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BMJ Open Mar 2017Multiple sclerosis (MS) is a chronic, neurodegenerative autoimmune disorder affecting the central nervous system. Relapsing-remitting MS (RRMS) is the most common... (Comparative Study)
Comparative Study Meta-Analysis Review
OBJECTIVE
Multiple sclerosis (MS) is a chronic, neurodegenerative autoimmune disorder affecting the central nervous system. Relapsing-remitting MS (RRMS) is the most common clinical form of MS and affects ∼85% of cases at onset. Highly active (HA) and rapidly evolving severe (RES) RRMS are 2 forms of RRMS amenable to disease-modifying therapies (DMT). This study explored the efficacy of fingolimod relative to other DMTs for the treatment of HA and RES RRMS.
METHODS
A systematic literature review (SLR) was conducted to identify published randomised controlled trials in HA and RES RRMS. Identified evidence was vetted, and a Bayesian network meta-analysis (NMA) was performed to evaluate the relative efficacy of fingolimod versus dimethyl fumarate (DMF) in HA RRMS and versus natalizumab in RES RRMS.
RESULTS
For HA RRMS, the SLR identified 2 studies with relevant patient subgroup data: 1 comparing fingolimod with placebo and the other comparing DMF with placebo. 3 studies were found for RES RRMS: 1 comparing fingolimod with placebo and 2 studies comparing natalizumab with placebo. NMA results in the HA population showed a favourable numerical trend of fingolimod versus DMF assessed for annualised relapse rate (ARR) and 3-month confirmed disability progression. For the RES population, the results identified an increase of ARR and 3-month confirmed disability progression for fingolimod versus natalizumab (not statistically significant). Sparse study data and the consequently high uncertainty around the estimates restricted our ability to demonstrate statistical significance in the studied subgroups.
CONCLUSIONS
Data limitations are apparent when conducting an informative indirect comparison for the HA and RES RRMS subgroups as the subgroups analyses were retrospective analyses of studies powered to indicate differences across entire study populations. Comparisons across treatments in HA or RES RRMS will be associated with high levels of uncertainty until new data are collected for these subgroups.
Topics: Dimethyl Fumarate; Female; Fingolimod Hydrochloride; Humans; Immunologic Factors; Immunosuppressive Agents; Male; Multiple Sclerosis, Relapsing-Remitting; Natalizumab; Recurrence; Severity of Illness Index
PubMed: 28283486
DOI: 10.1136/bmjopen-2016-013430 -
Journal of Dental Research Mar 2011Treatment of dentin hypersensitivity with oxalates is common, but oxalate efficacy remains unclear. Our objective was to systematically review clinical trials reporting... (Meta-Analysis)
Meta-Analysis Review
Treatment of dentin hypersensitivity with oxalates is common, but oxalate efficacy remains unclear. Our objective was to systematically review clinical trials reporting an oxalate treatment compared with no treatment or placebo with a dentin hypersensitivity outcome. Risk-of-bias assessment and data extraction were performed independently by two reviewers. Standardized mean differences (SMD) were estimated by random-effects meta-analysis. Of 677 unique citations, 12 studies with high risk-of-bias were included. The summary SMD for 3% monohydrogen-monopotassium oxalate (n = 8 studies) was -0.71 [95% Confidence Interval: -1.48, 0.06]. Other treatments, including 30% dipotassium oxalate (n = 1), 30% dipotassium oxalate plus 3% monohydrogen monopotassium oxalate (n = 3), 6% monohydrogen monopotassium oxalate (n = 1), 6.8% ferric oxalate (n = 1), and oxalate-containing resin (n = 1), also were not statistically significantly different from placebo treatments. With the possible exception of 3% monohydrogen monopotassium oxalate, available evidence currently does not support the recommendation of dentin hypersensitivity treatment with oxalates.
Topics: Bias; Controlled Clinical Trials as Topic; Dentin Desensitizing Agents; Dentin Sensitivity; Humans; Oxalates; Pain Measurement
PubMed: 21191127
DOI: 10.1177/0022034510389179 -
The American Journal of Clinical... Oct 2017Vitamin B-12 (cobalamin) deficiency may produce severe neurologic and hematologic manifestations. Approximately 20-25% of circulating cobalamin binds to transcobalamin... (Meta-Analysis)
Meta-Analysis Review
Association of rs1801198 c.776G>C polymorphism with markers of one-carbon metabolism and related diseases: a systematic review and meta-analysis of genetic association studies.
Vitamin B-12 (cobalamin) deficiency may produce severe neurologic and hematologic manifestations. Approximately 20-25% of circulating cobalamin binds to transcobalamin 2 (TCN2), which is referred to as active vitamin B-12. The G allele of the c.776G>C (rs1801198) polymorphism has been associated with a lower plasma concentration of holotranscobalamin. However, genotype association studies on rs1801198 have led to conflicting results regarding its influence on one-carbon metabolism (OCM) markers or its association with pathologic conditions. We assessed the association of rs1801198 genotypes with OCM marker concentrations and primary risks of congenital abnormalities, cancer, and Alzheimer disease. We conducted a systematic review of the literature that was published from January 1966 to February 2017 and included all studies that assessed the association between rs1801198 and OCM markers or a pathologic condition. Thirty-four studies met the inclusion criteria. Subjects with the rs1801198 GG genotype had significantly lower concentrations of holotranscobalamin [standardized mean difference (SMD): -0.445 (95% CI: -0.673, -0.217; < 0.001); = 48.16% (95% CI: 0.00%, 78.10%; = 0.07)] and higher concentrations of homocysteine (European descent only) [SMD: 0.070 (95% CI: 0.020, 0.120; = 0.01); = 0.00% (95% CI: 0.00%, 49.59%; = 0.73)] than did subjects with the rs1801198 CC genotype. The meta-analysis on the association between rs1801198 and methylmalonic acid (MMA) lacked statistical power. No significant difference was observed regarding cobalamin, folate, and red blood cell folate. No significant association was observed between rs1801198 and primary risks of congenital abnormalities, cancer, or Alzheimer disease. Meta-analysis results indicate an influence of rs1801198 on holotranscobalamin and homocysteine concentrations in European-descent subjects. In addition, well-designed and -powered studies should be conducted for assessing the association between rs1801198 and MMA and clinical manifestations that are linked to a decreased availability of cobalamin. This review was registered at www.crd.york.ac.uk/prospero as CRD42017058504.
Topics: Adult; Aged; Alleles; Alzheimer Disease; Carbon; Child; Congenital Abnormalities; Female; Genotype; Homocysteine; Humans; Male; Methylmalonic Acid; Neoplasms; Polymorphism, Single Nucleotide; Transcobalamins; Vitamin B 12; Vitamin B 12 Deficiency; White People
PubMed: 28814397
DOI: 10.3945/ajcn.117.156349 -
Journal of Dentistry Jul 2013This review defines dentine sensitivity (DS), its prevalence, its aetiology, the mechanism(s) responsible for DS, its diagnosis and its treatment. The review then... (Review)
Review
OBJECTIVE
This review defines dentine sensitivity (DS), its prevalence, its aetiology, the mechanism(s) responsible for DS, its diagnosis and its treatment. The review then examines the modes of action of various treatments for DS including potassium salts, strontium salts, bioglasses, arginine/calcium carbonate and professional treatments such as adhesives and oxalates. The methods used to evaluate the various treatment modalities are discussed, including laboratory studies and randomised controlled clinical trials.
DATA SOURCES AND STUDY SELECTION
A literature search was conducted using PubMed, Ovid Medline and Cochrane reviews for information on DS and its treatments, as well as laboratory and clinical studies used to evaluate the efficacy of various DS treatments. With regard to efficacy of treatments for DS only reports of clinical studies that were randomised, controlled and blinded were reviewed. The authors offer new insights into the shortcomings of the recent systematic review of the use of oxalates for DS.
CONCLUSION
The authors introduce the concept of a novel desensitising mouthrinse containing 1.4% potassium oxalate: Listerine® Advanced Defence Sensitive mouthrinse. Readers of this supplement issue of the Journal of Dentistry are invited to review the significance of managing the clinical problem of DS. They are also invited to assess data from laboratory and randomised controlled clinical studies in order to understand the advantages offered by regular use of 1.4% potassium oxalate-containing mouthrinse, Listerine Advanced Defence Sensitive, in particular its resistance to daily erosive and/or abrasive challenges.
Topics: Dental Pulp; Dentin; Dentin Desensitizing Agents; Dentin Sensitivity; Humans; Oxalic Acid; Tooth Wear; Treatment Outcome
PubMed: 23929643
DOI: 10.1016/S0300-5712(13)70002-2 -
Journal of the American Academy of... Jan 2007Rosacea is a common chronic skin and ocular condition. It is unclear which treatments are most effective. We have conducted a Cochrane review of rosacea therapies. This... (Review)
Review
BACKGROUND
Rosacea is a common chronic skin and ocular condition. It is unclear which treatments are most effective. We have conducted a Cochrane review of rosacea therapies. This article is a distillation of that work.
OBJECTIVE
We sought to assess the evidence for the efficacy and safety of rosacea therapies.
METHODS
Multiple databases were systematically searched. Randomized controlled trials in people with moderate to severe rosacea were included. Study selection, assessment of methodologic quality, data extraction, and analysis were carried out by two independent researchers.
RESULTS
In all, 29 studies met inclusion criteria. Topical metronidazole is more effective than placebo (odds ratio 5.96, 95% confidence interval 2.95-12.06). Azelaic acid is more effective than placebo (odds ratio 2.45, 95% confidence interval 1.82-3.28). Firm conclusions could not be drawn about other therapies.
LIMITATIONS
The quality of the studies was generally poor.
CONCLUSIONS
There is evidence that topical metronidazole and azelaic acid are effective. There is some evidence that oral metronidazole and tetracycline are effective. More well-designed, randomized controlled trials are required to provide better evidence of the efficacy and safety of other rosacea therapies.
Topics: Administration, Cutaneous; Administration, Oral; Anti-Bacterial Agents; Benzoyl Peroxide; Cosmetics; Dicarboxylic Acids; Diet; Double-Blind Method; Drug Therapy, Combination; Humans; Metronidazole; Omeprazole; Permethrin; Randomized Controlled Trials as Topic; Research Design; Rosacea; Single-Blind Method; Sunscreening Agents; Tetracyclines; Treatment Outcome
PubMed: 17190628
DOI: 10.1016/j.jaad.2006.04.084 -
The Cochrane Database of Systematic... 2000To assess the effects of salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis. (Review)
Review
OBJECTIVES
To assess the effects of salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis.
SEARCH STRATEGY
We searched Medline up to 1995, and Excerpta Medica (June 1974-95). Search terms were psoriasis, arthritis, therapy and/or controlled trial. This was supplemented by manually searching bibliographies of previously published reviews, conference proceedings and contacting drug companies. All languages were included in the initial search.
SELECTION CRITERIA
All randomized trials comparing salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis. The main outcome measures included individual component variables derived from Outcome Measures in Rheumatology Clinical Trials (OMERACT). These include Acute Phase Reactants, Disability, Pain, Patient Global Assessment, Physician Global Assessment, Swollen joint count, Tender joint count and radiographic changes of joints in any trial of 1 year or longer [Tugwell 1993], and the change in pooled disease index. Only English trials were included in the review.
DATA COLLECTION AND ANALYSIS
Data were independently extracted from the published reports by two of the reviewers. An independent blinded quality assessment was also performed.
MAIN RESULTS
Nineteen randomized trials were identified of which eleven were included in the quantitative analysis with data from 777 subjects. Although all agents were better than placebo, parenteral high dose methotrexate (not included), salazopyrin, azathioprine and etretinate were the agents that achieved statistical significance in a global index of disease activity (although it should be noted that only one component variable was available for azathioprine and only one trial was available for etretinate suggesting some caution is necessary in interpreting these results). Analysis of response in individual disease activity markers was more variable with considerable differences between different medications and responses. In all trials the placebo group improved over baseline (pooled improvement 0.43 DI units, 95% CI 0. 28-0.59). There was insufficient data to examine toxicity.
REVIEWER'S CONCLUSIONS
Parenteral high dose methotrexate and salazopyrin are the only two agents with well demonstrated published efficacy in psoriatic arthritis. The magnitude of the effect seen with azathioprine, etretinate, oral low dose methotrexate and perhaps colchicine suggests that they may be effective but that further multicentre clinical trials are required to establish their efficacy. Furthermore, the magnitude of the improvement observed in the placebo group strongly suggests that uncontrolled trials should not be used to guide management decisions in this condition.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Auranofin; Azathioprine; Dermatologic Agents; Etretinate; Fumarates; Humans; Immunosuppressive Agents; Methotrexate; Sulfasalazine
PubMed: 10796328
DOI: 10.1002/14651858.CD000212 -
Canadian Journal of Gastroenterology &... Nov 2014Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided... (Review)
Review
BACKGROUND
Constipation is an uncomfortable and common condition that affects many, irrespective of age. Since 1500 BC and before, health care practitioners have provided treatments and prevention strategies to patients for chronic constipation despite the significant variation in both medical and personal perceptions of the condition.
OBJECTIVE
To review relevant research evidence from clinical studies investigating the efficacy and safety of commercially available pharmacological laxatives in Canada, with emphasis on studies adopting the Rome criteria for defining functional constipation.
SEARCH METHODS
PubMed, Medline, Embase and Evidence-Based Medicine Reviews databases were searched for blinded or randomized clinical trials and meta-analyses assessing the efficacy of nonstimulant and stimulant laxatives for the treatment of functional constipation.
RESULTS
A total of 19 clinical studies and four meta-analyses were retrieved and abstracted regarding study design, participants, interventions and outcomes. The majority of studies focused on polyethylene glycol compared with placebo. Both nonstimulant and stimulant laxatives provided better relief of constipation symptoms than placebo according to both objective and subjective measures. Only one study compared the efficacy of a nonstimulant versus a stimulant laxative, while only two reported changes in quality of life. All studies reported minor side effects due to laxative use, regardless of treatment duration, which ranged from one week to one year. Laxatives were well tolerated by both adults and children.
Topics: Bisacodyl; Canada; Citrates; Constipation; Dioctyl Sulfosuccinic Acid; Humans; Lactulose; Laxatives; Magnesium Oxide; Organometallic Compounds; Paraffin; Picolines; Polyethylene Glycols; Psyllium; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25390617
DOI: 10.1155/2014/631740 -
World Journal of Urology Nov 2023The goal of this systematic review was to examine the current literature on the urinary microbiome and its associations with noninfectious, nonmalignant, urologic... (Review)
Review
PURPOSE
The goal of this systematic review was to examine the current literature on the urinary microbiome and its associations with noninfectious, nonmalignant, urologic diseases. Secondarily, we aimed to describe the most common bioinformatics used to analyze the urinary microbiome.
METHODS
A comprehensive literature search of Ovid MEDLINE using the keywords "microbiota" AND "prostatic hyperplasia," "microbiota" AND "urinary bladder, overactive," "microbiota" AND "pelvic pain," and "microbiota" AND "urolithiasis" OR "nephrolithiasis" OR "urinary calculi" AND "calcium oxalate" was performed to identify relevant clinical microbiome studies associated with noninfectious benign urological conditions published from 2010 to 2022. We included human studies that evaluated the urinary, stone, or semen microbiota, or any combination of the above-mentioned locations.
RESULTS
A total of 25 human studies met the inclusion criteria: 4 on benign prostatic hyperplasia (BPH), 9 on overactive bladder (OAB), 8 on calcium oxalate stones, and 4 on chronic pelvic pain syndrome (CPPS). Specific taxonomic profiles in the urine microbiome were associated with each pathology, and evaluation of alpha- and beta-diversity and relative abundance was accounted for most of the studies. Symptom prevalence and severity were also analyzed and showed associations with specific microbes.
CONCLUSION
The study of the urogenital microbiome is rapidly expanding in urology. Noninfectious benign urogenital diseases, such as BPH, calcium oxalate stones, CPPS, and OAB were found to be associated with specific microbial taxonomies. Further research with larger study populations is necessary to solidify the knowledge of the urine microbiome in these conditions and to facilitate the creation of microbiome-based diagnostic and therapeutic approaches.
Topics: Male; Humans; Prostatic Hyperplasia; Calcium Oxalate; Microbiota; Urinary Bladder, Overactive; Urinary Calculi; Pelvic Pain
PubMed: 37737900
DOI: 10.1007/s00345-023-04588-5 -
The Cochrane Database of Systematic... 2000To assess the effects of salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, efamol marine and methotrexate, in psoriatic arthritis. (Review)
Review
OBJECTIVES
To assess the effects of salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, efamol marine and methotrexate, in psoriatic arthritis.
SEARCH STRATEGY
We searched Medline up to February 2000, and Excerpta Medica (June 1974-95). Search terms were psoriasis, arthritis, therapy and/or controlled trial. This was supplemented by manually searching bibliographies of previously published reviews, conference proceedings, contacting drug companies and referring to the Cochrane Clinical Trials Register. All languages were included in the initial search.
SELECTION CRITERIA
All randomized trials comparing salazopyrin, auranofin, etretinate, fumaric acid, IMI gold, azathioprine, and methotrexate, in psoriatic arthritis. Following a published a priori protocol, the main outcome measures included individual component variables derived from Outcome Measures in Rheumatology Clinical Trials (OMERACT). These include acute phase reactants, disability, pain, patient global assessment, physician global assessment, swollen joint count, tender joint count and radiographic changes of joints in any trial of one year or longer [Tugwell 1993], and the change in pooled disease index (DI). Only English trials were included in the review.
DATA COLLECTION AND ANALYSIS
Data were independently extracted from the published reports by two of the reviewers (MC, GJ). An independent blinded quality assessment was also performed.
MAIN RESULTS
Twenty randomized trials were identified of which thirteen were included in the quantitative analysis with data from 1022 subjects. Although all agents were better than placebo, parenteral high dose methotrexate (not included), salazopyrin, azathioprine and etretinate were the agents that achieved statistical significance in a global index of disease activity (although it should be noted that only one component variable was available for azathioprine and only one trial was available for etretinate suggesting some caution is necessary in interpreting these results). Analysis of response in individual disease activity markers was more variable with considerable differences between different medications and responses. In all trials the placebo group improved over baseline (pooled improvement 0.39 DI units, 95% CI 0.26-0.54). There was insufficient data to examine toxicity.
REVIEWER'S CONCLUSIONS
Parenteral high dose methotrexate and salazopyrin are the only two agents with well demonstrated published efficacy in psoriatic arthritis. The magnitude of the effect seen with azathioprine, etretinate, oral low dose methotrexate and perhaps colchicine suggests that they may be effective but that further multicentre clinical trials are required to establish their efficacy. Furthermore, the magnitude of the improvement observed in the placebo group strongly suggests that uncontrolled trials should not be used to guide management decisions in this condition.
Topics: Antirheumatic Agents; Arthritis, Psoriatic; Auranofin; Azathioprine; Dermatologic Agents; Etretinate; Fumarates; Humans; Immunosuppressive Agents; Methotrexate; Sulfasalazine
PubMed: 10908464
DOI: 10.1002/14651858.CD000212 -
Epidemiologic Reviews 2013Current recommendations on vitamin B12 intake vary from 1.4 to 3.0 μg per day and are based on the amount needed for maintenance of hematologic status or on the amount... (Review)
Review
Current recommendations on vitamin B12 intake vary from 1.4 to 3.0 μg per day and are based on the amount needed for maintenance of hematologic status or on the amount needed to compensate obligatory losses. This systematic review evaluates whether the relation between vitamin B12 intake and cognitive function should be considered for underpinning vitamin B12 recommendations in the future. The authors summarized dose-response evidence from randomized controlled trials and prospective cohort studies on the relation of vitamin B12 intake and status with cognitive function in adults and elderly people. Two randomized controlled trials and 6 cohort studies showed no association or inconsistent associations between vitamin B12 intake and cognitive function. Random-effects meta-analysis showed that serum/plasma vitamin B12 (50 pmol/L) was not associated with risk of dementia (4 cohort studies), global cognition z scores (4 cohort studies), or memory z scores (4 cohort studies). Although dose-response evidence on sensitive markers of vitamin B12 status (methylmalonic acid and holotranscobalamin) was scarce, 4 of 5 cohort studies reported significant associations with risk of dementia, Alzheimer's disease, or global cognition. Current evidence on the relation between vitamin B12 intake or status and cognitive function is not sufficient for consideration in the development of vitamin B12 recommendations. Further studies should consider the selection of sensitive markers of vitamin B12 status.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Cognition; Cognition Disorders; Dementia; Diet; Humans; Methylmalonic Acid; Transcobalamins; Vitamin B 12
PubMed: 23221971
DOI: 10.1093/epirev/mxs003