Medical care disruptions during the first six months of the COVID-19 pandemic: the experience of older breast cancer survivors.

PURPOSE: Older cancer survivors required medical care during the COVID-19 pandemic, but there are limited data on medical care in this age group. METHODS: We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors aged 60-98 from five US regions (n = 321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included interruptions in seeing or speaking to doctors, receiving medical treatment or supportive therapies, or filling prescriptions since the pandemic began. Logistic regression models evaluated associations between care disruptions and education, medical, psychosocial, and COVID-19-related factors. Multivariate models included age, county COVID-19 death rates, comorbidity, and post-diagnosis time. RESULTS: There was a high response rate (n = 262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were higher with each year of education (OR 1.22, 95% CI 1.08-1.37, p = < 0.001) and increased depression by CES-D score (OR 1.04, CI 1.003-1.08, p = 0.033) while increased tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99, p = 0.012). There was a trend between disruptions and comorbidities (unadjusted OR 1.13 per comorbidity, 95% CI 0.99-1.29, p = 0.07). Adjusting for covariates, higher education years (OR1.23, 95% CI 1.09-1.39, p = 0.001) and tangible social support (OR 0.98 95% CI 0.97-1.00, p = 0.006) remained significantly associated with having care disruptions. CONCLUSION: Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions. CLINICALTRIALS. GOV IDENTIFIER: NCT03451383.

Medical Care Disruptions During the First Six-Months of the COVID19 Pandemic: The Experience of Older Breast Cancer Survivors.

PurposeOlder cancer survivors required medical care during the COVID-19 pandemic despite infection risks, but there are limited data on medical care in this age group. METHODS: We evaluated care disruptions in a longitudinal cohort of non-metastatic breast cancer survivors ages 60-98 from five US regions (n=321). Survivors completed a web-based or telephone survey from May 27, 2020 to September 11, 2020. Care disruptions included self-reported interruptions in ability to see doctors, receive treatment or supportive therapies, or fill prescriptions. Logistic regression models evaluated bivariate and multivariate associations between care disruptions and education, medical, psychosocial and COVID-19-related factors. Multivariate models included age, county COVID-19 rates, comorbidity and post-diagnosis time. RESULTS: There was a high response rate (n=262, 81.6%). Survivors were 32.2 months post-diagnosis (SD 17.5, range 4-73). Nearly half (48%) reported a medical disruption. The unadjusted odds of care disruptions were significantly higher with more education (OR 1.23 per one-year increase, 95% CI 1.09-1.39, p =0.001) and greater depression (OR 1.04 per one-point increase in CES-D score, CI 1.003-1.08, p=0.033); tangible support decreased the odds of disruptions (OR 0.99, 95% CI 0.97-0.99 per one-point increase, p=0.012). There was a trend for associations between disruptions and comorbidity (unadjusted OR 1.13 per 1 added comorbidity, 95% CI 0.99-1.29, p=0.07). Adjusting for covariates, only higher education (p=0.001) and tangible social support (p=0.006) remained significantly associated with having care disruptions. CONCLUSIONS: Older breast cancer survivors reported high rates of medical care disruptions during the COVID-19 pandemic and psychosocial factors were associated with care disruptions.

Feasibility of measuring memory response to increasing dexmedetomidine sedation in children.

BACKGROUND: The memory effect of dexmedetomidine has not been prospectively evaluated in children. We evaluated the feasibility of measuring memory and sedation responses in children during dexmedetomidine sedation for non-painful radiological imaging studies. Secondarily, we quantified changes in memory in relation to the onset of sedation. METHODS: A 10 min bolus of dexmedetomidine (2 mcg kg-1) was given to children as they named simple line drawings every five s. The absence of sedation was identified as any verbal response, regardless of correctness. After recovery, recognition memory was tested with correct Yes/No recognitions (50% novel pictures) and was matched to sedation responses during the bolus period (subsequent memory paradigm). RESULTS: Of 64 accruals, 30 children (mean [SD]6.1 (1.2) yr, eight male) received dexmedetomidine and completed all study tasks. Individual responses were able to be modelled successfully in the 30 children completing all the study tasks, demonstrating feasibility of this approach. Children had 50% probability of verbal response at five min 40 s after infusion start, whereas 50% probability of subsequent recognition memory occurred sooner at four min five s. CONCLUSIONS: Quantifying memory and sedation effects during dexmedetomidine infusion in verbal children was possible and demonstrated that memory function was present until shortly before verbal unresponsiveness occurred. This is the first study to investigate the effect of dexmedetomidine on memory in children. CLINICAL TRIAL REGISTRATION: NCT 02354378.

Brain structure and function in patients with ovarian cancer treated with first-line chemotherapy: a pilot study.

Women with ovarian cancer often undergo chemotherapy involving multiple agents. However, little is known about treatment-related central neurotoxicity in this population. The goal of this cross-sectional study was to assess brain structure and function and neurocognitive abilities in patients with ovarian cancer following first-line chemotherapy. Eighteen patients with ovarian, peritoneal and fallopian tube cancer and eighteen healthy controls matched for gender, age and education participated in the study. The patients were evaluated 1-4 months following completion of first-line taxane/platinum chemotherapy. All participants underwent structural and functional magnetic resonance imaging (MRI), and completed neuropsychological tests of attention, memory and executive functions. Neuroimaging assessments included voxel-based morphometry (VBM) for measuring gray matter (GM) volume, and functional MRI (fMRI) during the N-back working memory task. The results of VBM showed that patients had significantly reduced GM volume compared to healthy controls in the right middle/superior frontal gyrus, and in the left supramarginal gyrus and left inferior parietal lobule. fMRI results indicated significantly decreased activation in patients relative to healthy controls in the left middle frontal gyrus and left inferior parietal lobule during the N-back task (1/2/3-back >0-back). There were no statistically significant differences between the two groups on the neuropsychological tests. This is the first study showing structural and functional alterations involving frontal and parietal regions in patients with ovarian cancer treated with first-line chemotherapy. These findings are congruent with studies involving women with breast cancer, and provide additional supporting evidence for central neurotoxicity associated with taxane/platinum chemotherapy.

Prospective assessment of white matter integrity in adult stem cell transplant recipients.

Hematopoietic stem cell transplantation (HSCT) is often used in the treatment of hematologic disorders. Although it can be curative, the pre-transplant conditioning regimen can be associated with neurotoxicity. In this prospective study, we examined white matter (WM) integrity with diffusion tensor imaging (DTI) and neuropsychological functioning before and one year after HSCT in twenty-two patients with hematologic disorders and ten healthy controls evaluated at similar intervals. Eighteen patients received conditioning treatment with high-dose (HD) chemotherapy, and four had full dose total body irradiation (fTBI) and HD chemotherapy prior to undergoing an allogeneic or autologous HSCT. The results showed a significant decrease in mean diffusivity (MD) and axial diffusivity (AD) in diffuse WM regions one year after HSCT (p-corrected <0.05) in the patient group compared to healthy controls. At baseline, patients treated with allogeneic HSCT had higher MD and AD in the left hemisphere WM than autologous HSCT patients (p-corrected <0.05). One year post-transplant, patients treated with allogeneic HSCT had lower fractional anisotropy (FA) and higher radial diffusivity (RD) in the right hemisphere and left frontal WM compared to patients treated with autologous HSCT (p-corrected <0.05).There were modest but significant correlations between MD values and cognitive test scores, and these were greatest for timed tests and in projection tracts. Patients showed a trend toward a decline in working memory, and had lower cognitive test scores than healthy controls at the one-year assessment. The findings suggest a relatively diffuse pattern of alterations in WM integrity in adult survivors of HSCT.

Effect of propofol on the medial temporal lobe emotional memory system: a functional magnetic resonance imaging study in human subjects.

BACKGROUND: Subclinical doses of propofol produce anterograde amnesia, characterized by an early failure of memory consolidation. It is unknown how propofol affects the amygdala-dependent emotional memory system, which modulates consolidation in the hippocampus in response to emotional arousal and neurohumoral stress. We present an event-related functional magnetic resonance imaging study of the effects of propofol on the emotional memory system in human subjects. METHODS: Thirty-five healthy subjects were randomized to receive propofol, at an estimated brain concentration of 0.90 µg ml(-1), or placebo. During drug infusion, emotionally arousing and neutral images were presented in a continuous recognition task, while blood-oxygen-level-dependent activation responses were acquired. After a drug-free interval of 2 h, subsequent memory for successfully encoded items was assessed. Imaging analysis was performed using statistical parametric mapping and behavioural analysis using signal detection models. RESULTS: Propofol had no effect on the stereotypical amygdalar response to emotional arousal, but caused marked suppression of the hippocampal response. Propofol caused memory performance to become uncoupled from amygdalar activation, but it remained correlated with activation in the posterior hippocampus, which decreased in proportion to amnesia. CONCLUSIONS: Propofol is relatively ineffective at suppressing amygdalar activation at sedative doses, but abolishes emotional modulation and causes amnesia via mechanisms that commonly involve hyporesponsiveness of the hippocampus. These findings raise the possibility that amygdala-dependent fear systems may remain intact even when a patient has diminished memory of events. This may be of clinical importance in the perioperative development of fear-based psychopathologies, such as post-traumatic stress disorder. CLINICAL TRIAL REGISTRATION: NCT00504894.

A prospective evaluation of changes in brain structure and cognitive functions in adult stem cell transplant recipients.

Hematopoietic stem cell transplantation (HSCT) is an efficacious treatment for many hematologic malignancies. However, the conditioning regimen of high-dose (HD) chemotherapy with or without total body irradiation (TBI) can be associated with neurotoxicity. In this prospective study, we used quantitative neuroimaging techniques to examine regional gray matter and ventricular volumes, and standardized neuropsychological tests to assess cognitive function before and 1 year after HSCT in 28 patients with hematologic malignancies and in ten healthy controls evaluated at similar intervals. Nineteen patients received conditioning treatment with HD chemotherapy alone and nine had both TBI and HD chemotherapy. There was a significant reduction in gray matter volume in the middle frontal gyrus bilaterally and in the left caudate nucleus in the patient group (all patients combined) but not among healthy controls over the 1-year follow-up period. There was a significant increase in left lateral ventricle volume and in total ventricle volume in the patient group, relative to healthy controls. Similar brain structural changes were seen for patients treated with HD chemotherapy alone. The neuropsychological results showed that 21% of patients could be classified as impaired at baseline. The Reliable Change Index suggested no significantly different rates of cognitive decline between patients and healthy controls. The findings suggest that HSCT patients may be at an increased risk for developing regional brain volume loss, and that subgroups may experience cognitive dysfunction prior to and 1 year following the transplant.

Human fear-related motor neurocircuitry.

Using functional magnetic resonance imaging and an experimental paradigm of instructed fear, we observed a striking pattern of decreased activity in primary motor cortex with increased activity in dorsal basal ganglia during anticipation of aversive electrodermal stimulation in 42 healthy participants. We interpret this pattern of activity in motor neurocircuitry in response to cognitively-induced fear in relation to evolutionarily-conserved responses to threat that may be relevant to understanding normal and pathological fear in humans.

Dynamic variations in affective priming.

The present study investigates the dynamics of emotional processing and awareness using an affective facial priming paradigm in conjunction with a multimodal assessment of awareness. Key facial primes are visually masked, and are presented for brief (unconscious) and extended (conscious) durations. Using a preference measure, we examine whether the effects of the primes differ qualitatively (Murphy & Zajonc, 1993). We show that: (a) unconscious affective priming with faces emerges strongly in initial presentations and diminishes rapidly with repetition; (b) conscious affective priming also emerges strongly in initial presentations, however it persists in strength with repetition; and (c) in contrast to other reports on the salience of negative stimuli, happy faces appear more salient than sad faces when presented outside awareness. We discuss the limits and extensions of unconscious affective priming with faces, and consider several methodological and conceptual questions concerning emotional processing out of awareness.