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Epidural analgesia is an effective way to manage pain for labor and delivery, surgery, trauma, cancer, and neuropathic pain. It involves the administration of local anesthetics and/or opioids into the epidural space. To ensure its efficacy and safety, nurses must understand the basic anatomy and pharmacology of epidural analgesia, considerations when monitoring patients, and identify its adverse reactions. To ensure the efficacy and safety of epidural analgesia, nurses must understand the basic anatomy and pharmacology of epidural analgesia, know the considerations when monitoring patients, and identify its adverse reactions. [ABSTRACT FROM AUTHOR]

Introduction: Miltefosine is a new drug that was recently approved for the treatment of tegumentary leishmaniasis (TL) by the Brazilian health system. It has a teratogenic potential and requires follow-up of patients undergoing treatment. Improving compliance with best practices is essential to ensure the safe and appropriate use of this drug. Objective: This project aimed to implement best practices for the safe and appropriate use of miltefosine in the treatment of TL in the state of Minas Gerais, Brazil. Methods: This project was guided by the JBI Evidence Implementation Framework. Five best practice criteria were established based on the best available evidence. A baseline audit was conducted to measure current practice against best practice. Barriers to best practice were then identified and a follow-up audit was conducted to evaluate changes after the implementation of improvement strategies. Two sites were analyzed: a leishmaniasis reference service in Belo Horizonte, the capital of Minas Gerais, and 28 regional offices. Results: The baseline audit evaluated data from 197 miltefosine requests distributed across 13 regional sites. All requests from the reference service were compliant (100%). This is in contrast to the 60% compliance rate at the regional offices. The improvement strategies included intensifying direct communication with the regional health professionals, which increased the average compliance rate to 79.5%, 6 months after the interventions were introduced. Conclusion: This best practice implementation project effectively increased the compliance rate for the audited procedures. Communication from the reference site with the regional health professionals successfully increased compliance with best practices and promoted the safe and appropriate use of miltefosine. These strategies should analyzed and applied to improve other programs. http://links.lww.com/IJEBH/A184 [ABSTRACT FROM AUTHOR]

The article discusses the practical approach to subcutaneous infliximab (SC IFX) for inflammatory bowel diseases, focusing on its efficacy, safety, and evidence supporting its use. Clinical trials and real-world studies have shown comparable efficacy and safety between SC IFX and intravenous IFX. Patients switching to SC IFX have shown high acceptance and persistence rates. The article also highlights the importance of monitoring before and after maintenance switch, managing disease relapse, and addressing data gaps for future considerations. [Extracted from the article]

Perianal Crohn's disease affects25%-35%of patients with Crohn's disease and has proven to be one of the most difficult complications of the disease to treat. Patients with perianal Crohn's disease have lower health-related quality of life scores typically related to pain and fecal incontinence. In addition, patients with perianal Crohn's disease have higher rates of hospitalizations, surgeries, and overall healthcare costs. A multidisciplinary approach is necessary for the successful management of Crohn's disease with perianal fistula. Medical management is required to treat the underlying immune dysregulation to heal the luminal inflammation and the inflammation within the fistula tracts. Current options for medical therapy include biologics, dual therapy with thiopurines, therapeutic drug monitoring, and a close follow-up. Surgical management is critical to drain abscesses before immunosuppressive therapy and place setons when appropriate. Once the patient's inflammatory burden is well managed, definitive surgical therapies including fistulotomies, advancement flaps, and ligation of intersphincteric fistula tract procedures can be considered. Most recently, the use of stem cell therapy in the treatment of perianal fistula has given new hope to the cure of perianal fistula in Crohn's disease. This review will outline the most current data in the medical and surgical management of perianal Crohn's disease. [ABSTRACT FROM AUTHOR]

Drug therapy for patients with systemic lupus erythematosus (SLE) aims to decrease symptom severity. Pharmacologic interventions are divided into four categories: antimalarials, glucocorticoids (GCs), immunosuppressants (ISs), and biological agents. Hydroxychloroquine, the most commonly used antimalarial treatment for this disease, is a mainstay in treating all patients with SLE. The multitude of adverse reactions of GCs has led clinicians to minimize their dosages or discontinue them whenever possible. To speed up the discontinuation or minimization of GCs, ISs are used for their steroid-sparing properties. Furthermore, certain ISs such as cyclophosphamide are recommended as maintenance agents to prevent flares and reduce the reoccurrence and severity of the disease state. Biological agents are recommended when other treatment options have failed due to intolerance or inefficacy. This article presents pharmacologic approaches for managing SLE in patients based on clinical practice guidelines and data from randomized controlled trials. Drug therapy for patients with systemic lupus erythematosus (SLE) aims to decrease symptom severity. Pharmacologic interventions are divided into four categories: antimalarials, glucocorticoids, immunosuppressants, and biological agents. Hydroxychloroquine, an antimalarial, is a mainstay in SLE treatment. Glucocorticoids should be tapered or discontinued whenever possible due to their multitude of adverse reactions. Immunosuppressants are often used for their steroid-sparing properties and as maintenance agents to prevent flares and reduce disease severity. Biological agents may be used for refractory disease. This article presents pharmacologic approaches for managing SLE in patients based on clinical practice guidelines and data from randomized controlled trials. [ABSTRACT FROM AUTHOR]

The article is a response to a meta-analysis on lower blood pressure targets as a protective hemodynamic strategy for critically ill patients. The authors raise concerns about the primary outcome measure used in the meta-analysis, which was all-cause mortality at the longest follow-up available. They argue that combining studies with different follow-up durations may overestimate mortality risk and increase heterogeneity in the results. The authors suggest that further discussion and consideration of these issues are necessary. [Extracted from the article]

The article discusses the use of estimated glomerular filtration rate (GFR) in the treatment of critically ill patients. The authors argue that GFR estimations based on plasma levels are unreliable and suggest using 24-hour urine collections and creatinine plasma levels to measure GFR instead. They also mention that therapeutic drug monitoring is a more reliable method for dosing drugs based on renal function. The authors acknowledge the need for further research in developing equitable approaches to kidney function assessment in critical care practice. [Extracted from the article]

A study published in Critical Care Medicine examined the optimal dosing of levetiracetam, a medication used to prevent seizures, in critically ill neurological ICU patients with augmented renal clearance (ARC). The study found that this population required higher doses of levetiracetam to achieve target levels, with a dose of at least 1000 mg twice daily being recommended. ARC, characterized by high creatinine clearance, is common in critically ill patients, especially those in neurological ICUs. The study recommends dose titration guided by measured creatinine clearance and/or therapeutic drug monitoring to minimize the risk of seizures. It is important for clinicians to measure creatinine clearance and consider screening high-risk ICU patients for ARC to avoid underdosing of medications and potential treatment failures. [Extracted from the article]

The article discusses the challenges faced by clinicians in providing care for patients with inflammatory bowel disease (IBD). Despite the availability of new medications and society guidelines, clinicians often encounter difficulties due to prior authorization (PA) requirements imposed by insurance companies. The study highlights the misalignment between society guidelines and insurance algorithms for medication use, leading to delays in treatment and potential negative outcomes for patients. The authors suggest that improved communication, collaboration between specialty societies and health plans, and government intervention may be necessary to address these issues and improve patient care. [Extracted from the article]

Preoperative narcotic use is associated with poor postoperative pain management and worse outcomes after total joint arthroplasty (TJA). Therefore, identifying controlled substance use preoperatively is necessary. Electronic medical records (EMRs), prescription monitoring programs (PMP), or urine toxicology screening (UTS) are most commonly used. This study aims to compare the accuracy of EMR and PMP versus UTS to determine whether UTS should be implemented as standard of care in TJA preoperative assessment. Preoperative UTS was performed for primary or revision TJA from November 1, 2018, to March 31, 2019. Patient demographics, medical history, prescription history, and UTS results were retrospectively recorded. Prescription monitoring program and EMR were queried for prescription history in the past 2 years. The accuracy of EMR and PMP compared with UTS was calculated. Multivariable logistic regression analysis was performed to identify patient predictors associated with UTS+. Thirty of 148 patients had UTS+. Positive urine toxicology screening was more common in patients younger than 58 years, White race, and undergoing revision surgery. Electronic medical record and PMP documentation had the highest sensitivity (73.3%), specificity (92.4%), positive predictive value (71.0%), and negative predictive value (93.2%). Patients with higher odds of UTS+ include current/former smokers, those with a history of alcohol abuse, drug abuse, hepatitis C diagnosis, and mental illness. For patients without any risk factors for having a UTS+, the use of EMR and PMP may be sufficient to evaluate for controlled substance use; however, UTS should be considered in patients who present with one of the risk factors for UTS+. [ABSTRACT FROM AUTHOR]

Management of anticoagulation in individuals undergoing operative procedures is a complex situation. Each case should be assessed individually with proper risk assessment, monitoring, and plan for perioperative and postoperative anticoagulation. Clinical evidence for the management of these patients is relatively scarce, and clinicians are often assessing each individual case with minimal guidance. This review provides nurses with a summary of available literature on the assessment, laboratory monitoring, timing of adjusting anticoagulation, and bridging prior to procedures. In addition to general perioperative anticoagulation management, this review discusses perioperative management in special populations and provides a summary on principles when anticoagulation should be resumed following a procedure. [ABSTRACT FROM AUTHOR]

Coagulopathy of liver disease is a complex pathology that may result in thrombosis and/or bleeding complications. Routine laboratory values are not always reflective of the degree of these risks. Additionally, prophylaxis and treatment of venous thromboembolism in patients with cirrhosis require careful evaluation when selecting and monitoring drug therapy for these indications. Therefore, this article aims to provide insight regarding coagulopathy of liver disease, influence on laboratory values, and anticoagulant therapy considerations for critical care nurses assuming care for patients with cirrhosis. [ABSTRACT FROM AUTHOR]

Transgender and gender-nonbinary patients may present to primary care providers seeking gender-affirming hormone therapy. Patients who meet criteria for diagnosis of gender incongruence may start or continue hormone therapy after providing informed consent. Prescribing and monitoring of masculinizing and feminizing hormone therapy can be managed in primary care settings. [ABSTRACT FROM AUTHOR]

The document is a reply to a letter regarding the need for further research on the suggested target serum concentrations of levetiracetam and its correlation with clinical outcomes. The authors emphasize the importance of conducting studies with a more homogeneous patient population to accurately evaluate the drug's impact on patient outcomes. They express gratitude for the attention to their concerns and hope that their letter contributes to the ongoing discussion on the optimal utilization of levetiracetam in the context of neurocritical illness. The document also briefly mentions the authors' affiliations and conflicts of interest. [Extracted from the article]

The article discusses the reliability of serum levetiracetam levels as a primary endpoint in neurocritical illness. The authors express reservations about using serum concentrations as the primary outcome, as the link between these concentrations and clinical efficacy is not well-established for levetiracetam. They also question the validity of the existing reference range for serum levetiracetam concentrations. Additionally, they raise concerns about the generalizability of the study's findings due to the mixed group of patients with varying admission diagnoses. The authors suggest that further research is needed to validate the suggested target serum concentrations of levetiracetam and their correlation with clinical outcomes. [Extracted from the article]

Fluoroquinolones (FQs) are highly effective, well-tolerated, broad-spectrum antibiotics, making them desirable treatment options for infections. However, their adverse reactions as well as recent trends in antibiotic susceptibility must be considered. This article discusses the spectrum of activity and adverse reactions of FQs to guide nurses in caring for patients receiving this class of antibiotics. This article discusses the spectrum of activity and adverse reactions of fluoroquinolones to guide nurses in caring for patients receiving this class of antibiotics. [ABSTRACT FROM AUTHOR]

Therapeutic drug monitoring (TDM) of biologics is a rapidly evolving field. We aimed to provide a consensus statement regarding the clinical utility of TDM for biologics in inflammatory bowel disease (IBD). A modified Delphi method was applied to develop consensus statements. A comprehensive literature review was performed regarding TDM of biologic therapies in IBD, and 45 statements were subsequently formulated on the potential application of TDM in IBD. The statements, along with literature, were then presented to a panel of 10 gastroenterologists with expertise in IBD and TDM who anonymously rated them on a scale of 1–10 (1 5 strongly disagree and 10 5 strongly agree). An expert consensus development meeting was held virtually to review, discuss, refine, and reformulate statements that did not meet criteria for agreement or that were ambiguous.During the meeting, additional statements were proposed. Panelists then confidentially revoted, and statements rated ≥7 by 80% or more of the participants were accepted. During the virtual meeting, 8 statements were reworded, 7 new statements were proposed, and 19 statements were rerated. Consensus was finally reached in 48/49 statements. The panel agreed that reactive TDM should be used for all biologics for both primary nonresponse and secondary loss of response. Itwas recommended that treatment discontinuation should not be considered for infliximab or adalimumab until a drug concentration of at least 10–15 mg/mL was achieved. Consensus was also achieved regarding the utility of proactive TDM for anti–tumor necrosis factor therapy. It was recommended to perform proactive TDMafter induction and at least once during maintenance. Consensus was achieved inmost cases regarding the utility of TDM of biologics in IBD, specifically for reactive and proactive TDM of anti–tumor necrosis factors. [ABSTRACT FROM AUTHOR]

INTRODUCTION: There are only limited data regarding the role of therapeutic drug monitoring in fistulizing Crohn's disease (CD). We investigated the association between both induction and maintenance serum infliximab concentrations and favorable therapeutic outcomes in patients with fistulizing CD. METHODS: This was a post hoc analysis of the ACCENT-II trial evaluating patients with fistulizing CD receiving induction (n=282) and maintenance infliximab therapy (n=139). Investigated therapeutic outcomes at both week 14 and week 54 included fistula response, complete fistula response, C-reactive protein (CRP) normalization (≤5 mg/L) in patients with an elevated baseline CRP, and a more stringent outcome of composite remission, defined as combined complete fistula response and CRP normalization. Associations between serum infliximab concentrations and outcomes were assessed by multivariable logistic regression models. RESULTS: Higher week 14 infliximab concentrations were independently associated with week 14 fistula response (odds ratio [OR]: 1.16; 95% confidence interval [CI]: 1.02-1.32; P = 0.019), and composite remission (OR: 2.32; 95% CI: 1.55-3.49; P < 0.001). Higher week 14 infliximab concentrations were also independently associated with week 54 composite remission (OR: 2.05; 95% CI: 1.10-3.82; P=0.023). Based on receiver operating characteristic curve analysis, week 14 infliximab concentrations thresholds with combined maximal sensitivity and specificity of ≥20.2 μg/mL at week 2, ≥15 μg/mL at week 6, and ≥7.2 μg/mL at week 14 were associated with week 14 composite remission. DISCUSSION: Higher post-induction infliximab concentrations are associated with early and long-term favorable therapeutic outcomes in patients with fistulizing CD. [ABSTRACT FROM AUTHOR]

Background: Adherence is critical to achieve the benefits of antiretroviral therapy. A smart-pill bottle service that transmits real-time adherence data via cellular networks to a central service and prompts nonadherent patients with phone or text messages may improve adherence. Methods: Adults with HIV taking a tenofovir-containing regimen with suboptimal adherence were randomized to adherence counseling ± a smart-pill bottle service for 12 weeks. Tenofovir diphosphate (TFV-DP) levels by dried blood spot, HIV RNA levels, CD4 cell counts, and self-reported adherence were collected. Results: Sixty-three participants (22% women; 48% black, 25% Latino) were randomized: 30 to the smart-pill bottle (2 of whom were lost to follow-up before the baseline visit), and 33 to control arms. At baseline, 49% of participants had HIV RNA ≤20 copies/mL and 61% reported 100% adherence with ART over 4 days. From baseline to week 12, median TFV-DP levels were +252 and -41 fmol/punch in the bottle and control arms, respectively (P = 0.10). Exploratory exclusion of 3 participants with known or suspected drug-drug interactions found median TFV-DP levels of +278 and -38 fmol/punch, respectively (P = 0.04). There were no differences in study discontinuations, HIV RNA suppression, CD4 cell counts, or self-reported adherence at week 12. Conclusions: In a diverse group of participants with suboptimal adherence to ART, the smart-pill bottle service was associated with higher TFV-DP levels. [ABSTRACT FROM AUTHOR]

Objective: To identify factors associated with serum estradiol (E2) levels among healthy postmenopausal women using hormone therapy (HT).Methods: This is an unplanned post hoc analysis of data from ELITE (Early versus Late Intervention Trial with Estradiol), a randomized controlled trial of 1 mg oral E2 with or without vaginal progesterone in healthy early compared with late (<6 years compared with 10 or more years since menopause) postmenopausal women. We included results from visits when women reported at least 80% compliance with HT. Mixed-effects linear models identified factors associated with serum E2 levels while participants were taking HT, assessed every 6 months over a median follow-up of 4.8 years and adjusted for baseline E2 level, visit, and reduced E2 dose. Possible correlates evaluated included demographics, clinical characteristics, medication use, and biomarkers of liver and kidney metabolic function.Results: The analysis included 2,160 E2 measurements in 275 postmenopausal women. Mean±SD age was 55.4±3.9 vs 64.4±5.5 years, and mean±SD time since menopause was 3.6±1.8 vs 16.0±5.6 years for early vs late postmenopausal women. Adjusted for pretreatment E2 level, visit, and reduced dose indicator, higher serum E2 levels were associated with higher body mass index (BMI), higher weight, surgical menopause, alcohol use, and antihypertensive medication use. Current and past smoking and antifungal medication use were associated with lower serum E2 levels. In the multivariable model, higher BMI and alcohol use were associated with higher serum E2 levels, whereas current and past smoking were associated with lower serum E2 levels. These factors were similar between early and late postmenopausal women.Conclusion: Factors associated with serum E2 levels among postmenopausal women taking HT include BMI, alcohol use, and smoking. As serum E2 levels relate to HT effect, achievement of desirable E2 levels may be maximized through personalized intervention.Clinical Trial Registration: ClinicalTrials.gov, NCT00114517. [ABSTRACT FROM AUTHOR]

Objective: To compare maternal and cord blood penicillin concentrations in women with and without obesity who are receiving intrapartum group B streptococcus (GBS) prophylaxis.Methods: We performed a prospective cohort study of term women receiving intrapartum penicillin prophylaxis for GBS colonization (determined by antenatal rectovaginal culture). The following outcomes were compared between obese (body mass index [BMI] 35 or higher at delivery) and nonobese (BMI less than 30 at delivery) groups: penicillin concentration in maternal blood (after two penicillin doses) and umbilical cord blood, GBS rectovaginal colonization status on admission and after two completed doses, and neonatal GBS colonization (using a postnatal ear swab). Fifty-five women were needed to detect a 0.75 SD difference in cord blood penicillin concentrations.Results: Fifty-five women were enrolled and had all specimens collected; 49 had complete data for analysis (obese n=25, nonobese n=24). There was no difference in the median maternal penicillin concentration between groups (obese 4.2 micrograms/mL vs nonobese 4.0 micrograms/mL, P=.58). There was, however, a 60% lower median cord blood penicillin concentration in the obese compared with the nonobese group (2.7 micrograms/mL vs 6.7 micrograms/mL, respectively, P<.01), with no significant difference in time from last penicillin dose to delivery (obese 2.9 hours vs nonobese 1.7 hours, P=.07). The difference in cord blood concentrations remained significant after adjustment for nulliparity, hypertensive disorders, and time from last penicillin dose to delivery. Only 59.6% of women tested positive for GBS by rectovaginal culture on admission (obese 60.9% vs nonobese 58.3%, P=.86).Conclusion: The median cord blood penicillin concentration was 60% lower in neonates born to women with obesity compared with those born to women without obesity. However, all concentrations exceeded the minimum inhibitory concentration. Maternal penicillin levels were not significantly different between groups. More than 40% of women who previously tested positive for GBS by antenatal culture tested negative for GBS on admission for delivery. [ABSTRACT FROM AUTHOR]

Study Design: Retrospective study.Objective: To determine risk factors for prolonged opioid use and to investigate whether opioid-tolerance affects patient-reported outcomes following ACDF surgery.Summary Of Background Data: There is a lack of consensus on risk factors that can affect continued opioid use after cervical spine surgery and the influence of opioid use on patient-reported outcomes.Methods: Ninety-two patients who underwent ACDF for degenerative cervical pathologies were retrospectively identified and their opioid usage before surgery was investigated using a state-sponsored prescription drug monitoring registry. Opioid-naïve and opioid tolerant groups were defined using criteria most consistent with the Federal Drug Administration (FDA) definition. Patient-reported outcomes were then collected, including the Short Form-12 (SF-12) Physical Component (PCS-12) and Mental Component (MCS-12), the Neck Disability Index (NDI), the Visual Analogue Scale Neck (VAS neck) and the Visual Analogue Scale Arm (VAS Arm) pain scores. Logistic regression was used to determine predictors for prolonged opioid use following ACDF. Univariate and multivariate analyses were conducted to compare change in outcomes over time between the two groups.Results: Logistic regression analysis demonstrated that opioid tolerance was a significant predictor for prolonged opioid use after ACDF (OR: 18.2 [1.46, 226.4], p = 0.02). Duration of usage was also found to be a significant predictor for continued opioid use after surgery (OR: 1.10 [1.0, 1.03], p = 0.03). No other risk factors were found to be significant predictors. Both groups overall experienced improvements in patient-reported outcomes after surgery. Multiple linear regression analysis, controlling for patient demographics, demonstrated that opioid-tolerant user status positively affected change in outcomes over time for NDI (β = -13.7 [-21.8, -5.55], p = 0.002) and PCS-12 (β = 6.99 [2.59, 11.4], p = 0.003) but no other outcomes measured.Conclusion: Opioid tolerance was found to be a significant predictor for prolonged opioid use after ACDF. Additionally, opioid-naïve and opioid-tolerant users experienced overall improvements across PROMs following ACDF. Opioid-tolerance was associated with NDI and PCS-12 improvements over time compared to opioid-naïve users.Level Of Evidence: 4. [ABSTRACT FROM AUTHOR]

Dried blood spot (DBS) analysis is a novel analytical method for therapeutic drug monitoring to identify nonadherence to antihypertensive drugs. This study was conducted to evaluate the clinical applicability of measuring drug concentrations of 8 antihypertensive drugs, using DBS and venipuncture. Furthermore, this study aimed to provide more insight into the between-patient variability in drug concentrations. False-negative values from DBS compared with a venipuncture were determined to assess drug adherence. A generalized estimating equation was used to estimate the model parameters, including sex, dose, age, weight, and the time interval, between drug intake and sampling, on the Cplasma (drug concentration in plasma). No false-negative values were found when measuring nonadherence using DBS compared with venipuncture. A high variability in Cplasma between patients was observed, especially at peak concentrations with a fold change reaching from 2.3 to 35.2. The time of intake was significantly related to the height of the Cplasma in 7 of the 8 measured drugs with a P<0.05, but the influence of dose, weight, age, and sex on drug levels differed largely between the measured drugs. DBS is a reliable and convenient method to assess nonadherence to antihypertensive drugs in clinical practice. The Cplasma of the 8 antihypertensive drugs in this study show a large interindividual difference, and therefore, low plasma concentrations do not necessarily mean nonadherence. Nonadherence can only be confirmed if drug levels are undetectable, that is, values below the lower limit of detection. [ABSTRACT FROM AUTHOR]

HIV preexposure prophylaxis (PrEP) is an opportunity for clinicians to curb the 40,000 HIV infections occurring annually in the United States. PrEP is medication used by HIV-negative patients to reduce their risk of acquiring the virus. This article provides a baseline understanding of PrEP indications, prescribing, and monitoring, including a review of previously approved medication and an update on newly approved drugs, including emtricitabine/tenofovir alafenamide (F/TAF). Sexual and gender minorities are often underrepresented in the literature about PrEP, but clinicians should address risk focused on specifi c behaviors rather than population-level characteristics. As one of few professions with prescriptive authority, PAs have an obligation to understand and manage PrEP. [ABSTRACT FROM AUTHOR]

New evidence and increased use of intracranial devices have increased the frequency of intraventricular (JVT) medication administration in the neurologic intensive care unit. Significant benefits and risks are associated with administration of medications directly into the central nervous system. This review summarizes important literature, along with key information for clinicians regarding the administration, dosing, monitoring, and adverse effects related to IVT medication usage. Multiple medications have supporting literature for their use in critically ill patients including amphotericin B, aminoglycosides, colistimethate, daptomycin, quinupristin/dalfopristin, vancomycin, alteplase, and nicardipine. Sterile preparation and delivery, along with different types of devices that support medication administration, are also reviewed. One randomized, placebocontrolled trial of alteplase demonstrated decreased mortality but no change in good functional outcome. Other reports of IVT medication use are mainly limited to case reports and retrospective case series. There is a need for increased research on the topic; however, several practical barriers decrease the likelihood of a large, placebo-controlled, prospective study for most indications. Providers should consider implementing protocols to maximize safety of IVT medication delivery to ensure optimal patient outcomes. [ABSTRACT FROM AUTHOR]

As a plethora of data emerges on therapeutic drug monitoring (TDM) of biologics in inflammatory bowel disease, guidance on its application is needed. In this literature review and consensus statement, the authors recommend reactive TDM for all biologics, summarize concentration targets, and provide guidance on TDM in various scenarios. Proactive TDM with tumor necrosis factor-antagonist monotherapy is recommended as an alternative to the combination of tumor necrosis factor-antagonists with immunomodulators. Although observational data support this approach, randomized controlled trials do not. We argue that there is considerable work left to be performed before embracing proactive TDM as an equivalent alternative to combination therapy in inflammatory bowel disease. [ABSTRACT FROM AUTHOR]

Background: Risperidone is an atypical antipsychotic drug used to treat irritability and aggression in children and adolescents with autism spectrum disorder. In an earlier study, the sum trough concentration of risperidone and its metabolite (9-hydroxyrisperidone) was positively correlated with weight gain and effectiveness. The aim of this study was to determine the therapeutic window for risperidone sum trough concentrations that balances weight gain with treatment effectiveness in this population. In addition, the effect of therapeutic drug monitoring (TDM) on treatment optimization was simulated., Methods: In a retrospective cohort (n = 24 children), the target window for risperidone leading to the least increase in body mass index z-scores while retaining effectiveness as measured by the irritability subscale of the Aberrant Behavior Checklist was determined using receiver operating curve analysis. This target range was used to simulate the effect of TDM using a population PK model implemented in the software platform InsightRX. Dosing advice was based on plasma trough concentrations and the dose administered at 12 weeks to simulate whether more children would be on target at 24 weeks after the start of treatment., Results: A risperidone sum trough target range of 3.5-7.0 mcg/L would minimize increase in body mass index z-score and optimize effectiveness. Dosing advice using TDM and a population PK model would lead to a larger proportion of children achieving the target concentration range (62.5% versus 16.7%)., Conclusions: TDM may be a useful tool for optimizing risperidone treatment in children and adolescents with autism spectrum disorder., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

Background: Clozapine (CLZ) use is hampered by the risk of granulocyte toxicity, which is associated with the formation of nitrenium ions and the concurrent use of valproic acid (VPA). These highly reactive nitrenium ions cannot be measured in vivo. Instead, deactivated cysteinyl conjugates may potentially be detected. The aim of this study was to develop a novel method for identifying cysteinylated derivates of CLZ nitrenium ions to investigate the effect of VPA on their formation using therapeutic drug monitoring data., Methods: A population comprising 93 VPA comedicated and 162 control patients from a therapeutic drug monitoring (TDM) service in Oslo, Norway, was included. Reprocessing of ultraperformance liquid chromatography high-resolution mass spectra (UHPLC-HR-MS) of previously analyzed TDM samples, combined with the assessment of MS/MS fragmentation patterns, was performed to identify the CLZ cysteinyl conjugates. Smoking, which induces CLZ metabolism, was assessed by detecting cotinine in the reprocessed mass spectra., Results: By reprocessing the UHPLC-HR-MS files of the TDM analyses and reviewing the MS/MS fragment profiles, four cysteinyl conjugates of CLZ were identified. The formations of CLZ cysteinyl (CLZ-Cys 1+ ) and CLZ- N -oxide cysteinyl (CLZ-NOX-Cys 1+ ) were 1.5-fold ( P = 0.038) and 2.1-fold ( P < 0.001) higher in VPA-treated patients than those in the controls. In agreement with previous studies, a 45% reduction in N -desmethylclozapine formation was observed in VPA-treated patients ( P < 0.001)., Conclusions: A novel method for detecting cysteinyl conjugates of CLZ was developed. Application of this method indicated that VPA significantly increased the formation of CLZ-Cys 1+ metabolites, which might explain the granulocyte toxicity reported after adding VPA to CLZ treatment. The developed method opens new avenues for investigating CLZ toxicity, e.g. by correlating cysteinyl conjugates and granulocyte counts in patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: To assess the pharmacokinetic correlates of reported adverse drug reactions (ADRs) under antidepressant treatment with escitalopram (ESC) using a large therapeutic drug monitoring database., Methods: A large naturalistic sample of inpatients and outpatients prescribed ESC was analyzed. ADRs were classified using the Udvalg for Kliniske Undersogelser side effect rating scale. We compared ESC-treated patients with (n = 35) and without ADRs (n = 273) using ESC plasma concentrations as the primary outcome. We also compared ADR rates in the 2 groups based on 2 cut-off ESC levels reflecting the recommended upper thresholds of the therapeutic reference range of 80 ng/mL, suggested by the consensus therapeutic drug monitoring guidelines, and 40 ng/mL, based on recent meta-analysis data. The effects of age, sex, smoking, daily ESC dose, plasma concentrations, and concentrations corrected for daily dose were included in a binary logistic regression model to predict ADRs., Results: No differences in clinical, demographic, or pharmacokinetic parameters were observed between patients with and without ADRs ( P > 0.05). Patients with ESC-related ADRs were more frequently diagnosed with psychotic disorders than those without (25% vs. 7.1%, P = 0.004). None of the variables was associated with ADR risk. Overall, ADR rates were not significantly different in patients above versus below thresholds of ESC concentrations (ESC concentrations >40 [n = 59] vs. ≤40 ng/mL [n = 249] and >80 [n = 8] vs. ≤80 ng/mL [n = 300]; P = 0.56 and P = 1.0, respectively)., Conclusions: No distinct pharmacokinetic patterns underlying ESC-associated ADRs were observed. Further studies with more specific assessments of ADRs in larger cohorts are required to better identify potential underlying patterns., Competing Interests: M. Kuzin has received travel grants from Sunovion Pharmaceutical (Basel, Switzerland) and Otsuka Pharmaceutical (Glattbrugg, Switzerland). He also received a travel grant, participated, and obtained a grant at speaker board of Lundbeck (Zurich, Switzerland). M. Paulzen has received speaker fees from the following pharmaceutical companies: Neurax Pharm, Lundbeck, Janssen, Otsuka, Idorsia, and Rovi. He has served as a consultant for Neurax Pharm, Otsuka, Lundbeck, Idorsia, and Rovi. He is an editor of PSIAC, an Internet-based drug–drug interaction program for psychopharmacotherapy ( www.psiac.de ). He reports no conflict of interest with this publication. Dr. Schoretsanitis has served as a consultant for Dexcel Pharma, HLS Therapeutics, and Thermo Fisher and has received speaker fees from HLS Therapeutics. The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

Background: The American Psychiatric Association guidelines for the treatment of patients with schizophrenia state that the utility of antipsychotic therapeutic drug monitoring (TDM) remains unclear, except for clozapine or assessing adherence. The aim of this study was to investigate the extent and impact of antipsychotic TDM in inpatient practice to improve its utilization., Methods: Patients with antipsychotic blood levels drawn between May 1, 2021 and January 31, 2023 were invited to consent for retrospective chart data analysis to determine the influence of antipsychotic blood levels on their treatment. Approximately 42% of patients consented. Data collected from the patients' electronic medical records included age, ethnicity, race, sex, diagnosis, comorbidities, adverse drug reactions, medications, doses and frequency, antipsychotics and levels, laboratory values, and treatment history. Comparisons were made between antipsychotic levels that were within and outside the therapeutic range and the status of antipsychotic regimen adjustments., Results: A total of 135 antipsychotic levels from 40 inpatients were analyzed. Approximately 48% of the levels were appropriately drawn, whereas 52% were inappropriately drawn. Clozapine had the highest TDM rate (59%) and the most common diagnoses were schizophrenia (45%) and schizoaffective disorder (32.5%). More levels were appropriately drawn for clozapine (47.3% versus 24.3%) than for risperidone (41% versus 46.2%). Appropriately drawn clozapine levels correlated with higher daily doses and levels at or above the therapeutic threshold of 350 ng/mL., Conclusions: Most antipsychotic drug levels were inappropriately drawn, emphasizing the complexity and potential for errors in TDM. Although more patients were prescribed risperidone, clozapine had the highest TDM rate. Clinicians were more likely to keep antipsychotic regimens unchanged for appropriately drawn levels and adjust doses for inappropriately drawn levels., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: To determine whether best practice advisories improved sedation protocol compliance and could mitigate potential propofol-related hazardous conditions.Design: Retrospective observational cohort study.Setting: Two adult ICUs at two academic medical centers that share the same sedation protocol.Patients: Adults 18 years old or older admitted to the ICU between January 1, 2016, and January 31, 2018, who received a continuous infusion of propofol.Interventions: Two concurrent best practice advisories built in the electronic health record as a clinical decision support tool to enforce protocol compliance with triglyceride and lipase level monitoring and mitigate propofol-related hazardous conditions.Measurements and Main Results: The primary outcomes were baseline and day 3 compliance with triglyceride and lipase laboratory monitoring per protocol and time to discontinuation of propofol in the setting of triglyceride and/or lipase levels exceeding protocol cutoffs. A total of 1,394 patients were included in the study cohort (n = 700 in the pre-best practice advisory group; n = 694 in the post-best practice advisory group). In inverse probability weighted regression analyses, implementing the best practice advisory was associated with a 56.6% (95% CI, 52.6-60.9) absolute increase and a 173% relative increase (risk ratio, 2.73; 95% CI, 2.45-3.04) in baseline laboratory monitoring. The best practice advisory was associated with a 34.0% (95% CI, 20.9-47.1) absolute increase and a 74% (95% CI, 1.39-2.19) relative increase in day 3 laboratory monitoring after inverse probability weighted analyses. Among patients with laboratory values exceeding protocol cutoffs, implementation of the best practice advisory resulted in providers discontinuing propofol an average of 16.6 hours (95% CI, 4.8-28.3) sooner than pre-best practice advisory. Findings from alternate analyses using interrupted time series were consistent with the inverse probability weighted analyses.Conclusions: Best practice advisories can be effectively used in ICUs to improve sedation protocol compliance and may mitigate potential propofol-related hazardous conditions. Best practice advisories should undergo continuous quality assurance and optimizations to maximize clinical utility and minimize alert fatigue. [ABSTRACT FROM AUTHOR]

Managing severe valvular heart disease with mechanical valve replacement necessitates lifelong anticoagulation with a vitamin K antagonist. Optimal anticoagulation intensity for patients with mechanical valves remains uncertain; current recommendations are inconsistent across guideline bodies and largely based on expert opinion. In this review, we outline the history of anticoagulation therapy in patients with mechanical heart valves and critically evaluate current antithrombotic guidelines for these patients. We conclude that randomized trials evaluating optimal anticoagulation intensity in patients with mechanical valves are needed, and that future guidelines must better justify antithrombotic treatment recommendations. [ABSTRACT FROM AUTHOR]

Chronic pain, stemming primarily from musculoskeletal conditions and severe headaches, is a growing problem in the United States, affecting as many as 43% of adults. Opioids are frequently prescribed to manage chronic pain despite limited data on their long-term efficacy and the potential risks of long-term use. In 2017, more than 47,000 people died as a result of an opioid overdose involving illicit opioids (such as heroin), illicitly manufactured opioids, diverted opioids, prescription opioids, or some combination thereof. Although it's been more than three years since the nationwide opioid crisis prompted the Centers for Disease Control and Prevention (CDC) to release a guideline outlining safe practices for prescribing opioids to patients with chronic pain (unrelated to active cancer or palliative and end-of-life care), opioid misuse remains a significant concern. Historically, physicians have been tasked with the primary responsibility for implementing opioid safety measures, but nurses in the primary care setting are being increasingly relied on to incorporate these measures as part of their practice. In this article, we discuss the use of five tools outlined in the CDC guideline: prescription opioid treatment agreements, urine drug screening, prescription drug monitoring program databases, calculation of morphine milligram equivalents, and naloxone kits. Primary care nurses can use these tools to promote opioid safety among patients receiving opioid therapy for chronic pain. [ABSTRACT FROM AUTHOR]

Purpose: This study assessed the impact of process standard work, a quality improvement tool, on staff adherence to nurse-driven unfractionated heparin (UFH) protocols in adult patients at a community teaching hospital. Methods: This was a retrospective quality improvement project, and statistical analysis was performed by a senior research specialist at the facility. Results: In total, 109 venous thromboembolism or cardiac UFH anticoagulant protocols were included in the final analysis, accounting for 445 activated partial thromboplastin time results. Conclusion: There was no change in adherence to a nurse-driven UFH protocol among adult patients after the implementation of process standard work. [ABSTRACT FROM AUTHOR]

Ketamine has been used as an anesthetic agent for over 50 years. At the upper end of the dosing range, it displays dissociative anesthetic and amnestic effects, while at lower doses, it acts as an analgesic and demonstrates opioid-sparing capabilities. Ketamine is unique in its preservation of hemodynamic stability and respiratory function, and is used extensively in the emergency department (ED) for procedural sedation and the facilitation of brief painful procedures. Despite evidence supporting its safety and efficacy as an analgesic agent at sub-dissociative doses, its use in the ED for the management of acute pain remains uncommon. New guidelines were published in July 2018 by the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, and the American Society of Anesthesiologists that provide a framework for identifying patients who are likely to benefit from the use of Ketamine in an acute pain setting. [ABSTRACT FROM AUTHOR]

Opioid-related morbidity and mortality have increased to epidemic proportions over the past 20 years. Gynecologists play an integral role in addressing this epidemic through management of patients with pain, specifically through prescribing and monitoring practices. Practical recommendations are provided for clinicians caring for noncancer patients on chronic opioid therapy. Recommendations are largely based on national consensus guidelines with a focus on frequency and content of follow-up, identification of high risk behaviors, and reassessment of goals of treatment. [ABSTRACT FROM AUTHOR]

Chronic pelvic pain is a commonly encountered clinical entity, and many women with this chronic pain condition will be treated at some point in time with opioids for management of their pain. Clinicians in women's health are frequently asked and expected to participate in the care of women with chronic pelvic pain, as well as other gynecologic pain conditions, and should be familiar with the role of opioid therapy for these conditions. The goal of this article is to help determine which patients may be appropriate candidates for the initiation or continuation of opioid therapy for gynecologic pain. In addition, this article will help the clinician to establish treatment goals, select appropriate medications, monitor the efficacy of treatment, and to determine when discontinuation of medications is appropriate. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify the factors that influence voriconazole (VCZ) plasma concentrations and optimize the doses of VCZ in patients with end-stage liver disease (ESLD)., Methods: Patients with ESLD who received a VCZ maintenance dose of 100 mg twice daily (group A, n = 57) or the VCZ maintenance dose of 50 mg twice daily (group B, n = 37), orally or intravenously, were enrolled in this study. Trough plasma concentrations (Cmin) of VCZ between 1 and 5 mg/L were considered within the therapeutic target range., Results: The VCZ Cmin was determined in 94 patients with ESLD. The VCZ Cmin of patients in group A was remarkably higher than those in group B (4.85 ± 2.53 mg/L vs 2.75 ± 1.40 mg/L; P < 0.001). Compared with group A, fewer patients in group B had VCZ Cmin outside the therapeutic target (23/57 vs. 6/37, P = 0.021). Univariate and multivariate analyses suggested that both body weight and Model for End-Stage Liver Disease scores were closely associated with the VCZ Cmin in group B., Conclusions: These data indicate that dose optimization based on body weight and Model for End-Stage Liver Disease scores is required to strike an efficacy-safety balance during VCZ treatment in patients with ESLD., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Optimal cefepime dosing is a challenge because of its dose-dependent neurotoxicity. This study aimed to determine individualized cefepime dosing for febrile neutropenia in patients with lymphoma or multiple myeloma., Methods: This prospective study enrolled 16 patients receiving cefepime at a dose of 2 g every 12 hours. Unbound concentrations were determined at 0.5 hours, 7.2 hours [at the 60% time point of the 12 hours administration interval (C7.2h)], and 11 hours (trough concentration) after the first infusion (rate: 2 g/h). The primary and secondary end points were the predictive performance of the area under the unbound concentration-time curve (AUC unbound ) and the effect of unbound cefepime pharmacokinetic parameters on clinical response, respectively., Results: The mean (SD) AUC unbound was 689.7 (226.6) mcg h/mL, which correlated with C7.2h (R 2 = 0.90), and the Bayesian posterior AUC unbound using only the trough concentration (R 2 = 0.66). Although higher exposure was more likely to show a better clinical response, each parameter did not indicate a statistical significance between positive and negative clinical responses ( P = 0.0907 for creatinine clearance (Ccr), 0.2523 for C7.2h, 0.4079 for trough concentration, and 0.1142 for AUC unbound ). Cutoff values were calculated as 80.2 mL/min for Ccr (sensitivity: 0.889, specificity: 0.714), 18.6 mcg/mL for C7.2h (sensitivity: 0.571, specificity: 1.000), and 9.2 mcg/mL for trough concentration (sensitivity: 0.571, specificity: 1.000). When aiming for a time above 100% the minimum inhibitory concentration, both continuous infusion of 4 g/d and intermittent infusion of 2 g every 8 hours achieved a probability of approximately 100% at a minimum inhibitory concentration of 8 mcg/mL., Conclusions: Therapeutic drug monitoring by sampling at C7.2h or trough can facilitate rapid dose optimization. Continuous infusion of 4 g/d was recommended. Intermittent dosing of 2 g every 8 hours was alternatively suggested for patients with a Ccr of 60-90 mL/min., Competing Interests: K. Oda received funding from Grant-in-Aid for Young Scientists (B) 20K17467 from the Ministry of Education, Culture, Sports, Science, and Technology of Japan. None of the other authors declare any conflicts of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Janus kinase inhibitors are antirheumatic immunosuppressive drugs that target intracellular Janus kinases (JAKs). Baricitinib is a selective and reversible orally administered JAK1/JAK2 inhibitor approved for treating rheumatoid arthritis, atopic dermatitis, and alopecia areata in adult patients. Expanded access to baricitinib has been approved for treating pediatric patients affected by rare Mendelian autoinflammatory diseases with type I interferon-mediated damage. Knowledge of the pharmacokinetic properties and target plasma levels of baricitinib in pediatric patients is limited. In this study, a novel LC-MS/MS method for measuring baricitinib in plasma, validated according to the ICH M10 guidelines, is presented., Methods: Sample preparation was performed by adding 10 µL of IS working solution (150 ng/mL) and 200 µL of MeOH to each plasma sample. Chromatographic separation was conducted using a Thermo Scientific Accucore Polar Premium column (50 mm × 2.1 mm, i.d. 2.6 m). This method was applied to 7 real anonymous plasma samples obtained from pediatric patients treated with baricitinib at IRCCS Istituto Giannina Gaslini (Genoa, Italy). Patients of both sexes had a median age of 14 years (range, 10-17 years)., Results: The LC-MS/MS method resulted linear over wide concentration ranges (1.024-100 ng/mL) and was accurate and reproducible in the absence of matrix effects, allowing for robust, specific, and rapid quantification of baricitinib from a low amount of plasma (50 µL). The plasma concentration of baricitinib in the samples of the patients, expressed as mean ± SD, was 11.25 ± 10.86 ng/mL., Conclusions: This novel LC-MS/MS method is suitable for the therapeutic drug monitoring of baricitinib and can help guide therapy optimization in pediatric patients., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association of Therapeutic Drug Monitoring and Clinical Toxicology.)

Abstract: Ceftazidime-avibactam (CTZ-AVM) is a novel cephalosporin/beta-lactamase inhibitor with broad-spectrum activity against multidrug-resistant Pseudomonas aeruginosa . Ceftazidime-induced neurotoxicity is a well-described adverse effect, particularly in patients with renal insufficiency. However, appropriate dosing of ceftazidime-avibactam in patients undergoing renal replacement therapy (RRT) is sparsely investigated, and therapeutic drug monitoring to guide dosing remains lacking. Furthermore, when dose adjustment for impaired renal function is based on CTZ-AVM product information, inferior cure rates have been obtained compared with those with the standard therapy for intra-abdominal infections. Maintaining an effective dose while avoiding toxicity in these patients is challenging. Here, the authors describe the case of a critically ill patient, undergoing 2 modalities of RRT, who developed ceftazidime-induced neurotoxicity as confirmed using ceftazidime therapeutic drug monitoring. This case illustrates a therapeutic drug monitoring-based approach for guiding ceftazidime-avibactam dosing in this context and in diagnosing the cause of neurological symptoms and signs., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Therapeutic drug monitoring (TDM) is recommended for opioid maintenance therapy with levomethadone. However, TDM has not yet been applied to monitor opioid withdrawal therapy clinically, although tools to improve it are required., Methods: In this observational cohort study, repeated TDM with levomethadone was performed according to a prospective opioid withdrawal study protocol. Objective and subjective opioid withdrawal symptoms were measured using validated rating scales and correlated to levomethadone plasma concentrations. Plasma levels were measured using high-pressure liquid chromatography with column switching and spectroscopic detection of methadone and its major metabolite., Results: This study included 31 opioid-dependent patients who participated in standardized opioid withdrawal therapy. The serum levels of levomethadone were found to be highly variable and below the recommended therapeutic reference range of 250 ng/mL for maintenance therapy. These serum levels were positively correlated with dosage (r = 0.632; P < 0.001) and inversely correlated with subjective (r = -0.29; P = 0.011) and objective (r = -0.28; P = 0.014) withdrawal symptoms., Conclusions: The evidence provided sheds light on how to improve levomethadone withdrawal therapy in patients with opioid dependence. It seems likely that higher initial doses at the beginning and lower dose reductions would have been advantageous. TDM can enhance the safety of opioid withdrawal therapies, minimize withdrawal symptoms, and reduce dropout rates., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Sunitinib (SUN) malate is an oral, multitargeted, tyrosine kinase inhibitor approved for the treatment of metastatic renal cell carcinoma, imatinib-resistant or imatinib-intolerant gastrointestinal stromal tumors, and pancreatic neuroendocrine tumors. SUN has a narrow therapeutic window and high variability in interpatient pharmacokinetic parameters. Clinical detection methods for SUN and N -desethyl SUN limit the application of SUN to therapeutic drug monitoring. All published methods for quantifying SUN in human plasma require strict light protection to avoid light-induced isomerism or the use of additional quantitative software. To avoid these difficult processes in clinical routines, the authors propose a novel method that merges the peaks of the E -isomer and Z -isomer of SUN or N -desethyl SUN into a single peak., Methods: The E -isomer and Z -isomer peaks of SUN or N -desethyl SUN were merged into a single peak by optimizing the mobile phases to decrease the resolution of the isomers. A suitable chromatographic column was selected to obtain a good peak shape. Thereafter, the conventional and single-peak methods (SPM) were simultaneously validated and compared according to the guidelines published by the Food and Drug Administration in 2018 and the Chinese Pharmacopoeia in 2020., Results: The verification results showed that the SPM was superior to the conventional method in the matrix effect and met the requirements for biological sample analysis. SPM was then applied to detect the total steady-state concentration of SUN and N -desethyl SUN in tumor patients who received SUN malate., Conclusions: The established SPM makes the detection of SUN and N -desethyl SUN easier and faster without light protection or extra quantitative software, making it more appropriate for routine clinical use. The clinical application results showed that 12 patients took 37.5 mg per day, with a median total trough steady-state concentration of 75.0 ng/mL., Competing Interests: The authors declare no conflict of interest., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Abstract: Therapeutic drug monitoring to optimize drug therapy typically relies on the inconvenience of repeated plasma sampling. Sweat is a potential alternative biofluid convenient for sampling. However, limited information exists regarding the range of drugs excreted in sweat and their correlation with plasma concentrations. This study evaluated drugs in sweat and plasma of an ambulatory clinical cohort. Pilocarpine-induced sweat was collected from ambulatory participants at a single instance using an absorbent nylon mesh, followed by concurrent blood sampling for ratio and correlation analyses. In a model drug study, the pharmacokinetics of acetaminophen in sweat and plasma were compared. Of the 14 drugs and 2 metabolites monitored in the clinical study, all compounds were present in sweat and plasma; however, the sweat-to-plasma ratio varied substantially across the drugs. Opioids and methocarbamol demonstrated the highest concentrations in sweat, sometimes exceeding plasma concentrations. Selected antidepressants and muscle relaxants were also detected in sweat at a 2-10-fold dilution to the plasma. Others, such as gabapentin and pregabalin, were highly diluted (>30-fold) in sweat compared with plasma. Together, these data suggest that molecular attributes, specifically hydrophobicity (logP) and charge state at physiologic pH (7.4), enable reasonable prediction of sweat-to-plasma drug correlation. These findings demonstrated that sweat could be used as an alternative biofluid for therapeutic drug monitoring. The findings also suggest that although it has been broadly accepted that small hydrophobic molecules most likely have a strong plasma correlation, there is a small window of hydrophobicity and charge state that permits sweat partitioning., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose of Review: This review describes current knowledge of ganciclovir (GCV) and valganciclovir (ValGCV) pharmacokinetic/pharmacodynamic characteristics, highlighting the likely contribution from host genetic factors to interpatient variability. The evidence and challenges surrounding optimization of drug dosing through therapeutic drug monitoring (TDM) are examined, with recommendations made., Recent Findings: Pharmacokinetic studies of current dosing guidelines have shown high interindividual and intraindividual variability of GCV concentrations. This is sometimes associated with a slow decline in cytomegalovirus (CMV) viral load in some transplant recipients. A high incidence of GCV-associated myelosuppression has limited the use of this drug in the transplant setting. Patient groups identified to benefit from GCV TDM include pediatric patients, cystic fibrosis with lung transplantation, obese with kidney transplantation, and patients with fluctuating renal function or on hemodialysis. The emergence of refractory resistant CMV, particularly in immune compromised patients, highlights the importance of appropriate dosing of these antivirals. Host genetic factors need to be considered where recently, two host genes were shown to account for interpatient variation during ganciclovir therapy. Therapeutic Drug Monitoring has been shown to improve target antiviral-level attainment. The use of TDM may guide concentration-based dose adjustment, potentially improving virological and clinical outcomes. However, evidence supporting the use of TDM in clinical practice remains limited and further study is needed in the transplant cohort., Summary: Further studies examining novel biomarkers are needed to guide target concentrations in prophylaxis and treatment. The use of TDM in transplant recipients is likely to improve the clinical efficacy of current antivirals and optimize outcomes in transplant recipients., (Copyright © 2023 Wolters Kluwer Health, Inc. All rights reserved.)

Anticoagulants serve as the primary strategy for the prevention and treatment of both arterial and venous thromboembolism. Anticoagulants disrupt coagulation by interfering at various points in the coagulation cascade. This class of medications does not lyse clots that already exist; rather, it prevents thrombus formation and prevents or slows the extension of an existing clot. For decades, the standard therapy for patients requiring oral anticoagulation was warfarin. However, due to some of the shortcomings of warfarin, including the need for continuous routine monitoring, longtime onset and offset of anticoagulation effect, major food and drug interactions, and high incidence of bleeding, newer agents, termed direct oral anticoagulants, or DOACs were developed. This article will provide a review of clinically important information regarding the most commonly used anticoagulants and their reversal agents. [ABSTRACT FROM AUTHOR]