Nivolumab in gastric/gastroesophageal junction cancer: real-world data from UK Early Access to Medicines Scheme.

Aim: This study provides real-world insight into patient profile, clinical effectiveness and health-related quality of life among patients with advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma treated with nivolumab. Materials & methods: Data were collected from medical records of patients with advanced GEJ adenocarcinoma treated with nivolumab in a UK Early Access to Medicines Scheme and from the patient-reported EuroQoL five dimensions questionnaire. Results: Evaluable patients (n = 113; median age 62 years) were predominantly male (76.1%), White (87.4%) and with GEJ adenocarcinoma (61.9%). Median follow-up was 2.8 months. The 6-month progression-free survival and overall survival were 31.6 and 56.7%, respectively. Mean EuroQoL five dimensions questionnaire index utility scores at baseline, 8, 16 and 24 weeks were 0.795, 0.831, 0.870 and 0.793, respectively. Conclusion: Progression-free survival was consistent with trial results and health-related quality of life remained stable over time.

Lay abstract This study looked at the characteristics and quality of life (QoL) of patients who were taking the drug, nivolumab, and how well it works for advanced gastric/gastroesophageal junction (GEJ) adenocarcinoma. GEJ adenocarcinoma is a rare type of cancer that starts in the GEJ, the area where the esophagus and stomach join. Information was collected from the medical records of patients who had advanced GEJ adenocarcinoma and were treated with nivolumab as part of a UK program that gives people access to new treatments that are not yet licensed. Patients also filled out a questionnaire called the EuroQoL five dimensions questionnaire that focuses on a patient's quality of life (QoL). In total, 113 patients were a part of the study. The midpoint of all patients' ages was 62 years and they were mostly males (76.1%), Whites (87.4%) and with GEJ adenocarcinoma (61.9%). The midpoint of follow-up time was 2.8 months. The percentages of patients meeting progression-free survival for 6 months, a period when a patient lives with GEJ adenocarcinoma but it does not get worse, and overall survival were 31.6 and 56.7%, respectively. Mean EuroQoL five dimensions questionnaire index scores (comprised between zero and one, the higher the better) at treatment start, 8, 16 and 24 weeks were 0.795, 0.831, 0.870 and 0.793, respectively. Progression-free survival was similar to clinical trial results and QoL was constant over time.

Early Access to Medicines Scheme: real-world data collection.

Real-world data (RWD) generated during the pre-approval phase could be supplementary to primary clinical trial outcomes; however, as we discuss here, a data collection framework is needed to ensure the validity and applicability of these data.

Extracting data from a chemotherapy prescription platform for real-world oncology research in the UK: a pilot study.

Aim: In the UK, there are limited data sources for evaluating real-world research questions related to oncology therapy. We conducted a pilot study to investigate the feasibility of extracting data directly from a chemotherapy prescription platform (ChemoCare®) utilized in standard care. Patients & methods: Concordance was compared with data extracted manually for patients with advanced melanoma as part of a concurrent chart review (gold-standard) using Cohen's kappa and the intraclass correlation coefficient. Results: There was high concordance between data automatically extracted from the prescription platform and chart review data. Conclusion: This pilot can be used as a framework for future studies using direct, automated extraction from prescription platforms.

Physical activity pre- and post-dementia: English Longitudinal Study of Ageing.

BACKGROUND: To inform public health interventions, further investigation is needed to identify: (1) frequency/intensity of everyday physical activity (PA) needed to reduce dementia risk; (2) whether post-diagnosis reduction in PA is associated with cognitive outcomes in people with dementia. METHODS: Data from 11,391 men and women (aged ≥50) were obtained from the English Longitudinal Study of Ageing cohort. Assessments were carried out at baseline (2002-2003) and at biannual follow-ups (2004-2013). RESULTS: Older adults who carried out moderate to vigorous activity at least once per week had a 34%-50% lower risk for cognitive decline and dementia over an 8-10 year follow-up period. From pre- to post-dementia diagnosis, those who decreased PA levels had a larger decrease in immediate recall scores, compared to those who maintained or increased PA levels (analyses were adjusted for changes in physical function). CONCLUSION: PA was associated with cognitive outcomes in a dose-dependent manner. Reduction in PA after diagnosis was associated with accelerated cognitive decline and maintaining PA may reduce symptom progression in dementia.

Nutrition research in cognitive impairment/dementia, with a focus on soya and folate.

Observational studies and treatment trials investigating nutrition and cognitive function, with a focus on folate and soya and dementia, were reviewed. Data suggested that effects of folic acid based interventions may only be shown before cognitive decline is evident and/or if people are folate deficient. In older people in Indonesia, Hawai'i and China, tofu, which can contain high levels of phytoestrogens, was found to increase dementia risk. This association was not mediated by a vegetarian diet, socioeconomic status, formaldehyde, thyroid function, or loss of teeth. On the other hand, human observational and animal treatment studies suggested that tempe, a fermented soya product containing phytoestrogens and folate, reduced dementia risk and improved memory. High oestrogen levels were found to increase dementia risk in older women. However, in women with adequate serum folate, high oestrogen levels did not confer additional dementia risk and may protect ageing neurons. In conclusion, reviews seem to suggest that folic acid interventions are only effective on cognitive outcomes in people who are folate deficient and do not have cognitive impairment. Frequent consumption of tofu may have detrimental effects on memory and increase dementia risk in older East Asian people, while tempe may reduce these risks. Possibly folate in tempe offsets the potential negative effects of oestrogenic compounds on ageing neurons.

Phytoestrogens and cognitive function: a review.

Neuroprotective effects of phytoestrogen compounds (found in soy) have been demonstrated in animal research and cell culture studies. In particular, phytoestrogens have been shown to reduce Alzheimer's Disease (AD) related pathology, potentially alleviating risk of AD progression. In addition to their antioxidant properties, soy products also have the ability to affect cognition via interaction with estrogen receptors. However, observational studies and randomised controlled trials in humans have resulted in inconclusive findings within this domain. There are several possible reasons for these discrepant data. Studies which report no effect of phytoestrogens on cognition have mainly been carried out in European cohorts, with an average low dietary consumption. In contrast, investigation of Asian populations, with a higher general intake of tofu (a non-fermented soy product) have shown negative associations with cognitive function in those over the age of 65. Consideration of type of soy product is important, as in the latter sample, protective effects of tempe (fermented soy) were also observed. Limited data provide evidence that effects of phytoestrogens on cognition may be modified by dosage, duration of consumption and cognitive test used. Additionally, characteristics of the study population including age, gender, ethnicity and menopausal status appear to be mediating variables. Phytoestrogen treatment interventions have also shown time-limited positive effects on cognition. These findings are consistent with estrogen treatment studies, where initial positive short-term cognitive effects may occur, which reverse with long-term continuous use in elderly women. Well controlled, large scale studies are needed to assess the effects of phytoestrogens on the aging brain and provide further understanding of this association.

Identification of a narrow post-ovulatory window of vulnerability to distressing involuntary memories in healthy women.

Psychological disorders characterised by intrusive memories are more prevalent in women than men. The biological, social and cognitive processes underlying this gender-difference have yet to be fully elucidated. Some evidence suggests that (fluctuations in) ovarian hormone levels are responsible for altered sensitivity to emotional stimuli during certain phases in the menstrual-cycle and this may form the basis of a specific vulnerability to psychological disorders in women. The post-ovulatory (luteal) phase has been identified as a period of particular vulnerability to the development of post-traumatic stress disorder (PTSD). Using an experimental model of PTSD, we examine whether differences are detectable between discrete phases in the menstrual-cycle in the experience of intrusive memories. Women (18-35 years-old) in one of three tightly-defined periods within the menstrual cycle--mid-follicular (n=15), early-luteal (n=15) and late-luteal (n=11)--provided saliva samples for ovarian-hormone assay and watched a distressing film. Subsequent intrusive memories, assessed using a daily online-diary, occurred significantly more frequently in the early-luteal group compared to mid-follicular and late-luteal groups. Intrusion frequency was negatively correlated with the estradiol-to-progesterone ratio, but not estradiol or progesterone alone, suggesting that the interactive effect of low estradiol and high progesterone at encoding contributes to the observed effect. Our results support the need for further research in a clinical context with naturally-cycling women who experience a traumatic event, since assessment of days-since-last-menses and ovarian hormone levels may help to identify those at greatest risk of developing re-experiencing symptoms akin to those seen in psychological disorder such as depression and PTSD.

Gender, personality, and involuntary autobiographical memory.

We utilised the recently developed continuous word association task (CWAT) to investigate whether attributes of involuntary autobiographical memory, including gender and cue valence effects, were similar to those found for voluntary autobiographical memory, as well as investigating the role of individual differences in memory production. A total of 80 undergraduate volunteers reported involuntary memories that came to mind during the word association task and completed measures of trait dissociation and psychosis-proneness. Involuntary memories showed similar cue valence effects to those typically found with voluntary memories but the usual gender effect was only apparent once participants learned the task involved autobiographical memory. The total number of involuntary autobiographical memories produced in response to negative cue words was related to greater trait dissociation and psychosis-proneness. The implications for differences between voluntary and involuntary autobiographical memory are discussed.