Trajectories of Quality of Life after Hematopoietic Cell Transplantation: Secondary Analysis of BMT CTN 0902 Data

Quality of life is increasingly recognized as an important secondary endpoint of hematopoietic cell transplantation (HCT). The current study examined the extent to which attrition results in biased estimates of patient quality of life. The study also examined whether patients differ in terms of trajectories of quality of life in the first six months post-transplant. A secondary data analysis was conducted of 701 participants who enrolled in the Blood and Marrow Transplantation Clinical Trials Network (BMT CTN) 0902 trial. Participants completed the SF-36, a measure of quality of life, prior to transplant and 100 and 180 days post-transplant. Results indicated that attrition resulted in slightly biased overestimates of quality of life but the amount of overestimation remained stable over time. Patients could be grouped into three distinct classes based on physical quality of life: 1) low and stable; 2) average and declining, then stable; and 3) average and stable. Four classes of patients emerged for mental quality of life: 1) low and stable; 2) average, improving, then stable; 3) higher than average (by almost 1 SD) and stable; and 4) average and stable. Taken together, these data provide a more comprehensive understanding of quality of life that can be used to educate HCT recipients and their caregivers

Frailty in randomised controlled trials for dementia or mild cognitive impairment measured via the frailty index: prevalence and prediction of serious adverse events and attrition

Background: Frailty and dementia have a bidirectional relationship. However, frailty is rarely reported in clinical trials for dementia and mild cognitive impairment (MCI) which limits assessment of trial applicability. This study aimed to use a frailty index (FI)—a cumulative deficit model of frailty—to measure frailty using individual participant data (IPD) from clinical trials for MCI and dementia. Moreover, the study aimed to quantify the prevalence of frailty and its association with serious adverse events (SAEs) and trial attrition. Methods: We analysed IPD from dementia (n = 1) and MCI (n = 2) trials. An FI comprising physical deficits was created for each trial using baseline IPD. Poisson and logistic regression were used to examine associations with SAEs and attrition, respectively. Estimates were pooled in random effects meta-analysis. Analyses were repeated using an FI incorporating cognitive as well as physical deficits, and results compared. Results: Frailty could be estimated in all trial participants. The mean physical FI was 0.14 (SD 0.06) and 0.14 (SD 0.06) in the MCI trials and 0.24 (SD 0.08) in the dementia trial. Frailty prevalence (FI > 0.24) was 6.9%/7.6% in MCI trials and 48.6% in the dementia trial. After including cognitive deficits, the prevalence was similar in MCI (6.1% and 6.7%) but higher in dementia (75.4%). The 99th percentile of FI (0.31 and 0.30 in MCI, 0.44 in dementia) was lower than in most general population studies. Frailty was associated with SAEs: physical FI IRR = 1.60 [1.40, 1.82]; physical/cognitive FI IRR = 1.64 [1.42, 1.88]. In a meta-analysis of all three trials, the estimated association between frailty and trial attrition included the null (physical FI OR = 1.17 [0.92, 1.48]; physical/cognitive FI OR = 1.16 [0.92, 1.46]), although higher frailty index values were associated with attrition in the dementia trial. Conclusion: Measuring frailty from baseline IPD in dementia and MCI trials is feasible. Those living with more severe frailty may be under-represented. Frailty is associated with SAEs. Including only physical deficits may underestimate frailty in dementia. Frailty can and should be measured in future and existing trials for dementia and MCI, and efforts should be made to facilitate inclusion of people living with frailty

The efficacy and safety of ketamine for depression in patients with cancer: A systematic review

Management of depression in the oncology population includes supportive psychotherapeutic interventions with or without psychotropic medication, which take time to demonstrate effectiveness. Fast-acting interventions, like ketamine, can provide a rapid antidepressant effect; however, there has been limited research on effects of ketamine among cancer patients. The objective of this review is to provide an overview of research on the efficacy and safety of ketamine on depression in patients with cancer. We reviewed the published literature in MEDLINE® (via PubMed®), EMBASE, and Scopus from 1 January 1982 to 20 October 2022. We screened the retrieved abstracts against inclusion criteria and conducted a full-text review of eligible studies. Following extraction of data from included studies, we used a framework analysis approach to summarize the evidence on using ketamine in patients with cancer. All 5 included studies were randomized clinical trials conducted in inpatient settings in China. In all included studies ketamine was administered intravenously. Three studies used only racemic ketamine, and two studies used both S-ketamine and racemic ketamine. All included studies reported ketamine a tolerable and effective drug to control depression symptoms. Included studies showed administration of sub-anesthesia ketamine significantly improves postoperative depression among patients with cancer. [Abstract copyright: © 2023 The Author(s).

Use of a Cancer Registry to Evaluate Patient-Reported Outcomes of Immune Checkpoint Inhibitors.

Immune checkpoint inhibitors (ICIs) are increasingly used for advanced lung cancer, butfew studies have reported on patient-reported outcomes (PROs) outside the context of a clinicaltrial. The goal of the current study was to assess PROs in participants of a lung cancer registry whohad been treated with an ICI. Patients participating in the GO2Foundation’s Lung Cancer Registrywho reported receiving atezolizumab, durvalumab, nivolumab, or pembrolizumab were invited toparticipate in a survey about their experiences during treatment. Quality of life was evaluated usingthe Functional Assessment of Cancer Therapy–General (FACT-G). Common symptomatic adverseevents were evaluated using an item bank generated for ICIs. Internationally, 226 patients (meanage 61, 75% female) participated. Patients reported worse quality of life at the time of assessmentthan U.S. population and cancer normative samples. The most common moderate to severe adverseevents during ICI treatment were fatigue (41%), aching joints (27%), and aching muscles (20%). Dueto toxicity, 25% reported a treatment delay, 11% an emergency room visit, and 9% a hospitalization.This study is among the first to our knowledge to report on PROs of ICIs outside the context of aclinical trial. Results suggest higher rates of adverse events than previously reported in clinical trials

Planet-induced Stellar Pulsations in HAT-P-2's Eccentric System

Extrasolar planets on eccentric short-period orbits provide a laboratory in which to study radiative and tidal interactions between a planet and its host star under extreme forcing conditions. Studying such systems probes how the planet's atmosphere redistributes the time-varying heat flux from its host and how the host star responds to transient tidal distortion. Here, we report the insights into the planet–star interactions in HAT-P-2's eccentric planetary system gained from the analysis of ~350 hr of 4.5 μm observations with the Spitzer Space Telescope. The observations show no sign of orbit-to-orbit variability nor of orbital evolution of the eccentric planetary companion, HAT-P-2 b. The extensive coverage allows us to better differentiate instrumental systematics from the transient heating of HAT-P-2 b's 4.5 μm photosphere and yields the detection of stellar pulsations with an amplitude of approximately 40 ppm. These pulsation modes correspond to exact harmonics of the planet's orbital frequency, indicative of a tidal origin. Transient tidal effects can excite pulsation modes in the envelope of a star, but, to date, such pulsations had only been detected in highly eccentric stellar binaries. Current stellar models are unable to reproduce HAT-P-2's pulsations, suggesting that our understanding of the interactions at play in this system is incomplete

Observational and Dynamical Characterization of Main-Belt Comet P/2010 R2 (La Sagra)

We present observations of comet-like main-belt object P/2010 R2 (La Sagra) obtained by Pan-STARRS 1 and the Faulkes Telescope-North on Haleakala in Hawaii, the University of Hawaii 2.2 m, Gemini-North, and Keck I telescopes on Mauna Kea, the Danish 1.54 m telescope at La Silla, and the Isaac Newton Telescope on La Palma. An antisolar dust tail is observed from August 2010 through February 2011, while a dust trail aligned with the object's orbit plane is also observed from December 2010 through August 2011. Assuming typical phase darkening behavior, P/La Sagra is seen to increase in brightness by >1 mag between August 2010 and December 2010, suggesting that dust production is ongoing over this period. These results strongly suggest that the observed activity is cometary in nature (i.e., driven by the sublimation of volatile material), and that P/La Sagra is therefore the most recent main-belt comet to be discovered. We find an approximate absolute magnitude for the nucleus of H_R=17.9+/-0.2 mag, corresponding to a nucleus radius of ~0.7 km, assuming an albedo of p=0.05. Using optical spectroscopy, we find no evidence of sublimation products (i.e., gas emission), finding an upper limit CN production rate of Q_CN<6x10^23 mol/s, from which we infer an H2O production rate of Q_H2O<10^26 mol/s. Numerical simulations indicate that P/La Sagra is dynamically stable for >100 Myr, suggesting that it is likely native to its current location and that its composition is likely representative of other objects in the same region of the main belt, though the relatively close proximity of the 13:6 mean-motion resonance with Jupiter and the (3,-2,-1) three-body mean-motion resonance with Jupiter and Saturn mean that dynamical instability on larger timescales cannot be ruled out.Comment: 23 pages, 13 figures, accepted for publication in A

Pre-treatment psychoneurological symptoms and their association with longitudinal cognitive function and quality of life in older breast cancer survivors

Context Symptoms affect quality of life (QOL), functional status, and cognitive function in cancer survivors, but older survivors are understudied. Objectives To identify prototypical pre-systemic therapy psychoneurological symptom clusters among older breast cancer survivors, and determine whether these symptom clusters predicted cognition and QOL over time. Methods Women with newly diagnosed non-metastatic breast cancer (n=319) and matched non-cancer controls (n=347) aged 60+ completed questionnaires and neuropsychological tests before systemic therapy and 12- and 24-months later. Latent class analysis identified clusters of survivors based upon their pre-therapy depression, anxiety, fatigue, sleep disturbance, and pain. Linear mixed-effects models examined changes in objective cognition, perceived cognition, and functional status (instrumental activities of daily living (IADL) disability, functional well-being, and breast cancer-specific QOL) by group, controlling for covariates. Results Nearly one-fifth of older survivors were classified as having a high pre-therapy symptoms (n=51; 16%); the remainder had a low symptoms (n=268; 84%); both groups improved over time on all outcomes. However, compared to the low symptom group and controls, survivors with high symptoms had lower baseline objective cognition and lower perceived cognition at baseline and 24-months, lower functional well-being at baseline and 12-months, greater IADL disability at baseline, and lower breast cancer-specific QOL at all time points (all p<0.05). Conclusion Nearly one-fifth of older breast cancer survivors had high psychoneurological symptoms at diagnosis, which, predict clinically meaningful decrements in perceived cognition and function in the first 24 months post-diagnosis. Pre-treatment psychoneurological symptom clusters could identify survivors for monitoring or intervention

Symptom burden among older breast cancer survivors: The Thinking and Living With Cancer (TLC) study

Background: Little is known about longitudinal symptom burden and its consequences for well-being, and if lifestyle moderates burden in older survivors. Methods: We report on 36-month data from survivors 60+ with newly diagnosed non-metastatic breast cancer and non-cancer controls recruited August 2010-June 2016. Symptom burden was a sum of self-reported symptoms/diseases: pain (yes/no), fatigue (FACT-fatigue), cognitive (FACT-cog), sleep problems (yes/no), depression (CES-D), anxiety (STAI), and cardiac problems and neuropathy (yes/no). Well-being was measured using the FACT-G, scaled from 0–100. Lifestyle included smoking, alcohol use, BMI, physical activity, and leisure activities. Mixed models assessed relationships between treatment group (chemotherapy +/− hormonal, hormonal only, control) and symptom burden, lifestyle, and covariates. Separate models tested the effects of fluctuations in symptom burden and lifestyle on function. Results: All groups reported high baseline symptoms, and levels remained high over time; survivor-control differences were most notable for cognitive and sleep problems, anxiety, and neuropathy. The adjusted burden score was highest among chemotherapy-exposed survivors, followed by hormonal therapy vs. controls (p<.001). Burden score was related to physical, emotional, and functional well-being (e.g., survivors with lower vs. higher burden scores had 12.4-point higher physical well-being score). The composite lifestyle score was not related to symptom burden or well-being, but physical activity was significantly associated with each outcome (<.005). Conclusions: Cancer and its treatments are associated with a higher level of actionable symptoms and greater loss of well-being over time in older breast cancer survivors than comparable non-cancer populations, suggesting the need for surveillance and opportunities for intervention

Cancer-Related Cognitive Outcomes Among Older Breast Cancer Survivors in the Thinking and Living With Cancer Study

Purpose To determine treatment and aging-related effects on longitudinal cognitive function in older breast cancer survivors. Methods Newly diagnosed nonmetastatic breast cancer survivors (n = 344) and matched controls without cancer (n = 347) 60 years of age and older without dementia or neurologic disease were recruited between August 2010 and December 2015. Data collection occurred during presystemic treatment/control enrollment and at 12 and 24 months through biospecimens; surveys; self-reported Functional Assessment of Cancer Therapy-Cognitive Function; and neuropsychological tests that measured attention, processing speed, and executive function (APE) and learning and memory (LM). Linear mixed-effects models tested two-way interactions of treatment group (control, chemotherapy with or without hormonal therapy, and hormonal therapy) and time and explored three-way interactions of ApoE (ε4+ v not) by group by time; covariates included baseline age, frailty, race, and cognitive reserve. Results Survivors and controls were 60 to 98 years of age, were well educated, and had similar baseline cognitive scores. Treatment was related to longitudinal cognition scores, with survivors who received chemotherapy having increasingly worse APE scores (P = .05) and those initiating hormonal therapy having lower LM scores at 12 months (P = .03) than other groups. These group-by-time differences varied by ApoE genotype, where only ε4+ survivors receiving hormone therapy had short-term decreases in adjusted LM scores (three-way interaction P = .03). For APE, the three-way interaction was not significant (P = .14), but scores were significantly lower for ε4+ survivors exposed to chemotherapy (−0.40; 95% CI, −0.79 to −0.01) at 24 months than ε4+ controls (0.01; 95% CI, 0.16 to 0.18; P < .05). Increasing age was associated with lower baseline scores on all cognitive measures (P < .001); frailty was associated with baseline APE and self-reported decline (P < .001). Conclusion Breast cancer systemic treatment and aging-related phenotypes and genotypes are associated with longitudinal decreases in cognitive function scores in older survivors. These data could inform treatment decision making and survivorship care planning

Parent and child interactions with two contrasting anti-obesity advertising campaigns: A qualitative analysis

Background: Social marketing has been proposed as a framework that may be effectively used to encourage behaviour change relating to obesity. Social advertising (or mass media campaigning) is the most commonly used social marketing strategy to address the issue of obesity. While social advertising has the potential to effectively communicate information about obesity, some argue that the current framing and delivery of these campaigns are ineffective, and may cause more harm than good. Methods: We used a qualitative advertising reception study. 150 family groups (comprised of 159 parents and 184 children) were shown two Australian government anti-obesity advertisements: Measure Up (focused on problems associated with obesity) and Swap It (focused on solutions for obesity). Families were engaged in a discussion about the visual appeals, verbal messages and their perceptions about the impact of the advertisements on behavioural change. Open coding techniques and a constant comparative method of analysis was used to interpret the data.Results: Many parents had strong personal resonance with the visual imagery within the campaigns. While Swap It had strong ‘likeability’ with children, many children believed that the messages about overweight and obesity were less personally relevant because they did not perceive themselves to be overweight. The content and delivery style of the verbal messages (the serious risk focused message in Measure Up compared to the upbeat, fun practical message in Swap It) influenced how different audiences (parents and children) interpreted the information that was presented. Parents assimilated practical and instructive messages, while children assimilated messages about weight loss and weight gain. Parents and children recognised that the campaigns were asking individuals to take personal responsibility for their weight status, and were at times critical that the campaigns did not tackle the broader issues associated with the causes and consequences of obesity. The lack of practical tools to encourage behavioural change was a key barrier for obese parents. Conclusions: Well-funded, targeted social marketing campaigns will play an important role in the prevention and management of obesity. It is important that these campaigns are comprehensively evaluated and are backed up with structural supports to enable and encourage population subgroups to act upon messages