William Clarke

William Clarke
Johns Hopkins Medicine | JHUSOM · Department of Pathology

PhD, MBA

About

149
Publications
26,284
Reads
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3,078
Citations
Additional affiliations
January 2004 - December 2013
Johns Hopkins Medicine
January 2003 - December 2012
Johns Hopkins University
July 1995 - June 2000
University of Nebraska at Lincoln
Position
  • PhD Student

Publications

Publications (149)
Article
Full-text available
Background: The addition of a calibration curve with every run is both time-consuming and expensive for clinical mass spectrometry assays. We present alternative calibration strategies that eliminate the need for a calibration curve except as required by laboratory regulations. Methods: We measured serum nortriptyline concentrations prospectivel...
Article
Busulfan pharmacokinetic (PK) monitoring of the area under the concentration-time curve (AUC) is necessary to minimize adverse events associated with both under- and over-dosing of busulfan during hematopoietic stem cell transplantation (HSCT). Three strategies are frequently used to calculate the AUC including in-house polynomial methods, the trap...
Article
Introduction: Universal HIV testing and treatment (UTT) has individual and public health benefits. HPTN 071 (PopART), a community-randomized trial in Zambia and South Africa, demonstrated that UTT decreased HIV incidence. This endpoint was assessed in a cohort of >48,000 randomly selected adults in the study communities. We evaluated the impact of...
Article
Full-text available
Background Assays and multi-assay algorithms (MAAs) have been developed for population-level cross-sectional HIV incidence estimation. These algorithms use a combination of serologic and/or non-serologic biomarkers to assess the duration of infection. We evaluated the performance of four MAAs for individual-level recency assessments. Methods Sampl...
Article
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Background Emergency Departments (EDs) have served as critical surveillance sites for infectious diseases. We sought to determine the prevalence and temporal trends of acute (by PCR) and convalescent (by antibody [Ab]) SARS-CoV-2 infection during the earliest phase of the pandemic among patients in an urban ED in Baltimore City. Methods We tested...
Article
Background: We assessed the performance of CoronaCHEK lateral flow assay on samples from Uganda and Baltimore to determine the impact of geographic origin on assay performance. Methods: Plasma samples from SARS-CoV-2 PCR+ individuals (Uganda: 78 samples from 78 individuals and Baltimore: 266 samples from 38 individuals) and from pre-pandemic indivi...
Preprint
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Background: We assessed the performance of CoronaCHEK lateral flow assay on samples from Uganda and Baltimore to determine the impact of geographic origin on assay performance. Methods: Serum samples from SARS-CoV-2 PCR+ individuals (Uganda: 78 samples from 78 individuals and Baltimore: 266 samples from 38 individuals) and from pre-pandemic indi...
Article
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Objectives HPTN 075 enrolled men who have sex with men (MSM) and transgender women (TGW) in sub-Saharan Africa. Persons in HIV care or on antiretroviral treatment (ART) were not eligible to enroll. We evaluated antiretroviral (ARV) drug use, viral suppression, and drug resistance in this cohort over a 12-month follow-up period. Methods Assessments...
Article
Objective: Vietnam, Indonesia, and Ukraine have major burdens of injection drug use (IDU) and HIV. We estimated prevalence of depressive symptoms at baseline among people living with HIV (PLWH) who inject drugs, evaluated associations between depression at baseline and 12-month HIV care outcomes and medication-assisted treatment (MAT), and evaluat...
Article
Background. Rapid point-of-care tests (POCTs) for SARS-CoV-2-specific antibodies vary in performance. A critical need exists to perform head-to-head comparison of these assays. Methods. Performance of fifteen different lateral flow POCTs for the detection of SARS-CoV-2-specific antibodies was performed on a well characterized set of 100 samples. Of...
Article
Accurate serological assays to detect antibodies to SARS-CoV-2 are needed to characterize the epidemiology of SARS-CoV-2 infection and identify potential candidates for COVID-19 convalescent plasma (CCP) donation. This study compared the performance of commercial enzyme immunoassays (EIAs) to detect IgG or total antibodies to SARS-CoV-2 and neutral...
Article
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Objective Female sex workers (FSW) have increased risk of HIV infection. Antiretroviral treatment (ART) can improve HIV outcomes and prevent HIV transmission. We analyzed antiretroviral (ARV) drug use and HIV drug resistance among HIV-positive FSW in the Dominican Republic and Tanzania. Methods Plasma samples collected at study entry with viral lo...
Article
Immunosuppressant medications help suppress the immune system response through inhibition of various checkpoints in the regulatory biochemical pathway. This is useful in prevention of organ rejection in transplantation or in the treatment of autoimmune diseases such as lupus or rheumatoid arthritis. Quantification of immunosuppressive drugs in bloo...
Article
Bone marrow transplantation is used to treat particular types of cancers such as lymphoma, leukemia, and multiple myeloma. Appropriate dosing of busulfan during the preparative phase is critical for a successful allograft; if blood concentrations get too high significant liver toxicity can occur, if blood concentrations are too low, then graft‐vers...
Article
Full-text available
Background Persons who inject drugs (PWID) have high HIV incidence and prevalence, and may have limited access to antiretroviral therapy (ART) in some settings. We evaluated HIV drug resistance in PWID in a randomized clinical trial (HPTN 074). The study intervention included ART at any CD4 cell count with enhanced support for ART and substance use...
Article
A one-site immunometric assay based on affinity microcolumns was developed for the analysis of alpha1-acid glycoprotein (AGP) as a model protein biomarker. In this assay, a sample containing AGP was incubated with an excess amount of a labeled binding agent, such as fluorescein-labeled anti-AGP antibodies or Fab fragments. The excess binding agent...
Article
Full-text available
We used antiretroviral (ARV) drug testing to evaluate the accuracy of self-reported data for HIV status and antiretroviral treatment (ART) among people who inject drugs enrolled in an HIV prevention trial. ARV drugs were detected in enrollment samples from 72/482 = 14.9% HIV-infected participants (39/52 = 75.0% who reported being on ART; 33/430 = 7...
Article
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Some HIV-infected individuals in research studies may choose not to disclose knowledge of their HIV status to study staff. We evaluated the accuracy of self-reported HIV status among African men and transgender women who have sex with men and who were screened for a research study. Sixty-seven of 183 HIV-infected participants reported a prior HIV d...
Chapter
Human alpha1-acid glycoprotein (AGP) is an acute phase glycoprotein that has a heterogeneous glycosylation pattern. This pattern can change in certain diseases, which has resulted in interest in using AGP glycoforms as potential biomarkers for these diseases. This report describes a method that uses capillary electrophoresis to characterize and ana...
Article
Human alpha1-acid glycoprotein (AGP) is an acute phase glycoprotein that has a heterogeneous glycosylation pattern. This pattern can change in certain diseases, which has resulted in interest in using AGP glycoforms as potential biomarkers for these diseases. This report describes a method that uses capillary electrophoresis to characterize and ana...
Article
Background: Some individuals control HIV replication without antiretroviral (ARV) therapy. Objective: To analyze viral suppression in young women in rural South Africa enrolled in a trial evaluating a behavioral intervention for HIV prevention. Methods: Plasma samples were obtained from women ages 13–24 (81 infected at enrollment, 164 seroconverter...
Article
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Introduction People who inject drugs (PWID) experience high HIV incidence and face significant barriers to engagement in HIV care and substance use treatment. Strategies for HIV treatment as prevention and substance use treatment present unique challenges in PWID that may vary regionally. Understanding differences in the risk structure for HIV tran...
Article
Background: Antiretroviral (ARV) drugs are used for HIV treatment and prevention. We analyzed ARV drug use and HIV drug resistance in a cohort of young women in rural South Africa enrolled in the HPTN 068 study, which evaluated use of a cash transfer conditional on school attendance to reduce HIV incidence. Methods: ARV drug testing was performe...
Article
Objective: To analyze antiretroviral drug use and HIV drug resistance among HIV-infected MSM and transgender women who were screened for participation in the HIV Prevention Trials Network 075 study. Methods: A qualitative assay was used to detect 20 antiretroviral drugs in five drug classes; this assay is based on liquid chromatography coupled w...
Article
A method based on capillary electrophoresis (CE) with electrophoretic injection and absorbance detection was developed for the direct analysis of AGP glycoforms in human serum. Electrophoretic injection of AGP was performed in the reversed-polarity mode of CE with a capillary coated with poly(ethylene oxide) and that had minimal electroosmotic flow...
Article
A method that combined on-line immunoextraction with high-performance affinity chromatography was developed to examine the binding of drugs with α1-acid glycoprotein (AGP). Affinity microcolumns containing immobilized polyclonal anti-AGP antibodies were developed that had a capture efficiency of up to 98.4% for AGP and a binding capacity of 0.72nmo...
Article
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Antiretroviral pre-exposure prophylaxis (PrEP) has been demonstrated to decrease HIV acquisition in multiple efficacy trials, but medication adherence is critical, and was suboptimal in several studies. Fifty HIV-uninfected at risk men who have sex with men (MSM) were randomized to a cognitive behavioral intervention condition or a time and session...
Article
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Daily oral tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) is a safe and effective intervention for HIV pre-exposure prophylaxis (PrEP). We evaluated the performance of a qualitative assay that detects 20 antiretroviral (ARV) drugs for assessing recent PrEP exposure (multi-drug assay; detection limit: 2-20 ng/mL). Samples were obtained from 2...
Article
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Objectives: New data have emerged from ambulatory and acute care settings about adverse patient events, including death, attributable to erroneous blood glucose meter measurements and leading to questions over their use in critically ill patients. The U.S. Food and Drug Administration published new, more stringent guidelines for glucose meter manu...
Chapter
Over the past decade, mass spectrometry has grown from a primary use as an analytical method relegated to research or industrial applications to a method routinely applied in clinical settings. The utilization of mass spectrometry in a clinical setting requires accurate and robust measurement of diverse sets of analytes from a variety of matrices....
Chapter
Health care is increasingly challenged by issues of clinically managing obese patients; this is of increased interest because the proportion of obese people in the general population is higher than ever and continues to increase. Obesity impacts the distribution of drugs and has been shown to impact metabolism and renal clearance as well. One clini...
Chapter
Therapeutic drug monitoring (TDM) is a key component of patient management for a select group of drugs that demonstrate significant interindividual variability in their pharmacokinetics and pharmacodynamics. Using pharmacokinetically guided dose adjustment is also a critical piece of personalized medicine in many cases. This chapter covers the emer...
Chapter
In this chapter, practical aspects of integrating therapeutic drug monitoring (TDM) in a hospital system are discussed with special emphasis on how frequently drug monitoring should be ordered, turnaround time, who should interpret results (pharmacist vs laboratory professionals), and overall cost savings to the hospital due to TDM.
Article
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Background HIV populations often diversify in response to selective pressures, such as the immune response and antiretroviral drug use. We analyzed HIV diversity in Black men who have sex with men who were enrolled in the HIV Prevention Trials Network 061 study. Methods A high resolution melting (HRM) diversity assay was used to measure diversity...
Data
High resolution melting (HRM) scores and demographic, behavioral, and clinical factors of HIV-infected men analyzed using the HRM diversity assay in HPTN 061. (CSV)
Article
Background: Antiretroviral (ARV) drug treatment benefits the treated individual and can prevent HIV transmission. We assessed ARV drug use in a community-randomized trial that evaluated the impact of behavioral interventions on HIV incidence. Methods: Samples were collected in a cross-sectional survey after a 3-year intervention period. ARV drug...
Conference Paper
Full-text available
Background: Men who have sex with men (MSM) are the highest risk group for HIV in the U.S.. Pre-exposure prophylaxis (PrEP) in the form of oral antiretroviral therapy (tenofovir disoproxil fumarate (TDF)/emtricitabine (FTC) combination) has been shown to decrease HIV incidence in MSM. Optimal protection, however, is dependent on medication adherenc...
Article
Full-text available
In response to the 2014-2015 Ebola Virus Disease outbreak in West Africa, Johns Hopkins Medicine created a biocontainment unit to care for patients infected with Ebola virus and other high-consequence pathogens. The unit team examined published literature and guidelines, visited two existing U.S. biocontainment units, and contacted national and int...
Article
Background Current methods for the detection of single nucleotide polymorphisms (SNPs) associated with aberrant drug-metabolizing enzyme function are hindered by long turnaround times and specialized techniques and instrumentation. In this study, we describe the development and validation of a high-resolution melting (HRM) curve assay for the rapid...
Article
Full-text available
Objective: The Johns Hopkins Hospital Emergency Department has served as a window on the HIV epidemic for 25 years, and as a pioneer in emergency department-based screening/linkage-to-care (LTC) programs. We document changes in the burden of HIV and HIV care metrics to the evolving HIV epidemic in inner-city Baltimore. Design/methods: We analyze...
Article
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Hydroxychloroquine (HQ) is used routinely in the treatment of autoimmune disorders such as rheumatoid arthritis and lupus erythematosus. Issues such as marked pharmacokinetic variability and patient non-compliance make therapeutic drug monitoring of HQ a useful tool for management of patients taking this drug. Quantitative measurements of HQ may ai...
Article
Tricyclic antidepressants (TCA) are used to treat major depressive disorder and other psychological conditions. The efficacy of these drugs is tied to a narrow therapeutic window. Inappropriately high drug concentrations can result in serious side effects such as hypotension, tachycardia, or coma. As a result, concentrations of tricyclic antidepres...
Article
Docetaxel is a second-generation taxane and is used clinically as an anti-neoplastic agent in cancer chemotherapy via an anti-mitotic mechanism. Its efficacy is limited to a narrow therapeutic window. Inappropriately high concentrations may cause erythema, fluid retention, nausea, diarrhea, and neutropenia. As a result, dosing recommendations have...
Article
Full-text available
Antiretroviral (ARV) drug use was analyzed in HIV-uninfected women in an observational cohort study conducted in 10 urban and periurban communities in the United States with high rates of poverty and HIV infection. Plasma samples collected in 2009-2010 were tested for the presence of 16 ARV drugs. ARV drugs were detected in samples from 39 (2%) of...
Article
Full-text available
Objective: Hydroxychloroquine (HCQ) is used for its effect on systemic lupus erythematosus (SLE) disease activity and longterm benefits. This can be limited by adherence. One way to assess adherence is to measure blood levels. Conflicting data exist regarding blood levels and disease activity. There is disagreement about dosing; rheumatologists re...
Article
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SESSION TITLE: Critical Care Posters III SESSION TYPE: Original Investigation Poster PRESENTED ON: Wednesday, October 28, 2015 at 01:30 PM - 02:30 PM PURPOSE: In response to the Ebola Virus Disease (EVD) crisis in West Africa, Johns Hopkins Medicine (JHM) created a new biocontainment and treatment unit (BCU) to safely care for patients with EVD and...
Article
Introduction: Modern lipid analysis requires mass spectrometric techniques, though to date these have been developed and applied primarily to histological serial sections. As such, there has been little emphasis on using mass spectrometry in such a way that the same specimen can yield both chemical and morphological information. Here, we present a...
Article
Full-text available
Background Therapeutic drug monitoring for hydroxychloroquine (HCQ) has been suggested to assess nonadherence and optimize treatment efficacy in systemic lupus erythematosus patients. Materials & methods After protein precipitation, HCQ and its metabolites, desethylhydroxychloroquine and desethylchloroquine were separated on a phenyl column and mo...
Article
Full-text available
Development and validation of a selective, robust high-performance liquid chromatography-tandem mass spectrometric (HPLC/MS-MS) method for the quantification of morphine, morphine-3-β-glucuronide, morphine-6-β-glucuronide, hydromorphone, and normorphine in human serum. Drug-free human serum samples spiked with morphine, morphine-3-β-glucuronide, mo...
Article
There is a high coincidence between obesity and psychiatric disorders including depression. Depressive disorders are commonly treated with antidepressants, including the selective serotonin reuptake inhibitor Lexapro (escitalopram). Although candidates for elective Roux-en-Y gastric bypass (RYGB) surgery may be treated with escitalopram, drug dosin...
Article
Full-text available
Background Hydroxychloroquine (HCQ) is used for systemic lupus erythematosus (SLE) disease activity and its long-term benefits. Its effectiveness is limited by adherence. One way to assess adherence is blood levels of HCQ. There are conflicting data on the relationship between HCQ levels in blood and disease activity. Controversy also exists regard...
Article
HPTN 061 enrolled Black men who have sex with men in the United States. Some men with low/undetectable HIV RNA had unusual patterns of antiretroviral (ARV) drug use or had drugs detected in the absence of viral suppression. This report includes a comprehensive analysis of ARV drug use and drug resistance among men in HPTN 061 who were not virally s...
Article
In resource-limited settings, HIV infection is often diagnosed using two rapid tests. If the results are discordant, a third tie-breaker test is often used to determine HIV status. This study characterized samples with discordant rapid tests and compared different testing strategies for determining HIV status in these cases. Samples were previously...
Article
The immunosuppressants cyclosporine, tacrolimus, sirolimus, everolimus, and probably also mycophenolic acid, require therapeutic drug monitoring (TDM)-guided dosing to ensure that blood concentrations are kept within the target range in transplant patients. Reliable, accurate and precise test methods are therefore essential in order to effectively...
Article
The differences in free fraction serum valproic acid concentrations between inpatients and outpatients were compared, and factors associated with therapeutic discordance were evaluated. This retrospective, single-center, cross-sectional study included patients with both a free and a total valproic acid concentration drawn within 30 minutes of each...
Article
Fourth-generation HIV assays detect both antigen and antibody, facilitating detection of acute/early HIV infection. The Bio-Rad GS HIV Combo Ag/Ab assay (Bio-Rad Combo) is an enzyme immunoassay that simultaneously detects HIV p24 antigen and antibodies to HIV-1 and HIV-2 in serum or plasma.Objective To evaluate the performance of the Bio-Rad Combo...
Article
Full-text available
Lack of human immunodeficiency virus (HIV) infection awareness may be a driver of racial disparities in HIV infection among men who have sex with men (MSM). Lack of awareness is typically measured by comparing HIV test result to self-reported HIV status. This measure may be subject to reporting bias and alternatives are needed. The InvolveMENt stud...
Article
HIV RNA levels are usually high early in HIV infection. In the HPTN 061 study, men were tested for HIV infection every six months; six (21.4%) of 28 men who acquired HIV infection during the study had low or undetectable HIV RNA at the time of HIV diagnosis. Antiretroviral drugs were not detected at the time of HIV diagnosis. False-negative HIV tes...
Article
Objectives: Depression is a rapidly growing issue in the United States. There are many drug classes that may be used to treat depression, including the selective serotonin-reuptake inhibitors (SSRIs) citalopram (Celexa®) and sertraline (Zoloft®), as well as the aminoketone bupropion (Wellbutrin®). However, therapeutic efficacy and treatment succes...
Article
Full-text available
: Immunosuppressant drugs (ISDs) are commonly prescribed to solid organ transplant patients. Their narrow therapeutic index and potential for toxicity necessitates careful monitoring of blood concentrations. Liquid chromatography tandem mass spectrometry (LC-MS/MS) methods are increasingly used for ISD measurement. However, there remain many challe...
Article
Full-text available
High resolution mass spectrometers have directly enabled clinical applications of high clinical utility. These types of mass spectrometers are less known to the general public than their low resolution counterparts and are often ascribed to proteomics or biomarker discovery. This perception is rapidly changing as high resolution mass spectrometers...
Article
Full-text available
Background: In the HIV Prevention Trials Network (HPTN) 061 study, 8 (2.3%) of 348 HIV-infected participants identified as HIV uninfected at study enrollment using a single HIV rapid test for screening were found to be HIV infected after additional testing. Objectives: To evaluate the performance of different HIV assays for detection of HIV infe...
Article
Full-text available
American Black men who have sex with men (MSM) are disproportionately affected by HIV, but the factors associated with this concentrated epidemic are not fully understood. Black MSM were enrolled in 6 US cities to evaluate a multi-component prevention intervention, with the current analysis focusing on the correlates of being newly diagnosed with H...