A pilot randomised controlled trial of acceptance and commitment therapy for medication decision-making and quality of life in women with breast cancer: The ACTION trial.

OBJECTIVE: Non-adherence to adjuvant endocrine therapy (AET) in women with breast cancer is common and associated with medication side-effects and distress. We co-designed an Acceptance and Commitment Therapy intervention (ACTION) to enhance medication decision-making and quality of life (QoL). We undertook a pilot trial of ACTION to inform the feasibility of a phase III trial, and to examine intervention acceptability. METHODS: This was a multi-site, exploratory, two-arm, individually randomised external pilot trial. Women with early breast cancer prescribed AET were randomised (1:1) to receive usual care (UC) or UC + ACTION. The ACTION intervention comprised a remotely delivered one-to-one ACT session followed by three group sessions delivered by clinical psychologists, alongside a website containing ideas for the self-management of side effects. RESULTS: Of the 480 women screened for eligibility, 260 (54.2%) were approached and 79 (30.4%) randomised. 71 (89.9%) women provided data at 3-month and 70 (88.6%) at 6-month 40 women were randomised to receive UC + ACTION and 32 (80.0%) completed the intervention. Most (75.0%) accessed the website at least once. ACTION was acceptable to participants (Borkovec & Nau Scale: mean = 7.8 [SD = 2.7] out of 10). Signals of effectiveness in favour of the UC + ACTION arm were observed for medication adherence (Adherence Starts with Knowledge questionnaire-12), QoL (work and social adjustment scale), health-related QoL (functional assessment of cancer therapy[FACT] general and FACT-ES-19/23), distress (generalised anxiety disorder -7, patient health questionnaire-9) and psychological flexibility (valuing questionnaire). CONCLUSIONS: The ACTION intervention was acceptable to patients. There were promising signals for effectiveness on primary and secondary outcomes. A phase III randomised controlled trial is feasible. TRIAL REGISTRATION: ISRCTN12027752.

Pacritinib is a potent ACVR1 inhibitor with significant anemia benefit in patients with myelofibrosis.

In patients with cytopenic myelofibrosis, treatment with the JAK2/IRAK1 inhibitor pacritinib was associated with anemia benefit in the phase 3 PERSIST-2 study. The impact of pacritinib on transfusion independence (TI) has not been previously described, nor has the mechanism by which pacritinib improves anemia been elucidated. Because it has been previously postulated that inhibition of activin A receptor, type 1 (ACVR1)/activin receptor-like kinase-2 improves anemia in patients with myelofibrosis via suppression of hepcidin production, we assessed the relative inhibitory potency of pacritinib compared with other JAK2 inhibitors against ACVR1. Pacritinib inhibited ACVR1 with greater potency (half-maximal inhibitory concentration [IC50] = 16.7 nM; Cmax:IC50 = 12.7) than momelotinib (IC50 = 52.5 nM; Cmax:IC50 = 3.2), fedratinib (IC50 = 273 nM; Cmax:IC50 = 1.0), or ruxolitinib (IC50 > 1000; Cmax:IC50 < 0.01). Pacritinib's inhibitory activity against ACVR1 was corroborated via inhibition of downstream SMAD signaling in conjunction with marked suppression of hepcidin production. Among patients on PERSIST-2 who were not transfusion independent at baseline based on Gale criteria, a significantly greater proportion achieved TI on pacritinib compared with those treated on best available therapy (37% vs 7%, P = .001), and significantly more had a ≥50% reduction in transfusion burden (49% vs 9%, P < .0001). These data indicate that the anemia benefit of the JAK2/IRAK1 inhibitor pacritinib may be a function of potent ACVR1 inhibition.

Maternal and newborn plasma oxytocin levels in response to maternal synthetic oxytocin administration during labour, birth and postpartum - a systematic review with implications for the function of the oxytocinergic system.

BACKGROUND: The reproductive hormone oxytocin facilitates labour, birth and postpartum adaptations for women and newborns. Synthetic oxytocin is commonly given to induce or augment labour and to decrease postpartum bleeding. AIM: To systematically review studies measuring plasma oxytocin levels in women and newborns following maternal administration of synthetic oxytocin during labour, birth and/or postpartum and to consider possible impacts on endogenous oxytocin and related systems. METHODS: Systematic searches of PubMed, CINAHL, PsycInfo and Scopus databases followed PRISMA guidelines, including all peer-reviewed studies in languages understood by the authors. Thirty-five publications met inclusion criteria, including 1373 women and 148 newborns. Studies varied substantially in design and methodology, so classical meta-analysis was not possible. Therefore, results were categorized, analysed and summarised in text and tables. RESULTS: Infusions of synthetic oxytocin increased maternal plasma oxytocin levels dose-dependently; doubling the infusion rate approximately doubled oxytocin levels. Infusions below 10 milliunits per minute (mU/min) did not raise maternal oxytocin above the range observed in physiological labour. At high intrapartum infusion rates (up to 32 mU/min) maternal plasma oxytocin reached 2-3 times physiological levels. Postpartum synthetic oxytocin regimens used comparatively higher doses with shorter duration compared to labour, giving greater but transient maternal oxytocin elevations. Total postpartum dose was comparable to total intrapartum dose following vaginal birth, but post-caesarean dosages were higher. Newborn oxytocin levels were higher in the umbilical artery vs. umbilical vein, and both were higher than maternal plasma levels, implying substantial fetal oxytocin production in labour. Newborn oxytocin levels were not further elevated following maternal intrapartum synthetic oxytocin, suggesting that synthetic oxytocin at clinical doses does not cross from mother to fetus. CONCLUSIONS: Synthetic oxytocin infusion during labour increased maternal plasma oxytocin levels 2-3-fold at the highest doses and was not associated with neonatal plasma oxytocin elevations. Therefore, direct effects from synthetic oxytocin transfer to maternal brain or fetus are unlikely. However, infusions of synthetic oxytocin in labour change uterine contraction patterns. This may influence uterine blood flow and maternal autonomic nervous system activity, potentially harming the fetus and increasing maternal pain and stress.

Risk-adjusted safety analysis of the oral JAK2/IRAK1 inhibitor pacritinib in patients with myelofibrosis.

The safety profile of the novel oral JAK2/IRAK1 inhibitor pacritinib in patients with cytopenic myelofibrosis was described in the Phase 2 PAC203 and Phase 3 PERSIST-2 studies. To account for longer treatment durations on the pacritinib arms compared to best available therapy (BAT), we present a risk-adjusted safety analysis of event rates accounting for different time on treatment. While the rate of overall events was higher on pacritinib compared to BAT, the rate of fatal events was lower, and there was no excess in bleeding, cardiac events, secondary malignancy, or thrombosis on pacritinib, including in patients with severe thrombocytopenia.

Efficacy and Safety of Pacritinib vs Placebo for Patients With Severe COVID-19: A Phase 2 Randomized Clinical Trial.

Importance: The morbidity and mortality associated with COVID-19 remain high despite advances in standard of care therapy, and the role of anti-inflammatory agents that inhibit the interleukin 6/JAK2 pathway is still being elucidated. Objective: To evaluate the efficacy and safety of the oral JAK2/IRAK1 inhibitor pacritinib vs placebo in the treatment of adults with severe COVID-19. Design, Setting, and Participants: This phase 2, double-blind, placebo-controlled, randomized clinical trial enrolled hospitalized adult patients with severe COVID-19 at 21 centers across the US between June 2020 and February 2021, with approximately 1.5 months of safety follow-up per patient. Data analysis was performed from September 2021 to July 2022. Interventions: Patients were randomized 1:1 to standard of care plus pacritinib (400 mg per os on day 1 followed by 200 mg twice daily on days 2-14) vs placebo, for 14 days. Main Outcomes and Measures: The primary end point was death or need for invasive mechanical ventilation (IMV) or extracorporeal membrane oxygenation (ECMO) by day 28. All-cause mortality and safety were also assessed. Results: A total of 200 patients were randomized to pacritinib (99 patients; 56 men [56.6%]; median [range] age, 60 [19-87] years) or placebo (101 patients; 64 men [63.4%]; median [range] age 59 [28-94] years). The percentage requiring supplementary oxygen was 99.0% (98 patients) in the pacritinib group vs 98.0% (99 patients) in the placebo group. The percentage who progressed to IMV, ECMO, or death was 17.2% (17 patients) in the pacritinib group vs 22.8% (23 patients) in the placebo group (odds ratio, 0.62; 95% CI, 0.28-1.35; P = .23). Among patients with elevated interleukin 6, the rate was 17.5% (11 of 63 patients) in the pacritinib group vs 30.4% (21 of 96 patients) in the placebo group. The adverse event rate was similar for pacritinib vs placebo (78.1% [75 patients] vs 80.2% [81 patients]), with no excess in infection (14.6% [14 patients] vs 19.8% [20 patients]), bleeding (8.3% [8 patients] vs 10.9% [11 patients]), or thrombosis (8.3% [8 patients] vs 7.9% [8 patients]). Rates of grade 3 or higher adverse events were lower with pacritinib than placebo (29.2% [28 patients] vs 40.6% [41 patients]). Conclusions and Relevance: The study did not meet its primary end point in patients with severe COVID-19. Subgroup analyses may indicate specific populations with hyperinflammation that could benefit from pacritinib, although further clinical trials would be needed to confirm these effects. Trial Registration: ClinicalTrials.gov Identifier: NCT04404361.

Acceptance and Commitment Therapy to support medication decision-making and quality of life in women with breast cancer: protocol for a pilot randomised controlled trial.

BACKGROUND: Adherence to adjuvant endocrine therapy is affected by medication side-effects and associated distress. Previous interventions focused on educating women to enhance adherence have proved minimally effective. We co-designed an Acceptance and Commitment Therapy (ACT) intervention to enhance medication decision-making and quality of life by targeting a broader range of factors, including side-effect management and psychological flexibility. This study aims to establish key trial parameters, assess the acceptability of the intervention and the extent to which it can be delivered with fidelity, and to demonstrate "proof of principle" regarding its efficacy on primary and process outcomes. METHODS: The ACTION intervention includes an individual 1:1 ACT session followed by three group sessions involving 8-10 women and two practitioner psychologists. Participants are also provided with access to a website containing evidence-based methods for self-managing side-effects. The ACT sessions were adapted during the COVID-19 pandemic to be remotely delivered via video conferencing software. To evaluate the feasibility and acceptability of this intervention, a multi-site, exploratory, two-arm, individually randomised external pilot trial with a nested qualitative study will be undertaken. Eighty women with early stage breast cancer prescribed adjuvant endocrine therapy will be randomised (1:1) to receive treatment as usual or treatment as usual plus the ACTION intervention. The planned future primary outcome is medication adherence assessed by the ASK-12 measure. Progression to a phase III RCT will be based on criteria related to recruitment and follow-up rates, acceptability to patients, competency and fidelity of delivery, and proof of principle for change in medication adherence. DISCUSSION: This external pilot trial will be used to ascertain the feasibility of undertaking a future phase III RCT to definitively evaluate an ACT-based intervention to support medication taking behaviour and quality of life in women with early stage breast cancer on adjuvant endocrine therapy. TRIAL REGISTRATION: ISRCTN: 12027752. Registered 24 December 2020, https://doi.org/10.1186/ISRCTN12027752.

Sentiment analysis of user feedback on the HSE's Covid-19 contact tracing app.

BACKGROUND: Digital Contact Tracing is seen as a key tool in reducing the propagation of Covid-19. But it requires high uptake and continued participation across the population to be effective. To achieve sufficient uptake/participation, health authorities should address, and thus be aware of, user concerns. AIM: This work manually analyzes user reviews of the Irish Heath Service Executive's (HSE) Contact Tracker app, to identify user concerns and to lay the foundations for subsequent, large-scale, automated analyses of reviews. While this might seem tightly scoped to the Irish context, the HSE app provides the basis for apps in many jurisdictions in the USA and Europe. METHODS: Manual analysis of (1287) user reviews from the Google/Apple playstores was performed, to identify the aspects of the app that users focused on, and the positive/negative sentiment expressed. RESULTS: The findings suggest a largely positive sentiment towards the app, and that users thought it handled data protection and transparency aspects well. But feedback suggests that users would appreciate more targeted feedback on the incidence of the virus, and facilities for more proactive engagement, like notifications that prompt users to submit their health status daily. Finally, the analysis suggests that the "android battery" issue and the backward-compatibility issue with iPhones seriously impacted retention/uptake of the app respectively. CONCLUSION: The HSE have responded to the public's desire for targeted feedback in newer versions, but should consider increasing the app's proactive engagement. The results suggest they should also raise the backward compatibility issue, regarding older iPhones, with Apple.

Retrospective analysis of pacritinib in patients with myelofibrosis and severe thrombocytopenia.

Thrombocytopenia is common in patients with myelofibrosis (MF) and is a well-established adverse prognostic factor. Both of the approved Janus kinase (JAK) inhibitors, ruxolitinib and fedratinib, can worsen thrombocytopenia and have not been evaluated in patients with severe thrombocytopenia (platelet counts <50×109/L). Pacritinib, a novel JAK2/interleukin-1 receptor-associated kinase 1 inhibitor, has been studied in two phase III trials (PERSIST-1 and PERSIST- 2), both of which enrolled patients with MF and severe thrombocytopenia. In order to better characterize treatment outcomes for this population with advanced disease, we present a retrospective analysis of efficacy and safety data in the 189 patients with severe thrombocytopenia treated in the PERSIST studies. The proportion of patients in the pacritinib group meeting efficacy endpoints was greater than in the BAT group for ≥35% spleen volume reduction (23% vs. 2%, P=0.0007), ≥50% modified Total Symptom Score reduction (25% vs. 8%, P=0.044), and self-reported symptom benefit ("much" or "very much" improved; 25% vs. 8%, P=0.016) at the primary analysis time point (week 24). The adverse event profile of pacritinib was manageable, and dose modification was rarely required. There was no excess in bleeding or death in pacritinib-treated patients. These results indicate that pacritinib is a promising treatment for patients with MF who lack safe and effective therapeutic options due to severe thrombocytopenia.

The role of oxidative stress in HIV-associated neurocognitive disorders.

HIV-associated neurocognitive disorders (HAND) are a leading cause of morbidity in up to 50% of individuals living with HIV, despite effective treatment with antiretroviral therapy (ART). Current evidence suggests that chronic inflammation associated with HIV is especially attributed to the dysregulated production of reactive oxygen species (ROS) that contribute to neurodegeneration and poor clinical outcomes. While ROS have beneficial effects in eliciting immune responses to infection, chronic ROS production causes damage to macromolecules such as DNA and lipids that has been linked to altered redox homeostasis associated with antioxidant dysregulation. As a result, this disruption in the balance between antioxidant-dependent mechanisms of ROS inactivation and ROS production by enzymes such as the nicotinamide adenine dinucleotide phosphate (NADPH) oxidase family, as well as from the electron transport chain of the mitochondria can result in oxidative stress. This is particularly relevant to the brain, which is exquisitely susceptible to oxidative stress due to its inherently high lipid concentration and ROS levels that have been linked to many neurodegenerative diseases that have similar stages of pathogenesis to HAND. In this review, we discuss the possible role and mechanisms of ROS production leading to oxidative stress that underpin HAND pathogenesis even when HIV is suppressed by current gold-standard antiretroviral therapies. Furthermore, we highlight that pathological ROS can serve as biomarkers for HIV-dependent HAND, and how manipulation of oxidative stress and antioxidant-dependent pathways may facilitate novel strategies for HIV cure.

Pacritinib demonstrates spleen volume reduction in patients with myelofibrosis independent of JAK2V617F allele burden.

Myelofibrosis (MF) has heterogeneous clinical manifestations, with some patients exhibiting a myelodepletive phenotype characterized by cytopenias and an absent or low JAK2V617F allele burden. Ruxolitinib may be less effective in these patients. We assessed the efficacy of pacritinib, a JAK2/IRAK1 inhibitor, in MF patients with low JAK2V617F allele burden. In this post hoc analysis of the PERSIST-1 and -2 trials, patients with MF randomized to pacritinib or best available therapy (BAT) were stratified by JAK2V617F allele burden quartile for spleen response of ≥35% and improvement in total symptom score of ≥50%. Five hundred thirty-six patients were included. Patients with lower JAK2V617F allele burden had smaller baseline spleens and lower hemoglobin and platelet counts as compared with higher allele burden patients. Among pacritinib-treated patients, spleen responses were observed across all JAK2V617F allele burden quartiles and in JAK2V617F- disease. No spleen responses were observed among BAT-treated patients with allele burden ≤50% or JAK2V617F- disease. The intention-to-treat response rate was significantly higher on the pacritinib arm for JAK2V617F- disease (23.0% vs 0%; P = .033), and for the lowest allele burden quartiles (0%-25%: 20.9% vs 0%, P < .001; 25%-50%: 15.4% vs 0%, P = .020). There were significantly more symptom responders with pacritinib vs BAT in the 0% to 25% and 25% to 50% cohorts. Pacritinib treatment led to superior spleen and symptom burden reduction compared with BAT in patients with absent or low JAK2V617F allele burden, suggesting that pacritinib may be uniquely suited for patients with myelodepletive MF.

A case series of rapidly growing mycobacterial catheter-related bloodstream infections among immunocompetent patients.

Rapidly growing mycobacteria (RGM) are ubiquitous in the environment and can cause a variety of human infections. Catheter-related bloodstream infections (CRBSI) caused by RGM have been reported predominantly among immunocompromised patients. Removal of central lines and antimicrobial therapy with at least 2 active agents are generally recommended for immunocompromised patients. RGM bloodstream infections (BSIs) are rare in immunocompetent patients and clinical data are very limited. Retrospective medical record review was conducted on patients with blood cultures positive for RGM from July 2012 through March 2015 at Lemuel Shattuck Hospital, a public teaching hospital in Jamaica Plain, Massachusetts, United States. RGM was suspected by presence of beaded Gram-positive bacilli on Gram staining of positive conventional blood cultures and it was confirmed as RGM by Massachusetts State Public Health Laboratory. Nineteen episodes of RGM BSI were identified in 17 patients who had no known immunocompromised conditions that predispose them to opportunistic pathogens. They were predominantly young male with history of intravenous drug use. Peripherally inserted central catheter (PICC) was present in all episodes of RGM BSI and 74% of them clinically improved with PICC removal alone without specific antibiotic therapy for RGM. They were followed up for median duration of 45 days (interquartile range 25-385). The patients remained alive and asymptomatic until the end of follow-up periods. In immunocompetent patients, removal of catheters alone without adding specific antibiotics may be sufficient for RGM CRBSI.

Determining the recommended dose of pacritinib: results from the PAC203 dose-finding trial in advanced myelofibrosis.

PAC203 is a randomized dose-finding study of pacritinib, an oral JAK2/IRAK1 inhibitor, in patients with advanced myelofibrosis who are intolerant of or resistant to ruxolitinib. Patients were randomized 1:1:1 to pacritinib 100 mg once per day, 100 mg twice per day, or 200 mg twice per day. Enhanced eligibility criteria, monitoring, and dose modifications were implemented to mitigate risk of cardiac and hemorrhagic events. Efficacy was based on ≥35% spleen volume response (SVR) and ≥50% reduction in the 7-component total symptom score (TSS) through week 24. Of 161 patients, 73% were intolerant of and 76% had become resistant to ruxolitinib; 50% met criteria for both. Severe thrombocytopenia (platelet count <50 × 103/µL) was present in 44%. SVR rates were highest with 200 mg twice per day (100 mg once per day, 0%; 100 mg twice per day, 1.8%; 200 mg twice per day, 9.3%), particularly among patients with baseline platelet counts <50 × 103/µL (17%; 4 of 24). Although TSS response rate was similar across doses (100 mg once per day, 7.7%; 100 mg twice per day, 7.3%; 200 mg twice per day, 7.4%), median percent reduction in TSS suggested a dose-response relationship (-3%, -16%, and -27%, respectively). Pharmacokinetic and pharmacodynamic modeling based on all available data showed greatest SVR and TSS reduction at 200 mg twice per day compared with lower doses. Common adverse events were gastrointestinal events, thrombocytopenia, and anemia. There was no excess of grade ≥3 hemorrhagic or cardiac events at 200 mg twice per day. Pacritinib 200 mg twice per day demonstrated clinical activity and an acceptable safety profile and was selected as the recommended dose for a pivotal phase 3 study in patients with myelofibrosis and severe thrombocytopenia. This trial was registered at www.clinicaltrials.gov as #NCT03165734.

Maternal plasma levels of oxytocin during breastfeeding-A systematic review.

INTRODUCTION: Oxytocin is a key hormone in breastfeeding. No recent review on plasma levels of oxytocin in response to breastfeeding is available. MATERIALS AND METHODS: Systematic literature searches on breastfeeding induced oxytocin levels were conducted 2017 and 2019 in PubMed, Scopus, CINAHL, and PsycINFO. Data on oxytocin linked effects and effects of medical interventions were included if available. RESULTS: We found 29 articles that met the inclusion criteria. All studies had an exploratory design and included 601 women. Data were extracted from the articles and summarised in tables. Breastfeeding induced an immediate and short lasting (20 minutes) release of oxytocin. The release was pulsatile early postpartum (5 pulses/10 minutes) and coalesced into a more protracted rise as lactation proceeded. Oxytocin levels were higher in multiparous versus primiparous women. The number of oxytocin pulses during early breastfeeding was associated with greater milk yield and longer duration of lactation and was reduced by stress. Breastfeeding-induced oxytocin release was associated with elevated prolactin levels; lowered ACTH and cortisol (stress hormones) and somatostatin (a gastrointestinal hormone) levels; enhanced sociability; and reduced anxiety, suggesting that oxytocin induces physiological and psychological adaptations in the mother. Mechanical breast pumping, but not bottle-feeding was associated with oxytocin and prolactin release and decreased stress levels. Emergency caesarean section reduced oxytocin and prolactin release in response to breastfeeding and also maternal mental adaptations. Epidural analgesia reduced prolactin and mental adaptation, whereas infusions of synthetic oxytocin increased prolactin and mental adaptation. Oxytocin infusion also restored negative effects induced by caesarean section and epidural analgesia. CONCLUSIONS: Oxytocin is released in response to breastfeeding to cause milk ejection, and to induce physiological changes to promote milk production and psychological adaptations to facilitate motherhood. Stress and medical interventions during birth may influence these effects and thereby adversely affect the initiation of breastfeeding.

Birth as a neuro-psycho-social event: An integrative model of maternal experiences and their relation to neurohormonal events during childbirth.

BACKGROUND: Psychological aspects of labor and birth have received little attention within maternity care service planning or clinical practice. The aim of this paper is to propose a model demonstrating how neurohormonal processes, in particular oxytocinergic mechanisms, not only control the physiological aspects of labor and birth, but also contribute to the subjective psychological experiences of birth. In addition, sensory information from the uterus as well as the external environment might influence these neurohormonal processes thereby influencing the progress of labor and the experience of birth. METHODOLOGY: In this new model of childbirth, we integrated the findings from two previous systematic reviews, one on maternal plasma levels of oxytocin during physiological childbirth and one meta-synthesis of women´s subjective experiences of physiological childbirth. FINDINGS: The neurobiological processes induced by the release of endogenous oxytocin during birth influence maternal behaviour and feelings in connection with birth in order to facilitate birth. The psychological experiences during birth may promote an optimal transition to motherhood. The spontaneous altered state of consciousness, that some women experience, may well be a hallmark of physiological childbirth in humans. The data also highlights the crucial role of one-to-one support during labor and birth. The physiological importance of social support to reduce labor stress and pain necessitates a reconsideration of many aspects of modern maternity care. CONCLUSION: By listening to women's experiences and by observing women during childbirth, factors that contribute to an optimized process of labor, such as the mothers' wellbeing and feelings of safety, may be identified. These observations support the integrative role of endogenous oxytocin in coordinating the neuroendocrine, psychological and physiological aspects of labor and birth, including oxytocin mediated. decrease of pain, fear and stress, support the need for midwifery one-to-one support in labour as well as the need for maternity care that optimizes the function of these neuroendocrine processes even when birth interventions are used. Women and their partners would benefit from understanding the crucial role that endogenous oxytocin plays in the psychological and neuroendocrinological process of labor.

The initiation of labour at term gestation: Physiology and practice implications.

Little is known about the physiology of labour onset at term, and there is a debate about what signs and symptoms should be used to define it. In low resource settings, particularly for remote and rural communities, delay in recognising labour onset may mean a delay in seeking a skilled birth attendant. This chapter presents the most recent evidence about the physiology of labour onset, including the complex neuro-hormonal, biophysical, psychological and emotional factors that contribute. The symptoms of labour onset are explored from the perspective of both pregnant women and service providers in a range of sociocultural contexts. Early labour presents challenges for pregnant women, their families, communities and health care professionals. The chapter discusses how maternity care services should be designed, and delivered to ensure that women get the optimum advice and care at the beginning of labour.

Development and validation of the AML-QOL: a quality of life instrument for patients with acute myeloid leukemia.

There is currently no validated quality of life (QOL) instrument specific to patients with acute myeloid leukemia (AML). A previous cross-sectional interview-based study elicited concepts for inclusion in a novel QOL instrument. Here, we further develop and validate this new instrument, the AML-QOL. Iterative revisions of the draft AML-QOL were refined based on feedback from 16 patients, 8 medical providers, and 3 psychometricians. The instrument underwent factor analysis based on responses from 202 patients with AML and analogous aggressive myeloid neoplasms receiving AML-like therapy. A prospective validation study was then undertaken in 50 patients who completed the AML-QOL at multiple time points while undergoing a cycle of intensive chemotherapy to establish test-retest reliability and sensitivity to change. The final AML-QOL contains 27 items and is categorized into 5 domains (Physical, Social, Cognitive, Anxiety, Depression), one Symptom Index, a single item assessing overall quality of life, and a Summary Score. The AML-QOL domains show high internal consistency (median alpha: 0.85), good test-retest reliability (median interclass correlation: 0.82), and had convergent and divergent validity when compared to a non-disease-specific instrument (the EORTC QLQ-C30). The Summary Score demonstrated good sensitivity to change when anchored to patient perception of QOL change. The AML-QOL is a reliable and valid measure of QOL in patients with AML and analogous aggressive myeloid neoplasms. A clinically meaningful difference is 8-10 points out of 100 on the Summary Score.