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PubMed1992

Poland-US collaborative study on cardiovascular epidemiology: classification agreement between US National Cholesterol Education Program and European Atherosclerosis Society hyperlipidemia guidelines in selected Polish and US populations.

Data from two epidemiological studies are used to measure the degree to which two well-known guidelines agree in measuring hyperlipidemia in population samples in the US and Poland. The epidemiological studies are the US Lipid Research Clinics Program Prevalence Study and the Pol-MONICA project in Poland and the guidelines are those adopted by the US National Cholesterol Program (USNCEP) and by the European Atherosclerosis Society (EAS). EAS guidelines were analyzed in two ways: Method 1 used triglycerides and total cholesterol only in classifying persons as hyperlipidemics or non-hyperlipidemics; Method 2 used triglycerides, total cholesterol and nine additional risk factors in the classification process. USNCEP guidelines used total cholesterol, low density lipoprotein cholesterol and the same additional nine risk factors used in EAS Method 2 in classifying hyperlipidemics. Classification differences between the two sets of guidelines were high when EAS Method 1 guidelines were compared with USNCEP guidelines. However, EAS Method 2 which included risk factors, compared favorably with USNCEP guidelines in all three populations under study.

Adult↗
PubMed2006

Investigating placebo effects in irritable bowel syndrome: a novel research design.

Little is known about placebo effects with scientific precision. Poor methodology has confounded our understanding of the magnitude and even the existence of the placebo effect. Investigating placebo effects presents special research challenges including: the design of appropriate controls for studying placebo effects including separating such effects from natural history and regression to the mean, the need for large sample sizes to capture expected small effects, and the need to understand such potential effects from a patient's perspective. This article summarizes the methodology of an ongoing NIH-funded randomized controlled trial aimed at investigating whether the placebo effect in irritable bowel syndrome (IBS) exists and whether the magnitude of such an effect can be manipulated to vary in a manner analogous to "dose dependence." The trial also uses an innovative combination of quantitative and qualitative methods.

Acupuncture Therapy↗
PubMed2003

Modelling muscle motor conformations using low-angle X-ray diffraction.

New results on myosin head organization using analysis of low-angle X-ray diffraction patterns from relaxed insect flight muscle (IFM) from a giant waterbug, building on previous studies of myosin filaments in bony fish skeletal muscle (BFM), show that the information content of such low-angle diffraction patterns is very high despite the 'crystallographically low' resolution limit (65 A) of the spacings of the Bragg diffraction peaks being used. This high information content and high structural sensitivity arises because: (i) the atomic structures of the domains of the myosin head are known from protein crystallography; and (ii) myosin head action appears to consist mainly of pivoting between domains which themselves stay rather constant in structure, thus (iii) the intensity distribution among diffraction peaks in even the low resolution diffraction pattern is highly determined by the high-resolution distribution of atomically modelled domain mass. A single model was selected among 5000+ computer-generated variations as giving the best fit for the 65 reflections recorded within the selected resolution limit of 65 A. Clear evidence for a change in shape of the insect flight muscle myosin motor between the resting (probably like the pre-powerstroke) state and the rigor state (considered to mimic the end-of-powerstroke conformation) has been obtained. This illustrates the power of the low-angle X-ray diffraction method. The implications of these new results about myosin motor action during muscle contraction are discussed.

Journal Article↗
PubMed1989

Water suppression with B0 field gradient homospoil pulses in high-resolution NMR spectroscopy.

The combination of a frequency nonselective excitation suppression method (1331 sequence) with selective excitation followed by gradient-induced dephasing of water transverse magnetization yielded suppression ratios of greater than 10,000:1. The need for gradient preemphasis and correction of B0 field shifts is discussed. The suppression efficiency of this method compared favorably to results obtained using the CPMG spin-echo technique to observe metabolite resonances in a urine sample.

Equipment Design↗
PubMed2006

Assessment of fitness for purpose of an insect bioassay using the desert locust (Schistocerca gregaria L.) for the detection of paralytic shellfish toxins in shellfish flesh.

We have developed a bioassay using 5th instar desert locusts (Schistocerca gregaria L.) for the detection of saxitoxin-the paralytic shellfish poison in shellfish flesh. The bioassay procedure is to inject 10 locusts with a shellfish extract, and assess their conditions at time points up to 2h post injection, looking for an endpoint of paralysis. From the proportion responding, the equivalent dose of pure saxitoxin could be estimated. Performance characteristics of the bioassay were assessed using shellfish samples spiked with saxitoxin, and we found the bioassay could detect and quantify toxin levels in the range of regulatory relevance. Relative toxicities of selected saxitoxin analogues differed from those reported in mammalian systems. Variation for repeatability conditions was acceptable but variation was higher under reproducibility conditions. This was related to (a) batches of insects from different suppliers, (b) different operators, and (c) different observers assessing the endpoint. We also noted adverse reactions with some shellfish species. These problems may be resolved by further refinement of the method and operator training, before formal validation. Nevertheless, we suggest the method potentially offers a simple, ethically acceptable, broad-specificity functional bioassay, which is desirable in any toxin-monitoring programme.

Animals↗
PubMed2006

Reconciling disparate prevalence rates of PTSD in large samples of US male Vietnam veterans and their controls.

BACKGROUND: Two large independent studies funded by the US government have assessed the impact of the Vietnam War on the prevalence of PTSD in US veterans. The National Vietnam Veterans Readjustment Study (NVVRS) estimated the current PTSD prevalence to be 15.2% while the Vietnam Experience Study (VES) estimated the prevalence to be 2.2%. We compared alternative criteria for estimating the prevalence of PTSD using the NVVRS and VES public use data sets collected more than 10 years after the United States withdrew troops from Vietnam. METHODS: We applied uniform diagnostic procedures to the male veterans from the NVVRS and VES to estimate PTSD prevalences based on varying criteria including one-month and lifetime prevalence estimates, combat and non-combat prevalence estimates, and prevalence estimates using both single and multiple indicator models. RESULTS: Using a narrow and specific set of criteria, we derived current prevalence estimates for combat-related PTSD of 2.5% and 2.9% for the VES and the NVVRS, respectively. Using a more broad and sensitive set of criteria, we derived current prevalence estimates for combat-related PTSD of 12.2% and 15.8% for the VES and NVVRS, respectively. CONCLUSION: When comparable methods were applied to available data we reconciled disparate results and estimated similar current prevalences for both narrow and broad definitions of combat-related diagnoses of PTSD.

Case-Control Studies↗
PubMed2006

Results of a randomized, double-blind, vehicle-controlled efficacy trial of pimecrolimus cream 1% for the treatment of moderate to severe facial seborrheic dermatitis.

BACKGROUND: Seborrheic dermatitis is commonly treated with anti-inflammatory products, including topical corticosteroids. Pimecrolimus cream 1% also exerts anti-inflammatory activity by inhibiting T-cell cytokine production. OBJECTIVE: We sought to compare the efficacy and safety of twice-daily pimecrolimus for treatment of moderate to severe facial seborrheic dermatitis. METHODS: This double-blind, vehicle-controlled, 4-week trial randomized patients with seborrheic dermatitis to pimecrolimus or vehicle (1:1). Clinical assessments (erythema [0-3] and scaling [0-3] combined for a total area score [0-6]) were performed at weeks 0, 2, and 4. Inclusion criteria included total area score 4 or greater and erythema 2 or greater. The prespecified primary variable, change from baseline in total area score at week 4, was analyzed using a two-sample t test for intent-to-treat and per protocol populations. RESULTS: In all, 96 adults of mean age 59.6 years, 88.5% male, were randomized (n = 47 pimecrolimus; 49 vehicle). At week 4, the mean change from baseline in total area score was 3.7 versus 3.3 for pimecrolimus and vehicle groups, respectively (intent-to-treat: P = .1913; 95% confidence interval (CI) for difference [-0.195, 0.961]). Per protocol analysis (n = 41 pimecrolimus; 46 vehicle) indicated a significant difference between groups (mean change 3.9 pimecrolimus vs 3.2 vehicle; P = .0156; CI [0.129, 1.197]). The superiority of pimecrolimus was observed as early as week 2 (intent-to-treat: P = .0062; CI [0.132, 0.777]; per protocol: P = .0012; CI [0.410, 1.593]). No drug-related serious adverse events occurred. The most frequent drug-related adverse events were local, mild, and transient (pimecrolimus = 26%; vehicle = 12%). LIMITATIONS: Generalizability is limited by the elderly male study population. CONCLUSION: This study suggests that pimecrolimus cream 1% is an effective and well-tolerated treatment for moderate to severe facial seborrheic dermatitis.

Adult↗
PubMed2002

3D in-vivo optical skin imaging for topographical quantitative assessment of non-ablative laser technology.

BACKGROUND: A new method for treating facial rhytides and acne scars with nonablative laser and light source techniques has recently been introduced. Given the inherent limitations of photographic and clinical evaluation to assess subtle changes in rhytides and surface topography, a new noninvasive objective assessment is required to accurately assess the outcomes of these procedures. OBJECTIVE: The purpose of this study was to measure and objectively quantify facial skin using a novel, noninvasive, In-vivo method for assessing three-dimensional topography. This device was used to quantify the efficacy of five treatment sessions with the 1064 nm QS Nd:YAG laser for rhytides and acne scarring, for up to six months following laser treatment. METHODS: Two subjects undergoing facial rejuvenation procedures were analyzed before and after therapy using a 30-mm, three-dimensional microtopography imaging system (PRIMOS, GFM, Teltow, Germany). The imaging system projects light on to a specific surface of the skin using a Digital Micromirror Device (DMD Texas Instruments, Irving, TX) and records the image with a CCD camera. Skin Surface microtopography is reconstructed using temporal phase shift algorithms to generate three-dimensional images. Measurements were taken at baseline, at various times during the treatment protocol, and then at three and six-month follow-up visits. Silicone skin replicas (FLEXICO, Herts, England) were also made before and after the laser treatment protocol for comparison to In-vivo acquisition. RESULTS: Skin roughness decreased by 11% from baseline after three treatment sessions in the wrinkles subject, while a 26% improvement of skin roughness was recorded by 3D In-vivo assessment six months following the fifth treatment session. The subject with acne scarring demonstrated a 33% decrease in roughness analysis after three treatment sessions by 3D In-vivo assessment. A 61% improvement in surface topography was recorded 3-months following the fifth treatment session, which was maintained at the 6-month follow-up. CONCLUSION: Three-dimensional In-vivo optical skin imaging provided a rapid and quantitative assessment of surface topography and facial fine lines following multiple treatment sessions with a 1064-nm QS Nd:YAG laser, correlating with clinical and subjective responses. This imaging technique provided objective verification and technical understanding of nonablative laser technology. Wrinkle depth and skin roughness decreased at the three and six-month follow-up evaluations by 3D In-vivo assessment, indicating ongoing dermal collagen remodeling after the laser treatment protocol. Future applications may include comparison of nonablative laser technology, optimization of treatment regimens, and objective evaluation of other aesthetic procedures performed by dermatologists.

Acne Vulgaris↗
PubMed2006

The HPTN 024 Study: the efficacy of antibiotics to prevent chorioamnionitis and preterm birth.

OBJECTIVE: The use of antibiotics to prevent preterm birth has achieved mixed results. Our goal in this study was to determine if antibiotics given prenatally and during labor reduce the incidence of preterm birth and histologic chorioamnionitis. STUDY DESIGN: A double-blind randomized placebo-controlled trial of antibiotics to reduce preterm birth was conducted in 4 African sites. Both HIV-infected and uninfected pregnant women were given 2 courses of antibiotics, prenatally at 24 weeks (metronidazole 250 mg and erythromycin 250 mg tid orally for 7 days), and during labor (metronidazole 250 mg and ampicillin 500 mg q 4 hours) or identically appearing placebos. Two thousand ninety-eight HIV-infected and 335 HIV-uninfected women had evaluable end points, including gestational age determined by both obstetric and pediatric criteria and birth weight (BWT). Pre- and post-treatment rates of various sexually transmitted infections (STI) were determined and placentas were evaluated for histologic chorioamnionitis. RESULTS: Comparing antibiotic versus placebo treated HIV-infected and uninfected women, there were few differences in mean gestational age at delivery, the percent of preterm births, the time between randomization and delivery, or BWT. Four weeks after the 24-week antibiotic/placebo course, bacterial vaginosis, and trichomoniasis were reduced by 49% to 61% in the antibiotic groups compared with the placebo groups. However, in both the HIV-infected and uninfected groups, the placentas showed no difference in the rate of histologic chorioamnionitis. There were significant differences between HIV-infected and uninfected women, with the former having less education, a history of more stillbirths, more STIs, and in this pregnancy, a lower BWT (2949 vs 3100 g, P < .0001). CONCLUSION: Despite reducing the rate of vaginal infections, the antibiotic regimen used in this study did not reduce the rate of preterm birth, increase the time to delivery, or increase BWT. Failure of this regimen to reduce the rate of histologic chorioamnionitis may explain the reason the antibiotics failed to reduce preterm birth.

Anti-Bacterial Agents↗
PubMed2005

Determination of total and free concentrations of the enantiomers of methadone and its metabolite (2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine) in human plasma by enantioselective liquid chromatography with mass spectrometric detection.

A sensitive enantioselective liquid chromatographic assay with mass spectrometric detection (LC-MS) has been validated for the determination of total and free plasma concentrations of (R)- and (S)-methadone (Met) and (R)- and (S)-2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP, the primary metabolite of Met), using their respective deuterium-labeled compounds as internal standards [(R,S)-d3-Met and (R,S)-d3-EDDP]. For total drug determinations, 1 ml human plasma was extracted, using a cation-exchange solid-phase extraction cartridge; the eluate was evaporated, reconstituted in the mobile phase, and injected into the LC-MS system. The free fractions of Met and EDDP were determined, using 500 microl of plasma, which were placed in an ultrafiltration device and centrifuged at 2000 x g until 250 microl of filtrate was collected. The filtrate was extracted as described above and analyzed. Enantioselective separations were achieved using an alpha1-acid glycoprotein chiral stationary phase, a mobile phase composed of acetonitrile-ammonium acetate buffer [10 mM, pH 7.0] (18:82, v/v), a flow rate of 0.9 ml/min at 25 degrees C. Under these conditions, enantioselective separations were observed for Met (alpha = 1.30) and EDDP (alpha = 1.17) within 15 min. Met, EDDP, [2H3]-Met and [2H3]-EDDP were detected using selected ion monitoring at m/z 310.30, 278.20, 313.30, and 281.20, respectively. Linear relationships between peak height ratio and drug-enantiomer concentrations were obtained for Met in the range 1.0-300.0 ng/ml, and for EDDP from 0.1 to 25.0 ng/ml with correlation coefficients greater than 0.999, where the lower limit of quantification (LLOQ) was 1 ng/ml for Met and 0.1 ng/ml for EDDP. The relative standard deviation (R.S.D.) expressed as R.S.D. for the intra- and inter-day precision of the method were < 5.3% and the R.S.D. for accuracy was < 5.0%. The method was used to analyze plasma samples obtained from patients enrolled in a Met-maintenance program.

Calibration↗
PubMed2006

Animal models for endoscopic simulation.

Animal models for GI endoscopy are a safe, reliable, and reproducible method for teaching diagnostic and therapeutic procedures and for developing techniques that have the potential to advance GI endoscopy. Although these methods never can replace human endoscopy as a modality for endoscopic training, animal models may serve as an adjunct to standard endoscopic training and safely enhance the hands-on experience.

Animals↗
PubMed1975

Vertebral trephine biopsy.

Vertebral trephine biopsy is a safe and swift method of diagnosis of vertebral abnormality. The procedure is no more disturbing for the patient than lumbar puncture, and saves the patient, radiologist and clinician, considerable time and effort.

Biopsy↗
PubMed2006

Omega-3 fatty acid treatment in 174 patients with mild to moderate Alzheimer disease: OmegAD study: a randomized double-blind trial.

BACKGROUND: Epidemiologic and animal studies have suggested that dietary fish or fish oil rich in omega-3 fatty acids, for example, docosahexaenoic acid and eicosapentaenoic acid, may prevent Alzheimer disease (AD). OBJECTIVE: To determine effects of dietary omega-3 fatty acid supplementation on cognitive functions in patients with mild to moderate AD. DESIGN: Randomized, double-blind, placebo-controlled clinical trial. PARTICIPANTS: Two hundred four patients with AD (age range [mean +/- SD], 74 +/- 9 years) whose conditions were stable while receiving acetylcholine esterase inhibitor treatment and who had a Mini-Mental State Examination (MMSE) score of 15 points or more were randomized to daily intake of 1.7 g of docosahexaenoic acid and 0.6 g of eicosapentaenoic acid (omega-3 fatty acid-treated group) or placebo for 6 months, after which all received omega-3 fatty acid supplementation for 6 months more. MAIN OUTCOME MEASURES: The primary outcome was cognition measured with the MMSE and the cognitive portion of the Alzheimer Disease Assessment Scale. The secondary outcome was global function as assessed with the Clinical Dementia Rating Scale; safety and tolerability of omega-3 fatty acid supplementation; and blood pressure determinations. RESULTS: One hundred seventy-four patients fulfilled the trial. At baseline, mean values for the Clinical Dementia Rating Scale, MMSE, and cognitive portion of the Alzheimer Disease Assessment Scale in the 2 randomized groups were similar. At 6 months, the decline in cognitive functions as assessed by the latter 2 scales did not differ between the groups. However, in a subgroup (n = 32) with very mild cognitive dysfunction (MMSE >27 points), a significant (P<.05) reduction in MMSE decline rate was observed in the omega-3 fatty acid-treated group compared with the placebo group. A similar arrest in decline rate was observed between 6 and 12 months in this placebo subgroup when receiving omega-3 fatty acid supplementation. The omega-3 fatty acid treatment was safe and well tolerated. CONCLUSIONS: Administration of omega-3 fatty acid in patients with mild to moderate AD did not delay the rate of cognitive decline according to the MMSE or the cognitive portion of the Alzheimer Disease Assessment Scale. However, positive effects were observed in a small group of patients with very mild AD (MMSE >27 points).

Aged↗
PubMed1999

Prospective, randomized trial of template-assisted versus undirected written recording of physician records in the emergency department.

STUDY OBJECTIVE: To determine whether use of the T-System (Emergency Services Consultants, Irving, TX) template-generated medical documentation system (1) decreases physician evaluation time in the emergency department, (2) increases gross billing under the 1997 Health Care Financing Administration guidelines by minimizing downcoding caused by inadequate documentation, and (3) increases physician satisfaction with the documentation process, compared with the undirected written narrative format. METHODS: A prospective, randomized, unblinded, controlled, convenience trial of documentation with the T-System of ED templates versus undirected written documentation was conducted in the ED of a county-owned, university-affiliated hospital. All patients seen between the hours of 7 AM and 10 PM during a 16-day period were included. The intervention was varying the method of documentation of the emergency physician. Adequacy of randomization to the 2 documentation groups was assessed by comparing ED triage classification, patient disposition, level of training of the evaluating physician, and whether ED consultation with other services occurred. Outcome measurements included emergency physician total evaluation and treatment time, professional bill, and satisfaction, as evaluated by a questionnaire completed after the study period. The 2 documentation groups were compared by an intention-to-treat analysis and by Student's t test and the median test as appropriate. RESULTS: A total of 1,228 patient encounters were included. Emergency physician total evaluation and treatment time with template-directed documentation was 4.6 minutes less than with undirected recording, a difference that was not significant (95% confidence interval [CI], -9.2 to 18.3). Gross billing was $29. 60 more per patient (95% CI, $22.20 to $37.00) with the T-System, as assessed by our hospital coders. This difference was caused by a mean.50 (95% CI,.39 to.60) higher level of evaluation and management coding. Physicians preferred the T-System (P <.0005). CONCLUSION: Use of template-assisted documentation in the ED was associated with higher gross billing and physician satisfaction but no significant decrease in emergency physician total evaluation time.

Attitude of Health Personnel↗
PubMed1987

Calcium signals recorded from cut frog twitch fibers containing tetramethylmurexide.

The Ca indicator tetramethylmurexide was introduced into cut fibers, mounted in a double-Vaseline-gap chamber, by diffusion from the end-pool solutions. The indicator diffused rapidly to the central region of a fiber where optical recording was done and, if removed, diffused away equally fast. The time course of concentration suggests that, on average, a fraction 0.27 of indicator was reversibly bound to myoplasmic constituents and the free diffusion constant was 1.75 x 10(-6) cm2/s at 18 degrees C. The shape of the resting absorbance spectrum suggests that a fraction 0.11-0.15 of tetramethylmurexide inside a fiber was complexed with Ca. After action potential stimulation, there was a rapid transient change in indicator absorbance followed by a maintained change of opposite sign. The wavelength dependence of both changes matched a cuvette Ca-difference spectrum. The amplitude of the early peak varied linearly with indicator concentration and corresponded to an average rise in free [Ca] of 17 microM. These rather diverse findings can be explained if the sarcoplasmic reticulum membranes are permeable to Ca-free indicator. Both Ca-free and Ca-complexed indicator inside the sarcoplasmic reticulum would appear to be bound by diffusion analysis and the Ca-complexed form would be detected by the resting absorbance spectrum. The transient change in indicator absorbance would be produced by myoplasmic Ca reacting with indicator molecules that freely diffuse in myoplasmic solution. The maintained signal, which reports Ca dissociating from indicator complexed at rest, would come from changes within the sarcoplasmic reticulum. A method, based on these ideas, is described for separating the two components of the tetramethylmurexide signal. The estimated myoplasmic free [Ca] transient has an average peak value of 26 microM at 18 degrees C. Its time course is similar to, but possibly faster than, that recorded with antipyrylazo III (Maylie, J., M. Irving, N. L. Sizto, and W. K. Chandler. 1987. Journal of General Physiology. 89:83-143).

Action Potentials↗
PubMed1975

Parasitology survey and seroepidemiology of amoebiasis in South Kalimantan (Borneo), Indonesia.

A parasitology surevy was conducted among inhabitants of 7 villages in 3 regencies in South Kalimantan Province, Indonesia. A total of 2,169 stool specimens, 2,756 blood smears and 1,027 serum specimens were obtained, representing samples from approximately 10%, 12% and 5% of the population, respectively. One to 8 different intestinal parasitic infections were detected in 97% of the people. Those parasites most frequently found were Trichuris trichiura (83%), Ascaris lumbricoides (79%), and hookworm (65%), followed by Entamoeba coli (37%), Endolimaxnana (12%), Entamoeba histolytica (12%), Iodamoeba bütschlii (11%), Giardia lamblia (5%), Entamoeba hartmanni (2%), Chilomastix mesnili (2%). Other parasites found were Enterobius vermicularis, Strongyloides stercoralis, Capillaria sp., Echinostoma sp., Hymenolepis diminuta, and Trichomonas hominis. Giardia lamblia was found more often in younger people and Entamoeba coli, Iodamoeba bütschlii and hookworm in the older age group. Ascaris lumbricoides occurred more frequently in females, and hookworm in males. Plasmodium vivax and Plasmodium falciparum were found in the blood smears of 4.4% of the people, mostly in the younger age groups. Seroepidemiological studies on amoebiasis were done by use of the indirect hemagglutination test with antigens prepared from the HK9 strain of Entamoeba histolytica maintained in axenic cultures. The frequency distribution of the reciprocal antibody titers showed a bimodal distribution with 34% of the population demonstrating positive reactions at titers of 1:128 or greater.

Adolescent↗
PubMed2006

Simultaneous determination of buprenorphine, norbuprenorphine and the enantiomers of methadone and its metabolite (EDDP) in human plasma by liquid chromatography/mass spectrometry.

A previously reported enantioselective LC-MS assay for the determination of (R)- and (S)-methadone [Met] and (R)- and (S)-2-ethylidene-1,5-dimethyl-3,3-diphenyl-pyrrolidine [EDDP] (the primary metabolite of Met) has been adapted for use in the simultaneous determination of the plasma concentrations of Met, EDDP, buprenorphine (Bu) and norbuprenorphine (norBu). All of the target compounds were separated within 15 min using an alpha1-acid glycoprotein chiral stationary phase, a mobile phase composed of acetonitrile: ammonium acetate buffer [10 mM, pH 7.0] in a ratio of 18:82 (v/v), a flow rate of 0.9 ml/min at 25 degrees C. Deuterium labeled compounds were used as internal standards [d4-Bu, d3-norBu, (R,S)-d3-Met and (R,S)-d3-EDDP] and linear relationships between peak height ratios and drug concentrations were obtained for Bu and norBu in the range 0.2-12 ng/ml with correlation coefficients greater than 0.999. The relative standard deviations (%R.S.D.) for the intra- and inter-day precision of the method were <4.5% and for accuracy was <4.0%. The method was validated and used to analyze plasma samples obtained from opioid dependent methadone-maintained adults enrolled in a research study.

Buprenorphine↗