Humanistic Burden Research Articles

Economic Burden of Late-Stage Age-Related Macular Degeneration in Bulgaria, Germany, and the US

Age-related macular degeneration (AMD) is a highly prevalent and debilitating retinal condition that affects more than 200 million people globally, with the severe late-stage forms-neovascular AMD (nAMD) and geographic atrophy (GA)-affecting more than 11 million people globally. However, much is unknown about the economic burden of the disease. To estimate the economic burden associated with late-stage AMD in Bulgaria, Germany, and the US at the societal level. This study used the prevalence approach cost-of-illness economic modeling to estimate costs attributable to late-stage AMD. Data on health care resource utilization, well-being, and productivity were obtained via primary data collection. Additional data required for the model were sourced from available published literature. Data were collected from January 2021 to March 2022, and analyzed from April to July 2022. Participants older than 50 years residing in Bulgaria, Germany, and the US who were diagnosed with late-stage AMD (nAMD or any form of GA) in 1 or both eyes and caregivers who care for people diagnosed with late-stage AMD were recruited through ophthalmological clinics in Bulgaria and Germany and via online newsletters and social media in the US. The main outcomes were direct medical costs (disease-related health care expenditures), indirect medical costs (care support and assistive technology), well-being cost (loss of well-being), and productivity cost (loss in productivity due to the diseases for both patient and caregivers). Of the 128 individuals with late-stage AMD in this study, 80 (62%) were female, and 120 (94%) were aged 60 years or older. Of the 61 caregivers, 43 (70%) were female and 55 (91%) were aged 45 years or older. Estimated per-annum total costs attributable to late-stage AMD were €449.5 million ($512.5 million) in Bulgaria, €7.6 billion ($8.6 billion) in Germany, and €43.2 billion ($49.4 billion) in the US. Across all countries, 10% to 13% of the total cost incurred was attributed to direct medical costs. In Germany and Bulgaria, the biggest contributor to the total economic burden was reduced well-being (67% and 76%, respectively), whereas in the US, loss of productivity (42%) was the biggest contributor. The findings of this study indicate a substantial burden of late-stage AMD on patients and caregivers in the US, Germany, and Bulgaria. Across the 3 countries, reduced well-being and loss of productivity were relatively large contributors to the total economic burden. Implementing measures to reduce AMD incidence, delay disease progression, and alleviate humanistic burden may help reduce the economic burden of late-stage AMD.

Literature Review to Understand the Burden and Current Non-surgical Management of Moderate-Severe Pain Associated with Knee Osteoarthritis.

To conduct a literature review exploring the humanistic burden, costs, and guideline recommendations for non-surgical management of moderate-severe pain in knee osteoarthritis (KOA). Published studies (2018-25 April 2023) assessing the burden of moderate-severe pain in KOA were identified by searching Medline, Embase, EconLit, and Cochrane database, supplemented with grey literature hand searches and reference list snowballing. Treatment guidelines were also identified for key countries. This review included 106 publications and 37 treatment guidelines. Patients with moderate-severe pain were found to experience a low quality of life (QoL) and an impaired ability to perform daily tasks. The economic burden of KOA was substantial, including cost of medical visits, non-operative treatment (physical therapy and hyaluronic acid [HA] being key drivers) and productivity losses. Non-steroidal anti-inflammatory drugs (NSAIDs) were among the most frequently used pharmacological treatments, with intra-articular (IA) injections used to varying degrees. Opioid use was also frequently reported. Guidelines universally recommended NSAIDs, albeit with limited dose and duration for oral NSAIDs. IA-corticosteroids were conditionally/moderately recommended for short-term use by most guidelines, while IA-HA and opioids were rarely recommended. Guidelines are not specific to patients with moderate-severe pain and do not distinguish between different KOA phenotypes. KOA with moderate-severe pain is associated with substantial humanistic and economic burden. Real-world data suggest that some treatments are regularly used at high cost regardless of the lack of evidence-based recommendations. There remains a need for new treatment options that successfully relieve pain, improve QoL and delay the need for surgery. Graphical abstract available for this article.

A real-world evidence study of interhospital variability in the surgical treatment of patients with benign prostatic hyperplasia: the REVALURO study.

Lower urinary tract symptoms associated with benign prostatic hyperplasia (LUTS/BPH) is a growing condition in males associated with a high clinical, economic and humanistic burden. Several surgical techniques are available for the treatment of LUTS/BPH; thus, the aim of this study was to describe and explore the variability in the use of surgical procedures among Spanish hospitals. The REVALURO was a retrospective, observational study conducted by collecting data from the clinical records of patients with LUTS/BPH aged ≥ 35years, from 5 national reference hospitals, who were surgically treated between 2018 and 2022. Among the 3038 patients who underwent 3084 surgeries, 66% were invasive (2018: 57.5%, 2022: 71.5%), 22% were minimally invasive (MISTs) (2018: 20.7%, 2022: 20.2%) and 12% were highly invasive (2018: 21.8%, 2022: 8.4%). A total of 22.4% of patients' complications, with a maximum incidence of 28.6% (open prostatectomy) and a minimum 0.8% (water vapor thermal therapy (WVTT)] (p < 0.001). The reintervention rate was 1.5% over the study period. The median length of hospital stay after surgery increased from 0days (interquartile range [IQR]: 0) with WVTT to 5days (IQR: 4-8) with open prostatectomy (p < 0.001). Trends in surgical treatment showed that the use of invasive techniques increased, while the use of highly invasive techniques decreased, and the use of MISTs remained constant. However, given the heterogeneity among hospitals, national clinical guidelines and recommendations are needed to guide the decision on which technique should be used and to homogenize the criteria.

Life After Invasive Meningococcal Disease: Insights from Survivors and Their Caregivers.

Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness that is preventable via vaccination. Even with treatment, up to 10-15% of cases are fatal, and many survivors may experience severe long-term sequelae. Building upon the acute-phase findings presented in the Part1 manuscript for this study, we describe the long-term physical, social, psychological, and economic burden of IMD on US survivors and their caregivers in this Part2 manuscript. This was a novel, non-interventional, mixed-methods study among US survivors and their caregivers using a bespoke survey and qualitative interviews. Ten adult survivors, one adolescent survivor, and three caregivers participated in this study. Survivors described extensive physical, neurological, and systemic sequelae, including difficulty walking (11/11), repeat secondary infections (9/11), and numbness (6/11), among others, which were echoed by caregivers. Survivors shared that IMD had negatively impacted their long-term quality of life, citing long-term impacts including emotional impacts (11/11), social impacts (10/11), memory (7/11) and attention (5/11) problems, and difficulty with functional (10/11), self-care (7/11), and physical (6/11) activities. Caregivers were also impacted, describing emotional trauma (3/3), sleep problems (2/3), and day-to-day challenges (2/3). Long-term financial challenges related to healthcare resource utilization were substantial, with specialized care and rehabilitation therapy expenses (11/11), insurance challenges (8/11), and high out-of-pocket costs (6/11) for survivors. Productivity losses were also commonly described by survivors (9/11); sequelae hindered ability to attend school (9/11) or work full time (8/11). Caregivers (2/3) described taking leave from their employment, affecting family income. The humanistic burden of IMD on survivors and their caregivers is substantial and persistent. A comprehensive approach, including preventative measures (e.g., vaccination) and long-term medical, psychological, and financial support for those affected, is needed to mitigate the burden of IMD. A video abstract is available with this article. Video abstract (MP4 1,17,430kb).

Initial Experiences with Invasive Meningococcal Disease: Insights from Survivors and Their Caregivers.

Invasive meningococcal disease (IMD) has a low incidence but is a life-threatening illness with a 10-15% mortality rate. Even with timely treatment, survivors may experience acute and long-term health complications. While meningococcal vaccines are recommended for adolescents and young adults in the USA, vaccination coverage remains uneven across serotypes. This study investigated the physical, social, psychological, and economic burden of IMD on survivors and their caregivers in the USA during the acute phase (Part1, presented in this manuscript) and the long-term phase (Part2, presented in a separate manuscript) of IMD. This study implemented a non-interventional, mixed-methods approach using a bespoke survey and qualitative interviews (designed on the basis of a preliminary conceptual model of IMD) with US survivors and their caregivers. A total of 11 survivors (1 adolescent, 10 adults) and 3 caregivers participated in the study. Survivors contracted IMD during infancy (n = 2), childhood (n = 3), or adulthood (n = 6), and often described leading healthy lives pre-IMD. At IMD onset, interactions with the healthcare system impacted participants' experiences; confusion and care delays were common, and procedures were often invasive (e.g., amputations). Survivors commonly experienced symptoms including skin rash (7/11), fever (6/11), and unconsciousness (6/11), consistent with caregivers' reports. Survivors able to report on the short-term impacts of IMD (n = 9) described functional limitations (9/9), emotional impacts (6/9) such as fear and trauma, and school (6/9), work (4/9), and financial (5/9) challenges. Caregivers also experienced emotional impacts (3/3) and family (2/3), work (3/3), and financial (3/3) impacts during the acute phase. IMD places a significant humanistic burden on survivors and their caregivers during the acute phase. Results from Part1 of this study indicate a need for increased disease awareness and healthcare provider education, expeditious diagnosis, and improved access to prevention methods such as available meningococcal vaccines. A video abstract is available with this article. Video abstract (MP4 1,24,432kb).

The humanistic burden of immunoglobulin A nephropathy on patients and care-partners in the United States.

This cross-sectional survey study quantified the humanistic burden of immunoglobulin A nephropathy (IgAN), in terms of physical and mental health-related quality of life (HRQoL) and work productivity, among adults with primary IgAN and their care-partners. HRQoL was assessed (01/31/22 - 05/31/23) with validated tools including the KDQoL-36 (with SF-12), GAD-7 (anxiety), PHQ-9 (depression), and WPAI: SHP (work productivity). Participant characteristics and total/domain scores were summarized; selected outcomes were compared to an external, kidney disease-free cohort. 117 adults with IgAN and their care-partner pairs, and one adult without a care-partner, were included. The mean ages of patients and care-partners were 38.0 (SD: 8.6) and 40.2 (11.8) years, respectively; 55.9% and 43.6% were female. Mean physical and mental SF-12 scores for patients were 46.7 (SD: 8.0) and 41.9 (9.2), respectively, and 50.7 (7.3) and 43.7 (10.24) for care-partners. Both SF-12 components for patients, and the mental component for care-givers, were significantly worse compared to the US general population. Among patients, 27.1% had moderate/severe anxiety and 49.2% reported at least moderate depression. Compared to external controls, patients experienced significantly higher severity of anxiety (6.6 vs. 5.4) and depression (8.1 vs. 6.6; both p < 0.0001). Among care-partners, 13.7% experienced moderate anxiety and 37.8% experienced moderate/moderately-severe depression. Among employed individuals, both groups reported IgAN-related absenteeism (8.8-9.4%), presenteeism (25.1-25.9%), and overall work impairment (30.4-30.5%). US adults with IgAN and their care partners experience impairments to mental and physical HRQoL and heightened levels of depression and anxiety, underscoring the need for effective IgAN therapies and care-partner support.

Future Therapeutic Strategies for Alzheimer’s Disease: Focus on Behavioral and Psychological Symptoms

Alzheimer’s disease (AD) is a progressive, degenerative brain disorder that impairs memory and thinking skills, leading to significant economic and humanistic burdens. It is associated with various neuropsychiatric symptoms (NPS) such as anxiety, agitation, depression, aggression, apathy, and psychosis. NPSs are common in patients with AD, affecting up to 97% of individuals diagnosed with AD. The severity of NPS is linked to disease progression and cognitive decline. NPS in Alzheimer’s disease leads to increased morbidity, mortality, caregiver burden, earlier nursing home placement, and higher healthcare costs. Despite their significant impact, clinical research on NPS in AD is limited. In clinical settings, accurately distinguishing and diagnosing NPS related to AD remains a challenge. Additionally, conventional treatments for NPS in AD are often ineffective, highlighting the need for new therapies that target these specific symptoms. Understanding these comorbidities can aid in early diagnosis and better management of AD. In this review, we provide a summary of the various neurological and psychiatric symptoms (NPS) associated with AD and new candidates under development for the treatment of NPS based on their therapeutic targets and mechanisms. On top of the conventional NPS studied so far, this review adds recent advancements in the understanding of social functional impairment in AD. This review also provides information that can contribute to the advancement of studies and translational research in this field by emphasizing therapeutic targets and mechanisms of action focused on AD-related NPS rather than conventional mechanisms targeted in AD drug development. Above all, considering the relative lack of research in this new field despite the importance of clinical, medical, and translational research, it may increase interest in NPS in AD, its pathophysiological mechanisms, and potential therapeutic candidates such as molecules with antioxidant potential.

Clinical and Humanistic Burden of IgAN in Adult Patients: A Global Real-World Survey.

Immunoglobulin A nephropathy (IgAN) is a chronic, progressive kidney disease in which proteinuria, reduced estimated glomerular filtration rate (eGFR), pain and fatigue are common. How symptoms interact and impact patient quality of life (QoL) in real-world practice is poorly studied. This study investigated how patient and physician symptom perceptions differ and how proteinuria and eGFR correlate with pain, fatigue, and QoL in adult IgAN patients. Data were drawn from the Adelphi IgAN Disease Specific Programme™, a cross-sectional survey of physicians and their biopsy confirmed IgAN patients in China, France, Germany, Italy, Spain, the United Kingdom, United States, and Japan, from June-October 2021. Physicians provided demographics and clinical characteristics, including pain and fatigue severity. The same patients completed a self-completion form containing questions on symptom severity, the EQ-5D-5L, Kidney Disease Quality of Life, and Work Productivity and Activity Impairment questionnaires. Symptom scores were grouped by severity and patients grouped by proteinuria and eGFR. Analysis of variance, chi-squared or Fisher's exact tests were performed as appropriate and Dunn's multiple comparisons with Bonferroni adjustment for pair-wise comparisons. Overall, 1515 patients were included (mean [standard deviation] age: 43 [15] years, 60% [n=903] male, 70% [n=1020/1459] diagnosed >1 year ago). Pain was reported by 46% (n=374) of physicians and 47% (n=384) of patients and fatigue by 65% (n=530) of physicians and 76% (n=620) of patients. Both pain and fatigue increased with increased proteinuria and reduced eGFR (all p<0.001). Finally, patients with increased proteinuria and reduced eGFR experienced worse (p<0.05) QoL and work productivity across all measures (except work absenteeism). Patients with higher proteinuria and lower eGFR face higher symptom burden and reduced QoL than their counterparts. Physicians underestimated fatigue levels faced by patients. In order to improve QoL, more effective treatments are needed to prevent high proteinuria and preserve eGFR.

The hidden burden of atopic dermatitis in central and Eastern European countries

ABSTRACT Background Atopic dermatitis (AD) imposes a hidden burden through its negative effects on quality of life and productivity. We aim to estimate this hidden burden in adults and adolescents in Central and Eastern European (CEE) countries. Methods We created a burden of disease model to quantify AD’s hidden burden. Humanistic burden was calculated by estimating the monetary value of quality-adjusted life years (QALYs) lost, using prevalence data from the Global Burden of Disease study and gross domestic product (GDP) per capita for each country. Indirect economic burden was estimated based on productivity loss from absenteeism and presenteeism, adjusted for labor force participation and unemployment rates. Total hidden burden was determined by combining productivity losses and QALYs lost. Results QALY loss due to AD ranged from 1,832 to 58,596 annually in CEE countries, equating to 38 million to approximately 1 billion Euros per country. Productivity losses ranged from 3.6 to 148.9 million Euros annually. The total hidden burden of AD represents 0.11% to 0.43% of the GDP. Conclusions Our estimates reflect significant differences in population size, prevalence, and economic strength among CEE countries. Adjusting findings to country-specific GDP provided insights into AD’s true hidden burden, offering valuable information for decision-making.

Marginal health care expenditures and health-related quality of life burden in patients with migraine.

Migraine, characterized by recurrent, severe headaches, presents a considerable challenge for patients, health care systems, and employers in the United States. However, there is a lack of recent estimates of the economic and humanistic burden in this population. To assess the incremental burden of migraine on the total all-cause health care costs and health-related quality of life (HRQoL) in the United States, using data from the Medical Expenditure Panel Survey (MEPS). This retrospective cross-sectional study included adults (≥18 years) with and without migraine on the 2019-2021 full-year consolidated MEPS Household Component and Medical Provider Component data files. Descriptive analyses were conducted to compare health care expenditures and HRQoL among patients with and without migraine. To estimate the marginal effect of migraine on total health care spending, a two-part model generalized linear models was employed. HRQoL was evaluated using physical component summary (PCS) and mental component summary (MCS) scores based on the items in the Veterans Rand 12 Health Survey. A multivariate linear regression with log-link was conducted to understanding the factors associated with PCS and MCS scores. All analyses accounted for complex survey design of MEPS. The study included approximately 1.14 million patients with migraine and approximately 184 million patients without migraine. The patients with migraine were majorly female (82.81%), aged 18-45 years (50.24%), and residing in the southern region of the United States (41.45%). A two-part model revealed that marginal total health care expenditures among patients with migraine were $6,078.56 (95% CI = $4,618.45-$8,141.34) higher compared with those without migraine. In terms of HRQoL, average PCS scores in migraine and nonmigraine groups were 39.79 and 42.15, respectively. The average MCS scores were 46.63 and 49.95 for migraine and nonmigraine groups, respectively. After adjusting for sociodemographic characteristics, multivariable linear regression models revealed that the PCS score was 2.14 (95% CI = 1.17-4.55) units lower, and the MCS score was 3.19 (95% CI = 2.51-6.07) units lower among patients with migraine compared with those without. Migraine imposes a substantial economic burden on both health care payers and patients in the United States. Notably, prescription drugs make up nearly half of the overall cost. Additionally, patients with migraine experience lower levels of physical and mental HRQoL compared with those without migraine.

Clinical and Humanistic Burden of Non-inhibitor HaemophiliaA in Five European Countries: Insights from the CHESSII Study.

HaemophiliaA (HA) is a congenital bleeding disorder caused by a deficiency/absence of factorVIII (FVIII) and characterised by frequent, acute and prolonged spontaneous or traumatic bleeding events, often leading to haemophilic arthropathy and progressive joint deterioration. HA severity is characterized by endogenous FVIII activity: mild (> 5-40%), moderate (1-5%), or severe (< 1%). HA poses a substantial clinical and socioeconomic burden on people with HA (PWHA), their caregivers, and society. This analysis evaluates clinical and patient-centric outcomes of a cohort of individuals with non-inhibitor HA sampled from France, Germany, Italy, Spain, and the UK in the 'Cost of Haemophilia in Europe: A Socioeconomic Survey II' (CHESSII) study. CHESSII was a cross-sectional burden-of-illness study collecting clinical and socioeconomic data on adult (≥ 18years) individuals with haemophiliaA or B of any severity with or without inhibitors from eight European countries. Descriptive analyses were conducted examining physician-reported demographics, clinical and health resource utilisation information. PWHA-reported health-related quality of life (HRQoL) using the EQ-5D-5L and Work Productivity and Activity Impairment (WPAI) were also examined. Outcomes were stratified by HA severity and reported at country level. Demographics and clinical characteristics of the cohort (N = 880) were generally consistent across countries. Individuals with severe HA experienced more frequent bleeding events and joint disease despite broad use of factor replacement therapy long-term prophylaxis. A minority of those with mild or moderate HA also experienced such challenges. HRQoL and workforce participation diminished, and chronic pain increased, with increasing HA severity. This analysis provides up-to-date insights on the impact of HA across five European countries. Increasing HA severity was generally associated with worse clinical outcomes, HRQoL and workforce participation. These findings suggest a place for continued evidence-based tailored treatment and clinical management approaches in addressing the residual burden of HA.

Patient-Reported and Economic Racial and Ethnic Disparities in Patients with Psoriatic Arthritis: Results from the National Health and Wellness Survey.

Psoriatic arthritis (PsA) is a chronic, autoimmune form of arthritis that is associated with a substantial humanistic and economic burden. Potential differences in patient-reported outcomes (PROs) and economic outcomes among groups of varying PsA severity and different races/ethnicities have not been well studied. This cross-sectional study assessed sociodemographic data, PROs, and economic outcomes for participants with PsA from the National Health and Wellness Survey (2018-2020). Multivariable analyses were used to assess the association of self-reported PsA severity and race/ethnicity with health-related quality of life (HRQoL), work productivity and activity impairment (WPAI), healthcare resource utilization (HCRU), and medical costs. This study included 1544 participants with PsA (1073 non-Hispanic white, 114 non-Hispanic Black, 223 Hispanic, and 134 Other). Self-reported moderate/severe PsA was associated with significantly worse HRQoL and WPAI, greater HCRU, and higher costs than self-reported mild PsA. Black participants reported more absenteeism (31.11% vs. 16.69%; P = 0.007) and activity impairment (54.27% vs. 47.96%; P = 0.047) than white participants, and fewer healthcare provider (5.93 vs. 7.42; P = 0.039) and rheumatologist visits (0.29 vs. 0.53; P = 0.028) over the past 6months. No differences in outcomes were observed between Hispanic and white participants. Race/ethnicity moderated the association of perceived PsA severity and PROs and HCRU, such that white participants with self-reported moderate/severe PsA had a higher likelihood of depression (P < 0.001), lower HRQoL (P < 0.001), and more emergency room visits (P = 0.001) than those with self-reported mild PsA. Race/ethnicity did not moderate the relationship of PROs, HCRU, and economic outcomes among Black or Hispanic participants. Participants with self-reported moderate/severe PsA reported a greater burden than those with self-reported mild PsA. Black participants had a greater humanistic burden than white participants but reported lower HCRU. Moderation results were driven by white participants, suggesting important differences in PROs, HCRU, and perception of PsA severity across race/ethnicity groups. Small sample sizes in Hispanic and non-Hispanic racial/ethnic groups limited ability to discern differences related to disease severity in these groups. Further research is needed to better understand the differential burden of PsA among individuals with varying perceptions of PsA severity across different racial/ethnic groups.

Epidemiology and burden of chronic insomnia disorder in Europe: an analysis of the 2020 National Health and Wellness Survey

Introduction Chronic insomnia disorder (CID) is considered a significant worldwide public health concern; however, its exact burden is unknown. We estimate its prevalence across France, Germany, Italy, Spain, and the United Kingdom, and assess the economic and humanistic burden for a broader insomnia population. Methods This retrospective, cross-sectional, observational study used 2020 National Health and Wellness Survey (NHWS) data. Patients reporting insomnia were characterized to define CID. Health-related quality of life (HRQoL), work productivity, and healthcare resource use (HCRU) outcomes were assessed in four cohorts according to insomnia diagnosis and treatment status and examined using multivariable analyses according to Insomnia Severity Index categories. Results Among 62,319 respondents, 9,035 (21.2%) reported experiencing insomnia over the previous 12 months. CID prevalence rates were 5.5% to 6.7% across the five countries and 6.0% overall. HRQoL outcomes were persistently poorer in cohorts of patients diagnosed with insomnia than those with undiagnosed insomnia. Undiagnosed and treated insomnia patients reported the highest work presenteeism and total work productivity impairment and the highest number of emergency room and hospitalization visits than patients with insomnia (either treated or untreated). After adjusting for covariates, patients with severe insomnia reported significantly worse EQ-5D-5L utility scores, higher absenteeism and presenteeism rates, and more healthcare provider visits over the past 6 months than patients without insomnia (all p < 0.01). Conclusions Our prevalence rates for CID align with published literature. A diagnosis of insomnia, use of sleep medications, and severity of insomnia are associated with poor quality of life, loss of work productivity, and higher HCRU, confirming the high unmet need and substantial humanistic and economic burden of CID.

Systematic literature review of the humanistic and economic burden of focal epilepsy and primary generalized tonic-clonic seizures in adults.

This systematic literature review (SLR) assessed the humanistic and economic burden of focal epilepsy and primary generalized tonic-clonic seizures (PGTCS) in adults to evaluate these domains in both populations and identify evidence gaps to inform future research. A search was conducted on December 7, 2022, using MEDLINE and Embase to identify studies published from 2012 onwards reporting humanistic burden (patient-reported or caregiver-reported outcomes or utilities, qualitative evaluations), economic burden (productivity loss, caregiver and societal costs of epilepsy), and sleep-related outcomes. Of the 2830 citations identified, 136 were included. Most studies were in the focal epilepsy population; very few studies reported outcomes in the PGTCS population. The presence of epilepsy-specific instruments varied based on the domain evaluated. Epilepsy exerted considerable humanistic and economic burden. Indicators of poor disease control (e.g., high seizure frequency, resistance to anti-seizure medications, polypharmacy) increased epilepsy burden. Seizure frequency and type, disease severity, and polypharmacy also affected work productivity. Adults with epilepsy, particularly focal epilepsy, reported higher indirect costs, more sick days accrued, and early entry into retirement. Caregivers similarly reported high productivity loss and absenteeism related to caregiving duties. The results of this SLR highlight the high humanistic and economic burden of focal epilepsy and PGTCS, although limited data were available for the PGTCS population. The results include patient-reported outcome data specific to focal epilepsy and PGTCS, expanding the limited humanistic burden evidence identified in previous reviews, and show the effect of poor disease control on individuals' lives and as a driver of indirect costs. PLAIN LANGUAGE SUMMARY: Our systematic literature review identified studies that evaluated the impact of focal epilepsy and primary generalized tonic-clonic seizures on patients and their caregivers. We found that focal epilepsy negatively impacted patients' mental health and sleep and was associated with higher indirect costs and lower work productivity in people with more severe disease. The impact of primary generalized tonic-clonic seizures on patients was rarely reported, and future research is needed.

The role of cardiac acoustic biomarkers in monitoring patients with heart failure: A systematic literature review.

Heart failure (HF) creates a considerable clinical, humanistic and economic burden on patients and caregivers as well as on healthcare systems. To attenuate the significant burden of HF, there is a need for enhanced management of patients with HF. The use of digital tools for remote non-invasive monitoring of heart parameters is gaining traction, and cardiac acoustic biomarkers (CABs) have been proposed as a complementary set of measures to assess heart function alongside traditional methods such as electrocardiogram and echocardiography. We conducted a systematic literature review to evaluate associations between CABs and HF outcomes. Embase and MEDLINE databases were searched for recent studies published between 2013 and 2023 that evaluated CABs in patients with HF. Additional grey literature (i.e., conference, congress and pre-print publications from January 2021 to May 2023) searches were included. Two reviewers independently examined all articles; a third resolved conflicts. Data were extracted from articles meeting inclusion criteria. Extracted studies underwent quality and bias assessments using the Joanna Briggs Institute (JBI) critical appraisal tools. In total, 3074 records were screened, 73 full-text articles were assessed for eligibility and 27 publications were included. Third heart sound (S3) and electromechanical activation time (EMAT) were the CABs most often reported in the literature for monitoring HF. Fifteen publications discussed changes in S3 characteristics and its role in HF detection or outcomes: six studies highlighted S3 assessment among various groups of patients with HF; four studies evaluated the strength or amplitude of S3 with clinical outcomes; five studies assessed the relationship between S3 presence and clinical outcomes; and one study assessed both S3 presence and amplitude in relation to HF clinical outcomes. Eleven publications reported on EMAT and its derivatives: five studies on the relationship between EMAT and HF and six studies on the association of EMAT and HF clinical outcomes. Studies reporting the first and fourth heart sound, left ventricular ejection time and systolic dysfunction index were limited. Published literature supported S3 and EMAT as robust CAB measures in HF that may have value in remote clinical monitoring and management of patients with HF. Additional studies designed to test the predictive power of these CABs, and others less well-characterized, are needed. This work was funded by Astellas Pharma Inc.

Return on investment of tobacco control measures: a systematic review protocol.

The objective of this systematic review will be to estimate the return on investment (ROI) and social return on investment (SROI) on tobacco control measures. Tobacco consumption has been proven to be associated with a huge epidemiological, humanistic, and economic burden. National and international organizations are making concerted efforts to control tobacco use. However, currently, there are no conclusive estimates of the ROI and SROI of such programs and policies. This review will include all studies that evaluate the ROI or SROI on tobacco control programs and policies on tobacco users and probable tobacco users globally. This review will follow the JBI methodology for systematic reviews of economic evidence. Databases to be searched will include Embase (Ovid), MEDLINE (PubMed), Cochrane Central Register of Controlled Trials (CENTRAL), Health Economic Evaluation Database (HEED), National Health Service Economic Evaluation Database (NHS EED), CEA Registry, LILACS, Science Direct, Web of Science, EconLit, and Google Advanced Search. Gray literature will also be searched for in non-academic databases, including the websites of various civil societies and non-governmental organizations involved in tobacco control. Two independent reviewers will screen titles/abstracts, and later full-text studies. Critical appraisal will be conducted using the JBI checklist for economic evaluations and the SROI Quality Framework. Data will be extracted and synthesized using JBI data extraction forms and synthesis tools. The MPOWER framework will be considered for data synthesis across all selected studies using narrative synthesis, tables, and figures. PROSPERO CRD42023391591.

Disease Burden, Treatment Patterns and Asthma Control in Adult Patients with Asthma in China: A Real-World Study.

To inform better asthma management in China, this study aimed to comprehensively investigate clinical characteristics, treatment patterns, asthma control status, exacerbations, and humanistic burden among adult patients seeking hospital-based asthma care by analyzing data from Adelphi Asthma Disease Specific Program conducted in China. All information was collected on survey date (August-December 2018) from medical records, physicians, or patients, without follow-up being conducted. Results are summarized descriptively for the overall population as well as subgroups defined by GINA 2018 treatment step. Of the included 765 patients, 46.0%, 40.4%, and 29.2% had undergone lung function, blood eosinophil count, and specific immunoglobulin E/radioallergosorbent testing, and 17.2%, 24.1%, and 58.7% were managed at GINA Steps 1-2, 3, and 4-5, respectively. Asthma was not well controlled in 57.3% of patients based on definitions adapted from the ERS/ATS and 10.7% of patients had experienced ≥1 severe exacerbation in the preceding year. According to patient self-reporting (n=603), the mean (SD) was 0.9 (0.1) for utility on EQ-5D-3L and was 7.8% (10.4%), 36.9% (20.0%), 40.8% (22.2%), and 37.9% (22.3%) for absenteeism, presenteeism, work productivity loss, and activity impairment, respectively, on WPAI. Both asthma control and humanistic burden worsened with progressive GINA treatment steps. In patients seeking hospital-based asthma care in China, lung function and biomarker tests were underutilized, impairment in productivity and quality of life was observed, and more than half did not achieve well-controlled asthma despite approximately 60% being managed at GINA treatment Steps 4-5. These findings highlight the urgent need for optimizing asthma management in China.

Epidemiology and Burden of Peripheral Artery Disease in People With Type 2 Diabetes: A Systematic Literature Review.

Type 2 diabetes (T2D) and lower-extremity peripheral artery disease (PAD) are growing global health problems associated with considerable cardiovascular (CV) and limb-related morbidity and mortality, poor quality of life and high healthcare resource use and costs. Diabetes is a well-known risk factor for PAD, and the occurrence of PAD in people with T2D further increases the risk of long-term complications. As the available evidence is primarily focused on the overall PAD population, we undertook a systematic review to describe the burden of comorbid PAD in people with T2D. The MEDLINE, Embase and Cochrane Library databases were searched for studies including people with T2D and comorbid PAD published from 2012 to November 2021, with no restriction on PAD definition, study design or country. Hand searching of conference proceedings, reference lists of included publications and relevant identified reviews and global burden of disease reports complemented the searches. We identified 86 eligible studies, mostly observational and conducted in Asia and Europe, presenting data on the epidemiology (n = 62) and on the clinical (n = 29), humanistic (n = 12) and economic burden (n = 12) of PAD in people with T2D. The most common definition of PAD relied on ankle-brachial index values ≤ 0.9 (alone or with other parameters). Incidence and prevalence varied substantially across studies; nonetheless, four large multinational randomised controlled trials found that 12.5%-22% of people with T2D had comorbid PAD. The presence of PAD in people with T2D was a major cause of lower-limb and CV complications and of all-cause and CV mortality. Overall, PAD was associated with poor quality of life, and with substantial healthcare resource use and costs. To our knowledge, this systematic review provides the most comprehensive overview of the evidence on the burden of PAD in people with T2D to date. In this population, there is an urgent unmet need for disease-modifying agents to improve outcomes.

Understanding the Sequelae of Invasive Meningococcal Disease in the United States.

Invasive meningococcal disease (IMD) is an uncommon but serious and potentially fatal condition that can result in reduced life expectancy and a broad spectrum of sequelae, many of which may be lifelong and devastating for those who survive the acute disease period. In the United States of America (USA), vaccination is available against the five meningococcal serogroups (A, B, C, W, and Y), but meningococcal vaccination rates among healthy USA adolescents and individuals at high risk because of medical conditions are low, rendering them vulnerable to IMD and its sequelae. Despite the severity of the disease, the clinical impact and rates of IMD sequelae in the USA are poorly understood, as USA-specific data are limited, and the methodology of existing research is heterogenous. This commentary presents clinical experts' perspectives on IMD sequelae based on the available published evidence and direct clinical experience. Among sequelae previously identified in a global systematic literature review, 16 conditions were considered as related to IMD by the present authors. These sequelae include short- and long-term physical, neurological, and emotional consequences that impose a substantial humanistic burden on survivors and their caregivers and result in considerable healthcare and societal costs. This commentary highlights existing knowledge gaps concerning IMD sequelae, including the unclear relationship between IMD and mental health disorders, the contribution of sequelae to the disease burden, prevalence of late-onset sequelae among survivors, and timing of the development of sequelae in different age groups. Addressing these knowledge gaps can inform decisions regarding clinical management in the post-acute period and help quantify the impact of prevention through meningococcal vaccination.

The clinical, economic, and humanistic burden of treatments for exocrine pancreatic insufficiency and cost-effectiveness of treatments: A systematic literature review.

To examine the burden of exocrine pancreatic insufficiency (EPI), specifically the clinical impact of EPI on patients, their quality of life (QoL) and the cost-effectiveness of existing treatments. A systematic literature review was conducted using key search terms for the clinical, economic, and humanistic burden. Databases were searched from 2010 to 2022, with articles screened independently by 2 reviewers at abstract and full-text stage against pre-defined eligibility criteria. Seventy-one publications were identified that reported relevant clinical, humanistic, and economic data. Prevalence and incidence of EPI varied across identified studies; EPI appears to be especially prevalent as a comorbid condition in patients with cystic fibrosis. EPI has a large impact on QoL, with lower QoL scores in patients with EPI compared with those without EPI. The instruments used to assess QoL, however, were inconsistent across studies. Where reported, economic burden studies highlighted that patients with EPI have higher healthcare resource utilization compared with those without, with costs increasing with disease severity. This systematic literature review highlights that patients with EPI have higher treatment costs and lower QoL scores than patients without EPI. The prevalence of EPI as a comorbid condition is high, particularly in patients with cystic fibrosis.