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      Lessons Learned From the Clinical Presentation of Common Variable Immunodeficiency Disorders: A Systematic Review and Meta-Analysis

      systematic-review

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          Abstract

          Background

          Diagnostic delay in common variable immunodeficiency disorders (CVID) is considerable. There is no generally accepted symptom-recognition framework for its early detection.

          Objective

          To systematically review all existing data on the clinical presentation of CVID.

          Methods

          PubMed, EMBASE and Cochrane were searched for cohort studies, published January/1999-December/2019, detailing the clinical manifestations before, at and after the CVID-diagnosis.

          Results

          In 51 studies (n=8521 patients) 134 presenting and 270 total clinical manifestations were identified. Recurrent upper and/or lower respiratory infections were present at diagnosis in 75%. Many patients had suffered severe bacterial infections (osteomyelitis 4%, meningitis 6%, septicemia 8%, mastoiditis 8%). Bronchiectasis (28%), lymphadenopathy (27%), splenomegaly (13%), inflammatory bowel disease (11%), autoimmune cytopenia (10%) and idiopathic thrombocytopenia (6%) were also frequently reported. A bimodal sex distribution was found, with male predominance in children (62%) and female predominance in adults (58%). 25% of CVID-patients developed other manifestations besides infections in childhood, this percentage was much higher in adults (62%). Immune-dysregulation features, such as granulomatous-lymphocytic interstitial lung disease and inflammatory bowel disease, were more prominent in adults.

          Conclusions

          The shift from male predominance in childhood to female predominance in adults suggests differences in genetic and environmental etiology in CVID and has consequences for pathophysiologic studies. We confirm the high frequency of respiratory infections at presentation, but also show a high incidence of severe bacterial infections such as sepsis and meningitis, and immune dysregulation features including lymphoproliferative, gastrointestinal and autoimmune manifestations. Early detection of CVID may be improved by screening for antibody deficiency in patients with these manifestations.

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          Most cited references99

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          Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement

          Systematic reviews should build on a protocol that describes the rationale, hypothesis, and planned methods of the review; few reviews report whether a protocol exists. Detailed, well-described protocols can facilitate the understanding and appraisal of the review methods, as well as the detection of modifications to methods and selective reporting in completed reviews. We describe the development of a reporting guideline, the Preferred Reporting Items for Systematic reviews and Meta-Analyses for Protocols 2015 (PRISMA-P 2015). PRISMA-P consists of a 17-item checklist intended to facilitate the preparation and reporting of a robust protocol for the systematic review. Funders and those commissioning reviews might consider mandating the use of the checklist to facilitate the submission of relevant protocol information in funding applications. Similarly, peer reviewers and editors can use the guidance to gauge the completeness and transparency of a systematic review protocol submitted for publication in a journal or other medium.
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            Meta-analysis of observational studies in epidemiology: a proposal for reporting. Meta-analysis Of Observational Studies in Epidemiology (MOOSE) group.

            Because of the pressure for timely, informed decisions in public health and clinical practice and the explosion of information in the scientific literature, research results must be synthesized. Meta-analyses are increasingly used to address this problem, and they often evaluate observational studies. A workshop was held in Atlanta, Ga, in April 1997, to examine the reporting of meta-analyses of observational studies and to make recommendations to aid authors, reviewers, editors, and readers. Twenty-seven participants were selected by a steering committee, based on expertise in clinical practice, trials, statistics, epidemiology, social sciences, and biomedical editing. Deliberations of the workshop were open to other interested scientists. Funding for this activity was provided by the Centers for Disease Control and Prevention. We conducted a systematic review of the published literature on the conduct and reporting of meta-analyses in observational studies using MEDLINE, Educational Research Information Center (ERIC), PsycLIT, and the Current Index to Statistics. We also examined reference lists of the 32 studies retrieved and contacted experts in the field. Participants were assigned to small-group discussions on the subjects of bias, searching and abstracting, heterogeneity, study categorization, and statistical methods. From the material presented at the workshop, the authors developed a checklist summarizing recommendations for reporting meta-analyses of observational studies. The checklist and supporting evidence were circulated to all conference attendees and additional experts. All suggestions for revisions were addressed. The proposed checklist contains specifications for reporting of meta-analyses of observational studies in epidemiology, including background, search strategy, methods, results, discussion, and conclusion. Use of the checklist should improve the usefulness of meta-analyses for authors, reviewers, editors, readers, and decision makers. An evaluation plan is suggested and research areas are explored.
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              Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: guidelines for reporting observational studies.

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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/583782
                URI : https://loop.frontiersin.org/people/1039346
                URI : https://loop.frontiersin.org/people/188786
                Journal
                Front Immunol
                Front Immunol
                Front. Immunol.
                Frontiers in Immunology
                Frontiers Media S.A.
                1664-3224
                23 March 2021
                2021
                : 12
                : 620709
                Affiliations
                [1] 1 Department of Tranzo, Tilburg University , Tilburg, Netherlands
                [2] 2 Department of Pediatrics, Amalia Children’s Hospital , Nijmegen, Netherlands
                [3] 3 Department of Pediatric Infectious Diseases and Immunology, Wilhelmina Children’s Hospital, University Medical Center Utrecht , Utrecht, Netherlands
                [4] 4 Laboratory of Medical Microbiology and Immunology, Elisabeth-Tweesteden Hospital , Tilburg, Netherlands
                Author notes

                Edited by: Waleed Al-Herz, Kuwait University, Kuwait

                Reviewed by: Charlotte Cunningham-Rundles, Icahn School of Medicine at Mount Sinai, United States; Hassan Abolhassani, Karolinska Institute, Sweden

                *Correspondence: Esther de Vries, e.devries@ 123456tilburguniversity.edu

                This article was submitted to Primary Immunodeficiencies, a section of the journal Frontiers in Immunology

                Article
                10.3389/fimmu.2021.620709
                8021796
                33833753
                3ce9f422-a60a-4244-a6c8-40b642c46c97
                Copyright © 2021 Janssen, van der Flier and de Vries

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 23 October 2020
                : 24 February 2021
                Page count
                Figures: 4, Tables: 2, Equations: 0, References: 105, Pages: 16, Words: 6227
                Categories
                Immunology
                Systematic Review

                Immunology
                humoral immunodeficiency,antibody deficiency,common variable immunodeficiency disorders,non-infectious complications,clinical manifestations

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