Age-Stratified Lithium Therapeutic Ranges for Older Adults with Bipolar Disorder - from Awareness to an Action Plan.

Lithium is the first-line treatment for maintenance therapy in bipolar disorder. It is an effective mood stabilizer agent, and may have potential benefits in neuroprotection and reducing the risk of suicide. Toxicity has been a concern in recent decades, particularly in older adults (≥60 years). In 2019, the Older Adults Task Force within the International Society for Bipolar Disorder (ISBD) published recommendations for age-stratified lithium therapeutic ranges for therapy of Older Age Bipolar Disorder (OABD), namely 0.4 - 0.8 mmol/L for ages 60 to 79 and 0.4 - 0.7 mmol/L for ages 80 and above. Clinical laboratory practice surveys in Canada indicated that adoption and implementation of the proposed ranges has been limited to date. In this article, we describe the approach and steps taken to evaluate and implement recommended lithium therapeutic ranges in Ontario and other provinces in Canada for laboratory quality improvement. Sources of variation in lithium reporting practices are discussed and shared here to highlight potential barriers to implementation. The overall goal of this article is to bring attention across the global laboratory community that lower lithium therapeutic target ranges in older patients are crucial for patient safety in OABD.

Lot verification practices in Ontario clinical chemistry laboratories - Results of a patterns-of-practice survey.

Objectives: Verifying new reagent or calibrator lots is crucial for maintaining consistent test performance. The Institute for Quality Management in Healthcare (IQMH) conducted a patterns-of-practice survey and follow-up case study to collect information on lot verification practices in Ontario. Methods: The survey had 17 multiple-choice questions and was distributed to 183 licensed laboratories. Participants provided information on materials used and approval/rejection criteria for their lot verification procedures for eight classes of testing systems. The case study provided a set of lot comparison data and was distributed to 132 laboratories. Responses were reviewed by IQMH scientific committees. Results: Of the 175 laboratories that responded regarding reagent lot verifications, 74% verified all tests, 11% some, and 15% none. Of the 171 laboratories that responded regarding calibrator lot verifications, 39% verified all calibrators, 4% some, and 57% none. Reasons for not performing verifications ranged from difficulty performing parallel testing to high reagent cost. For automated chemistry assays and immunoassays, 23% of laboratories did not include patient-derived materials in reagent lot verifications and 42% included five to six patient materials; 58% of laboratories did not include patient-derived materials in calibrator lot verifications and 23% included five to six patient materials. Different combinations of test-specific rules were used for acceptance criteria. For a failed lot, 98% of laboratories would investigate further and take corrective actions. Forty-three percent of laboratories would accept the new reagent lot in the case study. Conclusion: Responses to the survey and case study demonstrated variability in lot verification practices among laboratories.

A Randomized Control Trial Using a Validated Prediction Model for Diagnosing Acute Heart Failure in Undifferentiated Dyspneic Emergency Department Patients-Results of the GASP4Ar Study.

BACKGROUND: Diagnosing acute heart failure (AHF) in undifferentiated dyspneic emergency department (ED) patients can be challenging. We prospectively studied a validated diagnostic prediction model for AHF that uses patient age, clinician pretest probability for AHF, and N-terminal pro-B-type natriuretic peptide (NT-proBNP) as a continuous value to determine its utility and performance. METHODS AND RESULTS: This was a multicenter randomized controlled trial of undifferentiated dyspneic patients with an indeterminate pretest probability of AHF as assessed by the treating emergency physician (EP). After recording its components, the calculated model results with validated treatment threshold guidelines were provided to EPs for patients randomized to the intervention arm. Final diagnoses with the use of 60-day follow-up information were adjudicated by 2 independent cardiologists. The primary outcomes were accuracy of the model and of physician diagnosis comparing intervention and standard care arms. A total of 197 patients were randomized and had outcome data recorded; 41% were determined to have had heart failure. Final EP diagnostic accuracy was 76% (sensitivity 68.2%, specificity 83.9%) with no significant difference between exposed versus blinded arms (accuracy 77% vs 74%; P = .77). Area under the model receiver operating characteristic curve was 0.93. Using the model treatment thresholds would have redirected 48% of patients with 95% accuracy. CONCLUSIONS: This study prospectively validated the diagnostic accuracy of our AHF model in a significant proportion of indeterminate dyspneic ED patients, but provision of this information did not improveEP diagnostic accuracy. Future studies should determine how such a clinical prediction tool could be effectively integrated into routine practice and improve early management of suspected AHF patients in the ED.

Thyroid storm caused by a chinese herb contaminated with thyroid hormones.

BACKGROUND: We report a case of thyroid storm caused by consuming a Chinese herb contaminated with thyroid hormones. CASE REPORT: A 70-year-old man presented to an emergency department after 2 days of nausea, vomiting, and weakness. Three days previously, he had started taking Cordyceps powder and "Flower Man Sang Hung" as recommended by his Chinese physician. Following admission, the patient deteriorated and was eventually diagnosed with thyroid storm complicated by rapid atrial fibrillation requiring cardioversion, intubation, and intensive care admission. The analysis of the Chinese herb "Flower Man Sang Hung" was positive for levothyroxine. The patient was extubated 11 days after admission and discharged to a rehabilitation centre after 17 days of hospitalization. The Chinese medicine physician was informed of the events. CONCLUSIONS: Herbal products can be the source of illness, medication interactions, and contamination. Awareness should be raised among Chinese medicine physicians, allopathic physicians, and their patients. Clinicians should also have a low threshold of suspicion to seek laboratory analysis of suspect substances when the cause of the clinical presentation is unclear.

The impact of adoption of the international association of diabetes in pregnancy study group criteria for the screening and diagnosis of gestational diabetes.

OBJECTIVE: The objective of the study was to compare the International Association of Diabetes in Pregnancy Study Group (IADPSG) and the Canadian Diabetes Association (CDA) criteria for the diagnosis of gestational diabetes mellitus (GDM). STUDY DESIGN: This was a retrospective cohort study involving all pregnant women who underwent screening for GDM at a tertiary medical center between 2008 and 2011. Diagnosis of GDM during the study period was based on the CDA 2008 recommendations of universal screening with a 50 g oral glucose challenge test (GCT; threshold 140 mg/dL [7.8 mmol/L]) and a diagnostic test using a fasting 2 hour, 75 g oral glucose tolerance test (OGTT). Diagnosis of GDM required the presence of 2 or more abnormal values, whereas a single abnormal value was diagnostic of impaired glucose intolerance. Because the OGTT thresholds based on the IADPSG criteria are lower than the CDA 2008 thresholds (92 mg/dL [5.1 mmol], 180 mg/dL [10.0 mmol/L], and 153 mg/dL [8.5 mmol/L]), we identified a group of women who would have been diagnosed as GDM based on the IADPSG criteria but not the CDA 2008 criteria (OGTT-IADPSG group). The pregnancy outcome of that group as well as that of women with a positive OGTT according to the CDA 2008 criteria (OGTT-CDA group) and women with a negative OGTT (OGTT-NEGATIVE group) was compared with that of a control group consisting of women with a negative GCT (GCT-NEGATIVE group). RESULTS: Overall, 5429 women were eligible for the study, of which 4183 were included in the GCT-NEGATIVE group, 526 in the OGTT-NEGATIVE group, 155 in the OGTT-IADPSG group, and 385 in the OGTT-CDA group. Applying the IADPSG criteria to the study population would increase the rate of GDM from 3.2% (7.3% when including impaired glucose intolerance) to 10.3%. The majority of the increase in the rate of GDM was attributed to the use of a single abnormal value to define GDM (5.3% increase) rather than the use of lower threshold values (1.8% increase). Of the 3 threshold values, the lower 1 hour threshold was the most significant contributor to the higher GDM rate. A positive OGTT in both the OGTT-IADPSG group and the OGTT-CDA group was independently associated with a higher rate of the composite adverse outcome (odds ratio, 1.4; 95% confidence interval, 1.1-1.9). CONCLUSION: The use of the IADPSG criteria instead of the CDA criteria would result in a considerable increase in the rate of GDM, but this also appears to identify additional women at similar risk of adverse pregnancy outcome. Further studies are needed to determine whether this observation persists after controlling for confounders such as body mass index as well as whether treatment in these cases would improve perinatal outcome.

Plasmapheresis and steroid treatment of levamisole-induced vasculopathy and associated skin necrosis in crack/cocaine users.

BACKGROUND: Levamisole was removed from the market due to complications of agranulocytosis and skin necrosis. Levamisole has been reported in a high proportion of seized cocaine in North America and has been associated with multiple cases of skin necrosis. OBJECTIVE: We report three cases of levamisole/cocaine-induced skin necrosis who responded to treatment with plasmapheresis and immunosuppression. RESULTS: Three patients presented with painful necrotic skin lesions on the ears, cheeks, breasts, and buttocks. The extremities were involved in two patients and the upper respiratory tract mucosa in one patient. All had markers of immune activation, with elevated C-reactive protein, antinuclear antibody, and perinuclear antineutrophil cytoplasmic antibody. Skin biopsy in all cases revealed a mixed pattern of thrombosis and vasculitis within dermal vessels, with overlying ischemic ulceration of skin and soft tissues. One patient required extensive débridement of the skin and soft tissue of the calves and also had respiratory involvement. All patients were treated with plasmapheresis and immunosuppression with rapid stabilization and/or improvement of the lesions. CONCLUSION: Levamisole is frequently added to crack/cocaine; we report three patients who developed vascular lesions and skin necrosis after using cocaine/levamisole. These improved with plasmapheresis and immunosuppression as well as abstention from the drugs; one patient with severe disease required débridement and skin grafting.

Performance evaluation of three liquid chromatography mass spectrometry methods for broad spectrum drug screening.

BACKGROUND: Liquid chromatography-mass spectrometry (LC-MS) and tandem LC-MS (LC-MS/MS) are increasingly used in toxicology laboratories as a complementary method to gas chromatography-mass spectrometry (GC-MS) and liquid chromatography-ultraviolet detection (LC-UV) for comprehensive drug screening (CDS). This study was designed to characterize the sensitivity and specificity of three LC-MS(/MS) vendor-supplied methods for targeted CDS and identify the current limitations associated with the use of these technologies. METHODS: Five methods for broad spectrum CDS, including LC-UV (REMEDi), full scan GC-MS, LC-MS (ZQ-Mass Detector with MassLynx-software), LC-QTRAP-MS/MS (3200-QTRAP with Cliquid-software) and LC-LIT-MS/MS (LXQ Linear Ion Trap with ToxID-software) were evaluated based on their ability to detect drugs in 48 patient urine samples. RESULTS: The tandem MS methods identified 15% more drugs than the single stage MS or LC-UV methods. Use of two broad spectrum screening methods identified more drugs than any single system alone. False negatives and false positives generated by the LC-MS(/MS) software programs were identified upon manual review of the raw data. CONCLUSIONS: The LC-MS/MS methods detected a broader menu of drugs; however, it is essential to establish manual data review criteria for all LC-MS(/MS) drug screening methods. Use of an EI-GC-MS and ESI-LC-MS/MS combination for targeted CDS may be optimal due to the complementary nature of the chromatographic and ionization techniques.

Comparing folic acid pharmacokinetics among women of childbearing age: single dose ingestion of 1.1 versus 5 MG folic acid.

BACKGROUND: A 2001 study suggested that supplementation with 5 mg folic acid, among women of childbearing age, is needed to render maximum protection against neural tube defects (NTD). No human study is presently available which examined the pharmacokinetics of 5 mg folic acid. OBJECTIVE: To compare the pharmacokinetics of ingesting a single dose of 5 mg versus 1.1 mg folic acid contained in 2 prenatal multivitamins (PregVit and PregVit-Folic 5), and to estimate its contribution to steady-state folate levels. METHOD: The pharmacokinetics of 1.1 mg folic acid was determined in a previously published study. The method was replicated among 6 healthy, non-pregnant women who were given 5 mg folic acid to ingest. Blood samples were drawn and serum folate concentrations were measured at various time points during 10 hours post-ingestion. Standard pharmacokinetic parameters were determined and compared with Student's t-test, when appropriate. RESULTS: The mean area under the curve (AUC) of 1.1 mg and 5 mg folic acid were 147.6 +/- 52.8 (ng/mL) x hr and 997.5 +/- 271.9 (ng/mL) x hr, respectively (p<0.0002). An approximate 5-fold difference was detected in the peak concentrations (Cmax) between the 2 groups (p<0.0005), alongside a slight difference in the times to peak (Tmax) (p=0.02). The estimated steady-state serum folate concentrations produced by 1.1 mg and 5 mg folic acid were 6.2 +/- 2.2 ng/mL and 41.6 +/- 11.3 ng/mL, respectively (p<0.0002), prior to its summation with initial (baseline) steady-state levels. CONCLUSION: Single dose administration between 1.1 mg and 5 mg folic acid demonstrated linear pharmacokinetics, with approximately a 5-fold difference between the 2 doses in serum folate contribution to steady-state levels, under ideal adherence.