This chapter presents four steps in a drug's journey through the body: absorption, distribution, metabolism, and excretion. These processes determine the time frame during which a drug can be detected in blood, urine, and other body fluids. The study of drug absorption, distribution, metabolism, and excretion – what the body does to a drug – is called pharmacokinetics. Drugs that are very lipid soluble may distribute into adipose tissue, accumulate there, and eventually diffuse back into the circulation. The purpose of metabolism is to transform lipid-soluble compounds, which readily enter tissues, into a more water-soluble form that can be excreted. People who are slow metabolizers may experience toxicity from a drug at doses considered therapeutic. Disease of the kidneys or liver can impair excretion, causing drug levels in blood and other body fluids to rise.

An Introduction to Testing for Drugs of Abuse presents a distilled set of facts about the major drugs of abuse that are encountered in clinical practice. Individual chapters highlight the similarities in chemical structure, mechanism of action, and physiologic effects of each drug group, as well as their metabolism, therapeutic uses and potential for misuse or abuse. Special attention is given to the testing process, with an emphasis on interpretation of test results.

This chapter highlights the similarities in chemical structure, mechanism of action, and physiologic effects of benzodiazepines and Z-drugs, as well as their metabolism, therapeutic uses and potential for misuse or abuse. Special attention is given to the testing process, with an emphasis on interpretation of test results. The benzodiazepines are a class of sedative-hypnotic drugs. Benzodiazepines depress the activity of the central nervous system by enhancing the effects of gamma-aminobutyric acid. Benzodiazepines are safer than barbiturates and have largely replaced them as sedative-hypnotic agents. Screening immunoassays for benzodiazepines can detect most of the commonly prescribed drugs in this group. Zaleplon, zolpidem, and zopiclone are all short-acting hypnotic drugs. These compounds are often referred to as "Z-drugs" because they begin with the letter Z and have similar pharmacological properties. Most clinical laboratories do not include Z-drugs in their screening panels for drugs of abuse.

Objectives To describe the h-index as a measure of scientific output. Methods The formula for this index is based on (1) the number of papers published by an author and (2) the number of citations per paper. The h-index can be used to evaluate performance by individuals or by groups of scientists working in university departments or research institutes. Results While the h-index is both objective and quantitative, it has some deficiencies. It does not take into account first or last author publications, numbers of coauthors, or self-citations. Numerous alternative indices have been proposed to better reflect scientists' contributions in their fields. Conclusions Pathologists and clinical laboratory scientists should be familiar with the h-index, as it may be used in decisions about professional advancement.

Abstract Aim We conducted a responsibility analysis to determine whether drivers injured in motor vehicle collisions who test positive for Δ‐9‐tetrahydrocannabinol (THC) or other drugs are more likely to have contributed to the crash than those who test negative. Design Prospective case–control study. Setting Trauma centres in British Columbia, Canada. Participants Injured drivers who required blood tests for clinical purposes following a motor vehicle collision. Measurements Excess whole blood remaining after clinical use was obtained and broad‐spectrum toxicology testing performed. The analysis quantified alcohol and THC and gave semiquantitative levels of other impairing drugs and medications. Police crash reports were analysed to determine which drivers contributed to the crash (responsible) and which were ‘innocently involved’ (non‐responsible). We used unconditional logistic regression to determine the likelihood (odds ratio: OR) of crash responsibility in drivers with 0 < THC < 2 ng/ml, 2 ng/ml ≤ THC < 5 ng/ml and THC ≥ 5 ng/ml (all versus THC = 0 ng/ml). Risk estimates were adjusted for age, sex and presence of other impairing substances. Findings We obtained toxicology results on 3005 injured drivers and police reports on 2318. Alcohol was detected in 14.4% of drivers, THC in 8.3%, other drugs in 8.9% and sedating medications in 19.8%. There was no increased risk of crash responsibility in drivers with THC < 2 ng/ml or 2 ≤ THC < 5 ng/ml. In drivers with THC ≥ 5 ng/ml, the adjusted OR was 1.74 [95% confidence interval (CI) = 0.59–6.36; P = 0.35]. There was significantly increased risk of crash responsibility in drivers with blood alcohol concentration (BAC) ≥ 0.08% (OR = 6.00;95% CI = 3.87–9.75; P < 0.01), other recreational drugs detected (OR = 1.82;95% CI = 1.21–2.80; P < 0.01) or sedating medications detected (OR = 1.45; 95%CI = 1.11–1.91; P < 0.01). Conclusions In this sample of non‐fatally injured motor vehicle drivers in British Columbia, Canada, there was no evidence of increased crash risk in drivers with Δ‐9‐tetrahydrocannabinol < 5 ng/ml and a statistically non‐significant increased risk of crash responsibility (odds ratio = 1.74) in drivers with Δ‐9‐tetrahydrocannabinol ≥ 5 ng/ml.

Objectives Determine the prevalence of drug use in injured drivers and identify associated demographic factors and crash characteristics. Design Prospective cross-sectional study. Setting Seven trauma centres in British Columbia, Canada (2010–2012). Participants Automobile drivers who had blood obtained within 6 h of a crash. Main outcome measures We analysed blood for cannabis, alcohol and other impairing drugs using liquid chromatography/mass spectrometry (LCMS). Results 1097 drivers met inclusion criteria. 60% were aged 20–50 years, 63.2% were male and 29.0% were admitted to hospital. We found alcohol in 17.8% (15.6% to 20.1%) of drivers. Cannabis was the second most common recreational drug: cannabis metabolites were present in 12.6% (10.7% to 14.7%) of drivers and we detected Δ-9-tetrahydrocannabinol (Δ-9-THC) in 7.3% (5.9% to 9.0%), indicating recent use. Males and drivers aged under 30 years were most likely to use cannabis. We detected cocaine in 2.8% (2.0% to 4.0%) of drivers and amphetamines in 1.2% (0.7% to 2.0%). We also found medications including benzodiazepines (4.0% (2.9% to 5.3%)), antidepressants (6.5% (5.2% to 8.1%)) and diphenhydramine (4.7% (3.5% to 6.2%)). Drivers aged over 50 years and those requiring hospital admission were most likely to have used medications. Overall, 40.1% (37.2% to 43.0%) of drivers tested positive for alcohol or at least one impairing drug and 12.7% (10.7% to 14.7%) tested positive for more than one substance. Conclusions Alcohol, cannabis and a broad range of other impairing drugs are commonly detected in injured drivers. Alcohol is well known to cause crashes, but further research is needed to determine the impact of other drug use, including drug–alcohol and drug–drug combinations, on crash risk. In particular, more work is needed to understand the role of medications in causing crashes to guide driver education programmes and improve public safety.

Background The safety and efficacy of Ciprodex® has been demonstrated for treatment of chronic suppurative otitis media (CSOM). However, symptoms fail to resolve in 9-15% of patients. The objective of this study is to evaluate the efficacy of N-acetylcysteine (NAC) on S. aureus, and planktonic and sessile (biofilm forming) P. aeruginosa in vitro using clinical isolates from patients with CSOM. Methods 1) Stability was assessed using liquid chromatography-mass spectrometry for each component in a prepared mixture of Ciprodex® and NAC over 15 days. Sterility was assessed by measuring bacterial growth on a blood agar plate. Efficacy was assessed using a disc diffusion method by inoculating plates with S. aureus ATCC 29513 and P. aeruginosa ATCC 27853, and measuring the clearance zone. 2) Fifteen P. aeruginosa strains were isolated from patients with CSOM and tested in vitro using the bioFILM PA™ antimicrobial susceptibility assay. Treatment solutions included Ciprodex® & ciprofloxacin +/- NAC, and NAC alone (0.25%, 0.5% & 1.25%). Results 1) NAC combined with Ciprodex® demonstrated stability, sterility, and efficacy over a two-week period 2) P. aeruginosa strains in the sessile (33%-40%) and planktonic (13%) state demonstrated resistance to Ciprodex® and ciprofloxacin. When NAC ≥0.5% was used in isolation or as an adjunct to either of these medications, no resistance was found in the sessile or planktonic state among all 15 strains. Conclusion 1) Ciprodex® combined with NAC has a shelf life of at least two weeks given the documented preservation of stability, sterility, and clinical efficacy of the mixed compounds. 2) P. aeruginosa strains demonstrated resistance to both Ciprodex® and ciprofloxacin. NAC ≥0.5% overcomes issues with resistance and shows promise in the treatment of CSOM.

Background: The use of oligoclonal bands (OCBs) and cerebrospinal fluid (CSF) parameters are established in the diagnosis of MS, but poorly as markers of disease. Objective: To investigate the role of OCBs in disease course and progression. Methods: CSF data for 1120 patients with MS were analyzed for associations between OCBs and CSF parameters and clinical data (disease course [relapsing-onset MS (ROMS) vs primary-progressive MS (PPMS)]), disability progression (proportion reaching Expanded Disability Status Scale 6 within 10 years of onset and progression index) and ethnicity. Results: Of patients with MS, 72.5% had detectable OCBs. For patients with detectable OCBs, 84.6% had ROMS and 15.4% PPMS versus 89.7% and 10.3%, respectively for those without detectable OCBs (p=0.04). Total CSF IgG and protein levels were higher in PPMS compared with ROMS (p<0.001). Disease progression appeared independent of OCB status. Patients with CSF (vs without) data were more likely to be male, older at onset, have PPMS and lack optic neuropathy at onset (p<0.001). Conclusions: OCB positivity and elevated total CSF IgG and protein were moderately associated with a PPMS disease course, but not disease progression. Patients with atypical clinical presentations were more likely to have had CSF work-up, suggesting a testing bias.

Amyloidosis is a disease characterized by abnormal deposition of amyloid protein within tissues throughout the body. The site of deposition can differ between patients, and therefore, clinical presentation can vary. Here, we present a case of previously undiagnosed amyloidosis presenting with sudden death. Autopsy demonstrated amyloid infiltration of intramural myocardial vessels, in the absence of myocardial involvement, leading to acute myocardial infarction and death. Postmortem analysis on femoral blood demonstrated an increase in the concentration of free lambda light chains with a significantly decreased kappa-to-lambda ratio, confirming the amyloidosis to be of AL type. While cardiac involvement in AL amyloidosis is not uncommon, isolated intramural vessel involvement is rarely seen, and to our knowledge, no reported cases have resulted in sudden death. This case highlights the importance of investigating angina-like symptoms in patients with amyloidosis. It also demonstrates that free light chain analysis can be a useful tool for diagnosing and classifying amyloidosis in postmortem investigations.

Study Type – Therapy (case series)Level of Evidence 4What's known on the subject? and What does the study add?Previous reports, with small numbers of patients, have described the problem of incomplete testosterone suppression (>1.1 or 1.7 nmol/L) with LHRH agonists. Various predisposing factors have been suggested: different drug agents and patient factors such as age, pretreatment testosterone levels and weight. Such incomplete testosterone suppression has been shown in one small report to be associated with increased PSA failure rates and in another report in those with metastases, with worse survival.This study used testosterone assays that are more accurate at low levels than those used in most previous reports in a large dataset of 2196 men, and confirmed incomplete testosterone suppression (breakthrough) rates >1.7 nmol/L of 3.4% and >1.1 nmol/L of 6.6%. We showed that younger age was strongly associated with the risk of breakthrough, with a minor effect of increasing body mass index. Repeated breakthroughs were more common (16%) in those who had already had one breakthrough. Interim measures of cancer control (PSA kinetics during LHRH therapy) were inferior in those with a breakthrough, and those with breakthroughs between 1.1 and 1.7 nmol/L had worse long‐term biochemical control rates.OBJECTIVES To describe breakthrough rates above castrate levels of testosterone, in a population‐based series of men undergoing adjuvant luteinizing hormone‐releasing hormone (LHRH) agonist therapy with curative radiation therapy. To explore the predisposing factors for such breakthroughs and their impact on subsequent outcomes. PATIENTS AND METHODS All men treated for prostate cancer between 1998 and 2007 with curative radiation in the province of British Columbia, Canada were potentially eligible (n= 11 752). Of these, 2196 fulfilled the eligibility criteria. Serial testosterone measurements were obtained during continuous LHRH therapy. Breakthrough rates >1.1 nmol/L and >1.7 nmol/L were calculated for each LHRH injection and for each patient course. Predisposing factors were identified, and early surrogates of oncological outcome (neoadjuvant nadir and post‐treatment nadir) were determined. RESULTS The risk of a breakthrough >1.1 nmol/L was 6.6%, and >1.7 nmol/L was 3.4% per patient course and 5.4% and 2.2% per LHRH injection (inclusive ranges). Repeated breakthroughs occurred in 16% of patients. Younger men were more liable to breakthroughs (P < 0.001). Early PSA kinetic surrogates of cancer control were inferior in those with breakthroughs. Neither overall biochemical non‐evidence of disease (bNED) nor survival were compromised, although subgroup analysis showed inferior 5‐year bNED in those with breakthroughs of 1.1–1.7 nmol/L vs those without (58% vs 73%, respectively; P= 0.048). CONCLUSIONS Breakthroughs with LHRH agonists occur occasionally per injection, but occur commonly per patient course of treatment, and adversely affect early surrogate measures of outcome. The monitoring of testosterone levels during therapy is therefore advised.

BACKGROUNDLiterature cautions against applying lidocaine 15%/prilocaine 5% over an area larger than 300 cm2. The area of the face, neck, and chest is 400 cm2 or greater.OBJECTIVETo investigate the safety of lidocaine 15%/prilocaine 5% topical anesthetic ointment used as anesthesia for intense pulsed light (IPL) treatment.METHODS AND MATERIALSLidocaine 15%/prilocaine 5% ointment was applied to the face only (n=10) for 30 +/- 15 minutes or to the face, neck, and chest (n=10) for a total of 60 +/- 15 minutes before IPL. Blood lidocaine and prilocaine levels were measured. Adverse events were recorded.RESULTSFor the entire cohort, blood was drawn 25.6 +/- 6.6 minutes after IPL was completed. In the face only group, the mean lidocaine level was 0.122 +/- 0.125 mu g/mL, and the mean prilocaine level was 0.048 +/- 0.029 mu g/mL. In the face, neck, and chest group, the mean lidocaine level was 0.272 +/- 0.208 mu g/mL, and the mean prilocaine level was 0.087 +/- 0.060 mu g/mL. No adverse events related to systemic toxicity were observed or reported to the nurse. At the 24-hour follow-up, no subject reported symptoms of systemic toxicity after leaving the clinic.CONCLUSIONUnder the conditions of this study, topical lidocaine 15%/prilocaine 5% produces low levels of systemic absorption.The authors have indicated no significant interest with commercial supporters.

Introduction. 2-butoxyethanol (2BE) is a solvent commonly incorporated into household and industrial cleaning products. Its ingestion causes rapid central nervous system depression, hypotension, and metabolic acidosis attributable to metabolism of the parent compound to butoxyacetic acid (BAA) by alcohol dehydrogenase. Lactic acidosis is also reported to develop in some cases. Published treatment strategies include the use of ethanol infusion, ethanol with concomitant dialysis, dialysis alone, and fomepizole. Case Report: We present an unusual case of a coingestion of ethanol and 150-250 mL of pure 2BE, which resulted in rapid obtundation, severe airway edema, hypotension, and prolonged acidosis despite the coingestion of ethanol and the administration of a loading dose of fomepizole. Continuous veno-venous hemodialysis was employed to treat the acidosis. Ingestion was confirmed by gas chromatography and mass spectrometric determinaiton of 2BE and BAA. The patient recovered without sequelae. Conclusion. Alcohol dehydrogenase inhibitors may not be adequate to prevent acidosis in significant ingestions to 2BE and extracorporeal treatments may be necessary.

As the 100th anniversary of the Flexner report nears, medical student education is being reviewed at many levels. One area of concern, expressed in recent reports from some national health care organizations, is the adequacy of training in the discipline of laboratory medicine (also termed clinical pathology). The Academy of Clinical Laboratory Physicians and Scientists appointed an ad hoc committee to review this topic and to develop a suggested curriculum, which was subsequently forwarded to the entire membership for review. The proposed medical student laboratory medicine curriculum defines goals and objectives for training, provides guidelines for instructional methods, and gives examples of how outcomes can be assessed. This curriculum is presented as a potentially helpful outline for use by medical school faculty and curriculum committees.

In the past few years, the term Web 2.0 has become a descriptor for the increased functionality of Web sites, including those with medical content. Most physicians do not know what Web 2.0 means or how it can impact their work lives. This review provides some background on the evolution of Web 2.0 and describes how its features are being incorporated into medical Web sites. Some potential applications of Web 2.0 in pathology and laboratory medicine are discussed, as are the issues that must be considered when adopting this new technology.

In the past few years, the term Web 2.0 has become a descriptor for the increased functionality of Web sites, including those with medical content. Most physicians do not know what Web 2.0 means or how it can impact their work lives. This review provides some background on the evolution of Web 2.0 and describes how its features are being incorporated into medical Web sites. Some potential applications of Web 2.0 in pathology and laboratory medicine are discussed, as are the issues that must be considered when adopting this new technology.

A PDA (personal digital assistant) program containing information on 193 laboratory tests was provided to students during the 8-week core clerkship in internal medicine. Students used the program at their own discretion. The number of times each test was accessed during the clerkship was recorded by the program's database. Ten tests were accessed by more than 40% of the students: serum enzymes (lactate dehydrogenase, amylase, alkaline phosphatase, creatine kinase, and gamma-glutamyl transferase), electrolytes (sodium and potassium), renal function tests (urea and creatinine), and a plasma protein (albumin). The most frequently looked up test category was the CBC, followed by liver-related tests, plasma proteins, electrolytes, and autoantibodies. Students at the 2 hospitals where the clerkship was offered had similar test lookup patterns. We conclude that students seek information about laboratory tests that are frequently ordered and directly relevant to the diagnosis and management of their patients.

We provided a laboratory test program for the personal digital assistant (PDA) to a cohort of third year medical students during their internal medicine clerkship. At the end of each rotation, students were interviewed about their experience with the program, and tracking information was downloaded from their PDAs. Students found the program helpful and easy to use, accessed it more often during patient care activities than as a study aid, and considered the program a better way to learn about laboratory tests than formal teaching sessions. The program was accessed an average of 4 or 5 times per week, although individual use was highly variable. There was no relationship between end-of-clerkship examination scores and the number of tests that were accessed. The PDA program is an effective way to introduce laboratory facts and concepts into an internal medicine clerkship.