Introduction  The prevalence of otitis media (OM) is substantial all over the world. Epidemiological data related to the economic burden of OM globally is minimal. The present systematic review was undertaken to estimate the economic burden of this disease in various parts of the world. Objectives  An extensive literature search was done using PRISMA guidelines to identify relevant studies that estimated the economic burden of OM in monetary terms. The databases searched were PubMed Central, Ovid, and Embase. The cost estimation was done for one specific year and then compared considering the inflation rate. Data Synthesis  The literature search led to the inclusion of 10 studies. The studies evaluated direct and indirect costs in monetary terms. Direct costs (health system and patient perspective) ranged from USD (United States Dollar) 122.64 (Netherlands) to USD 633.6 (USA) per episode of OM. Looking at only the patient perspective, the costs ranged from USD 19.32 (Oman) to USD 80.5 (Saudi Arabia). The total costs (direct and indirect) ranged from USD 232.7 to USD 977 (UK) per episode of OM. The economic burden per year was highest in the USA (USD 5 billion). The incidence of OM episodes was found more in children < 5 years old. Introduction of pneumococcal conjugate vaccines decreased the incidence in children and now the prevalence in adults is of concern. Conclusion  The economic burden of OM is relatively high globally and addressing this public health burden is important. Approaches for the prevention, diagnosis, and treatment should be undertaken by the health system to alleviate this disease burden.

Atrial fibrillation (AF) is the most common cardiac arrhythmia, with an increasing incidence and prevalence because of progressively aging populations. Costs related to AF are both direct and indirect. This systematic review aims to identify the main cost drivers of the illness, assess the potential economic impact resulting from changes in care strategies, and propose interventions where they are most needed.
A systematic literature search of the PubMed and Scopus databases was performed to identify analytical observational studies defining the cost of illness in cases of AF. The search strategy was based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) 2020 recommendations.
Of the 944 articles retrieved, 24 met the inclusion criteria. These studies were conducted in several countries. All studies calculated the direct medical costs, whereas 8 of 24 studies assessed indirect costs. The median annual direct medical cost per patient, considering all studies, was €9409 (13 333 US dollars in purchasing power parities), with a very large variability due to the heterogeneity of different analyses. Hospitalization costs are generally the main cost drivers. Comorbidities and complications, such as stroke, considerably increase the average annual direct medical cost of AF.
In most of the analyzed studies, inpatient care cost represents the main component of the mean direct medical cost per patient. Stroke and heart failure are responsible for a large share of the total costs; therefore, implementing guidelines to manage comorbidities in AF is a necessary step to improve health and mitigate healthcare costs.

Out-of-pocket (OOP) health care expenditures in the United States have increased significantly in the past 5 decades. Most research on OOP costs focuses on expenditures related to insurance and cost-sharing payments or on costs related to specific conditions or settings, and does not capture the full picture of the financial burden on patients and unpaid caregivers. The aim for this systematic literature review was to identify and categorize the multitude of OOP costs to patients and unpaid caregivers, aid in the development of a more comprehensive catalog of OOP costs, and highlight potential gaps in the literature. The authors found that OOP costs are multifarious and underestimated. Across 817 included articles, the authors identified 31 subcategories of OOP costs related to direct medical (eg, insurance premiums), direct nonmedical (eg, transportation), and indirect spending (eg, absenteeism). In addition, 42% of articles studied an expenditure that the authors did not label as \"OOP.\" A holistic and comprehensive catalog of OOP costs can inform future research, interventions, and policies related to financial barriers to health care in the United States to ensure the full range of costs for patients and unpaid caregivers are acknowledged and addressed.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive and therapy-resistant form of breast cancer with a significant economic burden on patients and healthcare systems. Therefore, we completed a systematic review to classify and synthesize the literature on the direct and indirect costs of TNBC.
METHODS: Databases including ISI Web of Science, Scopus, PubMed, and Google Scholar were searched for all related articles assessing the economic burden of TNBC from 2010 until December 2022. The quality and eligibility assessments were done accordingly. We adjusted all costs to January 2023 $US.
RESULTS: From 881 records, 15 studies were eligible. We found that studies are widely disparate in the timetable, study design, patient populations, and cost components assessed. The annual per-patient direct costs of metastatic TNBC (mTNBC) were about $24,288 to $316,800. For early TNCB patients (eTNBC) this was about $21,120 to $105,600. Cancer management anticancer therapy costs account for the majority of direct costs. Along with an increase in cancer stage and line of therapy, healthcare costs were increased. Moreover, the indirect costs of patients with mTNBC and eTNBC were about $1060.875 and about $186,535 for each patient respectively.
CONCLUSIONS: The results showed that the direct and indirect costs of TNBC, mainly those of mTNBC, were substantial, suggesting attention to medical progress in cancer prognosis and therapy approaches.

UNASSIGNED: To identify and synthesize evidence regarding how coronavirus disease 2019 (COVID-19) interventions, including vaccines and outpatient treatments, have impacted healthcare resource use (HCRU) and costs in the United States (US) during the Omicron era.
UNASSIGNED: A systematic literature review (SLR) was performed to identify articles published between 1 January 2021 and 10 March 2023 that assessed the impact of vaccination and outpatient treatment on costs and HCRU outcomes associated with COVID-19. Screening was performed by two independent researchers using predefined inclusion/exclusion criteria.
UNASSIGNED: Fifty-eight unique studies were included in the SLR, of which all reported HCRU outcomes, and one reported costs. Overall, there was a significant reduction in the risk of COVID-19-related hospitalization for patients who received an original monovalent primary series vaccine plus booster dose vs. no vaccination. Moreover, receipt of a booster vaccine was associated with a lower risk of hospitalization vs. primary series vaccination. Evidence also indicated a significantly reduced risk of hospitalizations among recipients of nirmatrelvir/ritonavir (NMV/r), remdesivir, sotrovimab, and molnupiravir compared to non-recipients. Treated and/or vaccinated patients also experienced reductions in intensive care unit (ICU) admissions, length of stay, and emergency department (ED)/urgent care clinic encounters.
UNASSIGNED: The identified studies may not represent unique patient populations as many utilized the same regional/national data sources. Synthesis of the evidence was also limited by differences in populations, outcome definitions, and varying duration of follow-up across studies. Additionally, significant gaps, including HCRU associated with long COVID and various high-risk populations and cost data, were observed.
UNASSIGNED: Despite evidence gaps, findings from the SLR highlight the significant positive impact that vaccination and outpatient treatment have had on HCRU in the US, including periods of Omicron predominance. Continued research is needed to inform clinical and policy decision-making in the US as COVID-19 continues to evolve as an endemic disease.

Due to the COVID-19 pandemic, the pressure on healthcare systems has been tremendous and it is having a huge economic impact. The objective of this paper is to carry out a systematic literature review of the publications that have analysed the costs derived from COVID-19 from the patient\'s perspective. Not only is this study aimed at measuring the impact of COVID-19 in economic terms, but also in qualitative terms, analysing, for instance, the types of costs (direct and indirect) and their variations depending on the geographical area under study. Searches were conducted in PubMed, Cochrane Library, Web of Science and Scopus. The time frame for the analysis was from the start of the pandemic until 9th December 2021. A total of 322 papers were found. The number of articles assessed for eligibility was 32, and after applying the exclusion criteria, 13 papers were included in the qualitative synthesis. Most of the studies analysed only direct costs (69.23%) and were focused on Asia (61.54%), where the larger indirect costs, as well as the greater total costs, were found. However, the higher costs per patient and year were shown for the United States. This investigation showed the importance of COVID-19 in national, regional and local budgets. More studies are to be developed in Europe due to both the existing differences in the health care systems and financing by country and the difference in the incidence of COVID-19 by country and wave.

We performed a systematic literature review and narrative synthesis according to a pre-registered protocol (Prospero: CRD42022376561) to identify the evidence associated with the burden of illness in Dravet syndrome (DS), a developmental and epileptic encephalopathy characterized by drug-resistant epilepsy with neurocognitive and neurobehavioral impairment. We searched MEDLINE, Embase, and APA PsychInfo, Cochrane\'s database of systematic reviews, and Epistemonikos from inception to June 2022. Non-interventional studies reporting on epidemiology (incidence, prevalence, and mortality), patient and caregiver health-related quality of life (HRQoL), direct and indirect costs and healthcare resource utilization were eligible. Two reviewers independently carried out the screening. Pre-specified data were extracted and a narrative synthesis was conducted. Overall, 49 studies met the inclusion criteria. The incidence varied from 1:15 400-1:40 900, and the prevalence varied from 1.5 per 100 000 to 6.5 per 100 000. Mortality was reported in 3.7%-20.8% of DS patients, most commonly due to sudden unexpected death in epilepsy and status epilepticus. Patient HRQoL, assessed by caregivers, was lower than in non-DS epilepsy patients; mean scores (0 [worst] to 100/1 [best]) were 62.1 for the Kiddy KINDL/Kid-KINDL, 46.5-54.7 for the PedsQL and 0.42 for the EQ-5D-5L. Caregivers, especially mothers, were severely affected, with impacts on their time, energy, sleep, career, and finances, while siblings were also affected. Symptoms of depression were reported in 47%-70% of caregivers. Mean total direct costs were high across all studies, ranging from $11 048 to $77 914 per patient per year (PPPY), with inpatient admissions being a key cost driver across most studies. Mean costs related to lost productivity were only reported in three publications, ranging from approximately $19 000 to $20 000 PPPY ($17 596 for mothers vs $1564 for fathers). High seizure burden was associated with higher resource utilization, costs and poorer HRQoL. The burden of DS on patients, caregivers, the healthcare system, and society is profound, reflecting the severe nature of the syndrome. Future studies will be able to assess the impact that newly approved therapies have on reducing the burden of DS.

BACKGROUND: Chronic migraine (CM) is a significant neurological condition affecting a substantial portion of the global population. The economic burden of CM includes both direct healthcare costs and indirect costs resulting from productivity losses and intangible impacts on patients\' quality of life. However, there is limited research that comprehensively evaluates all cost components associated with CM, highlighting the need for a systematic review.
METHODS: We conducted a systematic literature search in databases including MEDLINE, Embase, and CINAHL to identify studies estimating the cost of illness of chronic migraines. The search was restricted to English language articles published from inception to October 2021, and only findings from Organisation for Economic Co-operation and Development (OECD) countries were included. Methodology features and key findings were extracted from the studies, and reported costs were converted to GBP for cross-country comparisons.
RESULTS: Thirteen cost-of-illness studies on CM from various OECD countries were included in this review. The studies demonstrated substantial variations in monetary estimates, but consistently highlighted the considerable economic burden of CM. Direct costs, particularly hospitalisation and medication expenses, were identified as the highest contributors. However, indirect costs, such as productivity losses due to absenteeism and presenteeism, were often underexplored in the reviewed studies. Additionally, intangible costs related to emotional and social impacts on patients were largely overlooked.
CONCLUSIONS: Chronic migraine imposes a significant economic burden on individuals, healthcare systems, and society. Policymakers and healthcare stakeholders should consider both direct and indirect cost components, as well as intangible costs, in developing targeted strategies for effective CM management and resource allocation. Further research focusing on comprehensive cost assessments and sensitivity analyses is needed to enhance the understanding of CM\'s economic implications and inform evidence-based healthcare policy decisions. Addressing these research gaps can alleviate the economic burden of CM and improve patient outcomes.

The clinical benefits of advanced therapies (i.e., biologics and small-molecule drugs) in the treatment of moderate-to-severe ulcerative colitis (UC) have been demonstrated; however, there is less clarity regarding the economic and health-related quality of life (HRQoL) impact of these treatments. We conducted a systematic literature review to synthesize data on cost, healthcare resource utilization (HCRU), and HRQoL for patients who received approved advanced therapies for moderate-to-severe UC in the United States and Europe.
Databases including MEDLINE, Embase, the Database of Abstracts of Reviews of Effects (DARE), the National Health Service Economic Evaluation Database (NHS EED), and EconLit were searched systematically to identify observational studies published between January 1, 2010 and October 14, 2021 that assessed the impact of advanced therapies on cost, HCRU, and/or HRQoL in adults with moderate-to-severe UC. Supplementary gray literature searches of conference proceedings from the past 4 years (January 2018 to October 2021) were also performed.
47 publications of 40 unique cost/HCRU studies and 13 publications of nine unique HRQoL studies were included. Findings demonstrated that biologics have a positive impact on indirect costs (i.e., productivity, presenteeism, and absenteeism) and HRQoL. High costs of biologics were not always fully offset by reductions in cost and HCRU associated with disease management. For many patients, treatment switching and dose escalations were required, thus increasing drug costs, particularly when switching across treatment classes.
These findings highlight a high unmet need for therapies for moderate-to-severe UC that can reduce the healthcare burden and impact on society. Further research is warranted, as the reported evidence was limited by the small sample sizes of some treatment groups within a study.
Although advanced therapies, such as biologics and small-molecule drugs, have shown clinical benefit in treating moderate-to-severe ulcerative colitis, their economic impact and effect on patients’ quality of life is less clear. This study comprehensively reviewed the cost and use of healthcare resources associated with starting treatment with advanced therapies for ulcerative colitis, as well as the impact of these treatments on quality of life. We found that while biologics have a benefit on work productivity, work attendance, work absence, and quality of life, the high costs of biologics were not always fully met by reductions in disease management costs and healthcare resources. Many patients needed to switch treatments or required dose increases, which were expensive. There is a high unmet need for therapies for moderate-to-severe ulcerative colitis that can reduce healthcare costs, use of healthcare resources, and effect on society.

Lennox-Gastaut syndrome (LGS) is a severe developmental and epileptic encephalopathy characterized by drug-resistant epilepsy with multiple seizure types starting in childhood, a typical slow spike-wave pattern on electroencephalogram, and cognitive dysfunction.
We performed a systematic literature review according to the PRISMA guidelines to identify, synthesize and appraise the burden of illness in LGS (including \"probable\" LGS). Studies were identified by searching MEDLINE, Embase and APA PsychInfo, Cochrane\'s database of systematic reviews, and Epistemonikos. The outcomes were epidemiology (incidence, prevalence or mortality), direct and indirect costs, healthcare resource utilization, and patient and caregiver health-related quality of life (HRQoL).
The search identified 22 publications evaluating the epidemiology (n = 10), direct costs and resource (n = 10) and/or HRQoL (n = 5). No studies reporting on indirect costs were identified. With no specific ICD code for LGS in many regions, several studies had to rely upon indirect methods to identify their patient populations (e.g., algorithms to search insurance claims databases to identify \"probable\" LGS). There was heterogeneity between studies in how LGS was defined, the size of the populations, ages of the patients and length of the follow-up period. The prevalence varied from 4.2 to 60.8 per 100,000 people across studies for probable LGS and 2.9-28 per 100,000 for a confirmed/narrow definition of LGS. LGS was associated with high mortality rates compared to the general population and epilepsy population. Healthcare resource utilization and direct costs were substantial across all studies. Mean annual direct costs per person varied from $24,048 to $80,545 across studies, and home-based care and inpatient care were significant cost drivers. Studies showed that the HRQoL of patients and caregivers was adversely affected, although only a few studies were identified. In addition, studies suggested that seizure events were associated with higher costs and worse HRQoL. The risk of bias was low or moderate in most studies.
LGS is associated with a significant burden of illness featuring resistant seizures associated with higher costs and worse HRQoL. More research is needed, especially in evaluating indirect costs and caregiver burden, where there is a notable lack of studies.