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Nonpoint source (NPS) water quality trading (WQT) is a market-based approach to improving water quality. Past work has shown that these programs could increase localized pollutant loadings, in part by exporting water quality controls from urban to rural areas. Virginia's NPS WQT program has enabled thousands of transactions and may provide a model for other programs, but its impacts on urban water quality have not been thoroughly assessed. We quantify the impact of NPS WQT purchases in Virginia on water quality and hydrology in an urban catchment. We go on to assess outcomes of a policy alternative where buyers and sellers are collocated in the urban catchment. Simulation results show that NPS WQT increased total phosphorus (TP) loading by an average of 0.8 lbs TP/year for each 1.0 offsite credits purchased in the analyzed catchment. The TP loading increased in years with greater rainfall, such that TP loads were increased by up to 1.2 lbs TP/year for each offsite credit purchased. These loading increases may or may not be acceptable, depending on the cumulative number of purchases within an urban catchment and existing local water quality issues. In our policy alternative with buyers and sellers collocated in the catchment, we found that the TP increase from development was completely offset at the catchment scale, with a decrease of 4.3 lbs TP/year for each 1.0 credits purchased. This suggests that credits awarded for urban mitigation practices are undervalued compared with water quality requirements for credit purchasers. This undervaluation is a result of the Virginia trading program using one approach to compute the credit value for buyers and a different approach to compute the credit value for sellers. We demonstrate how using a single model to determine both buyer and seller credit values in urban areas could provide greater transparency and mitigate the risk of urban pollution hot spots. This work demonstrates the importance of consistency in the scale of pollutant load calculations between buyers and sellers for NPS WQT, and contributes novel insight into the implications of WQT for urban NPS pollution.

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Forty per cent of French subjects over 65 years old with Alzheimer's disease and related disorders (ADRD) are chronically exposed to antidepressants, suggesting an overuse of these drugs. The main objective of our study was to estimate the prevalence of the overuse of antidepressants in this population and the factors associated with this. METHODOLOGY: a single-centre, prospective, cross-sectional study carried out at the Bretonneau outpatient department between 1st December 2014 and 31st May 2015. All patients aged 70 and above, suffering from ADRD (according to DSM IV criteria) and currently being prescribed an antidepressant were eligible. "Overuse" was defined as off-label prescriptions or prescriptions that went beyond the recommended duration of treatment. This was assessed by the geriatrician in charge and validated by an expert committee, who were blind to the geriatrician's assessment. RESULTS: Fifty-four patients were included in the study (mean age: 82.9 years (± 5.4); 70.4% women; 60% with mild to moderate dementia). The main indication of antidepressant treatment was a major depressive episode (59.3%). The geriatrician could not reach a conclusion on overuse in 10 cases (18.5%). Inter-rater agreement between geriatricians and the expert committee was good (kappa coefficient: 0.73 [0.5-0.95]). Finally, 33 (61%) of these patients were overusing antidepressants: a third had an off-label prescription and two thirds had exceeded the recommended treatment duration. The only factor associated with this overuse was co-prescription of psychotropic drugs (p = 0.009). CONCLUSIONS: the overuse of antidepressants is common in older patients with dementia, particularly overuse due to exceeding the treatment duration. This is significantly associated with co-prescription with another psychotropic drug, suggesting that this represents a more global problem of the overuse of psychotropic drugs.

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Forty per cent of French subjects over 65 years old with Alzheimer's disease and related disorders (MATA) are chronically exposed to antidepressants suggesting an overuse of these drugs. The main objective of our study was to estimate the prevalence and factors associated with overuse by antidepressants in this population. METHODOLOGY: Single-center, prospective, cross-sectional study carried out at the Bretonneau Day Hospital (HDJ) between December, 1st 2014 and May, 31 2015. Consecutive patients with ≥70 years of age, suffering from MATA (according to DSM IV criteria) and current prescription of antidepressant were eligible. Overuse was defined by off-label prescriptions or prescriptions beyond the recommended duration of treatment. It was assessed by the geritrician in charge and validated by an expert committee, blind from the geriatrician's assessment. RESULTS: Fifty-four patients were included in the study (mean age 82.9 years (+/- 5.4), 70.4% of women, 60% with mild to moderate dementia). The main indication of antidepressant treatment was a major depressive episode (59.3%). The geriatrician could not deal with overuse for 10 cases (18.5%). Inter-rater agreement between geriatricians and expert committee was good (kappa coefficient 0.73 [0.5-0.95]). Finally 33 (61%) of these patients had overuse of antidepressants: 1/3 had an off-label prescription and 2/3 had an exceeded treatment duration. The only factor associated with this overuse was coprescription of psychotropic drugs (p=0.009). CONCLUSIONS: Antidepressant overuse is common in demented older outpatients, especially overuse due to exceeded treatment duration. It is significantly associated with coprescription with another psychotropic drug, suggesting that it fits into a more global problem of overuse in psychotropic drugs.

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INTRODUCTION: Neuroinflammation is thought to be important in Alzheimer's disease pathogenesis. Mast cells are a key component of the inflammatory network and participate in the regulation of the blood-brain barrier's permeability. Masitinib, a selective oral tyrosine kinase inhibitor, effectively inhibits the survival, migration and activity of mast cells. As the brain is rich in mast cells, the therapeutic potential of masitinib as an adjunct therapy to standard care was investigated. METHODS: A randomised, placebo-controlled, phase 2 study was performed in patients with mild-to-moderate Alzheimer's disease, receiving masitinib as an adjunct to cholinesterase inhibitor and/or memantine. Patients were randomly assigned to receive masitinib (n = 26) (starting dose of 3 or 6 mg/kg/day) or placebo (n = 8), administered twice daily for 24 weeks. The primary endpoint was change from baseline in the Alzheimer's Disease Assessment Scale - cognitive subscale (ADAS-Cog) to assess cognitive function and the related patient response rate. RESULTS: The rate of clinically relevant cognitive decline according to the ADAS-Cog response (increase >4 points) after 12 and 24 weeks was significantly lower with masitinib adjunctive treatment compared with placebo (6% vs. 50% for both time points; P = 0.040 and P = 0.046, respectively). Moreover, whilst the placebo treatment arm showed worsening mean ADAS-Cog, Alzheimer's Disease Cooperative Study Activities of Daily Living Inventory, and Mini-Mental State Examination scores, the masitinib treatment arm reported improvements, with statistical significance between treatment arms at week 12 and/or week 24 (respectively, P = 0.016 and 0.030; P = 0.035 and 0.128; and P = 0.047 and 0.031). The mean treatment effect according to change in ADAS-Cog score relative to baseline at weeks 12 and 24 was 6.8 and 7.6, respectively. Adverse events occurred more frequently with masitinib treatment (65% vs. 38% of patients); however, the majority of events were of mild or moderate intensity and transitory. Severe adverse events occurred at a similar frequency in the masitinib and placebo arms (15% vs. 13% of patients, respectively). Masitinib-associated events included gastrointestinal disorders, oedema, and rash. CONCLUSIONS: Masitinib administered as add-on therapy to standard care during 24 weeks was associated with slower cognitive decline in Alzheimer's disease, with an acceptable tolerance profile. Masitinib may therefore represent an innovative avenue of treatment in Alzheimer's disease. This trial provides evidence that may support a larger placebo-controlled investigation. TRIAL REGISTRATION: Clinicaltrials.gov NCT00976118.

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