GnRH analogues showed inconsistent results in reducing hirsutism they do have significant side effects.Further research should consist of well-designed, rigorously reported, head-to-head trials examining OCPs combined with antiandrogens or 5α-reductase inhibitor against OCP monotherapy, as well as the different antiandrogens and 5α-reductase inhibitors against each other. Outcomes should be based on standardised scales of participants' assessment of treatment efficacy, with a greater emphasis on change in quality of life as a result of treatment.
Topics: 5-alpha Reductase Inhibitors; Adult; Androgen Antagonists; Body Mass Index; Contraceptive Agents, Female; Cyproterone Acetate; Desogestrel; Drug Combinations; Eflornithine; Ethinyl Estradiol; Female; Finasteride; Flutamide; Hirsutism; Humans; Hypoglycemic Agents; Metformin; Quality of Life; Randomized Controlled Trials as Topic; Spironolactone
PubMed: 25918921
DOI: 10.1002/14651858.CD010334.pub2