Sensorimotor smoking stimuli are important determinants of cigarette use. The present study aimed to determine whether denicotinized cigarettes lose their reinforcing and/or subjective effects over a 9-day outpatient period when they are smoked with or without concurrent transdermal nicotine. After a preferred brand baseline, 68 participants were randomized into one of four conditions based on the dose (mg) of transdermal nicotine and the type of cigarettes (dose/cigarette): 0/nicotine, 0/ denicotinized, 7/denicotinized, and 21/denicotinized. Under placebo patch conditions, participants smoked a similar number of nicotine and denicotinized cigarettes and no group differences emerged over repeated testing. The total volume of smoke inhaled was lower in the denicotinized group, although this decrease dissipated over time. Denicotinized cigarettes were rated as having low positive and high negative subjective effects. Compared to placebo, transdermal nicotine decreased the number of denicotinized cigarette smoked, produced a lasting decrease in the total volume of denicotinized cigarette smoke inhaled, but had little effect on the subjective effects of denicotinized cigarettes. Transdermal nicotine attenuated withdrawal during initial smoking abstinence; however, once participants were allowed to smoke withdrawal symptoms were relatively low regardless of patch condition. The persistent use of denicotinized cigarettes may result from the presence of nicotine withdrawal and/or the degree to which smoking becomes somewhat independent of the outcome of the behavior (i.e., habit learning). Additional studies would be useful to determine what factors drive continued use of denicotinized cigarettes, whether their use subsides as withdrawal dissipates, and whether they address motives for smoking distinct from current pharmacotherapy.

Background Anthracycline drugs are effective anticancer agents, but their optimal use is limited in many patients by the associated cardiotoxicity, even at designated safe doses. As conventionally sensitive cardiac troponin-I assays fail to reliably quantify concentrations of cardiac troponin-I below 30 ng/L, we investigated the potential role of high-sensitive cardiac troponin-I in the detection of subclinical cardiomyocyte injury in patients treated with anthracycline agents. Methods Serial high-sensitive cardiac troponin-I concentrations were assessed in 84 patients, receiving anthracycline-containing ( n = 38) and non-anthracycline-containing ( n = 46) regimens. Results were assessed for change from pretreatment levels and evaluated according to unisex and gender-specific 99th percentiles (25 ng/L and M: 34 ng/L, F: 16 ng/L, respectively). Results A significant increase in high-sensitive cardiac troponin-I was observed in the anthracycline cohort following five cycles of treatment, with the greatest change correlating to an absolute δ increase of 30.7 ng/L in the early-dose group (early-dose group: P < 0.0001, late-dose group: P < 0.01 and continuous-dose group: P < 0.0001). Doxorubicin dose did not correlate directly with high-sensitive cardiac troponin-I concentrations (Spearman r < -0.22). No significant changes in high-sensitive cardiac troponin-I were reported among the non-anthracycline cohort with all measurements below the 99th percentiles. Conclusions Treatment with anthracycline-based chemotherapeutic regimen demonstrated significant elevations of high-sensitive cardiac troponin-I, indicative of subclinical cardiomyocyte damage. This study demonstrates a role for high-sensitive cardiac troponin-I in evaluating those patients where cardiotoxicity is a concern and a potential future role as a biomarker in optimizing cardioprotective treatments in patients receiving anthracycline therapy.

ObjectivesCreatinine is the biomarker of choice for use in estimates of kidney function in oncology patients. However as non-renal factors such as muscle mass can influence creatinine concentrations, we evaluated cystatin C as an alternative biomarker and its incorporation in GFR estimating formulae in an oncology setting. Measured GFR is infrequently undertaken in adult clinical practice with the consequent reliance on calculated GFR for patient assessment.Design and methodsCystatin C and creatinine concentrations were evaluated from 134 oncology patients prior to commencing chemotherapeutic cycles. Estimates of creatinine clearance (Cockroft-Gault) and GFR (using Hoek, Jonsson, MDRD and CKD-EPI) were evaluated. Cystatin C-based GFR estimates (using CKD-EPI CysC and CKD-EPI SCr/CysC) were compared with the creatinine-based GFR estimates (CG, MDRD and CKD-EPI SCr) within the GFR ranges of 60–89, 45–59 and ≤44 mL/min/1.73 m2.ResultsCystatin C concentrations were significantly higher in oncology patients both prior to commencing chemotherapy (F: P<0.01 and M: P<0.0001) and during cycles of treatment (F: P<0.0001 and M: P<0.01) when compared with a reference population. Cystatin C concentrations also increased significantly during chemotherapy (P<0.0001) in a subset of female patients evaluated. Poor agreement (average 42%) was demonstrated between CKD-EPI CysC and creatinine-based GFR estimates within the investigated GFR ranges, with improved agreement (average 55%) when using the combined CKD-EPI SCr/CysC formula.ConclusionsThis study demonstrated a malignancy and treatment-mediated effect on cystatin C measures, which may confound its clinical utility in estimating GFR in oncology patients.

No abstract

No abstract