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The Cochrane Database of Systematic... Aug 2020Medications licensed for the treatment of dementia have limited efficacy against cognitive impairment or against the distressed behaviours (behavioural and psychological... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Medications licensed for the treatment of dementia have limited efficacy against cognitive impairment or against the distressed behaviours (behavioural and psychological symptoms, or behaviour that challenges) which are also often the most distressing aspect of the disorder for caregivers. Complementary therapies, including aromatherapy, are attractive to patients, practitioners and families, because they are perceived as being unlikely to cause adverse effects. Therefore there is interest in whether aromatherapy might offer a safe means of alleviating distressed behaviours in dementia.
OBJECTIVES
To assess the efficacy and safety of aromatherapy for people with dementia.
SEARCH METHODS
We searched ALOIS, the Cochrane Dementia and Cognitive Improvement Group Specialized Register, on 5 May 2020 using the terms: aromatherapy, lemon, lavender, rose, aroma, alternative therapies, complementary therapies, essential oils. In addition, we searched MEDLINE, Embase, PsycINFO (all via Ovid SP), Web of Science Core Collection (via Thompson Web of Science), LILACS (via BIREME), CENTRAL (via the Cochrane Library), ClinicalTrials.gov and the World Health Organization (WHO) trials portal (ICTRP) on 5 May 2020.
SELECTION CRITERIA
We included randomised controlled trials which compared fragrance from plants in an intervention defined as aromatherapy for people with dementia with placebo aromatherapy or with treatment as usual. All doses, frequencies and fragrances of aromatherapy were considered. Participants in the included studies had a diagnosis of dementia of any subtype and severity.
DATA COLLECTION AND ANALYSIS
Two reviewers independently selected studies for inclusion, extracted data and assessed risk of bias in included studies, involving other authors to reach consensus decisions where necessary. We did not perform any meta-analyses because of heterogeneity between studies, but presented a narrative synthesis of results from the included trials. Because of the heterogeneity of analysis methods and inadequate or absent reporting of data from some trials, we used statistical significance (P ≤ or > 0.5) as a summary metric when synthesising results across studies. As far as possible, we used GRADE methods to assess our confidence in the results of the trials, downgrading for risk of bias and imprecision.
MAIN RESULTS
We included 13 studies with 708 participants. All participants had dementia and in the 12 trials which described the setting, all were resident in institutional care facilities. Nine trials recruited participants because they had significant agitation or other behavioural and psychological symptoms in dementia (BPSD) at baseline. The fragrances used were lavender (eight studies); lemon balm (four studies); lavender and lemon balm, lavender and orange, and cedar extracts (one study each). For six trials, assessment of risk of bias and extraction of results was hampered by poor reporting. Four of the other seven trials were at low risk of bias in all domains, but all were small (range 18 to 186 participants; median 66), reducing our confidence in the results. Our primary outcomes were agitation, overall behavioural and psychological symptoms, and adverse effects. Ten trials assessed agitation using various scales. Among the five trials for which our confidence in the results was moderate or low, four trials reported no significant effect on agitation and one trial reported a significant benefit of aromatherapy. The other five trials either reported no useable data or our confidence in the results was very low. Eight trials assessed overall BPSD using the Neuropsychiatric Inventory and we had moderate or low confidence in the results of five of them. Of these, four reported significant benefit from aromatherapy and one reported no significant effect. Adverse events were poorly reported or not reported at all in most trials. No more than two trials assessed each of our secondary outcomes of quality of life, mood, sleep, activities of daily living, caregiver burden. We did not find evidence of benefit on these outcomes. Three trials assessed cognition: one did not report any data and the other two trials reported no significant effect of aromatherapy on cognition. Our confidence in the results of these studies was low.
AUTHORS' CONCLUSIONS
We have not found any convincing evidence that aromatherapy (or exposure to fragrant plant oils) is beneficial for people with dementia although there are many limitations to the data. Conduct or reporting problems in half of the included studies meant that they could not contribute to the conclusions. Results from the other studies were inconsistent. Harms were very poorly reported in the included studies. In order for clear conclusions to be drawn, better design and reporting and consistency of outcome measurement in future trials would be needed.
Topics: Aromatherapy; Behavioral Symptoms; Bias; Dementia; Humans; Oils, Volatile; Psychomotor Agitation; Randomized Controlled Trials as Topic
PubMed: 32813272
DOI: 10.1002/14651858.CD003150.pub3 -
Journal of Drugs in Dermatology : JDD Jul 2022Coconut, castor, and argan oils are popular commercial hair oils culturally rooted in current and historical Indian and African heritages. Dermatologists treating hair...
Coconut, castor, and argan oils are popular commercial hair oils culturally rooted in current and historical Indian and African heritages. Dermatologists treating hair and scalp conditions often face challenging patient questions of whether over-the-counter hair oils should be used. This is particularly challenging given the deeply rooted cultural practices of some skin of color patients. As a result, many dermatologists recommend patients to continue using hair oils not based on clinical efficacy but rather lack of foreseeable side effects. We analyzed the literature to investigate claims to substantiate whether these hair oils can improve hair growth, hair quality, and treat infestation clinically. Based on 22 articles that met inclusion criteria, coconut oil has been shown to treat both brittle hair and hair infestation clinically, with limited evidence regarding its impact on hair growth. There is weaker evidence for castor oil improving hair quality by increasing hair luster, and no strong evidence supporting its use for hair growth or treatment of infestation. Argan oil does not have any significant evidence supporting its use to improve hair growth, quality, or treatment of infestation. J Drugs Dermatol. 2022;21(7):751-757. doi:10.36849/JDD.6972.
Topics: Humans; Castor Oil; Cocos; Hair; Plant Oils; Hair Preparations; Ethnic and Racial Minorities
PubMed: 35816075
DOI: 10.36849/JDD.6972 -
Phytomedicine : International Journal... Jul 2023Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between... (Review)
Review
BACKGROUND
Every day the skin is constantly exposed to several harmful factors that induce oxidative stress. When the cells are incapable to maintain the balance between antioxidant defenses and reactive oxygen species, the skin no longer can keep its integrity and homeostasis. Chronic inflammation, premature skin aging, tissue damage, and immunosuppression are possible consequences induced by sustained exposure to environmental and endogenous reactive oxygen species. Skin immune and non-immune cells together with the microbiome are essential to efficiently trigger skin immune responses to stress. For this reason, an ever-increasing demand for novel molecules capable of modulating immune functions in the skin has risen the level of their development, particularly in the field of natural product-derived molecules.
PURPOSE
In this review, we explore different classes of molecules that showed evidence in modulate skin immune responses, as well as their target receptors and signaling pathways. Moreover, we describe the role of polyphenols, polysaccharides, fatty acids, peptides, and probiotics as possible treatments for skin conditions, including wound healing, infection, inflammation, allergies, and premature skin aging.
METHODS
Literature was searched, analyzed, and collected using databases, including PubMed, Science Direct, and Google Scholar. The search terms used included "Skin", "wound healing", "natural products", "skin microbiome", "immunomodulation", "anti-inflammatory", "antioxidant", "infection", "UV radiation", "polyphenols", "polysaccharides", "fatty acids", "plant oils", "peptides", "antimicrobial peptides", "probiotics", "atopic dermatitis", "psoriasis", "auto-immunity", "dry skin", "aging", etc., and several combinations of these keywords.
RESULTS
Natural products offer different solutions as possible treatments for several skin conditions. Significant antioxidant and anti-inflammatory activities were reported, followed by the ability to modulate immune functions in the skin. Several membrane-bound immune receptors in the skin recognize diverse types of natural-derived molecules, promoting different immune responses that can improve skin conditions.
CONCLUSION
Despite the increasing progress in drug discovery, several limiting factors need future clarification. Understanding the safety, biological activities, and precise mechanisms of action is a priority as well as the characterization of the active compounds responsible for that. This review provides directions for future studies in the development of new molecules with important pharmaceutical and cosmeceutical value.
Topics: Humans; Skin Aging; Reactive Oxygen Species; Biological Products; Antioxidants; Inflammation; Anti-Inflammatory Agents; Polyphenols; Peptides; Polysaccharides
PubMed: 37119762
DOI: 10.1016/j.phymed.2023.154824 -
Complementary Therapies in Medicine Aug 2022Despite advances in the diagnosis and treatment of cancer, patients still suffer from the various physical and psychological complications of cancer. The aim of this... (Review)
Review
OBJECTIVE
Despite advances in the diagnosis and treatment of cancer, patients still suffer from the various physical and psychological complications of cancer. The aim of this research was to integrate and synthesize relevant scientific evidence about the effect of lavender on cancer complications.
METHODS
A systematic review of the international literature was undertaken. The search process encompassed four databases of PubMed [including MEDLINE], Web of Science, Scopus, and Cochrane library without time and language limits. All types of interventional studies examining the effects of lavender on cancer complications were included in data analysis and research synthesis. Relevant data were obtained from eligible studies after quality appraisal using appropriate methodological tools. Given that meta-analysis could not performed, the review findings were synthesized narratively.
RESULTS
Thirteen studies were included in this review with a total of 838 patients. Nine studies used a randomized controlled trial design and the majority of them were conducted on patients with multiple types of cancer. Lavender was often used as inhalation aromatherapy. In the majority of the included studies, lavender was significantly effective in the reduction of anxiety and pain, and improved sleep quality and vital signs.
CONCLUSIONS
This review provides scientific evidence regarding the effectiveness of lavender in mitigating cancer complications. Healthcare providers are suggested to use lavender in patient care along with other healthcare interventions to relieve cancer complications.
Topics: Anxiety; Anxiety Disorders; Aromatherapy; Humans; Lavandula; Neoplasms; Oils, Volatile; Pain; Plant Oils; Randomized Controlled Trials as Topic
PubMed: 35462027
DOI: 10.1016/j.ctim.2022.102836 -
Phytomedicine : International Journal... Dec 2019Anxiety is one of the uprising psychiatric disorders of the last decades and lavender administration has been traditionally suggested as a possible treatment. The... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Anxiety is one of the uprising psychiatric disorders of the last decades and lavender administration has been traditionally suggested as a possible treatment. The objective of this review is to assess the efficacy of lavender, in any form and way of administration, on anxiety and anxiety-related conditions.
METHODS
The PRISMA guidelines were followed. Retrieved data were qualitatively and quantitatively synthesized. Randomized Controlled Trials (RCTs) and Non-Randomized Studies (NRSs) which investigated the efficacy of lavender, in any form and way of administration, on patients with anxiety, involved in anxiety-inducing settings or undergoing anxiety-inducing activities, compared to any type of control, without language restrictions, were identified through electronic database searches. Medline via PubMed, Scopus, Web of Science, Cochrane Library, EMBASE, and Google Scholar were systematically searched. All databases were screened up to November 2018. Risk of bias was assessed with the Cochrane risk-of-bias tool and the following domains were considered: randomization, allocation sequence concealment, blinding, incomplete outcome data, selective outcome reporting, and other biases.
RESULTS
65 RCTs (7993 participants) and 25 NRSs (1200 participants) were included in the qualitative synthesis and 37 RCTs (3964 participants) were included in the quantitative synthesis. Overall, the qualitative synthesis indicated that 54 RCTs and 17 NRSs reported at least a significant result in favor of lavender use for anxiety. The quantitative synthesis showed that lavender inhalation can significantly reduce anxiety levels measured with any validated scale (Hedges' g = -0.73 [95% CI -1.00 to -0.46], p < 0.00001, 1682 participants), as well as state anxiety (Spielberger's state-trait anxiety inventory (STAI)-State mean difference = -5.99 [95% CI -9.39 to -2.59], p < 0.001, 901 participants) and trait anxiety (STAI-Trait mean difference = -8.14 [95% CI -14.44 to -1.84], p < 0.05, 196 participants). Lavender inhalation did not show a significant effect in reducing systolic blood pressure as a physiological parameter of anxiety. A significant effect in diminishing anxiety levels was also found in favor of the use of oral Silexan® 80 mg/die for at least 6 weeks (Hamilton Anxiety Scale mean difference = -2.90 [95% CI -4.86 to -0.95], p = 0.004, 1173 participants; Zung Self-rating Anxiety Scale mean difference = -2.62 [95% CI -4.84 to -0.39], p < 0.05, 451 participants) or of the administration of massage with lavender oil (Hedges' g = -0.66 [95% CI -0.97 to -0.35], p < 0.0001, 448 participants).
DISCUSSION
The most important limitation of this review is the low average quality of available studies on the topic. The majority of included RCTs were characterized by a high overall risk of bias. Another limitation regards the heterogeneity of study designs, especially with regard to non-oral ways of administration. Overall, oral administration of lavender essential oil proves to be effective in the treatment of anxiety, whereas for inhalation there is only an indication of an effect of reasonable size, due to the heterogeneity of available studies. Lavender essential oil administered through massage appears effective, but available studies are not sufficient to determine whether the benefit is due to a specific effect of lavender. Further high-quality RCTs with more homogeneous study designs are needed to confirm these findings. Available information outlines a safe profile for lavender-based interventions, although more attention should be paid to the collection and reporting of safety data in future studies. Considering these findings, since treatments with lavender essential oil generally seem safe, and, in the case of inhalation, also simple and inexpensive, they are a therapeutic option which may be considered in some clinical contexts.
OTHER
The present systematic review was not funded and was registered in PROSPERO under the following number: CRD42019130126.
Topics: Administration, Inhalation; Administration, Oral; Anxiety; Anxiety Disorders; Blood Pressure; Humans; Lavandula; Oils, Volatile; Plant Oils; Randomized Controlled Trials as Topic
PubMed: 31655395
DOI: 10.1016/j.phymed.2019.153099 -
Medicine Mar 2021This systematic review investigated the clinical effects of inhalation aromatherapy for the treatment of sleep problems such as insomnia. (Meta-Analysis)
Meta-Analysis
BACKGROUND
This systematic review investigated the clinical effects of inhalation aromatherapy for the treatment of sleep problems such as insomnia.
METHODS
Studies on sleep problems and inhalation aromatherapy, published in Korean and international journals, were included in the meta-analysis. Five domestic and international databases, respectively each, were used for the literature search. Keywords included sleep disorder, sleep problems, insomnia, and aroma inhalation, and the related literature was further searched. After the screening, selected articles were assessed for their quality and conducted the risk of bias using RevMan 5.0, a systematic literature review was then conducted. A meta-analysis comparing the averages was conducted on studies that reported numerical values. Additionally, meta-analysis of variance and meta-regression analyses were performed.
RESULTS
Meta-analysis of the 34 studies using the random-effects model revealed that the use of aromatherapy was highly effective in improving sleep problems such as insomnia, including quantitative and qualitative sleep effects (95% confidence interval [CI], effect sizes = 0.6491). Subgroup analysis revealed that the secondary outcomes including stress, depression, anxiety, and fatigue were significantly effective. The single aroma inhalation method was more effective than the mixed aroma inhalation method. Among the single inhalation methods, the lavender inhalation effect was the greatest.
CONCLUSION
Inhalation aromatherapy is effective in improving sleep problems such as insomnia. Therefore, it is essential to develop specific guidelines for the efficient inhalation of aromatherapy.
ETHICS AND DISSEMINATION
Ethical approval is not required because individual patient data are not included. The findings of this systematic review were disseminated through peer-reviewed publications or conference presentations.
PROSPERO REGISTRATION NUMBER
CRD42020142120.
Topics: Administration, Inhalation; Adult; Aromatherapy; Female; Humans; Lavandula; Male; Middle Aged; Oils, Volatile; Plant Oils; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Sleep Wake Disorders; Treatment Outcome; Young Adult
PubMed: 33655928
DOI: 10.1097/MD.0000000000024652 -
Clinical Nutrition (Edinburgh, Scotland) Dec 2022Some large prospective studies on olive oil consumption and risk of chronic disease suggested protective effects. (Meta-Analysis)
Meta-Analysis
BACKGROUND
Some large prospective studies on olive oil consumption and risk of chronic disease suggested protective effects.
OBJECTIVE
We conducted an outcome-wide systematic review and meta-analysis of prospective cohort studies and randomized controlled trials (RCT) assessing the association between olive oil consumption and the primary risk of 4 different outcomes: cardiovascular disease (CVD), cancer, type 2 diabetes (T2D) or all-cause mortality through January 2022.
METHODS
Thirty-six studies were included in the systematic review and twenty-seven studies (24 prospective cohorts and 3 different reports from one RCT) were assessed in 4 quantitative random-effects meta-analyses. They included a total of 806,203 participants with 49,223 CVD events; 1,285,064 participants with 58,892 incident cases of cancer; 680,239 participants with 13,389 incident cases of T2D; and 733,420 participants with 174,081 deaths. Olive oil consumption was most frequently measured with validated food frequency questionnaires. Studies follow-up ranged between 3.7 and 28 years.
RESULTS
A 16% reduced risk of CVD (relative risk [RR]: 0.84; 95% confidence interval [CI]: 0.76 to 0.94), standardized for every additional olive oil consumption of 25 g/d was found. No significant association with cancer risk was observed (RR: 0.94; 95% CI: 0.86 to 1.03, per 25 g/d). Olive oil consumption was associated with a 22% lower relative risk of T2D (RR: 0.78; 95% CI: 0.69 to 0.87, per 25 g/d) without evidence of heterogeneity. Similarly, it was inversely associated with all-cause mortality (RR: 0.89; 95% CI: 0.85 to 0.93, per 25 g/d). Only the results for T2D were homogeneous. Specific sources of heterogeneity for the other 3 outcomes were not always apparent.
CONCLUSIONS
Prospective studies supported a beneficial association of olive oil consumption with CVD, T2D and all-cause mortality, but they did not show any association with cancer risk.
Topics: Humans; Olive Oil; Cardiovascular Diseases; Diabetes Mellitus, Type 2; Neoplasms; Prospective Studies
PubMed: 36343558
DOI: 10.1016/j.clnu.2022.10.001 -
Alimentary Pharmacology & Therapeutics Sep 2022Irritable bowel syndrome (IBS) is one of the most common disorders of gut-brain interaction, with a complex pathophysiology. Antispasmodics are prescribed as first-line... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Irritable bowel syndrome (IBS) is one of the most common disorders of gut-brain interaction, with a complex pathophysiology. Antispasmodics are prescribed as first-line therapy because of their action on gut dysmotility. In this regard, peppermint oil also has antispasmodic properties.
AIM
To update our previous meta-analysis to assess efficacy and safety of peppermint oil, particularly as recent studies have cast doubt on its role in the treatment of IBS METHODS: We searched the medical literature up to 2nd April 2022 to identify randomised controlled trials (RCTs) of peppermint oil in IBS. Efficacy and safety were judged using dichotomous assessments of effect on global IBS symptoms or abdominal pain, and occurrence of any adverse event or of gastro-oesophageal reflux. Data were pooled using a random effects model, with efficacy and safety reported as pooled relative risks (RRs) with 95% confidence intervals (CIs).
RESULTS
We identified 10 eligible RCTs (1030 patients). Peppermint oil was more efficacious than placebo for global IBS symptoms (RR of not improving = 0.65; 95% CI 0.43-0.98, number needed to treat [NNT] = 4; 95% CI 2.5-71), and abdominal pain (RR of abdominal pain not improving = 0.76; 95% CI 0.62-0.93, NNT = 7; 95% CI 4-24). Adverse event rates were significantly higher with peppermint oil (RR of any adverse event = 1.57; 95% CI 1.04-2.37).
CONCLUSIONS
Peppermint oil was superior to placebo for the treatment of IBS, but adverse events were more frequent, and quality of evidence was very low. Adequately powered RCTs of peppermint oil as first-line treatment for IBS are needed.
Topics: Abdominal Pain; Humans; Irritable Bowel Syndrome; Mentha piperita; Parasympatholytics; Plant Oils; Treatment Outcome
PubMed: 35942669
DOI: 10.1111/apt.17179 -
The Cochrane Database of Systematic... Dec 2019Polyunsaturated fatty acid (PUFA) supplements, involving omega-3 and/or omega-6 components, have been proposed as a therapy for dry eye. Omega-3 PUFAs exist in both... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Polyunsaturated fatty acid (PUFA) supplements, involving omega-3 and/or omega-6 components, have been proposed as a therapy for dry eye. Omega-3 PUFAs exist in both short- (alpha-linolenic acid [ALA]) and long-chain (eicosapentaenoic acid [EPA] and docosahexaenoic acid [DHA]) forms, which largely derive from certain plant- and marine-based foods respectively. Omega-6 PUFAs are present in some vegetable oils, meats, and other animal products.
OBJECTIVES
To assess the effects of omega-3 and omega-6 polyunsaturated fatty acid (PUFA) supplements on dry eye signs and symptoms.
SEARCH METHODS
CENTRAL, Medline, Embase, two other databases and three trial registries were searched in February 2018, together with reference checking. A top-up search was conducted in October 2019, but the results have not yet been incorporated.
SELECTION CRITERIA
We included randomized controlled trials (RCTs) involving dry eye participants, in which omega-3 and/or omega-6 supplements were compared with a placebo/control supplement, artificial tears, or no treatment. We included head-to-head trials comparing different forms or doses of PUFAs.
DATA COLLECTION AND ANALYSIS
We followed standard Cochrane methods and assessed the certainty of the evidence using GRADE.
MAIN RESULTS
We included 34 RCTs, involving 4314 adult participants from 13 countries with dry eye of variable severity and etiology. Follow-up ranged from one to 12 months. Nine (26.5%) studies had published protocols and/or were registered. Over half of studies had high risk of bias in one or more domains. Long-chain omega-3 (EPA and DHA) versus placebo or no treatment (10 RCTs) We found low certainty evidence that there may be little to no reduction in dry eye symptoms with long-chain omega-3 versus placebo (four studies, 677 participants; mean difference [MD] -2.47, 95% confidence interval [CI] -5.14 to 0.19 units). We found moderate certainty evidence for a probable benefit of long-chain omega-3 supplements in increasing aqueous tear production relative to placebo (six studies, 1704 participants; MD 0.68, 95% CI 0.26 to 1.09 mm/5 min using the Schirmer test), although we did not judge this difference to be clinically meaningful. We found low certainty evidence for a possible reduction in tear osmolarity (one study, 54 participants; MD -17.71, 95% CI -28.07 to -7.35 mOsmol/L). Heterogeneity was too substantial to pool data on tear break-up time (TBUT) and adverse effects. Combined omega-3 and omega-6 versus placebo (four RCTs) For symptoms (low certainty) and ocular surface staining (moderate certainty), data from the four included trials could not be meta-analyzed, and thus effects on these outcomes were unclear. For the Schirmer test, we found moderate certainty evidence that there was no intergroup difference (four studies, 455 participants; MD: 0.66, 95% CI -0.45 to 1.77 mm/5 min). There was moderate certainty for a probable improvement in TBUT with the PUFA intervention relative to placebo (four studies, 455 participants; MD 0.55, 95% CI 0.04 to 1.07 seconds). Effects on tear osmolarity and adverse events were unclear, with data only available from a single small study for each outcome. Omega-3 plus conventional therapy versus conventional therapy alone (two RCTs) For omega-3 plus conventional therapy versus conventional therapy alone, we found low certainty evidence suggesting an intergroup difference in symptoms favoring the omega-3 group (two studies, 70 participants; MD -7.16, 95% CI -13.97 to -0.34 OSDI units). Data could not be combined for all other outcomes. Long-chain omega-3 (EPA and DHA) versus omega-6 (five RCTs) For long-chain omega-3 versus omega-6 supplementation, we found moderate certainty evidence for a probable improvement in dry eye symptoms (two studies, 130 participants; MD -11.88, 95% CI -18.85 to -4.92 OSDI units). Meta-analysis was not possible for outcomes relating to ocular surface staining, Schirmer test or TBUT. We found low certainty evidence for a potential improvement in tear osmolarity (one study, 105 participants; MD -11.10, 95% CI -12.15 to -10.05 mOsmol/L). There was low level certainty regarding any potential effect on gastrointestinal side effects (two studies, 91 participants; RR 2.34, 95% CI 0.35 to 15.54).
AUTHORS' CONCLUSIONS
Overall, the findings in this review suggest a possible role for long-chain omega-3 supplementation in managing dry eye disease, although the evidence is uncertain and inconsistent. A core outcome set would work toward improving the consistency of reporting and the capacity to synthesize evidence.
Topics: Dry Eye Syndromes; Fatty Acids, Omega-3; Fatty Acids, Omega-6; Humans; Lubricant Eye Drops; Ophthalmic Solutions; Randomized Controlled Trials as Topic
PubMed: 31847055
DOI: 10.1002/14651858.CD011016.pub2