Barbarajean Magnani

ASSOCIATION OF FIRST-TRIMESTER THYROID FUNCTION TEST VALUES WITH THYROPEROXIDASE ANTIBODY STATUS, SMOKING, AND MULTIVITAMIN USE

OBJECTIVE To determine first-trimester thyroid function values and associations with thyroperoxidase antibody (TPO-Ab) status, smoking, emesis, and iodine-containing multivitamin use. METHODS We collected information by interview, questionnaire, and blood draw at the initial obstetric visit in 668 pregnant women without known thyroid disease. We compared thyroid-stimulating hormone (TSH), total thyroxine (T4), and free T4 index (FT4I) values by TPO-Ab status. Multiple regression was used to identify characteristics associated with thyroid function values. RESULTS The following median (range containing 95% of the data points) thyroid function test values were obtained in 585 TPO-Ab-negative women: TSH, 1.1 mIU/L (0.04-3.6); FT4I, 2.1 (1.5-2.9); and T4, 9.9 microg/dL (7.0-14.0). The following median (range containing 95% of the data points) thyroid function test values were obtained in 83 TPO-Ab-positive women: TSH, 1.8 mIU/L (0.3-6.4) (P<.001); FT4I, 2.0 (1.4-2.7) (P = .06); and T4, 9.3 microg/dL (6.8-13.0) (P = .03) (P values denote statistically significant differences between TPO-Ab-positive and negative participants). Among TPO-Ab-negative participants, TSH level was not associated with use of iodine-containing multivitamins, smoking, or race. TSH increased 0.03 mIU/L for every year of maternal age (P = .03) and decreased by 0.3 mIU/L for every increase in parity (P<.001). T4 decreased 0.04 microg/dL for every year of maternal age (P = .04). Mean FT4I was 2.05 in smokers and 2.20 in nonsmokers (P<.01). There were no relationships between T4 or FT4I and parity, race, or iodine-containing multivitamin use. CONCLUSION TPO-Ab status of pregnant women should be considered when constructing trimester-specific reference ranges because elevated serum TPO-Ab levels are associated with higher TSH and lower T4 values.

Serum free light-chain responses after high-dose intravenous melphalan and autologous stem cell transplantation for AL (primary) amyloidosis

Summary:Serum free light-chain (FLC) concentrations were measured by a sensitive nephelometric immunoassay in 66 patients with AL amyloidosis before and after treatment with high-dose melphalan and autologous stem cell transplantation (HDM/SCT). At 1 year after HDM/SCT, 27 patients (41%) achieved a complete hematologic response (CR), that is, disappearance of the monoclonal gammopathy previously evident by immunofixation electrophoresis (IFE) in serum and urine and of plasma cell clonality in the bone marrow. Abnormally elevated FLC levels became normal in 27 patients (41%), and decreased by >90% in 37 (56%). Average improvements in FLC were 94% for patients who achieved a CR and 72% for those who did not (P=0.0001). However, a reduction in FLC of >90% was associated with a similar high likelihood of clinical improvement and prolonged survival, whether or not patients achieved a CR. While CR, as defined by standard criteria, is a more stringent indicator of hematologic response than are decreases in abnormally elevated FLC levels per se, these measures of hematologic response are complementary, and decreases in FLC are more readily detected early after treatment than are the changes in IFE and marrow studies required to determine CR.

Quantitative serum free light chain assay in the diagnostic evaluation of AL amyloidosis

We compared a new serum immunoassay for quantitation of serum free light chains (FLC) with the conventional tests for clonal immunoglobulin production: bone marrow immunohistochemistry, serum immunofixation electrophoresis, and urine immunofixation electrophoresis. Serum samples from 169 patients with AL amyloidosis and 20 controls were examined. Elevated levels of κ-FLC and λ-FLC were found in 94% and 93% of patients with the respective clonal disease. However, false positive elevations of κ-FLC and λ-FLC were found in 30% and 44% of patients with clonal disease of the other light chain subtype. We found that the FLC level was a reliable test for the diagnosis of clonal disease when the FLC κ:λ ratio was abnormal and was comparable to the conventional tests in patients with AL amyloidosis. After a histologic tissue diagnosis of amyloidosis, determining the type as AL amyloidosis relies on a panel of hematologic tests to determine light chain clonality and the exclusion other forms of amyloidosis.

N-Acetylcysteine Reduces Methemoglobin in Vitro

STUDY OBJECTIVE To determine whether N-acetylcysteine (NAC reduces methemoglobin. METHODS We carried out an in vitro laboratory experiment in which five healthy adult volunteers donated blood. Each sample was divided equally among three test tubes. Tube 1 served as a negative control. Sodium nitrite .18 mol/L with dextrose .23 mol/L was added to tube 2 and to tube 3. Next, phosphate-buffered saline solution (PBS) was added to tube 2 and NAC (200 mg/mL) to tube 3. Serial methemoglobin levels were measured over 5.5 hours. RESULTS Maximum methemoglobin levels were observed at 1.5 hours for both the NAC-nitrite and the PBS-nitrite sample (62.7% +/- 8.1% and 65.1% +/- 7.0%, respectively; data expressed as mean +/- SD). The mean difference in methemoglobin between NAC-nitrite and PBS-nitrite was significant at 4.5 hours (29.3% +/- 23.0%, P = .046). The mean rate of methemoglobin decline in NAC-nitrite samples was also different from that of PBS-nitrite samples (10.7% +/- 1.0% versus 2.9% +/- 2.3%, P = .002). The rate of decline was linea (zero order) in the NAC nitrite samples and represented by the equation: % change methemoglobin = .18 x time in minutes. Area under the concentration-time curve was also different among groups (P < .05). CONCLUSION In this in vitro model, NAC reduced chemically induced methemoglobin.

The opioid abuse and misuse epidemic: Implications for pharmacists in hospitals and health systems

PURPOSE The current epidemic of prescription opioid abuse and misuse in the United States is discussed, with an emphasis on the pharmacists role in ensuring safe and effective opioid use. SUMMARY U.S. sales of prescription opioids increased fourfold from 1999 to 2010, with an alarming rise in deaths and emergency department visits associated with the use of fentanyl, hydrocodone, oxycodone, and other opioid medications. Signs and symptoms of opioid toxicity may include altered mental status, hypoventilation, decreased bowel motility, central nervous system and respiratory depression, peripheral vasodilation, pulmonary edema, hypotension, bradycardia, and seizures. In patients receiving long-term opioid therapy for chronic pain, urine drug testing is an important tool for monitoring and assessment of therapy; knowledge of opioid metabolic pathways and assay limitations is essential for appropriate use and interpretation of screening and confirmatory tests. In recent years, there has been an increase in federal enforcement actions against pharmacies and prescription drug wholesalers involved in improper opioid distribution, as well as increased reliance on state-level prescription drug monitoring programs to track patterns of opioid use and improper sales. Pharmacies are urged to implement or promote appropriate guidelines on opioid therapy, including the use of pain management agreement plans; policies to ensure adequate oversight of opioid prescribing, dispensing, and waste disposal; and educational initiatives targeting patients as well as hospital and pharmacy staff. CONCLUSION Pharmacists in hospitals and health systems can play a key role in recognizing the various forms of opioid toxicity and in preventing inappropriate prescribing and diversion of opioids.

Abuse of Telazol: An Animal Tranquilizer

Background: Telazol® (tiletamine hydrochloride 50 mg/mL, zolazepam hydrochloride 50 mg/mL) is utilized in veterinary medicine as a small-animal anesthetic. Telazol is comparable to ketamine in efficacy, and in conjunction with ketamine, has been responsible for one reported human fatality. We report a case of a woman who abused telazol. Case Report: A 30-year-old female employee at a local zoo was found unresponsive by fellow workers in a clean animal treatment room. Initial reports were that she had injected veterinary-grade diazepam and telazol. On-scene paramedics reported her as obtunded and arousable to deep painful stimuli, with gag reflex intact. Systolic blood pressure was 90 mm Hg by palpation. A fresh needle puncture mark was present on her right arm; nearby were a syringe, tourniquet, and bottles of each drug. Emergency Department assessment included airway, breathing, circulation, and intravenous access. She was lavaged and given activated charcoal with a cathartic. Shortly after arrival, she became alert and oriented. Family members insisted this was not an overdose. The patient had been previously evaluated for reported episodes of syncope, “only in the evening, while at work,” and was prescribed diazepam for anxiety. Product information on telazol was limited to the Veterinary Drug Physicians Desk Reference. A urine drugs-of-abuse screen was positive for benzodiazepines and cannabinoids. The patient subsequently revealed a history of recreational use of telazol. She was discharged to an in-patient detoxification facility, 12 hours postadmission. Conclusion: Telazol used in veterinary medicine as an anesthetic agent, is structurally related to ketamine. Telazol causes almost immediate anesthetic effects; and sudden alertness is not uncommon as the effects of the drug subside. Urine drugs-of-abuse screens are unlikely to identify telazol. We report a veterinary worker who abused telazol.

Urine Drug Testing for Pain Management

An epidemic of prescription drug abuse in the United States has increased the burden on clinical toxicology testing laboratories. Urine drug testing provides objective evidence for compliance and aberrant drug behavior in patients on chronic (non-cancer) pain management. This article describes the testing menu, drug testing assays including tandem mass spectrometry and their limitations, interpretation of opiate results and clinical considerations.

Inhaled Nitric Oxide Does Not Inhibit Platelet Activation in Infants with Persistent Pulmonary Hypertension of the Newborn (PPHN). † 844

Inhaled Nitric Oxide Does Not Inhibit Platelet Activation in Infants with Persistent Pulmonary Hypertension of the Newborn (PPHN). † 844

What is Your Guess? Conflicting Calcium Concentrations in the Presence of Low Albumin after Bone Marrow Transplantation

### CASE DESCRIPTION A leukemia patient was admitted to the hospital for a bone marrow transplant. Calcium boluses were administered before transplantation for hypocalcemia [Ionized calcium: 0.97 mmol/L (3.9 mg/dL); reference interval, 1.05–1.27 mmol/L (4.2–5.1 mg/dL). Total calcium: 2.00 mmol/L (8.0 mg/dL); reference interval, 2.22–2.67 mmol/L (8.9–10.7 mg/dL)]. After undergoing transplantation, the patient developed hypertension and had a low hematocrit and platelet count. His calcium concentration continued to be low despite the calcium administration. By 12 …

Debates in pain management testing

The annual healthcare costs associated with chronic pain are significant. Chronic pain also has important societal implications including the increasing availability of prescription narcotics. Recent literature and several professional societies have recommended urine drug testing to monitor adherence to prescription medications and to detect drug abuse and/or misuse. The technical benefits of urine drug testing using definitive testing methods such as LC-MS/MS are well documented. However, the guidelines, literature, and expert consensus on other aspects of pain management testing are sparse and/or more controversial. While many institutions and laboratories perform some form of validity and adulterant testing, the extent and utility of testing in pain management is not standardized. The benefits of point-of-care testing and the resources required to maintain a robust testing program are also not well studied. Furthermore, while urine testing is currently the gold standard in pain management, recent literature has shown some benefits of testing oral fluid and other matrices. There continue to be analytical and billing challenges with pain management testing. The utility of quantitative, definitive testing is controversial. Some laboratories only report qualitative results, while others find value in reporting some or all results quantitatively. Furthermore, the practice of laboratory professionals providing formal consultations for pain management testing and/or billing for interpretations is variable. Finally, pharmacogenomic testing is not routinely done in pain management, but some studies suggest it may be beneficial. Here we ask 7 individuals their expert opinion on different aspects of drug testing to assess compliance in pain management. Which validity and adulterant testing (e.g., observation of specimen collection, recording urine temperature immediately after collection, chain of custody, creatinine, specific gravity, pH, oxidants, nitrites) should be required? William Clarke: If there is a low suspicion for adulteration, measuring temperature, specific gravity, and creatinine should be sufficient. If tampering with the specimen …