Anti-Diabetic Drugs: Cure or Risk Factors for Cancer?

Anti-diabetic drugs are an important group of therapeutics used worldwide. Different anti-diabetic drugs lower blood glucose level by different mechanisms. In recent years, numerous investigations have been performed based on both comparative and cohort studies, in order to establish the relationship between anti-diabetic pharmacotherapy and cancer incidence as well as mortality due to cancer. Some anti-diabetic drugs have been found to exhibit anti-cancer activity while others might increase the risk for cancer. The underlying cause for this disparity is likely to be the varying mechanisms of action of these drugs in controlling blood glucose level. This review discusses the various carcinogenic and/or anti-cancer effects of commonly used anti-diabetic drugs. The information is vital in view of the fact that diabetes mellitus is a commonly occurring disease with a rising incidence rate.     

Modulation of Binge-like Ethanol Consumption by IL-10 Signaling in the Basolateral Amygdala

Excessive ethanol consumption alters the neuroimmune system and particularly impacts the cytokine milieu of the CNS. Cytokine dysregulation has been shown to underlie addictive-like behaviors including alcohol abuse; however, many studies focus primarily on the proinflammatory cytokine profile during alcohol dependence. The current study furthers this research by determining the impact of excessive ethanol consumption on interleukin-10 (IL-10) and interleukin-4 (IL-4) activity in a model of non-dependent binge consumption called the “drinking in the dark” (DID) paradigm. Furthermore, the ability of IL-10 to modulate ethanol consumption was tested using site-directed pharmacology. Immunohistochemistry analyses determined that ethanol decreased IL-10 by 50 % in the basolateral amygdala (BLA) but had no effect on IL-4. Neither IL-10 nor IL-4, however, were altered in the central amygdala (CEA). Enzyme linked immunosorbent assays confirmed that IL-10 was decreased in the amygdala but not in the serum, suggesting changes of this cytokine with the DID paradigm are restricted to the central nervous system. Finally, bilateral infusions of IL-10 into the BLA, but not CeA, reduced binge-like drinking and corresponding blood ethanol concentrations without impacting either locomotor activity or anxiety-like behavioral correlates. Together, these data support the idea that alcohol abuse dysregulates specific anti-inflammatory cytokines; however, ameliorating alcohol-induced effects on cytokines, like IL-10, may prove to be an effective therapy in curbing excessive consumption.     

Evaluation of transcutaneous and end-tidal carbon dioxide levels during inhalation sedation in volunteers

Measurement of end-tidal carbon dioxide (P_ETCO₂) is useful because of its noninvasiveness, continuity, and response time when sudden changes in ventilation occur during inhalation sedation. We compared the accuracy of P_ETCO₂ using a nasal mask and nasal cannula with the accuracy of transcutaneous carbon dioxide (TC-CO₂) and determined which method is more useful during inhalation sedation in volunteers. We used a modified nasal mask (MNM) and modified nasal cannula (MNC) for measurement of P_ETCO₂. The capnometer measured P_ETCO₂ in the gas expired from the nasal cavity by means of two devices. The volunteers received supplemental O₂ by means of each device at a flow rate of 6 L/min. After the volunteers lay quietly for 5 min with a supply of 100 % O₂, they received supplemental N₂O by means of each device at concentrations of 10, 20, and 25 % for 5 min and 30 % for 25 min. The correlation coefficient was poorer in the MNM than in the MNC, and the mean difference between TC-CO₂ and P_ETCO₂ in the MNM was greater than that in the MNC. The difference between the TC-CO₂ and P_ETCO₂ ranged from 3 to 6 mmHg in the MNM and from 2 to 5 mmHg in the MNC. The difference between two variables against the TC-CO₂ and the CO₂ waveforms obtained by means of the two devices were within the clinically acceptable range. Our two devices can provide continuous monitoring of P_ETCO₂ with a supply of N₂O/O₂ in patients undergoing inhalation sedation.     

Are clinical trial eligibility criteria representative of older patients with lung cancer? A population-based data linkage study

ObjectivesOlder adults constitute the majority of patients with lung cancer. However, they are under-represented in clinical trials as eligibility criteria often restrict enrolment based on comorbidities that are common with aging. We aimed to describe comorbidities relating to trial exclusion criteria in older adults with lung cancer, determine the proportion that would typically be excluded from trials, and examine the impact on treatment uptake.Materials and MethodsWe conducted a population-based study of people aged ≥65 years diagnosed with metastatic lung cancer using linked data for clients of the Australian Government Department of Veterans' Affairs (2005–2015). We defined trial-typical patients based on the absence of comorbidities related to the following: inadequate organ (cardiac, renal, hepatic, marrow) function; cognitive dysfunction; poor performance status (PS); prior malignancy within 5 years. We report systemic therapy uptake within 3 months of diagnosis.ResultsOur study included 677 patients (median age 84). Over half (53.4%) were not trial-typical, with the most common reasons being poor PS (37.5%), cardiac disease (19.2%), and prior cancer (12.9%). Eighty-two (12.1%) received systemic therapy. Patients with poor PS, cardiac disease, and dementia had lower treatment uptake rates. However, there was no significant difference in treatment uptake between trial-typical and non-trial-typical patients (13.4 vs 11.0%).ConclusionMore than half of older adults with advanced lung cancer would be typically excluded from trial participation. Future clinical trials of older adults need to consider broader eligibility criteria to better reflect this population to gain the best evidence for their care.     

An assessment of the construct validity of the CHU9D in the Australian adolescent general population

Purpose  

To assess the construct validity of the CHU9D in an adolescent general population sample. The CHU9D is a new generic preference-based measure of health-related quality of life developed specifically for application in the economic evaluation of health care treatments and interventions for young people.