Hydroxychloroquine (HCQ) is an immunomodulator used in dermatology and rheumatology. Side effects may be observed on routine monitoring studies before they become clinically apparent. The goal of this retrospective chart review was to assess laboratory abnormalities in dermatologic and rheumatologic patients taking HCQ. Medical records of patients prescribed HCQ were retrospectively reviewed. Demographics, reported side effects, and parameters on baseline and follow-up complete blood count (CBC) and comprehensive metabolic panel (CMP) were recorded and graded. Laboratory abnormalities were considered severe if they were grade 3 or greater according to Common Terminology Criteria for Adverse Events v3.0 and persistent if they continued beyond subsequent laboratory testing. Of 646 eligible charts, 289 had monitoring studies for review. There were 35 severe (grade 3 or 4, 35/289; 12%) adverse events that developed, as noted on CBC or CMP. Of these 35 severe adverse events, 25 self-corrected on subsequent testing, and 10 (10/289, 3%) across 9 patients were persistent, including glomerular filtration rate, alanine transferase, alkaline phosphatase, glucose, hemoglobin and lymphopenia abnormalities. Of these 10 abnormalities, 7/10 (70%) were unlikely due to hydroxychloroquine use according to the calculated Naranjo score for each patient. Severe laboratory abnormalities while taking hydroxychloroquine are rare, even in a population with a high rate of comorbidities. Among the abnormalities observed, the majority of them (70%) were likely due to disease progression or a medication other than hydroxychloroquine. CBC and CMP monitoring for the reason of observing abnormalities while on HCQ should be at the discretion of the prescribing physician.

A universal calibrator for the determination of all anti-Xa inhibitors would support laboratory processes. We aimed to test the clinical performance of an anti-Xa assay utilizing a universal edoxaban calibrator to determine clinically relevant concentrations of all anti-Xa inhibitors. Following a pilot study, we enrolled 553 consecutive patients taking rivaroxaban, edoxaban, or apixaban from nine study centers in a prospective cross-sectional study. The Technochrom® anti-Xa assay was conducted using the Technoview® edoxaban calibrator. Using ultra-high-performance liquid chromatography-tandem mass spectrometry (LC-MS/MS), anti-Xa inhibitor drug concentrations were determined. Sensitivities and specificities to detect three clinically relevant drug concentrations (30 µgL-1, 50 µgL-1, 100 µgL-1) were determined. Overall, 300 patients treated with rivaroxaban, 221 with apixaban, and 32 with edoxaban were included. The overall correlation coefficient (rs) was 0.95 (95% CI 0.94, 0.96). An area under the receiver operating characteristic curve of 0.96 for 30 µgL-1, 0.98 for 50 µgL-1, and 0.99 for 100 µgL-1 was found. The sensitivities were 92.3% (95% CI 89.2, 94.6), 92.7% (89.4, 95.1), and 94.8% (91.1, 97.0), respectively (specificities 82.2%, 93.7%, and 94.4%). In conclusion, the clinical performance of a universal, edoxaban-calibrated anti-Xa assay was solid and most drug concentrations were predicted correctly.

UNASSIGNED: Applying a single anti-Xa assay, calibrated to unfractionated heparin to measure rivaroxaban, apixaban, and edoxaban would simplify laboratory procedures and save healthcare costs.
UNASSIGNED: We hypothesized that a heparin-calibrated anti-Xa assay would accurately measure rivaroxaban, apixaban, and edoxaban drug concentrations and correctly predict clinically relevant drug levels.
UNASSIGNED: This analysis is part of the Simple-Xa study, a prospective multicenter cross-sectional study conducted in clinical practice. Patients treated with rivaroxaban, apixaban, or edoxaban were included. Anti-Xa activity was measured using the Siemens INNOVANCE® Heparin assay. Drug concentrations were determined using ultra-high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS). Cut-off levels were determined in a derivation dataset (50% of patients) and sensitivities and specificities were calculated in a verification dataset (50% of patients).
UNASSIGNED: Overall, 845 patients were available for analysis. Correlation coefficients (r s ) between the heparin-calibrated anti-Xa assay and drug concentrations were 0.97 (95% CI 0.97, 0.98) for rivaroxaban, 0.96 (0.96, 0.97) for apixaban, and 0.96 (0.94, 0.99) for edoxaban. The area under the receiver operating characteristics curve (ROC) was 0.99 for all clinically relevant drug concentrations. In the verification dataset, the sensitivity was 94.2% (95% CI 90.8-96.6) for 30 μg L-1, 95.8% (92.4-98.0) for 50 μg L-1, and 98.7% (95.5-99.9) for 100 μg L-1. Specificities were 86.3% (79.2-91.7), 89.8% (84.5-93.7), and 88.7% (84.2-92.2), respectively.
UNASSIGNED: In a large prospective study in clinical practice, a strong correlation of heparin-calibrated anti-Xa measurements with LC-MS/MS results was observed and clinically relevant drug concentrations were predicted correctly.

Background: The thrombin generation assay (TG) is a promising approach to measure the degree of anticoagulation in patients treated with direct oral anticoagulants (DOAC). A strong association with plasma drug concentrations would be a meaningful argument for the potential use to monitor DOAC. Objectives: We aimed to study the correlation of TG with rivaroxaban, apixaban, and edoxaban drug concentrations in a large, prospective multicenter cross-sectional study. Methods: Five-hundred and fifty-nine patients were included in nine tertiary hospitals. The Technothrombin® TG was conducted in addition to an anti-Xa assay; LC-MS/MS was performed as the reference standard. Results: Correlation (rs) between thrombin generation measurements and drug concentrations was -0.72 for peak thrombin generation (95% confidence interval, CI, -0.77, -0.66), -0.55 for area under the curve (AUC; 95% CI -0.61, -0.48), and 0.80 for lag time (95% CI 0.75, 0.84). In contrast, rs was 0.96 with results of the anti-Xa activity (95% CI 0.95-0.97). Sensitivity with regard to the clinically relevant cut-off value of 50 μgL-1 was 49% in case of peak thrombin generation (95% CI, 44, 55), 29% in case of AUC (95% CI, 24, 34), and 64% in case of lag time (95% CI, 58, 69). Sensitivity of the anti-Xa assay was 95% (95% CI, 92, 97). Conclusions: The correlation of thrombin generation measurements with DOAC drug concentrations was weak, and clinically relevant drug levels were not predicted correctly. Our results do not support an application of TG in the monitoring of DOAC.

OBJECTIVE: Literature regarding the cost and necessity of laboratory monitoring during oral antifungal treatment in adults has recently been published. However, consensus guidelines for the treatment and monitoring of pediatric patients with systemic antifungals for onychomycosis are lacking. We sought to evaluate both the practice trends and perspectives of pediatric dermatology providers who treat pediatric onychomycosis.
METHODS: An electronic survey was administered to providers belonging to the Society for Pediatric Dermatology (SPD) and/or Pediatric Dermatology Research Alliance (PeDRA) regarding their clinical practice and reasoning for laboratory monitoring during the treatment of pediatric onychomycosis.
RESULTS: One hundred and twenty-one providers completed the survey (12.5%). 77% identified themselves as pediatric dermatologists. A majority practice in the academic setting (51%), and 54% were primarily only pediatric providers. All respondents prescribe oral terbinafine for onychomycosis. 88% of respondents always or almost always confirm the diagnosis of onychomycosis prior to prescribing oral terbinafine for onychomycosis. 39% always or almost always routinely order baseline laboratory tests while 40% never or almost never do. 41% never or almost never order monitoring laboratory tests during treatment while 32% always or almost always do. 91.5% have never discovered a significant reaction to terbinafine with routine monitoring.
CONCLUSIONS: Pediatric dermatology providers are very likely to confirm the diagnosis of onychomycosis prior to systemic treatment. Significant variability was found in pretreatment and treatment laboratory monitoring, reasons for laboratory monitoring or deferral of testing, and timing of testing among providers. Knowledge of current practice trends as well as provider perspectives may be useful in the future development of consensus guidelines.

OBJECTIVE: Tuberculosis (TB) is the leading cause of death in HIV-positive people. In Kenya, 140 000 new TB cases occurred in 2019, and 13 000 HIV-positive patients died due to TB. The objective of this study was to investigate the role of high-sensitivity C-reactive protein (HS-CRP) in TB diagnosis and the prediction of mortality in HIV-positive patients.
METHODS: The IDEA-TB Study enrolled HIV-positive adult patients attending three DREAM centres in Kenya who were suspected of having TB. A lateral flow urine lipoarabinomannan assay (LF-LAM), serum HS-CRP, and GeneXpert MTB/RIF assay (Xpert MTB/RIF) were performed. Six-month survival was evaluated.
RESULTS: A total of 574 patients were enrolled. The median (interquartile range) age, body mass index, and CD4 count were 45 years (37-54 years), 20.5 kg/m2 (18.5-23.69 kg/m2), and 477 cells/mL (290-700 cells/mL), respectively. TB was confirmed in 87 (15.2%) patients. Concordance between the Xpert MTB/RIF and LF-LAM tests was 87.1%. HS-CRP was higher in TB patients (35.39 mg/l vs 9.21 mg/l). Malnutrition and elevated HS-CRP were associated with TB: odds ratio (OR) 2.5 (95% confidence interval (CI) 1.14-5.72) and OR 6.6 (95% CI 3.87-11.52), respectively. Nine (1.6%) patients died during follow-up. No single factor was associated with mortality. Only the combination of malnutrition and elevated HS-CRP was highly predictive of death (odds ratio (OR) 9.8, 95% CI 1.88-50.95); the association was stronger in TB patients (33.3% vs 1.0%; OR 47.6, 95% CI 7.03-322.23).
CONCLUSIONS: TB diagnosis in HIV-positive patients remains challenging. HS-CRP could play a role in predicting early mortality in symptomatic patients.

BACKGROUND: The objectives of this retrospective cohort study are to describe rates of adherence to laboratory testing 6 months to 3 years post-liver transplantation and to examine demographic and clinical factors related to lab non-adherence and the association with medication adherence and clinical outcomes.
METHODS: Medical chart review was conducted for 54 youth (mean age = 5.0 years) transplanted between 2003 and 2014. Lab adherence (≥80%) was measured as the proportion of completed labs out of the number expected. Immunosuppressant drug-level variability was used as a proxy for medication adherence. Clinical outcomes included LAR, viral infection, hospitalization, and non-routine clinic visit ≥12 months after transplant.
RESULTS: Lab adherence decreased substantially over time. Single-parent household (aOR 5.86; 95% CI: 1.38-24.93) and no history of early rejection (aOR 3.96; 95% CI: 1.04-15.24) were independently associated with non-adherence. Lab non-adherence was significantly associated with medication non-adherence (P < .05), LAR (P = .02), and non-routine clinic visits (P = .03).
CONCLUSIONS: Systematic monitoring of lab adherence may help in identifying pediatric LT recipients at increased risk for excessive healthcare use and adverse outcomes possibly due to poor disease management.

UNASSIGNED: Spironolactone is an off-label acne treatment that is commonly prescribed due to its low cost, efficacy, and tolerability.
UNASSIGNED: This study aimed to classify the most common adverse reactions associated with spironolactone in women of all ages and analyze the relative risk of hyperkalemia for different age groups.
UNASSIGNED: The U.S. Food and Drug Administration Adverse Event Reporting System (FAERS) database was analyzed for common adverse reactions associated with female patients taking spironolactone. Reported hyperkalemia adverse events with spironolactone were further subdivided by age group. Google Trends was used to examine public interest, and Altmetric was used to quantitate scholarly mentions of spironolactone. Yearly data were compared with adverse events in the FAERS database.
UNASSIGNED: The most common adverse reaction in women taking spironolactone was hyperkalemia (16.1% of all adverse events), but it was extremely uncommon in women age ≤45 years (1.9% of all hyperkalemia cases). Increased Google searches and scholarly mentions in the Altmetric database for spironolactone were also associated with increased reporting of adverse events in the FAERS database for men and women combined.
UNASSIGNED: Women taking spironolactone should be counseled that hyperkalemia is the most common adverse event but is uncommon in those age ≤45 years. Public and academic interest in spironolactone has increased in recent years, and although prescribing data are not available, this interest may account for the increased reporting to FAERS during the same time period.

National guidelines in Botswana recommend baseline CD4 count measurement and both CD4 and HIV viral load (VL) monitoring post-antiretroviral therapy (ART) initiation. We evaluated the utility of CD4 count measurement in Botswana in the era of universal ART.
CD4 and VL data were analysed for HIV-infected adults undergoing CD4 count measurement in 2015-2017 at the Botswana Harvard HIV-Reference Laboratory. We determined (1) the proportion of individuals with advanced HIV disease (CD4 count < 200 cells/µL) at initial CD4 assessment, (2) the proportion with an initial CD4 count ≥ 200 cells/µL experiencing a subsequent decline in CD4 count to < 200 cells/µL, and (3) the proportion of these immunologically failing individuals who had virological failure. Logistic regression modelling examined factors associated with advanced HIV disease. CD4 count trajectories were assessed using locally weighted scatterplot smoothing (LOWESS) regression.
Twenty-five per cent (3571/14 423) of individuals with an initial CD4 assessment during the study period had advanced HIV disease at baseline. Older age [≥ 35 years; adjusted odds ratio (aOR) 1.9; 95% confidence interval (CI) 1.8-2.1] and male sex were associated with advanced HIV disease. Fifty per cent (7163/14 423) of individuals had at least two CD4 counts during the study period. Of those with an initial CD4 count ≥ 200 cells/µL, 4% (180/5061) experienced a decline in CD4 count to < 200 cells/µL; the majority of CD4 count declines were in virologically suppressed individuals and transient.
One-quarter of HIV-positive individuals in Botswana still present with advanced HIV disease, highlighting the importance of baseline CD4 count measurement to identify this at-risk population. Few with a baseline CD4 count ≥ 200 cells/µL experienced a drop below 200 cells/µL, suggesting limited utility for ongoing CD4 monitoring.

With liver-directed gene therapy, congenital haemophilia has the potential to progress from an incurable to a phenotypically curable condition. However, the proportion of haemophilia population likely to benefit from gene therapy remains to be established. Achieving a phenotypic curative goal is presently hampered by: 1) availability of effective treatments (e.g. extended half-life products, non-factor therapies) that address major unmet needs in haemophilia; 2) key differences between hope and reality that patients undergoing gene therapy face (e.g. unknown risks and long-term follow-up, durability of the therapeutic effect, possibility of re-administering the vector), 3) lack of expertise of health care professionals (HCP) in managing/monitoring unexpected side effects in patients, and 4) lack of expertise of HCP in advising payers on key issues for cost-effectiveness analyses of gene therapy (e.g., eligibility criteria, predictability of response, unknown risks, long-term complications). There is also uncertainty about the possibility to absorb the cost of the \"one-time, one-dose cure\" by payers that are used to different payment models. An active partnership between regulators, payers, patients and health care professionals is key to identify patient sub-populations that might benefit the most from gene therapy, and to align the interests of patients (needing effective disease correction and improved quality of life) and pharma companies (reluctant to lose the profitability of lifelong repeated treatments). Educational programs will provide the healthcare chain with information on the strategy that is expected to transform morbidity and mortality patterns and how it should be regarded as part of the future therapeutic options in haemophilia.