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Reumatologia Clinica 2018To develop recommendations for the use of parenteral methotrexate (MTX) in rheumatic diseases, mainly rheumatoid arthritis, based on best evidence and experience.
OBJECTIVE
To develop recommendations for the use of parenteral methotrexate (MTX) in rheumatic diseases, mainly rheumatoid arthritis, based on best evidence and experience.
METHODS
A group of 21 experts on parenteral MTX use was selected. The coordinator formulated 13 questions about parenteral MTX (indications, efficacy, safety and cost-effectiveness). A systematic review was conducted to answer the questions. Using this information, inclusion and exclusion criteria were established, as were the search strategies (involving Medline, EMBASE and the Cochrane Library). Three different reviewers selected the articles. Evidence tables were created. Abstracts from the European League Against Rheumatism (EULAR) and American College of Rheumatology (ACR) were evaluated. Based on this evidence, the coordinator proposed preliminary recommendations that the experts discussed and voted in a nominal group meeting. The level of evidence and grade of recommendation were established using the Oxford Center for Evidence-Based Medicine and the level of agreement with the Delphi technique (2 rounds). Agreement was established if at least 80% of the experts voted yes (yes/no).
RESULTS
Most of the evidence involved rheumatoid arthritis. A total of 13 preliminary recommendations on the use of parenteral MTX were proposed; 11 of them were accepted. Two of the 13 were not voted and are commented on in the main text.
CONCLUSIONS
The manuscript aims to solve frequent questions and help in decision-making strategies when treating patients with parenteral MTX.
Topics: Antirheumatic Agents; Arthritis, Rheumatoid; Biological Availability; Clinical Decision-Making; Dose-Response Relationship, Drug; Drug Administration Routes; Evidence-Based Medicine; Humans; Medication Adherence; Methotrexate; Patient Education as Topic; Practice Guidelines as Topic; Quality of Life; Randomized Controlled Trials as Topic; Rheumatic Diseases; Self Administration
PubMed: 28082032
DOI: 10.1016/j.reuma.2016.12.001 -
Folate-Methionine Cycle Disruptions in ASD Patients and Possible Interventions: A Systematic Review.Genes Mar 2023Autism Spectrum Disorder (ASD) has become a major public health concern due to its rapidly rising incidence over the past few years. Disturbances in folate or methionine... (Review)
Review
Autism Spectrum Disorder (ASD) has become a major public health concern due to its rapidly rising incidence over the past few years. Disturbances in folate or methionine metabolism have been identified in many individuals with ASD, suggesting that the folate-methionine cycle may play an essential role in the pathogenesis of autism. Thus, changes in metabolite concentrations associated with this cycle could be used as potential biomarkers and therapeutic targets for ASD. The aim of this systematic review is to elucidate the perturbations of this cycle and the possible interventions that may be proposed in this context. Several studies have shown that high levels of homocysteine and low levels of vitamins B12 and folate are associated with ASD. These changes in serum metabolites are influenced by poor diet. In fact, children with ASD tend to eat selectively, which could compromise the quality of their diet and result in nutrient deficiencies. Moreover, these disturbances may also be caused by genetic predispositions such as polymorphisms of the gene. Few studies have demonstrated the beneficial effects of the use of nutritional supplements in treating ASD children. Therefore, larger, well-structured studies are recommended to examine the impact of vitamin B12 and folate supplementation on homocysteine levels.
Topics: Child; Humans; Folic Acid; Methionine; Autism Spectrum Disorder; Vitamin B 12; Dietary Supplements; Racemethionine
PubMed: 36980981
DOI: 10.3390/genes14030709 -
European Journal of Clinical Nutrition Apr 2023Diet related non-communicable diseases (NCDs), as well as micronutrient deficiencies, are of widespread and growing importance to public health. Authorities are... (Review)
Review
Diet related non-communicable diseases (NCDs), as well as micronutrient deficiencies, are of widespread and growing importance to public health. Authorities are developing programs to improve nutrient intakes via foods. To estimate the potential health and economic impact of these programs there is a wide variety of models. The aim of this review is to evaluate existing models to estimate the health and/or economic impact of nutrition interventions with a focus on reducing salt and sugar intake and increasing vitamin D, iron, and folate/folic acid intake. The protocol of this systematic review has been registered with the International Prospective Register of Systematic Reviews (PROSPERO: CRD42016050873). The final search was conducted on PubMed and Scopus electronic databases and search strings were developed for salt/sodium, sugar, vitamin D, iron, and folic acid intake. Predefined criteria related to scientific quality, applicability, and funding/interest were used to evaluate the publications. In total 122 publications were included for a critical appraisal: 45 for salt/sodium, 61 for sugar, 4 for vitamin D, 9 for folic acid, and 3 for iron. The complexity of modelling the health and economic impact of nutrition interventions is dependent on the purpose and data availability. Although most of the models have the potential to provide projections of future impact, the methodological challenges are considerable. There is a substantial need for more guidance and standardization for future modelling, to compare results of different studies and draw conclusions about the health and economic impact of nutrition interventions.
Topics: Humans; Folic Acid; Iron; Sodium; Sugars; Vitamin D; Vitamins
PubMed: 36195747
DOI: 10.1038/s41430-022-01199-y -
Journal of Osteopathic Medicine Apr 2023Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly affects joints. Although many treatment options exist, the most common, disease-modifying... (Meta-Analysis)
Meta-Analysis Review
CONTEXT
Rheumatoid arthritis (RA) is a systemic autoimmune disease that commonly affects joints. Although many treatment options exist, the most common, disease-modifying antirheumatic drugs (DMARDs), have been associated with pulmonary infections. These types of infections (specifically pneumonia) can be detrimental to RA patients. This leads providers to utilize other treatment modalities such as glucocorticoids (GCs). GCs are commonly utilized to treat RA; however, the role of GCs in the onset of pneumonia in RA patients is not fully understood.
OBJECTIVES
The goal of this study was to systematically review and statistically analyze pooled data documenting pneumonia as an adverse event in RA patients on DMARDs as a monotherapy vs RA patients on DMARDs and GCs as combination therapy utilizing the Population, Intervention, Comparison, and Outcomes (PICO) framework.
METHODS
On August 1, 2021, a search was conducted and completed on six databases: Embase, MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, International Pharmaceutical Abstracts (IPA), and ClinicalTrials.gov. A total of 12 researchers were involved with the search and screening of articles (K.E., P.R.; V.A., D.P.C.; C.B., D.C.; T.A., E.S.; S.H., L.B.; K.S., C.S.). Search terms were identified utilizing Medical Subject Headings (MeSH) and Emtree and included "glucocorticoids," "rheumatoid arthritis," "pneumonia," and "respiratory tract infections," Inclusion criteria included human subjects over the age of 18 with seropositive RA, on a combination of GC (prednisone, methylprednisolone, or prednisolone) with DMARD (methotrexate [MTX], hydroxychloroquine [HCQ], or sulfasalazine [SSZ]) and developed pneumonia of bacterial, viral, or fungal origin. The control groups were on a DMARD monotherapy regimen. Articles were excluded if they were not in English, had less than 20 participants, were case reports or literature reviews, included animal subjects, and did not adhere to the established PICO framework. Five teams of two researchers individually sorted through abstracts of articles based on the inclusion and exclusion criteria. The same teams individually sorted through full-text articles of selected abstracts based on the same criteria. Conflicts between each team were resolved by a separate researcher. Odds ratios were utilized to quantify the effect sizes of combined studies from a random effects model. Chi-square tests and I2 statistics were utilized to analyze heterogeneity.
RESULTS
A total of 3360 articles were identified from all databases, and 416 duplicate articles were removed. Thus, a total of 2944 articles abstracts were screened, of which 2819 articles either did not meet the inclusion criteria or did meet the exclusion criteria. A total of 125 articles were retrieved and assessed for full-text eligibility, of which only three observational articles were included for meta-analysis. Statistical results revealed that patients treated with DMARDs monotherapy are 95% (95% CI: 0.65-0.99) less likely to develop pneumonia compared to patients treated with a DMARD and GCs (p=0.002).
CONCLUSIONS
Our data suggest that RA patients have a higher probability of developing pneumonia on combination therapy with GCs, compared to monotherapy with DMARDs. To our knowledge, our findings are the first to systematically review and statistically evaluate the relationship between the use of GCs and show an increased chance of developing pneumonia.
Topics: Humans; Adult; Middle Aged; Glucocorticoids; Arthritis, Rheumatoid; Antirheumatic Agents; Methotrexate; Pneumonia
PubMed: 36691851
DOI: 10.1515/jom-2022-0177 -
Journal of Alzheimer's Disease : JAD 2023Nutrition has relevant role in the pathogenesis of dementia. However, in Latin American Countries (LAC), it is unknown which type of diet the subjects with dementia and...
BACKGROUND
Nutrition has relevant role in the pathogenesis of dementia. However, in Latin American Countries (LAC), it is unknown which type of diet the subjects with dementia and cognitive dysfunction have.
OBJECTIVE
The main purpose of this study was to determine micro- and macronutrients and food frequency intake among the LAC population with mild cognitive impairment (MCI) and dementia.
METHODS
A systematic review using PubMed, Cochrane, Lilacs, and Scielo databases. Energy intake as well as micro- and macronutrients intake were analyzed using a random-effect model and presented in a forest plot.
RESULTS
Nine articles were included, an estimated energy intake of 1598.47 kcal (95% CI 1351.07-1845.88) was obtained. A daily consumption of 73.64 g/day (95% CI 64.07-83.2) of protein; 262.17 g/day (95% CI 214.51-309.93) of carbohydrates, and 57.91 g/day (95% CI 49.16-66.66) of fats were reported. A micronutrients daily intake consumption of 201.35μg/day of vitamin B9 (95% CI 125.32-277.38); 5.61μg/day of vitamin B12 (95% CI 2.53-8.70), and 139.67 mg/day of vitamin C (95% CI 59.33-220.02). Mineral intake of 637.32 mg/day of calcium (95% CI 288.54-986.11) and 9 mg/day of iron (95% CI 2.28-15.71) was obtained. A low intake of fruits and vegetables was found.
CONCLUSION
Individuals with MCI and dementia from LAC have a nutritional deficiency characterized by a lower intake of fruits and vegetables, a high consumption of carbohydrates and protein, adequate fats intake and vitamins B12, vitamin C, and iron consumption, but a low intake of vitamin B9 and calcium.
Topics: Humans; Latin America; Calcium; Cognitive Dysfunction; Vitamins; Folic Acid; Energy Intake; Vitamin B 12; Ascorbic Acid; Eating; Dementia; Iron
PubMed: 37302035
DOI: 10.3233/JAD-230231 -
World Journal of Urology Aug 2023The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank... (Meta-Analysis)
Meta-Analysis
Comparison between different neoadjuvant chemotherapy regimens and local therapy alone for bladder cancer: a systematic review and network meta-analysis of oncologic outcomes.
PURPOSE
The present systematic review and network meta-analysis (NMA) compared the current different neoadjuvant chemotherapy (NAC) regimes for bladder cancer patients to rank them.
METHODS
We used the Bayesian approach in NMA of six different therapy regimens cisplatin, cisplatin/doxorubicin, (gemcitabine/cisplatin) GC, cisplatin/methotrexate, methotrexate, cisplatin, and vinblastine (MCV) and (MVAC) compared to locoregional treatment.
RESULTS
Fifteen studies comprised 4276 patients who met the eligibility criteria. Six different regimes were not significantly associated with a lower likelihood of overall mortality rate compared to local treatment alone. In progression-free survival (PFS) rates, cisplatin, GC, cisplatin/methotrexate, MCV and MVAC were not significantly associated with a higher likelihood of PFS rate compared to locoregional treatment alone. In local control outcome, MCV, MVAC, GC and cisplatin/methotrexate were not significantly associated with a higher likelihood of local control rate versus locoregional treatment alone. Nevertheless, based on the analyses of the treatment ranking according to SUCRA, it was highly likely that MVAC with high certainty of results appeared as the most effective approach in terms of mortality, PFS and local control rates. GC and cisplatin/doxorubicin with low certainty of results was found to be the best second options.
CONCLUSION
No significant differences were observed in mortality, progression-free survival and local control rates before and after adjusting the type of definitive treatment in any of the six study arms. However, MVAC was found to be the most effective regimen with high certainty, while cisplatin alone and cisplatin/methotrexate should not be recommended as a neoadjuvant chemotherapy regime.
Topics: Humans; Cisplatin; Neoadjuvant Therapy; Methotrexate; Bayes Theorem; Network Meta-Analysis; Gemcitabine; Antineoplastic Combined Chemotherapy Protocols; Urinary Bladder Neoplasms; Doxorubicin; Vinblastine; Cystectomy
PubMed: 37347252
DOI: 10.1007/s00345-023-04478-w -
The Cochrane Database of Systematic... Jan 2017The therapeutic management of people with metastatic colorectal cancer (CRC) who did not respond to first-line treatment represents a formidable challenge. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The therapeutic management of people with metastatic colorectal cancer (CRC) who did not respond to first-line treatment represents a formidable challenge.
OBJECTIVES
To determine the efficacy and toxicity of second-line systemic therapy in people with metastatic CRC.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (the Cochrane Library 2016, Issue 4), Ovid MEDLINE (1950 to May 2016), Ovid MEDLINE In-process & Other Non-Indexed Citations (1946 to May 2016) and Ovid Embase (1974 to May 2016). There were no language or date of publication restrictions.
SELECTION CRITERIA
Randomized controlled trials (RCTs) assessing the efficacy (survival, tumour response) and toxicity (incidence of severe adverse effects (SAEs)) of second-line systemic therapy (single or combined treatment with any anticancer drug, at any dose and number of cycles) in people with metastatic CRC that progressed, recurred or did not respond to first-line systemic therapy.
DATA COLLECTION AND ANALYSIS
Authors performed a descriptive analysis of each included RCT in terms of primary (survival) and secondary (tumour response, toxicity) endpoints. In the light of the variety of drug regimens tested in the included trials, we could carry out meta-analysis considering classes of (rather than single) anticancer regimens; to this aim, we applied the random-effects model to pool the data. We used hazard ratios (HRs) and risk ratios (RRs) to describe the strength of the association for survival (overall (OS) and progression-free survival (PFS)) and dichotomous (overall response rate (ORR) and SAE rate) data, respectively, with 95% confidence intervals (CI).
MAIN RESULTS
Thirty-four RCTs (enrolling 13,787 participants) fulfilled the eligibility criteria. Available evidence enabled us to address multiple clinical issues regarding the survival effects of second-line systemic therapy of people with metastatic CRC.1. Chemotherapy (irinotecan) was more effective than best supportive care (HR for OS: 0.58, 95% CI 0.43 to 0.80; 1 RCT; moderate-quality evidence); 2. modern chemotherapy (FOLFOX (5-fluorouracil plus leucovorin plus oxaliplatin), irinotecan) is more effective than outdated chemotherapy (5-fluorouracil) (HR for PFS: 0.59, 95% CI 0.49 to 0.73; 2 RCTs; high-quality evidence) (HR for OS: 0.69, 95% CI 0.51 to 0.94; 1 RCT; moderate-quality evidence); 3. irinotecan-based combinations were more effective than irinotecan alone (HR for PFS: 0.68, 95% CI 0.60 to 0.76; 6 RCTs; moderate-quality evidence); 4. targeted agents improved the efficacy of conventional chemotherapy both when considered together (HR for OS: 0.84, 95% CI 0.77 to 0.91; 6 RCTs; high-quality evidence) and when bevacizumab was used alone (HR for PFS: 0.67, 95% CI 0.60 to 0.75; 4 RCTs; high-quality evidence).With regard to secondary endpoints, tumour response rates generally paralleled the survival results; moreover, higher anticancer efficacy was generally associated with worse treatment-related toxicity, with the important exception of bevacizumab-containing regimens, where the addition of the targeted agent to chemotherapy did not result in a significant increase in the rate of SAE. Finally, we found that oral (instead of intravenous) fluoropyrimidines significantly reduced the incidence of adverse effects (without compromising efficacy) in people treated with oxaliplatin-based regimens.We could not draw any conclusions on other debated aspects in this field of oncology, such as ranking of treatments (not all possible comparisons have been tested and many comparisons were based on single trials enrolling a small number of participants) and quality of life (virtually no data available).
AUTHORS' CONCLUSIONS
Systemic therapy offers a survival benefit to people with metastatic CRC who did not respond to first-line treatment, especially when targeted agents are combined with conventional chemotherapeutic drugs. Further research is needed to define the optimal regimen and to identify people who most benefit from each treatment.
Topics: Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Bevacizumab; Camptothecin; Colorectal Neoplasms; Fluorouracil; Humans; Irinotecan; Leucovorin; Organoplatinum Compounds; Randomized Controlled Trials as Topic; Survival Rate
PubMed: 28128439
DOI: 10.1002/14651858.CD006875.pub3 -
RMD Open Jul 2023Interstitial lung disease (ILD) is an important cause of mortality in some patients with rheumatoid arthritis (RA). Patient-level factors may predict which patients...
Interstitial lung disease (ILD) is an important cause of mortality in some patients with rheumatoid arthritis (RA). Patient-level factors may predict which patients with RA are at the highest risk of developing ILD and are therefore candidates for screening for this complication of the underlying disease. A systematic literature review was performed using PubMed, Embase and Scopus over a 10-year period up to July 2021. Publications reporting patient-level factors in patients with RA with and without ILD that were assessed before development of ILD (or were unchanged over time and therefore could be extrapolated to before development of ILD) were retrieved for assessment of evidence. Genetic variation in and treatment with methotrexate were not included in the assessment of evidence because these factors have already been widely investigated for association with ILD. We found consistent associations of age, sex, smoking status and autoantibodies with development of ILD. For biomarkers such as Krebs von den Lungen 6, which have been shown to be diagnostic for ILD, there were no publications meeting criteria for this study. This analysis provides an initial step in the identification of patient-level factors for potential development of a risk algorithm to identify patients with RA who may be candidates for screening for ILD. The findings represent a useful basis for future research leading to an improved understanding of the disease course and improved care for patients with RA at risk of development and progression of ILD.
Topics: Humans; Arthritis, Rheumatoid; Lung Diseases, Interstitial; Methotrexate; Autoantibodies; Smoking
PubMed: 37507209
DOI: 10.1136/rmdopen-2023-003059 -
BMJ Open Nov 2023This study aims to estimate the prevalence of neural tube defects (NTDs) and to identify potential risk factors in the Ethiopian context. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
This study aims to estimate the prevalence of neural tube defects (NTDs) and to identify potential risk factors in the Ethiopian context.
STUDY DESIGN
Systematic review and meta-analysis.
STUDY PARTICIPANTS
A total of 611 064 participants were included in the review obtained from 42 studies.
METHODS
PubMed (Medline), Embase and Cochrane Library databases in combination with other potential sources of literature were systematically searched, whereby studies conducted between January 2010 and December 2022 were targeted in the review process. All observational studies were included and heterogeneity between studies was verified using Cochrane Q test statistics and I test statistics. Small study effects were checked using Egger's statistical test at a 5% significance level.
RESULT
The pooled prevalence of all NTDs per 10 000 births in Ethiopia was 71.48 (95% CI 57.80 to 86.58). The between-study heterogeneity was high (I= 97.49%, p<0.0001). Birth prevalence of spina bifida (33.99 per 10 000) was higher than anencephaly (23.70 per 10 000), and encephalocele (4.22 per 10 000). Unbooked antenatal care (AOR 2.26, 95% CI (1.30 to 3.94)), preconception intake of folic acid (AOR 0.41, 95% CI (0.26 to 0.66)), having chronic medical illness (AOR 2.06, 95% CI (1.42 to 2.99)), drinking alcohol (AOR 2.70, 95% CI (1.89 to 3.85)), smoking cigarette (AOR 2.49, 95% CI (1.51 to 4.11)), chewing khat (AOR 3.30, 95% CI (1.88 to 5.80)), exposure to pesticides (AOR 3.87, 95% CI (2.63 to 5.71)), maternal age ≥35 (AOR 1.90, 95% CI (1.13 to 3.25)), maternal low educational status (AOR 1.60, 95% CI (1.13 to 2.24)), residing in urban areas (AOR 0.75, 95% CI (0.58 to 0.97))and family history of NTDs (AOR 2.51, 95% CI (1.36 to 4.62)) were associated with NTD cases.
CONCLUSION
The prevalence of NTDs in Ethiopia is seven times as high as in other Western countries where prevention measures are put in place. Heredity, maternal and environmental factors are associated with a high prevalence of NTDs. Mandatory fortification of staple food with folic acid should be taken as a priority intervention to curb the burden of NTDs. To smoothen and overlook the pace of implementation of mass fortification, screening, and monitoring surveillance systems should be in place along with awareness-raising measures.
PROSPERO REGISTRATION NUMBER
CRD42023413490.
Topics: Female; Pregnancy; Humans; Prevalence; Ethiopia; Neural Tube Defects; Folic Acid; Risk Factors; Food, Fortified
PubMed: 37940152
DOI: 10.1136/bmjopen-2023-077685 -
The Cochrane Database of Systematic... May 2016People with end-stage kidney disease (ESKD) have high rates of cardiovascular events. Randomised controlled trials (RCTs) of homocysteine-lowering therapies have not... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
People with end-stage kidney disease (ESKD) have high rates of cardiovascular events. Randomised controlled trials (RCTs) of homocysteine-lowering therapies have not shown reductions in cardiovascular event rates in the general population. However, people with kidney disease have higher levels of homocysteine and may have different mechanisms of cardiovascular disease. We performed a systematic review of the effect of homocysteine-lowering therapies in people with ESKD.
OBJECTIVES
To evaluate the benefits and harms of established homocysteine lowering therapy (folic acid, vitamin B6, vitamin B12) on all-cause mortality and cardiovascular event rates in patients with ESKD.
SEARCH METHODS
We searched Cochrane Kidney and Transplant's Specialised Register to 25 January 2016 through contact with the Information Specialist using search terms relevant to this review.
SELECTION CRITERIA
Studies conducted in people with ESKD that reported at least 100 patient-years of follow-up and assessed the effect of therapies that are known to have homocysteine-lowering properties were included.
DATA COLLECTION AND ANALYSIS
Two authors independently extracted data using a standardised form. The primary outcome was cardiovascular mortality. Secondary outcomes included all-cause mortality, incident cardiovascular disease (fatal and nonfatal myocardial infarction and coronary revascularisation), cerebrovascular disease (stroke and cerebrovascular revascularisation), peripheral vascular disease (lower limb amputation), venous thromboembolic disease (deep vein thrombosis and pulmonary embolism), thrombosis of dialysis access, and adverse events. The effects of homocysteine-lowering therapies on outcomes were assessed with meta-analyses using random-effects models. Prespecified subgroup and sensitivity analyses were conducted.
MAIN RESULTS
We included six studies that reported data on 2452 participants with ESKD. Interventions investigated were folic acid with or without other vitamins (vitamin B6, vitamin B12). Participants' mean age was 48 to 65 years, and proportions of male participants ranged from 50% to 98%.Homocysteine-lowering therapy probably leads to little or no effect on cardiovascular mortality (4 studies, 1186 participants: RR 0.93, 95% CI 0.70 to 1.22). There was no evidence of heterogeneity among the included studies (I² = 0%). Homocysteine-lowering therapy had little or no effect on all-cause mortality or any other of this review's secondary outcomes. All prespecified subgroup and sensitivity analyses demonstrated little or no difference. Reported adverse events were mild and there was no increase in the incidence of adverse events from homocysteine-lowering therapies (3 studies, 1248 participants: RR 1.12, 95% CI 0.51 to 2.47; I(2) = 0%). Overall, studies were assessed as being at low risk of bias and there was no evidence of publication bias.
AUTHORS' CONCLUSIONS
Homocysteine-lowering therapies were not found to reduce mortality (cardiovascular and all-cause) or cardiovascular events among people with ESKD.
Topics: Aged; Cardiovascular Diseases; Cause of Death; Female; Folic Acid; Homocysteine; Humans; Hyperhomocysteinemia; Kidney Failure, Chronic; Male; Middle Aged; Myocardial Infarction; Renal Dialysis; Stroke; Venous Thrombosis; Vitamin B 12; Vitamin B 6; Vitamin B Complex
PubMed: 27243372
DOI: 10.1002/14651858.CD004683.pub4