Effective diabetes complication management is a step toward a carbon-efficient planet: an economic modeling study.

BACKGROUND: The management of diabetes-related complications accounts for a large share of total carbon dioxide equivalent (CO2e) emissions. We assessed whether improving diabetes control in people with type 2 diabetes reduces CO2e emissions, compared with those with unchanging glycemic control. METHODS: Using the IQVIA Core Diabetes Model, we estimated the impact of maintaining glycated hemoglobin (HbA1c) at 7% (53 mmol/mol) or reducing it by 1% (11 mmol/mol) on total CO2e/patient and CO2e/life-year (LY). Two different cohorts were investigated: those on first-line medical therapy (cohort 1) and those on third-line therapy (cohort 2). CO2e was estimated using cost inputs converted to carbon inputs using the UK National Health Service's carbon intensity factor. The model was run over a 50-year time horizon, discounting total costs and quality adjusted life years (QALYs) up to 5% and CO2e at 0%. RESULTS: Maintaining HbA1c at 7% (53 mmol/mol) reduced total CO2e/patient by 18% (1546 kgCO2e/patient) vs 13% (937 kgCO2e/patient) in cohorts 1 and 2, respectively, and led to a reduction in CO2e/LY gain of 15%-20%. Reducing HbA1c by 1% (11 mmol/mol) caused a 12% (cohort 1) and 9% (cohort 2) reduction in CO2e/patient with a CO2e/LY gain reduction of 11%-14%. CONCLUSIONS: When comparing people with untreated diabetes, maintaining glycemic control at 7% (53 mmol/mol) on a single agent or improving HbA1c by 1% (11 mmol/mol) by the addition of more glucose-lowering treatment was associated with a reduction in carbon emissions.

T Cell Primary Effusion Lymphoma in an HIV-Negative Man with Liver Cirrhosis.

BACKGROUND Primary effusion lymphoma (PEL) is a rare and aggressive non-Hodgkin lymphoma (NHL) that is responsible for 1% of all lymphomas not related to human immunodeficiency virus (HIV). PEL is characterized by human herpesvirus-8 (HHV-8) positivity in the absence of overt tumor burden that does not exhibit typical B cell or T cell immunophenotype characteristics. The exact mechanism of development is unknown, but it is hypothesized to develop from post-germinal B cell origin. Although it is most common in HIV patients, other immunocompromising comorbidities can be seen in conjunction with PEL, including liver cirrhosis. CASE REPORT We present the case of a 73-year-old HIV-seronegative man with alcohol-induced liver cirrhosis who was found to have T cell PEL of the pleural space diagnosed by thoracentesis. CONCLUSIONS Little is known regarding oncogenesis of T cell PEL, and few studies exist regarding appropriate treatment regimens for PEL as a whole, prompting need for further investigation and discussion to improve survival rates. Even in the absence of active HIV infection, PEL should be considered as a potential cause of pleural effusion in cirrhotic patients in order to prompt earlier treatment for the best chance of survival.

Analyzing the Efficacy and Cost-effectiveness of Anti-platelet Therapy in Unstable Angina/Non-ST Elevation Myocardial Infarction: A Decision Analysis.

Current pretreatment guidelines for coronary angiography in unstable angina (UA) and non-ST elevation myocardial infarction (NSTEMI) involve the use of dual antiplatelet therapy (DAPT: aspirin + adenosine diphosphate (ADP) P2Y12 inhibitor), whereas the use of triple antiplatelet therapy (TAPT: aspirin + ADP P2Y12 inhibitor + GpIIb/IIIa inhibitor) has limited data due to the increased bleeding risk. However, a study directly comparing the efficacy and cost-effectiveness of DAPT vs. TAPT has not been done. A decision analysis was constructed to determine the ideal pretreatment antiplatelet regimen for UA/NSTEMI patients. The parameters were calculated based on published randomized clinical trials. They consisted of probabilities based on a pretreatment strategy (DAPT, TAPT), interventions (percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), medical management), and 30-day outcomes (no event, bleeding, vascular event, death). A 10,000 run Monte Carlo simulation provided two outputs: estimated life-years extended and costs for each treatment modality. Quality-adjusted life-years (QALYs) were taken into consideration using calculated coefficients from the literature. The cost/QALY ratio was $1,923/QALY for DAPT vs. $4,734/QALY for TAPT. The use of DAPT for pretreatment was favored (2.46 more cost-effective than TAPT). These results will aid clinicians in providing the most clinically sound and fiscally responsible care for UA/NSTEMI patients.

Fendiline Enhances the Cytotoxic Effects of Therapeutic Agents on PDAC Cells by Inhibiting Tumor-Promoting Signaling Events: A Potential Strategy to Combat PDAC.

The L-type calcium channel blocker fendiline has been shown to interfere with Ras-dependent signaling in K-Ras mutant cancer cells. Earlier studies from our lab had shown that treatment of pancreatic cancer cells with fendiline causes significant cytotoxicity and interferes with proliferation, survival, migration, invasion and anchorage independent growth. Currently there are no effective therapies to manage PDACs. As fendiline has been approved for treatment of patients with angina, we hypothesized that, if proven effective, combinatorial therapies using this agent would be easily translatable to clinic for testing in PDAC patients. Here we tested combinations of fendiline with gemcitabine, visudyne (a YAP1 inhibitor) or tivantinib (ARQ197, a c-Met inhibitor) for their effectiveness in overcoming growth and oncogenic characteristics of PDAC cells. The Hippo pathway component YAP1 has been shown to bypass K-Ras addiction, and allow tumor growth, in a Ras-null mouse model. Similarly, c-Met expression has been associated with poor prognosis and metastasis in PDAC patients. Our results presented here show that combinations of fendiline with these inhibitors show enhanced anti-tumor activity in Panc1, MiaPaCa2 and CD18/HPAF PDAC cells, as evident from the reduced viability, migration, anchorage-independent growth and self-renewal. Biochemical analysis shows that these agents interfere with various signaling cascades such as the activation of Akt and ERK, as well as the expression of c-Myc and CD44 that are altered in PDACs. These results imply that inclusion of fendiline may improve the efficacy of various chemotherapeutic agents that could potentially benefit PDAC patients.