Global Burden of Anxiety and Depression among Cystic Fibrosis Patient: Systematic Review and Meta-Analysis

Aims This systemic review and meta-analysis were aimed at determining the level of anxiety and depression among cystic fibrosis patients in the world. Methods We conducted a systematic search of published studies from PubMed, EMBASE, MEDLINE, Cochrane, Scopus, Web of Science, CINAHL, and manually on Google Scholar. This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of studies was assessed by the modified Newcastle-Ottawa Scale (NOS). Meta-analysis was carried out using a random-effects method using the STATA™ Version 14 software. Trim and fill analysis was done to correct the presence of significant publication bias. Result From 419,820 obtained studies, 26 studies from 2 different parts of the world including 9766. The overall global pooled prevalence of anxiety and depression after correction for publication bias by trim and fill analysis was found to be 24.91(95% CI: 20.8-28.9) for anxiety. The subgroup analyses revealed with the lowest prevalence, 23.59%, (95% CI: 8.08, 39.09)) in North America and the highest, 26.77%, (95% CI: 22.5, 31.04) seen in Europe for anxiety and with the highest prevalence, 18.67%, (95% CI: 9.82, 27.5) in North America and the lowest, 13.27%, (95% CI: -10.05, 16.5) seen in Europe for depression. Conclusion The global prevalence of anxiety and depression among cystic fibrosis patients is common. Therefore, close monitoring of the patient, regularly screening for anxiety and depression, and appropriate prevention techniques is recommended.


Background
Depression is a mental disorder characterized by feelings of depressed mood, loss of interest or pleasure in activities, and loss of energy that lasts for 2 weeks or more [1]. Depression disorder presents with depressed mood, loss of interest or pleasure, decreased energy, feelings of guilt or low selfworth, disturbed sleep or appetite, poor concentration, the problem of thinking and making decisions, and, in severe stages, recurring thoughts of death or suicide [2], whereas anxiety is a vague, subjective, nonspecific feeling of uneasiness, apprehension, tension, (excessive nervousness) fears, and a sense of impending doom, irrational avoidance of objects or situation, and anxiety attack [3]. Anxiety and depression are the most frequently occurring mental disorders in the general population [4]. Moreover, depression often comes with symptoms of anxiety. These problems can become chronic or recurrent and lead to substantial impairments in an individual's ability to take care of his or her everyday responsibilities [5].
According to the WHO report in 2017, 300 million people around the world have depression and also, the burden of depression and other mental health conditions is on the rise globally [6]. Similarly in another study, globally more than 264 million people affected with depression [7]. The high prevalence suggests that immediate preventive measures should be implemented, such as the setting up of psychopedagogic support services for those in need [8]. Moreover, depression is a significant determinant of quality of life and survival, accounting for approximately 50% of psychiatric consultations and 12% of all hospital admissions [9]. Cystic fibrosis (CF) is a common genetic, life-shortening chronic illness, leading to frequent infections and progressive failure of most organ systems (e.g., lungs and pancreas) [10]. The disease is highly burdensome with progressive multisystem nvolvement, mostly problematic due to persistent lung infections, frequent hospitalizations, and time-consuming treatment regimens taking 2 to 4 hours per day on average [11,12]. It is a severe and progressive disease characterized by decreased physical activities and excessive dyspnea on exertion [13]. Chronically ill patients experience emotional difficulties that can sometimes even manifest themselves in anxiety and depression [14]. The study showed that individuals with chronic medical conditions have a 41% increased risk of having a psychiatric disorder [15]. Respiratory diseases have an increased risk for comorbid anxiety and depression [16]. Depression, anxiety, and cognitive impairment are common among patients with chronic obstructive pulmonary disease (COPD) and may both affect the delivery of pulmonary rehabilitation and be modified by pulmonary rehabilitation [17]. Studies show that compared with nondepressed patients, the odds are 3 times greater than depressed patients that will be noncompliant with medical treatment recommendations [18]. Symptoms of depression and anxiety have negative consequences for disease management, health-related quality of life, and health outcomes [19]. Studies measuring psychological distress in individuals with CF have found high rates of both depression and anxiety, and the prevalence of depression and anxiety ranges from 13-33% and 30% to 33% among adults, respectively [20,21]. Depressive symptoms are prevalent among adults with CF and are associated with poorer health-related quality of life even after controlling for the lung function [14]. The study indicated that people with CF and parents who take care of children with CF are more likely to experience depression than people in the general population [22]. Since the presence of depression and anxiety has a negative influence on the quality of life, healthcare cost, and self-care, this meta-analysis contributes its own to give attention to CF patients especially to focus on prevention and screen for depression and anxiety and treat accordingly.

Methods and Materials
2.1. Study Design and Search Strategy. This systematic review and meta-analysis were conducted under the Preferred Reporting Items guidelines for Systematic Reviews and Meta-analyses (PRISMA) statement [23,24]. We made the searching of articles published in the English language regardless of the year of publication that was taken from PubMed, EMBASE, MEDLINE, Cochrane, Scopus, the web of Science CINAHL, and manually on Google Scholar. The search was performed using key terms such as CF, cystic fibrosis, anxiety, depression, patient, and worldwide.

Study Selection and Eligibility Criteria
(i) All adults who were diagnosed with CF were included (ii) Both published and unpublished studies conducted worldwide regardless of study design were included 2.3. Study Extraction and Quality Appraisal. The data were extracted by three independent authors (MT, TT, and NA) using a data extraction format prepared in a Microsoft Excel 2010 spreadsheet. The extracted data were the first author's name, publication year, country, region, design, sample size, sampling method, and prevalence of anxiety and depression among CF patient. The quality of each study was assessed using the modified Newcastle-Ottawa Scale (NOS) for cross-sectional studies [25]. Studies were included with a score of 5 and more on the NOS [26]. Each study's quality was evaluated independently by five authors (TT, MT, RO, GD, and TL), and any disagreements were resolved by discussion and consensus.   International Journal of Chronic Diseases was conducted by using I − squared (I 2 ) statistics. The pooled prevalence of anxiety and depression among CF patient was carried out using a random-effects (DerSimonian and Laird) method. To minimize the potential random variations between studies, heterogeneity sources were analyzed using subgroup analysis and metaregression.

Study Selection.
Initially, a total of 419,820 studies were retrieved from the databases and manual searching. From this, 124,917 duplicates were found and removed. Their title screened the remaining 119,920 articles, and abstract 4,912 irrelevant studies were removed. Eighty-five full-text articles were assessed for eligibility, and 59 of them were excluded due to not reporting the outcome of interest and low methodological quality. Finally, a total of 26 studies fulfilled the inclusion criteria and enrolled in the study (Figure 1).

Discussion
Primary studies suggest that CF does have a negative impact on physical functioning aspects of quality of life. Depression and anxiety are the main factors in decreasing individual's quality of life. The prevalence of anxiety and depression among adults with cystic fibrosis patients found to be 22.2% and 42.4%, respectively [14]. In another finding, the cystic fibrosis patients have significantly worse quality of life reflecting their significantly impaired scores for physical functioning [43].

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International Journal of Chronic Diseases and for general health perception, but to have similar scores for most psychosocial measures [44,45]. Since Cystic fibrosis is a genetic disorder that damages many of the body's organs, on the top of medical treatment psychological treatment also helps to reduce anxiety and depression, improve adjustment, quality of life, and even medical outcomes, as well as knowledge, skills, and decisions regarding care.
This systematic review and meta-analysis estimated the pooled global prevalence of anxiety and depression among cystic fibrosis patients. Twenty-two studies were included in the analysis, which selected based on an inclusion criterion. To the best of our knowledge, this systematic review and meta-analysis provide a comprehensive estimation of the global pooled prevalence of anxiety and depression among cystic fibrosis patients. Depression and anxiety are more commonly observed in chronic diseases compared to the general population [46].
In this systematic review and meta-analysis, the overall pooled prevalence of anxiety and depression among cystic fibrosis patients was 26.22% (95% CI: 22.1, 30.2) and 12.66% (95% CI: 10.6, 14.6), respectively. This suggests that anxiety and depressive symptoms are common in CF patients, and it needs intensive and multifactorial approach that is required to combat the CF-related complications. Since CF is a life-threatening and incurable chronic medical disease, untreated anxiety and depression have a substantial impact on CF patients' quality of life, physical function, and healthcare utilization. Routine screening for symptoms of anxiety and depression is a worthy endeavor, and those identified with elevated clinical symptoms should be referred to     The strength of the systematic review and meta-analysis is the use of an extensive search strategy to incorporate the studies. On the other hand, studies are reported from a limited number of the country in the world and that may create underrepresentation. This systematic review and meta-analysis presented up-to-date evidence on the global prevalence of anxiety and depression among cystic fibrosis patients.
This systematic review and meta-analysis might have faced the following limitations. First, the lack of primary studies other than Europe and northern America and may affect the generalizability of the finding. Secondly, due to there is significant heterogeneity and publication bias, the result needs to be interpreted cautiously. Thirdly, using different scales of the primary studies included in this systematic review and meta-analysis for screening depression and anxiety among CF patients might affect the pooled prevalence. Our final limitation is having difficulties in comparing our finding due to a lack of summarized and regional-wide systematic reviews and meta-analysis on the prevalence of anxiety and depression among CF patient.

Conclusion
The global prevalence of anxiety and depression among CF patient is common. Therefore, close monitoring of the patient, regularly screening for anxiety and depression and appropriate prevention techniques is recommended.

CI:
Confidence interval NOS: Newcastle Ottawa Scale OR: Odds ratio PRISMA: Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Data Availability
Datasets are available through the corresponding author upon rational appeal.

Conflicts of Interest
All the authors declare that they have no competing interests.

Authors' Contributions
MT and TT developed the protocol and involved in the design, selection of study, data extraction, quality assessment, statistical analysis, results from interpretation, and developing the initial and final drafts of the manuscript.NA, RO, GD, and TL Involved in data extraction, quality assessment, statistical analysis, and revising subsequent drafts. All authors read and approved the final draft of the manuscript.