Impact of sarcopenia on treatment tolerance in United States veterans with diffuse large B‐cell lymphoma treated with CHOP‐based chemotherapy

While sarcopenia has been associated with decreased overall survival in diffuse large B‐cell (DLBCL) patients, the impact of sarcopenia on treatment tolerance has not been well‐studied. We evaluated the association of sarcopenia with febrile neutropenia hospitalization, treatment‐related mortality, and ability to complete standard number of cycles in a retrospective cohort of United States veterans diagnosed with DLBCL between 1998 and 2008 and treated with cyclophosphamide, doxorubicin, vincristine, and prednisone, with or without rituximab. Baseline body composition parameters were evaluated using computed tomography analysis. In total, 522 patients were included in the study, of whom 245 (47%) had baseline sarcopenia. After controlling for other variables, baseline sarcopenia was independently associated with increased risk of febrile neutropenia hospitalization (adjusted Odds Ratio (aOR) 1.64, 95% confidence interval (CI) 1.01–2.65) and inability to complete standard number of treatment cycles (aOR 1.49, 95% CI 1.02–2.16) compared with no baseline sarcopenia. There was a non‐statistically significant trend toward higher treatment‐related mortality in sarcopenic patients than non‐sarcopenic patients (aOR 1.77, 95% CI 0.92–3.41). Sarcopenia is associated with increased risk of treatment intolerance and may be useful in guiding treatment planning and supportive care measures. Am. J. Hematol. 91:1002–1007, 2016. © 2016 Wiley Periodicals, Inc.     

War Experiences and General Health Among People in Bosnia‐Herzegovina and Kosovo

War experiences may have an extensive impact on the health status of the exposed populations. This population‐based study aimed to examine the relationship between war experiences and self‐reported general health in representative sample surveys from Bosnia‐Herzegovina (n = 3,313) and Kosovo (n = 1,000). Data were collected with face‐to‐face interviews fielded in the winter of 2003–2004. Logistic regression analysis was used to compute unadjusted and adjusted odds ratios (ORs). The adjusted effects of the extensiveness of war experiences on poor health were positive in both countries, but they were statistically significant only for Bosnia‐Herzegovina: OR = 1.04, 95% CI [1.00, 1.08] for Bosnia‐Herzegovina and OR = 1.03, 95% CI [0.98, 1.09] for Kosovo. The strongest observed effect was found for Kosovo only: The extensiveness of war experiences was relatively strongly related to longstanding health problems, OR = 1.09, 95% CI [1.03, 1.15]. We found that war experiences may contribute to increased poorer health in the exposed populations; however, the effects 4–9 years after the war ended were modest. Hence, war experiences seemed to be more strongly related to war‐related distress and posttraumatic stress disorder than to self‐reported general health.     

Eosin B as a novel antimalarial agent for drug-resistant Plasmodium falciparum

4',5'-Dibromo-2',7'-dinitrofluorescein, a red dye commonly referred to as eosin B, inhibits Toxoplasma gondii in both enzymatic and cell culture studies with a 50% inhibitory concentration (IC(50)) of 180 microM. As a non-active-site inhibitor of the bifunctional T. gondii dihydrofolate reductase-thymidylate synthase (DHFR-TS), eosin B offers a novel mechanism for inhibition of the parasitic folate biosynthesis pathway. In the present study, eosin B was further evaluated as a potential antiparasitic compound through in vitro and cell culture testing of its effects on Plasmodium falciparum. Our data revealed that eosin B is a highly selective, potent inhibitor of a variety of drug-resistant malarial strains, with an average IC(50) of 124 nM. Furthermore, there is no indication of cross-resistance with other clinically utilized compounds, suggesting that eosin B is acting via a novel mechanism. The antimalarial mode of action appears to be multifaceted and includes extensive damage to membranes, the alteration of intracellular organelles, and enzymatic inhibition not only of DHFR-TS but also of glutathione reductase and thioredoxin reductase. In addition, preliminary studies suggest that eosin B is also acting as a redox cycling compound. Overall, our data suggest that eosin B is an effective lead compound for the development of new, more effective antimalarial drugs.     

Two brief alcohol-screening tests From the Alcohol Use Disorders Identification Test (AUDIT): validation in a female Veterans Affairs patient population

BACKGROUND: Primary care physicians need a brief alcohol questionnaire that identifies hazardous drinking and alcohol use disorders. The Alcohol Use Disorders Identification Test (AUDIT) questions 1 through 3 (AUDIT-C), and AUDIT question 3 alone are effective alcohol-screening tests in male Veterans Affairs (VA) patients, but have not been validated in women. METHODS: Female VA patients (n = 393) completed self-administered questionnaires, including the 10-item AUDIT and a previously proposed modification to AUDIT question 3 with a sex-specific threshold for binge drinking (>/=4 drinks/occasion), and in-person interviews with the Alcohol Use Disorder and Associated Disabilities Interview Schedule. The AUDIT-C, AUDIT question 3 alone, and the 10-item AUDIT were each evaluated with and without the sex-specific binge question and compared with past-year hazardous drinking (>7 drinks/week or >/=4 drinks/occasion) and/or active Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition alcohol abuse or dependence, based on interviews. RESULTS: Eighty-nine women (22.6%) met interview criteria for past-year hazardous drinking and/or active alcohol abuse or dependence. Standard and sex-specific AUDIT-Cs were sensitive (0.81 and 0.84, respectively) and specific (0.86 and 0.85, respectively). Their areas under the receiver operating characteristic curves were equivalent (0.91, and 0.92, respectively) and slightly higher than for the standard 10-item AUDIT (0.87). A single, sex-specific question about binge drinking (modified AUDIT question 3) had a sensitivity of 0.69 and specificity of 0.94, whereas the standard AUDIT question 3 was specific (0.96) but relatively insensitive (0.45). CONCLUSIONS: The standard and sex-specific AUDIT-Cs are effective screening tests for past-year hazardous drinking and/or active alcohol abuse or dependence in female patients in a VA study.