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Background: Triplet or quadruplet therapies incorporating proteasome inhibitors, immunomodulators, and anti-CD38 antibodies have led to prolonged survival among patients with newly diagnosed multiple myeloma; however, most patients have a relapse. Frontline lenalidomide therapy has increased the number of patients with lenalidomide-refractory disease at the time of the first relapse., Methods: In this phase 3, randomized, open-label trial, we evaluated belantamab mafodotin, pomalidomide, and dexamethasone (BPd), as compared with pomalidomide, bortezomib, and dexamethasone (PVd), in lenalidomide-exposed patients who had relapsed or refractory myeloma after at least one line of therapy. The primary end point was progression-free survival. Disease response and safety were also assessed., Results: A total of 302 patients underwent randomization; 155 were assigned to the BPd group, and 147 to the PVd group. At a median follow-up of 21.8 months (range, <0.1 to 39.2), the 12-month estimated progression-free survival with BPd was 71% (95% confidence interval [CI], 63 to 78), as compared with 51% (95% CI, 42 to 60) with PVd (hazard ratio for disease progression or death, 0.52; 95% CI, 0.37 to 0.73; P<0.001). Data on overall survival were immature. The percentage of patients with a response to treatment (partial response or better) was 77% (95% CI, 70 to 84) in the BPd group and 72% (95% CI, 64 to 79) in the PVd group; 40% (95% CI, 32 to 48) and 16% (95% CI, 11 to 23), respectively, had a complete response or better. Grade 3 or higher adverse events occurred in 94% of the patients in the BPd group and 76% of those in the PVd group. Ocular events occurred in 89% of the patients who received BPd (grade 3 or 4 in 43%) and 30% of those who received PVd (grade 3 or 4 in 2%); ocular events in the BPd group were managed with belantamab mafodotin dose modification. Ocular events led to treatment discontinuation in 9% of the patients in the BPd group and in no patients in the PVd group., Conclusions: Among lenalidomide-exposed patients with relapsed or refractory myeloma, BPd conferred a significantly greater benefit than PVd with respect to progression-free survival, as well as deeper, more durable responses. Ocular events were common but were controllable by belantamab mafodotin dose modification. (Funded by GSK; DREAMM-8 ClinicalTrials.gov number, NCT04484623; EudraCT number, 2018-004354-21.)., (Copyright © 2024 Massachusetts Medical Society.)

Daniel Eek,1 Meaghan Krohe,2 Iyar Mazar,2 Alison Horsfield,3 Farrah Pompilus,2 Rachel Friebe,2 Alan L Shields2 1AstraZeneca, Gothenburg, Sweden; 2Adelphi Values, Boston, MA, USA; 3AstraZeneca, Macclesfield, UK Objective: The emergence of various modes of administration for cancer treatment, including oral administration, brings into focus the importance of patient preference for administration. The purpose of this research was to evaluate the administration preferences of cancer patients, specifically between oral and intravenous (IV) treatment, as well as the factors contributing to preference. Methods: A literature search was conducted in OvidSP to identify research in which the preferences of cancer patients for oral or IV treatment have been evaluated. Data were analyzed in two stages: 1) those articles that directly compared preference between modes of administration were tallied to determine explicit preference for oral or IV treatment; and 2) all attributes associated with patient preference were documented. Results: Of the 48 abstracts identified as part of the initial OvidSP search, eight articles were selected for full-text review. One article was removed following full-text review, and seven additional articles were identified through a gray literature search, yielding a total of 14 articles for evaluation. In Stage 1, 13 of the 14 articles compared preference, of which eleven articles (84.6%) reported that patients preferred oral treatment over IV, while two (15.4%) stated that cancer patients preferred IV treatment over oral. In Stage 2, the most frequently reported attributes contributing to preference included convenience, ability to receive treatment at home, treatment schedule, and side effects. Discussion: Evidence suggests that oncology patients prefer oral treatment to IV. Rationale for preference was due to a number of factors, including convenience, perception of efficacy, and past experience. Further evaluation should be conducted, given the limited data on patient preference in oncology. Keywords: oncology, patient preference, mode of administration, literature review, mode of administration, oncology, treatment

Introduction: NUT (nuclear protein of the testis) carcinoma (NUTca) is a rare and aggressive cancer that is genetically hallmarked by a chromosomal abnormality in the NUT gene, and presents with tumors in the head, neck, and lungs. Currently there is no standard of care, but patients may undergo surgery, radiation, and/or chemotherapy. There is a lack of published research describing the patient experience of NUTca. The objective of this study was to develop a conceptual framework (CF) that describes patients' experience of NUTca to inform the selection of outcome measures and design of patient-centric endpoints for future clinical research., Methods: Individual, semi-structured telephone interviews were conducted with patients and caregivers of patients who have/had NUTca (caregivers interviewed due to recruitment challenges resulting from the rarity of NUTca). Participants were asked about their disease symptoms, impacts, and treatment experience. Interviews were audio-recorded, transcribed, and analyzed using inductive coding. The CF was developed through inductive categorization of concepts, sub-domains, and domains., Results: Twenty-seven interviews were completed (patients n = 10; caregivers n = 17). Participants reported systemic symptoms (e.g., fatigue) and symptoms related to the location of the tumor (e.g., nose blockage for head/neck tumor). Pain emerged as an important and bothersome symptom across tumor locations. Participants reported impacts on their daily activities (e.g., showering), emotions (e.g., preoccupation), sleep, social life (e.g., isolation), roles (e.g., caring for children), and finances. The final CF was organized into four symptom domains [systemic, location-specific (head/neck, lung), pain, and digestive] and six impact domains (daily activities, emotional, sleep, social, role, and financial)., Conclusions: This study describes the patient experience of NUTca and proposes an evidence-based CF that informs both the clinical community's understanding of the disease and selection of a patient-reported outcome (PRO) measure to assess treatment benefit in future NUTca trials., (© 2021. The Author(s).)

Purpose: Physical functioning and fatigue are key patient concerns in myelodysplastic syndromes (MDS), chronic myelomonocytic leukemia (CMML), and acute myeloid leukemia (AML). The objective of this research was to generate supportive quantitative evidence for modular physical functioning and fatigue measures based on the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire Core 30 items (QLQ-C30) and a customized selection of 10 supplemental items from the EORTC Item Library., Methods: The 40 items were completed online cross-sectionally by 51 patients (higher risk [HR] MDS: 53%; CMML: 26%; AML: 10%). Psychometric analyses based on Rasch measurement theory (RMT) were conducted on the QLQ-C30 physical functioning and fatigue domains as well as measures combining QLQ-C30 and supplemental items. A measure of anemia-related symptoms composed of QLQ-C30 and supplemental items covering fatigue, dyspnea, and dizziness was also investigated., Results: The QLQ-C30 physical functioning and fatigue domains showed good targeting to the sample and adequate reliability, with few conceptual gaps identified. Combining the QLQ-C30 and supplemental physical functioning and fatigue items improved the conceptual coverage and the reliability of the measures. The patient-reported anemia-related symptom measure showed good measurement performance, underpinned by a clinically meaningful characterization of severity of these symptoms over a spectrum, starting with fatigue, then dyspnea, and finally dizziness (most severe)., Conclusion: The modular measurement approach of combining EORTC QLQ-C30 and Item Library offers a promising pragmatic solution to the measurement of physical functioning and fatigue, as well as anemia-related symptoms in clinical trials conducted in HR MDS, CMML, and AML., (© 2021. The Author(s).)

While open surgery has been the primary surgical approach for adult degenerative scoliosis, minimally invasive surgery (MIS) represents an alternative option and appears to be associated with reduced morbidity. Given the lack of consensus, we aimed to conduct a systematic review on available literature comparing MIS versus open surgery for adult degenerative scoliosis. PubMed, Embase, and Cochrane databases were searched through December 16, 2019, for studies that compared both MIS and open surgery in patients with degenerative scoliosis. Four cohort studies reporting on 350 patients met the inclusion criteria. In two studies, patients undergoing open surgery were younger and had more severe disease at baseline as compared with MIS. Patients who underwent MIS had less blood loss, shorter length of stay, and a reduced rate of complications and infections. Both MIS and open surgery resulted in a significant change in pain and disability scores and both approaches provided significant correction of deformity in all studies, although open surgery was associated with a greater change in pelvic incidence-lumbar lordosis mismatch (PI-LL) and sagittal vertical axis (SVA) in two and three studies, respectively. In patients with adult degenerative scoliosis undergoing surgery, both MIS and open approaches appeared to offer comparable improvements in pain and function. However, MIS was associated with better safety outcomes, while open surgery provided greater correction of spinal deformity. Further studies are needed to identify specific subset of patients who may benefit from one approach versus the other.

Background: Patient-reported outcome (PRO) instruments provide robust and effective means of evaluating patients' treatment experience; however, none adequately cover experience using self-injection devices with enhanced features, such as an electromechanical autoinjector (e-Device). The aim of this study was to develop a PRO instrument that accurately assesses patient experience of using an e-Device and to evaluate its psychometric properties., Methods: A mixed-methods approach was taken; two parallel, targeted literature reviews were conducted to identify relevant concepts and existing self-injection PRO instruments that could be adapted. Patient feedback obtained from two focus groups was used to inform initial instrument development. The pilot instrument was then administered in a multicenter, open-label, phase 3 clinical study in which patients self-injected certolizumab pegol using an e-Device, to gather evidence of its psychometric qualities. Exit interviews were conducted with a sub-sample of patients enrolled in the study to confirm the appropriateness and clarity of the items included and cognitively debrief the instrument. Confirmatory factor analysis (CFA) was conducted on all items, and each domain's internal consistency was measured using Cronbach's ɑ., Results: The literature searches identified several e-Device-specific concepts related to device features, device function, side effects/reactions/pain, confidence, and interference/convenience in daily life. Seven existing PRO instruments were identified. The Self-Injection Assessment Questionnaire (SIAQ), containing pre- and post-injection questionnaire modules, was selected as most suitable and adapted using feedback from 19 patients in the two focus groups to form the pilot Assessment of Self-Injection (ASI) questionnaire. CFA resulted in some changes to the grouping of items in the post-injection module domains following psychometric evaluation of the ASI. Internal consistency was satisfactory for all pre- and post-injection domains (ɑ > 0.8). Cognitive debriefing results from 12 patient exit interviews confirmed the ASI's appropriateness and clarity., Conclusions: The ASI was developed iteratively with patient input and was evaluated in its intended clinical context of use. Psychometric analyses indicated promising cross-sectional results; the ASI was well understood and considered relevant by patients self-injecting using the e-Device, suggesting that it could be used in real-world settings to aid with clinical decision making., Trial Registration: NCT03357471.

Background: Novel, pragmatic, patient-centered strategies are needed to ensure fit-for-purpose patient-reported outcomes (PRO) instruments in clinical trial research for rare diseases such as myelodysplastic syndromes (MDS), acute myeloid leukemia (AML), and chronic myelomonocytic leukemia (CMML). The objective of the current study was to select supplemental items to add to the European Organization for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) to ensure content coverage of all important clinical concepts in patients with higher-risk (HR) MDS, low-blast count (LB) AML, and CMML, thus, improving the instrument's ability to detect clinically meaningful treatment benefit for this context of use., Methods: Our mixed methods approach comprised literature review, clinician consultation (n = 3), and qualitative and quantitative analysis of two stages of patient interview data (n = 14, n = 18) to select library bank items to supplement a generic cancer PRO, the EORTC QLQ-C30., Results: Unique symptom (n = 54) and impact (n = 72) concepts were organized into conceptual frameworks of treatment benefit, compared with EORTC QLQ-C30 items and conceptual gaps identified. Supplemental items (n = 13) addressing those gaps were selected from the EORTC Item Library and tested with patients. Supplemental item endorsement frequencies met World Health Organization Quality of Life criteria, suggesting good targeting and relevance for this sample. However, three supplemental items were confirmed as problematic based upon cognitive debriefing results, and expert clinical consultations. Ultimately, 10 supplemental items (n = 7 symptom; n = 3 impact) were selected for the MDS/AML/CMML context., Conclusion: Supplemental items were selected to enhance the conceptual coverage of the EORTC QLQ-C30 in the areas of fatigue, shortness of breath, and functioning.

Background: The goal of the research reported here was to understand the patient experience of living with myelofibrosis (MF) and establish content validity of the Modified Myeloproliferative Neoplasm Symptom Assessment Diary (MPN-SD)., Methods: Qualitative interviews were performed in patients with MF, including both concept elicitation and cognitive debriefing. Patients with MF were asked to spontaneously report on their signs, symptoms, and impacts of MF, as well as their understanding of the MPN-SD content, and use of the tool on an electronic platform. A supplementary literature review and meetings with MF experts were also performed., Results: Twenty-three patients with MF participated in qualitative interviews. Signs and symptoms most commonly reported by ruxolitinib-experienced patients (n = 16) were: fatigue and/or tiredness (n = 16, 100%), shortness of breath (n = 11, 69%), pain below the ribs on the left side and/or stomach pain and/or abdominal pain (n = 9, 56%), and enlarged spleen (n = 9, 56%) and for ruxolitinib-naïve patients (n = 7) were: fatigue and/or tiredness (n = 6, 86%), pain below the ribs on the left side (n = 6, 86%), enlarged spleen (n = 4, 57%), full quickly/filling up quickly (n = 4, 57%), night sweats and/or general sweats (n = 4, 57%), and itching (n = 4, 57%). Patients demonstrated that they were able to read, understand, and provide meaningful responses to the MPN-SD. The final version of the MPN-SD includes the 10 most commonly reported concepts from the MF patient interviews., Conclusions: The findings demonstrate the comprehensiveness of the MPN-SD in assessing MF symptoms in both ruxolitinib-experienced and ruxolitinib-naïve patients, while remaining easy for patients to understand and complete.

Objective: Acute intermittent porphyria is a rare metabolic disorder that affects heme synthesis. Patients with acute intermittent porphyria may experience acute debilitating neurovisceral attacks that require frequent hospitalizations and negatively impact quality of life. Although clinical aspects of acute intermittent porphyria attacks have been documented, the experience of patients is not well known, particularly for those more severely affected patients who experience frequent attacks. The aim of the present study was to qualitatively characterize the experience of patients with acute intermittent porphyria who have frequent attacks, as well as the impact of the disease on daily living., Methods: Patients with acute intermittent porphyria who experience frequent attacks were recruited and took part in 2-h qualitative one-on-one interviews with a semi-structured guide. Interviews were anonymized, transcribed, and coded. The inductive coding approach targeted textual data related to acute intermittent porphyria attack symptoms, chronic symptoms, and the impact of the disease. Saturation analysis was conducted to assess whether the research elicited an adequate account of patients' experiences., Results: In total, 19 patients with acute intermittent porphyria were interviewed (mean age 40 years; 79% female). Eighteen patients (95%) experienced both attack and chronic symptoms. Patients described attacks as the onset of unmanageable symptoms that generally lasted 3-5 days requiring hospitalization and/or treatment. Pain, nausea, and vomiting were considered key attack symptoms; pain, nausea, fatigue, and aspects of neuropathy (e.g., tingling and numbness) were considered key chronic symptoms., Conclusions: In this study population of acute intermittent porphyria with frequent attacks, most patients had symptoms during and between attacks. In these patients, acute intermittent porphyria appears to have acute exacerbations as well as chronic day-to-day manifestations, and is not just intermittent as its name implies. As a result, patients reported limitations in their ability to function across multiple domains of their lives on a regular basis and not just during acute attacks.

Background and Objective: The 12-item Multiple Sclerosis Walking Scale (MSWS-12) is a patient-reported outcome instrument that quantifies the progressive loss of walking ability from the patient perspective. However, previous psychometric analyses indicated floor and ceiling effects across the multiple sclerosis severity spectrum. This study aimed to address floor effects by creating a gait module that can be used in conjunction with the MSWS-12 for better measurement of treatment benefit in the higher functioning multiple sclerosis population., Methods: We used a step-wise mixed methods study design, with relapsing-remitting multiple sclerosis patients (wave 1, n =88; wave 2, n =30), combining qualitative (concept elicitation and cognitive debriefing interviews) and quantitative (Rasch Measurement Theory) data collection and analytical techniques and consultation interviews with three neurologists specializing in multiple sclerosis., Results: Thirty-seven walking ability concepts were identified, and a five-domain conceptual framework was created. Draft items were generated and refined with patient and neurologist input. Draft items covered gait-related concepts such as dragging, shuffling, limping, tripping and falling. Rasch measurement theory psychometric analysis indicated administering MSWS-12 plus gait items improved measurement precision in targeted populations with better walking ability., Conclusion: Study findings indicate that new gait items could improve sensitivity to detect clinical change in walking ability for higher functioning multiple sclerosis patients.

Background: ABILHAND, a manual ability patient-reported outcome instrument originally developed for stroke patients, has been used in multiple sclerosis clinical trials; however, psychometric analyses indicated the measure's limited measurement range and precision in higher-functioning multiple sclerosis patients., Objective: The purpose of this study was to identify candidate items to expand the measurement range of the ABILHAND-56, thus improving its ability to detect differences in manual ability in higher-functioning multiple sclerosis patients., Methods: A step-wise mixed methods design strategy was used, comprising two waves of patient interviews, a combination of qualitative (concept elicitation and cognitive debriefing) and quantitative (Rasch measurement theory) analytic techniques, and consultation interviews with three clinical neurologists specializing in multiple sclerosis., Results: Original ABILHAND was well understood in this context of use. Eighty-two new manual ability concepts were identified. Draft supplementary items were generated and refined with patient and neurologist input. Rasch measurement theory psychometric analysis indicated supplementary items improved targeting to higher-functioning multiple sclerosis patients and measurement precision. The final pool of Early Multiple Sclerosis Manual Ability items comprises 20 items., Conclusion: The synthesis of qualitative and quantitative methods used in this study improves the ABILHAND content validity to more effectively identify manual ability changes in early multiple sclerosis and potentially help determine treatment effect in higher-functioning patients in clinical trials.

Objectives: The aim was to document, from the perspective of the empirical literature, the primary symptoms of functional dyspepsia (FD), evaluate the extent to which existing questionnaires target those symptoms, and, finally, identify any missing evidence that would impact the questionnaires' use in regulated clinical trials to assess treatment efficacy claims intended for product labeling., Methods: A literature review was conducted to identify the primary symptoms of FD and existing symptom-based FD patient-reported outcome (PRO) instruments. Following a database search, abstracts were screened and articles were retrieved for review. The primary symptoms of FD were organized into a conceptual model and the PRO instruments were evaluated for conceptual coverage as well as compared against evidentiary requirements presented in the FDA's PRO Guidance for Industry., Results: Fifty-six articles and 16 instruments assessing FD symptoms were reviewed. Concepts listed in the Rome III criteria for FD (n = 7), those assessed by existing FD instruments (n = 34), and symptoms reported by patients in published qualitative research (n = 6) were summarized in the FD conceptual model. Except for vomiting, all of the identified symptoms from the published qualitative research reports were also specified in the Rome III criteria. Only three of the 16 instruments, the Dyspepsia Symptom Severity Index (DSSI), Nepean Dyspepsia Index (NDI), and Short-Form Nepean Dyspepsia Index (SF-NDI), measure all seven FD symptoms defined by the Rome III criteria. Among these three, each utilizes a 2-week recall period and 5-point Likert-type scale, and had evidence of patient involvement in development. Despite their coverage, when these instruments were evaluated in light of regulatory expectations, several issues jeopardized their potential qualification for substantiation of a labeling claim., Conclusions: No existing PRO instruments that measured all seven symptoms adhered to the regulatory principles necessary to support product labeling. As such, the development of a new FD symptom PRO instrument is supported., Competing Interests: Compliance with Ethical Standards The authors meet criteria for authorship as recommended by the International Committee of Medical Journal Editors (ICMJE) and were fully responsible for all aspects of manuscript development. Fiona Taylor participated in planning and executing the study, analyzing and interpreting the data, and drafting the manuscript; Catherine Foley and Farrah Pompilus participated in planning and executing the study, collecting, analyzing and interpreting the data, and drafting the manuscript; Ramon Iovin participated in collecting, analyzing, and interpreting the data and drafting the manuscript; Alan L. Shields participated in planning and executing the study, interpreting the data, and drafting the manuscript; David S. Reasner provided input on the study design and drafting of the manuscript; Robyn T. Carson, Linda S. Deal, Debra G. Silberg, and Jason Lundy provided input on the study design and manuscript. FT, CF, and ALS are employees of Adelphi Values, which received payment from the sponsors to conduct the research; RI and FP were employees of Adelphi Values at the time this research was conducted. DSR is a member of Albemarle Scientific Consulting and an employee of Ironwood Pharmaceuticals, and owns stock and stock options in Ironwood. RTC is an employee of Allergan and owns stock and stock options in Allergan. At the time of the research, LSD and DGS were employees of Shire, and have shareholdings in Shire and other pharmaceutical companies through stocks and mutual funds. JJL was an employee of the Critical Path Institute at the time this research was conducted. Any views expressed in this publication represent the personal opinions of the authors, not those of their respective employer. The authors’ respective organizations were given the opportunity to review the manuscript for medical and scientific accuracy as well as intellectual property considerations.

Background: Facial lines or wrinkles are among the most visible signs of aging, and minimally invasive cosmetic procedures are becoming increasingly popular., Aims: The aim of this study was to develop and validate the Facial Line Satisfaction Questionnaire (FLSQ) for use in adults with upper facial lines (UFL)., Methods: A literature review, concept elicitation interviews (n = 33), and cognitive debriefing interviews (n = 23) of adults with UFL were conducted to develop the FLSQ. The FLSQ comprises Baseline and Follow-up versions and was field-tested with 150 subjects in a US observational study designed to assess its psychometric performance. Analyses included acceptability (item and scale distribution [i.e. missingness, floor, and ceiling effects]), reliability, and validity (including concurrent validity)., Results: In total, 69 concepts were elicited during patient interviews. Following cognitive debriefing interviews, the FLSQ-Baseline version included 11 items and the Follow-up version included 13 items. Response rates for the FLSQ were 100% and 73% at baseline and follow-up, respectively; no items had excessive missing data. Questionnaire scale scores were normally distributed. Most domain scores demonstrated good internal consistency reliability (Cronbach's α ≥ 0.70). Most items within their respective domains exhibited good convergent (item-scale correlations > 0.40) and discriminant (items had higher correlation with their hypothesized scales than other scales) validity. Concurrent validity correlation coefficients of the FLSQ domain scores with the associated concurrent measures were acceptable (range: r = 0.40-0.70). Six FLSQ items demonstrated reliability and validity as stand-alone items outside their domains., Conclusions: The FLSQ is a valid questionnaire for assessing treatment expectations, satisfaction, impact, and preference in adults with UFL., (© 2015 The Authors. Journal of Cosmetic Dermatology Published by Wiley Periodicals, Inc.)

Simple Summary: The use of oral anticancer agents (OAAs) is increasing, and even more people need to monitor and manage their treatment pathway. A clear map of self-care outcomes studied so far can provide insights for clinical practice and future studies. The study revealed that all included articles considered, as intervention, treatment adherence and, as outcomes, mortality, survival, disease recurrence and quality of life. Adherence to OAA treatment has been found to reduce mortality and increase survival. However, important outcomes such as economic, social or psychological outcomes should be assessed in future studies to provide a complete picture of improvements that can be derived from self-care behaviours. Background/Objectives: The use of oral anticancer agents (OAA) dates to the late 20th century in cancer treatment. It is crucial that patients implement self-care behaviours to keep their disease stable and manage their OAA treatment. The three dimensions of self-care according to Riegel et al., self-care maintenance, self-care monitoring, and self-care management, may be implemented to avoid negative outcomes. This paper seeks to identify outcomes associated with self-care in breast cancer patients during treatment with OAA and to compare which of these outcomes fall into the core outcome categorizations in oncology (minimal set of outcomes that research on a given health issue should measure). Methods: A systematic review with narrative synthesis was conducted. This study included patients with breast cancer taking any kind of OAA and described outcomes of self-care. The search was performed on MEDLINE, Web of Science and CINAHL/PsycINFO; Results: Of 4173 records, eight studies were selected and reviewed. The core outcomes mainly considered were mortality, survival, disease recurrence and quality of life. All studies focused only on pharmacological adherence outcome; none of them focused on other dimensions of self-care. Conclusions: This systematic review highlighted that there is a great lack of research on outcomes related to self-care in patients with breast cancer taking OOA. Even though pharmacological adherence to OAA is important, other behaviours are also important to improve patients' outcomes, but they have not been studied. Further research is needed to study how self-care behaviours can impact patients' outcomes. [ABSTRACT FROM AUTHOR]

Objective: Facial acne has been associated with impaired health-related quality of life, which is an essential patient outcome for evaluating the success of acne treatment. In consideration of the US Food and Drug Administration's (FDA) new recommendations on patient reported outcome (PRO) measures, the objectives of this study were to (1) establish the need for a new PRO measure that assesses facial acne outcomes and satisfies the criteria set forth by the FDA and (2) develop the content of a new facial acne PRO measure appropriate for use in both adolescents and adults as well as adherent to the FDA PRO Guidance., Methods: A literature and PRO review, patient interviews (concept elicitation), and input from clinical experts were used to develop a conceptual framework for the outcomes deemed important to facial acne patients, and to construct items for a preliminary PRO measure: the Acne Symptom and Impact Scale (ASIS). Cognitive interviews were conducted to pilot test the ASIS., Results: A review of the literature and PROs revealed that, of the 34 measures identified, no suitable PRO measure for the population of interest was available. The conceptual framework comprised two main themes: symptoms and psychosocial impacts. Concept elicitation interviews included a diverse set of patients (n=48) with facial acne, of various ages: 12-17 years (n=15), 18-25 years (n=20), and 26-50 years (n=13). The most frequently reported symptoms were: pimples, oily skin, scabs/scars/marks, blackheads, acne, and whiteheads. The most frequently reported impacts were impacts on appearance, self-consciousness, annoyance, bothersomeness, mood, social criticism, embarrassment, confidence, and social withdrawal. These reported symptoms and impacts constituted the 15-item draft ASIS. The draft ASIS was modified following the analysis of 20 cognitive interviews, resulting in the current 17-item ASIS., Conclusions: Results from both the concept elicitation and cognitive interviews demonstrated that the ASIS is content valid in both adolescents and adults with facial acne. The ASIS will undergo psychometric evaluation to further support its validity in both adolescents and adults with facial acne.

Background: Chronic low back pain (CLBP) is the most common chronic pain condition and is associated with clinical, economic, social, and public health impacts. The effect of CLBP on patients' health-related quality of life (HRQoL) is significant. The symptoms and impacts most often associated with CLBP include pain and disability; patients most affected are often crippled by the condition. CLBP also affects patients' mental, physical, and psychosocial well-being. A variety of self-report measures have been developed for the assessment of CLBP, such as the Roland Morris Disability Questionnaire (RMDQ); however, existing measures may not meet current regulatory expectation for the development, documentation, and use of patient-reported outcomes (PRO) questionnaires (U.S. Department of Health and Human Services, Food and Drug Administration, 2009)., Objectives: This report describes the qualitative development of the Chronic Low Back Pain Impact Questionnaire (CLBP-IQ), created for use in clinical trials., Methods: A total of 22 CLBP patients recruited by clinicians participated in concept elicitation interviews to identify target measurement concepts. An instrument development team generated the instructions, items, and response options guided by patient input. Cognitive debriefing interviews were conducted with 21 patients recruited by the same clinicians who recruited for concept elicitation interviews. During cognitive interviews, a draft instrument composed of 28 items was presented to individuals with CLBP to evaluate its readability and comprehensiveness. All research activities were conducted in the US., Results: During concept elicitation interviews, participants reported a variety of physical, emotional, and social impacts associated with CLBP. Participants also reported CLBP impacts on sleep, energy, daily activities, work, household activities, leisure activities, cognition, self-care, and sex life. Impacts deemed simple, important, and relevant to CLBP patients became targets of measurement for the CLBP-IQ. During cognitive debriefing, seventeen items were interpreted as intended by at least 90 % of participants, and no items were interpreted incorrectly by more than five patients (24 %). Additionally, seventeen items were experienced by at least 90 % of participants, and no single item was experienced by less than 67 % of participants (n = 14)., Conclusions: The CLBP-IQ was developed in accordance with current US Food and Drug Administration guidance on instrument development. Results from both concept elicitation and cognitive debriefing interviews support the content validity of the CLBP-IQ in patients with CLBP. Future development should proceed with psychometric evaluation.

Androgen deprivation therapy (ADT) is a mainstay treatment for metastatic prostate cancer, improving progression-free survival. ADT suppresses the production of testosterone and reduces circulating levels of the hormone. Luteinizing hormone-releasing hormone (LH-RH) agonists are the most commonly used ADT modality. They can be given alone or in combination with androgen synthesis inhibitors or androgen receptor antagonists. An estimated 40% of prostate cancer patients will receive ADT as part of their therapy during their lifetime. However, ADT has numerous adverse effects, including an increased cardiovascular risk that impacts quality of life. Relugolix is an alternative form of ADT. It is the only oral gonadotropin-releasing hormone antagonist, circumventing injection site reactions, making it easier for patients to take, and thus increasing compliance. Testosterone suppression with relugolix is excellent and testosterone recovery after discontinuation is rapid. This paper reviews the ADT and anti-androgen treatment options for men with prostate cancer and the cardiovascular effects of these therapies. There is accumulating evidence that cardiovascular risk with relugolix is lower than with other ADT medications and also lower than with androgen synthesis inhibitors and androgen receptor antagonists. This paper provides insight into the use of different ADT regimens based on the cardiovascular status and circumstances. It explores strategies to mitigate negative cardiovascular consequences and highlights the need for further study. [ABSTRACT FROM AUTHOR]

Gene expression appears altered in apparently normal tissue surrounding tumor tissue. The observed biological alterations in the tumor microenvironment play a crucial role in cancer development and are named the cancer field effect (FE). A robust set of overexpressed FE genes in tissue surrounding colorectal cancer (CRC) tumor were identified in previous studies. Our study aimed to investigate the influence of common medication intake and modifiable risk factors on FE gene expression using a colonic mucosa sample dataset of healthy individuals (BarcUVa-Seq). We applied expression enrichment analysis of the FE genes for each studied medication and factor. Both observational and instrumental (Mendelian randomization) analysis were conducted, and the results were validated using independent datasets. The findings from the observational and instrumental analyses consistently showed that medication intake, especially metformin, considerably downregulated the FE genes. Chemopreventive effects were also noted for antihypertensive drugs targeting the renin–angiotensin system. Conversely, benzodiazepines usage might upregulate FE genes, thus fostering a tumor-promoting microenvironment. In contrast, the findings from the observational and instrumental analyses on modifiable risk factors showed some discrepancies. The instrumental results indicated that obesity and smoking might promote a tumor-favorable microenvironment. These findings offer insights into the biological mechanisms through which risk factors might influence CRC development and highlight the potential chemopreventive roles of metformin and antihypertensive drugs in CRC risk. [ABSTRACT FROM AUTHOR]

Background: Acute hepatic porphyria is a group of multisystem disorders of which acute intermittent porphyria is the most common subtype. Givosiran, a subcutaneously administered RNA interference therapeutic targeting liver ALAS mRNA, is approved for treating these disorders. This Phase 1/2 open-label extension study (NCT02949830) evaluated the long-term safety and efficacy of givosiran in adults with acute intermittent porphyria, with follow-up of up to 48 months, which is the longest follow-up of givosiran treatment to date. Participants were adults aged 18–65 years who completed part C of the Phase 1 givosiran study (NCT2452372). Methods: Enrollees received givosiran for up to 48 months. Primary and secondary endpoints included the incidence of adverse events, changes in urinary delta-aminolevulinic acid (ALA) and porphobilinogen (PBG) levels, annualized rate of porphyria attacks, and annualized hemin use. Quality of life was assessed using the EQ-5D-5L instrument as an exploratory endpoint. Results: Sixteen patients (median age: 39.5 years) participated. Common adverse events included abdominal pain, nasopharyngitis, and nausea (50% each), with injection-site erythema (38%) and injection-site pruritus (25%) noted as frequent treatment-related reactions. Givosiran therapy reduced annualized rates of porphyria attacks and hemin use by 97% and 96%, respectively. From months > 33 to 48, all patients were free from attacks requiring significant medical intervention and did not use hemin. There were substantial reductions in median urinary ALA and PBG of 95% and 98%, respectively. Additionally, a clinically meaningful improvement in quality of life was observed. Conclusions: In the longest follow-up of givosiran-treated patients reported to date, the therapy maintained an acceptable safety profile and demonstrated sustained improvements in clinical outcomes over 4 years in patients with acute intermittent porphyria. [ABSTRACT FROM AUTHOR]

Background: In the last two decades, the use of oral anticancer agents (OAAs) has increased in cancer patients. Despite this, patients and their caregivers face some challenging issues (side effects, drug-to-drug interactions, etc.) related to OAA administration. The three dimensions of self-care by Riegel et al., self-care maintenance (i.e., stability of patient condition), self-care monitoring (i.e., detection of side effects), and self-care management (i.e., management of side effects), may be implemented to avoid negative outcomes. However, knowledge of self-care determinants is necessary to recognise people at risk of poor self-care behaviours. Aims: Determine which are the predictors of self-care maintenance, self-care monitoring and self-care management in patients with cancer taking OAA. Methods: A systematic review with narrative synthesis was conducted. We included studies on adult patients with cancer using any kind of oral anticancer agent and describing a predictor of self-care. The search was performed on PubMed, CINAHL/PsycINFO, and Web of Science. Results: Of 3,061 records, 45 studies were included in this review. Forty-six predictors organised into 14 categories were identified. In general, all studies focused only on adherence, considered as a self-care maintenance component, and none of them focused on other dimensions of self-care. The predictors of OAA adherence most reported were age, side effects, and socioeconomic factors (e.g., insurance status, and annual income). Conclusions: This systematic review highlighted the literature gap on the analysis of determinants of self-care behaviours in patients taking OAAs. This element could be a starting point for future research that can provide elements to support the oncology nursing research agenda, aimed at recognising patients at risk of poor self-care. [ABSTRACT FROM AUTHOR]

Tyrosine kinase inhibitors (TKIs) have emerged as a leading targeted cancer therapy, reducing the side effects often seen with non-targeted treatments, especially the damage to healthy cells. To tackle resistance, typically caused by epidermal growth factor receptor (EGFR) mutations, four generations of TKIs have been developed. Each generation has shown improved effectiveness and fewer side effects, resulting in better patient outcomes. For example, patients on gefitinib, a first-generation TKI, experienced a progression-free survival (PFS) of 10 months compared to 5 months with conventional chemotherapy. Second-generation TKI afatinib outperformed erlotinib and extended PFS to 11.1 months compared to 6.9 months with cisplatin. Third-generation TKIs further increased survival to 38.6 months, compared to 31.8 months with first-generation TKIs. This progress demonstrates the ability of newer TKIs to overcome resistance, particularly the T790M mutation, while reducing adverse effects. Ongoing research focuses on overcoming resistance from newer mutations like C797S to further improve patient survival. These developments highlight the significant progress in TKI therapy and the continued effort to refine cancer treatment. Recent research in South Korea shows that third-generation TKIs are ineffective against non-small cell lung cancer (NSCLC) with the C797S mutation. Several trials have started showing promising in vitro and in vivo results, but more trials are needed before clinical approval. This review underscores notable advancements in the field of EGFR TKIs, offering a comprehensive analysis of their mechanisms of action and the progression of various TKI generations in response to resistance. [ABSTRACT FROM AUTHOR]

Background: Since the European approval of CDK4/6 inhibitors in 2016, the treatment of patients with hormone-receptor-positive, HER2-negative metastatic breast cancer has changed significantly. Compared with chemotherapy, endocrine-based therapy has different treatment regimens and is associated with new side effects. Oral therapy aims for optimal drug efficacy and long treatment times while maintaining maximum independence and quality of life resulting in the conservation of medical staff resources. Methods: A monocentric analysis of therapy preferences of practitioners (25 nurses and physicians) and patients (11 on endocrine monotherapy, 17 on endocrine-based therapy, and 14 on intravenous chemotherapy) was performed using specific questionnaires. Preferences were assessed using a four-point Likert scale or bidirectional response options. Results: All patients were highly supportive of oral therapy (mean agreement score on the Likert scale 1.3, p < 0.001 vs. all other options) and a consultation interval of 4 weeks (2.0, p = 0.015 vs. 3 weeks). Practitioners also preferred oral therapy (1.4) and visits every 4 weeks (1.6). In general, patients on oral therapies reported higher compatibility of their therapy with daily life than patients on chemotherapy (1.6 and 1.7 vs. 2.6, p = 0.006). Outpatient oncology is the main source of information for all patients, mainly in case of side effects (2.0) and open questions (1.8). Regarding oral antitumor therapy regimens, patients do not show a significant preference for a specific regimen, while practitioners prefer a continuous regimen (1.6) over a 21/7 regimen (21 days on and 7 days off therapy, 2.5). Patients are likely to accept mild side effects (e.g., neutropenia, diarrhea, polyneuropathy, fatigue) and would still adhere to their initial choice of regimen (continuous or 21/7). Only when side effects occur with a severity of CTCAE grade 3 do patients prefer the regimen in which the side effects occur for a shorter period of time. Conclusion: Patients and practitioners prefer oral antitumor therapy—both continuous and 21/7 regimens—over other application forms. Patient education and proper therapy management, supported by additional tools, contribute to the specific management of side effects and high adherence. This allows quality of life to be maintained during long-term therapy with CDK4/6 inhibitors in patients with metastatic breast cancer. [ABSTRACT FROM AUTHOR]

Background: The Huntington's Disease (HD) Everyday Functioning (Hi-DEF) is a new patient-reported outcome (PRO) instrument designed to measure the impact of cognitive impairment on daily functioning in the early stages of HD. Objective: To assess the measurement properties and finalize item content of the Hi-DEF. Methods: A cross-sectional, observational psychometric validation study was conducted among individuals with early stages of HD at 9 US centers of excellence. Rasch Measurement Theory (RMT) analysis of the initial draft version of the Hi-DEF (47 items) and subscales (i.e., 'Home', 'At work', 'Driving', and 'Communication') was conducted to examine measurement properties including sample-to-scale targeting, suitability of response scale (ordering of response thresholds), scale cohesiveness (item fit), local independence, and person fit. Results: 151 participants (mean age 47 years (SD 12), 59% female) were included. Seven items were removed based on dependency and item fit. The remaining 40-item version of the Hi-DEF demonstrated good measurement properties. Across the four subscales, targeting ranged from 49–70% (72% full scale), reliability ascertained by person separation index ranged from 0.53–0.87 (0.92 full scale), response scales were ordered for 25–100% of items (75% full scale), 0–12% items displayed misfit (2% full scale), and 0–1% (2% full scale) item pairs displayed dependency. Conclusions: Our study supports the psychometric integrity of the Hi-DEF as a reliable and valid new PRO instrument designed to assess the impact of cognitive impairment on daily functioning in the early stages of HD. Future work will evaluate the external validity and utility in clinical trial applications. [ABSTRACT FROM AUTHOR]

Background: Standard oblique cages cannot cover endplates side-to-side, which is an important biomechanical factor for reducing the risk of cage subsidence and for restoring correct segmental lordosis. The aim of this study is to evaluate the radiological and clinical results of a new oblique lumbar interbody fusion (OLIF) axially expandable cage. Methods: This is a prospective observational case–control study. From March 2018 to June 2020, 28 consecutive patients with lumbar degenerative disease underwent an ATP approach, with the insertion of a new axially expandable cage, which was used as a stand-alone procedure or followed by posterior percutaneous pedicle fixation. Results: Twenty-eight patients in both groups met the inclusion criteria. The mean follow-up time was 31.2 months (range of 13–37). The clinical results were not significantly different, although in the control group, two major intraoperative complications were recorded, and slight improvements in ODI and SF-36 scores were observed in the study group. The radiological results showed a less frequent incidence of subsidence and a higher rate of fusion in the study group compared to controls. Conclusions: The axially expandable oblique cage for lumbar inter body fusion, specifically designed for the ATP approach, represents an innovation and a technical improvement. The insertion and the axial expansion technique are safe and easy. The large footprint could obtain solid and effective arthrodesis, potentially reducing the risk of subsidence. [ABSTRACT FROM AUTHOR]

Simple Summary: Poor adherence to trametinib, an oral anticancer drug, may be the consequence of side effects that severely impact the patient's quality of life. The significant interindividual variability associated with poor adherence results in suboptimal drug exposure and consequently in unfavourable patient outcomes. By characterizing the pharmacokinetics of trametinib, this study aims to assess (i) the adequacy of recommended doses to achieve efficacy thresholds and (ii) the impact of non-adherence on drug exposure. The latter was assessed by simulating different scenarios of missing one or more doses per week to highlight the risk of treatment failure associated with poor adherence. These results promote interprofessional collaboration and patient partnership to address patients' needs in order to ensure adherence to trametinib and in fine therapeutic success. Trametinib is a targeted therapy used for the treatment of solid tumours, with significant variability reported in real-life studies. This variability increases the risk of suboptimal exposure, which can lead to treatment failure or increased toxicity. Using model-based simulation, this study aims to characterize and investigate the pharmacokinetics and the adequacy of the currently recommended doses of trametinib. Additionally, the simulation of various suboptimal adherence scenarios allowed for an assessment of the impact of patients' drug adherence on the treatment outcome. The population data collected in 33 adult patients, providing 113 plasmatic trametinib concentrations, were best described by a two-compartment model with linear absorption and elimination. The study also identified a significant positive effect of fat-free mass and a negative effect of age on clearance, explaining 66% and 21% of the initial associated variability, respectively. Simulations showed that a maximum dose of 2 mg daily achieved the therapeutic target in 36% of male patients compared to 72% of female patients. A dose of 1.5 mg per day in patients over 65 years of age achieved similar rates, with 44% and 79% for male and female patients, respectively, reaching the therapeutic target. Poor adherence leads to a significant drop in concentrations and a high risk of subtherapeutic drug levels. These results underline the importance of interprofessional collaboration and patient partnership along the patient's journey to address patients' needs regarding trametinib and support medication adherence. [ABSTRACT FROM AUTHOR]

Background: While patients with cancer have traditionally received oncology treatments through intravenous (IV) administration, some therapies are becoming available via alternative modes of administration, such as subcutaneous (SC). This study aimed to evaluate IV versus SC therapy administration from the perspectives of the patient, healthcare provider (HCP), and healthcare system., Methods: A systematic review was conducted, searching MEDLINE and Embase databases from 2000 to 2022. This was supplemented with grey literature searches of additional sources such as conference proceedings. Observational studies and clinical trials were included if they assessed adult patients with any cancer type who were treated with pharmacologic therapies administered via IV or SC and included patient- or HCP-reported outcomes or healthcare system perspectives on the mode of administration. Records identified by the literature search were screened by two independent reviewers. Included studies were data extracted by a single reviewer and validated by a second reviewer and synthesized using a narrative approach., Results: After screening, 33 unique studies were included in the systematic review. Patients and HCPs reported substantially more favorable preference rates for SC over IV treatment. Additionally, from the patient perspective there were reductions in treatment time and economic burden for SC compared with IV therapy. From the HCP's perspective, treatment time was consistently reduced by SC compared with IV treatment administration. Although information on the impact of SC and IV treatments for oncology on healthcare systems was limited, the use of SC formulations showed consistent cost savings (direct costs) and time savings from this perspective considering various uptake scenarios compared with IV administration., Conclusion: Compared with IV administration, SC oncology treatment is a preferred option by patients and HCPs, increasing optionality and reducing treatment time while simultaneously increasing capacity and reducing the financial burden on healthcare systems., (© 2024. Merck & Co., Inc., Rahway, NJ, USA and its affiliates & Iain Fotheringham, Lalith Mittal, Smit Pathak.)

Systematically predicting the effects of mutations on protein fitness is essential for the understanding of genetic diseases. Indeed, predictions complement experimental efforts in analyzing how variants lead to dysfunctional proteins that in turn can cause diseases. Here we present our new fitness predictor, FiTMuSiC, which leverages structural, evolutionary and coevolutionary information. We show that FiTMuSiC predicts fitness with high accuracy despite the simplicity of its underlying model: it was among the top predictors on the hydroxymethylbilane synthase (HMBS) target of the sixth round of the Critical Assessment of Genome Interpretation challenge (CAGI6) and performs as well as much more complex deep learning models such as AlphaMissense. To further demonstrate FiTMuSiC's robustness, we compared its predictions with in vitro activity data on HMBS, variant fitness data on human glucokinase (GCK), and variant deleteriousness data on HMBS and GCK. These analyses further confirm FiTMuSiC's qualities and accuracy, which compare favorably with those of other predictors. Additionally, FiTMuSiC returns two scores that separately describe the functional and structural effects of the variant, thus providing mechanistic insight into why the variant leads to fitness loss or gain. We also provide an easy-to-use webserver at https://babylone.ulb.ac.be/FiTMuSiC, which is freely available for academic use and does not require any bioinformatics expertise, which simplifies the accessibility of our tool for the entire scientific community. [ABSTRACT FROM AUTHOR]

Rosavin, a phenylpropanoid in Rhodiola rosea's rhizome, and an adaptogen, is known for enhancing the body's response to environmental stress. It significantly affects cellular metabolism in health and many diseases, particularly influencing bone tissue metabolism. In vitro, rosavin inhibits osteoclastogenesis, disrupts F-actin ring formation, and reduces the expression of osteoclastogenesis-related genes such as cathepsin K, calcitonin receptor (CTR), tumor necrosis factor receptor-associated factor 6 (TRAF6), tartrate-resistant acid phosphatase (TRAP), and matrix metallopeptidase 9 (MMP-9). It also impedes the nuclear factor of activated T-cell cytoplasmic 1 (NFATc1), c-Fos, the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB), and mitogen-activated protein kinase (MAPK) signaling pathways and blocks phosphorylation processes crucial for bone resorption. Moreover, rosavin promotes osteogenesis and osteoblast differentiation and increases mouse runt-related transcription factor 2 (Runx2) and osteocalcin (OCN) expression. In vivo studies show its effectiveness in enhancing bone mineral density (BMD) in postmenopausal osteoporosis (PMOP) mice, restraining osteoclast maturation, and increasing the active osteoblast percentage in bone tissue. It modulates mRNA expressions by increasing eukaryotic translation elongation factor 2 (EEF2) and decreasing histone deacetylase 1 (HDAC1), thereby activating osteoprotective epigenetic mechanisms, and alters many serum markers, including decreasing cross-linked C-telopeptide of type I collagen (CTX-1), tartrate-resistant acid phosphatase 5b (TRACP5b), receptor activator for nuclear factor κ B ligand (RANKL), macrophage-colony-stimulating factor (M-CSF), and TRAP, while increasing alkaline phosphatase (ALP) and OCN. Additionally, when combined with zinc and probiotics, it reduces pro-osteoporotic matrix metallopeptidase 3 (MMP-3), interleukin 6 (IL-6), and tumor necrosis factor α (TNF-α), and enhances anti-osteoporotic interleukin 10 (IL-10) and tissue inhibitor of metalloproteinase 3 (TIMP3) expressions. This paper aims to systematically review rosavin's impact on bone tissue metabolism, exploring its potential in osteoporosis prevention and treatment, and suggesting future research directions. [ABSTRACT FROM AUTHOR]

Purpose: This study aimed to compare the functional and radiographic outcomes of two surgical interventions for adult spinal deformity (ASD): anterior lumbar interbody fusion with anterior column realignment (ALIF-ACR) and posterior approach using Smith–Peterson osteotomy with transforaminal lumbar interbody fusion and pedicle screw fixation (TLIF-Schwab2). Methods: A retrospective cohort study included 61 ASD patients treated surgically between 2019 and 2020 at a single tertiary orthopedic specialty hospital. Patients were divided into two groups: Group 1 (ALIF-ACR, 29 patients) and Group 2 (TLIF-Schwab2, 32 patients). Spinopelvic radiographic parameters and functional outcomes were evaluated at 3, 6, and 12 months postsurgery. Results: Perioperative outcomes favored the ALIF-ACR group, with significantly smaller blood loss, shorter hospital stay, and operative time. Radiographic and functional outcomes were similar for both groups; however, the ALIF-ACR group did have a greater degree of correction in lumbar lordosis at 12 months. Complication profiles varied, with the ALIF-ACR group experiencing mostly hardware-related complications, while the TLIF-Schwab2 group faced dural tears, wound dehiscence, and proximal junctional kyphosis. Both groups had similar revision rates. Conclusion: Both ALIF-ACR and TLIF-Schwab2 achieved similar radiographic and functional outcomes in ASD patients with moderate sagittal plane deformity at 1-year follow-up. However, the safety profiles of the two techniques differed. Further research is required to optimize patient selection for each surgical approach, aiming to minimize perioperative complications and reoperation rates in this challenging patient population. [ABSTRACT FROM AUTHOR]

Real-world studies permit inclusion of a more diverse patient population and provide more information on the effectiveness of treatments used in routine clinical practice. This prospective, multicenter, observational study investigated the effectiveness and safety of ixazomib plus lenalidomide and dexamethasone (IRd) in 295 patients with relapsed/refractory multiple myeloma (RRMM) in routine clinical practice in Japan. Patients had a median age of 74 years, 80.0% were aged ≥ 65 years, 42.0% had received ≥ 3 lines of prior treatment, and 28.5% were "frail" according to the International Myeloma Working Group frailty score. After a median follow-up of 25.0 months, median progression-free survival (PFS) was 15.3 (95% CI 12.4–19.5) months, while median overall survival was not reached. The overall response rate was 53.9%, and 31.5% of patients had a very good partial response or better. In the subgroup analysis, median PFS was better in patients with 1 versus 2 or ≥ 3 lines of prior treatment (29.0 vs 19.2 or 6.9 months) and paraprotein versus clinical relapse (16.0 vs 7.9 months), but median PFS was not notably affected by frailty score or age group. Dose adjustment was more frequent among patients aged > 75 years, especially early after IRd treatment initiation. Treatment-emergent adverse events (TEAEs) of any grade occurred in 84.4% of patients and 24.7% of patients discontinued treatment due to TEAEs; no new safety concerns were found. These findings suggest that oral IRd triplet regimen is an effective and tolerable treatment option for RRMM patients in real-world settings outside of clinical trials. ClinicalTrials.gov identifier: NCT03433001; Date of registration: 14 February 2018. [ABSTRACT FROM AUTHOR]

Purpose: Successful treatment of facial lines with botulinum toxin is largely dependent on patient satisfaction; thus, a structured treatment journey that uses patient-reported outcomes (PROs) is helpful for maximizing botulinum toxin results. To develop a patient-centric approach for botulinum toxin injections in facial aesthetics, a group of clinicians met to provide opinions on an optimal treatment journey that uses PROs to quantify treatment benefits on patient quality of life. Patients and Methods: A multidisciplinary panel of 9 clinicians with expertise in facial aesthetic procedures convened for an advisory board that was preceded by and followed up with a structured, multistep consensus discussion. Based on current literature, the panel's expertise, structured questions, and group discussion, panelists assessed, reconciled, and agreed upon on a patient journey for botulinum toxin treatment in facial aesthetics. Results: Panelists agreed that an optimal patient journey includes screening, assessment, treatment, posttreatment, and follow-up visits. A compact, easy-to-complete, and digital PRO questionnaire should be provided before the visit. During screening, thorough assessments are integral for a successful patient journey because they provide an opportunity to understand treatment goals, address patient concerns, discuss risks and benefits, obtain medication lists/medical history, and take pretreatment photographs. Treatment strategies should include discussing and educating on the approach/choice of botulinum toxin and ensuring patients are comfortable. Posttreatment, clinicians should request intense muscle movements to enhance product uptake and be available to address patient concerns. Finally, during follow-up, PRO questionnaires can be provided to gauge patient satisfaction with treatment, and pretreatment photographs can be provided to allow patients to track their progression. Follow-ups should be scheduled with new patients or those reporting low satisfaction. Conclusion: Establishing a relationship, being aware of the patient's goals, and developing an individualized care plan allows for a structured, patient-centered treatment journey that promotes positive aesthetic outcomes. [ABSTRACT FROM AUTHOR]

Background: No specific measures exist to assess patient-reported symptoms experienced by individuals with chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) or mantle cell lymphoma (MCL). This study was conducted to elicit patient-reported CLL/SLL- and MCL-related symptoms and their impact on patients' lives. The study qualitatively and quantitatively evaluated sets of conceptually-selected EORTC Item Library items for assessing CLL/SLL- and MCL-related symptoms. Methods: The qualitative component of the research included a literature review, clinician consultations, and patient interviews. Concepts important to patients were identified and coded; cognitive debriefing of the selected library items was completed with patients. CLL/SLL and MCL-related symptoms and impacts were organized in a structured conceptual model, which was mapped to item sets from the Item Library. The quantitative component comprised exploratory macro-level Rasch measurement theory (RMT) analysis conducted to provide supportive quantitative insight on the item sets. Results: 41 patients (21-MCL; 20-CLL/SLL) and 5 clinicians participated in the qualitative study; 57 unique patients (30-MCL; 27-CLL/SLL) completed the EORTC items. The conceptual models generated from the qualitative work included symptoms and functional impacts of CLL/SLL and MCL. Symptom domains included swollen lymph nodes, B symptoms, abdominal issues, pain, fatigue, subjective cognitive impairment, anemia-related symptoms, bleeding, infection, and other issues (appetite loss, temperature fluctuation, rash, weight gain, sleep problems, cough). Impacts included physical function, role function, and other functions (psychological, social). Cognitive debriefing demonstrated that the separate item sets for CLL/SLL and MCL-related symptoms were well understood and aligned with patients' experiences. All selected items were included in the conceptual models. The exploratory RMT analysis showed that the item sets provided adequate coverage of the continuum of CLL/SLL- and MCL-related symptom severity. Conclusions: This study gathered qualitative and early quantitative evidence supporting use of the EORTC Item Library to assess CLL/SLL- and MCL-related symptoms and impacts. These items are promising candidates for measurement of patient-reported disease symptoms in these populations. A larger sample size will be essential to establish the psychometric properties necessary to support use in clinical trials. Plain English summary: Patients who suffer from rare cancers of the blood, bone marrow, and lymph nodes can experience chronic and debilitating symptoms. At present, however, there are no dedicated instruments for assessing the patient's experience of symptoms of conditions like chronic lymphocytic leukemia (CLL)/small lymphocytic lymphoma (SLL) or mantle cell lymphoma (MCL), or for assessing their impact on patients' lives. This research project aimed to address that need. The researchers selected relevant and clinically meaningful symptoms from the EORTC Item Library that assess fatigue, B symptoms, and CLL/SLL- and MCL-specific symptoms. Using patients and clinician interviews as well as quantitative analyses, the research revealed no major concerns with using these item sets to assess symptoms of CLL/SLL and MCL. Interviews with patients demonstrated that the separate item sets for CLL/SLL and MCL-related symptoms were well understood and aligned with patients' experiences. All selected items were included in the conceptual models. Item sets identified in this study can potentially be used to assess patient-reported symptom endpoints in clinical trial settings in these disease areas. [ABSTRACT FROM AUTHOR]