Improvements In HRQoL Research Articles

QOL-08. HEALTH-RELATED QUALITY-OF-LIFE (HRQOL) IN ADULTS AND CHILDREN WITH NEUROFIBROMATOSIS TYPE 1-ASSOCIATED PLEXIFORM NEUROFIBROMA (NF1-PN) TREATED WITH MIRDAMETINIB: PIVOTAL, PHASE 2B RENEU TRIAL

Abstract Patients with NF1-PN experience pain and other symptoms that negatively impact functioning and quality-of-life. We present patient- and parent proxy-reported HRQoL outcomes from ReNeu (NCT03962543), a pivotal, phase 2b trial of mirdametinib, an investigational MEK1/2 inhibitor, in adults and children (≥2 y) with NF1-PN causing morbidities. Fifty-eight adults and 56 children received mirdametinib (2 mg/m2 BID; 3-weeks-on/1-week-off, 28-d cycles). Change in HRQoL was assessed by Pediatric QoL Inventory (PedsQL) 4.0 Generic Core Scales from baseline across the 24-cycle treatment phase; change from baseline at Cycle 13 (C13) was a prespecified secondary endpoint. PedsQL is a HRQoL measure for adults and children with a Total Score (TS) and 4 subscales: physical, emotional, social, and school/work. Items are reported on a 0-100 scale (higher scores=better HRQoL). Clinically meaningful improvement was defined as change from baseline >9.7 points for adults, >8.5 points for child self-report, and >9.0 points for parent proxy-report. PedsQL-TS improvement (least-squares mean, LSM [SE] change) from baseline at C13 was 3.9 (1.6; P=.018; n=34) for adults, 4.0 (2.4; P=.096; n=38) for children by self-report, and 5.6 (1.9; P=.005; n=43) by parent proxy-report. PedsQL-TS improvements for adults and children by parent proxy-report (not by children self-report) were observed early (at C5 and C3, respectively) and sustained through C24. Clinically meaningful improvement in PedsQL-TS from baseline at C13 was achieved by 37% (10/27) adults, 45% (13/29) children by self-report, and 47% (15/32) children by parent proxy-report (among patients who could have achieved a clinically meaningful change from baseline). Significant (P<.05) improvement from baseline to C13 was reported for physical (adults, children, and parent proxy-report), school/work (adults), and emotional and social (parent proxy-report) subscales. Adults and children (by parent proxy-report) with NF1-PN had clinically meaningful, early, and sustained improvement in HRQoL over the course of mirdametinib treatment.

Improvement in health-related quality of life questionnaires with biologic treatment in severe asthma and comorbid chronic rhinosinusitis with or without nasal polyposis: a real-life experience.

Patients with severe asthma frequently have comorbid chronic rhinosinusitis (CRS) with or without nasal polyps, that can increase the symptom burden and complicate treatment. Real-life clinical data on the impact of biologic treatments on CRS-specific quality-of-life questionnaires are still lacking. In this retrospective real-life study, we collected data from patients with severe asthma with comorbid CRS with/without nasal polyposis at baseline, and after 3, 6 and 12 months of treatment with omalizumab, mepolizumab, benralizumab or dupilumab. In particular, we evaluated improvements in HRQoL as measured by SinoNasal Outcome Test-22 (SNOT-22, 0 - 110), Visual Analog Scale symptom scores (VAS, 0-10), and Asthma Control Test (ACT, 5-25) and the proportion of patients meeting the minimal clinically important difference (MCID). Disease-specific HRQoL, as measured by SNOT 22 and VAS score improved in all patients at 3, 6, and 12 months of treatment compared with baseline (SNOT-22: 14, IQR: 0-52 vs 10, IQR:0-30 vs 0, IQR:0-15 vs 0, IQR:0-12, p < 0.001, VAS score: 1, IQR: 0-5 vs 0, IQR:0-3 vs 0, IQR:0-2 vs 0, IQR 0-1, p < 0.001). After 3 months of treatment >80% of patients reached the MCID for ACT, while only patients on dupilumab showed to reach a MCID in 100% of cases. The effect size depended upon the symptom burden at baseline. The study confirms the efficacy of omalizumab, mepolizumab, benralizumab, and dupilumab in a real-life setting, with a rapid improvement in CRS-specific HRQoL and general health status. These data highlight the importance of targeting type 2 inflammation in asthmatic patients with co-existing upper and lower airways disease.The Authors disclose that preliminary data and analysis of the present study have been presented in abstract form during the "X International Workshop on Lung Health - Respiratory Disease and Immune Response", held in Nice on 19-21 January 2023.

Patient- vs Physician-Initiated Response to Symptom Monitoring and Health-Related Quality of Life

Online symptom monitoring through patient-reported outcomes can enhance health-related quality of life and survival. However, widespread adoption in clinical care remains limited due to various barriers including the need to reduce health care practitioners' workload. To report the effects of patient-reported outcome (PRO) symptom monitoring on HRQOL and survival up to 1 year after initiation of any treatment in patients with lung cancer. SYMPRO-Lung is a multicenter stepped-wedge cluster randomized trial including patients with stage I to IV lung cancer. The inclusion period was from October 24, 2019, until September 16, 2021, and data collection ended October 8, 2022. Data analysis was conducted from November 9, 2023, until March 18, 2024. Patients in the intervention group reported PRO symptoms weekly using the Patient Reported Outcomes version of the Common Toxicity Criteria for Adverse Events lung cancer subset. If symptoms exceeded a validated threshold, an alert was sent to the health care practitioner (active intervention subgroup) or to the patient (reactive intervention subgroup). Patients in the control group received standard care. Health-related quality of life was measured by the European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire at baseline, 15 weeks (T1), 6 months (T2), and 1 year (T3), with the summary score (SS) and physical functioning (PF) as primary end points. Linear mixed-effects modeling was used to assess mean differences over time. Effect size (ES) of 0.40 or greater was considered clinically relevant. Cox proportional hazards regression survival analyses were performed to estimate the effect of the intervention on progression-free survival and overall survival (OS). Data were analyzed on an intention-to-treat basis. A total of 515 patients (266 [51.7%] men; mean [SD] age, 65.4 [9.4] years) were included in the study (266 in the control group; 249 in the pooled intervention group). Most baseline characteristics were balanced between groups; however, the most notable exception was the distribution in cancer staging: the intervention group had a higher proportion of patients with stage IV cancer compared with the control group (139 [56%] vs 118 [44%]). The pooled intervention group had a significantly better SS (mean difference T1, 5.22; 95% CI, 2.72-7.73; P < .001; ES = 0.33; mean difference T2, 6.28; 95% CI, 3.65-8.92; P < .001; ES = 0.40; mean difference T3, 3.97; 95% CI, 1.15-6.80; P = .006; ES = 0.25) compared with the control group. Group differences improved more in PF but did not meet the ES greater than or equal to 0.40 threshold (mean difference T1, 7.00; 95% CI, 3.65-10.35; P < .001; ES = 0.27; mean difference T2, 6.79; 95% CI, 3.26-10.31; P < .001; ES = 0.26; mean difference T3, 5.01; 95% CI, 1.23-8.79; P = .009; ES = 0.19). No significant differences in HRQOL were observed between the reactive (n = 89) and active (n = 160) intervention groups. The HR for progression-free survival for the active intervention group compared with the control group was 0.78 (95% CI, 0.58-1.04); the finding was not statistically significant. The HR for overall survival for both interventions groups compared with the control group were not statistically significant.(active: HR, 0.80; 95% CI, 0.55-1.15; reactive: HR, 0.69; 95% CI, 0.42-1.15). In this 1-year follow-up of a stepped-wedge cluster randomized trial, PRO symptom monitoring yielded improvements in long-term HRQOL in patients with lung cancer. The reactive approach proved equally effective as the active approach. A nonsignificant potential survival benefit was observed for the intervention group. These positive results provide further evidence for the usefulness of routine PRO symptom monitoring in lung cancer care. The Netherlands trial register Identifier: NL7897.

Changes in COPD-related anxiety symptoms during pulmonary rehabilitation: a prospective quantitative and qualitative study.

Fear-avoidance in COPD can have detrimental effects on pulmonary rehabilitation (PR) outcomes and is therefore important to address. This prospective study examined changes in and management of COPD-related anxiety symptoms over the course of a PR program. Patients with COPD referred to 9-weeks of PR in the municipality of Vejle, Denmark from January to December 2022 completed a six-minute walk test (6MWT) and the following questionnaires, both before and after PR: COPD Anxiety Questionnaire 20-item version (CAF-R), measuring COPD-related anxiety; COPD Assessment Test (CAT), measuring COPD-related disability; 12-Item Short-Form Health Survey (SF-12), measuring health-related quality of life (HR-QoL); sociodemographic and disease-related information. After PR, a subsample of the patients took part in semi-structured interviews exploring their understanding of how they managed COPD-related anxiety during PR. Pre- and post-assessment of COPD-related anxiety and other PR outcomes were analysed with t-tests and correlation analyses. Qualitative interviews were analysed using a thematic analysis approach. A total of 72 patients with COPD (mean ± SD age 71 ± 8, 53% female) were included in the study, and 13 took part in qualitative interviews. A significant decrease in COPD-related anxiety was observed from before to after PR, corresponding to a small effect size (Cohen's d = 0.32; p = 0.018). Reductions in COPD-related anxiety were not associated with improvements in COPD-related disability, HR-QOL, or functional exercise capacity. The qualitative findings identified four anxiety management strategies, i.e., "planning", "problem-solving", "accepting", and "confronting", which were influenced by interactions with healthcare professionals and co-patients as well as patients' own perception. COPD-related anxiety symptoms was reduced after PR, potentially through the use of various management strategies. The strategies appeared to be influenced by interactional factors during the PR program.

P50 Increasingly Stringent Clinical Responses and the Association with Improvements in Pain, HRQoL, and Work Productivity in Patients with Hidradenitis Suppurativa: 16-Week Results from Phase 3 Studies BE HEARD I&II

P50 Increasingly Stringent Clinical Responses and the Association with Improvements in Pain, HRQoL, and Work Productivity in Patients with Hidradenitis Suppurativa: 16-Week Results from Phase 3 Studies BE HEARD I&II

Population-level norm values by EQ-5D-3L in Hungary - a comparison of survey results from 2022 with those from 2000

PurposeAlthough population norms of the EQ-5D-3L instrument had been available in Hungary since 2000, their evaluation was based on a United Kingdom (UK) value set. Our objective was to estimate the population norms for EQ-5D-3L by using the new Hungarian value set available since 2020, to extend the scope to adolescents, and to compare with norms from 2000.MethodsA cross sectional EQ-5D-3L survey representative of the Hungarian population was conducted in 2022. The EQ-5D-3L dimensional responses were analyzed by age and sex and compared with the survey from 2000, by estimating population frequencies with their 95% confidence intervals; index values were evaluated by both value sets.ResultsAltogether, 11,910 respondents, aged 12 or more (578 between 12 and 17), completed the EQ-5D-3L. There was a notable improvement in reporting problems for both sexes (age 35–64) regarding the pain/discomfort and anxiety/depression compared to 2000. Below the age 44, both sexes had an EQ-5D-3L index plateau of 0.98, while above the age 55, men tended to have numerically higher index values compared to women, with the difference increasing with older age. Improvement in dimensional responses were also translated to numerically higher index values for both sexes between ages 18 and 74 compared to 2000. Multivariate regression analysis showed that higher educational attainment, lower age, larger household size, and active occupational status were associated with higher index values.ConclusionOver the past 22 years, there was a large improvement in HRQoL of the middle-aged to elderly men and women in Hungary.

Health resource utilization expenditures in oncology within a virtual primary cancer survivor care clinic.

e13785 Background: Unprecedented cancer treatment efficacy has led to high rates of disease sequelae. Lancet recently declared the failure to care for the human dimensions of cancer treatment a "humanitarian crisis." To address this humanitarian crisis, real-world economic evidence can improve patient access to whole person care through insurance reimbursement policies. Methods: We implemented a virtual primary cancer survivor care clinic that follows ASCO and NCCN guidelines for cancer survivors with emphasis on mental health, nutrition, physical activity, and sleep optimization. Our clinic utilizes medical oncologists, physician associates, mental health therapists, registered dietitians, and occupational therapists. Patient reported outcomes (PRO) monitor health status and inform treatment pathways. To reduce test fatigue, we use the SF12 Vitality Enhanced scale (SF12v2). The SF12v2 measures physical functioning, activities of daily living, pain, vitality, social functioning, and mental health. Total medical expenditures (MEs) is the sum of payments for hospital inpatient events, emergency room visits, home care, prescribed medicines, office-based and out-patient visits, and medical equipment. Patient SF12v2 summary scores predict a patient's total MEs. A one-point better physical component summary score and mental component summary score are associated with 2% lower MEs; 3 and 5 point score increases are associated with 10% and 18% lower MEs. Results: Patients were referred from a Utah community oncology clinic, other medical clinics, or self-referred (N=99). The mean patient age was 52 years. 84% were female, 16% were male. At enrollment, 35% had started treatment, 21% were on post treatment aromatase therapy or adjuvant hormonal therapy, 65% were post treatment. Baseline PRO reveal significant disease burden: 82% report poor mental health; 72% report poor physical health; 79% report poor cognitive health; 83% report sleep disorders. For patients who completed at least three PRO measurement time points (n=54): 91% had a positive clinical outcome for mental health; 70% had a positive clinical outcome for physical health; 89% had a positive clinical outcome for cognitive health; 76% had a positive clinical outcome for sleep health. As a result of these extraordinary outcomes, 74% of patients had lower predicted MEs. The average predicted reduction in MEs was 16% with an average annual savings of $1,629.49. Conclusions: Cancer is associated with high disease sequelae and high MEs. We believe this is the first study that reports real-world clinical evidence and predicts MEs for patients enrolled in a virtual primary cancer survivor care clinic. Real-world evidence demonstrates both clinically significant improvements in HRQoL and reductions in patient MEs. These results can inform insurance reimbursement policies, ensuring equitable access to cancer survivor care.

EHealth mindfulness-based music therapy for patients undergoing allogeneic hematopoietic stem cell transplantation: A pilot randomized controlled trial protocol

BackgroundAllogeneic stem cell transplantation (allo-SCT) is the preferred therapy for patients with high-risk or relapsed hematologic malignancies, but may be complicated by psychological distress (e.g., depression, anxiety) and symptom burden (e.g., fatigue, pain). Mindfulness-based music therapy (MBMT), a relatively novel integrative medicine intervention that draws from mindfulness and music therapy principles, has shown promise in improving psychosocial outcomes and symptom burden in cancer patients. We outline an eHealth-based MBMT (eMBMT) intervention protocol examining: (1) feasibility, acceptability, and intended effects of eMBMT in improving HRQOL, symptom burden, and clinical markers of disease activity (e.g., infections), and (2) the extent to which eMBMT music therapy component-associated improvements in HRQOL, symptom burden, and disease activity are mediated by improvements in psychosocial and physiological (e.g., systemic inflammation, immune recovery) adaptation. MethodsParticipants (n = 60) with a hematologic malignancy undergoing allo-SCT will be randomized to receive eMBMT or an eHealth-based mindfulness meditation (eMM) intervention. eMBMT includes eight 60-min sessions facilitated by a music therapist focusing on mindfulness and music therapy. eMM includes eight 60-min self-led MM practices. ResultsFeasibility, acceptability, HRQOL, symptom burden, disease activity, and mediation effects of psychosocial and physiological adaptation will be assessed at baseline, pre-infusion, and post-engraftment with blood collection at baseline and post-engraftment. ConclusionThe current pilot RCT is the first eMBMT intervention to address the HRQOL and symptom burden of patients who are undergoing allo-SCT. Results will inform a fully powered RCT to establish preliminary efficacy of eMBMT on improvements in HRQOL, symptom burden, and disease activity.

Clinical and radiological outcomes of gradual reduction and circumferential fusion of high-grade spondylolisthesis in adolescents: a prospective cohort study of 29 young patients.

The objective of this study was to evaluate the safety and efficacy of a novel technique of formal reduction and circumferential fusion for pediatric high-grade spondylolisthesis (HGS). The safety and efficacy of formal reduction for high-grade spondylolisthesis (HGS) has never been thoroughly examined. This study reports the outcomes of 29 children with HGS who underwent a procedure of gradual reduction and circumferential fusion. 29 children (13 males, 16 females) were recruited between 2006 and 2010. Radiographic measurements (including % of slip, lumbosacral angle-LSA, pelvic incidence-PI, pelvic tilt-PT, sacral slope-SS, and proximal femoral angle-PFA) and quality of life assessment (SRS-22 questionnaire) were prospectively obtained at baseline and at the last post-operative follow-up (> 2years post-op). Radiological measurements were used to classify patients according to the Spine Deformity Study Group (SDSG) classification. Mean baseline slip % was 69.9 ± 16.5%. There were 13 patients with a balanced pelvic (SDSG Type 4) and 16 with an unbalanced pelvis (SDSG Type 5 and 6). On average, a reduction of 45.5 ± 15.3% (range 20-86%) was achieved safely with no major complication. In particular, of the 29 patients, only 3 had a L5 radiculopathy postoperatively that was self-resolved at follow-up. From a radiological standpoint, we observed a mean improvement of LSA from 80.3 ± 17.9° to 91.7 ± 13.6°. We also observed a statistically significant improvement in global HRQOL, and in the function and body image domains. This prospective study suggests that formal reduction of HGS followed by circumferential fusion is safe when using a standardized surgical technique based on gradual reduction. Performing this intervention could also help improve QOL in some patients.

Remission after CAR T-cell therapy: Do lymphoma patients recover a normal life?

Chimeric antigen receptor T cells (CAR T cells) can induce prolonged remission in a substantial subset of patients with relapse/refractory lymphoma. However, little is known about patients' life after CAR T-cell therapy. We prospectively assessed the multidimensional recovery of lymphoma patients in remission, before leukapheresis, before CAR T-cell infusion, and 3, 6, and 12 months thereafter. Validated tools were used to measure lymphoma-related and global health-related quality of life (HRQoL; Functional Assessment of Cancer Therapy-Lymphoma [FACT-Lym] and EQ-5D-5L), cognitive complaint (FACT-Cognition), fatigue (FACIT-Fatigue subscale), psychological status (Hospital Anxiety and Depression Scale, Post-Traumatic Check List Scale), and sexuality (Relationship and Sexuality Scale). Beyond 12 months of remission, we also surveyed physical, professional, sexual, and general life status. At 3, 6, and 12 months, 53, 35, and 23 patients were evaluable, respectively. Improvement in lymphoma-related HRQoL was clinically relevant at 3, 6, and 12 months with a mean change from baseline of 10.9 (95% confidence interval [CI]: 5.8; 16.1), 12.2 (95% CI: 4.2; 20.1), and 11.72 (95% CI: 2.06; 21.38), respectively. Improvement in global HRQoL, fatigue, and anxiety was clinically relevant, but 20%-40% of patients experienced persistent fatigue, psychological distress, and cognitive complaints over time. Beyond 12 months after CAR T cells, 81.8% of 22 evaluable patients were satisfied with their daily life. Physical activity, professional, sexual, and global well-being had returned to prediagnosis levels in nearly half of the patients. We found an improvement in HRQoL after CAR T-cell therapy including anxiety, depression, sexual satisfaction, and general well-being. However, not all patients recover a "normal life." Further research is needed to determine which patients are at risk of quality-of-life impairment to improve recovery after CAR T-cell infusion.

Improvements in the health-related quality-of-life benefit of cancer drugs approved in China, 2005–2020: an observational study

BackgroundHealth-related quality of life (HRQoL), along with overall survival (OS), is a critical study endpoint for measuring the clinical benefits of cancer drugs. Previous studies have examined the OS benefit of new cancer drugs approved in China. However, their HRQoL benefits have not been systematically evaluated. We aimed to characterise the measurement and improvement of HRQoL associated with cancer drugs approved in China. MethodsThis mixed-methods study comprises of a literature review and a cross-sectional study, including all antineoplastic agents approved in China between January 1, 2005 and December 31, 2020. A systematic search was conducted on December 31, 2023 to extract HRQoL information of identified drugs. We extracted information on the characteristics of HRQoL assessment and statistically significant HRQoL gains compared with the control treatment. FindingsA total of 64 novel cancer drugs, corresponding to 115 cancer indications, supported by randomised clinical trials were approved in China between 2005 and 2020. Among the indications, 78 (67·8%) used HRQoL as an endpoint in the pivotal trial. By December 31, 2023, after a median follow-up of 5·3 (range, 3·0-18·8) years from approval, HRQoL information was available for more than half of the indications (75, 65·2%). Thirty-three indications (28·7%) reported statistically significant improvement in HRQoL, with 22 (19·1%) also having documented OS benefit. Approximately one-third of the indications (39, 33·9%) showed no difference in HRQoL, with 21 (18·3%) having documented OS gains. Three indications (2·6%) reported worsening HRQoL. The most commonly used HRQoL measurements were individual disease-specific instruments (62 of 75, 82·7%) while the most frequently employed analysis metric was the mean change scores from baseline (56 of 75, 74·7%). InterpretationFewer than one-third of cancer indications approved in China had shown HRQoL improvements. There was considerable heterogeneity in the analysis and reporting of HRQoL benefits associated with new cancer drugs approved in China. These findings emphasise the important role of HRQoL evaluation and analysis in clinical research and the necessity of improving the standardization of HRQoL assessment. FundingNational Natural Science Foundation of China (72274004)

127 Durable Treatment of Painful Diabetic Neuropathy With 10 kHz Spinal Cord Stimulation

INTRODUCTION: Approximately 25% of people with diabetes experience painful diabetic neuropathy (PDN), but conventional medical management (CMM) is ineffective for many patients. We previously presented partial study results showing that high-frequency (10 kHz) spinal cord stimulation (SCS) provides substantial symptom relief. Here we report full study results through 24-month (24M) follow-up. METHODS: We conducted a multicenter RCT to evaluate 10 kHz SCS in PDN patients. Key study inclusion criteria were: PDN symptoms = 12M refractory to medications, lower limb pain intensity = 5cm (0-10 cm visual analog scale [VAS]), and hemoglobin A1c = 10%. Patients (n = 216) were randomized 1:1 to 10 kHz SCS plus CMM or CMM alone, with optional treatment crossover at 6M. RESULTS: Patients randomized to 10 kHz SCS experienced significantly greater pain relief at 6M than those treated with CMM alone (p &lt; 0.001). For all patients who received 10 kHz SCS, at 24M post-implantation the average pain relief was 80% from pre-implantation (p &lt; 0.001), and the treatment responder rate was 90%. Clinician-assessed sensory function showed significant improvements with 10 kHz SCS. At 6M, 59% of patients treated with 10 kHz SCS had sensory improvement versus 9% of those treated with CMM alone (p &lt; 0.001). At 24M, 10 kHz SCS improved sensory function for 65% of patients. Patients receiving 10 kHz SCS also experienced significant improvements in health-related quality of life (HRQoL, p &lt; 0.001). At 24M, the mean HRQoL improvement was 2.9-4.8 times the minimum clinically important difference for patients with type 2 diabetes. CONCLUSIONS: The results demonstrate that 10 kHz SCS provides significant, durable reductions in pain and improvements in sensory function and HRQoL. Sensory function improvements support the unique disease-modifying potential of 10 kHz SCS.

High Intensity Functional Training for Patients Diagnosed with Cancer: A Study Evaluating the Feasibility of a Pragmatic Intervention

Abstract Purpose To investigate the feasibility of a municipality-based 16-week group-based HIFT-program (e.g. CrossFit) as a part of the physical rehabilitation of cancer survivors at different stages of cancer treatment. Methods Non-randomised clinical feasibility study. Younger adult patients (age 18–44 years) diagnosed with cancer who were referred to rehabilitation between August 2019 to December 2019 were eligible for inclusion. The group-based HIFT intervention was designed as a 16-week program with two sessions weekly (1.25 h each). The intervention program was not developed with pre-defined progression in terms of gradually added resistance, intensity, or volume during the 16 weeks period but the physiotherapist leading the sessions was trained in scalability. Feasibility was evaluated as retention, adherence, and accrual rates. Data on quality of life and cancer-related fatigue were measured EORTC QLQ-C-30 and evaluated using paired t-tests or Wilcoxon signed-rank test. Results Eighty-three percent of the eligible patients were included and initiated the HIFT program. However, 25% of the patients were not adherent to the intervention and only 34% of the patients were still adherent to the intervention after 4 months. Nonetheless, a significant improvement in cancer specific HRQoL was found from baseline [Mean = 53.4, 95%CI (47.6, 59.1)] to the end of the intervention [Mean = 66.3, 95%CI (60.8, 71.9)]. Conclusion It is possible to recruit patients diagnosed with cancer to a municipality-based HIFT rehabilitation program, however, adherence to the intervention is found to be difficult for the majority of the patients.

Can Pharmacological Conditioning as an Add-On Treatment Optimize Standard Pharmacological Treatment in Patients with Recent-Onset Rheumatoid Arthritis? A Proof-of-Principle Randomized Clinical Trial.

Medication regimens using conditioning via variable reinforcement have shown similar or improved therapeutic effects as full pharmacological treatment, but evidence in patient populations is scarce. This proof-of-principle double-blind randomized clinical trial examined whether treatment effects in recent-onset rheumatoid arthritis (RA) can be optimized through pharmacological conditioning. After four months of standardized treatment (n = 46), patients in clinical remission (n = 19) were randomized to the Control group (C), continuing standardized treatment (n = 8), or the Pharmacological Conditioning (PC) group, receiving variable treatment according to conditioning principles (n = 11). After eight months, treatment was tapered and discontinued linearly (C) or variably (PC). Standard treatment led to large improvements in disease activity and HRQoL in both groups. The groups did not differ in the percentage of drug-free clinical remission obtained after conditioning or continued standard treatment. The PC group did show a larger decrease in self-reported disease activity (Cohen's d = 0.9) and a smaller increase in TNF-α levels (Cohen's d = 0.7) than the C group. During all phases, more differences between groups were found for the patients who followed protocol than for the intention-to-treat sample. Although the results are not conclusive, pharmacological conditioning may have some advantages in terms of disease progression and stability, especially during the conditioning phase, compared with standard clinical treatment. The effects may be particularly beneficial for patients who show a good initial response to increased medication dosages.

Effectiveness and Feasibility of Nonpharmacological Interventions for People With Parkinson’s Disease and Cognitive Impairment on Patient‐Centred Outcomes

Background: Cognitive impairment is common in Parkinson’s disease (PD) but has limited treatment options. Medication has shown some benefits but accompanied by risk of adverse events. We aimed to investigate effectiveness and feasibility of nonpharmacological interventions for people with PD and cognitive impairment on patient‐centred outcomes.Methods: Systematic searches of five databases (MEDLINE, Embase, CINAHL, PsycINFO and Web of Science) were performed for studies evaluating nonpharmacological interventions for people with PD and cognitive impairment, reporting health‐related quality of life, function (activities of daily living) or wellbeing outcomes, published up to 15 May 2023. Two reviewers independently assessed full‐text articles and one reviewer extracted data, with a second reviewer reliability checking all data extraction. Randomised controlled trials (RCTs) were synthesised through meta‐analysis using a random‐effects meta‐analysis with restricted maximum likelihood method pooled estimate and observational studies through narrative synthesis.Results: Eleven RCTs and three noncontrolled studies were included, studying a range of interventions: cognitive training, cognitive stimulation, cognitive rehabilitation, physical and cognitive exercise, goal management training, psychoeducation with mindfulness, broader rehabilitation programs and a psychological intervention. Feasibility was demonstrated. The majority showed effectiveness for their primary outcome. Meta‐analysis showed no significant improvement in HrQoL (seven RCTs: pooled effect, standardised mean difference, −0.20 [−0.57−0.18]) or function (four RCTs: 0.08 [−0.36, 0.52]), and wellbeing measurement was infrequent and indirect. Quality of evidence was judged as very low, limiting the conclusions drawn.Conclusion: Whilst nonpharmacological trials for cognitive impairment in PD have shown promise, we found no evidence of effectiveness on HrQoL, function or wellbeing. However, this is based on very low‐quality evidence from a small number of diverse studies, not powered for these outcomes. Feasibility of a range of interventions has been demonstrated in both PD‐mild cognitive impairment and PD‐dementia. There is a need for more robust, adequately powered studies.

Association between pulse width and health-related quality of life after electroconvulsive therapy in patients with unipolar or bipolar depression: an observational register-based study

Aims To examine the association between pulse width and HRQoL measured within one week after electroconvulsive therapy (ECT) and at six-month follow-up in patients with unipolar or bipolar depression. Methods This was an observational register study using data from the Swedish National Quality Registry for ECT (2011–2019). Inclusion criteria were: age ≥18 years; index treatment for unipolar/bipolar depression; unilateral electrode placement; information on pulse width; EQ-5D measurements before and after ECT. Multiple linear regressions were performed to investigate the association between pulse width (<0.5 ms; 0.5 ms; >0.5 ms) and HRQoL (EQ-5D-3L index; EQ VAS) one week after ECT (primary outcome) and six months after ECT (secondary outcome). Results The sample included 5,046 patients with unipolar (82%) or bipolar (18%) depression. At first ECT session, 741 patients (14.7%) had pulse width <0.5 ms, 3,639 (72.1%) had 0.5 ms, and 666 (13.2%) had >0.5 ms. There were no statistically significant associations between pulse width and HRQoL one week after ECT. In the subsample of patients with an EQ-5D index recorded six months after ECT (n = 730), patients receiving 0.5 ms had significantly lower HRQoL (−0.089) compared to <0.5 ms, after adjusting for demographic and clinical characteristics (p = .011). The corresponding analysis for EQ VAS did not show any statistically significant associations. Conclusion No robust associations were observed between pulse width and HRQoL after ECT. On average, significant improvements in HRQoL were observed one week and six months after ECT for patients with unipolar or bipolar disease, independent of the pulse width received.

Improvements in Patient-Reported Outcomes in Relapsed or Refractory Large B-Cell Lymphoma Patients Treated With Epcoritamab

BackgroundPatient-reported outcomes were evaluated in EPCORE NHL-1 in patients with relapsed or refractory (R/R) large B-cell lymphoma (LBCL) treated with epcoritamab monotherapy (NCT03625037). Materials and MethodsAdults with R/R CD20+ LBCL and ≥2 prior systemic antilymphoma therapies, including anti-CD20, completed the Functional Assessment of Cancer Therapy–Lymphoma (FACT-Lym) and EQ-5D-3L. A subgroup of patients provided additional feedback in one-on-one qualitative interviews. FACT-Lym and EQ-5D-3L score changes from baseline (CFB) to cycle 9 or end of treatment were interpreted using published minimally important differences (MID). ResultsIn total, 157 patients (88.5% with diffuse LBCL) were treated (median age, 64 years). In total, 70.7% had ≥3 prior treatments, 61.1% had primary refractory disease, and 82.8% were refractory to last systemic therapy. FACT-Lym scores exceeded MID thresholds: mean (SD) CFB were 4.4 (15.2), MID 3.0 to 7.0 (FACT-General); 5.9 (7.6), MID 2.9 to 5.4 (FACT-Lymphoma subscale); 8.4 (15.2), MID 5.5 to 11.0 (FACT-Trial Outcome Index); 10.3 (20.2), MID 6.5 to 11.2 (FACT-Lym total score). EQ-5D-3L index scores, 0.09 (0.20), MID 0.08, and EQ-VAS scores, 16.6 (22.8), MID 7.0, improved. In 20 qualitative interviews, 88.2% reported symptom improvements; 80.0% were “very satisfied” or “satisfied” with epcoritamab. ConclusionsR/R LBCL patients reported consistent, clinically meaningful improvements in symptoms and HRQoL and satisfaction with epcoritamab.

Association of baseline and changes in health related quality of life with mortality following myocardial infarction: multicentre longitudinal linked cohort study

Abstract Background/Introduction Health related quality of life (HRQoL) for patients following myocardial infarction (MI) is frequently impaired and often deteriorates. However, the association between HRQoL and clinical endpoints in patients with MI is unknown. Purpose To investigate the association of baseline and temporal changes in HRQoL with long term all-cause mortality following MI. Methods This nationwide longitudinal linked health record study includes individuals with MI admitted to 77 hospitals in England between 1st November 2011 and 24th June 2015 in the EMMACE-3 and -4 studies. Self-reported HRQoL was collected using the EuroQol EQ-5D-3L (EuroQOL Visual Analogue Scale (EQ-VAS) and EuroQOL 5-Dimensional Classification (EQ-5D)) instrument during hospitalisation and at 1, 6 and 12-months following hospital discharge. Flexible parametric and multilevel survival models estimated associations of baseline and change in HRQoL with long term all-cause mortality. Results Of 9,474 individuals with MI, 25% (2,360) were women and 22.5% (2,135) participants died during the 9 years follow up period (median 6.9 years). There was an improvement in HRQoL over 12 months following MI (baseline mean, mean increase: EQ-5D 0.76, 0.003 per month; EQVAS 69.0, 0.5 per month). Better HRQoL at baseline was inversely associated with mortality (HR 0.55, 95% CI 0.47-0.63) (Figure 1A). At baseline, problems with self-care (HR 1.73, 95% CI 1.56-1.92), mobility (1.65, 1.50-1.81), usual activities (1.34, 1.23-1.47) and pain/discomfort (1.34, 1.22-1.46), were associated with increased mortality (Figure 1A). Improvements in EQ-5D (HR 0.69, 95% CI 0.60-0.80), but not EQ-VAS reduced the risk of death (Figure 1B). Deterioration in mobility, pain/discomfort, usual activities and self-care over 12 months increased the risk of death (HR 1.43, 95% CI 1.31-1.58; 1.21, 95% CI 1.11-1.32; 1.20, 95% CI 1.10-1.32; 1.44, 95% CI 1.30-1.59, respectively) (Figure 1B). Conclusions For patients with MI, poor HRQoL at baseline, its dimensions and deterioration over time are associated with mortality. Measuring HRQoL in routine clinical practice could delineate an at-risk group for targeted interventions to improve prognosis.Figure 1

Patients’ experience and utilization patterns of diclofenac gel in Germany: a real-world study with a prospective longitudinal survey and a retrospective analysis of pharmacy data

Objective Describe and characterize treatment patterns, satisfaction, improvement in pain and functional impairment (health-related quality of life [HRQoL]) in users of over the counter (OTC) Voltaren gel diclofenac (VGD) 2.32% and 1.16% in a real-world setting. Methods This observational real-world German study had prospective and retrospective components. The prospective data were collected from electronic surveys completed by adults who purchased VGD to treat their musculoskeletal pain at baseline and 4 and 12 weeks after baseline. Retrospective data were from a 12-month (March 2019 to February 2020) abstraction from dispensing software platforms used in select German pharmacies. Results Surveys from 467 participants (mean age 60.8 years) were analyzed. Average pain severity at baseline was 6.0 on an 11-point Numeric Rating Scale (0 = no pain, 10 = worst possible pain), improving by 0.8 and 1.2 points at Weeks 4 and 12, respectively. Performance of functional activities (daily/physical/social activities and errands/chores) improved and the proportion of participants with at least moderate interference decreased at both follow-up timepoints. Retrospective analyses indicated that majority of patients receiving VGD (n = 95,085) were ≥65 years old (67.9%), had one dispensed tube (70.8%) and did not switch to another topical treatment (including other NSAIDs) (77.3%), and were co-prescribed at least one cardiovascular medication (74.3%). Conclusions This study provides the first real-world insights into OTC VGD use in Germany. The participants using VGD reported a decrease in pain severity and an improvement of HRQoL while under treatment, as well as resulting satisfaction with treatment. Patients infrequently switched to alternate topical therapies/NSAIDs.

A nurse-led multicomponent behavioral activation intervention for patients with atrial fibrillation: a randomized controlled trial

Abstract Funding Acknowledgements Type of funding sources: Public grant(s) – National budget only. Main funding source(s): Research Grants Committee of Hong Kong through the General Research Fund Introduction Patients with atrial fibrillation (AF) often play a passive role in the treatment decision-making process, rendering jeopardized health-related quality of life, suboptimal medication optimization and self-care. Purpose This study aimed to examine the effects of a Nurse-led Multicomponent Behavioral Activation (N-MBA) intervention on HRQoL, knowledge about AF, medication adherence and psychological distress among patients with AF. Methods This parallel two-arm randomized controlled trial recruited community-dwelling patients aged ≥65 years with a confirmed diagnosis of atrial fibrillation, moderate to high risk of stroke but not receiving oral anticoagulation. Participants were randomized in a 1:1 ratio to receive the N-MBA intervention or standard care. The 13-week intervention adopted a novel behavioral activation approach to equip AF patients as an active agent to manage the disease. It consisted of care components to prepare patients for shared decision-making by using a decision aid, an empowerment-based educational module covering relevant AF self-care topics and continuous support through telephone calls. A set of validated instruments was administered at baseline, immediate and 6 months post-intervention. Results A total of 252 participants were randomized to the intervention (n = 127) or control (n = 125) group. Compared with the control group, the intervention group showed greater improvements in HRQoL [β = 10.617, 95% confidence interval (CI) = 1.285 – 20.501, p = 0.023] and AF knowledge (β = 2.129, 95% CI =1.026 – 5.712, p &amp;lt;0.001) at immediate post-intervention. The effects on both outcomes sustained at 6-month follow-up time point. No significant between-group changes in medication adherence, anxiety and depression were detected. Participants in the intervention group were activated to raise their concerns about AF and its treatment with the attending doctors, and they perceived higher compatibility between patient and physician decisions of OAC use upon completion of the intervention. Conclusion The empowerment-based nurse-led intervention is effective at sustaining improvements in HRQoL, AF knowledge and treatment decision making in AF patients with moderate to high stroke risk. It does not increase their psychological distress.