Rapid and Sensitive Detection of Fentanyl and Its Analogs by a Novel Chemiluminescence Immunoassay.

BACKGROUND: Abuse of fentanyl and its analogs is a major contributor to the opioid overdose epidemic in the United States, but detecting and quantifying trace amounts of such drugs remains a challenge without resorting to sophisticated mass spectrometry-based methods. METHODS: A sensitive immunoassay with a sub-picogram limit of detection for fentanyl and a wide range of fentanyl analogs has been developed, using a novel high-affinity antibody fused with NanoLuc, a small-size luciferase that can emit strong and stable luminescence. When used with human urine samples, the assay has a sub-picogram limit of detection for fentanyl, with results fully concordant with LC-MS. RESULTS: When applied to clinical samples, the novel chemiluminescence immunoassay can detect low positive fentanyl missed by routine screening immunoassays, with a limit of detection of 0.8 pg/mL in human urine. When applied to environmental samples, the assay can detect levels as low as 0.25 pg fentanyl per inch2 of environment surface. Assay turnaround time is less than 1 h, with inexpensive equipment and the potential for high-throughput automation or in-field screening. CONCLUSIONS: We have established a novel assay that may have broad applications in clinical, environmental, occupational, and forensic scenarios for detection of trace amounts of fentanyl and its analogs.

Use of the DMAIC Lean Six Sigma quality improvement framework to improve beta-lactam antibiotic adequacy in the critically ill.

BACKGROUND: Beta-lactam antibiotics are widely used in the intensive care unit due to their favorable effectiveness and safety profiles. Beta-lactams given to patients with sepsis must be delivered as soon as possible after infection recognition (early), treat the suspected organism (appropriate), and at a dose that eradicates the infection (adequate). Early and appropriate antibiotic delivery occurs in >90% of patients, but less than half of patients with sepsis achieve adequate antibiotic exposure. This project aimed to address this quality gap and improve beta-lactam adequacy using the DMAIC Lean Six Sigma quality improvement framework. METHODS: A multidisciplinary steering committee was formed and completed a stakeholder analysis to define the gap in practice. An Ishikawa cause and effect (Fishbone) diagram was used to identify the root causes and an impact/effort grid facilitated prioritization of interventions. An intervention which included bundled education with the use of therapeutic drug monitoring (TDM; i.e., drug level testing) was projected to have the highest impact relative to the amount of effort and selected to address beta-lactam inadequacy in the critically ill. RESULTS: The education and TDM intervention were deployed through a Plan, Do, Study, Act (PDSA) cycle. In the three months after 'go-live,' 54 episodes of beta-lactam TDM occurred in 41 unique ICU patients. The primary quality metric of beta-lactam adequacy was achieved in 94% of individuals after the intervention. 94% of clinicians gauged the education provided as sufficient. The primary counterbalance of antimicrobial days of therapy, a core antimicrobial stewardship metric, was unchanged over time (favorable result; p=0.73). CONCLUSIONS: Application of the DMAIC Lean Six Sigma quality improvement framework effectively improved beta-lactam adequacy in critically ill patients. The approach taken in this quality improvement project is widely generalizable to other drugs, drug classes, or settings to increase the adequacy of drug exposure.

Population pharmacokinetic model of cefepime for critically ill adults: a comparative assessment of eGFR equations.

Cefepime exhibits highly variable pharmacokinetics in critically ill patients. The purpose of this study was to develop and qualify a population pharmacokinetic model for use in the critically ill and investigate the impact of various estimated glomerular filtration rate (eGFR) equations using creatinine, cystatin C, or both on model parameters. This was a prospective study of critically ill adults hospitalized at an academic medical center treated with intravenous cefepime. Individuals with acute kidney injury or on kidney replacement therapy or extracorporeal membrane oxygenation were excluded. A nonlinear mixed-effects population pharmacokinetic model was developed using data collected from 2018 to 2022. The 120 included individuals contributed 379 serum samples for analysis. A two-compartment pharmacokinetic model with first-order elimination best described the data. The population mean parameters (standard error) in the final model were 7.84 (0.24) L/h for CL1 and 15.6 (1.45) L for V1. Q was fixed at 7.09 L/h and V2 was fixed at 10.6 L, due to low observed interindividual variation in these parameters. The final model included weight as a covariate for volume of distribution and the eGFRcr-cysC (mL/min) as a predictor of drug clearance. In summary, a population pharmacokinetic model for cefepime was created for critically ill adults. The study demonstrated the importance of cystatin C to prediction of cefepime clearance. Cefepime dosing models which use an eGFR equation inclusive of cystatin C are likely to exhibit improved accuracy and precision compared to dosing models which incorporate an eGFR equation with only creatinine.

Elementary Overview of Heavy Metals.

BACKGROUND: Exposure to heavy metals is common as a result of environmental contamination of air, water, and soil as well as accumulation in food, tobacco, herbal medicines, and occupational contact. However, clinically relevant toxicity is much less prevalent. Toxic effects, when they occur, may present with non-specific symptoms, resulting in a very large differential for clinicians to consider. CONTENT: Arsenic, cadmium, lead, and mercury are four heavy metals with no biological role in humans. However, these metals are commonly used in industrial applications and consumer products. Since these elements are not biodegradeable, their potential toxic effects may be long-lasting within the environment. These heavy metals have the potential to accumulate in vital organs such as the brain, heart, and kidney where they may disrupt normal cellular functioning and if exposures are repetitive or of high concentration, toxicity may result. SUMMARY: The objective of this review is to provide an overview of arsenic, cadmium, lead, and mercury physical properties, common sources of exposure, basic toxicokinetics and health effects, and to review clinical guidelines and treatment strategies. Acute and chronic symptoms and recommended laboratory biomarker testing are also discussed.

Association of adverse effects with high serum posaconazole concentrations.

Posaconazole therapeutic drug monitoring (TDM) is widely utilized to assess therapeutic efficacy and safety; however, clinical effects of very high serum concentrations are unknown. A retrospective review of 90 patients receiving posaconazole for treatment or prophylaxis of invasive fungal infections with serum concentrations ≥3000 ng/mL from 1/1/2019 to 4/30/2021 evaluated the incidence and type of adverse drug reactions (ADRs). Symptomatic ADRs were very common in patients with posaconazole concentrations of ≥5000 ng/mL and 3000-4999 ng/mL (80% vs. 58.8%; P = 0.31). Posaconazole TDM should be performed for both treatment and prophylaxis indications and dose decrease for serum concentrations >3000 ng/mL should be considered.

Drug level monitoring is commonly used to evaluate appropriate dosing and effectiveness of posaconazole, a medication used to treat fungal infections. Patients with high levels commonly had side effects. Posaconazole monitoring should be completed, and doses reduced when levels are high.

Why is the Implementation of Beta-Lactam Therapeutic Drug Monitoring for the Critically Ill Falling Short? A Multicenter Mixed-Methods Study.

BACKGROUND: Beta-lactam therapeutic drug monitoring (BL TDM; drug level testing) can facilitate improved outcomes in critically ill patients. However, only 10%-20% of hospitals have implemented BL TDM. This study aimed to characterize provider perceptions and key considerations for successfully implementing BL TDM. METHODS: This was a sequential mixed-methods study from 2020 to 2021 of diverse stakeholders at 3 academic medical centers with varying degrees of BL TDM implementation (not implemented, partially implemented, and fully implemented). Stakeholders were surveyed, and a proportion of participants completed semistructured interviews. Themes were identified, and findings were contextualized with implementation science frameworks. RESULTS: Most of the 138 survey respondents perceived that BL TDM was relevant to their practice and improved medication effectiveness and safety. Integrated with interview data from 30 individuals, 2 implementation themes were identified: individual internalization and organizational features. Individuals needed to internalize, make sense of, and agree to BL TDM implementation, which was positively influenced by repeated exposure to evidence and expertise. The process of internalization appeared more complex with BL TDM than with other antibiotics (ie, vancomycin). Organizational considerations relevant to BL TDM implementation (eg, infrastructure, personnel) were similar to those identified in other TDM settings. CONCLUSIONS: Broad enthusiasm for BL TDM among participants was found. Prior literature suggested that assay availability was the primary barrier to implementation; however, the data revealed many more individual and organizational attributes, which impacted the BL TDM implementation. Internalization should particularly be focused on to improve the adoption of this evidence-based practice.

Does metabolite matter? Defining target itraconazole and hydroxy-itraconazole serum concentrations for blastomycosis.

BACKGROUND: Itraconazole is the recommended first-line treatment for mild-to-moderate blastomycosis and consolidation treatment of moderate-to-severe disease. Itraconazole is metabolised into three metabolites, including an active metabolite hydroxy-itraconazole. Literature provides little evidence indicating whether therapeutic drug monitoring targets should be based on itraconazole parent compound alone or a sum of itraconazole and hydroxy-itraconazole serum concentrations. OBJECTIVES: This study aims to compare clinical outcomes and adverse drug events (ADEs) of combined itraconazole and hydroxy-itraconazole concentrations versus itraconazole parent compound alone in patients with blastomycosis. PATIENTS/METHODS: This study was a retrospective cohort review of patients ≥18 years with probable or proven Blastomyces infection who received itraconazole with at least one documented serum itraconazole concentration. The primary outcome was rate of partial or complete treatment response across three patient groups: (1) Itraconazole parent compound >1.0 mcg/ml (parent), (2) parent compound <1.0 mcg/ml, but a combined itraconazole and hydroxy-itraconazole >1.0 mcg/ml (combined) and (3) failure to achieve a combined or parent concentration >1.0 mcg/ml (subtherapeutic) for >75% of the duration of itraconazole therapy. RESULTS: A total of 80 patients were included (parent = 32, combined = 36, subtherapeutic = 12). No statistically significant difference was observed for rate of partial or complete treatment response (97% parent vs 94% combined, p = .99). Significantly higher mortality due to blastomycosis was observed in patients in the subtherapeutic group (0% parent vs 3% combined vs 25% subtherapeutic, p = .01). CONCLUSIONS: This study supports an itraconazole therapeutic target combining itraconazole and hydroxy-itraconazole >1.0 mcg/ml for blastomycosis treatment.

Neurologic Effects of Gadolinium Retention in the Brain after Gadolinium-based Contrast Agent Administration.

Background Concerns over the neurotoxic potential of retained gadolinium in brain tissues after intravenous gadolinium-based contrast agent (GBCA) administration have led to pronounced worldwide use changes, yet the clinical sequelae of gadolinium retention remain undefined. Purpose To assess clinical and neurologic effects and potential neurotoxicity of gadolinium retention in rats after administration of various GBCAs. Materials and Methods From March 2017 through July 2018, 183 male Wistar rats received 20 intravenous injections of 2.5 mmol per kilogram of body weight (80 human equivalent doses) of various GBCAs (gadodiamide, gadobenate, gadopentetate, gadoxetate, gadobutrol, gadoterate, and gadoteridol) or saline over 4 weeks. Rats were evaluated 6 and 34 weeks after injection with five behavioral tests, and inductively coupled plasma mass spectrometry, transmission electron microscopy, and histopathology were performed on urine, serum, cerebrospinal fluid (CSF), basal ganglia, dentate nucleus, and kidney samples. Dunnett post hoc test and Wilcoxon rank sum test were used to compare differences between treatment groups. Results No evidence of differences in any behavioral test was observed between GBCA-exposed rats and control animals at either 6 or 34 weeks (P = .08 to P = .99). Gadolinium concentrations in both neuroanatomic locations were higher in linear GBCA-exposed rats than macrocyclic GBCA-exposed rats at 6 and 34 weeks (P < .001). Gadolinium clearance over time varied among GBCAs, with gadobutrol having the largest clearance (median: 62% for basal ganglia, 70% for dentate) and gadodiamide having no substantial clearance. At 34 weeks, gadolinium was largely cleared from the CSF and serum of gadodiamide-, gadobenate-, gadoterate-, and gadobutrol-exposed rats, especially for the macrocyclic agents (range: 70%-98% removal for CSF, 34%-94% removal for serum), and was nearly completely removed from urine (range: 96%-99% removal). Transmission electron microscopy was used to detect gadolinium foci in linear GBCA-exposed brain tissue, but no histopathologic differences were observed for any GBCA. Conclusion In this rat model, no clinical evidence of neurotoxicity was observed after exposure to linear and macrocyclic gadolinium-based contrast agents at supradiagnostic doses. © RSNA, 2022 Online supplemental material is available for this article.

Evaluation of Self-Collected Midturbinate Nasal Swabs and Saliva for Detection of SARS-CoV-2 RNA.

Rapid and accurate diagnostic testing is essential to bring the ongoing COVID-19 pandemic to an end. As the demand for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) testing continues to increase amid supply shortages, many laboratories have investigated the use of sources other than nasopharyngeal (NP) swabs. Saliva and midturbinate (MT) nasal swabs are attractive alternatives, as they allow for self-collection and are well accepted by patients. Saliva also requires limited consumables. We compared the performance of health care provider-collected NP swabs, patient-collected MT swabs, and patient-collected saliva specimens for SARS-CoV-2 detection using a laboratory-developed PCR assay that had received Emergency Use Authorization by the FDA. Of 281 total evaluable samples, 33 (11.7%) NP swabs, 33 (11.7%) MT swabs, and 32 (11.4%) saliva specimens were positive for SARS-CoV-2 following resolution of discordant results. Compared to NP swabs, saliva exhibited a sensitivity of 90.9% (30/33) and specificity of 99.2% (246/248), while patient-collected MT swabs exhibited a sensitivity of 93.9% (31/33) and specificity of 99.2% (246/248). When comparing to the consensus standard, the sensitivity was found to be 100% (31/31) for both NP and MT swabs and 96.8% (30/31) for saliva specimens, while specificity was the same in both NP swabs and saliva specimens (98.8% [247/250]) and 99.2% (248/250) for MT swabs. Pretreatment of saliva with proteinase K and heating for 15 min prior to extraction reduced the invalid rate from 26.7% (52/195) to 0% (0/195). These data show that midturbinate nasal swabs and saliva are suitable sources for self-collection in individuals who require routine monitoring for SARS-CoV-2 infection.

The North American Opioid Epidemic.

BACKGROUND: The culmination of the widespread overprescription of opioids, a resurgence of heroin use, and increased accessibility and use of illicit synthetic opioids is commonly referred to as the opioid epidemic in North America. METHODS: This article is not intended to provide a comprehensive systematic literature review, but rather summarized recent publications and online governmental reports and datasets for English-written literature primarily published between January 1, 2015 and July 1, 2020. RESULTS: In both the United States and Canada, opioids represent one of the most widely prescribed classes of medications. According to the US Centers for Disease Control and Prevention (CDC), an unprecedented increase in the use of opioid pain relievers has led to one of the worst drug overdose epidemics in US history and continues to be an ongoing major public health crisis based on recent Centers for Disease Control and Prevention mortality data, where almost two-thirds of all overdose deaths still involve opioids, including heroin and illicit opioids. In addition to the high mortality rates in both the United States and Canada, there has also been an increase in emergency department visits for nonmedical use of opioid pain relievers, along with additional individuals seeking treatment for opioid addiction, and a rise in neonatal abstinence syndrome. CONCLUSIONS: This article highlights the history, underlying issues, ongoing national regulatory efforts, and future strategies and therapies to help mitigate the opioid crisis in North America.

Synovial Fluid Metal Ion Levels are Superior to Blood Metal Ion Levels in Predicting an Adverse Local Tissue Reaction in Failed Total Hip Arthroplasty.

BACKGROUND: Adverse local tissue reactions (ALTR) are associated with total hip arthroplasty (THA) failure in patients with metal-on-metal bearings and/or taper corrosion, which can also occur in metal-on-polyethylene articulations. Patients are monitored with blood cobalt (Co) and chromium (Cr) concentrations which do not always correlate with the degree of soft tissue reaction at revision THA. The purpose of this study was to determine how the blood and prosthetic hip synovial fluid levels of Co and Cr correlate with one another, and determine which concentration is more predictive of ALTR. METHODS: Synovial fluid and blood samples were collected at the time of revision THA in patients with (n = 26) and without ALTR (n = 27). Whole blood, serum, and synovial fluid metal ion concentrations were correlated with one another and clinical findings. RESULTS: The ratio of synovial fluid to whole blood Co concentration in ALTR and non-ALTR hips was 120:1 and 18:1 (P = .006). The mean ratio of synovial fluid to whole blood Cr concentration in ALTR and non-ALTR hips was 414:1 and 24:1 (P = .01). The mean synovial fluid Co/Cr concentrations were elevated in patients with ALTR compared with those without (2007.3 vs. 12.4 ppb, P = .007) and (3188.2 vs. 10.3 ppb, P = .02). The synovial fluid Co concentration was the most accurate test for detecting ALTR (cut off: 19.75 PPB, AUC 0.973). CONCLUSION: In patients with ALTR, synovial fluid Co and Cr levels were 120 times higher and 414 times higher than whole blood Co and Cr levels. Synovial fluid Co ion concentration was the most accurate in predicting ALTR. LEVEL OF EVIDENCE: Diagnostic level II.

Relationship of Ganciclovir Therapeutic Drug Monitoring with Clinical Efficacy and Patient Safety.

The clinical utility of ganciclovir therapeutic drug monitoring (TDM) is unknown. We retrospectively analyzed adult patients treated for cytomegalovirus (CMV) infection with ganciclovir with TDM between 2005 and 2015. The primary outcome was an association between ganciclovir TDM and clinical efficacy endpoints within 30 days, defined by viral load and symptomatology. Secondary outcomes included safety endpoints, evaluated within 7 days of the last administered dose of ganciclovir. Of 175 patients evaluated, 82 patients with CMV infection were included in our analysis with a median (interquartile range) baseline CMV viral load of 5,500 (3,000 to 15,200) copies/ml. The majority achieved undetectable or reduced CMV viral load below the lower limit of quantification (74.4%) with improvement in symptomatology (70.7%) at 30 days. Among patients with detectable CMV viremia at 30 days, the viral load had declined to a median of 1,000 (1,000 to 3,090) copies/ml. We did not observe significant associations between the efficacy outcomes and ganciclovir trough (P = 0.20 and P = 0.20, respectively) or peak concentrations (P = 0.14 and P = 0.14, respectively). Similarly, there was no significant association between ganciclovir trough or peak concentrations and safety endpoints, including leukopenia (P = 0.48 and P = 0.69), neutropenia (P = 0.59 and P = 0.69), thrombocytopenia (P = 0.29 and P = 0.37), anemia (P = 0.51 and P = 0.35), nephrotoxicity (P = 0.41 and P = 0.57), and neurotoxicity (P = 0.22 and P = 0.48). We did not observe any associations between ganciclovir TDM and clinical efficacy or safety endpoints. Routine ganciclovir TDM may be of limited value. Future studies may be warranted to identify specific populations with unpredictable pharmacokinetic and pharmacodynamics profiles in whom ganciclovir TDM may be of benefit.

The Fentanyl Epidemic and Evolution of Fentanyl Analogs in the United States and the European Union.

BACKGROUND: Since 2013, an unprecedented surge in fentanyl overdose deaths has been caused by heroin laced with illicitly produced fentanyl and/or fentanyl analogs (FAs) sold as heroin. The US Drug Enforcement Agency's National Forensic Laboratory Information System reported a >300% increase in fentanyl encounters from 4697 in 2014 to 14440 in 2015. In 2015, the CDC reported 9580 deaths caused by synthetic opioids, primarily fentanyl, a 72% increase from 2014. The European Monitoring Centre for Drugs and Drug Addiction has also encountered several new FAs in the heroin supply. Counterfeit pharmaceuticals containing mixtures of fentanyl and FAs continue to be a poorly recognized worldwide problem despite the WHO classifying several FAs as a serious threat to public health. CONTENT: This review covers the epidemiology of fentanyl abuse and discusses the clinical practice implications of widespread fentanyl abuse. It includes a historical perspective on the illicit FAs that have appeared in the US and European Union and reviews the methods available to identify FAs and emerging technologies useful for identifying previously undescribed analogs. A compilation of structural and mass spectral data on FAs reported thus far is provided. SUMMARY: Fentanyl and FAs have evolved into a global public health threat. It is important to understand the analytical, clinical, and regulatory efforts underway to assist communities affected by the current fentanyl epidemic.

Accumulation of Gadolinium in Human Cerebrospinal Fluid after Gadobutrol-enhanced MR Imaging: A Prospective Observational Cohort Study.

Purpose To determine whether gadolinium accumulates within cerebrospinal fluid (CSF) in patients recently exposed to the macrocyclic agent gadobutrol and identify factors that may affect this accumulation. Materials and Methods In this prospective observational cohort study, gadolinium was quantified by using inductively coupled plasma mass spectrometry of CSF samples from patients who underwent gadobutrol-enhanced magnetic resonance (MR) imaging followed by lumbar puncture within 30 days (gadobutrol group) or patients who underwent lumbar puncture without history of gadolinium-enhanced MR imaging (control group). CSF total protein level of 35 mg/dL or lower was used as a surrogate marker of an intact blood-brain barrier (BBB). Associations between gadolinium CSF concentration and patient characteristics were examined by using log (e)-linear regression models. Results A total of 82 patients (68 in gadobutrol group, 14 in control group; 42 male and 40 female patients; median age, 47 years [interquartile range, 25-65 years]) were included in this study. Gadolinium was detected in the CSF of all 68 patients in the gadobutrol group (100% [95% confidence interval: 94.7, 100]; range, 0.2-1494 ng/mL). CSF total protein level higher than 35 mg/dL and patient age of at least 18 years were associated with higher gadolinium concentrations (estimate: 1.1, with standard error [SE] of 0.26 [P < .001] and 0.91, with SE of 0.37 [P = .02], respectively). Conclusion Intravenous administration of the macrocyclic agent gadobutrol results in gadolinium accumulation within the CSF, even in the setting of normal renal function and no BBB dysfunction.

Antibacterial and Biocompatible Titanium-Copper Oxide Coating May Be a Potential Strategy to Reduce Periprosthetic Infection: An In Vitro Study.

BACKGROUND: Periprosthetic infections are devastating for patients and more efficacious preventive strategies are needed. Surface-modified implants using antibacterial coatings represent an option to cope with this problem; however, manufacturing limitations and cytotoxicity have curbed clinical translation. Among metals with antibacterial properties, copper has shown superior in vitro antibacterial performance while maintaining an acceptable cytotoxicity profile. A thin film containing copper could prevent early biofilm formation to limit periprosthetic infections. This pilot study presents the in vitro antibacterial effect, cytotoxicity, and copper ion elution pattern of a thin film of titanium-copper oxide (TiCuO). QUESTIONS/PURPOSES: (1) Do titanium alloy (Ti6Al4V) discs coated with a thin film of TiCuO reduce Staphylococcus epidermidis biofilm and planktonic cell density compared with uncoated discs? (2) Do Ti6Al4V discs coated with a thin film of TiCuO affect normal human osteoblast viability compared with untreated cells? (3) Is copper ion concentration generated by coated discs lower than previously published copper ion concentrations that cause 50% toxicity in similar human cell lines in vitro (TC50)? METHODS: Ninety Ti6Al4V discs (12.5 mm diameter; 1.25 mm thick) were used in this study. Seventy-two Ti6Al4V discs were coated with a thin film of either titanium oxide (TiO) or TiCuO containing 20%, 40%, or 80% copper using high-power impulse magnetron sputtering (HiPIMS). Eighteen Ti6Al4V discs remained uncoated for control purposes. We tested antibacterial properties of S epidermidis grown on discs in wells containing growth medium. After 24 hours, planktonic bacteria as well as biofilms removed by sonication were quantitatively cultured. Annexin/Pi staining was used to quantify in vitro normal human osteoblast cell viability at 24 hours and Day 7, respectively. Copper elution was measured at Days 1, 2, 3, 7, 14, and 28 using an inductively coupled plasma mass spectrometer to analyze aliquots of culture medium. Copper ion concentration achieved at 24 hours was compared with previously published TC50 for gingival fibroblast, a phenotypically similar cell line with available data regarding copper ion exposure. RESULTS: Discs coated with TiCuO 80% copper showed greater biofilm and planktonic cell density reduction when compared with other tested compositions (analysis of variance [ANOVA]; p < 0.001). Discs coated with TiCuO 80% copper showed mean biofilm and planktonic cell density of 4.0 log10 (SD = 0.4) and 5.7 log10 (SD = 0.2). Discs coated with TiCuO 80% showed a mean difference in biofilm and planktonic cell density of 2.5 log10 (95% confidence interval [CI], 1.9-3.1 log10; p < 0.001) and 1.2 (95% CI, 0.6-1.8; p < 0.001), respectively, when compared with uncoated discs. Normal human osteoblast viability did not differ among all groups at 24 hours (ANOVA; p = 0.2) and Day 7 (ANOVA; p = 0.7). Discs coated with TiCuO 80% copper showed a mean difference (95% CI) in relative cell viability (%) at 24 hours and Day 7 of 31.1 (95% CI, -19.4 to 81.7; p = 0.4) and -5.0 (95% CI, -7.8 to 17.9; p = 0.9), respectively, when compared with untreated cells. For all TiCuO-coated discs, copper ion elution peaked at 24 hours and slowly decreased in a curvilinear fashion to nearly undetectable levels by Day 28. Discs coated with TiCuO 80% copper showed mean copper ion concentration at 24 hours of 269.4 µmol/L (SD = 25.2 µmol/L) and this concentration was lower than previously published TC50 for similar human cell lines at 24 hours (344 µmol/L, SEM = 44 µmol/L). CONCLUSIONS: This pilot study demonstrates a proof of concept that a thin-film implant coating with TiCuO can provide a potent local antibacterial environment while remaining relatively nontoxic to a human osteoblast cell line. Further research in an animal model will be necessary to establish efficacy and safety of this technique and whether it might be useful in the design of implants. CLINICAL RELEVANCE: A thin film coating with TiCuO demonstrates high antibacterial activity and low cellular cytotoxicity to human osteoblasts in vitro. Taken together, these properties represent a potential strategy for preventing periprosthetic infection if further work in animal models can confirm these results in vivo.

Effective Use of Mass Spectrometry in the Clinical Laboratory.

BACKGROUND: Historically the success of mass spectrometry in the clinical laboratory has focused on drugs of abuse confirmations, newborn screening, and steroid analysis. Clinical applications of mass spectrometry continue to expand, and mass spectrometry is now being used in almost all areas of laboratory medicine. CONTENT: A brief background of the evolution of mass spectrometry in the clinical laboratory is provided with a discussion of future applications. Prominent examples of mass spectrometry are covered to illustrate how it has improved the practice of medicine and enabled physicians to provide better patient care. With increasing economic pressures and decreasing laboratory test reimbursement, mass spectrometry testing has been shown to provide cost-effective solutions. In addition to pointing out the numerous benefits, the challenges of implementing mass spectrometry in the clinical laboratory are also covered. SUMMARY: Mass spectrometry continues to play a prominent role in the field of laboratory medicine. The advancement of this technology along with the development of new applications will only accelerate the incorporation of mass spectrometry into more areas of medicine.