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2.  Blockade of Astrocytic Glutamate Uptake in Rats Induces Signs of Anhedonia and Impaired Spatial Memory 
Neuropsychopharmacology  2010;35(10):2049-2059.
Mood disorders are associated with regional brain abnormalities, including reductions in glial cell and neuron number, glutamatergic irregularities, and differential patterns of brain activation. Because astrocytes are modulators of neuronal activity and are important in trafficking the excitatory neurotransmitter glutamate, it is possible that these pathologies are interrelated and contribute to some of the behavioral signs that characterize depression and related disorders. We tested this hypothesis by determining whether depressive-like signs were induced by blocking central astrocytic glutamate uptake with the astrocytic glutamate transporter (GLT-1) inhibitor, dihydrokainic acid (DHK), in behavioral tests that quantify aspects of mood, including reward and euthymia/dysthymia: intracranial self-stimulation (ICSS) and place conditioning. We found that DHK elevated ICSS thresholds, a depressive-like effect that could reflect reduced sensitivity to reward (anhedonia) or increased aversion (dysphoria). However, DHK treatment did not establish conditioned place aversions, suggesting that this treatment does not induce dysphoria. To identify the brain regions mediating the behavioral effects of DHK, we examined c-Fos expression in areas implicated in motivation and emotion. DHK increased c-Fos expression in many of these regions. The dentate gyrus of the hippocampus was robustly activated, which led us to explore whether DHK alters hippocampal learning. DHK impaired spatial memory in the MWM. These findings identify disruption of astrocyte glutamate uptake as one component of the complex circuits that mediate anhedonia and cognitive impairment, both of which are common symptoms of depression. These finding may have implications for the etiology of depression and other disorders that share the features of anhedonia and cognitive impairment.
PMCID: PMC3055299  PMID: 20531459
glia; glutamate; dihydrokainic acid; ICSS; depression; animal models; Animal models; Glutamate; Neuropharmacology; Depression, Unipolar / Bipolar; Astrocyte; Glia; Dihydrokainic acid; ICSS
3.  Economic Evaluation of Home Blood Pressure Monitoring With or Without Telephonic Behavioral Self-Management in Patients With Hypertension 
American journal of hypertension  2009;23(2):142-148.
The Take Control of Your Blood Pressure trial evaluated the effect of a multicomponent telephonic behavioral lifestyle intervention, patient self-monitoring, and both interventions combined compared with usual care on reducing systolic blood pressure during 24 months. The combined intervention led to a significant reduction in systolic blood pressure compared with usual care alone. We examined direct and patient time costs associated with each intervention.
We conducted a prospective economic evaluation alongside a randomized controlled trial of 636 patients with hypertension participating in each study intervention. Medical costs were estimated using electronic data representing medical services delivered within the health system. Intervention-related costs were derived using information collected during the trial, administrative records, and published unit costs.
During 24 months, patients incurred a mean of $6965 (SD, $22,054) in inpatient costs and $8676 (SD, $9368) in outpatient costs, with no significant differences among the intervention groups. With base-case assumptions, intervention costs were estimated at $90 (SD, $2) for home blood pressure monitoring, $345 (SD, $64) for the behavioral intervention ($31 per telephone encounter), and $416 (SD, $93) for the combined intervention. Patient time costs were estimated at $585 (SD, $487) for home monitoring, $55 (SD, $16) for the behavioral intervention, and $741 (SD, $529) for the combined intervention.
Our analysis demonstrated that the interventions are cost-additive to the health care system in the short term and that patients’ time costs are nontrivial.
PMCID: PMC2901769  PMID: 19927132
Costs and Cost Analysis; Hypertension; Patient Compliance
4.  Two Self-management Interventions to Improve Hypertension Control: A Randomized Trial 
Annals of internal medicine  2009;151(10):687-695.
Less than 40% of Americans with hypertension have adequate blood pressure (BP) control.
To compare two self-management interventions for improving BP control among hypertensive patients.
A 2 by 2 randomized trial stratified by enrollment site and patient literacy status with two-year follow-up (5/2004-1/2008).
Two university-affiliated primary care clinics.
636 patients were randomized (31% recruitment rate) among the 2060 eligible hypertensive patients.
Research assistants randomized eligible patients via a centralized blinded and stratified randomization algorithm to receive either: 1) usual care; 2) bi-monthly tailored nurse-administered telephone intervention targeting hypertension-related behaviors; 3) BP monitoring consisting of measuring BP three times per week, or; 4) a combination of the two interventions.
The primary outcome was BP control evaluated at six-month intervals over 24 months. 475 (75%) completed the 24-month BP follow-up.
Improvements in proportion of BP control for the intervention groups relative to the usual care group at 24 months were: behavioral group, 4.3% (95% CI: −4.5%, 12.9); home BP monitoring group, 7.6% (95% CI: −1.9%, 17.0%); and, combined interventions, 11.0% (95% CI: 1.9%, 19.8%). For systolic BP, relative to usual care, the 24 month difference was, +0.6 mmHg (95% CI: −2.2, 3.4) for the behavioral intervention group, −0.6 mmHg (95% CI: −3.6, 2.3) for the home monitoring group, and −3.9 mmHg (95% CI: −6.9, −0.9) for the combined interventions. Similar patterns were observed for diastolic BP at 24 months.
Changes in medication use and diet were only monitored in intervention participants; 25% lacked 24 month outcome data; 73% had adequate BP control at baseline; the study setting was an academic health center, all factors that potentially limit generalizability.
Combined home BP monitoring and tailored behavioral telephone intervention improved BP control, systolic BP, and diastolic BP at 24 months relative to usual care.
PMCID: PMC2892337  PMID: 19920269
Hypertension; Lifestyle; Clinical Trial; Self-management; Adherence
5.  Take Control of Your Blood pressure (TCYB) study: A multifactorial tailored behavioral and educational intervention for achieving blood pressure control 
Patient education and counseling  2007;70(3):338-347.
Evaluating a randomized controlled trial involving a tailored behavioral intervention conducted to improve blood pressure control.
Adults with hypertension from two outpatient primary care clinics were randomly allocated to receive a nurse-administered behavioral intervention or usual care. In this ongoing study, patients receive the tailored behavioral intervention bi-monthly for two years via telephone; the goal of the intervention is to promote medication adherence and improve hypertension-related health behaviors. Patient factors targeted in the tailored behavioral intervention include perceived risk of hypertension and knowledge, memory, medical and social support, patients' relationship with their health care provider, adverse effects of medication therapy, weight management, exercise, diet, stress, smoking, and alcohol use.
The sample randomized to the behavioral intervention consisted of 319 adults with hypertension (average age = 60.5 years; 47% African-American). A comparable sample of adults was assigned to usual care (n=317). We had a 96% retention rate for the overall sample for the first 6 months of the study (93% at 12 months). The average phone call has lasted 18 minutes (range 2 to 51 minutes). From baseline to six months, self-reported medication adherence increased by 9% in the behavioral group vs. 1% in the non-behavioral group.
The intervention is easily implemented and is designed to enhance adherence with prescribed hypertension regimen. The study includes both general and patient-tailored information based upon need assessment. The study design ensures internal validity as well as the ability to generalize study findings to the clinic settings.
Practice Implications
Despite knowledge of the risks and acceptable evidence, a large number of hypertensive adults still do not have their blood pressure under effective control. This study will be an important step in evaluating a tailored multibehavioral intervention focusing on improving blood pressure control.
PMCID: PMC2276731  PMID: 18164894
Behavioral Intervention; hypertension; adherence; tailored; health communication
6.  Utilization of the PICO framework to improve searching PubMed for clinical questions 
Supporting 21st century health care and the practice of evidence-based medicine (EBM) requires ubiquitous access to clinical information and to knowledge-based resources to answer clinical questions. Many questions go unanswered, however, due to lack of skills in formulating questions, crafting effective search strategies, and accessing databases to identify best levels of evidence.
This randomized trial was designed as a pilot study to measure the relevancy of search results using three different interfaces for the PubMed search system. Two of the search interfaces utilized a specific framework called PICO, which was designed to focus clinical questions and to prompt for publication type or type of question asked. The third interface was the standard PubMed interface readily available on the Web. Study subjects were recruited from interns and residents on an inpatient general medicine rotation at an academic medical center in the US. Thirty-one subjects were randomized to one of the three interfaces, given 3 clinical questions, and asked to search PubMed for a set of relevant articles that would provide an answer for each question. The success of the search results was determined by a precision score, which compared the number of relevant or gold standard articles retrieved in a result set to the total number of articles retrieved in that set.
Participants using the PICO templates (Protocol A or Protocol B) had higher precision scores for each question than the participants who used Protocol C, the standard PubMed Web interface. (Question 1: A = 35%, B = 28%, C = 20%; Question 2: A = 5%, B = 6%, C = 4%; Question 3: A = 1%, B = 0%, C = 0%) 95% confidence intervals were calculated for the precision for each question using a lower boundary of zero. However, the 95% confidence limits were overlapping, suggesting no statistical difference between the groups.
Due to the small number of searches for each arm, this pilot study could not demonstrate a statistically significant difference between the search protocols. However there was a trend towards higher precision that needs to be investigated in a larger study to determine if PICO can improve the relevancy of search results.
PMCID: PMC1904193  PMID: 17573961
7.  BRIEF REPORT: How Well Do Clinic-Based Blood Pressure Measurements Agree with the Mercury Standard? 
Obtaining accurate blood pressure (BP) readings is a challenge faced by health professionals. Clinical trials implement strict protocols, whereas clinical practices and studies that assess quality of care utilize a less rigorous protocol for BP measurement.
To examine agreement between real-time clinic-based assessment of BP and the standard mercury assessment of BP.
Prospective reliability study.
One hundred patients with an International Classification of Diseases—9th edition code for hypertension were enrolled.
Two BP measurements were obtained with the Hawksley random-zero mercury sphygmomanometer and averaged. The clinic-based BP was extracted from the computerized medical records.
Agreement between the mercury and clinic-based systolic blood pressure (SBP) was good, intraclass correlation coefficient (ICC)=0.91 (95% confidence interval (CI): 0.83 to 0.94); the agreement for the mercury and clinic-based diastolic blood pressure (DBP) was satisfactory, ICC=0.77 (95% CI: 0.62 to 0.86). Overall, clinic-based readings overestimated the mercury readings, with a mean overestimation of 8.3 mmHg for SBP and 7.1 mmHg for DBP. Based on the clinic-based measure, 21% of patients were misdiagnosed with uncontrolled hypertension.
Health professionals should be aware of this potential difference when utilizing clinic-based BP values for making treatment decisions and/or assessing quality of care.
PMCID: PMC1490157  PMID: 16050862
blood pressure measurement assessment; clinic method; mercury device
British Medical Journal  1910;1(2566):603.
PMCID: PMC2330964

Results 1-8 (8)