Burden of Wilson Disease among patients and care partners in the United States: results from a cross-sectional survey.

OBJECTIVE: This study assessed the burden of Wilson Disease (WD) among patients and care partners (WD-CPs) in the US and compared it to a US general population of adults (GPs) and care partners (GP-CPs). METHODS: This cross-sectional, self-reported survey included patients with WD and WD-CPs aged ≥18 years recruited through the Wilson Disease Association (WDA), while data for GPs and GP-CPs were obtained from the 2022 National Health and Wellness Survey. GPs and GP-CPs were propensity score matched (3:1) with WD patients and WD-CPs for demographics and health characteristics. Bivariate analysis evaluated differences in comorbidity burden and health-related outcomes of the WD cohorts compared to matched GP cohorts. RESULTS: Thirty-seven patients with WD and 53 WD-CPs completed the survey. Most patients reported some treatment burden (73.3%), experienced sleep problems (60%), and visited a healthcare provider (HCP) in the past 6 months (91.9%). Compared with matched GPs, patients with WD had a significantly higher mortality risk (p < .001) and reported greater rates of chronic liver disease, cirrhosis (both, p < .001), migraines (p = .032), non-alcoholic steatohepatitis (p = .004), sleep problems (p = .009) and HCP visits (p = .002). Most WD-CPs (75.5%) reported high burden of caring (mean ZBI-12 score, 26.5) and more negative impact on esteem than GP-CPs. CONCLUSION: This study highlights the burden of WD experienced by patients and WD-CPs, with patients experiencing high treatment burden, comorbidity burden and healthcare resource utilization, and WD-CPs experiencing high impact of caring, including impact on employment and self-esteem.

Wilson Disease (WD) is a rare genetic disorder that results from copper building up in the liver and the central nervous system. The management of WD has been consistent for the past 50 years. We surveyed patients with WD and family members of patients with WD ("care partners," hereby referred to as WD-CPs) residing in the US, to understand the burden of WD. We also used data from the 2022 National Health and Wellness Survey to compare patients with and WD-CPs to a sample of adults and care partners of adults in the general population (hereby referred to as GP and GP-CPs). The study found that the majority of the patients with WD reported some treatment burden (73.3%), experienced sleep problems (60.0%), and visited a healthcare provider (HCP) in the past 6 months (91.9%). Compared to GPs, patients with WD had a significantly higher risk of dying in the next 10 years and reported greater rates of other health conditions (chronic liver disease, cirrhosis, migraines, and non-alcoholic steatohepatitis), sleep problems, and visits to healthcare providers in the last 6 months. The majority of WD-CPs (75.5%) reported high burden of caring and more negative impact on their self-esteem than GP-CPs. Overall, this study highlights the burden of WD and suggests the need for more effective treatments that can reduce this burden.

Evaluating Oncologists' Practice Patterns and Decision-Making in Locally Advanced or Metastatic Urothelial Carcinoma: The US Physician PARADIGM Study.

BACKGROUND: The treatment landscape for locally advanced/metastatic urothelial carcinoma (la/mUC) has evolved. This study examined US prescribing patterns and clinical decision-making for first-line (1L) and first-line maintenance (1LM) treatment. MATERIALS AND METHODS: US-based oncologists (N = 150) completed an online survey on patient demographics, practice patterns, and important factors considered in 1L/1LM selection. Multivariable logistic regression was used to assess factors associated with more vs less frequent 1L/1LM prescribing. RESULTS: Physician reports estimated that 23% of patients with la/mUC had not received any systemic therapy in the previous 6 months; however, 46% received 1L, 32% received second-line, and 22% received subsequent-line systemic treatments. Of patients who were receiving 1L treatment, 72% were estimated to be receiving 1L platinum-based chemotherapy. Around 69% of patients eligible for 1LM received the treatment. Physicians categorized as frequent prescribers reported overall survival (OS), disease control rate (DCR), and rate of grade 3/4 adverse events (AEs) as factors associated with 1L treatment selection (all P < .05). OS, rate of grade 3/4 immune-mediated AEs, and inclusion in institutional guidelines were reported as attributes used in 1LM treatment selection (all P < .05). Multivariable analysis revealed OS, DCR, and rate of grade 3/4 AEs as important factors in oncologists' 1L treatment selection; academic practice setting and use of Response Evaluation Criteria in Solid Tumors version 1.1 were associated with 1LM use (all P < .05). CONCLUSION: OS and AEs were found to be relevant factors associated with offering 1L and 1LM treatment. Variability exists in physicians' decision-making in the real-world setting for la/mUC.

The clinical, economic, and patient-centric burden of insomnia symptom severity in adults with major depressive disorder in the United States.

INTRODUCTION: Insomnia is prevalent in adults with major depressive disorder (MDD) and is a key diagnostic criterion of MDD; however, little is understood about the burden of insomnia symptom severity in MDD. We evaluated the relationship between insomnia symptom severity and the clinical, economic, and patient-centric burden among community-dwelling individuals with MDD. METHODS: Respondents with diagnosed depression who reported insomnia symptoms in the past 12 months (N = 4402) were identified from the 2019 United States National Health and Wellness Survey. Multivariable analyses assessed the association of Insomnia Severity Index (ISI) with health-related outcomes while controlling for sociodemographic and health characteristics. Further analyses also controlled for depression severity (9-item Patient Health Questionnaire). RESULTS: Mean ISI score was 14.3 ± 5.6. Higher ISI was associated with greater depression severity (r = .51, p < .001). After adjustments, a one-standard deviation (5.6-point) increase in ISI score was significantly associated with higher depression (rate ratio [RR] = 1.36), anxiety (RR = 1.33) and daytime sleepiness (RR = 1.16) levels, more healthcare provider (RR = 1.13) and emergency room visits (RR = 1.31), hospitalizations (RR = 1.21), work productivity and activity impairment (RRs = 1.27 and 1.23, respectively), and poorer mental and physical health-related quality of life (ß = -3.853 and -1.999, respectively) (p < .001). These findings remained statistically significant when controlling for concurrent depression severity. CONCLUSION: In adults with MDD, greater insomnia symptom severity is associated with worse health-related outcomes, which suggests the importance of addressing insomnia symptoms as a clinical target for treating MDD.

Profile and quality of life of the adult population in good health according to the level of vitality: European NHWS cross sectional analysis.

BACKGROUND: The World Health Organization's definition of health highlights the importance of mental and physical wellbeing and not only disease state. However, lack of awareness on the burden of impaired vitality and its impact on the quality of life of the general healthy population prevents healthcare providers from delivering appropriate solutions and advice. This study aims to better characterize this population in Europe and identify the profile and the health reported outcomes associated with impaired vitality. METHODS: This retrospective observational study included National Health and Wellness Survey (NHWS) data collected in healthy participants aged 18-65 years from five European Union countries in 2018. Socio-demographic and lifestyle characteristics, comorbidities, attitudes towards healthcare systems, Patient Activation Measure, health-related quality of life outcomes (EQ-5D), and work productivity and activity impairment were analysed according to SF-12 vitality score subgroups (≥ 60, 50- < 60, 40- < 50, < 40). RESULTS: A total of 24,295 participants were enrolled in the main analysis. Being a female, younger, having a lower income and being obese or having sleep and mental disorders was associated with an increased risk of impaired vitality. This was associated with a higher consumption of healthcare resources along with having a weak patient-physician relationship. Participants who were disengaged in the self-management of their health were 2.6 times more likely to have a low level of vitality. For participants in the lowest vitality group, odds of mobility problems increased by 3.4, impairment of usual activity by 5.8, increased of pain and discomfort by 5.6 and depression and anxiety by 10.3, compared with participants in the highest vitality group. Also, odds of presenteeism increased by 3.7, overall work impairment by 3.4 and daily activity losses by 7.1. CONCLUSION: Evidence-based trends facilitate the identification of a healthy population with impaired vitality in real-world practice. This study highlights the actual burden of low vitality on daily life activities, particularly on mental health and reduced work productivity. Additionally, our results underline the importance of self-engagement in the management of vitality impairment and highlights the need to implement strategies to address this public health concern in the affected population (HCP-patient communication, supplements, meditation).

Understanding the Association between Red Blood Cell Transfusion Utilization and Humanistic and Economic Burden in Patients with ß-Thalassemia from the Patients' Perspective.

We assessed the humanistic and economic burden of chronic red blood cell (RBC) transfusions on patients with ß-thalassemia. This cross-sectional, US-based study included adults (≥18 years) who self-reported a ß-thalassemia physician diagnosis and had received ≥1 RBC transfusion in the past 6 months. The outcomes included the Functional Assessment of Cancer Therapy-Anemia (FACT-An), Patient Health Questionnaire-9, Generalized Anxiety Disorder-7, and ad hoc questions about treatment experience, side effects, direct/indirect costs, and psychological burden. Overall, 100 patients completed the survey, of whom 70% experienced "moderate" to "extremely high" burden due to RBC transfusions, 81% reported iron overload, 42% reported compromised social lives. The mean FACT-An score was 132 (higher score indicates better outcomes; 0-188). Mean scores were 33/52 for fatigue and 20/28 for anemia symptoms in the previous 7 days. Health-related quality of life (HRQoL) temporarily improved after RBC transfusion, although patients continued to experience mild-to-severe depression and anxiety, substantial direct costs, compromised employment, and suboptimal quality of life. Over 6 months, patients dedicated a mean of 173 h to transfusion requirements and incurred out-of-pocket costs of USD 2239 for transfusions and USD 896 for additional care costs. These findings highlight the need for new treatment options to improve patient HRQoL and economic outcomes.

The real-world burden of adults with major depressive disorder with moderate or severe insomnia symptoms in the United States.

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.

Physicians' experience in blood supply shortages and the top factors that impact the clinical, economic, and humanistic outcomes of patients with myelodysplastic syndromes in 5 European countries.

OBJECTIVE: Blood supply shortages may create unnecessary burden, including treatment delay, worsened quality of life, or increased healthcare resource utilization in patients with myelodysplastic syndromes (MDS). This study examined physicians' experience with blood supply shortages in the MDS population. Additionally, physicians' perspectives on the factors that impact clinical, economic, and humanistic outcomes of patients with MDS were investigated. METHODS: A total of 378 physicians primarily specializing in hematology/oncology across the UK, France, Germany, Italy, and Spain completed the survey (n ≈ 75 in each country). Physicians answered questions regarding adequacy of blood supply for patients with MDS who require red blood cell (RBC) transfusions and identified factors impacting the clinical, economic, and humanistic outcomes in the MDS population. RESULTS: Over 65% of physicians reported that their patients with MDS requiring RBC transfusions encountered RBC transfusion delays due to blood supply shortage. Among physicians who reported delays, 13.8% of patients were impacted, ranging from 11.0% in Spain to 19.4% in Italy. On average, patients experienced a 4.2-day delay in receiving RBC transfusions due to blood supply shortages, and 16.7% of patients required additional healthcare provider visits. Eastern Cooperative Oncology Group performance status, threshold hemoglobin levels, and age were the top factors reported by more than two-thirds of physicians that impact outcomes of patients with MDS. CONCLUSION: Our findings support the need for new treatments in MDS that reduce transfusions and thus blood supply needs, and that would have a beneficial effect on clinical, humanistic, and economic outcomes.

Association between transfusion status and clinical and economic outcomes in patients with myelodysplastic syndromes from the physicians' perspective.

BACKGROUND: The current study investigated physicians' understanding of the impact of transfusion status (TS) on clinical and economic outcomes in patients with myelodysplastic syndromes (MDS). MATERIALS & METHODS: 378 physicians primarily specializing in hematology/oncology across five European countries completed the survey. The survey asked physicians for their perspectives on the impact of TS on risk of death, risk of progression to acute myeloid leukemia (AML), chance of leukemia-free survival, and number of significant bleeding events, infection events, hospitalizations, and emergency room (ER) visits. RESULTS: Physicians estimated that compared to transfusion-dependent (TD) patients, transfusion-independent (TI) patients had a 37.6% reduced risk of death, lower risk of progression to AML, and lower risk of non-leukemic death, for all MDS risk levels. TD patients who became TI after treatment were estimated to have 40.6% reduced risk of death and 34% reduced risk of progression to AML, compared to TD patients who remained TD. CONCLUSIONS: Compared with TD patients, physicians estimated that TI patients have fewer events of infection and significant bleeding, and experience fewer hospitalizations and ER visits per person per year. Overall, physicians reported better outcomes for TI patients. New treatment options for patients with MDS to reduce or eliminate transfusion burden are warranted.

The burden of illness of patients with paroxysmal nocturnal haemoglobinuria receiving C5 inhibitors: clinical outcomes and medical encounters from the patient perspective.

OBJECTIVES: To assess the clinical and healthcare resource burden among C5 inhibitor (C5i)-treated patients with paroxysmal nocturnal haemoglobinuria (PNH), using patient-reported data. METHODS: This web-based, cross-sectional survey (01FEB2021-31MAR2021) of adults with PNH treated with eculizumab (France, Germany, UK) or ravulizumab (Germany) included: patient characteristics; treatment patterns/dosage; haematological outcomes (haemoglobin [Hb] levels, transfusions, thrombotic events, breakthrough haemolysis); and medical encounters. Treatment and Hb-level subgroup differences were assessed with statistical significance tests. RESULTS: Among 71 patients, 98.6% were C5i-treated for ≥3 months. The majority (with reported Hb levels) had levels ≤12.0 g/dL (85.7%; n = 54/63). The mean Hb level was 10.2 g/dL (standard deviation [SD]: 2.0; median 10.0 g/dL). Treatment with above label-recommended doses was reported by 30.4% (eculizumab) and 5.3% (ravulizumab) of patients. Within the past 12 months among patients treated with C5i for ≥1 year: 24.1% had ≥1 transfusion; 3.2% had ≥1 thrombosis; and 28.6% had ≥1 breakthrough haemolysis. Among all patients, 26.8% and 31.0% reported emergency department/room [ER] and inpatient visits, respectively. Mean annual, per-patient all-cause medical encounters were: 0.5 (ER); 1.9 (inpatient); and overall outpatient visits ranged by setting from 2.0 to 6.4. Most encounters were PNH-related, with means of 0.4 (ER); 1.8 (inpatient); and 1.6-5.4 (outpatient). Primary haematological and medical encounter outcomes were similar between treatment as well as Hb-level subgroups, with almost no statistically significant differences. CONCLUSIONS: Despite at least 3 months of C5i treatment, high proportions of patients with PNH reported low haemoglobin levels and required transfusions and hospitalizations, which suggests remaining unmet needs.

The burden of illness of patients with paroxysmal nocturnal haemoglobinuria receiving C5 inhibitors in France, Germany and the United Kingdom: Patient-reported insights on symptoms and quality of life.

OBJECTIVES: To assess the clinical, humanistic and economic burden of paroxysmal nocturnal haemoglobinuria (PNH) among C5 inhibitor (C5i)-treated patients with PNH. METHODS: This was a web-based, cross-sectional survey (01FEB2021-31MAR2021) of adults with PNH treated with eculizumab (France, Germany, United Kingdom) or ravulizumab (Germany). Self-reported outcomes included: patient characteristics; patient-reported symptoms; and standardised patient-reported outcomes (e.g. Functional Assessment of Chronic Illness Therapy [FACIT]-Fatigue, European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 [EORTC QLQ-C30]). RESULTS: Among 71 included patients, 98.6% were C5i-treated for ≥3 months (88.7% ≥12 months); among those with self-reported haemoglobin (Hb) levels (n = 63), most (85.7%) were anaemic (defined as ≤12.0 g/dL). Fatigue was the most common symptom at both diagnosis (73.2%) and survey time (63.4%); there were no statistically significant differences in symptom prevalence between treatment subgroups (eculizumab vs. ravulizumab). Total FACIT-Fatigue and EORTC QLQ-C30 scores were substantially lower than European general population references, but there were no statistically significant differences between treatment subgroups. Hb-level subgroups (<10.5 g/dL vs. ≥10.5 d/dL) followed similar trends for all measures, with few significant subgroup differences. CONCLUSIONS: Results suggest that there remains a considerable burden and unmet need among C5i-treated patients with PNH that requires improved therapies.

Characterizing Outcomes and Unmet Needs Among Patients in the United States with Mild-to-Moderate Plaque Psoriasis Using Prescription Topicals.

INTRODUCTION: Topical therapies are considered first-line treatment in the management of plaque psoriasis (PSO). However, data on patient-reported outcomes for topicals are scarce. We designed a survey to record the treatment experience of patients with mild-to-moderate PSO using prescription topicals. METHODS: An online cross-sectional survey was conducted among adult patients on prescription topicals for mild-to-moderate PSO (body surface area [BSA] ≤ 10%) in the US. Data on treatment goals, changes in PSO after current treatment, satisfaction with current treatment (assessed with the Treatment Satisfaction Questionnaire for Medication [TSQM]), and treatment adherence (how often current treatment was taken as instructed) were collected. Descriptive analysis was used to evaluate outcomes. RESULTS: Of the 175 patients with mild-to-moderate PSO who completed the survey, 67.4% were female, with a median age of 55.0 years and 10.8 years since PSO diagnosis. Patients reported (medians) the use of three topicals since diagnosis, with 5 years on the current prescription topical. The top three treatment goals for current topical treatment were improvements in visible skin, 97.1%; non-skin related symptoms, 62.9%; and social/emotional well-being, 60.0%. Overall, 43.4% of patients reported 0% BSA change and 5.7% reported ≥ 75% BSA reduction. Approximately 75.0% each reported improvement in itch and pain symptoms. Embarrassment/self-consciousness because of skin symptoms persisted in 72.6% of patients. Median TSQM scores for global satisfaction, convenience, and effectiveness ranged between 58 and 72, indicating partial treatment satisfaction, except for side effects, which was high (median: 100). Approximately half of patients (49.7%) reported not being highly adherent to treatment. CONCLUSION: Contrary to their treatment goals, patients with mild-to-moderate PSO using prescription topicals reported partial effectiveness, incomplete symptom resolution, impacted emotional and social well-being, and suboptimal global satisfaction, effectiveness, adherence, and convenience. Our findings highlight several unmet needs among topical-experienced, systemic-naïve patients with mild-to-moderate PSO using prescription topicals.

Psoriasis is a chronic skin disease caused by inflammation in the body. Raised areas, called plaques, are one of the main symptoms. These plaques may be red, flaky, itchy, and/or painful. Living with psoriasis can negatively impact a person's well-being, especially when it affects visible areas such as the head, face, hands and nails, and/or sensitive areas like the genitals. Topical treatments, such as creams and lotions, are often the first therapy a doctor prescribes for psoriasis. Since these treatments are applied directly on the plaques, they can be messy and inconvenient. We conducted an online survey of adults with mild-to-moderate psoriasis, meaning that less than 10% of their body had plaques. We wanted to learn how they felt about their disease and their prescription topical treatments. Most people had psoriasis for about 10 years and had been using their current prescription topical for about 5 years. Approximately three of four people reported embarrassment/self-consciousness because of skin symptoms. Although three of four people reported some improvement in itch and pain, almost all people desired better resolution of plaques in visible areas. People also reported that: their current prescription topical did not completely resolve their symptoms, their emotional and social well-being was still suboptimal, they did not always apply their therapy as often as instructed, and they were not completely satisfied with their treatment overall. These results highlight the need for additional treatment options for people with mild-to-moderate psoriasis, particularly options that offer improved symptom control and are more convenient to use.