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European Journal of Neurology Jan 2023Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND AND PURPOSE
Primary Sjögren syndrome (pSS) is a chronic, systemic, autoimmune disorder characterized by lymphocytic infiltrates of the exocrine organs, leading to sicca symptoms and parotid enlargement. pSS has been linked to various neurological manifestations, including peripheral neuropathy (PN). We aimed to provide a comprehensive analysis of the currently available evidence regarding pSS-related PN.
METHODS
A literature search in the PubMed database was performed, and 49 papers were eligible to be included in this systematic review and meta-analysis.
RESULTS
The pooled prevalence of PN in pSS is estimated to be 15.0% (95% confidence interval = 10.7%-20.7%). The mean age of pSS patients at PN diagnosis is 59 years. Among the patients with pSS and PN, 83% are females. Neuropathic symptoms usually precede or lead to the pSS diagnosis at a 2:1 ratio in patients with pSS-related PN. The commonest type of pSS-related PN is distal axonal polyneuropathy (80% of patients with pSS-related PN), followed by sensory ganglionopathy. Peripheral and cranial mononeuropathies-particularly trigeminal-are also frequent. Risk factors for developing PN include increasing age and presence of vasculitis. Immune-mediated pathogenetic mechanisms are discussed. Glucocorticoids are the most commonly used treatment option for managing pSS-related PN, when associated with vasculitis, followed by the use of intravenous immunoglobulin.
CONCLUSIONS
PN is very common in pSS patients. Evidence on long-term prognosis of PN in pSS is limited, and further research is needed. Research into the use of immunosuppressive medication in nonvasculitic neuropathies in the context of pSS merits further consideration.
Topics: Female; Humans; Middle Aged; Male; Sjogren's Syndrome; Peripheral Nervous System Diseases; Vasculitis; Immunoglobulins, Intravenous
PubMed: 36086910
DOI: 10.1111/ene.15555 -
European Respiratory Review : An... Mar 2023Interstitial lung disease (ILD) is a frequent manifestation of connective tissue disease (CTD) with substantial variability in prevalence and outcomes reported across... (Meta-Analysis)
Meta-Analysis Review
INTRODUCTION
Interstitial lung disease (ILD) is a frequent manifestation of connective tissue disease (CTD) with substantial variability in prevalence and outcomes reported across CTD subtypes. This systematic review summarises the prevalence, risk factors and ILD patterns on chest computed tomography of CTD-ILD.
METHODS
A comprehensive search was performed in Medline and Embase to identify eligible studies. Meta-analyses were completed using a random effects model to determine the pooled prevalence of CTD-ILD and ILD patterns.
RESULTS
11 582 unique citations were identified with 237 articles included. Pooled prevalence of ILD was 11% in rheumatoid arthritis (95% CI 7-15%), 47% in systemic sclerosis (44-50%), 41% in idiopathic inflammatory myositis (33-50%), 17% in primary Sjögren's syndrome (12-21%), 56% in mixed connective tissue disease (39-72%) and 6% in systemic lupus erythematosus (3-10%). Usual interstitial pneumonia was the most prevalent ILD pattern in rheumatoid arthritis (pooled prevalence of 46%), while nonspecific interstitial pneumonia was the most common ILD pattern in all other CTD subtypes (pooled prevalence range 27-76%). Across all CTDs with available data, positive serology and higher inflammatory markers were risk factors for development of ILD.
DISCUSSION
We identified substantial variability in ILD across CTD subtypes suggesting that CTD-ILD is too heterogenous to be considered a single entity.
Topics: Humans; Prevalence; Lung Diseases, Interstitial; Connective Tissue Diseases; Risk Factors; Arthritis, Rheumatoid
PubMed: 36889782
DOI: 10.1183/16000617.0210-2022 -
Frontiers in Immunology 2019During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have...
During the past years biologic agents (also termed biologicals or biologics) have become a crucial treatment option in immunological diseases. Numerous articles have been published on biologicals, which complicates the decision making process on the use of the most appropriate biologic for a given immune-mediated disease. This systematic review is the first of a series of articles assessing the safety and efficacy of B cell-targeting biologics for the treatment of immune-mediated diseases. To evaluate rituximab's safety and efficacy for the treatment of immune-mediated disorders compared to placebo, conventional treatment, or other biologics. The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 4 October 2016 and 26 July 2018 concentrating on immune-mediated disorders. The literature search identified 19,665 articles. After screening titles and abstracts against the inclusion and exclusion criteria and assessing full texts, 105 articles were finally included in a narrative synthesis. Rituximab is both safe and effective for the treatment of acquired angioedema with C1-inhibitor deficiency, ANCA-associated vasculitis, autoimmune hemolytic anemia, Behçet's disease, bullous pemphigoid, Castleman's disease, cryoglobulinemia, Goodpasture's disease, IgG4-related disease, immune thrombocytopenia, juvenile idiopathic arthritis, relapsing-remitting multiple sclerosis, myasthenia gravis, nephrotic syndrome, neuromyelitis optica, pemphigus, rheumatoid arthritis, spondyloarthropathy, and systemic sclerosis. Conversely, rituximab failed to show an effect for antiphospholipid syndrome, autoimmune hepatitis, IgA nephropathy, inflammatory myositis, primary-progressive multiple sclerosis, systemic lupus erythematosus, and ulcerative colitis. Finally, mixed results were reported for membranous nephropathy, primary Sjögren's syndrome and Graves' disease, therefore warranting better quality trials with larger patient numbers.
Topics: Animals; Antigens, CD20; B-Lymphocytes; Disease Progression; Humans; Immune System Diseases; Immunotherapy; Lymphocyte Depletion; Rituximab; Treatment Outcome
PubMed: 31555262
DOI: 10.3389/fimmu.2019.01990 -
Frontiers in Immunology 2022The cytokine interleukin (IL)-1 plays a pivotal role in immune-mediated disorders, particularly in autoinflammatory diseases. Targeting this cytokine proved to be...
BACKGROUND
The cytokine interleukin (IL)-1 plays a pivotal role in immune-mediated disorders, particularly in autoinflammatory diseases. Targeting this cytokine proved to be efficacious in treating numerous IL-1-mediated pathologies. Currently, three IL-1 blockers are approved, namely anakinra, canakinumab and rilonacept, and two additional ones are expected to receive approval, namely gevokizumab and bermekimab. However, there is no systematic review on the safety and efficacy of these biologics in treating immune-mediated diseases.
OBJECTIVE
To evaluate safety and efficacy of anakinra, canakinumab, rilonacept, gevokizumab, and bermekimab for the treatment of immune-mediated disorders compared to placebo, standard-of-care treatment or other biologics.
METHODS
The PRISMA checklist guided the reporting of the data. We searched the PubMed database between 1 January 1984 and 31 December 2020 focusing on immune-mediated disorders. Our PubMed literature search identified 7363 articles. After screening titles and abstracts for the inclusion and exclusion criteria and assessing full texts, 75 articles were included in a narrative synthesis.
RESULTS
Anakinra was both efficacious and safe in treating cryopyrin-associated periodic syndromes (CAPS), familial Mediterranean fever (FMF), gout, macrophage activation syndrome, recurrent pericarditis, rheumatoid arthritis (RA), and systemic juvenile idiopathic arthritis (sJIA). Conversely, anakinra failed to show efficacy in graft-versus-host disease, Sjögren's syndrome, and type 1 diabetes mellitus (T1DM). Canakinumab showed efficacy in treating CAPS, FMF, gout, hyper-IgD syndrome, RA, Schnitzler's syndrome, sJIA, and TNF receptor-associated periodic syndrome. However, use of canakinumab in the treatment of adult-onset Still's disease and T1DM revealed negative results. Rilonacept was efficacious and safe for the treatment of CAPS, FMF, recurrent pericarditis, and sJIA. Contrarily, Rilonacept did not reach superiority compared to placebo in the treatment of T1DM. Gevokizumab showed mixed results in treating Behçet's disease-associated uveitis and no benefit when assessed in T1DM. Bermekimab achieved promising results in the treatment of hidradenitis suppurativa.
CONCLUSIONS
This systematic review of IL-1-targeting biologics summarizes the current state of research, safety, and clinical efficacy of anakinra, bermekimab, canakinumab, gevokizumab, and rilonacept in treating immune-mediated disorders.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42021228547.
Topics: Arthritis, Juvenile; Arthritis, Rheumatoid; Biological Products; Cryopyrin-Associated Periodic Syndromes; Diabetes Mellitus, Type 1; Familial Mediterranean Fever; Gout; Humans; Immune System Diseases; Interleukin 1 Receptor Antagonist Protein; Interleukin-1; Pericarditis
PubMed: 35874710
DOI: 10.3389/fimmu.2022.888392 -
Journal of Immunology Research 2021Sjögren's syndrome (SS) is a chronic autoimmune disease of unknown etiology that mainly involves exocrine glands. Patients present with dry mouth and eyes, fever,...
Sjögren's syndrome (SS) is a chronic autoimmune disease of unknown etiology that mainly involves exocrine glands. Patients present with dry mouth and eyes, fever, arthralgia, and other systemic symptoms. In severe cases, the quality of life of patients is affected. At present, there is no cure for SS, and the treatment options are extremely limited. In recent years, studies of patients and animal models have identified abnormalities of immune cell function and cytokines to be involved in SS. A systematic review of the literature may clarify the etiology and pathogenesis of SS, as well as provide a theoretical basis for the development of new drugs for the treatment of SS.
Topics: Animals; Cytokines; Disease Models, Animal; Exocrine Glands; Humans; Immunologic Factors; Quality of Life; Severity of Illness Index; Signal Transduction; Sjogren's Syndrome
PubMed: 34660815
DOI: 10.1155/2021/5928232 -
RMD Open 2019To evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome (SjS) to inform European League... (Meta-Analysis)
Meta-Analysis Review
OBJECTIVE
To evaluate current evidence on the efficacy and safety of topical and systemic medications in patients with primary Sjögren syndrome (SjS) to inform European League Against Rheumatism treatment recommendations.
METHODS
The MEDLINE, EMBASE and Cochrane databases were searched for case-control/prospective cohort studies, randomised controlled trials (RCTs) and systematic reviews.
RESULTS
Current evidence in primary SjS patients fulfilling the 2002 criteria is based on the data from 9 RCTs, 18 prospective cohort studies and 5 case-control studies. Two Cochrane systematic literature reviews (SLRs) have reported that topical treatments for dry mouth and dry eye are safe and effective. Ocular cyclosporine A was safe and effective in two RCTs including 1039 patients with dry eye syndrome. Two Cochrane SLRs on serum tear drops and plugs showed inconsistency in possible benefits, both for symptoms and objective measures. Five RCTs reported significant improvements in oral dryness and salivary flow rates for pilocarpine and cevimeline. An RCT showed no significant placebo-differences for hydroxychloroquine 400 mg/day for the primary outcome (visual analogue scale (VAS) composite of dryness, fatigue and pain). We identified seven RCTs carried out in primary SjS patients. RCTs using infliximab, anakinra and baminercept found no placebo-differences for the primary outcomes. The two largest RCTs randomised 255 patients to receive rituximab or placebo and reported no significant results in the primary outcome (VAS composite), while prospective studies suggested efficacy in systemic disease.
CONCLUSION
The current evidence supporting the use of the main topical therapeutic options of primary SjS is solid, while limited data from RCTs are available to guide systemic therapies.
Topics: Clinical Trials as Topic; Combined Modality Therapy; Disease Management; Humans; Sjogren's Syndrome; Treatment Outcome
PubMed: 31749986
DOI: 10.1136/rmdopen-2019-001064 -
International Journal of Environmental... Sep 2022Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by clinical heterogeneity and irregularities in its course. The etiology and... (Review)
Review
Systemic lupus erythematosus (SLE) is a chronic autoimmune disease that is characterized by clinical heterogeneity and irregularities in its course. The etiology and pathogenesis of this pathology are not well-understood, so there is difficulty in establishing a diagnosis and treatment plan with certainty. The aim of this systematic review is to present a qualitative synthesis of studies referring to the oral manifestations of systemic lupus erythematosus (SLE). This systematic review was performed following the PRISMA guideline. On this basis, a search for articles was performed in the PubMed, Web of Science, and Scopus databases on 19 November 2021 and updated on 15 February 2022. We chose articles published between 2012 and 2022 that analyzed the oral manifestations of SLE patients. The quality of all these studies was analyzed following the STROBE scale. A total of 15 articles were included in this study after selection. The selected articles were cross-sectional, case-control, and cohort studies. The most frequently associated oral manifestations with SLE were oral ulcers, hyposalivation, pigmentations, glossodynia, cleft tongue, cheilitis, arthritis, and secondary Sjögren's syndrome. However, despite the importance of the perception of these oral manifestations in the early diagnosis of SLE, there are still not enough studies about them.
Topics: Arthritis; Autoimmune Diseases; Humans; Lupus Erythematosus, Systemic; Sjogren's Syndrome; Xerostomia
PubMed: 36231212
DOI: 10.3390/ijerph191911910 -
Journal of Stomatology, Oral and... Oct 2022This systematic review aimed to evaluate complications and survival rates of dental implants placed in patients suffering from autoimmune diseases.
PURPOSE
This systematic review aimed to evaluate complications and survival rates of dental implants placed in patients suffering from autoimmune diseases.
MATERIALS AND METHODS
A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses systematic review guidelines (PRISMA), using Google scholar and PubMed electronic databases with a stop date of September 2021. The eligibility criteria included all full text human studies in the English language literature reporting on patients with autoimmune diseases treated with dental implants.
RESULTS
Fifty-five studies reporting on nine distinct autoimmune diseases were analyzed: 17 on Sjögren's syndrome (SS), 11 on oral lichen planus (OLP), 8 on Type 1 diabetes, 6 on rheumatoid arthritis (RA), 4 on systemic scleroderma (SSc), 3 on Crohn's disease (CD), 3 on systemic lupus erythematosus (SLE), 2 on mucous membrane pemphigoid (MMB) and 1 on pemphigus vulgaris (PV). Despite the heterogeneity and methodological limitations of most of the studies, results showed that dental implant survival rates were comparable to those reported in the general population. However, patients with secondary SS or erosive OLP were more susceptible to developing peri-mucositis and increased marginal bone loss.
CONCLUSION
This review suggested that dental implants may be considered as a safe and viable therapeutic option in the management of edentulous patients suffering from autoimmune diseases. Nevertheless, scrupulous maintenance of oral hygiene and long-term follow-up emerge as being the common determinants for uneventful dental implant treatment.
Topics: Dental Implants; Humans; Lichen Planus, Oral; Sjogren's Syndrome
PubMed: 35033725
DOI: 10.1016/j.jormas.2022.01.005 -
EBioMedicine Jun 2022Emerging evidence suggests that dysbiosis in gut microbiota may contribute to the occurrence or development of several rheumatic diseases. Since gut microbiota dysbiosis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Emerging evidence suggests that dysbiosis in gut microbiota may contribute to the occurrence or development of several rheumatic diseases. Since gut microbiota dysbiosis is potentially modifiable, it has been postulated to be a promising preventive or therapeutic target for rheumatic diseases. However, the current understanding on the potential associations between gut microbiota and rheumatic diseases is still inadequate. Therefore, we aimed to synthesise the accumulating evidence for the relation of gut microbiota to rheumatic diseases.
METHODS
The PubMed, Embase and Cochrane Library were searched from inception to March 11, 2022 to include observational studies evaluating the associations between gut microbiota and rheumatic diseases. Standardised mean difference (SMD) of α-diversity indices between rheumatic diseases and controls were estimated using random-effects model. β-diversity indices and relative abundance of gut microbes were summarised qualitatively.
FINDINGS
Of the included 92 studies (11,998 participants), 68 provided data for α-diversity. Taken together as a whole, decreases in α-diversity indices were consistently found in rheumatic diseases (observed species: SMD = -0.36, [95%CI = -0.63, -0.09]; Chao1: SMD = -0.57, [95%CI = -0.88, -0.26]; Shannon index: SMD = -0.33, [95%CI = -0.48, -0.17]; Simpson index: SMD = -0.32, [95%CI = -0.49, -0.14]). However, when specific rheumatic diseases were examined, decreases were only observed in rheumatoid arthritis (observed species: SMD = -0.51, [95%CI = -0.78, -0.24]; Shannon index: SMD = -0.31, [95%CI = -0.49, -0.13]; Simpson index: SMD = -0.31, [95%CI = -0.54, -0.08]), systemic lupus erythematosus (Chao1: SMD = -1.60, [95%CI = -2.54, -0.66]; Shannon index: SMD = -0.63, [95%CI = -1.08, -0.18]), gout (Simpson index: SMD = -0.64, [95%CI = -1.07, -0.22]) and fibromyalgia (Simpson index: SMD = -0.28, [95%CI = -0.44, -0.11]), whereas an increase was observed in systemic sclerosis (Shannon index: SMD = 1.25, [95%CI = 0.09, 2.41]). Differences with statistical significance in β-diversity were consistently reported in ankylosing spondylitis and IgG4-related diseases. Although little evidence of disease specificity of gut microbes was found, shared alterations of the depletion of anti-inflammatory butyrate-producing microbe (i.e., Faecalibacterium) and the enrichment of pro-inflammatory microbe (i.e., Streptococcus) were observed in rheumatoid arthritis, Sjögren's syndrome and systemic lupus erythematosus.
INTERPRETATION
Gut microbiota dysbiosis was associated with rheumatic diseases, principally with potentially non-specific, shared alterations of microbes.
FUNDING
National Natural Science Foundation of China (81930071, 81902265, 82072502 and U21A20352).
Topics: Dysbiosis; Gastrointestinal Microbiome; Humans; Lupus Erythematosus, Systemic; Rheumatic Diseases; Sjogren's Syndrome
PubMed: 35594658
DOI: 10.1016/j.ebiom.2022.104055 -
The Cochrane Database of Systematic... Sep 2019Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA...
BACKGROUND
Topical cyclosporine A (also known as ciclosporin A) (CsA) is an anti-inflammatory that has been widely used to treat inflammatory ocular surface diseases. Two CsA eyedrops have been approved by US Food and Drug Administration for managing dry eye: Restasis (CsA 0.05%, Allergan Inc, Irvine, CA, USA), approved in 2002, and Cequa (CsA 0.09%, Sun Pharma, Cranbury, NJ, USA), approved in 2018. Numerous clinical trials have been performed to assess the effectiveness and safety of CsA for dry eye; however, there is no universal consensus with regard to its effect.
OBJECTIVES
To assess the effectiveness and safety of topical CsA in the treatment of dry eye.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (which contains the Cochrane Eyes and Vision Trials Register) (2018, Issue 2); Ovid MEDLINE; Embase.com; PubMed; Latin American and Caribbean Health Sciences Literature Database (LILACS); ClinicalTrials.gov; and the World Health Organization (WHO) International Clinical Trials Registry Platform (ICTRP). We did not use any date or language restrictions in the electronic search for trials. We last searched the electronic databases on 16 February 2018.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) of people with dry eye regardless of age, sex, severity, etiology, or classification of dry eye. We included RCTs in which different concentrations of topical CsA were compared with one another or with artificial tears, placebo, or vehicle. We also included RCTs in which CsA in combination with artificial tears was compared to artificial tears alone.
DATA COLLECTION AND ANALYSIS
We followed the standard Cochrane methodology and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 30 RCTs (4009 participants) with follow-up periods ranging from 6 weeks to 12 months. We studied dry eye of various severity and underlying causes. The interventions investigated also varied across RCTs: CsA versus artificial tears; CsA with artificial tears versus artificial tears alone; and in some studies, more than one concentration of CsA. Artificial tears were used as adjunctive to study medication in all but five trials. Almost all trials had deficiencies in the reporting of results (e.g. reporting P values or direction only), precluding the calculation of between-group estimates of effect or meta-analysis.Eighteen trials compared topical CsA 0.05% plus artificial tears versus vehicle plus artificial tears or artificial tears alone. One trial reported subjective symptoms of dry eye at 6 months and the results were in favor of CsA (mean difference (MD) -4.80, 95% confidence interval (CI) -6.41 to -3.19; low-certainty evidence). Two trials reported MD in ocular surface dye staining at 6 months, but the results were inconsistent in these two trials (MD -0.35, 95% CI -0.69 to -0.01 in one and MD 0.58, 95% CI 0.06 to 1.10 in the other; low-certainty evidence). Four trials reported MD in Schirmer test scores at 6 months and the estimates ranged from -4.05 (95% CI -6.67 to -1.73) to 3.26 (95% CI -1.52 to 5.00) (low-certainty evidence). Three trials reported risk ratio (RR) of improved Schirmer test scores at 6 months; estimates ranged from 0.98 (95% CI 0.83 to 1.17) to 3.50 (95% CI 2.09 to 5.85) (low-certainty evidence). Four trials reported MD in tear film stability measured by tear break-up time at 6 months and the estimates ranged from -1.98 (95% CI -3.59 to -0.37) to 1.90 (95% CI 1.44 to 2.36) (low-certainty evidence). Three trials reported RR of improved tear break-up time at 6 months and the estimates ranged from 0.90 (95% CI 0.77 to 1.04) to 4.00 (95% CI 2.25 to 7.12) (low-certainty evidence). Three trials reported frequency of artificial tear usage at 6 months without providing any estimates of effect; the direction of effect seem to be in favor of CsA (low-certainty evidence). Because of incomplete reporting of the results data or considerable statistical heterogeneity, we were only able to perform a meta-analysis on mean conjunctival goblet cell density. Mean conjunctival goblet cell density in the CsA treated group may be greater than that in the control group at the end of follow-up at four and 12 months (MD 22.5 cells per unit, 95% CI 16.3 to 28.8; low-certainty evidence). All but two trials reported adverse events that included burning and stinging. Participants treated with CsA may be more likely to have treatment-related adverse events than those who treated with vehicle (RR 1.33, 95% CI 1.00 to 1.78; low-certainty evidence).Other comparisons evaluated were CsA 0.05% plus artificial tears versus higher concentrations of CsA plus artificial tears (4 trials); CsA 0.05% versus placebo or vehicle (4 trials); CsA 0.1% plus artificial tears versus placebo or vehicle plus artificial tears (2 trials);CsA 0.1% cationic emulsion plus artificial tears versus vehicle plus artificial tears (2 trials); CsA 1% plus artificial tears versus placebo plus artificial tears (3 trials); and CsA 2% plus artificial tears versus placebo plus artificial tears (3 trials). Almost all of these trials reported P value or direction of effect only (mostly in favor of CsA), precluding calculation of between-group effect estimates or meta-analyses.
AUTHORS' CONCLUSIONS
Despite the widespread use of topical CsA to treat dry eye, we found that evidence on the effect of CsA on ocular discomfort and ocular surface and tear film parameters such as corneal fluorescein staining, Schirmer's test, and TBUT is inconsistent and sometimes may not be different from vehicle or artificial tears for the time periods reported in the trials. There may be an increase in non-serious, treatment-related adverse effects (particularly burning) in the CsA group. Topical CsA may increase the number of conjunctival goblet cells. However, current evidence does not support that improvements in conjunctival mucus production (through increased conjunctival goblet cells) translate to improved symptoms or ocular surface and tear film parameters. All published trials were short term and did not assess whether CsA has longer-term disease-modifying effects. Well-planned, long-term, large clinical trials are needed to better assess CsA on long-term dry eye-modifying effects. A core outcome set, which ideally includes both biomarkers and patient-reported outcomes in the field of dry eye, is needed.
Topics: Cyclosporine; Dry Eye Syndromes; Humans; Lubricant Eye Drops; Randomized Controlled Trials as Topic
PubMed: 31517988
DOI: 10.1002/14651858.CD010051.pub2