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Candida auris is an emerging multi-drug resistant yeast that can cause life-threatening infections. A recent report clarified the ability of C. auris to form a biofilm with enhanced drug resistance properties in the host skin's deep layers. The formed biofilm may initiate further bloodstream spread and immune escape. Therefore, we propose that secreted chemicals from the biofilm may facilitate fungal pathogenesis. In response to this interaction, the host skin may develop potential defensive mechanisms. Comparative transcriptomics was performed on the host dermal cells in response to indirect interaction with C. auris biofilm through Transwell inserts compared to planktonic cells. Furthermore, the effect of antifungals including caspofungin and fluconazole was studied. The obtained data showed that the dermal cells exhibited different transcriptional responses. Kyoto Encyclopedia of Genes and Genomes and Reactome analyses identified potential defensive responses employed by the dermal cells and potential toxicity induced by C. auris. Additionally, our data indicated that the dominating toxic effect was mediated by ferroptosis; which was validated by qRT-PCR, cytotoxicity assay, and flow cytometry. On the other hand, the viability of C. auris biofilm was enhanced and accompanied by upregulation of MDR1, and KRE6 upon interaction with dermal cells; both genes play significant roles in drug resistance and biofilm maturation, respectively. This study for the first-time shed light on the dominating defensive responses of human dermal cells, microbe colonization site, to C. auris biofilm and its toxic effects. Further, it demonstrates how C. auris biofilm responds to the defensive mechanisms developed by the human dermal cells.
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Antifúngicos , Biofilmes , Candida auris , Ferroptose , Perfilação da Expressão Gênica , Humanos , Biofilmes/efeitos dos fármacos , Biofilmes/crescimento & desenvolvimento , Candida auris/genética , Candida auris/efeitos dos fármacos , Antifúngicos/farmacologia , Ferroptose/efeitos dos fármacos , Fluconazol/farmacologia , Caspofungina/farmacologia , Pele/microbiologia , Interações Hospedeiro-PatógenoRESUMO
INTRODUCTION: Atopic dermatitis (AD) is a chronic skin disease that poses a significant burden on both patients and the society. AD causes the highest loss in disability-adjusted life years compared with other skin diseases. This study aimed to estimate the economic and humanistic burden of AD in adults and adolescents in seven countries in the Middle East and Africa region (Egypt, Lebanon, Saudi Arabia, Kuwait, Algeria, South Africa, and United Arab Emirates). METHODS: We conducted a literature review to identify country-specific data on this disease. Subsequently, meetings were organized with experts from each country to complete the missing data. The data were aggregated and calculation models were created to estimate the value of the humanistic and economic burden of the disease in each country. Finally, we conducted meetings with local experts to validate the results, and the necessary adjustments were made. RESULTS: On average, a patient with AD loses 0.19 quality-adjusted life years (QALYs) annually owing to this disease. The average annual healthcare cost per patient is highest in the United Arab Emirates, with an estimated value of US $3569 and a population-level indirect cost of US $112.5 million. The included countries allocated a range of 0.20-0.77% of their healthcare expenditure to AD-related healthcare services and technologies. The indirect cost of AD represents approximately 67% of the total disease cost and, on average, approximately 0.043% (range 0.022-0.059%) of the gross domestic product (GDP) of each country. CONCLUSION: Although the humanistic and economic burdens differ from country to country, AD carries a significant socioeconomic burden in all countries. The quality of life is severely affected by the disease. If AD is controlled, the costs, especially indirect costs, could decrease and the disease burden could be alleviated significantly.
Atopic dermatitis is a chronic condition characterized by inflamed and itchy skin. The prevalence and symptoms of atopic dermatitis are observed to increase in dry weather. Owing to its high prevalence in children, the majority of studies on atopic dermatitis are in children. Although it is also prevalent in adults and adolescents, its burden on adults has not been sufficiently studied, especially in Africa and the Middle East. This study quantified the burden of atopic dermatitis in adults and adolescents in seven countries in the Middle East and Africa. We estimated the economic and humanistic burden of this disease. We conducted a literature review and expert interviews to determine the effects on patients and caregivers. We created mathematical models to calculate the disease burden in each country, and local experts in each country validated the data. The study results showed that atopic dermatitis significantly affects the quality of life of patients. The direct medical costs of treatment in each country were calculated. The management of atopic dermatitis consumes around 0.200.77% of the healthcare expenditure in a country. The indirect cost of atopic dermatitis represents 0.0220.059% of the gross domestic product (GDP) of a country. The country-specific burden data are essential to guide decision-makers in arriving at evidence-based decisions and efficiently allocating available resources. This study focused on the significant indirect economic burden of the disease, which can sometimes be underestimated because the disease is not fatal.
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Aims: Atopic dermatitis (AD) is a chronic skin disease that creates a significant burden to patients and society. There is scarcity in local data about the burden of AD in the Kingdom of Saudi Arabia (KSA). We aimed to fill in this gap and quantify the humanistic and economic burden of AD among adults and adolescents in KSA.Materials and methods: A literature search and local expert interviews were conducted to assess the disease burden. Prevalence values were estimated through the literature. International data about health-related quality of life lost owing to AD was adjusted to age and prevalence in KSA. Direct and indirect costs were calculated using a bottom-up approach. Resource utilization data were collected from local dermatologists through online interviews, and indirect costs were based on absenteeism and presenteeism estimates. Validation meetings were conducted with local experts to adjust the final estimates.Results: The age-standardized health loss per patient due to AD is 0.187 quality-adjusted life-years (QALYs) annually, aggregating to 64 thousand lost QALYs in KSA. The annual average direct cost for a patient with AD was 2924 Saudi Riyal (SAR; 780 USD), totaling 373 million SAR in KSA (99.5 million USD). This value represents 0.2% of the annual health expenditure in KSA. The total productivity loss due to AD was 1.36 billion SAR (363.7 million USD). Overall, the economic burden of AD consumes up to 0.059% of the national gross domestic product.Limitations: Local quality of life and productivity lost data were not available for KSA, so global averages were used, assuming these numbers also apply to KSA.Conclusion: Indirect costs represent a large proportion of AD burden in KSA. The disease has a substantial effect on patient quality of life and social well-being. Alleviating the burden might result in significant savings in resources to society.
Atopic dermatitis is one of the most common skin diseases. Mild cases of the disease cause inflamed and itchy skin, while severe cases may cause painful episodes of itching and cracked skin. Patients with atopic dermatitis and their families suffer lower quality of life as the severity of the disease increases. In countries with hot weather like Saudi Arabia, skin is more susceptible to become dry, so the disease is very prevalent. Therefore, the disease poses a significant quality of life burden as well as an economic burden due to the direct costs of treatment and the indirect costs that arise because patients become non-productive or absent from work or school. Our study aimed to quantify the economic and quality of life burden of atopic dermatitis in Saudi Arabia to understand it's real burden and help decision makers quantify its impact on the patients and society. We conducted a literature search and interviewed local experts to determine estimates of costs and quality of life effects. The results of this study should help in prioritizing treatment disease areas in Saudi Arabia and other countries with similar circumstances.
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Dermatite Atópica , Adulto , Humanos , Adolescente , Lactente , Arábia Saudita/epidemiologia , Estresse Financeiro , Qualidade de Vida , Efeitos Psicossociais da DoençaRESUMO
INTRODUCTION: Although previously regarded as a children's disease, it is clear that atopic dermatitis (AD) is also highly prevalent in adults. Because AD is not associated with mortality, it is usually neglected compared with other, fatal diseases. However, several studies have highlighted that AD burden is significant due to its substantial humanistic burden and psychosocial effects. This study aims to summarize and quantify the clinical, economic, and humanistic burden of AD in adults and adolescents. METHODS: A systematic literature search was performed in PubMed, Scopus, Cochrane, Centre for Reviews and Dissemination (CRD), EconPapers, The Professional Society for Health Economics and Outcomes Research (ISPOR), The National Institute for Health and Care Excellence (NICE), and The Canadian Agency for Drugs and Technologies in Health (CADTH). Studies were included if they reported clinical, economic, or humanistic effects of AD on adults or adolescents, from January 2011 to December 2020. The Grading of Recommendations Assessment tool was used to assess risk of bias for the included studies. Regression models were used to explain the correlation between factors such as disease severity and quality of life (QoL). RESULTS: Among 3400 identified records, 233 studies were included. Itch, depression, sleep disturbance, and anxiety were the most frequently reported parameters related to the clinical and humanistic burden of AD. The average utility value in studies not stratifying patients by severity was 0.779. The average direct cost of AD was 4411 USD, while the average indirect cost was 9068 USD annually. CONCLUSIONS: The burden of AD is significant. The hidden disease burden is reflected in its high indirect costs and the psychological effect on QoL. The magnitude of the burden is affected by the severity level. The main limitation of this study is the heterogeneity of different studies in terms of data reporting, which led to the exclusion of potentially relevant data points from the summary statistics.
Atopic dermatitis is a very common skin disease among children and adults. The disease is nonfatal but may lead to patients and families having a low quality of life and decreased productivity, especially in its severe state. Because atopic dermatitis is more common in children than adults, most published research is directed to studying the effect of the disease on children. Atopic dermatitis affects patients' health, quality of life, financial state, and productivity. Therefore, our study aims to study and quantify the burden caused by the disease represented in the clinical burden, humanistic burden, and economic burden. We conducted a systematic literature review to determine all relevant studies providing specific values for the burden. The studies included are those providing information on the percentage of patients affected by specific symptoms, costs paid for treatment, number of days of productivity lost due to the disease, and quality-of-life questionnaire results for patients with atopic dermatitis or their caregivers. We analyzed the data from all relevant studies to calculate average values and quantify the burden. The results of our study should help healthcare sector decision-makers in understanding the real effect of the disease on adults and adolescents and rearrange their priorities for treating different diseases based on the specific burden of each disease.