Evaluation of the clinical impact of concomitant acid suppression therapy in colorectal cancer patients treated with capecitabine monotherapy.

BACKGROUND: Capecitabine is an oral chemotherapeutic agent used in colorectal cancer. Two prior studies found a negative impact with the concomitant use of proton pump inhibitor agents during treatment with capecitabine in patients with early colorectal and gastroesophageal cancers. OBJECTIVE: To determine if there is a clinical impact of the concomitant use of capecitabine and acid suppression therapy in patients with local and metastatic colorectal cancer. METHODS: This was a single-center retrospective cohort study of adult patients with colorectal cancer on capecitabine monotherapy between 2011 and 2017. Progression-free survival (PFS) and overall survival were compared between patients on acid suppression therapy and those not on acid suppression therapy. RESULTS: A total of 70 patients were included. Patients on acid suppression therapy at capecitabine initiation (21%) had decreased progression-free survival versus those not on acid suppression therapy (HR 2.24, 95% CI 1.06-4.41, p = 0.035), after adjusting for disease severity and age. Acid suppression therapy use was associated with a numerical decrease in overall survival (HR 1.86, 95% CI 0.81-3.91, p = 0.14). In patients on any concomitant acid suppression therapy (25%), there was a decreased rate of progression-free survival (HR 6.21, 95% CI 2.56-14.32, p = 0.0001) but not overall survival (HR 1.64, 95% CI 0.68-3.54, p = 0.25) versus those without concomitant acid suppression therapy, after adjusting for age and disease severity. CONCLUSIONS: Concurrent use of acid suppression therapy and capecitabine was associated with decreased progression-free survival, and there was a trend towards decreased overall survival. Due to the demonstrated potential of decreased efficacy, concurrent use of proton pump inhibitors or histamine 2 receptor antagonists should be avoided in colorectal cancer patients on treatment with capecitabine monotherapy.

No Effect of Omega-3 Fatty Acid Supplementation on Cognition and Mood in Individuals with Cognitive Impairment and Probable Alzheimer's Disease: A Randomised Controlled Trial.

Findings from epidemiological and observational studies have indicated that diets high in omega-3 polyunsaturated fatty acids (PUFAs) such as docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) may reduce the risk of cognitive decline and Alzheimer's disease (AD). To determine if increasing intake of DHA and EPA through supplementation is beneficial to cognition and mood in individuals with cognitive impairment no dementia (CIND) or Alzheimer's disease (AD) a four month, randomised, double-blind, placebo controlled study was conducted. Fifty-seven participants with CIND and nineteen with AD were randomised to receive either omega-3 PUFAs (600 mg EPA and 625 mg DHA per day) or placebo (olive oil) over a four month period. Elevating depleted levels of EPA and DHA through supplementation in individuals with CIND or AD was found to have negligible beneficial effect on their cognition or mood. These findings confirm an overall negligible benefit of omega-3 PUFA supplementation for those with cognitive impairment and dementia. More intervention studies need to be undertaken with longer study durations and larger sample sizes. It may prove fruitful to examine effects of different doses as well as effects in other dementia subtypes.

Lower omega-3 fatty acid intake and status are associated with poorer cognitive function in older age: A comparison of individuals with and without cognitive impairment and Alzheimer's disease.

OBJECTIVES: Various strands of evidence suggest that low intake of omega-3 fatty acids increases risk of cognitive decline and dementia. The present study investigated differences in dietary intake and blood plasma content of eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (DHA; 22:6n-3) in individuals with cognitive impairment no dementia (CIND), individuals with Alzheimer's disease (AD), and healthy volunteers (HV). METHODS: A total of 135 individuals aged between 55 and 91 years (19 AD, 55 CIND, and 61 HV) were assessed predominantly within a hospital setting. RESULTS: Compared with age and sex-matched HV, individuals with AD or CIND performed poorly on a majority of tests of cognitive function. Impairment was greatest for delayed and verbal recognition memory. CIND individuals were less impaired than AD individuals. Omega-3 intake and the percentage of EPA and DHA in plasma phosphatidylcholine (PC) showed a similar pattern (AD < HV, with intermediate scores for CIND). Across the whole sample, and after controlling for age, years of education, level of socio-economic deprivation, and gender, omega-3 intake, plasma PC DHA, and plasma PC EPA were all significant positive predictors of memory functioning. DISCUSSION: These results are consistent with the possibility that omega-3 fatty acid nutrition has an impact on cognitive decline, but could equally be explained by dietary changes that occurred after onset of cognitive decline. It is also possible that the results could be explained by unknown confounding factors.

Holistic aboveground ecological productivity efficiency modeling using data envelopment analysis in the southeastern U.S.

Aboveground net primary productivity (ANPP) of an ecosystem is among the most important metrics of valued ecosystem services. Measuring the efficiency scores of ecological production (ESEP) based on ANPP using relevant variables is valuable for identifying inefficient sites. The efficiency scores computed by the Data Envelopment Analysis (DEA) may be influenced by the number of input variables incorporated into the models and two DEA settings-orientations and returns-to-scales (RTSs). Therefore, the objectives were threefold to: (1) identify soil-environmental variables relevant to ANPP, (2) assess the sensitivity of ESEP to the number of input variables and DEA settings, and (3) assess local management relations with ESEP. The ANPP rates were calculated for pine forests in the southeastern U.S. where 10 management types were used. This was followed by an all-relevant variable selection technique based on 696 variables that cover biotic, pedogenic, climatic, geological, and topographical factors. Five minimal-optimal variable selection techniques were further applied to create five parsimonious sets that contain a different number of variables used as DEA inputs. After setting ANPP as the output variable, two DEA orientations (input/output) and six RTS were applied to compute ESEP. The variable selection methods succeeded in objectively identifying the major factors relevant to ANPP variation. The site index showed the highest correlation with ANPP (r = 0.39), while various precipitation factors were negatively correlated (r = - 0.15~ - 0.29, p < 0.01). Parsimonious ESEP models observed a decrease in score variances as the number of input variables increased. Various RTS produced similar scores across orientations. Of the DEA settings, an output orientation with decreasing RTS produced the most progressive ESEP with large variation. Results also suggested that macro- and micronutrient fertilization is the best combination of management strategies to achieve high ESEP. This holistic benchmark approach can be applied to other ecological functions in diverse regions.

Use of a physostigmine continuous infusion for the treatment of severe and recurrent antimuscarinic toxicity in a mixed drug overdose.

INTRODUCTION: Physostigmine was once a widely used antidote for the treatment of antimuscarinic toxicity. However, reports describing the association of physostigmine with asystole and seizures in severe tricyclic antidepressant poisoning resulted in a decrease in use. Recent literature has demonstrated that physostigmine is a safe and effective antidote for the treatment of antimuscarinic toxicity. There are only two previously published articles regarding the use of physostigmine administered as a continuous intravenous infusion for persistent antimuscarinic toxicity. We present a case of physostigmine continuous infusion for the treatment of antimuscarinic symptoms in a polydrug overdose due to the ingestion of diphenhydramine along with bupropion, citalopram, acetaminophen, and naproxen. CASE PRESENTATION: A 13-year-old female presented with hyperthermia, myoclonus and rigidity, hallucinations, severe agitation, and antimuscarinic toxicity including inability to sweat after a polydrug overdose. Several doses of lorazepam were administered followed by physostigmine which produced resolution of hallucinations and attenuation of the antimuscarinic symptoms including perspiration, temperature improvement, and decreased agitation. After periods of improvement and recurrence of antimuscarinic effects, a continuous infusion of physostigmine was administered at 2 mg/h and continued for almost 8 h to maintain attenuation of symptoms. GABAergic agents including lorazepam and phenobarbital were used later in the hospital course for presumed symptoms of serotonergic and adrenergic toxicity after resolution of antimuscarinic effects. The patient did not experience any adverse effects of physostigmine administration. DISCUSSION: Physostigmine administered as a continuous infusion may be a reasonable treatment option for severe and recurrent symptoms related to antimuscarinic toxicity.