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Introduction: 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., Methods: 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., Results: 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 6 months. 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., Conclusion: 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., (© 2024. The Author(s).)

Purpose: To evaluate the prevalence of chronic comorbidities according to BMI classes and assess the interplay between excess body weight and blood glucose abnormalities in increasing the risk of major chronic diseases., Methods: The study is based on data from the Health Search/IQVIA Health LPD Longitudinal Patient Database, an Italian general practice registry, with data obtained from electronic clinical records of 800 general practitioners throughout Italy. Data relative to the year 2018 were analyzed. The study population was classified according to BMI (normal weight, overweight, and obesity classes 1, 2 and 3) and glucose metabolism status (normoglycemia-NGT; impaired fasting glucose-IFG; diabetes mellitus-DM). Comorbidities were identified through ICD-9 CM codes., Results: Data relative to 991,917 adults were analyzed. The prevalence of overweight was 39.4%, while the prevalence of obesity was 11.1% (class 1: 7.9%, class 2: 2.3%, class 3: 0.9%). In the whole population, the prevalence of DM and IFG was 8.9% and 4.2%, respectively. Both overweight and obesity were associated with an increasing prevalence of glucose metabolism alterations and a large array of different chronic conditions, including cardio-cerebrovascular diseases, heart failure, chronic kidney disease, osteoarticular diseases, depression, sleep apnea, and neoplasms of the gastrointestinal tract. Within each BMI class, the presence of IFG, and to a greater extent DM, identified subgroups of individuals with a marked increase in the risk of concomitant chronic conditions., Conclusion: Addressing the double burden of excess weight and hyperglycemia represents an important challenge and a healthcare priority., (© 2024. The Author(s).)

Idiopathic hypersomnia (IH) is a rare neurological sleep disorder, characterized by excessive daytime sleepiness despite normal sleep duration, that can significantly impact patient's lives. The burden of IH goes beyond excessive daytime sleepiness, pervading all aspects of everyday life. Characteristic and burdensome symptoms of IH include sleep inertia/drunkenness, long sleep duration, and daytime cognitive dysfunction. This systematic review assessed current knowledge regarding IH diagnostic challenges and burden of illness. Literature searches for original epidemiological, clinical, humanistic, or economic research relevant to IH published between 2012 and 2022 in MEDLINE, Embase, Cochrane, gray literature (diagnostic criteria and treatment guidelines), conferences (2019-2022), and clinical trial databases yielded 97 articles. Findings indicate that IH remains a poorly defined diagnosis of exclusion that is difficult to distinguish from narcolepsy type 2 because of symptom overlap and inadequacies of objective testing. Consequently, individuals with IH endure diagnostic delays of up to 9 years. The economic burden of IH has not been characterized to any appreciable extent. Pharmacological treatment options can improve symptoms and functional status, but rarely restores normal levels of functioning. These findings highlight the need to reclassify central disorders of hypersomnolence. Further collaboration is now required between research groups to identify and validate objective markers to help redefine diagnostic criteria for IH. This would move IH into a position that could benefit from future targeted therapeutic interventions. The study was funded by Takeda Development Center Americas, Inc., (© The Author(s) 2024. Published by Oxford University Press on behalf of Sleep Research Society.)

This systematic literature review evaluated frontline treatment burden in pediatric and adolescent/young adult (AYA) patients with high-risk classical Hodgkin lymphoma (cHL) among studies originating from the United States. Data were extracted from 32 publications (screened: total, n = 3115; full-text, n = 98) representing 12 studies (randomized controlled trials [RCTs], n = 2; non-comparative, non-randomized, n = 7; observational, n = 3). High-risk disease definitions varied across studies. Five-year event-free survival (EFS)/progression-free survival (PFS) was 86%-100% and 79%-94%, and complete response rates were 35%-100% and 5%-64% for brentuximab vedotin (BV)-containing and chemotherapy-alone regimens, respectively. In identified RCTs, BV-containing compared with chemotherapy-alone regimens demonstrated significantly longer 3-year EFS/5-year PFS. Hematological and peripheral neuropathy were the most commonly reported adverse events of interest, although safety data were inconsistently reported. Few studies evaluated humanistic and no studies evaluated economic burden. Results from studies with the highest quality of evidence indicate an EFS/PFS benefit for frontline BV-containing versus chemotherapy-alone regimens for pediatric/AYA patients with high-risk cHL., (© 2024 Wiley Periodicals LLC.)

Disclaimer: In an effort to expedite the publication of articles, AJHP is posting manuscripts online as soon as possible after acceptance. Accepted manuscripts have been peer-reviewed and copyedited, but are posted online before technical formatting and author proofing. These manuscripts are not the final version of record and will be replaced with the final article (formatted per AJHP style and proofed by the authors) at a later time., Purpose: Severe ADAMTS13 deficiency (activity <10%) is the diagnostic threshold for thrombotic thrombocytopenic purpura (TTP) and is associated with various clinical symptoms, abnormal laboratory results, and long-term complications., Methods: This retrospective, noninterventional cohort study used the Premier Healthcare Database to identify patients with ADAMTS13 activity of <10% in US hospitals from January 1, 2016, through March 31, 2020. The objective was to describe patient characteristics, laboratory results, comorbidities (as measured by the Elixhauser comorbidity index), symptoms, length of stay, treatment patterns, mortality, inpatient costs, and readmission rates (summarized descriptively). Inpatient costs were calculated as total cost to the hospital., Results: There were 211 patients with severe ADAMTS13 deficiency; 89% of patients had a TTP-related diagnosis, of whom 62% had a primary diagnosis of thrombotic microangiopathy. Over 80% of patients with available data had a decreased platelet count and elevated lactate dehydrogenase; schistocytes were detected in 99%. The most prevalent symptoms/complications were neurological, bleeding, and pain. Most patients (86%) had 2 or more Elixhauser comorbidities. Over 80% of patients received 1 or more TTP-related treatments, mostly plasma exchange. The mean length of stay was 11.5 days; 5% of patients died during their stay. Readmission rates at 30, 60, and 90 days were 20%, 26%, and 28%, respectively. The median (interquartile range) total inpatient cost to the hospital throughout the index admission was $33,221 ($19,431-$64,901)., Conclusion: Patients with severe ADAMTS13 deficiency have substantial clinical burden, have high mortality and readmission rates, and generate high costs for hospitals. There is a high need for a therapy that replaces ADAMTS13, thus addressing the root cause of the symptoms and complications caused by this deficiency., (© American Society of Health-System Pharmacists 2024.)

Background: This systematic study aims to assess the global epidemiologic, economic, and humanistic burden of illness associated with all types of hereditary angioedema., Methods: A systematic search for articles reporting the epidemiologic, economic, and humanistic burden associated with patients with HAE was conducted using English and Chinese literature databases from the inception to May 23, 2022. The selected studies were assessed for their quality and risk of bias. The study was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses and registered with the International Prospective Register of Systematic Reviews (PROSPERO; CRD42022352377)., Results: In total, 65 articles that met the search inclusion criteria reported 10,310 patients with HAE, of whom 5861 were female patients. Altogether, 4312 patients (81%) and 479 patients (9%) had type 1 and type 2 HAE, respectively, whereas 422 patients (8%) had HAE-normal C1-INH. The overall prevalence of all types of HAE was between 0.13 and 1.6 cases per 100,000. The mean or median delay from the first onset of a symptom of HAE to confirmed diagnosis ranged from 3.9 to 26 years. The estimated risk of death from asphyxiation was 8.6% for patients with HAE. Hospitalization, medication, unnecessary surgeries, doctor visits, specialist services, and nursing costs are direct expenses that contribute to the growing economic burden. The indirect cost accounted mostly due to missing work ($3402/year) and loss of productivity ($5750/year). Furthermore, impairment of QoL as reported by patient-reported outcomes was observed. QoL measures identified depression, anxiety, and stress to be the most common symptoms for adult patients and children., Conclusion: This study highlights the importance of early diagnosis and the need for improving awareness among health care professionals to reduce the burden of HAE on patients and society., (© 2024. The Author(s).)

Context: Tumor-induced osteomalacia (TIO) is an ultra-rare, paraneoplastic syndrome caused by tumors that secrete fibroblast growth factor 23 (FGF23). Initial signs and musculoskeletal symptoms can be non-specific and unrecognized, leading to long delays in diagnosis and treatment, which results in severe and progressive disability in patients with TIO. This review aimed to identify published evidence on healthcare resource use in TIO to better understand the burden of the disease., Evidence Acquisition: A targeted literature review was conducted to identify publications reporting on disease characteristics and healthcare resource use associated with TIO., Evidence Synthesis: In total, 414 publications were included in the review, of which 376 were case reports. From the case reports, data on 621 patients were extracted. These patients had a mean (standard deviation) age of 46.3 (15.8) years; 57.6% were male. Mean time from first symptoms to diagnosis of TIO was 4.6 (4.7) years and, in cases where imaging tests were reported, patients underwent a mean of 4.1 (2.7) procedures. Tumor resection was attempted in 81.0% of patients and successful in 67.0%. Fracture was reported in 49.3% of patients. Results from association analyses demonstrated that longer time to diagnosis was associated with poorer tumor resection outcomes and a higher probability of tumor recurrence. Unfavorable tumor resection outcomes were associated with greater use of pharmacologic treatment and a greater likelihood of orthopedic surgery., Conclusion: TIO is associated with a substantial healthcare resource burden. Improvements in the diagnostic process could lead to better management of TIO, thereby benefiting patients and reducing that burden., (© The Author(s) 2024. Published by Oxford University Press on behalf of the Endocrine Society.)

Obesity-related comorbidities (ORCs) cause significant economic and clinical burdens for people with obesity and the US health care system. A reduction in weight at the population level may reduce incident ORC diagnoses and associated costs of treatment. The aim of this work is to describe obesity burden in the United States through the prevalence and direct treatment costs of ORCs, as well as the clinical and economic value of 15% weight loss in a population of adults with obesity. The IQVIA Ambulatory US electronic medical record database was used to create a cohort (7,667,023 individuals 20-69 years of age, body mass index of 30-50 kg/m 2 ), utilized to characterize the prevalence of 10 ORCs. Direct treatment costs were collected from literature reports. A risk model was leveraged to estimate the number and cost of additional ORC diagnoses over 5 years from baseline through two scenarios: stable weight and 15% lower body weight at baseline for all members of the population. Prevalence, incidence, and cost data were scaled down to a representative subset of 100,000 individuals. In 2022, the annual treatment costs for all 10 ORCs exceeded $918 million for the representative cohort. In a stable-weight scenario, these costs were estimated to increase to ≈$1.4 billion by 2027. With 15% lower body weight at baseline, $221 million in cumulative savings was estimated, corresponding to $2205 in savings/patient over 5 years. Consequently, weight loss in this population may correspond to significantly reduced numbers of incident ORC complications translating to substantial cost savings.

Introduction: The potential consequences of repeated concussions in sport are well documented. However, it remains unclear whether the cumulative impact of sports-related concussions differs between different contact sports. Therefore, the aim of the current study was to investigate the cumulative effects of sports-related concussions on clinical and neurocognitive health in different contact sports., Materials and Methods: In a prospective multicenter study, we examined 507 (74 females) active professional athletes between 18 and 40 years of age from five different contact sports (soccer, handball, American football, basketball, and ice hockey). Data collection involved concussion history, clinical symptom evaluation, neurocognitive assessment, and the collection of other sports-related information. Composite scores were built for clinical symptoms (such as neck pain and balance disturbances) and for neurocognitive symptoms (such as memory and attention impairments)., Results: Athletes having suffered 3+ concussions in the past showed disproportionally higher clinical symptom severity than athletes with less than three concussions across all sports. The level of clinical symptom burden in athletes with 3+ concussions indicated mild impairment. The number of past concussions did not affect neurocognitive performance., Discussion: Repeated sports-related concussions appear to have a cumulative impact on clinical-but not cognitive-symptom severity. Although clinical symptom burden in athletes with 3+ concussions in the past was not alarmingly high yet in our sample, increased caution should be advised at this point. Despite few exceptions, results are similar for different contact sports, suggesting a similar multidisciplinary concussion management across all types of sport., (© 2024 The Authors. Scandinavian Journal of Medicine & Science In Sports published by John Wiley & Sons Ltd.)

Background: Food allergies are serious and potentially life-threatening, and often place a large burden on patients and their caregivers, including impacts on quality of life., Objective: To assess the real-world patient burden of food allergies, using self-reported data available from the Food Allergy Research & Education (FARE) Patient Registry (NCT04653324)., Methods: The FARE Patient Registry is voluntary and captures real-world experiences of adults and pediatric patients in the United States, and their caregivers, through a series of surveys assessing patient health and experiences with food allergies. Self-reported data were descriptively analyzed., Results: The FARE study cohort included 5587 patients with food allergies; 82% had multiple food allergies and 62% were aged <18 years. About half of the patients were first diagnosed by an allergist/immunologist (53%), most commonly with a skin prick test (71%) or a serum immunoglobulin E test (62%). This analysis found that food allergies (most commonly peanut [66%], tree nuts [61%], egg [43%], and milk [37%]) impart a large clinical burden on patients, many of whom experience food-related allergic reactions and comorbidities. Many patients experienced >1 food-related allergic reaction per year (42%), with 46% experiencing food-induced anaphylaxis. Half of all food-related allergic reactions occurred at home. Accidental exposures to food allergens were experienced by 77% of patients. The most common allergic comorbidities reported by patients with food allergies were atopic dermatitis (48%), asthma (46%), and allergic rhinitis (39%). The clinical burden of food allergies were found to be greater in patients with multiple food allergies, and different for adults versus pediatric patients., Conclusion: This is the first study to assess patient experience and disease burden information from patients contributing to the FARE Patient Registry, thus providing a unique insight into the lives of patients in the United States with food allergies. These insights may assist clinicians and other public health stakeholders in the management of patients with food allergies., (© 2024 The Authors.)

Background: Anxiety and depression are common in patients with chronic obstructive pulmonary disease (COPD), especially older adult patients. This can complicate the disease progression and lead to increased clinical and economic burden. We sought to investigate the clinical and economic burdens associated with the presence of anxious and/or depressive symptoms among older adult COPD patients., Methods: We screened 579 patients aged over 60 years and diagnosed with COPD via a lung function test following the 2017 Global Initiative Chronic Obstructive Lung Disease (GOLD) guidelines. Anxiety and depression were measured using the Hospital Anxiety and Depression Scale (HADS) through face-to-face interviews at admission. Follow-up was conducted by telephone calls at 6, 12, 18, 24, and 36 months after discharge to assess clinical and economic burden. COPD-anxiety and/or depression patients were matched to patients without anxiety and depression (COPD-only) using propensity scores. Multivariate regression models were used to compare clinical and economic burden between COPD-anxiety and/or depression and COPD-only groups., Results: Compared with COPD-only patients, COPD patients complicated with anxiety and/or depression had increased clinical burden, including higher COPD-related outpatient visits, COPD-related hospitalizations, and length of COPD-related hospitalizations ( p  < 0.001). Moreover, they also had an increased economic burden, including higher annual total healthcare costs, medical costs, and pharmacy costs ( p  < 0.001)., Conclusion: Older adult COPD patients with anxiety or depression had significantly higher clinical and economic burdens than patients without these comorbidities. These findings deserve further exploration and may be useful for the formulation of relevant healthcare policies., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhao, Liu, Liu, Zou, Huang, Chen, Li, Wu, Wu, Huang and Wu.)

Aims: We aimed to describe the clinical, economic, and societal burdens of cystic fibrosis (CF) and impact of CF transmembrane conductance regulator modulator (CFTRm) treatment on people with CF, caregivers, and healthcare systems., Material and Methods: This retrospective study used linked real-world data from Swedish national population-based registries and the Swedish CF Quality Registry to assess clinical, economic, and societal burden and CFTR impact in CF. Records from people with CF and a ten-fold control population without CF matched by sex, birth year, and location were compared during 2019. Outcomes for a subset aged >6 years initiating lumacaftor/ivacaftor (LUM/IVA) in 2018 were compared 12 months pre- and post-treatment initiation., Results: People with CF ( n  = 743) had >10 times more inpatient and outpatient specialist visits annually vs controls ( n  = 7406). Those aged >18 had an additional 77·7 (95% CI: 70·3, 85·1) days of work absence, at a societal cost of €11,563 (95% CI: 10,463, 12,662), while caregivers of those aged <18 missed an additional 6.1 (5.0, 7.2) workdays. With LUM/IVA treatment, people with CF ( n  = 100) had significantly increased lung function (mean change in ppFEV 1 [3·8 points; 95% CI: 1·1, 6·6]), on average 0·5 (95% CI: -0·8, -0·2) fewer pulmonary exacerbations and 45·2 (95% CI: 13·3, 77·2) fewer days of antibiotics. Days of work lost by caregivers of people with CF aged <18 decreased by 5·4 days (95% CI: 2·9, 7·9)., Conclusion: CF is associated with a high clinical economic and societal burden in Sweden. Improvements in clinical status observed in people with CF treated with LUM/IVA were reflected in reduced caregiver and societal burden.

Background and Objective: Leptomeningeal disease (LMD) is associated with poor survival and health-related quality of life (HRQoL). There is an urgent need for clinical research in this area to improve the outcomes. The purpose of this study is to summarize the areas of active clinical research in LMD, identify the knowledge gap, and suggest future research directions., Methods: A narrative review of clinical trials in LMD was conducted based on a search in clinicatrials.gov using the search term "leptomeningeal" under "condition or disease". Clinical trials in patients with LMD arising from solid malignancy that were labelled as "not yet recruiting", "recruiting", "enrolling by invitation" or "active, not recruiting" were included. Studies which were deemed to have significant impact on future research direction in LMD were selected for discussion., Key Content and Findings: A total of 38 clinical trials were included. Of these 38 trials, 19 are discussed in this review, with focus on their research questions and impact on future research directions. Most of the studies that were not selected for discussion focused on biomarker-driven interventions. Four key areas of research were identified, namely the (I) diagnosis, response assessment or molecular profiling of LMD (n=2); (II) advances in radiotherapy (n=3); (III) intrathecal treatment (n=13); (IV) novel drug carrier for systemic treatment (n=1). The research questions in the 19 discussed clinical trials included the tumour microenvironment of LMD, the role of novel molecular techniques in LMD, combination of radiotherapy with drugs, and cell-based immunotherapy. Among these 19 studies, 11 were phase 1 trials, 3 were phase 2 or phase 1/2 trials, 2 were phase 3 or phase 2/3 trials and the study phase was not reported in the remaining 3 studies. The existing knowledge gaps are discussed, including the lack of primary site-specific prognostic tools, cost-effectiveness studies, dedicated HRQoL assessment tools for LMD and sequencing of treatment., Conclusions: The current clinical trials in LMD offer the promise to improve the diagnosis and treatment outcomes of patients with LMD. More research is needed to overcome the potential hurdles in the current treatment and bridge the knowledge gaps as identified in this review, to improve patients' quantity and quality of survival.

Introduction: Long-term complications of chronic hepatitis B (CHB) viral infection, such as cirrhosis, hepatocellular carcinoma (HCC), and liver failure, cause a large disease burden. This study aimed to describe the epidemiology, clinical outcomes, and treatment patterns of CHB infection and co-infection with hepatitis D virus (HDV) in South Korea., Methods: The retrospective, observational study used existing data from the Health Insurance Review and Assessment Service (HIRA) database. Confirmed cases of (CHB) and HBV/HDV co-infection were identified between 2013 and 2019. Hepatitis C virus co-infections and acute HBV infections were excluded. Incident cases diagnosed between 2015 and 2018 with no prior disease history up to 2 years were included. Patient characteristics, clinical outcomes, economic burden, and healthcare-resource utilization were described., Results: The estimated 7-year prevalence of CHB and HBV/HDV co-infection were 0.9% and 0.0024%, respectively. The prevalence was higher among 45-54 years old (CHB: 1.6%, HBV/HDV: 0.0049%) and males (1.1%, 0.0035%). The 5-year cumulative incidences of compensated cirrhosis, decompensated cirrhosis, HCC, and liver transplantation were 13.3%, 7.1%, 8.4%, and 0.7%, respectively. Hyperlipidemia (40.6%), hypertension (23.5%), and peptic ulcer (23.7%) were the more prevalent comorbidities. Among CHB patients, 48.1% received ≥ 1 prescribed anti-HBV drug including interferon or nucleos(t)ide analogues and 64.4% had ≥ 1 hospitalization compared to 80.4% and 79.4% HBV/HDV patients. Estimated total healthcare costs for CHB and HBV/HDV were US$786 million and $62 million, respectively., Conclusions: These findings provide insights to the epidemiology, clinical burden, treatment patterns, and healthcare costs of CHB and HBV/HDV co-infection in South Korea., (© 2023. The Author(s).)

Background: Severe asthma treatment with oral corticosteroids (OCS) added to inhaled corticosteroids and a long-acting β2-agonist (ICS-LABA) may result in more treatment burden and increased adverse effects., Objective and Methods: This ambispective multicenter observational study aimed at describing the clinical burden in patients with severe asthma on stable high-dose ICS-LABA who received OCS during ≥6 months (maintenance group) or ≥2 cycles in the previous 12 months (bursts group). Data collection comprised a retrospective 12-month baseline period and 2 follow-up visits at 3 and 6 months., Results: Eighty-nine patients were evaluable (30 on maintenance, 59 on bursts). At baseline, mean (SD) daily prednisone equivalent exposure in the total population was 24.6 (14.7) mg: 13.8 (9.4) mg on maintenance and 29.9 (14.3) mg on bursts. During the 6-month follow-up period, mean (SD) daily dose in the total cohort was 22.5 (18.8) mg: 17.2 (18.6) mg on maintenance and 28.4 (20.6) mg on bursts. The overall annual severe exacerbations rate during the 12-month baseline period was 2.05 per patient-year and 1.5 per patient-year over the 6-month follow-up, and frequency of hospitalizations and emergency department visits were similar on both maintenance and bursts use., Conclusions: Results show a suboptimal control of severe asthma despite such high doses of OCS and persistence of disease burden regardless of the prescribing pattern in maintenance or bursts. There is therapeutic inertia to continue using OCS despite the increased risk of adverse effects and the availability of biologics.

Introduction: Angiographic vasospasm (VSP), the narrowing of intracranial arteries, is a complication of aneurysmal subarachnoid hemorrhage (aSAH) and often results in delayed cerebral ischemia (DCI) and cerebral infarction. The objective of this systematic review was to summarize the clinical burden of angiographic VSP and its related complications (DCI and cerebral infarction) after aSAH., Methods: Systematic searches of MEDLINE, Embase, and the Cochrane Library were conducted (in January 2021) in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines to identify studies reporting clinical outcomes of angiographic VSP and its related complications after aSAH. Study outcomes included measures of functional status (modified Rankin Scale [mRS], Glasgow Outcome Scale [GOS], extended Glasgow Outcome Scale [GOS-E], modified Barthel Index, or the modified National Institutes of Health Stroke Scale), cognitive status (Montreal Cognitive Assessment or the Mini Mental State Exam), clinical events (rebleeding), and mortality. Study selection, data extraction, and qualitative analyses were conducted., Results: Of 5704 abstracts reviewed, 110 studies were selected: 20 comparative and 39 regression-based studies were included in the qualitative synthesis, 51 descriptive studies were excluded. Most studies (51) were observational and conducted in a single country (53). The occurrence of angiographic VSP and its related complications after aSAH resulted in significantly poorer functional outcomes in three of nine comparative and 11 of 13 regression-based studies, measured by the mRS, and in five of six comparative and eight of nine regression-based studies, measured by the GOS and GOS-E. Angiographic VSP and its related complications were significantly associated with poor cognitive status in all five regression-based studies. Numerically or significantly higher mortality rates in patients with versus those without angiographic VSP and its related complications were reported in five of ten comparative studies and in eight of nine regression-based studies. Six studies looked at specific VSP populations (e.g., by severity or timing of VSP)., Conclusion: Patients with angiographic VSP and its related complications often had poor functional, neurological, and cognitive outcomes and reduced odds of survival both in hospital and at follow-up. We estimate that angiographic VSP and its related complications, DCI and cerebral infarction, lead to an approximately threefold higher odds of poor functional and cognitive outcomes, and about a twofold increase in the odds of death., (© 2023. The Author(s).)

Background: Although insomnia is a common core symptom of major depressive disorder (MDD), the burden of moderate-to-severe insomnia symptoms in patients with MDD is not well-understood. This study quantified the clinical, patient-centric, and economic burden of adults with MDD with moderate-to-severe insomnia symptoms (MDDIS) compared to adults with MDD with no-to-mild insomnia symptoms (other-MDD) and adults without MDD., Methods: Data from 2019 US National Health and Wellness Survey identified adults self-reporting physician-diagnosed depression, stratified by insomnia status (MDDIS: Insomnia Severity Index [ISI] score ≥15; other-MDD: ISI score <15), and adults not reporting depression (non-MDD). Other-MDD and non-MDD were matched 2:1 to MDDIS on age/sex/race. Matched bivariate analyses examined differences in health-related outcomes by depression-insomnia status., Results: Of 74,994 survey respondents, 2045 (2.7%) were classified as MDDIS, 8220 (11.0%) as other-MDD, and 59,859 (79.8%) as non-MDD. MDDIS respondents (vs other-MDD and non-MDD) reported greater depression severity, anxiety severity, daytime sleepiness, activity impairment, direct costs, and costs due to work productivity impairments, and lower mental and physical functioning (all P < 0.05)., Limitations: Depression diagnosis was not based on clinical/diagnostic interview; causal relationships cannot be determined due to the cross-sectional design., Conclusions: Among US adults with MDD, presence of moderate-to-severe insomnia symptoms is associated with additional burden and notable impairments across several health outcomes versus those with MDD but no-to-minimal insomnia symptoms and general population without MDD. This study highlights the burden of MDDIS and the need for better identification and management of moderate-to-severe insomnia symptoms in adults with MDD., Competing Interests: Conflict of interest K. Joshi and A. Pfau are employees of Janssen Scientific Affairs, LLC, and own stock in Johnson & Johnson. M.J. Cambron-Mellott and H. Costantino are employees of Cerner Enviza, which received funding from Janssen Scientific Affairs, LLC, to conduct and report on the study. M.K. Jha has received contract research grants from Acadia Pharmaceuticals, Neurocrine Biosciences, Navitor/Supernus, and Janssen Research & Development; an educational grant to serve as section editor of the Psychiatry & Behavioral Health Learning Network; consultant fees from Eleusis Therapeutics US, Inc., Janssen Global Services, Worldwide Clinical Trials/Eliem Therapeutics, and Guidepoint; and honoraria from the North American Center for Continuing Medical Education, WebMD/Medscape, and Global Medical Education. Dr. Jha did not receive any honoraria/payments for work presented here., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Aims: The diagnostic history in the years leading up to the definitive diagnosis of patients with obstructive hypertrophic cardiomyopathy (HCM) has not been studied., Methods: Patients with a delay in the definitive diagnosis of obstructive HCM from January 2009 to March 2019 were identified in the US IBM MarketScan Commercial and Medicare Supplemental Databases if they had an alternative diagnosis indicating a misdiagnosis during the 24 months before the definitive obstructive HCM diagnosis. Resource use and costs associated with the delay were estimated during the same period., Results: Of 3,888 eligible patients with obstructive HCM, 59.5% had a delay in definitive diagnosis. Patients received a mean of 4.0 misdiagnoses before the definitive obstructive HCM diagnosis, most of which were other cardiovascular conditions. Consequently, 15.7% of patients may have received inappropriate treatment. Approximately 78.4% of patients visited a cardiologist (mean 4.7 visits) before the definitive obstructive HCM diagnosis. Additionally, 26.8% and 32.1% of patients had an inpatient and emergency room visit, respectively. Annualized healthcare costs associated with the delay were $4,379 per patient., Limitations: The current study used administrative claims data for a commercially insured population. Therefore, the results may not be generalizable to other populations (e.g. those insured by Medicare or Medicaid and the uninsured). Like other database studies, the current study may have suffered from miscoding or undercoding, which may have caused misclassification of patients. Owing to insufficient data, the study could not evaluate all potential consequences of a delay in definitive diagnosis., Conclusions: Most patients with obstructive HCM had a delay of ≤ 2 years before receiving the definitive diagnosis. The diagnostic journey involved multiple potential misdiagnoses, predominantly cardiovascular, as well as a substantial clinical and economic burden on patients and the healthcare system.

In this retrospective cohort study, data from an integrated US healthcare system containing both electronic medical record data and linked claims data (from 01/2004 to 12/2020) were used to evaluate the clinical burden, treatment patterns, and healthcare resource use (HRU) in patients with von Willebrand disease (VWD). Two patient cohorts were analyzed: the overall VWD population (n  =  396) and a subset of these patients (n  =  75) who were considered potentially eligible for prophylaxis treatment with von Willebrand factor (VWF) based on a history of severe and frequent bleeding. HRU (hospitalizations, outpatient visits, and emergency department visits) were measured in patients with linked claims data (n  =  110, overall VWD patients; n  =  23 potentially VWF-prophylaxis-eligible VWD patients). In general, patients with VWD experienced a substantial burden of bleeding events, comorbidities, and HRU. Patients with VWD who were considered potentially eligible for prophylaxis owing to severe and frequent bleeds suffered from a higher clinical burden and HRU than the overall VWD population, and thus may benefit from VWF prophylactic treatment. The findings from this study could help improve clinical outcomes and manage HRU for patients with VWD.

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., (© 2022. The Author(s).)

Background: Coronavirus disease 2019 (COVID-19) has spread worldwide since 2020, placing a huge burden on medical facilities. In the field of respiratory medicine, there has been a decrease in the number of patients. While many pulmonologists have been receiving patients with COVID-19, the actual effects on respiratory care have not been elucidated. Therefore, we conducted this study to clarify the effects of COVID-19 on medical care in the field of respiratory medicine., Methods: We conducted a questionnaire survey among 749 hospitals belonging to the Board-Certified Member system of the Japanese Respiratory Society on the effects of COVID-19 from November 2021., Results: Responses were obtained from 170 hospitals (23%), in approximately 70% of which the respiratory medicine department was the main department involved in managing COVID-19. The number of spirometry and bronchoscopy tests decreased by 25% and 15%, respectively, and the number of both outpatients and inpatients decreased in 93% of hospitals. Among respiratory diseases, the number of patients hospitalized for usual pneumonia, bronchial asthma, and chronic obstructive pulmonary disease decreased greatly by 30%-45%. In 62% of hospitals, the biggest effect of the COVID-19 pandemic was the greater burden in terms of the clinical workload due to COVID-19., Conclusions: Although the number of tests and non-COVID-19 outpatients and inpatients decreased in respiratory medicine departments during the COVID-19 pandemic, the workload increased due to COVID-19, resulting in a great increase in the clinical burden., Competing Interests: Conflict of Interest The authors have no conflicts of interest., (Copyright © 2022 The Japanese Respiratory Society. Published by Elsevier B.V. All rights reserved.)

Background: The epidemiology, clinical features, and socioeconomic burden associated with detection of rhinoviruses (RV)/enteroviruses (EV) from individuals in the community with acute respiratory infections (ARIs) are not fully understood., Methods: To assess the clinical and socioeconomic burden associated with RV/EV, a secondary analysis of data collected during a prospective, community-based ARI surveillance study was performed. From December 2012 to September 2017, adult and pediatric participants with ARIs had nasopharyngeal specimens obtained and tested by multiplex polymerase chain reaction assay. Characteristics and socioeconomic burden including missed school or work and/or antibiotic use among participants who did and did not seek medical care and among participants with and without co-detection of another respiratory pathogen with RV/EV were compared., Results: Throughout the study period, RV/EV was detected in 54.7% (885/1617) of ARIs with a respiratory pathogen detected. Most ARI episodes associated with RV/EV occurred in females (59.1%) and children ≤17 years old (64.2%). Those ≤17 years were more likely to seek medical care. Compared to those not seeking medical care (n = 686), those seeking medical care (n = 199) had a longer duration of illness (5 vs. 7 days) and were more likely to miss work/school (16.4% vs. 47.7%) and/or use antibiotics (3.6% vs. 34.2%). Co-detection occurred in 8% of ARIs of which 81% occurred in children. Co-detection was not associated with longer illness, more missed work/or school, or antibiotic use., Conclusion: Non-medically attended and medically attended ARIs associated with RV/EV resulted in clinical and socioeconomic burden, regardless of co-detection of other respiratory pathogens., (© 2022 The Authors. Influenza and Other Respiratory Viruses published by John Wiley & Sons Ltd.)

Background: Allogeneic hematopoietic cell transplant (allo-HCT) recipients are at increased risk for respiratory viral infections (RVIs), which invoke substantial morbidity and mortality. Limited effective antiviral options and drug resistance often hamper successful RVI treatment, creating additional burden for patients and the health care system., Methods: Using an open-source health care claims database, we examined differences in clinical outcomes, health resource utilization, and total reimbursements during the 1-year period following allo-HCT in patients with and without any RVI infection (respiratory syncytial virus, influenza, parainfluenza virus, and human metapneumovirus). RVIs were diagnosed at any time ≤1 year after allo-HCT and identified by International Classification of Disease codes. Analyses were stratified by the presence or absence of acute or chronic graft-versus-host disease (GVHD)., Results: The study included 13 363 allo-HCT patients, 1368 (10.2%) of whom had a diagnostic code for any RVI. A higher proportion of patients with any RVI had pneumonia ≤1 year after allo-HCT compared to patients without any RVI, with or without GVHD. Patients with any RVI had higher all-cause mortality risk, longer length of post-allo-HCT hospital stay, higher readmission rate, and higher number of hospital days after allo-HCT compared to patients without the infection (all p < .05). Total unadjusted median reimbursements were higher for those with any RVI and each specific RVI assessed than those without the specific infection, with or without GVHD., Conclusion: Allo-HCT patients with RVIs had significantly worse clinical outcomes and increased health resource utilization and reimbursements during the year following allo-HCT, with or without GVHD., (© 2022 The Authors. Transplant Infectious Disease published by Wiley Periodicals LLC.)

What Is Known and Objective: Mucormycosis is an opportunistic fungal infection associated with low incidence but high mortality. Few studies have shown the treatment and disease burden of mucormycosis in China. This study aims at collecting all the reported cases to describe the characteristics and treatment patterns and to assess the economic burden of mucormycosis in China., Methods: We conducted a literature review of mucormycosis case reports in Chinese patients to summarize the characteristics and treatment patterns of the disease in China. An economic model was built to evaluate the total cost of mucormycosis per person, including direct medical cost, direct non-medical cost and indirect cost., Results and Discussion: A total of 676 case reports showed that the most common type of mucormycosis was pulmonary mucormycosis (299/676, 44.2%), and rhinocerebral mucormycosis had the highest case fatality rate (122/185, 68.5%). Among those who used empiric therapies, 48.8% (231/473) did not include anti-mucor drugs; 79.8% (336/421) of the therapies include amphotericin B (AMB) or AMB-lipo after detection of mucormycetes; 98.6% (69/70) of the reported adverse events were associated with AMB and AMB-lipo. The duration of treatment ranged from 90 to 180 days; the length of stay ranged from 22 to 95 days. The average total cost per patient was 166 thousand Chinese Yuan (CNY), of which 93.1% was the direct medical cost (155 thousand CNY)., What Is New and Conclusion: There are a limited number of antifungal treatment options for mucormycosis in China. This study highlights the critical need to introduce innovative and broader spectrum antifungal drugs with improved safety, better clinical efficacy, easier administration and reduced economic burden to Chinese mucormycosis patients., (© 2022 The Authors. Journal of Clinical Pharmacy and Therapeutics published by John Wiley & Sons Ltd.)

Background/objectives: While the clinical manifestations of myasthenia gravis (MG) are well understood, its humanistic impact is not. The objective of this systematic literature review (SLR) was to provide a comprehensive understanding of the humanistic burden of MG with regards to psychological symptoms and health-related quality of life (HRQoL) according to patients and caregivers., Methods: A systematic search was conducted on December 27, 2019, in MEDLINE and Embase to identify English-language studies that were published from January 1, 2009-December 27, 2019 and presented relevant information on the humanistic burden among adults with MG and their caregivers. Title/abstract and full-text screening was performed by two investigators, with any discrepancies resolved by a third investigator., Results: Sixty-seven publications were included in the SLR. Compared with the general population, patients with MG experienced worse HRQoL. Studies reporting on psychological symptoms of MG, including depression, anxiety, fatigue, and sleep, were heterogeneous in terms of the scales and instruments used to assess patients, as well as the patient populations themselves. However, in general those with more severe symptoms and hospitalization days had worse depression and anxiety, and fatigue and sleep improved with disease remission and/or improvement. Scores were worse for females compared with males and where evaluated, HRQoL scores generally improved following treatment., Conclusion: While the literature demonstrates that symptoms associated with MG get better with disease improvement and remission, additional options in efficacious therapy that adequately address the disease-related symptoms and also improve HRQoL may contribute to beneficial outcomes in a greater number of patients with MG., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

Despite advances in preventative interventions, invasive pneumococcal disease and pneumonia cause significant morbidity and mortality in children. We studied the annual incidence of pneumococcal-specific and syndromic invasive disease and non-invasive pneumonia in children <15 years of age during the early (2010−2013) and late (2014−2017) 13-valent pneumococcal conjugate vaccine (PCV13) periods in Veneto, Italy. In this retrospective observational study, pneumococcal-specific and syndromic invasive disease and non-invasive pneumonia cases were identified from several sources, including the Pedianet database. Interrupted time series analysis and Mann−Kendall tests were conducted to explore trends in incidence rates (IRs). Among 72,570 patients <15 years of age between 2010−2017, 88 episodes of pneumococcal-specific and syndromic invasive disease and 3926 episodes of non-invasive pneumonia were reported. Overall IR of pneumococcal-specific and syndromic invasive disease was 0.4/1000 person-years and did not change significantly (p = 0.46) throughout the study. Overall IR of non-invasive pneumonia was 10/1000 person-years and decreased significantly (−0.64, p = 0.026) over the study period. Following PCV13 introduction, the IRs of non-invasive pneumonia in children <15 years of age declined significantly, with no significant change in the IRs of pneumococcal-specific and syndromic invasive disease. There is a continuing clinical burden associated with pediatric pneumococcal diseases in Veneto, Italy.

Hemophilia A is characterized by unpredictable spontaneous bleeds and chronic comorbidities. However, limited data exists at the national level into detailed management patterns related to patient clinical characteristics, representative real-world dosing and treatment frequency, and costs. To assess and characterize the US severe hemophilia A (SHA) population, including subgroups of patients, in terms of clinical and demographic characteristics, healthcare resource utilization received at hemophilia treatment centers (HTCs), and projected annual costs of treatment utilizing data from the ATHNdataset of the American Thrombosis and Hemostasis Network (ATHN). Adult male people with SHA (PwSHA) (FVIII < 1%) were identified in the ATHNdataset between January 2013 and September 2019. This retrospective cohort study described patients' demographic and clinical characteristics, clinical history, as well as the HTC-related health resource utilization (HRU), treatment utilization, and projected annual treatment costs of US PwSHA received over the most recent year. Results are reported for the overall population and for three mutually exclusive subpopulations of patients: PwSHA with a history of and/or current inhibitors, PwSHA without a history of inhibitors but with (or a history of) one or more transfusion-transmitted infections (hepatitis B virus [HBV], hepatitis C virus [HCV], or human immunodeficiency virus [HIV]), and PwSHA without a history of inhibitors or of transfusion-transmitted infections (HBV, HCV, or HIV). Of the overall PwSHA cohort ( N  = 3677), there was a high prevalence of HCV (24.1%) and HIV (13.7%), while the prevalence of HBV (4.9%) was lower. Note that 20.5% of PwSHA overall currently or ever had FVIII inhibitors. On average, PwSHA had 2.8 total HTC visits per year, including 0.9 comprehensive care visits, 1.1 telephone contact visits, 0.5 office visits, and 0.1 surgeries or other procedures. However, 23.3% of PwSHA were not seen at an HTC, and 33.8% of PwSHA did not have a comprehensive care visit during their most recent year of data. HTC-related HRU was similar between the overall cohort and across the patient subpopulations, although PwSHA and inhibitors had more frequent HTC visits (a mean of 3.6 visits annually vs. 2.5-2.8 in the other groups). Using reported treatment frequency and dosing, estimated mean annual hemophilia treatment costs varied by treatment and across the three subpopulations: extended half-life factor product ($893,609-934,301 by subpopulation), standard half-life factor product ($798,700-930,812), plasma-derived factor product ($613,220-801,061), and non-factor product treatment ($765,289-833,240). This study summarized recent sociodemographic and clinical characteristics, HTC-related HRU, and HA treatments and projected costs among adult PwSHA, including among key subpopulations of PwSHA. PwSHA experience substantial clinical and resource burden on a chronic basis, despite the care coordination efforts of ATHN-affiliated HTCs. These findings motivate further exploration of the drivers of resource utilization, observed differences across subpopulations and other disparities, and ongoing monitoring of clinical and treatment burden in the face of an evolving care landscape., Competing Interests: This study was funded by BioMarin. Hinds, Chen, and Solari are or were employees of BioMarin and own stock/stock options at the time of the analysis. Solari is currently an employee of Spark Therapeutics. Cheng, He, and Recht are, or were at the time of this study, employees of American Thrombosis and Hemostasis Network (ATHN), which has received ATHNdataset licensing and other fees from BioMarin.  Research funding to Dr. Recht's employers has come from Bayer, BioMarin, CSL Behring, Genentech, Grifols, Hema Biologics, LFB, Novo Nordisk, Octapharma, Pfizer, Sanofi, Spark, Takeda, and uniQure.  Dr. Recht has worked as a consultant for Catalyst Biosciences, CSL Behring, Genentech, Hema Biologics, Kedrion, Novo Nordisk, Pfizer, Sanofi, Takeda, and uniQure.  Dr. Recht sits on the board of directors of the Foundation for Women and Girls with Blood Disorders and Partners in Bleeding Disorders.  Dr. Recht is an employee of the American Thrombosis and Hemostasis Network and Oregon Health and Science University., (© 2022 The Authors. eJHaem published by British Society for Haematology and John Wiley & Sons Ltd.)

Objectives: To estimate eosinophilic granulomatosis with polyangiitis (EGPA) prevalence and disease burden in patients with newly diagnosed EGPA in Japan., Methods: This retrospective descriptive cohort study (GSK ID: 209751, HO-18-19652) used administrative claim data from patients (aged ≤74 years) with EGPA (study period: January 1, 2005-December 31, 2017), identified from their first ICD-10 code for EGPA (index). Data were examined during the 12 months before (baseline) and 12 months following the index date (follow-up). EGPA prevalence, respiratory comorbidities, all-cause healthcare utilization, and oral corticosteroid (OCS) use were assessed., Results: EGPA prevalence (95%CI) increased from 4.2 (0,23.7)/million people (2005) to 38.0 (31.8,45.1)/million people (2017), was generally more common in females versus males, and increased with age. Of the 45 patients with newly diagnosed EGPA, 57.8% had acute bronchitis and 42.2% had upper respiratory tract infections during baseline. During follow-up, 60.0% of patients were hospitalized at least once and 77.8% used OCS (OCS dependent [≥80% of days]: 73.1%)., Conclusions: In Japan, EGPA prevalence increased over time, was generally more common in females, and increased with patient age. EGPA burden was high; respiratory comorbidities were common, and most patients required hospitalization and OCS use. Our data suggest additional EGPA treatment options are needed., (© Japan College of Rheumatology 2022. Published by Oxford University Press.)

Background: Neisseria meningitidis is an encapsulated Gram-negative diplococcus that asymptomatically colonises the upper respiratory tract in up to 25% of the population (mainly adolescents and young adults). Invasive meningococcal disease (IMD) caused by Neisseria meningitidis imposes a substantial public health burden,. The case fatality rate (CFR) of IMD remains high. IMD epidemiology varies markedly by region and over time, and there appears to be a shift in the epidemiology towards older adults. The objective of our review was to assess the published data on the epidemiology of IMD in older adults (those aged ≥ 55 years)in North America and Europe. Such information would assist decision-makers at national and international levels in developing future public health programmes for managing IMD., Methods: A comprehensive literature review was undertaken on 11 August 2020 across three databases: EMBASE, Medline and BIOSIS. Papers were included if they met the following criteria: full paper written in the English language; included patients aged ≥ 56 years; were published between 1/1/2009 11/9/2020 and included patients with either suspected or confirmed IMD or infection with N. meningitidis in North America or Europe. Case studies/reports/series were eligible for inclusion if they included persons in the age range of interest. Animal studies and letters to editors were excluded. In addition, the websites of international and national organisations and societies were also checked for relevant information., Results: There were 5,364 citations identified in total, of which 76 publications were included in this review. We identified that older adults with IMD were mainly affected by serogroups W and Y, which are generally not the predominant strains in circulation in most countries. Older adults had the highest CFRs, probably linked to underlying comorbidities and more atypical presentations hindering appropriate timely management. In addition, there was some evidence of a shift in the incidence of IMD from younger to older adults., Conclusions: The use of meningococcal vaccines that include coverage against serogroups W and Y in immunization programs for older adults needs to be evaluated to inform health authorities' decisions of the relative benefits of vaccination and the utility of expanding national immunization programmes to this age group., (© 2022. The Author(s).)

Background: Some reports have suggested that the clinical and economic burdens of asthma are associated with blood eosinophil levels. The association between clinical burden and blood eosinophil counts were evaluated in a Korean adult asthma cohort., Methods: Clinical information including blood eosinophil counts that were not affected by systemic corticosteroids were extracted from the Cohort for Reality and Evolution of Adult Asthma in Korea database. Clinical burden was defined as 1) asthma control status, 2) medication demand and 3) acute exacerbation (AE) events during 1 consecutive year after enrollment. All patients were divided into atopic and non-atopic asthmatics. The associations between asthma outcomes and the blood eosinophil count were evaluated., Results: In total, 302 patients (124 atopic and 178 non-atopic asthmatics) were enrolled. In all asthmatics, the risk of severe AE was higher in patients with blood eosinophil levels < 100 cells/µL than in patients with levels ≥ 100 cells/µL (odds ratio [OR], 5.406; 95% confidence interval [CI], 1.266-23.078; adjusted P = 0.023). Among atopic asthmatics, the risk of moderate AE was higher in patients with blood eosinophil levels ≥ 300 cells/µL than in patients with levels < 300 cells/µL (OR, 3.558; 95% CI, 1.083-11.686; adjusted P = 0.036). Among non-atopic asthmatics, the risk of medication of Global Initiative for Asthma (GINA) steps 4 or 5 was higher in patients with high blood eosinophil levels than in patients with low blood eosinophil levels at cutoffs of 100, 200, 300, 400, and 500 cells/µL., Conclusion: The baseline blood eosinophil count may predict the future clinical burden of asthma., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2022 The Korean Academy of Medical Sciences.)

Background: Mismatch between need and mental healthcare (MHC) use (under-and overuse) has mainly been studied with cross-sectional designs, not accurately capturing patterns of persistence or change in clinical burden and MHC-use among persons with depressive and/or anxiety disorders., Aims: Determining and describing [mis]match of longitudinal trajectories of clinical burden and MHC-use., Methods: Six-year longitudinal burden and MHC-use data came from the Netherlands Study of Depression and Anxiety (n=2981). The sample was split into four subgroups: I) no clinical burden but constant MHC use, II) constant clinical burden but no MHC-use, III) changing clinical burden and MHC-use, and IV) healthy non-users. Within subgroups I)-III), specific clinical burden and MHC trajectories were identified (growth mixture modeling). The resulting classes' associations with predisposing, enabling, and need factors were investigated (regression analysis)., Results: Subgroups I-III revealed different trajectories. I) increasing MHC without burden (4.1%). II) slightly increasing (1.9%), strongly increasing (2.4%), and decreasing (9.5%) burden without MHC. III) increasing (41.4%) or decreasing (19.4%) burden and concurrently increasing MHC use (first underuse, then matched care), thus revealing delayed MHC-use. Only having suicidal ideation (p<.001, Cohen's d= .6-1.5) was a significant determinant of being in latter classes compared to underusers (strongly increasing burden without MHC-use)., Limitations: More explanatory factors are needed to explain [mis]match., Conclusion: Mismatch occurred as constant underuse or as delayed MHC-use in a high-income country (Netherlands). Additionally, no meaningful class revealed constantly matched care on average. Presence of suicidal ideation could influence the probability of symptomatic individuals receiving matched MHC or not., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: There are limited published data on the burden of moderate/severe uncontrolled asthma., Methods: We conducted a systematic literature review to better understand the impact of moderate-to-severe asthma in the US, the UK, Germany, France, Italy, Spain, Canada, Japan, and Australia in terms of prevalence, clinical measures, health-related quality of life (HRQoL) and economic burden, for patients whose asthma is uncontrolled despite inhaled corticosteroid/long-acting β 2 -agonist (ICS/LABA) therapy., Results: The prevalence of uncontrolled asthma among patients with moderate/severe disease varied but was as high as 100% in some subgroups. Patients with uncontrolled asthma generally had poor lung function (mean/median pre-bronchodilator forced expiratory volume in 1 second [FEV 1 ]: 1.69-2.45 L; mean/median pre-bronchodilator percent predicted FEV 1 : 57.2-79.7). There was also a substantial but variable exacerbation burden associated with uncontrolled asthma, with the annualised rate of exacerbations ranging from 1.30 to 7.30 when considering various patient subgroups. Furthermore, the annualised rate of severe exacerbations ranged from 1.66 to 3.60. The HRQoL burden measured using disease-specific and generic instruments consistently demonstrated substantial impairment of HRQoL for those with uncontrolled asthma; Asthma Quality of Life Questionnaire scores ranged from 3.00 to 5.20, whilst EurQol-5 Dimensions index scores ranged from 0.53 to 0.59. Direct, indirect and total costs together with consumption of other healthcare resources associated with managing uncontrolled asthma were also substantial in the population studied; no caregiver burden was identified., Conclusions: Our findings suggest that significant unmet needs exist for patients with uncontrolled asthma despite the availability of ICS/LABA therapy. Novel treatments are needed to help reduce the burden to patients, healthcare systems and society., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Sleep disturbances are frequent in Alzheimer's disease (AD)., Objective: To summarize the impact of sleep disturbances on AD patients and their caregivers and the effects of currently available sleep therapies., Methods: Published studies (January 1985-March 2020) assessing the burden associated with insomnia/sleep disturbances in the AD population and insomnia treatment effects were identified by searching PubMed, Embase, and Cochrane Library and screened against inclusion criteria., Results: 58 studies assessing patient and caregiver burden, institutionalization, and insomnia treatments in AD patients with sleep disturbances were identified. Sleep disturbances were associated with worse cognition, functional ability, and behavioral and neuropsychological functioning. Health status and quality of life of both patients and caregivers were reduced in the presence of sleep disturbances. Sleep disturbances were also associated with institutionalization. Although significant associations between sleep problems and clinical outcomes were apparent, there was generally no control for other influencing factors (e.g., cognitive status). Bright light and behavioral therapies as well as drugs showed some promise in AD patients, but studies were primarily small and limited data were available, particularly in regard to the effect on associated clinical burden., Conclusion: Sleep disturbances are a significant problem for AD patients and caregivers, associated with behavioral and psychological problems and cognitive decline. However, they remain poorly characterized and under-researched. As the global population is aging and AD is on thes rise, data from larger, prospective trials are required to fully understand the clinical correlates of sleep disturbances and the impact insomnia treatments can have.

Objectives: The burden and treatment landscape of RA is poorly understood. This research aimed to identify evidence on quality of life, caregiver burden, economic burden, treatment patterns and clinical outcomes for patients with moderate RA in the United Kingdom., Methods: A systematic literature review was performed across multiple databases and screened against pre-defined inclusion criteria., Results: A total of 2610 records were screened; seven studies presenting evidence for moderate RA were included. These patients were found to incur substantial burden, with moderate to severe levels of disability. Compared with patients in remission, moderate RA patients reported higher levels of disability and decreased EQ-5D utility scores. The majority of patients did not feel that their current therapy adequately controlled their disease or provided sufficient symptom relief. In the United Kingdom, the National Institute for Health and Care Excellence (NICE) have not approved advanced therapies (such as biological disease-modifying anti-rheumatic drugs) for patients with moderate disease, which restricts access for these patients., Conclusion: The evidence available on the burden of moderate RA is limited. Despite current treatments, moderate RA still has a substantial negative impact, given that a DAS28 disease activity score defined as being in the moderate range does not qualify them for access to advanced therapies in the United Kingdom. For these patients, there is a particular need for further studies that investigate their burden and the impact of treating them earlier. Such information would help guide future treatment decisions and ensure the most effective use of resources to gain the best outcomes for patients with moderate RA., (© The Author(s) 2021. Published by Oxford University Press on behalf of the British Society for Rheumatology.)

Objective: Acromegaly is a rare, pituitary hormonal disorder that requires improved awareness worldwide. The objective of this analysis was to quantify the clinical and economic burden of comorbidities for patients with acromegaly and examine the influence of biochemical control on these outcomes., Study Design: Markov cohort decision analytic model consisting of two states, including alive (with and without comorbidity) and dead., Methods: A cohort of patients with acromegaly who had achieved biochemical control, a cohort of patients with acromegaly who had not achieved biochemical control, and a cohort of individuals from the general US population were tracked over a lifetime time horizon. The model tracked the proportion of the alive population that had each comorbidity based on age, sex, presence of acromegaly, and biochemical control status. The proportion of patients with each acromegaly-associated comorbidity were assigned comorbidity-associated costs, disutilities, and increased risk of mortality., Results: Compared with the general population, controlled acromegaly resulted in $192,000 additional comorbidity-related costs, 0.7 fewer years of life, 2.9 fewer quality-adjusted life years, and 1.1 more comorbidities across the remaining lifespan. Compared with the general population, uncontrolled acromegaly resulted in $285,000 additional comorbidity-related costs, 0.9 fewer years of life, 4.2 fewer quality-adjusted life years, and 1.6 more comorbidities across the remaining lifespan., Conclusions: Achieving biochemical control is associated with improvements in cost, quality of life, and mortality, albeit not to the level of the general population. A multimodal treatment strategy including biochemical control and management of comorbidities is necessary to improve patient outcomes., (Copyright © 2021. Published by Elsevier Ltd.)

Background and Objectives: Group B Streptococcus (GBS) is the leading cause of sepsis and meningitis in infants <90 days. In this study, the burden of GBS disease and mortality in young infants in England was assessed., Methods: Using linked hospitalization records from every National Health Service (NHS) hospital from April 1, 1998 to March 31, 2017, we calculated annual GBS incidence in infants aged <90 days and, using regression models, compared their perinatal factors, rates of hospital-recorded disease outcomes, and all-cause infant mortality rates with those of the general infant population., Results: 15 429 infants aged <90 days had a hospital-recorded diagnosis of GBS, giving an average annual incidence of 1.28 per 1000 live births (95% CI 1.26-1.30) with no significant trend over time. GBS-attributable mortality declined significantly from 0.044 (95% CI .029-.065) per 1000 live births in 2001 to 0.014 (95% CI .010-.026) in 2017 (annual percentage change -6.6, 95% CI -9.1 to -4.0). Infants with GBS had higher relative rates of visual impairment (HR 7.0 95% CI 4.1-12.1), cerebral palsy (HR 9.3 95% CI 6.6-13.3), hydrocephalus (HR 17.3 95% CI 13.8-21.6), and necrotizing enterocolitis (HR 18.8 95% CI 16.7-21.2) compared with those without GBS., Conclusions: Annual rates of GBS disease in infants have not changed over 19 years. The reduction in mortality is likely multifactorial and due to widespread implementation of antibiotics in at-risk mothers and babies, as well as advances in managing acutely unwell infants. New methods for prevention, such as maternal vaccination, must be prioritized., (© The Author(s) 2020. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Aims: Obstructive hypertrophic cardiomyopathy (oHCM) is a disease of the cardiomyocyte in which dynamic left ventricular outflow track obstruction may lead to heart failure, valvular disease, and sudden death. Little is known about healthcare resource utilization (HRU) and costs associated with oHCM. This study investigated the clinical and economic burden of oHCM in patients with or without symptoms associated with oHCM., Methods: We used the US IBM MarketScan Commercial and Medicare Supplemental database to identify patients with oHCM (January 2009-March 2019). Control patients without cardiomyopathy were matched to each patient with oHCM based on age, sex, region, and index year (3:1 ratio). One-year HRU and cost data were compared between all oHCM, symptomatic oHCM, and asymptomatic oHCM subgroups, and their respective controls., Results: Among 11,401 eligible patients with oHCM (mean age 57 years, 42% female), 5,667 (50%) were symptomatic (23% chest pain, 57% dyspnea, 29% fatigue, 17% syncope). oHCM was associated with significant increases in all-cause hospitalizations, hospital days, outpatient visits, and total healthcare costs (mean ± standard deviation: $26,929 ± 77,720 vs. $6,808 ± 25,712, p <.001) compared with matched controls. These differences were driven mainly by the clinical and economic burden of symptomatic oHCM, which was associated with significant increases in 1-year hospitalization rates (38.0 vs. 6.9%), hospital days (3.7 ± 9.9 vs. 0.4 ± 3.0), and total healthcare costs ($43,586 ± 103,756 vs. $6,768 ± 27,618; all p <.001). Adjustment for comorbidities had minimal impact on these differences., Limitations: The use of claims data relies on International Classification of Diseases (ICD-9 and ICD-10) diagnosis codes, which might be inaccurate. Only commercially insured patients were included., Conclusion: In a real-world population, oHCM was associated with substantial increases in HRU and incremental costs of ∼$20,000/year when compared with matched controls-a difference that increased to ∼$35,000/year among symptomatic patients. Further studies are warranted to understand the potential impact of specific therapies on HRU and the economic burden of oHCM.

Background/aims: To investigate epidemiologic characteristics, clinical and economic burdens, and factors associated with mortality in complicated skin and skin structure infection (cSSSI) patients in Korea., Methods: A retrospective, observational, nationwide study was conducted between April to July 2012 at 14 tertiary-hospitals in Korea. Eligible patients were hospitalized adults with community acquired cSSSI, who underwent surgical intervention and completed treatment between November 2009 and October 2011. Data on demography, clinical characteristics, outcomes and medical resource utilization were collected through medical record review. Direct medical costs were calculated by multiplying quantities of resources utilized by each unit price in Korea., Results: Of 473 patients enrolled, 449 patients (except 24 patients with no record on surgical intervention) were eligible for analysis. Microbiological testing was performed on 66.1% of patients and 8.2% had multiple pathogens. Among culture confirmed pathogens (n = 297 patients, 340 episodes), 76.2% were gram-positive (Staphylococcus aureus; 41.2%) and 23.8% were gram-negative. The median duration of hospital stay was 16 days. Among treated patients, 3.3% experienced recurrence and 4.2% died in-hospital. The mean direct medical costs amounted to $4,195/ person, with the greatest expenses for hospitalization and antibiotics. The in-hospital mortality and total medical costs were higher in combined antibiotics therapy than monotherapy (p < 0.05). Charlson's comorbidity index ≥ 3, standardized early warning scoring ≥ 4, sub-fascia infections and combined initial therapy, were all found to be associated with higher mortality., Conclusion: Korean patients with community-onset cSSSI suffer from considerable clinical and economic burden. Efforts should be made to reduce this burden through appropriate initial treatment.

Objectives: We conducted a systematic literature review (SLR) to determine the epidemiology and clinical burden of chronic rhinosinusitis with nasal polyps (CRSwNP) and to describe how the addition of biologics has affected outcomes for patients with CRSwNP., Methods: The SLR adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Embase, MEDLINE, and Evidence-Based Medicine Reviews databases were searched using OVID. Relevant studies published between 1 January 2008 and 8 February 2019, for epidemiology, and 1 January 2008 and 16 February 2019, for clinical burden, and relevant conference abstracts from 1 January 2017 to 7 March 2019, for epidemiology and 1 January 2017-16 February 2019 for clinical burden were included., Results: For the epidemiology and clinical burden SLR, 147 and 119 records, respectively, met the inclusion criteria. We found the prevalence of CRSwNP was 1-2.6% and was greater in men. Asthma, allergy, and allergic rhinitis were the most common comorbidities identified. Reported risk factors included asthma, gene polymorphisms, age, and eosinophilia. Studies indicated that dupilumab, mepolizumab, and omalizumab each improved different clinical outcomes. Non-biologics (drugs such as corticosteroids or antibiotics, surgery, or aspirin desensitization) improved clinical outcomes as well., Conclusions: CRSwNP is fairly prevalent in the general population. Despite the significant efficacy of existing treatments, several unmet needs remain. The high burden of uncontrolled symptoms, frequent recurrence of nasal polyps after surgery, and long-term adverse effects of oral corticosteroids indicate that new therapies addressing these unmet needs should be developed. Although data on biologics from randomized controlled trials look promising, the efficacy of biologics in the real world has yet to be established. The SLR of the epidemiology and clinical burden of CRSwNP revealed key gaps in the literature. There was a paucity of prevalence data across many geographic areas, and no prevalence projections could be determined. Studies showed varying efficacy of non-biologics and no studies directly compared biologics for efficacy. Data regarding clinical efficacy of agents for eosinophilic CRSwNP or severe CRSwNP were lacking, and these patient populations would be served by more trials.

Aim: Non-alcoholic steatohepatitis (NASH) is the progressive form of non-alcoholic fatty liver disease (NAFLD) and prevalence is rising in Asia due to increasing rates of urbanization, sedentary lifestyles, and poor nutrition., Methods: We built a Markov model with 20-year horizon to estimate the burden of NASH in Hong Kong. Cohort size was determined by population size, prevalence of NAFLD, and incidence of NASH in 2017. Health states include hepatic steatosis, fibrosis stages 0-3, compensated and decompensated cirrhosis, hepatocellular carcinoma, post-liver transplant, and liver-related, cardiovascular, and background mortality. Transition probabilities were estimated from published reports and we converted 2017 Gazette price from the Hospital Authority of Hong Kong to US dollars. We discounted costs by 3% annually. Health utilities were assumed to be the same as in the USA., Results: Non-alcoholic steatohepatitis will cost $1.32 billion and 124 liver transplants over 20 years, with average cost per person-year of $257. Sensitivity analyses show our model is robust in predicting costs for the prevalent population but likely overestimates costs for the incident population., Conclusions: Non-alcoholic steatohepatitis will contribute to a significant clinical and economic burden in Hong Kong over the next two decades. Due to the limited number of donors and small number of liver transplants undertaken annually, patients with advanced liver disease due to NASH in Hong Kong are more likely to die from NASH than their counterparts in North America and Europe. Thus, rising prevalence of metabolic syndrome in elderly adults in Hong Kong make NASH an important consideration for clinicians and policy makers., (© 2020 The Japan Society of Hepatology.)

Background: Carbapenem resistant Klebsiella pneumoniae (CRKP), Pseudomonas aeruginosa (CRPA), and Acinetobacter baumannii (CRAB) pose significant threats to public health. However, the clinical and economic impacts of CRKP, CRPA, and CRAB remain largely uninvestigated in China. This study aimed to examine the clinical and economic burden of CRKP, CRPA, and CRAB compared with carbapenem susceptible cases in China. Method: We conducted a retrospective and multicenter study among inpatients hospitalized at four tertiary hospitals between 2013 and 2015 who had K. pneumoniae , P. aeruginosa , and A. baumannii positive clinical samples. Propensity score matching (PSM) was used to balance the impact of potential confounding variables, including age, sex, insurance, number of diagnosis, comorbidities (disease diagnosis, and Charlson comorbidity index), admission to intensive care unit, and surgeries. The main indicators included economic costs, length of stay (LOS), and mortality rate. Results: We included 12,022 inpatients infected or colonized with K. pneumoniae , P. aeruginosa , and A. baumannii between 2013 and 2015, including 831 with CRKP and 4328 with carbapenem susceptible K. pneumoniae (CSKP), 1244 with CRPA and 2674 with carbapenem susceptible P. aeruginosa (CSPA), 1665 with CRAB and 1280 with carbapenem susceptible A. baumannii (CSAB). After PSM, 822 pairs, 1155 pairs, and 682 pairs, respectively were generated. Compared with carbapenem-susceptible cases, those with CRKP, CRPA, and CRAB were associated with statistically significantly increased total hospital cost ($14,252, p < 0.0001; $4605, p < 0.0001; $7277, p < 0.0001) and excess LOS (13.2 days, p < 0.0001; 5.4 days, p = 0.0003; 15.8 days, p = 0.0004). In addition, there were statistically significantly differences in hospital mortality rate between CRKP and CSKP, and CRAB and CSAB group (2.94%, p = 0.024; 4.03%, p = 0.03); however, the difference between CRPA and CSPA group was marginal significant (2.03%, p = 0.052). Conclusion: It highlights the clinical and economic impact of CRKP, CRPA, and CRAB to justify more resources for implementing antibiotic stewardship practices to improve clinical outcomes and to reduce economic costs.

Background: The epidemiology of acute kidney injury (AKI) in nonexacerbated chronic obstructive pulmonary disease (NECOPD) patients is unknown. This study investigated the factors associated with AKI and the association between AKI and in-hospital mortality in the hospitalized NECOPD population., Methods: The electronic medical records of 2897 patients hospitalized with NECOPD were analyzed retrospectively. Demographic information, medicine used before AKI, diagnosis records and laboratory data were collected. AKI was classified as community-acquired (CA-) or hospital-acquired (HA-) AKI according to the serum creatinine criteria. Risk factors for HA-AKI and in-hospital mortality were analyzed by logistic regression analyses. To avoid an interaction between cor pulmonale and AKI, the association between AKI and in-hospital morality was further analyzed with cor pulmonale stratification., Results: The incidence rates of CA- and HA-AKI were 7.1 and 12.0%, respectively. Increased age, female sex, cor pulmonale comorbidity, chronic kidney disease stage, diuretic and glycopeptide use before AKI and iodine-containing contrast medium exposure were independently associated with HA-AKI. A total of 5.7% of the patients died. After adjustment for age, sex, cor pulmonale, chronic kidney disease, Charlson comorbidity index score (without renal disease) and hemoglobin level, HA-AKI was an independent risk factor for in-hospital mortality [OR 13.909 (95% CI 8.699-22.238) in non-cor pulmonale subgroup; OR 26.604 (95% CI 12.166-58.176) in cor pulmonale subgroup], whereas CA-AKI was not., Conclusions: AKI is common in the NECOPD population. Diuretics and contrast media are associated with HA-AKI in this population. The patients with HA-AKI have a higher mortality risk than the patients without AKI.

Background and Aim: Crigler-Najjar syndrome (CNS) results from biallelic mutations of UGT1A1 causing partial or total loss of uridine 5'-diphosphate glucuronyltransferase activity leading to unconjugated hyperbilirubinemia and its attendant risk for irreversible neurological injury (kernicterus). CNS is exceedingly rare and has been only partially characterized through relatively small studies, each comprising between two and 57 patients., Methods: A systematic literature review was conducted to consolidate data on the patient, caregiver, and societal burden of CNS., Results: Twenty-eight articles on clinical aspects of CNS were identified, but no published data on its humanistic or economic burden were found. In patients with complete UGT1A1 deficiency (type 1 CNS [CNS-I]), unconjugated bilirubin levels increase 3-6 mg/dL/day during the newborn period and reach neurologically dangerous levels between 5 and 14 days of age. Phototherapy is the mainstay of treatment but poses significant challenges to patients and their families. Despite consistent phototherapy, patients with CNS-I have worsening hyperbilirubinemia with advancing age. Liver transplantation is the only definitive therapy for CNS-I and is increasingly associated with excellent long-term survival but also incurs high costs, medical and surgical morbidities, and risks of immunosuppression., Conclusions: Crigler-Najjar syndrome is associated with a substantial burden, even with existing standards of care. The development of novel disease-modifying therapies has the potential to reduce disease burden and improve the lives of CNS patients and their families., (© 2019 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.)

Introduction : Palmoplantar pustulosis (PPP) is a chronic, relapsing and refractory disease characterized by sterile pustules appearing on the palms and/or soles, accompanied by erythema, blistering, scales and/or keratinization. The overall burden of PPP in terms of its clinical impact, effect on patients and families, and economic consequences has not previously been investigated in a structured manner. Areas covered : A structured search focused on identification of studies in PPP using specific search terms in PubMed and EMBASE® from 2005 onwards, with additional back-referencing and pragmatic searches. Outcomes of interest included clinical burden, humanistic burden, and economic burden. Expert opinion : In cross-sectional studies, approximately 75% of all PPP patients suffer from active disease, with risk of relapse remaining constant over time. Patients' health-related quality of life is significantly impaired, as expected for a disease affecting hands and feet. Tools have been described that assess the clinical as well as patient-reported burden of PPP; their performance in larger cohorts and/or clinical trials remains to be investigated. The key data limitations identified include inconsistent definitions for characterizing remission/relapse, and limited humanistic and economic burden data; future studies are required to address these evidence gaps.

Introduction : Generalized pustular psoriasis (GPP) is characterized by widespread erythema and edema, superficial sterile coalescing pustules, and lakes of pus. Although the impact of GPP is thought to be substantial, emerging literature on its clinical, humanistic, and economic burden has not previously been described in a structured way. Areas covered : A structured search focused on the identification of studies in GPP using specific search terms in PubMed and EMBASE® from 2005 onwards, with additional back-referencing and pragmatic searches. Outcomes of interest included clinical, humanistic, and economic burden. Expert opinion : Despite its significant clinical, humanistic, and economic burden, GPP is poorly classified and inadequately studied. A recent European (ERASPEN) consensus classifies GPP into relapsing and persistent disease and classifies patients on the presence or absence of psoriasis vulgaris. Classification of GPP lesions involving >30% body surface area or use of hospitalization as a surrogate may be a way to identify significant flares. Given the frequency of flares, the impaired quality of life during the post-flare period, and safety/tolerability issues, it is clear that current treatment options are not sufficient. Long-term studies utilizing the European consensus statement with subclassifiers are required to supplement our current understanding of the burden of GPP.

Objective: To explore and describe potential subgroups within the treatment-resistant schizophrenia (TRS) population, using data from a survey of US psychiatrists., Methods: Psychiatrists completed an online survey of demographic/clinical characteristics and treatment history for two of their patients with TRS. Patients were stratified according to number of suicide attempts, number of hospitalizations, employment status, and TRS onset time frame., Results: Of the 408 patients with TRS described by psychiatrists, 37.5% had ≥1 suicide attempt, 78.9% had ≥2 hospitalizations, 74.5% were unemployed, 45.0% had TRS onset within 5 years of first treatment (a further 8.0% had TRS from first treatment), and 31.5% had TRS onset after 5 years (15.5% unknown). Patients with ≥1 (vs 0) suicide attempts had statistically significantly more psychiatric (3.6 vs 2.2) and physical (2.2 vs 1.6) comorbidities. Patients with ≥2 (vs ≤1) hospitalizations were statistically significantly more likely to have hallucinations, conceptual disorganization, social withdrawal, and cognitive dysfunction, and had more psychiatric (3.0 vs 1.9) and physical (2.0 vs 1.1) comorbidities. Unemployed (vs employed) patients were statistically significantly more likely to have delusions, hallucinations, blunted affect, social withdrawal, and cognitive dysfunction, and had more psychiatric (2.9 vs 2.3) and physical (2.1 vs 1.2) comorbidities. Patients with TRS onset ≤5 (vs >5) years were statistically significantly younger (35.0 vs 43.7 years), less likely to have hallucinations and social withdrawal, and had fewer psychiatric (2.6 vs 3.3) and physical (1.7 vs 2.3) comorbidities., Conclusions: Greater clinical burden in TRS is associated with greater illness severity and chronicity markers, suggesting a dimensional gradient from non-TRS to mild-moderate and more severe forms of TRS. Time to onset of TRS may have implications for outcomes, with data indicating greater burden in those with late-onset TRS. Accumulation of illness over time may be more important than time to onset., Competing Interests: CUC has been a consultant and/or advisor to or has received honoraria from: Alkermes, Allergan, Angelini, Boehringer Ingelheim, Gedeon Richter, Gerson Lehrman Group, Indivior, IntraCellular Therapies, Janssen/J&J, LB Pharma, Lundbeck, MedAvante-ProPhase, Medscape, Merck, Neurocrine, Noven, Otsuka, Pfizer, Recordati, Rovi, Servier, Sumitomo Dainippon, Sunovion, Supernus, Takeda, and Teva. He has provided expert testimony for Bristol-Myers Squibb, Janssen, and Otsuka. He served on a Data Safety Monitoring Board for Boehringer Ingelheim, Lundbeck, Rovi, Supernus, and Teva. He received royalties from UpToDate and grant support from Janssen, and Takeda. He is a shareholder of LB Pharma. TB and CB are employees of H. Lundbeck A/S. The authors report no other conflicts of interest in this work., (© 2019 Correll et al.)

Aims: To assess the real-world clinical burden and healthcare resource utilization (HRU) among patients with chronic hypoparathyroidism, overall and by adequately controlled (AC) vs not adequately controlled (NAC) disease, informed by guideline-recommended clinical management targets, including biochemistry and symptoms. Materials and methods: In this retrospective online chart review, endocrinologists in the US, Canada, the UK, France, Germany, Italy, and Spain were randomly selected to review the medical charts of adult patients with chronic hypoparathyroidism receiving calcium and activated vitamin D. Patients' demographics, disease characteristics, symptoms, comorbidities, and hypoparathyroidism-related HRU during the 1 year before the review date were assessed. Clinical burden and HRU were compared between patients with NAC and AC hypoparathyroidism. Results: Of 614 patients with hypoparathyroidism (AC, N = 442; NAC, N = 172), the mean age was 43.6 years, and the majority were female (61.6%), Caucasian (78.8%), and had post-surgical hypoparathyroidism (74.4%). Mean duration of hypoparathyroidism was 46.0 months. Hypoparathyroidism-related symptoms and comorbidities were reported in 59.4% and 46.7% of patients, respectively; 90.7% of patients had ≥1 hypoparathyroidism-related HRU event. More patients with NAC (57.6%) vs AC (42.5%) hypoparathyroidism experienced ≥1 comorbidity including calcium/phosphate imbalances, and brain, cardiovascular, metabolic, and renal disorders (all p  < 0.01). More patients with NAC vs AC hypoparathyroidism incurred ≥1 hypoparathyroidism-related hospitalization (27.9% vs 16.3%) and emergency room visits (47.7% vs 38.5%), and patients with NAC vs AC hypoparathyroidism had a higher number of outpatient visits (3.6 vs 2.6; all p  < 0.05), in the 1-year observation period. Limitations and conclusions: Limitations of this online chart review include possible under-estimation of disease burden, limited sample size, and the inability to rule out selection bias. Findings indicate that patients with chronic hypoparathyroidism experience substantial symptomatic and comorbid burdens resulting in frequent HRU, suggesting an unmet need, particularly in NAC disease.

A literature review has been carried out to analyse the clinical burden, the economic impact of influenza and the efficiency of influenza vaccination programmes in Spain. The average incidence rate of influenza in Spain is 2,069 cases per 100,000 inhabitants, with a significant impact on mortality and a reduction of health-related quality of life. In terms of its associated costs, influenza causes a significant burden on primary care, hospitals, treatments and absences from work every year, which could total one billion euros per year. Vaccination is an efficient measure for its prevention and can generate savings for the healthcare system. In conclusion, influenza is a significant health problem which generates a major economic and clinical burden annually; the profiling and measurement of which must be improved., (Copyright © 2018 Elsevier España, S.L.U. All rights reserved.)