Outcomes and Patient Experience in Individuals With Longstanding Dizziness.

PURPOSE: This study aimed to describe the relationship between changes in pre and post self-perceived dizziness handicap, scores on the patient health questionnaire, and perceptions of patient's value of being evaluated and managed by a multidisciplinary team. METHOD: Seventy-eight patients completed the Dizziness Handicap Inventory (DHI) and Patient Health Questionnaire-Fourth Edition (PHQ-4) questionnaires post multidisciplinary clinical consultations and testing for the chief complaints of dizziness, unsteadiness, vertigo, or balance problems. The diagnoses of each patient were recorded from the clinical reports of each specialty consultation and were classified as structural, functional, or psychiatric. They were contacted by phone at least 6 months after their visit to obtain feedback regarding their symptoms and overall patient experience. RESULTS: The change in DHI total score did not differ significantly by diagnosis (p = .56), indicating that patients experienced an improvement in DHI total score regardless of diagnosis. PHQ-4 anxiety scores worsened by a mean of 0.7 points for those with structural diagnoses (p = .04), improved by a mean of 0.7 points for psychiatric diagnoses (p = .16), and improved by a mean of 0.3 points for functional diagnoses (p = .39). Only seven patients would not recommend the team to a family or friend; these patients tended to report worsening DHI total scores (p = .27) compared to the significant improvement in DHI total scores for patients who would make such a recommendation (p < .001). Similarly, only 13 patients did not feel the information they received had a positive impact; these patients tended to report worsening DHI total scores (p = .18) compared to the significant improvement in DHI total scores for patients who did feel the information had a positive impact (p < .001). DISCUSSION: The assessment and management of patients with chronic dizziness is challenging due to symptoms arising from multiple etiologies. Our finding of a vast difference between high satisfaction and relatively unchanged dizziness handicap suggests that there is value in seeing a multidisciplinary team where consultations are unhurried, care is coordinated, and expectations regarding treatment can be managed.

Long-Term Performance of Monolithic Silica Aerogel with Different Hydrophobicities: Physical and Color Rendering Properties after an Accelerated Aging Process.

Due to its excellent properties, monolithic silica aerogel is a promising material for innovative glazing systems. Since glazing systems are exposed to deteriorating agents during building service life, it is essential to investigate the long-term performance of aerogel. In the present paper, several 12.7 mm-thick silica aerogel monoliths produced by a rapid supercritical extraction method were tested, including both hydrophilic and hydrophobic samples. After fabrication and characterization of hydrophobicity, porosity, optical and acoustic properties, and color rendering, the samples were artificially aged by combining temperature and solar radiation effects in an experimental device specifically developed at the University of Perugia. The length of the experimental campaign was determined using acceleration factors (AFs). Temperature AF was evaluated according to the Arrhenius law using thermogravimetric analysis to estimate the aerogel activation energy. A natural service life of 12 years was achieved in about 4 months, and the samples' properties were retested. Contact angle tests supported by FT-IR analysis showed loss of hydrophobicity after aging. Visible transmittance values in the 0.67-0.37 range were obtained for hydrophilic and hydrophobic samples, respectively. The aging process involved optical parameter reduction of only 0.02-0.05. There was also a slight loss in acoustic performance (noise reduction coefficient (NRC) = 0.21-0.25 before aging and NRC = 0.18-0.22 after aging). For hydrophobic panes, color shift values in the 10.2-59.1 and 8.4-60.7 ranges were obtained before and after aging, respectively. The presence of aerogel, regardless of hydrophobicity, results in a deterioration in light-green and azure tones. Hydrophobic samples had lower color rendering performance than hydrophilic aerogel, but this did not worsen after the aging process. This paper makes a significant contribution to the progressive deterioration assessment of aerogel monoliths for applications in sustainable buildings.

Aesthetically Enhanced Silica Aerogel Via Incorporation of Laser Etching and Dyes.

A procedure for aesthetically enhancing silica aerogel monoliths by laser etching and incorporation of dyes is described in this manuscript. Using a rapid supercritical extraction method, large silica aerogel monolith (10 cm x 11 cm x 1.5 cm) can be fabricated in about 10 h. Dyes incorporated into the precursor mixture result in yellow-, pink- and orange-tinged aerogels. Text, patterns, and images can be etched onto the surface (or surfaces) of the aerogel monolith without damaging the bulk structure. The laser engraver can be used to cut shapes from the aerogel and form colorful mosaics.

The Impact of Systematic Safety Precautions on COVID-19 Risk Exposure and Transmission Rates in Outpatient Healthcare Workers.

We evaluated the impact of safety protocols, including rapid testing and contact tracing, on coronavirus disease 2019 (COVID-19) risk exposure and transmission rates amongst healthcare workers in the outpatient care setting. Over an 11-week period, a total of 254 employees representing 38% of our total workforce had potential COVID-19 exposure and underwent voluntary COVID-19 testing. Data was stratified based on severity of risk exposure and job description. During this period, the probability of a COVID exposure being high risk decreased in Administrative (-93.0%; P < 0.01) and Clinical (-77.0%; P < 0.01) staff; simultaneously, viral transmission rates declined in Administrative (-73.4%; P = 0.03) and Clinical (-69.9%; P = 0.04) staff as well. Systematic safety protocols effectively reduce exposure risk and transmission rates in outpatient healthcare workers and should be ubiquitously adopted.

Role of Temperature and Growth Period in the Synthesis of Hydrothermally Grown TiO2 Nanorods.

Highly uniformed, surfactant free and vertically oriented titanium-di-oxide (TiO2) nanorods were grown on pre-treated fluorine doped tin oxide (FTO) using hydrothermal method through titanium tetra butoxide (Ti(OBu)4) as titanium source. Three different temperatures 130 °C, 150 °C and 180 °C were followed to grow the nanorods at a fixed reaction time of 4 h. The prepared TiO2 nanorods were annealed at the temperatures of 550 °C and 600 °C for 3 h. X-ray diffraction (XRD) analysis shows that obtained nanorods exhibit pure rutile phase. From scanning electron microscopy (SEM) analysis, it was found that increasing temperature led to decreasing the diameter of the nanorods. In addition to these, formation of hierarchical type TiO2 nanorods was also observed at 130 °C. UV-visible spectra analysis was carried out to find the influence of diameter of the nanorods on its optical properties. The plausible mechanism of the growth process is also discussed.

Endothelin 1 Is Associated with Heart Failure Hospitalization and Long-Term Mortality in Patients with Heart Failure with Preserved Ejection Fraction and Pulmonary Hypertension.

BACKGROUND: The prevalence of pulmonary hypertension (PH) in heart failure with preserved ejection fraction (HFpEF) is increasing. We aim to study the role of big endothelin 1 (Big ET1), endothelin 1 (ET1), and neprilysin (NE) in HFpEF with PH. METHOD: This was a single center prospective cohort study including 90 HFpEF patients; 30 with no PH, 30 with postcapillary PH, and 30 with combined post- and precapillary PH. After enrollment, pulmonary venous and pulmonary arterial samples of Big ET1, ET1, and NE were collected during right heart catheterization. Subjects were then followed long term for adverse outcomes which included echocardiographic evidence of right ventricular dysfunction, heart failure hospitalization, and all-cause mortality. RESULTS: Patients with HFpEF-PH were found to have increased ET1 in pulmonary veins (endothelin from the wedge; ET1W) compared to controls (2.3 ± 1.4 and 1.6 ± 0.9 pg/mL, respectively). ET1W levels were associated with both PH (OR 2.7, 95% CI 1.5-4.7, p = 0.01) and pulmonary vascular resistance (OR 1.6, 95% CI 1.04-2.3, p = 0.03). No evidence of right ventricular dysfunction was observed after 1 year of follow-up. ET1W (OR 1.8, 95% CI 1.2-2.6, p = 0.01) and ET1 gradient (ET1G; OR 1.4, 95% CI 1.04-2, p = 0.03) were predictive of 1-year hospitalization. ET1G ≥0.2 pg/mL was associated with long-term mortality (log-rank 4.8, p = 0.03). CONCLUSION: In HFpEF patients, ET1W and ET1G are predictive of 1-year heart failure hospitalization, while elevated ET1G levels were found to be associated with long-term mortality in HFpEF. This study highlights the role of ET1 in developing PH in HFpEF patients and also explores the potential of ET1 as a prognostic biomarker.

Histologic Changes in Prostate Cancer Detected Subsequent to the 2012 United States Preventive Services Task Force (USPSTF) Prostate Cancer Screening Recommendation.

We report changes in the histopathology of prostate cancer diagnosed in a large urology group practice after the final United States Preventive Services Task Force (USPSTF) Grade D recommendation against prostate-specific antigen screening. All prostate biopsies performed from 2011 through 2015 in a large urology group practice were retrospectively reviewed; 2012 was excluded as a transition year. The changes in biopsy data in years following the USPSTF decision (2013-2015) were then compared with baseline (2011). A total of 10,944 biopsies were evaluated during the study period. Positive biopsy rates rose from 39.1% at baseline to 45.2% in 2015 (P < 0.01) with a marked shift toward more aggressive cancer throughout the study period. The absolute number of patients presenting with Gleason Grade Group 4 or 5 increased from 155/year at baseline to 231, 297, and 285 in 2013, 2014, and 2015, respectively (P < 0.05), unrelated to age or racial changes over time. Black men represented 16% of the cohort. Since the USPSTF recommendation against prostate cancer screening, trends toward a substantial upward grade migration and increased volume of cancers were noted in a cohort of nearly 11,000 patients in a real-world clinical practice. Additionally, continuing reductions in cancer detection in the United States may exacerbate these trends.

Fabrication and Testing of Catalytic Aerogels Prepared Via Rapid Supercritical Extraction.

Protocols for preparing and testing catalytic aerogels by incorporating metal species into silica and alumina aerogel platforms are presented. Three preparation methods are described: (a) the incorporation of metal salts into silica or alumina wet gels using an impregnation method; (b) the incorporation of metal salts into alumina wet gels using a co-precursor method; and (c) the addition of metal nanoparticles directly into a silica aerogel precursor mixture. The methods utilize a hydraulic hot press, which allows for rapid (<6 h) supercritical extraction and results in aerogels of low density (0.10 g/mL) and high surface area (200-800 m2/g). While the work presented here focuses on the use of copper salts and copper nanoparticles, the approach can be implemented using other metal salts and nanoparticles. A protocol for testing the three-way catalytic ability of these aerogels for automotive pollution mitigation is also presented. This technique uses custom-built equipment, the Union Catalytic Testbed (UCAT), in which a simulated exhaust mixture is passed over an aerogel sample at a controlled temperature and flow rate. The system is capable of measuring the ability of the catalytic aerogels, under both oxidizing and reducing conditions, to convert CO, NO and unburned hydrocarbons (HCs) to less harmful species (CO2, H2O and N2). Example catalytic results are presented for the aerogels described.

Bupropion for the treatment of methamphetamine dependence in non-daily users: a randomized, double-blind, placebo-controlled trial.

AIM: Bupropion was tested for efficacy to achieve methamphetamine (MA) abstinence in dependent, non-daily users. METHODS: A randomized, double-blind, placebo-controlled trial, with 12-week treatment and 4-week follow-up, was conducted with 204 treatment-seeking participants having MA dependence per DSM-IV, who used MA on a less-than-daily basis. 104 were randomized to matched placebo and 100 to bupropion, sustained-release 150mg, twice daily. Participants were seen three times weekly to obtain urine for MA and bupropion assays, study assessments, and thrice weekly, 90-min, group psychotherapy. There was no biomarker for placebo adherence. The primary outcome was achievement of abstinence throughout the last two weeks of treatment; 'success' requiring at least two urine samples during each of Weeks 11 and 12, and all samples MA-negative (<300ng/mL). RESULTS: Bupropion and placebo groups did not differ significantly in the percentage achieving abstinence for the last 2 weeks of treatment (chi-square, p=0.32). Subgroup analysis of participants with lower baseline MA use (≤18 of last 30 days before consent) also revealed no difference in success between groups (p=0.73). Medication adherence per protocol (detectable bupropion, >5ng/mL, in ≥50% of urine samples from Study Weeks 1-10 and ≥66% of urine samples from Weeks 11 to 12) was achieved by 47% of participants taking bupropion. CONCLUSIONS: These data indicate that bupropion did not increase abstinence in dependent participants who were using MA less-than-daily. Medication non-adherence was a limitation in this trial. Psychosocial therapy remains the mainstay of treatment for MA dependence. Further research on subgroups who may respond to bupropion may be warranted.

Utility of PTEN and ERG immunostaining for distinguishing high-grade PIN from intraductal carcinoma of the prostate on needle biopsy.

Intraductal carcinoma of the prostate and high-grade prostatic intraepithelial neoplasia (PIN) have markedly different implications for patient care but can be difficult to distinguish in needle biopsies. In radical prostatectomies, we demonstrated that PTEN and ERG immunostaining may be helpful to resolve this differential diagnosis. Here, we tested whether these markers are diagnostically useful in the needle biopsy setting. Separate or combined immunostains were applied to biopsies containing morphologically identified intraductal carcinoma, PIN, or borderline intraductal proliferations more concerning than PIN but falling short of morphologic criteria for intraductal carcinoma. Intraductal carcinoma occurring with concurrent invasive tumor showed the highest rate of PTEN loss, with 76% (38/50) lacking PTEN and 58% (29/50) expressing ERG. Of biopsies containing isolated intraductal carcinoma, 61% (20/33) showed PTEN loss and 30% (10/33) expressed ERG. Of the borderline intraductal proliferations, 52% (11/21) showed PTEN loss and 27% (4/15) expressed ERG. Of the borderline cases with PTEN loss, 64% (7/11) had carcinoma in a subsequent needle biopsy specimen, compared with 50% (5/10) of PTEN-intact cases. In contrast, none of the PIN cases showed PTEN loss or ERG expression (0/19). On needle biopsy, PTEN loss is common in morphologically identified intraductal carcinoma yet is very rare in high-grade PIN. Borderline intraductal proliferations, especially those with PTEN loss, have a high rate of carcinoma on resampling. If confirmed in larger prospective studies, these results suggest that PTEN and ERG immunostaining may provide a useful ancillary assay to distinguish intraductal carcinoma from high-grade PIN in this setting.

Preparing silica aerogel monoliths via a rapid supercritical extraction method.

A procedure for the fabrication of monolithic silica aerogels in eight hours or less via a rapid supercritical extraction process is described. The procedure requires 15-20 min of preparation time, during which a liquid precursor mixture is prepared and poured into wells of a metal mold that is placed between the platens of a hydraulic hot press, followed by several hours of processing within the hot press. The precursor solution consists of a 1.0:12.0:3.6:3.5 x 10(-3) molar ratio of tetramethylorthosilicate (TMOS):methanol:water:ammonia. In each well of the mold, a porous silica sol-gel matrix forms. As the temperature of the mold and its contents is increased, the pressure within the mold rises. After the temperature/pressure conditions surpass the supercritical point for the solvent within the pores of the matrix (in this case, a methanol/water mixture), the supercritical fluid is released, and monolithic aerogel remains within the wells of the mold. With the mold used in this procedure, cylindrical monoliths of 2.2 cm diameter and 1.9 cm height are produced. Aerogels formed by this rapid method have comparable properties (low bulk and skeletal density, high surface area, mesoporous morphology) to those prepared by other methods that involve either additional reaction steps or solvent extractions (lengthier processes that generate more chemical waste).The rapid supercritical extraction method can also be applied to the fabrication of aerogels based on other precursor recipes.

Utilization trends and positive biopsy rates for prostate biopsies in the United States: 2005 to 2011.

This article assesses the positive biopsy rate and core sampling pattern in patients undergoing needle biopsy of the prostate in the United States at a national reference laboratory (NRL) and anatomic pathology laboratories integrated into urology group practices, and analyzes the relationship between positive biopsy rates and the number of specimen vials per biopsy. For the years 2005 to 2011 we collected pathology data from an NRL, including number of urologists and urology practices referring samples, total specimen vials submitted for prostate biopsies, and final pathologic diagnosis for each case. The diagnoses were categorized as benign, malignant, prostatic intraepithelial neoplasia, or atypical small acinar proliferation. Over the same period, similar data were gathered from urology practices with in-house laboratories performing global pathology services (urology practice laboratories; UPLs) as identified by a survey of members of the Large Urology Group Practice Association. For each year studied, positive biopsy rate and number of specimen vials per biopsy were calculated in aggregate and separately for each site of service. From 2005 to 2011, 437,937 biopsies were submitted in > 4.23 million vials (9.4 specimen vials/biopsy); overall positive biopsy rate was 40.3%-this was identical at both the NRL and UPL (P = .97). Nationally, the number of specimen vials per biopsy increased sharply from a mean of 8.8 during 2005 to 2008 to a mean of 10.3 from 2009 to 2011 (difference, 1.5 specimen vials/biopsy; P = .03). For the most recent 3-year period (2009-2011), the difference of 0.6 specimen vials per biopsy between the NRL (10.0) and UPL (10.6) was not significant (P = 0.08). Positive biopsy rate correlated strongly (P < .01) with number of specimen vials per biopsy. The positive prostate biopsy rate is 40.3% and is identical across sites of service. Although there was a national trend toward increased specimen vials per biopsy from 2005 to 2011, from 2009 to 2011 there was no significant difference in specimen vials per biopsy across sites of service. Increased cancer detection rate correlated significantly with increased number of specimens examined. Segregation of prostate biopsy cores into 10 to 12 unique specimen vials has been widely adopted by urologists across sites of service.

Safety of atomoxetine in combination with intravenous cocaine in cocaine-experienced participants.

OBJECTIVES: Atomoxetine has been considered as an agonist replacement therapy for cocaine. We investigated the safety of the interaction of atomoxetine with cocaine and also whether cognitive function was affected by atomoxetine during short-term administration. METHODS: In a double-blind placebo-controlled inpatient study of 20 cocaine-dependent volunteers, participants received atomoxetine 80 mg daily followed by 100 mg daily for 5 days each. On the fourth and fifth day at each dose, cocaine (20 and 40 mg) was infused intravenously in sequential daily sessions. RESULTS: Preinfusion mean systolic pressures showed a small but statistically significant difference between placebo and both doses of atomoxetine. Preinfusion mean diastolic pressures were significant between placebo and atomoxetine 80 mg only. The diastolic pressure response to 40 mg cocaine was statistically significant only between the 80- and 100-mg atomoxetine doses. All electrocardiogram parameters were unchanged. Visual Analog Scale (VAS) scores for "bad effect" in the atomoxetine group were significantly higher at baseline, then declined, and for "likely to use" declined with atomoxetine treatment. On the Addiction Research Center Inventory, the atomoxetine group scored significantly lower on amphetamine, euphoria, and energy subscales (P < 0.0001). Other VAS descriptors, Brief Substance Craving Scale, Profile of Moods State, and Brief Psychiatric Rating Scale showed no differences. Atomoxetine did not affect cocaine pharmacokinetics. In tests of working memory, sustained attention, cognitive flexibility, and decision-making, atomoxetine improved performance on the visual n-back task. There were no differences in any pharmacokinetic parameters for cocaine with atomoxetine. CONCLUSIONS: Atomoxetine was tolerated safely by all participants. Certain cognitive improvements and a dampening effect on VAS scores after cocaine were observed, but should be weighed against small but significant differences in hemodynamic responses after atomoxetine.

Topiramate for the treatment of methamphetamine addiction: a multi-center placebo-controlled trial.

AIMS: Topiramate has shown efficacy at facilitating abstinence from alcohol and cocaine abuse. This double-blind, placebo-controlled out-patient trial tested topiramate for treating methamphetamine addiction. DESIGN: Participants (n = 140) were randomized to receive topiramate or placebo (13 weeks) in escalating doses from 25 mg/day [DOSAGE ERROR CORRECTED] to the target maintenance of 200 mg/day in weeks 6-12 (tapered in week 13). Medication was combined with weekly brief behavioral compliance enhancement treatment. SETTING: The trial was conducted at eight medical centers in the United States. PARTICIPANTS: One hundred and forty methamphetamine-dependent adults took part in the trial. MEASUREMENTS: The primary outcome was abstinence from methamphetamine during weeks 6-12. Secondary outcomes included use reduction versus baseline, as well as psychosocial variables. FINDINGS: In the intent-to-treat analysis, topiramate did not increase abstinence from methamphetamine during weeks 6-12. For secondary outcomes, topiramate reduced weekly median urine methamphetamine levels and observer-rated severity of dependence scores significantly. Subjects with negative urine before randomization (n = 26) had significantly greater abstinence on topiramate versus placebo during study weeks 6-12. Topiramate was safe and well tolerated. CONCLUSIONS: Topiramate does not appear to promote abstinence in methamphetamine users but can reduce the amount taken and reduce relapse rates in those who are already abstinent.

Modafinil for the treatment of methamphetamine dependence.

AIM: Modafinil was tested for efficacy in decreasing use in methamphetamine-dependent participants, compared to placebo. METHODS: This was a randomized, double-blind, placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Eight outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, who all had a DSM-IV diagnosis of methamphetamine dependence; 68 participants to placebo, 72 to modafinil 200mg, and 70 to modafinil 400mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments, urine drug screens, and group psychotherapy. The primary outcome measure was a methamphetamine non-use week, which required all the week's qualitative urine drug screens to be negative for methamphetamine. RESULTS: Regression analysis showed no significant difference between either modafinil group (200 or 400mg) or placebo in change in weekly percentage having a methamphetamine non-use week over the 12-week treatment period (p=0.53). Similarly, a number of secondary outcomes did not show significant effects of modafinil. However, an ad-hoc analysis of medication compliance, by urinalysis for modafinil and its metabolite, did find a significant difference in maximum duration of abstinence (23 days vs. 10 days, p=0.003), between those having the top quartile of compliance (>85% of urines were positive for modafinil, N=36), and the lower three quartiles of modafinil 200 and 400mg groups (N=106). CONCLUSIONS: Although these data suggest that modafinil, plus group behavioral therapy, was not effective for decreasing methamphetamine use, the study is probably inconclusive because of inadequate compliance with taking medication.

Advantages of Joint Modeling of Component HIV Risk Behaviors and Non-Response: Application to Randomized Trials in Cocaine-Dependent and Methamphetamine-Dependent Populations.

The HIV risk-taking behavior scale (HRBS) is an 11-item instrument designed to assess the risks of HIV infection due to self-reported injection-drug use and sexual behavior. A retrospective analysis was performed on HRBS data collected from approximately 1,000 participants pooled across seven clinical trials of pharmacotherapies for either the treatment of cocaine dependence or methamphetamine dependence. Analysis faced three important challenges. The sample contained a high proportion of missing assessments after randomization. Also, the HRBS scale consists of two distinct behavioral components which may or may not coincide in response patterns. In addition, distributions of responses on the subscales were highly concentrated at just a few values (e.g., 0, 6). To address these challenges, a single probit regression model was fit to three outcomes variables simultaneously - the two subscale totals plus an indicator variable for assessments not obtained (non-response). This joint-outcome regression model was able to identify that those who left assessment early had higher self-reported risk of injection-drug use and lower self-reported risky sexual behavior because the model was able to draw on information on associations among the three outcomes collectively. These findings were not identified in analyses performed on each outcome separately. No evidence for an effect of pharmacotherapies was observed, except to reduce missing assessments. Univariate-outcome modeling is not recommended for the HRBS.

A double-blind, placebo-controlled assessment of the safety of potential interactions between intravenous cocaine, ethanol, and oral disulfiram.

BACKGROUND: A majority of cocaine addicts have a comorbid alcohol use disorder. Previous studies demonstrated efficacy of disulfiram in the treatment of cocaine dependence among patients with comorbid alcohol use disorder or opioid dependence. However, the cardiac risks of a disulfiram-ethanol reaction (DER) in individuals who drink, when coupled with the cardiac effects of cocaine, could result in significant toxicity or lethality due to the 3-way drug interaction. AIMS: This study examined the safety of combining cocaine (30 mg i.v.) and ethanol (0.4 g/kg i.v.) in disulfiram-treated (0, 250, and 500 mg/d, p.o.) cocaine-dependent research volunteers. RESULTS: The results showed that disulfiram did not enhance the cardiovascular effects of cocaine and may have reduced the subjective high from cocaine. In contrast, ethanol produced adverse ECG changes including QTc prolongation and a DER consisting of hypotension, tachycardia, nausea, and flushing in disulfiram-treated subjects. The severity of the DER was related to disulfiram dose and the trial with 500 mg/d was stopped prematurely due to safety concerns. The DER-related hypotension and tachycardia seen with ethanol infusion alone in disulfiram-treated subjects, was not exacerbated when combined with cocaine. In fact, cocaine tended to counteract the ethanol-related hypotension though it did exacerbate the tachycardia in two of seven subjects. CONCLUSIONS: Though conclusions are limited by the moderate doses of cocaine, ethanol, and disulfiram tested, the data do suggest that the risks of the moderate use of cocaine and ethanol in individuals treated with moderate doses of disulfiram (≤ 250 mg/d) may not be as problematic as some may assume.

Modafinil for the treatment of cocaine dependence.

AIM: Modafinil was tested for efficacy in facilitating abstinence in cocaine-dependent patients, compared to placebo. METHODS: This was a double-blind placebo-controlled study, with 12 weeks of treatment and a 4-week follow-up. Six outpatient substance abuse treatment clinics participated in the study. There were 210 treatment-seekers randomized, having a diagnosis of cocaine dependence; 72 participants were randomized to placebo, 69 to modafinil 200mg, and 69 to modafinil 400mg, taken once daily on awakening. Participants came to the clinic three times per week for assessments and urine drug screens, and had one hour of individual psychotherapy weekly. The primary outcome measure was the weekly percentage of cocaine non-use days. RESULTS: The GEE regression analysis showed that for the total sample, there was no significant difference between either modafinil group and placebo in the change in average weekly percent of cocaine non-use days over the 12-week treatment period (p>0.79). However, two secondary outcomes showed significant effects by modafinil 200mg: the maximum number of consecutive non-use days for cocaine (p=0.02), and a reduction in craving (p=0.04). Also, a post hoc analysis showed a significant effect of modafinil that increased the weekly percentage of non-use days in the subgroup of those cocaine patients who did not have a history of alcohol dependence (p<0.02). CONCLUSIONS: These data suggest that modafinil, in combination with individual behavioral therapy, was effective for increasing cocaine non-use days in participants without co-morbid alcohol dependence, and in reducing cocaine craving.

Evaluation of subjective effects of aripiprazole and methamphetamine in methamphetamine-dependent volunteers.

A variety of neuropharmacological strategies are being pursued in the search for an effective treatment for methamphetamine (Meth) addiction. In this study, we investigated the safety and potential efficacy of aripiprazole, an antipsychotic agent acting on both dopamine and serotonin systems. We conducted a double-blind in-patient clinical pharmacology study to assess potential interactions between intravenous (i.v.) Meth (15 mg and 30 mg) and oral aripiprazole (15 mg). In addition, the effects of aripiprazole treatment on abstinence-related craving and cue-induced craving were evaluated. Participants included non-treatment-seeking, Meth-dependent patients (n=16), aged 18-45 yr, currently using Meth. Following baseline Meth dosing (15 mg and 30 mg), participants received 2 wk treatment with aripiprazole (n=8) or placebo (n=8). Participants then completed cue exposure sessions using neutral and Meth-related cues. Meth dosing (15 mg and 30 mg) was then repeated. Aripiprazole treatment had no effect on cue-induced Meth craving, or on daily baseline craving assessed over the course of medication treatment, although aripiprazole treatment was associated with increased craving independent of Meth dosing. Aripiprazole treatment was associated with significantly higher ratings on Addiction Research Center Inventory (ARCI) subscales reflecting euphoria and amphetamine-like effects following Meth dosing. Aripiprazole treatment was also associated with significant reductions in ratings of 'bad effects' and reductions on the ARCI subscale for sedation effects following Meth dosing. Aripiprazole treatment reduced the increase in systolic blood pressure following Meth dosing, but had no other effects on cardiovascular responses to Meth. Aripiprazole treatment did not alter the pharmacokinetics of Meth. These findings indicate that aripiprazole treatment appears to be safe in volunteers with Meth dependence, although the finding that aripiprazole increased some of the rewarding and stimulatory effects produced by acute Meth suggests that 15 mg aripiprazole is unlikely to be efficacious for the treatment of Meth dependence. Further research with lower doses of aripiprazole, possibly using study designs aimed at evaluating efficacy for relapse prevention, are needed before ruling out aripiprazole as a treatment for Meth dependence.