The efficacy and safety of remdesivir in the treatment of patients with COVID-19: a systematic review and meta-analysis

AbstractBackgroundThe global total of COVID-19 cases will reach 20 million this week, with 750,000 deaths. It has spread to more than 200 countries and regions around the world. At present, the global pandemic continues to rise and continues to spread worldwide. It is necessary to explore the effective and safe treatment of COVID-19 as soon as possible. Remdesiviras was an antiviral agent with therapeutic potential, but it was still controversial.ObjectiveThrough systematic review and meta-analysis, to evaluate the effect and safety of remdesivir in the treatment of patients with COVID-19, and will provide a reliable reference for the treatment of COVID-19.MethodsWe used the following search string: “COVID-19” [Mesh], “remdesivir” [Mesh], “randomized controlled trial” [Mesh]. We used the Medical Subject Heading (MeSH) terms and corresponding keywords to make the search strategy. We searched six databases, PubMed, EMBASE, Cochrane Library, Web of Science, clinical trials.gov and chictr.org.cn. Data analyses were conducted by using the software Review Manager 5.3 and STATA version 14.0.ResultsOur systematic search identified 5 meta-analyses of RCTs, including 1782 patients with COVID-19.The clinical improvement of remdesivir in the treatment of COVID-19 was superior to the placebo-controlled group (relative risk (RR) =1.17, 95% confidence interval (CI)=1.07-1.29, p=0.0009). The following are the Single-Arm Study, Meta-analysis results. The pooled prevalence of clinical improvement significant findings was 62% (95% CI = 59-65%, p=0.00), during treatment of COVID-19 with remdesivir. The incidence rates of Acute kidney injury, Hepatic enzyme increased, Any serious adverse event were 5% (95%CI=3-7%, p=0.00), 11%(95%CI=5-16%, p=0.00), 22%(95%CI=18-27%, p=0.00), respectively, and the mortality was 13%(95%CI=8-19%, p=0.00), during treatment of COVID-19 with remdesivir.ConclusionThis analysis confirms that remdesivir is effective in the clinical improvement of COVID-19 patients, and the rate of clinical improvement was 62%. In addition, adverse events and mortality should also be paid attention to. Future research should aim that more large-scale studies were needed to confirm the results, to further elucidate the underlying mechanisms.

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Community-based interventions for childhood asthma using comprehensive approaches: a systematic review and meta-analysis

Allergy Asthma & Clinical Immunology ◽

10.1186/s13223-021-00522-9 ◽

2021 ◽

Vol 17 (1) ◽

Author(s):

Mei Chan ◽

Melinda Gray ◽

Christine Burns ◽

Louisa Owens ◽

Susan Woolfenden ◽

...

Keyword(s):

Systematic Review ◽

Childhood Asthma ◽

Action Plan ◽

Controlled Trial ◽

Meta Analysis ◽

Mean Difference ◽

Cochrane Library ◽

Care Utilization ◽

Community Based Interventions ◽

Community Based

Abstract Objective We conducted a systematic review and meta-analysis to determine the effectiveness of comprehensive community-based interventions with ≥ 2 components in improving asthma outcomes in children. Methods A systematic search of Medline, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Excerpta Medica Database (EMBASE), Cochrane Library and hand search of reference collections were conducted to identify any research articles published in English between 2000 and 2019. All studies reporting community-based asthma interventions with ≥ 2 components (e.g., asthma self-management education, home environmental assessment or care coordination etc.) for children aged ≤ 18 years were included. Meta-analyses were performed using random-effects model to estimate pooled odds ratio (OR) with 95% confidence intervals (CIs). Results Of the 2352 studies identified, 21 studies were included in the final analysis: 19 pre-post interventions, one randomised controlled trial (RCT) and one retrospective study. Comprehensive asthma programs with multicomponent interventions were associated with significant reduction in asthma-related Emergency Department (ED) visits (OR = 0.26; 95% CI 0.20–0.35), hospitalizations (OR = 0.24; 95% CI 0.15–0.38), number of days (mean difference = − 2.58; 95% CI − 3.00 to − 2.17) and nights with asthma symptoms (mean difference = − 2.14; 95% CI − 2.94 to − 1.34), use of short-acting asthma medications/bronchodilators (BD) (OR = 0.28; 95% CI 0.16–0.51), and increase use of asthma action plan (AAP) (OR = 8.87; 95% CI 3.85–20.45). Conclusion Community-based asthma care using more comprehensive approaches may improve childhood asthma management and reduce asthma related health care utilization.

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Anemia as a risk factor for tuberculosis: a systematic review and meta-analysis

Environmental Health and Preventive Medicine ◽

10.1186/s12199-020-00931-z ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Yemataw Gelaw ◽

Zegeye Getaneh ◽

Mulugeta Melku

Keyword(s):

Systematic Review ◽

Risk Factor ◽

Infectious Diseases ◽

Low Socioeconomic Status ◽

Meta Analysis ◽

Public Health Problem ◽

Cochrane Library ◽

Major Public Health Problem ◽

Double Burden ◽

Mesh Terms

Abstract Background Tuberculosis is a major public health problem caused by Mycobacterium tuberculosis, occurring predominantly in population with low socioeconomic status. It is the second most common cause of death from infectious diseases. Tuberculosis becomes a double burden among anemic patients. Anemia increases an individual’s susceptibility to infectious diseases including tuberculosis by reducing the immunity level. Therefore, the purpose of this study was to determine whether anemia is a risk factor for tuberculosis. Method Relevant published articles were searched in electronic databases like PubMed, Google Scholar, EMBASE, and Cochrane Library using the following MeSH terms: risk factor, predictors, tuberculosis, TB, Anaemia, Anemia, hemoglobin, Hgb, and Hb. Articles written in the English, observational studies conducted on the incidence/prevalence of tuberculosis among anemic patients, or papers examined anemia as risk factors for tuberculosis were included. From those studies meeting eligibility criteria, the first author’s name, publication year, study area, sample size and age of participants, study design, and effect measure of anemia for tuberculosis were extracted. The data were entered using Microsoft Excel and exported to Stata version 11 for analysis. The random-effects model was applied to estimate the pooled OR and HR, and 95% CI. The sources of heterogeneity were tested by Cochrane I-squared statistics. The publication bias was assessed using Egger’s test statistics. Results A total of 17 articles with a 215,294 study participants were included in the analysis. The odd of tuberculosis among anemic patients was 3.56 (95% CI 2.53–5.01) times higher than non-anemic patients. The cohort studies showed that the HR of tuberculosis was 2.01 (95% CI 1.70–2.37) times higher among anemic patients than non-anemic patients. The hazard of tuberculosis also increased with anemia severity (HR 1.37 (95% CI 0.92–2.05), 2.08 (95% CI 1.14–3.79), and 2.66 (95% CI 1.71–4.13) for mild, moderate, and severe anemia, respectively). Conclusion According to the current systematic review and meta-analysis, we can conclude that anemia was a risk factor for tuberculosis. Therefore, anemia screening, early diagnose, and treatment should be provoked in the community to reduce the burden of tuberculosis.

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The Role of Local Bupivacaine Irrigation in Postoperative Pain Control After Augmentation Mammoplasty: A Systematic Review and Meta-Analysis

Plastic Surgery ◽

10.1177/2292550317693816 ◽

2017 ◽

Vol 25 (1) ◽

pp. 32-39

Author(s):

Shan Shan Qiu ◽

Marta Roque ◽

Yi-Chieh Chen

Keyword(s):

Systematic Review ◽

Postoperative Pain ◽

Normal Saline ◽

Pain Control ◽

Meta Analysis ◽

A Priori ◽

Cochrane Collaboration ◽

Cochrane Library ◽

Augmentation Mammoplasty ◽

Mesh Terms

Background: The objective of this study is to analyze the efficacy of local bupivacaine irrigation after augmentation mammoplasty for the control of postoperative pain. Methods: A systematic review and meta-analysis was conducted including all randomized controlled trials (RCTs) that compared the irrigation of bupivacaine (±ketorolac) versus normal saline or no irrigation for pain control after breast augmentation. The primary outcome was postoperative pain measured by visual analog scale. The study protocol was established a priori according to the recommendations of the Cochrane Collaboration. A bibliographical search was conducted in September 2015 in the following Cochrane Library databases: CENTRAL, MEDLINE, EMBASE, and Scielo. The strategy used for the search was ((augmentation AND (“mammoplasty”[MeSH Terms] OR “mammoplasty”)) OR ((“breast”[MeSH Terms] OR “breast”) AND augmentation)) AND ((“pain, postoperative”[MeSH Terms])). Results: Four RCTs with a total of 264 participants were included. Two trials compared bupivacaine alone versus placebo (normal saline or no irrigation) and 3 trials compared bupivacaine plus ketorolac versus placebo. The combined irrigation of bupivacaine and ketorolac showed a clinically significant reduction of pain in the first postoperative hour and on postoperative day 5. The irrigation with bupivacaine compared with placebo significantly reduced pain assessed on postoperative day 4. Conclusion: The irrigation of bupivacaine with or without ketorolac was associated with a reduction of postoperative pain compared with control groups for the first 5 postoperative days. Due to the few number of trials included, these results should be correlated further clinically.

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Repurposing of drugs for Covid-19: a systematic review and meta-analysis

10.1101/2020.06.07.20124677 ◽

2020 ◽

Cited By ~ 1

Author(s):

Pinky Kotecha ◽

Alexander Light ◽

Enrico Checcucci ◽

Daniele Amparore ◽

Cristian Fiori ◽

...

Keyword(s):

Systematic Review ◽

Clinical Trials ◽

Adverse Events ◽

Clinical Improvement ◽

Case Reports ◽

Meta Analysis ◽

Case Series ◽

Cochrane Library ◽

Control Group ◽

Significant Difference

AbstractObjectiveThe aim of this systematic review is to evaluate the data currently available regarding the repurposing of different drugs for Covid-19 treatment. Participants with suspected or diagnosed Covid-19 will be included. The interventions being considered are drugs being repurposed, and comparators will include standard of care treatment or placebo.MethodsWe searched Ovid-MEDLINE, EMBASE, Cochrane library, clinical trial registration site in the UK(NIHR), Europe (clinicaltrialsregister.eu), US (ClinicalTrials.gov) and internationally (isrctn.com), and reviewed the reference lists of articles for eligible articles published up to April 22, 2020. All studies in English that evaluated the efficacy of the listed drugs were included. Cochrane RoB 2.0 and ROBINS-I tool were used to assess study quality. This systematic review adheres to the PRISMA guidelines. The protocol is available at PROSPERO (CRD42020180915).ResultsFrom 708 identified studies or clinical trials, 16 studies and 16 case reports met our eligibility criteria. Of these, 6 were randomized controlled trials (763 patients), 7 cohort studies (321 patients) and 3 case series (191 patients). Chloroquine (CQ) had a 100% discharge rate compared to 50% with lopinavir-ritonavir at day 14, however a trial has recommended against a high dosage due to cardiotoxic events. Hydroxychloroquine (HCQ) has shown no significant improvement in negative seroconversion rate which is also seen in our meta-analysis (p=0.68). Adverse events with HCQ have a significant difference compared to the control group (p=0.001). Lopinavir-ritonavir has shown no improvement in time to clinical improvement which is seen in our meta-analyses (p=0.1). Remdesivir has shown no significant improvement in time to clinical improvement but this trial had insufficient power.DiscussionDue to the paucity in evidence, it is difficult to establish the efficacy of these drugs in the treatment of Covid-19 as currently there is no significant clinical effectiveness of the repurposed drugs. Further large clinical trials are required to achieve more reliable findings. A risk-benefit analysis is required on an individual basis to weigh out the potential improvement in clinical outcome and viral load reduction compared to the risks of the adverse events. (1-16)

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Is oral lichen planus a risk factor for peri-implant diseases? A systematic review and meta-analysis

10.21203/rs.3.rs-15960/v3 ◽

2020 ◽

Author(s):

Xiaoqin Xiong ◽

Tiantian Xu ◽

Xinhong Wang ◽

Wenguang Qin ◽

Ting Yu ◽

...

Keyword(s):

Systematic Review ◽

Risk Factor ◽

Lichen Planus ◽

Oral Lichen Planus ◽

Large Scale ◽

Meta Analysis ◽

Healthcare Research ◽

Cochrane Library ◽

Oral Lichen

Abstract Background : To evaluate whether oral lichen planus (OLP) is a risk factor for peri-implant diseases (PIDs) with a systematic review and meta-analysis. Methods : Five electronic databases including Medline, Embase, Web of Science, the Cochrane Library and Scopus were searched. The included studies are observational human studies written in English. The population of interest included those with/without OLP who received dental implant treatment. The follow-up time after implantation was from one month to 20 years. The quality of the included articles regarding risk of bias and methodology were assessed with the Newcastle-Ottawa Scale or the Agency for Healthcare Research and Quality. The data involving exposure (OLP), primary outcomes (implants having PIDs) and secondary outcomes (probing depth/PD, bleeding on probing/BOP and bone loss/BL) and potential confounders were extracted. Heterogeneity was assessed by I² test. Dichotomous data are expressed as the risk ratio (RR) and 95% confidence interval (CI) which were calculated with a fixed effect model. Results : Of the 66 articles, two studies were enrolled and evaluated as high quality, which totally contained 68 participants receiving 222 (OLP vs. non-OLP, 112 vs. 110) implants with 12 to 120-month follow-up time. Proportions of implants with PIDs between OLP and non-OLP groups were as follows: 19.6% (22/112) vs. 22.7% (25/110) for PIM and 17.0% (19/112) vs. 10.9% (12/110) for PI. The meta-analysis revealed no recognizable difference in number of implants with PIDs (PI: RR = 1.49, 95% CI 0.77-2.90, P = 0.24; PIM:RR = 0.88, 95% CI 0.53 -1.46, P = 0.61; PIDs: RR = 1.08, 95% CI 0.75 -1.55, P = 0.68) or BOP (RR = 0.90, 95% CI: 0.70-1.15, P = 0.40) between OLP and non-OLP groups. Conclusions : Available articles regarding the effects of OLP on PIDs remains very limited. Existing evidence does not support OLP as a suspected risk factor for PIDs. Large-scale prospective trials are required to validate the findings.

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The effectiveness of mHealth interventions on postpartum depression: A systematic review and meta-analysis

Journal of Telemedicine and Telecare ◽

10.1177/1357633x20917816 ◽

2020 ◽

pp. 1357633X2091781

Author(s):

Chuqing Zhou ◽

Hua Hu ◽

Chunyi Wang ◽

Ziyu Zhu ◽

Gengchen Feng ◽

...

Keyword(s):

Systematic Review ◽

Postpartum Depression ◽

Large Scale ◽

Meta Analysis ◽

Clinical Care ◽

Intervention Group ◽

Depression Scale ◽

Clinical Effectiveness ◽

Well Being ◽

Cochrane Library

Introduction Postpartum depression (PPD) is a common psychiatric condition during the postnatal period that negatively impacts the well-being of both the mother and her infant. This study describes a systematic review and preliminary meta-analysis to assess the efficacy of mobile health (mHealth) interventions, which is defined as the use of portable electronic devices to support public health and medical practice, in addressing depressive symptoms among postpartum women. Methods Databases including PubMed, PsycINFO, the Cochrane Library, Embase and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) assessing the effectiveness of mHealth interventions on PPD from database inception to December 2019. Results The initial search identified 754 studies, of which, 11 studies fulfilled the inclusion criteria. These studies evaluated four types of distinct mHealth interventions and involved 2424 participants across six countries. Pooled results demonstrated that compared to the controls, the Edinburgh Postnatal Depression Scale score decreased in the mHealth intervention group (mean difference: –1.09, 95% confidence interval: –1.39 to –0.79). Discussion Our study suggested that mHealth interventions may be a promising tool to complement routine clinical care in the prevention and treatment of PPD, but the clinical effectiveness of mHealth interventions needs to be better established. While most studies focused on telephone-based interventions, recent researches have also suggested the superiority and effectiveness of short messaging service (SMS) and smartphone applications, but the exact efficacy needs further evaluation. Therefore, more high-quality RCTs on app-based and SMS-based interventions are needed before the large-scale roll-out of these interventions in clinical practice.

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What Is the Clinical Evidence Supporting Trauma Team Training (TTT): A Systematic Review and Meta-Analysis

Medicina ◽

10.3390/medicina55090551 ◽

2019 ◽

Vol 55 (9) ◽

pp. 551

Author(s):

Noonan ◽

Olaussen ◽

Mathew ◽

Mitra ◽

Smit ◽

...

Keyword(s):

Systematic Review ◽

Clinical Outcomes ◽

Patient Outcomes ◽

Meta Analysis ◽

Ct Scanning ◽

Trauma Team ◽

Team Training ◽

Cochrane Library ◽

Medical Subject Headings ◽

Mesh Terms

Background and Objectives: Major trauma centres manage severely injured patients using multi-disciplinary teams but the evidence-base that targeted Trauma Team Training (TTT) improves patients’ outcomes is unclear. This systematic review aimed to identify the association between the implementation of TTT programs and patient outcomes. Methods: We searched OVID Medline, PubMed and The Cochrane Library (CENTRAL) from the date of the database commencement until 10 of April 2019 for a combination of Medical Subject Headings (MeSH) terms and keywords relating to TTT and clinical outcomes. Reference lists of appraised studies were also screened for relevant articles. We extracted data on the study setting, type and details about the learners, as well as clinical outcomes of mortality and/or time to critical interventions. A meta-analysis of the association between TTT and mortality was conducted using a random effects model. Results: The search yielded 1136 unique records and abstracts, of which 18 full texts were reviewed. Nine studies met final inclusion, of which seven were included in a meta-analysis of the primary outcome. There were no randomised controlled trials. TTT was not associated with mortality (Pooled overall odds ratio (OR) 0.83; 95% Confidence Interval; 0.64–1.09). TTT was associated with improvements in time to operating theatre and time to first computerized tomography (CT) scanning. Conclusions: Despite few publications related to TTT, its introduction was associated with improvements in time to critical interventions. Whether such improvements can translate to improvements in patient outcomes remains unknown. Further research focusing on the translation of standardised trauma team reception “actions” into TTT is required to assess the association between TTT and patient outcome.

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Global epidemiology of acromegaly: a systematic review and meta-analysis

Acta Endocrinologica ◽

10.1530/eje-21-0216 ◽

2021 ◽

Author(s):

Salvatore Crisafulli ◽

Nicoletta Luxi ◽

Janet Sultana ◽

Andrea Fontana ◽

Federica Spagnolo ◽

...

Keyword(s):

Systematic Review ◽

Large Scale ◽

Meta Analysis ◽

Geographic Area ◽

Cochrane Library ◽

Pooled Prevalence ◽

Global Epidemiology ◽

Study Heterogeneity ◽

Quality Assessments

Objective: To date, no systematic reviews and meta-analysis on the global epidemiology of acromegaly are available in literature. The aims of this study are to provide a systematic review and a meta-analysis of the global epidemiology of acromegaly and to evaluate the quality of study reporting for the identified studies. Methods: MEDLINE, EMBASE and The Cochrane Library databases were searched for studies assessing the epidemiology of acromegaly from inception until 31st January 2020. We included original observational studies written in English, reporting acromegaly prevalence and/or incidence for a well-defined geographic area. Two reviewers independently extracted data and performed quality assessments. Prevalence and incidence pooled estimates were derived performing a random-effects meta-analysis. Results: A total of 32 studies were included in the systematic review, and 22 of them were included in the meta-analysis. The pooled prevalence of acromegaly was 5.9 (95%CI: 4.4-7.9) per 100,000 persons, while the incidence rate (IR) was 0.38 (95%CI: 0.32-0.44) cases per 100,000 person-years. For both prevalence and IR, a considerable between-study heterogeneity was found (I2= 99.3% and 86.0%, respectively). The quality of study reporting was rated as medium for 20 studies and low for 12 studies. Conclusions: Although the largest amount of heterogeneity was due to the high precision of the studies’ estimates, data source and geographic area could represent relevant study-levels factors which could explain about 50% of the total between-study variability. Large-scale high quality studies on the epidemiology of acromegaly are warranted to help the public health system in making decisions.

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The effects of fennel on menstrual bleeding: A systematic review and meta-analysis

Journal of Complementary and Integrative Medicine ◽

10.1515/jcim-2017-0154 ◽

2018 ◽

Vol 15 (3) ◽

Cited By ~ 4

Author(s):

Nafiseh Ghassab Abdollahi ◽

Mojgan Mirghafourvand ◽

Sanaz Mollazadeh

Keyword(s):

Systematic Review ◽

Meta Analysis ◽

Intervention Group ◽

Poor Quality ◽

Mean Difference ◽

Menstrual Bleeding ◽

Cochrane Library ◽

Foeniculum Vulgare ◽

Mesh Terms ◽

Significant Difference

Abstract Introduction Fennel has many medicinal properties and is used in the treatment of dysmenorrhea. Given the widespread use of herbal medicine among women for menstrual problems and considering the fact that there has been no study to date about the effect of fennel on menstrual bleeding and duration of menstrual bleeding through systematic review, the present study was conducted to determine the effect of fennel on the amount (primary outcome) and duration of menstrual bleeding and its side-effects (secondary outcomes). Materials All articles, including Persian and English, with no time limit were searched for in the following databases: Medline (through PubMed), Scopus, EMBASE (through Ovid), Cochrane Library, Web of Sciences, Google Scholar, ProQuest, Clininaltrial.gov, SID, Magiran, Irandoc, and Iranmedex, using MeSH terms, including menstrual bleeding, menstruation, severity of bleeding, hypermenorrhea, menorrhagia, fennel, fennelin, Foeniculum vulgare, dysmenorrhea, and painful menstruation, which were searched separately or in combination. Two authors separately reviewed articles to determine the inclusion criteria, and any disagreement was resolved by reaching consensus with a third person. Results A total of 7993 articles were identified through searching the databases, of which 7327 were excluded as duplicates and 666 were screened for inclusion. Six hundread and forty six were excluded by title and abstract based on not being relevant to the review and being conducted on animals. Eventually, six articles were included in the study and four articles entered into the meta-analysis. The results from meta-analysis showed that using fennel caused a significant increase in mean menstrual bleeding in the first cycle after treatment in the intervention group compared to the control (Std. mean difference: 0.46; 95 % CI: 0.18–0.73; p = 0.001; I2 = 9 %). However, it had no significant effect on menstrual bleeding in the second cycle after treatment (Mean difference: 1.44; 95 % CI:-5.09 to 7.96; p = 0.67; I2 = 0 %). Conclusions The results of meta-analysis of four articles showed that in the first cycle after treatment, use of fennel increased menstrual bleeding in the intervention group compared to the control, but meta-analysis of two articles showed no significant difference between intervention and control groups in the amount of menstrual bleeding in the second cycle after treatment. Given the poor quality of articles, conducting clinical trials to determine the effect of fennel on menstrual bleeding appears necessary.

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Mood Disorders and Gluten: It’s Not All in Your Mind! A Systematic Review with Meta-Analysis

Nutrients ◽

10.3390/nu10111708 ◽

2018 ◽

Vol 10 (11) ◽

pp. 1708 ◽

Cited By ~ 9

Author(s):

Eleanor Busby ◽

Justine Bold ◽

Lindsey Fellows ◽

Kamran Rostami

Keyword(s):

Systematic Review ◽

Mood Disorders ◽

Prospective Studies ◽

Meta Analysis ◽

Cochrane Library ◽

Future Research ◽

One Year ◽

Randomised Controlled ◽

Meta Analyses ◽

The Relationship

Gluten elimination may represent an effective treatment strategy for mood disorders in individuals with gluten-related disorders. However, the directionality of the relationship remains unclear. We performed a systematic review of prospective studies for effects of gluten on mood symptoms in patients with or without gluten-related disorders. Six electronic databases (CINAHL, PsycINFO, Medline, Web of Science, Scopus and Cochrane Library) were searched, from inception to 8 August 2018, for prospective studies published in English. Meta-analyses with random-effects were performed. Three randomised-controlled trials and 10 longitudinal studies comprising 1139 participants fit the inclusion criteria. A gluten-free diet (GFD) significantly improved pooled depressive symptom scores in GFD-treated patients (Standardised Mean Difference (SMD) −0.37, 95% confidence interval (CI) −0.55 to −0.20; p < 0.0001), with no difference in mean scores between patients and healthy controls after one year (SMD 0.01, 95% CI −0.18 to 0.20, p = 0.94). There was a tendency towards worsening symptoms for non-coeliac gluten sensitive patients during a blinded gluten challenge vs. placebo (SMD 0.21, 95% CI −0.58 to 0.15; p = 0.25). Our review supports the association between mood disorders and gluten intake in susceptible individuals. The effects of a GFD on mood in subjects without gluten-related disorders should be considered in future research.

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