Ethnicity, disease severity, and survival in Canadian patients with primary biliary cholangitis.

BACKGROUND AND AIMS: We investigated associations between ethnicity, survival, and disease severity in a diverse Canadian cohort of patients with primary biliary cholangitis (PBC). APPROACH AND RESULTS: Patients with PBC were included from the Canadian Network for Autoimmune Liver Disease. Ethnicity was defined using a modified list adopted from Statistics Canada, and ethnicities with small samples were grouped. Clinical events were defined as liver decompensation, HCC, liver transplantation, or death. Clinical event-free and liver transplantation-free survival were analyzed using Cox regression. Trajectories of serum liver function tests were assessed over time using mixed-effects regression. Health-related quality of life was assessed using the Short Form 36, the PBC-40 questionnaire, and the 5-D Itch scale and analyzed using mixed-effects regression. The cohort included 1538 patients with PBC from six sites and was comprised of 82% White, 4.7% Indigenous, 5.5% East Asian, 2.6% South Asian, and 5.1% miscellaneous ethnicities. Indigenous patients were the only ethnic group with impaired liver transplant-free and event-free survival compared to White patients (HR, 3.66; 95% CI, 2.23-6.01; HR, 3.09; 95% CI, 1.94-4.92). Indigenous patients were more likely to have a clinical event before diagnosis (10%) than all other ethnic groups despite similar age at diagnosis. Indigenous patients presented with higher alkaline phosphatase, total bilirubin, and GLOBE scores than White patients; and these relative elevations persisted during follow-up. CONCLUSIONS: Indigenous Canadians with PBC present with advanced disease and have worse long-term outcomes compared to White patients.

Intraindividual variability in reaction time before and after neoadjuvant chemotherapy in women diagnosed with breast cancer.

OBJECTIVE: Women treated with chemotherapy for breast cancer experience subtle cognitive deficits. Research has focused on mean performance level, yet recent work suggests that within-person variability in reaction time performance may underlie cognitive symptoms. We examined intraindividual variability (IIV) in women diagnosed with breast cancer and treated with neoadjuvant chemotherapy. METHODS: Patients (n = 28) were assessed at baseline before chemotherapy (T1), approximately 1 month after chemotherapy but prior to surgery (T2), and after surgery about 9 months post chemotherapy (T3). Healthy women of similar age and education (n = 20) were assessed at comparable time intervals. Using a standardized regression-based approach, we examined changes in mean performance level and IIV (eg, intraindividual standard deviation) on a Stroop task and self-report measures of cognitive function from T1 to T2 and T1 to T3. RESULTS: At T1, women with breast cancer were more variable than controls as task complexity increased. Change scores from T1 to T2 were similar between groups on all Stroop performance measures. From T1 to T3, controls improved more than women with breast cancer. IIV was more sensitive than mean reaction time in capturing group differences. Additional analyses showed increased cognitive symptoms reported by women with breast cancer from T1 to T3. Specifically, change in language symptoms was positively correlated with change in variability. CONCLUSIONS: Women with breast cancer declined in attention and inhibitory control relative to pretreatment performance. Future studies should include measures of variability, because they are an important sensitive indicator of change in cognitive function.

Pretreatment Differences in Intraindividual Variability in Reaction Time between Women Diagnosed with Breast Cancer and Healthy Controls.

OBJECTIVES: Chemotherapy has adverse effects on cognitive performance in women treated for breast cancer, but less is known about the period before chemotherapy. Studies have focused on mean level of performance, yet there is increasing recognition that variability in performance within an individual is also an important behavioral indicator of cognitive functioning and underlying neural integrity. METHODS: We examined intraindividual variability (IIV) before chemotherapy and surgery in women diagnosed with breast cancer (n=31), and a healthy control group matched on age and education (n=25). IIV was calculated across trials of a computerized Stroop task, including an examination of the slowest and fastest trials of reaction time (RT) responses. RESULTS: The groups were equivalent on overall accuracy and speed, and participants in both groups were less accurate and slower on incongruent trials compared with congruent trials. However, women with breast cancer became more variable with increased task difficulty relative to healthy controls. Among the slowest RT responses, women with breast cancer were significantly more variable than healthy controls on incongruent trials. This suggests that a specific variability-producing process (e.g., attentional lapses) occurs in task conditions that require executive control (e.g., incongruent trials). CONCLUSIONS: Results are consistent with other evidence of executive dysfunction among women treated for breast cancer. These findings highlight the importance of pretreatment assessment and show that variability in performance provides information about cognition that measures of central tendency do not.

Pretreatment neurocognitive function and self-reported symptoms in patients with newly diagnosed head and neck cancer compared with noncancer cohort.

BACKGROUND: Newly diagnosed patients with head and neck cancer may be at risk for impaired neurocognitive function (NCF) due to disease, treatment, and lifestyle factors. METHODS: Eighty pretreatment patients with head and neck cancer and 40 control patients without cancer completed assessment of NCF and self-reported cognition, fatigue, and mood. Blood samples to evaluate organ reserves, hormones, and cytokines were collected. RESULTS: Patients experienced worse symptoms of cognitive dysfunction, fatigue, and anxiety than controls. In contrast, NCF was equivalent for patients and controls. Using published norms as comparison, groups had similar high rates of impairment in performance (9/80 patients and 3/40 controls scored in the abnormal range). CONCLUSION: Pretreatment patients with head and neck cancer reported cognitive disturbance. The frequency of impaired performance, albeit high, was consistent with the literature demonstrating false-positive "abnormal" neuropsychological test performance is not uncommon. Inclusion of a noncancer patient control cohort is essential because using solely normative data as a comparison may foster erroneous interpretation.

Association of Neurocognitive Deficits With Radiotherapy or Chemoradiotherapy for Patients With Head and Neck Cancer.

IMPORTANCE: Neurocognitive deficits (NCD) have been observed in noncentral nervous system cancers, yet short- and long-term neurocognitive data on patients treated for head and neck cancer (HNC) are lacking. OBJECTIVE: To assess objective neurocognitive function before and after definitive radiation therapy for HNC. DESIGN, SETTING, AND PARTICIPANTS: In a prospective, longitudinal study, neurocognitive function and self-reported symptoms were assessed in 80 patients with histologically proven HNC requiring definitive chemoradiotherapy or radiotherapy and in 40 healthy controls 4 times (baseline, 6, 12, and 24 months after baseline) prior to commencing treatment at Princess Margaret Cancer Centre, Toronto, Canada. MAIN OUTCOMES AND MEASURES: Neurocognitive test scores were converted to age-corrected z scores (mean, 0; standard deviation, 1) and reported as mean scores, standardized regression-based scores, and frequencies of impairments in intellectual capacity, concentration, memory, executive function, processing speed, and motor dexterity. Multivariable analysis was used to identify factors associated with NCD 2 years after treatment. RESULTS: Eighty patients and 40 healthy controls enrolled. Analyses revealed significant differences between patient and control mean performance in some domains, with patient deficits increasing over time: intellectual capacity (Cohen d, effect sizes [95% CIs] of -0.46 [-0.64 to 0.30], -0.51 [-0.72 to -0.30], and -0.70 [-0.92 to -0.49] for time points 6, 12, and 24 months, respectively); concentration/short-term attention span (-0.19 [-0.37 to 0.00], -0.38 [-0.55 to -0.21], -0.54 [-0.71 to -0.37]); verbal memory (-0.16 [-0.33 to 0.02], -0.38 [-0.64 to -0.12], -0.53 [-0.74 to -0.32]); executive function (-0.14 [-0.27 to 0.00], -0.34 [-0.52 to -0.16], -0.43 [-0.64 to -0.22]), and global cognitive function composite (-0.38 [-0.55 to -0.22], -0.75 [-0.92 to -0.58], -1.06 [-1.26 to -0.86]). There was an increased rate of impaired global neurocognitive functioning among patients (38%) at 24 months compared with controls (0%). Neurocognitive deficits were not associated with baseline cytokines. CONCLUSIONS AND RELEVANCE: Head and neck cancer survivors have neurocognitive sequelae up to 2 years after definitive chemoradiotherapy or radiation treatment. Patients and health care teams should know about such potential risks. Further research is warranted in search of strategies to avoid, reduce, and compensate for declines.