Corinne R. Fantz

Barriers to quality health care for the transgender population

The transgender community is arguably the most marginalized and underserved population in medicine. A special issue focusing on mens health would be incomplete without mention of this vulnerable population, which includes those transitioning to and from the male gender. Transgender patients face many barriers in their access to healthcare including historical stigmatization, both structural and financial barriers, and even a lack of healthcare provider experience in treating this unique population. Historical stigmatization fosters a reluctance to disclose gender identity, which can have dire consequences for long-term outcomes due to a lack of appropriate medical history including transition-related care. Even if a patient is willing to disclose their gender identity and transition history, structural barriers in current healthcare settings lack the mechanisms necessary to collect and track this information. Moreover, healthcare providers acknowledge that information is lacking regarding the unique needs and long-term outcomes for transgender patients, which contributes to the inability to provide appropriate care. All of these barriers must be recognized and addressed in order to elevate the quality of healthcare delivered to the transgender community to a level commensurate with the general population. Overcoming these barriers will require redefinition of our current system such that the care a patient receives is not exclusively linked to their sex but also considers gender identity.

VEGF disrupts the neonatal blood-brain barrier and increases life span after non-ablative BMT in a murine model of congenital neurodegeneration caused by a lysosomal enzyme deficiency

The course of certain congenital neurodegenerative diseases like lysosomal storage diseases (LSDs) begins shortly after birth and can progress quickly. Ideally, therapeutic interventions for LSDs, which include bone marrow transplantation (BMT), recombinant enzyme replacement, or systemic viral-mediated gene therapy, should be initiated at birth. However, the blood-brain barrier (BBB) remains an obstacle to effective therapy even when these strategies are initiated at birth. We studied whether VEGF, an endothelial cell mitogen and permeability factor, can open the BBB in newborn mice for therapeutic purposes. Intravenous (IV) administration of VEGF at birth increased BBB permeability within 2 h. The increased permeability persisted for at least 24 h, became undetectable 48 h after injection, and was restricted to newborns. Systemic VEGF treatment before BMT or administration of recombinant lentivirus resulted in increased numbers of both donor cells and virus-transduced cells, respectively, in the recipient brain. Administration of VEGF before BMT in newborn mice with a neurodegenerative LSD, globoid-cell leukodystrophy, resulted in a significant increase in life span compared to affected animals that were injected with saline before BMT.

Use of serum FSH to identify perimenopausal women with pituitary hCG

BACKGROUND Human chorionic gonadotropin (hCG) tests are performed on many female patients before performing medical procedures or administering medications that may harm a fetus. hCG of pituitary origin has been shown to increase with age. Therefore, mild increases in serum hCG in an older patient can be of pituitary origin and does not necessarily indicate pregnancy. The inability to rule out pregnancy in perimenopausal women can create clinical confusion and may delay needed therapies. Our objective was to determine the diagnostic utility of serum follicle-stimulating hormone (FSH) concentrations to rule out hCG of placental origin in perimenopausal women with a low concentration of serum hCG (5.0-14.0 IU/L). METHODS Seven testing centers performed 39 742 physician-ordered serum quantitative hCG tests over a 15-month period. From these, 100 samples from women 41-55 years of age with serum hCG concentrations 5-14 IU/L were identified. We performed FSH testing and patient chart review for each sample. RESULTS Twenty-three patients were found to have hCG of placental origin (pregnancy, resolving abortion, or gestational trophoblastic disease), and in those cases serum FSH was 0.4-43.8 IU/L. An FSH cutoff of 45.0 IU/L identified hCG of placental origin with 100% sensitivity and 75% specificity. FSH >45 IU/L was never observed when hCG was of placental origin (negative predictive value). CONCLUSIONS These data indicate that quantitative serum FSH can be used to rule out pregnancy and hCG of placental origin in women 41-55 years of age with mild increase in serum hCG concentrations.

The analytical specificity of human chorionic gonadotropin assays determined using WHO International Reference Reagents

BACKGROUND Human chorionic gonadotropin (hCG) is a heterodimeric glycoprotein hormone with considerable molecular heterogeneity. There is uncertainty regarding which hCG variants are detected by different hCG assays. The analytical specificity of 8 hCG assays was investigated. METHODS WHO International Reference Reagents for hCG, nicked hCG (hCGn), beta subunit (hCGbeta), nicked beta subunit (hCGbetan), and beta core fragment (hCGbetacf) were individually added to hCG-free human serum. Specimens were analyzed with 8 commercially available hCG assays. Equimolar detection of hCG variants was defined as a recovery of 90-110%. RESULTS All assays detected hCG and hCGn with mean recoveries of 98.3 and 94.6%, respectively. Seven assays detected hCGbeta (mean recovery 103.8%) but with high variation, and equimolar detection was observed only in four. The mean recovery of hCGbetan was 85.5% but was highly variable with only two assays showing equimolar detection. With a mean recovery of 53.4%, two assays detected hCGbetacf and both underestimated it considerably. Information provided by the assay manufacturer regarding hCG variant analytical specificity was inadequate or unclear in 75% of the assays. CONCLUSIONS hCG assays vary considerably in their ability to detect different hCG variants. Manufacturers of hCG assays should clearly indicate the hCG variant specificity of their reagent systems.

Diffusion tensor imaging detects axonal injury and demyelination in the spinal cord and cranial nerves of a murine model of globoid cell leukodystrophy.

Globoid cell leukodystrophy is an inherited neurodegenerative disorder caused by a deficiency of the lysosomal enzyme galactosylceramidase. In both human patients and the authentic murine Twitcher model, pathological findings include demyelination as well as axonal damage in both the central and peripheral nervous system. Diffusion tensor imaging (DTI) has emerged as a powerful noninvasive technique that is sensitive to these white matter disease processes. Increases in radial diffusivity (λ⟂) and decreases in axial diffusivity (λ∥) correlate with histopathological evidence of demyelination and axonal damage, respectively. Compared to age‐matched, normal littermates, DTI of optic nerve and trigeminal nerve in end‐stage Twitcher mice displayed a statistically significant increase in λ⟂ and decrease in λ∥, consistent with previously characterized demyelination and axonal damage in these regions. In the Twitcher spinal cord, a statistically significant decrease in λ∥ was identified in both the dorsal and ventrolateral white matter, relative to normal controls. These results were consistent with immunofluorescence evidence of axonal damage in these areas as detected by staining for nonphosphorylated neurofilaments (SMI32). Increase in λ⟂ in Twitcher spinal cord white matter relative to normal controls reached statistical significance in the dorsal columns and approached statistical significance in the ventrolateral region. Correlative reduced levels of myelin basic protein were detected by immunofluorescent staining in both these white matter regions in the Twitcher spinal cord. Fractional anisotropy, a nonspecific but sensitive indicator of white matter disease, was significantly reduced in the optic nerve, trigeminal nerve, and throughout the spinal cord white matter of Twitcher mice, relative to normal controls. This first reported application of spinal cord DTI in the setting of GLD holds potential as a noninvasive, quantitative assay of therapeutic efficacy in future treatment studies. Copyright

Patient Misidentifications Caused by Errors in Standard Bar Code Technology

BACKGROUND Bar code technology has decreased transcription errors in many healthcare applications. However, we have found that linear bar code identification methods are not failsafe. In this study, we sought to identify the sources of bar code decoding errors that generated incorrect patient identifiers when bar codes were scanned for point-of-care glucose testing and to develop solutions to prevent their occurrence. METHODS We identified misread wristband bar codes, removed them from service, and rescanned them by using 5 different scanner models. Bar codes were reprinted in pristine condition for use as controls. We determined error rates for each bar code-scanner pair and manually calculated internal bar code data integrity checks. RESULTS As many as 3 incorrect patient identifiers were generated from a single bar code. Minor bar code imperfections, failure to control for bar code scanner resolution requirements, and less than optimal printed bar code orientation were confirmed as sources of these errors. Of the scanner models tested, the Roche ACCU-CHEK® glucometer had the highest error rate. The internal data integrity check system did not detect these errors. CONCLUSIONS Bar code-related patient misidentifications can occur. In the worst case, misidentified patient results could have been transmitted to the incorrect patient medical record. This report has profound implications not only for point-of-care testing but also for bar coded medication administration, transfusion recipient certification systems, and other areas where patient misidentifications can be life-threatening. Careful control of bar code scanning and printing equipment specifications will minimize this threat to patient safety. Ultimately, healthcare device manufacturers should adopt more robust and higher fidelity alternatives to linear bar code symbologies.

Falsely Decreased Human Chorionic Gonadotropin (hCG) Results Due to Increased Concentrations of the Free β Subunit and the β Core Fragment in Quantitative hCG Assays

BACKGROUND Earlier studies have shown that increased concentrations of certain human chorionic gonadotropin (hCG) variants can cause false-negative results in some qualitative hCG devices. The objective of this study was to determine if increased concentrations of hCGβ and hCGβ core fragment (hCGβcf) cause falsely decreased results on 9 commercially available quantitative hCG assays. METHODS Several concentrations of purified hCGβ and hCGβcf were added to 2 sets of 6 serum samples with and without a fixed concentration of intact hCG. We examined 9 widely used immunoassays to measure immunoreactive hCG. Falsely decreased results were defined as those in which the measured hCG concentration was ≤50% of expected. RESULTS High concentrations of hCGβ (≥240 000 pmol/L) produced falsely decreased hCG measurements in 2 assays known to detect this variant. Similarly, high concentrations of hCGβcf (≥63 000 pmol/L) produced falsely decreased hCG measurements in 3 assays that do not detect purified hCGβcf. Two assays were identified that detected both hCGβ and hCGβcf, and neither produced falsely decreased results in the presence of high concentrations of these variants. CONCLUSIONS Extremely high concentrations of hCG variants can cause falsely decreased results in certain quantitative hCG assays. Of the 9 assays examined, none exhibited falsely decreased results in the presence of hCGβ concentrations typically associated with hCGβ-producing malignancies. Two assays exhibited decreased (>50%) hCG results in the presence of hCGβcf concentrations found during normal pregnancy.

Current Evidence and Future Perspectives on the Effective Practice of Patient-Centered Laboratory Medicine

BACKGROUND Systematic evidence of the contribution made by laboratory medicine to patient outcomes and the overall process of healthcare is difficult to find. An understanding of the value of laboratory medicine, how it can be determined, and the various factors that influence it is vital to ensuring that the service is provided and used optimally. CONTENT This review summarizes existing evidence supporting the impact of laboratory medicine in healthcare and indicates the gaps in our understanding. It also identifies deficiencies in current utilization, suggests potential solutions, and offers a vision of a future in which laboratory medicine is used optimally to support patient care. SUMMARY To maximize the value of laboratory medicine, work is required in 5 areas: (a) improved utilization of existing and new tests; (b) definition of new roles for laboratory professionals that are focused on optimizing patient outcomes by adding value at all points of the diagnostic brain-to-brain cycle; (c) development of standardized protocols for prospective patient-centered studies of biomarker clinical effectiveness or extraanalytical process effectiveness; (d) benchmarking of existing and new tests in specified situations with commonly accepted measures of effectiveness; (e) agreed definition and validation of effectiveness measures and use of checklists for articles submitted for publication. Progress in these areas is essential if we are to demonstrate and enhance the value of laboratory medicine and prevent valuable information being lost in meaningless data. This requires effective collaboration with clinicians, and a determination to accept patient outcome and patient experience as the primary measure of laboratory effectiveness.

Improving Quality of Patient Care in an Emergency Department A Laboratory Perspective

The purpose of our study was to improve the quality of care in an emergency department (ED) as measured by length of stay (LOS), total turnaround time (TAT) for laboratory result reporting, and the blood culture contamination rate. Data were included for patients who had at least 1 of 5 laboratory tests performed as part of their care. The study was conducted in 2 phases. First, phlebotomy was performed by a dedicated phlebotomist or nonlaboratory personnel. The second phase added a dedicated laboratory technologist. There was a significant reduction in total TAT for all tests (at least 46 and 75 minutes in the respective interventions), and blood culture contamination rates dropped from 5.0% to 1.1%, although the overall LOS did not change. Estimated cost avoidance is more than

Laboratory Monitoring of Heparin: Challenges and Opportunities

400,000 annually. Quality of care in an ED is improved when samples are collected by a dedicated phlebotomist, but overall LOS does not change.