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Cornea Mar 2016To examine the efficacy of corneal collagen cross-linking (CXL) for the treatment of keratoconus (KCN). (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To examine the efficacy of corneal collagen cross-linking (CXL) for the treatment of keratoconus (KCN).
METHODS
A systemic literature review and meta-analysis of ocular functional and structural parameters of patients with KCN undergoing cross-linking procedures were performed using PubMed and the web of science. A literature search was performed for relevant peer-reviewed publications on population-based studies. Data were analyzed with R software (Meta library), and heterogeneity was assessed with the Cochran Q and I. A random-effects model was used for high heterogeneity; otherwise a fixed model was used. Sensitivity analysis of particular tested groups was used to explain high heterogeneity. The main outcome measures extracted from the articles were corrected distance visual acuity, uncorrected distance visual acuity, and maximum K.
RESULTS
An improvement in visual acuity of 1 to 2 Snellen lines was found 3 months or more after undergoing CXL. Changes were more pronounced in uncorrected visual acuity. Some topography parameters were found to be improved (0.6-1 diopters) 12 to 24 months after CXL. The refractive cylinder improved by 0.4 to 0.7 diopters. Endothelial cell density decreased by 225 cells per square millimeter in the first 3 months and thereafter returned to normal. Corneal thickness was reduced by 10 to 20 μm in the year following CXL but not after 24 months. No changes in intraocular pressure were noted.
CONCLUSIONS
CXL is a safe and effective method for halting the deterioration of KCN, while slightly improving visual function.
Topics: Collagen; Corneal Endothelial Cell Loss; Corneal Topography; Cross-Linking Reagents; Humans; Intraocular Pressure; Keratoconus; Photochemotherapy; Photosensitizing Agents; Riboflavin; Visual Acuity
PubMed: 26751990
DOI: 10.1097/ICO.0000000000000723 -
European Journal of Dentistry Oct 2023Matrix metalloproteinase (MMP) enzymes participate in collagen matrix degradation, including in dentine, potentially compromising bond strength. Therefore, MMP...
Impact of Dentine Pretreatment with Matrix Metalloproteinase Inhibitors on Bond Strength of Coronal Composite Restorations: A Systematic Review and Meta-analysis of In Vitro Studies.
Matrix metalloproteinase (MMP) enzymes participate in collagen matrix degradation, including in dentine, potentially compromising bond strength. Therefore, MMP inhibitors have been hypothesized to improve restoration bond strength and stability. This systematic review aimed to evaluate the influence of different MMP inhibitors applied as dentine surface pretreatments on the immediate (24 hours) and longer term (months) bond strength of direct coronal composite restorations. This systematic literature review followed the Preferred Reporting Items for Systematic Review and Meta-analyses (PRISMA) statement. A systematic literature search of three databases (Ovid MEDLINE, Ovid Embase, and Google Scholar) was conducted independently by two reviewers from inception to April 2022. An adapted quality assessment tool was independently applied by two reviewers for risk of bias assessment. RevMan v5.4 software was used for meta-analyses. A randomeffectsmodel was used to generatemean differences with 95% confidence intervals for treatment and control comparisons. The Q-test and I2-test were used to test for heterogeneity. The proportion of total variance across studies attributable to heterogeneity rather than chance was calculated. Overall effects were tested using the Z-test, while subgroup differences were tested using Chi-squared tests. Of 934 studies, 64 studies were included in the systematic review and 42 in the meta-analysis. Thirty-one MMP inhibitors were reported, three of which were included in the meta-analysis: 2% chlorhexidine (CHX), 0.3M carbodiimide (EDC), and 0.1% riboflavin (RIBO). Pretreatment with 2% CHX for 30 and 60 seconds did not significantly improve bond strength compared with controls either immediately or after long-termageing. However, pretreatment with 0.3MEDC and 0.1% RIBO (but not CHX) significantly improved bond strength compared with control groups both immediately and over time. Most studies showed a medium risk of bias. These in vitro findings pave the way for rationale clinical trialing of dentine surface pretreatment with MMP inhibitors to improve clinical outcomes.
PubMed: 36400108
DOI: 10.1055/s-0042-1757582 -
The Cochrane Database of Systematic... Nov 2021Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial... (Review)
Review
BACKGROUND
Acute bacterial meningitis is a bacterial infection of the membranes that surround and protect the brain, known as the meninges. The primary therapy for bacterial meningitis is antibiotics and corticosteroids. Although these therapies significantly improve outcomes, bacterial meningitis still has a high risk of death and a high risk of neurological sequelae in survivors. New adjuvant therapies are needed to further reduce the risk of death and neurological sequelae in bacterial meningitis.
OBJECTIVES
To assess the effects of non-corticosteroid adjuvant pharmacological therapies for mortality, hearing loss, and other neurological sequelae in people with acute bacterial meningitis.
SEARCH METHODS
We searched CENTRAL, MEDLINE, Embase, CINAHL, and LILACS databases and ClinicalTrials.gov and WHO ICTRP trials registers up to 30 September 2021, together with reference checking, citation searching, and contact with study authors to identify additional studies.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) of any pharmacological adjuvant therapy for acute bacterial meningitis.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed and extracted data on methods, participants, interventions, and outcomes. We assessed risk of bias of studies with the Cochrane risk of bias tool and the certainty of the evidence using the GRADE approach. We presented results using risk ratios (RR) and 95% confidence intervals (CI) when meta-analysis was possible. All other results are presented in a narrative synthesis.
MAIN RESULTS
We found that five different adjuvant therapies have been tested in RCTs for bacterial meningitis. These include paracetamol (3 studies, 1274 participants who were children); immunoglobulins (2 studies, 49 participants; one study included children, and the other adults); heparin (1 study, 15 participants who were adults); pentoxifylline (1 study, 57 participants who were children); and a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (1 study, 30 participants who were children). Paracetamol may make little or no difference to mortality (paracetamol 35.2% versus placebo 37.4%, 95% CI 30.3% to 40.8%; RR 0.94, 95% CI 0.81 to 1.09; 3 studies, 1274 participants; I² = 0%; low certainty evidence); hearing loss (RR 1.04, 95% CI 0.80 to 1.34; 2 studies, 901 participants; I² = 0%; low certainty evidence); neurological sequelae other than hearing loss (RR 1.56, 95% CI 0.98 to 2.50; 3 studies, 1274 participants; I² = 60%; low certainty evidence); and severe hearing loss (RR 0.96, 95% CI 0.67 to 1.36; 2 studies, 901 participants; I² = 0%; low certainty evidence). Paracetamol may lead to slightly more short-term neurological sequelae other than hearing loss (RR 1.99, 95% CI 1.40 to 2.81; 2 studies, 1096 participants; I² = 0%; low certainty evidence) and slightly more long-term neurological sequelae other than hearing loss (RR 2.32, 95% CI 1.34 to 4.04; 2 studies, 901 participants; I² = 0%; low certainty evidence). No adverse events were reported in either group in any of the paracetamol studies (very low certainty evidence). Two paracetamol studies had a low risk of bias in most domains, and one had low or unclear risk of bias in all domains. We judged the certainty of evidence to be low for mortality due to limitations in study design (unclear risk of bias in at least one domain and imprecision (high level of uncertainty in absolute effects), and low for all other outcomes due to limitations in study design (unclear risk of bias in at least one domain), and imprecision (low sample size and few events) or inconsistency in effect estimates (heterogeneity). We were not able to perform meta-analysis for any of the other adjuvant therapies due to the limited number of included studies. It is uncertain whether immunoglobulins, heparin, or pentoxifylline improves mortality outcomes due to the very low certainty of the evidence. Zero adverse events were reported for immunoglobulins (very low certainty evidence), and allergic reactions occurred at a rate of 3.3% in participants receiving a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide (intervention group) (very low certainty evidence). None of our other outcomes (hearing loss, neurological sequelae other than hearing loss, severe hearing loss, and short-term or long-term neurological sequelae other than hearing loss) were reported in these studies, and all of these studies were judged to have a high risk of bias. All reported outcomes for all included adjuvant therapies, other than paracetamol, were graded as very low certainty of evidence due to limitations in study design (unclear or high risk of bias in at least four domains) and imprecision (extremely low sample size and few events).
AUTHORS' CONCLUSIONS
Few adjuvant therapies for bacterial meningitis have been tested in RCTs. Paracetamol may make little or no difference to mortality, with a high level of uncertainty in the absolute effects (low certainty evidence). Paracetamol may make little or no difference to hearing loss, neurological sequelae other than hearing loss, and severe hearing loss (all low certainty evidence). Paracetamol may lead to slightly more short-term and long-term neurological sequelae other than hearing loss (both outcomes low certainty evidence). There is insufficient evidence to determine whether any of the adjuvant therapies included in this review (paracetamol, immunoglobulins, heparin, pentoxifylline, or a mixture of succinic acid, inosine, nicotinamide, and riboflavin mononucleotide) are beneficial or detrimental in acute bacterial meningitis.
Topics: Acetaminophen; Adrenal Cortex Hormones; Adult; Anti-Bacterial Agents; Child; Hearing Loss; Humans; Meningitis, Bacterial
PubMed: 34813078
DOI: 10.1002/14651858.CD013437.pub2 -
Cornea Aug 2018To systematically compare standard epithelium-off corneal collagen cross-linking (SCXL) and transepithelial corneal collagen cross-linking (TECXL) for treating... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
To systematically compare standard epithelium-off corneal collagen cross-linking (SCXL) and transepithelial corneal collagen cross-linking (TECXL) for treating keratoconus.
METHODS
PubMed, EMBASE, the Cochrane Library, the US trial registry (ClinicalTrials.gov), VIP Database, Wanfang Databse, and China National Knowledge Infrastructure searches up to February 2017 were conducted. Primary outcomes were changes at 1 year in uncorrected distance visual acuity, maximum keratometry (Kmax), and mean keratometry (mean K). Secondary outcomes were changes at 1 year in corrected distance visual acuity, mean refractive spherical equivalent, central corneal thickness, endothelial cell density, and the occurrence of adverse events.
RESULTS
Eight studies with a total of 455 eyes were included. For primary outcomes, SCXL showed a greater reduction in mean K [standardized mean difference (SMD) 0.28; 95% confidence interval (CI), 0.03-0.53; P = 0.03] compared with TECXL. Subgroup analysis indicated that SCXL had a comparable effect on reducing mean K with TECXL protocols using chemical enhancers (SMD 0.05; 95% CI, -0.36 to 0.45; P = 0.82) but a greater reduction in mean K compared with TECXL with current iontophoretic protocols (SMD 0.43; 95% CI, 0.10-0.75; P = 0.01). For the other outcomes, there were no statistically significant differences.
CONCLUSIONS
With the exception of less reduction in mean K with current iontophoretic protocols, analysis of the limited number of comparative studies available seems to demonstrate that SCXL and TECXL have a comparable effect on visual, refractive, pachymetric, and endothelial parameters at 1 year after surgery. Further follow-up is required to determine whether these techniques are comparable in the long-term.
Topics: Collagen; Cornea; Corneal Pachymetry; Corneal Topography; Cross-Linking Reagents; Drug Administration Routes; Epithelium, Corneal; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Riboflavin; Ultraviolet Rays
PubMed: 29847492
DOI: 10.1097/ICO.0000000000001632 -
Public Health Nutrition Jun 2000While iron deficiency is regarded as the major cause of nutritional anaemia, changes in vitamins A, B12, C and E, folic acid and riboflavin status have also been linked... (Review)
Review
OBJECTIVE
While iron deficiency is regarded as the major cause of nutritional anaemia, changes in vitamins A, B12, C and E, folic acid and riboflavin status have also been linked to its development and control. This paper provides a systematic review of vitamin supplementation trials relating to the control of nutritional anaemia.
METHODS
A MEDLINE search was used to find reports of vitamin supplementation trials that reported changes in anaemia or iron status.
RESULTS
Vitamin A can improve haematological indicators and enhance the efficacy of iron supplementation. Both folate and vitamin B12 can cure and prevent megaloblastic anaemia. Riboflavin enhances the haematological response to iron, and its deficiency may account for a significant proportion of anaemia in many populations. Vitamin C enhances the absorption of dietary iron, although population-based data showing its efficacy in reducing anaemia or iron deficiency are lacking. Vitamin E supplementation given to preterm infants has not reduced the severity of the anaemia of prematurity. Vitamin B6 effectively treats sideroblastic anaemia. Multivitamin supplementation may raise haemoglobin (Hb) concentration, but few studies have isolated the effect of multivitamins from iron on haematological status.
CONCLUSIONS
In general, the public health impact of vitamin supplementation in controlling anaemia is not clear. Neither are the complex interactions involving multiple vitamins in haematopoiesis sufficiently understood to explain the observed variability in haematological responses to vitamins by age, population, vitamin mixture and dosages. Further research is needed to understand the roles of individual and combined vitamin deficiencies on anaemia to design appropriate micronutrient interventions to prevent anaemia.
Topics: Anemia; Anemia, Iron-Deficiency; Avitaminosis; Dietary Supplements; Global Health; Hematocrit; Hemoglobins; Humans; Vitamins
PubMed: 10948381
DOI: 10.1017/s1368980000000173 -
Journal of Neuromuscular Diseases 2021Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid...
BACKGROUND
Hereditary peripheral neuropathies are inherited disorders affecting the peripheral nervous system, including Charcot-Marie-Tooth disease, familial amyloid polyneuropathy and hereditary sensory and motor neuropathies. While the molecular basis of hereditary peripheral neuropathies has been extensively researched, interventional trials of pharmacological therapies are lacking.
OBJECTIVE
We collated evidence for the effectiveness of pharmacological and gene-based treatments for hereditary peripheral neuropathies.
METHODS
We searched several databases for randomised controlled trials (RCT), observational studies and case reports of therapies in hereditary peripheral neuropathies. Two investigators extracted and analysed the data independently, assessing study quality using the Oxford Centre for Evidence Based Medicine 2011 Levels of Evidence in conjunction with the Jadad scale.
RESULTS
Of the 2046 studies initially identified, 119 trials met our inclusion criteria, of which only 34 were carried over into our final analysis. Ascorbic acid was shown to have no therapeutic benefit in CMT1A, while a combination of baclofen, naltrexone and sorbitol (PXT3003) demonstrated some efficacy, but phase III data are incomplete. In TTR-related amyloid polyneuropathy tafamidis, patisiran, inotersen and revusiran showed significant benefit in high quality RCTs. Smaller studies showed the efficacy of L-serine for SPTLC1-related hereditary sensory neuropathy, riboflavin for Brown-Vialetto-Van Laere syndrome (SLC52A2/3) and phytanic acid-poor diet in Refsum disease (PHYH).
CONCLUSIONS
The 'treatable' variants highlighted in this project will be flagged in the treatabolome database to alert clinicians at the time of the diagnosis and enable timely treatment of patients with hereditary peripheral neuropathies.
Topics: Amyloid Neuropathies, Familial; Charcot-Marie-Tooth Disease; Hereditary Sensory and Motor Neuropathy; Humans
PubMed: 32773395
DOI: 10.3233/JND-200546 -
Journal of Cataract and Refractive... Oct 2021Corneal crosslinking (CXL) is the current mainstay treatment for progressive keratoconus. In the past 15 years, a variety of other indications have been tested. A...
Corneal crosslinking (CXL) is the current mainstay treatment for progressive keratoconus. In the past 15 years, a variety of other indications have been tested. A systematic review was conducted to examine these alternative indications for CXL. In total, 143 papers on crosslinking as a treatment for infectious keratitis, bullous keratopathy, pellucid marginal degeneration, and postlaser in situ keratomileusis (LASIK) ectasia and as a way to improve vision either on its own or in combination with other interventions were included. Post-LASIK ectasia is a definite indication for crosslinking. Surprisingly, only limited research has been performed on pellucid marginal degeneration, with no randomized trials available to date. Other interesting applications are the combined use of refractive lasers and crosslinking for suspicious or ectatic corneas and crosslinking as a standalone intervention for minor refractive errors. CXL might offer a solution for refractory bacterial keratitis. In bullous keratopathy, it seems to offer only a transient benefit.
Topics: Collagen; Cornea; Corneal Topography; Cross-Linking Reagents; Humans; Keratoconus; Keratomileusis, Laser In Situ; Photosensitizing Agents; Riboflavin; Ultraviolet Rays
PubMed: 33929804
DOI: 10.1097/j.jcrs.0000000000000663 -
Oxygen in Corneal Collagen Crosslinking to Treat Keratoconus: A Systematic Review and Meta-Analysis.Asia-Pacific Journal of Ophthalmology... Sep 2022Keratoconus is a disorder that results in visual loss from increased corneal high-order aberrations and irregular astigmatism and reduces quality of life. The primary... (Meta-Analysis)
Meta-Analysis
PURPOSE
Keratoconus is a disorder that results in visual loss from increased corneal high-order aberrations and irregular astigmatism and reduces quality of life. The primary treatment for progressive keratoconus is crosslinking (CXL). Recently, it has been suggested that oxygen enhances the type II photodynamic reaction of CXL that is oxygen dependent. Our study investigated the effect of increased oxygen availability in epithelium-on CXL on visual acuity and corneal curvature.
METHODS
We searched PubMed, EMBASE, Medline, Web of Science, and Scopus databases on November 3, 2021. We included studies that reported increased oxygen availability during CXL in patients with keratoconus published within the last 10 years. A meta-analysis on the primary outcomes, maximum keratometry, and corrected distance visual acuity, was conducted.
RESULTS
The search yielded 108 publications which were screened and assessed for eligibility. Six studies were included in the systematic review and 5 studies were included in our meta-analysis of the outcomes of increased oxygen availability in accelerated CXL. The meta-analysis on data after 6 months of follow-up found a significant decrease in mean maximum keratometry of 1.2 diopter (95% confidence interval: 0.2-2.3; P =0.02) and an improvement in mean corrected distance visual acuity by 0.08 logMAR (95% confidence interval, 0.02-0.13; P =0.01). There were no serious adverse events reported.
CONCLUSIONS
Increasing oxygen during epithelium-on CXL improved visual acuity and produced corneal flattening without any serious adverse events in patients with keratoconus. The demarcation line depth was significantly higher with oxygen compared to the control group. Further data are required with a control group and long-term follow-up across a range of CXL protocols for implementation into standard clinical practice.
Topics: Collagen; Corneal Stroma; Corneal Topography; Cross-Linking Reagents; Humans; Keratoconus; Oxygen; Photosensitizing Agents; Quality of Life; Riboflavin; Ultraviolet Rays
PubMed: 36094374
DOI: 10.1097/APO.0000000000000555 -
Clinical Breast Cancer Aug 2020Epidemiologic studies focusing on the association between 1-carbon metabolism-related vitamins (ie, folate, vitamin B, vitamin B, vitamin B) and breast cancer risk have... (Meta-Analysis)
Meta-Analysis
Epidemiologic studies focusing on the association between 1-carbon metabolism-related vitamins (ie, folate, vitamin B, vitamin B, vitamin B) and breast cancer risk have reported inconsistent findings. We conducted a systematic search of the reported data and performed a meta-analysis of prospective case-control and cohort studies to derive a more precise evaluation. The PubMed and EMBASE databases were searched to identify eligible studies. A total of 27 studies involving 49,707 cases and 1,274,060 individuals were included in the meta-analysis. The results indicated that a high intake of folate, vitamin B, and vitamin B might decrease the risk of breast cancer. The corresponding pooled relative risks (RRs) for the highest intake compared with the lowest were 0.93 (95% confidence interval [CI], 0.88-0.99; P = .018), 0.94 (95% CI, 0.89-1.00; P = .037) and 0.90 (95% CI, 0.82-0.99; P = .026). No significant association between vitamin B and breast cancer risk was found (RR, 0.99; 95% CI, 0.94-1.04; P = .604). Further study showed that folate and vitamin B might decrease the risk of estrogen receptor-negative (ER)/progesterone receptor-negative (PR) breast cancer but not ER/PR breast cancer. The dose-response meta-analysis indicated a significant linearity relationship between folate intake and a reduced risk of ER/PR breast cancer. An increment of folate intake (100 μg/d) corresponded to a 7% deceased risk of ER/PR breast cancer (RR, 0.93; 95% CI, 0.89-0.98; P = .007). In conclusion, a high intake of 1-carbon metabolism-related vitamins might contribute to the prevention of breast cancer, especially ER/PR breast cancer.
Topics: Breast; Breast Neoplasms; Case-Control Studies; Diet Surveys; Female; Folic Acid; Humans; Prospective Studies; Receptor, ErbB-2; Receptors, Estrogen; Receptors, Progesterone; Riboflavin; Risk Assessment; Risk Factors; Vitamin B 12; Vitamin B 6
PubMed: 32241696
DOI: 10.1016/j.clbc.2020.02.012 -
Cornea Jul 2022Corneal collagen cross-linking (CXL) is an effective treatment to slow down keratoconus (KC) progression in adults. Several studies have also shown efficacious outcomes...
PURPOSE
Corneal collagen cross-linking (CXL) is an effective treatment to slow down keratoconus (KC) progression in adults. Several studies have also shown efficacious outcomes in pediatric populations, yet no systematic analysis has been performed and no accepted definition for progression is available in children after CXL. This study aimed to establish the most commonly used criteria for progression and to conduct a systematic review of the literature with pooled analysis to assess children's keratoconus progression after CXL.
METHODS
A systemic literature review combined with pooled analysis was performed on full-length studies of KC after CXL treatment in a pediatric population and the methods used to report progression were analyzed.
RESULTS
Thirty-seven studies (2078 eyes) were identified on the rates of KC progression after CXL. The most common method to report progression was increased Kmax, Kmean, or Ksteep by ≥1.0 diopter (78.3% of studies). Using these criteria, the mean pooled progression rate after epithelium-off CXL was 9.9% (95% confidence interval: 6.1% -14.6%, total pooled sample size: 1508 eyes) with high heterogeneity between studies [I 2 = 86.48% (95% confidence interval: 80.98 - 90.39), P < 0.0001].
CONCLUSIONS
When considering KC progression after CXL in children, with an increase in Kmax, Kmean, or Ksteep ≥ 1.0 diopter, the progression risk was roughly 10%. We encourage clear quantitative reporting of KC progression in future studies evaluating CXL efficacy in pediatric populations.
Topics: Adult; Child; Collagen; Corneal Topography; Cross-Linking Reagents; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Riboflavin; Ultraviolet Rays; Visual Acuity
PubMed: 34294638
DOI: 10.1097/ICO.0000000000002808