Catherine A. Hammett-Stabler

Predictors of opioid misuse in patients with chronic pain: a prospective cohort study

BackgroundOpioid misuse can complicate chronic pain management, and the non-medical use of opioids is a growing public health problem. The incidence and risk factors for opioid misuse in patients with chronic pain, however, have not been well characterized. We conducted a prospective cohort study to determine the one-year incidence and predictors of opioid misuse among patients enrolled in a chronic pain disease management program within an academic internal medicine practice.MethodsOne-hundred and ninety-six opioid-treated patients with chronic, non-cancer pain of at least three months duration were monitored for opioid misuse at pre-defined intervals. Opioid misuse was defined as: 1. Negative urine toxicological screen (UTS) for prescribed opioids; 2. UTS positive for opioids or controlled substances not prescribed by our practice; 3. Evidence of procurement of opioids from multiple providers; 4. Diversion of opioids; 5. Prescription forgery; or 6. Stimulants (cocaine or amphetamines) on UTS.ResultsThe mean patient age was 52 years, 55% were male, and 75% were white. Sixty-two of 196 (32%) patients committed opioid misuse. Detection of cocaine or amphetamines on UTS was the most common form of misuse (40.3% of misusers). In bivariate analysis, misusers were more likely than non-misusers to be younger (48 years vs 54 years, p < 0.001), male (59.6% vs. 38%; p = 0.023), have past alcohol abuse (44% vs 23%; p = 0.004), past cocaine abuse (68% vs 21%; p < 0.001), or have a previous drug or DUI conviction (40% vs 11%; p < 0.001%). In multivariate analyses, age, past cocaine abuse (OR, 4.3), drug or DUI conviction (OR, 2.6), and a past alcohol abuse (OR, 2.6) persisted as predictors of misuse. Race, income, education, depression score, disability score, pain score, and literacy were not associated with misuse. No relationship between pain scores and misuse emerged.ConclusionOpioid misuse occurred frequently in chronic pain patients in a pain management program within an academic primary care practice. Patients with a history of alcohol or cocaine abuse and alcohol or drug related convictions should be carefully evaluated and followed for signs of misuse if opioids are prescribed. Structured monitoring for opioid misuse can potentially ensure the appropriate use of opioids in chronic pain management and mitigate adverse public health effects of diversion.

Urine drug screening in the medical setting.

BACKGROUND The term drug screen is a misnomer since it implies screening for all drugs, which is not possible. Current practice is to limit the testing to the examination of serum for several drugs such as ethanol, acetaminophen, salicylate, and of urine for several specific drugs or classes of drugs. In the emergency setting the screen should be performed in less than one hour. Controversies continue to exist regarding the value of urine drug testing in the medical setting. The reasons for these include the drugs involved, the sample, the methods utilized to perform the tests, and the level of understanding of the physician using the data, all of which are closely related to the other. METHODS Current automated methods provide rapid results demanded in emergency situations, but are often designed for, or adapted from, workplace testing and are not necessarily optimized for clinical applications. Furthermore, the use of these methods without consideration of the frequency in which the drugs are found in a given area is not cost-effective. The laboratory must understand the limitations of the assays used and provide this information to the physician. Additionally, the laboratory and the physicians using the data must cooperate to determine which drugs are appropriate and necessary to measure for their institution and clinical setting. In doing so it should be remembered that for many drugs, the sample, urine, contains the end product(s) of drug metabolism, not the parent drug. Furthermore, it is necessary to understand the pharmacokinetic parameters of the drug of interest when interpreting data. Finally, while testing for some drugs may not appear cost-effective, the prevention or reduction of morbidity and mortality may offset any laboratory costs. CONCLUSIONS While the literature is replete with studies concerning new methods and a few regarding physician understanding, there are none that we could find that thoroughly, objectively, and fully addressed the issues of utility and cost-effectiveness.

Effect of Plyometric Training on Swimming Block Start Performance in Adolescents

Bishop, DC, Smith, RJ, Smith, MF, and Rigby, HE. Effect of plyometric training on swimming block start performance in adolescents. J Strength Cond Res 23(7): 2137-2143, 2009-This study aimed to identify the effect of plyometric training (PT), when added to habitual training (HT) regimes, on swim start performance. After the completion of a baseline competitive swim start, 22 adolescent swimmers were randomly assigned to either a PT (n = 11, age: 13.1 ± 1.4 yr, mass: 50.6 ± 12.3 kg, stature: 162.9 ± 11.9 cm) or an HT group (n = 11, age: 12.6 ± 1.9 yr, mass: 43.3 ± 11.6 kg, stature: 157.6 ± 11.9 cm). Over an 8-week preseason period, the HT group continued with their normal training program, whereas the PT group added 2 additional 1-hour plyometric-specific sessions, incorporating prescribed exercises relating to the swimming block start (SBS). After completion of the training intervention, post-training swim start performance was reassessed. For both baseline and post-trials, swim performance was recorded using videography (50Hz Canon MVX460) in the sagital plane of motion. Through the use of Silicon Coach Pro analysis package, data revealed significantly greater change between baseline and post-trials for PT when compared with the HT group for swim performance time to 5.5 m (−0.59 s vs. −0.21 s; p < 0.01) and velocity of take-off to contact (0.19 ms−1 vs. −0.07 ms−1; p < 0.01). Considering the practical importance of a successful swim start to overall performance outcome, the current study has found that inclusion of suitable and safely implemented PT to adolescent performers, in addition to HT routines, can have a positive impact on swim start performance.BACKGROUND 5-Fluorouracil (5-FU) is the most widely used chemotherapy drug, primarily against gastrointestinal, head and neck, and breast cancers. 5-FU has large pharmacokinetic variability resulting in unexpected toxicity or ineffective treatment. Therapeutic drug management of 5-FU minimizes toxicity and improves outcome. A nanoparticle-based immunoassay was developed to provide oncologists with a rapid, cost-effective tool for determining 5-FU plasma concentrations. METHODS Monoclonal antibodies, bound to nanoparticles, were used to develop an immunoassay for the Olympus AU400. Assay precision, linearity, calibration stability, and limit of detection were run at multiple centers; interference, cross-reactivity, lower limit of quantitation and recovery at 1 center. Clinical samples collected from 4 cancer centers were analyzed for 5-FU concentrations by liquid chromatography-tandem mass spectrometry and compared with the immunoassay results. RESULTS With calibrators from 0 to 1800 ng/mL 5-FU and autodilution, concentrations up to 9000 ng/mL could be determined. Time to first result was 10 minutes, and 400 samples per hour could be quantitated from a standard curve stored for >30 days. Imprecision across all laboratories was <5%, and the assay was linear upon dilution over the entire range. Cross-reactivities for dihydro-5-FU, uracil, capecitabine, and tegafur were <1%, 9.9%, 0.05%, and 0.23%, respectively. The limit of detection was 52 ng/mL with a lower limit of quantitation of 86 ng/mL. Assay results of clinical samples (93-1774 ng/mL) correlated with liquid chromatography-tandem mass spectrometry results: (R = 0.9860, slope 1.035, intercept 10.87 ng/mL). CONCLUSIONS This novel immunoassay is suitable for quantitating 5-FU plasma concentrations with advantages of speed, small sample size, minimal sample pretreatment, and application on automated instrumentation. These advantages enable efficient therapeutic drug management of 5-FU in clinical practice.

Performance Comparison of Capillary and Agarose Gel Electrophoresis for the Identification and Characterization of Monoclonal Immunoglobulins

The objective of this study was to compare gel- and capillary-based serum protein electrophoresis methods to identify and characterize monoclonal immunoglobulins (M proteins). Five reviewers interpreted 149 consecutively ordered serum specimens following agarose gel electrophoresis (AGE), capillary electrophoresis (CE), immunofixation electrophoresis (IFE), and subtraction immunotyping (IT). As a screening test for detecting M proteins, AGE and CE displayed similar sensitivity (91% and 92%, respectively). CE was less specific (74%) than AGE (81%). An analysis of interinterpreter agreement revealed that interpretations were more consistent using gel-based methods than capillary-based methods, with 80% of the gel interpretations being in complete (5/5) agreement compared with 67% of the capillary interpretations. After implementing the capillary-based methods, the number of tests per reportable result increased (from 1.58 to 1.73). CE is an analytically suitable alternative to AGE, but laboratories implementing it will need to continue IFE testing to characterize all M proteins detected by CE.

Multi-center evaluation of a commercial Kit for tacrolimus determination by LC/MS/MS

OBJECTIVES A multi-center evaluation (3 sites) of the LC/MS/MS MassTrak tacrolimus Immunosuppressants Kit (Kit) was undertaken. DESIGN AND METHODS Ten aspects of the analytical performance of the Kit were investigated based on FDA and CLSI guidelines. RESULTS The linear analytical range of the procedure was between 0.68 and 31.7ng/mL. Within-run and total imprecision were <6% and <8% (n=240), respectively. Recoveries of tacrolimus added to clinical samples that contained between 5 and 10ng/mL of tacrolimus before addition were 99, 102 and 105% at 5.0, 10 and 20ng/mL, respectively. Comparison of in-house and Kit procedures in samples from liver (n=50-58) or kidney (n=50 or 51) transplant recipients yielded method mean biases between -2.0 and +10.7% at 5 and 15ng/mL. CONCLUSIONS This evaluation indicates that the Kit is suitable for the monitoring of tacrolimus in kidney and liver transplant recipients.

Signify ER Drug Screen Test evaluation: comparison to Triage Drug of Abuse Panel plus tricyclic antidepressants.

Signify ER Drug Screen Test (Signify ER) and Triage Drug of Abuse Panel plus TCA (Triage DOA Panel) rapid drug screening devices were compared at four laboratories. Both assay systems are point of care immunoassays, measuring phencyclidine, barbiturates, amphetamine, cocaine metabolite, methamphetamine, tricyclic antidepressants, opiates, marijuana metabolite, and benzodiazepines in human urine. The performance of these two assay systems, including a cutoff verification and cross-reactivity using spiked urine specimens and accuracy using clinical urine samples, was investigated. The cutoff verification study showed that the Signify ER had 95.4% precision for all drugs tested at concentrations of 50%, 75%, 125%, 150%, and 200% of cutoffs compared to 90% precision obtained with Triage DOA Panel. Accuracy studies testing 53 negative urine samples demonstrated that both Signify ER and Triage DOA Panel have 100% specificity. Testing of 693 positive urine samples demonstrated that Signify ER and Triage DOA Panel have sensitivities of 99.8% and 99.3%, respectively, with an accuracy of 99.9% and 99.6%. A total of 527 compounds were tested for the cross-reactivity study. Eighty-seven structurally related drugs and metabolites were found to cross-react with at least one of the nine tests of the Signify ER. Four hundred forty structurally unrelated compounds that can be found in human urine were shown not to cross-react with the Signify ER. In terms of operating characteristics, the Signify ER device is simpler since only a single pipetting step is required, and reaction completed within 8 min.

HbA1c as a Postmortem Tool to Identify Glycemic Control

Estimates suggest that more than 5A million U.S. citizens unknowingly have diabetes and are at increased risk of morbidity and mortality. We evaluated an immunoturbidimetric measurement of glycated hemoglobin (%HbA1c) as a postmortem tool to identify such individuals. Although postmortem samples undergo some degradation, the effects are not sufficient to invalidate the use of the test or method. Using two study populations whose medical history of diabetes was known, we found the mean %HbA1c of the non-diabetics (5.8+/-0.3) to be statistically different from that of the diabetics (12.4+/-2.8). For the population whose disease status was unknown, the %HbA1c ranged from 4.7 to 16.8. For six unknowns whose values exceeded 7.0%. the mean was 11.7%, which did not differ statistically from the diabetic mean (p = 0.6615). These studies suggest that postmortem blood samples can be used to characterize HbA1c values.

Follicle-stimulating hormone is independently associated with lean mass but not BMD in younger postmenopausal women

PURPOSE Increased follicle-stimulating hormone (FSH) has been associated with lower bone mineral density (BMD) in animal models and longitudinal studies of women, but a direct effect has not been demonstrated. METHODS We tested associations between FSH, non-bone body composition measures and BMD in 94 younger (aged 50 to 64 years) postmenopausal women without current use of hormone therapy, adjusting for sex hormone concentrations and clinical risk factors for osteoporosis. Lean mass, fat mass and areal BMD (aBMD) at the spine, femoral neck and total hip were measured using dual energy X-ray absorptiometry (DXA). Volumetric BMD (vBMD) was measured at the distal radius using peripheral quantitative computed tomography (pQCT). RESULTS FSH was inversely correlated with lean and fat mass, bioavailable estradiol, spine and hip aBMD, and vBMD at the ultradistal radius. In the multivariable analysis, FSH was independently associated with lean mass (β=-0.099, p=0.005) after adjustment for age, race, years since menopause, bioavailable estradiol, bioavailable testosterone, LH, PTH, SHBG and urine N-telopeptide. FSH showed no statistically significant association with aBMD at any site or pQCT measures at the distal radius in adjusted models. Race was independently associated with aBMD, and race and urine N-telopeptide were independently associated with bone area and vBMD. CONCLUSIONS After adjustment for hormonal measures and osteoporosis risk factors, higher concentrations of FSH were independently associated with lower lean mass, but not with BMD. Previously reported correlations between FSH and BMD might have been due to indirect associations via lean mass or weight.

Clinical Applications of Mass Spectrometry

Clinical laboratories around the world are recognizing the power of mass spectrometry. This technique, especially when coupled to gas chromatography or liquid chromatography, is revolutionizing the analysis of many analytes. Unlike many other techniques which measure one analyte at a time, these techniques can measure multiple analytes (>40) at one time. In recent years the scope of testing using these techniques has expanded from toxicological purposes to newborn screening to hormones, proteins, and enzymes. It is not uncommon any more to see mass spectrometry being used in the routine clinical laboratories.

Evaluation of high resolution gel β2-transferrin for detection of cerebrospinal fluid leak

Abstract Background: Cerebrospinal fluid (CSF) leaks are potentially life-threatening conditions that can be diagnosed by detection of β2-transferrin using protein electrophoresis. Another less commonly available test is β-trace protein quantitation using immunoassay. The objectives of this study were to evaluate a new immunofixation-based β2-transferrin test for detection of CSF leaks and to compare it to an existing agarose gel electrophoresis test and β-trace protein immunoassay. Methods: For method comparison, 63 consecutive samples from physician-ordered β2-transferrin tests were analyzed using two different electrophoresis methods, agarose gel fractionation followed by acid-violet staining, and high resolution agarose gel electrophoresis followed by β2-transferrin immunofixation. A subset of samples (16/63) were analyzed for β-trace protein. Results were compared against patient chart data for the presence of a CSF leak. Additional studies were performed to assess the stability, detection limit, and analytical specificity of the β2-transferrin immunofixation test. Results: The β2-transferrin immunofixation test had a sensitivity of 100% (40/40) and specificity of 71% (12/17) for detection of CSF leaks. By comparison, the agarose gel test had a sensitivity of 87% (35/40) and specificity of 94% (16/17). β-trace protein had a sensitivity of 100% (10/10) and specificity of 86% (5/6). Serum and saliva could be differentiated from CSF by the β2-transferrin immunofixation test based on their migration patterns. However, whole blood samples appeared positive for β2-transferrin at a threshold of ∼4 g/L hemoglobin. At a cut-off of 3 mg/L, β-trace protein was increased in 10/10 cases with documented CSF leak and in 1/6 patients without CSF leak. Conclusions: Both the new immunofixation test for β2-transferrin and the β-trace protein were effective at detecting CSF leaks. Users of the β2-transferrin immunofixation test should be cautioned against interpreting samples with blood contamination.