Community mental health centers and the “Seed Money” concept: Effects of terminating federal funds

What happens to community mental health centers when federal funding ends? Analysis of the funding patterns of a cohort of “graduate” community mental health centers indicates that these centers remained fiscally viable subsequent to termination of basic federal grants. However, further analysis revealed two distinct funding patterns within the cohort. One group relied primarily on increased third-party reimbursements to offset the end of basic federal grants. The other sought more state funds and additional federal grants available through the Community Mental Health Center Amendments of 1975. As more centers “graduate”, federal “floor funding” may be necessary to insure the survival of some of them.     

Maternal dietary supplementation with pomegranate juice is neuroprotective in an animal model of neonatal hypoxic-ischemic brain injury

Neonatal hypoxic-ischemic brain injury remains a significant cause of morbidity and mortality and lacks effective therapies for prevention and treatment. Recently, interest in the biology of polyphenol compounds has led to the discovery that dietary supplementation with foods rich in polyphenols (e.g. blueberries, green tea extract) provides neuroprotection in adult animal models of ischemia and Alzheimer's disease. We sought to determine whether protection of the neonatal brain against a hypoxic-ischemic insult could be attained through supplementation of the maternal diet with pomegranate juice, notable for its high polyphenol content. Mouse dams were provided ad libitum access to drinking water with pomegranate juice, at one of three doses, as well as plain water, sugar water, and vitamin C water controls during the last third of pregnancy and throughout the duration of litter suckling. At postnatal day 7, pups underwent unilateral carotid ligation followed by exposure to 8% oxygen for 45 min. Brain injury was assessed histologically after 1 wk (percentage of tissue area loss) and biochemically after 24 h (caspase-3 activity). Dietary supplementation with pomegranate juice resulted in markedly decreased brain tissue loss (>60%) in all three brain regions assessed, with the highest pomegranate juice dose having greatest significance (p < or = 0.0001). Pomegranate juice also diminished caspase-3 activation by 84% in the hippocampus and 64% in the cortex. Ellagic acid, a polyphenolic component in pomegranate juice, was detected in plasma from treated but not control pups. These results demonstrate that maternal dietary supplementation with pomegranate juice is neuroprotective for the neonatal brain.     

7-hydroperoxycholesterol and oxysterols as indices of oxidative stress: chronic ethanol feeding and rat skeletal muscle

The present study is undertaken to determine if ethanol affects 7-hydroperoxycholesterol or oxysterols in rat skeletal muscle after chronic ethanol feeding. Wistar rats were fed a liquid diet containing ethanol as 35% of total calories. After 6 weeks, soleus (Type I fibre-predominant) and plantaris (Type II fibre-predominant) skeletal muscles were dissected out. We measured 7alpha- and 7beta-hydroperoxycholest-5-en-3beta-ol (7alpha-OOH and 7beta-OOH) as well as 7alpha- and 7beta-hydroxycholesterol (7alpha-OH and 7beta-OH) and 3beta-hydroxycholest-5-en-7-one (7-keto). We found that in response to chronic alcohol feeding, there were significant increases in soleus 7alpha-OH (P=0.0005), 7beta-OH (P=0.0005) and 7-keto (P=0.0007), but in the plantaris, 7beta-OH increased (P=0.0418). Their elevation in chronic experimental alcoholism, together with increases in cholesterol hydroperoxides, may possibly represent evidence of increased oxidative stress.     

Pharmacokinetic/pharmacodynamic analysis of anti-hyperprolactinemic effect of terguride based on dopamine D2 receptor occupancy

Terguride has been widely used for the treatment of hyperprolactinemia via partial agonistic action on dopamine D2 receptors in the pituitary. The present study analyzed retrospectively the dopamine D2 receptor binding occupancy (phi) of terguride. The average phi value was estimated to be 14.1% after oral administration of the average/standard therapeutic dose of terguride. Taking the intrinsic activity (alpha) into consideration, the value of alpha. phi was 2.33%. These results suggest that the antihyperprolactinemic effect of terguride was elicited despite the low receptor occupancy. Furthermore, we developed a pharmacokinetic/pharmacodynamic model for ascertaining the serum prolactin-lowering effect of terguride, considering both the reversible binding to D2 receptors and the effect on the increase rate in the prolactin level. The developed model fit well with the actual data. Although this model could be improved, it could explain the long duration of the antihyperprolactinemic activity of terguride and might be useful for designing its rational dosage regimen.     

Exploration of oncologists’ attitudes toward and perceived value of patient-reported outcomes

Purpose

To understand oncologists’ attitudes toward patient-reported outcome (PRO) measures and to learn how PRO data influence their clinical decision-making.

Methods

Twenty practicing oncologists participated in 1 of 4 semi-structured focus groups.

Results

Most oncologists had no experience with PRO measures, but were able to identify several concepts appropriate for patient-reported assessment. Participants agreed that clinical measures such as performance status were more meaningful to them, but acknowledged that PRO measures were more appropriate for assessing patient symptoms and treatment response. All oncologists believed that clinical efficacy and toxicity data were of primary importance, but that PROs become increasingly important when multiple treatments are available, in advanced or incurable disease, and in palliative care. Several issues prevented oncologists from being able to draw meaningful conclusions from PRO data: lack of familiarity with PRO measures, being presented with too much data to process, lack of clarity around a meaningful change in PRO measure scores, and lack of standardization in the use of PRO measures.

Conclusions

Oncologists indicated that PRO data are most influential in advanced or incurable disease and in palliative care. Improving the interpretability of PRO measures could increase the usefulness of PRO data in treatment decision-making.     

Accounting for Attribute‐Level Non‐Attendance in a Health Choice Experiment: Does it Matter?

An extensive literature has established that it is common for respondents to ignore attributes of the alternatives within choice experiments. In most of the studies on attribute non‐attendance, it is assumed that respondents consciously (or unconsciously) ignore one or more attributes of the alternatives, regardless of their levels. In this paper, we present a new line of enquiry and approach for modelling non‐attendance in the context of investigating preferences for health service innovations. This approach recognises that non‐attendance may not just be associated with attributes but may also apply to the attribute's levels. Our results show that respondents process each level of an attribute differently: while attending to the attribute, they ignore a subset of the attribute's levels. In such cases, the usual approach of assuming that respondents either attend to the attribute or not, irrespective of its levels, is erroneous and could lead to misguided policy recommendations. Our results indicate that allowing for attribute‐level non‐attendance leads to substantial improvements in the model fit and has an impact on estimated marginal willingness to pay and choice predictions.Copyright © 2014 John Wiley & Sons, Ltd.     

Prediction of clinical effects of infliximab administered for inflammatory bowel disease based on pharmacokinetic and pharmacodynamic modeling

Infliximab (IFX) is used as a therapeutic agent for ulcerative colitis (UC) and Crohn's disease (CD). Although the dosage regimen has been established through clinical trial experience, it has yet to be assessed with a pharmacokinetic and pharmacodynamic model. The present study analysed sequential changes of clinical response in patients with ulcerative colitis and Crohn's disease following repeated administrations of infliximab using the pharmacokinetic/pharmacodynamic model. In addition, the dosage regimen presently used for patients with ulcerative colitis was evaluated, as well as the potential efficacy gained by increasing the dose and/or reducing the interval of administration for patients with Crohn's disease. Furthermore, the possibility of evaluating the difference between both diseases with regard to the efficacy of infliximab was investigated. Sequential changes in the clinical response values obtained with our model were in good agreement with the observed values following administration of infliximab in patients with ulcerative colitis and Crohn's disease. The results showed the importance of a loading dose for patients with ulcerative colitis, as well as the efficacy of increasing the dose and reducing the interval for patients with Crohn's disease. Also, the efficacy of infliximab for both diseases is suggested to be similar. In conclusion, our results show a possible modeling scenario that can accommodate the clinical response to infliximab administered for ulcerative colitis and Crohn's disease. Furthermore, it provides confirmation for the present dosage regimens given for these diseases.     

The Effects of an Herbicide and Antibiotic Mixture on Aquatic Primary Producers and Grazers

Widespread use of agrochemicals increases their likelihood of entering aquatic systems in mixture. Despite different modes of action, atrazine (herbicide) and tetracycline (antibiotic) adversely affect non-target photosynthetic organisms individually, but the effects of simultaneous exposure to both contaminants are untested. We created microcosms containing microalgae (Chlorella sp.), floating macrophytes (Lemna minor), and a zooplankton grazer (Daphnia magna). Microcosms were exposed to environmentally relevant concentrations of atrazine and tetracycline, alone and together, for 10 days. Atrazine decreased Chlorella sp. abundance, but not enough to reduce food availability to D. magna whose reproduction and mortality were unaffected. In contrast, tetracycline and atrazine appeared to have additive effects on L. minor abundance and growth inhibition. These additive adverse effects suggest increased potential for L. minor population decline over the long term, and potential for altered species interactions in aquatic systems receiving agricultural runoff.