Reduced Volume and Faster Infusion Rate of Activated Prothrombin Complex Concentrate: A Phase 3b/4 Trial in Adults with Hemophilia A with Inhibitors.

Background Activated prothrombin complex concentrate (aPCC) is indicated for bleed treatment and prevention in patients with hemophilia with inhibitors. The safety and tolerability of intravenous aPCC at a reduced volume and faster infusion rates were evaluated. Methods This multicenter, open-label trial (NCT02764489) enrolled adults with hemophilia A with inhibitors. In part 1, patients were randomized to receive three infusions of aPCC (85 ± 15 U/kg) at 2 U/kg/min (the approved standard rate at the time of the study), in a regular or 50% reduced volume, and were then crossed over to receive three infusions in the alternative volume. In part 2, patients received three sequential infusions of aPCC in a 50% reduced volume at 4 U/kg/min and then at 10 U/kg/min. Primary outcome measures included the incidence of adverse events (AEs), allergic-type hypersensitivity reactions (AHRs), infusion-site reactions (ISRs), and thromboembolic events. Results Of the 45 patients enrolled, 33 received aPCC in part 1 and 30 in part 2. In part 1, 24.2 and 23.3% of patients with regular and reduced volumes experienced AEs, respectively; 11 AEs in eight patients were treatment related. AHRs and ISRs occurred in four (12.1%) and two (6.1%) patients, respectively. In part 2, 3.3 and 14.3% of patients with infusion rates of 4 and 10 U/kg/min experienced AEs, respectively; only one AE in one patient was treatment related; no AHRs or ISRs were reported. Most AEs were mild/moderate in severity. Overall, no thromboembolic events were reported. Conclusions aPCC was well tolerated at a reduced volume and faster infusion rates, with safety profiles comparable to the approved regimen.

Measuring treatment burden in people with Type 2 Diabetes Mellitus (T2DM): a mixed-methods systematic review.

BACKGROUND: Measuring treatment burden is important for the effective management of Type 2 Diabetes Mellitus (T2DM) care. The purpose of this systematic review was to identify the most robust approach for measuring treatment burden in people with T2DM based on existing evidence. METHODS: Articles from seven databases were retrieved. Qualitative, quantitative, and mixed-methods studies examining treatment burden in adults with T2DM and/or reporting relevant experiences were included. A convergent segregated approach with a mixed-methods design of systematic review was employed, creating a measurement framework in a narrative review for consistent critical appraisal. The quality of included studies was assessed using the Joanna Briggs Institute tool. The measurement properties of the instruments were evaluated using the Consensus based Standards for selection of Health Measurement Instruments (COSMIN) checklist. RESULTS: A total of 21,584 records were screened, and 26 articles were included, comprising 11 quantitative, 11 qualitative, and 4 mixed-methods studies. A thematic analysis of qualitative data extracted from the included articles summarised a measurement framework encompassing seven core and six associated measurements. The core measurements, including financial, medication, administrative, lifestyle, healthcare, time/travel, and medical information burdens, directly reflect the constructs pertinent to the treatment burden of T2DM. In contrast, the associated measurement themes do not directly reflect the burdens or are less substantiated by current evidence. The results of the COSMIN checklist evaluation demonstrated that the Patient Experience with Treatment and Self-management (PETS), Treatment Burden Questionnaire (TBQ), and Multimorbidity Treatment Burden Questionnaire (MTBQ) have robust instrument development processes. These three instruments, with the highest total counts combining the number of themes covered and "positive" ratings in COSMIN evaluation, were in the top tertile stratification, demonstrating superior applicability for measuring T2DM treatment burden. CONCLUSIONS: This systematic review provides evidence for the currently superior option of measuring treatment burden in people with T2DM. It also revealed that most current research was conducted in well-resourced institutions, potentially overlooking variability in under-resourced settings.

'The burden is very much on yourself': A qualitative study to understand the illness and treatment burden of hearing loss across the life course.

INTRODUCTION: Hearing loss is a chronic health condition that rises sharply with age. The way people respond to and cope with health conditions is influenced by their capacity to perform illness and treatment-related work. The aim was to explore the cumulative burdens of living with hearing loss and the resources mobilised to ease the burdens. METHODS: A qualitative design was used with semi-structured interviews (online or in-person) with participants recruited through audiology services and nonclinical services, such as lip-reading classes. Forty-six participants with hearing loss aged between 16 and 96 years were interviewed. An abductive approach, informed by May et al.'s burden of treatment theory, was used to analyse the data. RESULTS: The illness burden involved participants working to make sense of their hearing loss, engaging in emotional work in response to changes in sound, social interactions and identity and coping with the daily frustrations required to communicate with others. Abandonment and uncertainty characterised the treatment burden; participants engaged in emotional work to adjust to hearing technology and deal with the uncertainty of how their hearing might progress. To ameliorate the burdens, participants drew on internal resources (psychological, health literacy, cognitive) and external resources (social support, financial, information, technology). CONCLUSIONS: The workload of hearing loss appears largely devolved to the patient and is not always visible. Our work indicates the need to widen approaches in audiological care through the implementation of lifeworld-led care, family-centred care and peer support to build support for those with hearing loss. PATIENT OR PUBLIC CONTRIBUTION: We developed the project in consultation with members of the public who have lived experience of hearing loss recruited through Aston University and volunteer links to audiology services. We also consulted people more likely to be affected by hearing loss adults including adults with learning disabilities, older adults in residential care and people from South Asia (Bangladeshi, Indian and Pakistani communities). These individuals commented on the study aims, interview schedule and participant recruitment practices. One of our co-authors (expert by experience) contributed to the development and interpretation of themes and preparation of the final manuscript.

Patient Experience Survey of Anti-Vascular Endothelial Growth Factor Treatment for Neovascular Age-Related Macular Degeneration and Diabetic Macular Edema.

INTRODUCTION: Understanding patient perspectives of treatment may improve adherence and outcomes. This study explored real-world patient experiences with anti-vascular endothelial growth factor (anti-VEGF) treatment for diabetic macular edema (DME) and neovascular age-related macular degeneration (nAMD). METHODS: This multinational, non-interventional, quantitative, cross-sectional, observational survey assessed treatment barriers/burden, patient-reported visual functioning, and treatment satisfaction in DME and nAMD patients in the USA, the UK, Canada, France, Italy, and Spain. Treatment patterns and visual outcomes were extracted from medical charts. Regression models evaluated relationships between adherence, total missed visits, number of anti-VEGF injections, and clinical and patient-reported outcomes for visual functioning. Association between treatment satisfaction and aspects of burden were assessed. RESULTS: The survey was completed by 183 DME and 391 nAMD patients. Patients had moderately high vision-related functioning (25-item National Eye Institute Visual Functioning Questionnaire score: mean = 74.8) and were satisfied with their current treatment (mean total score: Macular Disease Treatment Satisfaction Questionnaire = 59.2; Retinopathy Treatment Satisfaction Questionnaire = 61.3). Treatment satisfaction scores were worse with higher time-related impacts of treatment (nAMD/DME), higher impacts on finances and daily life (nAMD), negative impacts on employment and lower expectations for treatment effectiveness (DME). Most patients reported ≥1 barrier (66.1% DME, 49.2% nAMD patients) related to treatment (35.0%), clinic (32.6%), and COVID-19 (21.1%). Moreover, 44.9% of patients reported some impairment in activities of daily living. Work absenteeism was observed among >60% of working patients. Nearly one-quarter (24.2%) of patients needed ≥1 day to recover from intravitreal injections; most reported ≥30 min of travel time (73.7%) and clinic wait time (54.2%). In unadjusted univariable analyses, treatment adherence (vs. nonadherence) was related to higher most recent visual acuity (ß = 8.98 letters; CI, 1.34-16.62) and lower odds of visual acuity below driving vision (≤69 letters) (OR = 0.50; CI, 0.25-1.00). CONCLUSION: More durable treatments with reduced frequency of injections/visits may reduce treatment burden and improve patient satisfaction, which may enhance adherence and visual outcomes.

Impact of Digital Interventions on the Treatment Burden of Patients With Chronic Conditions: Protocol for a Systematic Review.

BACKGROUND: There is great potential for delivering cost-effective, quality health care for patients with chronic conditions through digital interventions. Managing chronic conditions often includes a substantial workload required for adhering to the treatment regimen and negative consequences on the patient's function and well-being. This treatment burden affects adherence to treatment and disease outcomes. Digital interventions can potentially exacerbate the burden but also alleviate it. OBJECTIVE: The objective of this review is to identify, summarize, and synthesize the evidence of how digital interventions impact the treatment burden of people with chronic conditions. METHODS: The search, selection, and data synthesis processes were designed according to the PRISMA-P (Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols) 2015. A systematic search was conducted on October 16, 2023, from databases PubMed, Scopus, Web of Science, ACM, PubMed Central, and CINAHL. RESULTS: Preliminary searches have been conducted, and screening has been started. The review is expected to be completed in October 2024. CONCLUSIONS: As the number of patients with chronic conditions is increasing, it is essential to design new digital interventions for managing chronic conditions in a way that supports patients with their treatment burden. To the best of our knowledge, the proposed systematic review will be the first review that investigates the impact of digital interventions on the treatment burden of patients. The results of this review will contribute to the field of health informatics regarding knowledge of the treatment burden associated with digital interventions and practical implications for developing better digital health care for patients with chronic conditions. TRIAL REGISTRATION: PROSPERO CRD42023477605; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=477605. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/54833.

Real-world experience of using stereotactic radiotherapy combined with anti-vascular endothelial growth factor to treat neovascular AMD.

INTRODUCTION: Adjunctive treatment or longer-acting drugs are required to treat nAMD to help ease burdens for patients and hospital clinics alike. Stereotactic therapy is one such option, providing a reduction in the number of injections over time. OBJECTIVE: To determine the clinical outcomes in a cohort of patients with nAMD receiving a combination therapy of stereotactic radiotherapy (SRT) with intravitreal anti-VEGF injections (IVI). METHOD: A retrospective analysis of 74 patients with nAMD, who had received IVI and SRT (16 Gray maximum dose to the macula) at a large tertiary university eye hospital, between March 2018 and September 2019 was performed. The number of IVIs, visual acuity (VA), and central retinal thickness (CRT) were evaluated at 12, 24, and 36 months after patients received SRT and compared to the same time interval prior to SRT. RESULTS: Follow-up data at 12, 24, and 36 months following and prior to SRT was available for 74, 48, and 22 patients respectively. Overall there was a significant reduction in the number of injections post-SRT. Twelve months following SRT, the median number of IVI was reduced by 1 (p < 0.05). The reduction in the median number of IVI was significantly reduced by 3 and 6 injections at 24- and 36-month follow-up respectively (p < 0.05). The CRT was significantly reduced post-SRT compared to the baseline values at all time periods. There was no statistically significant difference in VA at 12-month follow-up compared to baseline. The VA, however, significantly decreased at 24- and 36-month follow-up (p < 0.05). CONCLUSION: A therapy combining SRT with IVI has shown an overall reduction in the number of injections required in nAMD patients at 12, 24, and 36 months following SRT compared to IVI treatment alone. These real-world outcomes are comparable to other studies while also confirming the maintenance of the reduced frequency of required IVI for patients with nAMD.

Social Disconnectedness in Individuals with Cardiovascular Disease: Associations with Health Literacy and Treatment Burden.

BACKGROUND: Knowledge is limited on associations between social disconnectedness (i.e. loneliness and social isolation), health literacy and perceived treatment burden in individuals with cardiovascular disease (CVD). However, understanding these associations may be important for clinical practice. METHODS: This study used cross-sectional self-reported data from the 2017 Danish health and morbidity survey entitled 'How are you?', investigating the associations of loneliness and social isolation with low health literacy and high treatment burden in individuals with CVD (n = 2521; mean age = 65.7 years). RESULTS: Logistic regression analysis showed that loneliness and social isolation were associated with low health literacy in terms of difficulties in 'understanding health information' (loneliness: adjusted odds ratio (AOR) = 1.32, 95% confidence intervals (CI) [1.16, 1.50]; social isolation: AOR = 1.47, 95% CI [1.24, 1.73]) and 'engaging with healthcare providers' (loneliness: AOR = 1.53, 95% CI [1.37, 1.70]; social isolation: AOR = 1.21, 95% CI [1.06, 1.40]) and associated with high treatment burden (loneliness: AOR = 1.49, 95% CI [1.35, 1.65]; social isolation: AOR = 1.20, 95% CI [1.06, 1.37]). CONCLUSIONS: Our findings show that loneliness and social isolation coexisted with low health literacy and high treatment burden in individuals with CVD. These findings are critical as socially disconnected individuals experience more health issues. Low health literacy and a high treatment burden may potentially exacerbate these issues.

Burden of Topical Treatments in Psoriasis and Preferred Criteria of Choice: A Survey-Based Evaluation of Patients in Europe.

INTRODUCTION: Topical treatments (TT) are widely used in psoriasis management. While psoriasis itself has been associated with diminished quality of life and mental well-being, the impact of TT remains underexplored. This study aimed to evaluate the burden of TT on the daily lives of patients with psoriasis, the convenience of the TT, and the choice criteria. METHODS: Patients were recruited across five countries (France, Germany, Italy, Spain, UK) by Wefight and the International Federation of Psoriasis Associations (IFPA) to complete a 29-item online survey. RESULTS: A total of 766 patients completed the survey (54% female, mean age of 53 years). The mean body surface area covered by psoriasis was 7%, predominantly on the scalp and elbows. Participants had been living with psoriasis for a mean duration of 18 years. Of the respondents, 34% reported feeling affected by their TT in their daily routines and activities. Those feeling affected were more likely to have a more complex disease, be using more treatments, or be diagnosed more recently compared to those less affected. Among those most affected by their TT, 27% reported a strong impact on mental health, 30% on sexual life, and 25% on physical activities, compared to 7%, 6% and 4% in those least affected, respectively. Both cohorts considered tolerability factors such as "does not cause itching/burning" and "good tolerability" as most important when choosing a topical. However, only least affected participants regarded convenience factors such as "does not run off," "ease of application," "does not leave stains" among others equally as important. CONCLUSION: Overall, one-third of patients report a significant burden of TT on their daily lives. These patients have different criteria of choice, highlighting the importance of communication between physicians and patients to tailor treatment to individual preferences, thereby enhancing adherence and treatment outcomes.

Perceived burden of respiratory physiotherapy in people with cystic fibrosis taking elexacaftor-tezacaftor-ivacaftor combination: a 1-year observational study.

BACKGROUND: To limit the progression of disease, people with cystic fibrosis (pwCF) perform daily respiratory physiotherapy, which is perceived as the most burdensome routine in managing their condition. The elexacaftor-tezacaftor-ivacaftor (ETI) combination has changed respiratory management. OBJECTIVE: To investigate how the perceived treatment burden changed in 1 year of treatment with ETI. DESIGN: Prospective observational study. METHODS: Ad hoc questionnaires for the pwCF and for the caregivers of pwCF < 18 years were administered before the initiation of ETI therapy and then at 6-12 months. The Cystic Fibrosis Questionnaire-Revised (CFQ-R) and the Sinonasal Outcome Test (SNOT-22) were administered to explore disease-related symptoms and social limitations. The International Physical Activity Questionnaire was used to determine levels of physical activity. Mixed-effect models were fitted to explore whether the time engaged in respiratory physiotherapy changed during 1 year. RESULTS: The study included 47/184 pwCF aged 21.4 (5.7) years, who completed 1 year of ETI therapy. At 6 months, time on aerosol therapy was decreased by 2.5 (95% CI -32.9 to 27.8) min/day, time on airway clearance therapies (ACTs) was decreased by 8.8 (95% CI -25.9 to 8.3) min/day, and time for cleaning and disinfecting respiratory equipment was decreased by 10.6 (95% CI -26.5 to 5.3) min/day. At 1 year, gains in time saved were nearly 15 min/day on average. At 1 year, 5/47 (10.6%) pwCF reported that they had discontinued positive expiratory pressure mask. CONCLUSION: PwCF on ETI may note less time engaged in their daily respiratory physiotherapy routine. Nonetheless, aerosol therapy, ACTs and maintaining respiratory equipment were still perceived as time-consuming daily activities.

Understanding the challenges of respiratory physiotherapy in individuals with cystic fibrosis using triple therapy: a one-year study.In order to slow down the progression of their disease, people with cystic fibrosis typically do daily respiratory physiotherapy, which they find to be the most challenging part of managing their condition. The elexacaftor-tezacaftor-ivacaftor combination has changed how they manage their respiratory health. We wanted to see how the perceived difficulty of the treatment changed over one year of using elexacaftor-tezacaftor-ivacaftor. We gave questionnaires to people with cystic fibrosis and to their caregivers before they started the triple therapy and again at 6-12 months. We also used two international questionnaires to learn about symptoms and social limitations related to the disease. The International Physical Activity Questionnaire helped us understand their physical activity levels. We used statistical models to see if the time spent on respiratory physiotherapy changed over the year. Our study involved 47 individuals with cystic fibrosis, with an average age of 21 years, who completed one year of elexacaftor-tezacaftor-ivacaftor therapy. After 6 months, time spent on aerosol therapy decreased by 2.5 minutes per day, time on airway clearance therapies decreased by 8.8 minutes per day, and time for cleaning respiratory equipment decreased by 10.6 minutes per day. By the end of the year, they were saving almost 15 minutes per day on average. At one year, 5 out of 47 said they had stopped using the positive expiratory pressure mask. People with cystic fibrosis using elexacaftor-tezacaftor-ivacaftor may find that they spend less time on their daily respiratory physiotherapy routine. However, activities like aerosol therapy, airway clearance therapies, and maintaining respiratory equipment were still seen as time-consuming.

Determinants of hyperparathyroidism in children after kidney transplantation.

INTRODUCTION: Hyperparathyroidism (HPT) can contribute to metabolic bone disease following kidney transplantation. We evaluated post-transplant trends in intact parathyroid hormone (iPTH) and determined predictors of HPT in pediatric kidney transplant (KTx) recipients. METHODS: In this single-center study, retrospective data were collected on 88 children from 2013 to 2019. Data collected included dialysis vintage, biochemical parameters, post-transplant trends in iPTH, 25(OH)Vitamin D levels and estimated glomerular filtration rate (eGFR ml/min/1.73 m2 ). Pre-transplant treatment for HPT was quantified with a Treatment Burden score (TB, score range: 0-100). After log-transforming skewed variables (iPTH and eGFR), multivariable linear regression was performed to determine predictors of log {iPTH} at 6 and 36 months (mo) post-transplant. RESULTS: Median age was 12.8 (range: 1.9-20.5) years, and dialysis vintage was 11.2 (range: 0.0-112.9) months. The majority were of Hispanic and African Ancestry (77.3%). Median post-transplant iPTH was 69.5 (range: 1.8-306.8) pg/ml at 6 mo with a gradual downward trend to 59.0 (range: 28.0-445.0) pg/ml at 36 mo. Significant multivariable predictors of higher log {iPTH} post-transplant included longer dialysis vintage, higher TB, and lower log{eGFR} at 6 mo, and higher TB, lower log{eGFR}, and deceased donor transplant at 36 mo. CONCLUSIONS: Recognition of risk factors for HPT and monitoring iPTH post-transplant may facilitate timely interventions to mitigate cardiovascular and bone disease in pediatric KTx recipients. KEY MESSAGE: Describe serial trends in intact PTH after kidney transplantation. Pre- and post-transplant factors that contribute to persistence or re-occurrence of hyperparathyroidism after kidney transplantation in children include longer dialysis vintage, high pre-transplant treatment burden and decreased post-transplant GFR. Recognition of these factors, and monitoring intact PTH after kidney transplantation, could facilitate timely interventions to mitigate cardiovascular and bone disease in children.

Exploring treatment burden in people with type 2 diabetes mellitus: a thematic analysis in china's primary care settings.

BACKGROUND: Understanding treatment burden is a critical element to the effective management of Type 2 Diabetes Mellitus (T2DM). The current study aims to address the knowledge gap surrounding treatment burden of T2DM from the patient's perspective in China's primary care settings. METHODS: A narrative review informed the creation of an a priori coding structure to identify aspects of T2DM treatment burden. Focus groups were conducted, employing a maximum variation sampling strategy to select participants from diverse sociodemographic backgrounds across urban, suburban, rural, and remote areas in China. Participants included adults with T2DM care in primary care settings for over a year and a Treatment Burden Questionnaire score of 25 or higher. Deductive thematic analysis, guided by the coding structure, facilitated a comprehensive exploration and further development of the conceptual framework of T2DM treatment burden. RESULTS: Four focus groups, each comprising five participants from diverse areas, were conducted. Utilising the Cumulative Complexity Model and Normalisation Process Theory as theoretical underpinnings, the thematic analysis refined the conceptual framework based on the coding structure from the narrative review. Five key themes were refined, encompassing medical information, medication, administration, healthcare system, and lifestyle. Additionally, the financial and time/travel themes merged into a new theme termed "personal resources", illustrating their overlapping within the framework. Participants in these focus groups highlighted challenges in managing medical information, an aspect often underrepresented in prior treatment burden research. The thematic analysis culminated in a finalised conceptual framework, offering a comprehensive understanding of the treatment burden experiences of people with T2DM in China's primary care settings. This framework includes six key constructs, delineating T2DM treatment burden and associated factors, such as antecedents and consequences. CONCLUSIONS: This study provides insights into the treatment burden of T2DM. A conceptual framework was finalised to deepen the understanding of the multifaceted constructs and the nature of treatment burden in people with T2DM. Furthermore, it emphasises the need to tailor T2DM treatment to individual capacities, considering their personal resource allocation and treatment utilisation.

Above and Beyond Number of Illnesses: A Two-Sample Replication of Current Approaches to Depressive Symptoms in Multimorbidity.

OBJECTIVES: To expand current models of depressive symptoms in older adults with multimorbidity (MM) beyond the number of illnesses as a predictor of worsened mental health. METHODS: Two-sample replication study of adults ≥62 years old with ≥ two chronic illnesses, who completed validated questionnaires assessing depressive symptoms, and disease- and treatment-related stressors. Data were analyzed using hierarchical linear regression. RESULTS: The model of cumulative number of illnesses was worse at explaining variance in depressive symptoms (Sample 1 R2 = .035; Sample 2 R2 = .029), compared to models including disease- and treatment-related stressors (Sample 1 R2 = .37; Sample 2 R2 = .47). Disease-related stressors were the strongest factor associated with depressive symptoms, specifically, poor subjective cognitive function (Sample 1: b = -.202, p = .013; Sample 2: b = -.288, p < .001) and greater somatic symptoms (b = .455, p < .001; Sample 2: b = .355, p < .001). CONCLUSIONS: Using the number of illnesses to understand depressive symptoms in MM is a limited approach. Models that move beyond descriptive relationships between MM and depressive symptoms are needed. CLINICAL IMPLICATIONS: Providers should consider the role of somatic symptom management in patients with MM and depressive symptoms.

European Unmet Needs in the Management of Neovascular Age-Related Macular Degeneration in Daily Practice: Data from the Fight Retinal Blindness! Registry.

PURPOSE: To evaluate the proportion, predictors, and outcomes of patients with neovascular age-related macular degeneration (nAMD) treated with a high burden of VEGF inhibitor intravitreal (IVT) injections after 2 years in routine clinical practice. DESIGN: Retrospective analysis of data from a prospectively designed observational outcomes registry, the Fight Retinal Blindness! Project, of patients treated in European centers. PARTICIPANTS: Treatment-naïve eyes (1 eye per patient) starting VEGF inhibitors for nAMD from January 2017 to March 2020 with 24 months of follow-up. We analyzed the following 3 treatment-burden groups defined by the mean interval of the 3 closest injections to the 24-month visit: (1) those with a high-treatment burden had injection intervals ≤ 42 days, (2) those with a low-treatment burden had injection intervals between 43 and 83 days; and (3) those with tolerable treatment burden had injection intervals between 84 and 365 days. METHODS: Multinomial regression was used to evaluate baseline risk predictors of patients requiring a high-treatment burden. MAIN OUTCOME MEASURES: The proportion of patients that experienced a high-treatment burden at 2 years and its predictors. RESULTS: We identified 2038 eligible patients completing 2 years of treatment (2038/3943 patients [60%]) with a median (quartile 1, quartile 3) of 13 (10, 17) injections. The proportion of patients with a high-treatment burden was 25% (516 patients) at 2 years. Younger patients (odds ratio [OR], 0.97; 95% confidence interval [CI], 0.96-0.99; P < 0.01) were more likely to have high-treatment burden, whereas eyes with type 3 choroidal neovascular lesions at baseline were significantly less likely (OR, 0.26; 95% CI, 0.13-0.52; P < 0.01). Regarding type of fluid, patients with subretinal fluid only at baseline (OR, 3.85; 95% CI, 1.34-11.01; P = 0.01) and persistent active intraretinal (OR, 1.56; 95% CI, 1.18-2.06; P < 0.01) or subretinal fluid only (OR, 2.21; 95% CI, 1.52-3.21; P < 0.01) after the loading phase had a higher risk of high treatment burden at 2 years. CONCLUSIONS: High treatment burden is a common issue in routine clinical practice in Europe, with a quarter of patients requiring injections of conventional VEGF inhibitors every 6 weeks at 2 years and 40% discontinuing treatment within 2 years. FINANCIAL DISCLOSURE(S): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.

Intravitreal Aflibercept for Neovascular Age-Related Macular Degeneration Beyond One Year of Treatment: AZURE, a Randomized Trial of Treat-and-Extend vs. Fixed Dosing.

INTRODUCTION: AZURE was a 76-week, randomized, open-label, parallel-group, phase IIIb noninferiority study comparing the efficacy and safety of intravitreal aflibercept (IVT-AFL) in a treat-and-extend (T&E) regimen with fixed dosing in patients with neovascular age-related macular degeneration (nAMD) previously receiving IVT-AFL for ≥ 1 year. METHODS: Patients were aged ≥ 51 years and had completed ≥ 1 year of IVT-AFL treatment prior to enrollment (IVT-AFL once per month [- 1 or + 2 weeks] for 3 months followed by IVT-AFL every 2 months [6-12 weeks]). Patients were randomly assigned (1:1) to receive IVT-AFL 2 mg in either a T&E (minimum treatment interval of 8 weeks with no upper limit, adjusted according to functional and anatomic outcomes, as assessed by the investigator; n = 168), or a fixed dosing regimen (treatment every 8 weeks [± 3 days]; n = 168). The primary endpoint was best-corrected visual acuity (BCVA) change from baseline to week (W) 52. The key secondary endpoint was the proportion of patients maintaining vision (< 15-letter loss) at W52. RESULTS: The full analysis set comprised 332 patients (T&E: n = 165; fixed dosing: n = 167). Mean BCVA change (baseline to W52) was - 0.3 ± 7.5 vs. - 0.5 ± 8.4 letters (T&E vs. fixed dosing; least-squares mean difference [95% CI]: 0.22 [- 1.51 to 1.96] letters; P < 0.0001 for noninferiority test [5-letter margin]). From baseline to W52, 95.2% (T&E) and 94.0% (fixed dosing) of patients maintained vision. Mean central subfield thickness change from baseline to W52 was - 24 ± 55 (T&E) and - 33 ± 47 (fixed dosing) µm. Last treatment interval to W76 was ≥ 12 weeks for 37.0% of T&E patients. No new safety signals were identified. CONCLUSION: IVT-AFL T&E can achieve similar functional and anatomic outcomes to fixed dosing every 8 weeks over 52 weeks in patients with nAMD who have completed ≥ 1 year of treatment, while reducing treatment burden. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02540954.

Translation, cross-cultural adaptation and validation of the Arabic multimorbidity treatment burden questionnaire (MTBQ-A): A study of adults with multimorbidity.

BACKGROUND: Studies internationally have found that a high treatment burden is associated with several long-term conditions and poor quality of life. OBJECTIVES: To translate, culturally adapt, and provide evidence of reliability, validity, and factor structure of the Multimorbidity Treatment Burden Questionnaire for use among Arabic-speaking adults with multimorbidity. METHODS: Standard guidelines for the cross-cultural adaptation of self-report measures were followed. The original 10-item MTBQ was translated into Arabic by professional translators using forward-backward translation. An expert group, including the creator of the MTBQ, participated in the cultural adaptation and content validity, followed by cognitive interviewing and pilot testing. The questionnaire was then tested on 177 Arabic-speaking patients with multimorbidity recruited from community pharmacies in the United Arab Emirates. The distribution of responses, dimensionality, internal consistency reliability, and construct validity were examined. RESULTS: The content validity of the MTBQ-A was good (Content Validity Index = 0.94), and cognitive interviews found that the items were well understood. The scale showed positive skewness and high floor effects. Factor analysis supported a two-dimensional structure (factor loadings >0.4): factor one was named "Self-management and social support," and factor two was named "Burden of visiting health care services and health care professionals". The questionnaire had good internal consistency (α = 0.83). As predicted, a higher MTBQ score in both factors was associated with poor health-related quality of life in all dimensions: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression (p values < 0.05); and negatively correlated with self-efficacy in taking medication (p < 0.01) and in learning about medication (p < 0.01). CONCLUSIONS: The Arabic MTBQ is a valid and reliable measure of treatment burden with good construct validity and internal consistency. This easy-to-understand questionnaire can be used to assess the perceived treatment burden among Arabic-speaking patients with multimorbidity.

Patient-Centred, Technology-Based Interventions for High Treatment Burden: An Overview of the State of the Art.

This study provides an overview of recent efforts to develop technology-based interventions for patients with high treatment burden. Adoption of a technological intervention for high treatment burden will depend on a range of factors, including: the reliability and accessibility of the technology, patient factors including age, socio-economic factors, technology literacy, overall health status and personal priorities - as well as the perceived benefits provided by the technology intervention, from the perspectives of both patients and clinicians.

Geriatric assessment-derived deficit accumulation and patient-reported treatment burden in older adults with bladder cancer.

BACKGROUND: When a person's workload of healthcare exceeds their resources, they experience treatment burden. At the intersection of cancer and aging, little is known about treatment burden. We evaluated the association between a geriatric assessment-derived Deficit Accumulation Index (DAI) and patient-reported treatment burden in older adults with early-stage, non-muscle-invasive bladder cancer (NMIBC). METHODS: We conducted a cross-sectional survey of older adults with NMIBC (≥65 years). We calculated DAI using the Cancer and Aging Research Group's geriatric assessment and measured urinary symptoms using the Urogenital Distress Inventory-6 (UDI-6). The primary outcome was Treatment Burden Questionnaire (TBQ) score. A negative binomial regression with LASSO penalty was used to model TBQ. We further conducted qualitative thematic content analysis of responses to an open-ended survey question ("What has been your Greatest Challenge in managing medical care for your bladder cancer") and created a joint display with illustrative quotes by DAI category. RESULTS: Among 119 patients, mean age was 78.9 years (SD 7) of whom 56.3% were robust, 30.3% pre-frail, and 13.4% frail. In the multivariable model, DAI and UDI-6 were significantly associated with TBQ. Individuals with DAI above the median (>0.18) had TBQ scores 1.94 times greater than those below (adjusted IRR 1.94, 95% CI 1.33-2.82). Individuals with UDI-6 greater than the median (25) had TBQ scores 1.7 times greater than those below (adjusted IRR 1.70, 95% CI 1.16-2.49). The top 5 themes in the Greatest Challenge question responses were cancer treatments (22.2%), cancer worry (19.2%), urination bother (18.2%), self-management (18.2%), and appointment time (11.1%). CONCLUSIONS: DAI and worsening urinary symptoms were associated with higher treatment burden in older adults with NMIBC. These data highlight the need for a holistic approach that reconciles the burden from aging-related conditions with that resulting from cancer treatment.

Profiles of financial toxicity and influencing factors among cancer patients: A latent profile analysis.

BACKGROUND: While cancer treatment has improved patient prognosis, it has also become more costly. The high hospitalization expenses for cancer patients place a significant financial burden on individuals, families, and society. OBJECTIVES: To identify the potential categories and characteristics of Financial Toxicity (FT) among cancer patients and explore the associated influencing factors. METHODS: A cross-sectional study was conducted on 299 cancer patients in southwest China from February 2023 to May 2023(response rate 96.45 %). FT was measured by Financial Toxicity based on Patient-Reported Outcome Measures (COST-PROM), emotional inhibition was measured by the emotional inhibition scale (EIS), and treatment burden was measured by the Treatment Burden Questionnaire (TBQ). We used latent profile analysis (LPA) by Mplus.8.0 to identify latent classes of the FT. Multinomial logistic regression analysis was used to analyze the relevant factors on the different categories. RESULTS: The FT of cancer patients can be identified into 3 groups: high-level (43.1 %), medium-level (36.1 %), and low-level (20.7 %) groups. Literacy, annual household income, health problem dimension scores, verbal inhibition scores, and self-control scores can be the predictors of FT among different profiles. CONCLUSIONS: Our findings may provide a new viewpoint for managing FT among cancer patients. Healthcare providers should pay attention to the FT of cancer patients and develop targeted interventions to reduce their FT levels.

Medicine burden experiences of people living with HIV and association with stigma.

The medicine burden of people living with HIV (PLWH) is unknown. Between 2018 and 2020, participants completed a survey comprising outcome measures for medicine burden (LMQ-3) and stigma experiences (SSCI-8). Participants were HIV+ adults (≥18 years), using antiretrovirals (ARV) with or without non-ARV medicines, recruited via two outpatient clinics in southeast England and online via HIV charities across the UK. Spearman's correlations between medicine burden levels and stigma scores were calculated. Participants were mostly males (72%, 101/141) of mean (SD) age 48.6 (±12.31) years. Total number of medicines ranged from 1-20. High medicine burden was self-reported by 21.3% (30) and was associated with polypharmacy (≥ 5 medicines) (101.52 Vs 85.08, p = 0.006); multiple doses versus once daily regimes (109.31 Vs 85.65, p = 0.001); unemployment (98.23 Vs 84.46, p = 0.004); and ethnicity (97 Vs 86.85, p = 0.041 for non-White versus White participants). A correlation between medicine burden and stigma was observed (r = 0.576, p < 0.001). The LMQ-3 demonstrated adequate construct validity and reliability (domain loadings ranging 0.617-0.933 and Cronbach's α of 0.714-0.932). Assessment of medicine burden and psychosocial stigma in PLWH could enable identification of those needing additional support in future research and practice.