Self-report and urine drug screen concordance among women with co-occurring PTSD and substance use disorders participating in a clinical trial: Impact of drug type and participant characteristics.

BACKGROUND: Self-report measures are important in substance use assessment, yet they are susceptible to reporting errors. Urine drug screens (UDS) are often considered a more valid alternative. However, collecting in-person UDS may not always be feasible, contributing to the need to understand factors that influence the validity of self-reported substance use. METHODS: In this secondary analysis of data from 295 women with co-occurring PTSD and substance use disorders (SUD) who participated in a clinical trial testing behavioral interventions, we examined concordance and discordance between self-reported drug use and associated UDS results. Generalized linear mixed models were used to examine the impact of treatment type and participant characteristics on the associations between self-reported drug use and UDS results. RESULTS: Findings revealed higher disagreement between self-report and UDS for opioids and sedatives (ranging from.77 to.90) and lower disagreement rates for cannabis and cocaine (ranging from.26 to.33). Treatment type was not a significant moderator of the associations between self-report and UDS across all drugs. Among those with a positive opioid UDS, those who reported employment in the past three years were more likely to self-report no opioid use compared to their counterparts without employment in the past three years. CONCLUSIONS: Findings add to the literature that supports the validity of self-reported cannabis and cocaine use. The greater discrepancies between self-report and UDS test results of opioids and sedatives suggest adjunctive UDS may be required, although a variety of factors other than inaccurate self-report may be associated with this discrepancy.

Prediction of relative glomerular filtration rate in adults: new improved equations based on Swedish Caucasians and standardized plasma-creatinine assays.

OBJECTIVE: To evaluate newly developed equations predicting relative glomerular filtration rate(GFR) in adult Swedish Caucasians and to compare with the Modification of Diet in Renal Disease(MDRD) and Mayo Clinic equations using enzymatic and zero-calibrated plasma creatinine assays. MATERIAL AND METHODS: GFR was measured with iohexol clearance adjusted to 1.73 m(2). One population sample (n=436/Lund) was used to derive an equation based on plasma-creatinine/age/gender, and a second with the addition of lean body mass (LBM). Both equations were validated in a separate sample (n=414/Malmö). The coefficients of the equations were eventually fine-tuned using all 850 patients and yielding Lund-Malmö equations without (LM) and with LBM-term (LM(LBM)). Their performance was compared with the MDRD(CC) (conventional creatinine calibration), MDRD(IDMS) (isotope dilution mass spectroscopy traceable calibration) and Mayo Clinic equations. RESULTS: The Lund equations performed similarly in both samples. In the combined set, the Mayo Clinic/MDRD(CC) resulted in +19.0/+10.2 % median bias, while bias for the other equations was < 10 %. LM(LBM) had the highest accuracy (86 % of estimates within 30 % of measured GFR), significantly (p < 0.001) better than for MDRD(IDMS) (80 %). In men with BMI < 20 kg/m(2), MDRD(IDMS)/LM had +46 %/+19 % median bias. MDRD(IDMS) also overestimated GFR by 22 %/14 % in men/women above 80 years of age. The LM(LBM) equation had < 10 % bias irrespective of BMI, age or GFR except for a 15 % negative bias at GFR > 90 mL/min/1.73 m(2). CONCLUSION: The newly developed Lund-Malmö equations for GFR estimation performed better than the MDRD(IDMS) and Mayo Clinic equations in a Swedish Caucasian sample. Inclusion of an LBM term improved performance markedly in certain subgroups.

Standardization of p-creatinine assays and use of lean body mass allow improved prediction of calculated glomerular filtration rate in adults: a new equation.

OBJECTIVE: To evaluate the Cockcroft-Gault (CG) equation, using various body weight expressions, and the Sawyer equation in predicting glomerular filtration rate (GFR) using an enzymatic and zero-calibrated Jaffe plasma-creatinine assay, and to derive a new robust equation in adults. MATERIAL AND METHODS: The CG weight measures included total, ideal and adjusted body weight (ABW; lowest of total and ideal) and two lean body mass (LBM) expressions, while the Sawyer equation is based primarily on LBM. Iohexol clearance was used to measure GFR. One derivation set (n = 436; enzymatic assay) was used to evaluate and bias-adjust existing equations when indicated, and to derive a new equation based on plasma-creatinine, age, gender and the body weight measure yielding the best adjusted R2. All equations were then validated in a separate set (n = 414; Jaffe assay). RESULTS: The existing equations all performed similarly in both sets. Prediction errors of equations based on LBM showed no correlation with BMI. The CGABW and Sawyer equations performed best. The new equation with LBM yielded the highest adjusted R2. In the combined set (n = 850), its accuracy (86 %/98 % of estimates within 30 %/50 % of measured GFR) was significantly better than for the CGABW (79 %/95 %) and Sawyer equations (79 %/93 %) (p<0.001) for each 30 mL/min GFR subgroup within +/-30 % and +/-50 %, except within +/-30 % >120 mL/min. Prediction error did not correlate with BMI, age or gender. CONCLUSION: A new creatinine-based equation derived in a mainly Caucasian patient sample is a better predictor of GFR than CG-type equations irrespective of the body weight measure used or, if bias-adjusted, when using zero-calibrated creatinine assays.

Exposure therapy in the treatment of PTSD among cocaine-dependent individuals: description of procedures.

An estimated 30% to 50% of cocaine-dependent individuals meet criteria for lifetime PTSD. This comorbidity has detrimental effects on clinical presentation, and treatment course and outcome. Cocaine dependence is associated with increased rates of exposure to trauma, more severe symptoms, higher rates of treatment attrition and retraumatization, and greater vulnerability to PTSD when compared to other substance use disorders. These associations underscore the need for effective treatments that address issues particular to PTSD in a manner tolerable to cocaine-dependent individuals. This article describes a manualized psychotherapy developed specifically for individuals with PTSD and cocaine dependence. Concurrent Treatment of PTSD and Cocaine Dependence (CTPCD) provides coping skills training, cognitive restructuring techniques, and relapse prevention strategies to reduce cocaine use. In-vivo and imaginal exposure therapy techniques are incorporated to reduce PTSD symptom severity. Primary treatment goals include psychoeducation specific to the interrelationship between PTSD and cocaine dependence, and clinically meaningful reductions in cocaine use and PTSD symptomatology. Secondary goals include a reduction in HIV high-risk behaviors and improved functioning in associated areas, such as anger and negative affect management.

Exposure therapy in the treatment of PTSD among cocaine-dependent individuals: preliminary findings.

Individuals (n = 39) participated in an outpatient, 16-session individual, manual-guided psychotherapy designed to treat concurrent PTSD and cocaine dependence. Therapy consisted of a combination of imaginal and in-vivo exposure therapy techniques to treat PTSD symptoms and cognitive-behavioral techniques to treat cocaine dependence. Although the dropout rate was high, treatment completers (i.e., patients who attended at least 10 sessions; n = 15) demonstrated significant reductions in all PTSD symptom clusters and cocaine use from baseline to end of treatment. Significant reductions in depressive symptomatology, as measured by the Beck Depression Inventory, and psychiatric and cocaine use severity, as measured by the Addiction Severity Index, were also observed. These improvements in PTSD symptoms and cocaine use were maintained over a 6-month follow-up period among completers. The average pre- to posttreatment effect size was 1.80 for PTSD symptoms and 1.26 for drug and alcohol use severity. Baseline comparisons between treatment completers and noncompleters revealed significantly higher avoidance symptoms, as measured by the Impact of Events Scale, and fewer years of education among treatment noncompleters as compared to completers. This study provides preliminary evidence to suggest that exposure therapy can be used safely and may be effective in the treatment of PTSD in some individuals with cocaine dependence. However, the study is limited by the uncontrolled nature of the study design, small number of subjects, and high dropout rate.

Towards common reference intervals in clinical chemistry. An attempt at harmonization between three hospital laboratories in Skåne, Sweden.

The population sample of the Kristianstad survey, a reference intervals survey in the county of Kristianstad, was used to establish new reference intervals in clinical chemistry at the laboratories of the Central Hospital in Kristianstad, the University Hospital in Lund and the University Hospital in Mälmo. Three-hundred and fifty nine subjects, male and female, aged 20-80+ years, were invited to participate in the study, with a participation rate of 70%. Up to 70 analyses were performed on each subject, general clinical chemistry parameters in all three laboratories, specialized analyses where available. Separate a priori exclusion criteria were defined for each test. In addition, the test pattern of each individual was evaluated for signs of preclinical disease. Twelve cases of preclinical disease were discovered and clinically confirmed. Details on all test methods are presented along with information concerning instruments used, calibration procedures, methods of calculation and obtained reference intervals. Although the methods were in general calibrated against acknowledged reference materials, in some instances differences were found that made common reference intervals across all laboratories impossible. Problems relating to the practical use of international recommendations and the establishment of reliable reference intervals are discussed.

Hemodialysis for elimination of the nonionic contrast medium iohexol after angiography in patients with impaired renal function.

We examined the kinetics of contrast agent elimination during hemodialysis in 7 patients with end-stage renal disease on regular hemodialysis treatment (group I) and in 13 patients with impaired renal function (serum creatinine 214-657 mumol/l; group II). The nonionic agent iohexol was administered at a dose of 0.4-4.5 g/kg, and a 6-hour hemodialysis was performed with 1-18 h delay. This procedure removed 60-90% (mean 77%) of the iohexol present in the circulation at the start of dialysis treatment. The mean extraction ratio across the dialysis membrane was 0.47 and was inversely related to blood flow. The total clearance of iohexol was 70.4 +/- 24.6 ml/min and was very close to dialyzer clearance, as estimated from blood flow and extraction ratio. The plasma iohexol level after dialysis was related to the dose administered, iohexol clearance, and the patients' body weight. During peritoneal dialysis (36-60 liters dialysis fluid), 43-72% of the iohexol dose was removed from the patients' circulation. In patients of group II no further impairment of the renal function (increase of serum creatinine) in conjunction with angiography was observed. We conclude that hemodialysis and peritoneal dialysis are effective methods for removal of iohexol. Our observations suggest also that accelerated elimination of contrast media by prophylactic dialysis can be beneficial in preventing further reduction in renal function after angiographic procedures in high-risk patients.

Glomerular filtration rate in pregnancy: a study in normal subjects and in patients with hypertension, preeclampsia and diabetes.

We have studied renal function during pregnancy using plasma clearance of iohexol to determine the glomerular filtration rate (GFR). In normal pregnancy, GFR was elevated by 40% throughout pregnancy and during the first week post partum, and fell to levels similar to those in non-pregnant women within 1 month. The development of GFR in diabetic pregnant women and in women with gestational hypertension was similar to that recorded in normal pregnancy. In subjects with preeclampsia the rise in GFR observed in normal pregnancy was absent, and no change in GFR was recorded after delivery. We conclude that the development of proteinuria and fluid retention typical of preeclampsia is paralleled by a deterioration of GFR.

Determination of glomerular filtration rate using iohexol clearance and capillary sampling.

Glomerular filtration rate can be conveniently quantified by monitoring the plasma clearance of iohexol. In this study we have evaluated the possibility of further simplifying the investigation by using capillary sampling. Eight women and two men were given a single injection of iohexol (5 ml Omnipaque). Three to 4 h after the injection plasma and capillary samples were taken. Iohexol concentrations in whole blood and in plasma were measured by high-performance liquid chromatography after precipitation with perchloric acid. Iohexol in blood was quantitatively distributed to the plasma compartment. Plasma concentrations of iohexol calculated from the capillary blood concentration and erythrocyte volume fraction were in good agreement with actual plasma concentrations (r = 0.98). The imprecision of iohexol determination in capillary samples was 3.5% (CV) and clearance measurements using venous and capillary sampling also agreed well.

Age dependence of renal function: clearance of iohexol and p-amino hippurate in healthy males.

Iohexol, a newly developed non-ionic contrast agent, has been recently documented as a reliable glomerular filtration marker. This study describes the age dependence of the single injection clearance of iohexol in a sample of healthy male volunteers ranging from 21 to 77 years of age. In parallel, renal plasma flow was studied by measuring the total clearance of p-amino hippuric acid administered as a continuous infusion. In subjects older than 50 years a negative correlation to age was found for both p-amino hippuric acid and iohexol clearance, with a reduction of 52 ml/min and 12 ml/min per decade, respectively, whereas no age dependence was found for younger subjects. Correlation between p-amino hippuric acid and iohexol clearances was 0.81. However, the filtration fraction, defined as the ratio of iohexol to p-amino hippuric acid clearance, was higher in the elderly subjects. A consistent discrepancy was found between total and renal clearances of p-amino hippuric acid, indicating significant renal metabolism. Renal clearance of creatinine was poorly correlated to iohexol clearance and did not show any relationship to age.

A simple chemical method for the quantification of the contrast agent iohexol, applicable to glomerular filtration rate measurements.

We present a method for the quantification of the contrast agent iohexol in serum. Iohexol is deiodinated by alkaline hydrolysis and the released iodine subsequently measured according to the ceric arsenite method. The assay requires 50 microliters of serum and has a high capacity as it involves few analytical steps. The high precision (2% CV) and sensitivity make the method applicable to the recently developed procedure for the determination of glomerular filtration rate, which is based on the assessment of the clearance of iohexol from serum. The method is simple and rapid and requires no expensive equipment.

Contrast media and glomerular filtration: dose dependence of clearance for three agents.

Determination of plasma clearance of contrast agents has been advocated as a means to assess glomerular filtration rate. To evaluate the feasibility of different agents for this purpose, we have compared, in healthy volunteers, the dose dependence of plasma clearance for three contrast media (iohexol, a nonionic agent, and iothalamate and metrizoate, which are ionic substances), with special emphasis on the lower dose range (2-20 mL corresponding to 0.9-12.9 g, depending on dose and agent). Iohexol and iothalamate were cleared at constant rates, irrespective of given dose, whereas metrizoate clearance increased significantly at lower doses. In general, the clearances or iothalamate and metrizoate were, respectively, moderately and markedly higher than that of iohexol. The clearance of different doses of metrizoate (2 mL versus a radiographic dose of 40 mL or more) was also compared with the clearance of [51Cr]EDTA in two groups of patients with reduced renal function. When compared with [51Cr]EDTA in patients with renal dysfunction, metrizoate was cleared significantly faster after a 2-mL dose, whereas clearances were identical when the metrizoate dose was 40 mL or more. These findings indicate that tubular secretion plays an active role in the elimination of metrizoate. The pharmacokinetic properties of iohexol, in combination with its low toxicity, make it a suitable agent for determination of glomerular filtration rate in clinical practice.

Contrast media as markers for glomerular filtration: a pharmacokinetic comparison of four agents.

In this study methods for the assay of the iodine-containing radiographic contrast agents metrizoate, amidotrizoate and iothalamate found in serum and urine have been developed. The method involved reverse-phase high-pressure liquid chromatography with spectrophotometric detection. This technique was used to compare the clearance of these agents, in a group of healthy female volunteers, after a single small-dose injection (5 ml, 2275-3235 mg). In the period 0-4 h after injection, serum elimination was approximated by a two-compartment model. However, a full description of drug fate in the body required at least three compartments. Plasma clearance was significantly different between agents with means of 191, 130, 144 and 121 ml/min for metrizoate, amidotrizoate, iothalamate and iohexol, respectively, whereas no difference was found between the renal/plasma clearance ratio. Protein binding measured with equilibrium dialysis did not suggest binding to serum proteins by any of these agents irrespective of concentration.

Plasma clearance of a new contrast agent, iohexol: a method for the assessment of glomerular filtration rate.

We developed a rapid and precise method for the chemical determination of a new contrast agent, iohexol (N,N'-bis(2,3-dihydroxypropyl)-5-N-(2,3-dihydroxypropyl)-acetamido-2,4, 6-triiodoisophtalamide). Its sensitivity allows the monitoring of plasma concentrations for at least 6 hours after the injection of a single small dose. The elimination rate of iohexol was constant after approximately 90 minutes; plasma clearance in healthy volunteers averaged 127 ml/min. The injected dose was quantitatively recovered in urine. Determination of plasma clearance on two different occasions demonstrated a total variation of 11% (coefficient of variation); the methodologic imprecision was minor compared with the biologic variation. In 42 patients with normal to moderately impaired renal function, a comparison of iohexol and 51Cr-ethylenediaminetetraacetic acid clearances demonstrated an excellent correlation (correlation coefficient 0.98). The simplicity and rapidity of the new method makes it an attractive alternative to current methods for the assessment of glomerular filtration rate.

Chemical assay, involving liquid chromatography, for aminoglycoside antibiotics in serum.

We describe a chemical assay involving "high-pressure" liquid chromatography for the quantitative determination of three aminoglycosides: netilmicin, tobramycin, and gentamicin. The drugs are separated from serum by means of precipitation of the serum proteins with acetonitrile after dilution with a buffer. The aminoglycosides are quantitatively extracted into the supernate, which is further purified by a two-step partition procedure involving derivatization of the drugs with o-phthalaldehyde. The drug derivatives are separated by reversed-phase chromatography and detected by on-line fluorometry. Sensitivity is 1 mg/L for tobramycin and 0.5 mg/L for netilmicin and gentamicin. Intra- and interassay variation was below 8%. Analytical recovery of each of the three drugs was 92 to 100%. Correlation with microbiological and radioimmunological assay methods was good. The assay is rapid (about 30 min), precise, and specific, and seems suitable for use in a routine clinical laboratory.