A prospective observational study of on-treatment plasma homocysteine levels as a biomarker of toxicity, depression and vitamin supplementation lead-in time pre pemetrexed, in patients with non-small cell lung cancer and malignant mesothelioma

OBJECTIVES: Vitamin supplementation reduces pemetrexed toxicity. Raised plasma homocysteine reflects deficiency in vitamin B12 and folate, and is suppressed by supplementation. This observational study of 112 patients receiving pemetrexed-based chemotherapy assessed homocysteine levels after 3 weeks of vitamin supplementation, hypothesising high levels would correlate with ongoing deficiency, thus increased toxicity. MATERIAL AND METHODS: Primary endpoint was the composite of proportion of patients with treatment delay/ dose reduction/ drug change or hospitalisation during the first six weeks of chemotherapy, comparing those with normal plasma homocysteine (successfully supplemented, SS) and those with high homocysteine (unsuccessfully supplemented, USS). Secondary endpoints included toxicity and analyses for depression. Post-hoc analysis examined correlation between interval of vitamin and folate supplementation and pemetrexed on primary endpoint and grade 3-4 toxicities. RESULTS: Eighty-four patients (84%) were successfully supplemented (SS group). The proportion of patients undergoing a treatment delay/ dose reduction/ drug change or hospitalisation in SS group was 44.0% (95% confidence interval [CI] 33.2%-55.3%) and in USS group was 18.8% (95% CI 4.0%-45.6%) (p = 0.09). Twelve percent of patients gave a past history of depression however 66% of patients had an on study Hospital Anxiety and Depression (HAD) score of >7. Supplementation status was not associated with depression. The median overall survival (OS) was 11.8 months (95% CI 8.6-16.5) in the SS group and 8.8 months (95% CI 6.6-16.2) in the US group (p = 0.5). The number of days (<7 or ≥ 7 days) between vitamin B12 and folate initiation and pemetrexed administration, had no effect on the primary endpoint and grade 3-4 toxicities. CONCLUSION: On-treatment homocysteine levels were not a biomarker of toxicity or depression. Standard vitamin supplementation is adequate in the majority of patients receiving pemetrexed. High HAD score were noted in this population giving an opportunity for mental health intervention. The lead-in time for vitamin supplementation can be short

The role of the purinergic P2X(7 )receptor in inflammation

The inflammatory process, orchestrated against a variety of injurious stimuli, is composed of three inter-related phases; initiation, propagation and resolution. Understanding the interplay between these three phases and harnessing the beneficial properties of inflammation whilst preventing its damaging effects, will undoubtedly lead to the advent of much needed therapies, particularly in chronic disease states. The P2X(7 )receptor (P2X(7)R) is increasingly recognised as an important cell surface regulator of several key inflammatory molecules including IL-1β, IL-18, TNF-α and IL-6. Moreover, as P2X(7)R-dependent cytokine production is driven by activating the inflammasome, antagonists of this receptor are likely to have therapeutic potential as novel anti-inflammatory therapies. The function of the P2X(7)R in inflammation, immunity and its potential role in disease will be reviewed and discussed

The role of the purinergic P2X(7 )receptor in inflammation

The inflammatory process, orchestrated against a variety of injurious stimuli, is composed of three inter-related phases; initiation, propagation and resolution. Understanding the interplay between these three phases and harnessing the beneficial properties of inflammation whilst preventing its damaging effects, will undoubtedly lead to the advent of much needed therapies, particularly in chronic disease states. The P2X(7 )receptor (P2X(7)R) is increasingly recognised as an important cell surface regulator of several key inflammatory molecules including IL-1β, IL-18, TNF-α and IL-6. Moreover, as P2X(7)R-dependent cytokine production is driven by activating the inflammasome, antagonists of this receptor are likely to have therapeutic potential as novel anti-inflammatory therapies. The function of the P2X(7)R in inflammation, immunity and its potential role in disease will be reviewed and discussed

The developmental relations between spatial cognition and mathematics in primary school children

Spatial thinking is an important predictor of mathematics. However, existing data do not determine whether all spatial sub-domains are equally important for mathematics outcomes nor whether mathematics-spatial associations vary through development. This study addresses these questions by exploring the developmental relations between mathematics and spatial skills in children aged 6 -10 years (N = 155). We extend previous findings by assessing and comparing performance across Uttal et al.'s (2013), four spatial sub-domains. Overall spatial skills explained 5-14% of the variation across three mathematics performance measures (standardised mathematics skills, approximate number sense and number line estimation skills), beyond other known predictors of mathematics including vocabulary and gender. Spatial scaling (extrinsic-static sub-domain) was a significant predictor of all mathematics outcomes, across all ages, highlighting its importance for mathematics in middle childhood. Other spatial sub-domains were differentially associated with mathematics in a task and age dependent manner. Mental rotation (intrinsic-dynamic skills) was a significant predictor of mathematics at 6 and 7 years only which suggests that at approximately 8 years of age there is a transition period regarding the spatial skills that are important for mathematics. Taken together, the results support the investigation of spatial training, particularly targeting spatial scaling, as a means of improving both spatial and mathematical thinking