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Journal of Neuromuscular Diseases 2021Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective...
BACKGROUND
Metabolic myopathies are a heterogenous group of muscle diseases typically characterized by exercise intolerance, myalgia and progressive muscle weakness. Effective treatments for some of these diseases are available, but while our understanding of the pathogenesis of metabolic myopathies related to glycogen storage, lipid metabolism and β-oxidation is well established, evidence linking treatments with the precise causative genetic defect is lacking.
OBJECTIVE
The objective of this study was to collate all published evidence on pharmacological therapies for the aforementioned metabolic myopathies and link this to the genetic mutation in a format amenable to databasing for further computational use in line with the principles of the "treatabolome" project.
METHODS
A systematic literature review was conducted to retrieve all levels of evidence examining the therapeutic efficacy of pharmacological treatments on metabolic myopathies related to glycogen storage and lipid metabolism. A key inclusion criterion was the availability of the genetic variant of the treated patients in order to link treatment outcome with the genetic defect.
RESULTS
Of the 1,085 articles initially identified, 268 full-text articles were assessed for eligibility, of which 87 were carried over into the final data extraction. The most studied metabolic myopathies were Pompe disease (45 articles), multiple acyl-CoA dehydrogenase deficiency related to mutations in the ETFDH gene (15 articles) and systemic primary carnitine deficiency (8 articles). The most studied therapeutic management strategies for these diseases were enzyme replacement therapy, riboflavin, and carnitine supplementation, respectively.
CONCLUSIONS
This systematic review provides evidence for treatments of metabolic myopathies linked with the genetic defect in a computationally accessible format suitable for databasing in the treatabolome system, which will enable clinicians to acquire evidence on appropriate therapeutic options for their patient at the time of diagnosis.
Topics: Glycogen; Glycogen Storage Disease Type II; Humans; Lipid Metabolism; Metabolism, Inborn Errors; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Muscle Weakness; Mutation
PubMed: 33720849
DOI: 10.3233/JND-200621 -
The British Journal of Nutrition Dec 2009A systematic literature search identified studies validating the methodology used for measuring the usual dietary intake in infants, children and adolescents. The... (Review)
Review
A systematic literature search identified studies validating the methodology used for measuring the usual dietary intake in infants, children and adolescents. The quality of each validation study selected was assessed using a European micronutrient Recommendations Aligned-developed scoring system. The validation studies were categorised according to whether the study used a reference method that reflected short-term intake ( < 7 d), long-term intake ( > or = 7 d) or used biomarkers. A correlation coefficient for each nutrient was calculated from the mean of the correlation coefficients from each study weighted by the quality of the study. Thirty-two articles were included in the present review: validation studies from infants (1-23 months); child preschool (2-5 years); children (6-12 years); adolescents (13-18 years). Validation of FFQ studies in infants and preschool children using a reference method that reflected short-term intake showed good correlations for niacin, thiamin, vitamins B6, D, C, E, riboflavin, Ca, K, Mg, Fe and Zn (with correlations ranging from 0.55 for vitamin E to 0.69 for niacin).Regarding the reference method reflecting short-term intake in children and adolescents, good correlations were seen only for vitamin C (r 0.61) and Ca (r 0.51). Using serum levels of micronutrient demonstrated that the 3 d weighed dietary records was superior to the FFQ as a tool to validate micronutrient intakes. Including supplement users generally improved the correlations between micronutrient intakes estimated by any of the dietary intake methods and respective biochemical indices.
Topics: Adolescent; Biomarkers; Child; Child Nutritional Physiological Phenomena; Diet; Diet Records; Diet Surveys; Dietary Supplements; Epidemiologic Methods; Europe; Humans; Infant; Micronutrients; Nutrition Assessment; Nutritional Sciences; Reproducibility of Results; Surveys and Questionnaires
PubMed: 20100370
DOI: 10.1017/S0007114509993163 -
Seminars in Ophthalmology 2016To describe the infectious complications and the group of pathogens involved in the infection following corneal crosslinking, the visual outcome, and the treatment... (Review)
Review
AIM
To describe the infectious complications and the group of pathogens involved in the infection following corneal crosslinking, the visual outcome, and the treatment proposed.
METHODS
A Medline (National Library of Medicine, Bethesda, MD, USA) search from October 2000 to October 2013 was performed to identify all articles describing infectious keratitis following corneal crosslinking treatment. Nineteen articles were selected. Ten articles reported infectious complications of corneal crosslinking treatment were included. Nine articles were excluded, because seven described sterile keratitis, one article was in German, and one reported general complication without describing the infection complication.
RESULTS
A total number of infections reported included 10 eyes. The infectious keratitis was associated with bacteria in five eyes (50%): gram-positive bacteria in three eyes (30%) (staphylococcus epidermidis, S. aureus and streptococcus salivarius plus S. oralis, respectively) and gram-negative bacteria in two eyes (20%) (E. coli; P. aeruginosa); there was herpes virus in two eyes, fungus in two eyes (Fusarium and Microsporidia) (20%), and Acanthamoeba in one eye (10%).
CONCLUSIONS
Only 10 cases of infectious keratitis following corneal crosslinking are published. The most virulent pathogens were Pseudomonas aeruginosa and Acanthamoeba. Less virulent organisms were Escherichia coli and S. epidermidis. Two cases of herpes keratitis were described, suggesting the possibility of systemic antiviral prophylaxis before corneal crosslinking treatment. The most common risk factor of infections identified was postoperative incorrect patient behavior.
Topics: Adult; Collagen; Corneal Stroma; Cross-Linking Reagents; Eye Infections; Humans; Keratitis; Photosensitizing Agents; Postoperative Complications; Riboflavin; Risk Factors; Ultraviolet Rays; Visual Acuity; Young Adult
PubMed: 25392046
DOI: 10.3109/08820538.2014.962176 -
Neuromuscular Disorders : NMD Mar 2021Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder with a dramatic clinical presentation. It was recently discovered that MADD may...
Multiple acyl-coenzyme A dehydrogenase deficiency (MADD) is a rare metabolic disorder with a dramatic clinical presentation. It was recently discovered that MADD may present at an advanced age. The clinical and laboratory data of an index patient and patients previously diagnosed at our institution were collected. A systematic review of previous studies retrieved from the PubMed, MEDLINE, and Embase databases published by February 1, 2020 was performed to collect patients with very-late-onset MADD (VLO-MADD, onset age > 60 years) globally and patients with late-onset MADD (LO-MADD, onset age < 60 years) in Taiwan. The clinical characteristics of the VLO-MADD patients were compared to those of LO-MADD patients. We report a patient with VLO-MADD who developed the first symptom at the age of 61 years. The patient presented with a Reye-like syndrome after taking aspirin for coronary artery disease. Repeated bouts of weakness were noted. Two variants of c.250 G > A (;) 419C > T were observed in the ETFDH gene. Another four patients with VLO-MADD were identified globally. Eighteen patients with LO-MADD were collected from our department and previously reported patients in Taiwan. There was no difference in the clinical symptoms (except for the onset age) or laboratory data between these two groups. Homozygous variants were not observed in any patients in the VLO-MADD group but were detected in 12 patients (66.6%) in the LO-MADD group (p = 0.014). Patients with MADD may first show symptoms in their 6th decade or beyond. The disease course may lead to erroneous diagnoses in this age group.
Topics: Acyl-CoA Dehydrogenase; Adult; Age of Onset; Aged; Cohort Studies; Female; Homozygote; Humans; Male; Middle Aged; Multiple Acyl Coenzyme A Dehydrogenase Deficiency; Muscle, Skeletal; Mutation; Riboflavin; Taiwan; Young Adult
PubMed: 33589341
DOI: 10.1016/j.nmd.2021.01.006 -
Ophthalmology Aug 2021To evaluate the safety and efficacy of transepithelial corneal cross-linking in comparison with the established epithelium-off technique for corneal ectasia. (Meta-Analysis)
Meta-Analysis
TOPIC
To evaluate the safety and efficacy of transepithelial corneal cross-linking in comparison with the established epithelium-off technique for corneal ectasia.
CLINICAL RELEVANCE
Considerable debate exists regarding whether transepithelial and epithelium-off cross-linking are comparable in their safety and efficacy.
METHODS
We searched 16 electronic databases, including Medline, Embase, Web of Science, and the grey literature, current to July 8, 2020, for randomized controlled trials comparing transepithelial and epithelium-off cross-linking for corneal ectasia. We excluded studies evaluating cross-linking for nonectatic indications, as well as non-randomized controlled trials. Our primary outcome was the change in maximal keratometry (K) at 12 months after cross-linking, and we considered additional topographic, visual, and safety outcomes. We summarized our analyses by calculating weighted mean differences (MDs) with associated 95% confidence intervals (CIs) for continuous outcomes and relative risks (RRs) with corresponding 95% CIs for dichotomous outcomes. We conducted trial sequential analysis to determine whether the required information size was met for each outcome. The quality of individual trials was evaluated using the Cochrane Collaboration's risk of bias assessment tool, and the evidence was assessed at an outcome level using the Grading of Recommendations Assessment, Development, and Evaluation methodology.
RESULTS
Twelve studies totaling 966 eyes were eligible. A significant difference was found between transepithelial and epithelium-off cross-linking groups in the change in K at 12 months (MD, 0.75; 95% CI, 0.23-1.28; P = 0.004; primary outcome) and at longest follow-up (MD, 1.20; 95% CI, 0.62-1.77; P < 0.001; secondary outcome) after treatment. No significant difference was found between the 2 groups when examining uncorrected distance visual acuity (MD, 0.04; 95% CI, -0.06 to 0.14; P = 0.386) or corrected distance visual acuity (MD, 0.01; 95% CI, -0.06 to 0.09; P = 0.732). Transepithelial cross-linking was associated with significantly fewer complications than the epithelium-off approach (RR, 0.22; 95% CI, 0.06-0.79; P = 0.020), although it was associated with an increased rate of disease progression at 12 months after treatment (RR, 4.49; 95% CI, 1.24-16.25; P = 0.022). The required information size was met for our primary outcome and trial sequential analysis supported the conventional meta-analysis. The quality of evidence was rated as moderate using the Grading of Recommendations Assessment, Development, and Evaluation methodology.
DISCUSSION
The efficacy of transepithelial cross-linking remains inferior to the epithelium-off approach, although it is significantly safer.
Topics: Collagen; Corneal Stroma; Cross-Linking Reagents; Debridement; Dilatation, Pathologic; Epithelium, Corneal; Humans; Keratoconus; Photochemotherapy; Photosensitizing Agents; Randomized Controlled Trials as Topic; Riboflavin; Ultraviolet Rays; Visual Acuity
PubMed: 33383093
DOI: 10.1016/j.ophtha.2020.12.023 -
Graefe's Archive For Clinical and... Sep 2023The success of corneal collagen cross-linking in altering keratoconus' clinical course has driven a search for further uses of this procedure. This literature review...
PURPOSE
The success of corneal collagen cross-linking in altering keratoconus' clinical course has driven a search for further uses of this procedure. This literature review aims to analyze the scientific evidence available for the benefit of cross-linking in the management of ophthalmic diseases other than progressive keratoconus or ectasia induced by corneal refractive procedures.
METHODS
A systemic literature review.
RESULTS
We reviewed 97 studies. We found that collagen cross-linking can limit the progression of several other corneal ectasias, thus reducing and limiting the need for keratoplasty. Collagen cross-linking also can reduce the refractive power of the cornea and can be considered for a moderate degree of bacterial keratitis or when the organism is unidentified, which is refractive to antibiotics alone. However, the comparative rarity of these procedures has limited the extent of evidence. In fungal, Acanthamoeba, and herpes virus keratitis, the evidence is inconclusive of the safety and efficacy of cross-linking.
CONCLUSION
Current clinical data is limited, and laboratory data has not fully correlated with published clinical data.
Topics: Humans; Collagen; Corneal Cross-Linking; Cross-Linking Reagents; Keratitis, Herpetic; Keratoconus; Photochemotherapy; Photosensitizing Agents; Riboflavin; Ultraviolet Rays
PubMed: 36881260
DOI: 10.1007/s00417-023-05994-6 -
The Cochrane Database of Systematic... Mar 2015Keratoconus is a condition of the eye that affects approximately 1 in 2000 people. The disease leads to a gradual increase in corneal curvature and decrease in visual... (Review)
Review
BACKGROUND
Keratoconus is a condition of the eye that affects approximately 1 in 2000 people. The disease leads to a gradual increase in corneal curvature and decrease in visual acuity with consequent impact on quality of life. Collagen cross-linking (CXL) with ultraviolet A (UVA) light and riboflavin (vitamin B2) is a relatively new treatment that has been reported to slow or halt the progression of the disease in its early stages.
OBJECTIVES
The objective of this review was to assess whether there is evidence that CXL is an effective and safe treatment for halting the progression of keratoconus compared to no treatment.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 7), Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid MEDLINE Daily, Ovid OLDMEDLINE (January 1946 to August 2014), EMBASE (January 1980 to August 2014), Latin American and Caribbean Health Sciences Literature Database (LILACS) (1982 to August 2014), Cumulative Index to Nursing and Allied Health Literature (CINAHL) (1982 to August 2014), OpenGrey (System for Information on Grey Literature in Europe) (www.opengrey.eu/), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the World Health Organisation International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We used no date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 28 August 2014.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) where CXL with UVA light and riboflavin was used to treat people with keratoconus and was compared to no treatment.
DATA COLLECTION AND ANALYSIS
Two review authors independently screened the search results, assessed trial quality, and extracted data using standard methodological procedures expected by Cochrane. Our primary outcomes were two indicators of progression at 12 months: increase in maximum keratometry of 1.5 dioptres (D) or more and deterioration in uncorrected visual acuity of more than 0.2 logMAR.
MAIN RESULTS
We included three RCTs conducted in Australia, the United Kingdom, and the United States that enrolled a total of 225 eyes and analysed 219 eyes. The total number of people enrolled was not clear in two of the studies. Only adults were enrolled into these studies. Out of the eyes analysed, 119 had CXL (all using the epithelium-off technique) and 100 served as controls. One of these studies only reported comparative data on review outcomes. All three studies were at high risk for performance bias (lack of masking), detection bias (only one trial attempted to mask outcome assessment), and attrition bias (incomplete follow-up). It was not possible to pool data due to differences in measuring and reporting outcomes. We identified a further three unpublished trials that potentially had enrolled a total of 195 participants.There was limited evidence on the risk of progression. Analysis of the first few participants followed up to one year in one study suggested that eyes given CXL were less likely to have an increase in maximum keratometry of 1.5 D or more at 12 months compared to eyes given no treatment, but the confidence intervals (CI) were wide and compatible with no effect or more progression in the CXL group (risk ratio (RR) 0.12, 95% CI 0.01 to 2.00, 19 eyes). The same study reported the number of eyes with an increase of 2 D or more at 36 months in the whole cohort with a RR of 0.03 favouring CXL (95% CI 0.00 to 0.43, 94 eyes). Another study reported "progression" at 18 months using a different definition; people receiving CXL were less likely to progress, but again the effect was uncertain (RR 0.14, 95% CI 0.01 to 2.61, 44 eyes). We judged this to be very low-quality evidence due to the risk of bias of included studies, imprecision, indirectness and publication bias but noted that the size of the potential effect was large.On average, treated eyes had a less steep cornea (approximately 2 D less steep) (mean difference (MD) -1.92, 95% CI -2.54 to -1.30, 94 eyes, 1 RCT, very low-quality evidence) and better uncorrected visual acuity (approximately 2 lines or 10 letters better) (MD -0.20, 95% CI -0.31 to -0.09, 94 eyes, 1 RCT, very low-quality evidence) at 12 months. None of the studies reported loss of 0.2 logMAR acuity. The data on corneal thickness were inconsistent. There were no data available on quality of life or costs. Adverse effects were not uncommon but mostly transient and of low clinical significance. In one trial, 3 out of 12 participants treated with CXL had an adverse effect including corneal oedema, anterior chamber inflammation, and recurrent corneal erosions. In one trial at 3 years 3 out of 50 participants experienced adverse events including mild diffuse corneal oedema and paracentral infiltrate, peripheral corneal vascularisation, and subepithelial infiltrates and anterior chamber inflammation. No adverse effects were reported in the control groups.
AUTHORS' CONCLUSIONS
The evidence for the use of CXL in the management of keratoconus is limited due the lack of properly conducted RCTs.
Topics: Adult; Collagen; Confidence Intervals; Cross-Linking Reagents; Disease Progression; Humans; Keratoconus; Photosensitizing Agents; Randomized Controlled Trials as Topic; Riboflavin; Ultraviolet Therapy
PubMed: 25803325
DOI: 10.1002/14651858.CD010621.pub2 -
Journal of Cataract and Refractive... Aug 2021Corneal crosslinking is a U.S. Food and Drug Administration--approved therapy to stiffen the cornea and prevent progression of corneal ectasia in patients with...
Corneal crosslinking is a U.S. Food and Drug Administration--approved therapy to stiffen the cornea and prevent progression of corneal ectasia in patients with keratoconus. The standard procedure involves removal of the corneal epithelium (epithelial-off) prior to treatment. Variations to the standard procedure include accelerated crosslinking and transepithelial procedures. This study reviewed what is known regarding the risk for infection after epithelial-off crosslinking, the spectrum of pathogens, and clinical outcomes. 26 publications were identified. All eyes were fit with a bandage contact lens postoperatively. Available data indicate that the overall frequency of infectious keratitis after epithelium-off crosslinking is low. Bacterial infections are the most common, with a mean time of presentation of 4.8 days postoperatively. The use of steroids and bandage contact lenses in the immediate postoperative period and/or a history of atopic or herpetic disease were associated with infection. These patients require intense postoperative care with prophylactic antiviral therapy when appropriate.
Topics: Collagen; Cornea; Cross-Linking Reagents; Humans; Keratitis; Keratoconus; Photosensitizing Agents; Riboflavin
PubMed: 33769765
DOI: 10.1097/j.jcrs.0000000000000620 -
Graefe's Archive For Clinical and... Jun 2024Corneal collagen crosslinking (CXL) is the primary treatment for progressive keratoconus which has a significant impact on vision and quality of life. Our study aimed to... (Meta-Analysis)
Meta-Analysis Review
PURPOSE
Corneal collagen crosslinking (CXL) is the primary treatment for progressive keratoconus which has a significant impact on vision and quality of life. Our study aimed to compare the efficacy and safety of epithelium-on versus epithelium-off CXL to treat keratoconus.
METHODS
We searched PubMed, Medline, Embase, Web of Science, and Scopus databases. We included studies that compared standard epithelium-off with epithelium-on CXL. The primary outcome measures were changes in corrected distance visual acuity (CDVA) and maximum keratometry (Kmax), and the secondary outcomes were uncorrected distance visual acuity (UDVA), central corneal thickness (CCT), and adverse events. A meta-analysis was performed on the primary and secondary outcomes based on the weighted mean differences between baseline to 12-month follow-up.
RESULTS
The search retrieved 887 publications with 27 included in the systematic review. A total of 1622 eyes (1399 patients; age 25.51 ± 4.02 years) were included in comparisons of epithelium-off to epithelium-on CXL in keratoconus. Epithelium-off CXL treated 800 eyes and epithelium-on CXL for 822 eyes. At 12-month follow-up, CDVA and Kmax showed no significant difference between the epithelium-off and epithelium-on CXL. The secondary outcomes showed that UDVA was better in epithelium-off CXL (- 0.11D, 95% CI - 0.12, - 0.1; p < 0.001) and there was more thinning in CCT in epithelium-off CXL (- 3.23 μm, 95% CI - 4.64, - 1.81; p <0.001).
CONCLUSION
Epithelium-off and epithelium-on CXL were both effective to treat progressive keratoconus. Further research is needed to compare the long-term outcomes and safety of both CXL protocols for adaptation into clinical practice.
Topics: Keratoconus; Humans; Cross-Linking Reagents; Collagen; Photosensitizing Agents; Epithelium, Corneal; Photochemotherapy; Visual Acuity; Riboflavin; Ultraviolet Rays; Corneal Topography; Corneal Stroma
PubMed: 37938377
DOI: 10.1007/s00417-023-06287-8 -
The Journal of Nutrition Nov 2010A systematic review was conducted to identify all studies that were published between 1988 and 2008 reporting micronutrient intakes of women in resource-poor settings.... (Review)
Review
A systematic review was conducted to identify all studies that were published between 1988 and 2008 reporting micronutrient intakes of women in resource-poor settings. Inclusion criteria were study location (resource-poor), dietary assessment method (24-h recall, estimated/weighed record, or locally validated FFQ), energy and 1 or more micronutrient intakes reported (vitamin A, vitamin B-6, vitamin B-12, vitamin C, thiamin, riboflavin, niacin, folate, iron, or zinc), age range (15-50 y), sample size (≥30), and sex (female). Of the 1560 papers identified, 52 papers were included. Results showed that, except for vitamin A (29%), vitamin C (34%), and niacin (34%), the reported mean/median intakes in over 50% of studies were below the Estimated Average Requirement (EAR). Folate intake was most often below EAR (91% of studies). Regional differences were apparent for intakes of vitamins A, C, and B-6 and riboflavin; mean/median intakes in Latin America exceeded the EAR, whereas in Asia, reported mean/median intakes of vitamin C, vitamin A, and riboflavin were below the EAR in 47, 50, and 77% of the studies, respectively, as was the case for vitamin B-6 in 75% of the studies in Africa. These results suggest that inadequate intakes of multiple micronutrients are common among women living in resource-poor settings and emphasize the need for increased attention to the quality of women's diets. There is a need for more high-quality studies of women's micronutrient intakes.
Topics: Adolescent; Adult; Deficiency Diseases; Developing Countries; Diet; Female; Humans; Micronutrients; Middle Aged; Poverty Areas; Risk Factors; Young Adult
PubMed: 20881075
DOI: 10.3945/jn.110.123463